Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases.

MCM10 plays a vital role in genome duplication and is crucial for DNA replication initiation, elongation, and termination. It coordinates several proteins to assemble at the fork, form a functional replisome, trigger origin unwinding, and stabilize the replication bubble. MCM10 overexpression is associated with increased aggressiveness in breast, cervical, and several other cancers. Disruption of MCM10 leads to altered replication timing associated with initiation site gains and losses accompanied by genome instability. Knockdown of MCM10 affects the proliferation and migration of cancer cells, manifested by DNA damage and replication fork arrest, and has recently been shown to be associated with clinical conditions like CNKD and RCM. Loss of MCM10 function is associated with impaired telomerase activity, leading to the accumulation of abnormal replication forks and compromised telomere length. MCM10 interacts with histones, aids in nucleosome assembly, binds BRCA2 to maintain genome integrity during DNA damage, prevents lesion skipping, and inhibits PRIMPOL-mediated repriming. It also interacts with the fork reversal enzyme SMARCAL1 and inhibits fork regression. Additionally, MCM10 undergoes several post-translational modifications and contributes to transcriptional silencing by interacting with the SIR proteins. This review explores the mechanism associated with MCM10's multifaceted role in DNA replication initiation, chromatin organization, transcriptional silencing, replication stress, fork stability, telomere length maintenance, and DNA damage response. Finally, we discuss the role of MCM10 in the early detection of cancer, its prognostic significance, and its potential use in therapeutics for cancer treatment.

Decoding Substrate Selectivity of an Archaeal RlmCD-like Methyltransferase Through Its Salient Traits.

5-Methyluridine (m5U) rRNA modifications frequently occur at U747 and U1939 (Escherichia coli numbering) in domains II and IV of the 23S rRNA in Gram-negative bacteria, with the help of S-adenosyl-l-methionine (SAM)-dependent rRNA methyltransferases (MTases), RlmC and RlmD, respectively. In contrast, Gram-positive bacteria utilize a single SAM-dependent rRNA MTase, RlmCD, to modify both corresponding sites. Notably, certain archaea, specifically within the Thermococcales group, have been found to possess two genes encoding SAM-dependent archaeal (tRNA and rRNA) m5U (Arm5U) MTases. Among these, a tRNA-specific Arm5U MTase (PabTrmU54) has already been characterized. This study focused on the structural and functional characterization of the rRNA-specific Arm5U MTase from the hyperthermophilic archaeon Pyrococcus horikoshii (PhRlmCD). An in-depth structural examination revealed a dynamic hinge movement induced by the replacement of the iron-sulfur cluster with disulfide bonds, obstructing the substrate-binding site. It revealed distinctive characteristics of PhRlmCD, including elongated positively charged loops in the central domain and rotational variations in the TRAM domain, which influence substrate selectivity. Additionally, the results suggested that two potential mini-rRNA fragments interact in a similar manner with PhRlmCD at a positively charged cleft at the interface of domains and facilitate dual MTase activities akin to the protein RlmCD. Altogether, these observations showed that Arm5U MTases originated from horizontal gene transfer events, most likely from Gram-positive bacteria.

Unidirectional Freezing of Polymer Solution Droplets.

Ice templating provides a means of generating textures with a well-defined topography. Recent applications involve the freezing of water droplets, with or without colloids, on flat or textured surfaces. An interesting feature of water droplets freezing on a substrate is the formation of a pointy tip at a constant angle, regardless of the substrate temperature, surface energy, or droplet volume. Here, by adding the polymer to water, we demonstrate how to manipulate and even prevent the formation of such an icy tip. We find that the sharpness of the tip decreases with increasing polymer concentration until completely disappearing above the overlap concentration, while the total freezing time increases concomitantly. Building on these observations, we combined simple geometrical arguments with heat flux measurements to model and connect the spatial and temporal evolution of polymer droplets under unidirectional freezing. Together our results provide new ways to control the shape of frozen droplets for ice templating or microstructure fabrication, with applications in tissue engineering, separation membranes, and soft robotics.

Interventions for preventing haemodialysis dysequilibrium syndrome.

