Changes in estimated glomerular filtration rate over the first year following repeat heart transplant in children and young adults.

BACKGROUND: Renal function is reduced in patients undergoing heart transplant due to hemodynamic compromise, cardiorenal syndrome, and nephrotoxin exposure. No current studies evaluate renal function in retransplants. METHODS: We reviewed all heart transplants at our center from 1995 to 2021 and matched first-time heart transplants with retransplants, based on age at transplant, sex, and race. Estimated glomerular filtration rate (eGFR) was derived from CKiD-U25 calculator using creatinine and measured prior to transplant, 1-week post-transplant, 1-3, 6, and 12 months post-transplant, and recent follow-up. Changes in eGFR were measured within and between patients using a piecewise linear mixed effect model with matching. Exploratory univariate analysis was performed to evaluate pre-transplant risk factors for decreased eGFR. RESULTS: The unmatched cohort included 393 heart transplant recipients, with 47 being retransplants. Thirty-eight patients in both groups with at least 1 year of follow-up underwent matching. Both retransplants and first-time transplants had an initial decline in eGFR. eGFR rebounded to baseline or above baseline at 1-3 months post-transplant, but eGFR in retransplants remained significantly lower. At 1-year post-transplant, the average eGFR was 67.8 ± 4.3 mL/min/1.73 m2 versus 104.7 ± 4.3 mL/min/1.73 m2 (p < .001) in the retransplants and first-time transplants group, respectively. CONCLUSION: This study provides data on anticipated renal trajectory following retransplantation.

Food insecurity during COVID-19 in children with end-stage kidney disease: a pilot study.

BACKGROUND: Food insecurity, an important social determinant of health among children, has become more common during the COVID-19 pandemic. Children with chronic diseases including end-stage kidney disease (ESKD) are at higher risk of food insecurity due to their complex care needs, medication burden, and dietary restrictions. No data exists describing food insecurity prevalence in pediatric ESKD patients during the COVID-19 pandemic. METHODS: Food insecurity was assessed among families of children (age 0-18 years) with ESKD on chronic dialysis at two pediatric academic medical centers. Families were screened in April 2020 using the Hunger Vital Sign, a validated 2-question screening tool. We assessed impact of COVID-19 on food insecurity. We compared serum phosphorus "pre-COVID" (January/February 2020) to "during COVID" (April/May 2020). RESULTS: A total of 29 families enrolled in this study. 62% (18/29) of children with ESKD lived in food insecure households, and of those, 72% (13/18) reported that COVID-19 had worsened their food insecurity status. During the COVID-19 pandemic, food insecure patients experienced greater rise in their serum phosphorus levels (1.1 mg/dL vs. 0 mg/dL, p = 0.03) and decreased likelihood of having adequate phosphorus control (50% vs. 11%, p = 0.03). CONCLUSION: Food insecurity was common among children with ESKD on chronic dialysis during the COVID-19 pandemic. Children with food insecurity had a greater increase in their phosphorus levels during the pandemic than did food secure children. Further exploration into how food resources such as an onsite food pantry impacts food insecurity and phosphorus control in children with ESKD is essential.

Achievement goal profiles and their associations with math achievement, self-efficacy, anxiety and instructional quality: A single and multilevel mixture study.

BACKGROUND: There is growing interest in studying the co-occurrence of multiple achievement goals and how different goal profiles relate to educational outcomes. Further, contextual aspects of the classroom have been known to influence the goals students pursue but existing studies remain confined within certain traditions and confounded by methods not well suited for studying classroom climate effects. AIMS: This study sought to investigate achievement goal profiles in mathematics and their associations with background covariates (i.e., gender, prior achievement) and correlates at the student-level (i.e., achievement, self-efficacy, anxiety) and class-level (instructional quality dimensions of classroom management, supportive climate, instructional clarity and cognitive activation). SAMPLE: Participants were 3836 Secondary-3 (Grade-9) students from 118 mathematics classes in Singapore. METHODS: Achievement goal profiles and their relationships with covariates and student-level correlates were examined with updated procedures of latent profile analysis. Subsequently, multilevel mixture analysis assessed the associations of student-level goal profiles and different class-level dimensions of instructional quality. RESULTS: Four profiles were identified: Average-All, Low-All, High-All and High-Approach. These profiles differed across covariates and correlates, with High-Approach students associated with positive outcomes and High-All students with math anxiety. Cognitive activation and instructional clarity predicted stronger membership in High-Approach profile than Average-All and Low-All, but not High-All. CONCLUSION: Certain goal profile patterns were consistent with past studies and supported the fundamental separation of approach and avoidance goals. Less differentiating profiles were associated with undesirable educational outcomes. Instructional quality can be considered as an alternative framework for examining classroom climate effects of achievement goals.

