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Tuan Dinh Le, 1,* Nga Phi Thi Nguyen, 2, 3,* Son Tien Nguyen, 2, 3 Hien Thi Nguyen, 4 Hoa Thanh Thi Tran, 5 Thi Ho Lan Nguyen, 6 Cuong Duy Nguyen, 7 Giang Thi Nguyen, 6 Xuan Thanh Nguyen, 8 Bac Duy Nguyen, 9 Son The Trinh, 10 Tuan Anh Ngo, 11 Binh Nhu Do, 12, 13 Thuc Cong Luong 8, 14 1Department of Internal Medicine, Thai Binh University of Medicine and Pharmacy, Thai Binh, Vietnam; 2Department of Endocrinology, Military Hospital 103, Ha Noi, Vietnam; 3Department of Rheumatology and Endocrinology, Vietnam Military Medical University, Ha Noi, Vietnam; 4Department of Physiology, Thai Binh university of Medicine and Pharmacy, Thai Binh, Vietnam; 5Department of Intensive Care Unit, National Hospital of Endocrinology, Ha Noi, Vietnam; 6Department of Internal Medicine, National Hospital of Endocrinology, Ha Noi, Vietnam; 7Department of Intensive Care Unit, Thai Binh university of Medicine and Pharmacy, Thai Binh, Vietnam; 8Department of Vascular Cardiology, Military Hospital 103, Ha Noi, Vietnam; 9Department of Anatomy, Vietnam Military Medical University, Ha Noi, Vietnam; 10Military Institute of ClinicalEmbryology and Histology, Vietnam Military Medical University, Ha Noi, Vietnam; 11Department of Health Economic, Vietnam Military Medical University, Ha Noi, Vietnam; 12Department of Infectious Disease, Vietnam Military Medical University, Ha Noi, Vietnam; 13Division of Military Science, Military Hospital 103, Ha Noi, Vietnam; 14Director Office, Military Hospital 103, Ha Noi, Vietnam*These authors contributed equally to this workCorrespondence: Thuc Cong Luong; Son The Trinh Email lcthuc@gmail.com; trinhtheson@vmmu.edu.vnIntroduction: Endothelium dysfunction and decrease of incretin effects occur early in type 2 diabetes mellitus and these changes contribute to diabetic cardiovascular complications such as atherosclerosis, thick intima-media, coronary, and peripheral arterial diseases. In patients with diabetes, the femoral artery is a site of a high incidence of injury in peripheral vascular diseases, and atherosclerotic changes may appear earlier in the femoral artery compared to the carotid artery. This study was conducted to determine the prevalence of increased femoral artery intima-media thickness (IMT) and atherosclerotic plaque and their correlation with serum glucagon-like peptide-1 (GLP-1) levels in newly-diagnosed patients with type 2 diabetes mellitus.Materials and Methods: A cross-sectional study was conducted on 332 patients with nT2D in the National Endocrinology Hospital, Vietnam from January 2015 to May 2018. IMT was measured by Doppler ultrasound and GLP-1 by enzyme-linked immunosorbent assay (ELISA). All data were analyzed with SPSS version 26 for Windows (SPSS Inc, Chicago, IL).Results: Prevalence of thick femoral artery IMT and atherosclerotic plaque was 38.2 and 22.3%, respectively. There was a relationship between IMT and age, waist to hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting GLP-1, high sensitive CRP (hsCRP) and 24-hour microalbuminuria secretion (24-h MAUS). The fasting serum GLP-1 (fGLP-1) levels were reduced significantly in patients with thickness and atherosclerosis femoral artery (p = 0.001). After adjusting with other related factors, namely, DBP and estimated glomerular filtration rate (eGFR), whilst hsCRP and 24-h MAUS showed a significantly positive correlation to IMT (Standardized B and p of 0.242, 0.004 and 0.178, 0.043, respectively), fGLP-1 showed a significantly negative correlation to IMT (Standardized B = − 0.288, p = 0.001).Conclusion: Among n2TD, the percentage for femoral artery thick IMT and atherosclerosis was 38.2% and 22.3% respectively, and serum GLP-1 was negatively correlated with thick IMT and atherosclerosis.Keywords: newly diagnosed type 2 diabetes mellitus, intima-media thickness and atherosclerotic plaque, femoral artery, serum glucagon-like peptide-1 levels

The PET/CT exam is mostly remarkable for the diffusely prominent tracer uptake by the colonic interposition and remainder of the colon (fig. a & b) with corresponding retrosternal location of the colonic interposition on chest radiograph and chest CT (Fig. c & d). (c & d) Corresponding features of the anterior mediastinal colonic interposition on lateral chest radiograph and sagittal chest CT (arrowheads). gl Epidermolysis bullosa (EB) represents a group of skin diseases, with different phenotypes, characterized by blistering lesions of the dermal-epidermal basement membrane. The diffusely prominent F-18 FDG PET/CT features of the colonic interposition and remainder of the colon may be related to our patient's subsequent inflammatory involvement occurring through the clinical course of EB. [Extracted from the article]

