Ammonium fluoride's analogy to ice: Possibilities and limitations.
Ammonium fluoride, NH4F, is often seen as an analog to ice, with several of its solid phases closely resembling known ice phases. While its ionic and hydrogen-ordered nature puts topological constraints on the ice-like network structures it can form, it is not clear what consequences these constraints have for NH4F compound formation and evolution. Here, we explore computationally the reach and eventual limits of the ice analogy for ammonium fluoride. By combining data mining of known and hypothetical ice networks with crystal structure prediction and density functional calculations, we explore the high-pressure phase diagram of NH4F and host-guest compounds of its hydrides. Pure NH4F departs from ice-like behavior above 80 GPa with the emergence of close-packed ionic structures. The predicted stability of NH4F hydrides shows that NH4F can act as a host to small guest species, albeit in a topologically severely constraint configuration space. Finally, we explore the binary NH3-HF chemical space, where we find candidate structures for several unsolved polyfluoride phases; among them is the chemical analog to H2O2 dihydrate.


Cytomegalovirus as a risk factor in living-related renal transplantation. A prospective study.
Forty-four living-related donor kidney (LRD) recipients (19 HLA-identical and 25 haploidentical) were followed prospectively to determine the posttransplant incidence and sequelae of cytomegalovirus (CMV) infection as they relate to the CMV status of recipients and donors. CMV titers were measured in all patients before transplantation by an immunofluorescent assay (IFA). Recipients similarly had CMV titers measured at selected intervals after transplant and during febrile episodes. Appropriate viral cultures were simultaneously performed. Laboratory evidence of infection was correlated with symptoms and signs of active CMV disease. Mean follow-up period was 20 +/- 12 months with a range of 3-51 months. Three patients were excluded due to early acute rejection resulting in graft loss. Twenty-eight of 41 donors (68%) and 22 of 41 recipients (54%) had positive CMV titers before transplantation. Six of 41 recipients (15%) subsequently developed clinical and laboratory evidence of CMV infection: three of 19 seronegative recipients and three of 22 seropositive recipients. All six patients received kidneys from seropositive donors. Four patients had severe CMV disease (2 seronegative, 2 seropositive), whereas two patients had leukopenia and fever only. Two patients with severe CMV infections subsequently lost their grafts due to unrelated causes. Overall, actual patient and graft survival of the entire group is 95% and 82%, respectively. In conclusion, individuals who receive LRD kidneys from seronegative individuals are unlikely to develop CMV infection, and transplantation of seropositive LRD kidneys may be associated with transmission of CMV in susceptible recipients regardless of their serologic status. With appropriate management of CMV illness in the posttransplant period, LRD kidney donation is safe and efficacious and should not be discouraged on the basis of pretransplant CMV serology in any donor-recipient pairing.


Iridium catalyzed acceptor/acceptor carbene insertion into N-H bonds in water.
The chemistry of A and D/A carbenes (D and A are donor and acceptor groups, respectively) is known to a great extent in the literature. Nevertheless the chemistry of the A/A class of carbenes is less explored, although the A/A class of carbenes is more important in natural product synthesis. The known catalysts for A/A carbene chemistry are also less in number and are found to be efficient only in typical organic solvents. These limitations prompted us to search for new catalysts and environmentally benign reaction conditions for the A/A class of carbenes. The present study reveals that [(COD)IrCl]2 is found to be an efficient catalyst for the A/A class of carbenes, and Pd2(dba)3 for the D/A class of carbenes, for insertion into N-H bonds in water under mild reaction conditions. A reactivity comparison study with different classes of carbenes revealed that silver based catalysts are the right choice for the D/D class of carbenes for insertion into N-H bonds in water. A large number of α-amino malonates and amino esters, which are important for the synthesis of heterocycles and several natural products, have been synthesized by following the current methodology, and characterized using standard analytical and spectroscopic techniques.


Estimation of instantaneous median frequency in surface electromyography signals using quadratic time frequency distribution.
Surface electromyography (sEMG) technique gives a non-stationary and multi component signal which can be used for neuromuscular analysis, ergonomics, rehabilitation and sports biomechanics. It records the electrical activity of skeletal muscles. The sEMG signals are often analyzed in the time domain, frequency domain and time-frequency domain. Although several methods of signal analyses are reported in the literature, the extraction of useful information still remains a challenging task. In this work, an attempt has been made to analyze sEMG signals in fatigue and non-fatigue conditions by using the quadratic time frequency distribution (QTFD). Signals are recorded for 25 normal control adult subjects during dynamic contractions in biceps brachii muscle. The acquired signals are subjected to QTFD by using a modified B distribution. The median frequency is extracted from the processed signal. The result shows that median frequency is distinct for fatigue and non fatigue conditions. Further it shows variation with flexion and extension. Thus the study seems to be clinically useful for the dynamic analysis of neuromuscular conditions.


A new species of Dignomus Wollaston (Coleoptera: Ptinidae) from Eocene Baltic amber.
Dignomus francescovitalii sp. nov. is described and illustrated based on a well-preserved specimen from Eocene Baltic amber. This new extinct species is placed into D. irroratus species-group. The distribution of the genus Dignomus including fossil records is mapped.


Evaluation of Sex Differences in the Elasticity of Demand for Nicotine and Food in Rats.
Animal studies can inform policy regarding nicotine levels in tobacco products and e-cigarette solutions. Increasing the price of nicotine-containing products decreases their use, but it is unknown how the relationship between price and consumption is affected by both sex and nicotine dose. A behavioral economics procedure was used to determine the demand elasticity for nicotine in male and female rats. Demand elasticity describes the relationship between price and consumption. A high level of elasticity indicates that consumption is relatively sensitive to increases in price. The rats self-administered a low dose (0.01 mg/kg/inf) or a standard dose (0.03 mg/kg/inf) of nicotine for 9 days under a fixed-ratio (FR) 1 schedule. Then the price (FR schedule) of nicotine was increased, and a demand analysis was conducted. A similar study was conducted with palatable food pellets. There were no sex differences in nicotine or food intake under the FR1 schedule. However, demand for 0.03 mg/kg/inf of nicotine was more elastic in females than males. Demand for 0.01 mg/kg/inf of nicotine and food was more elastic in males than females. These findings indicate that there are no differences in nicotine and food intake between males and females when the price is low. When the price of nicotine or food is increased, males maintain their old level of intake longer than females when they have access to a standard dose of nicotine, and females maintain their intake longer when they have access to a low dose of nicotine or food. This behavioral economics analysis indicates that there is no sex difference in nicotine intake when the price of nicotine is low. Increasing the price of nicotine decreases nicotine intake in a dose- and sex-specific manner. Males maintain their old level of intake longer when they have access to a standard dose of nicotine and females when they have access to a low dose. This has implications for tobacco regulatory policy. In a regulatory environment where only low nicotine-containing products are allowed, increasing the price of nicotine products may lead to a greater decrease in nicotine use in males than females.


Speculation on the meaning of cerebral metabolic hypofrontality in schizophrenia.
Cerebral metabolic hypofrontality in schizophrenia is a controversial research finding. In this article we discuss some of the issues that fuel this controversy, and we speculate on the neural mechanisms that may be responsible for the finding. Most regional cerebral blood flow (rCBF) studies using radioactive xenon have found hypofrontality; the results of positron emission tomography (PET) studies have been less consistent. Several technical factors are discussed that might contribute to the inconsistencies, including airway artifacts with xenon, limitations of tomography in studying the cortex, and approaches to data analysis. The possibility that hypofrontality is a result of medication is also critically examined. The medication factor is still unclear, but most studies of patients before and after neuroleptic medication find that cerebral metabolism goes up, not down, after treatment. The role of patient behavior and experience during an rCBF or PET procedure is an important variable that has not been adequately controlled in most studies. We suggest that this has been the most important variable in interpreting cerebral metabolic data in schizophrenia. Studies of patients examined during a behavior that normally activates prefrontal cortex have consistently found hypofrontality. One theoretical mechanism that could account for hypofrontality as well as many clinical and research findings in schizophrenia is dysfunction of dopaminergic neural transmission at the level of the prefrontal cortex.


Circulating beta-atrial natriuretic factor in congestive heart failure in humans.
beta-Atrial natriuretic factor (beta-ANF) is an antiparallel dimer of alpha-ANF (alpha-ANF) with diminished cyclic GMP generation in vitro. To date, the presence of beta-ANF in the circulation of humans with severe congestive heart failure (CHF) remains controversial. The current study was designed to determine the presence and magnitude of circulating beta-ANF in severe CHF, to correlate plasma beta-ANF with the degree of ventricular dysfunction, and to investigate the role of human plasma and atrial tissue in the degradation of beta-ANF. Venous plasma samples were obtained from patients (n = 12) with severe CHF and normal volunteers (n = 8). Total plasma ANF was measured by radioimmunoassay. alpha-ANF and beta-ANF in nonextracted plasma were separated by gel filtration chromatography using a P-6 column. Right atrial tissue samples (n = 5) were collected from a different group of patients at the time of open-heart surgery. 125I beta-ANF and I125 ANF were incubated with atrial tissue or plasma. The corresponding peak areas of beta-ANF were determined by Tamaya Digital Planimeter. beta-ANF represented 61% of total plasma ANF in CHF patients and was not detected in normal human plasma. The elevation of beta-ANF correlated with the severity of ventricular dysfunction. Thirty percent of beta-ANF and 100% alpha-ANF were converted to smaller peptide fragments in atrial tissue no conversion in plasma. beta-ANF is the principal form of circulating ANF in patients with severe CHF and correlates with the degree of left ventricular dysfunction. beta-ANF is not generated from alpha-ANF and may be degraded rapidly in atrial tissue to smaller peptide fragments that do not occur in plasma. As beta-ANF is reported to have reduced biological action, the current studies may support the conclusion that the ANF system in CHF has reduced functional activity despite increases in circulation concentrations.


Altered shape and cell cycle characteristics of fibroblasts expressing the E2F1 transcription factor.
To gain an understanding of the role the E2F1 transcription factor plays in cell physiology, the full length protein (E2F1) and an amino terminal deletion of 87 amino acids (E2F1d87) were constitutively expressed in NIH3T3 fibroblasts. Multiple cell lines were generated for each construct. These cells do not proliferate in media containing low serum and do not proliferate in soft agar, indicating that they are likely not transformed. However, both sets of cell lines show increased DNA synthesis and increased numbers of cells in S phase when cultured in media containing low serum, compared to the control cell lines. Cells expressing E2F1d87 (but not E2F1) have an extremely rounded morphology when cultured in 10% serum-containing media. These rounded cells lack detectable microfilaments, microtubules, and focal contacts. However, when these cells are cultured in low serum-containing media (0.5%), they attain the flattened morphology and cytoskeletal structure of normal NIH3T3 cells.


