Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure.
The 1.85 A crystal structure of endonuclease III, combined with mutational analysis, suggests the structural basis for the DNA binding and catalytic activity of the enzyme. Helix-hairpin-helix (HhH) and [4Fe-4S] cluster loop (FCL) motifs, which we have named for their secondary structure, bracket the cleft separating the two alpha-helical domains of the enzyme. These two novel DNA binding motifs and the solvent-filled pocket in the cleft between them all lie within a positively charged and sequence-conserved surface region. Lys120 and Asp138, both shown by mutagenesis to be catalytically important, lie at the mouth of this pocket, suggesting that this pocket is part of the active site. The positions of the HhH motif and protruding FCL motif, which contains the DNA binding residue Lys191, can accommodate B-form DNA, with a flipped-out base bound within the active site pocket. The identification of HhH and FCL sequence patterns in other DNA binding proteins suggests that these motifs may be a recurrent structural theme for DNA binding proteins.


Trichothecene mycotoxins produced byFusarium sporotrichioides strain P-11.
A highly toxic strain ofFusarium sporotrichioides Sherb. (P-11) isolated from wheat in Poland produced on rice culture up to 11 trichothecenes, which are: T-2 toxin (750 ppm), neosolaniol (300 ppm), HT-2 toxin (75 ppm), acetyl T-2 toxin (35ppm), 3'-hydroxy-T-2 (20ppm), T-2 triol (12.5ppm), 3'-hydroxy-HT-2 (1.2ppm), 4-acetoxy-T-2 tetraol (1.1 ppm), 15-acetoxy-T-2 tetraol (0.65 ppm), 8-acetoxy-T-2 tetraol (0.45 ppm), and T-2 tetraol (0.2 ppm). The presence of most of these trichothecenes, including the 3'-hydroxy-derivatives, in the excreta of animals treated with T-2 toxin indicates the existence of some correlation between T-2 toxin metabolism in animals and microorganisms, respectively.


Longitudinal Linkages among Parents' Educational Expectations, Youth's Educational Expectations, and Competence in Mexican-origin Families.
The contribution that parental educational expectations for youth and youth's perceptions of academic competence can have on youth's own educational expectations across early to late adolescence is not well-understood. In a sample of Mexican-origin families, the current study examined longitudinal (from early to late adolescence) associations among mothers, fathers, and youth's educational expectations, how youth's educational expectations were associated with perceived academic competence, and the potential mediating role of youth's perceived academic competence. Data from two-parent families which included one focal child (7th grade: N= 469; youth: Mage = 12.31, 50% female) at three waves (7th, 9th, and 11th grade) were utilized. Structural equation modeling and multi-group analysis were implemented to assess the study's goals. Results revealed significant associations among parents' 7th grade educational expectations and youth's 9th and 11th grade educational expectations. The findings also revealed three significant associations among youth's perceived academic competence and educational expectations between 7th and 11th grade. Specifically, youth's 7th grade perceived academic competence predicted youth's 9th grade educational expectations, youth's 7th grade educational expectations predicted youth's 9th grade perceived academic competence, and youth's 9th grade perceived academic competence predicted youth's 11th grade educational expectations. Multigroup analysis did not reveal gender differences for the associations tested. The findings highlight the long-term significance of parents' educational expectations on youth's educational expectations and underscore youth's academic competence, an individual level factor, as critical to consider for understanding educational expectations across adolescence for Mexican-origin youth.


Fistula elevation procedure: experience with 295 consecutive cases during a 7-year period.
Up to 50% of AV fistulas fail to mature, primarily because of problems with fistula cannulation. Fistula elevation procedure (FEP) is a simple superficialization procedure where the fistula is surgically exposed, mobilized, and elevated into a more superficial position for the purpose of facilitating AV fistula cannulation. The purpose of this study is to review use of FEP as an adjunct to fistula maturation. Two hundred ninety-five FEPs were performed between February 1999 and December 2005. FEP was performed if the fistula was considered too deep to cannulate or if nurses were unable to cannulate the fistula. Kaplan-Meier life-table analysis was used to determine patency and for a subanalysis by location of FEP performed (172 brachial-cephalic, 70 brachial-basilic, 46 radial-cephalic, 7 superficial femoral vein). Survival curves were compared using log-rank test. Functional primary patency rates for patients undergoing an adjunctive FEP were 73% at 6 months, 60% at 1 year, and 46% at 2 years. Secondary functional patency rates were 81% at 6 months, 71% at 1 year, and 59% at 2 years. There was no statistical significance in any outcomes based on anatomic site of elevation. AV fistulas that might otherwise have been abandoned because of excessive depth or tortuosity can be successfully salvaged by an adjunctive FEP and achieve satisfactory longterm functional patency. FEP is a valuable adjunct to AV fistula creation, which will enhance fistula maturation rates.


Changes in beclin-1 and micro-calpain expression in tri-ortho-cresyl phosphate-induced delayed neuropathy.
Tri-ortho-cresyl phosphate (TOCP) can cause toxic neuropathy known as organophosphate-induced delayed neuropathy (OPIDN), which is pathologically characterized by the swollen axon containing aggregations of neurofilaments, microtubules, and multivesicular vesicles. Autophagy is a self-degradative process which plays a housekeeping role in removing misfolded proteins and damaged organelles. The current study was designed to investigate the possible roles of autophagy in the pathogenesis of OPIDN. Adult hens were treated with a dose of 750mg/kg TOCP by gavage, or injected subcutaneously with 60mg/kg phenylmethanesulfonyl fluoride (PMSF) dissolved in DMSO 24h earlier and subsequently treated with TOCP, then sacrificed on the time-points of 0, 1, 5, 10, and 21 days after dosing of TOCP respectively. The levels of beclin-1 and μ-calpain in tibial nerves and spinal cords were determined by immunoblotting. The results showed that in both tissues TOCP increased the expression of μ-calpain while decreased that of beclin-1. When given before TOCP administration, PMSF pretreatment could protect hens against the delayed neuropathy. In the meantime, pretreatment with PMSF reduced calpain expression below basal and increased beclin-1 expression above basal in tibial nerve, whereas it simply returned calpain and beclin-1 expression to their basal levels in spinal cord. In conclusion, the intoxication of TOCP was associated with a significant change of beclin-1 in hen nervous tissues, which suggested that disruption of autophagy-regulated machinery in neurons might be involved in the pathogenesis of OPIDN.


Cut-Off Value of Serum Uric Acid for Development of Gout Disease in Patients with Multiple Co-Morbidities.
This study aimed to determine the association between hyperuricemia, comorbid diseases and risk of developing gout disease in a Turkish population in a long follow-up period. A total of 2000 Turkish adults were cross-sectionally analysed for serum urate levels in 2009 at the Pamukkale University Faculty of Medicine. All patients on regular follow-up at our tertiary health center (n=1322) were included in this study. Demographic features (age and gender), comorbid clinical conditions, and medication use were noted. The risk of developing gout and the determinant factors were investigated. Multivariate logistic regression analysis was performed to analyse causative effects of factors while receiver operating characteristic (ROC) curve analysis was used to identify optimal cut-off values of uric acid level for predicting the development of gout. Among 1322 patients, the mean age was 56.9 (SD:14.68) years. 57.3% (n=758) of the patients were female. The most common co-morbid disease was chronic kidney disease (581, 43%), followed by hypertension (522, 39.4%). Gout developed in 25 patients (1.8%). Gout development risk and presence of all the above comorbidities were significantly higher in patients with serum urate ≥7mg/dl compared with <7mg/dl. Male gender and not using urate lowering drugs were the main risk factors for developing gout disease. ROC analysis of serum uric acid levels identified a cut-off value of >7 (AUC: 0.776, sensitivity 86.96%, specificity 66.74%). There is still a dilemma concerning the culprit effects of both comorbidities and hyperuricemia on the risk of developing gout disease.


Using data from seed-dispersal modelling to manage invasive tree species: the example of Fraxinus pennsylvanica Marshall in Europe.
Management strategies to control invasive species need information about dispersal distances to predict establishment potential. Fraxinus pennsylvanica is a North American anemochorous tree species that is invasive in many Central European floodplain forests. To predict seed-dispersal potential, the stochastic model WaldStat was used, which enables different options for directionality (isotropic and anisotropic) to be simulated. In this article, we (1) show empirical results of fructification and seed dispersal for this tree species. The model predicts approximately 250,000 seeds for one F. pennsylvanica tree. These results were used to (2) calculate species-specific dispersal distances and effects of wind direction. To consider the influence of wind on dispersal potential of the tree species, long-distance dispersal (LDD [95th percentile dispersal distance]) was calculated. Mean dispersal distances varied between 47 and 66 m. LDD values modelled along the main wind direction ranged from 60 to 150 m. Seed production, dispersal distance, and direction data were (3) incorporated into theoretical management scenarios for forest ecosystems. Finally (4), we discuss management options and the practical relevance of model scenarios in relation to the accuracy of spatial dispersal predictions. Further analyses should be focused on possible, well-adapted management concepts at stand level that could restrict the potential spread of invasive species.


Outcome of surgery for Graves' disease re-examined.
The outcome of surgery for Graves' disease in terms of early and late morbidity was studied in 161 patients undergoing subtotal thyroidectomy in the 10-year period 1976-1985. Eighty of these patients had a minimum follow-up of 5 years. There was a low operative morbidity and a zero mortality. The weight of thyroid tissue preserved (in the range 5-10 g) influenced the prevalence of hypothyroidism at one year and at five years. There was a cumulative incidence of hypothyroidism which could not be reliably predicted from biochemical results during the first year. Over 60 per cent of patients with subclinical hypothyroidism at 4 months (63 per cent) or 1 year (70 per cent) did not subsequently need thyroxine replacement within 5 years. Patients remained at risk of developing recurrent toxicity indefinitely and the risk was significantly greater in patients with small goitres (less than 50 g). Our results may be improved by leaving larger remnants (9-10 g) in most patients and smaller remnants (2-4 g) in those with small glands in whom alternative treatment, which is to be preferred, is not acceptable. After subtotal thyroidectomy for Graves' disease lifelong follow-up is necessary.


