Altered effects of perspective-taking on functional connectivity during self- and other-referential processing in adults with autism spectrum disorder

In interactive social situations, it is often crucial to be able to take another person’s perspective when evaluating one’s own or another person’s specific trait; individuals with autism spectrum disorder (ASD) critically lack this social skill. To examine how perspective-dependent self- and other-evaluation processes modulate functional connectivity in ASD, we conducted a functional magnetic resonance imaging study in which 26 high-functioning adults with ASD and 24 typically developed (TD) controls were asked to decide whether an adjective describing a personality trait correctly described the participant himself/herself (“self”) or the participant’s mother (“other”) by taking either the first (1P) or third person (3P) perspective. We observed that functional connectivity between the left sensorimotor cortex and the left middle cingulate cortex was enhanced in TD control individuals taking the 3P perspective, this enhancement was significantly reduced in ASD, and the degree of reduction was significantly correlated with the severity of autistic traits. Furthermore, the self-reference effect on functional connectivity between the left inferior frontal cortex and frontopolar cortices was significantly enhanced in TD control individuals taking the 3P perspective, whereas such effect was reversed in ASD. These findings indicate altered effects of perspective on the functional connectivity, which may underlie the deficits in social interaction and communication observed in individuals with ASD.     

Three-dimensional changes in the condyle during development of an asymmetrical mandible in a rat: a microcomputed tomography study.

A rapidly growing postnatal animal model was used to study changes in the calcified tissue of the mandibular condyle during altered muscle function. A maxillary occlusal splint was designed to shift the mandible laterally (left) during closure. Groups of 5 Wistar rats were killed at 5, 9, 15, 21, 30, and 40 weeks (n = 30), with an equal number of controls. The experimental animals developed shorter, asymmetrical mandibles compared with the control animals. The left condyle became larger and thicker than the right condyle. Microcomputed tomography assessment of the left and right condylar trabecular bone indicated that both had less bone volume than the control condyle. The right masseter muscle significantly lost fiber size and type IIA oxidative fibers, suggesting that the right masseter muscle was used with less tension development. In contrast, the left masseter maintained its fiber size and was similar to the control masseter fiber diameters. Comparison in the sequence of changes indicated that the morphologic changes occurred first in the ramus (age, 5 weeks), before the corpus (age, 15 weeks), and before changes in masseter fiber size and composition (age, 9 weeks). This study showed that both the mandible and the condyle modified their shape and size, as well as the trabecular bone of the condyle, during shifting of the mandible to one side as it closed.     

Abnormal lipid metabolism and oxidative stress in hemodialysis patients

Oxidative stress is enhanced in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Bioincompatibility represents an important source of reactive oxygen species. HD patients exhibit altered antioxidative defenses, and antioxidative vitamins such as vitamin E and C are altered in uremia. Frequently, HD patients also suffer from atherosclerotic cardiac disease. We previously reported that low-density lipoprotein (LDL) of HD patients is rich in malondialdehyde (MDA), an end product of lipid peroxidation. MDA-rich LDL is thought to be an atherogenic lipoprotein because of its enhancement of macrophage foam-cell formation. We conducted a controlled study for 2 years comparing the effects of a vitamin E-coated cellulose membrane dialyzer and an ordinary cellulose membrane dialyzer on lipid metabolism and the progress of atherosclerosis. LDL MDA and oxidized LDL (ox-LDL) were measured in HD patients by using these two types of dialyzers. Plasma vitamin E and lipid concentrations were also evaluated. Aortic calcification index (ACI) was evaluated by CT scan to assess the progress of atherosclerosis before and every year after initiation of the treatment. The use of a vitamin E-coated cellulose membrane dialyzer for 6 months, 1 year, and 2 years resulted in a significant reduction in LDL-MDA and ox-LDL compared with that obtainal with the use of the ordinary cellulose membrane dialyzer. The treatment with a vitamin E-coated dialyzer significantly reduced the percent increase in ACI after 24 months as compared with control. There were no significant differences in plasma vitamin E and lipid concentrations between the two groups. These results suggest that oxidative stress could be one of the factors stimulating abnormal lipid metabolism and atherosclerosis in ESRD patients.     

