Fast track dialysis: Improving emergency department and hospital throughput for patients requiring hemodialysis.

OBJECTIVE: To describe the impact of a novel communication and triage pathway called fast track dialysis (FTD) on the length of stay (LOS), resource utilization, and charges for unscheduled hemodialysis for end stage renal disease (ESRD) patients presenting to the emergency department (ED). METHODS: Prospective and retrospective cohorts of ESRD patients meeting requirements of routine or urgent hemodialysis at a tertiary academic hospital from September 25th, 2016 to September 25th, 2018 in 1 year cohorts. Two sample t-tests were used to compare most outcomes of the cohorts with a Mann-Whitney U test used for skewed data. Nephrology group outcomes were analyzed by two-way ANOVA and Kruskal-Wallis and chi-square tests. RESULTS: There were 98 encounters in the historical cohort and 143 encounters in the fast track dialysis cohort. FTD had significantly lowered median ED LOS (4.05 h, vs 5.3 h, p < 0.001), median hospital LOS (12.8 h vs 27 h, p < 0.001), time to hemodialysis (4.78 h vs 7.29 h, p < 0.001), and median hospital charges ($26,040 vs $30,747, p < 0.016). The FTD cohort had increased 30 day ED return for each encounter compared to the historical cohort (1.85 visits vs 0.73 visits, p < 0.001), however no significant increase in 1 year ED visits (6.52 visits vs 5.80, p = 0.4589) or 1 year readmissions (5.89 readmissions vs 4.81 readmissions, p = 0.3584). Most nephrology groups had significantly lower time to hemodialysis order placement and time to start hemodialysis. CONCLUSION: A multidisciplinary approach with key stakeholders using a standard pathway can lead to improved efficiency in throughput, reduced charges, and hospital resource utilization for patients needing urgent or routine hemodialysis. A study with a dedicated geographic observation unit for protocolized short stay patients including conditions ranging from low risk chest pain to transient ischemic events that incorporates FTD patients under this protocol should be considered.

Making sense of DialysisConnect: a qualitative analysis of stakeholder viewpoints on a web-based information exchange platform to improve care transitions between dialysis clinics and hospitals.

BACKGROUND: U.S. hospitals and dialysis centers are penalized for 30-day hospital readmissions of dialysis patients, despite little infrastructure to facilitate care transitions between these settings. We are developing a third-party web-based information exchange platform, DialysisConnect, to enable clinicians to view and exchange information about dialysis patients during admission, hospitalization, and discharge. This health information technology solution could serve as a flexible and relatively affordable solution for dialysis facilities and hospitals across the nation who are seeking to serve as true partners in the improved care of dialysis patients. The purpose of this study was to evaluate the perceived coherence of DialysisConnect to key clinical stakeholders, to prepare messaging for implementation. METHODS: As part of a hybrid effectiveness-implementation study guided by Normalization Process Theory, we collected data on stakeholder perceptions of continuity of care for patients receiving maintenance dialysis and a DialysisConnect prototype before completing development and piloting the system. We conducted four focus groups with stakeholders from one academic hospital and associated dialysis centers [hospitalists (n = 5), hospital staff (social workers, nurses, pharmacists; n = 9), nephrologists (n = 7), and dialysis clinic staff (social workers, nurses; n = 10)]. Transcriptions were analyzed thematically within each component of the construct of coherence (differentiation, communal specification, individual specification, and internalization). RESULTS: Participants differentiated DialysisConnect from usual care variously as an information dashboard, a quick-exchange communication channel, and improved discharge information delivery; some could not differentiate it in terms of workflow. The purpose of DialysisConnect (communal specification) was viewed as fully coherent only for communicating outside of the same healthcare system. Current system workarounds were acknowledged as deterrents for practice change. All groups delegated DialysisConnect tasks (individual specification) to personnel besides themselves. Partial internalization of DialysisConnect was achieved only by dialysis clinic staff, based on experience with similar technology. CONCLUSIONS: Implementing DialysisConnect for clinical users in both settings will require presenting a composite picture of current communication processes from all stakeholder groups to correct single-group misunderstandings, as well as providing data about care transitions communication beyond the local context to ease resistance to practice change.

Predicting Polycyclic Aromatic Hydrocarbon Bioavailability to Mammals from Incidentally Ingested Soils Using Partitioning and Fugacity.

