Polymer Coatings Affect Transport and Remobilization of Colloidal Activated Carbon in Saturated Sand Columns: Implications for In Situ Groundwater Remediation.

Colloidal activated carbon (CAC) is an emerging technology for the in situ remediation of groundwater impacted by per- and polyfluoroalkyl substances (PFAS). In assessing the long-term effectiveness of a CAC barrier, it is crucial to evaluate the potential of emplaced CAC particles to be remobilized and migrate away from the sorptive barrier. We examine the effect of two polymer stabilizers, carboxymethyl cellulose (CMC) and polydiallyldimethylammonium chloride (PolyDM), on CAC deposition and remobilization in saturated sand columns. CMC-modified CAC showed high mobility in a wide ionic strength (IS) range from 0.1 to 100 mM, which is favorable for CAC delivery at a sufficient scale. Interestingly, the mobility of PolyDM-modified CAC was high at low IS (0.1 mM) but greatly reduced at high IS (100 mM). Notably, significant remobilization (release) of deposited CMC-CAC particles occurred upon the introduction of solution with low IS following deposition at high IS. In contrast, PolyDM-CAC did not undergo any remobilization following deposition due to its favorable interactions with the quartz sand. We further elucidated the CAC deposition and remobilization behaviors by analyzing colloid-collector interactions through the application of Derjaguin-Landau-Verwey-Overbeek theory, and the inclusion of a discrete representation of charge heterogeneity on the quartz sand surface. The classical colloid filtration theory was also employed to estimate the travel distance of CAC in saturated columns. Our results underscore the roles of polymer coatings and solution chemistry in CAC transport, providing valuable guidelines for the design of in situ CAC remediation with maximized delivery efficiency and barrier longevity.

Insights into child abuse and neglect: Findings from the Minnesota Longitudinal Study of Risk and Adaptation.

The Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) is a landmark prospective, longitudinal study of human development focused on a sample of mothers experiencing poverty and their firstborn children. Although the MLSRA pioneered a number of important topics in the area of social and emotional development, it began with the more specific goal of examining the antecedents of child maltreatment. From that foundation and for more than 40 years, the study has produced a significant body of research on the origins, sequelae, and measurement of childhood abuse and neglect. The principal objectives of this report are to document the early history of the MLSRA and its contributions to the study of child maltreatment and to review and summarize results from the recently updated childhood abuse and neglect coding of the cohort, with particular emphasis on findings related to adult adjustment. While doing so, we highlight key themes and contributions from Dr Dante Cicchetti's body of research and developmental psychopathology perspective to the MLSRA, a project launched during his tenure as a graduate student at the University of Minnesota.

The natural history of celiac artery aneurysms.

OBJECTIVES: The goal of this study was to document the natural history of celiac artery aneurysms (CAAs). BACKGROUND: Celiac artery aneurysms are rare. Existing literature is skewed towards outcomes after intervention of large, symptomatic aneurysms but the behavior of untreated CAAs is poorly understood. METHODS: This is a single institution, retrospective analysis of patients with CAA diagnosed by CT imaging (2015-2019) identified through an institutional radiology database. Radiologic, demographic, and follow-up data were analyzed. The primary endpoint was the mean growth rate of CAAs. RESULTS: Of the 76 patients included, 86.8% were men with a mean age at presentation of 69.8 years. The mean CAA diameter on index imaging was 15.4 +/- 3.8 mm (range, 7-30 mm). All were classified as true aneurysms and 76.3% were saccular. All patients had clinical follow-up with mean follow-up 31.2 months +/- 21.6 months. No patient developed symptoms or rupture. The mean radiological follow-up among 45 patients was 25.2 +/- 16.8 months. Over this period, 16 CAAs (35.6%) enlarged, while 29 (64.4%) remained stable. One patient (1.3%) underwent intervention for increasing size in the setting of a chronic dissection. On multivariate analysis, age <70 was significantly associated with increased risk of aneurysm growth. CONCLUSIONS: In this institutional review of patients with CAAs, the majority of aneurysms remained stable in size, with no patients developing symptoms or rupture over clinical follow-up. Given the observed benign behavior of these aneurysms, guidelines that suggest conservative management of CAAs less than 2 cm seems appropriate.

