umin.ac.jp/ctr Identifier: C000000412.

PURPOSEIt is not well known how the omission of whole-brain radiotherapy (WBRT) affects the neurocognitive function of patients with 1-4 brain metastases who are treated with stereotactic radiosurgery (SRS). MATERIALS AND METHODSIn a prospective randomized trial between WBRT+SRS and SRS-alone in patients with 1-4 brain metastases, neurocognitive function was assessed by the Mini-Mental Score Examination (MMSE). Among 132 enrolled patients, MMSE scores were available for 110 patients. RESULTSIn the baseline MMSE analyses, statistically significant differences were observed for total tumor volume, extent of tumor edema, age, and KPS. Among 92 patients who received follow-up MMSE, 39 patients had a baseline MMSE of 27 or lower (17 in the WBRT+SRS group, 22 in the SRS-alone group).Improvements of >=3 points in the MMSEs of 9 WBRT+SRS patients and 11 SRS-alone patients (P=0.85) were observed. Among 82 patients who had baseline MMSEs >=27 or whose baseline MMSEs were <=26 but improved to >=27 after the initial brain treatment, the 12-, 24-, and 36-month actuarial free Aoyama H et al. 4 rates of the 3-point drop in MMSE were 76.1%, 68.5%, and 14.7% in the WBRT+SRS group, and were 59.3%, 51.9%, and 51.9% in the SRS-alone group.The average duration until deterioration was 16.5 months in WBRT+SRS and 7.6 months in SRS-alone patients (P=0.05). CONCLUSIONSThe current study revealed that, for the majority of brain metastatic patients, control of the brain tumor is the most important factor for stabilizing neurocognitive function. However, the long-term adverse effect of WBRT on neurocognitive function may not be negligible.

Because awareness of emotional states in the self is a prerequisite to recognizing such states in others, alexithymia (ALEX), difficulty in identifying and expressing one's own emotional states, should involve impairment in empathy. Using functional magnetic resonance imaging (fMRI), we compared an ALEX group (n = 16) and a non-alexithymia (non-ALEX) group (n = 14) for their regional hemodynamic responses to the visual perception of pictures depicting human hands and feet in painful situations. Subjective pain ratings of the pictures and empathy-related psychological scores were also compared between the 2 groups. The ALEX group showed less cerebral activation in the left dorsolateral prefrontal cortex (DLPFC), the dorsal pons, the cerebellum, and the left caudal anterior cingulate cortex (ACC) within the pain matrix. The ALEX group showed greater activation in the right insula and inferior frontal gyrus. Furthermore, alexithymic participants scored lower on the pain ratings and on the scores related to mature empathy. In conclusion, the hypofunction in the DLPFC, brain stem, cerebellum, and ACC and the lower pain-rating and empathy-related scores in ALEX are related to cognitive impairments, particularly executive and regulatory aspects, of emotional processing and support the importance of self-awareness in empathy.

To evaluate the role of dietary factors in the etiology of inflammatory bowel disease (IBD), we conducted a multicenter hospital-based case-control study in a Japanese population. Cases were IBD patients aged 15 to 34 years [ulcerative colitis (UC) 111 patients; Crohn's disease (CD) 128 patients] within 3 years after diagnosis in 13 hospitals. One control subject was recruited for each case who was matched for sex, age, and hospital. A semiquantitative food frequency questionnaire was used to estimate preillness intakes of food groups and nutrients. All the available control subjects (n = 219) were pooled, and unconditional logistic models were applied to calculate odds ratios (ORs). In the food groups, a higher consumption of sweets was positively associated with UC risk [OR for the highest versus lowest quartile, 2.86; 95% confidence interval (CI), 1.24 to 6.57], whereas the consumption of sugars and sweeteners (OR, 2.12; 95% CI, 1.08 to 4.17), sweets (OR, 2.83; 95% CI, 1.38 to 5.83), fats and oils (OR, 2.64; 95% CI, 1.29 to 5.39), and fish and shellfish (OR, 2.41; 95% CI, 1.18-4.89) were positively associated with CD risk. In respect to nutrients, the intake of vitamin C (OR, 0.45; 95% CI, 0.21 to 0.99) was negatively related to UC risk, while the intake of total fat (OR, 2.86; 95% CI, 1.39 to 5.90), monounsaturated fatty acids (OR, 2.49; 95% CI, 1.23 to 5.03) and polyunsaturated fatty acids (OR, 2.31; 95% CI, 1.12 to 4.79), vitamin E (OR, 3.23; 95% CI, 1.45 to 7.17), and n-3 (OR, 3.24; 95% CI, 1.52 to 6.88) and n-6 fatty acids (OR, 2.57; 95% CI, 1.24 to 5.32) was positively associated with CD risk. Although this study suffers from the shortcoming of recall bias, which is inherent in most retrospective studies (prospective studies are warranted to confirm the associations between diet and IBD risk), the present findings suggest the importance of dietary factors for IBD prevention.