Soil and dust ingestion is one of the major human exposure pathways to contaminated soil; however, pollutant transfer from ingested substances to humans cannot currently be confidently predicted. Soil polycyclic aromatic hydrocarbon (PAH) bioavailability is likely dependent upon properties linked to chemical potential and partitioning such as fugacity, fugacity capacity, soil organic carbon, and partitioning to simulated intestinal fluids. We estimated the oral PAH bioavailability of 19 historically contaminated soils fed to juvenile swine. Between soils, PAH blood content, with the exception of benzo(a)pyrene, was not linked to fugacity. In contrast, between individual PAHs, using partitioning explained PAH blood content (area under the curve = 0.47 log fugacity + 0.34, r(2) = 0.68, p < 0.005, n = 14). Soil fugacity capacity predicts PAH soil concentration with an average slope of 0.30 (µg PAH g(-1) soil) Pa(-1) and r(2)'s of 0.61-0.73. Because PAH blood content was independent of soil concentration, soil fugacity correlated to PAH bioavailability via soil fugacity's link to soil concentration. In conclusion, we can use fugacity to explain PAH uptake from a soil into blood. However, something other than partitioning is critical to explain the differences in PAH uptake into blood between soils.

Does open or closed reduction with internal fixation reduces the incidence of complications in neck of femur fractures in pediatrics: a meta-analysis and systematic review.

The neck of femur fracture (FNF) in children is a rare injury with a high incidence of complications such as avascular necrosis (AVN), coxa-vara and nonunion. The aim of this review is to compare the incidence of complications between open reduction with internal fixation (ORIF) and closed reduction with internal fixation (CRIF) of FNF in children. Two independent reviewers searched EMBASE, MEDLINE, COCHRANE and PUBMED databases from inception until April 2022 according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Studies included comparison of complications between open and closed approaches with fixation of FNF in patients less than 18 years old. Publication bias was assessed using Egger's test while the Newcastle-Ottawa tool was used to assess the methodological quality of the studies. A total of 724 hip fractures from 15 included studies received either ORIF or CRIF. Overall, the rate of AVN was approximately 21.7% without statistical significance between both reduction methods [relative risk (RR) = 0.909, using fixed effect model at 95% confidence interval (CI, 0.678-1.217)]. No significant heterogeneity among AVN studies ( I2  = 3.79%, P  = 0.409). Similarly, neither coxa-vara nor nonunion rates were statistically significant in both treatment groups (RR = 0.693 and RR = 0.506, respectively). Coxa-vara studies showed mild heterogeneity ( I2  = 27.8%, P  = 0.218), while significant publication bias was encountered in nonunion studies ( P  = 0.048). No significant difference in the incidence of AVN, coxa-vara and nonunion between ORIF or CRIF of FNF in children. High-quality studies as Randomised Controlled Trials can resolve the inconsistency and heterogeneity of other risk factors including age, initial displacement, fracture type, reduction quality and time to fixation.

Rare Delayed Ifosfamide Encephalopathy: A Case Report of Chemotherapeutic Neurotoxicity.

Introduction: Neurotoxicity is a well-documented side effect of ifosfamide chemotherapy. The presentation includes hallucinations, seizures, disorientation, coma, and death. Treatment with methylene blue can shorten the duration and severity of symptoms. Ifosfamide neurotoxicity almost always happens during or shortly after drug infusion and so is usually immediately recognized. Here, we describe a case of ifosfamide neurotoxicity with onset 14 days after treatment started. Case Presentation: A 25-year-old woman with round cell sarcoma of the jaw presented to the emergency department with 2 days of encephalopathy and bizarre behavior. Antipsychotic medications and benzodiazepines produced no benefit. After consultation, oncology recommended methylene blue, hypothesizing that her symptoms could be a rare presentation of delayed ifosfamide-induced neurotoxicity, 14 days after first administration. After 4 days of methylene blue infusion, her functioning returned to baseline. Conclusion: Delayed ifosfamide-related neurotoxicity is a rare side effect of this chemotherapeutic agent and should be considered in the workup of altered mental status, even if symptoms occur after the previously accepted 5-day standard. In such patients, delayed symptomology may require extended use of methylene blue as treatment.