Multidimensional profiles of parent involvement: Antecedents and impact on student engagement.

BACKGROUND: Parent involvement in school is a consistent predictor of educational success. However, research has been inconsistent in addressing how parent involvement ought to be defined and measured, which has led to varied findings across schools and educational systems. AIMS: Attending to the multidimensionality of the construct, this study adopted a person-centred approach to identify subpopulations of school-based parent involvement. Subsequently, profile differences were investigated in relation to student engagement and three antecedent variables (gender, socio-economic status, and authoritative parenting). SAMPLE: Data were obtained from primary (10-year old; N = 4,284) and secondary (14-year old; N = 3,346) school students in Singapore. METHODS: Latent profile analysis was conducted on student-rated surveys of multiple parent involvement behaviours in school and their perceptions. Subsequently, the manual BCH method was employed to concurrently model covariates and outcomes on the latent profile model. Pairwise comparisons between profiles were examined for statistical significance. RESULTS: Consistent across both cohorts, four distinct profiles emerged that revealed high, moderate, selective, and low parent involvement patterns. High parent involvement reflected high ratings across multiple activities, combined with positive perceptions of parental involvement. These profiles differed significantly in terms of their antecedent characteristics, particularly, authoritative parenting, and in relation to their impact on student engagement. CONCLUSION: Results from this study clarify relations between multi-faceted dimensions of parent involvement in school. Additionally, there is a case for continued school-family partnerships among secondary students as students remain academically engaged when parents are involved in school and students relate positively to their involvement.

Disruptive Behaviors and Intellectual Disability: Creating a New Script.

Background: Terms currently used to describe the so-called challenging and disruptive behaviors (CBDs) of children with intellectual disabilities (ID) have different connotations depending on guiding contextual frameworks, such as academic and cultural settings in which they are used. A non-judgmental approach, which does not attempt to establish existing categorical diagnoses, but which describes in a neutral way, is missing in the literature. Therefore, we tried to describe CDBs in youth with ID in an explorative study. Methods: Interviews with families investigated the CDBs of five youth with Down syndrome. At home, families tracked youth's sleep/wake behaviors and physical activity. Youth were observed in a summer school classroom. The collected information and suggested explanatory models for observed CDBs were reviewed with the families. Results: We grouped CDBs as challenging, if they were considered to be reactive or triggered, or unspecified, if no such explanatory model was available. A third category was created for light-hearted CDBs: goofy, acknowledging the right to laugh together with peers. We found some relationships between sleep, physical activity, and CDBs and developed an explorative approach, supporting a child-centered perspective on CDBs. Conclusion: The controversial discussions on terminology and management of CDBs in the literature demonstrate the need for a non-judgmental approach. Such an explorative approach, allowing non-professionals to not label, has been missing. The fact that, up to now, the light-hearted behaviors of an individual with ID have not been integrated in commonly-used behavioral checklists as their natural right, proves our concept and indicates that a paradigm change from judgment-based to exploratory-driven approaches is needed.

Hypocomplementemic Atypical IgA Vasculitis: A Case Report.

IgA vasculitis (IgAV, also known as Henoch-Schönlein purpura or HSP) is a vasculitis of small vessels involving multiple organs, particularly of the joints, gastrointestinal tract, skin, and kidneys. Growing laboratory evidence has shown that complement plays a key role in the pathogenesis of IgAV, although direct evidence of this association in patients is lacking. We report a child with IgAV associated with clinical features of hypertension, nephrotic range proteinuria, acute kidney injury, and low serum C3, with histopathologic findings on renal biopsy of membranoproliferative glomerulonephritis with C3 and IgA co-dominance, and extensive complement derangements. This case report suggests that complement modifies the pathogenesis of IgAV, and further investigation into complement-targeted therapy in cases of refractory IgAV may be beneficial.

