Efficacy of a type 2 PRRSV modified live vaccine (PrimePac™ PRRS) against a Thai HP-PRRSV challenge.
The Chinese highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has caused a severe threat to the pig population in Southeast Asian countries. The purpose of this study was to investigate the efficacy of a type 2 PRRSV modified live vaccine (PrimePac™ PRRS, lineage 7) against a Thai HP-PRRSV (10PL01, lineage 8). Three-week-old PRRSV-free pigs were randomly assigned into three groups. Vaccinated challenged group (group 1, n = 16) was immunized with PrimePac™ PRRS vaccine at 3 weeks old. The unvaccinated challenged group (group 2, n = 16) was injected with PBS at 3 weeks old, and unvaccinated unchallenged group (group 3, n = 10) was served as a negative control. At 9 weeks old, all groups, except the negative control group, were challenged with the Thai HP-PRRSV. All pigs were monitored daily during 10 days post-infection (dpi) and were necropsied at 10 and 17 dpi. The results revealed that vaccinated challenged pigs showed significantly lower (p < 0.05) mean rectal temperatures, clinical respiratory scores, lung lesion scores, and levels of virus load in serum and lung tissue compared with the unvaccinated challenged pigs. Moreover, vaccinated challenged pigs exhibited PRRSV-specific serum neutralizing antibodies at the end of the experiment. Our findings indicated that the studied type 2 PRRSV vaccine provided partial protection against the Thai HP-PRRSV infection based on the body temperature, levels of viremia, and the severity of lung lesions. These results demonstrated that partial protection of PrimePac™ PRRS vaccine might be useful for controlling HP-PRRSV infection in the endemic area.


Verification of a new gene on Saccharomyces cerevisiae chromosome III.
We present verification of the existence of a previously unannotated, intron-containing gene of 134 amino acids (predicted molecular weight approximately 15.5 kDa) located on chromosome III of Saccharomyces cerevisiae. Strains carrying a deletion of this gene, which we have called YCL012C, reveal no apparent phenotype. Orthologues of YCL012C are present in related species S. bayanus, S. paradoxus and Ashbya gossypii. Comparison with other fungal sequences reveals that orthologues of this gene are likely present in Schizosaccharomyces pombe, Neurospora crassa and Cryptococcus neoformans as well, indicating that YCL012C is a widely conserved fungal gene.


Aspirin inhibits Ca2+-stimulated fatty acid release from human washed platelets.
Ca2+ at 2mM concentration stimulates the release of saturated and unsaturated fatty acids from intact washed platelets incubated at 37 degrees C with stirring. Aspirin at a concentration of 0.4 mM inhibits both cyclo-oxygenase activity and fatty acid efflux induced by Ca2+. Thus, in intact washed platelets, aspirin reduces formation of cyclo-oxygenase products by direct inhibition of the enzyme and by reducing the availability of precursor arachidonate.


Pre-emptive analgesic effectiveness of meloxicam versus tramadol after mandibular third molar surgery: a pilot study.
To compare the pre-emptive analgesic effectiveness of 15 mg of meloxicam and 50 mg of tramadol after mandibular third molar surgery. This pilot study was a double-blind, randomized, parallel-group clinical trial. The patients were randomized into 2 treatment groups, each with 15 patients, by use of a series of random numbers: group A was administered 15 mg of meloxicam intramuscularly (IM) 50 minutes before the surgery and group B was given 50 mg of tramadol IM 50 minutes before the surgery. We evaluated pain intensity, analgesic consumption, swelling, and trismus. The group receiving 15 mg of meloxicam IM showed differences in pain intensity evaluated by the area under the curve of the visual analog scale and total analgesic consumption when compared with the group receiving 50 mg of tramadol IM. The patients receiving 15 mg of preoperative meloxicam had less pain intensity and total analgesic consumption than those receiving 50 mg of preoperative tramadol.


Effect of diazepam on muscle weakness in a model of myasthenia gravis in rats.
Rats chronically received alpha-bungarotoxin which caused a reduction of nicotinic acetylcholine receptors and weakness, especially of lip muscles. It was found that diazepam (0.75-2 mg kg-1, s.c.), after a 15 min period of excitation and increased lip weakness, caused sedation and some improvement of the lip. Even after 5 mg kg-1 diazepam, muscle function was not markedly affected and breathing appeared normal. It is concluded that sedation in rats by diazepam does not entail aggravation of the muscle weakness caused by a partial neuromuscular block.


Steroids and related products. XLVII. Cardiotonic steroids. VII. The 14 beta-hydroxylation of 17 beta-substituted steroids. Part II.
The most efficient method for introducing a 14 beta-hydroxy group into a steroid with a 17 beta-side chain is reported. It can be used in the presence of an unsaturated lactone ring.


The enteric nervous system and cholera toxin-induced secretion.
This article reviews briefly some general aspects of the enteric nervous system (ENS). Furthermore, the ENS control of epithelial transport is exemplified by a description of the enteric nervous reflexes activated by cholera toxin.


Lead-Free, Water-Stable A3 Bi2 I9 Perovskites: Crystal Growth and Blue-Emitting Quantum Dots [A=CH3 NH3 + , Cs+ , and (Rb0.05 Cs2.95 )+ ].
Despite the great success in the increase in the power conversion efficiency of lead halide perovskite solar cells, the toxicity of lead and the unstable nature of the materials are still major concerns for their wider implementation at the industrial level. Herein, large-size single crystals (SCs) are developed in HI solution by using a temperature lowering method and nanocrystals (NCs) of A3 Bi2 I9 perovskites [where A=CH3 NH3 + (MA)+ , Cs+ , and (Rb0.05 Cs2.95 )+ ] are formed in ethanol (EtOH) and toluene (TOL). The stability of A3 Bi2 I9 perovskite is investigated by immersing the SCs for 24 h and pellets for 12 h in water. Moreover, the A3 Bi2 I9 perovskite NCs displays a promising photoluminescence quantum yield of 17.63 % and a long lifetime of 8.20 ns.


Radial head replacement in capitellocondylar total elbow arthroplasty. 2- to 6-year follow-up evaluation in rheumatoid arthritis.
We reviewed six capitellocondylar metal-to-plastic total elbow replacement prostheses with radial head components, implanted in patients with rheumatoid arthritis. At an average of 4.7 +/- 1.5 years, relief of pain, improvement of function, and a functional range of motion were preserved. Five of the six elbows (83%) were clinically rated good or excellent. Radiolucent lines were seen at the bone-cement interface in 50% of the humeral component stems and in all ulnar component boats within 2 years after surgery; none had progressed at subsequent examination. Most were less than or equal to 1 mm wide, and none were associated with clinical deterioration. Only one of the humeral components was radiographically loose. No radiolucent lines were seen along the stems of the ulnar or radial components. There were no postoperative dislocations when the radial component was used, presumably because the prosthetic radial head provided increased constraint. None of these elbows have required revision. Radial head replacement in capitellocondylar arthroplasty had been discontinued because radiolucent lines were observed at early review. However, the absence of clinical failure, dislocation, or progression of radiolucency at long-term follow-up examination favor radial head replacement in primary unconstrained total elbow arthroplasty.


RETention of urine After INguinal hernia Elective Repair (RETAINER study I and II).
Post-operative urinary retention (POUR) is a well-recognised complication of inguinal hernia repair (IHR). The magnitude of the problem is unclear, and contradictory evidence surrounds postulated risk factors. POUR risks patient distress, catheter-complications and a financial and logistical burden to services. Separately, in the field of IHR, there has been a lack of research into patients' perceptions of surgical 'success'. Our aim is to perform a two-phase, multi-centre prospective study to:Assess the rate, risk factors and impact related to POUR post IH repair.Develop and validate a patient reported outcome measure (PROM) for inguinal hernia repair. RETAINER I: We propose a 24-week prospective study with voluntary international participation in 4 week blocks. All patients undergoing elective IH repair (minimally-invasive/open) will be eligible. Standardised data collection will include patient and perioperative factors. Primary outcome will be development of POUR, defined as the need for insertion of a urinary catheter as determined by the treating clinician. Secondary outcomes will be identification of factors predisposing to POUR and the impact of POUR.RETAINER II: A patient reported outcome measure will be developed using representative patient focus groups for item generation, from which an initial questionnaire will be developed and piloted. Validity, reliability, sensitivity and reproducibility will be assessed using the QQ-10 and standard psychometric methodology. Using an international multicentre collaborative approach will produce the necessary volume of patients, whilst capturing inter-centre variability, to accurately reflect POUR rates and allow analysis of risk factors. This patient pool will provide an excellent opportunity to develop a PROM using appropriate qualitative methodology. RETAINER (RETention of urine After INguinal hernia Elective Repair) I is a prospective, multicentre, international observational study.RETAINER I aims to explore the incidence of and risk factors for urinary retention following elective inguinal hernia repair.Urinary retention following inguinal hernia repair has a marked impact on patients and creates a significant financial and logistical burden for hospital services.RETAINER II is a prospective, qualitative study, recruiting patients to guide the creation of a patient-reported outcome measure (PROM) for elective inguinal hernia repair.


Complete Genome of a Panresistant Pseudomonas aeruginosa Strain, Isolated from a Patient with Respiratory Failure in a Canadian Community Hospital.
We report here the complete genome sequence of a panresistant Pseudomonas aeruginosa strain, isolated from a patient with respiratory failure in Canada. No carbapenemase genes were identified. Carbapenem resistance is attributable to a frameshift in the oprD gene; the basis for colistin resistance remains undetermined.


The long-term outcomes of CIS patients in the Barcelona inception cohort: Looking back to recognize aggressive MS.
To explore the long-term outcomes of patients with clinically isolated syndromes from the Barcelona cohort. We selected patients with a follow-up longer than 10 years to (1) estimate the risks of multiple sclerosis (MS) and disability accumulation according to the baseline number of T2 lesions and to compare treated versus untreated patients and early versus delayed treatment, and (2) to study baseline features of patients with aggressive MS (Expanded Disability Status Scale (EDSS) ⩾6.0 at 10 years). In all, 401 patients were included (mean follow-up of 14.4 (standard deviation of 2.9) years). A higher number of T2 lesions was associated with an earlier MS diagnosis and an earlier risk of irreversible disability. Early treatment was associated with a decreased risk of EDSS of 3.0: adjusted hazard ratio = 0.4, 95% confidence interval = (0.2, 0.7). Patients with aggressive MS differed in their baseline brain magnetic resonance images: The median (interquartile range) number of T2 lesions and contrast-enhancing lesions (CEL) was 71 (28-95) versus 7 (1-19) and 3 (1-24) versus 0 (0-1), respectively. The cut-offs that better classified patients with aggressive MS were 20 for T2 lesions and 2 for CEL. Although MS natural history is changing, a high lesion load at onset is helpful to identify patients at risk of presenting an aggressive MS.