Somatic mutations in FAS pathway increase hemophagocytic lymphohistiocytosis risk in T- and/or NK-cell lymphoma patients.

While significant progress has been made in understanding the genetic basis of primary hemophagocytic lymphohistiocytosis (HLH), the pathogenesis of secondary HLH, the more prevalent form, remains unclear. Among the various conditions giving rise to secondary HLH, HLH in lymphoma patients (HLH-L) accounts for a substantial proportion. In this study, we investigated the role of somatic mutations in the pathogenesis of HLH-L in a cohort of patients with T- and/or NK-cell lymphoma. We identified a 3-time higher frequency of mutations in FAS pathway in patients with HLH-L. Patients harbouring these mutations had a 5-time increased HLH-L risk. These mutations were independently associated with inferior outcome. Hence, our study demonstrates the association between somatic mutations in FAS pathway and HLH-L. Further studies are warranted on the mechanistic role of these mutations in HLH-L.

Associations of childhood BMI traits with blood pressure and glycated haemoglobin in 6-9-year-old Samoan children.

INTRODUCTION: Prevalence and risk factors for elevated glycated haemoglobin (HbA1c) and blood pressure (BP) are poorly understood among Pacific children. We examined associations of HbA1c and BP in 6-9 year-olds with body mass index (BMI) at ages 2, 5, and BMI velocity between 2-9 years in Samoa. METHODS: HbA1c (capillary blood) and BP were measured in n = 410 Samoan children who were part of an ongoing cohort study. Multilevel models predicted BMI trajectory characteristics. Generalized linear regressions assessed associations of childhood characteristics and BMI trajectories with HbA1c and BP treated as both continuous and categorical outcomes. Primary caregiver-reported childhood characteristics were used as covariates. RESULTS: Overall, 12.90% (n = 53) of children had high HbA1c (≥5.7%) and 33.17% (n = 136) had elevated BP. BMI at 5-years and BMI velocity were positively associated with high HbA1c prevalence in males. A 1 kg/m2 per year higher velocity was associated with a 1.71 (95% CI: 1.07, 2.75) times higher prevalence of high HbA1c. In females, higher BMI at 5-years and greater BMI velocity were associated with higher BP at 6-9 years (95% CI: 1.12, 1.40, and 1.42, 2.74, respectively). CONCLUSION: Monitoring childhood BMI trajectories may inform cardiometabolic disease screening and prevention efforts in this at-risk population.

Cystic echinococcosis in cattle and sheep caused by Echinococcus granulosus sensu stricto genotypes G1 and G3 in the USA.

BACKGROUND: Endemic domestic dog-ruminant cycles and human cystic echinococcosis caused by Echinococcus granulosus have been sporadically reported in the United States. However, there is a paucity of molecular data describing the genotypes and haplotypes of this important cestode in domestic ruminant hosts. METHODS: Ninety-four cysts from the lungs and/or livers of slaughtered beef cattle (76 samples), dairy cows (five samples) and sheep (13 samples) were collected from abattoirs in four states of the USA. Samples were genotyped at two mitochondrial loci, cox1 and nad5. Sequences were used to determine species, genotypes and haplotypes using median joining networks and Bayesian phylogenetic analyses. Cyst fertility was assessed in hematoxylin and eosin-stained sections. Additionally, previously reported autochthonous E. granulosus infections in the USA in various hosts were mapped. RESULTS: Based on cox1 sequences obtained from 94 cysts, 89 (94.7%) were identified as E. granulosus G1/G3, while five (5.3%) were Taenia hydatigena. Taenia hydatigena were only isolated from sheep. Based on nad5 sequences obtained from 89 hydatid cysts, 96.6% and 3.4% belonged to E. granulosus sensu stricto genotypes G1 and G3 respectively. Two haplotypes were found among E. granulosus cox1 sequences, neither of which was geographically unique. Six haplotypes were found among nad5 sequences in genotype G1, of which five were novel, while one haplotype was found in genotype G3. In the concatenated cox1-nad5 dataset, seven haplotypes were identified, of which six were geographically unique. All cysts from cattle were non-fertile. Four cysts from sheep were fertile. CONCLUSIONS: All genotyped samples belonged to E. granulosus s.s. This is the first study to our knowledge to confirm the presence of genotypes G1 and G3 in domestic cattle and sheep intermediate hosts in the USA and provide data for future diagnostic and epidemiological studies. Sequences have been deposited in GenBank (cox1 sequences: OR398494-OR398496, nad5 sequences: OR400695-OR400702).

