Treatment with YIGSR peptide ameliorates mouse tail lymphedema by 67 kDa laminin receptor (67LR)-dependent cell-cell adhesion.

Impaired microcirculation can cause lymphatic leakage which leads to a chronic swelling in the tissues of the body. However, no successful treatment gives any protection against lymphedema due to the lack of well-revealed pathophysiology of secondary lymphedema. Binary image of laminin immunohistochemical expression revealed that distribution of laminin expression localized during surgically induced lymphedema. 67 kDa laminin receptor (67LR) mRNA expression showed a peak at during lymphedema exacerbation. Since the response of 67LR molecules may affect the prevention of inflammation and edema, here we have hypothesized that 67LR ligand of YIGSR peptide could permit reconstructive environment for amelioration of lymphedema and evaluated the effect of YIGSR in a mouse tail model of lymphedema. Indeed, intra-abdominal injections of YIGSR for the first 3 days after inducing lymphedema in the mouse tail model reduced the tail lymphedema on day 14 by 27% (P = 0.035). Histology showed that YIGSR treatment protected lymphedema impairment in epidermis and dermis, and it also inhibited the expansion of intercellular spaces and enhanced especially cell adhesion in the basement membrane as revealed by transmission electron microscopy. Interestingly, the treatment also reduced the local expression of transforming growth factor (TGF)ß. Further elucidation of the mechanisms of 67LR-facilitated lymphangiogenesis contributes to find potential targets for the treatment of lymphedema.

Stimulating peristalsis improves esophagogastric junction observation during sedated esophagogastroduodenoscopy in children and adolescents.

Background and study aims: Sedation impairs full visualization of the esophagogastric junction (EGJ) and Z line (the squamocolumnar junction) during esophagogastroduodenoscopy (EGD). The aim of this study was to determine whether induction of esophageal peristalsis could improve the ability to evaluate the Z line in children and adolescents. Patients and methods: Study 1: Consecutive patients (10-15 years) undergoing EGD with propofol or midazolam sedation were enrolled. The proportion of Z line observed was compared between the two groups. Study 2: The effect of an air infusion near the EGJ following deflation of the stomach to induce esophageal peristalsis was investigated in the patients (15-18 years), undergoing EGD with propofol sedation. The proportion of Z line observed was compared between the stimulated group and control group. Results: Study 1: 149 patients were evaluated; 87 received propofol (43 boys; average age 13.2 years (range, 10-15)) and 62 received midazolam (30 boys; average age 12.8 years (range, 10-15)). The proportion of the Z line visualized was low but was greater with propofol vs. midazolam sedation (36.8% vs 16.1%, P=0.0059). Study 2: 102 patients were evaluated; 62 had induction of peristalsis (34 boys; average age 16.2 years (range, 15-18)) and 40 controls (20 boys; average age 16.8 years (range, 15-18)). Complete visualization of the Z line achieved in 95% (59 of 62) following induction of peristalsis vs. 37.5% (15 of 40) of controls (P>0.001). Conclusions: Induction of esophageal peristalsis greatly improved visualization of the Z line during sedated EGD in children and adolescents.

Depression prevention in healthcare workers during the COVID-19 pandemic.

BACKGROUND: Few studies have assessed depression in healthcare workers (HCWs) in Japan owing to the coronavirus disease 2019 (COVID-19) pandemic, and no studies have proposed effective interventions to help support their mental health. AIMS: To test the hypothesis that enhancing access to mental healthcare professionals helps to improve HCWs' mental health. METHODS: This cross-sectional study assessed depressive symptoms in HCWs at three hospitals in Osaka prefecture between May and July, 2020. The survey obtained information on HCWs' mental state and related situations/perceptions. Multivariable logistic regression analysis was performed to identify factors associated with depressive symptoms. RESULTS: Of the 3291 eligible HCWs, 1269 (39%) completed the survey. Of all HCWs, 87 (7%) were physicians, and 700 (55%) were nurses. A total of 181 (14%) HCWs had moderate-to-severe symptoms of depression. Being a frontline worker was not significantly associated with depressive symptoms (odds ratio: 0.86 [95% confidence intervals: 0.54-1.37], P = 0.50). The unwillingness to consult with anyone was significantly associated with more severe depressive symptoms (1.70 [1.10-2.63], P < 0.01). HCWs who had no opportunity to confide in family/friends (1.66 [1.10-2.52], P < 0.01) or colleagues/supervisors (3.19 [2.22-4.58], P < 0.001) were significantly more likely to have depressive symptoms. CONCLUSIONS: Being a frontline HCW in a Japanese hospital treating patients with COVID-19 was not significantly associated with having depressive symptoms. The study highlights that encouraging daily communication with close persons (family, friends, colleagues and supervisors), rather than improving access to mental health professionals, might help to prevent depression in HCWs during the COVID-19 pandemic.