An investigation of the effect of gastrointestinal microbial activity on oral arsenic bioavailability.

In vitro gastrointestinal (GI) microbial activity in the colon compartment facilitates the arsenic release from soils into simulated GI fluids. Consequentially, it is possible that in vitro models that neglect to include microbial activity underestimate arsenic bioaccessibility when calculating oral exposure. However, the toxicological relevance of increased arsenic release due to microbial activity is contingent upon the subsequent absorption of arsenic solubilized in the GI lumen. The objectives of this research are to: (1) assess whether microbes in the in vitro small intestine affect arsenic solubilization from soils, (2) determine whether differences in the GI microbial community result in differences in the oral bioavailability of soil-borne arsenic. In vitro GI microbial activity in the distal small intestine increased arsenic release from soils; however, these effects were unlikely to be relevant since they were transient and demonstrated small effect sizes. In vivo arsenic absorption for juvenile swine was unaffected by antibiotic treatment. Therefore, it appears that microbial effects on arsenic release do not result in increased arsenic bioavailability. However, it remains to be seen whether the results for the limited set of soils described herein can be extrapolated to arsenic contaminated sites in general.

A Distinction Without a Difference? A Multi-Method Approach to Understanding PTSD and Depression Symptom Overlap Among Disaster-Exposed Adolescents.

Among adolescents exposed to trauma, posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) commonly co-occur. Despite the prevalence of comorbidity, the question of how PTSD and MDD are related and appropriate conceptual models for understanding their linkage in adolescence remains unclear. This study applies a multi-methodological approach to advance conceptual and theoretical understanding of the overlap between PTSD and MDD diagnoses/symptoms. We tested three methodological approaches with three distinct theoretical underpinnings on the structure of each disorder proposed in the literature: confirmatory factor analysis (CFA) with dimensional constructs, latent class analysis (LCA) with person-based categorical constructs, and network analysis with symptom-to-symptom associations. Across the three different analytical approaches, there was a significant overlap between PTSD and MDD. Overall, there was no compelling evidence for distinct boundaries between disorders among trauma-exposed adolescents. Instead, we found considerable evidence that the typical latent-construct-based conceptualizations, whether categorical or dimensional, may need revision.

Exploring an Unknown Corner of a Well-Known Topic: HIIE Influence on Renal Health and Filtration in Healthy Individuals Free of Cardiometabolic Diseases.

Aerobic exercise, specifically high-intensity interval exercise (HIIE), and its effects on renal health and filtration (RHF) are not well understood. Several studies support incorporating contemporary biomarkers serum cystatin C (CyC) and urine epidermal growth factor (uEGF) to combat the volatility of serum creatinine (sCr). Using these biomarkers, we examined the acute influences HIIE has on RHF to determine if there is a ceiling effect in healthy populations. The purpose was to determine the influence of an acute bout of HIIE on RHF. Thirty-six participants (n = 22 males; n = 14 females; age 37.6 ± 12.4 years.; BF% 19.2 ± 7.1%; VO2max 41.8 + 7.4 mL/kg/min) completed 30 min of HIIE on a treadmill (80% and 40% of VO2reserve in 3:2 min ratio). Blood and urine samples were obtained under standardized conditions before, 1 h, and 24 h post-exercise. CyC, sCR, uEGF, urine creatinine (uCr), uCr/uEGF ratio, and multiple estimates of glomerular filtration rate (eGFR) Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations were used. The analysis employed paired sample t-tests and repeated measures ANOVAs. CyC, uEGF, uCr, and uCr/uEGF ratio concentrations were not altered between timepoints. sCr increased 1 h post-exercise (p > 0.002) but not at 24 h post-exercise. eGFR decreased in the MDRD and CKD-EPI equations at 1 h (p > 0.012) with no changes at 24 h post-exercise. CyC and sCr/CyC demonstrated no significant changes. CyC and uEGF are not altered by acute HIIE. The results demonstrate a potential ceiling effect in contemporary and traditional biomarkers of RHF, indicating improvements in RHF may be isolated to populations with reduced kidney function.

Forecasting emergence of COVID-19 variants of concern.