BACKGROUND: Dialysis dysequilibrium syndrome (DDS) refers to neurological symptoms usually seen during or after new initiation or following reinitiation of haemodialysis (HD) after missing multiple sessions. DDS is associated with death and morbidity. We studied interventions aimed at preventing DDS. OBJECTIVES: To evaluate the benefits and harms of different types of interventions for preventing DDS. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 8 May 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any intervention against standard care, including individuals initiated on HD, regardless of age. DATA COLLECTION AND ANALYSIS: Two authors independently determined study eligibility, assessed quality and extracted data. Data were collected on methods, interventions, participants, and outcomes (DDS incidence, severe DDS, death, adverse events). Risk ratios (RR) and confidence intervals (CI) were calculated. Study quality was assessed using the Cochrane Risk of Bias 2 (ROB2) tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included two RCTs, enrolling 32 adult participants. Interventions included were slow dialysis, sodium modelling, standard sodium dialysate, and high sodium dialysate. The risk of bias was of some concern to high risk of bias in both studies. Slow dialysis compared to sodium modelling (1 study, 15 participants) may result in little to no difference in DDS, severe DDS, and death (low certainty evidence) and has uncertain effects on adverse events (RR 1.33, 95% CI 0.15 to 11.64; very low certainty evidence). Standard sodium dialysate compared to high sodium dialysate (1 study, 17 participants) has uncertain effects on the incidence of DDS (RR 0.07, 95% CI 0.00 to 1.12), severe DDS (RR 0.47, 95% CI 0.02 to 10.32), and adverse events (RR 0.29, 95% CI 0.08 to 1.02) (very low certainty evidence). AUTHORS' CONCLUSIONS: In HD patients, sodium modelling, compared to slow dialysis, may result in little to no difference in DDS and death (low certainty evidence) and has uncertain effects on adverse events (very low certainty evidence). The evidence is very uncertain for the effect of high-sodium dialysate and standard sodium dialysate on DDS, death and adverse events (very low certainty evidence).

Effect of chronic kidney disease on adverse drug reactions to anti-tubercular treatment: a retrospective cohort study.

INTRODUCTION: Patients with chronic kidney disease (CKD) are at increased risk of developing tuberculosis (TB). These patients may also be at higher risk of developing antitubercular treatment (ATT)-associated adverse drug reactions (ADRs). Although dose modification has been recommended, data regarding the impact of impaired kidney function on ATT-associated ADRs is sparse. We studied the incidence and profile of ATT-associated ADRs in patients with CKD and compared them with those with normal kidney function. METHODOLOGY: This retrospective study analyzed all patients initiated on ATT from January 2016 to August 2019. Patients were grouped into CKD and normal kidney function based on their eGFR. Data on ATT-associated ADRs were collected from medical records. Predictors of ADRs were assessed using univariable and multivariable logistic regression. Additionally, Propensity score matching and analysis were done for CKD and normal kidney function in 1:3 ratio. RESULTS: Of 1815 patients on ATT, 75 (4.1%) had CKD. ADRs were more frequent [36/75 (48.0%) vs. 239/1740 (13.7%), p ≤ 0.0001] and more severe [15/46 (32.6%) vs. 43/283 (15.1%), p = 0.010] in CKD than those with normal kidney function. The most common ADRs were hepatobiliary [23/75 (30.6%) vs. 156/1740 (8.9%), p ≤ 0.0001], neuropsychiatric [8/75(10.6%) vs. 21/1740(1.2%), p ≤ 0.0001], renal [4/75(5.3%) vs. 8/1740(0.4%), p = 0.001], and gastrointestinal [5/75(6.6%) vs. 34/1740 (1.9%), p = 0.020]. CKD was an independent predictor for ADRs (OR -4.96, 95% CI: 2.79-8.82; p ≤ 0.0001). The matched cohort showed similar results. CONCLUSION: ATT-associated ADRs were more common and severe in patients with CKD, despite drug dose modifications. Optimal dosing of ATT in CKD needs to be further evaluated.

The 5 Ws of Ambulatory Blood Pressure Monitoring.

Blood pressure (BP) measurement is affected by multiple variables which influence clinical management decisions and patient outcomes. Around 24-hour ambulatory blood pressure monitoring (ABPM) avoids incorrect diagnosis of hypertension (HT), and unnecessary treatment and provides the best prediction of cardiovascular (CV) risk. Clinically important phenotypes of HT such as masked HT (masked HT), white coat HT (white coat HT), and nocturnal HT (nocturnal HT) may be missed by not incorporating ambulatory BP monitoring in practice. However, lack of device availability, operational difficulties, and cost remain barriers to its widespread acceptance in India. In this review, we discuss the when, what, who, why, and where (5Ws) relevant to ABPM measurement.