Immunohistochemical retrieval of the principal HIV antigens p24, gp41, and gp120 in formalin fixed tissue: an investigation using HIV infected lymphoblasts and postmortem brain tissue from AIDS cases.
This paper describes the use of an autoclaving procedure followed by immunocytochemistry to enhance the detection of the human immunodeficiency virus (HIV) antigens p24, gp41, and gp120. This procedure greatly improved the detection rate of the p24 and gp41 HIV surface antigens in formalin fixed, paraffin wax embedded, HIV positive central nervous system (CNS) tissue while restricting staining to areas of the CNS showing evidence of neuropathology. However, the technique did not improve retrieval of the gp120 antigen in either HIV positive, formalin fixed CNS tissue or HIV infected T lymphoblasts. The inclusion of the high temperature autoclave step was validated using both HIV infected lymphoblasts and pre-adsorption of the specific antibodies with the appropriate recombinant HIV proteins. Using the methodology described here, formalin fixed CNS tissue from potential or known HIV positive cases can be processed reliably and safely. To ensure the reliability of this technique, it is recommended that an assessment of both the p24 and gp41 antigens is undertaken.


Chromatin structure and nucleic acid synthesis in human lymphocyte activation by phytohemagglutinin.
Alterations in chromatin structure were explored as a function of time following phytohemagglutinin (PHA) activation of human lymphocytes. Nuclear refringency (related to chromatin status), ultrastructural changes, and modifications of nucleic acid synthesis were compared. Chromatin dispersion was observed within 20 min of stimulation, with a concomitant increase in [3H]uridine incorporation; both were inhibited by actinomycin D. Recondensation of chromatin had occurred at 60 min when RNA synthesis was still increasing. The early chromatin dispersion thus was a reversible step and one of the most striking cellular events during the first phase of PHA activation. Late chromatin dispersion of blastic cells during the second phase of PHA response (after 24 h) was related to DNA synthesis in mitotic cells. This step was also inhibited by actinomycin D. These results suggest a relationship between the morphological changes in chromatin structure and the induction of RNA and DNA syntheses. The regulation of transcriptional and replicational states of the nucleus is discussed in terms of modifications of chromatin structure, considering PHA-induced calcium and cyclic nucleotide metabolism and interleukin II receptor expression.


Total removal of an intramedullary cavernous angioma by transthoracic approach.
Intramedullary cavernous angiomas are rare vascular malformations; all published cases have been surgically approached posteriorly by standard laminectomy. We describe the case of a 63-year-old man with an intramedullary cavernous angioma, anteriorly located in the thoracic spinal cord. The angioma was operated on by transthoracic approach and totally removed.


The growth potential of Escherichia coli O157:H7, Salmonella spp. and Listeria monocytogenes in dairy manure-based compost in a greenhouse setting under different seasons.
The pathogen growth in dairy compost was studied in a greenhouse setting under different seasons. The five-strain mixtures of each Escherichia coli O157:H7, Salmonella spp. and Listeria monocytogenes were inoculated separately into dry compost to yield c.1 log CFU g(-1) . After acclimation at room temperature, the inoculated compost was initially adjusted to moisture levels of 10-50% and then kept in a greenhouse under different seasons. The populations of all three pathogens increased by 2·1-3·9log CFU g(-1) within 3 days in autoclaved compost with initial moisture content of at least 40%. Listeria monocytogenes multiplied up to 2·4 log CFU g(-1) in compost with initial moisture content of 30% and was detected up to 28 days for all seasons, whereas populations of both E. coli O157:H7 and Salmonella increased by c. 1 log in compost with initial moisture content of 30% during winter months only. No pathogen growth in nonautoclaved compost was detected. Bacterial species, temperature, light intensity and moisture content affected the growth potential and survival of pathogens in compost when the population of background microflora was low. Keeping compost as dry as possible and maintaining certain levels of background microflora may be critical to prevent the growth of pathogens.


The efficacy and safety of Fufangdanshen tablets (Radix Salviae miltiorrhizae formula tablets) for mild to moderate vascular dementia: a study protocol for a randomized controlled trial.
Vascular dementia (VaD) is the second most common subtype of dementia after Alzheimer's disease (AD). Currently, there are no medications approved for treating patients with VaD. Fufangdanshen (FFDS) tablets (Radix Salviae miltiorrhizae formula tablets) are a traditional Chinese medicine that has been reported to improve memory. However, the existing evidence for FFDS tablets in clinical practice derives from methodologically flawed studies. To further investigate the safety, tolerability, and efficacy of FFDS tables in the treatment of mild to moderate VaD, we designed and reported the methodology for a 24-week randomized, double-blind, parallel, multicenter study. This ongoing study is a double-blind, randomized, parallel placebo-controlled trial. A total of 240 patients with mild to moderate VaD will be enrolled. After a 2-week run-in period, the eligible patients will be randomized to receive either three FFDS or placebo tablets three times per day for 24 weeks, with a follow-up 12 weeks after the last treatment. The primary efficacy measurement will be the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary efficacy measurements will include the Mini Mental State Examination (MMSE) and activities of daily living (ADL). Adverse events will also be reported. This randomized trial will be the first rigorous study on the efficacy and safety of FFDS tablets for treating cognitive symptoms in patients with VaD using a rational design. ClinicalTrials.gov: NCT01761227 . Registered on 2 January 2013.


Effects of transferrin conjugated multi-walled carbon nanotubes in lung cancer delivery.
The aim of this study was to develop multi-walled carbon nanotubes (MWCNT) which were covalently conjugated with transferrin by carbodiimide chemistry and loaded with docetaxel as a model drug for effective treatment of lung cancer in comparison with the commercial docetaxel injection (Docel™). d-Alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as amphiphilic surfactant to improve the aqueous dispersity and biocompatibility of MWCNT. Human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) of the docetaxel/coumarin-6 loaded MWCNT. The cellular uptake results of transferrin conjugated MWCNT showed higher efficiency in comparison with free C6. The IC50 values demonstrated that the transferrin conjugated MWCNT could be 136-fold more efficient than Docel™ after 24h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells appeared significantly (P<0.05) in the sub-G1 phase for transferrin conjugated MWCNT in comparison with Docel™. Results of transferrin conjugated MWCNT have showed better efficacy with safety than Docel™.


ENaC regulation by phospholipids and DGK explained through mathematical modeling.
Cystic fibrosis is a condition caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). It is also thought to increase the activity of epithelial sodium channels (ENaC). The altered function of these ion channels is one of the causes of the thick dehydrated mucus that characterizes the disease and is partially responsible for recurrent pulmonary infections and inflammation events that ultimately destroy the lungs of affected subjects. Phosphoinositides are signaling lipids that regulate numerous cellular processes and membrane proteins, including ENaC. Inhibition of diacylglycerol kinase (DGK), an enzyme of the phosphoinositide pathway, reduces ENaC function. We propose a computational analysis that is based on the combination of two existing mathematical models: one representing the dynamics of phosphoinositides and the other explaining how phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) influences ENaC activity and, consequently, airway surface liquid. This integrated model permits, for the first time, a detailed assessment of the intricate interactions between DGK and ENaC and is consistent with available literature data. In particular, the computational approach allows comparisons of two competing hypotheses regarding the regulation of ENaC. The results strongly suggest that the regulation of ENaC is primarily exerted through the control of PI(4,5)P2 production by type-I phosphatidylinositol-4-phosphate 5-kinase (PIP5KI), which in turn is controlled by phosphatidic acid (PA), the product of the DGK reaction.


Early development of the skin microbiome: therapeutic opportunities.
As human skin hosts a diverse microbiota in health and disease, there is an emerging consensus that dysregulated interactions between host and microbiome may contribute to chronic inflammatory disease of the skin. Neonatal skin is a unique habitat, structurally similar to the adult but with a different profile of metabolic substrates, environmental stressors, and immune activity. The surface is colonized within moments of birth with a bias toward maternal strains. Initial colonists are outcompeted as environmental exposures increase and host skin matures. Nonetheless, early life microbial acquisitions may have long-lasting effects on health through modulation of host immunity and competitive interactions between bacteria. Microbial ecology and its influence on health have been of interest to dermatologists for >50 years, and an explosion of recent interest in the microbiome has prompted ongoing investigations of several microbial therapeutics for dermatological disease. In this review, we consider how recent insight into the host and microbial factors driving development of the skin microbiome in early life offers new opportunities for therapeutic intervention. IMPACT: Advancement in understanding molecular mechanisms of bacterial competition opens new avenues of investigation into dermatological disease. Primary development of the skin microbiome is determined by immunological features of the cutaneous habitat. Understanding coordinated microbial and immunological development in the pediatric patient requires a multidisciplinary synthesis of primary literature.


Purification of togavirus haemagglutinins by chromatography on controlled pore glass.
Purified preparations of haemagglutinins from Sindbis, West Nile and tick-borne encephalitis (TBE) viruses could be obtained from infected mouse brains by alkaline extraction, precipitation with protamine and chromatography on polyethylene glycol-coated controlled pore glass with 242 A pore diameter.


Wound care with antibacterial honey (Medihoney) in pediatric hematology-oncology.
The physiologic process of wound healing is impaired and prolonged in pediatric patients receiving chemotherapy. Due to profound immunosuppression, wound infection can easily spread and act as the source of sepsis. Referring to in vitro studies, which confirmed the antibacterial potency of special honey preparations against typical isolates of nosocomially acquired wound infections (including Methicillin-resistant Staphylococcus aureus and Vancomycin-resistant enterococci) and considering the encouraging reports from other groups, Medihoney has now been used in wound care at the Department of Pediatric Oncology, Children's Hospital, University of Bonn for 3 years. Supplemented with clinical data from pediatric oncology patients, this article reviews the scientific background and our promising experience with Medihoney in wound care issues at our institution. To collect and analyze the available experience, we prepare an internet-based data documentation module for pediatric wound care with Medihoney.


