Ruminant model for hemodialysis cannulation.

BACKGROUND: Preventative strategies that minimize hemodialysis access complications remain limited. OBJECTIVE: This study aimed to address this gap by developing a Caprine cannulation model to investigate the impact of repeated cannulations on vascular access patency rates. RESEARCH DESIGN AND MEASURES: In this pilot study, a meta-analysis was conducted using experimental control data from four trials to explore the impact of Caprine breed (independent variable) on the dependent variables that affect hemodialysis cannulation, including AVF growth, AVF depth, and flow rate. SUBJECTS: Arteriovenous Fistulas (AVFs) were created using the carotid artery and jugular vein in the necks of seven goats from the French alpine, dwarf, and pygmy breeds. All seven AVFs exhibited vessel remodeling patterns similar to that observed in humans and remained patent, enabling hemodialysis access over the 6 month study. RESULTS: Over the course of 18 weeks, a total of 291 cannulations were completed using standard 15 g dialysis needles without complications demonstrating the feasibility of using the Caprine species as a cannulation model. The ease of access coupled with the animals' cooperative behavior further contributes to the suitability of the Caprine species for hemodialysis investigations. Notably, no infections or clinically significant incidents were observed throughout the study. CONCLUSIONS: The stability of AVF patency and flow underscores the viability and potential of the Caprine species animal model as a valuable research platform for exploring interventions aimed at improving vascular access survival in hemodialysis patients.

Taqman PACMAN: a simple molecular approach for positive rapid antigen test confirmation during periods of low prevalence.

Antigen-based rapid diagnostic tests (Ag-RDTs) were widely deployed to enhance SARS-CoV-2 testing capacity during the COVID-19 pandemic. Consistent with national guidance for low prevalence settings, positive Ag-RDTs were confirmed using nucleic acid amplification tests (NAATs) to avoid false positive results. However, increasing demands for positive Ag-RDT confirmation competed with other testing priorities in clinical laboratories. This work hypothesized that real-time RT-PCR without nucleic acid extraction (NAE) would be sufficiently sensitive to support positive Ag-RDT confirmation. Ag-RDT and NAAT results from community-based asymptomatic testing sites prior to the omicron variant wave were compared to calculate the weekly false positive rate (FPR) and false detection rate (FDR). Real-time RT-PCR was compared with and without NAE using 752 specimens previously tested positive for SARS-CoV-2 using commercial NAATs and 344 specimens from Ag-RDT-positive individuals. The impact of SARS-CoV-2 prevalence on laboratory resources required to sustain Ag-RDT confirmation was modeled for the RT-PCR with and without NAE. Overall, FPR was low [0.07% (222/330,763)] in asymptomatic testing sites, but FDR was high [30.7% (222/724)]. When RT-PCR was compared with and without NAE, 100% concordance was obtained with NAAT-positive specimens, including those from Ag-RDT-positive individuals. NAE-free RT-PCR significantly reduced time to results, human resources, and overall costs. A 30.7% FDR reaffirms the need for NAAT-based confirmation of positive Ag-RDT results during low SARS-CoV-2 prevalence. NAE-free RT-PCR was shown to be a simple and cost-sparing NAAT-based solution for positive Ag-RDT confirmation, and its implementation supported data-driven broader Ag-RDT deployment into communities, workplaces, and households. IMPORTANCE: Rapid antigen testing for SARS-CoV-2 was widely deployed during the COVID-19 pandemic. In settings of low prevalence, national guidance recommends that positive antigen test results be confirmed with molecular testing. Given the high testing burden on clinical laboratories during the COVID-19 pandemic, the high volume of positive antigen tests submitted for confirmatory testing posed challenges for laboratory workflow. This study demonstrated that a simple PCR method without prior nucleic acid purification is an accurate and cost-effective solution for positive rapid antigen test confirmation. Implementing this method allowed molecular confirmatory testing for positive antigen tests to be sustained as antigen testing was expanded into large populations such as workplaces, schools, and households.

