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Anomalous aortic origin of the coronary artery (AAOCA) is a rare disease associated with sudden cardiac death, usually related to physical effort in young people. Clinical routine tests fail to assess the ischemic risk, calling for novel diagnostic approaches. To this aim, some recent studies propose to assess the coronary blood flow (CBF) in AAOCA by computational simulations but they are limited by the use of data from literature retrieved from normal subjects. To overcome this limitation and obtain a reliable assessment of CBF, we developed a fully patient-specific lumped parameter model based on clinical imaging and in-vivo data retrieved during invasive coronary functional assessment of subjects with AAOCA. In such a way, we can estimate the CBF replicating the two hemodynamic conditions in-vivo analyzed. The model can mimic the effective coronary behavior with high accuracy and could be a valuable tool to quantify CBF in AAOCA. It represents the first step required to move toward a future clinical application with the aim of improving patient care. The study was registered at Clinicaltrial.gov with (ID: NCT05159791, date 2021-12-16).

The beetle Anthonomus grandis Boheman, 1843, is the main cotton pest, causing enormous losses in cotton. The breeding of genetically modified plants with A. grandis resistance is seen as an important control strategy. However, the identification of molecules with high toxicity to this insect remains a challenge. The susceptibility of A. grandis larvae to proteins (Cry1Ba, Cry7Ab, and Mpp23Aa/Xpp37Aa) from Bacillus thuringiensis Berliner, 1915, with toxicity reported against Coleopteran, has been evaluated. The ingestion of different protein concentrations (which were incorporated into an artificial diet) by the larvae was tested in the laboratory, and mortality was evaluated after one week. All Cry proteins tested exhibited higher toxicity than that the untreated artificial diet. These Cry proteins showed similar results to the control Cry1Ac, with low toxicity to A. grandis, since it killed less than 50% of larvae, even at the highest concentration applied (100 μg·g−1). Mpp/Xpp proteins provided the highest toxicity with a 0.18 μg·g−1 value for the 50% lethal concentration. Importantly, this parameter is the lowest ever reported for this insect species tested with B. thuringiensis proteins. This result highlights the potential of Mpp23Aa/Xpp37Aa for the development of a biotechnological tool aiming at the field control of A. grandis.

•Impaired functional hyperemia (FH) in aging contributes to vascular dementia. We validate functional ultrasound (fUS) as a novel approach for preclinical assessment of FH in aging.•We demonstrate that fUS can also be used to detect age-related changes in cerebrovascular density through ultrasound localization microscopy, enabling longitudinal tracking of vascular changes with age.•fUS offers greater imaging depth and resolution than other preclinical imaging modalities for FH, enabling detection of changes in smaller vessels and longitudinal studies. Backgrounds and Objectives: Aging is associated with impaired cerebrovascular function, including reduced functional hyperemia (FH), which contributes to cognitive decline and dementia. Unraveling the mechanisms responsible for FH decline during aging is crucial for developing interventions to promote healthy brain aging and mitigate cognitive impairment. Currently, laser speckle contrast imaging (LSCI) serves as the standard method for assessing FH in mouse models of cognitive dysfunction and aging. However, as a terminal procedure, long-term monitoring of changes in FH using LSCI is not possible. Functional ultrasound imaging (fUS) has improved spatial and temporal resolution compared to LSCI and is a promising alternative, but surgical manipulation of the mouse model is necessary to assess FH using fUS. Research Design and Methods: Here, we validated fUS as a novel method for assessing FH and vascular density in mice using a chronological aging model and compared different surgical paradigms. Young and aged mice underwent consecutive imaging with fUS and LSCI following surgical placement of a cranial window. Mice were imaged either acutely or 14 days post window placement. Results: Our findings revealed a robust correlation between the FH measurements obtained from fUS and LSCI in mice allowed to recover for 14 days post window-implantation, underscoring the reliability of fUS as a measurement tool. Similarly, the ability of fUS ultrasound localization microscopy (ULM) to detect age-related vascular rarefaction was improved by the 14-day recovery time after window implantation. Discussion and Implications: This study not only highlights the potential of fUS in FH assessment but also suggests the importance of recovery time post-surgery for optimal cerebrovascular imaging results.

