Early intervention with faecal microbiota transplantation: an effective means to improve growth performance and the intestinal development of suckling piglets.

Recent studies indicate that early postnatal period is a critical window for gut microbiota manipulation to optimise the immunity and body growth. This study investigated the effects of maternal faecal microbiota orally administered to neonatal piglets after birth on growth performance, selected microbial populations, intestinal permeability and the development of intestinal mucosal immune system. In total, 12 litters of crossbred newborn piglets were selected in this study. Litter size was standardised to 10 piglets. On day 1, 10 piglets in each litter were randomly allotted to the faecal microbiota transplantation (FMT) and control groups. Piglets in the FMT group were orally administrated with 2ml faecal suspension of their nursing sow per day from the age of 1 to 3 days; piglets in the control group were treated with the same dose of a placebo (0.1M potassium phosphate buffer containing 10% glycerol (vol/vol)) inoculant. The experiment lasted 21 days. On days 7, 14 and 21, plasma and faecal samples were collected for the analysis of growth-related hormones and cytokines in plasma and lipocalin-2, secretory immunoglobulin A (sIgA), selected microbiota and short-chain fatty acids (SCFAs) in faeces. Faecal microbiota transplantation increased the average daily gain of piglets during week 3 and the whole experiment period. Compared with the control group, the FMT group had increased concentrations of plasma growth hormone and IGF-1 on days 14 and 21. Faecal microbiota transplantation also reduced the incidence of diarrhoea during weeks 1 and 3 and plasma concentrations of zonulin, endotoxin and diamine oxidase activities in piglets on days 7 and 14. The populations of Lactobacillus spp. and Faecalibacterium prausnitzii and the concentrations of faecal and plasma acetate, butyrate and total SCFAs in FMT group were higher than those in the control group on day 21. Moreover, the FMT piglets have higher concentrations of plasma transforming growth factor-ß and immunoglobulin G, and faecal sIgA than the control piglets on day 21. These findings indicate that early intervention with maternal faecal microbiota improves growth performance, decreases intestinal permeability, stimulates sIgA secretion, and modulates gut microbiota composition and metabolism in suckling piglets.

Self-sensing porphysomes for fluorescence-guided photothermal therapy.

Porphysomes are highly quenched unilamellar porphyrin-lipid nanovesicles with structurally dependent photothermal properties. The high packing density of porphyrin molecules in the lipid bilayer enables their application in photothermal therapy, whereas the partial disruption of the porphysome structure over time restores the porphyrin fluorescence and enables the fluorescence-guided photothermal ablation. This conversion is a time-dependent process and cannot be easily followed using existing analytical techniques. Here we present the design of a novel self-sensing porphysome (FRETysomes) capable of fluorescently broadcasting its structural state through Förster resonance energy transfer. By doping in a near-infrared emitting fluorophore, it is possible to divert a small fraction of the absorbed energy toward fluorescence emission which provides information on whether the vesicle is intact or disrupted. Addition of bacteriopheophorbide-lipid into the vesicle bilayer as a fluorescence acceptor (0.5-7.5 mol %) yields a large separation of 100 nm between the absorption and fluorescence bands of the nanoparticle. Furthermore, a progressive increase in FRET efficiency (14.6-72.7%) is observed. Photothermal heating and serum stability in FRETysomes is comparable with the undoped porphysomes. The fluorescence arising from the energy transfer between the donor and acceptor dyes can be clearly visualized in vivo through hyperspectral imaging. By calculating the ratio between the acceptor and donor fluorescence, it is possible to determine the structural fate of the nanovesicles. We observe using this technique that tumor accumulation of structurally intact porphyrin-lipid nanovesicles persists at 24 and 48 h postinjection. The development of FRETysomes offers a unique and critical imaging tool for planning porphysome-enabled fluorescence-guided photothermal treatment, which maximizes light-induced thermal toxicity.

Genome-wide association study of bipolar I disorder in the Han Chinese population.

We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, ß-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

Effect of endorectal coils on staging of rectal cancers by magnetic resonance imaging.

