Management of thoracic outlet syndrome in patients with hemodialysis access.

Patients with threatened arteriovenous access are often found to have central venous stenoses at the ipsilateral costoclavicular junction, which may be resistant to endovascular intervention. Stenoses in this location may not resolve unless surgical decompression of thoracic outlet is performed to relieve the extrinsic compression on the subclavian vein. The authors reviewed the management of dialysis patients with central venous lesions at the thoracic outlet, as well as the role of surgical decompression with first-rib resection or claviculectomy for salvage of threatened, ipsilateral dialysis access.

CDC7 inhibition drives an inflammatory response and a p53-dependent senescent-like state in breast epithelial cells.

Drugs that block DNA replication prevent cell proliferation, which may result in anticancer activity. The latter is dependent on the drug's mode of action as well as on cell type-dependent responses to treatment. The inhibition of Cell division cycle 7-related protein kinase (CDC7), a key regulator of DNA replication, decreases the efficiency of origin firing and hampers the restarting of paused replication forks. Here, we show that upon prolonged CDC7 inhibition, breast-derived MCF10A cells progressively withdraw from the cell cycle and enter a reversible senescent-like state. This is characterised by the rewiring of the transcriptional programme with the induction of cytokine and chemokine expression and correlates with the accumulation of Cyclic GMP-AMP synthase (cGAS)-positive micronuclei. Importantly, cell fate depends on Cellular tumour antigen p53 (p53) function as cells no longer enter senescence but are funnelled into apoptosis upon p53 knockout. This work uncovers key features of the secondary response to CDC7 inhibitors, which could aid the development of these compounds as anticancer drugs.

Molecular identification of Crimean-Congo haemorrhagic fever virus in Hyalomma rufipes and Amblyomma variegatum in the Upper East Region of Ghana.

Sampled ticks were screened for Crimean-Congo haemorrhagic fever virus (CCHFV) using an assay that targets the nucleoprotein gene region of the S segment, a conserved region of the CCHFV genome. Minimum infection rates of 0.34% and 0.10% were obtained when testing pools of Hyalomma rufipes and Amblyomma variegatum, respectively. Next-generation sequencing and phylogenetic analysis showed that the S and L segments of the CCHFV isolate clustered with those of similar isolates of genotype III. However, analysis of the M segment showed that reassortment had occurred, causing this segment to cluster with those of isolates of genotype I, providing the first evidence of such an occurrence in Ghana.

The impact of race and other demographic factors on the false positive rates of five embedded Performance Validity Tests (PVTs) in a Veteran sample.

INTRODUCTION: It is common to use normative adjustments based on race to maintain accuracy when interpreting cognitive test results during neuropsychological assessment. However, embedded performance validity tests (PVTs) do not adjust for these racial differences and may result in elevated rates of false positives in African American/Black (AA) samples compared to European American/White (EA) samples. METHODS: Veterans without Major Neurocognitive Disorder completed an outpatient neuropsychological assessment and were deemed to be performing in a valid manner (e.g., passing both the Test of Memory Malingering Trial 1 (TOMM1) and the Medical Symptom Validity Test (MSVT), (n = 531, EA = 473, AA = 58). Five embedded PVTs were administered to all patients: WAIS-III/IV Processing Speed Index (PSI), Brief Visuospatial Memory Test-Revised: Discrimination Index (BVMT-R), TMT-A (secs), California Verbal Learning Test-II (CVLT-II) Forced Choice, and WAIS-III/IV Digit Span Scaled Score. Individual PVT false positive rates, as well as the rate of failing two or more embedded PVTs, were calculated. RESULTS: Failure rates of two embedded PVTs (PSI, TMT-A), and the total number of PVTs failed, were higher in the AA sample. The PSI and TMT-A remained significantly impacted by race after accounting for age, education, sex, and presence of Mild Neurocognitive Disorder. There were PVT failure rates greater than 10% (and considered false positives) in both groups (AA: PSI, TMT-A, and BVMT-R, 12-24%; EA: BVMT-R, 17%). Failing 2 or more PVTs (AA = 9%, EA = 4%) was impacted by education and Mild Neurocognitive Disorder but not by race. CONCLUSIONS: Individual (timed) PVTs showed higher false positive rates in the AA sample even after accounting for demographic factors and diagnosis of Mild Neurocognitive Disorder. Requiring failure on 2 or more embedded PVTs reduced false positive rates to acceptable levels across both groups (10% or less) and was not significantly influenced by race.

