Search

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

IgG 4 -related disease (IgG 4 -RD) is an immune-mediated fibrotic disorder that has been linked to CD4+ cytotoxic T lymphocytes (CD4+CTLs). The effector phenotype of CD4+CTLs and the relevance of both CD8+ cytotoxic T lymphocytes (CD8+CTLs) and apoptotic cell death remain undefined in IgG 4 -RD. We sought to define CD4+CTL heterogeneity, characterize the CD8+CTL response in the blood and in lesions, and determine whether enhanced apoptosis may contribute to the pathogenesis of IgG 4 -RD. Blood analyses were undertaken using flow cytometry, cell sorting, transcriptomic analyses at the population and single-cell levels, and next-generation sequencing for the TCR repertoire. Tissues were interrogated using multicolor immunofluorescence. Results were correlated with clinical data. We establish that among circulating CD4+CTLs in IgG 4 -RD, CD27loCD28loCD57hi cells are the dominant effector subset, exhibit marked clonal expansion, and differentially express genes relevant to cytotoxicity, activation, and enhanced metabolism. We also observed prominent infiltration of granzyme A–expressing CD8+CTLs in disease tissues and clonal expansion in the blood of effector/memory CD8+ T cells with an activated and cytotoxic phenotype. Tissue studies revealed an abundance of cells undergoing apoptotic cell death disproportionately involving nonimmune, nonendothelial cells of mesenchymal origin. Apoptotic cells showed significant upregulation of HLA-DR. CD4+CTLs and CD8+CTLs may induce apoptotic cell death in tissues of patients with IgG 4 -RD with preferential targeting of nonendothelial, nonimmune cells of mesenchymal origin. [ABSTRACT FROM AUTHOR]

Heat Shock Protein 90 (HSP90) is a potential drug target for cancer therapy as it is often dysregulated in several cancers, including lung, breast, pancreatic, and prostate cancers. In cancer, HSP90 fails to maintain the structural and functional integrity of its several client proteins which are involved in the hallmarks of cancer such as cell proliferation, invasion, migration, angiogenesis, and apoptosis. Several small molecule inhibitors of HSP90 have been shown to exhibit anticancer effects in vitro and in vivo animal models. However, a few of them are currently under clinical studies. The status and potential limitations of these inhibitors are discussed here. Studies demonstrate that several noncoding RNAs (ncRNAs) such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) regulate HSP90 and its client proteins to modulate cellular processes to exhibit oncogenic or tumor suppressing properties. Over the last decade, miRNAs and lncRNAs have drawn significant interest from the scientific community as therapeutic agents or targets for clinical applications. Here, we discuss the detailed mechanistic regulation of HSP90 and its client proteins by ncRNAs. Moreover, we highlight the significance of these ncRNAs as potential therapeutic agents/targets, and the challenges associated with ncRNA-based therapies. This article aims to provide a holistic view on HSP90-regulating ncRNAs for the development of novel therapeutic strategies to combat cancer. • Heat Shock Protein 90 • Cancer therapy • Non-coding RNA • Therapeutic RNA [ABSTRACT FROM AUTHOR]

With the dawn of the information age, the number of choices that each person has to make each day has seen an explosive growth. Every minute, users are bombarded with so many different options for everything user do, from buying clothes to watching TV, that one live in a state of constant information overload, feeling stressed out by this imposed free will then be liberated by it. One ways in which user have now become used to mitigating this constant barrage of incessant information is by the usage of Recommender Systems. These systems are software components that use some form of rating provided by a user to generate recommendations for items that they may be interested in. Unfortunately, recommender systems face a major problem called the "Cold – Start problem", which essentially means that a recommender system in an online setting has no information about the user when the user first signs up. Many approaches have been proposed to solve this, but the one this paper shall be taking is to use information from social networks, specifically Twitter, to get this initial information. Implicitly infer user interest with good accuracy is proposed here and this understanding of interests can later be updated by observing user actions as they interact with the system. We leverage the power of the categorical information stored in the Wikipedia database to allow us to assign relative weights to entities that a user follows on Twitter. This proposed approach for creating the rating vector for each user by mining the Twitter account of the users' is evaluated using the RMSE and MAE metrics. [ABSTRACT FROM AUTHOR]