Pachychoroid Associated With Acute Retinal Necrosis Secondary to Varicella Zoster Virus.

Purpose: To report a case of pachychoroid associated with acute retinal necrosis secondary to the varicella zoster virus (VZV). Methods: A retrospective review of a single case was performed. Results: The VZV-related acute retinal necrosis with pachychoroid resolved with quiescence of the acute infectious process. Conclusions: Acute retinal necrosis can result in choroidal thickening adjacent to retinitis. Previous reports have described choroidal sparing in these cases.

Inattentional blindness in medicine.

People often fail to notice unexpected stimuli when their attention is directed elsewhere. Most studies of this "inattentional blindness" have been conducted using laboratory tasks with little connection to real-world performance. Medical case reports document examples of missed findings in radiographs and CT images, unintentionally retained guidewires following surgery, and additional conditions being overlooked after making initial diagnoses. These cases suggest that inattentional blindness might contribute to medical errors, but relatively few studies have directly examined inattentional blindness in realistic medical contexts. We review the existing literature, much of which focuses on the use of augmented reality aids or inspection of medical images. Although these studies suggest a role for inattentional blindness in errors, most of the studies do not provide clear evidence that these errors result from inattentional blindness as opposed to other mechanisms. We discuss the design, analysis, and reporting practices that can make the contributions of inattentional blindness unclear, and we describe guidelines for future research in medicine and similar contexts that could provide clearer evidence for the role of inattentional blindness.

A Prospective Multicenter Standard of Care Study of Outpatient Laparoscopic Sleeve Gastrectomy.

A global shift is occurring as hospital procedures move to ambulatory surgical settings. Surgeons have performed outpatient sleeve gastrectomy (SG) in bariatric surgery since 2010. However, prospective trials are needed to ensure its safety before widespread adoption. PURPOSE: The study aimed to present a comprehensive report on the prospective data collection of 30-day outcomes of outpatient primary laparoscopic SG (LSG). This trial seeks to assess whether outpatient LSG is non-inferior to hospital-based surgery in selected patients who meet the outpatient surgery criteria set by the American Society for Metabolic and Bariatric Surgery. MATERIALS AND METHODS: This study is funded by the Society of American Gastrointestinal and Endoscopic Surgeons and has been approved by the Advarra Institutional Review Board (Pro00055990). Cognizant of the necessity for a prospective approach, data collection commenced after patients underwent primary LSG procedures, spanning from August 2021 to September 2022, at six medical centers across the USA. Data centralization was facilitated through ArborMetrix. Each center has its own enhanced recovery protocols, and no attempt was made to standardize the protocols. RESULTS: The analysis included 365 patients with a mean preoperative BMI of 43.7 ± 5.7 kg/m2. Rates for 30-day complications, reoperations, readmissions, emergency department visits, and urgent care visits were low: 1.6%, .5%, .2%, .2%, and 0%, respectively. Two patients (0.5%) experienced grade IIIb complications. There were no mortalities or leaks reported. CONCLUSION: The prospective cohort study suggests that same-day discharge following LSG seems safe in highly selected patients at experienced US centers.

COSMIC-dFBA: A novel multi-scale hybrid framework for bioprocess modeling.

