A Phase 1b, Open-Label Study to Evaluate the Safety and Tolerability of the Putative Remyelinating Agent, Liothyronine, in Individuals with MS.
Thyroid hormones are essential during developmental myelination and may play a direct role in remyelination and repair in the adult central nervous system by promoting the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes. Since tri-iodothyronine (T3) is believed to mediate the majority of important thyroid hormone actions, liothyronine (synthetic T3) has the potential to induce reparative mechanisms and limit neurodegeneration in multiple sclerosis (MS). We completed a phase 1b clinical trial to determine the safety and tolerability of ascending doses of liothyronine in individuals with relapsing and progressive MS. A total of 20 people with MS were enrolled in this single-center trial of oral liothyronine. Eighteen participants completed the 24-week study. Our study cohort included mostly women (11/20), majority relapsing MS (12/20), mean age of 46, and baseline median EDSS of 3.5. Liothyronine was tolerated well without treatment-related severe/serious adverse events or evidence of disease activation/clinical deterioration. The most common adverse events included gastrointestinal distress and abnormal thyroid function tests. No clinical thyrotoxicosis occurred. Importantly, we did not observe a negative impact on secondary clinical outcome measures. The CSF proteomic changes suggest a biological effect of T3 treatment within the CNS. We noted changes primarily in proteins associated with immune cell function and angiogenesis. Liothyronine appeared safe and was well tolerated in people with MS. A larger clinical trial will help assess whether liothyronine can promote oligodendrogenesis and enhance remyelination in vivo, limit axonal degeneration, or improve function.


A Novel RHCE*cE (c.827C>A) Allele, Containing the Single-Nucleotide Change, Encodes Altered c/E Antigens.
The RH blood group system is the most complex with over 50 antigens. So far over hundreds of RhCE variant alleles have been described resulting in weakened and/or partial expression of RhCE antigens [1], some variant Rh phenotypes are caused by exchange of genetic material between the RHD and RHCE genes, resulting in many hybrid genes, other phenotypes result from missense mutations. Variant alleles encode altered phenotypes with either weakened antigens, lacked antigens, or unexpected antigens. Besides, the mutation of RH blood group genes may lead to the changes of Rh antigen epitopes. RHCE gene mutations or polymorphisms may bring about altered RH antigens in quality and quantity [2]. Serologic weaknesses or discrepancies are regularly faced by blood transfusion laboratories, and molecular background explaining this feature can be precisely characterized only by the molecular biological methods.


Antibiotic use in the first year of life and risk of atopic disease in early childhood.
Reduced post-natal microbial stimulation resulting from improvements in public health measures, smaller family size, and through increased antibiotic use has been postulated to account for the increasing prevalence of atopic diseases seen predominantly in developed countries. To investigate use of antibiotics in the first year of life and subsequent development of atopic disease in early childhood. A prospective birth cohort of 198 children at high atopic risk was recruited prenatally and followed for 5 years. Illnesses and antibiotic use were ascertained through daily diaries, and diagnoses of asthma and hayfever were collected by questionnaire interviews. The children were examined regularly for eczema, and atopic status was defined by skin prick tests and serum total IgE. The effect of antibiotic use on subsequent atopic disease was examined using logistic regression with propensity score adjustment. 54.0% (107/198) of children received at least one course of antibiotics, mainly for acute respiratory illnesses (ARI). Thirty-three percent (329/984) of the ARI involved the lower respiratory tract (LRI). Twenty-three percent (222/984) of ARI were treated with antibiotics, with LRI significantly more likely to receive antibiotics. Antibiotic use was associated with asthma (unadjusted odds ratio 2.3; 95% confidence interval 1.2-4.5; P=0.01) but this association was reduced after propensity score adjustment. No associations were found between antibiotic use and eczema, current wheeze, current asthma, atopic asthma, allergic rhinoconjunctivitis or atopy. Although this was a small study, systematic and careful monitoring of ARI, antibiotic use, and asthma and atopic diseases did not indicate that receipt of antibiotics early in life led to subsequent asthma or atopy at 5 years.


Emergency nurses' experience with violence: does it affect nursing care of battered women?
To determine what effect nurses' experience of interpersonal violence had on proposed nursing care of battered women ED patients. One hundred ninety-five emergency nurses completed surveys on their personal experiences with violence involving patients or intimate partners and on their proposed nursing care of battered women given 2 vignettes. Seventy percent of participants experienced violence perpetrated by a patient; 40% of the nurses reported violence perpetrated by their intimate partners; and 19% had used force on their partners. Prior assault of a nurse by a patient or partner did not affect the proposed nursing care that would be provided by that nurse to battered women ed patients. Female nurses who committed violence against their intimate partners proposed less nursing care than did those who did not commit violence against their intimate partners for the vignette describing a woman who had received minor injuries. This study documents the vulnerability of nurses to assault by patients and intimate partners. This vulnerability does not affect their proposed nursing care of battered women. An exception is nurses who themselves commit violence against intimate partners. Findings point to the need to increase safety for nurses in the workplace and provide employee assistance to help nurses confront violence at home.


Fast dissolving oral films for drug delivery prepared from chitosan/pullulan electrospinning nanofibers.
In this study, Chitosan/pullulan composite nanofiber fast dissolving oral films (FDOFs) were prepared via electrospinning technology. The ratio of chitosan/pullulan (C/P) had an influence on solution property and nanofiber morphology, with the increase of chitosan, viscosity and conductivity of solutions increased, the morphology obtained by scanning electron microscopy indicated that the diameter of nanofibers decreased initially then increased. The Fourier transform infrared spectra indicated hydrogen bond interactions between chitosan and pullulan molecules. X-ray diffraction analysis proved that electrospinning process decreased the crystallinity of materials. Thermal analysis showed that melting point, degradation temperature and glass transition temperature increased with the addition of chitosan content in the FDOF. Water solubility test proved that the FDOF can dissolve in water completely within 60 s. Finally, in order to prove its practicability in future, a model drug of aspirin was encapsulated in the FDOF successfully.


Comfort zone-design free stalls: do they influence the stall use behavior of lame cows?
The behavior of 59 cows in 4 herds, each with Comfort Zone-design free stalls with dimensions suitable for 700-kg, mature Holstein dairy cows, was filmed for a 48-h period. Comparison was made between nonlame, slightly lame, and moderately lame cows on either rubber-crumb-filled mattress stall surfaces bedded with a small amount of sawdust (2 herds) or a Pack Mat design, which consisted of a rubber-crumb-filled mattress pad installed 5 cm below a raised rear curb, bedded with 5 to 8 cm of sand bedding (2 herds). All other stall design components were similar. Despite adequate resting space and freedom to perform normal rising and lying movements, lame cows on mattresses stood in the stall for >2 h longer than nonlame cows. Although a significant increase in stall standing behavior was observed in lame cows on Pack Mat stalls, the mean (95% confidence interval) standing time in the stall was only 0.7 (0 to 3.0) h/d for nonlame cows and 1.6 (0 to 4.2) h/d for moderately lame cows, which was less than the 2.1 (0 to 4.4), 4.3 (1.6 to 6.9), and 4.9 (2.5 to 7.3) h/d spent standing in the stall for nonlame, slightly lame, and moderately lame cows on mattresses, respectively. This observation supports the hypothesis that it is the nature of the stall surface that dictates changes in stall standing behavior observed in lame cows, rather than other components of stall design. The finding that only 5 to 8 cm of sand over a mattress pad provides most of the benefits of deep sand-bedded stalls, along with other advantages related to stall maintenance and manure handling, gives farmers another useful housing alternative with which to improve cow comfort and well-being.