• Reduced nociceptive flexion reflex threshold indicate aberrant spinal nociceptive system in fibromyalgia patients. • Chronicity of the disease and number of tender points may not directly affect the altered spinal nociception in FMS. • The study correlates spinally mediated NFR threshold and clinical symptoms (pain duration and tender points) of FMS. Pain sensitivity is a recognized feature of fibromyalgia syndrome (FMS) but the contribution of spinal nociceptive circuitry to this phenomenon is unknown. Therefore, the objectives were to study the changes in spinal nociception i.e. nociceptive flexion reflex (NFR) in patients with FMS and to investigate correlation if any, between NFR threshold, pain duration and tender points in FMS. One hundred and three patients with FMS and 74 healthy volunteers participated in the study. To record NFR, sural nerve was stimulated in the retro malleolar region and the reflex response was recorded from the short head of biceps femoris muscle. NFR was elicited at significantly lower [21.0(18.0–25.0)V] thresholds in FMS group when compared to healthy subjects [30.0(24.75–35.0)V; p = 0.001] indicating hyperalgesic response to electrocutaneous stimulation in FMS patients. The latency and other parameters of NFR were comparable in both the groups. No significant correlation was found among NFR threshold and pain duration or tender points. On the basis of results of present study, it may be concluded that the functional deficit of the spinal nociceptive system can contribute to hyperalgesia in FMS. This is first study that correlates a marker of central hyper-excitability (NFR threshold) with clinical symptoms (pain duration and tender points) of FMS. [ABSTRACT FROM AUTHOR]

Summary Introduction Voiding cystourethrogram (VCUG) provides a wealth of data on urinary tract function and anatomy, but few standards exist for reporting VCUG findings. Objective We aimed to assess variability in VCUG reports and to test our hypothesis that VCUG reports from pediatric facilities and pediatric radiologists are more complete than those performed at other facilities or by non-pediatric radiologists. Study design We analyzed original VCUG reports from children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial. A 23-item checklist was created and used to evaluate reporting of technical (e.g. catheter size), anatomic (e.g. vesicoureteral reflux (VUR) presence and grade, bladder shape), and functional information (e.g. bladder emptying). Radiologists were classified as pediatric or non-pediatric radiologists. Facilities were categorized as to whether they were a free-standing pediatric hospital (FSPH), a pediatric “hospital within a hospital” (PHWH), a non-pediatric hospital (NPH), or an outpatient radiology facility (ORF). Multivariate linear regression was used to analyze factors associated with the completeness of the VCUG reports (percent of items reported from the 23-item checklist). Results Six-hundred and two VCUGs were performed at 90 institutions. Of those, 76% were read by a pediatric radiologist, and 49% were performed at a FSPH (Table). On average, less than half of the 23 items in our standardized assessment tool were included in VCUG reports (mean 48%, SD 12). The completeness of reports varied by facility type: 51% complete at FSPH (SD 11), 50% at PHWH (SD 10), 36% at NPH (SD 11), and 43% at ORF (SD 8) ( p < 0.0001). In multivariate analysis, VCUG reports generated at NPH or ORF had 8% fewer items included (95% CI 3.0–12.8, p < 0.01), and those generated at PHWH did not differ from those generated at FSPH. Reports read by a non-pediatric radiologist had 6% fewer items included (95% CI 3–9.7; p < 0.01) compared with those read by a pediatric radiologist. Discussion There is substantial underreporting of findings in VCUG reports when assessing a widely represented sample of routine, community-generated reports using an idealized standard. Although VUR was often reported, other crucial anatomic and functional findings of the VCUG were consistently underreported across all facility types. Conclusion Although pediatric radiologist and pediatric hospitals generated more complete VCUG reports compared with those having non-pediatric origins, the differences are small when considering the substantial underreporting of VCUG findings in general. This underscores the opportunities for improvement in reporting of VCUG findings. Table Summary of population and results. Characteristic No. of VCUG reports analyzed 602 Gender of participants Male 49 (8.1%) Female 553 (91.9%) Median age in months at VCUG (IQR) 11 (5,30) VCUG read by a Pediatric radiologist 459 (76.2%) Non-pediatric radiologist 134 (22.3%) VCUG performed at b FSPH 297 (49.3%) PHWH 184 (30.6%) NPF 87 (14.5%) ORF 33 (5.5%) Overall frequency of item being reported (8 items selected from 23 total) Indication from procedure 557 (93) Presence of VUR 601 (99) Grade of VUR 585 (97) Cyclic study 95 (16) Complete bladder emptying 429 (71) Bladder appearance 517 (86) Urethra appearance 447 (74) Delayed images assessing upper tracts 151 (25) FSPH = free-standing pediatric hospital; NPH = non-pediatric hospital; ORF = outpatient radiology facility; PHWH = pediatric ‘hospital within a hospital’; VCUG = voiding cystourethrogram; VUR = vesicoureteral reflex. a Nine reports lacked information to identify the radiologist. b One facility type was unknown. [ABSTRACT FROM AUTHOR]