Metabolism governs cell performance in biomanufacturing, as it fuels growth and productivity. However, even in well-controlled culture systems, metabolism is dynamic, with shifting objectives and resources, thus limiting the predictive capability of mechanistic models for process design and optimization. Here, we present Cellular Objectives and State Modulation In bioreaCtors (COSMIC)-dFBA, a hybrid multi-scale modeling paradigm that accurately predicts cell density, antibody titer, and bioreactor metabolite concentration profiles. Using machine-learning, COSMIC-dFBA decomposes the instantaneous metabolite uptake and secretion rates in a bioreactor into weighted contributions from each cell state (growth or antibody-producing state) and integrates these with a genome-scale metabolic model. A major strength of COSMIC-dFBA is that it can be parameterized with only metabolite concentrations from spent media, although constraining the metabolic model with other omics data can further improve its capabilities. Using COSMIC-dFBA, we can predict the final cell density and antibody titer to within 10% of the measured data, and compared to a standard dFBA model, we found the framework showed a 90% and 72% improvement in cell density and antibody titer prediction, respectively. Thus, we demonstrate our hybrid modeling framework effectively captures cellular metabolism and expands the applicability of dFBA to model the dynamic conditions in a bioreactor.

Short-term outcomes of endovascular management of acute limb ischemia using aspiration mechanical thrombectomy.

OBJECTIVE: Management of acute limb ischemia (ALI) has seen greater utilization of catheter-based interventions over the last two decades. Data on their efficacy is largely based on comparisons of catheter-directed thrombolysis (CDT) and open thrombectomy. During this time, many adjuncts to CDT have emerged with different mechanisms of action, including pharmacomechanical thrombolysis (PMT) and aspiration mechanical thrombectomy (AMT). However, the safety and efficacy of newer adjuncts like AMT have not been well established. This study is a retrospective analysis of the contemporary management of ALI comparing patients treated with aspiration mechanical thrombectomy to patients treated with the more established CDT adjunct, pharmacomechanical thrombolysis. METHODS: Patients undergoing peripheral endovascular intervention for ALI using an adjunctive device were identified through query of the Vascular Quality Initiative (VQI) Peripheral Vascular Intervention (PVI) module from 2014 to 2019. Patients with a nonviable extremity (Rutherford ALI Stage 3), prior history of ipsilateral major amputation, popliteal aneurysm, procedures that were deemed elective (>72 h from admission), procedures that did not utilize an endovascular adjunctive device, and patients without short-term follow-up were all excluded from analysis. The primary outcome was a composite outcome of freedom from major amputation and/or death in the perioperative time period. RESULTS: We identified 528 patients with Rutherford ALI Stage 1 or 2 who were treated with an endovascular adjunct. 433 patients did not undergo aspiration mechanical thrombectomy (no AMT group) and 95 patients did undergo aspiration mechanical thrombectomy (AMT group). The amputation-free survival across all patients was 93.4%. There were significant differences in demographic, comorbidity, and treatment variables between groups (e.g., gender, prior percutaneous coronary intervention (PCI), history of prior peripheral artery disease intervention, and history of prior infra-inguinal PVI), so a propensity score matched analysis was included to account for these group differences. In the propensity score matched analysis, there was no significant difference in major amputation (AMT 7.4% vs no AMT 3.2%, p = 0.13) or death (AMT 95.8% survival vs no AMT 98.4% survival, p = 0.23) with the use of aspiration mechanical thrombectomy. However, there was significantly worse amputation-free survival with the use of aspiration mechanical thrombectomy (AMT 88.4% vs no AMT 95.3%, p = 0.03). On multivariate analysis, prior supra-inguinal bypass (OR 4.85, 1.70-13.84, p = 0.003), Rutherford ALI Stage 2B (OR 3.13, 1.47-6.67, p = 0.003), and aspiration mechanical thrombectomy (OR 2.71, 1.03-7.17, p = 0.05) were associated with the composite outcome. CONCLUSIONS: Short-term amputation-free survival rates of endovascular management of acute limb ischemia are adequate across all modalities. However, aspiration mechanical thrombectomy was associated with significantly worse amputation-free survival compared to other endovascular adjuncts alone (i.e., pharmacomechanical thrombolysis). Severe limb ischemia (Rutherford ALI Stage 2B) and prior supra-inguinal bypass were associated with worse amputation-free survival regardless of the choice of endovascular intervention.