Novel molecular diagnostic technique for detecting the different species of Plasmodium.
Sensitive diagnostic techniques are needed for timely detection of malaria parasite and disease control. Molecular diagnostic techniques involving Polymerase chain reaction (PCR) with 18 s rRNA as a known diagnostic target with an overall sensitivity of 10 parasites per microliter is used as a gold standard. Till date, no attempt has been undertaken to develop a technique for the identification of four Plasmodium species in a single step PCR combined with restriction digestion with enzymes. Plasmodium species-specific polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays have been developed, based on RFLP of amplified PCR product of mitochondrial gene as a target. This approach identifies Plasmodium species in two steps involving amplification of mitochondrial (Mt) gene by PCR followed by digestion with restriction enzymes. A total of 36 clinical samples were subjected to PCR-RFLP for the diagnosis and detection of malaria parasites targeting mitochondrial gene (Mt). The findings of the method were compared with gold standard methods (Microscopy, RDTs and Nested PCR) and was able to detect mixed infection with a sensitivity of 100% and specificity of 93.8% with respect to nested PCR. The results obtained by PCR-RFLP were validated with Sanger sequencing (n = 32) and were found to be consistent with the method. This method identifies and distinguishes four species of human malaria parasite namely P. falciparum (Pf), P. vivax (Pv), P. malariae (Pm) and P. ovale (Po) in approximately 4 h. To overcome and address PCR difficulties, continuous efforts are needed for the development of newer diagnostic techniques.


Effects of Stromal Cell Conditioned Medium and Antipurinergic Treatment on Macrophage Phenotype.
The immunomodulatory capacity of the human mesenchymal stromal cell (MSC) secretome has been a critical driver for the development of cell-free MSC products, such as conditioned medium (CM), for regenerative medicine applications. This is particularly true as cell-free MSC products present several advantages over direct autologous or allogeneic MSC delivery with respect to safety, manufacturability, and defined potency. Recently, significant effort has been placed into creating novel MSC CM formulations with an immunomodulatory capacity tailored for specific regenerative contexts. For instance, the immunoregulatory nature of MSC CM has previously been tuned through a number of cytokine-priming strategies. Herein, we propose an alternate method to tailor the immunomodulatory "phenotype" of cytokine-primed MSC CM through coupling with the pharmacological agent, suramin. Suramin interferes with the signaling of purines including extracellular adenosine triphosphate (ATP), which plays a critical role in the activation of the innate immune system after injury. Toward this end, human THP-1-derived macrophages were activated to a proinflammatory phenotype and treated with (1) unprimed/native MSC CM, (2) interferon-γ/tumor necrosis factor α-primed MSC CM (primed CM), (3) suramin alone, or (4) primed MSC CM and suramin (primed CM/suramin). Markers of key macrophage functions-cytokine secretion, autophagy, oxidative stress modulation, and activation/migration-were assessed. Consistent with previous literature, primed CM elevated macrophage secretion of several proinflammatory and pleiotropic cytokines relative to native CM; whereas addition of suramin imparted consistent shifts in terms of TNFα (↓), interleukin-10 (↓), and hepatocyte growth factor (↑) irrespective of CM. In addition, both primed CM and suramin, individually and combined, increased reactive oxygen species production relative to native CM, and addition of suramin to primed CM shifted levels of CX3CL1, a factor involved in ATP-associated macrophage regulation. Varimax rotation assessment of the secreted cytokine profiles confirmed that primed CM/suramin resulted in a THP-1 phenotypic shift away from the lipopolysaccharide-activated proinflammatory state that was distinct from that of primed CM or native CM alone. This altered primed CM/suramin-associated phenotype may prove beneficial for healing in certain regenerative contexts. These results may inform future work coupling antipurinergic treatments with MSC-derived therapies in regenerative medicine applications.


Characterization of a laboratory-derived, high-level ampicillin-resistant Salmonella enterica serovar Typhimurium strain that caused meningitis in an infant.
A Salmonella enterica serovar Typhimurium strain that harbored a plasmid carrying a TEM-1-type beta-lactamase gene was isolated from the blood and cerebrospinal fluid of an infant with meningitis. This 3.2-kb plasmid was further characterized to be a nonconjugative pGEM series cloning vector containing a foreign insert. The strain was likely laboratory derived and contaminated the environment before it caused the infection.


The Wells rule does not adequately rule out deep venous thrombosis in primary care patients.
Using data from secondary care outpatients, Wells and colleagues developed a diagnostic rule to estimate the probability of the presence of deep venous thrombosis (DVT). The accuracy of the Wells rule has not been properly validated for use in primary care patients in whom DVT is suspected. To validate the diagnostic accuracy of the Wells rule, with and without D-dimer testing, in a primary care setting. Cross-sectional study with prospective data collection from 1 January 2002 to 1 March 2003. 110 primary care practices in a circumscribed geographic region in The Netherlands. 1295 consecutive patients who consulted their primary care physician about symptoms suggestive of DVT. All patients underwent history-taking and physical examination to calculate the Wells rule score, and D-dimer testing. Repeated leg ultrasonography was the reference standard to determine the true presence or absence of DVT. In the primary care setting, 12.0% of patients in the low-risk group had DVT; the original study by Wells and colleagues reported a rate of 3% among such patients. When combined with negative results on a D-dimer test, the Wells rule yielded a prevalence of DVT of 2.9% in the lowest-risk group, whereas the prevalence was 0.9% in the original study. Patients with previous DVT were included, and the diagnostic reference standard was different from that used in Wells and colleagues' original study. The Wells rule, alone or in combination with D-dimer testing, does not guarantee accurate estimation of risk in primary care patients in whom DVT is suspected.


Asynchronous ripening behavior of cactus pear (Opuntia ficus-indica) cultivars with respect to physicochemical and physiological attributes.
Physicochemical and physiological ripening events in cactus pear (Opuntia ficus-indica) fruit of cultivars 'Ntopia' and 'Hercules' were profiled against skin coloration from mature-green (S1) to over-mature (S5). Fructose and glucose accumulation were linear in 'Ntopia' but peaked near S3 in 'Hercules' synchronously to the appearance of sucrose. Betalains increased steadily in 'Ntopia' (103.2mg/l) but peaked before full skin coloration in 'Hercules' (49.7mg/l); whereas phenolic content remained invariable and ascorbate content peaked near S5 in both 'Ntopia' (108.6μg/g) and 'Hercules' (163.1μg/g). Cell wall material diminished with maturity though textural changes with ripening appeared not related to pectin solubilization but to weakening of glycan bonding and loss of neutral sugars. Fruit firmness rather was correlated to seed weight (r=0.89) and seed-to-pulp ratio (r=0.73). Cultivar differences highlighted in the chronology of ripening events are critical for defining optimum harvest maturity and postharvest handling protocols for premium quality cactus pear fruit.


Reliability of continuous cardiac output measurement during intra-abdominal hypertension relies on repeated calibrations: an experimental animal study.
Monitoring cardiac output (CO) may allow early detection of haemodynamic instability, aiming to reduce morbidity and mortality in critically ill patients. Continuous cardiac output (CCO) monitoring is recommended in septic or postoperative patients with high incidences of intra-abdominal hypertension (IAH). The aim of the present study was to compare the agreement between three CCO methods and a bolus thermodilution CO technique during acute IAH and volume loading. Ten pigs were anaesthetised and instrumented for haemodynamic measurements. Cardiac output was obtained using CCO by pulse power analysis (PulseCO; LiDCO monitor), using CCO by pulse contour analysis (PCCO; PiCCO monitor) and using CCO by pulmonary artery catheter thermodilution (CCOPAC), and was compared with bolus transcardiopulmonary thermodilution CO (COTCP) at baseline, after fluid loading, at IAH and after an additional fluid loading at IAH. Whereas PulseCO was only calibrated at baseline, PCCO was calibrated at each experimental step. PulseCO and PCCO underestimated CO, as the overall bias +/- standard deviation was 1.0 +/- 1.5 l/min and 1.0 +/- 1.1 l/min compared with COTCP. A clinically accepted agreement between all of the CCO methods and COTCP was observed only at baseline. Whereas IAH did not influence the CO, increased CO following fluid loading at IAH was only reflected by CCOPAC and COTCP, not by uncalibrated PulseCO and PCCO. After recalibration, PCCO was comparable with COTCP. The CO obtained by uncalibrated PulseCO and PCCO failed to agree with COTCP during IAH and fluid loading. In the critically ill patient, recalibration of continuous arterial waveform CO methods should be performed after fluid loading or before a major change in therapy is initiated.


Relationship between premenopausal dietary intake and postmenopausal subclinical atherosclerosis.
This study examines the association of premenopausal dietary intake with postmenopausal subclinical atherosclerosis. A prospective population-based cohort of 401 premenopausal women from the Healthy Women Study. Baseline premenopausal dietary intake was determined with the use of single 24-h recall. Coronary and aortic calcium scores were measured by electron beam computed tomography 8 years after menopause, and carotid plaque index was measured by carotid ultrasound scan 5 years after menopause. Prevalence of coronary, aortic, and carotid subclinical atherosclerosis were 47.3%, 75.4%, and 52.1%, respectively. In unadjusted analysis, the relative risks (RR) of saturated fat intake for coronary calcification in second, third and highest quartile groups compared to the lowest were 1.82 (95% confidence interval, 1.00-3.30), 1.49 (0.82-2.70), and 1.99 (1.09-3.62), while those of carbohydrate intake were 0.48 (95% confidence interval, 0.26-0.88), 0.47 (0.26-0.86), and 0.35 (0.19-0.64), respectively. None of the dietary components were significantly associated with aortic calcification or carotid plaque. The association between premenopausal dietary intake and postmenopausal subclinical atherosclerosis supports the recommended premenopausal dietary intervention for the prevention of cardiovascular disease.


Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus.
To determine the features associated with acute onset systemic lupus erythaematosus (SLE). A total of 631 SLE patients from LUMINA (for "lupus in minority populations: nature vs nurture"), a multiethnic (Hispanics, African-Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of > or = 4 American College of Rheumatology (ACR) criteria for the classification of SLE in < or = 4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortality, autoantibodies, HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (chi(2) and Student t test) and multivariable (stepwise logistic regression) analyses. A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076-3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005-1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956-0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827-0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249-0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142-0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE.


Non-motor symptoms in Parkinson's disease.
With the growing awareness of the presence of non-motor symptoms in Parkinson's disease (PD) has come the realization that these non-motor features play a tremendously important, and sometimes dominant, role in the management and even the diagnosis of the disorder. Despite this, a reluctance to formally address and treat the non-motor symptoms of PD remains and quality of life for PD patients suffers. This review provides an overview of the impact non-motor symptoms have on persons with PD, along with a brief description of some of the more common non-motor features of PD.