Calcineurin inhibitors exacerbate coronary arteritis via the MyD88 signalling pathway in a murine model of Kawasaki disease.

Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)-/- and myeloid differentiation primary response gene 88 (MyD88)-/- mice. We also performed in-vitro studies with vascular and monocytic cells and vascular tissues. A histopathological analysis showed that both cyclosporin A and tacrolimus exacerbated the NOD1-mediated coronary arteritis in a dose-dependent manner. Cyclosporin A induced the exacerbation of coronary arteritis in mice only in high doses, while tacrolimus exacerbated it within the therapeutic range in humans. Similar effects were obtained in SCID and CARD9-/- mice but not in MyD88-/- mice. CNIs enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells in our KD model. These data indicated that both vascular and monocytic cells were involved in the exacerbation of coronary arteritis. Activation of MyD88-dependent inflammatory signals in both vascular cells and macrophages appears to contribute to their adverse effects. Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD.

BTK gene targeting by homologous recombination using a helper-dependent adenovirus/adeno-associated virus hybrid vector.

X-linked agammaglobulinemia (XLA) is one of the most common humoral immunodeficiencies, which is caused by mutations in Bruton's tyrosine kinase (BTK) gene. To examine the possibility of using gene therapy for XLA, we constructed a helper-dependent adenovirus/adeno-associated virus BTK targeting vector (HD-Ad.AAV BTK vector) composed of a genomic sequence containing BTK exons 6-19 and a green fluorescence protein-hygromycin cassette driven by a cytomegalovirus promoter. We first used NALM-6, a human male pre-B acute lymphoblastic leukemia cell line, as a recipient to measure the efficiency of gene targeting by homologous recombination. We identified 10 clones with the homologous recombination of the BTK gene among 107 hygromycin-resistant stable clones isolated from two independent experiments. We next used cord blood CD34⁺ cells as the recipient cells for the gene targeting. We isolated colonies grown in medium containing cytokines and hygromycin. We found that the targeting of the BTK gene occurred in four of the 755 hygromycin-resistant colonies. Importantly, the gene targeting was also observed in CD19⁺ lymphoid progenitor cells that were differentiated from the homologous recombinant CD34⁺ cells during growth in selection media. Our study shows the potential for the BTK gene therapy using the HD-Ad.AAV BTK vector via homologous recombination in hematopoietic stem cells.

PET in infancy predicts long-term outcome during adolescence in cryptogenic West syndrome.

BACKGROUND AND PURPOSE: Developmental and seizure outcomes in patients with cryptogenic West syndrome are variable. Our aim was to clarify the relationship between FDG-PET findings in infancy and long-term seizure and developmental outcome in cryptogenic West syndrome. MATERIALS AND METHODS: From 1991 to 1999, we prospectively performed FDG-PET from the onset of cryptogenic West syndrome in 27 patients. PET was performed at onset and at 10 months of age. In 2012, we evaluated the educational status, psychomotor development, and seizure outcome in 23 of the 27 patients (13-22 years of age). The correlation between PET findings and outcome was evaluated. RESULTS: At onset, PET showed hypometabolism in 13 patients (57%). The second PET after the initial treatment revealed cortical hypometabolism in 7 patients (30%). While hypometabolism at onset disappeared on the second PET in 9 patients, it was newly revealed in 3 patients on the second PET. In 2012, seven patients had persistent or recurrent seizures. Eight patients had intellectual impairment. The first PET did not correlate with seizure or developmental outcome. Five of 7 patients (71%) with hypometabolism seen on the second PET had persistent or recurrent seizures, while 14 of 16 (88%) patients with normal findings on the second PET were free of seizures. Five of 7 patients (71%) showing hypometabolism on the second PET had intellectual impairment. Thirteen of 16 (81%) patients with normal findings on the second PET showed normal intelligence. A significant correlation was found between the second PET and long-term seizure (P = .01) or developmental outcome (P = .03). CONCLUSIONS: Cortical hypometabolism is not permanent; it changes with clinical symptoms. Hypometabolism after initial treatment predicts long-term seizures and poor developmental outcome.