Outcomes and predictors of amputation-free survival in patients undergoing below-knee popliteal-distal bypass.

OBJECTIVE: The infrageniculate popliteal artery is a potential source for inflow in lower extremity bypass surgery in patients with isolated tibial artery disease. The objective of our study was to assess the short- and long-term outcomes of popliteal-distal bypasses using data from the Vascular Quality Initiative (VQI). METHODS: The VQI registry was queried between 2003 and 2021 for patients undergoing surgical revascularizations with the below-knee popliteal artery serving as inflow. Demographics, comorbidities, intraoperative characteristics, and postoperative complications were analyzed. Kaplan-Meier models were used to estimate amputation-free survival, survival, and freedom from amputation. Cox regression analysis was conducted to determine factors associated with major amputation or death. RESULTS: A total of 1884 procedures were analyzed. The mean age of the included patients was 67.7 years. The most frequently observed preoperative comorbidities included insulin-dependent diabetes (52.3%), coronary disease (32.4%), and end-stage renal disease (14.4%). Of all the patients, 670 (35.6%) had a history of ipsilateral endovascular intervention. The procedures were performed for a variety of indications, including tissue loss (84.3%), rest pain (10.9%), and claudication (4.8%). Intraoperatively, the outflow targets were the dorsalis pedis (31.4%), the posterior tibial (24.4%), and the anterior tibial arteries (15.6%). Vein conduit was used in 92.1% of cases. The rate of perioperative myocardial infarction (MI) was 2.4%, and the 30-day mortality was 1.9%. The median length of follow up was 371 days. Amputation-free survival was found to be 85.6% (95% confidence interval [CI], 84.0%-87.2%) at 6 months and 78.6% (95% CI, 76.6%-80.4%) at 12 months. Survival was found to be 93.4% (95% CI, 92.2%-94.5%) at 6 months and 88.6% (95% CI, 87.1%-90.0%) at 12 months. Freedom from amputation was found to be 92.0% (95% CI, 90.7%-93.3%) at 6 months and 89.0% (95% CI, 87.3%-90.4%) at 12 months. Cox regression analysis demonstrated that age greater than 65 years, congestive heart failure, coronary artery disease, and end-stage renal disease were associated with a higher risk of major amputation or death (P < .05). CONCLUSIONS: Below-knee popliteal-distal bypass is a safe and effective approach to treat severe tibial vessel occlusive disease in this challenging patient cohort. Patients exhibited low perioperative complication rates and good amputation-free survival at 1 year.

Choclo virus (CHOV) recovered from deep metatranscriptomics of archived frozen tissues in natural history biorepositories.

BACKGROUND: Hantaviruses are negative-stranded RNA viruses that can sometimes cause severe disease in humans; however, they are maintained in mammalian host populations without causing harm. In Panama, sigmodontine rodents serve as hosts to transmissible hantaviruses. Due to natural and anthropogenic forces, these rodent populations are having increased contact with humans. METHODS: We extracted RNA and performed Illumina deep metatranscriptomic sequencing on Orthohantavirus seropositive museum tissues from rodents. We acquired sequence reads mapping to Choclo virus (CHOV, Orthohantavirus chocloense) from heart and kidney tissue of a two-decade old frozen museum sample from a Costa Rican pygmy rice rat (Oligoryzomys costaricensis) collected in Panama. Reads mapped to the CHOV reference were assembled and then validated by visualization of the mapped reads against the assembly. RESULTS: We recovered a 91% complete consensus sequence from a reference-guided assembly to CHOV with an average of 16X coverage. The S and M segments used in our phylogenetic analyses were nearly complete (98% and 99%, respectively). There were 1,199 ambiguous base calls of which 93% were present in the L segment. Our assembled genome varied 1.1% from the CHOV reference sequence resulting in eight nonsynonymous mutations. Further analysis of all publicly available partial S segment sequences support a clear relationship between CHOV clinical cases and O. costaricensis acquired strains. CONCLUSIONS: Viruses occurring at extremely low abundances can be recovered from deep metatranscriptomics of archival tissues housed in research natural history museum biorepositories. Our efforts resulted in the second CHOV genome publicly available. This genomic data is important for future surveillance and diagnostic tools as well as understanding the evolution and pathogenicity of CHOV.

