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.

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.

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.

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.

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.

Fermi LARGE AREA TELESCOPE OBSERVATIONS OF BLAZAR 3C 279 OCCULTATIONS BY THE SUN.

Observations of occultations of bright γ-ray sources by the Sun may reveal predicted pair halos around blazars and/or new physics, such as, e.g., hypothetical light dark matter particles-axions. We use Fermi Gamma-Ray Space Telescope (Fermi) data to analyze four occultations of blazar 3C 279 by the Sun on October 8 each year from 2008 to 2011. A combined analysis of the observations of these occultations allows a point-like source at the position of 3C 279 to be detected with significance of ≈3σ, but does not reveal any significant excess over the flux expected from the quiescent Sun. The likelihood ratio test rules out complete transparency of the Sun to the blazar γ-ray emission at a 3σ confidence level.

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.

High-precision alignment of electron tomography tilt series using markers formed in helium-ion microscope.

Tungsten nanodots formed in a helium-ion microscope (HIM) provide a practical means of aligning markers of electron tomography tilt series with a high degree of precision. The nanodots were formed using a HIM equipped with a W(CO)6 gas injection system, enabling the precise placement of the nanodots at desired locations of a sample. Template matching was applied to the markers formed in the HIM to detect the positions automatically. The relation between the positions of the markers and the accuracy of the alignment was also determined in order to achieve precise alignment. The method was applied to the markers in order to reconstruct three-dimensional (3D) images of a rod-shaped specimen that contained a 65-nm-diameter via structure in a Cu/Low-k interconnect.

Living-donor liver transplantation in 126 patients with biliary atresia: single-center experience.

OBJECTIVES: To describe our experience with 126 consecutive living-donor liver transplantation (LDLT) procedures performed because of biliary atresia and to evaluate the optimal timing of the operation. PATIENTS AND METHODS: Between May 2001 and January 2010,126 patients with biliary atresia underwent 130 LDLT procedures. Mean (SD) patient age was 3.3 (4.2) years, and body weight was 13.8 (10.7) kg. Donors included 64 fathers, 63 mothers, and 3 other individuals. The left lateral segment was the most commonly used graft (75%). Patients were divided into 3 groups according to body weight: group 1, less than 8 kg (n = 40); group 2,8 to 20 kg (n = 63); and group 3, more than 20 kg (n = 23). Medical records were reviewed retrospectively. Follow up was 4.5 (2.7) years. RESULTS: All group 3 donors underwent left lobectomy, and all group 1 donors underwent left lateral segmentectomy. No donors required a second operation or died. Comparison of the 3 groups demonstrated that recipient Pediatric End-Stage Liver Disease score in group 1 was highest, operative blood loss in group 2 was lowest (78 mL/kg), and operative time in group 3 was longest (1201 minutes). Hepatic artery complications occurred more frequently in group 1 (17.9%), and biliary stenosis (43.5%) and gastrointestinal perforation (8.7%) occurred more frequently in group 3. The overall patient survival rates at 1, 5, and 9 years was 98%, 97%, and 97%, respectively. Five-year patient survival rate in groups 1,2, and 3 were 92.5%, 100%, and 95.7%, respectively. Gastrointestinal perforation (n = 2) was the primary cause of death. CONCLUSIONS: Living-donor liver transplantation is an effective treatment of biliary atresia, with good long-term outcome. It seems that the most suitable time to perform LDLT to treat biliary atresia is when the patient weighs 8 to 20 kg.

Management of intra-abdominal drain after living donor liver transplantation.

BACKGROUND: There have been few reports on the management of intra-abdominal drains after living donor liver transplantation (LDLT). We retrospectively investigated changes in ascitic data related to management of an intra-abdominal drain. PATIENTS AND METHODS: Between March 2008 and June 2009, we performed 28 LDLT. On the first and the fifth postoperative day (POD) after LDLT, we examined the number of ascites cells and cell fractions as well as performed biochemical examination and cultures. RESULTS: The day of removal of the drain for massive ascites (10 mL/kg/d or more) was 14.2 ± 5.4 POD; for less than 10 mL/kg/d it was 8.7 ± 1.9 POD (P < .001). Nine patients were ascites culture positive; long-term placement of the drain caused an infection in two patients. CONCLUSIONS: When the amount of ascitic fluid on the fifth POD after LDLT was small, it was important to assess the properties of the ascitic fluid because of the possibility of a drain infection or of poor drainage. If the ascitic neutrophil count is less than 250/mm(3) or the examined ascites is normal, intra-abdominal drains should be removed.

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.

The role of internal duplication in the evolution of multi-domain proteins.

Many proteins consist of several structural domains. These multi-domain proteins have likely been generated by selective genome growth dynamics during evolution to perform new functions as well as to create structures that fold on a biologically feasible time scale. Domain units frequently evolved through a variety of genetic shuffling mechanisms. Here we examine the protein domain statistics of more than 1000 organisms including eukaryotic, archaeal and bacterial species. The analysis extends earlier findings on asymmetric statistical laws for proteome to a wider variety of species. While proteins are composed of a wide range of domains, displaying a power-law decay, the computation of domain families for each protein reveals an exponential distribution, characterizing a protein universe composed of a thin number of unique families. Structural studies in proteomics have shown that domain repeats, or internal duplicated domains, represent a small but significant fraction of genome. In spite of its importance, this observation has been largely overlooked until recently. We model the evolutionary dynamics of proteome and demonstrate that these distinct distributions are in fact rooted in an internal duplication mechanism. This process generates the contemporary protein structural domain universe, determines its reduced thickness, and tames its growth. These findings have important implications, ranging from protein interaction network modeling to evolutionary studies based on fundamental mechanisms governing genome expansion.