The effect of adaptive iterative dose reduction on image quality in 320-detector row CT coronary angiography.

OBJECTIVE: To evaluate the effect of adaptive iterative dose reduction (AIDR) on image noise and image quality as compared with standard filtered back projection (FBP) in 320-detector row CT coronary angiography (CTCA). METHODS: 50 patients (14 females, mean age 68 ± 9 years) who underwent CTCA (100 kV or 120 kV, 400-580 mA) within a single heartbeat were enrolled. Studies were reconstructed with FBP and subsequently AIDR. Image noise, vessel contrast and contrast-to-noise ratio (CNR) in the coronary arteries were evaluated. Overall image quality for coronary arteries was assessed using a five-point scale (1, non-diagnostic; 5, excellent). RESULTS: All the examinations were performed in a single heartbeat. Image noise in the aorta was significantly lower in data sets reconstructed with AIDR than in those reconstructed with FBP (21.4 ± 3.1 HU vs 36.9 ± 4.5 HU; p<0.001). No significant differences were observed between FBP and AIDR for the mean vessel contrast (HU) in the proximal coronary arteries. Consequently, CNRs in the proximal coronary arteries were higher in the AIDR group than in the FBP group (p<0.001). The mean image quality score was improved by AIDR (3.75 ± 0.38 vs 4.24 ± 0.38; p<0.001). CONCLUSION: The use of AIDR reduces image noise and improves image quality in 320-detector row CTCA.

Mastication suppresses initial gastric emptying by modulating gastric activity.

Because various mastication-related factors influence gastric activity, the functional relationship between mastication and gastric function has not been fully elucidated. To investigate the influence of mastication on gastric emptying and motility, we conducted a randomized trial to compare the effects of mastication on gastric emptying and gastric myoelectrical activity under conditions that excluded the influences of food comminution, taste, and olfaction. A (13)C-acetate breath test with electrogastrography and electrocardiography was performed in 14 healthy men who ingested a test meal with or without chewing gum. Autonomic nerve activity was evaluated by fluctuation analysis of heart rate. Gastric emptying was significantly delayed in the 'ingestion with mastication' group. Gastric myoelectrical activity was significantly suppressed during mastication and increased gradually in the post-mastication phase. A decrease in the high-frequency power of heart rate variability was observed coincidentally with gastric myoelectrical activity suppression. These findings suggest that initial gastric emptying is suppressed by mastication, and that the suppression is caused by mastication-induced inhibition of gastric activity (UMIN Clinical Trial Registration no. UMIN000005351).

Non-linear analysis of stabilograms with alcoholic intake.

Equilibrium function in the cerebellum (vestibulo-cerebellar system) can deteriorate under the influence of alcohol. In the Romberg posture, the center of gravity, which was measured every 50 ms by stabilometry, appeared to shift with alcohol ingestion. In the previous study, a locus in the center of gravity (stabilogram) was converted to values of statistical indices such as area of sway, total locus length, and locus length per unit area, although these indices could not always distinguish between the statokinesigrams sampled from seven healthy young males in sober and intoxicated states. This measurement was made with an AMTI force plate. In this study, "translation error" was estimated in a d-dimensional embedding space in order to compare statokinesigrams recorded before and after the ingestion of doubly diluted brandy in 30 s (1 ≤ d ≤ 10). We succeeded in validating a stochastic differential equation as a mathematical model of the body sway. The randomness in the model was preserved after alcohol intake and significantly increased in the medial/lateral direction. Visual information referred by the postural control system when standing might be interfered by the effects of intoxication, which was regarded as disturbance. This method is considered to be useful to diagnose the disorders of the vestibulocerebellar system.