Treatment of intraorbital arteriovenous fistulas with direct puncture: a case series and review of treatments since 1978.

Intraorbital arteriovenous fistulas (IOAVFs) are rare vascular pathologies that may be effectively treated with direct puncture (DP) of the venous supply and may offer a definitive and safe cure when done under ultrasound or stereotactic guidance. Here we present three new cases of DP treatment of IOAVFs, indications for safe use, and their potential complications in comparison to the existing literature on DP and other modalities.Three patients with IOAVFs were treated with DP with ultrasound guidance, stereotactic guidance, and fluoroscopy. Final digital subtraction angiography (DSA) revealed complete cure of IOAVFs. A literature review via PubMed was performed on treatments of IOAVFs since 1978.All three cases of DP resulted in successful cures with 2/3 cases resulting in complications from orbital hematoma formation. 49 total treatments including the cases herein have been documented. DP treatment constituted 5/49, conservative management 17/49, transarterial 8/49, transvenous 18/49, and surgical 3/49. Some cases received more than one mode of treatment. Transarterial and surgical managements were found to have higher complication rates than transvenous and DP.DP is a safe and effective treatment of IOAVFs that can be performed via multiple image guided methods and guarantees a definitive cure. Orbital hematomas are a potential complication of which operators should be aware.

A Genetic Locus in Elizabethkingia anophelis Associated with Elevated Vancomycin Resistance and Multiple Antibiotic Reduced Susceptibility.

The Gram-negative Elizabethkingia express multiple antibiotic resistance and cause severe opportunistic infections. Vancomycin is commonly used to treat Gram-positive infections and has also been used to treat Elizabethkingia infections, even though Gram-negative organisms possess a vancomycin permeability barrier. Elizabethkingia anophelis appeared relatively vancomycin-susceptible and challenge with this drug led to morphological changes indicating cell lysis. In stark contrast, vancomycin growth challenge revealed that E. anophelis populations refractory to vancomycin emerged. In addition, E. anophelis vancomycin-selected mutants arose at high frequencies and demonstrated elevated vancomycin resistance and reduced susceptibility to other antimicrobials. All mutants possessed a SNP in a gene (vsr1 = vancomycin-susceptibility regulator 1) encoding a PadR family transcriptional regulator located in the putative operon vsr1-ORF551, which is conserved in other Elizabethkingia spp as well. This is the first report linking a padR homologue (vsr1) to antimicrobial resistance in a Gram-negative organism. We provide evidence to support that vsr1 acts as a negative regulator of vsr1-ORF551 and that vsr1-ORF551 upregulation is observed in vancomycin-selected mutants. Vancomycin-selected mutants also demonstrated reduced cell length indicating that cell wall synthesis is affected. ORF551 is a membrane-spanning protein with a small phage shock protein conserved domain. We hypothesize that since vancomycin-resistance is a function of membrane permeability in Gram-negative organisms, it is likely that the antimicrobial resistance mechanism in the vancomycin-selected mutants involves altered drug permeability.

Development of the Circle of Willis Score (COWS) to help guide decision making during acute tandem occlusion treatment: Preliminary analysis.