Nutritional Status of Vegetarian Patients Before and After Bariatric Surgery: a Monocentric Retrospective Observational Case-Control Study.
The obesity pandemic is associated with an increasing number of bariatric surgeries which allow improvement in obesity-related comorbidities and life expectancy but potentially induce nutritional deficiencies. Vegetarianism becomes more and more popular and exposes as well to vitamin and micronutrient deficiencies. Only one study has explored the impact of vegetarianism on the preoperative nutritional status of eligible patients for bariatric surgery, but none in postoperative care. We conducted a retrospective case-control study in our cohort of bariatric patients, matching 5 omnivores for each vegetarian. We compared their biological profile regarding vitamin and micronutrient blood levels before and 3, 6, 12, and 30 months after surgery. We included 7 vegetarians including 4 lacto-ovo-vegetarians (57%), 2 lacto-vegetarians (29%), and one lacto-ovo-pesco-vegetarian (14%). Three years after surgery with equivalent daily standard vitamin supplementation, the two groups showed a similar biological profile including blood levels of ferritin (p = 0.6), vitamin B1 (p = 0.1), and B12 (p = 0.7), while the total median weight loss at 3 years was comparable (39.1% [27.0-46.6] in vegetarians vs 35.7% [10.5-46.5] in omnivores, p = 0.8). We observed no significant difference between vegetarians and omnivores before surgery regarding comorbidities and nutritional status. It seems that, after bariatric surgery, vegetarian patients taking a standard vitamin supplementation do not show an increased risk of nutritional deficiencies compared to omnivores. However, a larger study with a longer follow-up is needed to confirm these data, including an evaluation of different types of vegetarianism such as veganism.


Serine and arginine-rich splicing factor 3 promotes the activation of quiescent mouse neural stem cells.
The quiescence and activation of adult stem cells are regulated by many kinds of molecular mechanisms, and RNA alternative splicing participates in regulating lots of cellular processes. However, the relationship between stem cell quiescence and activation regulation and gene alternative splicing has yet to be studied. In the present study, we aimed to elucidate the regulation of stem cell quiescence and activation by RNA alternative splicing. The up-regulated genes in activated mouse NSCs (neural stem cells), MuSCs (muscle stem cells) and HSCs (hematopoietic stem cells) were collected for GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. The genes from three tissue stem cells underwent Venn analysis. The mouse NSCs were used for quiescence and reactivation induction. The immunostaining of cell-specific markers was performed to identify cell properties. The reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the gene expression and protein expression, respectively. We found that the up-regulated genes in activated stem cells from three tissues were all enriched in RNA splicing-related biological processes; the up-regulated RNA splicing-related genes in activated stem cells displayed tissue differences; mouse NSCs were successfully induced into quiescence and reactivation in vitro without losing differentiation potential; serine and arginine-rich splicing factor 3 (Srsf3) was highly expressed in the activated mouse NSCs, and the overexpression of SRSF3 protein promoted the activation of quiescent mouse NSCs and increased the neural cell production. Our data indicate that the alternative splicing change may underline the transition of quiescence and activation of stem cells. The manipulation of the splicing factor may benefit tissue repair by promoting the activation of quiescent stem cells.


Effect of procyanidolic oligomers of Vitis vinifera on the biosynthesis and excretion of corneal glycosaminoglycans.
Glycosaminoglycans (GAG) as hyaluronan and proteoglycans (PG) as dermatan sulfate (DSPG) and keratan sulfate (KSPG) play important role in the structure and physiological functions of cornea. Several corneal pathologies are associated with qualitative and quantitative alterations of GAG and/or PG biosynthesis. For these reasons we investigated the effect of procyanidolic oligomers (PCO) on the biosynthesis and excretion of GAG-s in bovine corneal explant cultures. This was accomplished by the determination of their chemical components, hexoses, hexosamines and uronic acids as well as the incorporation of (35)S-sulfate in the presence and without PCO in the culture medium. In presence of 1 mg/ml PCO total hexoses, hexosamines and uronic acids increased at 5 and 24 h of incubation, hexoses less than the two other components. Stimulation of biosynthesis concerned essentially the uronic acid containing GAG-s, DS and hyaluronan. (35)S-sulfate incorporation decreased in presence of PCO, showing a decreased sulfation of GAG-s. The most striking effect was however the strongly increased excretion of neosynthesized GAG-s in the culture medium. This effect could be beneficial in decreasing corneal hydration in inflammatory conditions, together with the previously demonstrated protection of corneal macromolecules against proteolytic degradation.


LINC00619 restricts gastric cancer progression by preventing microRNA-224-5p-mediated inhibition of OPCML.
Several long intergenic noncoding RNAs (lincRNAs) have been linked to carcinogenesis; however, little is known about the role of LINC00619 in gastric cancer (GC). LINC00619 was identified among differentially expressed lncRNAs linked to gastric cancer based on microarray analysis and its relationships with miR-224-5p and opioid binding protein/cell adhesion molecule-like gene (OPCML) were investigated. LINC00619, miR-224-5p, and OPCML expression were measured in GC tissues and cells. Ectopic expression and depletion experiments were conducted to assess the effects of LINC00619, miR-224-5p and OPCML on cell proliferation, invasion, migration and apoptosis as well as their effects on the expression of apoptosis- and metastasis-related genes (Bcl-2, Bax, MMP-2 and MMP-9). Tumorigenicity in the nude mice was also examined. Gastric cancer was characterized by downregulation of LINC00619 and OPCML and upregulation of miR-224-5p. Additionally, we found that miR-224-5p could interact with both LINC00619 and OPCML. Upregulation of LINC00619, which binds to miR-224-5p, led to decreased miR-224-5p expression while increasing the expression of OPCML, a target gene of miR-224-5p. Overexpression of LINC00619 or OPCML or downregulation of miR-224-5p suppressed cell proliferation, invasion, migration and tumorigenicity while promoting apoptosis in GC. Our results indicated that LINC00619 functions as a tumor suppressor in GC by impairing miR-224-5p-mediated inhibition of OPCML.


Chiral and Achiral Crystal Structures of Au25 (PET)18 0 Reveal Effects of Ligand Rotational Isomerization on Optoelectronic Properties.
The crystal structures of 4 ligand-rotational isomers of Au25 (PET)18 are presented. Two new ligand-rotational isomers are revealed, and two higher-quality structures (allowing complete solution of the ligand shell) of previously solved Au25 (PET)18 clusters are also presented. One of the structures lacks an inversion center, making it the first chiral Au25 (SR)18 structure solved. These structures combined with previously published Au25 (SR)18 structures enable an analysis of the empirical ligand conformation landscape for Au25 (SR)18 clusters. This analysis shows that the dihedral angles within the PET ligand are restricted to certain observable values, and also that the dihedral angle values are interdependent, in a manner reminiscent of biomolecule dihedral angles such as those in proteins and DNA. The influence of ligand conformational isomerism on optical and electronic properties was calculated, revealing that the ligand conformations affect the nanocluster absorption spectrum, which potentially provides a way to distinguish between isomers at low temperature.


Physician practices in the management of venous thromboembolism: a community-wide survey.
Although there is a broad consensus on the optimum approach to the management of venous thromboembolism, there are few data from which to assess the extent of compliance with these recommendations. A community-wide study was therefore conducted in 16 short-stay hospitals in central Massachusetts to assess the clinical management of venous thromboembolism. Based on validated discharge diagnostic codes, there were 1231 clinically recognized cases of venous thromboembolism, 0.8% of 148,730 discharges in the 18-month period from July 1, 1988, to December 31, 1989. Eighty-one percent of study patients were admitted with signs or symptoms of acute venous thromboembolism. Ninety-seven percent of patients were treated with either heparin, warfarin, or inferior vena caval filter. Intravenous heparin was given to 89% of patients (mean bolus 6674 IU; mean duration 6.6 days). After heparin administration, there was a mean delay of 2.3 days in starting warfarin. Assuming a corresponding decrease in the length of hospital stay, appreciable cost savings could have been realized by earlier start of oral anticoagulation. An inferior vena cava filter was placed in 14% of patients. There was a clinically recognized in-hospital recurrence of venous thromboembolism during treatment in 2% of patients. Despite a slightly lower rate of compliance with recommended treatment regimens in nonteaching hospitals, and despite less frequent use of the inferior vena cava filter, there was no significant difference in the rate of in-hospital recurrence of clinically recognized venous thromboembolism in 10 nonteaching hospitals compared with six teaching hospitals.(ABSTRACT TRUNCATED AT 250 WORDS)


Diagnosis and Treatment of Periimplant Mucositis and Periimplantitis: An Overview and Related Controversial Issues.
Periimplant mucositis and periimplantitis are common complications of dental implant. This article provides a comprehensive overview of the 2017 World Workshop's new definition, clinical and radiographic presentation, pathogenesis, risk factors, and classification of periimplant diseases. Also, the authors discuss various types of instruments, materials, and techniques commonly used for treatment of nonsurgical and surgical periimplantitis. Lastly, the authors include some controversial topics surrounding this subject.


Radiofrequency ablation in the management of unresectable intrahepatic cholangiocarcinoma.
To evaluate the efficacy of radiofrequency (RF) ablation for treatment of unresectable intrahepatic cholangiocarcinoma (ICC) and to explore the impact of prognostic variables on outcomes. From 2000-2010, 17 patients with 26 ICCs underwent RF ablation at a single institution. None of the patients were surgery candidates. Seven patients had 15 primary ICCs, and 10 patients had 11 recurrent ICCs. The median largest diameter was 4.4 cm (range 2.1-6.8 cm). A percutaneous approach was used in 15 patients, and an open approach was used in 2 patients. Early tumor necrosis, recurrence-free survival, and overall survival were analyzed. Univariate analysis was performed to evaluate 12 clinicopathologic and treatment-related variables associated with recurrence-free survival and overall survival. Early tumor necrosis was 96.2% (25 of 26 tumors). The median follow-up period after RF ablation was 29 months. The median recurrence-free survival and overall survival were 17 months and 33 months. The 1-year, 3-year, and 5-year survival rates were 84.6%, 43.3%, and 28.9%, with an overall complication rate of 3.6% (1 of 28 sessions). Three variables were found to be closely associated with recurrence-free survival: lymph node metastases (P = .023), tumor differentiation (P = .034), and tumor number (P = .035). The only variable significantly associated with overall survival was tumor differentiation (P = .033). Preliminary results showed that RF ablation may be an effective treatment for ICC because it achieved an acceptable survival rate in a small population. Prognostic factors might allow better patient selection and outcomes.