Summary Introduction Voiding cystourethrography (VCUG) is the modality of choice to diagnose vesicoureteral reflux (VUR). Although grading of VUR is essential for prognosis and clinical decision-making, the inter-observer reliability for grading has been shown to vary substantially. The Randomized Intervention for Children with VesicoUreteral Reflux (RIVUR) trial provides a large cohort of children with VUR to better understand the reliability of VCUG findings. Objective To determine the inter-observer consistency of the grade of VUR and other VCUG findings in a large cohort of children with VUR. Study design The RIVUR trial is a randomized controlled trial of antimicrobial prophylaxis in children with VUR diagnosed after UTI. Each enrollment VCUG was read by a local clinical (i.e. non-reference) radiologist, and independently by two blinded RIVUR reference radiologists. Reference radiologists' disagreements were adjudicated for trial purposes. The grade of VUR and other VCUG findings were extracted from the local clinical radiologist's report. The unit of analysis included individual ureters and individual participants. We compared the three interpretations for grading of VUR and other VCUG findings to determine the inter-observer reliability. Results Six-hundred and two non-reference radiology reports from 90 institutions were reviewed and yielded the grade of VUR for 560 left and 524 right ureters. All three radiologists agreed on VUR grade in only 59% of ureters; two of three agreed on 39% of ureters; and all three disagreed on 2% of ureters ( Table ). Agreement was better (≥92%) for other VCUG findings (e.g. bladder shape “normal”). The non-reference radiologists' grade of VUR differed from the reference radiologists' adjudicated grade by exactly one grade level in 19% of ureters, and by two or more grade levels in 2.2% of ureters. When the participant was the unit of analysis, all three radiologists agreed on the grade of VUR in both ureters in just 43% of cases. Discussion Our study shows considerable and clinically relevant variability in grading VUR by VCUG. This variability was consistent when comparing non-reference to the adjudicated reference radiologists' assessment and the reference radiologists to each other. This study was limited to children with a history of UTI and grade I–IV VUR and may not be generalizable to all children who have a VCUG. Conclusion The considerable inter-observer variability in VUR grading has both research and clinical implications, as study design, risk stratification, and clinical decision-making rely heavily on grades of VUR. Table Study summary Table Characteristic No. of VCUG reports analyzed 602 Gender of participants Male 49 Female 553 Age in months at time of VCUG (median) [IQR] 11 [5,30] No. of ureters analyzed 1081 Reflux grade agreement Between non-reference and each reference radiologist (three-way) All three agree 638/1081 (59%) Two agree, one disagree 417/1081 (39%) All three disagree 27 (2%) Between non-reference and adjudicated reference radiologists' score (two-way) Agree 805 (75%) Disagree 275 (25%) Kappa (95% CI) 0.66 (0.62–0.69) [ABSTRACT FROM AUTHOR]