Development and characterization of bioactive edible films from spider crab (Maja crispata) chitosan incorporated with Spirulina extract.
Active food packaging films based on crab chitosan and Spirulina extract (SE) were developed. The effects of the SE incorporation at different levels on physical (color, opacity water vapor and oxygen permeability) and mechanical (tensile strength and elongation at break) properties of chitosan films were investigated. FTIR was carried out to observe the potential modifications of the chitosan films when incorporated with SE. The obtained results suggested that incorporation of SE into chitosan films improved mechanical and barrier properties. The antioxidant activity of the chitosan/SE films was characterized by means of three different analytical assays (DPPH, FRAP and FIC). Crab chitosan edible films containing SE showed higher antioxidant activity, regardless concentrations and methods assayed. Furthermore, the antioxidant activity occurred in a concentration-dependent manner. The agar disc diffusion method was used to determine the antibacterial activities of chitosan edible films against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes, Salmonella typhimurium, Bacillus subtilis and Bacillus cereus. The chitosan/SE films were more effective (p<0.05) against five of the seven tested bacteria. The obtained crab chitosan edible films incorporated with SE showed great potential to be used for active food packaging due to its excellent antioxidant and antibacterial activities.


Examination of Critical Factors Related to Summer Chlorophyll a Concentration in the Sueo Dam Reservoir, Republic of Korea.
This study examined critical factors related to the short-term variation of algae growth in reservoirs during the summer. To this end, statistical tests were carried out at a small dam reservoir to determine how chemical factors (e.g., nutrient concentrations) and physical factors (e.g., theoretical and relative residence times, temperature) influenced the chlorophyll a (Chl-a) concentration. Statistical tests revealed that, although phosphorus (P) concentration was significant for Chl-a, residence time had much stronger relationship to Chl-a concentration than chemical factors. In addition, the study verified that relative residence time (RRT) best explained the relation of water status to algae growth. RRT was found to be useful in identifying water status related to the summer algae bloom. Finally, this study raised the possibility of inhibiting summer algae growth by operating dam reservoirs moderately. These findings need to be seriously considered when reservoir operators establish effective strategies for water quality management in summer.


Quality of patient education materials for rehabilitation after neurological surgery.
To evaluate the quality of online patient education materials for rehabilitation following neurological surgery. Materials were obtained from the National Institute of Neurological Disorders and Stroke (NINDS), U.S. National Library of Medicine (NLM), American Occupational Therapy Association (AOTA), and the American Academy of Orthopaedic Surgeons (AAOS). After removing unnecessary formatting, the readability of each site was assessed using the Flesch Reading Ease and Flesch-Kincaid Grade Level evaluations with Microsoft Office Word software. The average values of the Flesch Reading Ease and Flesch-Kincaid Grade Level were 41.5 and 11.8, respectively, which are well outside the recommended reading levels for the average American. Moreover, no online section was written below a ninth grade reading level. Evaluations of several websites from the NINDS, NLM, AOTA, and AAOS demonstrated that their reading levels were higher than that of the average American. Improved readability might be beneficial for patient education. Ultimately, increased patient comprehension may correlate to positive clinical outcomes.


Polymorphisms of apolipoprotein E and angiotensin-converting enzyme genes and carotid atherosclerosis in heavy drinkers.
To investigate the influence of apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) gene polymorphisms on carotid artery atherosclerosis in alcoholism. Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. Multivariate regression analysis showed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, LDL cholesterol and fasting plasma glucose levels. Subjects carrying the APO E epsilon4 allele were more liable to develop atherosclerotic changes in carotid arteries compared with subjects with the epsilon3/3 genotype, which showed statistical significance in patients under 50 years of age. No association was shown between ACE I/D polymorphism and carotid atherosclerosis. APO E polymorphism can increase the risk of carotid atherosclerosis development in an alcoholic subject. The association of the APO E epsilon4 allele with carotid atherosclerosis was significant in younger patients. Since the elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis the consequences could involve both cardiac and cerebrovascular events.


Modeling and analysis of optical properties of a gold nanoring based on electric and magnetic dipoles.
The optical behavior of a plane-wave excited gold nanoring (NR), originated from localized surface plasmon resonance is modeled by two coupled electric- and magnetic-point dipoles. Considering the extinction cross-section spectrum, it is found that the electric-dipole effect is dominant in comparison with the magnetic-dipole effect although the magnetic-dipole signature is observable in the near-field response of the NR. In addition, the far-field electromagnetic radiation pattern of the NR verifies the corresponding radiation pattern of the point dipoles. The numerical simulation near-field results are in agreement with the proposed electric- and magnetic-dipole theory.


Herd Immunity: A Brief Review.
Immunization is a means of protecting the greatest number of people. By reducing the number of susceptible in the community, it augments "herd immunity" making the infection more difficult to spread. It also reduces the risk for those individuals who have escaped vaccination or those who have not developed satisfactory protection. It is well to bear in mind that immunizations are not at all 100 per cent effective, particularly when an individual is exposed to a large dose of pathogenic organisms.


The Role of Inflammation in the Mechanisms of Bile Acid-Induced Liver Damage.
The mechanism by which bile acids induce liver injury in cholestasis remains controversial. Although high levels of bile acids are toxic when applied to liver cells, the level of toxic bile acids in the liver of most cholestatic animals and patients is <10 μM, indicating there must be alternative mechanisms. Recent studies suggest that the inflammatory response may play an important role in bile acid-induced liver injury, as pro-inflammatory cytokine expression is stimulated by bile acids in mouse hepatocyte cultures. To elucidate the mechanisms of bile acid-induced liver injury, we assessed signs of liver damage and gene expression in Abcb4-/- mice, a well-known model for cholestasis. Key Messages: Elevated plasma levels of bile acids were detected as early as 10 days after birth and at all later ages in Abcb4-/- mice compared to their wild-type littermate controls. Parallel increases in expression of Tnfα, Ccl2, Cxcl1, and Cxcl2 mRNA occurred at these early time points and throughout 12 weeks in Abcb4-/- livers. Marked hepatic neutrophil infiltration was first detected in 3-week mice, whereas histological evidence of liver injury was not detected until 6-weeks of age. Subsequent in vitro studies demonstrated that normal hepatocytes but not other non-parenchymal liver cells responded to bile acids with inflammatory cytokine induction. Bile acids induce the expression of pro-inflammatory cytokines in hepatocytes in Abcb4-/- mice that initiates an inflammatory response. This inflammatory response plays an important role in the development of cholestatic liver injury in this and other cholestatic conditions. Furthermore, understanding of these inflammatory mechanisms should lead to new therapeutic approaches for cholestatic liver diseases.


Photo-enhanced electrochemical and colorimetric dual-modal aptasensing for aflatoxin B1 detection based on graphene-gold Schottky contact.
A photo-enhanced electrochemical (PEEC) and colorimetric (CM) dual-modal aptasensor was developed with rGO-AuNP Schottky contact for AFB1 monitoring. The PEEC mode allowed the ultrasensitive quantitation based on the photo-enhanced electroactivity mechanism, while the CM mode offered a rapid threshold-level qualitative assay with a portable colorimeter.


Isolated bilateral zygomatic complex and zygomatic arch fractures with oral submucous fibrosis: an unusual and rare case report.
Zygomatic bone forms major buttress of the facial skeleton and plays an important role in facial contour. Fractures of zygomatic complex are second most common only next to nasal bone fractures. Motor vehicle accidents and interpersonal violence are common causes. Bilateral fractures of zygomatic complex and zygomatic arch are very rare. We present a case report of isolated fractures involving bilateral zygomatic complex and zygomatic arch with oral submucous fibrosis, which is unique and first of its kind to be reported.


Mapping unprocessed epitopes using deletion mutagenesis of gene fusions.
To locate the antigenic determinant recognized by a monoclonal antibody directed against a baculovirus capsid protein, a series of overlapping deletions of a fusion protein were immunologically screened with the monoclonal antibody. The immunoreactive fusion protein was derived from a restriction fragment which contained a large portion of a baculovirus capsid protein open reading frame fused in-frame with a truncated trpE gene in a bacterial (pATH3) expression system. To map the epitope, nested sets of 5' and 3' deletion mutants were generated. Mutants were characterized by the DNA insert size or by the size of the expressed fusion protein. Selected N- and C-termini truncated fusion proteins were Western blotted and incubated with the monoclonal antibody to identify mutants which retained the epitope. Plasmid DNA from mutants which flank the 5' and 3' junction of the antigenic determinant were sequenced to determine the epitope junction. By screening forty 3' deletions and sixty-four 5' deletions, the antigenic determinant was localized to a region of seven amino acids.


Positive Feedback Mechanism of Probe Sonication for the Perovskite Films in Solar Cells.
The performance of perovskite solar cells (PSCs) is governed by the quality of perovskite films, whereby compact, pinhole-free perovskite films are desired, in addition to its composition. We have demonstrated probe sonication as a processing technique to provide positive feedback for enhancing the perovskite film quality and photovoltaic parameters, with two systems, CH3NH3PbI3 (MAPbI3) and Cs0.17FA0.83Pb(I0.83Br0.17)3. In probe sonication, the ultrasound results in the formation, growth, and collapse of the bubbles through shock wave inside the gas phase of the collapsing bubble. This phenomenon has a chemical impact on the nucleation of the perovskite phases and interconnectivity of the grains. The 60 min sonicated films with stronger hydrogen bonding network are devoid of unwanted Pb0, δ-FAPbI3, and PbI2 phases, having tightly packed homogeneous grains, minimum electron-hole recombination pathways, and improved light absorption. The surface potential remains mostly unaltered across the grains and grain boundaries, and the realignment of the Fermi energy (EF) favors facile carrier transport. The photoconversion efficiency (PCE) of the MAPbI3 and Cs0.17FA0.83Pb(I0.83Br0.17)3 devices is improved by 28.1 and 17.2% in comparison to the pristine perovskites, respectively. The 60 min sonicated Cs0.17FA0.83Pb(I0.83Br0.17)3 PSC has 20.20 ± 0.40% PCE with 1000 h ambient stability having >60% retention of the original PCE.


