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Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites.

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the devastating kinetoplastid parasites of the genusLeishmania, the causative agents of diseases collectively termed leishmaniasis. More than 40 pathogenicLeishmaniaspecies are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. As no approved efficacious vaccine exists, available drugs are expensive and/or toxic, and resistance is emerging, management of sand fly populations to break transmission is currently the most effective disease control strategy. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two of the most important sand fly species:Phlebotomus papatasi, a cutaneous leishmaniasis vector, (distributed in the Middle East and North Africa) andLutzomyia longipalpis,a visceral leishmaniasis vector (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission ofLeishmaniaparasites.Author SummaryThe leishmaniases are a group of neglected tropical diseases caused by protist parasites from the GenusLeishmania. DifferentLeishmaniaspecies present a wide clinical profile, ranging from mild, often self-resolving cutaneous lesions that can lead to protective immunity, to severe metastatic mucosal disease, to visceral disease that is ultimately fatal.Leishmaniaparasites are transmitted by the bites of sand flies, and as no approved vaccine exists, available drugs are toxic and/or expensive and resistance is emerging, new dual control strategies to combat these diseases must be developed, combining interventions on human infections and integrated sand fly population management. Effective vector control requires a good understanding of the biology of sand flies. To this end, we sequenced and annotated the genomes of two sand fly species that are important leishmaniasis vectors from the Old and New Worlds. These genomes allow us to better understand, at the genetic level, processes important in the vector biology of these species, such as finding hosts, blood-feeding, immunity, and detoxification. These genomic resources highlight the driving forces of evolution of two majorLeishmaniavectors and provide foundations for future research on how to better prevent leishmaniasis by control of the sand fly vectors.

本研究は，商業施設で行う健康事業としての「健幸大学」への参加が高齢者の健康にどのような影響を与えたのか明らかにした。「健幸大学」は商業施設を活動の場とし，身体機能測定・講話・レクリエーションを中心としたプログラムで構成し，2019年度の活動は月1～2 回のペースで合計8回実施した。今回,「健幸大学」に複数回参加した高齢者にアンケートを実施し，参加するようになってから①健康への取り組みにどのような変化があったのか，②具体的な気持ちや行動の変化，に関して自由記載で回答を求めた。アンケート回収率81.5％，有効回答数は65 名（有効回答率86.6％）であった。得られた自由記載を，テキストマイニングを用いて単語頻度分析と共起分析を行った。分析の結果，総抽出語数は182 語で，単語頻度分析では，高頻度順に『運動』・『参加』（17 回），『身体』・『良い』（13回），『気を付ける』・『毎日』（11 回），『健康』・『自分』・『少しずつ』（10 回）と続いた。また，共起分析では，3 つのネットワークが形成された。日常生活と関連性が強い買い物が行える商業施設で行う健康事業は，高齢者にとって気軽に，そして繰り返し参加しやすい環境であった。このことが知識獲得の機会となり，複数回参加した高齢者に健康への関心の高まりと健康づくりに対する行動変容が少しずつ起き始めていた。今後は，地域との連携を含めた高齢者の健康行動が習慣化される仕掛けづくりを検討していく。

Reproduction-specific small RNAs are vital regulators of germline development in animals and plants. MicroRNA2118 (miR2118) is conserved in plants and induces the production of phased small interfering RNAs (phasiRNAs). To reveal the biological functions of miR2118, we describe here rice mutants with large deletions of the miR2118 cluster. Our results demonstrate that the loss of miR2118 causes severe male and female sterility in rice, associated with marked morphological and developmental abnormalities in somatic anther wall cells. Small RNA profiling reveals that miR2118-dependent 21-nucleotide (nt) phasiRNAs in the anther wall are U-rich, distinct from the phasiRNAs in germ cells. Furthermore, the miR2118-dependent biogenesis of 21-nt phasiRNAs may involve the Argonaute proteins OsAGO1b/OsAGO1d, which are abundant in anther wall cell layers. Our study highlights the site-specific differences of phasiRNAs between somatic anther wall and germ cells, and demonstrates the significance of miR2118/U-phasiRNA functions in anther wall development and rice reproduction., MicroRNA2118 induces the production of phased small interfering RNAs (phaisRNAs) in plants. Here the authors show that rice miR2118 is required for both male and female fertility and supports the production of atypical U-rich 21 nt phasiRNAs that are abundant in anther walls.

