Thrombogenicity of biodegradable metals.

Biodegradable metals offer a promising means to ameliorate many of the long-term risks associated with vascular devices made of conventional biostable stent metals. While numerous biodegradable metal alloys have been developed and characterized in animal models, knowledge of their blood reactivity and thrombogenicity remains unknown. Metal hemocompatibility is particularly valuable because current generation drug-eluting stents pose a significant long-term thrombosis risk. In this study, four pure metals, widely used as degradable base materials (Fe, Zn, Mg, and Mo), and three alloys commonly used in cardiovascular devices [NiTi, CoCr, and stainless steel (SS)] were evaluated. This work examined how each of these metals activate platelets, coagulation factors, and inflammation using in vitro hemocompatibility assays and a clinically relevant ex vivo non-human primate arteriovenous shunt model. Testing found that while all metals promoted a downstream activation of platelets and coagulation in flowing whole blood, platelet and fibrin attachment to Mg was markedly reduced. Additionally, Fe and Mo trended toward higher platelet attachment and contact pathway activation. Overall, the results suggest that Mg may delay clot initiation, but not eliminate clot formation, indicating the importance of understanding thrombosis in Mg alloys that are currently being developed for clinical use as biodegradable stents.

Production study of Fr, Ra and Ac radioactive ion beams at ISOLDE, CERN.

The presented paper discusses the production of radioactive ion beams of francium, radium, and actinium from thick uranium carbide (UC x ) targets at ISOLDE, CERN. This study focuses on the release curves and extractable yields of francium, radium and actinium isotopes. The ion source temperature was varied in order to study the relative contributions of surface and laser ionization to the production of the actinium ion beams. The experimental results are presented in the form of release parameters. Representative extractable yields per µ C are presented for 222 - 231 Ac, several Ra and Fr isotopes in the mass ranges 214 ≤ A ≤ 233 and 205 ≤ A ≤ 231 respectively. The release efficiency for several isotopes of each of the studied elements was calculated by comparing their yields to the estimated in-target production rates modeled by CERN-FLUKA. The maximal extraction efficiency of actinium was calculated to be 2.1(6)% for a combination of surface ionization using a Ta ion source and resonant laser ionization using the two-step 438.58 nm, and 424.69 nm scheme.

Urgent Spinal Surgery in a Lateral Decubitus on a Patient with a Left Ventricular Assist Device on Full Anticoagulation: A Case Report.

This case report aims to demonstrate the feasibility of performing spinal surgery in patients with a left ventricular assist device (LVAD), who are traditionally considered unsuitable candidates due to the need for anticoagulation and the challenges associated with the prone position. A case of a patient with an LVAD undergoing microdiscectomy in the left lateral decubitus position is presented. The procedure was carried out by a specialized interdisciplinary team with appropriate monitoring. The patient underwent the procedure safely, demonstrating that spinal surgery can be performed in patients with LVAD without reversing anticoagulation or resorting to the prone position. This approach mitigates the risk of thrombotic events and hemodynamic instability. This case study suggests that spinal surgery, specifically microdiscectomy, can be safely performed in patients with LVAD using the left lateral decubitus position. This finding has significant implications for patients who are unable to ambulate and therefore struggle to qualify for a heart transplant.

Can the Reboot coaching programme support critical care nurses in coping with stressful clinical events? A mixed-methods evaluation assessing resilience, burnout, depression and turnover intentions.

