What are the Key Factors in Managing Diversity and Inclusion Successfully in Large International Organizations?

Question: What are the key factors in managing diversity and inclusion successfully in large international organizations? Which companies are best in class and what does that entail

Initial Experience with Laparoendoscopic Single-Site Surgery by Use of a Homemade Transumbilical Port in Urology

Purpose: We present our initial experience with laparoendoscopic single-site surgery (LESS) by a single surgeon in the urologic field. Materials and Methods: From May 2009 to April 2010, 30 consecutive patients underwent LESS including seven cases of nephrectomy, five cases of nephroureterectomy with bladder cuff excision, four cases of ureterolithotomy, eight cases of marsupialization, and six cases of varicocelectomy. We performed a retrospective analysis of the medical records of the above patients. The single port was made with a surgical glove and an Alexis?? wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA). The wound retractor was put into the peritoneal space through an umbilical incision, and a laparoscopic triangle was secured by crossing both instruments. All operations were performed by the transperitoneal approach. Results: Mean patient age was 54.8 years. Mean operative time was 171.2??109.1 minutes. Mean estimated blood loss was 265.0??395.5 ml. Mean incision length was 3.2??1.4 cm. Mean length of hospitalization was 5.2??2.9 days. There was one laparoscopic conversion and two open conversions. There were two cases of transient ileus that improved with conservative treatment. Mean visual analogue pain scales on the operative day and first postoperative day were 6.3/10 and 3.1/10, respectively. Conclusions: In our experience, LESS for urologic surgery is feasible, safe, and clinically applicable. We consider the homemade single-port device to be a relatively cost-effective and convenient device. If surgical instruments for LESS and appropriate ports specified for LESS are developed, LESS would be a surgical treatment technique that could be used as an alternative to the conventional types of laparoscopic surgery. ?? The Korean Urological Association, 2010

PD-1 deficiency protects experimental colitis via alteration of gut microbiota

Programmed cell death-1 (PD-1) is a coinhibitory molecule and plays a pivotal role in immune regulation. Here, we demonstrate a role for PD-1 in pathogenesis of inflammatory bowel disease (IBD). Wild-type (WT) mice had severe wasting disease during experimentally induced colitis, while mice deficient for PD-1 (PD-1(-/-)) did not develop colon inflammation. Interestingly, PD-1(-/-) mice cohoused with WT mice became susceptible to colitis, suggesting that resistance of PD-1(-/-) mice to colitis is dependent on their gut microbiota. 16S rRNA gene-pyrosequencing analysis showed that PD-1(-/-) mice had altered composition of gut microbiota with significant reduction in Rikenellaceae family. These altered colon bacteria of PD-1(-/-) mice induced less amount of inflammatory mediators from colon epithelial cells, including interleukin (IL)-6, and inflammatory chemokines. Taken together, our study indicates that PD-1 expression is involved in the resistance to experimental colitis through altered bacterial communities of colon.112Ysciescopuskc

Computational Approach to Identify Enzymes That Are Potential Therapeutic Candidates for Psoriasis

Psoriasis is well known as a chronic inflammatory dermatosis. The disease affects persons of all ages and is a burden worldwide. Psoriasis is associated with various diseases such as arthritis. The disease is characterized by well-demarcated lesions on the skin of the elbows and knees. Various genetic and environmental factors are related to the pathogenesis of psoriasis. In order to identify enzymes that are potential therapeutic targets for psoriasis, we utilized a computational approach, combining microarray analysis and protein interaction prediction. We found 6,437 genes (3,264 upregulated and 3,173 downregulated) that have significant differences in expression between regions with and without lesions in psoriasis patients. We identified potential candidates through protein-protein interaction predictions made using various protein interaction resources. By analyzing the hub protein of the networks with metrics such as degree and centrality, we detected 32 potential therapeutic candidates. After filtering these candidates through the ENZYME nomenclature database, we selected 5 enzymes: DNA helicase (RUVBL2), proteasome endopeptidase complex (PSMA2), nonspecific protein-tyrosine kinase (ZAP70), I-kappa-B kinase (IKBKE), and receptor protein-tyrosine kinase (EGFR). We adopted a computational approach to detect potential therapeutic targets; this approach may become an effective strategy for the discovery of new drug targets for psoriasis

Characterization of Fabry mice treated with recombinant adeno-associated virus 2/8-mediated gene transfer