Novel EBP gene mutations in Conradi-Hünermann-Happle syndrome.
Conradi-Hünermann-Happle syndrome [X-linked dominant chondrodysplasia punctata type 2 (CDPX2); MIM no. 302960] is an X-linked dominant disorder of cholesterol metabolism that causes a wide spectrum of skeletal abnormalities and linear ichthyosiform skin lesions. Mosaicism is probably responsible for the variability of the phenotype. To describe new mutations in patients with variable manifestations of the disease. We studied three patients with CDPX2. We performed mutation analysis of the EBP (formerly known as CDPX2) gene and gas chromatography-mass spectroscopy on serum of two patients. We found two novel (3G-->T and 419-422delTTCT) and one known mutation in the EBP gene. We demonstrated the presence of increased levels of dehydrocholesterol and 8(9)-cholestenol in the two patients with new mutations, confirming the diagnosis of CDPX2 and strongly suggesting that the mutations are indeed pathogenic. One patient had a very mild phenotype, presenting with linear alopecia and a mild symmetrical epiphyseal dysplasia. X-inactivation studies in peripheral blood of all patients showed skewing in only the most severely affected patient. The strong phenotypic variability in our patients suggests that there is no clear genotype-phenotype correlation.


Effects of the plasma concentration of 5-fluorouracil and the duration of continuous venous infusion of 5-fluorouracil with an inhibitor of 5-fluorouracil degradation on Yoshida sarcomas in rats.
The correlations of the 5-fluorouracil (5-FU) level in the plasma and the duration of continuous 5-FU infusion with the antitumor activity of 5-FU on Yoshida sarcomas in rats were examined. The circadian variation in the plasma level of 5-FU during continuous infusion was prevented by treatment with 3-cyano-2,6-dihydroxypyridine (CNDP), which strongly inhibits 5-FU degradation. On continuous venous infusion of 2 to 30 mg/kg of 5-FU over 24 h with CNDP at a molar ratio of 1:10 into normal rats, the 5-FU level in the blood was linearly proportional to the dose of 5-FU. The optimum schedule for antitumor activity on Yoshida sarcomas in rats was found to be infusion of 5-FU at 5 mg/kg over 24 h for 6 consecutive days, which gave a plasma 5-FU level of 176 ng/ml. Continuous infusion of 5-FU to give a plasma level of 300 ng/ml for 6 consecutive days from day 5 after implantation of tumor cells, when the tumors weighed about 1.0 g, resulted in complete regression of the tumors in all rats.


Cytologic factors associated with prognosis in patients with peripheral adenocarcinoma of the lung measuring 3 cm or less in greatest dimension.
Recently, peripheral lung adenocarcinomas (PLA) measuring < or = 3 cm in greatest dimension often have been diagnosed using diagnostic radiology. The objective of the current study was to determine which cytologic factors are associated with a favorable outcome and an unfavorable outcome in patients with PLA. Imprint smears from 134 patients with PLA were examined. Sixteen cytologic factors, including necrosis, cellular distribution, overlapping of cell clusters, cluster aggregation, cluster size, cluster thickness, nuclear irregularity, nuclear size, variation in nuclear size, multinucleated cells, intranuclear inclusions, type of intranuclear inclusions, appearance of nucleoli, eosinophilic nucleoli, multinucleoli, and mitosis, were evaluated using univariate and multivariate analyses. A counting method was used to determine the prognosis for individual patients. In the univariate analysis, a cluster size that measured > or = 831 microm in short dimension (P = 0.0011), moderate or severe nuclear irregularity (P = 0.0030), > or = 5 multinucleated cells per 100 tumor cells (P = 0.0047), moderate or severe variation in nuclear size (P = 0.0061), medium or large nuclear size (P = 0.0169), and > or = 1 mitotic cell per 100 tumor cells (P = 0.0412) were associated significantly with a poor outcome. In the multivariate analysis, cluster size in short dimension (P = 0.0018), multinucleated cells (P = 0.0066), and nuclear irregularity (P = 0.0310) were found to be independent prognostic factors. The combination of cytologic features using intraoperative imprint smears, namely, cluster sizes < or = 830 microm in short dimension, < or = 4 multinucleated cells per 100 tumor cells, and mild nuclear irregularity, may provide favorable predictive information in patients with PLA.


A historical perspective on the immunodiagnosis of schistosomiasis in China.
The investigation and application of immunodiagnosis in schistomiasis have had a history of about 50 years so far in China. The author, in this paper, briefly review the progress of the technology involved here in the country, putting the stress on the latest issues during last decade. Also showed some limits in the use for control program of the disease through summary of some collaborative studies with the attempt in identifying guidelines for the implementation of serology in schistosomiasis immunodiagnosis. In addition, it was pointed out that a seroepidemiological approach in the identification of target individuals for treatment or re-treatment may be realistic and practical, which emphasized that the immunodiagnostic approach for public health use could ignore individual identification of the real infections. In this way, it became possible to bypass the complexity of interpreting the seroreactivity of an individual in assigning him/her with qualitative testing to the normal or infected person. Instead, one needs only to divide individuals in a community into 'normal' or 'infected' groups according to the titer distribution, which leads to identifying target groups for treatment.


Structural and digestibility properties of infrared heat-moisture treated maize starch complexed with stearic acid.
This study investigated the effects of using infrared heat-moisture treatment (IRHMT) on the properties of maize starch paste complexed with stearic acid (SA). Scanning electron micrographs showed that starch granules ghosts from IR HMT starch with SA did not show significant granular disintegration in comparison to conventionally HMT starch paste. The resistant starch (RS) content increased with SA-IR HMT, while extended pasting increased slowly digestible starch (SDS) content in IR HMT starch alone. The V polymorphs observed in XRD and DSC, and increased crystallinity from FTIR supported the changes in the properties of IRHMT starches. To a greater extent, the SA-IRHMT exerted more changes on starch micro- and molecular structural properties, and digestibility properties compared to conventional heat-moisture treatment (CHMT).


Improved solubility and pharmacokinetics of PEGylated liposomal honokiol and human plasma protein binding ability of honokiol.
PEGylated liposomal honokiol had been developed with the purpose of improving the solubility and pharmacokinetics compared with free honokiol. Human plasma protein binding ability of honokiol was also investigated. PEGylated liposomal honokiol was prepared by thin film evaporation-sonication method. Its mean particle size was 98.68 nm, mean zeta potential was -20.6 mV and encapsulation efficiency were 87.68±1.56%. The pharmacokinetics of PEGylated liposomal honokiol was studied after intravenous administration in Balb/c mice. There were significant differences of parameters T(1/2β) and AUC(0→∞) between them and liposome lengthened T(1/2β) and AUC(0→∞) values. The mean T(1/2β) value of PEGylated liposomal honokiol and free honokiol were 26.09 min and 13.46 min, respectively. The AUC(0→∞) ratio of PEGylated liposomal honokiol to free honokiol was about 1.85-fold (219.24 μg/mL min/118.68 μg/mL min) (P=0.000). Examination of protein binding ability showed that honokiol with 0.5, 8.0 and 20 μg/mL concentrations in human plasma achieved the percent of bound between 60% and 65%. The results suggested that PEGylated liposomal honokiol improved the solubility, increased the drug concentration in plasma, and withstanded the clearance. Besides, the percent of protein bound of honokiol in human plasma was between 60% and 65%.


The rapid determination of erythrocyte porphyrins using reversed-phase high performance liquid chromatography.
The extraction, separation and quantification of free acid erythrocyte porphyrins are described. The porphyrins are extracted from whole blood using 3:1 ethyl acetate/acetic acid (v/v) and separated using the reversed-phase mode of high performance liquid chromatography (RPLC). The compounds are detected on-line spectrofluorometrically using an excitation wavelength of 404 nm and an emission cut-off filter of 550 nm. Excellent resolution of the porphyrin free acids is achieved in less than 6 min. The analytical recoveries for protoporphyrin IX and zinc protoporphyrin IX were greater than 90% with relative standard deviations for day-to-day analysis under 6%.


Origin differentiation of heroin sample and its acetylating agent with (13)C isotope ratio mass spectrometry.
A novel method for deducing the origins of heroin and the reagent used for acetylation was established based on delta(13)C determinations of heroin and its hydrolysate, morphine, using gas chromatography (13)C isotope ratio mass spectrometry (GC-C-IRMS). The alkaline and acid hydrolysis conditions of heroin were optimized. Both yield and purity of morphine produced could meet the requirement for a GC-C-IRMS analysis. Using (2-diethylaminoethyl-2,2- diphenylvalerate) as internal standard the determinations of heroin and morphine contents were performed with a GC method in a linear range of 0.2 to 2.0 mg ml(1) that was required to gain the isotope ratio results. The hydrolysis and synthesis of heroin did not change the delta(13)C value of morphine. The precision for delta(13)C detection of both heroin and morphine was sufficient for origin differentiation of heroin samples. The information about the origins of acetylation reagents could be deduced from the difference of delta(13)C values between heroin and morphine. The results for origin differentiation of 10 heroin samples grouped into different regions and their acetylating agents were satisfactory.


Recent insights into the mechanism of action of glatiramer acetate.
Glatiramer acetate (GA, Copaxone®, co-polymer 1) is an immunomodulatory therapy approved in 1996 by the United States Food and Drug Administration for treatment of relapsing-remitting multiple sclerosis. GA has a good safety profile, moderate efficacy, and a unique mode of action. Recent evidence in an animal model of MS, experimental autoimmune encephalomyelitis (EAE), suggests that GA effects on NK cells and B cells may contribute to therapeutic efficacy. We review the mechanism of action of GA, with particular focus on recent data suggesting a role for regulatory B cells.


Acquisition and performance in a rat sequential reaction time task is not affected by subtotal ventral striatal 6-OHDA lesions.
Based on findings of experiments with humans, non-human primates and rodents, it is commonly accepted that dopaminergic basal ganglia processes play a crucial role in procedural and sequential learning. Primal evidence for this hypothesis came from serial reaction time tasks (SRTT) studies, demonstrating that healthy controls show increased reaction times when visual stimulus presentation switches from a previously learned sequence to random stimulus presentation. This so-called interference effect was reduced in patients with Parkinson's disease. Since ethical and methodical aspects limit neurobiological research in human subjects, we developed a rat version of the human SRTT, which can be used to study experimentally induced brain damage. In the present experiment we investigated the effects of bilateral 6-OHDA lesions of the ventral striatum on sequential learning. The lesions led to subtotal dopaminergic depletions in the ventral striatum (58-60%) and also minor depletions in the medial neostriatum (32-46%). These lesions impaired task acquisition only moderately and did not worsen sequential performance since lesion and control animals showed a comparable interference effect when the trained sequence was tested against random stimulus presentation or violated sequences. In contrast, in an earlier SRTT experiment with medial neostriatal dopaminergic lesions (58-66%), the lesion animals were clearly impaired in their sequential learning as compared to controls. Therefore, we assume that subtotal dopamine loss in the medial neostriatum, rather than the ventral striatum, has a substantial effect on sequential learning.