Recurrent atrial fibrillation after high-dose methylprednisolone therapy in a girl with lupus-associated hemophagocytic syndrome.

Hemophagocytic syndrome (HPS) is a serious complication of systemic lupus erythematosus (SLE). A 15-year-old female with lupus-nephritis developed HPS. Bone marrow study showed florid thrombophagocytosis. There was no associated infection. High-dose methylprednisolone therapy ameliorated HPS. However, atrial fibrillation (Af) repeated after the infusion and required direct-current cardioversion. No underlying diseases were found in the heart and endocrine system. Chest roentgenogram and echocardiography were normal. Electrocardiogram showed slightly prolonged PR interval in sinus rhythm. Af occurred at high circulating levels of interferon-γ and interleukin (IL)-10, but not IL-6, IL-2, tumor necrosis factor-α, C-reactive protein or catecholamines. This is the first observation that high-dose corticosteroid induced Af in a case of lupus-HPS. Af is unusual in SLE children without cardiac disease, while conduction defect occurs associated with lupus-myocarditis. Lupus-HPS may be an aggressive SLE subset with cardiac involvement. High-dose corticosteroid infusion controls lupus activity, but could disclose the cardiac stress in lupus-HPS patients.

Semiaphis dauci (Fabricius) (Insecta, Hemiptera, Aphididae) ­ formal record of occurrence on arracacha (Arracacia xanthorrhiza Bancr) (Apiaceae) in Brazil, morphological characterization, description of damages and arthropods associated to the culture / Semiaphis dauci (Fabricius) (Insecta, Hemiptera, Aphididae) ­ registro formal de ocorrência em mandioquinha­salsa (Arracacia xanthorrhiza Bancr) (Apiaceae) no Brasil, caracterização morfológica, descrição dos danos e artrópodes relacionados à cultura

This paper reports formally the occurrence and describes the damages by Semiaphis dauci (Fabricius, 1775) (Insecta, Hemiptera, Aphididae, Aphidinae, Macrosiphini) on arracacha (Arracaciaxanthorrhiza Bancr.) (Apiaceae) in Brazil. The infestation was initially noted on April/2002 at Núcleo de Produção de Mudas, Departamento de Sementes Mudas e Matrizes, Coordenadoria de Assistência Técnica Integral, Secretaria de Agricultura e Abastecimento, São Bento do Sapucaí, State of São Paulo. Posteriorly the occurrence was detected in other parts of the municipality of São Bento do Sapucaí such as Serrano, Paiol Grande and Cantagalo, being the incidence higher in localities at lower altitudes. The colonies, with large number of individuals, were settled on both sides of the leaves and also hidden under petiole, but with lower number of specimens. The adult plants were underdeveloped and the growing of aphid colonies induced the blossoming. In the seedlings the symptoms were severer with reduction in the development and death of plants. When the colonies were placed in the dorsal side of the leaves, there was a tendency to wrinkling and rolling to upper side that was used as shelter by the aphids. Morphological characterization, illustrations and notes on biology of S. dauci and a survey of the Arthropoda related with A. xanthorrhiza are also presented.