Food Insecurity During COVID-19 in Children with End-Stage Kidney Disease: A Pilot Study.

Background Food insecurity, an important social determinant of health among children, has become more common during the COVID-19 pandemic. Children with chronic diseases including end-stage kidney disease (ESKD) are at higher risk of food insecurity due to their complex care needs, medication burden, and dietary restrictions. No data exists describing food insecurity prevalence in pediatric ESKD patients during the COVID-19 pandemic. Methods Food insecurity was assessed among families of children (age 0-18 years) with ESKD on chronic dialysis at two pediatric academic medical centers. Families were screened in April 2020 using the Hunger Vital Sign, a validated 2-question screening tool. We assessed impact of COVID-19 on food insecurity. We compared serum phosphorus "pre-COVID" (January/February 2020) to "during COVID" (April/May 2020). Results A total of 29 families enrolled in this study. 62% (18/29) of children with ESKD lived in food insecure households, and of those, 72% (13/18) reported that COVID-19 had worsened their food insecurity status. During the COVID-19 pandemic, food insecure patients experienced greater rise in their serum phosphorus levels ( p =0.03) and decreased likelihood of having adequate phosphorus control ( p =0.03). Conclusion Food insecurity was common among children with ESKD on chronic dialysis during the COVID-19 pandemic. Children with food insecurity had a greater increase in their phosphorus levels during the pandemic than did food secure children. Further exploration into how food resources such as an onsite food pantry impacts food insecurity and phosphorus control in children with ESKD is essential.

Placement on COVID-19 Units Does Not Increase Seroconversion Rate of Pediatric Graduate Medical Residents.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease COVID-19 (coronavirus disease 2019) has presented graduate medical education (GME) training programs with a unique set of challenges. One of the most pressing is how should hospital systems that rely on graduate medical residents provide appropriate care for patients while protecting trainees. This question is of particular concern as healthcare workers are at high risk of SARS-CoV-2 exposure. Objective: This cross-sectional study sought to assess the impact of hospital COVID-19 patient placement on pediatric graduate medical residents by comparing rates of SARS-CoV-2 seroconversion rates of residents who worked on designated COVID-19 teams and those who did not. Methods: Forty-four pediatric and medicine-pediatric residents at Riley Children's Hospital (Indianapolis, IN) were tested for SARS-CoV-2 immunoglobulin M (IgM) and IgG seroconversion in May 2020 using enzyme-linked immunosorbent assays (Abnova catalog no. KA5826), 2 months after the first known COVID-19 case in Indiana. These residents were divided into two groups: those residents who worked on designated COVID-19 teams, and those who did not. Groups were compared using χ2 or Fisher exact test for categorical variables, and continuous variables were compared using Student t testing. Results: Forty-four of 104 eligible residents participated in this study. Despite high rates of seroconversion, there was no difference in the risk of SARS-CoV-2 seroconversion between residents who worked on designated COVID-19 teams (26% or 8/31) and those who did not (31% or 4/13). Eleven of 44 residents (25%) tested positive for SARS-CoV-2 IgG, whereas only 5/44 (11.4%) tested positive for SARS-CoV-2 IgM, without a detectable difference between exposure groups. Conclusion: We did not observe a difference in SARS-CoV-2 seroconversion between different exposure groups. These data are consistent with growing evidence supporting the efficacy of personal protective equipment. Further population-based research on the role of children in transmitting the SARS-CoV-2 virus is needed to allow for a more evidence-based approach toward managing the COVID-19 pandemic.

Fidgety Philip and the Suggested Clinical Immobilization Test: Annotation data for developing a machine learning algorithm.