The article presents a case study of a woman with history of endometrial carcinoma, hysterectomy and pelvic nodal dissection. It notes the patient's complaint of lower back pain to the right inguinal region, right proximal lower extremity, results of magnetic resonance imaging of lumbar spine and pelvis.

The article discusses the results of the F18-fluorodeoxyglucose-positron-emission tomography/computed tomography (FDG-PET/CT) imaging of a patient who was diagnosed with sinonasal teratocarcinosarcoma. The results of the FDG-PET/CT imaging were compared with magnetic resonance imaging (MRI) results. The article explains the course of the disease, treatments made, and the eventual progression of the disease leading to the patient's death.

Purpose: To evaluate, in a prospective study, the use of (111)In-capromab pendetide (ProstaScint) scan to guide the delivery of a concomitant boost to intraprostatic region showing increased uptake while treating the entire gland with intensity-modulated radiotherapy for localized prostate cancer. Methods and Materials: From September 2002 to November 2005, 71 patients were enrolled. Planning pelvic CT and (111)In-capromab pendetide scan images were coregistered. The entire prostate gland received 75.6 Gy/42 fractions, whereas areas of increased uptake in (111)In-capromab pendetide scan received 82 Gy. For patients with T3/T4 disease, or Gleason score ≥8, or prostate-specific antigen level >20 ng/mL, 12 months of adjuvant androgen deprivation therapy was given. In January 2005 the protocol was modified to give 6 months of androgen deprivation therapy to patients with a prostate-specific antigen level of 10-20 ng/mL or Gleason 7 disease. Results: Thirty-one patients had low-risk, 30 had intermediate-risk, and 10 had high-risk disease. With a median follow-up of 66 months, the 5-year biochemical control rates were 94% for the entire cohort and 97%, 93%, and 90% for low-, intermediate-, and high-risk groups, respectively. Maximum acute and late urinary toxicities were Grade 2 for 38 patients (54%) and 28 patients (39%) and Grade 3 for 1 and 3 patients (4%), respectively. One patient had Grade 4 hematuria. Maximum acute and late gastrointestinal toxicities were Grade 2 for 32 patients (45%) and 15 patients (21%), respectively. Most of the side effects improved with longer follow-up. Conclusion: Concomitant boost to areas showing increased uptake in (111)In-capromab pendetide scan to 82 Gy using intensity-modulated radiotherapy while the entire prostate received 75.6 Gy was feasible and tolerable, with 94% biochemical control rate at 5 years. [ABSTRACT FROM AUTHOR]

How enteric pathogens adapt their metabolism to a dynamic gut environment is not yet fully understood. To investigate how Salmonella enterica Typhimurium (S.Tm) colonizes the gut, we conducted an in vivo transposon mutagenesis screen in a gnotobiotic mouse model. Our data implicate mixed-acid fermentation in efficient gut-luminal growth and energy conservation throughout infection. During initial growth, the pathogen utilizes acetate fermentation and fumarate respiration. After the onset of gut inflammation, hexoses appear to become limiting, as indicated by carbohydrate analytics and the increased need for gluconeogenesis. In response, S.Tm adapts by ramping up ethanol fermentation for redox balancing and supplying the TCA cycle with α-ketoglutarate for additional energy. Our findings illustrate how S.Tm flexibly adapts mixed fermentation and its use of the TCA cycle to thrive in the changing gut environment. Similar metabolic wiring in other pathogenic Enterobacteriaceae may suggest a broadly conserved mechanism for gut colonization., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Women living with HIV/AIDS (WLHA) encounter numerous challenges, such as stigma and gender disparities, that hinder their access to care, especially in patriarchal societies like Vietnam. We developed a hybrid intervention with online and offline (in-person) components to empower WLHA in Vietnam. The intervention was pilot tested with 91 WLHA in Hanoi. During baseline and 4-month, study investigators delivered two in-person sessions, one Zoom session, and 15 weeks of Zalo (social media platform) discussions to enhance positive coping strategies, treatment utilization and adherence, and engagement of support from family and peers. The participants continued their Zalo discussions from 4-month to 6-month without investigators' involvement. Intervention outcomes, including active coping and perceived barriers to care, were evaluated at baseline, 4-, and 6-month surveys. Mixed-effects regression models showed that the