Kinetic movement analysis in adults with vision loss.
The purpose of this investigation was to assess movement capabilities of adults with visual impairments in comparison to sighted peers. Thirty participants (n = 15 visually impaired; n = 15 without vision loss) were age and gender matched and assessed on three functional movement measures. A Walk Across, Forward Lunge, and Sit to Stand were completed on a long force plate and analyzed using Group MANOVAs. Individuals with visual impairment were more cautious and conservative in their movement as evident by significantly reduced performance on both the Walk Across assessment and the Forward Lunge task. Performance between groups was similar on the Sit to Stand maneuver. It was concluded that individuals with visual impairments are more cautious and have more difficulty performing tasks when their center of gravity is outside of their base of support.


Enhanced expression of Bcl-2 in lymphocytes infiltrating into the liver of patients with primary biliary cirrhosis.
The Bcl-2 family proteins are important regulators of apoptosis and have been implicated in the occurrence of autoimmune diseases. There have been reports that Bcl-2-positive lymphocytes play important roles in pathogenesis of at least some types of autoimmune diseases, including autoimmune hepatitis. In this study, we examined the role of Bcl-2-positive lymphocytes in the development of primary biliary cirrhosis (PBC). The expression of Bcl-2 in lymphocytes infiltrating into the liver was evaluated from liver biopsy specimens of 25 patients with PBC (stage I/II/III/IV, 11/3/8/3) and 24 controls with chronic hepatitis B (CH-B) or chronic hepatitis C (CH-C). Bcl-2 expression in lymphocytes infiltrating into the liver was investigated by immunohistochemistry using a monoclonal antibody to Bcl-2 with an avidin-biotin complex system. Significant overexpression of Bcl-2 in lymphocytes infiltrating into the liver was observed in the early stage of PBC, especially in areas of destructed bile ducts. Most of Bcl-2-positive cells were CD45RO-positive helper T-cells visualized by the double staining method. These results suggest that Bcl-2-positive helper T-cells may have important roles in the pathogenesis of PBC.


[Decreasing atherogenic risks by an eicosapentaenoic acid-rich diet].
(n-3) diets rich in polyunsaturated fatty acids (PUFA) reduce the atherogenic lipoproteins, especially the VLDL (very low density lipoproteins) rich in triglycerides but also the LDL, more effectively than (n-6) PUFA-rich diets. Moreover also other parameters such as high blood pressure and aggregation of thrombocytes are positively influenced, similarly like after (n-6) PUFA-rich diet. Eicosapentaenoic acid (20:5, n-3) has a triglyceride- and cholesterol-reducing effect by inhibition of the VLDL-synthesis (apolipoprotein B, triglycerides) in the liver, inhibition of lipogenic liver enzymes, accelerated elimination of VLDL from the circulation, increased excretion of steroids and bile acids into the stools and amelioration of the fat tolerance. The prolongation of the period of haemorrhage and the decrease of the aggregation of thrombocytes is associated with the enrichment of EPA in the platelet membrane. In these cases the decreased thrombocyte-vascular vessel-interaction shall be caused by a changed metabolism of the eicosanoids (secondary products of unsaturated fatty acids with 20 carbon atoms) and eicosanoid-independent mechanisms.


Pressure sores: adopting the principles of risk management.
This article examines the continuing problem of pressure sores in the NHS from a purchasing and a providing manager's perspective. Risk management and the need for clinical effectiveness in treatment and prevention strategies are discussed. Reporting systems are advocated as a means to estimate risk and to form a store of information that will enable a response to made when problem areas are identified. Nursing advice and input into the contracting process is vital. The need for purchasers and NHS managers to work together to ensure that effective interventions are implemented to reduce both the financial burden on the NHS and the physiological insult offered to patients is stressed.


pH-Dependent Behavior of Novel Gellan Beads Loaded with Naproxen.
Oral administration of non-selective COX inhibitors involves the risk of serious side-effects. In the case of naproxen (NPX), the most frequent are those related to malfunctioning of the gastric mucosa. On the other hand, NPX and other NSAIDs are extensively studied in terms of colorectal cancer (CRC) prevention and inhibition, since it has been evidenced that COX-2 corresponds with the risk of the tumor occurrence and growth. Both side-effects in the stomach and possible antitumor activity of NPX justify the attempts to search for novel carriers for NPX with the site specific release in the colon. Thus, the aim of the work was to design, formulate and characterize low-acyl gellan gum (GG) macro beads as potential carriers for the delivery of NPX to the distal parts of the gastrointestinal tract. The beads were obtained by the ionotropic gelation technique. CaCl2 solution was used as a cross-linking medium. After production, the beads were dried and used for further experiments. First, pure NPX and the beads were evaluated by Raman spectroscopy and DSC studies. The surface and morphology of the beads were analyzed by SEM. Next, the drug encapsulation efficiency and content in the beads were determined. The swelling and degradation behavior of the beads were evaluated in four simulated gastrointestinal fluids at different pH (1.2; 4.5; 6.8 and 7.4). The NPX in vitro release studies were conducted on USP I apparatus (rotating basket) at pH=7.4 and compared to the commercial enteric tablet. The polymer content of 0.5 % was considered as too low to obtain spherical beads in the dried form. Raman spectra confirmed that NPX did not undergo structural changes during production process. DSC studies showed that thermal decomposition at lower temperatures was observed for formulations with the lowest amount of GG. It turned out that the most important factor which determined the morphology of the beads was the amount of gellan gum in the initial mixture. The beads revealed 13.9- 39.9% of drug loading and 75.3-99.7% drug encapsulation efficiency. Swelling of the beads was pHdependent as the beads remained stable in the acidic environment but started to absorb water. In pH=7.4 after 3 hours, the beginning of the physical decomposition of the polymer matrix was observed. The drug release studies showed that in pH=7.4 the commercial tablets released 90% of the drug after 45 minutes while the amount of NPX released from pellets after the same time was 40-80%. In general, it can be stated that gellan macro beads may be regarded as suitable for site specific delivery of NPX to the colon. However, these simple to obtain beads can be potentially used as carriers for many different drugs whenever it is necessary to omit the stomach.


Assessment of cyclodextrin-enhanced extraction of crude oil from contaminated porous media.
The purpose of this study was to evaluate the effects of cyclodextrin (CD) on the extraction of Macondo well oil from contaminated porous media over a range of hydroxypropyl-β-CD (HPβCD) concentrations. To our knowledge, this is the first dataset on this type of CD yet assembled for an actual crude oil. The results showed that HPβCD can significantly increase oil extraction efficiency, demonstrated by increasing concentrations of all tested normal alkanes (nC(15)-nC(35)) and polyaromatic hydrocarbons (PAHs) in the aqueous phase with increasing CD concentration. A linear relationship between the extraction enhancement effect and CD concentration were verified experimentally and high correlation coefficients for total PAHs (R(2) = 0.82) and alkanes (R(2) = 0.99) were determined. For a 20% CD solution, 3.13 wt% of alkanes and 32.12 wt% of total PAHs were extracted to the aqueous phase, which was significantly more than what was extracted with water only (0.04% and 0.21% for alkanes and PAHs, respectively). This result shows that the remediation of oil contaminated media can be significantly enhanced through the use of HPβCD solutions in flushing or pump and treat operations to remove sorbed oil. The CD extraction enhancement effect decreases with increasing n-alkane chain length for the carbon number range tested. CD significantly enhanced PAH extraction from sand and the enhancement effect increased in the order of parent compounds < C-1 substituted < C-2 substituted < C-3 substituted for most PAHs tested. This study provides important information to assess the feasibility of using CD as a near-shore agent to enhance the cleanup of oil contaminated porous media.


[Management for pregnancy and delivery in patients with a history of Kawasaki disease].
We report the results of pregnancy and delivery in patients with coronary artery lesions caused by Kawasaki disease. The mode of delivery should be primarily determined by obstetrical considerations, rather than the coronary arterial lesions caused by Kawasaki disease. An assisted second stage of labor using epidural anesthesia is recommended in patients with a low left ventricular ejection fraction and significant localized stenosis of a coronary artery. However, if the patients are symptomatic or they have ischemic sign, Caesarean section should be recommended based on their general condition. A holter electrocardiogram at the third trimester is useful for decision of the mode of delivery. Aspirin at low doses is considered to be safe during pregnancy and delivery.


Treatment of herpes zoster and postherpetic neuralgia.
Herpes zoster results from reactivation of latent varicella-zoster virus. It is most common in elderly patients and immunosuppressed patients, especially those with human immunodeficiency virus (HIV) infection. Zoster is often the earliest indicator of HIV infection. The acute course of herpes zoster is generally benign, but systemic complications may be fatal. Postherpetic neuralgia is the major chronic complication and is a difficult management problem. High-dose acyclovir (800 mg orally five times daily) has recently been approved for treatment of herpes zoster and, if started early, decreases the duration and severity of symptoms. In the prevention of postherpetic neuralgia, acyclovir does not appear to be effective, and the efficacy of steroids is questionable. The best therapy currently available for postherpetic neuralgia is amitriptyline, topical capsaicin and transcutaneous electrical stimulation.


Neuroendocrine tumors of the genital tract.
Neuroendocrine tumors are more common in the female than male genital tract; most are uterine small cell carcinomas or ovarian carcinoids. Primary ovarian carcinoids are divided into insular, trabecular, strumal, and mucinous types; most are benign. Carcinoids metastatic to the ovary are more aggressive; most arise in the gastrointestinal tract. Scattered neuroendocrine cells are seen in a variety of ovarian surface epithelial tumors; sporadic mucinous cystic tumors with neuroendocrine cells have been associated with Zollinger-Ellison syndrome. Frank neuroendocrine carcinomas in the ovary include small cell carcinoma and large cell neuroendocrine carcinoma, each with a poor prognosis and often associated with a conventional surface epithelial tumor Such carcinomas also occur in the endometrium and cervix. Uterine carcinoids are rare if strict criteria are applied. Small cell neuroendocrine carcinomas also occur rarely in the vagina and vulva. Most male genital tract neuroendocrine tumors are prostatic small cell carcinomas or testicular carcinoids. Extragonadal carcinoids of the male genital tract are rare. Testicular carcinoids should be distinguishedfrom metastatic tumors. It is important to distinguish prostatic small cell carcinoma from poorly differentiated adenocarcinoma with small cells. Small cell neuroendocrine carcinomas also occur rarely in the scrotum, penis, and penile urethra.


Electron microscopic localization of calcium in vascular smooth muscle.
Potassium pyroantimonate has been employed in this study to localize calcium in the vascular smooth muscle of the thoracic aorta of the rabbit. The pyroantimonate ion precipitates sodium, magnesium and calcium. Incubation of theisolated thoracic aorta in a high potassium bathing medium which does not contain sodium, magnesium or calcium depletes the tissue of sodium. Addition of 10.8 mM CaC12 to the incubation medium results in well-localized depositions of reaction product, presumably that of calcium pyroantimonate, in mitochondria, sarcoplasmic reticulum, and at the plasma membrane. Some or all of these organelles may, therefore, play a vital role in the contraction-relaxation cycle of vascular smooth muscle.