Loneliness and Psychological Distress Among Older Californians: The Moderating Roles of Citizenship Status and English Proficiency.

OBJECTIVES: Guided by the theory of stress proliferation, our study examined whether loneliness, citizenship status, and English proficiency were associated with psychological distress among older adults, and if citizenship status and English proficiency moderated these relationships. METHODS: Using the older adult subsample (65+ years) of the 2019-2020 California Health Interview Survey (N = 15,210), we assessed cross-sectional associations between loneliness, citizenship status, and English proficiency on psychological distress by conducting multivariable linear regression models. Interaction terms were included in subsequent models to determine if citizenship status and English proficiency moderated the relationship between loneliness and psychological distress. RESULTS: In unadjusted models, greater loneliness was associated with higher distress. Both naturalized citizens and noncitizens, and those with limited English proficiency (LEP) exhibited greater distress than US born citizens and those who speak English only (EO). After adjusting for sociodemographic and health covariables, loneliness remained significant for distress although the relationships between citizenship status and English proficiency became attenuated. With the inclusion of interactions, the magnitude of the relationship between loneliness and distress was stronger for naturalized citizens and those with LEP than native-born citizens and those who speak EO, respectively. DISCUSSION: Loneliness was the most consistent stressor affecting multiple life domains. However, our findings demonstrate that stress proliferation is occurring among older immigrant adults and the interplay between loneliness, citizenship status, and English proficiency is contributing to heightened distress. Further attention is needed in understanding the role of multiple stressors influencing mental health among immigrant older adults.

Have outcomes of trauma in centenarians changed in the last 15 years?

BACKGROUND: Centenarians are an often forgotten and under-reported group. Trauma in this population is a substantial cause of morbidity and mortality. 15 years ago, a small observational study examined the outcomes of trauma in centenarians in a single trauma unit, concluding that age alone should not be a determinant of treatment. Following implementation of national standards of care for trauma patients in older adults, this study re-examined outcomes in centenarians admitted secondary to trauma to assess if outcomes have changed. MATERIALS AND METHODS: We performed a retrospective cohort study examining patients aged over 100 years who had been admitted with trauma to an acute district general hospital and trauma unit. Patients were admitted from January 2020 to January 2022. Outcomes investigated included duration of hospital stay, complications, and mortality at three timepoints (inpatient, 30 days, 12 months). We compared this cohort to the cohort 15 years ago to assess for changes in outcomes. RESULTS: 29 patients met our eligibility criteria in this cohort. Common presenting injuries included hip fracture (13), pelvic ring fractures (8) and head injuries (8). There was significantly higher inpatient mortality within our cohort between patients who underwent operative versus non-operative treatment, but no significant difference in duration of hospital stay. There was no significant change in duration of hospital stay, inpatient mortality, or mortality at 30 days and 12 months between this cohort and 15 years ago. CONCLUSIONS: Outcomes of centenarians admitted secondary to trauma have been maintained but not improved in the last 15 years in our centre. Following this we must consider if more must be done to improve outcomes in this underreported but growing patient demographic.

Holding the Space: Individual- and Group-level Factors Predicting Member Retention in Gender-Sexuality Alliances.

Involvement in extracurricular groups is associated with positive outcomes for youth. Gender-Sexuality Alliances (GSAs) are school-based clubs that may provide benefits to sexual and gender minority (SGM) youth and their allies, yet little is known about what factors predict member retention. The current study explores individual- and group-level predictors of youth's sustained or discontinued membership in GSAs during a school year. Participants were 410 youth (Mage = 15.56; 83% sexual minority; 57% cisgender female; 70% White) and 50 advisors in 32 GSAs purposively sampled across Massachusetts who completed surveys at the beginning and end of the school year. Sexual minority youth and youth who took on more leadership roles at the beginning of the year were less likely to have left their GSA by the end of the school year. Youth who perceived higher levels of social support from their GSA trended less likely to leave their GSA as well, although the association was not significant. Youth who engaged in more advocacy were more likely to have left. Youth in GSAs with greater structure to their meetings were less likely to discontinue their membership; specifically, having a meeting agenda was uniquely predictive of member retention. Implications for GSA inclusivity and practices to promote retention within GSAs and similar social justice-oriented clubs are discussed.

