The use of cassava leaf silage as a substitute for concentrate feed in sheep.

We aimed to evaluate nutrient intake, performance and rumen fermentation of sheep fed cassava leaf silage (CLS). Sixteen growing Java thin-tailed male sheep (body weight (BW) 20.4 ± 1.9 kg) were fed one of the following dietary treatments: T0 (100 % forage); T1 (100 % chopped forage); T2 (80 % chopped forage + 20 % concentrate); and T3 (80 % chopped forage + 20 % CLS). Nutrient intake, production performance and rumen fermentation characteristics were measured. There was no significant effect on the consumption of dry matter, whereas there was a significant effect (P < 0.05) on the consumption of crude protein, fat, crude fibre and total digestible nutrients. Concentrate or CLS at a 20 % level could increase BW and feed efficiency. No significant difference was observed in total bacteria; however, concentrate could increase total protozoa (P < 0.05). Total volatile fatty acids were higher in T2 than in T3, but ammonia concentration was higher in T3 than in T2. In conclusion, feeding 20 % cassava leaf silage greatly improved sheep performance, approaching that achieved by feeding concentrate.

Genome-wide association study identifies a potent locus associated with human opioid sensitivity.

Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity. By conducting a multistage genome-wide association study (GWAS) in healthy subjects, we found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate single-nucleotide polymorphism (SNP), rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. These results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence.

Transmission electron microscopy of thick polymer and biological specimens.

We explore the properties of elastic and inelastic scattering in a thick organic specimen, together with the mechanisms that provide contrast in a transmission electron microscope (TEM) and scanning-transmission electron microscope (STEM). Experimental data recorded from amorphous carbon are used to predict the bright-field image intensity, mass-thickness contrast and dose-limited resolution as a function of thickness, objective-aperture size, and primary-electron energy E0. Combining this information with estimates of chromatic aberration, objective-aperture diffraction and beam broadening in the specimen, we calculate the achievable TEM and STEM resolution to be around 4 nm at E0 = 300 keV (or below 3 nm at MeV energies) for a 10 µm-diameter objective aperture and 1 - 2 µm thickness of hydrated biological tissue. The 3 MeV resolution for a 10-µm tissue sample is probably closer to 10 nm. We also comment on the error involved in quadrature addition of resolution factors, when one or more of the point-spread functions are non-Gaussian.

SADS: A new component of Fas-DISC is the accelerator for cell death signaling and is downregulated in patients with colon carcinoma.

Fas is the death receptor, transducing cell death signaling upon stimulation by Fas ligand. During Fas-initiated cell death signaling, the formation of Fas-death inducing signaling complex (Fas-DISC) is the first step. Here we have identified a new component of Fas-DISC which we call 'small-accelerator for death signaling' (SADS). SADS cDNA encodes a 150 amino acid polypeptide (Mr = 16,700). During Fas-mediated cell death, SADS enhances the interaction of Fas-death domain-interactive factors (FADD) and procaspase-8, and deletion mutant analysis has identified FADD- and caspase-8-interactive domains in SADS. Inhibition or removal of SADS delays Fas-mediated cell death. In addition, we demonstrate the deletion or mutation of SADS in patients with colon carcinoma and that exogenous SADS expression in human colon carcinoma SW480 cells that lack SADS leads to re-acquisition of Fas-mediated cell death. Here, we propose that SADS is one of the cell death-associated factors and enhances Fas-DISC formation, especially FADD and procaspase-8 recruitment.

Morphologic changes in hepatitis virus-related liver cirrhosis: Relationship to hemodynamics of portal vein on dynamic contrast-enhanced CT.