Prevalence of the reversed halo sign in neutropenic patients compared with non-neutropenic patients: Data from a single-centre study involving 27 patients with pulmonary mucormycosis (2003-2016).
Pulmonary mucormycosis (PM) is a life-threatening infection and the diagnosis can be challenging. The objective was to retrospectively explore the value of the RHS in our cohort of 27 patients with mucormycosis and its relation to neutropenia. This was a retrospective study including all patients with a diagnosis of probable or proven invasive PM according to the 2008 EORTC/MSG criteria between September 2003 to April 2016. Fisher's exact test and Mann-Whitney test, with a P-value statistically significant under .05 (P<.05), were used to compare neutropenic and non-neutropenic groups. 27 patients were eligible. The RHS could be identified in 78% of cases in the neutropenic group, and was less common in the non-neutropenic group (31%) (P<.05). Reticulations inside ground-glass opacity in case of RHS were present in 13 out of 15 patients (87%). Mucorales DNA detection by PCR on serum provided, a median time to the first PCR-positive sample of 3 days (-33 to +60 days) before diagnosis was confirmed. Six patients had IPA co-infection. In conclusion, RHS is more frequent in case of PM in neutropenic patients compare to non-neutropenic patients. Its presence in immunocompromised patients should be sufficient to promptly start Mucorales-active antifungal treatment, while its absence especially in non-neutropenic cases should not be sufficient to exclude the diagnosis.


Schipropins A-J, structurally diverse triterpenoids from Schisandra propinqua.
Schipropins A-J, a series of undescribed lanostane and cycloartane-type triterpenoids, were isolated from the stems and leaves of Schisandra propinqua. Their structures, most of which were characterized by C-3/C-4 cleavage, were elucidated by extensive spectroscopic analyses. Noteworthily, the absolute configurations of schipropins A, D-G, and I were determined by single-crystal X-ray diffraction. Furthermore, schipropins E and G were found to possess moderate NO production inhibitory activity.


Epigenetics in the mature mammalian brain: effects on behavior and synaptic transmission.
The role of epigenetic mechanisms in control of gene expression during mammalian development is well established. Associations between specific DNA or histone modifications and numerous neurodevelopmental and neurodegenerative disorders implies significant consequences of epigenetic dysregulation in both the developing and mature brain, the latter of which is the general focus of this review. Accumulating evidence suggests that epigenetic changes are involved in normal cognitive processes in addition to neurological and psychiatric disorders. Recent investigations into the regulation of epigenetic modifications in the adult brain have revealed novel and surprisingly dynamic mechanisms for controlling learning and memory-related behaviors as well as long-term synaptic plasticity. DNA methylation and histone acetylation have also been implicated in the modulation of basal synaptic transmission and the balance between excitation and inhibition in various brain regions. Studies have begun to uncover some of the alterations in gene expression that appear to mediate many of these effects, but an understanding of the precise mechanisms involved is still lacking. Nevertheless, the fundamental importance of epigenetic processes in influencing neuronal activity is becoming increasingly evident.


Fatigue and traumatic brain injury.
Fatigue is frequent and disabling in patients with traumatic brain injury (TBI). Its mechanisms are complex and multifactorial. We performed a literature review of reports of the condition using the following key words: brain injury, depression, neuroendocrine dysfunction, and treatment. Five scales have been used to evaluate fatigue in TBI patients: the Fatigue Severity Scale, the visual analog scale (VAS) for fatigue, the Fatigue Impact Scale, the Barrow Neurological Institute (BNI) Fatigue Scale and the Cause of Fatigue (COF) Questionnaire. The BNI Fatigue Scale and the COF Questionnaire have been designed specifically for brain-injured patients. Fatigue is present in 43-73% of patients and is one of the first symptoms for 7% of them. Fatigue does not seem to be significantly related to injury severity not to time since injury. It can be related to mental effort necessary to overcome attention deficit and slowed processing ("coping hypothesis"). It can also be related to sleeping disorders and depression, although the relation between fatigue and depression are debated. Finally, fatigue can also be related to infraclinical pituitary insufficiency (growth hormone insufficiency, hypocorticism). To date, no published study of treatment of fatigue after TBI exists.


Microdialysis for in vivo pharmacokinetic/pharmacodynamic characterization of anti-infective drugs.
Inadequate tissue penetration of antibiotics can lead to therapeutic failure and bacterial resistance. Pharmacokinetic evaluation of antibiotics should therefore be based on tissue rather than serum concentrations. Over several years, tissue concentration data obtained by methods such as tissue biopsies have flawed the correct interpretation of antibiotic tissue distribution. Microdialysis--a semi-invasive catheter-based sampling technique--has been employed for the in vivo measurement of antibiotic tissue pharmacokinetics. Owing to selective access to the target site for most anti-infective drugs, microdialysis satisfies regulatory requirements for pharmacokinetic distribution studies and might become a reference technique for tissue distribution studies in the near future. Furthermore, microdialysis might contribute to the definition of meaningful surrogate markers for antibiotic efficiency during drug development.


Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide.
Results are presented of the incidence of hepatitis, nearly always with jaundice, among 1686 patients in clinical trials of the treatment of spinal tuberculosis, of tuberculosis meningitis and of pulmonary tuberculosis with short-course regimens containing rifampicin, isoniazid, streptomycin and pyrazinamide. The incidence was high in patients treated with daily regimens of isoniazid and rifampicin: 16-39% in children with tuberculous meningitis, 10% in patients with spinal tuberculosis (non-surgical cases), and 2-8% in those with pulmonary tuberculosis. Hepatitis, in those receiving rifampicin occurred more often in slow than in rapid acetylators of isoniazid, the proportions amongst those whose acetylator phenotype had been determined being 11% of 317 slow acetylators and 1% of 244 rapid acetylators. In children with tuberculous meningitis, the risk of hepatitis with isoniazid 20 mg/kg (39%) was higher than that with 12 mg/kg (16%), and appreciably lower in patients given rifampicin twice-weekly (5%) rather than daily (21%). There was no indication that pyrazinamide contributed to the hepatic toxicity.


Efficacy of atropine as an endoscopic premedication.
To determine the efficacy of atropine as an endoscopic premedication, we prospectively evaluated in double-blind fashion 196 elective endoscopies performed on 189 consecutive consenting patients. Group 1 (95 endoscopies) received meperidine, 1.5 mg/kg, intramuscularly 30 min prior to endoscopy. Group 2 (101 endoscopies) additionally received atropine, 0.6 mg, in the same injection. Endoscopy was performed by one of two investigators using a 13-mm fiberoptic instrument. Endoscopists and patients filled out postendoscopy questionnaires. Both endoscopists (p less than 0.01) and patients (p less than 0.05) noted less oral secretions after atropine. Endoscopists noted less gastric motility after atropine (p less than 0.05) and guessed correctly whether or not atropine had been given in two thirds of cases. They noted no overall difference, however, in the ease of the endoscopy (p greater than 0.05). Moreover, there were no differences in the patients' assessments of the acceptability of the procedure between the two groups (p greater than 0.05). We concluded that although atropine does not improve patients' tolerance for the examination or the endoscopists' ability to do an adequate examination, it does objectively decrease the amount of gastric motility and oral secretions. This latter effect could potentially decrease the hazard of aspiration, but such a benefit could not be demonstrated in our series.


The isolation and characterization of a mutant strain of Saccharomyces cerevisiae that requires a long chain base for growth and for synthesis of phosphosphingolipids.
A mutant of Saccharomyces cerevisiae has been obtained that shows an absolute growth requirement for long chain bases found in sphingolipids. In the absence of a long chain base, the cells are unable to synthesize the phosphoinositol-containing sphingolipids characteristic of yeast. These results suggest that one or more of the yeast sphingolipids plays a vital biological role.


Spontaneous directional change of F waves in atrial flutter.
Spontaneous change in direction of F waves in atrial flutter is rare. Its analysis may lend some insight to the current uncertainty about mechanisms responsible for atrial flutter.


Encapsulation of starch hydrogel and doping nanomagnetite onto metal-organic frameworks for efficient removal of fluvastatin antibiotic from water.
Growing interests and efforts have been recently focused on design and assembly of novel hydrogel nanosorbents for removal of drugs from wastewater. Therefore, this work is aimed to immobilize and encapsulate starch hydrogel matrix onto metal organic frameworks (MOFs) and dope with nanomagnetite. The magnetic MOFs-Starch hydrogel (NFe3O4@Zn(GA)/Starch-Hydrogel) was synthesized via microwave irradiation process and characterized with high surface area (528.39 m2/g), mesoporous with pore size 2.90 nm and highly crystalline structure. The maximum swelling ratio (1000.0 %) was optimized at pH 10, 180 min and 25 °C. The validity of NFe3O4@Zn(GA)/Starch-Hydrogel for adsorptive removal of Fluvastatin statin drug provided maximum equilibrium adsorption capacity 782.05 mg g-1. The Langmuir isotherm and pseudo-second kinetics models were correlated well with the computed correlation coefficient values 0.9991 and 0.9997, respectively. The validity of NFe3O4@Zn(GA)/Starch-Hydrogel for removal of FLV statin drug from real water matrices was confirmed in the range 96.15-99.99 %.


Developmental outcomes in early compared with delayed surgery for glue ear up to age 7 years: a randomised controlled trial.
To investigate whether early versus delayed surgery for children severely affected by otitis media with effusion (OME) results in improved performance on developmental tests up to age 7 years. Follow-up of a randomised controlled trial. University of Bristol. One hundred and eighty-two children (mean age 35 months) with persistent OME, hearing loss and speech, language or behaviour problems who were originally eligible and randomised to either early surgery or delayed surgery after a period of watchful waiting were followed-up as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 4 1/2 and 7-8 years. Measures included behaviour, language, educational attainment tests, hearing, reading, cognition and coordination. Of the original randomised trial, 88 of 92 of the early surgery and 74 of 90 of the watchful waiting group were still participating in ALSPAC. Analysis was by intention to treat. At age 4 1/2 years there were significant differences in teacher assessment of language (adj OR 3.45, 95% CI: 1.42-8.39) and writing (adj OR 3.74, 95% CI: 1.51-9.27), in favour of early surgery. At age 7-8 years, there was a significant difference on teacher report of emotional problems (adj OR 4.11, 95% CI: 1.15-14.64) in favour of early surgery. There were no other significant differences. Early surgery for the child severely affected by OME may be associated with subtle benefits at age 4 1/2 years. This may continue to 7-8 years but the small study size makes it difficult to distinguish these effects from chance. A larger study is recommended.