Este trabalho efetua o registro formal de ocorrência e descreve os danos de Semiaphis dauci (Fabricius, 1775) (Insecta, Hemiptera, Aphididae, Aphidinae, Macrosiphini) em cultura de mandioquinha-salsa (Arracacia xanthorrhiza Bancr.) (Apiaceae) no Brasil. A infestação foi observada, inicialmente, em abril/2002, no Núcleo de Produção de Mudas, Departamento de Sementes Mudas e Matrizes, Coordenadoria de Assistência Técnica Integral, Secretaria de Agricultura e Abastecimento, São Bento do Sapucaí, SP. Posteriormente, a ocorrência foi detectada em outras localidades do município como Serrano, Paiol Grande e Cantagalo sendo que a incidência foi maior nas áreas de menor altitude. As colônias estavam localizadas em ambas as faces das folhas, e em menor número no pecíolo escondidas na bainha da folha. As plantas adultas apresentavam subdesenvolvimento e o aumento das colônias induzia o florescimento. Nas mudas os sintomas foram mais severos com redução no desenvolvimento e posterior morte das plantas. Quando havia formação de colônias na superfície superior das folhas, havia tendência de encarquilhamento e enrolamento para cima, servindo de abrigo para os pulgões. Caracterização morfológica, ilustrações, notas sobre a biologia de S. dauci e levantamento dos Arthropoda relacionados com A. xanthorrhiza também são apresentados.

Diffuse pollution by persistent organic pollutants as measured in plastic pellets sampled from various beaches in Greece.

Plastic pellets found stranded on beaches are hydrophobic organic materials and thus, they are a favourable medium for persistent organic pollutants to absorb to. In the present study, plastic pellets are used to determine the diffuse pollution of selected Greek beaches. Samples of pellets were taken from these beaches and were analyzed for PCBs, DDTs, HCHs, and PAHs. The observed differences among pellets from various sampling sites are related to the pollution occurring at each site. Plastic pellets collected in Saronikos Gulf beaches demonstrate much higher pollutant loading than the ones collected in a remote island or close to an agricultural area. Based on data collected in this study and the International Pellet Watch program, pollution in Saronikos Gulf, Greece, is comparable to other heavily industrialized places of the world. The present study demonstrates the potential of pellet watch to be utilized as a detailed-scale monitoring tool within a single country.

Susceptibilidade de Rhynchophorus palmarum à ação de Metarhizium anisopliae e compatibilidade do entomopatógeno com agrotóxicos utilizados na cultura da banana / Susceptibility of Rhynchophorus palmarum to the action of Metarhizium anisopliae and the compatibility of the entomopathogen with agrochemicals used in the banana crop

Este estudo teve o objetivo de selecionar isolados do fungo entomopatogênico Metarhizium anisopliae para o controle de adultos de Rhynchophorus palmarum (L.) (Coleoptera: Curculionidae) e avaliar a compatibilidade de agrotóxicos utilizados nesta cultura com o isolado que ocasionasse maior mortalidade dos adultos. Para tal, adultos do inseto foram imersos em suspensões de seis isolados do fungo na concentração de 109 conídios.mL-1 e, após 24 dias, o isolado IBCB 348 causou maior mortalidade (87,5%) e foi utilizado para o teste de compatilibidade, por meio do cálculo da fórmula de T, com inseticidas, herbicidas e fungicidas comerciais utilizados na cultura. Nenhum dos fungicidas e herbicidas testados foram compatíveis com o patógeno. Os inseticidas Calypso, Dipterex 500 e Sevin 480 SC, na concentração mínima recomendada pelo fabricante, foram os únicos produtos classificados como compatíveis com o isolado IBCB 348 de M. anisopliae.

This study was aimed to screen the entomopathogenic fungus Metarhizium anisopliae for the control of Rhynchophorus palmarum (L.) (Coleoptera: Curculionidae) adults and to evaluate the compatibility of agrochemicals used in this crop with the strain that caused the highest insect mortality. To this end, adult insects were immersed in suspensions of 6 strains at a concentration of 109 conidia.mL-1, and after 24 days the isolate IBCB 348 caused the highest mortality (87.5%) and was used in the compatibility test, using calculations by way of the T formula, with commercial insecticides, herbicides and fungicides used in the crop. Among the tested strains, IBCB 348 was the most efficient in the control of this pest, causing 87.5% of weevil mortality. None of the tested fungicides and herbicides were compatible with the pathogen. The insecticides Calypso, Dipterex 500 and Sevin 480 SC, at the lowest dose recommended by the manufacturer, were the only products classified as compatible with the strain IBCB 348 of M. anisopliae.

NEMO mutation as a cause of familial occurrence of Behçet's disease in female patients.