INTRODUCTION: The morphologic changes in the compensated stage of liver cirrhosis (cLC) are not diffuse atrophic changes. With cLC lobar or segmental changes combined with atrophy of the right lobe and medial segment together with hypertrophy of the caudate lobe and lateral segment are commonly seen. The purpose of this study was to evaluate the morphologic changes in hepatitis virus-related liver cirrhosis in relationship to haemodynamics of the portal vein on dynamic contrast-enhanced computed tomography (DCE-CT) METHODS: This study included 72 patients, 46 with hepatitis virus-related cirrhosis and 26 with a normally functioning liver, who underwent DCE-CT. In cirrhosis patients, the morphologic change index (MCI) of the liver was calculated and categorised into two groups, high-MCI (MCI ≥ 0.4) (n = 21) and low-MCI (MCI < 0.4) (n = 25). Cross-sectional areas of the main, right and left portal veins and the intra-portal distribution from splenic venous flow were evaluated for their relationships with the MCI and compared among three groups (normal-control, low MCI and high MCI). RESULTS: There was a significant difference in the cross-sectional area of the left portal vein between the high-MCI group and the low-MCI group (p = 0.013) and the control group (p = 0.008). A significant correlation was identified between the cross-sectional area of the left portal vein and the MCI (r = 0.508, p < 0.001). CONCLUSION: Cross-sectional area of the left portal vein may be a factor related to morphologic changes in hepatitis virus-related liver cirrhosis and could be a possible index of the left portal venous flow volume. IMPLICATIONS FOR PRACTICE: This study may be useful for predicting the degree of hepatic morphologic changes and the condition of cirrhosis in association with regional hepatic morphologic changes.

Living donor liver transplantation for neonates using segment 2 monosubsegment graft.

The prognosis of liver transplantation for neonates with fulminant hepatic failure (FHF) continues to be extremely poor, especially in patients whose body weight is less than 3 kg. To address this problem, we have developed a safe living donor liver transplantation (LDLT) modality for neonates. We performed LDLTs with segment 2 monosubsegment (S2) grafts for three neonatal FHF. The recipient age and body weight at LDLT were 13-27 days, 2.59-2.84 kg, respectively. S2 or reduced S2 grafts (93-98 g) obtained from their fathers were implanted using temporary portacaval shunt. The recipient portal vein was reconstructed at a more distal site, such as the umbilical portion, to have the graft liver move freely during hepatic artery (HA) reconstruction. The recipient operation time and bleeding were 11 h 58 min-15 h 27 min and 200-395 mL, respectively. The graft-to-recipient weight ratio was 3.3-3.8% and primary abdominal wall closure was possible in all cases. Although hepatic artery thrombosis occurred in one case, all cases survived with normal growth. Emergency LDLT with S2 grafts weighing less than 100 g can save neonates with FHF whose body weight is less than 3 kg. This LDLT modality using S2 grafts could become a new option for neonates and very small infants requiring LT.

Omega-3 polyunsaturated fatty acids and psychological intervention for workers with mild to moderate depression: A double-blind randomized controlled trial.

BACKGROUND: This study assessed whether a combined intervention of omega-3 polyunsaturated fatty acids (PUFAs) and psychoeducation better improved mild to moderate depression in workers compared to psychoeducation alone. METHODS: This study was a double-blinded, parallel group, randomized controlled trial that compared the intervention group, receiving omega-3 fatty acids, with a control group, receiving a placebo supplement. Participants receiving omega-3 fatty acids took 15 × 300 mg capsules per day for 12 weeks. The total daily dose of omega-3 PUFAs was 500 mg docosahexaenoic acid and 1000 mg eicosapentaenoic acid (EPA). The Beck Depression Inventory®-II (BDI-II) was used to assess the severity of depression after treatment. RESULTS: After 12 weeks of treatment, BDI-II scores were significantly lower in the placebo and omega-3 group, when compared to their respective baseline scores (Placebo: t = - 4.6, p < 0.01; Omega-3: t = - 7.3, p < 0.01). However, after 12 weeks of treatment, we found no significant difference between both groups with respect to changes in the BDI-II scores (0.7; 95% CI, - 0.7 to 2.1; p = 0.30). LIMITATIONS: This study did not measure blood omega-3 fatty acid concentration and presented a high-dropout rate. Moreover, our results may not be generalizable to other regions. CONCLUSIONS: The results show that a combination of omega-3 fatty acids and psychoeducation and psychoeducation alone can contribute to an improvement in symptoms in people with mild to moderate depression. However, there is no difference between the interventions in ameliorating symptoms of depression.