A multi-centric evaluation of self-learning GAN based pseudo-CT generation software for low field pelvic magnetic resonance imaging.

Purpose/objectives: An artificial intelligence-based pseudo-CT from low-field MR images is proposed and clinically evaluated to unlock the full potential of MRI-guided adaptive radiotherapy for pelvic cancer care. Materials and method: In collaboration with TheraPanacea (TheraPanacea, Paris, France) a pseudo-CT AI-model was generated using end-to-end ensembled self-supervised GANs endowed with cycle consistency using data from 350 pairs of weakly aligned data of pelvis planning CTs and TrueFisp-(0.35T)MRIs. The image accuracy of the generated pCT were evaluated using a retrospective cohort involving 20 test cases coming from eight different institutions (US: 2, EU: 5, AS: 1) and different CT vendors. Reconstruction performance was assessed using the organs at risk used for treatment. Concerning the dosimetric evaluation, twenty-nine prostate cancer patients treated on the low field MR-Linac (ViewRay) at Montpellier Cancer Institute were selected. Planning CTs were non-rigidly registered to the MRIs for each patient. Treatment plans were optimized on the planning CT with a clinical TPS fulfilling all clinical criteria and recalculated on the warped CT (wCT) and the pCT. Three different algorithms were used: AAA, AcurosXB and MonteCarlo. Dose distributions were compared using the global gamma passing rates and dose metrics. Results: The observed average scaled (between maximum and minimum HU values of the CT) difference between the pCT and the planning CT was 33.20 with significant discrepancies across organs. Femoral heads were the most reliably reconstructed (4.51 and 4.77) while anal canal and rectum were the less precise ones (63.08 and 53.13). Mean gamma passing rates for 1%1mm, 2%/2mm, and 3%/3mm tolerance criteria and 10% threshold were greater than 96%, 99% and 99%, respectively, regardless the algorithm used. Dose metrics analysis showed a good agreement between the pCT and the wCT. The mean relative difference were within 1% for the target volumes (CTV and PTV) and 2% for the OARs. Conclusion: This study demonstrated the feasibility of generating clinically acceptable an artificial intelligence-based pseudo CT for low field MR in pelvis with consistent image accuracy and dosimetric results.

Early Peanut Immunotherapy in Children (EPIC) trial: protocol for a pragmatic randomised controlled trial of peanut oral immunotherapy in children under 5 years of age.

INTRODUCTION: Food allergy is a major public health challenge in Australia. Despite widespread uptake of infant feeding and allergy prevention guidelines the incidence of peanut allergy in infants has not fallen, and prevalence of peanut allergy in school-aged children continues to rise. Therefore, effective and accessible treatments for peanut allergy are required. There is high-quality evidence for efficacy of oral immunotherapy in children aged 4-17 years old; however, few randomised trials have investigated peanut oral immunotherapy (OIT) in young children. Furthermore, the use of food products for OIT with doses prepared and administered by parents without requiring pharmacy compounding has the potential to reduce costs associated with the OIT product. METHODS AND ANALYSIS: Early Peanut Immunotherapy in Children is an open-label randomised controlled trial of peanut OIT compared with standard care (avoidance) to induce desensitisation in children aged 1-4 years old with peanut allergy. n=50 participants will be randomised 1:1 to intervention (daily peanut OIT for 12 months) or control (peanut avoidance). The primary outcome is the proportion of children in each group with a peanut eliciting dose >600 mg peanut protein as assessed by open peanut challenge after 12 months, analysed by intention to treat. Secondary outcomes include safety as assessed by frequency and severity of treatment-related adverse events, quality of life measured using age-appropriate food allergy-specific questionnaires and immunological changes during OIT. ETHICS: The trial is approved by the Child and Adolescent Health Service Human Research Ethics Committee and prospectively registered with the Australia and New Zealand Clinical Trials Registry. DISSEMINATION: Trial outcomes will be published in a peer-review journal and presented and local and national scientific meetings. TRIAL REGISTRATION NUMBER: ACTRN12621001001886.

Fully automated production of [11C]PiB for clinical use on Trasis-AllinOne synthesizer module.