Protracted anemia associated with chronic, relapsing systemic inflammation induced by arthropathic peptidoglycan-polysaccharide polymers in rats.
Mild hypoproliferative anemia with abnormal iron metabolism frequently accompanies chronic inflammation and infection in humans. To determine whether anemia is associated with chronic relapsing arthritis induced by bacterial cell wall polymers, serial determinations of the hematocrit were measured in rats injected intraperitoneally with sonicated peptidoglycan-polysaccharide fragments from group A streptococci. Acute anemia peaked 5 to 10 days after injection, and chronic, spontaneously relapsing anemia persisted for 309 days. 51Cr labeling demonstrated decreased erythrocyte survival, i.e., a half-life of 8.4 days in cell wall-injected rats versus 11.8 days in controls. Erythrocytes were mildly microcytic, and leukocyte counts were elevated during early spontaneous reactivation of arthritis, 15 days after injection of peptidoglycan-polysaccharide. Bone marrow myeloid/erythroid precursor ratios were elevated in arthritic rats (P less than 0.0001). Purified peptidoglycan produced an acute anemia lasting 10 days, while injection of group A streptococcal polysaccharide and mutanolysin-digested cell wall did not affect the hematocrit. The minimal effective dose of peptidoglycan-polysaccharide was 5 micrograms of rhamnose per g (body weight). Serum iron and transferrin levels were decreased in cell wall-injected rats (P less than 0.005) and were closely correlated with hematocrit values and joint inflammatory scores. Stainable iron was increased in the liver, spleen, and mesenteric lymph nodes and unchanged in the bone marrow of cell wall-injected rats. Anemia accompanying chronic, relapsing systemic inflammation induced by peptidoglycan-polysaccharide polymers appears to be an excellent animal model of the anemia of chronic disease.


Damage control surgery: an alternative approach for the management of critically injured patients.
Over the past 20 years, it has gradually become apparent that the results of prolonged and extensive surgical procedures performed on critically injured patients are often poor, even in experienced hands. The triad of hypothermia, coagulopathy, and metabolic acidosis effectively marks the limit of the patient's ability to cope with the physiological consequences of injury, and crossing this limit will frustrate even the most technically successful repair. These observations have led to the development of a new surgical strategy that sacrifices the completeness of immediate repair in order to adequately address the combined physiological impact of trauma and surgery. This approach is unfolded in three phases. During the initial operation, the surgeon carries out only the absolute minimum necessary to rapidly control exsanguination and prevent the spillage of intestinal contents and urine into the peritoneal cavity. Packing represents the traditional method for the management of major liver injuries. The second phase consists of secondary resuscitation in the intensive care unit, characterized by maximization of hemodynamics, correction of coagulopathy, rewarming, and complete ventilatory support. During the third phase, the intra-abdominal packing is removed and definitive repair of abdominal injuries is performed. The "damage control" concept has been shown to increase overall survival and is likely to modify the management of the critically injured patient.


SigmoID: a user-friendly tool for improving bacterial genome annotation through analysis of transcription control signals.
The majority of bacterial genome annotations are currently automated and based on a 'gene by gene' approach. Regulatory signals and operon structures are rarely taken into account which often results in incomplete and even incorrect gene function assignments. Here we present SigmoID, a cross-platform (OS X, Linux and Windows) open-source application aiming at simplifying the identification of transcription regulatory sites (promoters, transcription factor binding sites and terminators) in bacterial genomes and providing assistance in correcting annotations in accordance with regulatory information. SigmoID combines a user-friendly graphical interface to well known command line tools with a genome browser for visualising regulatory elements in genomic context. Integrated access to online databases with regulatory information (RegPrecise and RegulonDB) and web-based search engines speeds up genome analysis and simplifies correction of genome annotation. We demonstrate some features of SigmoID by constructing a series of regulatory protein binding site profiles for two groups of bacteria: Soft Rot Enterobacteriaceae (Pectobacterium and Dickeya spp.) and Pseudomonas spp. Furthermore, we inferred over 900 transcription factor binding sites and alternative sigma factor promoters in the annotated genome of Pectobacterium atrosepticum. These regulatory signals control putative transcription units covering about 40% of the P. atrosepticum chromosome. Reviewing the annotation in cases where it didn't fit with regulatory information allowed us to correct product and gene names for over 300 loci.


The PH-20 protein in human spermatozoa.
PH-20 is a sperm plasma-membrane protein that has been shown to have hyaluronidase activity in several mammalian species including nonhuman primates. In this investigation, the PH-20 protein was characterized in noncapacitated human sperm and in capacitated human sperm. Two forms of PH-20 were observed in immunoblots of sodium dodecylsulfate polyacrylamide-gel electrophoresis (SDS PAGE) using a polyclonal antibody to recombinant PH-20: a major band of 64 kDa appeared in noncapacitated and capacitated sperm extracts and a 53-kDa band that appeared only in the acrosome-reaction supernatant of acrosome-reacted sperm. Using hyaluronic acid substrate gel analysis, we demonstrated that noncapacitated sperm extracts, capacitated sperm extracts, and the acrosome-reaction supernatant had hyaluronidase activity at neutral pH (pH 7) and acid pH (pH 4). The 64-kDa form in all samples had hyaluronidase activity at both neutral and acid pH, but the 53-kDa form was only active at acid pH. Total hyaluronidase activity, as measured by a microplate assay, was higher at pH 7 than at pH 4. Very low hyaluronidase activity was detected in the acrosome-reaction supernatant. Transmission electron microscopy and immunogold labeling showed that PH-20 of acrosome-intact human sperm was located on the plasma membrane over the entire head but not on the sperm midpiece and tail. After the acrosome reaction, PH-20 was also located on the inner acrosomal membrane. The biochemical characteristics and the ultrastructural localization of PH-20 in human sperm suggest that this protein is the human sperm hyaluronidase and, therefore, has an important function during fertilization.