We consider whether one can forecast the emergence of variants of concern in the SARS-CoV-2 outbreak and similar pandemics. We explore methods of population genetics and identify key relevant principles in both deterministic and stochastic models of spread of infectious disease. Finally, we demonstrate that fitness variation, defined as a trait for which an increase in its value is associated with an increase in net Darwinian fitness if the value of other traits are held constant, is a strong indicator of imminent transition in the viral population.

The Effects of Acute and Chronic Exercise on Paraoxonase-1 (PON1): A Systematic Review With Meta-Analysis.

Purpose: To determine the acute and chronic effects of exercise on Paraoxonase-1 (PON1) concentration and activity. Methods: A literature search was performed using 16 electronic databases. Effect sizes (ES) were computed and two-tailed α values < .05 and non-overlapping 95% confidence intervals (95%CI) were considered statistically significant. Heterogeneity, inconsistency (I2), and small-study effects using the LFK index were examined. Results: Eighteen studies (n = 377 participants) met the criteria for inclusion. The acute effects of exercise on PON1 concentration were trivial and non-significant (ES = -.03, 95%CI = -.39 to .34, p > .05), heterogeneous (p = .05), moderately inconsistent (I2 = 48%), with minor asymmetry (LFK index = 1.34). The chronic effects of exercise on PON1 concentration were also trivial and non-significant (ES = -.04, 95%CI = -.53 to.45, p > .05), homogenous (p = .65), displayed low inconsistency (I2 = 0%), and minor asymmetry (LFK index = -1.14). The acute effects of exercise on PON1 activity were trivial and non-significant (ES = .11, 95%CI = -.02 to.24, p > .05), homogenous (p = .85), showed low inconsistency (I2 = 0%), and no asymmetry (LFK index = .82). The chronic effects of exercise on PON1 activity were trivial and non-significant (ES = .31, 95%CI = -.03 to.65, p > .05), homogenous (p = .17), moderately inconsistent (I2 = 36%), with no asymmetry (LFK index = .60). Conclusion: Acute and chronic exercise training, overall, exerted a trivial effect on PON1 concentration and activity.

Effectiveness of a Web-Based Provider Communications Platform in Reducing Hospital Readmissions Among Patients Receiving Dialysis: A Pilot Pre-Post Study.

Rationale & Objective: Suboptimal care coordination between dialysis facilities and hospitals is an important driver of 30-day hospital readmissions among patients receiving dialysis. We examined whether the introduction of web-based communications platform ("DialysisConnect") was associated with reduced hospital readmissions. Study Design: Pilot pre-post study. Setting & Participants: A total of 4,994 index admissions at a single hospital (representing 2,419 patients receiving dialysis) during the study period (January 1, 2019-May 31, 2021). Intervention: DialysisConnect was available to providers at the hospital and 4 affiliated dialysis facilities (=intervention facilities) during the pilot period (November 1, 2020-May 31, 2021). Outcomes: The primary outcome was 30-day readmission; secondary outcomes included 30-day emergency department visits and observation stays. Interrupted time series and linear models with generalized estimating equations were used to assess pilot versus prepilot differences in outcomes; difference-in-difference analyses were performed to compare these differences between intervention versus control facilities. Sensitivity analyses included a third, prepilot/COVID-19 period (March 1, 2020-October 31, 2020). Results: There was no statistically significant difference in the monthly trends in the 30-day readmissions pilot versus prepilot periods (-0.60 vs -0.13, P = 0.85) for intervention facility admissions; the difference-in-difference estimate was also not statistically significant (0.54 percentage points, P = 0.83). Similar analyses including the prepilot/COVID-19 period showed that, despite a substantial drop in admissions at the start of the pandemic, there were no statistically significant differences across the 3 periods. The age-, sex-, race-, and comorbid condition-adjusted, absolute pilot versus prepilot difference in readmissions rate was 1.8% (-3.7% to 7.3%); similar results were found for other outcomes. Limitations: Potential loss to follow-up and pandemic effects. Conclusions: In this pilot, the introduction of DialysisConnect was not associated with reduced hospital readmissions. Tailored care coordination solutions should be further explored in future, multisite studies to improve the communications gap between dialysis facilities and hospitals.

A Web-Based, Provider-Driven Mobile App to Enhance Patient Care Coordination Between Dialysis Facilities and Hospitals: Development and Pilot Implementation Study.