Hypertensive disorders in pregnancy (HDP) represent some of the most important problems faced by public health because HDP is a major cause of maternal and prenatal morbidity and mortality. Several epidemiological studies have been performed to determine the prevalence and risk factors of HDP as well as its subtypes. The prevalences of HDP, gestational hypertension and preeclampsia are 5.2-8.2%, 1.8-4.4% and 0.2-9.2%, respectively. Body mass index, anemia and lower education appear to be modifiable risk factors for HDP. Maternal age, primiparous, multiple pregnancy, HDP in previous pregnancy, gestational diabetes mellitus, preexisting hypertension, preexisting type 2 diabetes mellitus, preexisting urinary tract infection and a family history of hypertension, type 2 diabetes mellitus and preeclampsia appear to be nonmodifiable risk factors. Genetic variants including a single-nucleotide polymorphism in the angiotensinogen gene have also been reported to be nonmodifiable risk factors. Epidemiological studies have recently examined the associations between a history of HDP and its subtypes and future risks of other diseases. These studies have reported associations between a history of HDP and a risk of coronary heart disease, heart failure, dysrhythmia, stroke, hypertension, diabetes mellitus, end-stage renal dysfunction and cardiomyopathy. HDP is not associated with the future incidence of total cancer. In conclusion, HDP is not a rare complication of pregnancy and the influence of HDP remains for an extended duration. Physicians should consider the effects of HDP when treating chronic diseases in women.

Cystathionine gamma-lyase (CSE) is the last key enzyme in the trans-sulphuration pathway for biosynthesis of cysteine from methionine. Cysteine could be provided through diet; however, CSE has been shown to be important for the adequate supply of cysteine to synthesize glutathione, a major intracellular antioxidant. With a view to determining physiological roles of CSE in mice, we report the sequence of a complete mouse CSE cDNA along with its associated genomic structure, generation of specific polyclonal antibodies, and the tissue distribution and developmental expression patterns of CSE in mice. A 1.8 kb full-length cDNA containing an open reading frame of 1197 bp, which encodes a 43.6 kDa protein, was isolated from adult mouse kidney. A 35 kb mouse genomic fragment was obtained by lambda genomic library screening. It contained promoter regions, 12 exons, ranging in size from 53 to 579 bp, spanning over 30 kb, and exon/intron boundaries that were conserved with rat and human CSE. The GC-rich core promoter contained canonical TATA and CAAT motifs, and several transcription factor-binding consensus sequences. The CSE transcript, protein and enzymic activity were detected in liver, kidney, and, at much lower levels, in small intestine and stomach of both rats and mice. In developing mouse liver and kidney, the expression levels of CSE protein and activity gradually increased with age until reaching their peak value at 3 weeks of age, following which the expression levels in liver remained constant, whereas those in kidney decreased significantly. Immunohistochemical analyses revealed predominant CSE expression in hepatocytes and kidney cortical tubuli. These results suggest important physiological roles for CSE in mice.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

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