Effect of cardiopulmonary resuscitation on intubation using a Macintosh laryngoscope, the AirWay Scope, and the gum elastic bougie: A manikin study.

BACKGROUND: Physicians could encounter difficult intubation during cardiopulmonary resuscitation (CPR) in trauma patients due to the patient's movement from continuous chest compression and to cervical stabilisation. Therefore, first, we evaluated the impact of chest compression with or without cervical stabilisation on intubation with a Macintosh laryngoscope. Next, we compared difficulty in intubation among the Macintosh laryngoscope, AirWay Scope (AWS), and gum elastic bougie (GEB) with the Macintosh laryngoscope in three simulated CPR scenarios in a randomised, controlled, cross-over study design. METHODS: Twenty-three anaesthetists intubated the trachea of a manikin (ALS Skill Master, Laerdal Medical Japan, Tokyo, Japan) using the Macintosh laryngoscope, AWS, and GEB in the control scenario, chest compression scenario, and chest compression with cervical stabilisation scenario. Difficulty in intubation was rated on a 5-point scale and the intubation time was measured. RESULTS: Continuous chest compression increased difficulty in intubation with the Macintosh laryngoscope, compared with the control scenario. Concurrent application of cervical stabilisation further increased the difficulty, compared with application of chest compression alone. Of the three devices compared, the AWS facilitated the easiest intubation, and the GEB facilitated the second-easiest intubation in all scenarios, though the intubation time was slightly longer with the GEB than with other devices. CONCLUSION: CPR employing continuous chest compression with or without cervical stabilisation caused difficult intubation with the Macintosh laryngoscope. The AWS and GEB facilitated the easiest and second-easiest intubation, respectively, even during CPR employing continuous chest compression with or without cervical stabilisation in a manikin.

Living donor liver transplantation for congenital absence of the portal vein.

The congenital absence of the portal vein (CAPV) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. Liver transplantation (OLT) may be indicated for patients with symptomatic CAPV refractory to medical treatment, especially due to hyperammonemia, portosystemic encephalopathy, hepatopulmonary syndrome, or hepatic tumors. Because portal hypertension and collateral circulation do not occur with CAPV, significant splanchnic congestion may occur when the portocaval shunt is totally clamped during portal vein (PV) reconstruction in OLT. This phenomenon results in severe bowel edema and hemodynamic instability, which negatively impact the patient's condition and postoperative recovery. We have successfully reconstructed the PV in living donor liver transplantation (LDLT) using a venous interposition graft, which was anastomosed end-to-side to the portocaval shunt by a partial side-clamp, using a patent round ligament of the liver, which was anastomosed end-to-end to the graft PV with preservation of both the portal and caval blood flows. Owing to the differences in anatomy among patients, at LDLT for CAPV liver transplant surgeons should seek to preserve both portal and caval blood flows.

Distribution and enumeration of attractors in probabilistic Boolean networks.

Many mathematical models for gene regulatory networks have been proposed. In this study, the authors study attractors in probabilistic Boolean networks (PBNs). They study the expected number of singleton attractors in a PBN and show that it is (2 - (1/2)(L-1))(n), where n is the number of nodes in a PBN and L is the number of Boolean functions assigned to each node. In the case of L=2, this number is simplified into 1.5(n). It is an interesting result because it is known that the expected number of singleton attractors in a Boolean network (BN) is 1. Then, we present algorithms for identifying singleton and small attractors and perform both theoretical and computational analyses on their average case time complexities. For example, the average case time complexities for identifying singleton attractors of a PBN with L=2 and L=3 are O(1.601(n)) and O(1.763(n)), respectively. The results of computational experiments suggest that these algorithms are much more efficient than the naive algorithm that examines all possible 2(n) states.

Emergence of scale-free distribution in protein-protein interaction networks based on random selection of interacting domain pairs.

Recent analyses of biological and artificial networks have revealed a common network architecture, called scale-free topology. The origin of the scale-free topology has been explained by using growth and preferential attachment mechanisms. In a cell, proteins are the most important carriers of function, and are composed of domains as elemental units responsible for the physical interaction between protein pairs. Here, we propose a model for protein-protein interaction networks that reveals the emergence of two possible topologies. We show that depending on the number of randomly selected interacting domain pairs, the connectivity distribution follows either a scale-free distribution, even in the absence of the preferential attachment, or a normal distribution. This new approach only requires an evolutionary model of proteins (nodes) but not for the interactions (edges). The edges are added by means of random interaction of domain pairs. As a result, this model offers a new mechanistic explanation for understanding complex networks with a direct biological interpretation because only protein structures and their functions evolved through genetic modifications of amino acid sequences. These findings are supported by numerical simulations as well as experimental data.