Tunnelling Dynamics of Kicked Systems: A Route to Tunnelling Control.

The effects of discontinuously time-varying perturbations on the dynamics of a particle moving in harmonic, symmetric double well and symmetric triple well potentials, are investigated both classically and quantum mechanically. The quantum dynamics is followed using the time-dependent Fourier grid Hamiltonian (TDFGH) method while the classical dynamics is analyzed within the framework of classical Hamiltonian mechanics. Depending on the spatial symmetry of the perturbation and the characteristic features of the reversal time τ r ${\left( {\tau _r } \right)}$ , different types of 'phase space' structures are observed in each of the potentials. For symmetric double and triple well potentials, quantum dynamics reveals that complete destruction of tunnelling (CDT) can be achieved in the presence of a time-dependent spatially asymmetric perturbing field that is continuous in time. Any discontinuity in time-variation of the perturbation may induce over the barrier transition. The relevance of these results in the context of (i) tunnelling control and (ii) quantum computing with 3-state or 2-state quantum registers is briefly discussed.

Chronic kidney disease of unknown aetiology: A comprehensive review of a global public health problem.

The term chronic kidney disease of unknown aetiology (CKDu) refers to chronic kidney disease (CKD) in the absence of diabetes, long-standing hypertension, glomerulonephritis, obstructive uropathy or other apparent causes. An increasing number of CKDu cases have been reported from Latin America, Sri Lanka, India and others over the last two decades. These regional nephropathies share the following common attributes: (a) they affect low-to-middle income countries with tropical climates, (b) involve predominantly rural agricultural communities, (c) male predilection, (d) absence of significant proteinuria and hypertension, and (e) chronic tubulointerstitial nephritis on kidney biopsy. The current body of literature suggests that CKDu may be caused by heat stress, agrochemicals, contaminated drinking water or heavy metals; however, considerable regional disparities in CKDu research make it difficult to establish a common causal link. In the absence of a definite aetiology, specific preventive and therapeutic interventions are lacking. Improvement of working conditions of farmers and labourers, provision of safe drinking water and changes in agricultural practices are some of the measures that have been implemented; however, there is lack of data to assess their impact on the incidence and progression of CKDu. There is a need for a concerted global effort to address the current knowledge gaps, and to develop effective and sustainable strategies to tackle this devastating disease.

Kernel Smut and False Smut: The Old-Emerging Diseases of Rice-A Review.

Kernel smut, caused by Tilletia horrida, is a disease characterized by the replacement of rice grains with black sooty masses of teliospores or chlamydospores. Kernel smut differs from rice false smut, caused by Ustilaginoidea virens, in the color of chlamydospores. False smut is characterized by globose, velvety spore balls ranging from orangish yellow to greenish black in color. Both kernel smut and false smut have been persistent but are considered minor diseases in many countries since they were discovered in the late 1870s to the 1980s due to their sporadic outbreaks and limited economic impacts. In recent years, however, kernel smut and false smut have emerged as two of the most economically important diseases in rice, including organic rice, in many countries, especially in the United States. The increased use of susceptible rice cultivars, especially hybrids, excessive use of nitrogen fertilizer, and short crop rotations have resulted in an increase in kernel smut and false smut, causing significant losses in grain yield and quality. In this article, we provide a review of the distribution and economic importance of kernel smut; our current understanding of the taxonomy, biology, and epidemiology of kernel smut; and the genomics of the kernel smut fungus as compared with false smut and its causal agent. We also provide an update on the current management strategies of pathogen exclusion, cultivar resistance, fungicides, biological control, and cultural practices for kernel smut and false smut of rice.

Interventions for dialysis patients with hepatitis C virus (HCV) infection.