Behçet's disease is a chronic, relapsing, multisystem inflammatory disease of unknown etiology. Nuclear factor κB (NF-κB) essential modulator (NEMO) that is required for the activation of NF-κB plays an important role in inflammation. To investigate the role of NEMO in the pathogenesis of Behçet's disease, we analyzed NEMO gene and its expression pattern in tissues in a family with Behçet's disease. We found a heterozygous mutation (1217A> T, D406V) in a 6-year-old girl and her mother. Skewed X-chromosome inactivation was not observed in the peripheral blood mononuclear cells as well as in oral and intestinal mucosa of the patients. Accordingly, there was a significant proportion of peripheral blood monocytes that did not produce sufficient intracellular tumor necrosis factor-α with the stimulation of lipopolysaccharide. Heterozygous NEMO mutation is a cause of familial occurrence of Behçet's disease in female patients.

Unique activation status of peripheral blood mononuclear cells at acute phase of Kawasaki disease.

Although Kawasaki disease (KD) is characterized by a marked activation of the immune system with elevations of serum proinflammatory cytokines and chemokines at acute phase, the major sources for these chemical mediators remain controversial. We analysed the activation status of peripheral blood mononuclear cells (PBMCs) by flow cytometry, DNA microarray and quantitative reverse transcription-polymerase chain reaction. The proportions of CD69+ cells in both natural killer cells and gammadeltaT cells at acute-phase KD were significantly higher than those at convalescent-phase KD. Microarray analysis revealed that five genes such as NAIP, IPAF, S100A9, FCGR1A and GCA up-regulated in acute-phase KD and the pathways involved in acute phase KD were related closely to the innate immune system. The relative expression levels of damage-associated molecular pattern molecule (DAMP) (S100A9 and S100A12) genes in PBMCs at acute-phase KD were significantly higher than those at convalescent-phase KD, while those of TNFA, IL1B and IL6 genes were not significantly different between KD patients and healthy controls. Intracellular production of tumour necrosis factor-alpha, interleukin-10 and interferon-gamma in PBMCs was not observed in KD patients. The present data have indicated that PBMCs showed a unique activation status with high expression of DAMP genes but low expression of proinflammatory cytokine genes, and that the innate immune system appears to play a role in the pathogenesis and pathophysiology of KD.

WITHDRAWN: P.P.2 04 Chronological observation of glucose intolerance in myotonic dystrophy.

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Role of fatty acids in malignancy and visual impairment: epidemiological evidence and experimental studies.

International variation in breast and colon cancer incidence is positively related to total fat intake. However, total fat consists of different fatty acid families, e.g., saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-3 and n-6 polyunsaturated fatty acids (PUFAs). Epidemiological evidence and experimental studies suggest that these fatty acid families have different effects on breast and colon carcinogenesis. Therefore the action of each fatty acid on carcinogenesis should be evaluated separately. Although it is difficult to establish firm conclusions on the effect of each fatty acid in human epidemiological studies, experimental studies on animals and cultured cells suggest that n-6 PUFAs (linoleic acid and arachidonic acid) may have a tumor promoting effect, while n-3 PUFAs (eicosapentaenoic acid, docosahexaenoic acid and alpha-linolenic acid) and conjugated fatty acids (CFAs; a mixture of positional and geometric isomers of PUFAs with conjugated double bonds) exert an inhibitory effect on tumor growth. SFAs such as palmitic acid and stearic acid show little or no tumor promoting effect, and the action of oleic acid, a MUFA, is inconclusive. In addition to regulation of abnormal cell growth seen in cancers, fatty acids also control cell loss seen in degenerative eye diseases, such as degeneration of lens material in cataract and degeneration of photoreceptor cells in retinitis pigmentosa. Experiments suggest that n-6 PUFAs cause deleterious effects, while n-3 PUFAs result in beneficial effects on the lens and retina. In particular, docosahexaenoic acid is known to be effective in rescuing photoreceptor cells from damage. Thus, understanding the function of each fatty acid is likely to be important for making progress in treating these and other diseases.