Isolation and characterization of a proteinase K-sensitive PrPSc fraction.
Recent studies have shown that a sizable fraction of PrPSc present in prion-infected tissues is, contrary to previous conceptions, sensitive to digestion by proteinase K (PK). This finding has important implications in the context of diagnosis of prion disease, as PK has been extensively used in attempts to distinguish between PrPSc and PrPC. Even more importantly, PK-sensitive PrPSc (sPrPSc) might be essential to understand the process of conversion and aggregation of PrPC leading to infectivity. We have isolated a fraction of sPrPSc. This material was obtained by differential centrifugation at an intermediate speed of Syrian hamster PrPSc obtained through a conventional procedure based on ultracentrifugation in the presence of detergents. PK-sensitive PrPSc is completely degraded under standard conditions (50 mug/mL of proteinase K at 37 degrees C for 1 h) and can also be digested with trypsin. Centrifugation in a sucrose gradient showed sPrPSc to correspond to the lower molecular weight fractions of the continuous range of oligomers that constitute PrPSc. PK-sensitive PrPSc has the ability to convert PrPC into protease-resistant PrPSc, as assessed by the protein misfolding cyclic amplification assay (PMCA). Limited proteolysis of sPrPSc using trypsin allows for identification of regions that are particularly susceptible to digestion, i.e., are partially exposed and flexible; we have identified as such the regions around residues K110, R136, R151, K220, and R229. PK-sensitive PrPSc isolates should prove useful for structural studies to help understand fundamental issues of the molecular biology of PrPSc and in the quest to design tests to detect preclinical prion disease.


TIC10/ONC201 synergizes with Bcl-2/Bcl-xL inhibition in glioblastoma by suppression of Mcl-1 and its binding partners in vitro and in vivo.
Glioblastoma is the most frequent primary brain tumor in adults. Current therapeutic options are sparse and the prognosis of patients suffering from this disease is grim. Abundance in intratumoral heterogeneity among different deregulated signaling pathways is a hallmark of glioblastoma and likely accounts for its recurrence and resistance to treatment. Glioblastomas harbor a plethora of deregulated pathways driving tumor formation and growth. In this study, we show that TIC10/ONC201, a promising compound that is currently in planned clinical development, along with Bcl-2/Bcl-xL inhibition by ABT263 yields a strong synergistic antiproliferative effect on pediatric, adult, proneural glioblastoma and glioma stem-like cells. On the molecular level, treatment with TIC10/ONC201 results in a posttranslational decrease of the anti-apoptotic Bcl-2 family member, myeloid cell leukemia 1 (Mcl-1), through modulation of the chaperone Bag3 and the deubiquitinase Usp9X. Consistently, the combination treatment of TIC10/ONC201 and ABT263 required the presence of functional BAX and BAK to drive intrinsic apoptosis, but is surprisingly independent of the extrinsic apoptotic pathway. Moreover, the expression of Noxa protein was required for efficient apoptosis induction by TIC10/ONC201 and ABT263. Importantly, the drug combination of TIC10/ONC201 and the BH3-mimetic, ABT263, led to a regression of tumors in vivo, without any notable toxicity and side effects. Overall, TIC10/ONC201 along with Bcl-2/Bcl-xL inhibition holds significant promise as a novel potential approach for the treatment of recalcitrant tumors such as glioblastoma.


PKC-Dependent GlyT1 Ubiquitination Occurs Independent of Phosphorylation: Inespecificity in Lysine Selection for Ubiquitination.
Neurotransmitter transporter ubiquitination is emerging as the main mechanism for endocytosis and sorting of cargo into lysosomes. In this study, we demonstrate PKC-dependent ubiquitination of three different isoforms of the glycine transporter 1 (GlyT1). Incubation of cells expressing transporter with the PKC activator phorbol ester induced a dramatic, time-dependent increase in GlyT1 ubiquitination, followed by accumulation of GlyT1 in EEA1 positive early endosomes. This occurred via a mechanism that was abolished by inhibition of PKC. GlyT1 endocytosis was confirmed in both retinal sections and primary cultures of mouse amacrine neurons. Replacement of only all lysines in the N-and C-termini to arginines prevented ubiquitination and endocytosis, displaying redundancy in the mechanism of ubiquitination. Interestingly, a 40-50% reduction in glycine uptake was detected in phorbol-ester stimulated cells expressing the WT-GlyT1, whereas no significant change was for the mutant protein, demonstrating that endocytosis participates in the reduction of uptake. Consistent with previous findings for the dopamine transporter DAT, ubiquitination of GlyT1 tails functions as sorting signal to deliver transporter into the lysosome and removal of ubiquitination sites dramatically attenuated the rate of GlyT1 degradation. Finally, we showed for the first time that PKC-dependent GlyT1 phosphorylation was not affected by removal of ubiquitination sites, suggesting separate PKC-dependent signaling events for these posttranslational modifications.


Six-month evaluation of novel bioabsorbable scaffolds composed of poly-L-lactic acid and amorphous calcium phosphate nanoparticles in porcine coronary arteries.
Objective Using coronary angiography and intravascular ultrasound methods to evaluate the performance of the novel fully bioabsorbable scaffold (NFBS) composed of poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) at six-month follow-up by comparing with PLLA scaffolds Methods Twelve PLLA/ACP scaffolds and 12 PLLA scaffolds were implanted into the coronary arteries of 12 miniature pigs. Quantitative coronary angiography (QCA) was used to measure the reference vessel diameter (RVD), mean lumen diameter (MLD) and late lumen loss (LLL). According to IVUS images, we calculated the strut malapposition rate (SMR) at post implantation, strut overlap rate (SOR), reference vessel area (RVA), mean stent area (MSA), mean lumen area (MLA) and luminal patency rate (LPR) at six-month follow-up. The radial strength of the scaffold was evaluated using a catheter tensile testing machine. Results QCA results indicated that, at six month, MLD of PLLA/ACP scaffolds was greater than those of PLLA scaffolds (2.47 ± 0.22 mm vs. 2.08 ± 0.25 mm, P < 0.05); LLL of PLLA/ACP scaffolds was less than those of PLLA scaffolds (0.42 ± 0.20 mm vs. 0.75 ± 0.22 mm, P < 0.05). IVUS results showed the SMR and SOR were all significantly less with the PLLA/ACP scaffolds than the PLLA scaffolds (5.84% ± 3.56% vs. 17.72% ± 4.86%, P < 0.05) (6.17% ± 4.63% vs. 17.65% ± 4.29%, P < 0.05). MSA, MLA and LPR of the PLLA/ACP scaffolds were all greater than those of PLLA scaffolds (6.35 ± 0.45 mm2 vs. 5.35 ± 0.51 mm2, P < 0.05) (4.76 ± 0.46 mm2 vs. 3.77 ± 0.46 mm2, P < 0.05) (78.01% ± 12.29% vs. 61.69% ± 9.76%, P < 0.05). Radial strength of PLLA/ACP scaffold at six month was greater than that of PLLA scaffold (76.33 ± 3.14 N vs. 67.67 ± 3.63 N). Conclusion The NFBS had less stent recoil, better lumen patency rate and greater radial strength than PLLA scaffolds. The results suggest the NFBS scaffolds can maintain the structural strength and functional performance, which are effective for up to six months when implanted in porcine coronary arteries.


Detection of virus infection-associated antigen and 3D antibodies in cattle vaccinated against foot and mouth disease.
The analysis of sera obtained from animals vaccinated or revaccinated with inactivated vaccines against foot and mouth disease (FMD) virus showed that these vaccines induced antibodies against the virus infection-associated (VIA) antigen, detectable by agar gel immunodiffusion (AGID). The present study evaluates the antibody response to protein 3D and the VIA antigen (VIAA) of FMD virus induced by different vaccines in a group of 51 calves. This response was detected using AGID and a liquid-phase blocking sandwich enzyme-linked immunosorbent assay (ELISA) for anti-3D antibodies (ELISA-3D). No anti-VIAA or anti-3D antibodies were detected after the initial vaccination. Following revaccination, animals giving positive results were detected by both methods. This immune response disappeared 60-120 days post-revaccination (dprv) according to the AGID method, and 90-180 dprv when ELISA-3D was used. Samples of oesophageal-pharyngeal fluid obtained from animals that remained positive for anti-VIAA antibodies at 90-120 dprv gave negative results for viral isolation, indicating that the transitional antibody response induced by the vaccine was due to the presence of non-structural antigens in the vaccine and not to viral infection. These results indicate that the ELISA-3D method could be used as a complementary method for sero-epidemiological studies as an indirect indicator of viral activity, as long as the age and vaccination status of the animals being sampled are taken into consideration.


Binding of ZO-1 to α5β1 integrins regulates the mechanical properties of α5β1-fibronectin links.
Fundamental processes in cell adhesion, motility, and rigidity adaptation are regulated by integrin-mediated adhesion to the extracellular matrix (ECM). The link between the ECM component fibronectin (fn) and integrin α5β1 forms a complex with ZO-1 in cells at the edge of migrating monolayers, regulating cell migration. However, how this complex affects the α5β1-fn link is unknown. Here we show that the α5β1/ZO-1 complex decreases the resistance to force of α5β1-fn adhesions located at the edge of migrating cell monolayers while also increasing α5β1 recruitment. Consistently with a molecular clutch model of adhesion, this effect of ZO-1 leads to a decrease in the density and intensity of adhesions in cells at the edge of migrating monolayers. Taken together, our results unveil a new mode of integrin regulation through modification of the mechanical properties of integrin-ECM links, which may be harnessed by cells to control adhesion and migration.


Description of malaria vectors (Diptera: Culicidae) in two agricultural settlements in the Western Brazilian Amazon.
The majority of malaria cases in South America occur in rural areas of the Amazon region. Although these areas have a significant impact on malaria cases, few entomological studies have been carried out there. This study aimed to describe entomological parameters in settlements in Rondonia State, Brazil. Collections of anopheles were carried out using the Protected Human Attraction Technique (PHAT). The risk and the potential for malaria transmission were assessed using the human biting rate (HBR), the sporozoite rate (SR) and the entomological inoculation rate (EIR). The results confirmed that Nyssorhynchus darlingi is the predominant species in the two studied locations. Although settlement in the two study sites has occurred at different times, the species richness found was low, showing that environmental changes caused by anthropological actions have probably favor the adaptation of Ny. darlingi species. From the total of 615 anopheline mosquitoes assessed, seven (1.1%) were positive for Plasmodium sp. infections. The EIR revealed that Ny. darlingi contributes to malaria transmission in both locations, as it was responsible for 0.05 infectious bites in humans at night in the old settlement and 0.02 in the recent occupation. In the two study sites, the biting occurred more frequently at dusk. Nyssorhynchus darlingi was prevalent in areas of recent colonization but, even when present in a low density, this species could maintain the transmission of malaria in the older settlement. The entomological information obtained in this study is important and may aid the selection of vector control actions in these locations.


