Non-conventional yeast strains: Unexploited resources for effective commercialization of second generation bioethanol.

The conventional yeast (Saccharomyces cerevisiae) is the most studied yeast and has been used in many important industrial productions, especially in bioethanol production from first generation feedstock (sugar and starchy biomass). However, for reduced cost and to avoid competition with food, second generation bioethanol, which is produced from lignocellulosic feedstock, is now being investigated. Production of second generation bioethanol involves pre-treatment and hydrolysis of lignocellulosic biomass to sugar monomers containing, amongst others, d-glucose and D-xylose. Intrinsically, S. cerevisiae strains lack the ability to ferment pentose sugars and genetic engineering of S. cerevisiae to inculcate the ability to ferment pentose sugars is ongoing to develop recombinant strains with the required stability and robustness for commercial second generation bioethanol production. Furthermore, pre-treatment of these lignocellulosic wastes leads to the release of inhibitory compounds which adversely affect the growth and fermentation by S. cerevisae. S. cerevisiae also lacks the ability to grow at high temperatures which favour Simultaneous Saccharification and Fermentation of substrates to bioethanol. There is, therefore, a need for robust yeast species which can co-ferment hexose and pentose sugars and can tolerate high temperatures and the inhibitory substances produced during pre-treatment and hydrolysis of lignocellulosic materials. Non-conventional yeast strains are potential solutions to these problems due to their abilities to ferment both hexose and pentose sugars, and tolerate high temperature and stress conditions encountered during ethanol production from lignocellulosic hydrolysate. This review highlights the limitations of the conventional yeast species and the potentials of non-conventional yeast strains in commercialization of second generation bioethanol.

Infrared spectroscopy of an endohedral water in fullerene.

An infrared absorption spectroscopy study of the endohedral water molecule in a solid mixture of H2O@C60 and C60 was carried out at liquid helium temperature. From the evolution of the spectra during the ortho-para conversion process, the spectral lines were identified as para-H2O and ortho-H2O transitions. Eight vibrational transitions with rotational side peaks were observed in the mid-infrared: ω1, ω2, ω3, 2ω1, 2ω2, ω1 + ω3, ω2 + ω3, and 2ω2 + ω3. The vibrational frequencies ω2 and 2ω2 are lower by 1.6% and the rest by 2.4%, as compared to those of free H2O. A model consisting of a rovibrational Hamiltonian with the dipole and quadrupole moments of H2O interacting with the crystal field was used to fit the infrared absorption spectra. The electric quadrupole interaction with the crystal field lifts the degeneracy of the rotational levels. The finite amplitudes of the pure v1 and v2 vibrational transitions are consistent with the interaction of the water molecule dipole moment with a lattice-induced electric field. The permanent dipole moment of encapsulated H2O is found to be 0.50 ± 0.05 D as determined from the far-infrared rotational line intensities. The translational mode of the quantized center-of-mass motion of H2O in the molecular cage of C60 was observed at 110 cm-1 (13.6 meV).

Comparative effects of ascobin and glutathione on copper homeostasis and oxidative stress metabolism in mitigation of copper toxicity in rice.

Copper (Cu) pollution of agricultural land is a major threat to crop production. Exogenous chemical treatment is an easily accessible and rapid approach to remediate metal toxicity, including Cu toxicity in plants. We compared the effects of ascobin (ASC; ascorbic acid:citric acid at 2:1) and glutathione (GSH) in mitigation of Cu toxicity in rice. Plants subjected to Cu stress displayed growth inhibition and biomass reduction, which were connected to reduced levels of chlorophylls, RWC, total phenolic compounds, carotenoids and Mg2+ . Increased accumulation of ROS and malondialdehyde indicated oxidative stress in Cu-stressed plants. However, application of ASC or GSH minimized the inhibitory effects of Cu stress on rice plants by restricting Cu2+ uptake and improving mineral balance, chlorophyll content and RWC. Both ASC and GSH pretreatments reduced levels of ROS and malondialdehyde and improved activities of antioxidant enzymes, suggesting their roles in alleviating oxidative damage. A comparison on the effects of ASC and GSH under Cu stress revealed that ASC was more effective in restricting Cu2+ accumulation (69.5% by ASC and 57.1% by GSH), Ca2+ and Mg2+ homeostasis, protection of photosynthetic pigments and activation of antioxidant defence mechanisms [catalase (110.4%), ascorbate peroxidase (76.5%) and guaiacol peroxidase (39.0%) by ASC, and catalase (58.9%) and ascorbate peroxidase (59.9%) by GSH] in rice than GSH, eventually resulting in better protection of ASC-pretreated plants against Cu stress. In conclusion, although ASC and GSH differed in induction of stress protective mechanisms, both were effective in improving rice performance in response to Cu phytotoxicity.