BACKGROUND: Critical care nurses (CCNs) are routinely exposed to highly stressful situations, and at high-risk of suffering from work-related stress and developing burnout. Thus, supporting CCN wellbeing is crucial. One approach for delivering this support is by preparing CCNs for situations they may encounter, drawing on evidence-based techniques to strengthen psychological coping strategies. The current study tailored a Resilience-boosting psychological coaching programme [Reboot] to CCNs. Other healthcare staff receiving Reboot have reported improvements in confidence in coping with stressful clinical events and increased psychological resilience. The current study tailored Reboot for online, remote delivery to CCNs (as it had not previously been delivered to nurses, or in remote format), to (1) assess the feasibility of delivering Reboot remotely, and to (2) provide a preliminary assessment of whether Reboot could increase resilience, confidence in coping with adverse events and burnout. METHODS: A single-arm mixed-methods (questionnaires, interviews) before-after feasibility study design was used. Feasibility was measured via demand, recruitment, and retention (recruitment goal: 80 CCNs, retention goal: 70% of recruited CCNs). Potential efficacy was measured via questionnaires at five timepoints; measures included confidence in coping with adverse events (Confidence scale), Resilience (Brief Resilience Scale), depression (PHQ-9) and burnout (Oldenburg-Burnout-Inventory). Intention to leave (current role, nursing more generally) was measured post-intervention. Interviews were analysed using Reflexive Thematic Analysis. RESULTS: Results suggest that delivering Reboot remotely is feasible and acceptable. Seventy-seven nurses were recruited, 81% of whom completed the 8-week intervention. Thus, the retention rate was over 10% higher than the target. Regarding preliminary efficacy, follow-up measures showed significant increases in resilience, confidence in coping with adverse events and reductions in depression, burnout, and intention to leave. Qualitative analysis suggested that CCNs found the psychological techniques helpful and particularly valued practical exercises that could be translated into everyday practice. CONCLUSION: This study demonstrates the feasibility of remote delivery of Reboot and potential efficacy for CCNs. Results are limited due to the single-arm feasibility design; thus, a larger trial with a control group is needed.

Self-administered versus clinician-performed BinaxNOW COVID rapid test: a comparison of accuracy.

We conducted a single-center study at a free community testing site in Baltimore City to assess the accuracy of self-performed rapid antigen tests (RATs) for COVID-19. Self-administered BinaxNOW RATs were compared with clinician-performed RATs and against a reference lab molecular testing as the gold standard. Of the 953 participants, 14.9% were positive for SARS- CoV-2 as determined by RT-PCR. The sensitivity and specificity were similar for both self- and clinician-performed RATs (sensitivity: 83.9% vs 88.2%, P = 0.40; specificity: 99.8% vs 99.6%, P = 0.6). Subgroup comparisons based on age and race yielded similar results. Notably, 5.2% (95% CI: 1.5% to 9.5%) of positive results were potentially missed due to participant misinterpretation of the self-test card. However, the false-positive rate for RATs was reassuringly comparable in accuracy to clinician-administered tests. These findings hold significant implications for physicians prescribing treatment based on patient-reported, self-administered positive test results. Our study provides robust evidence supporting the reliability and utility of patient-performed RATs, underscoring their comparable accuracy to clinician-performed RATs, and endorsing their continued use in managing COVID-19. Further studies using other rapid antigen test brands are warranted.IMPORTANCEAccurate and accessible COVID-19 testing is crucial for effective disease control and management. A recent single-center study conducted in Baltimore City examined the reliability of self-performed rapid antigen tests (RATs) for COVID-19. The study found that self-administered RATs yielded similar sensitivity and specificity to clinician-performed tests, demonstrating their comparable accuracy. These findings hold significant implications for physicians relying on patient-reported positive test results for treatment decisions. The study provides robust evidence supporting the reliability and utility of patient-performed RATs, endorsing their continued use in managing COVID-19. Furthermore, the study highlights the need for further research using different rapid antigen test brands to enhance generalizability. Ensuring affordable and widespread access to self-tests is crucial, particularly in preparation for future respiratory virus seasons and potential waves of reinfection of SARS-CoV-2 variants such as the Omicron variant.

Psychosocial well-being and firearm storage practices: evidence from five US states.

OBJECTIVE: Gun safety practices can play a pivotal role in preventing suicide and unintentional injuries involving a firearm. This study aimed to assess whether psychosocial well-being, measured by emotional support, feeling of social isolation and life satisfaction, influenced safe storage practices among individuals who had firearms in or around their home. METHODS: Data are from the firearm safety module of the 2022 Behavioural Risk Factor Surveillance System survey of 11 722 individuals having firearms and living in California, Minnesota, Nevada, New Mexico and Ohio. Respondents were asked to identify how guns were stored in their homes including: (1) not loaded, (2) loaded but locked and (3) loaded and unlocked. Multinomial logistic regression models with controls for sociodemographic correlates assess the relative risks of certain storage measures. RESULTS: Relative to the base outcome of not loaded, the adjusted relative risks of having firearms loaded and unlocked among individuals who usually/always felt socially isolated were 1.72 (95% CI: 1.02 to 2.88) times that of individuals who never felt socially isolated. The adjusted risks among individuals who were dissatisfied with their life were 1.82 (95% CI: 1.02 to 3.24) times that of their counterparts who were very satisfied. The adjusted risks were not statistically significant among individuals who rarely/never received needed emotional support compared with individuals who always received support. CONCLUSION: The results suggest a strong relationship between social isolation and life satisfaction and safe storage practices at home. Policies designed to improve psychosocial well-being, therefore, may present an important opportunity for preventing unintentional firearm injuries.

First report of co-infections of Marek's disease virus and chicken infectious anaemia virus in poultry flocks in Nigeria.

Marek's disease (MD) and chicken infectious anaemia (CIA) are viral immunosuppressive diseases of poultry caused by the MD virus (MDV) and CIA virus (CIAV) respectively. Despite vaccination against MD, the incidence of the disease in vaccinated poultry flocks in Nigeria persists. However, underlying factors like co-infection with CIAV have not been investigated in the country. This study was designed to investigate possible co-infections of MDV and CIAV in poultry flocks in Nigeria. In 2016, tumorous tissue samples were collected from suspected cases of MD at necropsy in Jos, Plateau State, Nigeria. The samples collected were fixed in formalin for histopathological examination, genomic DNA was extracted from a second part and analysed by polymerase chain reaction (PCR), targeting the meq and VP1 genes of the MDV and CIAV, respectively. The histology results revealed that the cutaneous and proventricular lymphomas were characterized by large numbers of mononuclear cellular infiltrates admixed with heterophils. The PCR results revealed that MDV was detected in 66.7% (16/24), CIAV in 45.8% (11/24), and co-infections of MDV and CIAV were detected in 45.8% (11/24) of the samples analysed. In addition, co-infections of MD and CIA were recorded in 100% (6/6) and 27.7% (5/18) of broilers and layer/pullet' samples respectively. Phylogenetic analysis of the meq gene sequences revealed that the Nigerian MDV clusters with very virulent MDV from Egypt and Italy. While, CIAV sequences were genotype II and genotype III and clustered with CIAVs from Cameroon and China. This is the first report of co-infections of MD and CIA in Nigeria.

Correction to "Ligand Chromophore Modification Approach for Predictive Incremental Tuning of Metal-Organic Framework Color".

[This corrects the article DOI: 10.1021/acs.chemmater.3c01603.].

Molecular Pharmacology of Selective NaV1.6 and Dual NaV1.6/NaV1.2 Channel Inhibitors that Suppress Excitatory Neuronal Activity Ex Vivo.

Voltage-gated sodium channel (NaV) inhibitors are used to treat neurological disorders of hyperexcitability such as epilepsy. These drugs act by attenuating neuronal action potential firing to reduce excitability in the brain. However, all currently available NaV-targeting antiseizure medications nonselectively inhibit the brain channels NaV1.1, NaV1.2, and NaV1.6, which potentially limits the efficacy and therapeutic safety margins of these drugs. Here, we report on XPC-7724 and XPC-5462, which represent a new class of small molecule NaV-targeting compounds. These compounds specifically target inhibition of the NaV1.6 and NaV1.2 channels, which are abundantly expressed in excitatory pyramidal neurons. They have a > 100-fold molecular selectivity against NaV1.1 channels, which are predominantly expressed in inhibitory neurons. Sparing NaV1.1 preserves the inhibitory activity in the brain. These compounds bind to and stabilize the inactivated state of the channels thereby reducing the activity of excitatory neurons. They have higher potency, with longer residency times and slower off-rates, than the clinically used antiseizure medications carbamazepine and phenytoin. The neuronal selectivity of these compounds is demonstrated in brain slices by inhibition of firing in cortical excitatory pyramidal neurons, without impacting fast spiking inhibitory interneurons. XPC-5462 also suppresses epileptiform activity in an ex vivo brain slice seizure model, whereas XPC-7224 does not, suggesting a possible requirement of Nav1.2 inhibition in 0-Mg2+- or 4-AP-induced brain slice seizure models. The profiles of these compounds will facilitate pharmacological dissection of the physiological roles of NaV1.2 and NaV1.6 in neurons and help define the role of specific channels in disease states. This unique selectivity profile provides a new approach to potentially treat disorders of neuronal hyperexcitability by selectively downregulating excitatory circuits.

Environmentally relevant concentrations of aqueous atorvastatin produce alterations in cholesterol biosynthesis and gene expression patterns in Xenopus laevis.

Numerous studies report active pharmaceutical compounds detected in both wastewater effluent and surface waters. Exposure to statin drugs in general, and atorvastatin in particular, is likely to be a concern. We hypothesized that chronic exposure to low concentrations of atorvastatin in water would result in an adverse effect on production of steroids regulating growth and development of the model amphibian Xenopus laevis. The FETAX assay was used to evaluate the effects of a range of doses of atorvastatin on developing embryos. A 60 day metamorphosis assay assessed the effects of aqueous atorvastatin exposure at environmentally concentrations on metamorphosing tadpoles. A 60 day chronic flow-through exposure evaluated the effects of chronic low concentrations of atorvastatin on adults. The purpose of the FETAX assay was to confirm that atorvastatin can reduce circulating cholesterol in X. laevis with a similar manner to that expected in humans. The results of the 60-day flow-through exposure on metamorphosing tadpoles showed significant evidence of altered cholesterol biosynthesis. The dose-dependent increase in cyp19a1 expression also indicated that the steroidogenesis pathway was affected. The RNAseq analysis confirmed that exposure to environmentally relevant concentrations of atorvastatin does cause significant alterations to global transcriptional profiles in a manner consistent with dysregulation of the cholesterol biosynthesis pathway, both through the downregulation of many genes involved in that pathway, but also in the impacts to other, related pathways. The qPCR data for both adult males and adult females indicated only slight changes in expression with the exception that hmgcr was significantly downregulated in males, and cyp3a4 expression was significantly downregulated in females. The data we present here indicated that chronic exposure to environmentally relevant concentrations of atorvastatin does have the potential to impact early life stage frogs, particularly by altering expression of genes involved in critical molecular pathways.

Co-delivery of HIV pre-exposure prophylaxis (PrEP) and HIV testing among publicly insured adolescents and young adults (AYA) receiving medication for opioid use disorder (MOUD).

BACKGROUND: Low rates of HIV pre-exposure prophylaxis (PrEP) prescribing contribute to the disproportionate burden of HIV in the United States. Among adolescent and young adults (AYA) with opioid use disorder, HIV testing and PrEP co-prescription rates are poorly characterized. METHODS: We performed a retrospective analysis involving deidentified data from Philadelphia's Medicaid beneficiaries ages 16-29 years who were prescribed medication for opioid use disorder (MOUD) from 2015 to 2020 and continuously Medicaid-enrolled for ≥6 months prior to that prescription. After identifying the presence of a qualifying diagnosis signifying a PrEP indication, we examined the outcome of appropriate PrEP co-prescriptions and HIV testing using generalized estimating equations (GEE) modeling. RESULTS: We identified 795 AYA Medicaid beneficiaries with 1269 qualified treatment episodes. We calculated a PrEP prescribing rate of 29.47 per 1000 person-years among AYA receiving MOUD. The HIV testing rate was 63.47 per 1000 person-years among AYA receiving MOUD. GEE modeling revealed that individuals receiving methadone were more likely (aOR=2.62, 95% CI=1.06-6.49) to receive HIV testing within 6 months after a PrEP-qualifying diagnosis compared to those receiving other MOUD medications. Those who only saw outpatient behavioral health providers were less likely (aOR=0.48, 95% CI=0.24-0.99) to have received an HIV test within 6 months after the PrEP-qualifying diagnosis compared to those receiving inpatient behavioral health services. CONCLUSIONS: Co-prescription of PrEP and HIV testing among AYA receiving MOUD was rare in this large urban publicly insured population. Interventions are needed to increase HIV prevention services for this key population of AYA at risk for HIV infection.

Multicenter evaluation of BioCode GPP for syndromic molecular detection of gastrointestinal pathogens from stool specimens.

Acute gastroenteritis (AGE) is a leading cause of morbidity and mortality worldwide across all age groups that disproportionally affects young children in low- and middle-income countries and immunocompromised patients in high-income countries. Regional outbreaks of AGE are typically detected by traditional microbiological detection methods that target limited organisms and are associated with low sensitivity and lengthy time-to-results. Combined, these may result in repeat testing, imprecise or delayed treatment, and delayed recognition of outbreaks. We conducted a multi-site prospective study comparing the BioCode Gastrointestinal Pathogen Panel (BioCode GPP) for the detection of 17 common bacterial, viral, and protozoan causes of gastroenteritis with reference methods, including stool culture, enzyme immunoassays, pathogen-specific PCR assays, and sequencing. One thousand five hundred fifty-eight residual, de-identified stool samples (unpreserved stool and stool in Cary-Blair transport medium) were enrolled and tested for 11 bacterial, 3 viral, and 3 protozoan pathogens. BioCode GPP and reference methods were positive for 392 (25.2%) and 283 (18.2%) samples, respectively (P < 0.0001). In this study, the BioCode GPP and reference methods detected 69 and 65 specimens positive for Clostridioides difficile, 51 and 48 for enteroaggregative Escherichia coli, 33 and 27 for enterotoxigenic E. coli, 50 and 47 for norovirus GI/GII, and 30 and 22 for rotavirus A, respectively. The BioCode GPP showed good positive and negative agreements for each pathogen ranging from 89.5% to 100%, with overall sensitivity and specificity of 96.1% and 99.7%, post adjudication. The BioCode GPP detected >1 pathogens in 49 samples, representing 12.5% of the total 392 positive specimens. IMPORTANCE: This study highlights performance of a novel technology for timely and accurate detection and differentiation of 17 common bacterial, viral, and protozoan causes of gastroenteritis. Utilizing molecular tests such as the BioCode Gastrointestinal Pathogen Panel may improve the detection of gastrointestinal pathogens and provide actionable results, particularly for patient populations at most risk.

The functional microclimate of an urban arthropod pest: Urban heat island temperatures in webs of the western black widow spider.

Urbanization alters natural landscapes and creates unique challenges for urban wildlife. Similarly, the Urban Heat Island (UHI) effect can produce significantly elevated temperatures in urban areas, and we have a relatively poor understanding of how this will impact urban biodiversity. In particular, most studies quantify the UHI using broad-scale climate data rather than assessing microclimate temperatures actually experienced by organisms. In addition, studies often fail to address spatial and temporal complexities of the UHI. Here we examine the thermal microclimate and UHI experienced in the web of Western black widow spiders (Latrodectus hesperus), a medically-important, superabundant urban pest species found in cities across the Western region of North America. We do this using replicate urban and desert populations across an entire year to account for seasonal variation in the UHI, both within and between habitats. Our findings reveal a strong nighttime, but no daytime, UHI effect, with urban spider webs being 2-5 °C warmer than desert webs at night. This UHI effect is most prominent during the spring and least prominent in winter, suggesting that the UHI need not be most pronounced when temperatures are most elevated. Urban web temperatures varied among urban sites in the daytime, whereas desert web temperatures varied among desert sites in the nighttime. Finally, web temperature was significantly positively correlated with a spider's boldness, but showed no relationship with voracity towards prey, web size, or body condition. Understanding the complexities of each organism's thermal challenges, the "functional microclimate", is crucial for predicting the impacts of urbanization and climate change on urban biodiversity and ecosystem functioning.

One-stage surgical case management of a two-year-old Arabian horse affected by male-pseudo hermaphroditism.

A two-year-old Arabian horse presented for abnormal external genitalia and dangerous stallion-like behavior was diagnosed with disorder of sexual development (DSD), also known as intersex/hermaphroditism. Standing 1-stage surgical procedure performed under sedation, and local anesthesia to concurrently eliminate stallion-like behavior, risk of neoplastic transformation of intraabdominal gonads, and to replace ambiguous external genital with a functional, and cosmetically more acceptable anatomy. Step-1) Laparoscopic abdominal exploration and gonadectomy; Step-2) Rudimentary penis resection and perineal urethrostomy. The horse tolerated surgery well (combined surgery time 185 min) with no complications. At macroscopic examination of the gonads, they resembled hypoplastic testis-like tissues. Microscopic examination confirmed presence of seminiferous tubules, Leydig and Sertoli/granulosa cells. Cytogenetic evaluation revealed a 64,XX karyotype, SRY-negative. The stallion-like behavior subsided within days post-operatively. Long-term follow-up revealed the genitoplasty site healed without urine scalding or urethral stricture. The owner satisfaction was excellent and the horse could be used post-surgery as an athlete.

Factors associated with patient-to-healthcare personnel (HCP) and HCP-to-subsequent patient transmission of methicillin-resistant Staphylococcus aureus.

BACKGROUND: Transient acquisition of methicillin-resistant Staphylococcus aureus (MRSA) on healthcare personnel (HCP) gloves and gowns following patient care has been examined. However, the potential for transmission to the subsequent patient has not been studied. We explored the frequency of MRSA transmission from patient to HCP, and then in separate encounters from contaminated HCP gloves and gowns to a subsequent simulated patient as well as the factors associated with these 2 transmission pathways. METHODS: We conducted a prospective cohort study with 2 parts. In objective 1, we studied MRSA transmission from random MRSA-positive patients to HCP gloves and gowns after specific routine patient care activities. In objective 2, we simulated subsequent transmission from random HCP gloves and gowns without hand hygiene to the next patient using a manikin proxy. RESULTS: For the first objective, among 98 MRSA-positive patients with 333 randomly selected individual patient-HCP interactions, HCP gloves or gowns were contaminated in 54 interactions (16.2%). In a multivariable analysis, performing endotracheal tube care had the greatest odds of glove or gown contamination (OR, 4.06; 95% CI, 1.3-12.6 relative to physical examination). For the second objective, after 147 simulated HCP-patient interactions, the subsequent transmission of MRSA to the manikin proxy occurred 15 times (10.2%). CONCLUSION: After caring for a patient with MRSA, contamination of HCP gloves and gown and transmission to subsequent patients following HCP-patient interactions occurs frequently if contact precautions are not used. Proper infection control practices, including the use of gloves and gown, can prevent this potential subsequent transmission.

Expanding the genotype-phenotype spectrum in SCN8A-related disorders.

BACKGROUND: SCN8A-related disorders are a group of variable conditions caused by pathogenic variations in SCN8A. Online Mendelian Inheritance in Man (OMIM) terms them as developmental and epileptic encephalopathy 13, benign familial infantile seizures 5 or cognitive impairment with or without cerebellar ataxia. METHODS: In this study, we describe clinical and genetic results on eight individuals from six families with SCN8A pathogenic variants identified via exome sequencing. RESULTS: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Three novel and three reported variants were observed in SCN8A. Electrophysiological analysis in transfected cells revealed a loss-of-function variant in Patient 4. CONCLUSIONS: This work expands the clinical and genotypic spectrum of SCN8A-related disorders and provides electrophysiological results on a novel loss-of-function SCN8A variant.

Natural trait variation across Saccharomycotina species.

Among molecular biologists, the group of fungi called Saccharomycotina is famous for its yeasts. These yeasts in turn are famous for what they have in common-genetic, biochemical, and cell-biological characteristics that serve as models for plants and animals. But behind the apparent homogeneity of Saccharomycotina species lie a wealth of differences. In this review, we discuss traits that vary across the Saccharomycotina subphylum. We describe cases of bright pigmentation; a zoo of cell shapes; metabolic specialties; and species with unique rules of gene regulation. We discuss the genetics of this diversity and why it matters, including insights into basic evolutionary principles with relevance across Eukarya.