Autoimmune atrophic gastritis: The role of Helicobacter pylori infection in children.
Autoimmune atrophic gastritis (AIG) is very rare in children. Despite a better understanding of histopathologic changes and serological markers in this disease, underlying etiopathogenic mechanisms and the effect of Helicobacter pylori (H pylori) infection are not well known. We aimed to investigate the relation between AIG and H pylori infection in children. We evaluated the presence of AIG and H pylori infection in fifty-three patients with positive antiparietal cell antibody (APCA). Demographic data, clinical symptoms, laboratory and endoscopic findings, histopathology, and presence of H pylori were recorded. The children were aged between 5 and 18 years, and 28 (52.8%) of them were male. Mean age was 14.7 ± 2.6 years (median: 15.3; min-max: 5.2-18), and 10 (18.8%) of them had AIG confirmed by histopathology. In the AIG group, the duration of vitamin B12 deficiency was longer (P = .022), hemoglobin levels were lower (P = .018), and APCA (P = .039) and gastrin (P = .002) levels were higher than those in the non-AIG group. Endoscopic findings were similar between the two groups. Intestinal metaplasia was higher (P = .018) in the AIG group. None of the patients in the AIG group had H pylori infection (P = .004). One patient in the AIG group had enterochromaffin-like cell hyperplasia. Our results show that, in children, H pylori infection may not play a role in AIG. AIG could be associated with vitamin B12 deficiency, iron deficiency, and APCA positivity in children. APCA and gastrin levels should be investigated for the early diagnosis of AIG and intestinal metaplasia.


Neurocognitive function in patients with idiopathic Restless Legs Syndrome before and after treatment with dopamine-agonist.
Although a huge amount of clinical evidence for Restless Legs Syndrome (RLS) is present in literature, an exhaustive account of cognitive profile in RLS patients is still lacking. In this study we evaluated the neurocognitive function in RLS patients and the effects of a three-month treatment with a dopamine agonist (pramipexole) at low doses. Clinical and polysomnographic characteristics, cognitive abilities, quality of life and psychological clinical indices were assessed in 20 RLS patients and 15 age-matched controls. The neurocognitive results, obtained by untreated RLS patients (baseline), were firstly compared to those of controls and then to those of the same RLS group after treatment (follow-up). Increased Total Sleep Time, Slow Wave Sleep, Sleep Efficiency and decreased Sleep Latency, Wake After Sleep Onset and periodic leg movement index were found by polysomnographic recording after a three-month treatment. Results showed that cognitive functions, impaired at baseline when compared to control subjects, improved after the pharmacological treatment, reaching the scores of healthy subjects. Decision making, problem solving and categorizing abilities, investigated by the Iowa Gambling Task (IGT) and the Wisconsin Card Sorting Test (WCST), resulted lower in RLS patients at baseline than in controls. All these functions improved after pharmacological treatment, as well as quality of life, depressive and anxiety symptoms, and daytime sleepiness.


[Clinical evaluation on the bimanual microincision cataract surgery].
To compare the outcomes of bimanual microincision phacoemulsification with conventional small incision cataract surgery. A randomized prospective study of 280 consecutive cases (280 eyes) was conducted. All patients were randomly assigned to receive bimanual microincision cataract surgery (MICS group) or small incision cataract surgery (SICS group). The PHACO time (PT) and the average power (AP) were recorded, then absolute PHACO time (APT = PT x AP) was calculated. The differences in PT, AP, APT and BCVA between these two groups were compared. Visual acuity, anterior chamber flare value, thickened pachymetry and endothelial cells loss were recorded 1 day and 3 months after surgery. In addition, surgically induced astigmatism was analyzed. The mean PT, AP and APT of MICS group were significantly lower than those in the SICS group (0.76 +/- 0.36) min versus (0.87 +/- 0.49) min, 10.93% +/- 4.78% versus 16.09% +/- 7.38% and (8.99 +/- 7.23) min versus (15.27 + 12.10) min, respectively (P < 0.01). At 3 months, the vertical astigmatic changes of MICS group was statistically lower than that of the SICS group [(0.37 - 0.32) D versus (1.28 +/- 0.77) D, P = 0.000]. There were no significant differences in the visual acuity, anterior chamber flare value, endothelial cells loss and the thickened pachymetry at 1 day and 3 months after surgery between these two groups (P > 0.05). Bimanual microincision cataract surgery could significantly reduce PHACO power, enhance energy efficiency and reduce surgically induced astigmatism. However, MICS does not reduce surgical trauma and postoperative inflammation as compared to conventional SICS.


Evaluation of severity indexes of patients with paraquat poisoning.
1. Three indexes for evaluating the severity of paraquat poisoning based on plasma-paraquat concentration are presently in use; the curves of Proudfood et al. and Scherrmann et al. and the SIPP. Their effectiveness in determining the prognosis of patients with paraquat poisoning was evaluated. 2. To determine which index was more accurate, contigency tables of the three indexes were obtained and compared; Proudfoot's curve vs the SIPP Scherrmann's curve vs the SIPP. Proudfoot's curve and the SIPP were applied to patients admitted within 24 h after intoxication. Scherrmann's curve and the SIPP were applied to patients admitted more than 24 h after intoxication. The proportions of patients with true positive and true negative results to total patients were compared by a ratio test. 3. Proudfoot's curve was found to be more accurate than the SIPP for predicting the prognosis of patients admitted within 24 h (P less than 0.05). No significant difference, however, was noted between Scherrmann's curve and the SIPP in determining the prognosis of patients admitted after more than 24 h. 4. In conclusion, Proudfoot's curve proved a better index for predicting the outcome of patients who were admitted within 24 h. However, for the prognosis of patients admitted more than 24 h after the ingestion of paraquat, further study is required.


Transcatheter arterial chemoembolization combined with microwave coagulation therapy and the perioperative care for patients with hepatocellural carcinoma.
To explore the value of artificial hydrothorax microwave coagulation combined with transcatheter arterial chemoembolization (TACE) therapy in the treatment of ultrasound-invisible malignant tumors in the hepatic dome (mainly hepatocellular carcinoma/HCC) and the perioperative care for the patients. Sixty-eight patients with malignant liver tumors in the hepatic dome were treated with a combination therapy of TACE and microwave coagulation via an artificially induced hydrothorax. Their perioperative condition was under close observation and the nursing care was intensified. Paracentesis of the chest was successfully carried out via the positioning of ultrasound and guidance of microwave to the tumor site, so that the tumor could be treated with cold cycle microwave coagulation therapy. After treatment, 3/68 patients (4.4%) achieved complete tumor ablation, while 59/68 (86.8%) achieved tumor ablation >50% or tumor shrinkage >30%. Another 6/68 patients (8.8%) achieved tumor ablation <50% or tumor shrinkage <30%. Of 45 patients, 42 (93.3%) obtained a reduction of AFP level >50% post-therapy, 28/37 patients (75.7%) achieved a reduction of CEA level >50%, 23/29 patients (79.3%) achieved a reduction of CA19-9 level> 50%; 3/68 patients (4.4%) survived for 4 to 6 months, 31/68 (45.6%) survived >6 months and 34/68 (50%) survived >12 months. No bleeding, liver failure, infection or needle tract seeding occurred after the operation, and no treatment-related deaths occurred. Microwave coagulation combined with TACE for HCC in the hepatic dome is safe and effective. Perioperative observation and nursing care can not only reduce the complications but also improve the therapeutic effect and the patient quality of life.


Ultralow work function of the electride Sr3CrN3.
Electrides have valence electrons that occupy free space in the crystal structure, making them easier to extract. This feature can be used in catalysis for important reactions that usually require a high-temperature and high-pressure environments, such as ammonia synthesis. In this paper, we use density functional theory to investigate the behaviour of interstitial electrons of the 1-dimensional electride Sr3CrN3. We find that the bulk excess electron density persists on introduction of surface terminations, that the crystal termination perpendicular to the 1D free-electron channel is highly stable and we confirm an extremely low work function with hybrid functional methods. Our results indicate that Sr3CrN3 is a potentially important novel catalyst, with accessible, directional and extractable free electron density.


A crustacean Ca2+-binding protein with a glutamate-rich sequence promotes CaCO3 crystallization.
The DD4 mRNA of the penaeid prawn Penaeus japonicus was shown previously to be expressed in the epidermis adjacent to the exoskeleton specifically during the post-moult period, when calcification of the exoskeleton took place. The encoded protein possessed a Ca2+-binding site, suggesting its involvement in the calcification of the exoskeleton. In the present study, an additional ORF (open reading frame) of 289 amino acids was identified at the 5' end of the previous ORF. The newly identified part of the encoded protein included a region of approx. 120 amino acids that was highly rich in glutamate residues, and contained one or more Ca2+-binding sites. In an immunohistochemical study, signals were detected within calcified regions in the endocuticular layer of the exoskeleton. Bacterially expressed partial segments of the protein induced CaCO3 crystallization in vitro. Finally, a reverse transcription-PCR study showed that the expression was limited to an early part of the post-moult period, preceding significant calcification of the exoskeleton. These observations argue for the possibility that the encoded protein, renamed crustocalcin (CCN), promotes formation of CaCO3 crystals in the exoskeleton by inducing nucleation.


Transcriptional factor fur from Thermoplasma volcanium binds its own promoter DNA in a divalent cation-dependent manner.
Because archaea possess many respiratory enzymes or radical scavengers with catalytic domains that contain iron, the expression of the genes encoding these enzymes might be regulated by iron acquisition. The genome of an archaeon, Thermoplasma volcanium contains a gene that encodes Fur (TVN0292). The fur gene of T. volcanium was amplified by PCR, and cloned into plasmid pET28a. TvFur (T. volcanium Fur protein) was expressed in E. coli cells and then purified. EMSA revealed that TvFur binds to its own promoter DNA. The binding to its own promoter was in an Mn(2+)-, Zn(2+)-, and Ni(2+)-dependent manner. DNase I footprinting analysis revealed that the binding sequence of tvfur promoter was 5'-G TTATTAT G TTTATAT A TTAATTA G-3'. An analysis utilizing oligonucleotides in TvFur-binding sequences revealed that TvFur binds to the TATA-box or regions in the vicinity of the TATA-box in the promoter. These results indicated that TvFur regulates transcription depending on the availability of environmental divalent cations.