Fate of perfluoroalkyl and polyfluoroalkyl substances (PFAS) through two full-scale wastewater sludge incinerators.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are an emerging issue in wastewater treatment. High-temperature thermal processes, incineration being time-tested, offer the opportunity to destroy and change the composition of PFAS. The fate of PFAS has been documented through wastewater sludge incinerators, including a multiple hearth furnace (MHF) and a fluidized bed furnace (FBF). The dewatered wastewater sludge feedstock averaged 247- and 1280-µmol targeted PFAS per sample run in MHF and FBF feed, respectively. Stack emissions (reportable for all targeted PFAS from MHF only) averaged 5% of that value with shorter alkyl chain compounds comprising the majority of the targeted PFAS. Wet scrubber water streams accumulated nonpolar fluorinated organics from the furnace exhaust with an average of 0.740- and 0.114-mol F- per sample run, for the MHF and FBF, respectively. Simple alkane PFAS measured at the stack represented 0.5%-4.5% of the total estimated facility greenhouse gas emissions. PRACTITIONER POINTS: The MHF emitted six short chain PFAS from the stack, which were shorter alkyl chain compounds compared with sludge PFAS. The FBF did not consistently emit reportable PFAS from the stack, but contamination complicated the assessment. Five percent of the MHF sludge molar PFAS load was reported in the stack. MHF and FBF wet scrubber water streams accumulated nonpolar fluorinated organics from the furnace exhaust. Ultra-short volatile alkane PFAS measured at the stack represented 0.5%-4.5% of the estimated facility greenhouse gas emissions.

Pet collars containing tetrachlorvinphos (TCVP): evaluation of the results of torsion and on-animal release studies and implications for post-application consumer exposure and risk analysis.

Tetrachlorvinphos (TCVP) is the pesticidal active ingredient found in some flea and tick collars for dogs and cats. Recent studies sponsored by The Hartz Mountain Corporation, confirm the safety of TCVP as an active ingredient in pet collars. Based upon data from these new studies and results previously relied upon by the U.S. Environmental Protection Agency, the following conclusions have been made: Torsion study data clearly indicate that approximately 93% of released formulation from TCVP containing pet collars is in a liquid phase immediately following activation.Further, even more relevant to human health risk analysis associated with post-application exposures, in vivo data from dogs wearing TCVP pet collars definitively document that TCVP dust released from the collar is rapidly absorbed into the sebum. The maximum ratio of dust to liquid was 0.023% dust to 99.977% liquid.In vivo fur data provide scientific evidence confirming that the mechanism of dissemination of TCVP from pet collars is as a liquid suspended or dissolved in the animal's sebum, even though it may be released from the collar as a solid. Thus, potential post-application exposure to TCVP, including immediately following collar placement, is almost entirely to a liquid phase.Based upon EPA's refined and conservative "untrimmed" collar risk assessment, post-application incidental oral hand-to-mouth activity by children aged 1 to <2 years of age results in margins of exposure significantly greater than the level of concern of 1000, and therefore do not present unreasonable health risk.

Septic Arthritis of the Spinal Facet Joint: Review of 117 Cases.

Background: Septic arthritis of the spinal facet joints is increasingly recognized in the era of magnetic resonance imaging, but its epidemiology, clinical features, management, and prognosis are ill-defined. Methods: We review 101 previously published cases and report 16 cases occurring at our institutions between 2006 and 2018. Results: Most patients presented with fever (60%) and back or neck pain (86%). Radiation into the hip, buttock, or limb was present in 34%. The lumbosacral vertebral segments were involved in 78% of cases. Most cases (64%) were due to Staphylococcus aureus. Bacteremia was present in 66% and paraspinal muscle abscesses in 54%. While epidural abscesses were present in 56%, neurologic complications were seen in only 9%, likely because most abscesses arose below the conus medullaris. Neurologic complications were more common with cervical or thoracic involvement than lumbosacral (32% vs 2%, P < .0001). Extraspinal infection, such as endocarditis, was identified in only 22% of cases. An overall 98% of patients survived, with only 5% having neurologic sequelae. Conclusions: Septic arthritis of the facet joint is a distinct clinical syndrome typically involving the lumbar spine and is frequently associated with bacteremia, posterior epidural abscesses, and paraspinal pyomyositis. Neurologic outcomes are usually good with medical management alone.

