Optimal Hemoglobin A1c Levels for Screening of Diabetes and Prediabetes in the Japanese Population

The aim of this study was to evaluate the utility of hemoglobin A1c (HbA1c) to identify individuals with diabetes and prediabetes in the Japanese population. A total of 1372 individuals without known diabetes were selected for this study. A 75 g oral glucose tolerance test (OGTT) was used to diagnose diabetes and prediabetes. The ability of HbA1c to detect diabetes and prediabetes was investigated using receiver operating characteristic (ROC) analysis. The kappa (κ) coefficient was used to test the agreement between HbA1c categorization and OGTT-based diagnosis. ROC analysis demonstrated that HbA1c was a good test to identify diabetes and prediabetes, with areas under the curve of 0.918 and 0.714, respectively. Optimal HbA1c cutoffs for diagnosing diabetes and prediabetes were 6.0% (sensitivity 83.7%, specificity 87.6%) and 5.7% (sensitivity 60.6%, specificity 72.1%), respectively, although the cutoff for prediabetes showed low accuracy (67.6%) and a high false-negative rate (39.4%). Agreement between HbA1c categorization and OGTT-based diagnosis was low in diabetes (κ=0.399) and prediabetes (κ=0.324). In Japanese subjects, the HbA1c cutoff of 6.0% had appropriate sensitivity and specificity for diabetes screening, whereas the cutoff of 5.7% had modest sensitivity and specificity in identifying prediabetes. Thus, HbA1c may be inadequate as a screening tool for prediabetes

Evidence from nuclear DNA sequences sheds light on the phylogenetic relationships of pinnipedia: Single origin with affinity to musteloidea

Considerable long-standing controversy and confusion surround the phylogenetic affinities of pinnipeds, the largely marine group of "fin-footed" members of the placental mammalian order Carnivora. Until most recently, the two major competing hypotheses were that the pinnipeds have a single (monophyletic) origin from a bear-like ancestor, or that they have a dual (diphyletic) origin, with sea lions (Otariidae) derived from a bear-like ancestor, and seals (Phocidae) derived from an otter-, mustelid-, or musteloid-like ancestor. We examined phylogenetic relationships among 29 species of arctoid carnivorans using a concatenated sequence of 3228 bp from three nuclear loci (apolipoprotein B, APOB; interphotoreceptor retinoid-binding protein, IRBP; recombination-activating gene 1, RAG1). The species represented Pinnipedia (Otariidae: Callorhinus, Eumetopias; Phocidae: Phoca), bears (Ursidae: Ursus, Melursus), and Musteloidea (Mustelidae: Mustela, Enhydra, Melogale, Martes, Gulo, Meles; Procyonidae: Procyon; Ailuridae: Ailurus; Mephitidae: Mephitis). Maximum parsimony, maximum likelihood, and Bayesian inference phylogenetic analyses of separate and combined datasets produced trees with largely congruent topologies. The analyses of the combined dataset resulted in well-resolved and well-supported phylogeny reconstructions. Evidence from nuclear DNA evolution presented here contradicts the two major hypotheses of pinniped relationships and strongly suggests a single origin of the pinnipeds from an arctoid ancestor shared with Musteloidea to the exclusion of Ursidae

Major differences between human atopic dermatitis and murine models, as determined by using global transcriptomic profiling

Atopic dermatitis (AD) is caused by a complex interplay between immune and barrier abnormalities. Murine models of AD are essential for preclinical assessments of new treatments. While many models have been used to simulate AD, their transcriptomic profiles are not fully understood, and a comparison of these models with the human AD transcriptomic fingerprint is lacking. We sought to evaluate the transcriptomic profiles of six common murine models and determine how they relate to human AD skin. Transcriptomic profiling was performed using microarrays and qRT-PCR on biopsies from NC/Nga, flaky-tail, Flg-mutated, ovalbumin-challenged, oxazolone-challenged, and IL-23-injected mice. Gene expression data of AD, psoriasis, and contact dermatitis were obtained from previous patient cohorts. Criteria of fold-change/FCH≥2 and false discovery rate/FDR≤0.05 were used for gene arrays. IL-23-injected, NC/Nga, and oxazolone-challenged mice show the largest homology with our human meta-analysis derived AD (MADAD) transcriptome (37%, 18%, 17%, respectively). Similar to human AD, robust Th1, Th2, and also Th17 activation are seen in IL-23-injected and NC/Nga mice, with similar, but weaker, inflammation in ovalbumin-challenged mice. Oxazolone-challenged mice show a Th1-centered reaction and flaky-tail mice demonstrate a strong Th17 polarization. Flg-mutated mice display FLG down-regulation without significant inflammation. No single murine model fully captures all aspects of the AD profile; instead, each model reflects different immune or barrier disease aspects. Overall, among the six murine models, IL-23-injected mice best simulate human AD; still, the translational focus of the investigation should determine which model is most applicable. When testing new drugs for atopic dermatitis, murine models might be used to study barrier or immune features, but human trials are needed to determine effects on actual disease profile

Japanese Society for Cancer of the Colon and Rectum (JSCCR) Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (Translated Version)

Hereditary colorectal cancer accounts for less than 5% of all colorectal cancer cases. Some of the unique characteristics that are commonly encountered in cases of hereditary colorectal cancer include early age at onset, synchronous/metachronous occurrence of the cancer, and association with multiple cancers in other organs, necessitating different management from sporadic colorectal cancer. While the diagnosis of familial adenomatous polyposis might be easy because usually 100 or more adenomas that develop in the colonic mucosa are in this condition, Lynch syndrome, which is the most commonly associated disease with hereditary colorectal cancer, is often missed in daily medical practice because of its relatively poorly defined clinical characteristics. In addition, the disease concept and diagnostic criteria for Lynch syndrome, which was once called hereditary non‐polyposis colorectal cancer, have changed over time with continual research, thereby possibly creating confusion in clinical practice. Under these circumstances, the JSCCR Guideline Committee has developed the "JSCCR Guidelines 2016 for the Clinical Practice of Hereditary Colorectal Cancer (HCRC)," to allow delivery of appropriate medical care in daily practice to patients with familial adenomatous polyposis, Lynch syndrome, or other related diseases. The JSCCR Guidelines 2016 for HCRC were prepared by consensus reached among members of the JSCCR Guideline Committee, based on a careful review of the evidence retrieved from literature searches, and considering the medical health insurance system and actual clinical practice settings in Japan. Herein, we present the English version of the JSCCR Guidelines 2016 for HCRC