Background IgG 4 -related disease (IgG 4 -RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions with dense lymphoplasmacytic infiltrates. CD4 + T cells constitute the major inflammatory cell population in IgG 4 -RD lesions. Objective We used an unbiased approach to characterize CD4 + T-cell subsets in patients with IgG 4 -RD based on their clonal expansion and ability to infiltrate affected tissue sites. Methods We used flow cytometry to identify CD4 + effector/memory T cells in a cohort of 101 patients with IgG 4 -RD. These expanded cells were characterized by means of gene expression analysis and flow cytometry. Next-generation sequencing of the T-cell receptor β chain gene was performed on CD4 + SLAMF7 + cytotoxic T lymphocytes (CTLs) and CD4 + GATA3 + T H 2 cells in a subset of patients to identify their clonality. Tissue infiltration by specific T cells was examined by using quantitative multicolor imaging. Results CD4 + effector/memory T cells with a cytolytic phenotype were expanded in patients with IgG 4 -RD. Next-generation sequencing revealed prominent clonal expansions of these CD4 + CTLs but not CD4 + GATA3 + memory T H 2 cells in patients with IgG 4 -RD. The dominant T cells infiltrating a range of inflamed IgG 4 -RD tissue sites were clonally expanded CD4 + CTLs that expressed SLAMF7, granzyme A, IL-1β, and TGF-β1. Clinical remission induced by rituximab-mediated B-cell depletion was associated with a reduction in numbers of disease-associated CD4 + CTLs. Conclusions IgG 4 -RD is prominently linked to clonally expanded IL-1β– and TGF-β1–secreting CD4 + CTLs in both peripheral blood and inflammatory tissue lesions. These active, terminally differentiated, cytokine-secreting effector CD4 + T cells are now linked to a human disease characterized by chronic inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Background IgG 4 -related disease (IgG 4 -RD) is a poorly understood, multiorgan, chronic inflammatory disease characterized by tumefactive lesions, storiform fibrosis, obliterative phlebitis, and accumulation of IgG 4 -expressing plasma cells at disease sites. Objective The role of B cells and IgG 4 antibodies in IgG 4 -RD pathogenesis is not well defined. We evaluated patients with IgG 4 -RD for activated B cells in both disease lesions and peripheral blood and investigated their role in disease pathogenesis. Methods B-cell populations from the peripheral blood of 84 patients with active IgG 4 -RD were analyzed by using flow cytometry. The repertoire of B-cell populations was analyzed in a subset of patients by using next-generation sequencing. Fourteen of these patients were longitudinally followed for 9 to 15 months after rituximab therapy. Results Numbers of CD19 + CD27 + CD20 − CD38 hi plasmablasts, which are largely IgG4 + , are increased in patients with active IgG 4 -RD. These expanded plasmablasts are oligoclonal and exhibit extensive somatic hypermutation, and their numbers decrease after rituximab-mediated B-cell depletion therapy; this loss correlates with disease remission. A subset of patients relapse after rituximab therapy, and circulating plasmablasts that re-emerge in these subjects are clonally distinct and exhibit enhanced somatic hypermutation. Cloning and expression of immunoglobulin heavy and light chain genes from expanded plasmablasts at the peak of disease reveals that disease-associated IgG 4 antibodies are self-reactive. Conclusions Clonally expanded CD19 + CD27 + CD20 − CD38 hi plasmablasts are a hallmark of active IgG 4 -RD. Enhanced somatic mutation in activated B cells and plasmablasts and emergence of distinct plasmablast clones on relapse indicate that the disease pathogenesis is linked to de novo recruitment of naive B cells into T cell–dependent responses by CD4 + T cells, likely driving a self-reactive disease process. [ABSTRACT FROM AUTHOR]