Lucidity in the Deeply Forgetful: A Scoping Review.

Background: Even in severe states of Alzheimer's disease and related dementias (ADRD), accounts of an unexpected or paradoxical return of awareness and lucidity have been reported in some patients, documented formally, and studied. Objective: A scoping review was undertaken to survey the literature on the topic. Methods: Five databases were searched using pertinent search terms. Results were deduplicated and subsequently screened by title and abstract for relevance. Remaining reports were read and included or excluded using specific inclusion criteria. 30 results consisted of a mix of perspective papers, case reports, qualitative surveys of caregivers, law journal comments, and mechanistic speculation. Results: An equal mix of primary and secondary research was identified. Conclusions: The papers collected in this review provide a valuable methodological outline for researching the topic of lucid episodes in ADRD. The verified legitimacy and simultaneous inexplicability of these events promote philosophical discussion, mechanistic investigations, and sorely needed research in the field of ADRD.

Plant Development in the Garden Pea as Revealed by Mutations in the Crd/PsYUC1 Gene.

In common with other plant species, the garden pea (Pisum sativum) produces the auxin indole-3-acetic acid (IAA) from tryptophan via a single intermediate, indole-3-pyruvic acid (IPyA). IPyA is converted to IAA by PsYUC1, also known as Crispoid (Crd). Here, we extend our understanding of the developmental processes affected by the Crd gene by examining the phenotypic effects of crd gene mutations on leaves, flowers, and roots. We show that in pea, Crd/PsYUC1 is important for the initiation and identity of leaflets and tendrils, stamens, and lateral roots. We also report on aspects of auxin deactivation in pea.

Inequities in Family Planning in Low- and Middle-Income Countries.

INTRODUCTION: Inequities in reproductive health are widespread, and periodic surveys can trace trends in inequities to guide policies and program implementation. METHODS: We examined National Composite Index for Family Planning surveys from 2017 and 2021 that assessed inequities in access to 7 contraceptive methods and traced patterns of discrimination involving 5 subgroups in low- and middle-income countries. These surveys use 10-25 informants in each country who are knowledgeable at the national level. Measures are based on questionnaire ratings on a scale of 1-10. RESULTS: Access to contraceptive methods averages about half of the maximum of 100%, with substantial variation across regions and countries for the score levels. Score profiles are similar among high-scoring and low-scoring countries, suggesting that access to each method reflects common determinants in the nature of each method and the influences acting upon national family planning programs. Access to short-term methods (pill, injectable, and condom) is much better than for long-term methods (sterilization, intrauterine device, and implant). Community-based distribution of contraceptives averages low, as it is not part of some programs. Over time the scores have improved modestly. Correlations imply that better access leads to more contraceptive use. Inequity of use across wealth groups is less where overall equity has improved. Measures of discrimination against youth, unmarried women, postabortion clients, HIV carriers, and different wealth groups indicate a need for additional policies and considerable latitude for stronger actions by providers. CONCLUSIONS: The surveys in 2017 and 2021 demonstrate both progress and deficiencies for equitable access to contraceptive methods, with highly variable results among regions and countries. Much remains to be done to alleviate discriminatory practices against particular subgroups. Equity has improved for access to contraception and contraceptive use, and it can continue to do so with greater attention to policies and practices in national programs.

Estimated Dermal Penetration of Tetrachlorvinphos (TCVP) in Humans Based on In Silico Modeling and In Vitro and In Vivo Data.