Chain scission of hyaluronan by carbonate and dichloride radical anions: potential reactive oxidative species in inflammation?
The reactions of the carbonate and dichloride radical anions, CO3- and Cl2-, with the extracellular matrix glycosaminoglycan hyaluronan (HA) have been studied using the kinetic technique of pulse radiolysis and also by steady-state irradiation combined with gel permeation chromatography/multiangle laser light scattering(gpc/MALLS) to measure the rates of reaction with HA and the yield of HA chain scission, respectively. For comparison, the same measurements were made for the reactions of the free radicals *OH, Br2*-, and N3*. The carbonate and dichloride radical anions were found to react relatively quickly with HA (7.0 x 10(5) and 6.9 x 10(6) dm3 mol(-1) s(-1), respectively) although they are much less reactive than the hydroxyl radical, *OH. Significant yields (20 and 38%, respectively) of chain scission of HA by these radical anions were also determined from the gpc/MALLS experiments, providing some support for their potential participation in the depolymerization of HA in vivo. These results are compared with data obtained for the other free radicals (hydroxyl, azide radicals, and dibromide radical anions) investigated in this study in order to gain an insight into their mechanism of reaction with HA. Earlier chain scission yields of HA by hydroxyl radicals determined by the authors have also been revised using the gpc/MALLS technique employed in the current study. The yields of 52% (absence of air) and 44% (in air) are much lower than the previous values. In the current study, the effect of oxygen on the yields of HA chain breaks is discussed in terms of the reactivity of HA peroxyl radicals in the presence of superoxide radical anions. The relevance of the results of this study to mechanisms of inflammation is discussed.


Changing trends in total knee replacement.
This study evaluates a possible change in the demographics and surgical practice observed in a large cohort of patients undergoing total knee replacement (TKR). We performed a retrospective analysis of a prospectively collected data on two groups of consecutive patients undergoing primary TKR. Group one consisted of patients who underwent surgery between 1994 and 1998. Group two consisted of patients who had surgery between 2009 and 2012. The mean age of group two was significantly greater than that of group one: 68.9 years (68.1-69.7 years) for group one versus 70.1 years (69.6-70.6 years) for group two (p = 0.009). The mean BMI of group two was significantly greater than that of group one: 29.5 kg/m2 (29.0-29.9 kg/m2) for group one versus 32.0 kg/m2 (31.7-32.3 kg/m2) for group two (p < 0.001). The mean pain component of the AKSS was significantly worse in group one than in group two: 28.6 (27.2-30.0) for group one versus 35.5 (34.6-36.4) for group two (p < 0.001). The mean function component of the AKSS was significantly worse in group one than in group two: 48.6 (47.3-49.9) for group one versus 51.5 (50.7-52.3) for group two (p < 0.001). This study describes the change in demographics of patients undergoing TKR in our institution over the last two decades.


Elbow fractures and dislocations.
Elbow fractures are common in pediatric patients. Most injuries to the pediatric elbow are stable and require simple immobilization; however, more severe fractures can occur, often requiring operative stabilization and/or close monitoring. This article highlights the common fractures and dislocations about the pediatric elbow and discusses the history, evaluation, and treatment options for specific injuries.


Pulmonary infection with Mycobacterium malmoense--a review of treatment and response.
Thirty seven patients whose sputum cultures had yielded positive isolates of Mycobacterium malmoense during the years 1978-1983 have been reviewed. Significant pulmonary infection was present in 34 patients (92%), 3 of whom had only single isolates cultured from their sputum. The significance of isolates in the remaining 3 patients was not established. There was pre-existing pulmonary disease in 22 patients and another 4 were taking immuno-suppressive drugs. Various drug regimens were used to treat the condition but the best responses were seen in 5 patients (13.5%) who received 3 standard drugs given for between 18-24 months. Relapse occurred in 3 of another 5 who were treated with the same combination but given for less than 18 months. Omission of ethambutol from this standard regimen was associated with an unfavourable course in another 7 patients. Regimens which included the second line drugs ethionamide and cycloserine were given to 10 patients. The responses in this group were poor and were probably related to drug toxicity and poor patient compliance. Four of these patients eventually underwent successful resectional surgery.


A finger on the pulse of regeneration: insights into the cellular mechanisms of adult digit tip regeneration.
In mammals, multi-tissue regeneration is largely restricted to the distal portion of the digit tip and involves the formation of a blastema, a transient, proliferating cell mass that reforms the diverse tissues of the digit. Historically little was known about the mammalian blastema but with recent advances in single cell transcriptomic approaches and genetic lineage tracing, a more precise understanding of this critical structure has begun to emerge. In this review we summarise the cellular mechanisms underlying adult mammalian digit tip regeneration. We posit that understanding how some mammals naturally regenerate complex tissues will lead to strategies for enhancing regenerative abilities in humans.


Vitamins and monothiols efficacy in the restoration of adenosine nucleotide degradation enzymes altered during methylmercury intoxication.
Male albino mice were intoxicated with a daily dose of 1 mg/kg of methylmercury chloride (MMC) for 7 days, and were treated thereafter with glutathione, N-acetyl-DL-homocysteine thiolactone, vitamin B complex, and vitamin E, either alone or in combinations, for the next 7 days. The animals were sacrificed on the eighth day, with the exception of one group that was kept without toxic exposure for an additional 7 days and sacrificed on the fifteenth day. Brain, spinal cord, kidney, and liver of the animals were examined for changes in adenosine deaminase and 5' nucleotidase. We found a severe inhibition of these enzymes during MMC intoxication and significant recovery during monothiols and vitamins administration, indicating the effectiveness of these agents in methylmercury detoxication.


Remodelling of subchondral bone in osteoarthritis: a histomorphometric study.
To determine whether remodelling of subchondral bone in osteoarthritis is related to anatomical and mechanical factors operating on the joint surface. Ten femoral heads were examined. Patients due to have the femoral head removed because of osteoarthritis were given a double tetracycline label before surgery. The specimens were divided in three roughly equal parts, corresponding to the medial, central (weight bearing), and lateral aspects of the femoral heads. Undecalcified methylmethacrylate embedded sections were prepared. The subchondral bone was assessed for appositional bone formation by ultraviolet light microscopy, for resorptive activity by osteoclast count, and for trabecular bone volume by semiautomatic computerised image analysis. Appositional bone rate was also correlated with the presence or absence of overlying cartilage. Bone density was reduced in the medial aspect of the femoral heads but there was no significant difference between the appositional bone rate or the resorptive activity in the three areas. Nor was there any correlation between appositional bone rate in the subchondral bone and the presence or absence of overlying cartilage. Remodelling of subchondral bone in osteoarthritis, at least in the short term, is fairly constant and is not related to weight bearing.


Real-time device tracking under MRI using an acousto-optic active marker.
This work aims to demonstrate the use of an "active" acousto-optic marker with enhanced visibility and reduced radiofrequency (RF) -induced heating for interventional MRI. The acousto-optic marker was fabricated using bulk piezoelectric crystal and π-phase shifted fiber Bragg grating (FBGs) and coupled to a distal receiver coil on an 8F catheter. The received MR signal is transmitted over an optical fiber to mitigate RF-induced heating. A photodetector converts the optical signal into electrical signal, which is used as the input signal to the MRI receiver plug. Acousto-optic markers were characterized in phantom studies. RF-induced heating risk was evaluated according to ASTM 2182 standard. In vivo real-time tracking capability was tested in an animal model under a 0.55T scanner. Signal-to-noise ratio (SNR) levels suitable for real-time tracking were obtained by using high sensitivity FBG and piezoelectric transducer with resonance matched to Larmor frequency. Single and multiple marker coils integrated to 8F catheters were readout for position and orientation tracking by a single acousto-optic sensor. RF-induced heating was significantly reduced compared to a coax cable connected reference marker. Real-time distal tip tracking of an active device was demonstrated in an animal model with a standard real-time cardiac MR sequence. Acousto-optic markers provide sufficient SNR with a simple structure for real-time device tracking. RF-induced heating is significantly reduced compared to conventional active markers. Also, multiple RF receiver coils connected on an acousto-optic modulator can be used on a single catheter for determining catheter orientation and shape.


Synthesis of vertically aligned wafer-scale tantalum disulfide using high-Ar/H2S ratio plasma.
Nanostructural modification of two-dimensional (2D) materials has attracted significant attention for enhancing hydrogen evolution reaction (HER) activity. In this study, the nanostructure of TaS2films was controlled by controlling the Ar/H2S gas ratio used in plasma-enhanced chemical vapor deposition (PECVD). At a high Ar/H2S gas ratio, vertically aligned TaS2(V-TaS2) films were formed over a large-area (4 in) at a temperature of 250 °C, which, to the best of our knowledge, is the lowest temperature reported for PECVD. Furthermore, the plasma species formed in the injected gas at various Ar/H2S gas ratios were analyzed using optical emission spectroscopy to determine the synthesis mechanism. In addition, the 4 in wafer-scale V-TaS2was analyzed by x-ray photoelectron spectroscopy, transmission electron microscopy, and atomic force microscopy, and the HER performance of the as-synthesized TaS2fabricated with various Ar/H2S ratios was measured. The results revealed that, depending on the film structure of TaS2, the HER performance can be enhanced owing to its structural advantage. Furthermore, the excellent stability and robustness of V-TaS2was confirmed by conducting 1000 HER cycles and post-HER material characterization. This study provides important insights into the plasma-assisted nanostructural modification of 2D materials for application as enhanced electrocatalysts.


MiR-192-5p/RB1/NF-κBp65 signaling axis promotes IL-10 secretion during gastric cancer EMT to induce Treg cell differentiation in the tumour microenvironment.
Regulatory T (Treg) cells are important components of the tumour microenvironment (TME) that play roles in gastric cancer (GC) metastasis. Although tumour cells that undergo epithelial-mesenchymal transition (EMT) regulate Treg cell function, their regulatory mechanism in GC remains unclear. The miR-192-5p was identified by examining three Gene Expression Omnibus GC miRNA expression datasets. RNA immunoprecipitation (RIP) and dual-luciferase reporter assays were conducted to identify interactions between miR-192-5p and RB1. The role of miR-192-5p/RB1 in GC progression was evaluated based on EdU incorporation, wound healing and Transwell assays. An in vitro co-culture assay was performed to measure the effect of miR-192-5p/RB1 on Treg cell differentiation. In vivo experiments were conducted to explore the role of miR-192-5p in GC progression and Treg cell differentiation. MiR-192-5p was overexpressed in tumour and was associated with poor prognosis in GC. MiR-192-5p bound to the RB1 3'-untranslated region, resulting in GC EMT, proliferation, migration and invasion. MiR-192-5p/RB1 mediated interleukin-10 (IL-10) secretion by regulating nuclear factor-kappaBp65 (NF-κBp65), affecting Treg cell differentiation. NF-κBp65, in turn, promoted miR-192-5p expression and formed a positive feedback loop. Furthermore, in vivo experiments confirmed that miR-192-5p/RB1 promotes GC growth and Treg cell differentiation. Collectively, our studies indicate that miR-192-5p/RB1 promotes EMT of tumour cells, and the miR-192-5p/RB1/NF-κBp65 signaling axis induces Treg cell differentiation by regulating IL-10 secretion in GC. Our results suggest that targeting miR-192-5p/RB1/NF-κBp65 /IL-10 may pave the way for the development of new immune treatments for GC.