BACKGROUND: Acute tandem occlusions (TOs) are challenging to treat. Although acute carotid stenting of the proximal lesion is well tolerated, there are certain situations when the practitioner may be wary of acute stenting (bleeding concerns). OBJECTIVE: The purpose of this study was to retrospectively study patients with tandem occlusions who had re-occlusion of the extracranial ICA and develop a Circle of Willis Score (COWS) to help predict which patients could forego acute stenting. METHODS: This is a retrospective review of TO patients with a persistent proximal occlusion following intervention (either expected or unexpected). Pre intervention CTA and intraoperative DSA were reviewed, and each patient was assigned a score 2 (complete COW), 1a (patent A1-Acomm-A1), 1p (patent Pcomm), or 0 (incomplete COW). Findings from the DSA took precedence over the CTA. Two cohorts were created, the complete COW cohort (COWS 2) versus the incomplete COW cohort (COWS 1a,1p, or 0). Angiographic outcomes were assessed using the mTICI score (2b-3) and clinical outcomes were assessed using discharge mRS (good outcome mRS 0-3). RESULTS: Of 68 TO cases, 12 had persistent proximal occlusions. There were 5/12 (42 %) patients in the complete COW cohort, and 7/12 (58 %) in the incomplete COW cohort (5/12 with scores of 1a/1p and 2/12 with a score of 0). In the complete COW cohort, there were 2 ICA-ICA and 3 ICA-MCA occlusions. In the incomplete COW cohort, there was one ICA-ICA occlusion and 6 ICA-MCA occlusions. LKW-puncture was shorter in the complete COW cohort (208 min vs. 464 min, p = 0.16). Successful reperfusion was higher in the complete COW cohort (100 % vs. 71 %). There was a trend toward better clinical outcomes in the complete COW cohort (80 % vs 29 %, p = 0.079). CONCLUSION: The COWS is a simple score that may help predict a successful clinical outcome without proximal revascularization when concerned about performing an acute carotid stent during TO treatment. Evaluation in larger TO cohort is warranted.

Development and Validation of a Mixed-Reality Simulator for Reducing Biopsy Core Deviation During Simulated Freehand Systematic Prostate Biopsy.

INTRODUCTION: We describe the development and validation of a mixed-reality prostate biopsy (PBx) simulator with built-in guidance aids and real-time 3-dimensional visualization. METHODS: We evaluated our simulator during one-on-one training sessions with urology residents and attendings from 2018 to 2022. Participants performed freehand, side-fire, double-sextant transrectal ultrasound-guided systematic prostate biopsy (sPBx). After a baseline assessment (first set of 12 biopsy cores), participants trained for 25 minutes with visualization and cognitive aids activated. Training was followed by an exit set of 12 biopsy cores without visualization or cognitive aids and afterward, subjective assessment by trainees of the simulator. Deviation is the shortest distance of the center of a core from its intended template location. RESULTS: Baseline deviations (mean ± SD) for residents (n = 24) and attendings (n = 4) were 13.4 ± 8.9 mm and 8.5 ± 3.6 mm ( P < 0.001), respectively. Posttraining deviations were 8.7 ± 6.6 mm and 7.6 ± 3.7 mm ( P = 0.271), respectively. Deviations between baseline and exit were decreased significantly for residents ( P < 0.001) but not for attendings ( P = 0.093). Overall feedback from participants was positive. Confidence in performing a PBx increased in novices after training ( P = 0.011) and did not change among attendings ( P = 0.180). CONCLUSIONS: A new PBx simulator can quantify and improve accuracy during simulated freehand sPBx while providing visualization and graphical feedback. Improved simulated sPBx accuracy could lead to more even distribution of biopsy cores within the prostate when performed in clinical settings, possibly reducing the high risk of missing an existing lesion and thus decreasing the time to initiating treatment, if indicated.

Predictors of racial differences in weight loss: the PROPEL trial.

OBJECTIVE: Studies have consistently shown that African American individuals lose less weight in response to behavioral interventions, but the mechanisms leading to this result have been understudied. METHODS: Data were derived from the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) study, which was a cluster-randomized, two-arm trial conducted in primary care clinics. In the PROPEL trial, African American individuals lost less weight compared with patients who belonged to other racial groups after 24 months. In the current study, counterfactual mediation analyses among 445 patients in the intervention arm of PROPEL were used to determine which variables mediated the relationship between race and weight loss. The mediators included treatment engagement, psychosocial, and lifestyle factors. RESULTS: At 6 months, daily weighing mediated 33% (p = 0.008) of the racial differences in weight loss. At 24 months, session attendance and daily weighing mediated 35% (p = 0.027) and 66% (p = 0.005) of the racial differences in weight loss, respectively. None of the psychosocial or lifestyle variables mediated the race-weight loss association. CONCLUSIONS: Strategies specifically targeting engagement, such as improving session attendance and self-weighing behaviors, among African American individuals are needed to support more equitable weight losses over extended time periods.