Tetrachlorvinphos (TCVP) is the pesticidal active ingredient in some collars for dogs and cats. The objective of this study was to provide a refined estimate of dermal penetration of TCVP in humans using in silico predictions as well as in vitro and in vivo data. The in vivo dermal absorption of TCVP was previously studied in the rat and shown to be saturable, ranging from 21.7% (10 µg/cm2) down to 3% (1000 µg/cm2) Subsequent in silico predictions were conducted for rats and humans to provide initial evaluations of species and dose-dependent differences in dermal absorption. A definitive comparison of TCVP systemic exposure in rat and human following dermal application was then conducted via a standard in vitro assay. TCVP dose levels of 10, 100, or 1000 µg/cm2 were applied to excised rat and human skin mounted in flow-through diffusion cells. The vehicle was 1% hydroxypropylmethylcellulose (HPMC) in water. An additional 5 µg/cm2 dose was applied to excised human skin only. The in vitro dermal absorption of TCVP was also assessed from artificial sebum at dose levels of 5, 10, or 100 µg/cm2 applied to human skin only. Utilizing the so-called triple pack approach with in vitro and in vivo rat data and in vitro human data, dermal absorption for TCVP was calculated for humans. In silico modeling indicated absorption of TCVP through human skin might be 3- to 4- fold lower than rat skin at all application levels, with a maximum dermal absorption of 9.6% at the lowest exposure of 10 µg/cm2, down to 0.1% at 1000 µg/cm2. Similar species differences were also found in the definitive in vitro absorption assays. Modeling overestimated TCVP human dermal absorption (9.6%) as compared to excised human skin results (1.7%) for the HPMC vehicle at the lowest exposure (10 µg/cm2), with better agreement at the higher exposures. Conversely, modeling accurately predicted rat dermal absorption (27.9%) as compared to in vivo rat results (21.7%) at the lowest exposure in HPMC, with diminished agreement at the higher exposures. As a first approximation, in silico estimates of dermal absorption are useful; however, these tend to be more variable than in vitro or in vivo measurements. TCVP dermal penetration measured in vitro was lower in 1% HPMC vehicle as compared to artificial sebum. For the 1% HPMC vehicle, in vitro rat dermal absorption was similar to data obtained for in vivo rats, giving confidence in the triple pack approach. In consideration of the triple pack approach, estimated human dermal absorption from 1% HPMC was ≤2%. Based upon excised human skin determinations directly, estimated human dermal absorption of TCVP from artificial sebum was ≤7%.

Prospective multicenter study of a novel endovascular venous anastomotic procedure and device for implantation of an arteriovenous graft for hemodialysis.

INTRODUCTION: The traditional sutured venous anastomosis used during arteriovenous graft implantation is associated with a high incidence of subsequent stenosis that is attributed to neointimal hyperplasia. Hyperplasia results from multiple factors, including hemodynamic abnormalities and vessel trauma during implantation. A novel anastomotic connector device was designed to provide an alternative, less traumatic, endovascular venous anastomosis that may ameliorate the clinical challenges associated with a sutured anastomosis. A prospective single-arm multicenter study was performed to evaluate safety and effectiveness of graft implantation using the study device. METHODS: Patients requiring graft creation and who met the study criteria were enrolled between February 2018 and July 2021 and observed for 6 months. Collected data included baseline characteristics, graft patency and use for hemodialysis, graft interventions, and adverse events. The primary study endpoint was cumulative graft patency, compared to a pre-specified Performance Goal of 75%. Secondary endpoints included primary unassisted patency and serious adverse events, defined as the occurrence of death, graft infection, emergent surgery, significant bleeding, and pseudoaneurysm. RESULTS: A total of 158 patients were enrolled from 10 study sites, among which 144 subjects were evaluable at 6 months and 14 were censored with partial follow-up observation. Three patients died and the graft was abandoned in 12. The primary endpoint was met (p-value < 0.001). By Kaplan Meier survival analysis, cumulative patency was 92.08% with a lower 95% Confidence Bound of 86.98%. Primary unassisted patency was 60.21% with a lower 95% Confidence Bound of 50.84%. Graft infections occurred in six patients, all unrelated to the study device. There were no reports of emergent surgery, significant bleeding or pseudoaneurysm. CONCLUSION: These results demonstrate that the study device can be used for successful endovascular anastomosis of a vein to a graft for hemodialysis, with acceptable cumulative patency and safety profile at 6 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02532621.

Blastomycosis in New England: 5 Cases and a Review.

The geographic range of blastomycosis is thought to include New England, but documentation is sparse. We report 5 cases of infection with Blastomyces dermatitidis that were likely acquired in New England between 2011 and 2021. Our experience suggests that chart coding for the diagnosis of blastomycosis is imprecise and that mandatory reporting might help resolve uncertainties about the prevalence and extent of blastomycosis.