Outstanding photocatalytic nitrogen fixation performance of TiO2 QDs modified by Bi2O3/NaBiS2 nanostructures upon simulated sunlight.
Nowadays, a promising material for NH3 production under mild and safe conditions using heterogeneous photocatalysts is very important. In this regard, Bi2O3 and NaBiS2 nanoparticles were combined with TiO2 quantum dots (QDs) through a facile hydrothermal process. The TiO2 QDs/Bi2O3/NaBiS2 nanocomposites displayed excellent performance in the photofixation of nitrogen upon simulated sunlight. The NH3 generation rate constant over the optimum nanocomposite was 10.2 and 3.3-folds higher than TiO2 (P25) and TiO2 QDs photocatalysts, respectively. The spectroscopic and electrochemical studies affirmed more effective segregation and transfer of photo-induced charge carriers within ternary nanocomposite, due to the developing tandem n-n-p heterojunctions, which led to more lifetime of charges. Moreover, the impacts of solvent, pH, electron scavenger, and lake of nitrogen molecules on the NH3 generation were investigated. Finally, it was concluded that the TiO2 QDs/Bi2O3/NaBiS2 nanocomposite, with appealing features of more activity, high stability, and a facile one-pot synthesis method, is a promising photocatalyst in nitrogen fixation technology.


Non-ischemic cerebral enhancing lesions after thrombectomy: a multicentric retrospective French national registry.
To report the occurrence of non-ischemic cerebral enhancing (NICE) lesions following mechanical thrombectomy (MT) through the retrospective French nationwide registry of NICE lesions. All thrombectomy capable stroke centers (TSC) in France were invited to fill out a questionnaire disseminated through a trainee-led research network (JENI-RC: Jeunes en Neuroradiologie Interventionnelle-Research Collaborative). NICE lesions were defined according to previous literature as delayed onset punctate, nodular, or annular foci enhancements with peri-lesion edema and vascular distribution in the territory of the MT with no other confounding disease. All 43 TSC French centers responded. Three patients were reported by 3 different centers over a total of 34,824 MT (2015-2020). Patient no. 1 developed symptomatic NICE lesions 8 weeks after MT with combination of aspiration and stentriever for a right middle cerebral artery occlusion. Patient no. 2 developed asymptomatic NICE lesions 5 weeks after MT with direct thromboaspiration for a right middle cerebral artery occlusion. Patient no. 3 developed symptomatic NICE lesions 6 weeks after MT with direct thromboaspiration, and combination of aspiration and stentriever for a basilar artery occlusion. This study provides evidence that NICE lesions following MT are a possible rare complication with a similar presentation as previously described following endovascular aneurysm treatment. Both radiologists and neurologists should be aware of this adverse event and make use of MRI contrast agents in case of unexplained symptoms/images during follow-up after MT.


The optimal number of examined lymph nodes for accurate staging of intrahepatic cholangiocarcinoma: A multi-institutional analysis using the nodal staging score model.
This study aims to develop a nodal staging score (NSS) to determine the optimal number of lymph nodes (LNs) examined in intrahepatic cholangiocarcinoma (iCCA) patients. Clinicopathologic data were collected from the SEER database (development cohort, n = 2782) and seven Chinese tertiary hospitals (validation cohort, n = 363). NSS was constructed based on a binomial distribution to indicate the probability of nodal disease absence. In addition, its prognostic value was examined by survival analysis and multivariable modeling on pN0 patients. A model fit was performed in node-positive patients and a subgroup analysis was performed according to clinical characteristics. Statistically significant differences were only found in the subgroups when divided by the tumor size of 3 cm. As the number of examined lymph nodes (ELNs) increased, the likelihood of missing a metastatic LN decreased. NSS escalated as ELNs increased in groups with different tumor sizes, with plateaus at 7 and 11 LNs ensuring an NSS of 90.0% for ≤3 cm and >3 cm tumors, respectively. For pN0 patients, multivariate analysis revealed that NSS was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS). For accurate staging of iCCA, the optimal number of ELNs was related to tumor size. We recommend that at least 7 and 11 LNs should be examined for tumor size ≤3 cm and >3 cm, respectively. Therefore, the NSS model could be helpful to make clinical decisions for pN0 iCCA.


Efficacy of 6-month interferon therapy in chronic hepatitis B virus infection in Japan.
In Japan, there are few studies of long-term (more than 1 month) interferon (IFN) therapy for chronic hepatitis B (CHB). In this retrospective study, we investigated the efficacy and predictors of response to 6-month IFN therapy. We analyzed 66 Japanese patients with CHB who were treated with IFN for 6 months. They comprised patients who were hepatitis B e antigen (HBeAg)-positive (n=45) and -negative (n=21). One (2%), 8 (12%), and 51 (77%) patients were infected with hepatitis B virus (HBV) genotypes A, B, and C, respectively. Responders in patients positive for HBeAg were defined as those who showed normalization of serum alanine aminotransferase (ALT) level, HBeAg loss, and HBV DNA negativity at 6 months after completion of IFN therapy. In patients negative for HBeAg, responders were defined as those patients who showed normalization of ALT level and HBV DNA negativity at the same 6-month time point. Of the 45 patients with HBeAg at the commencement of IFN therapy, 9 (20%) were responders. Young patients, especially those with a high serum ALT level, were significantly more likely to respond to IFN therapy. Of the 21 patients negative for HBeAg, 13 (62%) were responders. There were no significant differences in clinical characteristics between responders and nonresponders among patients negative for HBeAg. Multivariate analyses identified HBeAg negativity and young age as independent factors associated with a positive response to 6-month IFN therapy. However, long-term follow-up of the treated patients showed a fall in the response rate. The response rate to 6-month IFN therapy among HBeAg-positive patients was low. However, young patients may require long-term IFN therapy.


A simple method for reducing ovarian dose during megavoltage irradiation of the breast.
Breast cancer in its early stages can be effectively treated with conservative surgery and irradiation. In young women who wish to subsequently bear children, reduction of ovarian dose during irradiation could be of great emotional significance. We describe a simple, convenient, cost-effective method by which ovarian dose was reduced from 18 cGy to 8 cGy during tangential irradiation of the intact breast with 6 MV photons.


Fungaemia in hospitalized patients.
At various clinics of IRCCS S. Matteo Hospital, Pavia, Italy, 269 blood cultures recovered from immunocompromised patients over 4 years have been examined mycologically. Of the 269 cultures, 101 were from HIV-infected patients and five were from cardiac transplant recipients. Of the total examined 96 blood cultures were positive (36%). The most frequent genus was Candida: C. albicans (48%), C. tropicalis and C. parapsilosis (8% each), C. glabrata and C. guillermondii (3% each). Cryptococcus neoformans was detected in 21 patients (22%).


Diagnostic accuracy of computed tomography-guided biopsy in pathological fractures.
Obtaining a histological diagnosis is essential for appropriate management of pathological fractures. Computed tomography (CT) is an accurate method of obtaining diagnosis for musculoskeletal tumours. We analysed whether diagnostic accuracy was maintained in the evaluation of pathological fractures. A retrospective review of 101 consecutive patients presenting to our tertiary musculoskeletal tumour centre with pathological fracture was performed. Patients underwent core needle biopsy under CT guidance of pathological fractures diagnosed by plain radiography and either CT or magnetic resonance imaging. The histopathology of the CT-guided biopsy was compared with the sample obtained from open biopsy or definitive surgery to determine diagnostic accuracy. The mean age at diagnosis was 52 ± 20 years (range: 18-85) in a cohort of 46 men and 55 women. Diagnostic accuracy of CT-guided biopsy was 82.18%. There were 65 malignant and 36 benign tumours with diagnostic accuracy of 86.15% and 80.56%, respectively. The positive predictive value for a malignant tumour was 98.21% whilst it was 93.1% for benign tumours. The femur (53 cases) and humerus (25 cases) were the commonest bones fractured. The most frequent diagnoses were metastasis (20.79%), giant cell tumour (17.82%), osteosarcoma (9.90%) and myeloma (9.90%). There were no complications of CT-guided biopsy. Pathological fracture does not confound the diagnosis of musculoskeletal tumours. CT-guided biopsy is an accurate diagnostic tool in the evaluation of pathological fractures. Final diagnosis and management should be made in the context of appropriate anatomical and functional imaging using a multidisciplinary approach.


Provider versus patient-centered approaches to health promotion with parents of young children: what works/does not work and why.
The purpose of this paper was to provide insight into why the health promotion approach now in general use does not work and to describe the rationale and specific steps that can be taken to enhance the effectiveness of preventive communications.


Protein and peptide-based therapeutics in periodontal regeneration.
Protein and peptide-based therapeutics provide a unique strategy for controlling highly specific and complex biologic actions that cannot be accomplished by simple devices or chemical compounds. This article reviews some of the key characteristics and summarizes the clinical effectiveness of protein and peptide-based therapeutics targeting periodontal regeneration. A literature search was conducted of randomized clinical trials and systematic reviews evaluating protein and peptide-based therapeutics for the regeneration of periodontal tissues of at least 6 months duration. Data sources included PubMed and Embase electronic databases, hand-searched journals, and the ClinicalTrials.gov registry. Commercially marketed protein and peptide-based therapeutics for periodontal regeneration provide gains in clinical attachment level and bone formation that are comparable or superior to other regenerative approaches. Results from several clinical trials indicate that protein and peptide-based therapies can accelerate repair and regeneration when compared with other treatments and that improvements in clinical parameters continue beyond 12 months. Protein and peptide-based therapies also exhibit the capacity to increase the predictability of treatment outcomes. Clinical and histologic studies support the effectiveness of protein- and peptide-based therapeutics for periodontal regeneration. Emerging evidence suggests that the delivery devices/scaffolds play a critical role in determining the effectiveness of this class of therapeutics.


Blocking Serum Amyloid-P Component from Binding to Macrophages and Augmenting Fungal Functional Amyloid Increases Macrophage Phagocytosis of Candida albicans.
Candida-macrophage interactions are important immune defense responses associated with disseminated and deep-seated candidiasis in humans. Cells of Candida spp. express functional amyloids on their surfaces during the pathogenesis of disseminated candidiasis. These amyloids become decorated with serum amyloid P-component (SAP) that binds to Candida cells and macrophages and downregulates the cellular and cytokine response to the fungi. In this report, further characterization of the interactions of SAP and fungal functional amyloid are demonstrated. Blocking the binding of SAP to macrophage FcγR1 receptors increases phagocytosis of yeast cells; seeding a pro-amyloid-forming peptide on the yeast cell surface also increases phagocytosis of yeasts by macrophages; and, lastly, miridesap, a small palindromic molecule, prevents binding of SAP to yeasts and removes SAP that is bound to C. albicans thus, potentially increasing phagocytosis of yeasts by macrophages. Some, or all, of these interventions may be useful in boosting the host immune response to disseminated candidiasis.