OBJECTIVE: To compare the use of endorectal plus phased-array coils with use of phased-array coil alone with respect to the accuracy of magnetic resonance imaging for detecting mesorectal involvement of rectal cancer. DESIGN: Retrospective study. SETTING: A tertiary referral centre in Hong Kong. PATIENTS: Ethnic Chinese patients with rectal adenocarcinoma who underwent staging magnetic resonance imaging during the years 2003 to 2008 in our centre were selected; those who received preoperative neoadjuvant therapy were excluded. Unless otherwise contra-indicated, endorectal coils have been used since 2006. MAIN OUTCOME MEASURES: Magnetic resonance images were retrieved and reviewed by two radiologists blinded to the pathological results. The radiological findings were then correlated with the pathological reports to determine diagnostic accuracy. RESULTS: A total of 50 patients were studied; 13 of the examinations were in patients having an endorectal coil. The overall accuracy of magnetic resonance imaging in detecting mesorectal tumour involvement was 80%. Subgroup analysis showed higher accuracy in the group with endorectal coils than in those with phased-array coils alone. Over-detection of mesorectal involvement was noted in 12% of the cases, with lower rate being observed in patients with endorectal coils. Underdetection of mesorectal tumour involvement was only noted in the group without endorectal coils. With the use of endorectal coils, the sensitivity reached 100% and the specificity increased to 86%. CONCLUSION: Use of endorectal coil in staging magnetic resonance imaging of the rectum improves diagnostic accuracy. Whenever feasible, endorectal coil use is therefore recommendable to enhance diagnostic accuracy. The study results substantiate the understanding of staging by magnetic resonance imaging of rectal cancer in the local Chinese population.

Sequential intravenous/oral antibiotic vs. continuous intravenous antibiotic in the treatment of pyogenic liver abscess.

AIM: Pyogenic liver abscesses result in substantial morbidity and mortality. Antimicrobial regimens using sequential intravenous/oral therapy may reduce the length of hospital stay. In this retrospective analysis, the efficacy of continuous intravenous antibiotic therapy (group I) vs. sequential intravenous/oral antibiotic therapy (group II) was studied in patients with pyogenic liver abscess. METHODS: One hundred and twelve consecutive patients (55 in group I and 57 in group II) with pyogenic liver abscess were analysed. Clinical response, length of hospital stay and relapse rates were examined. RESULTS: Group II had a significantly shorter duration of intravenous antibiotic treatment (3.2 weeks vs. 5.9 weeks, P < 0.01) and a shorter length of hospital stay (28 days vs. 42 days, P < 0.01) when compared to group I. Oral antibiotics were prescribed for a median duration of 2.9 weeks in group II after discharge. No relapse occurred within 6 weeks after the completion of treatment in both groups. The cost of therapy was significantly lower in group II than in group I by 33%. CONCLUSIONS: A sequential intravenous/oral antibiotic regime is a safe and effective treatment for pyogenic liver abscess. This reduces the cost of therapy and the length of hospital stay.

Prediction of oesophagogastric varices in patients with liver cirrhosis.

BACKGROUND: All patients with liver cirrhosis are recommended for evaluation of oesophagogastric varices (EGV) regularly. This prospective study was designed to develop a predictive model for EGV in cirrhotic patients. METHODS: Ninety-two patients were recruited. From all patients studied, the size of palpable spleen, liver chemistry value, platelet count, prothrombin time, diameter of main portal vein and splenic length as assessed by ultrasonography were determined. Upper endoscopy was performed. Oesophageal varices (EV) and gastric varices (GV) were graded (EV, grade 1-4; GV, grade 1-3). In the predictive model, the EGV was classified into two grades (low, grade 1-2 EV or grade 1 GV; high, grade 3-4 EV or grade 2-3 GV). RESULTS: There were 53 patients with EGV and 39 patients without EGV as determined by endoscopy. Patients with EGV had a significantly higher degree of ascites and hepatic encephalopathy, lower platelet count and longer splenic length than those without EGV. Low platelet count and presence of ascites were the significant independent predictors for high-grade EGV (concordance rate 0.83). The optimal critical value for the platelet count was 150 x 10(9)/L. Of patients without thrombocytopenia and ascites, 37% had low-grade EGV but none had high-grade EGV, whereas 38 and 35% of patients with thrombocytopenia or ascites had low and high-grade EGV, respectively. Therefore, this predictive model for high-grade varices had a positive and negative predictive value of 35 and 100%, respectively. CONCLUSION: Endoscopic screening for EGV was not necessary until thrombocytopenia or ascites occurred.

High alpha-fetoprotein level in HCV-related nodular liver cell dysplasia.

The diagnosis of hepatocellular carcinoma is generally made in patients with a mass lesion in the cirrhotic liver if the alpha-fetoprotein level is >1,000 ng/L. Other causes of elevation of alpha-fetoprotein to this extreme degree include nonseminomatous germ cell tumor and hepatic metastasis. However, it is extremely rare for benign hepatic lesions to cause alpha-fetoprotein of > 1,000 ng/ml. We report a Chinese patient with spontaneous normalization of alpha-fetoprotein with an initial value > 10,000 ng/ml due to nodular dysplasia complicating hepatitis C-related liver cirrhosis. The alpha-fetoprotein was secreted from the dysplastic liver cells.