Effect of attention bias modification on brain function and anxiety in patients with irritable bowel syndrome: A preliminary electroencephalogram and psycho-behavioral study.

BACKGROUND: Gastrointestinal symptoms of irritable bowel syndrome (IBS) show a reciprocal relationship with anxiety. In this intervention-based study, we investigated the utility of attention bias modification (ABM) therapy in patients with IBS. We hypothesized that IBS-related electroencephalographic abnormalities would be normalized after ABM therapy. METHODS: Seventeen patients with IBS and 13 healthy subjects completed five ABM intervention sessions over a 2-month period. Each session included 128 ABM trials, resulting in a total of 640 trials across the intervention period. For each trial, subjects viewed a pair of facial expression images and were instructed to indicate the position of the neutral face as quickly and accurately as possible by pressing one of two buttons on a button box. Electroencephalography data (alpha and beta power percentages) were collected during the 1st and 5th sessions. KEY RESULTS: Generalized estimating equations of relative alpha power revealed a significant effect of period was identified at O2 (P=.036). Paired t tests revealed that ABM significantly increased relative alpha power at O2 in patients with IBS. Generalized estimating equation of relative beta power revealed a significant effect of the group × period interaction was identified at Pz (P=.035). Paired t tests revealed that ABM significantly decreased relative beta power at Pz in patients with IBS. CONCLUSIONS & INFERENCES: Attention bias modification may normalize brain function related to attention and anxiety in patients with IBS.

Relationship between real-time monitoring of the graft motility and mucosal histology in swine intestinal transplantation.

We studied the correlation between the motility and the mucosal histology of the small bowel seeking to detect rejection in an early stage by real-time monitoring using a swine model. Intestinal transplantation (ITx) was performed orthotopically using FK506 immunosuppression. The distal about 20 cm segment of the allograft was exteriorized as a Thiry-Vella stoma for biopsies. Strain gauge (SG) force transducers were attached to the graft for real-time monitoring of graft motility. Pigs without ITx were used as controls (group 1). Rejection was classified into four groups by histologic findings: nonrejection (group 2), mild rejection (group 3), moderate rejection (group 4), and severe rejection (group 5). Migrating motor complex (MMC) phase III was analyzed for the following parameters: duration, amplitude, interval, motility index, velocity, and frequency of propagation. In group 2, all parameters were almost the same as those for group 1. In contrast, groups 4 and 5 showed most parameters significantly lower than those in group 1. In group 3, the contractility of the MMC was not significantly altered, but the frequency of the propagation was decreased significantly. In conclusion, graft motility detected by a real-time SG method correlated with the grade of mucosal histology. This method is useful to detect rejection at an early stage by examining the frequency of MMC propagation.

Growth inhibition by progestins in a human endometrial cancer cell line with estrogen-independent progesterone receptors.

The presence of estrogen-independent progesterone receptors (PgR) was demonstrated in a subline of a human endometrial cancer cell line, Ishikawa cells, although the original Ishikawa cells contained estrogen-inducible PgR. Scatchard plot analysis of cytoplasmic binding data in our subline (IK-90) revealed a high affinity binding site for R5020 (Kd, 1.0 nM) with maximum binding sites of 158 fmol/mg protein. Competition experiments showed a binding specificity similar to that of typical PgR. By low-salt sucrose gradient centrifugation, radioactive 8S and 4S peaks were found. The addition of 1 microM progesterone in culture medium resulted in a rapid nuclear translocation of cytoplasmic PgR. In contrast to the original cells, estrogen receptors could not be detected in IK-90 cells, and an addition of 17 beta-estradiol (10 nM) to culture medium failed to increase PgR. Accumulation of glycogen in cytoplasm of IK-90 cells in response to R5020 (0.1-1 microM) was observed by periodic acid-Schiff staining. The addition of R5020 to culture medium (0.1-1 microM) also caused a marked decrease in the growth of IK-90 cells, whereas the other steroids including 17 beta-estradiol, tamoxifen, testosterone, and cortisol had no significant effects. These results demonstrate for the first time the presence of a progestin-responsive human endometrial cancer cell line that contains estrogen-independent functional PgR. IK-90 cells appear to be an ideal model for studying the mechanism of the antiproliferative effect of progestin on endometrial cancer cells.