Interstimulus Intervals and Sensory Modality Modulate the Impact of a Cognitive Task on Postural Control.
The present literature not only reveals the use of a wide variety of cognitive tasks but variability in their interaction with postural control. The question then arises, as to, whether postural control is sensitive to specific features of a cognitive task. The present experiment assessed the impact of cognitive tasks with interstimulus intervals (ISI) of varied duration and sensory modality on postural control in young adults. Seventeen participants (23.71 ± 1.99 years old) were instructed to stand on a force platform while concurrently performing cognitive tasks with ISIs of two and 5 s. The tasks were presented both, auditorily and visually. The visual tasks consisted of counting the total occurrence of a single digit. The auditory tasks consisted of counting the total occurrence of a single letter. Performing the cognitive tasks with an ISI of 2 s resulted only in an increase in the anteroposterior mean power frequency. Presenting the tasks visually also significantly reduced area of 95% confidence ellipse and AP and mediolateral sway variability. These results may suggest that ISIs can modify postural performance by altering the allocation of attentional focus. Also, presenting tasks using a visual sensory modality appears to yield lower postural sway.


Dietary fiber extraction from citrus peel pomace: Yield optimization and evaluation of its functionality, rheological behavior, and microstructure properties.
Citrus fruits were widely used in processing and production, generating a large amount of peel pomace and a low utilization rate, resulting in substantial economic losses and environmental risks. It was important to extract compounds from citrus peel pomaces and find suitable preparation methods to improve their yield and physicochemical properties. Grapefruit peel pomace (GP) and navel orange peel pomace (OP) were used as raw materials in this study to prepare green and edible soluble dietary fiber (SDF) and insoluble dietary fiber (IDF). Analysis was done on the effects of solid-liquid ratio, cellulase hydrolysis time, cellulase dosage, and ultrasonic time on dietary fiber (DF) yield. To obtain the best DF preparation conditions, we used range analysis, variance analysis, and orthogonal experimental design. We also analyzed the structural, physicochemical, and rheological characteristics of SDF and IDF. According to the study's findings, SDF and IDF showed a loose and expansive structure with reduced particle size, higher specific surface area, and noticeably better physical and chemical properties after treating GP and OP with ultrasound-assisted composite enzyme method. Both SDF solution and IDF suspension were discovered through rheological analysis to be non-Newtonian pseudoplastic fluids, which was advantageous for expanding their applications in the field of food packaging. In conclusion, DF prepared using the ultrasound-assisted composite enzyme method was an excellent source of edible packaging materials, offering a benchmark for the recycling of other citrus peel wastes and ultimately paving the way for new methods of recycling citrus waste.


Characterization of Xenopus tissue inhibitor of metalloproteinases-2: a role in regulating matrix metalloproteinase activity during development.
Frog metamorphosis is totally dependent on thyroid hormone (T3) and mimics the postembryonic period around birth in mammals. It is an excellent model to study the molecular basis of postembryonic development in vertebrate. We and others have shown that many, if not all, matrix metalloproteinases (MMPs), which cleave proteins of the extracellular matrix as well as other substrates, are induced by T3 and important for metamorphosis. MMP activity can be inhibited by tissue inhibitors of metalloproteinase (TIMPs). There are 4 TIMPs in vertebrates and their roles in postembryonic development are poorly studied. We analyzed the TIMP2 genes in Xenopus laevis and the highly related species Xenopus tropicalis and discovered that TIMP2 is a single copy gene in Xenopus tropicalis as in mammals but is duplicated in Xenopus laevis. Furthermore, the TIMP2 locus in Xenopus tropicalis genome is different from that in human, suggesting an evolutionary reorganization of the locus. More importantly, we found that the duplicated TIMP2 genes were similarly regulated in the developing limb, remodeling intestine, resorbing tail during metamorphosis. Unexpectedly, like its MMP target genes, the TIMP2 genes were upregulated by T3 during both natural and T3-induced metamorphosis. Our results indicate that TIMP2 is highly conserved among vertebrates and that the TIMP2 locus underwent a chromosomal reorganization during evolution. Furthermore, the unexpected upregulation of TIMP2 genes during metamorphosis suggests that proper balance of MMP activity is important for metamorphosis.


Natural antibody responses to the capsid protein in sera of Dengue infected patients from Sri Lanka.
This study aims to characterize the antigenicity of the Capsid (C) protein and the human antibody responses to C protein from the four dengue virus (DENV) serotypes. Parker hydrophilicity prediction, Emini surface accessibility prediction and Karplus & Schulz flexibility predictions were used to bioinformatically characterize antigenicity. The human antibody response to C protein was assessed by ELISA using immune sera and an array of overlapping DENV2 C peptides. DENV2 C protein peptides P1 (located on C protein at 2-18 a.a), P11 (79-95 a.a) and P12 (86-101 a.a) were recognized by most individuals exposed to infections with only one of the 4 DENV serotypes as well as people exposed to infections with two serotypes. These conserved peptide epitopes are located on the amino (1-40 a.a) and carboxy (70-100 a.a) terminal regions of C protein, which were predicted to be antigenic using different bioinformatic tools. DENV2 C peptide P6 (39-56 a.a) was recognized by all individuals exposed to DENV2 infections, some individuals exposed to DENV4 infections and none of the individuals exposed to DENV1 or 3 infections. Thus, unlike C peptides P1, P11 and P12, which contain epitopes, recognized by DENV serotype cross-reactive antibodies, DENV2 peptide P6 contains an epitope that is preferentially recognized by antibodies in people exposed to this serotype compared to other serotypes. We discuss our results in the context of the known structure of C protein and recent work on the human B-cell response to DENV infection.


ncRNA-regulated immune response and its role in inflammatory lung diseases.
Despite the greatly expanded knowledge on the regulation of immune response by protein molecules, there is increasing understanding that noncoding RNAs (ncRNAs) are also an integral component of this regulatory network. Abnormal immune response serves a central role in the initiation, progression, and exacerbation of inflammatory lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome/acute lung injury. Dysregulation of ncRNAs has been linked to various immunopathologies. In this review, we highlighted the role of ncRNAs in the regulation of innate and adaptive immunity and summarized recent findings that ncRNAs participate in the pathogenesis of inflammatory lung diseases via their regulation of pulmonary immunity. We also discussed therapeutic potentials for targeting ncRNAs to treat these lung disorders.


Thebaine content of selections of Papaver bracteatum Lindl. at different ages.
Approximately 200 accessions of Papaver species were evaluated for identification as P. bracteatum Lindl. and for thebaine content. Fifteen authentic P. bracteatum accessions were selected on the basis of chromosome count. Statistical analyses of variation in alkaloid content were made for these accessions. Four of the 15 warranted further study based on the vigor of the plant and the total thebaine present in the tissue. Significant variability in thebaine content was found in wild strains of P. bracteatum, thus requiring genetic selection studies. The data showed that total yield potential of thebain should be considered in selecting P. bracteatum strains for commercial growth rather than concentrating on strains that produce the highest thebaine concentrations. A method for the quantitative estimation of thebaine from P. bracteatum is presented.