BACKGROUND: Hepatitis C virus (HCV) infection is common in chronic kidney disease (CKD) patients on dialysis, causes chronic liver disease, may increase the risk of death, and impacts kidney transplant outcomes. Direct-acting antivirals have replaced interferons because of better efficacy and tolerability. This is an update of a review first published in 2015. OBJECTIVES: We aimed to look at the benefits and harms of interventions for HCV in CKD patients on dialysis: death, disease relapse, treatment response/discontinuation, time to recovery, quality of life (QoL), cost-effectiveness, and adverse events. We aimed to study comparisons of available interventions, compared with placebo, control, with each other and with newer treatments. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 23 February 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE and EMBASE, handsearching conference proceedings, and searching the International Clinical Trials Register Portal (ICTRP) and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, first period of randomised cross-over studies on interventions for HCV in CKD on dialysis were considered. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Three studies were included in this update, therefore 13 studies (997 randomised participants) met our inclusion criteria. Overall, the risk of bias was judged low in seven studies, unclear in four, low to unclear in one, and high in one study. Interventions included standard interferon, pegylated (PEG) interferon, standard or PEG interferon plus ribavirin; direct-acting antivirals, and direct-acting antivirals plus PEG interferon plus ribavirin. Compared to placebo or control, standard interferon may make little or no difference to death (5 studies, 134 participants: RR 0.89, 95% CI 0.06 to 13.23) or relapse (low certainty evidence), probably improves end-of-treatment response (ETR) (5 studies, 132 participants: RR 8.62, 95% CI 3.03 to 24.55; I² = 0%) (moderate certainty evidence), and probably makes little or no difference to sustained virological response (SVR) (4 studies, 98 participants: RR 3.25, 95% CI 0.81 to 13.07; I² = 53%), treatment discontinuation (4 studies, 116 participants: RR 4.59, 95% CI 0.49 to 42.69; I² = 63%), and adverse events (5 studies, 143 participants: RR 3.56, 95% CI 0.98 to 13.01; I² = 25%) (moderate certainty evidence). In low certainty evidence, PEG interferon (1 study, 50 participants) may improve ETR (RR 1.53, 95% CI 1.09 to 2.15) but may make little or no difference to death (RR 0.33, 95% CI 0.01 to 7.81), SVR (RR 2.40, 95% CI 0.99 to 5.81), treatment discontinuation (RR 0.11, 95% CI 0.01 to 1.96), adverse events (RR 0.11, 95% CI 0.01 to 1.96) and relapses (21/38 relapsed) (RR 0.72, 95% CI 0.41 to 1.25) compared to standard interferon. In moderate certainty evidence, high-dose PEG interferon (alpha-2a and alpha-2b) may make little or no difference to death (2 studies, 97 participants: RR 4.30, 95% CI 0.76 to 24.33; I² = 0%), ETR (RR 1.42, 95% CI 0.51 to 3.90; I² = 20%), SVR (RR 1.19, 95% CI 0.68 to 2.07; I² = 0%), treatment discontinuation (RR 1.20, 95% CI 0.63 to 2.28; I² = 0%) or adverse events (RR 1.05, 95% CI 0.61 to 1.83; I² = 27%) compared to low-dose PEG interferon. High-dose PEG interferon may make little or no difference to relapses (1 study, 43 participants: RR 1.11, 95% CI 0.45 to 2.77; low certainty evidence). There were no significant subgroup differences. Standard interferon plus ribavirin may lead to higher treatment discontinuation (1 study, 52 participants: RR 2.97, 95% CI 1.19 to 7.36; low certainty evidence) compared to standard interferon alone.  In low certainty evidence, PEG interferon plus ribavirin (1 study, 377 participants) may improve SVR (RR 1.80, 95% CI 1.46 to 2.21), reduce relapses (RR 0.33, 95% CI 0.23 to 0.48), slightly increase the number with adverse events (RR 1.10, 95% CI 1.01 to 1.19), and may make little or no difference to ETR (RR 1.01, 95% CI 0.94 to 1.09) compared to PEG interferon alone. The evidence is very uncertain about the effect of PEG interferon plus ribavirin on treatment discontinuation (RR 1.71, 95% CI 0.69 to 4.24) compared to PEG interferon alone. One study reported grazoprevir plus elbasvir improved ETR (173 participants: RR 174.99, 95% CI 11.03 to 2775.78; low certainty evidence) compared to placebo. It is uncertain whether telaprevir plus ribavirin (high versus low initial dose) plus PEG interferon for 24 versus 48 weeks (1 study, 35 participants) improves ETR (RR 1.02, 95% CI 0.67 to 1.56) or SVR (RR 1.02, 95% CI 0.67 to 1.56) because the certainty of the evidence is very low.  Data on QoL, cost-effectiveness, cardiovascular outcomes and peritoneal dialysis were not available. AUTHORS' CONCLUSIONS: In dialysis patients with HCV infection grazoprevir plus elbasvir probably improves ETR. There is no difference in ETR or SVR for combinations of telaprevir, ribavirin and PEG interferon given for different durations and doses. Though no longer in use, PEG interferon was more effective than standard interferon for ETR but not SVR. Increasing doses of PEG interferon did not improve responses. The addition of ribavirin to PEG interferon may result in fewer relapses, higher SVR, and higher numbers with adverse events.

