Separating the effect of verbal cue on task-set activation into stimulus- and response-related processes: An eye-tracking study

In task selection, a verbal cue is interpreted as more meaningful, and thus, it can elicit a faster response than an arbitrary cue. To investigate the effect of verbal cues on activating target task information, we combined an eye-tracking technique with a task-switching paradigm using an arbitrary cue and a type of verbal cue—a word cue with a short cue–target interval (CTI) and long CTI. We measured stimulus-selection time (time to orienting a stimulus) and postselection response time (time to respond to a stimulus after orienting to the stimulus) and separately examined the differential effect of cue types on these divided response times. Consequently, we found that word cues reduced stimulus-selection time and postselection response time compared with arbitrary sign cues in both the long and short CTI conditions. The results suggest that verbal cues activate task information more quickly, including a stimulus dimension and stimulus–response rule, than arbitrary cues

A Case of Apoplexy Attack-Like Neuropathy due to Hereditary Neuropathy with Liability to Pressure Palsies in a Patient Diagnosed with Chronic Cerebral Infarction

Hereditary neuropathy with liability to pressure palsies is an inherited disease associated with the loss of a copy of the PMP22 gene. The condition leads to mononeuropathy due to compression and easy strangulation during daily life activities, resulting in sudden muscle weakness and sensory disturbance, and displaying symptoms similar to cerebrovascular diseases. We report the case of an 80-year-old man with left paralysis due to chronic cerebral infarction. His medical history indicated remarkable recovery from about 4 months after the onset of left hemiplegia with predominant involvement of the fingers. Despite subsequent recurrent monoplegia of the upper or lower limbs, brain magnetic resonance imaging consistently revealed only previous cerebral infarction in the right corona radiata without new lesions. Medical examination showed reduced deep tendon reflexes in his extremities on both the healthy and hemiplegic sides. Nerve conduction studies showed delayed conduction at the bilateral carpal and cubital tunnels and near the right caput fibulae. Genetic analysis revealed loss of a copy of the PMP22 gene. Thus, he was diagnosed with a cerebral infarction complicated by hereditary neuropathy with liability to pressure palsies. Stroke patients develop sudden muscle weakness and sensory disturbance. However, if such patients have no hyperactive deep tendon reflexes and show atypical recovery of paralysis that does not correspond to findings of imaging modalities, nerve conduction studies and genetic analysis may be necessary, considering the complication of hereditary neuropathy with liability to pressure palsies

Analysis of nivolumab related interstitial lung disease in patient with non-small-cell lung cancer.

ニボルマブに関連した間質性肺疾患（以下，ILD）の発現については，死亡例が報告され注意喚起がなされている。ILD 等の異常が認められた場合には，ニボルマブを中止し副腎皮質ステロイド剤の投与等の処置を行うこととされているが，十分なデータが得られているとは言えない。平成28年１～12月の間に非小細胞肺癌に対してニボルマブ投与を開始した患者の中でGrade 2及びGrade 3のILD各１名を経験し，メチルプレドニゾロンコハク酸エステルナトリウム１ g/day ×３日間投与後，経口プレドニゾロン投与し漸減することで軽快した。ILD の発現時期については，ニボルマブ２～ 12回目の投与時（中央値８回目）に発現しており定まっていなかった。今回経験したGrade ２以上の症例においては，副腎皮質ステロイドに対する反応性を認めた。The attention is given to Nivolumab induced interstitial lung disease （refered to as ILD）. In some cases, even deaths have been reported. The standard protocol is that once a sign of ILD is seen, stop Nivolumab and switch to corticosteriod, but there is no enough data to back up this protocol. Among the non-small cell lung cancer patients who were given Nivolumab between January 2016 and December 2016, there was one patient who experienced grade 2 ILD and another patient with grade 3 ILD. Both of these patients’ symptoms of ILD were mostly contained after given 1g/day of Methyprednisolone Soduim Succinate for 3 days, then oral prednisolones with gradually decreasing the dosage of it. Regarding the manifestation of ILD, it varied and it was somewhere bewteen second to 12th doses of Nivolumab with the median of 8th doses. This study was able to confirm the effective response to corticosteriod for grade 2 or higher cases of ILD

Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities

Heparin-binding EGF-like growth factor (HB-EGF) is first synthesized as a membrane-anchored form (proHB-EGF), and its soluble form (sHB-EGF) is released by ectodomain shedding from proHB-EGF. To examine the significance of proHB-EGF processing in vivo, we generated mutant mice by targeted gene replacement, expressing either an uncleavable form (HBuc) or a transmembrane domain–truncated form (HBΔtm) of the molecule. HBuc/uc mice developed severe heart failure and enlarged heart valves, phenotypes similar to those in proHB-EGF null mice. On the other hand, mice carrying HBΔtm exhibited severe hyperplasia in both skin and heart. These results indicate that ectodomain shedding of proHB-EGF is essential for HB-EGF function in vivo, and that this process requires strict control

Endometrial Cancer Diagnosed at an Early Stage during Lynch Syndrome Surveillance: A Case Report

Lynch syndrome is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair genes, resulting in multi-organ cancer. Annual transvaginal ultrasonography and endometrial biopsy are recommended for endometrial cancer surveillance in patients with Lynch syndrome in several guidelines; however, evidence is limited. Here, we present the case of a 51-year-old woman with endometrial cancer who underwent robot-assisted laparoscopic simple hysterectomy at an early stage detected by Lynch syndrome surveillance. The patient was a 51-year-old gravida zero woman without any medical history or symptoms. Her sister suffered from bladder, breast, rectal, and endometrial cancer and was diagnosed with Lynch syndrome using a hereditary cancer panel test (VistaSeq®). During gynecologic surveillance, the patient’s endometrial cytology was classified as Papanicolaou class III. Therefore, she underwent endometrial curettage with hysteroscopy and was diagnosed with atypical endometrial hyperplasia. Robot-assisted hysterectomy was performed with a final pathological diagnosis of endometrial cancer (endometrioid carcinoma, Grade 1), stage 1A. She has remained disease-free for more than 12 months. Owing to advances in genetic medicine, prophylactic and therapeutic surgeries for hereditary cancers are increasing. To achieve an early diagnosis and treatment of Lynch syndrome-associated cancers, the importance of Lynch syndrome surveillance should be more widely recognized

Same task rules, different responses:Goal neglect, stimulus-response mapping and response modalities

To complete complex tasks, individuals must actively maintain task rules to direct behavior correctly. Failure to use task rules appropriately, termed goal neglect, has been shown across both vocal and manual response modalities. However, previous goal maintenance studies have differed not only in the response modality that they require, but also in the complexity of the stimulus–response mappings that participants must use during the task. The present study examines the effects of both response modality and stimulus–response mapping complexity, separately, on the rate of goal neglect in a modification of a classic goal maintenance task. Seventy-two younger adults were administered a shape-monitoring task, with three between-subjects response conditions: a vocal response with a simple stimulus–response mapping, a vocal response with a complex stimulus–response mapping, and a manual response with a complex stimulus–response mapping. Contrasting the rate at which task rules were neglected between response conditions showed that participants using complex stimulus–response mappings committed more frequent goal neglect than those using simple mappings, but that participants using vocal or manual responses did not differ in their rate of goal neglect once both responses required complex mappings. This suggests that the need to represent novel and complex stimulus–response mappings, of any modality, at the same time as novel task rules within working memory leads to some task rules being insufficiently maintained

Variants of C-C Motif Chemokine 22 (CCL22) Are Associated with Susceptibility to Atopic Dermatitis: Case-Control Studies

Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1st population, 916 cases and 1,032 controls; 2nd population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10−6; OR, 0.74; 95% CI, 0.65–0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD

ORAI1 Genetic Polymorphisms Associated with the Susceptibility of Atopic Dermatitis in Japanese and Taiwanese Populations

Atopic dermatitis is a chronic inflammatory skin disease. Multiple genetic and environmental factors are thought to be responsible for susceptibility to AD. In this study, we collected 2,478 DNA samples including 209 AD patients and 729 control subjects from Taiwanese population and 513 AD patients and 1027 control subject from Japanese population for sequencing and genotyping ORAI1. A total of 14 genetic variants including 3 novel single-nucleotide polymorphisms (SNPs) in the ORAI1 gene were identified. Our results indicated that a non-synonymous SNP (rs3741596, Ser218Gly) associated with the susceptibility of AD in the Japanese population but not in the Taiwanese population. However, there is another SNP of ORAI1 (rs3741595) associated with the risk of AD in the Taiwanese population but not in the Japanese population. Taken together, our results indicated that genetic polymorphisms of ORAI1 are very likely to be involved in the susceptibility of AD