[Management of sickle cell disease].
Hypoxia, hemolysis and infection are more or less associated in patients affected with sickle cell disease. Treatment is based on a programme including regular lifestyle, hydration, folic acid supply, prevention of pneumococcal infections and cerebrovascular events in children, regular follow-up in specialised centres allowing precocious screening and treatment of organ deficiency. Some patients exhibit a severe form and need intensive preventive care, such as chronic transfusion, hydroxyurea or bone marrow transplantation for children and adolescent with an HLA-identical sibling. The choice between these strategies is multifactorial, excepted in patients with a severe cerebral vasculopathy, for whom chronic transfusion or bone marrow transplantation are preferable. We usually propose hydroxyurea as a first line treatment to patients with recurrent pain crises or acute chest syndromes. In cases of refusal, initial or secondary failure (which occur more frequently in adults), or intolerance of hydroxyurea, patients with a severe disease are chronically transfused, which leads them most of the time to necessitate iron chelation.


Rasch Analysis of the Michigan Hand Questionnaire.
The Michigan Hand Questionnaire (MHQ) is a commonly used evaluation for hand problems, but previous work reports conflicting evidence regarding the subscale structures. Rasch analysis uses probabilistic modeling of items and responses: if scale items can be fit to the Rasch model, it provides evidence of construct validity and interval-level measurement for precise statistical estimates. We conducted Rasch analysis on the MHQ to evaluate model fit, unidimensionality of the subscales, bias across person factors, and conversion to interval metrics. We conducted a secondary Rasch analysis of MHQ data from 924 persons with thumb basal joint osteoarthritis using the RUMM2030 software. Modeling was based on responses for the most affected hand and person factors including age, sex, type of work, whether the dominant side was the most affected, and surgical status. The analysis plan followed the published recommendations for examinations of person and item fit, with iterative adjustments as required. A total of 11 of the 37 items required rescoring to create orderly progression of scoring thresholds. Only the overall hand function and pain subscales could be fit to the Rasch model, demonstrating unidimensionality and good reliability of fit estimates. Dividing the activities of daily living subscale into unilateral and bilateral activities also allowed unilateral activities to fit the model. Persistent misfitting in other subscales suggested local dependency and response bias across multiple person factors. This Rasch analysis of the MHQ raises concerns regarding the validity and fundamental measurement properties of this widely used outcome evaluation when used as a summary score.


A study of SPECT/CT camera stability for quantitative imaging.
The purpose of this study was twofold: to evaluate the quantitative stability of a SPECT/CT gamma camera over time and to determine if daily flood acquisitions can reliably serve as calibration factors for quantitative SPECT. Using a cylindrical water phantom filled with measured amounts of (99m)Tc, factors were calculated to convert counts/cc to activity/cps. Measurements were made over an 18-month period. System sensitivity data calculated from (57)Co daily quality assurance (DQA) flood acquisitions were then compared to the (99m)Tc calibration factors to determine the relationship of the factors. The coefficient of variation is 2.7 % for the (99m)Tc cylinder conversion factors and 2.6 % for the (57)Co DQA flood data. The greatest difference between the cylinder conversion factors and the flood data is less than 3 %. Based on the results, the camera was stable within 3 % over an 18-month time period. The daily flood source acquisitions can be a reliable source for tracking camera stability and may provide information on updating the calibration factor for quantitative imaging.


Regulation of rat liver phenylalanine hydroxylase. I. Kinetic properties of the enzyme's iron and enzyme reduction site.
Tetrahydropterins react with phenylalanine hydroxylase at a redox site, a regulatory site, and the catalytic site, but neither the properties of nor relationships among these sites are well understood. We have studied the redox site using the fluorescent iron chelators 2,3-dihydroxynaphthalene and bathophenanthroline; these compounds act as site-specific reporter groups for reactions on oxidized and reduced enzyme, respectively. The chelators bind reversibly and specifically to the enzyme's iron with 1:1 stoichiometry, high affinity (Kd values approximately 1 nM), and complete quenching of their own fluorescence. The kinetic behavior of these and other iron chelators indicates that the enzyme's iron is solvent accessible and in a hydrophobic pocket of the protein. Both ferrous and ferric chelators inhibit phenylalanine hydroxylase activity. Bathophenanthroline inhibits by binding to Fe2+ on reduced, active enzyme. 2,3-Dihydroxynaphthalene inhibits by binding to Fe3+ on enzyme that is oxidized during catalysis. This oxidation occurs approximately 1/150 enzyme turnovers, and its rate is increased when p-chloro- or p-fluorophenylalanine is used as the reaction substrate. Studies of the reaction of tetrahydrobiopterin (BH4) at the enzyme's redox site showed that BH4 reduces the enzyme more slowly than 6-methyltetrahydropterin under catalytic and non-catalytic conditions. Reduction occurs at a distinct site whose binding determinants and reaction characteristics are different from those of the BH4 regulatory or catalytic sites, and phenylalanine-activated enzyme is reduced more rapidly than unactivated enzyme. In reducing phenylalanine activated enzyme, BH4 donates one electron/subunit (1/iron atom); the reduction kinetics suggest a trihydrobiopterin-free radical as a reaction intermediate.


Roll and square convection in binary liquids: a few-mode Galerkin model.
We present a few-mode Galerkin model for convection in binary fluid layers subject to an approximation to realistic horizontal boundary conditions at positive separation ratios. The model exhibits convection patterns in form of rolls and squares. The stable squares at onset develop into stable rolls at higher thermal driving. In between, a regime of a so-called cross roll structure is found. The results of our few-mode model are in good agreement with both experiments and numerical multimode simulations.


Coats' disease in a renal transplant recipient.
We report the first case, to our knowledge, of Coats' disease, an idiopathic exudative retinopathy, in a renal transplant recipient. Due to certain similarities in clinical presentation and confounding factors present in patients who have received kidney allografts, our patient was originally misdiagnosed as having cytomegalovirus retinitis. We emphasise the significance of this diagnostic distinction and the association of this retinal syndrome with renal disease.


Quality and accuracy of publicly accessible cancer-related physical activity information on the Internet: a cross-sectional assessment.
In this study, we assessed the quality of publicly available cancer-related physical activity (PA) information appearing on reputable sites from Canada and other English-speaking countries. A cross-sectional Internet search was conducted on select countries (Canada, USA, Australia, New Zealand, UK) using Google to generate top 50 results per country for the keywords "'physical activity' AND 'cancer'". Top results were assessed for quality of PA information based on a coding frame. Additional searches were performed for Canadian-based sites to produce an exhaustive list. Results found that many sites offered cancer-related PA information (94.5%), but rarely defined PA (25.2%). Top 50 results from each country did not differ on any indicator examined. The exhaustive list of Canadian sites found that many sites gave information about PA for survivorship (78.3%) and prevention (70.0%), but rarely defined (6.7%) or referenced PA guidelines (28.3%). Cancer-related PA information is plentiful on the Internet but the quality needs improvement. Sites should do more than mention PA; they should provide definitions, examples and guidelines. With improvements, these websites would enable healthcare providers to effectively educate their patients about PA, and serve as a valuable resource to the general public who may be seeking cancer-related PA information.