participants' active coping significantly increased from baseline (50.5 ± 9.4) to 4-month (53.8 ± 6.2; p = 0.0001), although there was a slight decrease at 6-month (52.8 ± 7.2), the change from 4-month to 6-month was not significantly significant (p = 0.3256). There was a significant reduction in participants' perceived barriers to care, from 19.8 ± 5.2 at baseline to 17.4 ± 5.2 at 4-month (p < 0.0001), which remained stable at 17.8 ± 4.3 at 6-month (p < 0.0001 compared to baseline). This intervention presents a promising model to empower WLHA in Vietnam and potentially in similar global contexts. Future interventions could benefit from leveraging natural peer leaders and adopting a more person-centered approach to meet WLHA's varying needs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Women living with HIV/AIDS (WLHA) in Vietnam encounter challenges stemming from HIV-related stigma and gender disparities. This study delves into the intersectionality of HIV-related stigma and gender disparities as perceived by WLHA. A cross-sectional survey was conducted among 91 WLHA in Hanoi, Vietnam. Two sets of identically worded scales were used to measure awareness, agreement, and application of stigma towards people living with HIV/AIDS (PLHA) and WLHA. A larger difference between stigma scores towards WLHA and that of PLHA represents a higher level of female-specific stigma. Univariate analyses and multiple regressions were conducted to identify demographic and psycho-social factors associated with the gendered differences in stigma measures. Multiple linear regression showed that WLHA who were currently married were more likely to apply stigma concepts to themselves due to gender identity (adjusted beta coefficient (aBeta Coef) = 0.223). Psychological capital was negatively associated with awareness of stigma towards female identity (aBeta Coef = -0.261). A higher perceived norm in women's equity and power was associated with less self-application of female-specific stigma (aBeta Coef = -0.294). Our findings underscore the importance of addressing psychological well-being and promoting gender equity norms as essential components in the efforts to reduce female-specific HIV-related stigma in WLHA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Delivering methadone treatment in community health facilities by primary care providers is a task-shifting strategy to expand access to drug use treatment, especially in rural mountainous areas. This study aims to investigate factors related to confidence in providing methadone treatment among primary care providers in Vietnam to inform good practice development., Methods: We conducted a cross-sectional survey with 276 primary care providers who were physicians, physician assistants, nurses, pharmacists or dispensing staff from 67 communes in a mountainous province in Northern Vietnam. Using self-report scales, we measured providers' confidence in providing methadone treatment, beliefs in harm reduction, perceived work-related support, perceived stigma and risk in working with drug-using patients, and empathy towards this population. We used multiple linear regression analyses to explore factors associated with providers' confidence in providing methadone treatment in the whole sample and to compare two groups of providers who did and did not have experience providing methadone. Potential associated factors were measured at facility and provider levels., Result: 114 (41.3%) participants had previously experience in providing methadone treatment. Providers with methadone treatment experiences had higher confidence in and more accurate knowledge of methadone treatment, perceived less stigma of working with drug-using patients, and reported more work-related support than those without experiences. Higher medical education is associated with lower confidence in providing methadone treatment among providers without methadone experiences, but higher confidence among providers with methadone experiences. Better methadone knowledge was associated with greater confidence in providing methadone treatment among inexperienced providers but not among those with experiences. Receiving work-related support was associated with greater confidence in providing treatment in both groups, regardless of their past methadone experiences., Conclusion: In rural provinces where methadone treatment has been expanded to primary care clinics, interventions to improve primary care providers' confidence should benefit professionals with diverse experiences in providing methadone treatment. Continued training and support at work for providers is essential to ensuring quality in decentralized methadone treatment., (© 2024. The Author(s).)