IRF4 in multiple myeloma-Biology, disease and therapeutic target.
Multiple Myeloma (MM) is an incurable hematologic malignancy characterized by abnormal proliferation of plasma cells. Interferon Regulatory Factor 4 (IRF4), a member of the interferon regulatory family of transcription factors, is central to the genesis of MM. IRF4 is highly expressed in B cells and plasma cells where it plays essential roles in controlling B cell to plasma cell differentiation and immunoglobulin class switching. Overexpression of IRF4 is found in MM patients' derived cells, often as a result of activating mutations or translocations, where it is required for their survival. In this review, we first describe the roles of IRF4 in B cells and plasma cells and then analyse the subversion of the IRF4 transcriptional network in MM. Moreover, we discuss current therapies for MM as well as direct targeting of IRF4 as a potential new therapeutic strategy.


Benefits and concerns of treating pre-dialysis and renal transplant patients with recombinant human erythropoietin.
The possibility of lower efficacy and the fear of an increased incidence of side effects may explain the reluctance to use recombinant human erythropoietin (r-HuEPO) in patients with impaired renal function who do not yet require dialysis, as well as in transplanted patients with a failing renal allograft. Several recent studies have clearly shown that r-HuEPO is effective in these patient populations and that the doses needed to control anaemia are comparable with or lower than those needed for dialysis patients. When started at a low dose, the risk of severe hypertension is minimal, although in a significant number of patients intensification of the antihypertensive regimen is needed. Moreover, there are no indications that the use of r-HuEPO accelerates the deterioration of residual renal function.


Stress-induced anhedonia in mice is associated with deficits in forced swimming and exploration.
In order to develop a model for a depression-like syndrome in mice, we subjected male C57BL/6 mice to a 4-week-long chronic stress procedure, consisting of rat exposure, restraint stress, and tail suspension. This protocol resulted in a strong decrease in sucrose preference, a putative indicator of anhedonia in rodents. Interestingly, predisposition for stress-induced anhedonia was indicated by submissive behavior in a resident-intruder test. In contrast, most mice with nonsubmissive behavior did not develop a decrease in sucrose preference and were regarded as nonanhedonic. These animals were used as an internal control for stress-induced behavioral features not associated with the anhedonic state, since they were exposed to the same stressors as the anhedonic mice. Using a battery of behavioral tests after termination of the stress procedure, we found that anhedonia, but not chronic stress per se, is associated with key analogues of depressive symptoms, such as increased floating during forced swimming and decreased exploration of novelty. On the other hand, increased anxiety, altered locomotor activity, and loss of body weight were consequences of chronic stress, which occurred independently from anhedonia. Thus, behavioral correlates of stress-induced anhedonia and of chronic stress alone can be separated in the present model.


Probing electronic states of Ne2+ and Ar2+ by measuring kinetic-energy-release distributions.
Dissociative decay of metastable, electronically excited neon and argon dimer ions produces fragment ions with strikingly dissimilar kinetic-energy-release distributions. The distributions have been modeled based on ab initio calculations of potential energy curves. The unusual bimodal distribution observed for dissociation of Ne2+ arises from competition between radiative and nonradiative decay of the long-lived II(1/2)(u) state. For Ar2+, however, electronic predissociation is insignificant.


The early variation of left ventricular twisting function in patients with lymphoma received anthracycline therapy assessed by three-dimensional speckle tracking echocardiography.
Anthracycline-induced cardiotoxicity remains a significant and unresolved issue in patients receiving chemotherapy. The aim of this study was to evaluate left ventricular (LV) twisting function by three-dimensional speckle tracking echocardiography (3D-STE) in patients with lymphoma after anthracycline therapy. One hundred and one patients with newly diagnosed diffuse large B-cell lymphoma who had planned to receive anthracycline chemotherapy were enrolled. LV apical rotation, basal rotation, twist, torsion, time to peak apical rotation and time to peak basal rotation were measured by 3D-STE at baseline, after the completion of two cycles and four cycles of the regimen, respectively. Apical-basal rotation delay was calculated as the difference between time to basal and time to apical rotation. The results showed that LV apical rotation, basal rotation, twist and torsion declined progressively during the whole procedure (baseline vs. two and four cycles of the regimen, apical rotation: 12.5 ± ± 4.5° vs. 8.8 ± 3.6° vs. 6.0 ± 3.2°; basal rotation: -7.7 ± 3.0° vs. -5.9 ± 2.6° vs. -4.4 ± 2.5°; twist: 20.0 ± 6.4° vs. 14.5 ± 5.1° vs. 9.8 ± 4.5°; torsion: 2.9 ± 0.9°/cm vs. 2.1 ± 0.9°/cm vs. 1.4 ± 0.7°/cm; all p < 0.01). Furthermore, apical-basal rotation delay increased significantly after two cycles as well as after four cycles of the regimen (38.3 ± 67.9 ms vs. 66.7 ± 73.9 ms vs. 92.6 ± 96.9 ms; p < 0.01). LV twisting function deteriorated in the early stage of anthracycline therapy in patients with lymphoma, which could be detected by 3D-STE sensitively.


[Sarcoidosis of the spermatic cord and epididymus].
Sarcoidosis (Boeck's disease) is of unknown etiology with an incidence of 10 - 40/10(5) people. In 75% of the cases, pulmonary manifestations are found, with histological findings of noncaseating epithelial granulomas. Bilateral enlargement of the hilus lymph nodes are common and divided into three grades of enlargement. The initial symptoms are cough, fever and dyspnea. We report a man, 43 years old, first admitted to our hospital in 1988 with a tumor at the right spermatic-cord. Histological examination revealed a granulomatous inflammation, fitting to sarcoidosis, which was verified in the same year by mediastinoscopy. Partial resection of the left epididymal testis was performed in 2001 due to marked rigidity and histological fibrosis. Urological manifestation of Boeck's disease is rare. Approximately 30 cases have been described in literature with various urological associations. In most cases, urological sarcoidosis is found accidentally during examination of the most common form, pulmonary sarcoidosis.


Trajectory of Spike-Specific B Cells Elicited by Two Doses of BNT162b2 mRNA Vaccine.
The mRNA vaccines for SARS-CoV-2 have demonstrated efficacy and immunogenicity in the real-world setting. However, most of the research on vaccine immunogenicity has been centered on characterizing the antibody response, with limited exploration into the persistence of spike-specific memory B cells. Here we monitored the durability of the memory B cell response up to 9 months post-vaccination, and characterized the trajectory of spike-specific B cell phenotypes in healthy individuals who received two doses of the BNT162b2 vaccine. To profile the spike-specific B cell response, we applied the tSNE and Cytotree automated approaches. Spike-specific IgA+ and IgG+ plasmablasts and IgA+ activated cells were observed 7 days after the second dose and disappeared 3 months later, while subsets of spike-specific IgG+ resting memory B cells became predominant 9 months after vaccination, and they were capable of differentiating into spike-specific IgG secreting cells when restimulated in vitro. Other subsets of spike-specific B cells, such as IgM+ or unswitched IgM+IgD+ or IgG+ double negative/atypical cells, were also elicited by the BNT162b2 vaccine and persisted up to month 9. The analysis of circulating spike-specific IgG, IgA, and IgM was in line with the plasmablasts observed. The longitudinal analysis of the antigen-specific B cell response elicited by mRNA-based vaccines provides valuable insights into our understanding of the immunogenicity of this novel vaccine platform destined for future widespread use, and it can help in guiding future decisions and vaccination schedules.


Metastasis of hepatocellular carcinoma to the supramaxillary gingiva and right ventricle.
We describe a rare double metastasis of hepatocellular carcinoma to the supramaxillary gingiva and papillary muscle of the right ventricle. The patient was a 72-year-old woman who underwent three sessions of transcatheter arterial embolization for the primary lesions. Control of bleeding from the supramaxillary gingival metastasis was difficult by conservative treatment such as compression with gauze soaked in epinephrine. Therefore, radiotherapy was performed, but it failed to control the bleeding. The patient subsequently died due to hepatic failure. Autopsy revealed metastases of hepatocellular carcinoma to the papillary muscle of the right ventricle and paraaortic lymph node in the abdomen in addition to the supramaxillary gingival metastasis. Histopathological examination showed moderately differentiated hepatocellular carcinoma of both the primary site and metastatic sites to the gingiva and the heart and poorly differentiated in the paraaortic lymph node.


Urolithiasis in Jordanian children. A report of 52 cases.
Fifty-two children with urinary calculi seen between 1975 and 1986 were reviewed. Males dominated the series. The age distribution ranged from 10 months to 14 years (mean 7.2 years); 71% presented after school age. Most patients had upper tract stones. The main presenting symptoms were abdominal pain, infection and haematuria. The causative factors or co-factors were infection, malformations and urodynamic abnormalities. Metabolic disorders were rare. Calcium oxalate and uric acid stones were found most often. Surgical management was required in 88% of patients and only 3.8% had a recurrence. Presenting symptoms are variable and so a high index of suspicion is required for diagnosis.


Adenoid cystic carcinoma of the lacrimal gland in a 14-year-old male.
Adenoid cystic carcinoma (ACC) of the lacrimal gland is an aggressive, malignant epithelial neoplasm. This tumor is rarely seen in adults and even less commonly seen in children and adolescents; thus, there have been no large studies to date describing the optimal treatment of this malignancy in the pediatric population. Here, we report a case of lacrimal gland ACC in a 14-year-old male treated with neoadjuvant intra-arterial chemotherapy followed by globe-sparing tumor resection and chemoradiation. At 2-year follow-up, he remains disease free without evidence of tumor recurrence.


Toxic effects of detergents on the corneal endothelium.
Eighteen patients developed a toxic endothelial cell destruction syndrome following normal intraocular surgery, caused by a detergent residue originating from irrigating cannulas. The residue occurred after the concentration of a detergent solution has been increased from 0.4% to 4%, in combination with insufficient cleaning of the cannulas. Mass spectrometric analysis revealed the detergent to contain a nonionic ethoxylated fatty alcohol (6% vol/vol). Quantitative endothelial vital staining and in vitro corneal endothelial perfusion demonstrated endothelial toxic effects at the 1% and 0.06% level for the detergent and the pure ethoxylated fatty alcohol, respectively. Permeability studies showed that the toxic effects occurred as a result of endothelial barrier breakdown.