Objective: The study aimed to examine the prevalence of cardiovascular risk factors in patients with bipolar disorder. Methods: By consecutive sampling, 93 inpatients (aged ≥20 years) diagnosed with bipolar disorder were evaluated for 10 year coronary heart disease (CHD) risk and 10-year cardiovascular mortality risk (CMR) on the Framingham (10-year all CHD events) function/risk equation and Systematic Coronary Risk Evaluation (SCORE) respectively. Results: Ten-year CHD risk was 3.36% and 10-year CMR was estimated to be 1.73%. One tenth (10.7%) of the sample was found to have very high/high CHD risk (≥10) and 6.45% of the sample had high CMR risk (≥5). More than half (54.88%) of patients had metabolic syndrome. Compared to females, males had higher Framingham function score (4.09±5.75 vs 1.59±1.05, U value - 634.5*, p<0.05) and had higher very high/high CHD risk (≥10) (15.1% vs 0, χ² 4.58, p<0.05). Conclusions: Findings of the present study suggest the presence of cardiovascular risk factors and higher rate of metabolic syndrome in patients with bipolar disorder. Considering this fact, there is an urgent need for routine screening for cardiovascular risk factors in these patients. Mental health professionals should be aware of these risks; there is need to develop preventive strategies to reduce the cardiovascular risk in this population. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This study was designed to examine the prevalence of psychiatric morbidity and its psychosocial and psychopathological correlates in patients with pemphigus in comparison to those with psoriasis. Materials and methods: Patients with pemphigus (n =50), group matched for demography, with those with psoriasis (n =30), and healthy controls (n =30), were subjected to cross-sectional assessment for duration, severity, and impact of dermatological disorder, attitude to appearance, social support, coping strategies, disability, quality of life, and psychiatric morbidity and diagnosis. Results: The pemphigus group recorded the psychiatric morbidity rates at 40% by GHQ-12 and 26% by ICD-10; the ICD-10 diagnoses included adjustment disorder (16%), depressive episode (8%), and acute and transient psychosis (2%). This comorbidity was not very different from that of the psoriasis group at 46.7% by GHQ-12 and 36.7% by ICD-10; the ICD-10 diagnoses including adjustment disorder (13.3%), depressive episode (10.0%), alcohol dependence (6.6%), paranoid schizophrenia (3.3%), and delusional disorder plus severe depressive episode with psychotic symptoms (3.3%). The pemphigus group scored higher on disability, despite the dermatological severity and psychosocial profile being similar. Dermatological severity, psychopathology, and certain psychosocial variables were correlated in the pemphigus group, as also in the psoriasis group. Conclusions: The high psychiatric and psychosocial morbidity in pemphigus and other chronic and severe dermatologic disorders indicates a need for more studies on the psychosocial aspect of these disorders and for sensitization by the dealing physicians with this aspect. [Copyright &y& Elsevier]

Abstract: Aim: To study relationship between the cognitive and the non-cognitive symptoms of delirium. Methods: Eighty-four patients referred to psychiatry liaison services and met DSM-IVTR criteria of delirium were assessed using the Delirium Rating Scale Revised-1998 (DRSR-98) and Cognitive Test for Delirium (CTD). Results: The mean DRS-R-98 severity score was 17.19 and DRS-R-98 total score was 23.36. The mean total score on CTD was 11.75. The mean scores on CTD were highest for comprehension (3.47) and lowest for vigilance (1.71). Poor attention was associated with significantly higher motor retardation and higher DRS-R-98 severity scores minus the attention scores. There were no significant differences between those with and without poor attention. Higher attention deficits were associated with higher dysfunction on all other domains of cognition on CTD. There was significant correlation between cognitive functions as assessed on CTD and total DRS-R-98 score, DRS-R-98 severity score and DRS-R-98 severity score without the attention item score. However, few correlations emerged between CTD domains and CTD total scores with cognitive symptom total score of DRS-R-98 (items 9–13) and non-cognitive symptom total score of DRS-R-98 (items 1–8). Conclusions: Our study suggests that in delirium, cognitive deficits are quite prevalent and correlate with overall severity of delirium. Attention deficit is a core symptom of delirium. [Copyright &y& Elsevier]