Feasibility and Outcomes of Direct Dual Portal Vein Anastomosis in Living Donor Liver Transplantation Using the Right Liver Graft With Anatomic Portal Vein Variations.

BACKGROUND: Portal vein (PV) reconstruction is a crucial factor in successful living donor liver transplantation (LDLT). In LDLT using the right liver grafts with anatomic PV variations, we sometimes encounter dual PV anastomosis. In this study we describe PV variations of donor liver in detail as well as our experiences with PV reconstruction in right liver grafts with PV variations. METHODS: We performed LDLT in 149 recipients between 2002 and 2016. PV variations of donor liver were classified into 3 major anatomic patterns, and we retrospectively analyzed the procedure and postoperative complications of PV anastomosis. RESULTS: PV variations in donor livers were classified as type A (normal type) in 125 patients, type B (trifurcation type) in 7 (4.7%), and type C (caudal origin of the right posterior branch) in 17 (11.4%). Among 75 right liver grafts, 10 (13.3%) had anatomic PV variations. In 9 of 10 recipients, dual PV of the graft were anastomosed to dual PV branches of the recipient in direct end-to-end fashion. In the remaining recipient, the posterior portal branch of the graft was anastomosed to the recipient portal trunk through the interposed venous graft in end-to-end fashion and the anterior portal branch of the graft was anastomosed to the side wall of the interposed venous graft. These 10 recipients did not develop any postoperative complications associated with PV anastomosis, although 3 of the 149 recipients (2.0%) developed complications associated with PV anastomosis, such as thrombosis and necrosis. CONCLUSION: Dual PV anastomosis of the right liver graft is safe and feasible in LDLT, even in anatomic PV variations.

Intravenous Administration of Tacrolimus Stabilizes Control of Blood Concentration Regardless of CYP3A5 Polymorphism in Living Donor Liver Transplantation: Comparison of Intravenous Infusion and Oral Administration in Early Postoperative Period.

BACKGROUND: We compared achievement rate of sufficient tacrolimus blood concentration in the early postoperative period and incidence of acute cellular rejection within 1 month after living donor liver transplantation (LDLT) between tacrolimus intravenous (IV) and oral administration groups. METHODS: From October 2005 to November 2016, 61 LDLT patients administered tacrolimus, who could be genotyped for CYP3A5*3 and *1, were chosen from the electronic record database. The patients were then divided into the 2 groups (an IV group [n = 38] and an oral group [n = 23]). We defined patients with 1*1 or *1*3 as expressors and those with *3*3 as nonexpressors. Sufficient trough level tacrolimus blood concentration on postoperative day (POD) 3 was defined as 10-20 ng/mL. RESULTS: Comparable concentrations were seen between the 2 groups, with mean blood concentration 13.7 ± 8.5 ng/mL in the oral group and 15.2 ± 4.3 ng/mL in the IV group. Achievement rate of sufficient tacrolimus concentration on POD 3 was significantly higher in the IV group than in oral group: 97% (37 of 38) vs 65% (15 of 23), respectively (P = .001). When we focused on achievement rate in the oral group according to CYP3A5 polymorphism, the frequency of expressors (17%) was significantly lower than that of nonexpressors (82%) (P = .016). However, in the IV group this negative influence was totally eliminated, resulting in high achievement rates regardless of CYP3A5 polymorphism. In terms of incidence of acute cellular rejection, there was no significant difference between the 2 groups (IV 32% vs oral 17%, P = .250). CONCLUSION: IV administration of tacrolimus allowed us to obtain more stable control of blood concentration regardless of CYP3A5 genotype.