Automatic finite element mesh generation for maxillary second premolar.

Developing three dimensional finite element mesh models for irregular geometric objects requires a large amount of manual efforts, hence limiting the three dimensional approach for dental structure analyses. An automatic procedure which can be used to generate a three dimensional finite element mesh for the maxillary second premolar was developed in this study. Firstly, a embedded second premolar was sliced and scanned parallel to the occlusal surface. A self-developed image processing system was employed to detect the boundaries of different materials within each section. An automatic mesh generation program was used on these boundaries to create tetrahedral elements based on moving nodes of uniform cube approach. Six mesh models of the second premolar with different element sizes using linear and quadratic elements were analyzed. Strain energy and von Mises stresses were reviewed for convergence in the crown regions.

N 2-methylguanosine is iso-energetic with guanosine in RNA duplexes and GNRA tetraloops.

Modified nucleotides are resource-intensive alternatives to the four nucleotides that constitute the bulk of natural RNAs. Yet, even in cases where modifications are highly conserved, their functions are difficult to identify. One possible function might be to modulate the stability of RNA structures. To investigate this possibility for N 2-methylguanosine (m2G), which is present in a wide variety of RNAs, we have determined the thermodynamic consequences of substituting m2G for G in G-C Watson-Crick pairs and G@U wobble pairs within RNA duplexes. The m2G substitution is iso-energetic with G in all cases, except for aninternal m2G@U pair, where it has a modest (0.3 kcal/mol) stabilizing effect. We have also examined theconsequences of replacing G by m2G, and A by N 6, N 6-dimethyladenosine (m26A) in the helix 45 tetraloop of 16S rRNA, which would otherwise be a standard GNRA tetraloop. This loop is a conserved, hypermethylated region of the ribosome where methylation appears to modulate activity. m26A substitution destabilizes the tetraloop, presumably because it prevents the formation of the G@A sheared pair it would otherwise contain. m2G substitution has no effect on tetraloop stability. Together, these results suggest that m2G is equally stable as either the s-cis or s-trans rotamer. The lack of a significant effect on secondary structural stability in these systems suggests that m2G is introduced into naturally occurring RNAs for reasons other than modulation of duplex stability.

Differential correlation between translocation and down-regulation of conventional and new protein kinase C isozymes in C6 glioma cells.

Correlation between translocation and down-regulation of conventional protein kinase C alpha (cPKC alpha) and new PKC delta (nPKC delta) induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) at different time courses (5 min, 30 min, 1 h, 3 h, 6 h, 10 h, 17 h, and 24 h) was studied in C6 glioma cells. From the dose-dependent translocations of these two isoforms by 10-min treatment with TPA (1, 3, 10, 30, 100, 300, and 1,000 nM), we found that cPKC alpha was translocated by 3-1,000 nM and nPKC delta was translocated by 10-1,000 nM TPA. Both isoforms were maximally translocated by 100-1,000 nM TPA, whereas 1 nM did not translocate these two isoforms. When the cells were treated with 1,000 nM TPA for 5 min to 17 h, the translocation of these two isoforms occurred rapidly after 5-min treatment and could be sustained for 1 h, whereas down-regulation occurred after 3-h treatment and almost complete down-regulation was observed after 17-h treatment. However, the extent of down-regulation of nPKC delta was greater than that of cPKC alpha at 3-, 6-, and 10-h treatment. Further studies by using different doses of TPA (100, 10, 3, and 1 nM) and extending the time to 24 h showed that cPKC alpha was more resistant to down-regulation. This conventional isoform was maintained at a translocation state even after long-term treatment with 3-100 nM TPA, and complete down-regulation was only shown after 1,000 nM treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Analysis of 15 cases with necrotic perforation and large area necrotic leakage of the gastric wall after operation of esophageal and cardial cancer].

From September 1964 to December 1971 and from January 1986 to December 1991, 15 cases were diagnosed as necrotic perforation and large area necrotic leakage of the gastric wall by iodipin roentgenography, barium meal examination and second operation. It is thought that the pathologic type of anastomotic leakage, the leakage of the anastomotic stoma region, and esophageal and gastric perforation caused by suture cuttings are virtually different from that of necrotic perforation and large area necrotic leakage of the gastric wall, and should be treated differently. The pathogenesis and clinical manifestation of the later two entities are discussed. In our opinion, the maintenance of good circulation of the right gastric and gastroepiploic arteries and veins, careful protection of the stomach wall, and avoiding great tension when the stomach is lifted are of vital importance to prevent the necrosis of gastric wall. In the case of necrotic perforation or large area necrotic leakage of the gastric wall, the early diagnosis is important and early operation is suggested.

