Next Directions in Measurement of the Home Mathematics Environment: An International and Interdisciplinary Perspective.

This article synthesizes findings from an international virtual conference, funded by the National Science Foundation (NSF), focused on the home mathematics environment (HME). In light of inconsistencies and gaps in research investigating relations between the HME and children's outcomes, the purpose of the conference was to discuss actionable steps and considerations for future work. The conference was composed of international researchers with a wide range of expertise and backgrounds. Presentations and discussions during the conference centered broadly on the need to better operationalize and measure the HME as a construct - focusing on issues related to child, family, and community factors, country and cultural factors, and the cognitive and affective characteristics of caregivers and children. Results of the conference and a subsequent writing workshop include a synthesis of core questions and key considerations for the field of research on the HME. Findings highlight the need for the field at large to use multi-method measurement approaches to capture nuances in the HME, and to do so with increased international and interdisciplinary collaboration, open science practices, and communication among scholars.

Low serum IgG4 level: a potential diagnostic biomarker for IgA nephropathy.

BACKGROUND: In contrast to intense investigations of galactose-deficient immunoglobulin A (IgA)1 specific immunoglobulin G (IgG), little is known about the IgG subclasses in IgA nephropathy (IgAN). Low IgG4 levels in IgAN were noticed in our preliminary experiment. We aimed to verify the low IgG4 levels and investigate the related immune mechanism in IgAN. METHODS: A total of 112 healthy controls (HC) and 112 newly diagnosed IgAN patients were enrolled in this study. Patients with idiopathic membranous nephropathy (IMN), minimal change disease (MCD), or lupus nephritis (LN) were selected as disease controls (DC) (n=122). Serum IgG4 and IgG levels were detected by enzyme-linked immunosorbent assay (ELISA). The IgG4+ B, T helper 1 (Th1), and Th2 cells were measured by flow cytometry. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic value of IgG4. RESULTS: Both IgG4 levels and IgG4/IgG in IgAN were lower than HC and DC (all P<0.001). Severe IgAN displayed lower IgG4 levels than mild IgAN (P=0.039). Patients with higher risk of renal progression (>50%) demonstrated lower IgG4 levels than lower-risk (≤15%) patients (P=0.019). The cutoff value of IgG4 in differentiating IgAN from HC and DC was 0.26 mg/mL [sensitivity 98.2%, specificity 82.4%, area under the curve (AUC): 0.941, P<0.0001] and 0.17 mg/mL (sensitivity 90.2%, specificity 85.2%, AUC: 0.937, P<0.0001), respectively. IgG4/IgG displayed similar diagnostic and differential ability. The IgG4+ B/B cells (P<0.0001) and Th2/Th (P=0.042) of IgAN were lower than HC. CONCLUSIONS: Serum IgG4 levels were low in IgAN. Lower IgG4 levels indicated more severe disease conditions and higher risk of renal progression. Low serum IgG4 seemed to be a potential diagnostic biomarker for IgAN. Decreased IgG4+ B cells and Th2 cells may contribute to the low IgG4 levels in IgAN.

Expression of immunoglobulin G in human proximal tubular epithelial cells.

Proximal tubular epithelial cells (PTECs) have innate immune characteristics, and produce proinflammatory factors, chemokines and complement components that drive epithelial­mesenchymal transition (EMT). Our previous studies revealed that human mesangial cells and podocytes were able to synthesize and secrete immunoglobulin (Ig)A and IgG, respectively. The aim of the present study was to evaluate the expression of Igs in PTECs. Firstly, IgG was detected in the cytoplasm, the cell membrane and the lumen of PTECs in the normal renal cortex by immunohistochemistry. Secondly, Igγ gene transcription and V(D)J recombination were detected in single PTECs by nested PCR and Sanger sequencing. Thirdly, Igγ, Igκ and Igλ were clearly detected in an immortalized PTEC line (HK­2) by immunostaining and western blotting, in which RP215 (an antibody that predominantly binds to non­B cell­derived IgG) was used. In addition, Igγ, Igκ and Igλ gene transcripts, conservative V(D)J recombination in the Igγ variable region, recombination activating gene 1/2 and activation­induced cytidine deaminase were all detected in HK­2 cells. These data suggested that PTECs may express IgG in a similar manner to B cells. Furthermore, IgG expression was upregulated by TGF­ß1 and may be involved in EMT.