Panax notoginseng and its components decreased hypertension via stimulation of endothelial-dependent vessel dilatation.
Ginsenoside Rb1 and Rg1 are major components of Panax notoginseng (P.N.), an herb with known clinical efficacy in hypertension and myocardial ischemia in Eastern countries. This investigation is to elicit the mechanism of these components in hypertension via their effect on vascular reaction. To assess the ability of P.N. in hypertension, P.N. extracts were injected in spontaneously hypertensive rats (SHR) via the vena caudalis; Low dosages of P.N. extracts significantly lowered blood pressure in SHR. Examination with Rb1 and Rg1 revealed significant vasodilatation using mouse coronary arteries in a dose-dependent manner. Rb1- and Rg1-induced vasodilatation was blocked by pre-incubation with eNOS and PI3K inhibitors. Coronaries of eNOS-/- mice showed attenuated vasodilatation with Rb1 and Rg1. In addition, both Rb1 and Rg1 induce nitric oxide (NO) generation through increasing the phosphorylation of eNOS, activating Na+-independent l-arginine transport, and stimulating cationic amino acid transport (CAT)-1 mRNA expression in cultured endothelial cells. Ginsenoside Rb1 and Rg1 increased endothelial-dependent vessel dilatation through the activation of NO by modulating the PI3K/Akt/eNOS pathway and l-arginine transport in endothelial cells. These findings may have important implications for understanding the mechanisms of clinical efficacy of the herb P.N. when used in the regulation of blood pressure.


Nanometric sponges made of water-soluble hydrophobic dendrimers.
The behavior of a fifth generation phosphorus dendrimer having a hydrophobic interior and hydrophilic end groups is studied in solution in water using the pulsed-field gradient spin-echo NMR technique. Addition of THF to this solution induces dramatic changes concerning the size of the dendrimer (+150% in volume), T1 relaxation of THF, and viscosity. This dendrimer behaves like a highly singular nanotool, able both to modify its environment and to be modified by it.


Combined effects of condition and density on post-settlement survival and growth of a marine fish.
For species with complex life cycles, variation in growth or condition during early life stages may affect survival in later stages or during important life-stage transitions. These effects on survival may be an important source of recruitment variability. However, survival during early stages is often density-dependent and it is unclear how the effects of early condition on recruitment compare to the effects of density alone. In this study, I investigated both the independent and interactive effects of condition and density on post-settlement survival and growth of bicolor damselfish (Stegastes partitus). In a field experiment, I crossed two levels of population density with two levels of condition (established by laboratory feeding of recent settlers) and measured growth and survivorship over a 30-day period. Low condition and high density both decreased survivorship. However, the effects of density were stronger and the effects of condition and density on survivorship were independent. In contrast, condition and density had interactive effects on growth in that density reduced growth only in the high-condition treatments. In a second experiment, I examined how condition and density affected intraspecific aggression and shelter use, two behaviors that may influence growth and survival. Shelter use was unaffected by density and condition. The rate of intraspecific chases was greater and increased more strongly with density when fish were in higher condition. Average growth rate of fish decreased with increasing rate of intraspecific chases, suggesting that the difference in aggression between condition levels was the mechanism leading to differences in density-dependent growth. These results suggest that variation in condition at settlement can significantly contribute to variation in population abundance, despite density dependence in survival. However, because behaviors that affect density-dependent growth can be altered by condition at settlement, the degree to which population biomass is regulated may depend on initial condition.


Advanced treatment of biologically pretreated coal gasification wastewater by a novel integration of catalytic ultrasound oxidation and membrane bioreactor.
Laboratorial scale experiments were conducted to investigate a novel system integrating catalytic ultrasound oxidation (CUO) with membrane bioreactor (CUO-MBR) on advanced treatment of biologically pretreated coal gasification wastewater. Results indicated that CUO with catalyst of FeOx/SBAC (sewage sludge based activated carbon (SBAC) which loaded Fe oxides) represented high efficiencies in eliminating TOC as well as improving the biodegradability. The integrated CUO-MBR system with low energy intensity and high frequency was more effective in eliminating COD, BOD5, TOC and reducing transmembrane pressure than either conventional MBR or ultrasound oxidation integrated MBR. The enhanced hydroxyl radical oxidation, facilitation of substrate diffusion and improvement of cell enzyme secretion were the mechanisms for CUO-MBR performance. Therefore, the integrated CUO-MBR was the promising technology for advanced treatment in engineering applications.


Comparative preimplantation genetic diagnosis policy in Europe and the USA and its implications for reproductive tourism.
Unlike many European nations, the USA has no regulations concerning the use of preimplantation genetic diagnosis (PGD), a technique employed during some fertility treatments to select embryos based on their genes. As such, PGD can and is used for a variety of controversial purposes, including sex selection, selection for children with disabilities such as deafness, and selection for 'saviour siblings' who can serve as tissue donors for sick relatives. The lack of regulation, which is due to particular features of the US political and economic landscape, has ethical and practical implications for patients seeking PGD around the world. This paper contrasts the absence of PGD oversight in the USA with existing PGD policies in Switzerland, Italy, France and the UK. The primary reasons why PGD is not regulated in the USA are addressed, with consideration of factors such as funding for assisted reproductive technology treatmemt and the proximity of PGD to the contentious abortion debate. The obstacles that would need to be overcome in the USA for PGD to be regulated in the future are outlined. Then, the significance of the current divergence in PGD policy for patients around the world are discussed. Regulatory differences create opportunities for reproductive tourism, which result in legal, health and moral challenges. The paper concludes with comments on the need for policymakers around the world to balance respect for the characters and constitutions of their individual countries with appreciation of the needs of infertile patients across the globe.


A tubulin binding molecule drives differentiation of acute myeloid leukemia cells.
Despite much progress in developing better drugs, many patients with acute myeloid leukemia (AML) still die within a year of diagnosis. This is partly because it is difficult to identify therapeutic targets that are effective across multiple AML subtypes. One common factor across AML subtypes is the presence of a block in differentiation. Overcoming this block should allow for the identification of therapies that are not dependent on a specific mutation for their efficacy. Here, we used a phenotypic screen to identify compounds that stimulate differentiation in genetically diverse AML cell lines. Lead compounds were shown to decrease tumor burden and to increase survival in vivo. Using multiple complementary target deconvolution approaches, these compounds were revealed to be anti-mitotic tubulin disruptors that cause differentiation by inducing a G2-M mitotic arrest. Together, these results reveal a function for tubulin disruptors in causing differentiation of AML cells.


Immune biomarkers and response to checkpoint inhibition of BRAFV600 and BRAF non-V600 altered lung cancers.
While 2-4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours. Clinical and genomic data were collected from 5945 patients with lung cancers whose tumours underwent next-generation sequencing between 2015 and 2018. Patients were followed through 2020. In total, 127 patients with metastatic BRAF-altered lung cancers were identified: 29 tumours had Class I mutations, 59 had Class II/III alterations, and 39 had variants of unknown significance (VUS). Tumour mutation burden was higher in Class II/III than Class I-altered tumours (8.8 mutations/Mb versus 4.9, P < 0.001), but this difference was diminished when stratified by smoking status. The overall response rate to immune checkpoint inhibitors (ICI) was 9% in Class I-altered tumours and 26% in Class II/III (P = 0.25), with median time on treatment of 1.9 months in both groups. Among patients with Class I-III-altered tumours, 36-month HR for death in those who ever versus never received ICI was 1.82 (1.17-6.11). Nine patients were on ICI for >2 years (two with Class I mutations, two with Class II/III alterations, and five with VUS). A subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen.


Growth factor responsiveness: role of MyoD and myogenin.
A differentiation-defective variant (DD-1) of the MM14 myoblasts acquired the ability to synthesize DNA in response to treatment with epidermal growth factor (EGF) (R. W. Lim and S. D. Hauschka, 1984, Dev. Biol. 105, 48) and no longer expressed myogenic determinant genes (i.e., MyoD and myogenin) (P.R. Mueller, and B. Wold, 1989, Science 246, 780). To determine the effect of expression of MyoD on EGF responsiveness, DD-1 cells were cotransfected with a MyoD expression vector and with pRSVneo. A clone, MyoDD-1 cells, which was G418 resistant, formed multinuclear syncitia, and also expressed MyoD and myogenin, was further characterized. EGF responsiveness, as assessed by DNA synthesis, was decreased 5- to 10-fold in the MyoDD-1 cells from that in G418-resistant control DD-1 cells, despite similar EGF receptor numbers and binding affinities of the receptors. Responsiveness of MyoDD-1 cells to fibroblast growth factor (FGF) was also diminished although to a lesser extent. To determine the effects of decreased myogenic determinant gene expression on mitogen responsiveness, MM14 myoblasts were grown in medium supplemented with 5 microM 5-bromo-2'-deoxyuridine (BUdR-MM14). BUdR-MM14 cells had decreased expression of MyoD and myogenin, did not fuse, and had an altered morphology, from round to flat. The BUdR effect on fusion and cell shape was reversed by growth in control medium. BUdR-MM14 cells were responsive to EGF and had enhanced responsiveness to FGF. The combined studies support the view that expression of MyoD and/or myogenin contributes to negative regulation of mitogen responsiveness.


Pain and Satisfaction Perceptions of Ultrasound-Guided Versus Conventional Peripheral Intravenous Catheterization: A Randomized Controlled Trial.
While many emergency department (ED) patients need peripheral vascular catheterization, diagnosis and treatment are often delayed by difficult intravenous access (DIVA). This study of ED patients with DIVA was designed to evaluate ultrasound (US)-guided peripheral intravenous (IV) catheterization, compare it with conventional catheterization, and analyse patient pain and satisfaction regarding catheterization. Randomized controlled clinical trial. Adult patients treated in the ED who scored >3 on the Adult-Difficult Venous Catheterization scale were randomly assigned to either US-guided or conventional peripheral IV catheterization. Data were collected from April to December 2016. Study variables were catheter insertion success, number of catheterization attempts, time required to perform the procedure, catheter length and calibre, puncture site, complications, and catheter functioning. Pain and patient satisfaction were also analysed for each group and the full sample. 120 and 138 patients were recruited for the US-guided and conventional peripheral IV catheterization groups, respectively. For the US-guided compared to the conventional procedure, insertion success was greater (91.75% versus 89.9%; p=0.04), the mean (SD) number of attempts was lower (1.29 (0.59) versus 1.81 (1.28); p<0.001), mean (SD) satisfaction was greater (7.59 (2.04) versus 6.69 (2.28); p=0.03), and the mean (SD) required time in minutes was greater (7.89 (7.13) versus 5.1 (3.69); p=0.045). Mean (SD) pain was moderate in both groups (4.6 (2.75) versus 4.33 (2.91) (p=0.32). Logistic regression for the full sample indicated that more attempts and greater pain were both associated with reduced satisfaction, while use of higher-calibre catheters was associated with greater satisfaction. US-guided compared to conventional peripheral IV catheterization in patients with DIVA was more successful, required fewer attempts, enabled use of longer and higher-calibre catheters, and led to greater patient satisfaction. Patients who underwent US-guided intravenous catheterization reported moderate pain, similar to that reported for the conventional procedure. US-guided peripheral intravenous catheterization improves ED patient care, as it requires fewer catheterization attempts. It is especially recommended for patients with DIVA.