A study on hepatic portoenterostomy for the treatment of atresia of the biliary tract.
The results of our investigation have shown the crucial points of hepatic portoenterostomy used by us which is different from Kasai's portoenterostomy. First, the dissection of the rudimentary extrahepatic bile duct should be performed under magnification. Second, the transection of the rudimentary extrahepatic bile duct should be done using the microsurgical technique. Third, histologic verification of patency of the rudimentary extrahepatic bile ducts with frozen section during the operation should be carried out and the transection should be repeated under microsurgical control until the patency of the intrahepatic bile ducts at the porta hepatis area is confirmed. Fourth, the opening of the jejunal loop should be anastomosed quite close to the cut edge of the rudimentary extrahepatic bile duct at the porta hepatis by removing the mucosa of the posterior aspect of the jejunal opening. Fifth, the Suruga II procedure has been extremely successful in decreasing the incidence of postoperative ascending cholangitis and in preventing death in those infants who have postoperative ascending cholangitis develop. Sixth, if bile flow ceases postoperatively in spite of the forementioned technical refinements, then the curettage procedure should be carried out to the anastomotic site at the porta hepatis in order to resume bile flow.


Immediate alleviation of chronic pain by bone drilling and probable involvement of bone tissue in pain sensitisation.
Three patients presented with severe spontaneous pain, allodynia and numbness on the lateral side of the left heal, foot and/or toe due to L5 and/or S1 root injury, as a result of repeated failed back surgeries including Love's surgery and laminaectomy (failed back surgery syndrome). The neuropathic pain in the lower extremities did not respond to somatic nerve block, lumbar-sympathetic ganglion block, spinal cord stimulation, and/or medications. At the spots in the foot showing the most severe allodynia, bones were drilled with fluoroscopic assistance. Spontaneous pain diminished immediately and allodynia was completely resolved. Visual analogue scale score decreased immediately after bone drilling. The analgesic effect was maintained for 30-45 weeks. In three patients, drilling until the marrow cavity of the bones at painful sites effectively relieved chronic neuropathic pain with lasting analgesic effect.


Cluster headache sine headache: two new cases in one family.
We report two cases of cluster headache sine headache occurring in a family of cluster headache sufferers. A 54-year-old female, suffered for 15 years from short-lasting, right-sided attacks of eye reddening, lacrimation, rhinorrea, palpebral oedema and miosis, seven to eight times per day, in periods of 20-30 days. She did not experience headache, either with or without these phenomena. Her son suffers from periorbital, short-lasting, right-sided painful attacks accompanied by eye reddening, lacrimation, rhinorrea and nasal stiffnesss, occurring in periods of 30-35 days. Soon after the end of the current cluster period he still had daily attacks lasting 10-15 min, with the oculo-nasal autonomic phenomena only. The occurrence of cluster headache sine headache and cluster headache in the same family strongly suggests that the first condition is related to the cluster headache syndrome. Cluster headache sine headache should be considered as a subtype of the cluster headache syndrome.


Main predictors of periphyton species richness depend on adherence strategy and cell size.
Periphytic algae are important components of aquatic ecosystems. However, the factors driving periphyton species richness variation remain largely unexplored. Here, we used data from a subtropical floodplain (Upper Paraná River floodplain, Brazil) to quantify the influence of environmental variables (total suspended matter, temperature, conductivity, nutrient concentrations, hydrology, phytoplankton biomass, phytoplankton species richness, aquatic macrophyte species richness and zooplankton density) on overall periphytic algal species richness and on the richness of different algal groups defined by morphological traits (cell size and adherence strategy). We expected that the coefficients of determination of the models estimated for different trait-based groups would be higher than the model coefficient of determination of the entire algal community. We also expected that the relative importance of explanatory variables in predicting species richness would differ among algal groups. The coefficient of determination for the model used to predict overall periphytic algal species richness was higher than the ones obtained for models used to predict the species richness of the different groups. Thus, our first prediction was not supported. Species richness of aquatic macrophytes was the main predictor of periphyton species richness of the entire community and a significant predictor of the species richness of small mobile, large mobile and small-loosely attached algae. Abiotic variables, phytoplankton species richness, chlorophyll-a concentration, and hydrology were also significant predictors, depending on the group. These results suggest that habitat heterogeneity (as proxied by aquatic macrophytes richness) is important for maintaining periphyton species richness in floodplain environments. However, other factors played a role, suggesting that the analysis of species richness of different trait-based groups unveils relationships that were not detectable when the entire community was analysed together.


Functional nonsynonymous single nucleotide polymorphisms from the TGF-beta protein interaction network.
Protein complexes mediated by protein-protein interactions are essential for many cellular functions. Transforming growth factor (TGF)-beta signaling involves a cascade of protein-protein interactions and malfunctioning of this pathway has been implicated in human diseases. Using an in silico approach, we analyzed the naturally occurring human genetic variations from the proteins involved in the TGF-beta signaling (10 TGF-beta proteins and 242 other proteins interacting with them) to identify the ones that have potential biological consequences. All proteins were searched in the dbSNP database for the presence of nonsynonymous single nucleotide polymorphisms (nsSNPs). A total of 118 validated nsSNPs from 63 proteins were retrieved and analyzed in terms of 1) evolutionary conservation status, 2) being located in a functional protein domain or motif, and 3) altering putative protein motif or phosphorylation sites. Our results indicated the presence of 31 nsSNPs that occurred at evolutionarily conserved residues, 37 nsSNPs were located in protein domains, motifs, or repeats, and 46 nsSNPs were predicted to either create or abolish putative protein motifs or phosphorylation sites. We undertook this study to analyze the human genetic variations that can affect the protein function and the TGF-beta signaling. The nsSNPs reported in here can be characterized by experimental approaches to elucidate their exact biological roles and whether they are related to human disease.


Screening patients with the corneal navigator.
To present a corneal topography screening device for the detection of corneal ectasias and various refractive procedures based on corneal topography patterns. A database of corneal topography patterns were analyzed and used to "train" a neural network on nine different corneal topography patterns using nineteen corneal topography indices of corneal shape and power. Sample normal and corneal topographies were recognized correctly. The use of the corneal navigator to screen various corneal topographies aids clinical diagnosis.


MiR-126 Regulates Growth Factor Activities and Vulnerability to Toxic Insult in Neurons.
Dysfunction of growth factor (GF) activities contributes to the decline and death of neurons during aging and in neurodegenerative diseases. In addition, neurons become more resistant to GF signaling with age. Micro (mi)RNAs are posttranscriptional regulators of gene expression that may be crucial to age- and disease-related changes in GF functions. MiR-126 is involved in regulating insulin/IGF-1/phosphatidylinositol-3-kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK) signaling, and we recently demonstrated a functional role of miR-126 in dopamine neuronal cell survival in models of Parkinson's disease (PD)-associated toxicity. Here, we show that elevated levels of miR-126 increase neuronal vulnerability to ubiquitous toxicity mediated by staurosporine (STS) or Alzheimer's disease (AD)-associated amyloid beta 1-42 peptides (Aβ1-42). The neuroprotective factors IGF-1, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and soluble amyloid precursor protein α (sAPPα) could diminish but not abrogate the toxic effects of miR-126. In miR-126 overexpressing neurons derived from Tg6799 familial AD model mice, we observed an increase in Aβ1-42 toxicity, but surprisingly, both Aβ1-42 and miR-126 promoted neurite sprouting. Pathway analysis revealed that miR-126 overexpression downregulated elements in the GF/PI3K/AKT and ERK signaling cascades, including AKT, GSK-3β, ERK, their phosphorylation, and the miR-126 targets IRS-1 and PIK3R2. Finally, inhibition of miR-126 was neuroprotective against both STS and Aβ1-42 toxicity. Our data provide evidence for a novel mechanism of regulating GF/PI3K signaling in neurons by miR-126 and suggest that miR-126 may be an important mechanistic link between metabolic dysfunction and neurotoxicity in general, during aging, and in the pathogenesis of specific neurological disorders, including PD and AD.


An Ultrasound-Induced Self-Clearance Hydrogel for Male Reversible Contraception.
Nearly half of pregnancies worldwide are unintended mainly due to failure of contraception, resulting in negative effects on women's health. Male contraception techniques, primarily condoms and vasectomy, play a crucial role in birth control, but cannot be both highly effective and reversible at the same time. Herein, an ultrasound (US)-induced self-clearance hydrogel capable of real-time monitoring is utilized for in situ injection into the vas deferens, enabling effective contraception and noninvasive recanalization whenever needed. The hydrogel is composed of (i) sodium alginate (SA) conjugated with reactive oxygen species (ROS)-cleavable thioketal (SA-tK), (ii) titanium dioxide (TiO2), which can generate a specific level of ROS after US treatment, and (iii) calcium chloride (CaCl2), which triggers the formation of the hydrogel. For contraception, the above mixture agents are one-time injected into the vas deferens, which can transform from liquid to hydrogel within 160 s, thereby significantly physically blocking the vas deferens and inhibiting movability of sperm. When fertility is needed, a noninvasive remedial ultrasound can make TiO2 generate ROS, which cleaves SA-tK to destroy the network of the hydrogel. Owing to the recanalization, the refertility rate is restored to 100%. Meanwhile, diagnostic ultrasound (D-US, 22 MHz) can monitor the occlusion and recanalization process in real-time. In summary, the proposed hydrogel contraception can be a reliable, safe, and reversible male contraceptive strategy that addresses an unmet need for men to control their fertility.


Biochar combined with different nitrogen fertilization rates increased crop yield and greenhouse gas emissions in a rapeseed-soybean rotation system.
Biochar as agricultural soil amendment has been extensively investigated for its potential to sequester carbon, to mitigate greenhouse gases (GHGs) emissions, to enhance soil fertility and enhance crop yields. In this study, we investigated the impact of varying N fertilization rates in conjunction with biochar on soil properties, crop yield, and GHGs emissions in a rapeseed (Brassica napus L.)-soybean (Glycine max (L.) Merrill) rotation system for one year. Biochar and N fertilizer were applied following a factorial combination design of three biochar (B0: 0 t hm-2, B1: 15 t hm-2, and B2: 60 t hm-2) and three N fertilizer application rates (H: 100%, M: 75%, and L: 50% of the conventional application rates). In general, there was no significant effect of N fertilizer and its interaction with biochar application on soil water content, pH, and total carbon content, but the addition of biochar significantly increased these parameters (P < 0.05). The yield of both crops were significantly augmented by biochar up to 75% compared to using N fertilization alone, potentially due to enhanced N use efficiency. However, biochar significantly increased the cumulative N2O and CH4 emissions by as much as 2.2 times and 19 times, respectively, during the rapeseed season, thereby elevating the global warming potential (GWP) and the yield-scaled GWP. Nevertheless, the significantly increased soil carbon content following biochar addition might boost soil carbon sequestration, which could counterbalance the escalating GWP induced by GHGs. Therefore, we recommend a comprehensive and long-term evaluation of biochar's impact by considering crop yield, GHGs emissions, and carbon sequestration in agricultural systems to ensure sustainable agricultural management.