Pittsburgh compound B ([11C]PiB) was the first broadly applied radiotracer with specificity for amyloid-ß (Aß) peptide aggregates in the brain and has since been established as the gold standard for positron emission tomography (PET) employed for clinical in vivo imaging of Aß plaques, used for imaging applications of Alzheimer's disease (AD), related dementia, and other tauopathies. The use of [11C]PiB for routine PET studies is dependent on the production capabilities of each radiochemistry laboratory, subsequently a continuous effort is made to develop suitable and sustainable methods on a variety of auto synthesis platforms. Here we report a fully automated, multi-step radio synthesis, purification, and reformulation of [11C]PiB for PET imaging using the Trasis AllinOne synthesis unit, a commonly used commercial radiochemistry module. We performed three validation runs to evaluate the reproducibility and to verify that the acceptable criteria were met for the release of clinical-grade [11C]PiB using a Trasis AllinOne auto radiosynthesis unit. Solid phase supported radiolabeling was performed through the capture of precursor (6-OH-BTA-0) on a C18 solid phase extraction (SPE) cartridge and subsequent flushing of gaseous [11C]Methyl triflate(MeOTf) through the Sep-Pak for carbon-11 (11C) N-methylation. Starting with 92.5 GBq [11C]CO2, [11C]PiB synthesis was completed in approximately 25 min after cyclotron end of bombardment with an injectable dose >7.0 GBq at end of the synthesis. The radiopharmaceutical product met all quality control criteria and specifications for use in human studies.

mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy.

Large genes including several CRISPR-Cas modules like gene activators (CRISPRa) require dual adeno-associated viral (AAV) vectors for an efficient in vivo delivery and expression. Current dual AAV vector approaches have important limitations, e.g., low reconstitution efficiency, production of alien proteins, or low flexibility in split site selection. Here, we present a dual AAV vector technology based on reconstitution via mRNA trans-splicing (REVeRT). REVeRT is flexible in split site selection and can efficiently reconstitute different split genes in numerous in vitro models, in human organoids, and in vivo. Furthermore, REVeRT can functionally reconstitute a CRISPRa module targeting genes in various mouse tissues and organs in single or multiplexed approaches upon different routes of administration. Finally, REVeRT enabled the reconstitution of full-length ABCA4 after intravitreal injection in a mouse model of Stargardt disease. Due to its flexibility and efficiency REVeRT harbors great potential for basic research and clinical applications.

Detection of Leishmania DNA in Phlebotomine Sand Flies in Tsatee, a Community in the Volta Region, Ghana.

Leishmania parasites, which are spread by infected female sand flies, are the cause of the disease leishmaniasis. Although cutaneous leishmaniasis has been found to occur in the Volta Region, there is limited data on vector species and reservoirs. This study focused on the Tsatee community, in the South Dayi District of the Volta Region, and is aimed at identifying the sand fly fauna and detecting the presence of Leishmania DNA by the use of primers that target the conserved region of Leishmania spp. minicircle DNA of the parasite kinetoplast. The miniature light traps and hand aspirators provided by the Centers for Disease Control and Prevention (CDC) were used to collect outdoor and indoor sand flies for five months in a guinea woodland and semideciduous forest area. From the collections, 4,580 phlebotomine sand flies were obtained and identified, and females were examined for Leishmania DNA using PCR. The male flies were 1,202 (26.24%), non-blood-fed females were 3,321 (72.51%), and 57 (1.25%) were blood-fed females. It was observed that Sergentomyia species constituted 99.91% of the total collected sand flies with S. africana (76.77%) as the predominant species. Phlebotomus rodhaini (0.09%) was the only Phlebotomus species identified from the study area. From 283 non-blood-fed sand fly pools and 57 individual blood-fed species screened, Leishmania DNA was detected in 12 (4.24%) pools and 8 (14.04%) individuals, respectively. It was observed that Leishmania DNA was detected in all the sand fly species identified except S. collarti. This study reports the first detection of Leishmania DNA in P. rodhaini in Ghana, with an infection rate of 33.33% (95% CI, 1.23-88.32). The findings suggest that the role of Phlebotomus in disease transmission in the study area cannot be discounted. Future studies should include continuous surveillance, blood meal preferences, and vector competence of the various infected phlebotomine sand flies to create effective control measures.

Endovascular embolization with EVOH for the treatment of a Rasmussen aneurysm.