Abstract: Aim: The current study was designed to study seroprevalence of anti-hepatitis C virus (anti-HCV) antibody in injecting drug users (IDUs) and non-injecting drug users (non-IDUs) with or without other HCV-related risk behaviour. Materials and methods: Serum of male inpatients of the three groups in a tertiary-care hospital in north India was screened for anti-HCV antibody by enzyme-linked immunosorbent assay (ELISA) for two years. The presence of risk behaviours or risk exposure (sharing needle or other drug-related paraphernalia, multiple sex partners, unprotected sex with commercial sex workers/strangers, and blood transfusion) was assessed with the risk questionnaire. Results: One-hundred and three IDUs (n =103), non-IDUs with other HCV-related risk (n =124) and non-IDUs without other HCV-related risk (n =245) were screened (mean age 31.2 (SD=7.92), 32.6 (SD=9.98) and 36.9 (SD=10.63) years, respectively). Almost 46% of the IDUs, 8.1% among the non-IDUs with HCV-related risk and 3.7% among the non-IDUs without HCV-related risk were seropositive for anti-HCV antibody (p <0.001). A majority of the IDUs have been actively using the drugs (76.7%) for a mean duration of 60.9months (SD=57.05) and a majority used injection buprenorphine in combination with promethazine and/or diazepam (70.9%). Other HCV-related risk behaviours were significantly more common among non-IDUs with other HCV-related risk behaviour. Conclusion: Seroprevalence of anti-HCV antibody is high in IDUs compared to non-IDUs, and it is primarily related to injecting risk behaviour. [Copyright &y& Elsevier]

Abstract: The relationship between substance use and psychotic disorder has been complex. Alcohol, cannabis, amphetamines, hallucinogens, and phencyclidine have been implicated as a causative factor for psychotic disorders. It is important to differentiate substance induced psychotic disorders (SIPDs) from primary psychotic disorders as management of the two conditions is different. There is paucity of research in the area of SIPD particularly from Asia. The present study was a retrospective study and it determines retrospectively the incidence rate and clinical characteristics of the SIPDs over a period of 13 years. The incidence of SIPDs was found to be 1.4% and all the subjects were males. In the present study, only alcohol and cannabis were implicated as causative agents for SIPDs. The most common type of psychosis was schizophrenia like psychosis, being more common in the cannabis group. The other forms of psychosis included delusional type, hallucinatory type and affective psychosis. 20% of the subjects had a change in diagnosis to either schizophrenia or affective psychosis on follow-up. The present study showed that the presentation of SIPDs is similar to the primary psychotic disorder and this has management implication. [Copyright &y& Elsevier]

Abstract: The current management of vesicoureteral reflux (VUR) focuses on the prevention of urinary tract infections (UTI), with curative surgery being limited to those children that fail conservative measures. This is based on the assumption that UTIs are preventable with the use of prophylatic antibiotics, leading to reduction of renal scarring, and the possibility that VUR in children can resolve spontaneously. Methods: Review of the recent literature has demonstrated a growing concern that antibiotic prophylaxis may not lead to prevention of UTIs. Additionally, data indicate that renal scarring may not be preventable with antibiotic prophylaxis or even surgical correction of VUR. An overview of all of the current controversies is presented in this paper. Results: Does antibiotic prophylaxis lead to reduction in UTIs in children with VUR? To address this question, the National Institutes of Health have developed a randomized placebo-controlled study of children with VUR (the RIVUR Study), identified following the development of a UTI. Conclusions: There are far reaching consequences of the results of the RIVUR Study. If antibiotic prophylaxis does not prevent UTI in children with VUR, or lead to reduction in renal scarring, does identification of VUR provide any benefits? Perhaps appropriate treatment of UTI may be all that is necessary for preserving renal function. Final answers will have to wait until the completion of this study. [Copyright &y& Elsevier]

Summary: Urinary tract infection (UTI) is a leading cause of serious bacterial infection in young children. Vesicoureteral reflux (VUR), a common pediatric urologic disorder, is believed to predispose to UTI, and both are associated with renal scarring. The complex interaction of bacterial virulence factors and host defense mechanisms influence renal damage. However, some renal parenchymal abnormalities associated with VUR are noninfectious in origin. Long-term, renal parenchymal injury may be associated with hypertension, pregnancy complications, proteinuria, and renal insufficiency. Optimal management of VUR and UTI is controversial because of the paucity of appropriate randomized controlled trials; there is a need for well-designed studies. The recently launched Randomized Intervention for children with VesicoUreteral Reflux (RIVUR) study hopefully will provide insight into the role of antimicrobial prophylaxis of UTI in children with VUR. [ABSTRACT FROM AUTHOR]