An efficient semi-supervised community detection framework in social networks.
Community detection is an important tasks across a number of research fields including social science, biology, and physics. In the real world, topology information alone is often inadequate to accurately find out community structure due to its sparsity and noise. The potential useful prior information such as pairwise constraints which contain must-link and cannot-link constraints can be obtained from domain knowledge in many applications. Thus, combining network topology with prior information to improve the community detection accuracy is promising. Previous methods mainly utilize the must-link constraints while cannot make full use of cannot-link constraints. In this paper, we propose a semi-supervised community detection framework which can effectively incorporate two types of pairwise constraints into the detection process. Particularly, must-link and cannot-link constraints are represented as positive and negative links, and we encode them by adding different graph regularization terms to penalize closeness of the nodes. Experiments on multiple real-world datasets show that the proposed framework significantly improves the accuracy of community detection.


Peritoneal transport in peritoneal dialysis patients is not affected by transitorily successful renal transplantation.
Patients returning to peritoneal dialysis (PD) from failed renal transplantation are recognized to be inflamed, and this situation might produce a high peritoneal solute transport status. We wanted to determine if a period of time with a kidney allograft induces a change in peritoneal function. We studied 19 PD patients who had been living with a graft for a mean of 47 +/- 39 months. We studied their peritoneal function upon starting PD (baseline), immediately before transplantation (pre-Tx), and after returning to PD when the graft failed (post-Tx). We analyzed the peritoneal mass transfer coefficients for urea (U-MTAC) and creatinine (Cr-MTAC), the dialysate-to-plasma ratio of creatinine (D/P-Cr), and net ultrafiltration (UF). We observed no significant differences in the various variables pre-Tx and post-Tx. The U-MTAC post-Tx was significantly lower than at PD baseline (25.9 +/- 8 mL/min vs. 20.2 +/- 5 mL/min, p = 0.03). The U-MTAC and Cr-MTAC post-Tx were not correlated with months on a graft or with MTAC values at baseline. In inherent high transporters (Cr-MTAC > or = 11.5 mL/min at baseline, n = 8), we observed a significant reduction in Cr-MTAC post-Tx (15.2 +/- 2 mL/min vs. 10.2 +/- 4 mL/min, p = 0.03). Three of these patients remained high transporters post-Tx. We conclude that peritoneal function upon reinitiating PD after transplantation is similar to function in the pre-transplantation phase; and that a high peritoneal transport status is more prevalent at first initiation onto PD than at return after transplantation, suggesting that inherently high transport is almost exclusively a feature of an intact, predialysis peritoneum.


Suppression of interferon-related promoter activation by hepatitis C virus proteins expressed in cultured cells.
Interferon is important for anti-viral defense of the host. The E2, NS3/4A, and NS5A proteins of hepatitis C virus (HCV) have recently been reported to confront anti-viral action induced by interferon. However, roles of the individual HCV proteins in anti-interferon action are still not well understood. We have isolated an HCV strain, HCV-K, from a patient with acute hepatitis. Nucleotide sequencing of the entire genomic DNA of HCV-K revealed that the isolate belongs to the genotype 1b, which is generally resistant to interferon therapy. In the present study, we expressed individual HCV-K proteins in mammalian cells and investigated effects of the proteins on interferon signal transduction. The results showed that the core, E1, NS4A, and NS4B proteins suppressed activation of interferon stimulation responsive element (ISRE) and gamma activation sequence (GAS) reporters. These results suggest that multiple HCV proteins have a function in suppression of the anti-viral effect by interferon and may indicate a novel role of E1 and NS4B proteins in interferon antagonism.


The role of bacterial hydrophobicity in infection: bacterial adhesion and phagocytic ingestion.
The role that bacterial surface hydrophobicity (surface tension) plays in determining the extent of adhesion of polymer substrates and phagocytic ingestion is reviewed. The early attachment phase in bacterial adhesion is shown to depend critically on the relative surface tensions of the three interacting phases; i.e., bacteria, substrate, and suspending liquid surface tension. When suspended in a liquid with a high surface tension such as Hanks balanced salt solution, the most hydrophobic bacteria adhere to all surfaces to the greatest extent. When the liquid surface tension (gamma LV) is larger than the bacterial surface tension (gamma BV), then for any single bacterial species the extent of adhesion decreases with increasing substrate surface tension (gamma SV). When gamma LV less than gamma BV then adhesion increases with increasing gamma SV. Bacterial surface tension also determines in part the extent of phagocytic ingestion and the degree to which antibodies specifically adsorb onto the bacterium resulting in opsonization. The nonspecific adsorption of antibodies results in a considerable modification in the surface properties of the bacteria. Bacterial surface hydrophobicity can be altered significantly through exposure to subinhibitory concentrations of antibiotics, surfactants, lectins, etc. The effect of these changes on subsequent phagocytic ingestion is discussed.


Clinicopathologic spectrum of cutaneous manifestations in systemic follicular lymphoma. A study of 11 patients.
Follicular lymphoma is rarely diagnosed on the basis of only a cutaneous biopsy. Eleven patients with primary follicular lymphoma of lymph nodes who developed skin lesions were studied. Skin lesions involved the scalp, head and neck, trunk, and buttocks and were small cleaved cell type in four cases, large cell type in three cases, and mixed type in four cases. The follicular pattern with a bottom-heavy distribution was identified in only six of the 11 cases. One case showed a nodular, perivascular pattern in the deep dermis and subcutaneous tissue. Four cases were characterized by a diffuse pattern of lymphocytic infiltrate. One patient with a diffuse pattern had an isolated subepidermal band of lymphoma cells representing primary cutaneous T-cell lymphoma. Cutaneous involvement by lymphoma previously diagnosed as low-grade (follicular growth pattern) transformed to higher grade disease in five of ten asynchronous cases. The 5-year survival rate was 60% among the transformed cases and 100% among the nontransformed cases. Extranodal cutaneous involvement in follicular lymphoma occurred in 3.8% of cases. The correct histologic diagnosis in a skin biopsy specimen can be established in cases with a follicular pattern (60%) with conventional histologic criteria such as redundancy of follicles, uniformity of follicular center cell composition, lack of interspersed phagocytic histiocytes, and absence of immunosecretory cellular elements such as plasma cells and immunoblasts.


Review of Common Alternative Herbal "Remedies" for Skin Cancer.
Alternative herbal remedies for skin cancer are commonly found on the Internet. Many websites contain inaccurate or false information regarding side effects and efficacy. To review the evidence behind several commonly advertised herbal remedies that claim to cure skin cancer: black salve, eggplant, frankincense, cannabis, black raspberry, milk thistle, St. John's wort, and turmeric. A PubMed search was performed using the common and scientific names of frequently advertised herbal remedies along with the terms "nonmelanoma skin cancer," or "basal cell carcinoma" or "squamous cell carcinoma," or "melanoma." Some preclinical studies have shown positive evidence that these substances can induce apoptosis in skin cancer, but clinical studies proving efficacy are either insufficient, nonexistent, or show negative evidence. Botanicals that were excluded are those that do not have published studies of their efficacy as skin cancer treatments. Online advertising may tempt patients to use botanical agents while citing efficacy found in preclinical studies. However, many agents lack strong clinical evidence of efficacy. Dermatologists must be aware of common herbal alternatives for skin cancer treatment to maintain effective patient communication and education.