Sirtuin 2 inhibition modulates chromatin landscapes genome-wide to induce senescence in ATRX-deficient malignant glioma.

BACKGROUND: Functional inactivation of ATRX characterizes large subgroups of malignant gliomas in adults and children. ATRX deficiency in glioma induces widespread chromatin remodeling, driving transcriptional shifts and oncogenic phenotypes. Effective strategies to therapeutically target these broad epigenomic sequelae remain undeveloped. METHODS: We utilized integrated multiomics and the Broad Institute Connectivity Map (CMAP) to identify drug candidates that could potentially revert ATRX-deficient transcriptional changes. We then employed disease-relevant experimental models to evaluate functional phenotypes, coupling these studies with epigenomic profiling to elucidate molecular mechanism(s). RESULTS: CMAP analysis and transcriptional/epigenomic profiling implicated the Class III HDAC Sirtuin2 (SIRT2) as a central mediator of ATRX-deficient cellular phenotypes and a driver of unfavorable prognosis in ATRX-deficient glioma. SIRT2 inhibitors reverted Atrx-deficient transcriptional signatures in murine neuroepithelial progenitor cells (mNPCs), impaired cell migration in Atrx/ATRX-deficient mNPCs and human glioma stem cells (GSCs), and increased expression of senescence markers in glioma models. Moreover, SIRT2 inhibition impaired growth and increased senescence in ATRX-deficient GSCs in vivo. These effects were accompanied by genome-wide shifts in enhancer-associated H3K27ac and H4K16ac marks, with the latter in particular demonstrating compelling transcriptional links to SIRT2-dependent phenotypic reversals. Motif analysis of these data identified the transcription factor KLF16 as a mediator of phenotype reversal in Atrx-deficient cells upon SIRT2 inhibition. CONCLUSIONS: Our findings indicate that SIRT2 inhibition selectively targets ATRX-deficient gliomas for senescence through global chromatin remodeling, while demonstrating more broadly a viable approach to combat complex epigenetic rewiring in cancer.

Socioeconomic inequalities in early child development in children aged under 36 months in South Asia: A systematic review.

BACKGROUND: In South Asia, 89 million children under 5 are at risk of not reaching their developmental potential. Household socioeconomic position (SEP) is a determinant of early child development (ECD). However, synthesised evidence for the association between ECD and SEP in young children in South Asia is not available. Therefore, this review synthesises evidence on the relationship of household SEP with ECD in children under 36 months of age in South Asia. METHOD: PubMed, Cochrane Library, MEDLINE and Scopus were systematically searched to identify studies from South Asian countries that reported evidence on the association between SEP and ECD. Search terms included items related to motor, cognitive, language and socioemotional development. Study quality was assessed using the QualSyst tool, with three quality levels (high/medium/low), and a narrative review for each ECD outcome was constructed (PROSPERO registration: CRD42019131533). RESULTS: Twelve of the 950 publications screened met the inclusion criteria (nine from India, two Nepal and one Bangladesh). The majority (n = 10, 83%) reported language development on its own or alongside another ECD outcome. Fewer articles assessed cognitive (n = 6, 50%), motor (n = 7, 58%) or socioemotional development (n = 3, 25%). Higher SEP was associated with better ECD for one third of the associations reported. One ECD outcome (socioemotional development) was negatively associated (with socioeconomic status) based on low quality evidence. Mother's education and family income were the major SEP constructs associated with ECD. One, four and seven studies were rated as having a low, medium and high risk of bias, respectively. CONCLUSION: This review reveals the scarcity of evidence exploring associations between household SEP and ECD in children under 36 months in South Asia, especially outside of India. Enhancing evidence for associations between ECD and SEP is needed for evidence-based policy making to reduce developmental delays associated with a disadvantaged SEP in the South Asian region.