Hypertension in Chronic Kidney Disease: An Update on Diagnosis and Management.

Hypertension (HTN) and chronic kidney disease (CKD) are pathophysiologic states that are intimately related, such that long-term HTN can lead to poor kidney function, and renal function decline can lead to worsening blood pressure (BP) control. HTN in CKD is caused by an interplay of factors, including salt and water retention, with extracellular volume expansion, sympathetic nervous system overactivity, renin-angiotensin-aldosterone system activation, and endothelial dysfunction. BP variability in the CKD population is significant, however, and thus requires close monitoring for appropriate management. With accumulating evidence, the diagnosis as well as management of HTN in CKD has been evolving in the last decade. In this comprehensive review based on current evidence and recommendations, we summarize the basics of pathophysiology, BP variability, diagnosis, and management of HTN in CKD with an emphasis on special populations with CKD.

Development and validation of a questionnaire to explore preferences of patients, family caregivers, and kidney care providers on advance care planning in an end-stage kidney disease setting.

OBJECTIVES: To develop and validate an English and Kannada version of the questionnaire to assess awareness and knowledge of advance care planning (ACP) among end-stage kidney disease (ESKD) patients, caregivers, and healthcare providers. METHODS: The questionnaire was developed from the published literature on ACP use in ESKD setting after a literature search. An expert panel consisting of nephrologists, palliative medicine physicians, ESKD patients, and their family caregivers participated in the content validity of the questionnaire using the Delphi process. The study was conducted between August 2021 and July 2022 at a tertiary care hospital in India. A validated questionnaire was administered to eligible 30 ESKD patients, 30 caregivers, and 10 health care professionals. A retest was carried out 1 week after the first administration. RESULTS: The content validity ratio of patient, caregiver, and health care professions questions ranged from 0.6 to 1 and Cronbach's α value was 0.737 to 0.925. The intraclass correlation coefficient values for the test-retest of all three sections of this questionnaire varied from 0.879 to 0.972. SIGNIFICANCE OF RESULTS: The developed questionnaire is a reliable and valid method for assessing the preference and knowledge of ACP in ESKD patients, family caregivers, and kidney care providers both in English and Kannada.

Kannada Translation and Validation of the ESAS-r Renal for Symptom Burden Survey in Patients with End-Stage Kidney Disease.

Objectives: End-stage kidney disease (ESKD) is a life-limiting illness that leads to significant health-related suffering for the patients and their caregivers. Moreover, disease-directed options such as dialysis and renal transplant might not be universally accessible. Inadequate assessment and management of symptoms often lead to diminished quality of life. For evaluating symptoms and their associated distress, various tools have been identified. However, these are not available for the native Kannada-speaking population for assessing ESKD symptom burden. In this study, we determined the reliability and validity of the Edmonton Symptom Assessment System Revised Renal (ESAS-r: Renal) in Kannada-speaking ESKD patients. Materials and Methods: ESAS-r: Renal English version was translated into Kannada using the forward and backward method. The translated version was endorsed by Nephrology, Palliative care, Dialysis technology and Nursing experts. As a pilot study, 12 ESKD patients evaluated the content of the questionnaires for appropriateness and relevance. The ESAS-r: Renal Kannada version was validated by administering this tool to 45 patients twice a fortnight. Result: The translated ESAS-r: Renal Kannada version questionnaire had an acceptable face and content validity. Experts' opinion was assessed by content validity ratio (CVR), and the value of CVR of ESAS-r: Renal Kannada version was-'1'-. Internal consistency of the tool was assessed among Kannada-speaking ESKD patients; its Cronbach's α was 0.785, and test-retest validity was 0.896. Conclusion: The validated Kannada version of ESAS-r: Renal was reliable and valid for assessing symptom burden in ESKD patients.