Early Enteral Feeding of Daikenchuto Stimulates Early Bowel Movement With Increased Portal Venous Blood Flow After Living Donor Liver Transplantation.

Daikenchuto (DKT), a Japanese Kampo medicine, had been reported to increase small intestinal blood flow after liver resection. The aim of this study was to evaluate the effects of early enteral feeding of DKT on portal venous flow and early bowel movement after living donor liver transplantation (LDLT) in an attempt to clarify whether these effects on bowel motility can prevent bacterial and/or fungal translocation. MATERIALS AND METHODS: Our prospective study included the consecutive 16 LDLT recipients at Mie University Hospital between June 2006 and September 2009. Sixteen patients were divided into the 2 groups according to enteral feeding starting postoperative day (POD) 1: 8 patients in DKT (15 g/d) administration (DKT group, for 1 week) and 8 patients in tepid water administration (non-DKT group, for 1 week). Portal venous flow, portal venous pressure, presence of fungal infection (serum level of ß-D-glucan and fungal polymerase chain reaction assay), time to first food intake, and time to first defecation were serially examined. RESULTS: Portal venous flow (mean [SD] velocity) was significantly increased in DKT group compared with non-DKT group: 47.5 (12.9) vs 31.8 (15.4) (P = .04) on POD 1, 46.8 (11.5) vs 28.8 (12.5) (P = .03) on POD 3, and 42.3 (17.2) vs 25.2 (9.0) (P = .05) on POD 5. However, mean (SD) portal venous pressures did not significantly change between the 2 groups. Between the 2 groups (DKT vs non-DKT), the day of first oral intake was not significantly different: 6.9 (2.5) vs 11.3 (8.7) (P = .061), but the mean (SD) day of first defecation was significantly shorter in the DKT group: 3.9 (1.1) vs 5.5 (2.6) (P = .02). Although fungal polymerase chain reaction assay was not significantly different between the 2 groups (4 vs 4 positive cases), the mean (SD) serum levels of ß-D-glucan were significantly lower in the DKT group than in the non-DKT group: 9.0 (7.4) vs 18.4 (15.9) pg/mL (P = .04). CONCLUSION: Early enteral feeding of DKT after LDLT increased portal vein blood flow without increasing portal vein pressure and stimulated early bowel movement, which in turn might prevent fungal translocation.

De Novo Malignancy Following Adult-to-Adult Living Donor Liver Transplantation Focusing on Posttransplantation Lymphoproliferative Disorder.

OBJECTIVE: In patients with living donor liver transplantation (LDLT), late-onset complications sometimes develop because of long-term use of immunosuppressive drugs. One of the immunosuppressive drug-related complications is de novo malignancies resulting in reduced survival. PATIENTS AND METHODS: Among 153 patients undergoing LDLT, we retrospectively reviewed the medical records of 97 adult recipients (February 2002 to May 2017), who had been followed-up at our hospital for more than one year after LDLT. The median age was 52 years old (20-70) and the median observational period was 6.9 years (2.4-15.3). RESULTS: De novo malignancy after adult LDLT developed in 11.3% (11/97) of patients, including posttransplantation lymphoproliferative disorder (PTLD) (n = 4) (2 in the brain and 2 in abdominal lymph nodes), lung cancer (n = 1), pancreatic cancer (n = 1), gastric cancer (n = 1), laryngeal cancer (n = 1), lower gingival cancer (n = 1), bladder cancer (n = 1), and melanoma (n = 1). Age at cancer diagnosis ranged from 36 to 70 years old with an average age of 61 years. The interval from LDLT to cancer diagnosis was 8.3 years (3.9-12.2). Four patients (36.6%) including PTLD (n = 2), lung cancer (n = 1), and pancreatic cancer (n = 1) died of cancer and all of them were diagnosed with cancer within 10 years after LDLT. Six patients were diagnosed with cancer more than 10 years after LDLT and all of them survived after treatment of cancer. CONCLUSION: De novo malignancy was found in 11.3% of LDLT patients, and more than half of this population subset developed tumors 10 years after LDLT. Long-term close follow-up should be performed by taking any kinds of de novo malignancy into consideration.