As Novel psychoactive substances (NPS) are conceived to mimic the effects of common illicit drugs, they represent a serious public health challenge due to the spike in intoxications and fatalities that have been linked to their use. This study aims to provide epidemiological data on NPS use in the USA, determining lifetime prevalence of use and defining demographic, socioeconomic, drug use patterns and mental health correlates. This study uses secondary data from the US National Survey on Drug Use and Health (NSDUH), which is a large cross-sectional population-based survey carried out annually in the USA. We analysed data from 2007-14 (N = 307,935) using bivariate descriptive analysis and binary logistic regression to calculate prevalence and determine factors underlying NPS consumption. Adjusted odds ratios (OR) with 95% CI's were calculated for a set of selected independent variables. Our analysis NSDUH from 2007-14 highlights an increase in NPS use among adults, especially among white young men aged 18 to 25. Although the level of education of NPS users was relatively higher as compared to non-users, NPS users seemed to have a less wealthy situation. However, socioeconomic vulnerability appeared to be less important than mental health issues as a correlate to NPS use. NPS users seem to have followed a pattern of polysubstance use throughout their life, which involves both traditional illicit drugs and classic synthetic drugs. As NPS use seemed to be more prevalent among people having mental health issues, the rise in their use may have a negative impact on population mental health outcomes. Further comparative research on trends in NPS use and potential public health responses would be instrumental for developing appropriate health interventions, including drug checking, education for users and training for healthcare professionals working both within emergency wards and in/outpatient addiction and mental health services.

Cancer cells have altered metabolism compared to normal cells, including dependence on glutamine (GLN) for survival, known as GLN addiction. However, some cancer cell lines do not require GLN for survival and the basis for this discrepancy is not well understood. GLN is a precursor for antioxidants such as glutathione (GSH) and NADPH, and GLN deprivation is therefore predicted to deplete antioxidants and increase reactive oxygen species (ROS). Using diverse human cancer cell lines we show that this occurs only in cells that rely on GLN for survival. Thus, the preference for GLN as a dominant antioxidant source defines GLN addiction. We show that despite increased glucose uptake, GLN addicted cells do not metabolize glucose via the TCA cycle when GLN is depleted, as revealed by 13 C-glucose labeling. In contrast, GLN independent cells can compensate by diverting glucose-derived pyruvate into the TCA cycle. GLN addicted cells exhibit reduced PDH activity, increased PDK1 expression, and PDK inhibition partially rescues GLN starvation-induced ROS and cell death. Finally, we show that combining GLN starvation with pro-oxidants selectively kills GLN addicted cells. These data highlight a major role for GLN in maintaining redox balance in cancer cells that lack glucose-dependent anaplerosis.