Automated 3D ultrasound enables novice users to measure arteriovenous fistula maturation parameters with comparable accuracy to conventional duplex by trained sonographers: Results of a benchtop study.

BACKGROUND: Arteriovenous fistulae (AVF) are considered the preferred hemodialysis access but up to 50% of all AVF created in the United States never mature. Doppler ultrasound (DUS) is useful for predicting fistula maturity and impending fistula failure. DUS is resource-intensive and is associated with poor compliance rates in dialysis patients, ranging from 12% to 33%. METHODS: EchoSure is an FDA-cleared 3D Doppler ultrasound device that automatically delivers quantitative blood flow and anatomic vascular information. The technology can be used at the bedside by personnel without formal sonographic training, nullifying limitations of traditional Duplex ultrasound imaging. This study compared the EchoSure system in the hands of inexpert personnel to a traditional expert-operated DUS for rapid assessment of a benchtop model vascular system with flow, diameter, and depth expected in a human AVF. RESULTS: Both Duplex and EchoSure performed within the expected tolerance of ultrasound readings (35%) for volume flow, with the average error (AE) between the observed measurement and the ground truth being 8% for Duplex and 8% for EchoSure. However, the average coefficient of variation (CV) for Duplex pooled over all flow rate measurements was 17% versus 4% for EchoSure. Regarding diameter, Duplex measurements had AE of 15% with an average CV of 6% across all measurements versus EchoSure AE of 4% and average CV of 2%. Duplex and EchoSure measurements over all depths had the same AE of 2%. The two modalities were not statistically different for depth measurement (p = 0.05) but EchoSure measured closer to the ground truth for flow rate and vessel diameter (flow: p = 0.028, ρ = -0.07; diameter: p < 0.001, ρ = 0.69). The inexpert personnel using EchoSure acquired data 62% faster than the expert sonographers using the Duplex ultrasound (141 min for Duplex vs 87 min for EchoSure). CONCLUSIONS: EchoSure may offer an accurate and convenient alternative for imaging fistulas in the clinic.

Chameleon™ PTA balloon catheter: A single device in managing thrombosed AV access.

Thrombectomy is a common procedure for maintenance of arteriovenous (AV) access and is critical to prolong access life. Techniques for performing thrombectomy are incredibly diverse, ranging from open surgical procedures to percutaneous interventions. Percutaneous interventions include a combination of thrombectomy devices to clear the thrombus and balloon angioplasty to treat the underlying lesion. In this case report we describe a novel technique using a single device, the Chameleon™ PTA balloon catheter (Medtronic, Minneapolis, MN) balloon catheter, to safely and efficiently perform a percutaneous intervention.

ASDIN white paper: Management of cephalic arch stenosis endorsed by the American Society of Diagnostic and Interventional Nephrology.

Brachiocephalic arteriovenous fistulas (AVF) makeup approximately one third of prevalent dialysis vascular accesses. The most common cause of malfunction with this access is cephalic arch stenosis (CAS). The accepted requirement for treatment of a venous stenosis lesion is ⩾50% stenosis associated with hemodynamically abnormalities. However, the correlation between percentage stenosis and a clinically significant decrease in access blood flow (Qa) is low. The critical parameter is the absolute minimal luminal diameter (MLD) of the lesion. This is the parameter that exerts the key restrictive effect on Qa and results in hemodynamic and functional implications for the access. CAS is the result of low wall shear stress (WSS) resulting from the effects of increased blood flow and the unique anatomical configuration of the CAS. Decrease in WSS has a linear relationship to increased blood flow velocity and neointimal hyperplasia exhibits an inverse relationship with WSS. The result is a stenotic lesion. The presence of downstream venous stenosis causes an inflow-outflow mismatch resulting in increased pressure within the access. Qa in this situation may be decreased, increased, or within a normal range. Over time, the increased intraluminal pressure can result in marked aneurysmal changes within the AVF, difficulties with cannulation and the dialysis treatment, and ultimately, increasing risk of access thrombosis. Complete characterization of the lesion both hemodynamically and anatomically should be the first step in developing a strategy for management. This requires both access flow measurement and angiographic imaging. Patients with CAS present a relatively broad spectrum as relates to both of these parameters. These data should be used to determine whether primary treatment of CAS should be directed toward the anatomical lesion (small MLD and low Qa) or the pathophysiology (large MLD and high Qa).