Intestinal epithelial cells (IECs) play pivotal roles in nutrient uptake and in the protection against gut microorganisms. However, certain enteric pathogens, such as Salmonella enterica serovar Typhimurium (S. Tm), can invade IECs by employing flagella and type III secretion systems (T3SSs) with cognate effector proteins and exploit IECs as a replicative niche. Detection of flagella or T3SS proteins by IECs results in rapid host cell responses, i.e., the activation of inflammasomes. Here, we introduce a single-cell manipulation technology based on fluidic force microscopy (FluidFM) that enables direct bacteria delivery into the cytosol of single IECs within a murine enteroid monolayer. This approach allows to specifically study pathogen-host cell interactions in the cytosol uncoupled from preceding events such as docking, initiation of uptake, or vacuole escape. Consistent with current understanding, we show using a live-cell inflammasome reporter that exposure of the IEC cytosol to S. Tm induces NAIP/NLRC4 inflammasomes via its known ligands flagellin and T3SS rod and needle. Injected S. Tm mutants devoid of these invasion-relevant ligands were able to grow in the cytosol of IECs despite the absence of T3SS functions, suggesting that, in the absence of NAIP/NLRC4 inflammasome activation and the ensuing cell death, no effector-mediated host cell manipulation is required to render the epithelial cytosol growth-permissive for S. Tm. Overall, the experimental system to introduce S. Tm into single enteroid cells enables investigations into the molecular basis governing host-pathogen interactions in the cytosol with high spatiotemporal resolution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ernst et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu's arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet's disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.

Microbiomes feature recurrent compositional structures under given environmental conditions. However, these patterns may conceal diverse underlying population dynamics that require intrastrain resolution. Here we developed a genomic tagging system, termed wild-type isogenic standardized hybrid (WISH)-tags, that can be combined with quantitative polymerase chain reaction and next-generation sequencing for microbial strain enumeration. We experimentally validated the performance of 62 tags and showed that they can be differentiated with high precision. WISH-tags were introduced into model and non-model bacterial members of the mouse and plant microbiota. Intrastrain priority effects were tested using one species of isogenic barcoded bacteria in the murine gut and the Arabidopsis phyllosphere, both with and without microbiota context. We observed colonization resistance against late-arriving strains of Salmonella Typhimurium in the mouse gut, whereas the phyllosphere accommodated Sphingomonas latecomers in a manner proportional to their presence at the late inoculation timepoint. This demonstrates that WISH-tags are a resource for deciphering population dynamics underlying microbiome assembly across biological systems., (© 2024. The Author(s).)