Minimally Invasive Laminate Veneers: Clinical Aspects in Treatment Planning and Cementation Procedures.

When a definitive aesthetic treatment is determined, it is crucial to grant the patient's wish with the necessary dental treatment. Thus, conservative treatments that are the solution to aesthetic problems involving morphologic modifications and provide the result that the patient expects should always be the first therapeutic option. In this context, ceramic laminate veneers, also known as "contact lens," are capable of providing an extremely faithful reproduction of the natural teeth with great color stability and periodontal biocompatibility. Minimal or no preparation veneers are heavily advertised as the answer to our patients' cosmetic needs, which they can be if they are used correctly in the appropriate case. This report is about ultraconservative restorations to achieve functional and aesthetic rehabilitation through treatment planning. Thus, clinicians should be aware that the preparation for laminate veneers remains within enamel, to ensure the bond strength and avoid or minimize the occurrence of postoperative sensitivity.

Survivin initiates cell cycle entry by the competitive interaction with Cdk4/p16(INK4a) and Cdk2/cyclin E complex activation.

Survivin is observed uniquely in tumor cells and developmental cells, which undergo either inappropriate or programmed cell growth. In the current study, we investigated the influence of Survivin on cell cycle. Overexpression of Survivin resulted in accelerated S phase shift, resistance to G1 arrest, and activated Cdk2/Cyclin E complex leading Rb phosphorylation. In addition, nuclear translocation of Survivin followed by an interaction with Cdk4 was detected. Interestingly, Survivin nuclear translocation coincided with S phase shift, and prevention of nuclear transport suppressed Survivin nuclear translocation and S phase shift. Further, we also observed that Survivin competitively interacted with the Cdk4/p16(INK4a) complex in a cell free system and in vivo. These results suggest that Survivin initiates the cell cycle entry as a result of nuclear translocation followed by an interaction with Cdk4.

Survivin initiates procaspase 3/p21 complex formation as a result of interaction with Cdk4 to resist Fas-mediated cell death.

Caspase 3 is an essential death factor for the Fas-mediated cell death, and its inactivation in cells is initiated by an interaction with p21 on mitochondria or with IAP family member ILP. Survivin is also a member of IAP family and is specifically expressed during embryogenesis and in tumor cells and suppresses cell death signaling. In our current study, we demonstrated that Survivin translocation into the nucleus is dependent on Fas stimulation and cell proliferation. Survivin also interacts with the cell cycle regulator Cdk4, leading to Cdk2/Cyclin E activation and Rb phosphorylation. As a result of Survivin/Cdk4 complex formation, p21 is released from its complex with Cdk4 and interacts with mitochondrial procaspase 3 to suppress Fas-mediated cell death. Here, we propose that Survivin supports procaspase 3/p21 complex formation as a result of interaction with Cdk4 resulting in suppression of cell death signaling.

Procaspase 3/p21 complex formation to resist fas-mediated cell death is initiated as a result of the phosphorylation of p21 by protein kinase A.

Caspase 3 is an essential factor for Fas-mediated cell death and exists endogenously in cells where its activation is suppressed by p21 and ILP. Inside the cell, procaspase 3 interacts with p21 on mitochondria. In the present study, we investigated the molecular basis for procaspase 3/p21 complex formation. During Fas-mediated cell death, mitochondria are damaged, accompanied by decreased mitochondrial membrane-potential and decreased intracellular ATP levels. This mitochondrial damage occurs before an estrangement of the procaspase 3/p21 complex, and we demonstrate that intracellular ATP-deprivation also initiates an estrangement of procaspase 3/p21 complex formation and accelerates Fas-mediated cell death. In addition, our current results revealed that the phosphorylated p21 by PKA interacts with procaspase 3. Here, we report that the mitochondrial role, especially for ATP synthesis, and PKA are necessary for the procaspase 3/p21 complex formation to resist Fas-mediated cell death.