Objective: To evaluate increased kidney echogenicity as a predictor of vesicoureteral reflux (VUR) in young children with first febrile urinary tract infection (UTI).Study Design: We performed a single center retrospective study of hospitalized children with first febrile UTI diagnosed in accordance with the American Academy of Pediatrics guidelines. All patients had kidney bladder ultrasound (KBUS) and voiding cystourethrography. Variables analyzed using χ2 test or Mann-Whitney U test as appropriate. Multivariable logistic regression analysis was performed for the abnormal KBUS findings and OR and 95% CI were calculated.Results: Our cohort included 415 children (830 kidney units) with median age of 5 months (1 month to 5 years) and 80% were female. One hundred thirty-two (31.8%) patients had abnormal KBUS, including increased echogenicity in 45 patients. Overall, 42.2% of patients with increased echogenicity had VUR vs 23.3% with normal ultrasound (P = .013) and 31.1% of patients with increased echogenicity had high-grade III-V VUR vs 8.1% with normal ultrasound (P = .001). In total, 24.3% of kidneys with increased echogenicity had VUR vs 20% with normal ultrasound (P = .246) and 20% of kidneys with increased echogenicity had high-grade III-V VUR vs 9.9%with normal ultrasound (P = .005).Conclusions: These data support adding increased kidney echogenicity to the list of other KBUS findings that are helpful in decision making about a need for voiding cystourethrography in young children with first febrile UTI. [ABSTRACT FROM AUTHOR]

Summary: Cystinuria is an inherited disorder characterized by the impaired reabsorption of cystine in the proximal tubule of the nephron and the gastrointestinal epithelium. The only clinically significant manifestation is recurrent nephrolithiasis secondary to the poor solubility of cystine in urine. Although cystinuria is a relatively common disorder, it accounts for no more than 1% of all urinary tract stones. Thus far, mutations in 2 genes, SLC3A1 and SLC7A9, have been identified as being responsible for most cases of cystinuria by encoding defective subunits of the cystine transporter. With the discovery of mutated genes, the classification of patients with cystinuria has been changed from one based on phenotypes (I, II, III) to one based on the affected genes (I and non–type I; or A and B). Most often this classification can be used without gene sequencing by determining whether the affected individual’s parents have abnormal urinary cystine excretion. Clinically, insoluble cystine precipitates into hexagonal crystals that can coalesce into larger, recurrent calculi. Prevention of stone formation is the primary goal of management and includes hydration, dietary restriction of salt and animal protein, urinary alkalinization, and cystine-binding thiol drugs. [ABSTRACT FROM AUTHOR]

• We describe a telemedicine-assisted synchronous, stepwise, direct-care healthcare model for substance use disorders. • The preliminary experience has been encouraging. • The major current challenges to service delivery are technical, legal, and ethical issues. Restricted access to healthcare during COVID-19 pandemic warranted an urgent adaptation of telemedicine practice. We describe a synchronous, stepwise (telephonic, video, and in-person consultation) direct-care model. From 18th May to 31st August 2020, 128 new and 198 follow-up patients received consultation. Eighty-nine percent of new patients required video-consultation. Sixty-eight percent of follow-up cases were managed by telephonic consultation. A third of new and a fifth of the follow-up patients had to be called for physical consultation. Limited access to and understanding of the technologies, potential breach in privacy, and restrictions imposed on online prescription of medications posed significant challenges. [ABSTRACT FROM AUTHOR]