A comparative study of hearing-impaired and normal-hearing young adults--verbal and nonverbal abilities.
This report describes the results of a study comparing three groups of hearing-impaired young adults with a group of normal-hearing young adults on various measures of perceptual and memory abilities. Twelve paper-and-pencil tests representing intellectual capacity, closure, association, nonverbal short-term memory, and verbal short-term memory were used as dependent variables. Results show that there was no difference between the four groups of subjects except for tests requiring some verbal facility.


One-year outcome of patients admitted after cardiac arrest compared to other causes of ICU admission. An ancillary analysis of the observational prospective and multicentric FROG-ICU study.
While cardiac arrest (CA) patients discharged alive from intensive care unit (ICU) are considered to have good one-year survival but potential neurological impairment, comparisons with other ICU sub-populations non-admitted for CA purpose are still lacking. This study aimed to compare long-term outcome and health-related quality of life (HRQOL) between CA patients and patients admitted to ICU for all other causes. In 1635 patients discharged alive from 21 European ICUs in an ancillary analysis of a prospective multicentric cohort, we compared CA causes of ICU admission to all other causes of ICU admissions (named non-CAs). The primary endpoint was one-year survival rate after ICU discharge. Secondary endpoints included HRQOL at 3, 6 and 12 months after ICU discharge using the outcome survey short form-36 (SF36). Propensity score matching was used to consider the probability of having CA. Of the 1635 patients, 1561 were included in this study comprised of 1447 non-CAs and 114 CAs. At one-year in the non-matched population, survival rate was greater in the CA group 89% versus the non-CA group 78% (log rank p = 0.0056). In the matched population, this difference persisted between CAs and non-CAs (log rank p = 0.049). The physical component summary of the SF36 scale was higher in the CA group than in the non-CA group at all time points in both non-matched and matched populations. CA patients discharged alive from ICU have a better one-year survival and a better HRQOL specifically on physical functions than patients admitted to ICU for other causes. ClinicalTrials.gov NCT01367093; registered on June 6, 2011.


Cholesterol embolism evaluated by polarized light microscopy after primary renal artery stent placement with filter protection.
Cholesterol microembolization may explain some treatment failures after renal artery stent placement. The identification of cholesterol crystals may provide significant help in diagnosing the real frequency and severity of this complication. The aim of the present study was to examine the efficacy of polarized light imaging in the detection of cholesterol emboli trapped in a protection device. During a period of 18 months, 15 significant atherosclerotic stenoses of the ostium of the main renal artery were treated with primary stent placement with embolic protection. The filter device used was made of polyurethane, with a pore size of 115 ?m. The device was mounted over a 0.014-inch guide wire. For pathologic analysis, the recaptured filter basket was compressed between two slides and examined in a microscope under polarized light. All the stenoses were successfully treated without clinical complications. All the filters were deployed and recaptured without difficulty. Cholesterol crystals were detected in 12 filters and no cholesterol was found in three. In one case, trouble with filter manipulation precluded pathologic analysis. No worsening of renal function was detected in any patient during follow-up. Microscopic analysis with polarized light easily detects the cholesterol crystals trapped in the filter device. This provides evidence that renal cholesterol microembolism is highly prevalent during renal artery stent placement.


Discovery of non-peptide inhibitors of Plasmepsin II by structure-based virtual screening.
Plasmepsin II (PM II) is an attractive target for anti-malaria drug discovery, which involves in host hemoglobin degradation in the acidic food vacuole. In this study, we demonstrated the successful use of structure-based virtual screening to identify inhibitors of PM II from two chemical database. Five novel non-peptide inhibitors were identified and revealed moderate inhibitory potencies with IC50 ranged from 4.62 ± 0.39 to 9.47 ± 0.71 μM. The detailed analysis of binding modes using docking simulations for five inhibitors showed that the inhibitors could be stabilized by forming multiple hydrogen bonds with catalytic residues (Asp 34 and Asp 214) and also with other key residues.


Unmasking the constitution and bonding of the proposed lithium nickelate "Li3NiPh3(solv)3": revealing the hidden C6H4 ligand.
More than four decades ago, a complex identified as the planar homoleptic lithium nickelate "Li3NiPh3(solv)3" was reported by Taube and co-workers. This and subsequent reports involving this complex have lain dormant since; however, the absence of an X-ray diffraction structure leaves questions as to the nature of the Ni-PhLi bonding and the coordination geometry at Ni. By systematically evaluating the reactivity of Ni(COD)2 with PhLi under different conditions, we have found that this classical molecule is instead a unique octanuclear complex, [{Li3(solv)2Ph3Ni}2(μ-η2:η2-C6H4)] (5). This is supported by X-ray crystallography and solution-state NMR studies. A theoretical bonding analysis from NBO, QTAIM, and ELI perspectives reveals extreme back-bonding to the bridging C6H4 ligand resulting in dimetallabicyclobutane character, the lack of a Ni-Ni bond, and pronounced σ-bonding between the phenyl carbanions and nickel, including a weak σC-Li → sNi interaction with the C-Li bond acting as a σ-donor. Employing PhNa led to the isolation of [Na2(solv)3Ph2NiCOD]2 (7) and [Na2(solv)3Ph2(NaC8H11)Ni(COD)]2 (8), which lack the benzyne-derived ligand. These findings provide new insights into the synthesis, structure, bonding and reactivity of heterobimetallic nickelates, whose prevalence in organonickel chemistry and catalysis is likely greater than previously believed.


Deep brain stimulation for the treatment of hyperkinetic movement disorders.
Deep brain stimulation effectiveness is well recognized for different movement disorders including Parkinson's disease, dystonia and essential tremor, however several other diseases in this field may benefit from the technique although experience is sparse and evidences of benefit and risks are not established. In this review, we explored available evidence for effectiveness and safety of DBS in selected hyperkinetic movement disorders, including tardive dyskinesia, Huntington's disease, neuroacanthocytosis, myoclonus-dystonia, Tourette syndrome, orthostatic and Holmes' tremor. Expert commentary: The data referenced and discussed showed potential effectiveness for DBS in these disabling and refractory diseases. On the other hand, these disorders are quite complex and multifaceted, often composed of different movement disorders, as well as other motor and non-motor symptoms. Therefore, the possible contribution of DBS in improving patients' quality of life should be weighted in a strictly individual basis, keeping in mind the progressive nature of most of these disorders, as well as risk/benefit ratio.


Teratoma of the pituitary gland in a young male rat.
A pituitary teratoma was found in a 5-week-old (37-day-old) male Donryu rat. The tumour (10 x 11 x 9 mm) was round in shape and white in colour. The cut surface was solid without haemorrhagic or cystic change. Histologically, it was composed of various kinds of tissue components including mature and immature elements derived from the three embryonic germ layers, i.e., nervous tissue, cartilage, bone, squamous epithelial element, glandular element lined by one or more layers of ciliated columnar or cuboidal epithelial cells, striated muscle tissue, adipose tissue and connective tissue. Neuroepithelial rosettes and immature or embryonal epithelium as well as immature cartilage were intermingled with mature somatic tissues.


Imaging of topographic viral CNS infections.
Infections caused by enteroviruses, rabies, adenoviruses, and Nipah and Hanta viruses are discussed. Several studies defined the pattern of MR imaging findings in these disease processes that reflect parenchymal infiltration with inflammatory cells, typically visualized as areas of low attenuation on CT, as well as of low T1 and high T2 signal intensity on MR imaging. Diffusion-weighted MR imaging has been shown to be superior to conventional magnetic resonance imaging for the detection of early signal abnormalities in encephalitis. Focal unilateral hyperperfusion as visualized by SPECT appears to be an indicator of severe inflammation of the brain tissue and was found to be an independent predictor of poor prognosis, whereas clinical outcome variables, CSF, or EEG findings are not.


Cimetidine impairs nitrazepam clearance.
The effect of cimetidine on hepatic clearance of the benzodiazepine derivative nitrazepam was evaluated in healthy subjects. Six received a single 5- or 10-mg oral nitrazepam dose in the drug-free state and again with therapeutic cimetidine doses. Nitrazepam kinetics were determined from multiple serum concentrations measured during the 72 hr after each dose. Cimetidine had no effect on nitrazepam absorption kinetics, since peak serum nitrazepam concentration and time of peak concentration were not altered. Cimetidine did not alter nitrazepam volume of distribution, but cimetidine consistently reduced nitrazepam clearance, from a mean of 1.41 ml/min/kg in the control state to 1.17 ml/min/kg during cimetidine treatment. This resulted in prolongation of nitrazepam elimination t1/2 from 22.2 to 27.8 hr. Thus the ability of cimetidine to impair drug oxidation in man extends to the capacity for clearance of nitrazepam, a compound biotransformed mainly by nitroreduction.


[New developments in measuring the cerebrospinal fluid pressure level and its controlled extraction].
To measure the spinal fluid pressure and its controlled extraction, including protracted drainage of the fluid-containing communications, a portable arrangement, in which a direct relationship between the extracted spinal fluid and its changing pressure is utilized, is recommended.


Extended-wear contact lenses in 525 aphakic eyes.
Extended-wear contact lenses were fitted to 225 patients with monocular aphakia and 150 with bilateral aphakia. They were observed from three months to three years. Eighty-eight of the 195 eyes fitted with a Softcon lens became red and painful within 14 days during extended wear. The Hydrocurve lens was better tolerated in 55, but many patients had acute congestion, pain, and tearing. Deposits accumulated rapidly on the Sauflon-PW lens. Some 90% of all patients can be fitted successfully with the cellulose acetate butyrate lens or the silicone lens. The silicone coating of the silicone lens is lost or damaged in about 20% of the patients because of excess mucous accumulation.