BACKGROUND: We piloted a web-based, provider-driven mobile app (DialysisConnect) to fill the communication and care coordination gap between hospitals and dialysis facilities. OBJECTIVE: This study aimed to describe the development and pilot implementation of DialysisConnect. METHODS: DialysisConnect was developed iteratively with focus group and user testing feedback and was made available to 120 potential users at 1 hospital (hospitalists, advanced practice providers [APPs], and care coordinators) and 4 affiliated dialysis facilities (nephrologists, APPs, nurses and nurse managers, social workers, and administrative personnel) before the start of the pilot (November 1, 2020, to May 31, 2021). Midpilot and end-of-pilot web-based surveys of potential users were also conducted. Descriptive statistics were used to describe system use patterns, ratings of multiple satisfaction items (1=not at all; 3=to a great extent), and provider-selected motivators of and barriers to using DialysisConnect. RESULTS: The pilot version of DialysisConnect included clinical information that was automatically uploaded from dialysis facilities, forms for entering critical admission and discharge information, and a direct communication channel. Although physicians comprised most of the potential users of DialysisConnect, APPs and dialysis nurses were the most active users. Activities were unevenly distributed; for example, 1 hospital-based APP recorded most of the admissions (280/309, 90.6%) among patients treated at the pilot dialysis facilities. End-of-pilot ratings of DialysisConnect were generally higher for users versus nonusers (eg, "I can see the potential value of DialysisConnect for my work with dialysis patients": mean 2.8, SD 0.4, vs mean 2.3, SD 0.6; P=.02). Providers most commonly selected reduced time and energy spent gathering information as a motivator (11/26, 42%) and a lack of time to use the system as a barrier (8/26, 31%) at the end of the pilot. CONCLUSIONS: This pilot study found that APPs and nurses were most likely to engage with the system. Survey participants generally viewed the system favorably while identifying substantial barriers to its use. These results inform how best to motivate providers to use this system and similar systems and inform future pragmatic research in care coordination among this and other populations.

Examining the associations between PTSD symptoms and aspects of emotion dysregulation through network analysis.

Despite the clearly established link between posttraumatic stress disorder (PTSD) and emotion dysregulation, little is known about how individual symptoms of PTSD and aspects of emotion dysregulation interrelate. The network approach to mental health disorders provides a novel framework for conceptualizing the association between PTSD and emotion dysregulation as a system of interacting nodes. In this study, we estimated the structural relations among PTSD symptoms and aspects of emotion dysregulation within a large sample of women who participated in a multi-site study of sexual revictimization (N = 463). We estimated expected influence to reveal differential associations among PTSD symptoms and aspects of emotion dysregulation. Further, we estimated bridge expected influence to identify influential nodes connecting PTSD symptoms and aspects of emotion dysregulation. Results highlighted the key role of concentration difficulties in expected influence and bridge expected influence. Findings highlight several PTSD symptoms and aspects of emotion dysregulation that may be targets for future intervention.

The Influence of an Acute Bout of Aerobic Exercise on Vascular Endothelial Function in Moderate Stages of Chronic Kidney Disease.

Chronic kidney disease (CKD) is directly influenced by the deleterious effects of systemic inflammation and oxidative stress. The vascular endothelium may transiently respond to aerobic exercise and improve post-exercise vascular renal function in moderate stages of CKD. Brachial artery flow-mediated dilation (FMD) is a nitric-oxide-dependent measure of endothelial function that is transiently potentiated by exercise. The purpose of the study was to determine the acute influence of a single bout of high-intensity interval exercise (HIIE) or steady-state moderate-intensity exercise (SSE) on endothelial dysfunction in moderate stages of CKD. Twenty participants (n = 6 men; n = 14 women) completed 30 min of SSE (65%) and HIIE (90:20%) of VO2reserve in a randomized crossover design. FMD measurements and blood samples were obtained before, 1 h, and 24 h post-exercise. FMD responses were augmented 1 h post-exercise in both conditions (p < 0.005). Relative to pre-exercise measures, total antioxidant capacity increased by 4.3% 24 h post-exercise (p = 0.012), while paraoxonase-1 was maintained 1 h and elevated by 6.1% 24 h after SSE, but not HIIE (p = 0.035). In summary, FMD can be augmented by a single episode of either HIIE or SSE in moderate stages of CKD. Modest improvements were observed in antioxidant analytes, and markers of oxidative stress were blunted in response to either SSE or HIIE.