Preoperative Prostate MRI Predictors of Urinary Continence Following Radical Prostatectomy.

Background Urinary continence after radical prostatectomy (RP) is an important determinant of patient quality of life. Anatomic measures at prostate MRI have been previously associated with continence outcomes, but their predictive ability and interrater agreement are unclear in comprehensive clinical models. Purpose To evaluate the predictive ability and interrater agreement of MRI-based anatomic measurements of post-RP continence when combined with clinical multivariable models. Materials and Methods In this retrospective cohort study, continence outcomes were evaluated in men who underwent RP from August 2015 to October 2019. Preoperative MRI-based anatomic measures were obtained retrospectively by four abdominal radiologists. Before participation, these radiologists completed measure-specific training. Logistic regression models were developed with clinical variables alone, MRI variables alone, and combined variables for predicting continence at 3, 6, and 12 months after RP; some patient data were missing at each time point. Interrater agreement of MRI variables was assessed by using intraclass correlation coefficients (ICCs). Results A total of 586 men were included (mean age ± standard deviation: 63 years ± 7). The proportion of patients with incontinence was 0.2% (one of 589) at baseline, 27% (145 of 529) at 3 months, 14% (63 of 465) at 6 months, and 9% (37 of 425) at 12 months. Longer coronal membranous urethra length (MUL) improved the odds of post-RP continence at all time points (odds ratio per 1 mm: 0.86 [95% CI: 0.80, 0.93], P < .001; 0.86 [95% CI: 0.78, 0.95], P = .003; and 0.79 [95% CI: 0.67, 0.91], P = .002, respectively) in models that incorporated both clinical and MRI predictors. No other MRI variables were predictive. Age and baseline urinary function score were the only other predictive clinical variables at every time point. Interrater agreement was moderate (ICC, 0.62) for MUL among readers with measure-specific prostate MRI training and poor among those without the training (ICC, 0.38). Conclusion Preoperative MRI-measured coronal membranous urethra length was an independent predictor of urinary continence after prostatectomy. © RSNA, 2022 Online supplemental material is available for this article.

Interrater Agreement of Bosniak Classification Version 2019 and Version 2005 for Cystic Renal Masses at CT and MRI.

Background The Bosniak classification system for cystic renal masses was updated in 2019 in part to improve agreement compared with the 2005 version. Purpose To compare and investigate interrater agreement of Bosniak version 2019 and Bosniak version 2005 at CT and MRI. Materials and Methods In this retrospective single-center study, a blinded eight-reader assessment was performed in which 195 renal masses prospectively considered Bosniak IIF-IV (95 at CT, 100 at MRI, from 2006 to 2019 with version 2005) were re-evaluated with Bosniak versions 2019 and 2005. Radiologists (four faculty members, four residents) who were blinded to the initial clinical reading and histopathologic findings assessed all feature components and reported the overall Bosniak class for each system independently. Agreement was assessed with Gwet agreement coefficients. Uni- and multivariable linear regression models were developed to identify predictors of dispersion in the final Bosniak class assignment that could inform system refinement. Results A total of 185 patients were included (mean age, 63 years ± 13 [standard deviation]; 118 men). Overall interrater agreement was similar between Bosniak version 2019 and version 2005 (Gwet agreement coefficient: 0.51 [95% CI: 0.45, 0.57] vs 0.46 [95% CI: 0.42, 0.51]). This was true for experts (0.54 vs 0.49) and novices (0.50 vs 0.47) and at CT (0.56 vs 0.51) and MRI (0.52 vs 0.43). Nine percent of masses prospectively considered cystic using Bosniak version 2005 criteria were considered solid using version 2019 criteria. In general, masses were more commonly classified in lower categories when radiologists used Bosniak version 2019 criteria compared with version 2005 criteria. The sole predictor of dispersion in Bosniak version 2019 class assignment was dispersion in septa or wall quality (ie, smooth vs irregular thickening vs nodule; 72% [MRI] and 60% [CT] overall model variance explained; multivariable P < .001). Conclusion Overall interrater agreement was similar between Bosniak version 2019 and version 2005; disagreements in septa or wall quality were common and strongly predictive of variation in Bosniak class assignment. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Eberhardt in this issue.