Motivation: DNA barcoding has become a powerful tool for assessing the fitness of strains in a variety of studies, including random transposon mutagenesis screens, attenuation of site-directed mutants, and population dynamics of isogenic strain pools. However, the statistical analysis, visualization, and contextualization of the data resulting from such experiments can be complex and require bioinformatic skills., Results: Here, we developed mBARq, a user-friendly tool designed to simplify these steps for diverse experimental setups. The tool is seamlessly integrated with an intuitive web app for interactive data exploration via the STRING and KEGG databases to accelerate scientific discovery., Availability and Implementation: The tool is implemented in Python. The source code is freely available (https://github.com/MicrobiologyETHZ/mbarq) and the web app can be accessed at: https://microbiomics.io/tools/mbarq-app., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: This study investigated women living with HIV/AIDS (WLHA)'s practices and decision-making regarding disclosure of HIV status in healthcare settings in Vietnam. Introduction: Disclosure of HIV status in healthcare settings is under-studied., Methods: We conducted in-depth interviews with 30 WLHA in Hanoi, Vietnam. Thematic analysis was conducted to investigate the patterns, considerations, and consequences of HIV disclosure. Results: Most participants chose a selective disclosure strategy based on the type of procedure and healthcare setting. They considered several factors: concerns about stigma/discrimination, risks of confidentiality breach, relevance to healthcare provision, and altruism towards protecting providers and other patients. Selective disclosure or non-disclosure often prevented participants from accessing comprehensive care. Conclusion: The study underscores the need to prepare WLHA to make informed decisions regarding disclosure and provide them with service navigations and support. It also highlights the necessity of reducing stigma and enhancing confidentiality protection to ensure safe disclosure in healthcare settings., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

TURBOMOLE is a highly optimized software suite for large-scale quantum-chemical and materials science simulations of molecules, clusters, extended systems, and periodic solids. TURBOMOLE uses Gaussian basis sets and has been designed with robust and fast quantum-chemical applications in mind, ranging from homogeneous and heterogeneous catalysis to inorganic and organic chemistry and various types of spectroscopy, light-matter interactions, and biochemistry. This Perspective briefly surveys TURBOMOLE's functionality and highlights recent developments that have taken place between 2020 and 2023, comprising new electronic structure methods for molecules and solids, previously unavailable molecular properties, embedding, and molecular dynamics approaches. Select features under development are reviewed to illustrate the continuous growth of the program suite, including nuclear electronic orbital methods, Hartree-Fock-based adiabatic connection models, simplified time-dependent density functional theory, relativistic effects and magnetic properties, and multiscale modeling of optical properties.

Background: Vietnam has one of the highest rates of antibiotic resistance in Asia. In 2020, the Vietnam Minister of Health introduced new legislation for the implementation of an antimicrobial stewardship program (ASP). The evidence for the effectiveness of ASP in small hospitals and hospitals located in provinces was limited compared with larger-scale and central city hospitals., Aim: Evaluation of the impact before and after the introduction of an antimicrobial stewardship program at Dong Thap General Hospital, from 2017 to 2021., Methods: Retrospective data was collected from June 2017 to June 2021. The impact of the ASP on changes in antibiotic use and the clinical outcome associated with the implementation of the ASP was evaluated using autoregressive integrated moving average modelling of controlled interrupted time-series analysis., Results: There was a significant and sustained decrease in antibiotic consumption level (step change) in 2 indicators, DOT/1000PD (129.55; P <0.01) and LOT/1000PD (99.95, P <0.01), immediately after the ASP intervention. There were no statistically significant changes identified in terms of consumption with DDD/1000PD, or in the clinical outcomes. The results showed no statistically significant change in consumption trend (ramps) in all evaluated indicators. No statistically significant changes in consumption levels and trends were observed in the control group., Conclusion: The ASP implemented in Dong Thap General Hospital from 2017 to 2021 showed a considerable influence on antibiotic consumption as indicated by the DOT/1000 PD and LOT/1000 PD during the initial stages. Moreover, controlling antibiotic consumption did not negatively impact patient outcomes., (© 2023 Published by Elsevier Ltd on behalf of The Healthcare Infection Society.)