Characterization of initiation factor 3 from wheat germ. 2. Effects of polyclonal and monoclonal antibodies on activity.
Rabbit polyclonal antibodies to wheat germ initiation factor 3 (eIF-3) were obtained and were shown to react strongly with 4 of the 10 subunits of eIF-3 (pp116, pp87, pp56, and pp36). Two mouse monoclonal antibodies were obtained, one of which reacts specifically with pp87 and one of which reacts specifically with pp36. Highly purified anti-pp87 has no effect on the activity of eIF-3. Highly purified polyclonal antibodies and anti-pp36 inhibit the ability of eIF-3 to support polypeptide synthesis in vitro and the ability of eIF-3 to support mRNA binding to 40S ribosomal subunits. These results provide additional evidence that pp116, pp87, and pp36 are in exposed positions in the eIF-3 particle and that pp36 is essential for activity.


Pathobiological and molecular connections involved in the high fructose and high fat diet induced diabetes associated nonalcoholic fatty liver disease.
Poor dietary habits such as an over consumption of high fructose and high fat diet are considered as the major culprit for the induction of diabetes associated liver injury. Diabetes mellitus is a metabolic disorder that affects various vital organs of the body especially the kidney, brain, heart, and liver. The high fructose and high fat (HFHF) diet worsen the metabolic conditions by producing various pathogenic burdens such as oxidative stress, inflammation, etc. on liver. The hyperlipidemic and hyperglycemic conditions induced by HFHF diet leads to the generation of various proinflammatory mediators like TNFα, interleukin and cytokines. The systematic bibliographical literature survey was done with the help of PubMed, Google scholar and MedLine to identify all pathological and molecular concerened with HFHF induced diabetic liver injury. The consumption of HFHF diet leads to an increase in mitochondrial oxidative stress thereby decreases the liver protective antioxidants required for cell viability. HFHF diet disturbs lipid and lipoprotein clearance by elevating the level of apolipoprotein CIII and impairing the hydrolysis of triglyceride. As a result, there is an increase in free fatty acid concentration, triglycerides and diacylglycerol in the liver which further triggers the situation of insulin resistance. The focus of present review is based upon the various pathological, genetic and molecular mechanism involved in the development of high-fat high fructose diet induced diabetic liver injury. However, the current review also documented few shreds of evidence related to various microRNAs (miR-31, miR-33a, miR-34a, miR-144, miR-146b, miR-150) concerned to HFHF diet which play an important role in the pathogenesis of diabetes associated liver injury Dietary life style modification may prove beneficial in the management of various metabolic disorders.


In situ nuclear organization of regulatory machinery.
Regulatory machinery for gene expression, replication, and repair are architecturally organized in nuclear microenvironments. This compartmentalization provides threshold concentrations of macromolecules for the organization and assembly of regulatory complexes for combinatorial control. A mechanistic under standing of biological control requires the combined application of molecular, cellular, biochemical, and in vivo genetic approaches. This chapter provides methodologies to characterize nuclear organization of regulatory machinery by in situ immunofluorescence microscopy.


An unusual case of post-nasal "clicking" after pituitary surgery.
We report a case of a 64-year-old female who represented two months after pituitary surgery with the novel complication of intermittent disabling post-nasal pulsatile "clicking". Imaging and endoscopic examination showed a residual sella cleft with the tumour capsule and diaphragma cupping against the anterior sella bony defect with each pulsation, causing the clicking. The clicking resolved following second redo surgical endoscopic repair to jail a fat graft within the residual cleft with a central barricade of conchal cartilage graft and onlay standard repair.


Neighborhood disadvantage and pediatric inpatient opioid prescription patterns.
To explore the role of children's residential environment on opioid prescribing patterns in a predominantly Latinx sample. We connected geocoded data from electronic medical records in a diverse sample of pediatric patients to neighborhood environments constructed using latent profile modeling techniques. We then estimated a series of multilevel models to determine whether opioid prescribing patterns vary by residential context. A stepwise pattern exists between neighborhood disadvantage and pediatric opioid prescription patterns, such that higher levels of disadvantage associate with a greater likelihood of opioid prescription, independent of the patient's individual profile. In a largely Latinx sample of children, the neighborhood in which a child lives influences whether or not they will receive opioids. Considering the differences in patient residential environment may reduce variation in opioid dispensing rates among pediatric patients.


Enhanced methane production from the anaerobic co-digestion of food waste plus fruit and vegetable waste.
Food waste (FW) and fruit, vegetable waste (FVW) are important components of municipal solid waste, yet the performance and related mechanisms of anaerobic co-digestion of FW and FVW for methane production have been rarely investigated. In order to get a deeper understanding of the mechanisms involved, the mesophilic FW and FVW anaerobic co-digestion in different proportions was investigated. The experimental results showed that when the ratio of FW and FVW was 1/1 (in terms of volatile suspended solid), the maximum biomethane yield of 269.9 mL/g TCOD from the codigested substrate is significantly higher than that in FW or FVW anaerobic digestion alone. FW and FVW co-digestion promoted the dissolution and biotransformation of organic matter. When the recommended mixing ratio was applied, the maximum concentration of dissolved chemical oxygen demand (COD) was high as 11971 mg/L. FW and FVW co-digestion reduced the accumulation of volatile fatty acids (VFA) in the digestive system, thus reducing its negative impact on the methanogenesis process. FW and FVW co-digestion process synergistically enhanced microbial activity. The analysis of microbial population structure showed that when FW and FVW were co-digested at the recommended ratio, the relative abundance of Proteiniphilum increased to 26.5%, and the relative abundances of Methanosaeta and Candidatus Methanofastidiosum were also significantly increased. The results of this work provide a certain amount of theoretical basis and technical support for the co-digestion of FW and FVW.


Neglected cervical spondyloptosis of the 5TH - 6TH cervical spine following cervical manipulation: A case report.
A 16-year-old boy was diagnosed with spondyloptosis of the cervical spine at the C5-6 level with a neurologic deficit following cervical manipulation. He could not move his upper and lower extremities, but the sensory and autonomic function was spared. The pre-operative American Spinal Cord Injury Association (ASIA) Score was B with SF-36 being 25%, and Karnofsky's score was 40%. The patient was disabled and required special care and assistance. We performed anterior decompression, cervical corpectomy at the level of C6 and lower part of C5, deformity correction, cage insertion, bone grafting, and stabilization with an anterior cervical plate. The patient's objective functional score had increased after six months follow up and assessed objectively with the ASIA Impairment Scale (AIS) E or Excellent, SF-36 score 94%, and Karnofsky score was 90%. The patient could carry on regular activity with minor signs or symptoms of the disease. This case report highlights severe complications following cervical manipulation, a summary of the clinical presentation, surgical treatment choices, and a review of the relevant literature. In addition, the sequential improvement of the patient's functional outcome after surgical correction will be discussed.


Long-term endothelial cell loss after phacoemulsification: peribulbar anesthesia versus intracameral lidocaine 1%: prospective randomized clinical trial.
To evaluate endothelial cell loss after phacoemulsification with posterior chamber intraocular lens implantation using peribulbar anesthesia or topical anesthesia combined with intracameral unpreserved lidocaine 1%. Department of Ophthalmology, Charité, Humboldt-University of Berlin, Berlin, Germany. Before and 20 months +/- 5.1 (SD) after surgery, specular microscopy was used to evaluate the number and morphology of endothelial cells in 78 eyes having peribulbar anesthesia or topical anesthesia combined with an intracameral injection of 0.15 cc unpreserved lidocaine 1%. The mean endothelial cell loss was 11.11% in the peribulbar group and 12.55% in the topical/lidocaine group. There was no statistically significant difference in the amount of endothelial cell loss or cell morphology between the 2 groups. The long-term postoperative endothelial cell course showed that topical anesthesia combined with an intracameral injection of 0.15 cc unpreserved lidocaine 1% is a safe alternative to peribulbar anesthesia.


Hexokinase II and reperfusion injury: TAT-HK2 peptide impairs vascular function in Langendorff-perfused rat hearts.
Mitochondrial-bound hexokinase II (HK2) was recently proposed to play a crucial role in the normal functioning of the beating heart and to be necessary to maintain mitochondrial membrane potential. However, our own studies confirmed that mitochondria from ischemic rat hearts were HK2-depleted, yet showed no indication of depolarization and responded normally to ADP. To establish whether the human TAT-HK2 peptide used to dissociate mitochondrial-bound HKII in the Langendorff-perfused heart may exert its effects indirectly by impairing coronary function. Ischemic preconditioning was blocked in rat hearts perfused with 2.5 µmol/L TAT-HK2 before ischemia or at the onset of reperfusion. However, TAT-HK2 also decreased the phosphocreatine:ATP ratio that correlated with reduced rate pressure product and increased diastolic pressure. These effects were preceded by increased aortic pressure (Langendorff constant flow) or decreased coronary flow (Langendorff constant pressure), which was also observed, albeit less pronounced, at 200 nmol/L TAT-HK2 and was prevented by coperfusion with the NO-donor diethylamine NONOate. Mitochondria from TAT-HK2-perfused hearts showed no loss of bound HK2, unlike mitochondria from ischemic hearts where the expected loss was prevented by ischemic preconditioning. In the perfused rat heart, TAT-HK2 should be used with caution and careful attention to dosage because some of its effects may be mediated by vasoconstriction of the coronary vasculature rather than dissociation of HK2 from myocyte mitochondria.


Extensor retinaculum graft for chronic boxer's knuckle.
Boxer's knuckle is a tear of the metacarpophalangeal (MCP) joint capsule that occurs while punching. Because of the nature of boxing, boxer's knuckle tends to be a chronic condition and often is associated with sagittal band rupture. Chronic cases often feature excessive scarring in the damaged area where the sagittal band and the MCP joint capsule become indistinguishable. The purpose of this study was to ascertain whether extensor retinaculum grafting to the defect is useful in treating chronic boxer's knuckle when direct repair of a capsular tear is not possible. In 5 professional boxers with chronic boxer's knuckle in whom capsular repair could have impaired MCP joint flexion, scar tissue of the damaged capsule and the sagittal band-if ruptured-were removed and an oval extensor retinaculum graft was sutured in the capsule/sagittal band defect. The mean age of the patients was 22 years. In all patients, surgery was performed on the middle finger. The capsule was damaged on the ulnar side in 3 patients and on the radial side in 2 patients. All boxers reported alleviation of pain when punching. The range of motion for the MCP joint was not restricted after surgery in any patient. Tendon dislocation did not occur after surgery in any patient. All 5 patients were able to return to professional competition. Extensor retinaculum grafting is useful in treating chronic boxer's knuckle if the damaged capsule cannot be repaired directly. Therapeutic, Level IV.