First-line treatment of pulmonary artery aneurysms/pseudoaneurysms (PAA/PAPA) is percutaneous or endovascular embolization. The present case of a Rasmussen aneurysm, a PAPA caused by Tuberculosis (TB), was successfully treated with ethylene-vinyl alcohol (EVOH), a radiopaque liquid embolic agent with favorable characteristics. A 35-year-old man presented as a new patient with hemoptysis, and CT imaging revealed multiple cavitary lesions and a 2.1 cm aneurysm in the upper right lobe. Endovascular treatment was delivered and a complete lack of filling of the lesion was noted on post-treatment angiography. The patient's history includes risk factors and past TB infection. Despite the suspicious imaging, diagnostic tests were negative for active TB in this patient. He was then found to have MRSA bacteremia and a mediastinal lymph node positive for M. avium. The etiology of this aneurysm is suspicious for the superinfection of a chronic tuberculous cavity with M. avium, MRSA, or both.

Perceived Racial/Ethnic Discrimination, Citizenship Status, and Self-Rated Health Among Immigrant Young Adults.

Both racial/ethnic discrimination and citizenship status are manifestations of racism. Few empirical studies have examined the role of multiple stressors and how both stressors are interlinked to influence health among immigrant young adults. Informed by the theory of stress proliferation, the current study seeks to examine the interplay between perceived racial/ethnic discrimination and citizenship status on health. We used the third wave of the Children of Immigrants Longitudinal Study (CILS) to examine the influence of perceived racial/ethnic discrimination and citizenship status on self-rated health (SRH) among immigrant young adults (N = 3344). Perceived racial/ethnic discrimination was initially associated with SRH. After adjusting for both predictors, those experiencing perceived racial/ethnic discrimination and non-citizen youth were less likely to report better health than youth who did not report perceived racial/ethnic discrimination or citizen youth. In fully adjusted multivariate regression models, racial/ethnic discrimination remained significant, while citizenship status was no longer associated with SRH. To test stress proliferation, an interaction term was included to assess whether the relationship between perceived racial/ethnic discrimination and SRH varied by citizenship status. The interaction term was significant; non-citizen young adults who experienced racial/ethnic discrimination were less likely to report better health in comparison to citizen young adults and those who did not report perceived racial/ethnic discrimination. Results suggest that the interplay between perceived racial/ethnic discrimination and citizenship status may be influential for health among immigrant young adults. These findings underscore the need for further assessment of the role of stress proliferation on immigrant young adults' health.

Going circular: history, present, and future of circRNAs in cancer.

To date, thousands of highly abundant and conserved single-stranded RNA molecules shaped into ring structures (circRNAs) have been identified. CircRNAs are multifunctional molecules that have been shown to regulate gene expression transcriptionally and post-transcriptionally and exhibit distinct tissue- and development-specific expression patterns associated with a variety of normal and disease conditions, including cancer pathogenesis. Over the past years, due to their intrinsic stability and resistance to ribonucleases, particular attention has been drawn to their use as reliable diagnostic and prognostic biomarkers in cancer diagnosis, treatment, and prevention. However, there are some critical caveats to their utility in the clinic. Their circular shape limits their annotation and a complete functional elucidation is lacking. This makes their detection and biomedical application still challenging. Herein, we review the current knowledge of circRNA biogenesis and function, and of their involvement in tumorigenesis and potential utility in cancer-targeted therapy.

First record of Babesia and Theileria parasites in ticks from Kassena-Nankana, Ghana.

Ticks are efficient vectors for transmitting pathogens that negatively affect livestock production and pose a risk to public health. In this study, Babesia and Theileria species were identified in ticks collected from cattle, sheep and goats from the Kassena-Nankana Districts of Ghana between February and December 2020. A total of 1550 ticks were collected, morphologically identified, pooled and screened for pathogens using primers that amplify a 560 bp fragment of the ssrRNA gene and Sanger sequencing. Amblyomma variegatum (62.98%) was the predominant tick species. From the 491 tick pools screened, 12/15 (2.44%) positive pools were successfully sequenced. The pathogen DNA identified were Theileria ovis in eight (15.38%) pools of Rhipicephalus evertsi evertsi, Theileria velifera in two (0.78%) pools of A. variegatum and Babesia occultans and Babesia sp. Xinjiang in one (1.72%) pool each of Hyalomma truncatum. It was further observed that T. ovis occurred in ticks collected from only sheep (p < 0.001) which were females (p = 0.023) and < =1 year old (p = 0.040). This study reports the first identification of these pathogens in ticks within Kassena-Nankana. With the constant trade of livestock, there is a need for effective tick control measures to prevent infection spread.