Biliary Complications During and After Donor Hepatectomy in Living Donor Liver Transplantation Focusing on Characteristics of Biliary Leakage and Treatment for Intraoperative Bile Duct Injury.

BACKGROUND: Biliary complication is one of the major donor complications during and after hepatectomy in living donor liver transplantation (LDLT). We evaluated risk factors for donor biliary complication in adult-to-adult LDLT. PATIENTS AND METHODS: From March 2002 to November 2016, 126 consecutive patients who underwent donor hepatectomy in adult-to-adult LDLT were divided into 2 groups according to biliary compilations: nonbiliary complication (non-BC) group (n = 114) and biliary complication (BC) group (n = 12). RESULTS: Among 126 donor hepatectomies, 35 patients (28%) experienced perioperative complications, including 10 (7.9%) with Clavien-Dindo classification grade III. Biliary complications occurred in 12 patients (9.5%): bile leakage in 10 and intraoperative bile duct injury in 2. Additional computed tomography- and/or ultrasound-guided drainage or exchange of original drain was required in 7 patients. In comparison between BC and non-BC groups, future remnant liver volume was significantly higher in the BC group than in the non-BC group (63% vs 40%; P = .02). In multivariate analysis, larger future remnant liver volume (P = .005) and shorter operating time (P = .02) were identified as independent risk factors for biliary complications. We had 2 patients with intraoperative bile duct injury: both were successfully treated by duct-to-duct biliary anastomosis with insertion of biliary stent or T-tube. CONCLUSION: Large remnant liver volume was a significant risk factor for biliary complications, especially biliary leakage, after donor hepatectomy. For intraoperative bile duct injury, duct-to-duct anastomosis with biliary stent is a feasible method to recover.

Recombinant Human Soluble Thrombomodulin Attenuates Hepatic Ischemia and/or Reperfusion Injury by Inhibiting Leukocyte Accumulation in Mice With Normal and Fatty Liver.

In an attempt to increase the number of donor livers, there has been an increased use of marginal donor livers, such as steatotic (fatty) livers that increase susceptibility to ischemia and reperfusion injury (IRI). Inflammatory cell accumulation has a greater role in IRI in steatotic liver than in normal liver. Although the recombinant human soluble thrombomodulin (rhsTM) attracts attention as a new treatment for disseminated intravascular coagulation, the therapeutic efficacy of rhsTM in hepatic IRI remains uncertain, especially in fatty livers. We aimed to demonstrate the effect of rhsTM on hepatic IRI using well-established in vivo experimental models with steatotic liver. METHODS: C57/BL6 mice were divided into 2 groups: normal liver (NL) group and fatty liver (FL) group, in which the steatotic liver was induced by high-fat diet for 9 weeks. The mice in the NL and FL groups were premedicated with venous injection of rhsTM (TM) or saline (Control) as control groups. All 4 groups (NL-Control vs NL-TM, FL-Control vs FL-TM) were subjected to partial hepatic warm ischemia followed by reperfusion. RESULTS: rhsTM significantly attenuated liver injury in the FL group as well as the NL group, as evidenced by transaminase levels and histologic finding after hepatic IRI. rhsTM remarkably decreased the accumulation of inflammatory cells, such as macrophages and neutrophils, in both NL and FL tissue after IRI. Furthermore, rhsTM depressed mRNA and protein expressions of adhesion molecules such as intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 in both NL and FL groups after IRI. CONCLUSION: Our results demonstrate that rhsTM has a protective effect on fatty liver as well as normal liver after hepatic IRI. They also suggest that rhsTM contributes to attenuation of leukocyte accumulation caused by depressing expressions of adhesion molecules that facilitate accumulation of leukocytes in liver tissue in hepatic IRI.

Isolated Biliary Fistula After Donor Right Hepatectomy and Its Novel Interventional Treatment: Isolated Liver-Punctured Drainage.