Effect of Prostate MRI Interpretation Experience on PPV Using PI-RADS Version 2: A 6-Year Assessment Among Eight Fellowship-Trained Radiologists.

BACKGROUND. Understanding the effect of specific experience in prostate MRI interpretation on diagnostic performance would help inform the minimum interpretation volume to establish proficiency. OBJECTIVE. The purpose of this article is to assess for an association between increasing experience in prostate MRI interpretation and change in radiologist-level PPVs for PI-RADS version 2 (v2) categories 3, 4, and 5. METHODS. This retrospective study included prostate MRI examinations performed between July 1, 2015, and August 13, 2021, that were assigned a PI-RADS v2 category of 3, 4, or 5 and with an MRI-ultrasound fusion biopsy available as the reference standard. All examinations were among the first 100-200 prostate MRI examinations interpreted using PI-RADS v2 by fellowship-trained abdominal radiologists. Radiologists received feedback through a quality assurance program. Radiologists' experience levels were classified using progressive subsets of 50 interpreted examinations. Change with increasing experience in distribution of individual radiologists' whole-gland PPVs for Gleason sum score 7 or greater prostate cancer, stratified by PI-RADS category, was assessed by hierarchic linear mixed models. RESULTS. The study included 1300 prostate MRI examinations in 1037 patients (mean age, 66 ± 7 [SD] years), interpreted by eight radiologists (median, 13 years of postfellow-ship experience; range, 5-22 years). Aggregate PPVs were 20% (68/340) for PI-RADS category 3, 49% (318/652) for category 4, and 71% (220/308) for category 5. Interquartile ranges (IQRs) of PPVs overlapped for category 4 (51%; IQR, 42-60%) and category 5 (70%; IQR, 54-75%) for radiologists' first 50 examinations. IQRs of PPVs did not overlap between categories of greater experience; for example, at the 101-150 examination level, PPV for category 3 was 24% (IQR, 20-29%), category 4 was 55% (IQR, 54-63%), and category 5 was 81% (IQR, 77-82%). Hierarchic modeling showed no change in radiologists' absolute PPV with increasing experience (category 3, p = .27; category 4, p = .71; category 5, p = .38). CONCLUSION. Absolute PPVs at specific PI-RADS categories did not change during radiologists' first 200 included examinations. However, resolution of initial overlap in IQRs indicates improved precision of PPVs after the first 50 examinations. CLINICAL IMPACT. If implementing a minimum training threshold for fellowship-trained abdominal radiologists, 50 prostate MRI examinations may be sufficient in the context of a quality assurance program with feedback.

Lessons Learned from Peer Learning Conference in Cardiothoracic Radiology.

Medical errors may lead to patient harm and may also have a devastating effect on medical providers, who may suffer from guilt and the personal impact of a given error (second victim experience). While it is important to recognize and remedy errors, it should be done in a way that leads to long-standing practice improvement and focuses on systems-level opportunities rather than in a punitive fashion. Traditional peer review systems are score based and have some undesirable attributes. The authors discuss the differences between traditional peer review systems and peer learning approaches and offer practical suggestions for transitioning to peer learning conferences. Peer learning conferences focus on learning opportunities and embrace errors as an opportunity to learn. The authors also discuss various types and sources of errors relevant to the practice of radiology and how discussions in peer learning conferences can lead to widespread system improvement. In the authors' experience, these strategies have resulted in practice improvement not only at a division level in radiology but in a broader multidisciplinary setting as well. The online slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2022.

Gestational age specific anthropometric postnatal percentile charts for neonates born at tertiary hospital in Eastern Nepal.