Triple-negative breast cancer (TNBC) represents around 15% of the 2.26 million breast cancers diagnosed worldwide annually and has the worst outcome. Despite recent therapeutic advances, there remains a lack of targeted therapies for this breast cancer subtype. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with biological roles in regulating development, xenobiotic metabolism, cell cycle progression and cell death. AhR activation by select ligands can promote tumor suppression in multiple cancer types. AhR can negatively regulate the activity of different oncogenic signaling pathways and can directly upregulate tumor suppressor genes such as p27 Kip1 . To determine the role of AhR in TNBC, we generated AhR-deficient cancer cells and investigated the impact of AhR loss on TNBC cell growth phenotypes. We found that AhR-deficient MDA-MB-468 TNBC cells have increased proliferation and formed significantly more colonies compared to AhR expressing cells. These cells without AhR expression grew aggressively in vivo. To determine the molecular targets driving this phenotype, we performed transcriptomic profiling in AhR expressing and AhR knockout MDA-MB-468 cells and identified tyrosine receptor kinases, as well as other genes involved in proliferation, survival and clonogenicity that are repressed by AhR. In order to determine therapeutic targeting of AhR in TNBC, we investigated the anti-cancer effects of the novel AhR ligand 11-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (11-Cl-BBQ), which belongs to a class of high affinity, rapidly metabolized AhR ligands called benzimidazoisoquinolines (BBQs). 11-Cl-BBQ induced AhR-dependent cancer cell-selective growth inhibition and strongly inhibited colony formation in TNBC cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Salmonella Typhimurium elicits gut inflammation by the costly expression of HilD-controlled virulence factors. This inflammation alleviates colonization resistance (CR) mediated by the microbiota and thereby promotes pathogen blooms. However, the inflamed gut-milieu can also select for hilD mutants, which cannot elicit or maintain inflammation, therefore causing a loss of the pathogen's virulence. This raises the question of which conditions support the maintenance of virulence in S. Typhimurium. Indeed, it remains unclear why the wild-type hilD allele is dominant among natural isolates. Here, we show that microbiota transfer from uninfected or recovered hosts leads to rapid clearance of hilD mutants that feature attenuated virulence, and thereby contributes to the preservation of the virulent S. Typhimurium genotype. Using mouse models featuring a range of microbiota compositions and antibiotic- or inflammation-inflicted microbiota disruptions, we found that irreversible disruption of the microbiota leads to the accumulation of hilD mutants. In contrast, in models with a transient microbiota disruption, selection for hilD mutants was prevented by the regrowing microbiota community dominated by Lachnospirales and Oscillospirales. Strikingly, even after an irreversible microbiota disruption, microbiota transfer from uninfected donors prevented the rise of hilD mutants. Our results establish that robust S. Typhimurium gut colonization hinges on optimizing its manipulation of the host: A transient and tempered microbiota perturbation is favorable for the pathogen to both flourish in the inflamed gut and also minimize loss of virulence. Moreover, besides conferring CR, the microbiota may have the additional consequence of maintaining costly enteropathogen virulence mechanisms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gül et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To determine the cost-effectiveness of the addition of chromosomal anomalies detectable by non-invasive prenatal screening (NIPS), in a prenatal screening programme targeting common aneuploidies., Design, Setting and Participants: A simulation study was conducted to study the addition of chromosomal anomalies detectable by NIPS (sex chromosome aneuploidies, 22q11.2 deletion syndrome, large deletion/duplication >7 Mb and rare autosomal trisomies) to five basic strategies currently aiming the common trisomies: three strategies currently offered by the public healthcare systems in Canada, whose first-tier test is performed with biochemical markers, and two programmes whose first-tier test consists of NIPS-based methods., Outcome Measures: The total number of cases of chromosomal anomalies detected and the costs related to the consumption of medical services., Results: The most effective and the most cost-effective option in almost all prenatal screening strategies is the option that includes all targeted additional conditions. In the strategies where NIPS is used as first-tier testing, the cost per additional case detected by adding all possible additional anomalies to a programme that currently targets only common trisomies is $C25 710 (95% CI $C25 489 to $C25 934) for massively parallel shotgun sequencing and $C57 711 (95% CI $C57 141 to $C58 292) for