Prediction Models for BMI and NAFLD

Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity. Disulfide bond‐forming oxidoreductase A‐like protein (DsbA‐L) is known to be a key molecule in protection against obesity and obesity‐induced inflammation. In the present study, we used a modeling and simulation approach in an attempt to develop body mass index (BMI) and BMI‐based NAFLD prediction models incorporating the DsbA‐L polymorphism to predict the BMI and NAFLD in 341 elderly subjects. A nonlinear mixed‐effect model best represented the sigmoidal relationship between the BMI and the logit function of the probability of NAFLD prevalence. The final models for BMI and NAFLD showed that DsbA‐L rs1917760 polymorphism, age, and gender were associated with the BMI, whereas gender, patatin‐like phospholipase 3 rs738409 polymorphism, HbA1c, and high‐density and low‐density lipoprotein cholesterol levels were associated with the risk of NAFLD. This information may aid in the genetic‐based prevention of obesity and NAFLD in the general elderly population

Effect of Intravesical Bacilli Calmette-Guerin Therapy After Second Transurethral Resection in Stage Ta T1 High-Grade Bladder Cancer

Background: To evaluate the efficacy of Bacilli Calmette-Guerin (BCG) induction instillation therapy after second transurethral resection (TUR) in stage Ta T1 high-grade bladder cancer. Methods: We performed a retrospective analysis of 49 consecutive new onset Ta T1 high-grade bladder cancer patients treated with second TUR at our affiliated institutions. Residual cancer rate, intravesical recurrence-free survival (RFS), and risk factors related to RFS were evaluated by univariate and multivariate Cox proportional hazard model analyses. Results: Thirty-one patients received BCG therapy after the second TUR (BCG group), and 18 patients were treated with second TUR alone (no BCG group). There were statistically significant differences in the RFS rates between the two groups, (P = 0.037). BCG therapy was the only factor predictive of intravesical recurrence after second TUR in both univariate and multivariate analyses. After the second TUR, BCG therapy significantly decreased intravesical recurrence in the patients with residual tumors (P = 0.014). However, there was no significant difference in intravesical recurrence in the patients with no residual tumors between the two groups (P = 0.359). Conclusion: BCG therapy after second TUR significantly decreased intravesical recurrence of residual tumors found at the second TUR

Monoclonal gammopathy of renal significance (MGRS)-related AL amyloidosis complicated by amyloid myopathy: a case report

BACKGROUND: Lately, monoclonal gammopathy of renal significance (MGRS) has been defined as a group of renal disorders that are strongly associated with monoclonal protein, including amyloid immunoglobulin light chain (AL) amyloidosis. Amyloid myopathy is rare (1.5% of all patients with amyloidosis) and the prognosis is poor. Furthermore, only approximately 20% of patients with amyloid myopathy are reported to have renal involvement, indicating a lack of data in the literature. CASE PRESENTATION: Here, we report a rare case of MGRS-related AL amyloidosis complicated by amyloid myopathy that presented with muscle weakness in the upper and lower limbs, neck and fingers, and nephrotic syndrome. Blood, urine, and bone marrow examination revealed monoclonal gammopathy of undetermined significance (MGUS) (Bence Jones protein-lambda). Muscle biopsy of the vastus lateralis muscle demonstrated amyloid proteins in the sarcolemma and in the blood vessel walls on Congo red staining, suggesting amyloid myopathy, and tiny inclusions in fibers on modified Gomori trichrome stain. Although we thought they were reminiscent of nemaline bodies, we could not confirm the nature of this structure. Renal biopsy demonstrated amyloid proteins in the mesangial region, part of the capillary walls, and the blood vessel walls on direct fast scarlet staining. As these amyloid proteins were positive for p-component staining and negative for amyloid A staining, β2-microglobulin, and pre-albumin, and as lambda light chains were positive in the mesangial region, we diagnosed the patient with MGRS-related AL amyloidosis. Although he was treated with melphalan and dexamethasone, his symptoms did not improve. CONCLUSIONS: AL amyloidosis involving the kidneys and muscles has a poor prognosis, and a delayed diagnosis of amyloid myopathy is common because of its rarity and frequent misdiagnosis, which increases organ function deterioration. Therefore, early detection, therapeutic intervention, and careful follow-up are crucial

ケニア キョウワコク ノ カレンC ショトウ ガッコウ ニオケル スウガク ノ ジュギョウ ケンキュウ : ケニアジン キョウシ ト ニホンジン キョウシ ニヨル ７ネンセイ ノ ブンスウ ノ ワリザン ノ ジュギョウ ジッセン オ ツウジテ