Use of various combinations of free, complexed and total prostate-specific antigen levels as predictors of the pathologic stage of prostate cancer

BACKGROUND: The efficacy of various combinations of total, free and complexed prostate-specific antigen (PSA) levels were assessed to predict the pathologic stage of prostate cancer. METHODS: Total PSA (tPSA), free PSA (fPSA) and complexed PSA (cPSA) levels were measured preoperatively in 52 patients with clinical localized prostate cancer who had undergone radical prostatectomy. Pathologic stages were classified as: organ-confined (n = 27); capsular penetration (n = 14); seminal vesicle involvement (n = 8); involvement of the surgical margins (n = 10); and lymph node involvement (n = 3). RESULTS: The fPSA/tPSA and fPSA/cPSA ratios significantly differed between patients with organ-confined disease and non-organ-confined disease (P = 0.035, P = 0.033, respectively) and between those with favorable versus unfavorable pathology (P = 0.001, P = 0.014, respectively), but tPSA, cPSA, fPSA and the cPSA/tPSA ratio did not. Using a fPSA/tPSA cutoff level of 11%, the prediction of organ-confined disease would increase from 52 to 67% and the rate of predicting favorable pathology would increase from 42 to 62%. A fPSA/cPSA cutoff level of 12% would increase the rate of predicting organ-confined disease to 79% and the rate of predicting favorable pathology would increase to 69%. The positive predictive value of the fPSA/cPSA ratio was higher than that of the fPSA/tPSA ratio, although the receiver operating characteristic curve of the fPSA/cPSA ratio was not different from that of the fPSA/tPSA ratio. CONCLUSION: Although there was no predictive difference found between fPSA/tPSA and fPSA/cPSA ratio, both ratios may help predict the pathologic stage of prostate cancer.     

Urticarial Vasculitis with Papular Lesions in a Patient with Type C Hepatitis and Cryoglobulinemia

We describe a case of urticarial vasculitis accompanied by erythematous wheals, palpable pupura, and subsequent necrotic ulcerated papular lesions in a patient with type C chronic hepatitis and type II cryoglobulinemia (IgM-kappa and polyclonal IgG). A 56-year-old man developed recurrent urticarial lesions on his lower extremities and trunk. The histology revealed leukocytoclastic vasculitis with perivascular immunoglobulin deposits. Subsequently, multiple reddish papular lesions with necrotic ulcerations appeared on the extensor aspect of his extremities and buttocks. Histology of these lesions showed cryoglobulinemic vasculitis with prominent fibrinoid necrosis of the vascular walls and cryoprecipitate within the vasculature as well as increased hyalinized collagen bundles. These papular lesions have not previously been described as cutaneous necrotizing venulitis to the best of our knowledge. It is suggested that the immune response to hepatitis C virus infection and cryoglobulins may be responsible for severe necrotizing venulitis, resulting in unusual cutaneous lesions.     

Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use

Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10⁻⁴⁰ with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10⁻¹⁰) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10⁻⁸), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10⁻⁴). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Subtypes of bladder mast cells in interstitial cystitis

BACKGROUND: Because the types of mast cells present in the bladder of patients with interstitial cystitis (IC) have not been elucidated, we have used immunohistochemical techniques to determine which of the mast cell types is present in biopsy specimens. METHODS: For all patients diagnosed with IC (n = 10; female) their symptoms satisfied the criteria proposed by the National Institutes of Health criteria of IC and six patients suffering from bladder tumors were selected as control patients. Adjacent sections of paraffin-embedded tissues that had been fixed in Carnoy's solution were reacted with either antitryptase or antichymase antibodies. RESULTS: In detrusor and in mucosa, the number of tryptase-positive and chymase-negative mast cells (MC(T)) was 146+/-25 and 81+/-31 cells/mm2, respectively, and the number of tryptase-positive and chymase-positive mast cells (MC(TC)) was 124+/-50 and 54+/-20 cells/mm2, respectively. These numbers were significantly greater than those of the control group. A significant negative correlation (P<0.005; R = 0.943) was observed between the number of MC(TC) and the bladder capacity. The number of mast cells obtained by toluidine blue staining in detrusor and in mucosa was 95+/-68 and 71+/-39 cells/mm2, respectively, suggesting that staining with toluidine blue underestimated the number of mast cells. CONCLUSIONS: Mast cells were significantly increased in number in both the mucosa and detrusor of bladder specimens from IC patients compared with those from control. The MC(TC) may be the type of mast cell dominantly present in the bladder of IC patients. The MC(TC) in detrusor increased with the progression of contracted bladder.