Human exposure assessment: a case study of 8 PAH contaminated soils using in vitro digestors and the juvenile swine model.

In vitro digestors can be used to provide bioaccessibility values to help assess the risk from incidental human ingestion of contaminated soils. It has been suggested that these digestors may need to include a lipid sink to mimic human uptake processes. We compare the correspondence between in vivo polycyclic aromatic hydrocarbon (PAH) uptake for eight different PAH contaminated soils with PAH release in in vitro digestors in the presence and absence of a lipid sink. Lipid sinks were essential to the success of the in vitro digestors in predicting juvenile swine PAH uptake. In the presence of the lipid sink, results of the In Vitro Digestion model (IVD) closely corresponded with a slope of 0.85 (r(2) = 0.45, P < 0.07) to the in vivo results. The Relative Bioaccessibility Leaching Procedure (RBALP) results did not correspond to the in vivo study but did tightly reflect total soil PAH concentration. We conclude that the basis of this difference between digestors is that the RBALP used an aggressive extraction technique that maximized PAH release from soil. Systemic uptake in juvenile swine was not linked to soil PAH concentration but rather to the thermodynamic properties of the soil.

TomoTherapy stereotactic body radiation therapy (SBRT) for the salvage treatment of locally recurrent esophageal adenocarcinoma following trimodality therapy: a case report.

Esophageal cancer patients with local recurrence after chemoradiation and surgery (trimodality therapy) have limited palliative treatment options. We present a case of local recurrence successfully palliated using TomoTherapy stereotactic body radiation therapy (SBRT). The patient was a 58-year-old man with distal esophageal adenocarcinoma initially treated with trimodality therapy. Symptomatic local recurrence developed 4 years later. Using TomoTherapy SBRT successful palliation was achieved with 3500 cGy in 7 fractions given every other weekday. He remained free of local recurrence without requiring further local therapies, eventually succumbing to metastatic disease 11 months after radiation. Presently there are no reported cases of malignant esophageal obstruction treated with SBRT. Radiosurgery is increasingly used in extracranial sites such as the liver, lung and spine. Reirradiation was convenient and well tolerated by our patient and the response durable. Palliation of local recurrence in esophageal cancer initially treated with trimodality therapy can be achieved using SBRT and is a reasonable option in appropriately selected patients. Further studies are needed to clarify its role in this and other body sites.

Anti-HIV reverse transcriptase plant polyphenolic natural products with in silico inhibitory properties on seven non-structural proteins vital in SARS-CoV-2 pathogenesis.

BACKGROUND: Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. This study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting in silico key sites in the structures of SARS-CoV-2 nsps. One hundred four anti-HIV phytochemicals were subjected to molecular docking with nsp3, 5, 10, 12, 13, 15, and 16. Top compounds in complex with the nsps were investigated further through molecular dynamics. The drug-likeness and ADME (absorption, distribution, metabolism, and excretion) properties of the top compounds were also predicted using SwissADME. Their toxicity was likewise determined using OSIRIS Property Explorer. RESULTS: Among the top-scoring compounds, the polyphenolic functionalized natural products comprised of biflavones 1, 4, 11, 13, 14, 15; ellagitannin 9; and bisisoquinoline alkaloid 19 were multi-targeting and exhibited strongest binding affinities to at least two nsps (binding energy = - 7.7 to - 10.8 kcal/mol). The top ligands were stable in complex with their target nsps as determined by molecular dynamics. Several top-binding compounds were computationally druggable, showed good gastrointestinal absorptive property, and were also predicted to be non-toxic. CONCLUSIONS: Twenty anti-HIV RT phytochemicals showed multi-targeting inhibitory potential against SARS-CoV-2 non-structural proteins 3, 5, 10, 12, 13, 15, and 16. Our results highlight the importance of polyhydroxylated aromatic substructures for effective attachment in the binding/catalytic sites of nsps involved in post-translational mechanism pathways. As such with the nsps playing vital roles in viral pathogenesis, our findings provide inspiration for the design and discovery of novel anti-COVID-19 drug prototypes.

The role of radiologic imaging and biopsy in renal tumor ablation.

PURPOSE: The rate of unintentionally discovered renal masses has been increasing along with a parallel increased incidence of renal cell carcinoma both in men and women. Ablation therapy has emerged as an alternative for the treatment of these small renal tumors. Several techniques have been developed for renal tumor ablation with cryoablation (CA) and radiofrequency ablation (RFA) being among the most widely used and studied. The purpose of this article is to review the role of imaging and renal mass biopsy in renal tumor ablation with focus on CA and RFA. METHODS: We performed a PubMed database search from January 2000 to January 2010 using the terms: renal tumor ablation, renal biopsy, indications, imaging, computed tomography (CT) guided, magnetic resonance imaging (MRI) guided and ultrasound (US) guided. CONCLUSION: Nephron-sparing procedures, such as cryoablation and RFA, offer an adequate treatment option for selected patients. Imaging techniques such as ultrasonography, CT and MRI are critical to targeting thermal ablation of renal masses. Intra-operative biopsy prior to treatment is becoming a standard procedure but controversy remains regarding pre-operative biopsy. Additionally, contradictory data exist on the value of post-ablation biopsy.

Uptake, toxicity, and maternal transfer of cadmium in the oribatid soil mite, Oppia nitens: Implication in the risk assessment of cadmium to soil invertebrates.

Cadmium (Cd) is a heavy metal of concern in contaminated sites because of its high toxicity to soil biota and humans. Typically, Cd exposure is thought to be dominated by dissolved Cd in soil pore water and, thus, dermal uptake. In this study, we investigated the uptake, toxicity, and maternal transfer of Cd in a standard soil invertebrate, the oribatid mite (Oppia nitens), which is common to boreal and temperate ecozones. We found total soil Cd predicted Cd uptake in adult and juvenile O. nitens with no significant uptake from pore water by juvenile mites. Cadmium significantly inhibited juvenile production and recruitment as well as reduced adult fecundity. Adult O. nitens maternally transferred 39-52% of their Cd body burden to juveniles (tritonymphs) while the maternally-acquired Cd accounted for 41% of the juvenile internal Cd load. Our results suggest that dermal adsorption of metal ions is not important for O. nitens and that maternal transfer of Cd in soil invertebrates has ecological and toxicological implications for populations of soil invertebrates. Maternal transfer should be incorporated as a criterion in setting environmental soil quality guidelines (SQGE) for cadmium and other non-essential heavy metals.

In vitro prediction of polycyclic aromatic hydrocarbon bioavailability of 14 different incidentally ingested soils in juvenile swine.

Predicting mammalian bioavailability of PAH mixtures from in vitro bioaccessibility results has proven to be an elusive goal. In an attempt to improve in vitro predictions of PAH soil bioavailability we investigated how energetic input influences PAH bioaccessibility by using a high and low energetic shaking method. Co-inertia analysis (COIA), and Structural Equation Modeling (SEM) were also used to examine PAH-PAH interactions during ingestion. PAH bioaccessibility was determined from 14 historically contaminated soils using the fed organic estimation of the human simulation test (FOREhST) with inclusion of a silicone rod as a sorption sink and compared to bioavailability estimates from the juvenile swine model. Shaking method significantly affected PAH bioaccessibility in the FOREhST model, with PAH desorption from the high energy FOREhST almost an order of magnitude greater compared to the low energy FOREhST. PAH-PAH interactions significantly influenced PAH bioavailability and when these interactions were used in a linear model, the model predicted benzo(a)anthracene bioavailability with an slope of 1 and r2 of 0.66 and for benzo(a)pyrene bioavailability has a slope of 1 and r2 of 0.65. Lastly, to confirm the effects as determined by COIA and SEM, we spiked low levels of benzo(a)anthracene into historically contaminated soils, and observed a significant increase in benzo(a)pyrene bioaccessibility. By accounting for PAH interactions, and reducing the energetics of in vitro extractions, we were able to use bioaccessibility to predict bioavailability across 14 historically contaminated soils. Our work suggests that future work on PAH bioavailability and bioaccessibility should focus on the dynamics of how the matrix of PAHs present in the soil interact with mammalian systems. Such interactions should not only include the chemical interactions discussed here but also the interactions of PAH mixtures with mammalian uptake systems.