IgG 4 -related disease (IgG 4 -RD) is a fibroinflammatory condition marked by rapid clinical improvement after selective depletion of B lymphocytes with rituximab. This feature suggests that B cells might participate in fibrogenesis and wound healing. In the present work we aimed to demonstrate that B lymphocytes contribute directly to tissue fibrosis in patients with IgG 4 -RD. Total circulating CD19+ B lymphocytes, naive B cells, memory B cells, or plasmablasts from patients with IgG 4 -RD were cultivated with human fibroblasts. Profibrotic soluble factors and collagen production in cocultures were assessed by using ELISAs and Luminex assays. RNA sequencing and quantitative RT-PCR were used to assess fibroblast activation in the presence of B cells, as well as induction of profibrotic pathways in B-cell subsets. Relevant profibrotic and inflammatory molecules were confirmed in vitro by using functional experiments and on IgG 4 -RD tissue sections by using multicolor immunofluorescence studies. B cells from patients with IgG 4 -RD (1) produced the profibrotic molecule platelet-derived growth factor B and stimulated collagen production by fibroblasts; (2) expressed enzymes implicated in extracellular matrix remodeling, such as lysyl oxidase homolog 2; (3) produced the chemotactic factors CCL4, CCL5, and CCL11; and (4) induced production of these same chemokines by activated fibroblasts. Plasmablasts expressed sets of genes implicated in fibroblast activation and proliferation and therefore represent cells with intrinsic profibrotic properties. We have demonstrated that B cells contribute directly to tissue fibrosis in patients with IgG 4 -RD. These unanticipated profibrotic properties of B lymphocytes, particularly plasmablasts, might be relevant for fibrogenesis in patients with other fibroinflammatory disorders and for wound-healing processes in physiologic conditions. [ABSTRACT FROM AUTHOR]

Background The antigenic trigger that drives expansion of circulating plasmablasts and CD4+ cytotoxic T cells in patients with IgG 4 -related disease (IgG 4 -RD) is presently unknown. Objective We sought to sequence immunoglobulin genes from single-cell clones of dominantly expanded plasmablasts and generate recombinant human mAbs to identify relevant antigens in patients with IgG 4 -RD by using mass spectrometry. Methods Paired heavy and light chain cDNAs from dominant plasmablast clones were expressed as mAbs and used to purify antigens by using immunoaffinity chromatography. Affinity-purified antigens were identified by using mass spectrometry and validated by means of ELISA. Plasma levels of the antigen of interest were also determined by using ELISA. Results mAbs expressed from the 2 dominant plasmablast clones of a patient with multiorgan IgG 4 -RD stained human pancreatic tissue sections. Galectin-3 was identified as the antigen specifically recognized by both mAbs. Anti–galectin-3 autoantibody responses were predominantly of the IgG 4 isotype (28% of the IgG 4 -RD cohort, P =.0001) and IgE isotype (11% of the IgG 4 -RD cohort, P =.009). No significant responses were seen from the IgG 1 , IgG 2 , or IgG 3 isotypes. IgG 4 anti–galectin-3 autoantibodies correlated with increased plasma galectin-3 levels (P =.001), lymphadenopathy (P =.04), total IgG level increase (P =.05), and IgG 4 level increase (P =.03). Conclusion Affinity chromatography using patient-derived mAbs identifies relevant autoantigens in patients with IgG 4 -RD. IgG 4 galectin-3 autoantibodies are present in a subset of patients with IgG 4 -RD and correlate with galectin-3 plasma levels. The marked increases in levels of circulating IgG 4 and IgE observed clinically are, at least in part, caused by the development of IgG 4 - and IgE-specific autoantibody responses. [ABSTRACT FROM AUTHOR]

Objective: To evaluate and characterize the degree of blood pressure (BP) control in children on chronic dialysis and to identify significant predictors of hypertension and BP control in these patients. Study design: Linear and logistic regression models were used to examine trends in BP and BP control in a cross-sectional sample of patients on chronic dialysis aged 1-21 years enrolled in the North American Pediatric Renal Trials and Collaborative Studies registry from 1992-2008. Results: At 6 months after dialysis initiation, 67.9% of patients had uncontrolled or untreated hypertension, and 57.8% were prescribed antihypertensive medications. More recent year of dialysis initiation was associated with a higher use of antihypertensive medication and lower systolic BP and diastolic BP z scores (P < .001) measured over time from 6 months to 3 years post dialysis initiation. Other factors associated with higher BP included black race, glomerular disease, younger age, hemodialysis (systolic BP only), and antihypertensive use. There were significant differences in BP control by dialysis modality and disease etiology, with patients on hemodialysis or those with glomerular diseases having the highest percentage of uncontrolled hypertension. Conclusions: Despite widespread antihypertensive use, many pediatric patients on dialysis are at risk for untreated or uncontrolled hypertension. Additional efforts are needed to improve management of hypertension in these children. [ABSTRACT FROM AUTHOR]