BACKGROUND AND OBJECTIVES: Birth weight, Head circumference (HC), and Length are important clinical indicators for evaluation of prenatal growth and identification of neonates requiring detail assessment and monitoring. Gestational age-specific percentile charts are essential tool for both obstetricians and pediatricians in their day to day practice. This study aimed to develop gestational age specific percentile chart of Birth weight, Length and HC for neonates. METHODS: In this Cross sectional observational study, HC, Birth weight and Length of live singleton neonates from 28 to 42 weeks of gestation fulfilling the inclusion criteria were measured over a period of one year. Mean, standard deviation, and percentiles values for different gestational age were calculated. Graphs were constructed using two way graph and Lowess smoothening method. RESULTS: Of total 2662 neonates, male: female ratio was 1.3:1 with maximum neonates in 40 weeks of gestation. The mean Birth weight, HC and Length was 2852.02 gm, 33.6 and 48.42 cm respectively. Overall males have more mean weight than females by 46.35gms. However, mean HC of male and female were similar 33.6 and 33.61 cm respectively and on average males were 0.27 cm longer compared to female. The mean Birth weight, HC and Length at 40 weeks was 3123.43gm (± 427.82), 34.249 cm (± 0.87) and 49.61 cm(± 1.85) respectively. The 10th, 50th and 90th percentile at 40 weeks for Birth weight being 2550gm, 3100gm and 3750gm respectively. The gestational age specific percentile chart and growth curve are appropriately placed in the manuscript. CONCLUSIONS: The percentile charts in this study may be used as reference for local population and similar data from various parts of the nation can provide a national reference curve for healthy neonates.

Conserved features of the MlaD domain aid the trafficking of hydrophobic molecules.

In Gram-negative bacteria, the maintenance of lipid asymmetry (Mla) system is involved in the transport of phospholipids between the inner (IM) and outer membrane. The Mla system utilizes a unique IM-associated periplasmic solute-binding protein, MlaD, which possesses a conserved domain, MlaD domain. While proteins carrying the MlaD domain are known to be primarily involved in the trafficking of hydrophobic molecules, not much is known about this domain itself. Thus, in this study, the characterization of the MlaD domain employing bioinformatics analysis is reported. The profiling of the MlaD domain of different architectures reveals the abundance of glycine and hydrophobic residues and the lack of cysteine residues. The domain possesses a conserved N-terminal region and a well-preserved glycine residue that constitutes a consensus motif across different architectures. Phylogenetic analysis shows that the MlaD domain archetypes are evolutionarily closer and marked by the conservation of a functionally crucial pore loop located at the C-terminal region. The study also establishes the critical role of the domain-associated permeases and the driving forces governing the transport of hydrophobic molecules. This sheds sufficient light on the structure-function-evolutionary relationship of MlaD domain. The hexameric interface analysis reveals that the MlaD domain itself is not a sole player in the oligomerization of the proteins. Further, an operonic and interactome map analysis reveals that the Mla and the Mce systems are dependent on the structural homologs of the nuclear transport factor 2 superfamily.

Testing-Related Health Impact of Transrectal and Transperineal Prostate Biopsy as Assessed by Health Utilities.

PURPOSE: We sought to assess the temporary health-related quality of life (health utility) of nonmagnetic resonance imaging-guided transrectal and transperineal prostate biopsy. MATERIALS AND METHODS: This is a 2-arm, prospectively enrolled, observational, patient-reported outcomes study, performed between June 2019 and November 2020 at a single academic medical center. Inclusion criteria were men undergoing an outpatient ultrasound-guided prostate biopsy (transrectal or transperineal approach, without magnetic resonance imaging guidance). Patients with a history of Gleason 7+ prostate cancer were excluded. Validated survey instruments were utilized to assess baseline (Short Form 12) and testing-related (Testing Morbidities Index [TMI]) health utility states. The primary outcome was the TMI summary testing-related quality-of-life score (summary utility score; scale: 0=death and 1=perfect health). The TMI is comprised of 7 domains, spanning before, during and after testing experiences. Each domain is scored from 1 (no health impact) to 5 (extreme health impact). Testing-related quality-of-life measures were compared with Mann-Whitney U test. RESULTS: Enrollment rates were 80% (60/75; transrectal) and 86% (60/70; transperineal). All patients (120/120) completed the questionnaire. The TMI summary score for transrectal biopsy was not significantly different from transperineal biopsy (0.86, 95% CI 0.84-0.88 vs 0.83, 95% CI 0.81-0.85; p=0.0774). The largest difference in the testing experiences was related to intraprocedural pain (transrectal biopsy: 2.3, 95% CI 2.1-2.4; transperineal biopsy: 2.9, 95% CI 2.6-3.1; p <0.001). CONCLUSIONS: Transperineal and transrectal prostate biopsies have similar effect on temporary health-related quality-of-life. Transient differences relate to intraprocedural pain. These data can inform clinical decision making and future cost-utility models.