The dialogical self in psychotherapy for persons with schizophrenia: a case study.
Schizophrenia often involves a profound experience of one's identity as diminished, which complicates adaptation to the demands of daily life. Within a backdrop of dialogical self-theory, we provide a report of an individual psychotherapy over the course of 4 years that assisted a patient suffering from schizophrenia to move from a state in which few aspects of self were available for internal or external conversation to one in which there was greater accessibility of multiple aspects of self, leading to richer dialogues, improved function, and a better quality of life. It is suggested a primary intervention of the therapist was continuously to offer the client a view of himself that invited him to experience himself in a plausible manner shared with and listened to by another.


Neuroimaging of CNS involvement in HIV.
Central nervous system involvement in HIV-positive patients is common with 40% of patients suffering neurological disease at some point in their lives. Neuroimaging is important to properly diagnose treatable conditions and to monitor response to treatment. In this article, we describe and illustrate the main CNS imaging findings. The following categories of pathology are addressed: direct neurological effects of HIV, opportunistic CNS infections and neoplasms, cerebrovascular complications of HIV and CNS effects of highly active retroviral therapy (HAART). Imaging techniques employed include computed tomography, magnetic resonance imaging, diffusion-weighted imaging, functional magnetic resonance imaging and magnetic resonance spectroscopy.


Endotoxin, (1 --> 3)-beta-D-glucans and fungal extra-cellular polysaccharides in New Zealand homes: a pilot study.
Bacterial endotoxin, fungal (1 --> 3)-beta-D-glucans, and extracellular polysaccharides from Aspergillus and Penicillium (EPS-Asp/Pen) have been suggested to be stable markers of microbial exposure. This paper describes a pilot study in which we measured endotoxin, (1 --> 3)-beta-D-glucans, EPS-Asp/Pen and mite allergen in house dust collected in 32 homes in Wellington, New Zealand. Endotoxin (GM 60,295 EU/g; GSD 2.4) and glucan (GM 2,687 microg/g; GSD 1.5) levels were higher in comparison to previous international studies, whereas EPS-Asp/Pen levels (37,347 Units/g; GSD 1.9) appeared comparable. Concentrations expressed per square meter were highly correlated among the measured components (p < 0.05). When expressed per gram of dust only (1 --> 3)- beta -D-glucans and EPS-Asp/Pen were correlated (r=0.55, p < 0.01; n=32). Endotoxin and glucan levels were higher (borderline statistically significant; p < 0.10) in homes with self-reported water damage. A positive association (p < 0.10) was also found for dust mite and a combination of self-reported mould, dampness and water damage. EPS levels were higher in homes where residents indicated the presence of mould spots on the wall, but this did not reach statistical significance. In conclusion, levels of microbial contaminants in a small random sample of New Zealand homes were high and weakly associated with water damage.


Coaches' assessment of their coaching efficacy compared to athletes' perceptions.
This study compared coaches' assessments of their own coaching efficacy with their athletes' perceptions of the coaches' efficacy. Coaching efficacy was measured with the Coaching Efficacy Scale. Participants were 9 football coaches and 76 football players from the same team. Analysis indicated coaches were confident in their coaching abilities (range 6.5 to 9.0 on a 9-point scale). For 7 of the 9 coaches the coaches' ratings of themselves were higher than the athletes' ratings. For the other 2 coaches, athletes' ratings of coaches' efficacy were higher than the coaches' ratings of themselves. All coaches' ratings fell within the 95% confidence interval based on the athletes' ratings of the coaches' efficacy. Results are discussed in terms of the interplay between athletes and coaches efficacy beliefs and its influence on behavior.


Time-resolved X-ray diffraction microprobe studies of the conversion of cellulose I to ethylenediamine-cellulose I.
Structural changes during the treatment of films of highly crystalline microfibers of Cladophora cellulose with ethylenediamine (EDA) have been studied by time-resolved X-ray microprobe diffraction methods. As EDA penetrates the sample and converts cellulose I to EDA-cellulose I, the measured profile widths of reflections reveal changes in the shapes and average dimensions of cellulose I and EDA-cellulose I crystals. The (200) direction of cellulose I is most resistant to EDA penetration, with EDA penetrating most effectively at the hydrophilic edges of the hydrogen bonded sheets of cellulose chains. Most of the cellulose chains in the initial crystals of cellulose I are incorporated into crystals of EDA-cellulose I. The size of the emerging EDA-cellulose I crystals is limited to about half of their size in cellulose I, most likely due to strains introduced by the penetration of EDA molecules. There is no evidence of any gradual structural transition from cellulose I to EDA-cellulose I involving a continuously changing intermediate phase. Rather, the results point to a rapid transition to EDA-cellulose I in regions of the microfibrils that have been penetrated by EDA.


Recent developments in the analysis of comparative data.
Comparative methods can be used to test ideas about adaptation by identifying cases of either parallel or convergent evolutionary change across taxa. Phylogenetic relationships must be known or inferred if comparative methods are to separate the cross-taxonomic covariation among traits associated with evolutionary change from that attributable to common ancestry. Only the former can be used to test ideas linking convergent or parallel evolutionary change to some aspect of the environment. The comparative methods that are currently available differ in how they manage the effects brought about by phylogenetic relationships. One method is applicable only to discrete data, and uses cladistic techniques to identify evolutionary events that depart from phylogenetic trends. Techniques for continuous variables attempt to control for phylogenetic effects in a variety of ways. One method examines the taxonomic distribution of variance to identify the taxa within which character variation is small. The method assumes that taxa with small amounts of variation are those in which little evolutionary change has occurred, and thus variation is unlikely to be independent of ancestral trends. Analyses are then concentrated among taxa that show more variation, on the assumption that greater evolutionary change in the character has taken place. Several methods estimate directly the extent to which ancestry can predict the observed variation of a character, and subtract the ancestral effect to reveal variation of phylogeny. Yet another can remove phylogenetic effects if the true phylogeny is known. One class of comparative methods controls for phylogenetic effects by searching for comparative trends within rather than across taxa. With current knowledge of phylogenies, there is a trade-off in the choice of a comparative method: those that control phylogenetic effects with greater certainty are either less applicable to real data, or they make restrictive or untestable assumptions. Those that rely on statistical patterns to infer phylogenetic effects may not control phylogeny as efficiently but are more readily applied to existing data sets.


What is talked about? Community living staff experiences of talking with older people with intellectual disability about dying and death.
The aim of this study was to explore what community living staff talked about and did with people with intellectual disability (ID) to assist them to understand dying and death. Guided by grounded theory methodology, focus groups and one-to-one interviews were conducted with 22 staff who had talked about any topic relating to dying and death with their clients. There was little evidence that staff talked with, or did things with clients to assist understanding of the end of life, both prior to and after a death. Prior to death staff assisted clients in a limited way to understand about determining wishes in preparation for death, and what dying looks like by observance of its passage. Following a death staff offered limited assistance to clients to understand the immutability of death, and how the dead can be honoured with ritual, and remembered. The findings have implications for why people with ID have only partial understanding of the end of life, the staff skills required to support clients' understanding, and when conversations about the end of life should occur.


L factor that is required for beta-galactosidase synthesis is the nusA gene product involved in transcription termination.
The DNA-dependent in vitro synthesis of Escherichia coli beta-galactosidase requires the presence of a soluble protein referred to as L factor [Kung, H., Spears, C. & Weissbach, H. (1975) J. Biol. Chem. 250, 1556-1562]. In the present study, comparison of physical, immunological, and biological properties shows that L factor is the product of the E. coli nusA gene. The nusA gene product is known to interact with bacteriophage lambda N gene protein and to prevent premature termination of transcription from the early lambda promoters. Our results suggest that premature transcription termination in the lac operon of E. coli may also be overcome by the nusA protein.


USING LIVED EXPERIENCES OF ADULTS TO UNDERSTAND CHRONIC PAIN: SICKLE CELL DISEASE, AN EXEMPLAR.
Healthcare provision pertaining to painful, chronic conditions can best be optimized by developing positive healthcare provider (HCP)-patient relationships that minimize fragmented care. Nurses, with their holistic, humanistic approach provide a multidimensional focus that fosters individualized and effective outcomes for chronic events. The chronic pain phenotype is subjective, difficult to assess, define and effectively manage. Individuals with one such chronic syndrome, sickle cell disease (SCD), are living longer with pain that is poorly defined and inadequately managed. In addition to using quantitative assessment, clinicians and researchers must use substantive qualitative inquiry to understand the pain from the individual's perspective, define, and appropriately manage the pain. Combined quantitative and qualitative inquiry can help clinicians and researchers gain insights into pain experiences. This manuscript summarizes the importance of including a narrative (qualitative) inquiry, to offer a holistic, comprehensive and humanistic approach to understanding chronic pain from the individual's perspective and subsequently positively impacting care delivery. All nurses in the academy-educators, clinicians and researches need to include a qualitative approach to care delivery, investigation and evaluation of the phenomenon pain, and intentionally demonstrate care. The experiences of individuals with chronic sickle cell disease (SCD) pain are used as an exemplar.


Effect of (S)-3,5-DHPG on learning, exploratory activity and anxiety in rats with experimental hypoxia.
We investigated the effects of (S)-3,5-DHPG, a selective agonist of group I metabotropic glutamate receptors (I mGluRs), on certain behaviors in rats after short-term hypoxia as a model of experimentally induced amnesia. The effect of (S)-3,5-DHPG administered intracerebroventriculary (icv) at doses of 0.01, 0.1 and 1.0 nmol was assessed using behavioral tests: the open field test, the passive avoidance response and the elevated "plus" maze test. (S)-3,5-DHPG did not change the number of crossed fields and rearings and only at a dose of 0.01 nmol it increased the number of bar approaches in the open field test. (S)-3,5-DHPG used at all doses improved consolidation, and at doses of 0.01 and 1.0 nmol it improved retrieval in the passive avoidance test. (S)-3,5-DHPG did not produce any significant effects in control rats in the elevated "plus" maze test. Hypoxia inhibited locomotor and exploratory activity of rats, significantly impaired consolidation and retrieval processes. We observed tendency to shortening the time spent in open arms and to decrease in the number of entries into open arms in the elevated "plus" maze in rats with underwent hypoxia. In hypoxia-treated groups of rats, (S)-3,5-DHPG inhibited locomotor and exploratory activity in comparison with the control groups administered (S)-3,5-DHPG. Hypoxia significantly inhibited beneficial effects of (S)-3,5-DHPG on consolidation and retrieval in passive avoidance. (S)-3,5-DHPG only at the dose of 1.0 nmol used before hypoxia improved consolidation and at the dose of 0.01 nmol enhanced retrieval in comparison with saline-treated group subjected to hypoxia. (S)-3,5-DHPG only at the dose of 1.0 nmol in hypoxia-treated group shortened the time spent in closed arms and increased the number of entries into closed and open arms in the elevated "plus" maze vs saline-treated group subjected to hypoxia. In rats subjected to hypoxia, (S)-3,5-DHPG, the agonist of I mGluRs, improved consolidation and retrieval and exhibited anxiolytic activity in dose-dependent manner.


Improvement of dissolution rate and oral bioavailability of a sparingly water-soluble drug, (+/-)-5-[[2-(2-naphthalenylmethyl)-5-benzoxazolyl]-methyl]- 2, 4-thiazolidinedione, in co-ground mixture with D-mannitol.
We investigated the usefulness and efficiency of the co-grinding method with D-mannitol to improve the bioavailability of a sparingly water-soluble drug, (+/-)-5-[[2-(2-naphthalenylmethyl)-5-benzoxazolyl]methyl]-2, 4-thiazolidinedione (174), and compared it with those of the single-grinding method. The co-ground mixtures in drug/carrier weight ratios up to 1:5 gave fine particle sizes of less than about 3 microns, which showed a marked increase in the dissolution rate with reduction of particle size, compared with the single-ground powder, even with a similar particle size. The oral bioavailability study of co-ground powders in beagle dogs exhibited a dramatic increase, as did the dissolution rate, according to finer particle size. Finally, complete bioavailability was obtained at the finest particle size of 1.2 microns (drug/carrier ratio of 1:5, w/w) as was a solution of the drug. Bioavailability had a good linear correlation with the dissolution rate. These findings suggested that the co-grinding method with D-mannitol dramatically increased the available surface area, caused by a reduction of particle size, which not only accelerated the dissolution rate but also resulted in greater enhancement of the bioavailability of 174.


Factors predicting the 1-year outcome of collagenase treatment for Dupuytren's disease.
Several studies have investigated the clinical outcome after collagenase treatment for Dupuytren's disease in terms of range of motion of the affected finger. However, good objective clinical outcome defined by a small remaining flexion contracture does not necessarily translate into satisfactory patient-subjective hand function. The aim of the present study was to identify predictors of patient-reported as well as objective clinical outcome in patients 1 year after collagenase treatment for Dupuytren's disease. Socio-demographic and disease-related data of 92 Dupuytren patients were collected prior to the intervention. Flexion contracture of the most affected finger was measured at baseline and 1 year after treatment. Patients also completed the brief Michigan Hand Outcomes Questionnaire (brief MHQ) before the intervention and at 1-year follow-up. First, univariate correlations using Pearson's correlation coefficient of the baseline variables with the two target variables were investigated. All variables with r > 0.35 were selected for a multivariate linear stepwise backwards regression model. The mean brief MHQ score increased between baseline (72 ± 14) and the 1-year follow-up (85 ± 15) (p ≤ 0.001) and baseline flexion contracture decreased from 76° (± 26) to 33° (± 31) (p ≤ 0.001). Higher hand function at baseline (R2 = 0.31) and less flexion contracture (R2 = 0.46) were identified as positive predictors for the outcome 1 year after collagenase treatment for Dupuytren's disease. Other variables such as age, gender, manual work and if the MCP or PIP joint was affected did not determine outcome in our patient series. Collagenase treatment resulted in considerable improvement in flexion contracture as well as patient-reported hand function at the 1-year follow-up. Clinicians can expect better outcome after collagenase infiltration in patients with less flexion contracture and in patients showing good initial self-reported hand function.


Economic Burden Analysis of Parkinson's Disease Patients in China.
Parkinson's Disease (PD) is a progressive neurodegenerative disorder, which is prevalent in people over 65 years old. PD reduces patients' quality of life and exerts a heavy economic burden on patients and their families. The purpose of this research is to identify the costs of PD and to evaluate the economic distribution of medical care for PD patients in China. A professional survey was administered to 116 patients with PD. Records of medical cost were reviewed. Direct and indirect costs were analyzed. The main cost-driving factors of PD were identified using multivariate regression analysis. The average annual cost per PD patient in China is $3,225.94, with direct and indirect costs accounting for $2,503.46 and $722.48, respectively. Direct costs consist of $556.27 for surgery, $44.67 for appointment fees, $605.67 for prescription medication, $460.29 for hospitalization, $71.03 for auxiliary examination, $35.64 for transportation, $10.39 for special equipment, and $719.50 for formal care. The total cost is closely related to surgical treatment, dopamine agonist, and levodopa costs. The cost of PD patients in China is considerable and exceeds average economic capacity, especially antiparkinson medication and caring costs. This study may provide a reference for PD healthcare optimization in the future.


Late Pleistocene echimyid rodents (Rodentia, Hystricognathi) from northern Brazil.
Echimyidae (spiny rats, tree rats and the coypu) is the most diverse family of extant South American hystricognath rodents (caviomorphs). Today, they live in tropical forests (Amazonian, coastal and Andean forests), occasionally in more open xeric habitats in the Cerrado and Caatinga of northern South America, and open areas across the southern portion of the continent (Myocastor). The Quaternary fossil record of this family remains poorly studied. Here, we describe the fossil echimyids found in karst deposits from southern Tocantins, northern Brazil. The analyzed specimens are assigned to Thrichomys sp., Makalata cf. didelphoides and Proechimys sp. This is the first time that a fossil of Makalata is reported. The Pleistocene record of echimyids from this area is represented by fragmentary remains, which hinders their determination at specific levels. The data reported here contributes to the understanding of the ancient diversity of rodents of this region, evidenced until now in other groups, such as the artiodactyls, cingulates, carnivores, marsupials, and squamate reptiles.


Surface chemistry of gold nanorods: origin of cell membrane damage and cytotoxicity.
We investigated how surface chemistry influences the interaction between gold nanorods (AuNRs) and cell membranes and the subsequent cytotoxicity arising from them in a serum-free cell culture system. Our results showed that the AuNRs coated with cetyl trimethylammonium bromide (CTAB) molecules can generate defects in the cell membrane and induce cell death, mainly due to the unique bilayer structure of CTAB molecules on the surface of the rods rather than their charge. Compared to CTAB-capped nanorods, positively charged polyelectrolyte-coated, i.e. poly(diallyldimethyl ammonium chloride) (PDDAC), AuNRs show improved biocompatibility towards cells. Thus, the present results indicate that the nature of surface molecules, especially their packing structures on the surface of AuNRs rather than surface charge, play a more crucial role in determining cytotoxicity. These findings about interfacial interactions could also explain the effects of internalized AuNRs on the structures or functions of organelles. This study will help understanding of the toxic nature of AuNRs and guide rational design of the surface chemistry of AuNRs for good biocompatibility in pharmaceutical therapy.


Septic arthritis: an extensive variety of pathology.
Septic arthritis typically presents as a hot, swollen joint. Rapid recognition and treatment of this condition is essential to prevent permanent joint damage. However, septic arthritis does not always present in a textbook manner. The case presented here concerns septic arthritis affecting the right sternoclavicular joint. The patient did not have any risk factors for septic arthritis and presented with a swollen tender joint that was not hot. He was treated with penicillin and then amoxicillin for a total of 12 weeks and made a full recovery. The organism isolated from his right sternoclavicular joint was Neisseria elongata, which is the first ever documented case of this organism causing septic arthritis. This case emphasises that the suspicion of septic arthritis should remain high when unexplained monoarthritis occurs and there should be a low threshold in treating monoarthritis as septic arthritis even in the absence of risk factors.


Collagenase Impacts the Quantity and Quality of Native Mesenchymal Stem/Stromal Cells Derived during Processing of Umbilical Cord Tissue.
Enzymes are commonly used as a biochemical means to liberate cells from a host of tissues for use in in vitro studies and/or in vivo transplantations. However, very little understanding exists of the biological and functional effects that enzymes have on cells during the process of releasing the native cells from a given tissue. One specific reason for this is that no technology has existed as a nonenzymatic control to compare baseline biology and function for a given processed tissue. We have developed a sterile, onetime use, disposable system (referred to as the AuxoCell Processing System or AC:Px®) that allows for processing of solid tissue in a closed, standardized system using mechanical means to liberate cells without the need and/or use of any biochemical, enzymatic digestion. In this report, for the first time, we directly compare the cellular outputs derived from processing the same umbilical cord tissue (UCT) in the presence and absence of collagenase. In the presence of collagenase, we observed on average, approximately a 2.7-fold reduction in native mesenchymal stem/stromal cell (MSC) yields and a reduction in MSC-specific markers CD90, CD29, CD105, CD73, CD44, CD36, CD49b, CD49a, CD146, CD295, and CD166 and in endothelial marker CD31. These data directly exhibit that the use of collagenase to process UCT to release cells impacts cell recovery with respect to number and cell surface marker expression and, hence, could affect the in vivo function of the recovered native cellular population.


Identification and characterization of a novel rat ov-serpin family member, trespin.
Serpins are responsible for regulating a variety of proteolytic processes through a unique irreversible suicide substrate mechanism. To discover novel genes regulated by transforming growth factor-beta1 (TGF-beta 1), we performed differential display reverse transcriptase-PCR analysis of NRP-152 rat prostatic epithelial cells and cloned a novel rat serpin that is transcriptionally down-regulated by TGF-beta and hence named trespin (TGF-beta-repressible serine proteinase inhibitor (trespin). Trespin is a 397-amino acid member of the ov-serpin clade with a calculated molecular mass of 45.2 kDa and 72% amino acid sequence homology to human bomapin; however, trespin exhibits different tissue expression, cellular localization, and proteinase specificity compared with bomapin. