Metagenomic and genomic sequences from a nitrate-reducing benzene-degrading enrichment culture.

Metagenome-assembled genomes (MAGs) were recovered from metagenomic assemblies from a nitrate-reducing benzene-degrading enrichment culture. Ten MAGs of high quality or functional interest to benzene degradation are reported, seven of which are single contig genomes.

Draft genome of an anaerobic nitrate-reducing, benzene-degrading member of the order Thermincolales.

We present a metagenome assembled genome (MAG) of an anaerobic bacterium from a nitrate-reducing, benzene-degrading enrichment culture (NRBC). The draft Thermincolales genome consists of 20 contigs with a total length of 4.09 Mbp and includes putative carboxylase genes likely involved in benzene activation.

Comprehensive clinical implementation, workflow, and FMEA of bespoke silicone bolus cast from 3D printed molds using open-source resources.

BACKGROUND: Bolus materials have been used for decades in radiotherapy. Most frequently, these materials are utilized to bring dose closer to the skin surface to cover superficial targets optimally. While cavity filling, such as nasal cavities, is desirable, traditional commercial bolus is lacking, requiring other solutions. Recently, investigators have worked on utilizing 3D printing technology, including commercially available solutions, which can overcome some challenges with traditional bolus. PURPOSE: To utilize failure modes and effects analysis (FMEA) to successfully implement a comprehensive 3D printed bolus solution to replace commercial bolus in our clinic using a series of open-source (or free) software products. METHODS: 3D printed molds for bespoke bolus were created by exporting the DICOM structures of the bolus designed in the treatment planning system and manipulated to create a multipart mold for 3D printing. A silicone (Ecoflex 00-30) mixture is poured into the mold and cured to form the bolus. Molds for sheet bolus of five thicknesses were also created. A comprehensive FMEA was performed to guide workflow adjustments and QA steps. RESULTS: The process map identified 39 and 30 distinct steps for the bespoke and flat sheet bolus workflows, respectively. The corresponding FMEA highlighted 119 and 86 failure modes, with 69 shared between the processes. Misunderstanding of plan intent was a potential cause for most of the highest-scoring failure modes, indicating that physics and dosimetry involvement early in the process is paramount. CONCLUSION: FMEA informed the design and implementation of QA steps to guarantee a safe and high-quality comprehensive implementation of silicone bolus from 3D printed molds. This approach allows for greater adaptability not afforded by traditional bolus, as well as potential dissemination to other clinics due to the open-source nature of the workflow.

Qualitative Assessment of Barriers to Buprenorphine Access: The Role of Pharmacies.

BACKGROUND: Patients continue to face challenges accessing medication for opioid use disorder (MOUD) despite attempts to loosen prescribing restrictions and streamline service provision. Past research has mainly focused on potential barriers surrounding prescribing practices for buprenorphine, but has had limited investigation into the role of pharmacies. OBJECTIVE: This study investigates the role of both pharmacists and pharmacies in creating or circumventing barriers to accessing buprenorphine for individuals in Georgia seeking medication for opioid use disorder (MOUD). METHODS: Semi-structured interviews of pharmacists across 12 access and no access pharmacies were used to create a codebook of 179 discreet statements. The (N = 12) 20-35-minute phone interviews included questions addressing substance use, pharmacy practices, treatment, harm reduction, and psychoeducation. RESULTS: Pharmacists widely agreed that opioid use has caused negative effects on community members (N = 11), that buprenorphine formulation stocking decisions are made based on patient needs (N = 11), and that buprenorphine is relatively easy to stock (N = 10). Additionally, respondents generally stated that buprenorphine is a helpful tool for treating opioid use disorder (OUD) (N = 12) but some reported positive experiences while others reported challenging or negative experiences with patients receiving buprenorphine (N = 7). Finally, few (N = 4) pharmacists agreed that they could benefit from extra training despite many asserting that training is important to inform their own practice (N = 8). CONCLUSION: Results from respondents generally show that training may be beneficial for pharmacists to develop an enhanced understanding of addiction and treatment. Enhanced effort to stock different formulations or dosages of buprenorphine and develop relationships with prescribers may increase community access.

Provision of digital devices and internet connectivity to improve synchronous telemedicine access in the U.S.: a systematic scoping review.

Introduction: The COVID-19 pandemic led to a dramatic increase in telemedicine use for direct patient care. Inequities in device/internet access can limit the extent to which patients can engage with telemedicine care and exacerbate health disparities. In this review, we examined existing literature on interventions designed to improve patient telemedicine access by providing digital devices including tablets, smartphones, and computers and/or internet connectivity. Methods: In this systematic scoping review, we searched four databases for peer-reviewed studies published 1/1/2000-10/19/2021 that described healthcare interventions that provided patients with devices and/or internet connectivity and reported outcomes related to telemedicine access and/or usage. Data extraction elements included: study population, setting, intervention design, details on device/connectivity provision, and outcomes evaluated. Results: Twelve articles reflecting seven unique interventions met inclusion criteria. Ten articles examined telemedicine utilization (83%) and reported improved patient show rates/utilization. Seven articles examined patient satisfaction with the interventions (58%) and reported positive experiences. Fewer articles examined health outcomes (17%; 2/12) though these also demonstrated positive results. Across included studies, study quality was low. There were no controlled trials, and the most rigorously designed studies (n = 4) involved pre/post-intervention assessments. Discussion: Findings from this review indicate that providing material technology supports to patients can facilitate telemedicine access, is acceptable to patients and clinicians, and can contribute to improved health outcomes. The low number and quality of existing studies limits the strength of this evidence. Future research should explore interventions that can increase equitable access to telemedicine services. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=183442, identifier, PROSPERO: CRD42020183442.

Reinterpretation of prostate cancer pathology by Appl1, Sortilin and Syndecan-1 biomarkers.

The diagnosis of prostate cancer using histopathology is reliant on the accurate interpretation of prostate tissue sections. Current standards rely on the assessment of Haematoxylin and Eosin (H&E) staining, which can be difficult to interpret and introduce inter-observer variability. Here, we present a digital pathology atlas and online resource of prostate cancer tissue micrographs for both H&E and the reinterpretation of samples using a novel set of three biomarkers as an interactive tool, where clinicians and scientists can explore high resolution histopathology from various case studies. The digital pathology prostate cancer atlas when used in conjunction with the biomarkers, will assist pathologists to accurately grade prostate cancer tissue samples.

Serine and glycine physiology reversibly modulate retinal and peripheral nerve function.

Metabolic homeostasis is maintained by redundant pathways to ensure adequate nutrient supply during fasting and other stresses. These pathways are regulated locally in tissues and systemically via the liver, kidney, and circulation. Here, we characterize how serine, glycine, and one-carbon (SGOC) metabolism fluxes across the eye, liver, and kidney sustain retinal amino acid levels and function. Individuals with macular telangiectasia (MacTel), an age-related retinal disease with reduced circulating serine and glycine, carrying deleterious alleles in SGOC metabolic enzymes exhibit an exaggerated reduction in circulating serine. A Phgdh+/- mouse model of this haploinsufficiency experiences accelerated retinal defects upon dietary serine/glycine restriction, highlighting how otherwise silent haploinsufficiencies can impact retinal health. We demonstrate that serine-associated retinopathy and peripheral neuropathy are reversible, as both are restored in mice upon serine supplementation. These data provide molecular insights into the genetic and metabolic drivers of neuro-retinal dysfunction while highlighting therapeutic opportunities to ameliorate this pathogenesis.

Host and pathogen genetic diversity shape vaccine-mediated protection to Mycobacterium tuberculosis.

To investigate how host and pathogen diversity govern immunity against Mycobacterium tuberculosis (Mtb), we performed a large-scale screen of vaccine-mediated protection against aerosol Mtb infection using three inbred mouse strains [C57BL/6 (B6), C3HeB/FeJ (C3H), Balb/c x 129/SvJ (C129F1)] and three Mtb strains (H37Rv, CDC1551, SA161) representing two lineages and distinct virulence properties. We compared three protective modalities, all of which involve inoculation with live mycobacteria: Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, delivered either subcutaneously or intravenously, and concomitant Mtb infection (CoMtb), a model of pre-existing immunity in which a low-level Mtb infection is established in the cervical lymph node following intradermal inoculation. We examined lung bacterial burdens at early (Day 28) and late (Day 98) time points after aerosol Mtb challenge and histopathology at Day 98. We observed substantial heterogeneity in the reduction of bacterial load afforded by these modalities at Day 28 across the combinations and noted a strong positive correlation between bacterial burden in unvaccinated mice and the degree of protection afforded by vaccination. Although we observed variation in the degree of reduction in bacterial burdens across the nine mouse/bacterium strain combinations, virtually all protective modalities performed similarly for a given strain-strain combination. We also noted dramatic variation in histopathology changes driven by both host and bacterial genetic backgrounds. Vaccination improved pathology scores for all infections except CDC1551. However, the most dramatic impact of vaccination on lesion development occurred for the C3H-SA161 combination, where vaccination entirely abrogated the development of the large necrotic lesions that arise in unvaccinated mice. In conclusion, we find that substantial TB heterogeneity can be recapitulated by introducing variability in both host and bacterial genetics, resulting in changes in vaccine-mediated protection as measured both by bacterial burden as well as histopathology. These differences can be harnessed in future studies to identify immune correlates of vaccine efficacy.

Inspirational Professional Practice Model Redesign Using Shared Decision-Making.

An integrated health system including 12 hospitals, an expansive network of ambulatory settings, and health insurance plans began a systematic review of the existing nursing professional practice model (PPM) created in 2007 to assess current relevancy. The goal was to determine PPM concepts and imagery that represent present-day nursing workforce. This article shares how a formal review of literature, utilization of focus groups, and system-wide shared decision-making influenced creation and evaluation of a revised PPM.

CAR/CETARS/CSAR Practice Guideline on Imaging the Adult Patient With Right Lower Quadrant Pain.

In 2023, the Canadian Society of Abdominal Radiology (CSAR) and Canadian Emergency, Trauma, and Acute Care Radiology Society (CETARS) received Canadian Association of Radiologists (CAR) member feedback that there was an unmet educational need for guidance in the imaging investigation of right lower quadrant (RLQ) pain. Members requested specific guidance on how to handle controversial scenarios including which test to order when, specifics of imaging protocols, and managing pregnant patients who have RLQ pain-all from a Canadian perspective. After conducting an exhaustive literature review, the working group agreed that a Canadian-specific set of guidelines was warranted. The management recommendations presented in this guideline were discussed as a group to achieve expert consensus. As the workup for RLQ pain can vary considerably in the paediatric population, the scope of this paper was restricted to adults (18 years of age or older). Whenever possible, the best evidence was used to inform the clinical guidance, and where gaps existed, the guidelines reflect consensus among experts in the field. The result is a framework to aid in this process of managing patients with RLQ pain across various clinical scenarios while addressing current questions and controversies, particularly those most relevant to the Canadian healthcare system.

Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge.

An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.

Factors Associated with Non-Completion of a Pediatric Metabolic and Bariatric Surgery Program.

BACKGROUND: Childhood obesity is a devastating disease process disproportionately affecting minority and low-income populations. Though bariatric surgery leads to durable weight loss and reversal of multiple obesity-related comorbidities, only a small fraction of pediatric patients undergoes the procedure. We sought to identify factors associated with non-completion in a pediatric bariatric surgery program. METHODS: Retrospective review of consecutive patients ≤18-years-old referred to an academic adolescent bariatric surgery program between 2017 and 2022 (n = 20 completers, 40 non-completers) was completed. Demographics and medical and psychosocial histories were summarized by completion status. RESULTS: Of the 33% (20/60; 85% female, 30% racial minorities) who successfully completed the program, the median age was 16 years [IQR 16, 17]. The median age of non-completers was 16 years [IQR 15, 17] (55% female, 56% racial minorities). Non-completion was associated with male gender (15% of completers vs 45% of non-completers, p = 0.022), neighborhood income <150% poverty level (0 completers vs 17.5% of non-completers, p = 0.047), and presence of environmental or family stressors (22% of completers vs 65% of non-completers, p = 0.008). Though not statistically significant, non-completers tended to be racial minorities (p = 0.054). CONCLUSIONS: Non-completion of the bariatric surgery pathway was more prevalent among male patients from lower-income neighborhoods with significant environmental or family stressors. These patients also tended to be racial and ethnic minorities. The findings underscore the need for further investigation into barriers to pediatric bariatric surgery. LEVEL OF EVIDENCE: Level III.

Artificial Intelligence Assists in the Early Identification of Cardiac Amyloidosis.

A 69-year-old female presented with symptomatic atrial fibrillation. Cardiac amyloidosis was suspected due to an artificial intelligence clinical tool applied to the presenting electrocardiogram predicting a high probability for amyloidosis, and the subsequent unexpected finding of left atrial appendage thrombus reinforced this clinical suspicion. This facilitated an early diagnosis by the biopsy of AL cardiac amyloidosis and the prompt initiation of targeted therapy. This case highlights the utilization of an AI clinical tool and its impact on clinical care, particularly for the early detection of a rare and difficult to diagnose condition where early therapy is critical.

Genomic Surveillance of Invasive Meningococcal Disease During a National MenW Outbreak in Australia, 2017-2018.

Background: In Australia, invasive meningococcal disease (IMD) incidence rapidly increased between 2014 and 2017 due to rising serogroup W (MenW) and MenY infections. We aimed to better understand the genetic diversity of IMD during 2017 and 2018 using whole genome sequencing data. Methods: Whole genome sequencing data from 440 Australian IMD isolates collected during 2017 and 2018 and 1737 international MenW:CC11 isolates collected in Europe, Africa, Asia, North America, and South America between 1974 and 2020 were used in phylogenetic analyses; genetic relatedness was determined from single-nucleotide polymorphisms. Results: Australian isolates were as follows: 181 MenW (41%), 144 MenB (33%), 88 MenY (20%), 16 MenC (4%), 1 MenW/Y (0.2%), and 10 nongenogroupable (2%). Eighteen clonal complexes (CCs) were identified, and 3 (CC11, CC23, CC41/44) accounted for 78% of isolates (343/440). These CCs were associated with specific serogroups: CC11 (n = 199) predominated among MenW (n = 181) and MenC (n = 15), CC23 (n = 80) among MenY (n = 78), and CC41/44 (n = 64) among MenB (n = 64). MenB isolates were highly diverse, MenY were intermediately diverse, and MenW and MenC isolates demonstrated the least genetic diversity. Thirty serogroup and CC-specific genomic clusters were identified. International CC11 comparison revealed diversification of MenW in Australia. Conclusions: Whole genome sequencing comprehensively characterized Australian IMD isolates, indexed their genetic variability, provided increased within-CC resolution, and elucidated the evolution of CC11 in Australia.

Validation of OpenCap: A low-cost markerless motion capture system for lower-extremity kinematics during return-to-sport tasks.

Low-cost markerless motion capture systems offer the potential for 3D measurement of joint angles during human movement. This study aimed to validate a smartphone-based markerless motion capture system's (OpenCap) derived lower extremity kinematics during common return-to-sport tasks, comparing it to an established optoelectronic motion capture system. Athletes with prior anterior cruciate ligament reconstruction (12-18 months post-surgery) performed three movements: a jump-landing-rebound, single-leg hop, and lateral-vertical hop. Kinematics were recorded concurrently with two smartphones running OpenCap's software and with a 10-camera, marker-based motion capture system. Validity of lower extremity joint kinematics was assessed across 437 recorded trials using measures of agreement (coefficient of multiple correlation: CMC) and error (mean absolute error: MAE, root mean squared error: RMSE) across the time series of movement. Agreement was best in the sagittal plane for the knee and hip in all movements (CMC > 0.94), followed by the ankle (CMC = 0.84-0.93). Lower agreement was observed for frontal (CMC = 0.47-0.78) and transverse (CMC = 0.51-0.6) plane motion. OpenCap presented a grand mean error of 3.85° (MAE) and 4.34° (RMSE) across all joint angles and movements. These results were comparable to other available markerless systems. Most notably, OpenCap's user-friendly interface, free software, and small physical footprint have the potential to extend motion analysis applications beyond conventional biomechanics labs, thus enhancing the accessibility for a diverse range of users.

Oligomeric amyloid beta prevents myelination in a clusterin-dependent manner.

Background: White matter loss is a well-documented phenomenon in Alzheimer's disease (AD) patients that has been recognized for decades. However, the underlying reasons for the failure of oligodendrocyte progenitor cells (OPCs) to repair myelin deficits in these patients remain elusive. A single nucleotide polymorphism (SNP) in Clusterin has been identified as a risk factor for late-onset Alzheimer's disease and linked to a decrease in white matter integrity in healthy adults, but its specific role in oligodendrocyte function and myelin maintenance in Alzheimer's disease pathology remains unclear. Methods: To investigate the impact of Clusterin on OPCs in the context of Alzheimer's disease, we employed a combination of immunofluorescence and transmission electron microscopy techniques, primary culture of OPCs, and an animal model of Alzheimer's disease. Results: Our findings demonstrate that Clusterin, a risk factor for late-onset AD, is produced by OPCs and inhibits their differentiation into oligodendrocytes. Specifically, we observed upregulation of Clusterin in OPCs in the 5xFAD mouse model of AD. We also found that the phagocytosis of debris, including amyloid beta (Aß), myelin, and apoptotic cells leads to the upregulation of Clusterin in OPCs. In vivo experiments confirmed that Aß oligomers stimulate Clusterin upregulation and that OPCs are capable of phagocytosing Aß. Furthermore, we discovered that Clusterin significantly inhibits OPC differentiation and hinders the production of myelin proteins. Finally, we demonstrate that Clusterin inhibits OPC differentiation by reducing the production of IL-9 by OPCs. Conclusion: Our data suggest that Clusterin may play a key role in the impaired myelin repair observed in AD and could serve as a promising therapeutic target for addressing AD-associated cognitive decline.