本研究の目的は，学生が実施している認知症高齢者への「聞き書き」の学びを明らかにすることである。A大学老年看護学実習において学生が行った認知症高齢者に対する「聞き書き」のリフレクションレポートを質的帰納的に分析した。その結果，【語り手の個人史や価値観の理解が深まる】【聞き書きは個別性のあるケアを創り出す】【語り手の豊かな感情を呼び起こす】【語ることで人生を振りかえり，過去の記憶や思い出に親しむ】【語りを引き出すための事前準備の重要性】【語りを傾聴し，ありのままを受けとめる姿勢の重要性】【記憶の想起を助ける工夫の重要性】【聞き書き中は語り手に合わせた状況判断が求められる】の8つのカテゴリが抽出された。学生は「聞き書き」を通して，認知症高齢者がもつコミュニケーション障害を考え，学生自らが相手に応じて瞬時に状況判断を行って工夫し，認知症高齢者との関係づくりに取り組めていたと考える。また学生は，「聞き書き」を通して，認知症高齢者に対する態度形成とQOLを高めるケア提供の機会を得ていたと考える。これらのことから，「聞き書き」は，学生が認知症高齢者との対話を通して，老年看護学教育において重要な認知症高齢者の理解が深まる機会になることが示唆された。教員は，今後も学生個々が「聞き書き」という相互行為を通して体験した内容，感情，思考などを言語化したものから，学生が認知症高齢者理解を深めていく過程を確認していくことが重要である。

The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells. These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.

OBJECTIVES To determine the incidence and preoperative risk factors of post-excisional hypoglycemia in patients undergoing pheochromocytoma resection. METHODS Patients who underwent surgical resection of pheochromocytoma at a single institution were retrospectively enrolled in the present study. The primary end-point was the development of post-excisional hypoglycemia; that is, a serum glucose level

Osborne-Mendel (OM) rats spontaneously develop glomerulopathy with progressive podocyte injury. Changes in protein expression levels in the foot processes of podocytes have been suggested to play an important role in the development of renal disease. The aim of this study was to investigate the temporal relationship between the expression of five podocyte proteins (nephrin, podocin, synaptopodin, α-actinin-4 and α3-integrin) and the development of podocyte injuries, proteinuria and glomerulosclerosis in OM rats. Male OM rats 5-20 weeks of age and age-matched Fischer 344 rats were used. Semiquantitative analysis of expression of the five podocyte proteins was performed by immunofluorescence labelling. Nephrin mRNA expression was determined by quantitative real-time reverse transcriptase polymerase chain reaction and nephrin protein expression was determined by mass spectrometry. Progressive reduction in expression of the podocyte proteins correlated with the progression of podocyte injuries, the development of proteinuria and the subsequent development of glomerulosclerosis. Nephrin mRNA expression and nephrin concentration also showed temporal decreases in OM rats. Altered expression of podocyte proteins preceded the development of proteinuria and glomerulosclerosis, suggesting that this event contributes to podocyte dysfunction and progression to glomerulosclerosis.

This report describes a spontaneous hybrid cyst in a Sprague-Dawley (SD) rat. A 52-week-old, male SD rat had a cutaneous cyst on the left mystacial pad. Histologically, the cyst wall showed infundibular differentiation with keratohyalin granules in the granular layer and matrical differentiation comprising basaloid epithelial cells with trichohyalin granules. The cyst cavity was filled with lamellar, flaky keratin and aggregates of shadow cells. Immunohistochemically, the infundibular-type epithelium was positive for cytokeratin (CK) AE1/AE3, CK KL1 and CK14 but negative for CK15, whereas the matrical-type epithelium was negative for all four CK isoforms examined. These immunohistochemical properties of the infundibular- and matrical-type epithelia were similar to those of the infundibulum and inferior segment of normal hair follicles, respectively. Based on these findings, the cyst was diagnosed as a hybrid cyst, comprising more than one type of cyst arising from various parts of the pilosebaceous unit.