No physiological costs of dual sequestration of chemically different plant toxins in the milkweed bug Spilostethus saxatilis (Heteroptera: Lygaeidae).
Many herbivorous insects not only cope with plant toxins but also sequester them as a defense against predators and parasitoids. Sequestration is a product of the evolutionary arms race between plants and herbivorous insects and has been hypothesized to incur physiological costs due to specific adaptations required. Contradictory evidence about these costs exists for insects sequestering only one class of toxin, but very little is known about the physiological implications for species sequestering structurally different classes of compounds. Spilostethus saxatilis is a milkweed bug belonging to the cardenolide-sequestering heteropteran subfamily Lygaeinae (Heteroptera: Lygaeidae) that has shifted to the colchicine-containing plant Colchicum autumnale, a resource of chemically unrelated alkaloids. Using feeding-assays on artificial diet and chemical analysis, we assessed whether S. saxatilis is still able to sequester cardenolides apart from colchicine and related metabolites (colchicoids), and tested the effect of (1) either a natural cardenolide concentration (using ouabain as a model compound) or a natural colchicine concentration, (2) an increased concentration of both toxins, and (3) seeds of either Asclepias syriaca (cardenolides) or C. autumnale (colchicoids) on a set of life-history traits. For comparison, we assessed the same life-history traits in the milkweed bug Oncopeltus fasciatus exposed to cardenolides only. Although cardenolides and colchicoids have different physiological targets (Na+/K+-ATPase vs tubulin) and thus require different resistance traits, chronic exposure and sequestration of both isolated toxins caused no physiological costs such as reduced growth, increased mortality, lower fertility, or shorter adult life span in S. saxatilis. Indeed, an increased performance was observed in O. fasciatus and an according trend was found in S. saxatilis when feeding on isolated ouabain and isolated colchicine, respectively. Positive effects were even more pronounced when insects were provided with natural toxic seeds (i.e. C. autumnale for S. saxatilis and A. syriaca for O. fasciatus), especially in O. fasciatus. Our findings suggest, that S. saxatilis can sequester two chemically unrelated classes of plant compounds at a cost-free level, and that colchicoids may even play a beneficial role in terms of fertility.


Clinical features, pathogenesis, and management of stroke-like episodes due to MELAS.
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a disease that should be considered as a differential diagnosis to acute ischemic stroke taking into account its onset pattern and neurological symptoms, which are similar to those of an ischemic stroke. Technological advancements in neuroimaging modalities have greatly facilitated differential diagnosis between stroke and MELAS on diagnostic imaging. Stroke-like episodes in MELAS have the following features: (1) symptoms are neurolocalized according to lesion site; (2) epileptic seizures are often present; (3) lesion distribution is inconsistent with vascular territory; (4) lesions are common in the posterior brain regions; (5) lesions continuously develop in adjacent sites over several weeks or months; (6) neurological symptoms and stroke-like lesions tend to be reversible, as presented on magnetic resonance imaging; (7) the rate of recurrence is high; and; (8) brain dysfunction and atrophy are slowly progressive. The m.3243ANG mutation in the MT-TL1 gene encoding the mitochondrial tRNALeu(UUR) is most commonly associated with MELAS. Although the precise pathophysiology is still unclear, one possible hypothesis for these episodes is a neuronal hyperexcitability theory, including neuron-astrocyte uncoupling. Supplementation, such as with L-arginine or taurine, has been proposed as preventive treatments for stroke-like episodes. As this disease is still untreatable and devastating, numerous drugs are being tested, and new gene therapies hold great promise for the future. This article contributes to the understanding of MELAS and its implications for clinical practice, by deepening their insight into the latest pathophysiological hypotheses and therapeutic developments.


CYP4A11 is repressed by retinoic acid in human liver cells.
CYP4A11, the major fatty acid omega-hydroxylase in human liver is involved in the balance of lipids, but its role and regulation are both poorly understood. We studied the effects of retinoids on the regulation of CYP4A11 in the human hepatoma cell line HepaRG. Treatment of HepaRG cells with all-trans-retinoic acid resulted in a strong decrease in CYP4A11 gene expression and apoprotein content and, furthermore, was associated with a 50% decrease in the microsomal lauric acid hydroxylation activity. Such a strong suppression of CYP4A11 expression by retinoids could have a major impact on fatty acid metabolism in the liver.


Risk of hematological malignancies associated with magnetic fields exposure from power lines: a case-control study in two municipalities of northern Italy.
Some epidemiologic studies have suggested an association between electromagnetic field exposure induced by high voltage power lines and childhood leukemia, but null results have also been yielded and the possibility of bias due to unmeasured confounders has been suggested. We studied this relation in the Modena and Reggio Emilia municipalities of northern Italy, identifying the corridors along high voltage power lines with calculated magnetic field intensity in the 0.1-<0.2, 0.2-<0.4, and > or = 0.4 microTesla ranges. We identified 64 cases of newly-diagnosed hematological malignancies in children aged <14 within these municipalities from 1986 to 2007, and we sampled four matched controls for each case, collecting information on historical residence and parental socioeconomic status of these subjects. Relative risk of leukemia associated with antecedent residence in the area with exposure > or = 0.1 microTesla was 3.2 (6.7 adjusting for socioeconomic status), but this estimate was statistically very unstable, its 95% confidence interval being 0.4-23.4, and no indication of a dose-response relation emerged. Relative risk for acute lymphoblastic leukemia was 5.3 (95% confidence interval 0.7-43.5), while there was no increased risk for the other hematological malignancies. Though the number of exposed children in this study was too low to allow firm conclusions, results were more suggestive of an excess risk of leukemia among exposed children than of a null relation.


COVID-19 Pandemic and Im/migrants' Elevated Health Concerns in Canada: Vaccine Hesitancy, Anticipated Stigma, and Risk Perception of Accessing Care.
Vaccine hesitancy has taken a toll on COVID-19 immunization globally. This study aims to characterize three COVID-19-related health concerns (i.e., vaccine hesitancy, anticipated stigma, and risk perception) in Canada and how they differ based on im/migration status and other social determinants. Data were obtained from a nationwide probability sample of the Canadian Perspective Survey Series 3 (June 15 to 21, 2020). Multivariable binary logistic regression analysis was performed to investigate the association between each COVID-19 concern and nativity status, while controlling for socio-demographics. Of 3522 participants aged ≥ 25 years, the estimated overall prevalence of vaccine hesitancy was 16.9%, with im/migrants being greater than non-immigrants (21.5% vs. 15.5%, p < 0.001). After controlling for all covariates, im/migrants had around two-fold greater odds of all three health concerns, including risk perception of accessing care (aOR 2.44, 95% CI 1.89-3.15), anticipated stigma of being targeted (aOR 2.24, 95% CI 1.81, 2.78) and COVID-19 vaccine hesitancy (aOR 1.99, 95% CI 1.57-2.52), compared to their Canadian-born peers. Among vaccine-hesitant individuals (n = 596), im/migrants reported higher concerns, than non-immigrants, on vaccine safety (71.3% vs. 49.5%), side effects (66.4% vs 47.3%) and mistrust in vaccinations (12.5% vs 6.6%) as possible reasons of vaccine refusal. For migrant justice, health authorities should ensure equitable access to COVID-19 vaccines and other health-enhancing resources for im/migrants to mitigate their heightened fear, stigma, and mistrust of new vaccines amidst turbulent times.


Alteration of the Condylar Oral Bone in Obese and Gastric Bypass Mice.
Obesity is the main cause of type 2 diabetes mellitus (T2DM). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for this obesity-related health problem. However, the adverse effects of T2DM on bone tissue persist or even aggravate after this surgical procedure. As studies on the mandibular condyle bone are scarce, the aim of the present study was to assess its compositional characteristics in T2DM and RYGB conditions. Thirty-two male C57BL/6 mice at 8 weeks of age were randomly assigned to receive either a high-fat or low-fat diet. After 14 weeks of high-fat diet intake, seven obese mice were subjected to RYGB surgery. All animals were euthanized at the age of 30 weeks. Mandibular bones were removed and the trabecular condyle region was assessed using Raman spectroscopy. A decreased mineralization was observed for both T2DM and RYGB condyle bones when compared to controls, with elevated carbonate substitutions for the RYGB group. No compositional differences in crystallinity and presence of advanced glycation end products were found between the groups, with the exception of an increased presence of N-carboxymethyl-lysine in RYGB bone compared to their T2DM counterpart. Site-specific measurements revealed a non-uniform bone composition, with increasing mineralization and carbonate substitutions towards the centre of the mandibular condyle. T2DM and RYGB surgery affect the mandibular condyle bone quality, as investigated at compositional level. Assessment of bone structural properties and remodelling should be carried out to further explore the effects of T2DM and RYGB surgery on this skeleton area.


Carcinoma lobulare in situ B in monozygotic twins.
Some form of predisposition to breast cancer can be inherited, but it is not known whether the same applies to precancerous lesions of the breast. We are reporting on an identical incidence of carcinoma lobulare in situ type B in monozygotic twins. The case report illustrates that in identical twins the environment is usually more similar than in the general population so it is difficult to determine the hereditary component in the manifestation of a specific histologic trait. The observation may support the hypothesis that there is not only a high incidence of multicentric disease in both breasts of one person, but in the breasts of identical twin sisters too.


Conceptualising integration: a framework for empirical research, taking marriage migration as a case study.
Enquiry into the factors which impact on 'integration' requires clarity on the nature of the integration processes in which individuals are engaged, the intersection of those processes and the factors that may affect their operation over time. Elaborating on debates among European scholars which conceptualise integration as a series of multi-directional, inter-active processes in related but separate domains, we use the term 'effectors' to explore five sets of factors which have been shown to facilitate or impede those processes, setting out a framework capable of empirical and comparative application. We demonstrate the utility of this model in a case study funded by the Economic and Social Research Council (2013-2015) exploring the impact of transnational marriages in the UK, illustrating the conceptual and empirical value of the model when investigating the complexity of the factors involved in shaping the outcomes of integration processes. The model is illustrated in diagrammatic form. The case study in turn informs the model, highlighting the relevance of family and life-course events within an understanding of the full range of factors impacting on the integration processes in which individuals are engaged.