The rapid rise in trade and use of NPS and the lack of information concerning their potential toxicity pose serious challenges to public health authorities across the world. Policy measures towards NPS taken so far have a special focus on their legal status, while the implementation of a public health strategy seems to be still missing. The aim of this study is to perform a general assessment of NPS-related policy (including regulatory measures and public health strategies) implemented by six European countries: Portugal, the Netherlands, Czech Republic, Poland, the United Kingdom and Sweden. Six EU countries were included in this scoping review study. Drug policies (including legal responses and public health strategies) were analysed. UNODC drug policy classification system was used as a benchmark, while path dependency approach was used for data analysis; a net of inter-dependencies between international, EU and national policies was highlighted. The countries included in this study can be placed in a wide spectrum according to their formulation of drug policy, from Portugal and the UK that have specific legal responses to NPS but have differently focused on harm reduction strategies at one end, to Sweden whose drug-free society goal is not translated into a specific regulation of NPS at the other end. The findings of the study reveal limited development towards harmonisation of national drug policies-particularly with regard to NPS. To tackle the challenge presented by NPS, EU Member states have formulated legislation and public health strategies independently. National approaches to NPS are therefore in line with their already existing drug policies, reflecting cultural values towards substance abuse and national political interests, while the homogenization at an international level has so far mostly been focused on law enforcement and drugs use preventive strategies.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive form of ovarian cancer. SCCOHT tumors have inactivating mutations in SMARCA4 (BRG1), one of the two mutually exclusive ATPases of the SWI/SNF chromatin remodeling complex. To address the role that BRG1 loss plays in SCCOHT tumorigenesis, we performed integrative multi-omic analyses in SCCOHT cell lines +/- BRG1 reexpression. BRG1 reexpression induced a gene and protein signature similar to an epithelial cell and gained chromatin accessibility sites correlated with other epithelial originating TCGA tumors. Gained chromatin accessibility and BRG1 recruited sites were strongly enriched for transcription-factor-binding motifs of AP-1 family members. Furthermore, AP-1 motifs were enriched at the promoters of highly upregulated epithelial genes. Using a dominant-negative AP-1 cell line, we found that both AP-1 DNA-binding activity and BRG1 reexpression are necessary for the gene and protein expression of epithelial genes. Our study demonstrates that BRG1 reexpression drives an epithelial-like gene and protein signature in SCCOHT cells that depends upon by AP-1 activity.

[This corrects the article DOI: 10.1371/journal.pone.0241056.].

Objective: The menstrual-related catamenial pneumothorax (CP) can be the first expression of thoracic endometriosis syndrome (TES), which is the presence of endometriotic lesions in the lungs and pleura, and pelvic endometriosis (PE). This study aims to analyze our experience with this specific correlation describing our multidisciplinary approach to CP. Methods: Hospital records of 32 women, operated for CP at our Department from January 2001 to December 2021 were reviewed. Surgical treatment consisted of videothoracoscopy and laparoscopy when indicated. Results: TES and PE were diagnosed in 13 (40.6%) and 12 (37.5%) women, respectively. The association of TES and PE was present in 11 cases (34%). Fifteen patients (46.9%) underwent laparoscopy, of which 11 concurrently with videothoracoscopy. Most of the patients affected had stage III–IV endometriosis (40.6%). All patients received hormonal therapy after surgery. Five patients with PE conceived spontaneously resulting in six live births. The mean follow-up was 117 ± 71 months (range 8–244). Pneumothorax recurrence occurred in six patients (18.8%). At present, all women are asymptomatic, with no sign of pneumothorax recurrence. Conclusions: CP might be the first expression of TES and/or PE. A multidisciplinary approach is advocated for optimal management of the disease.

Social movements never entirely win or lose, nor do they suddenly appear or disappear. Just as their component parts recombine and continue in other forms, so movements have dozens of impacts of various kinds. To make sense of this complexity we propose examining the outcomes of political interactions for a variety of players (including individuals) across a range of arenas. Given the acknowledged tradeoffs and dilemmas of collective action, we would expect packages of outcomes to appear together sometimes; for example, gains in street mobilization may lead to losses in the form of a damaged reputation or police repression. The first step to explaining such patterns is to identify and name them. We examine one of these outcome patterns, the arena-ownership package, through the case of Seattle's historic $15 per hour wage law passed in 2014, the first ever in a major U.S. city. The players who crafted the bill included an avowed Socialist, the owner of Seattle's iconic Space Needle tower, many representatives of the city's labor movement, and the newly elected Democratic Mayor Ed Murray. These diverse players moved through a series of complex arenas to arrive at the legislative outcome. In this case, we find players who create new arenas, rather than only using already-existing arenas. This move is associated with a typical package of gains and losses: increased control for the player on the one hand, but corresponding losses and risks—the alienation of excluded players and increased perception of responsibility. The creating player is blamed for the arena's failures as well as credited with its successes.