Membranous glomerulonephropathy can be experimentally induced in rats, but spontaneous cases have been rarely reported. In this report, we present a typical case of spontaneous membranous glomerulonephropathy in a rat. A male Hatano low-avoidance (LAA) strain rat had a tumor mass on the right auricle, and was sacrificed at 41 weeks of age. Urinary screening by reagent strips revealed intense proteinuria. Histological tests revealed frequent presence of irregularly sized eosinophilic hyaline materials on the capillary wall and in the mesangium of renal glomeruli. Immunofluorescence revealed granular deposits of IgG, IgM, and C3 in the glomeruli. Subepithelial dense deposits were observed by electron microscopy accompanied by podocyte foot process effacement and occasional irregular thickening of the glomerular basement membrane. The rat also developed chronic lymphocytic pancreatitis, and the tumor mass on the right auricle was diagnosed as a fibrosarcoma. Screening tests for antibodies against major infectious agents and antinuclear antibody were negative. Western blot and indirect immunofluorescence analyses suggested the presence of an autoantibody against the pancreatic component. The glomerulopathy was considered an early stage of membranous glomerulonephropathy.

Evaluation of the malignant potential of a pheochromocytoma (PCC) remains controversial. PCC is regarded as a neuroendocrine tumor (NET), and the classification of NETs has gradually been defined over the last decade, particularly for gastroenteropancreatic NET. The present study describes a case of locally advanced, carcinoma-like, nonfunctional PCC, which may be regarded as neuroendocrine carcinoma (NEC) rather than a malignant PCC. A 72-year-old man was referred to Saitama Red Cross Hospital (Saitama, Japan), presenting with a 2-month history of right flank pain. Computed tomography revealed a right adrenal gland tumor, which measured 6.0 cm in diameter, invading the hilum of the right kidney, liver and inferior vena cava (IVC). Radical surgery was performed with en bloc resection of the right kidney, and adjacent parts of the liver and IVC. Immunohistochemical examination demonstrated that all of the resected tissues were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin, cluster of differentiation 56 and Ki-67, and the specimen had a Ki-67 index of 80%. A diagnosis of carcinoma-like PCC or NEC of the adrenal gland was confirmed. Reports of NEC of the adrenal gland are extremely rare in the literature, and classification of PCC as a NET has not yet been fully discussed. The present case may therefore contribute to the classification of NETs in the adrenal gland.

We evaluated the clinical outcome of transurethral lithotripsy (TUL) using rigidflexible ureteroscopy and holmium : yttrium-aluminum-garnet (YAG) laser in our hospital. We retrospectively reviewed 100 consecutive transurethral lithotripsy procedures performed on 82 patients from May 2008 to June 2010 at our hospital. Twenty-five patients (30%) had multiple stones and 10 patients (12%) had bilateral stones. The main stones were located in the renal pelvis, ureteropelvic junction, upper ureter, middle ureter, and lower ureter in 14, 12, 26, 3, and 27 cases, respectively. Median operative time was 75 minutes (range, 18-238 minutes). Operative complications were 5 cases of pyelonephritis and 1 case of ureteral perforation that was managed conservatively with percutaneous nephrostomy. The average number of procedures was 1.22 with 65 patients requiring one, 16 requiring two, and 1 requiring three procedures. Three patients had shock wave lithotripsy (SWL) and two patients had minipercutaneous nephrolithotomy (mini-PNL) after first TUL. However, all of these patients eventually needed additional TUL. The overall success rate was 99% (81/82). Rigidflexible ureteroscopy and holmium : YAG laser lithotripsy achieved excellent results of treatment for urolithiasis. TUL gave a high stone-free rate with low complication rates. In Japan, where shock wave lithotripters are widely used, trend of treatment for urolithiasis will shift from SWL to TUL.