targeted massively parallel sequencing, respectively. The acceptability curves show that at a willingness-to-pay of $C50 000 per one additional case detected, the expansion of NIPS-based methods for the detection of all possible additional conditions has a 90% probability of being cost-effective., Conclusion: From an economic perspective, in strategies that use NIPS as a first-tier screening test, expanding the programmes to detect any considered chromosomal anomalies other than the three common trisomies would be cost-effective. However, the potential expansion of prenatal screening programmes also requires consideration of societal issues, including ethical ones., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Antibiotic resistance plasmids can be disseminated between different Enterobacteriaceae in the gut. Here, we investigate how closely related Enterobacteriaceae populations with similar nutrient needs can co-bloom in the same gut and thereby facilitate plasmid transfer. Using different strains of Salmonella Typhimurium (S.Tm SL1344 and ATCC14028) and mouse models of Salmonellosis, we show that the bloom of one strain (i.e., recipient) from very low numbers in a gut pre-occupied by the other strain (i.e., donor) depends on strain-specific utilization of a distinct carbon source, galactitol or arabinose. Galactitol-dependent growth of the recipient S.Tm strain promotes plasmid transfer between non-isogenic strains and between E. coli and S.Tm. In mice stably colonized by a defined microbiota (OligoMM 12 ), galactitol supplementation similarly facilitates co-existence of two S.Tm strains and promotes plasmid transfer. Our work reveals a metabolic strategy used by Enterobacteriaceae to expand in a pre-occupied gut and provides promising therapeutic targets for resistance plasmids spread., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recruitment of neutrophils into and across the gut mucosa is a cardinal feature of intestinal inflammation in response to enteric infections. Previous work using the model pathogen Salmonella enterica serovar Typhimurium (S.Tm) established that invasion of intestinal epithelial cells by S.Tm leads to recruitment of neutrophils into the gut lumen, where they can reduce pathogen loads transiently. Notably, a fraction of the pathogen population can survive this defense, re-grow to high density, and continue triggering enteropathy. However, the functions of intraluminal neutrophils in the defense against enteric pathogens and their effects on preventing or aggravating epithelial damage are still not fully understood. Here, we address this question via neutrophil depletion in different mouse models of Salmonella colitis, which differ in their degree of enteropathy. In an antibiotic pretreated mouse model, neutrophil depletion by an anti-Ly6G antibody exacerbated epithelial damage. This could be linked to compromised neutrophil-mediated elimination and reduced physical blocking of the gut-luminal S.Tm population, such that the pathogen density remained high near the epithelial surface throughout the infection. Control infections with a ssaV mutant and gentamicin-mediated elimination of gut-luminal pathogens further supported that neutrophils are protecting the luminal surface of the gut epithelium. Neutrophil depletion in germ-free and gnotobiotic mice hinted that the microbiota can modulate the infection kinetics and ameliorate epithelium-disruptive enteropathy even in the absence of neutrophil-protection. Together, our data indicate that the well-known protective effect of the microbiota is augmented by intraluminal neutrophils. After antibiotic-mediated microbiota disruption, neutrophils are central for maintaining epithelial barrier integrity during acute Salmonella-induced gut inflammation, by limiting the sustained pathogen assault on the epithelium in a critical window of the infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gül et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Triple-negative breast cancer (TNBC) remains a disease with a paucity of targeted treatment opportunities. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is involved in a wide range of physiological processes, including the sensing of xenobiotics, immune function, development, and differentiation. Different small-molecule AhR ligands drive strikingly varied cellular and organismal responses. In certain cancers, AhR activation by select small molecules induces cell cycle arrest or apoptosis via activation of tumor-suppressive transcriptional programs. AhR is expressed in triple-negative breast cancers, presenting a tractable therapeutic opportunity. Here, we identify a novel ligand of the aryl hydrocarbon receptor that potently and selectively induces cell death in triple-negative breast cancer cells and TNBC stem cells via the AhR. Importantly, we found that this compound, Analog 523, exhibits minimal cytotoxicity against multiple normal human primary cells. Analog 523 represents a high-affinity AhR ligand with potential for future clinical translation as an anticancer