Stroke literacy, behavior, and proficiency in a South Florida population.
Our goal was to assess stroke literacy, behavior, and proficiency in our South Florida service population. Data were obtained from the 2006 to 2010 Cleveland Clinic Florida annual "stroke prevention screening" questionnaires. "Stroke risk factor awareness" was attributed to participants correctly identifying at least 5 out of the 7 stroke risk factors presented. "Stroke symptom awareness" was assigned if one correctly selected all 5 listed stroke symptoms and not any of the 3 inappropriate responses. Participants had "stroke literacy" if they: (1) demonstrated stroke risk factor awareness; (2) demonstrated stroke symptom awareness; and (3) they correctly identified the brain as where a stroke occurs. To assess appropriate "stroke behavior," respondents had to choose "call 911 immediately" if one were to experience stroke symptoms. "Stroke proficiency" was attributed to individuals showing both stroke literacy and appropriate stroke behavior. There were a total of 298 participants. Sixty-seven percent of participants correctly identified the brain as the organ where stroke occurs. Almost three-fourths (74.2%) demonstrated stroke risk factor awareness, 28.2% had stroke symptom awareness, 17.8% had stroke literacy, 87.9% declared appropriate stroke behavior, and 16.1% had stroke proficiency. Stroke behavior and stroke proficiency are useful novel concepts in stroke epidemiology. Although our South Florida community is relatively well-educated and affluent, there are tangible gaps in knowledge, attitudes, and behavior as it pertains to stroke, similar to that seen in less advantaged populations. We recommend intensified usage of the media with information provided by qualified health professionals in a variety of formats and languages appropriate to the ethnic and cultural diversities that define this population.


Effects of elevated CO2 concentration on growth and water usage of tomato seedlings under different ammonium/nitrate ratios.
Increasing atmospheric CO2 concentration is generally expected to enhance photosynthesis and growth of agricultural C3 vegetable crops, and therefore results in an increase in crop yield. However, little is known about the combined effect of elevated CO2 and N species on plant growth and development. Two growth-chamber experiments were conducted to determine the effects of NH4+/NO3- ratio and elevated CO2 concentration on the physiological development and water use of tomato seedlings. Tomato was grown for 45 d in containers with nutrient solutions varying in NH4+/NO3- ratios and CO2 concentrations in growth chambers. Results showed that plant height, stem thickness, total dry weight, dry weight of the leaves, stems and roots, G value (total plant dry weight/seedling days), chlorophyll content, photosynthetic rate, leaf-level and whole plant-level water use efficiency and cumulative water consumption of tomato seedlings were increased with increasing proportion of NO3- in nutrient solutions in the elevated CO2 treatment. Plant biomass, plant height, stem thickness and photosynthetic rate were 67%, 22%, 24% and 55% higher at elevated CO2 concentration than at ambient CO2 concentration, depending on the values of NH4+/NO3- ratio. These results indicated that elevating CO2 concentration did not mitigate the adverse effects of 100% NH4(+)-N (in nutrient solution) on the tomato seedlings. At both CO2 levels, NH4+/NO3- ratios of nutrient solutions strongly influenced almost every measure of plant performance, and nitrate-fed plants attained a greater biomass production, as compared to ammonium-fed plants. These phenomena seem to be related to the coordinated regulation of photosynthetic rate and cumulative water consumption of tomato seedlings.


Reducing the impact of diabetes: is prevention feasible today, or should we aim for better treatment?
Type 2 diabetes prevention studies have shown that the onset of the disease can be delayed or prevented, chiefly by weight loss. But the current efforts to establish community-based lifestyle modification programs will not be very effective in preventing diabetes, largely because most overweight or obese people cannot maintain weight loss over time. A complex environment is driving greater food consumption along with less energy expenditure, making maintenance of weight loss extremely difficult. To improve the likelihood of achieving populationwide success in reducing the obesity pandemic, we need a better understanding of the biological processes that underlie the balance between intake and expenditure of energy. In the meantime, once diabetes develops, we can greatly reduce the likelihood of serious complications through early detection and proper medical management.


Intradural nerve root hematoma in the lumbar spine. A case report.
Intradural nerve root hematoma of the lumbar spine is extremely rare and can cause compression of the cauda equina. This case, which presented with low back pain and radiation to both lower extremities, diagnosed as an intradural hematoma of nerve root by magnetic resonance imaging (MRI) and was totally removed successfully. Intradural nerve root hematoma can present with or without a history of trauma or blood dyscrasia, where MRI is the best imaging modality, and can be well treated by surgery.


Pediatric Sinogenic Subdural Empyema: Case Report and Operative Technique.
Intracranial complications of sinusitis in the pediatric age are rare but potentially life threatening. They usually occur with nonspecific symptoms such as headache, fever, nausea and vomiting rather than a classic neurological presentation, but they may evolve in few hours, leading to significant morbidity with permanent brain damage and sometimes to death. For this reason, early diagnosis and prompt treatment are essential. Our case demonstrates a sinogenic subdural empyema in an immunocompetent young boy who reached our Emergency Department due to a continuous right-sided headache, unresponsive to pain relievers. The clinical history and the diagnostic process are described: at first, laboratory exams, neurologic and otolaryngological assessment were performed, together with a cranial CT scan showing an inflammatory involvement of the right frontal, ethmoidal and maxillary sinuses. Intravenous antibiotic therapy was initiated. After a few hours the patient showed a sudden worsening of his clinical conditions: he was drowsy with left lower extremity hyposthenia and ipsilateral deep tendon reflexes absence. Considering the patient's aggravated clinical presentation an emergent MRI with contrast enhancement was conducted, showing left midline shift, a widening of the liquor space on the right frontal and parietal convexity and noticeable meningeal enhancement after contrast injection. After a Neurosurgical and ENT evaluation the patient was taken to the operating room for a combined craniotomy and trans-nasal endoscopic drainage of the empyema. We present the surgical procedure with a pictorial step-by-step description. After the surgical procedure the patient's condition gradually improved. He regained full neurological function, was accompanied by a rehabilitation team on recovering full force on the left extremities. At discharge the patient had no apparent neurological deficits. Subdural empyema is a rare but severe complication of pediatric sinusitis. Early diagnosis with combined medical and surgical therapies play a key role to reduce morbidity and mortality.


Post-traumatic Stress Disorder.
Post-traumatic stress disorder (PTSD) is characterized by symptoms of re-experiencing, avoidance, negative alterations in cognition and mood, and marked alterations in arousal and reactivity following exposure to a traumatic event. PTSD can be assessed by structured interviews and screening measures in psychiatric and nonpsychiatric settings. Evidence-based psychotherapies are the first-line treatment of PTSD, with cognitive behavioral therapies, such as prolonged exposure, cognitive processing therapy, and eye movement desensitization and reprocessing having the largest body and highest quality of evidence. Serotonin reuptake inhibitors are the first-line pharmacologic treatments for PTSD and are often used in conjunction with other therapeutic interventions.


Human temporal learning with mixed signals.
The influence of cue informativeness on human temporal discrimination was evaluated using a peak-interval (PI) procedure. A target moved across the computer monitor, reaching the center at 2 or 4 s. Key presses shot the center of the screen. Participants earned points when shots hit the target and lost points for misses. The target was masked during occasional, extended PI trials, allowing for measurement of temporal discrimination. During PI trials, the screen background color could exert stimulus control by providing information about target speed. Cue informativeness was represented as the correlation (φ) between light or dark green backgrounds and the 2- or 4-s target and was manipulated across 4 conditions: a multiple schedule (φ = 1), mixed signals (φ = 0.8, 0.4), and a mixed schedule (φ = 0). In Experiment 1, participants were randomly assigned to one of the 4 conditions. In Experiment 2, each participant experienced all 4 conditions. Participants learned to respond at both intervals in all conditions. Cue informativeness did not affect peak time or spread. For the most part, temporal distributions of responses for the two background colors suggested a cover-both-bases strategy in the presence of mixed signals. Participants incorporated probabilistic information from cues to allocate responding in time.


Instability of the proximal tibiofibular joint associated with total knee arthroplasty.
To our knowledge, proximal tibiofibular joint instability has never been reported in a patient with a total knee arthroplasty (TKA). We present the case of a patient with anterolateral proximal tibiofibular joint instability associated with a complex primary TKA. In 2010, a male patient of 47 years was referred for TKA after posttraumatic osteoarthritis. The patient's history includes a fracture of the left lateral tibial plateau in 2008 and removal of osteosynthesis material in 2009. TKA with a lateral metal augment and intramedullary stem was performed in 2010. After TKA, instability of the left proximal tibiofibular joint (PTFJ) was diagnosed. The patient underwent PTFJ arthrodesis and, at 5 years' follow-up, had no residual pain, with full range of motion. In this case, arthrodesis was the only possible surgical option because reconstruction surgeries require the establishment of bone tunnels in the tibia and fibula for the passage of a graft. Low bone quality and the use of an intramedullary stem with a metal augment in the tibia made any reconstruction technique unfeasible because the proximal tibia was obliterated. Although several PTFJ reconstruction techniques are available, they are difficult to apply to patients with a complex TKA.