Naltrexone in the treatment of alcohol dependence.

Seventy male alcohol-dependent patients participated in a 12-week, double-blind, placebo-controlled trial of naltrexone hydrochloride (50 mg/d) as an adjunct to treatment following alcohol detoxification. Subjects taking naltrexone reported significantly less alcohol craving and days in which any alcohol was consumed. During the 12-week study, only 23% of the naltrexone-treated subjects met the criteria for a relapse, whereas 54.3% of the placebo-treated subjects relapsed. The primary effect of naltrexone was seen in patients who drank any alcohol while attending outpatient treatment. Nineteen (95%) of the 20 placebo-treated patients relapsed after they sampled alcohol, while only eight (50%) of 16 naltrexone-treated patients exposed to alcohol met relapse criteria. Naltrexone was not associated with mood changes or other psychiatric symptoms. Significant side effects (nausea) occurred in two naltrexone-treated subjects, and one naltrexone-treated subject complained of increased pain from arthritis. These results suggest that naltrexone may be a safe and effective adjunct to treatment in alcohol-dependent subjects, particularly in preventing alcohol relapse.

Alcohol and aldehyde dehydrogenase polymorphisms and the risk for alcoholism.

OBJECTIVE: The authors studied a large number of Japanese alcoholic patients and comparison subjects to establish the genotype frequencies of alcohol dehydrogenase-2 (ADH2) and mitochondrial aldehyde dehydrogenase (ALDH2) and to quantify the relative risk for alcoholism from the results. METHOD: The subjects were 655 alcoholic patients and 461 comparison subjects. ADH2 and ALDH2 were genotyped by the combination of polymerase chain reaction and hybridization methods. RESULTS: Active ALDH2 and usual ADH2 were significantly more frequent in the alcoholic patients. Inactive ALDH2 was not always associated with a low risk of alcoholism, and active ALDH2 was not always associated with high risk. In individuals with heterozygous inactive ALDH2 and usual ADH2, the odds ratio for alcoholism was high. CONCLUSIONS: The risk for alcoholism in Japanese has been accurately estimated on the basis of the genotype frequencies of ADH2 and ALDH2. Many Japanese may be protected from alcoholism by inactive ALDH2 and by higher frequencies of atypical ADH2.

Apolipoprotein E epsilon 4 allele and pupillary response to tropicamide.

OBJECTIVE: This study was designed to investigate in cognitively normal subjects the possible association between hypersensitive pupil dilation response to the cholinergic antagonist tropicamide and the presence of the apolipoprotein E epsilon 4 (APOE4) allele, a well-defined genetic risk factor for Alzheimer's disease. METHOD: The authors measured tropicamide-induced changes in pupil area in 44 cognitively normal Japanese subjects with and without the APOE4 allele. RESULTS: The subjects with the APOE4 allele had significantly greater increases in pupil area than the others. The significant correlation of changes in pupil area with age for the subjects with the APOE4 allele was lacking for those without this allele. CONCLUSIONS: The results suggest that a hypersensitive pupil dilation response to tropicamide is already present in cognitively normal individuals with the APOE4 allele. This association also suggests the potential involvement of APOE4 in the mechanism of pupil dilation.

Lethal catatonia.

Lethal catatonia, a life-threatening febrile neuropsychiatric disorder, was widely reported in this country and abroad before the introduction of modern psychopharmacologic treatments. A comprehensive review of the world literature indicates that although the prevalence of lethal catatonia may have declined, it continues to occur, now reported primarily in the foreign literature. Lack of recognition probably accounts for the scarcity of recent American reports. Furthermore, lethal catatonia is a syndrome rather than a specific disease and may develop in association with both functional and organic illnesses. Familiarity with the clinical features and varied etiologies is essential for effective management of this catastrophic reaction.