Isolated biliary leakage is difficult to manage, and afflicted patients often develop refractory fistula. The present case was a 43-year-old male donor whose wife developed acute fulminant liver failure. Computed tomography (CT) volumetry showed that the estimated remnant liver volume was only 394 mL (31%) if his right lobe would be harvested. Since remnant liver volume was marginal, our proposed cut line for the right hepatectomy was set in order to preserve branches of the middle hepatic vein draining segments 4b+8 and 5. Right hepatectomy was performed, but on postoperative day 14, the donor developed fever and right back pain, and enhanced CT showed a 6 cm intra-abdominal abscess at the site of cutting, and we diagnosed it as an isolated biliary fistula since the isolated segment 5/8 was receiving arterial blood supply and exhibiting regrowth. A transabdominal abscess drainage was performed, after which the patient lost 30 to 50 mL of bile juice per day in drainage until 2 months after the drainage procedure. Ethanol injection, acetic acid injection, and transarterial or portal embolization for the isolated liver were proposed, but these all were impossible to carry out because there were no accessible routes. Thus, re-abscess drainage with a 7-French drainage catheter was performed through the isolated liver on postoperative day 53, and the isolated functional liver was punctured to induce liver atrophy. After this drainage, the isolated liver started to shrink and bile output had been stopped. In conclusion, our punctured-liver drainage could be effective for the treatment of isolated biliary fistula, allowing physicians to avoid an invasive additional liver resection or other invasive percutaneous approach using chemical reagents.

Total hip arthroplasty after a previous pelvic osteotomy: A systematic review and meta-analysis.

BACKGROUND: There are several reports regarding total hip arthroplasty (THA) after a previous pelvic osteotomy (PO). However, to our knowledge, until now there has been no formal systematic review and meta-analysis published to summarize the clinical results of THA after a previous PO. Therefore, we conducted a systematic review and meta-analysis of results of THA after a previous PO. We focus on these questions as follows: does a previous PO affect the results of subsequent THA, such as clinical outcomes, operative time, operative blood loss, and radiological parameters. METHODS: Using PubMed, Web of Science, and Cochrane Library, we searched for relevant original papers. The pooling of data was performed using RevMan software (version 5.3, Cochrane Collaboration, Oxford, UK). A p-value<0.05 was judged as significant. Standardized mean differences (SMD) were calculated for continuous data with a 95% confidence interval (CI) was reported. Statistical heterogeneity was assessed based on I2 using standard χ2 test. When I2>50%, significant heterogeneity was assumed and a random-effects model was applied for the meta-analysis. A fixed-effects model was applied in the absence of significant heterogeneity. RESULTS: Eleven studies were included in this meta-analysis. The pooled results indicated that there was no significant difference in postoperative Merle D'Aubigne-Postel score (I2=0%, SMD=-0.15, 95% CI: -0.36 to 0.06, p=0.17), postoperative Harris hip score (I2=60%, SMD=-0.23, 95% CI: -0.50 to 0.05, p=0.10), operative time (I2=86%, SMD=0.37, 95% CI: -0.09 to 0.82, p=0.11), operative blood loss (I2=82%, SMD=0.23, 95% CI: -0.17 to 0.63, p=0.25), and cup abduction angle (I2=43%, SMD=-0.08, 95% CI: -0.25 to 0.09, p=0.38) between THA with and without a previous PO. However, cup anteversion angle of THA with a previous PO was significantly smaller than that of without a previous PO (I2=77%, SMD=-0.63, 95% CI: -1.13 to -0.13, p=0.01). CONCLUSION: Systematic review and meta-analysis of results of THA after a previous PO was performed. A previous PO did not affect the results of subsequent THA, except for cup anteversion. Because of the low quality evidence currently available, high-quality randomized controlled trials are required. LEVEL OF EVIDENCE: Level III, meta-analysis of case-control studies.

Evidence for the role of INSL3 on sperm production in boars by passive immunisation.

Insulin-like factor 3 (INSL3), previously called relaxin-like factor, is essential for foetal testis descent and has been implicated in sperm production in adult males. This study investigated the role of INSL3 in sperm production by examining the effect of neutralising INSL3 by passive immunisation on testicular function and sperm output in boars. Six male Duroc boars were randomly assigned to passive immunisation and control groups (n = 3 each). The immunisation group was intravenously injected with an IgG fraction of anti-INSL3 antibody developed against the B domain of INSL3 at 2-week intervals from 21-40 weeks of age. The control group was treated with normal IgG in the same manner. Antibody administration reduced testis weight and caused a fourfold increase in the frequency of apoptotic germ cells, which was associated with upregulation of the pro-apoptotic caspase 3 and BAX, and downregulation of the anti-apoptotic XIAP and BCL2, and a substantial marked reduction in sperm concentration. Neutralising INSL3 delivered by passive immunisation reduced testis weight and sperm concentration by inducing germ cell apoptosis, suggesting that INSL3 acts as a germ cell survival/anti-apoptotic factor in the maintenance of sperm production.

Surotomycin versus vancomycin in adults with Clostridium difficile infection: primary clinical outcomes from the second pivotal, randomized, double-blind, Phase 3 trial.

BACKGROUND: The available treatment options for Clostridium difficile infection (CDI) are limited by high recurrence rates. Surotomycin was a novel bactericidal cyclic lipopeptide in development to treat CDI that demonstrated non-inferiority to vancomycin in a Phase 2 trial. OBJECTIVES: To assess surotomycin safety and clinical response (non-inferiority versus vancomycin) at the end of treatment (EOT) of CDI. Additionally, to assess surotomycin response over time and sustained response at 30-40 days post-EOT (superiority versus vancomycin). PATIENTS AND METHODS: Patients with CDI were randomized (1:1) to receive twice-daily oral surotomycin 250 mg alternating with twice-daily placebo or four-times-daily oral vancomycin 125 mg for 10 days in this Phase 3, double-blind, multicentre, international trial. Clinical response over time and sustained clinical response were monitored until the end of the trial, through a follow-up period of 30-40 days. Clinical Trial Registration: NCT01598311. RESULTS: A total of 285 and 292 patients with confirmed CDI were randomized to receive surotomycin and vancomycin, respectively. Surotomycin-associated clinical response at EOT was non-inferior to vancomycin (surotomycin/vancomycin: 83.4%/82.1%; difference 1.4%, 95% CI - 4.9, 7.6). Following treatment with surotomycin, both clinical response over time (stratified log-rank test, P = 0.277) and sustained clinical response (63.3%/59.0%; difference 4.3%, 95% CI - 3.6, 12.2) did not demonstrate superiority versus vancomycin at end of trial. Both treatments were generally well tolerated. CONCLUSIONS: Surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at EOT. Surotomycin did not demonstrate superiority to vancomycin for clinical response over time or sustained clinical response rate.

Association of immunoglobulin G4 and free light chain with idiopathic pleural effusion.

The cause of pleural effusion remains uncertain in approximately 15% of patients despite exhaustive evaluation. As recently described immunoglobulin (Ig)G4-related disease is a fibroinflammatory disorder that can affect various organs, including the lungs, we investigate whether idiopathic pleural effusion includes IgG4-associated etiology. Between 2000 and 2012, we collected 830 pleural fluid samples and reviewed 35 patients with pleural effusions undiagnosed after pleural biopsy at Yamaguchi-Ube Medical Center. Importantly, IgG4 immunostaining revealed infiltration of IgG4-positive plasma cells in the pleura of 12 patients (34%, IgG4+ group). The median effusion IgG4 level was 41 mg/dl in the IgG4+ group and 27 mg/dl in the IgG4- group (P < 0·01). The light and heavy chains of effusion IgG4 antibodies of patients in the IgG4+ group were heterogeneous by two-dimensional electrophoresis, indicating the absence of clonality of the IgG4 antibodies. Interestingly, the κ light chains were more heterogeneous than the λ light chains. The measurement of the κ and λ free light chain (FLC) levels in the pleural fluids showed significantly different κ FLC levels (median: 28·0 versus 9·1 mg/dl, P < 0·01) and κ/λ ratios (median: 2·0 versus 1·2, P < 0·001) between the IgG4+ and IgG4- groups. Furthermore, the κ/λ ratios were correlated with the IgG4+ /IgG+ plasma cell ratios in the pleura of the IgG4+ group. Taken together, these results demonstrate the involvement of IgG4 in certain idiopathic pleural effusions and provide insights into the diagnosis, pathogenesis and therapeutic opportunities of IgG4-associated pleural effusion.

Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study.

BACKGROUND: Ustekinumab, a fully human monoclonal antibody against interleukin-12/23, may potentially be effective for severe atopic dermatitis (AD) treatment. OBJECTIVES: To evaluate efficacy and safety of ustekinumab 45 mg and 90 mg in patients with severe AD. METHODS: In this randomized, placebo-controlled, phase II study, Japanese patients (aged 20-65 years) with severe or very severe AD entered a 12-week double-blind treatment period during which they received (1 : 1 : 1) ustekinumab 45 mg, 90 mg or placebo subcutaneous injections at weeks 0 and 4, with follow-up until week 24. The primary efficacy end point was percentage change from baseline in Eczema Area and Severity Index (EASI) score at week 12. Major secondary efficacy end points included the proportion of patients achieving EASI 50, EASI 75, Investigator's Global Assessment score 0-1, change from baseline Atopic Dermatitis Itch Scale and Dermatology Life Quality Index. RESULTS: A total of 79 patients were randomized [ustekinumab 45 mg (n = 24), 90 mg (n = 28), placebo (n = 27)]. Ustekinumab treatment showed nonsignificant improvement in least square mean change from baseline EASI score at week 12 [45 mg: -38·2%, 95% confidence interval (CI) -21·02-19·51; P < 0·94 and 90 mg: -39·8%, 95% CI -21·84-17·14; P < 0·81] vs. placebo (-37·5%). A nonsignificant improvement in major secondary efficacy end points was observed in both ustekinumab groups vs. placebo. The most common treatment-emergent adverse events were nasopharyngitis and worsened AD (higher in placebo vs. ustekinumab groups). CONCLUSIONS: Ustekinumab 45 mg and 90 mg did not demonstrate meaningful efficacy in Japanese patients with severe AD. The treatment was generally well tolerated.

Pretransplant Serum Hyaluronic Acid Can Be a Biomarker as a Prognostic Predictor in Adult-to-Adult Living Donor Liver Transplantation.

OBJECTIVE: The goal of this study was to evaluate whether pretransplant serum hyaluronic acid (HA) levels can predict outcomes after adult-to-adult living donor liver transplantation (LDLT). METHODS: In study I, 21 patients who underwent LDLT (March 2002-February 2004) were divided into 2 groups: the H-I group (HA ≥500 ng/mL; n = 12) and the L-I group (HA <500 ng/mL; n = 9). The influence of pretransplantation HA levels on short-term surgical outcome was investigated. In study II, 77 LDLT patients (May 2004-December 2014) were also divided into 2 groups: the H-II group (HA ≥500 ng/mL; n = 40) and the L-II group (HA <500 ng/mL; n = 37). We compared long-term survival and investigated prognostic factors. RESULTS: In study I, HA levels significantly decreased after LDLT, and those in the H-I group were significantly higher compared with the L-I group at 1, 3, 5, and 7 days after LDLT. There were significant differences in postoperative peak total bilirubin levels (H-I vs L-I, 17.2 vs 6.2 mg/dL; P = .013), peak ascitic fluid volume (1327 vs 697 mL/d; P = .005), and the hepatocyte growth factor levels at 3 days after LDLT (1879 vs 1092 pg/mL; P = .03). In study II, the 1- and 5-year survival rates were significantly lower in the H-II group than in the L-II group (H-II vs L-II, 65.0% and 48.5% vs 86.5% and 80.8%; P = .004). In multivariate analysis, significant prognostic factors were preoperative HA ≥500 ng/mL (P = .004) and graft to recipient body weight ratio <0.8 (P = .042). CONCLUSIONS: Preoperative HA level can be a prognostic risk factor. Patients with high HA levels are vulnerable and should be carefully managed after LDLT.

Heterogeneous nucleation of catalyst-free InAs nanowires on silicon.

We report on the heterogeneous nucleation of catalyst-free InAs nanowires on Si(111) substrates by chemical beam epitaxy. We show that nanowire nucleation is enhanced by sputtering the silicon substrate with energetic particles. We argue that particle bombardment introduces lattice defects on the silicon surface that serve as preferential nucleation sites. The formation of these nucleation sites can be controlled by the sputtering parameters, allowing the control of nanowire density in a wide range. Nanowire nucleation is accompanied by unwanted parasitic islands, but careful choice of annealing and growth temperature allows us to strongly reduce the relative density of these islands and to realize samples with high nanowire yield.

D-MELD, the Product of Donor Age and Preoperative MELD, Predicts Surgical Outcomes After Living Donor Liver Transplantation, Especially in the Recipients With HCV-positive and Smaller Grafts.

BACKGROUND: Appropriate donor-recipient match has not been explored well in living-donor liver transplantation (LDLT) unlike deceased-donor liver transplantation. In this study, we evaluate the donor-recipient match using D-MELD (donor age × recipient Modified for End-stage Liver Disease [MELD] score) as a predictor of surgical outcomes in LDLT, paying attention to graft size and hepatitis C virus (HCV) status. PATIENT AND METHODS: The 120 consecutive recipients who received adult-to-adult LDLT from March 2002 to December 2014 were divided into the two groups according to D-MELD score: D-MELD <1000 (low-D-MELD: n = 101) and D-MELD ≥1000 (high-D-MELD: n = 19). RESULTS: The 90-day mortality rate was significantly higher in the high-DM group than in low-DM group: 36.8% versus 14.9% (P = .046). In the HCV-positive recipients, the 90-day mortality rate was significantly higher in high-DM group (n = 6) than in low-DM group (n = 37): 66.7% versus 13.5% (P = .012), and the 3-year survival rate was significantly lower in high-DM group than in the low-DM group: 33.3% versus 56.8% (P = .01). In the recipients with left graft, the 90-day mortality rate was significantly higher in the high-DM group (n = 8) than in the low-DM group (n = 41): 50% versus 14.6% (P = .044), and total bilirubin level on postoperative day 14 was significantly higher in the high-DM group than in the low-DM group: 17.4 mg/dL versus 9.2 mg/dL (P = .018). CONCLUSIONS: It was clarified that D-MELD could predict early and long-term surgical outcomes in the recipients who were HCV-positive and who had smaller grafts.

Long-Term Influence of CYP3A5 Gene Polymorphism on Pharmacokinetics of Tacrolimus and Patient Outcome After Living Donor Liver Transplantation.

BACKGROUND: We investigated a long-term association between donor/recipient CYP3A5 polymorphisms, pharmacokinetics of tacrolimus, and recipient outcomes in settings of living donor liver transplantation (LDLT). METHODS: From February 2002 to November 2009, 67 couples of donor/recipients with tacrolimus administration, who could be genotyped for CYP3A5*3 and *1, were eligible in this study. We compared the dose-adjusted trough levels (C/D ratio) and dose/weight ratio of tacrolimus at 1 to 36 months postoperatively and recipient prognosis according to donor/recipient CYP3A5 polymorphisms; *1*1 in 7, *1*3 in 15, and *3*3 in 45, based on recipient genotype, and *1*1 in 1, *1*3 in 28, and *3*3 in 38, based on donor genotype. RESULTS: On the basis of the data from C/D ratio and dose/weight ratio of tacrolimus, the recipients who had *1 allele and/or whose donor had *1allele required significantly high doses of tacrolimus with, compared with those without, all through 3 years after transplantation. These data allowed us to show the importance of not only recipient CYP3A5 polymorphisms but also donor polymorphisms to obtain the target tacrolimus blood concentration. The overall survival rates of the recipients with *1*1 (5-year survival rate: 28.6%) were significantly unfavorable, which might have been caused by over-immunosuppression, compared with those with *1*3 (5-year survival rate: 78.8%) and *3*3 genotype (5-year survival rate: 84.3%). CONCLUSIONS: Immune suppressive therapy with the use of tacrolimus should be tailored on the basis of CYP3A5 genotype, which may reduce the adverse effects and improve graft outcome.