Postovulatory treatment with GnRH on day 5 reduces pregnancy loss in recipients receiving an in vitro produced expanded blastocyst.
The present study tested the hypothesis that administration of GnRH on day 5 of the estrous cycle in embryo transfer (ET) recipients would increase progesterone (P4) concentrations, embryo size, and improve fertility. Holstein and cross-bred Holstein heifers (n = 1562) were synchronized using a modified 5-day CIDR-Synch protocol as follows (All AM treatments): D-8, CIDR inserted; D-3, CIDR removed and PGF2α (500 μg cloprostenol) treatment; D-2, second PGF2α; D0, GnRH (G1, 100 μg gonadorelin acetate) to induce ovulation. On D5 in the afternoon, heifers were assigned in a completely randomized design to one of two treatments: Control (untreated) or GnRH (200 μg). Transfer of day 7 fresh IVP embryos was performed between D6 and D8 after G1. Data collected from each heifer included: embryo stage and quality, body condition score, technician performing ET, interval from G1 to ET, and number of previous transfers. All heifers were evaluated by transrectal ultrasonography on D5, D33, and D60 and a subset of heifers was scanned on D12 (n = 718; to determine ovulation to treatment) and another subset on D33 (n = 295; 16 s video to determine embryo and amniotic vesicle size). Serum P4 was determined from a subset of heifers on D12 (n = 467) and on D21 (n = 837) and pregnancy specific protein B (PSPB) on D28 (n = 843). Pregnancies per ET (P/ET) were analyzed by logistic regression and continuous outcomes by ANOVA. Ovulation to D5 GnRH, defined by the presence of an accessory CL on D12, was 83.9% (302/360) in GnRH-treated heifers vs. 3.3% (12/358) in Controls (P < 0.001). On D12, P4 was greater (P < 0.001) in GnRH-treated heifers (7.2 ± 0.1 ng/ml) vs Controls (6.0 ± 0.1 ng/ml). There was greater P/ET at D33 and D60 of pregnancy for Stage 7 than Stage 6 embryos. Treatment with GnRH did not alter P/ET with either embryo stage but decreased pregnancy loss between D33 and D60 in heifers receiving Stage 7 embryos. Presence of an accessory CL at the D33 pregnancy diagnosis was associated with a larger reduction in pregnancy loss from D33 to D60 in recipients of Stage 7 embryos (11.6 vs 27.6%). Although there was no GnRH effect on embryo size, the presence of an accessory CL was associated (P < 0.05) with larger amniotic vesicle volume in recipients of Stage 7 embryos. In addition, greater PSPB was linked to greater amniotic vesicle volume (P = 0.01) and to reduced pregnancy loss (P < 0.0001). In conclusion, treatment with GnRH on D5 caused ovulation and formation of an accessory CL, increased circulating P4, and reduced pregnancy loss in heifers receiving a Stage 7 but not a Stage 6 IVP embryo.


Characterization of winemaking yeast by cell number-size distribution analysis through flow field-flow fractionation with multi-wavelength turbidimetric detection.
Yeasts are widely used in several areas of food industry, e.g. baking, beer brewing, and wine production. Interest in new analytical methods for quality control and characterization of yeast cells is thus increasing. The biophysical properties of yeast cells, among which cell size, are related to yeast cell capabilities to produce primary and secondary metabolites during the fermentation process. Biophysical properties of winemaking yeast strains can be screened by field-flow fractionation (FFF). In this work we present the use of flow FFF (FlFFF) with turbidimetric multi-wavelength detection for the number-size distribution analysis of different commercial winemaking yeast varieties. The use of a diode-array detector allows to apply to dispersed samples like yeast cells the recently developed method for number-size (or mass-size) analysis in flow-assisted separation techniques. Results for six commercial winemaking yeast strains are compared with data obtained by a standard method for cell sizing (Coulter counter). The method here proposed gives, at short analysis time, accurate information on the number of cells of a given size, and information on the total number of cells.


A new method for the determination of the ABO blood type of semen by immunoblotting using anti-ABH antibodies following immunoprecipitation.
A new method that enables the ABO blood type of semen to be determined by identifying the molecular weight of a blood group substance (BGS) has been developed. In order to produce an antibody against a BGS (p84) detected on the sperm plasma membrand (SPM), p84 was purified from seminal plasma, injected into a rabbit. When seminal plasma was immunoprecipitated with the anti-p84 antibody, SDS-PAGE analysis of the immune complex yielded three specific polypeptides with molecular masses of 84, 51 and 25 kDa. The first of these polypeptides, p84, showed ABH antigenic activity when subjected to immunoblotting. The 51 and 25 kDa proteins corresponded to rabbit IgG heavy and light chains, respectively. Using this method, ABH antigenic activity of a band with a molecular mass of 84 kDa was detected in 25 seminal plasma samples by immunoblotting. When serial two-fold dilutions of seminal plasma were analyzed using this method, clear immunoreactive 84 kDa bands were observed up to 60-fold dilution. When seminal plasma was mixed with vaginal fluid at varying ratios, ABH antigenic activity of 84 kDa immunoreactive bands could be detected until the seminal plasma: vaginal fluid mixture reached a ratio of 1:20. These results suggest that this method will be applicable to the analysis of forensic samples of semen contaminated by vaginal fluid, such as those obtained from victims of sexual assault.


PFKFB3-mediated Pro-glycolytic Shift in Hepatocellular Carcinoma Proliferation.
Metabolic reprogramming, in particular, glycolytic regulation, supports abnormal survival and growth of hepatocellular carcinoma (HCC) and could serve as a therapeutic target. In this study, we sought to identify glycolytic regulators in HCC that could be inhibited to prevent tumor progression and could also be monitored in vivo, with the goal of providing a theragnostic alternative to existing therapies. An orthotopic HCC rat model was used. Tumors were stimulated into a high-proliferation state by use of off-target liver ablation and were compared with lower-proliferating controls. We measured in vivo metabolic alteration in tumors before and after stimulation, and between stimulated tumors and control tumors using hyperpolarized 13C magnetic resonance imaging (MRI) (h13C MRI). We compared metabolic alterations detected by h13C MRI to metabolite levels from ex vivo mass spectrometry, mRNA levels of key glycolytic regulators, and histopathology. Glycolytic lactate flux increased within HCC tumors 3 days after tumor stimulation, correlating positively with tumor proliferation as measured with Ki67. This was associated with a shift towards aerobic glycolysis and downregulation of the pentose phosphate pathway detected by mass spectrometry. MRI-measured lactate flux was most closely coupled with PFKFB3 expression and was suppressed with direct inhibition using PFK15. Inhibition of PFKFB3 prevents glycolytic-mediated HCC proliferation, trackable by in vivo h13C MRI.


Exploring the role of protein DJ-1 in quality of pale, soft and exudative (PSE) and red, firm and non-exudative (RFN) pork during post-mortem aging.
The purpose of this study was to investigate the changes of oxidative attributes, protein DJ-1 expression, oxidized form (oxDJ-1), and cellular localization in RFN and PSE pork meat during the post-mortem aging. The longissimus thoracis of RFN and PSE groups were collected and classified by determination of pH, color and purge loss and then aged for 1, 3 and 7 d at 4 °C postmortem. Results showed that the content of DJ-1 and oxDJ-1 was continuously increased during 7 d of postmortem aging. A relatively higher protein DJ-1, oxDJ-1, oxygen reactive species and disulfide bond contents were found in PSE meat in comparison to RFN meat. Immunostaining showed that protein DJ-1 was located in cytoplasm, membrane and some nucleus of muscle cells. DJ-1 was shown to correlate with meat quality and oxidative attributes, suggesting a regulatory role in resisting oxidative stress and meat quality formation during post-mortem aging.


Pre-eclampsia: evidence of altered ventricular repolarization by standard ECG parameters and QT dispersion.
Pre-eclampsia complicates approximately 6-8% of all pregnancies. Epidemiologic studies have demonstrated a relationship between pre-eclampsia and cardiac morbidity and mortality later in life, but the effect of pre-eclampsia on electrical cardiac activity during the acute phase has not yet been understood. The aim of this study was to investigate ECG alterations during pre-eclampsia. Prepartum ECGs of 76 consecutive pre-eclamptic women were compared with those of 76 healthy pregnant women. All of the routine ECG parameters were considered, and ventricular repolarization was assessed by QT interval and QT dispersion (QTd). Pregnancies complicated by pre-eclampsia showed a significant alteration of ventricular repolarization compared with the control group. Among ECG parameters, QT and QTc intervals and QTd were more prolonged in pre-eclamptic women. Multivariate analysis also showed that pre-eclampsia was the only independent determinant of QTd. In conclusion, pre-eclampsia has a significant effect on ventricular repolarization. This alteration could, in part, explain the increased cardiovascular risk of women with a history of pre-eclampsia. Further studies are necessary to confirm the relationship between ventricular repolarization abnormalities and increased cardiovascular risk later in life.


A two-dimensional semiconductor transistor with boosted gate control and sensing ability.
Transistors with exfoliated two-dimensional (2D) materials on a SiO2/Si substrate have been applied and have been proven effective in a wide range of applications, such as circuits, memory, photodetectors, gas sensors, optical modulators, valleytronics, and spintronics. However, these devices usually suffer from limited gate control because of the thick SiO2 gate dielectric and the lack of reliable transfer method. We introduce a new back-gate transistor scheme fabricated on a novel Al2O3/ITO (indium tin oxide)/SiO2/Si "stack" substrate, which was engineered with distinguishable optical identification of exfoliated 2D materials. High-quality exfoliated 2D materials could be easily obtained and recognized on this stack. Two typical 2D materials, MoS2 and ReS2, were implemented to demonstrate the enhancement of gate controllability. Both transistors show excellent electrical characteristics, including steep subthreshold swing (62 mV dec-1 for MoS2 and 83 mV dec-1 for ReS2), high mobility (61.79 cm2 V-1 s-1 for MoS2 and 7.32 cm2 V-1 s-1 for ReS2), large on/off ratio (~107), and reasonable working gate bias (below 3 V). Moreover, MoS2 and ReS2 photodetectors fabricated on the basis of the scheme have impressively leading photoresponsivities of 4000 and 760 A W-1 in the depletion area, respectively, and both have exceeded 106 A W-1 in the accumulation area, which is the best ever obtained. This opens up a suite of applications of this novel platform in 2D materials research with increasing needs of enhanced gate control.


What endoscopic accessories do we really need?
This article is a speculative essay that reviews the current limitations of existing flexible endoscopic accessories. Suggestions are offered on future developments that may change endoscopic practice as it adopts an increasingly therapeutic role. There may be a potential for development in flexible endoscopic surgical techniques that will be comparable to those seen in rigid laparoscopic surgery. Low and high technology solutions are considered. Invention, common sense, and engineering efforts are needed to take flexible endoscopic surgery to a higher level of functional efficacy.