The cartoon Fidgety Philip, the banner of Western-ADHD diagnosis, depicts a 'restless' child exhibiting hyperactive-behaviors with hyper-arousability and/or hypermotor-restlessness (H-behaviors) during sitting. To overcome the gaps between differential diagnostic considerations and modern computing methodologies, we have developed a non-interpretative, neutral pictogram-guided phenotyping language (PG-PL) for describing body-segment movements during sitting (Journal of Psychiatric Research). To develop the PG-PL, seven research assistants annotated three original Fidgety Philip cartoons. Their annotations were analyzed with descriptive statistics. To review the PG-PL's performance, the same seven research assistants annotated 12 snapshots with free hand annotations, followed by using the PG-PL, each time in randomized sequence and on two separate occasions. After achieving satisfactory inter-observer agreements, the PG-PL annotation software was used for reviewing videos where the same seven research assistants annotated 12 one-minute long video clips. The video clip annotations were finally used to develop a machine learning algorithm for automated movement detection (Journal of Psychiatric Research). These data together demonstrate the value of the PG-PL for manually annotating human movement patterns. Researchers are able to reuse the data and the first version of the machine learning algorithm to further develop and refine the algorithm for differentiating movement patterns.

MyD88 intrinsically regulates CD4 T-cell responses.

Myeloid differentiation factor 88 (MyD88) is an essential adaptor protein in the Toll-like receptor-mediated innate signaling pathway, as well as in interleukin-1 receptor (IL-1R) and IL-18R signaling. The importance of MyD88 in the regulation of innate immunity to microbial pathogens has been well demonstrated. However, its role in regulating acquired immunity to viral pathogens and neuropathogenesis is not entirely clear. In the present study, we examine the role of MyD88 in the CD4(+) T-cell response following lymphocytic choriomeningitis virus (LCMV) infection. We demonstrate that wild-type (WT) mice developed a CD4(+) T-cell-mediated wasting disease after intracranial infection with LCMV. In contrast, MyD88 knockout (KO) mice did not develop wasting disease in response to the same infection. This effect was not the result of MyD88 regulation of IL-1 or IL-18 responses since IL-1R1 KO and IL-18R KO mice were not protected from weight loss. In the absence of MyD88, naïve CD4(+) T cells failed to differentiate to LCMV-specific CD4 T cells. We demonstrated that MyD88 KO antigen-presenting cells are capable of activating WT CD4(+) T cells. Importantly, when MyD88 KO CD4(+) T cells were reconstituted with an MyD88-expressing lentivirus, the rescued CD4(+) T cells were able to respond to LCMV infection and support IgG2a antibody production. Overall, these studies reveal a previously unknown role of MyD88-dependent signaling in CD4(+) T cells in the regulation of the virus-specific CD4(+) T-cell response and in viral infection-induced immunopathology in the central nervous system.

Is Fidgety Philip's ground truth also ours? The creation and application of a machine learning algorithm.

BACKGROUND: Behavioral observations support clinical in-depth phenotyping but phenotyping and pattern recognition are affected by training background. As Attention Deficit Hyperactivity Disorder, Restless Legs syndrome/Willis Ekbom disease and medication induced activation syndromes (including increased irritability and/or akathisia), present with hyperactive-behaviors with hyper-arousability and/or hypermotor-restlessness (H-behaviors), we first developed a non-interpretative, neutral pictogram-guided phenotyping language (PG-PL) for describing body-segment movements during sitting. METHODOLOGY & RESULTS: The PG-PL was applied for annotating 12 1-min sitting-videos (inter-observer agreements >85%->97%) and these manual annotations were used as a ground truth to develop an automated algorithm using OpenPose, which locates skeletal landmarks in 2D video. We evaluated the algorithm's performance against the ground truth by computing the area under the receiver operator curve (>0.79 for the legs, arms, and feet, but 0.65 for the head). While our pixel displacement algorithm performed well for the legs, arms, and feet, it predicted head motion less well, indicating the need for further investigations. CONCLUSION: This first automated analysis algorithm allows to start the discussion about distinct phenotypical characteristics of H-behaviors during structured behavioral observations and may support differential diagnostic considerations via in-depth phenotyping of sitting behaviors and, in consequence, of better treatment concepts.

Small-cell lung carcinoma and acute onset of antiglial nuclear antibody-positive limbic encephalitis.

Limbic encephalitis (LE) can present as a nonspecific manifestation preceding neoplastic disease. Having high clinical suspicion and using newer onconeural antibodies, like antiglial nuclear antibody (AGNA), can lead to an earlier diagnosis. We report a patient with AGNA-positive LE who is later diagnosed and treated for small-cell lung carcinoma.

A comparative study of patients' knowledge about hepatitis C in the United States and in urban and rural China.

BACKGROUND: Hepatitis C (HCV) is the predominant cause of chronic liver disease in the USA and is increasingly recognized as a common cause of liver disease in China. Studies of HCV patients in the US found major gaps in knowledge but little is known about HCV knowledge among patients in China. METHODS: We conducted a survey in three cohorts of HCV patients in Ann Arbor, MI, US, and in Beijing and Hebei, China, between April and November 2012 to compare patient knowledge about HCV in the US and in urban and rural China. RESULTS: A total of 525 patients (US 186; Beijing 186; Hebei 153) were enrolled. Mean ages of the three cohorts ranged from 52-56 years; 63% of US and 47% of Chinese patients were males; 63% of US and 39% of Beijing patients had college or postgraduate education compared to 0.7% in Hebei. More than half of the US and Beijing patients but only 13% of Hebei patients had received HCV treatment. The average HCV knowledge score out of a total of 16 in the US, Beijing, and Hebei was 12.7, 11.7, and 6.4, respectively (p < 0.001). Study site, education, gender, and prior HCV treatment were independent predictors of HCV knowledge. CONCLUSIONS: Knowledge about HCV in the US and Beijing patients was similar and significantly better than in Hebei patients. Our data show that efforts to improve HCV knowledge are necessary for all three cohorts and should be tailored to the education level and health literacy of the patients.

A comparative study of patients' attitudes toward clinical research in the United States and urban and rural China.

As the number of clinical trials conducted in China increases, understanding Chinese attitudes toward clinical research is critical for designing effective and ethical studies. Two survey studies were conducted in 2012 and 2013 to compare patient attitudes toward clinical research and factors affecting research participation in the United States and urban and rural China. We surveyed 525 patients in 2012 (186 US, 186 urban, 153 rural China) and 690 patients in 2013 (412 US, 206 urban, 72 rural China). US patients were more likely to have no concerns regarding research participation than Chinese patients. Most common concerns of US patients were safety, privacy and confidentiality, and time required. Safety was a top concern for many Chinese. Chinese patients, particularly rural Chinese, were more concerned about the likelihood of self-benefit, and receiving free medical care and financial incentive had greater influence on their participation. Being informed of the freedom to choose whether to participate or to leave a study was less important to Chinese patients. Our study provides important insights into Chinese patients' attitudes toward clinical research and the need to educate them about their rights. These findings help in designing cross-cultural clinical studies that maximize enrollment while upholding Western ethical standards.

CD109 represents a novel branch of the alpha2-macroglobulin/complement gene family.

We report here the genomic organization and phylogenic relationships of CD109, a member of the the alpha2-macroglobulin/complement (AMCOM) gene family. CD109 is a GPI-linked glycoprotein expressed on endothelial cells, platelets, activated T-cells, and a wide variety of tumors. We cloned full-length CD109 cDNA from the mammalian U373 cell line by RT-PCR and performed analysis of its corresponding genomic sequence. The CD109 cDNA spans 128 kb of chromosome 6q with its 33 exons constituting approximately 3.3% of the total CD109 genomic sequence. Sequence analysis revealed that CD109 contains specific motifs in its N-terminus, that are highly conserved in all AMCOM members. CD109 also shares motifs with certain other AMCOM members including: (1) a thioester 'GCGEQ" motif, (2) a furin site of four positively charged amino acids, and (3) a double tyrosine near the C-terminus. Based on a phylogenic analysis of human CD109 with other human homologs as well as orthologs from other mammalian species, C. elegans (ZK337.1) and E. coli homologs, we propose CD109 represents a novel and independent branch of the alpha2-macroglobulin/complement gene family (AMCOM) and may be its oldest member.

Pap testing, awareness, and acceptability of a human papillomavirus (HPV) vaccine among Chinese American women.

Little is known about the knowledge and opinions of human papillomavirus (HPV) vaccine among Chinese immigrants, nor the impact of framing HPV as a sexually transmitted infection in this population. A cross-sectional survey was conducted focusing on knowledge and experience with HPV, HPV vaccine, cervical cancer and Pap testing, and attitudes toward HPV vaccine in response to different message frames. Chinese American women were recruited in a community setting (n = 162). Only 19 % had heard of HPV and 38 % had had a Pap test in the last 3 years. Multivariate logistic regression showed that English proficiency was associated with vaccination acceptance and insurance status was associated with HPV awareness; there was no observed correlation with message framing. Chinese American women with limited English proficiency have low HPV awareness. Community-based, culturally appropriate education about cervical cancer and HPV vaccine should be directed toward limited-English proficient Chinese American women.

Discovery of a novel TLR2 signaling inhibitor with anti-viral activity.

Blockade of Toll-like receptor (TLR)-mediated inflammatory responses represents a new approach in the development of anti-inflammation therapeutics. In the present study, we have screened for TLR2-mediated inflammation inhibitors from small molecule compound libraries using a sensitive cell line stably expressing TLR2, CD14, and an NF-kappaB-driven-luciferase reporter gene. Lymphocytic choriomeningitis virus (LCMV) was used as a virus model. This arenavirus activates a TLR2/CD14-dependent NF-kappaB signaling pathway. We have identified 10 potential anti-inflammatory compounds out of 101,306 compounds. We further evaluated 1 of these positive compounds, E567. We demonstrated that compound E567 efficiently inhibits both LCMV and Herpes simplex virus 1 (HSV-1) induced cytokine responses in both human and mouse cell cultures. We also demonstrated that E567 inhibits cytokine responses in the mouse. Remarkably, E567 is also capable of inhibiting LCMV replication in mice. This is a new model for developing drugs for use in treating viral illnesses.

Periprosthetic osteolysis: characterizing the innate immune response to titanium wear-particles.

Osteolysis of bone following total hip replacement is a major clinical problem. Examination of the areas surrounding failed implants has indicated an increase in the bone-resorption-inducing cytokine, interleukin 1ß (IL-1ß). NALP3, a NOD-like receptor protein located in the cytosol of macrophages, signals the cleavage of pro-IL-1ß into its mature, secreted form, IL-1ß. Here we showed that titanium particles stimulate the NALP3 inflammasome. We demonstrated that titanium induces IL-1ß secretion from macrophages. This response depended on the expression of components of the NALP3 inflammasome, including NALP3, ASC, and Caspase-1. We also showed that titanium particles trigger the recruitment of neutrophils and that this acute inflammatory response depends on the expression of the IL-1 receptor and IL-1α/ß. Moreover, administration of the IL-1 receptor antagonist (IL-1Ra) diminished neutrophil recruitment in response to titanium particles. Together, these results suggest that titanium particle-induced acute inflammation is due to activation of the NALP3 inflammasome, which leads to increased IL-1ß secretion and IL-1-associated signaling, including neutrophil recruitment. Efficacy of IL-1Ra treatment introduces the potential for antagonist-based therapies for implant osteolysis.

Cutting Edge: Antibody-mediated TLR7-dependent recognition of viral RNA.

TLR7 recognizes the genome of ssRNA viruses such as Coxsackievirus B. Because TLR7 is expressed in intracellular compartments, viral RNA must be internalized before its recognition by TLR7. In this study, we define plasmacytoid dendritic cells (pDC) as peripheral blood mononuclear immune cells that respond to Coxsackievirus. pDC activation by Coxsackievirus B requires the presence of specific antiviral Abs. We show that Fc receptors mediate the recognition of virus-Ab complexes and that TLR7 is required for human and murine pDC production of cytokines. These data define a pathway by which intracellular TLR7 senses viral RNA and indicate a role for TLRs in association with Abs in sustaining virus-specific responses.

Role of MyD88 in route-dependent susceptibility to vesicular stomatitis virus infection.

TLRs are important components of the innate immune response. The role of the TLR signaling pathway in host defense against a natural viral infection has been largely unexplored. We found that mice lacking MyD88, an essential adaptor protein in TLR signaling pathway, were extremely sensitive to intranasal infection with vesicular stomatitis virus, and this susceptibility was dose dependent. We demonstrated that this increased susceptibility correlates with the impaired production of IFN-alpha and defective induction and maintenance of neutralizing Ab. These studies outline the important role of the TLR signaling pathway in nasal mucosae-respiratory tracts-neuroepithelium environment in the protection against microbial pathogen infections. We believe that these results explain how the route of infection, probably by virtue of activating different cell populations, can lead to entirely different outcomes of infection based on the underlying genetics of the host.