Characterizing Cochlear Implant Magnet-Related MRI Artifact.

OBJECTIVE: To evaluate cochlear implant (CI) magnet-related MRI artifact shape and size, as well as imaging indications and clinical adequacy of scans. METHODS: A retrospective chart review was performed for patients undergoing CI and subsequent MRI head imaging from 2014 to 2020 at a single institution. Indications and adequacy of each scan was recorded, and interpretability compared by indication. Magnet-related artifact size was determined by performing ellipsoid modeling at axial slice of greatest signal loss. Artifact radius in centimeters was calculated for 5 sequence categories, and size compared between sequences, manufacturers, and by time from implantation. RESULTS: Twenty patients underwent 58 head MRI scans. Approximately 76% of MRIs (n = 44) for 70% of patients (n = 14) were performed for indications known of prior to implantation; the remainder were performed during workup of new issues. Desired structures were interpretable in 23 (52%) of known-indication MRIs and 8 (57%) of new-indication MRIs, without significant difference (P = .751). Magnet-related artifact magnitude, compared to the reference T1-weighted fast spin echo (FSE) (4.47 cm), was similar in T2 FSE (4.57 cm, P = .068) and T1 gradient echo (GRE) sequences (4.79 cm, P = .28), but significantly greater in T2 GRE (6.86, P < .0001) and DWI (7.56 cm, P < .0001) sequences. CONCLUSIONS: DWI and T2 GRE sequences are less useful in MRI evaluation of CI patients. With a more favorable artifact profile, T1 FSE, T2 FSE, and T1 GRE sequences more likely yield clinically useful information. The large proportion of scans performed for known pathology represents an opportunity to optimize for magnet location preoperatively.

What's the point in even trying? Women's perception of glass ceiling drains hope.

In this study, we focus on glass ceiling perceptions, characterized by women's subjective feelings about their ability to move upward in their organization. Drawing on social information processing and hope theory, we propose that glass ceiling perceptions decrease women's citizenship behaviors and increase their turnover intentions by draining their hope in the workplace. Moreover, we suggest that the strength of the association between glass ceiling perceptions, drained hope in the workplace, and these two outcomes is conditional upon women's perceptions of their work-family conflict. Using a two-study design, we tested our hypothesized relationships. We found a mediating effect of drained hope in the workplace between glass ceiling perceptions and (a) turnover intention and (b) organizational citizenship behaviors. This effect is significant when work-family conflict is high. Finally, we discuss the implications of our findings regarding the tensions that women experience with simultaneously managing their careers and conflict in the family.

Mendel: From genes to genome.

Two hundred years after the birth of Gregor Mendel, it is an appropriate time to reflect on recent developments in the discipline of genetics, particularly advances relating to the prescient friar's model species, the garden pea (Pisum sativum L.). Mendel's study of seven characteristics established the laws of segregation and independent assortment. The genes underlying four of Mendel's loci (A, LE, I, and R) have been characterized at the molecular level for over a decade. However, the three remaining genes, influencing pod color (GP), pod form (V/P), and the position of flowers (FA/FAS), have remained elusive for a variety of reasons, including a lack of detail regarding the loci with which Mendel worked. Here, we discuss potential candidate genes for these characteristics, in light of recent advances in the genetic resources for pea. These advances, including the pea genome sequence and reverse-genetics techniques, have revitalized pea as an excellent model species for physiological-genetic studies. We also discuss the issues that have been raised with Mendel's results, such as the recent controversy regarding the discrete nature of the characters that Mendel chose and the perceived overly-good fit of his segregations to his hypotheses. We also consider the relevance of these controversies to his lasting contribution. Finally, we discuss the use of Mendel's classical results to teach and enthuse future generations of geneticists, not only regarding the core principles of the discipline, but also its history and the role of hypothesis testing.