Visual feedback improves movement illusions induced by tendon vibration after chronic stroke.
Illusion of movement induced by tendon vibration is commonly used in rehabilitation and seems valuable for motor rehabilitation after stroke, by playing a role in cerebral plasticity. The aim was to study if congruent visual cues using Virtual Reality (VR) could enhance the illusion of movement induced by tendon vibration of the wrist among participants with stroke. We included 20 chronic stroke participants. They experienced tendon vibration of their wrist (100 Hz, 30 times) inducing illusion of movement. Three VR visual conditions were added to the vibration: a congruent moving virtual hand (Moving condition); a static virtual hand (Static condition); or no virtual hand at all (Hidden condition). The participants evaluated for each visual condition the intensity of the illusory movement using a Likert scale, the sensation of wrist's movement using a degree scale and they answered a questionnaire about their preferred condition. The Moving condition was significantly superior to the Hidden condition and to the Static condition in terms of illusion of movement (p < 0.001) and the wrist's extension (p < 0.001). There was no significant difference between the Hidden and the Static condition for these 2 criteria. The Moving condition was considered the best one to increase the illusion of movement (in 70% of the participants). Two participants did not feel any illusion of movement. This study showed the interest of using congruent cues in VR in order to enhance the consistency of the illusion of movement induced by tendon vibration among participants after stroke, regardless of their clinical severity. By stimulating the brain motor areas, this visuo-proprioceptive feedback could be an interesting tool in motor rehabilitation. Record number in Clinical Trials: NCT04130711, registered on October 17th 2019 ( https://clinicaltrials.gov/ct2/show/NCT04130711?id=NCT04130711&draw=2&rank=1 ).


Regulation of gene-activation pathways by PIAS proteins in the immune system.
The protein inhibitor of activated STAT (PIAS) family of proteins has been proposed to regulate the activity of many transcription factors, including signal transducer and activator of transcription proteins (STATs), nuclear factor-kappaB, SMA- and MAD-related proteins (SMADs), and the tumour-suppressor protein p53. PIAS proteins regulate transcription through several mechanisms, including blocking the DNA-binding activity of transcription factors, recruiting transcriptional corepressors or co-activators, and promoting protein sumoylation. Recent genetic studies support an in vivo function for PIAS proteins in the regulation of innate immune responses. In this article, we review the current understanding of the molecular basis, specificity and physiological roles of PIAS proteins in the regulation of gene-activation pathways in the immune system.


The effect of dentin bonding agents on the microleakage of porcelain veneers.
This in vitro study was conducted to investigate the effect of dentin bonding agents on the microleakage of porcelain veneers cemented on dentin margins. Forty human premolars were prepared on both the buccal and palatal surfaces. Each half was randomly assigned to eight groups. The veneer preparation of one group was cut entirely within enamel, to serve as controls. The remaining groups had cervical margins extending 1 mm beyond the cemento-enamel junction. Six dentin bonding agents were tested. The specimens were subjected to thermocycling and evaluated for marginal leakage using a silver nitrate stain technique. After sectioning, the extent of microleakage was measured at four interfaces: (1) incisal porcelain-composite; (2) incisal tooth-composite; (3) cervical porcelain-composite; and (4) cervical tooth-composite. Statistical analysis showed that the cervical tooth-composite interface had a significantly higher leakage value (p < 0.05) than the other three interfaces when the cervical margins were in dentin. The dentin bonding agents tested did not significantly reduce the marginal leakage of the porcelain veneers cemented on dentin margins.


Spectropolarimetric determination of the guanine-cytosine content of DNA.
A circular dichroism technique for the determination of DNA base composition in terms of the guanine-cytosine content has been developed. A linear relationship between the ratio of ellipticities at 260 and 280 nm (theta 260/theta 280) and base composition of DNA is obtained in citrate-phosphate buffer, pH 3.0 at 20 degrees C. The DNA base composition obtained with this method is not only highly reproducible but is also the fastest method reported.


Facile fabrication of surface vulcanized Co-Fe spinel oxide nanoparticles toward efficient 4-nitrophenol destruction.
Developing efficient modulation strategies to boost the degradation efficiencies of non-noble metal catalysts for toxic phenolic compounds involving peroxymonosulfate (PMS)-based oxidation processes is essential but remains an arduous challenge. This study reports the one-pot construction of in-situ surface vulcanized CoFe2O4 @carbon (Sx-CF@C) to boost the PMS activation for 4-nitrophenol (4-NP) destruction. The direct pyrolysis of an aerogel precursor consisted of cobalt nitrate, ferric nitrate, melamine, and thiourea enables the as-formed Sx-CF@C with hierarchical structure, rich oxygen vacancies, and electron/mass transfer, thereby considerably promoting PMS activation performance of Sx-CF@C toward 4-NP degradation. Specifically, the optimal S0.2-CF@C can achieve a removal efficiency of 99% for 4-NP destruction (20 mg/L) through PMS activation. Meanwhile, the catalyst also has generality to degrade a variety of antibiotic and dye organic pollutants. The radical quenching and electron paramagnetic resonance tests reveal the radical and non-radical activation mechanism in the S0.2-CF@C/PMS system. The degradation pathway for 4-NP destruction over the S0.2-CF@C/PMS system is proposed. This study provides an efficient approach to modulate the PMS activation performance of ferrite spinel materials toward the degradation of acute phenolic compounds.


Manganese superoxide dismutase in pathogenic fungi: an issue with pathophysiological and phylogenetic involvements.
Manganese-containing superoxide dismutases (MnSODs) are ubiquitous metalloenzymes involved in cell defence against endogenous and exogenous reactive oxygen species. In fungi, using this essential enzyme for phylogenetic analysis of Pneumocystis and Ganoderma genera, and of species selected among Ascomycota, Basidiomycota and Zygomycota, provided interesting results in taxonomy and evolution. The role of mitochondrial and cytosolic MnSODs was explored in some pathogenic Basidiomycota yeasts (Cryptococcus neoformans var. grubii, Cryptococcus neoformans var. gattii, Malassezia sympodialis), Ascomycota filamentous fungi (Aspergillus fumigatus), and Ascomycota yeasts (Candida albicans). MnSOD-based phylogenetic and pathogenic data are confronted in order to evaluate the roles of fungal MnSODs in pathophysiological mechanisms.


Coronary artery revascularization evaluation--a multicenter registry with seven years of follow-up.
Data from randomized clinical trials comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) may not accurately reflect current clinical practice, in which there is off-label usage of drug-eluting stents (DES). We undertook a prospective registry of coronary revascularization by CABG on- and off-pump and PCI with bare-metal stents (BMSs), DESs, or percutaneous transluminal coronary angioplasty (PTCA) to determine clinical outcomes. All patients undergoing isolated coronary revascularization in 8 community-based hospitals were enrolled. Final follow-up was obtained after 5 years by patient and/or physician contact and the Social Security Death Index. ST-elevation myocardial infarction and salvage patients were excluded. Five or more years of follow-up was obtained on 81.5% (3156) of the eligible patients-968 CABG patients (82.0%) and 2188 PCI patients (81.3%). Overall follow-up was 63.5±27.9 months (median, 79.7 months). The incidence of initial major adverse cardiac events (MACEs) at follow-up for CABG versus PCI was 29.2% versus 41.8% (P<0.001). Analysis of stent subgroups showed more events with BMSs (equivalent to PTCA alone) compared with DESs. All stents had more events than on- or off-pump CABG groups. Using propensity score-matched groups, the odds ratio for CABG to PCI was 0.69 (95% confidence interval [CI], 0.56 to 0.85; P<0.001) for mortality and 0.58 (95% CI, 0.45 to 0.75; P<0.001) for any MACE. In the current era of DES and off-pump surgery, in a community hospital setting, comparable patients undergoing coronary revascularization appear to benefit from improved long-term survival and reduced MACE with CABG versus PCI.


Metabolic syndrome in children and adolescents--risk for sleep-disordered breathing and obstructive sleep-apnoea syndrome?
The clinical relevance of the term "metabolic syndrome", the definition criteria, and predictive power are being disputed. Inclusion of sleep-disordered breathing and sleep apnoea into a definition of metabolic syndrome is also controversial once children and/or adolescents are affected. Nevertheless, along with the increasing prevalence of childhood obesity, the prevalence of the metabolic syndrome in obese children is reported at 30%, irrespective of the definition applied. Moreover, childhood obesity is associated with sleep-disordered breathing. Adipocytokines, cytokines secreted from adipose tissue, are thought to play a major role in the pathophysiology of metabolic syndrome. Leptin was initially suggested as a promising "anti-obesity" hormone. New concepts indicate that in humans leptin and its soluble receptor may be more important in states of energy deficiency rather than a predictor of the metabolic syndrome. Adiponectin, on the other hand, is not only related to obesity and insulin resistance, but appears to be the strongest predictor for metabolic syndrome, even in children. In newborns and infants, both adipocytokines occur in high concentrations, even though this cannot completely explain the increased risk for ensuing metabolic disease later in life. Finally, low-grade systemic inflammation may underlie the clustering of metabolic risk factors. Overall factors from the adipose tissue may constitute not only markers but also mediators of metabolic sequelae of obesity.


Yeast DNA polymerases and their role at the replication fork.
The DNA polymerases of the yeast Saccharomyces cerevisiae serve as a model system for the study of the replication fork during DNA replication. To date, six S. cerevisiae DNA polymerases have been at least partially characterized (compared with four in mammals so far), with further candidates being identified as open reading frames in the yeast genome sequencing project. Here, we review the current state of knowledge of the yeast polymerases, and discuss, where possible, their biological role during DNA replication.


Ex vivo perfusion of the human placenta to investigate pregnancy pathologies.
Pregnancy pathologies including gestational diabetes, intrauterine fetal growth restriction, and pre-eclampsia are common and significantly increase the risk of poor pregnancy outcomes. Research to better understand the pathophysiology and improve diagnosis and treatment is therefore crucial. The ex vivo placenta perfusion model offers a unique system to study pregnancy pathology without the risk of harm to mother or fetus. The presence of a maternal and fetal circulation and intact villus tree, facilitates investigations into maternal-fetal transfer, altered hemodynamics and vascular reactivity in the human placenta. It also provides a platform to test novel therapeutic agents. Here we review the key studies which have utilized the ex vivo placenta perfusion model to study different aspects of such pregnancy pathologies.


Toxic shock syndrome following diagnostic peritoneal lavage.
We report the case of a 15-year-old girl who developed high fever, syncope, abdominal pain, nausea and vomiting, myalgia, pharyngitis, and a desquamating rash eight days after a diagnostic peritoneal lavage. The diagnostic peritoneal lavage wound was erythematous and tender. Incision of the site yielded 10 mL of exudate that cultured Staphylococcus aureus. The patient was treated with a first-generation cephalosporin and recovered without sequelae. To our knowledge, this is the first reported case of toxic shock syndrome following diagnostic peritoneal lavage.