Mesenteric actinomycosis.

We report a case of abdominal actinomycosis demonstrated on computed tomography (CT) as an isolated mesenteric mass with radiating linear and nodular densities. The lesion mimicked a mesenteric tumor with desmoplastic reaction. The clinical and radiological features of this uncommon entity are reviewed.

Assessment of atracurium during anesthesia and surgery.

Atracurium is a competitive neuromuscular blocking agent which goes through Hofmann elimination. It does not accumulate even after several bolus doses or infusion lasting several hours. The purpose of this study was to evaluate the effectiveness of atracurium on bolus injection for intubation and continuous infusion for subsequent surgery with the manufacturer's suggested dose. Forty-six patients (23-78 yr, ASA I-IV) undergoing laparotomy were included in the study. The patients were induced with Thropental and fentanyl, then a bolus of atracurium (0.5 mg/kg) was given and intubation done 90 sec later. Anesthesia was maintained with nitrous oxide, oxygen and isoflurane. Twenty minutes later atracurium 0.3 mg/kg/hr was infused continuously. The infusion continued until skin closure or an estimated 20-30 min before the end of the operation. Quality of muscle relaxation for intubation and surgery was evaluated by the surgeons and the anesthesiologists. Train-of-four (TOF) count was also recorded in the beginning and at the end of infusion. After extubation, residual curarization was evaluated clinically and with the TOF count method in the recovery room. Intubation quality was rated fair to poor in 67% of cases. Muscle relaxation assessed by the surgeons as excellent to good amounted to 96% of cases. All patients were extubated within 30 min after completion of surgery except for five patients who had poor postoperative conditions because of underlying diseases. No patient showed residual curarization or complication in the recovery room. With doses suggested by the manufacturer, our study indicated that intubation was not satisfactory while continuous infusion for muscle relaxation during surgery was acceptable.

[Resection of esophageal and gastric cardiac cancer and esophagogastrostomy by planting esophagus into the stomach: a report of cases].

105 cases of esophageal cancer and 46 cases of gastric cardia carcinoma were resected and the continuity of alimentary canal was resumed by planting esophagus into the stomach. This procedure had been designed by authors. There is neither anastomotic leakage nor stricture. Only 1 case died perioperatively. The anastomosis start by suturing the whole thickness of esophageal wall to the mucous membrane of stomach. Then the esophageal stump was telescoped into the stomach by suturing the secomuscular layer of stomach to the outer layer of esophageal muscles, with a distance of about 3 cm from the inner anastomatic line. When the anastomasis was finished, esophageal mucous membrane everted slightly, and prolapsed a little as food bolus passes. We suggest these are the mechanisms preventing the anastomosis from leaking or narrowing. Reflex of gastric content may be prevented too.

Evaluation of humoral immunity on leprosy patients in Taiwan: a preliminary report.

Twenty-four tuberculoid (T)-type and 31 lepromatous (L)-type leprosy patients from Taiwan Provincial Lo-Sheng Leprosarium were enrolled in this study. Twenty-six age- and sex- matched normal subjects were also studied as a control group. The evaluation of their general and specific humoral immunity included B-cell subpopulations, 3 major classes of immunoglobulin (G, A and M) and antibodies in the IgG class against lepromin suspension and Bacillus Calmette-Guerin (BCG) sonicate. T-type patients showed a larger B-cell percentage than L-type patients (p less than 0.01). In general, patients with leprosy, both T and L types, had higher serum immunoglobulin levels than the control group. T-type patients showed greater antibody levels than the control group (p less than 0.05 for anti-lepromin and p less than 0.0001 for anti-BCG). L-type patients demonstrated a higher anti-BCG IgG level than the control group (p less than 0.0001). The level of anti-BCG IgG was more frequently above the cutoff level than that of anti-lepromin IgG in leprosy patients (p less than 0.01 for T, p less than 0.005 for L). In conclusion, humoral immunity is not impaired in leprosy patients. Discrepancies for T- and L-type patients among B-cell subpopulation, serum immunoglobulin levels and specific antibody levels reflect different aspects of cell-mediated immunity impairment. Though leprosy patients had elevated anti-BCG IgG levels, it is impossible to differentiate L- and T-type patients; specific antigens are needed for serodiagnosis of leprosy patients in Taiwan.