鳴門教育大学では，教員教育国際協力センターの教員が中心となって，国別研修「ケニア初等理数科教授法改善プロジェクト」のフォローアップ調査を実施している．2016年3月にフォローアップ調査の一環として，ケニア共和国ナイロビ市内のカレンC初等学校で授業研究会が実施された．この授業研究では，ケニア人教師と日本人教師が7年生の分数の割り算の授業を行い，その後，それぞれの授業について，合同の授業検討会が開催された．本稿では，ケニア人教師と日本人教師の授業の様子を分析するとともに，授業検討会での意見をふまえてケニアの初等学校における数学授業の問題点について考察を行った

Isolation and characterization of post-splicing lariat–intron complexes

Pre-mRNA splicing occurs in a large complex spliceosome. The steps of both spliceosome assembly and splicing reaction have been extensively analyzed, and many of the factors involved have been identified. However, the post-splicing intron turnover process, especially in vertebrates, remains to be examined. In this paper, we developed a two-tag affinity purification method for purifying lariat intron RNA–protein complexes obtained from an in vitro splicing reaction. Glycerol gradient sedimentation analyses revealed that there are at least two forms of post-splicing intron complexes, which we named the ‘Intron Large (IL)’ and the ‘Intron Small (IS)’ complexes. The IL complex contains U2, U5 and U6 snRNAs and other protein splicing factors, whereas the IS complex contains no such U snRNAs or proteins. We also showed that TFIP11, a human homolog of yeast Ntr1, is present in the IL complex and the TFIP11 mutant protein, which lacks the interaction domain with hPrp43 protein, caused accumulation of the IL complex and reduction of IS complex formation in vitro. Taken together, our results strongly suggest that TFIP11 in cooperation with hPrp43 mediates the transition from the IL complex to the IS complex, leading to efficient debranching and turnover of excised introns

Nonsense mutation in CFAP43 causes normal-pressure hydrocephalus with ciliary abnormalities

OBJECTIVE: To identify genes related to normal-pressure hydrocephalus (NPH) in one Japanese family with several members with NPH. METHODS:We performed whole-exome sequencing (WES) on a Japanese family with multiple individuals with NPH and identified a candidate gene.Then we generated knockout mouse using CRISPR/Cas9 to confirm the effect of the candidate gene on the pathogenesis of hydrocephalus.RESULTS: In WES, we identified a loss-of-function variant in CFAP43 that segregated with the disease. CFAP43 encoding cilia- and flagella-associated protein is preferentially expressed in the testis.Recent studies have revealed that mutations in this gene cause male infertility owing to morphologic abnormalities of sperm flagella. We knocked out mouse ortholog Cfap43 using CRISPR/Cas9 technology, resulting in Cfap43-deficient mice that exhibited a hydrocephalus phenotype with morphologic abnormality of motile cilia. CONCLUSION: Our results strongly suggest that CFAP43 is responsible for morphologic or movement abnormalities of cilia in the brain that result in NPH

Reduced FOXO1 Expression Accelerates Skin Wound Healing and Attenuates Scarring

The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1 +/- mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a-/- mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1+/- mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring

Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair

UV-sensitive syndrome (UVSS) is a genodermatosis characterized by cutaneous photosensitivity without skin carcinoma1, 2, 3, 4. Despite mild clinical features, cells from individuals with UVSS, like Cockayne syndrome cells, are very UV sensitive and are deficient in transcription-coupled nucleotide-excision repair (TC-NER)2, 4, 5, which removes DNA damage in actively transcribed genes6. Three of the seven known UVSS cases carry mutations in the Cockayne syndrome genes ERCC8 or ERCC6 (also known as CSA and CSB, respectively)7, 8. The remaining four individuals with UVSS, one of whom is described for the first time here, formed a separate UVSS-A complementation group1, 9, 10; however, the responsible gene was unknown. Using exome sequencing11, we determine that mutations in the UVSSA gene (formerly known as KIAA1530) cause UVSS-A. The UVSSA protein interacts with TC-NER machinery and stabilizes the ERCC6 complex; it also facilitates ubiquitination of RNA polymerase IIo stalled at DNA damage sites. Our findings provide mechanistic insights into the processing of stalled RNA polymerase and explain the different clinical features across these TC-NER–deficient disorders