A two-year longitudinal study of post-stroke mood disorders: dynamic changes in associated variables over the first six months of follow-up.
We are prospectively studying a group of 103 stroke patients over the first 2 years after infarction to determine the variables which are associated with the development of depression. At both 3 and 6 months post-stroke, patients with left hemisphere infarcts showed a strong relationship between severity of depression and distance of the lesion on CT scan from the frontal pole. The strength of this association was unchanged from the immediate post-infarction period. In contrast, the correlation between degree of functional physical impairment and severity of depression steadily increased over the 6 month follow-up. The correlation between severity of depression and Mini-Mental score or between depression and social functioning score dropped between in-hospital and 3 months but then increased significantly between 3 and 6 months post-stroke. Age did not correlate with depression beyond the acute post-stroke period. Whether the increasing strength of the relationships between impairment and depression over the first 6 months post-stroke indicates that continued depression led to delayed recovery or whether continued severe impairments led to depression is not known, however, this issue will be addressed in further data evaluation from this prospective study.


Cellular dermal matrix used for root coverage: 18-month follow-up observation.
The goal of this study was to evaluate the long-term stability of the root coverage results obtained with an acellular dermal matrix. The mean root coverage at 12 weeks postoperative was 91.7%. The mean root coverage at the final postoperative evaluation (mean 18.6 months) was 87.0%. This difference was not statistically or clinically significant. The root coverage results obtained with an acellular dermal matrix were predictable, esthetic, and stable over time.


Repair of apical root resorption associated with periodontitis using a new intracanal medicament protocol.
Endodontic therapy is indicated for cases of traumatic tooth dislocation associated with pulp necrosis and/or inflammatory resorption. Here we describe the management of a maxillary left lateral permanent incisor that suffered lateral luxation, leading to pulp necrosis and root resorption, in a 13-year-old boy. The traumatized tooth was treated successfully by intracanal medication with calcium hydroxide, 2% chlorhexidine gel and zinc oxide for 12 months without any need to change the dressing, followed by conventional root canal filling. The postoperative course was uneventful and a stable clinical outcome was obtained with evidence of periapical lesion repair and stabilization of the resorption process.


Platypnea Orthodeoxia Syndrome Secondary to a Persistent Eustachian Valve.
Platypnea-Orthodeoxia syndrome (POS) is a rare and poorly understood syndrome characterized by platypnea and oxygen desaturation in the upright position that is relieved by recumbency. Here, we report a case of an 84-year-old woman who had chronic hypoxia in an upright position despite using home oxygen. The patient presented for hypoxia evaluation and was noted to have a restrictive pattern on pulmonary function tests (PFT). An echocardiogram showed a prominent eustachian valve extending from inferior to superior vena cava with contrast approaching the interatrial septum. The patient had a complete resolution of her platypnea following the closure of the patent foramen ovale.


[Prognosis of the systemic forms of juvenile chronic arthritis. Apropos of 100 cases].
The records of 100 children presenting with systemic juvenile rheumatoid arthritis were studied retrospectively. The precocity of onset and intensity of initial extra-articular signs did not seem to be correlated with a more severe outcome. On the other hand, the number of arthritides present during the first 6 months seemed to be associated with a different prognosis: the oligo- or abarticular forms generally had a better prognosis. In girls, onset was earlier and remissions were twice more frequent than in boys. Contrary to all other joints, the hip was susceptible of a radiological improvement in 25% of cases. Joint disabilities, especially of the wrist, were initially related to inflammation and pain; secondarily, they were chiefly related to the anatomic evolution, resulting in fusion of the joint spaces. At the last clinical examination after a 10 year's evolution, half of patients were in clinical remission, either without articular sequellae, with sequellae, the most severe of which being the hip involvement; 25% of patients still had systemic symptoms; 25% presented with polyarthritis with persisting biological and articular inflammatory signs.


Genomic Surveillance of Vancomycin-Resistant Enterococcus faecium Reveals Spread of a Linear Plasmid Conferring a Nutrient Utilization Advantage.
Healthcare-associated outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are a worldwide problem with increasing prevalence. The genomic plasticity of this hospital-adapted pathogen contributes to its efficient spread despite infection control measures. Here, we aimed to identify the genomic and phenotypic determinants of health care-associated transmission of VREfm. We assessed the VREfm transmission networks at the tertiary-care University Hospital of Zurich (USZ) between October 2014 and February 2018 and investigated microevolutionary dynamics of this pathogen. We performed whole-genome sequencing for the 69 VREfm isolates collected during this time frame and assessed the population structure and variability of the vancomycin resistance transposon. Phylogenomic analysis allowed us to reconstruct transmission networks and to unveil external or wider transmission networks undetectable by routine surveillance. Notably, it unveiled a persistent clone, sampled 31 times over a 29-month period. Exploring the evolutionary dynamics of this clone and characterizing the phenotypic consequences revealed the spread of a variant with decreased daptomycin susceptibility and the acquired ability to utilize N-acetyl-galactosamine (GalNAc), one of the primary constituents of the human gut mucins. This nutrient utilization advantage was conferred by a novel plasmid, termed pELF_USZ, which exhibited a linear topology. This plasmid, which was harbored by two distinct clones, was transferable by conjugation. Overall, this work highlights the potential of combining epidemiological, functional genomic, and evolutionary perspectives to unveil adaptation strategies of VREfm. IMPORTANCE Sequencing microbial pathogens causing outbreaks has become a common practice to characterize transmission networks. In addition to the signal provided by vertical evolution, bacterial genomes harbor mobile genetic elements shared horizontally between clones. While macroevolutionary studies have revealed an important role of plasmids and genes encoding carbohydrate utilization systems in the adaptation of Enterococcus faecium to the hospital environment, mechanisms of dissemination and the specific function of many of these genetic determinants remain to be elucidated. Here, we characterize a plasmid providing a nutrient utilization advantage and show evidence for its clonal and horizontal spread at a local scale. Further studies integrating epidemiological, functional genomics, and evolutionary perspectives will be critical to identify changes shaping the success of this pathogen.


FXR induces SOCS3 and suppresses hepatocellular carcinoma.
Suppressor of cytokine signaling 3 (SOCS3) is regarded as a vital repressor in the liver carcinogenesis mainly by inhibiting signal transducer and activator of transcription 3 (STAT3) activity. Farnesoid X Receptor (FXR), highly expressed in liver, has an important role in protecting against hepatocellular carcinoma (HCC). However, it is unclear whether the tumor suppressive activity of FXR involves the regulation of SOCS3. In the present study, we found that activation of FXR by its specific agonist GW4064 in HCC cells inhibited cell growth, induced cell cycle arrest at G1 phase, elevated p21 expression and repressed STAT3 activity. The above anti-tumor effects of FXR were dramatically alleviated by knockdown of SOCS3 with siRNA. Reporter assay revealed that FXR activation enhanced the transcriptional activity of SOCS3 promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay displayed that FXR directly bound to IR9 DNA motif within SOCS3 promoter region. The in vivo study in nude mice showed that treatment with FXR ligand GW4064 could decelerate the growth of HCC xenografts, up-regulate SOCS3 and p21 expression and inhibit STAT3 phosphorylation in the xenografts. These results suggest that induction of SOCS3 may be a novel mechanism by which FXR exerts its anti-HCC effects, and the FXR-SOCS3 signaling may serve as a new potential target for the prevention/treatment of HCC.


Hydroxyapatite microporous bioceramics as vancomycin reservoir: Antibacterial efficiency and biocompatibility investigation.
AbstarctInfections after bone reconstructive surgery are a real therapeutic and economic issue for the modern health care system. As the pathogen (most often Staphylococcus aureus) is able to develop a biofilm inside the bone, local delivery of antibiotics is of interest since high drug concentrations would be delivered directly at the target place. In this context, this study evaluated a porous hydroxyapatite implant as biocompatible bone substitute and vancomycin-delivery system to prevent post-operative infections. A simple method of impregnation with optimised conditions insured a high antibiotic loading (up to 2.3 ± 0.3 mg/m2), with a complete in vitro release obtained within 1-5 days. Additionally, the bacteriostatic and bactericidal effects of vancomycin were retained after loading on hydroxyapatite, as demonstrated after challenge with a Staphylococcus aureus strain. Regarding the biocompatibility, a wound healing assay of pre-osteoblastic MC3T3-E1 cells exposed to various concentrations of vancomycin revealed a dose-dependent reduction in cell migration for antibiotic concentrations higher than 1 mg/mL. Meanwhile, cells were able to proliferate normally on vancomycin-loaded scaffolds, although cell initial adhesion was seriously impaired for scaffolds loaded with 2.3 mg/m2 Loaded scaffolds could be stored up to three months at room temperature without any degradation of the antibiotic. Together, these results demonstrate the efficacy of these hydroxyapatite bone substitutes for local delivery of vancomycin in the context of bone infection.


Inactivation of HL-A antigens in vitro by action of antibiotics.
The effect of antibiotics on lymphocyte HL-A antigens in vitro is of variable character. All antibiotics under examination suppressed the absorption capacity of HL-A antigens after 2 hr of lymphocyte treatment at 37 degrees C. Ceporin and Kanamytrex inhibited even the cytotoxic reactivity of Hl-A antigens after 15-30 min of lymphocyte treatment. Chloramphenicol, aureomycin, streptomycin and oleandomycin, on the contrary, increased the specific cytotoxic reactivity of HL-A antigens after 15-30 min, after 1 hr they were ineffective for HL-A antigens, and after two or more hours they produced polyreactivity. Penicillin and erythromycin produced polyreactivity after only 15-30 min. The results show that for the follow-up of the drug effect on HL-A antigens the absorption test rather than the cytotoxicity test is of importance. The suppressed absorption capacity of HL-A antigens caused by the action of antibiotics proves their inactivation effect on the lymphocytes. The possibility of an analogous effect of antibiotics on lymphocyte HL-A antigens, even after administration to patients, is discussed.