agent., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Abstract: Keloids are pathological scars from exuberant fibroproliferative collagen response and excessive extracellular matrix production usually extending beyond the original wound margins. Although keloids are mostly of dermatological concern, they could be incidentally depicted on scintigraphic planar and PET/CT imaging and could mimic other types of skin diseases. The authors present a case of chest wall keloids documented on 18 F-piflufolastat PET/CT during the evaluation of prostate cancer recurrence., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and functions as a tumour suppressor in different cancer models. In the present study, we report detailed characterization of 11-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (11-Cl-BBQ) as a select modulator of AhR-regulated transcription (SMAhRT) with anti-cancer actions. Treatment of lung cancer cells with 11-Cl-BBQ induced potent and sustained AhR-dependent anti-proliferative effects by promoting G1 phase cell cycle arrest. Investigation of 11-Cl-BBQ-induced transcription in H460 cells with or without the AhR expression by RNA-sequencing revealed activation of p53 signalling. In addition, 11-Cl-BBQ suppressed multiple pathways involved in DNA replication and increased expression of cyclin-dependent kinase inhibitors, including p27 Kip1 , in an AhR-dependent manner. CRISPR/Cas9 knockout of individual genes revealed the requirement for both p53 and p27 Kip1 for the AhR-mediated anti-proliferative effects. Our results identify 11-Cl-BBQ as a potential lung cancer therapeutic, highlight the feasibility of targeting AhR and provide important mechanistic insights into AhR-mediated-anticancer actions., (© 2022 Federation of European Biochemical Societies.)

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated fibrosclerosing disease with tumefactive lesions infiltrated by IgG4-positive plasma cells. Initially described as autoimmune pancreatitis, IgG4-RD is now recognized as a discrete entity and is found to affect virtually any organ in the body. Common extrapancreatic sites include the biliary tree, salivary glands, periorbital tissue, lungs, kidneys, lymph nodes, aorta, retroperitoneum, and thyroid gland. Diagnosis-which relies on histopathologic, serologic, and radiologic features-can be challenging with the disease underdiagnosed, as IgG4-RD often mimics malignancy, infectious processes, or other immune-mediated conditions. Patients may present with signs of compression of nearby structures due to mass effect or with organ failure when the disease is left untreated. The clinical course is complex, with single- or multiorgan involvement and metachronous or synchronous occurrence of lesions. IgG4-RD responds well to glucocorticoid therapy, disease-modifying antirheumatic drugs, and B-cell-depleting biologic agents; prompt diagnosis is important to avoid delay in treatment and unnecessary pharmacologic or surgical intervention. While imaging features may not be specific for IgG4-RD, functional whole-body imaging with fluorine 18-fluorodeoxyglucose PET/CT is a useful adjunct for localizing extrapancreatic sites for biopsy, monitoring therapeutic response, and demonstrating disease relapse. The authors describe the pancreatic and extrapancreatic sites of involvement in IgG4-RD, with imaging features and patterns to aid in distinguishing IgG4-RD from its mimics through a multimodality approach with emphasis on functional imaging evaluation. © RSNA, 2023 Quiz questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates cell fate via activation of a diverse set of genes. There are conflicting reports describing the role of AhR in cancer. AhR-knockout mice do not develop tumors spontaneously, yet the AhR can act as a tumor suppressor in certain contexts. Loss of tumor suppression by p53 is common in human cancer. To investigate AhR function in the absence of p53, we generated mice lacking both AhR and p53. Mice deficient for AhR and p53 had shortened lifespan, increased tumorigenesis, and an altered tumor spectrum relative to control mice lacking only p53. In addition, knockout of both AhR and p53 resulted in reduced embryonic survival and neonatal fitness. We also examined the consequences of loss of AhR in p53-heterozygous mice and observed a significantly reduced lifespan and enhanced tumor burden. These findings reveal an important role for the AhR as a tumor suppressor in the absence of p53 signaling and support the development of anti-cancer therapeutics that would promote the tumor suppressive actions of the AhR., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Abstract: Hemorrhagic pseudotumor occurs in approximately 1% to 2% of patients with hemophilia. This lesion is exceptionally rare in nonhemophiliac individuals. The authors present a case of treated right ischial plasmacytoma with a progressively enlarging expansile hemorrhagic pseudotumor, documented on 18 F-FDG PET/CT and MRI and confirmed by histology., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)