<p>Abstract</p> <p>Background</p> <p>Enzyme replacement therapy (ERT) with α-galactosidase A (α-Gal A) is currently the most effective therapeutic strategy for patients with Fabry disease, a lysosomal storage disease. However, ERT has limitations of a short half-life, requirement for frequent administration, and limited efficacy for patients with renal failure. Therefore, we investigated the efficacy of recombinant adeno-associated virus (rAAV) vector-mediated gene therapy for a Fabry disease mouse model and compared it with that of ERT.</p> <p>Methods</p> <p>A pseudotyped rAAV2/8 vector encoding α-Gal A cDNA (rAAV2/8-hAGA) was prepared and injected into 18-week-old male Fabry mice through the tail vein. The α-Gal A expression level and globotriaosylceramide (Gb3) levels in the Fabry mice were examined and compared with Fabry mice with ERT. Immunohistochemical and ultrastructural studies were conducted.</p> <p>Results</p> <p>Treatment of Fabry mice with rAAV2/8-hAGA resulted in the clearance of accumulated Gb3 in tissues such as liver, spleen, kidney, heart, and brain with concomitant elevation of α-Gal A enzyme activity. Enzyme activity was elevated for up to 60 weeks. In addition, expression of the α-Gal A protein was identified in the presence of rAAV2/8-hAGA at 6, 12, and 24 weeks after treatment. α-Gal A activity was significantly higher in the mice treated with rAAV2/8-hAGA than in Fabry mice that received ERT. Along with higher α-Gal A activity in the kidney of the Fabry mice treated with gene therapy, immunohistochemical studies showed more α-Gal A expression in the proximal tubules and glomerulus, and less Gb3 deposition in Fabry mice treated with this gene therapy than in mice given ERT. The α-gal A gene transfer significantly reduced the accumulation of Gb3 in the tubules and podocytes of the kidney. Electron microscopic analysis of the kidneys of Fabry mice also showed that gene therapy was more effective than ERT.</p> <p>Conclusions</p> <p>The rAAV2/8-hAGA mediated α-Gal A gene therapy provided improved efficiency over ERT in the Fabry disease mouse model. Furthermore, rAAV2/8-hAGA-mediated expression showed a greater effect in the kidney than ERT.</p

A Patient with Mixed Type Evans Syndrome: Efficacy of Rituximab Treatment

Mixed type Evans syndrome is a very rare hematologic disease. Although mixed type Evans syndrome may initially respond well to steroids, this disease usually runs a chronic course with intermittent exacerbations. We describe here a 46-yr-old female with the steroid-refractory, mixed type Evans syndrome, and she had a prompt response to rituximab. She was diagnosed as having the mixed type Evans syndrome with the clinical features of symptomatic anemia, jaundice and thrombocytopenia. Prednisone therapy was commenced and her hemoglobin and platelet level returned to the normal. However, after 15 weeks, she relapsed with hemolytic anemia and thrombocytopenia. We started rituximab at the dose of 375 mg/m2 once weekly for a total of 4 doses, which was well-tolerated and this induced the normalization of hemoglobin, bilirubin and lactic dehydrogenase, and there was also a significant increase of the platelet count

Inhibition of Hypoxic Pulmonary Vasoconstriction of Rats by Carbon Monoxide

Hypoxic pulmonary vasoconstriction (HPV), a unique response of pulmonary circulation, is critical to prevent hypoxemia under local hypoventilation. Hypoxic inhibition of K+ channel is known as an important O2-sensing mechanism in HPV. Carbon monoxide (CO) is suggested as a positive regulator of Ca2+-activated K+ channel (BKCa), a stimulator of guanylate cyclase, and an O2-mimetic agent in heme moiety-dependent O2 sensing mechanisms. Here we compared the effects of CO on the HPV (Po2, 3%) in isolated pulmonary artery (HPVPA) and in blood-perfused/ventilated lungs (HPVlung) of rats. A pretreatment with CO (3%) abolished the HPVPA in a reversible manner. The inhibition of HPVPA was completely reversed by 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. In contrast, the HPVlung was only partly decreased by CO. Moreover, the partial inhibition of HPVlung by CO was affected neither by the pretreatment with ODQ nor by NO synthase inhibitor (L-NAME). The CO-induced inhibitions of HPVPA and HPVlung were commonly unaffected by tetraethylammonium (TEA, 2 mM), a blocker of BKCa. As a whole, CO inhibits HPVPA via activating guanylate cyclase. The inconsistent effects of ODQ on HPVPA and HPVlung suggest that ODQ may lose its sGC inhibitory action when applied to the blood-containing perfusate

Structural dynamics and divergence of the polygalacturonase gene family in land plants

A distinct feature of eukaryotic genomes is the presence of gene families. The polygalacturonase (PG) (EC3.2.1.15) gene family is one of the largest gene families in plants. PG is a pectin-digesting enzyme with a glycoside hydrolase 28 domain. It is involved in numerous plant developmental processes. The evolutionary processes accounting for the functional divergence and the specialized functions of PGs in land plants are unclear. Here, phylogenetic and gene structure analysis of PG genes in algae and land plants revealed that land plant PG genes resulted from differential intron gain and loss, with the latter event predominating. PG genes in land plants contained 15 homologous intron blocks and 13 novel intron blocks. Intron position and phase were not conserved between PGs of algae and land plants but conserved among PG genes of land plants from moss to vascular plants, indicating that the current introns in the PGs in land plants appeared after the split between unicellular algae and multicelluar land plants. These findings demonstrate that the functional divergence and differentiation of PGs in land plants is attributable to intronic loss. Moreover, they underscore the importance of intron gain and loss in genomic adaptation to selective pressure