Spatial Language of Young Children During Block Play in Kindergartens in Urban China.

Spatial language is an important predictor of spatial skills and might be inspired by peer interaction and goal-oriented building behaviors during block play. The present study investigated the frequency, type and level of children's spatial language during block play and their associations with the level of block play by observing 228 young children in classrooms equipped with unit blocks and allowing free play on a daily basis. The findings showed that during block play, young children used more words about spatial locations, deictic terms, dimensions, and shapes and fewer words about spatial features or properties and spatial orientations or transformations. Spatial locations were used most frequently, and young children tended to use vertical location words to represent the corresponding location. Most young children used gestures in conjunction with spatial deictic terms. Among shape words, tetragon words were frequently used, and the representation of spatial shapes showed alternatives, collective tendencies and gender differences. The use of spatial language during the play process had a significant positive correlation with age, the construction structure, and form of block building.

Idiopathic multicentric Castleman disease with Sjögren's syndrome and secondary membranous nephropathy: a case report and review of the literature.

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is an uncommon lymphoproliferative disorder and lacks treatment consensus. Herein, we report a case of iMCD complicated with Sjögren's syndrome (SS) and secondary membranous nephropathy (SMN). CASE PRESENTATION: A 45-year-old female with dry mouth for 3 months and anasarca and proteinuria for 2 months was admitted. She also experienced chest tightness, wheezing, fever, weight loss, moderate proteinuria and hypoalbuminemia. A computed tomography (CT) scan revealed a tissue mass in the thymus area and enlarged multiple lymph nodes. Her symptoms did not improve after resection of the thymus mass. The pathological findings were "reactive hyperplasia of the mediastinal lymph nodes and thymic hyperplasia". Lymph node biopsy findings confirmed iMCD with human herpes virus-8 (HHV-8) negativity. Based on anti-nuclear antibody (ANA) 1:320, anti-SSA and anti-SSB antibody positivity, salivary flow less than 0.1 ml/min and lip biopsy with focal lymphocytic sialadenitis, SS was diagnosed. Kidney biopsy showed secondary membranous nephropathy with endocapillary cell proliferation and infiltration of plasma cells and lymphocytes in the tubulointerstitium. Serum interleukin-6 (IL-6) levels were significantly increased, and therapy with tocilizumab (anti-IL-6 receptor antibody) worked well. The combination of cyclophosphamide (CyS) with methylprednisolone (MP) maintained satisfactory remission. CONCLUSIONS: Our case of iMCD with SS and SMN is rare. There is a need for increased awareness of the disease to avoid unnecessary procedures and misdiagnoses. IL-6 was extremely high, and there was a rapid response to anti-IL-6 receptor agents. The combination of CyS with MP maintained complete remission.

Single-cell RNA sequencing confirms IgG transcription and limited diversity of VHDJH rearrangements in proximal tubular epithelial cells.

Increasing evidence has confirmed that immunoglobulins (Igs) can be expressed in non-B cells. Our previous work demonstrated that mesangial cells and podocytes express IgA and IgG, respectively. The aim of this work was to reveal whether proximal tubular epithelial cells (PTECs) express Igs. High-throughput single-cell RNA sequencing (scRNA-seq) detected Igs in a small number of PTECs, and then we combined nested PCR with Sanger sequencing to detect the transcripts and characterize the repertoires of Igs in PTECs. We sorted PTECs from the normal renal cortex of two patients with renal cancer by FACS and further confirmed their identify by LRP2 gene expression. Only the transcripts of the IgG heavy chain were successfully amplified in 91/111 single PTECs. We cloned and sequenced 469 VHDJH transcripts from 91 single PTECs and found that PTEC-derived IgG exhibited classic VHDJH rearrangements with nucleotide additions at the junctions and somatic hypermutations. Compared with B cell-derived IgG, PTEC-derived IgG displayed less diversity of VHDJH rearrangements, predominant VH1-24/DH2-15/JH4 sequences, biased VH1 usage, centralized VH gene segment location at the 3' end of the genome and non-Gaussian distribution of the CDR3 length. These results demonstrate that PTECs can express a distinct IgG repertoire that may have implications for their role in the renal tubular epithelial-mesenchymal transition.

[Expression and role of soluble epoxide hydrolase in renal tissue of two kidneys one clip hypertension rats model].

OBJECTIVE: To investigate renal expression of soluble epoxide hydrolase (sEH) in 2-kidney-1-clip rats and explore the role of sEH in renal arterial stenosis hypertensive development. METHODS: Hypertensive models were established in Sprague-Dawly rats by chronic partial occlusion of left renal artery. In the study,16 male Sprague-Dawly rats were randomized into sham operation group and 2-kidney-1-lip (2K1C) group (n=8, each group), and were observed for 40 days. Before operation and every ten days after operation, systolic blood pressure (SBP) was measured and twenty-four-hour urine was collected. At the end of the observation, the blood and kidneys were harvested. The serum Na,24-hour urine protein excretion were measured. Renin activity and angiotensin II concentrition in plasm and renal tissue were evaluated by radioimmunoassay (RIA).The expression of sEH, peroxisome proliferator-activated receptor-γ (PPARγ) in kidneys were assessed by immunohistochemistry and Western blotting. Histology was analysed after kidney sections were stained by Grocott-Gomori methenamine-silver nitrate. RESULTS: After surgery, the systolic blood pressure in 2K1C group gradually became higher than that in sham group. Urine protein excretion was statistically increased in 2K1C group on the 30 th and 40 th days, while serum sodium was of no significant difference from those of the two groups. Renin-angiotensin system in both clipped and nonclipped kidneys were also invoked by the 2K1C surgery. Both sEH and PPARγ were upregulated in renocortex and renomedulla in 2K1C group. The two groups were compared: in SBP,on the 10 th day, (106.70±7.71) vs.(124.04±6.79) mmHg, P<0.001,and on the 40 th day,(107.80±10.01) vs. (150.40±11.76) mmHg, P<0.001; Urine protein excretion,on the 30 th day,(206.81±37.61)vs.(292.33±20.53)mg/d, P=0.005; Serum sodium, (179.76±29.20) vs. (157.72±51.00)mmol/L, P=0.44; Renin activity[plasm(50.00±13.66) vs.(132.90± 31.22)ng/(L×h),P=0.03; clipped kidney(128.40±36.88)vs.(324.90±56.66)ng/(g×h), P=0.01; nonclipped kidney(103.00±19.87)vs.(345.10±42.68)ng/(g×h), P<0.001]; Ang II [plasm(4 810.00±1 164.00)vs. (10 470.00±1 760.00) ng/L,P=0.02, clipped kidney(735.90±154.40)vs.(2 094.00±372.20)ng/g, P=0.005, nonclipped kidney(648.10±217.90)vs.(1 774.00±206.60)ng/g, P=0.002]; the expression of sEH (sEH/ß-actin) in renocortex [clipped kidney (0.33±0.08) vs. (1.73±0.12), P<0.001, nonclipped kidney (0.43±0.09)vs. (0.70± 0.05), P=0.04]; the expression of PPARγ (PPARγ/ß-actin) in renocortex [clipped kidney(0.17±0.05) vs. (0.89±0.11), P=0.002, and nonclipped kidney(0.27±0.07) vs. (0.56±0.07), P=0.04]. Clipped kidney showed more severe glomerulosclerosis and tubular atrophy in 2K1C group than in sham group. CONCLUSION: sEH probably plays an important role in the development of hypertension in the rat models of renovascular hypertension. The activation of PPAR-γ and RAAS by renal arterial stenosis are associated with sEH upregulation, suggesting that they might regulate sEH expression and take part in hypertensive development.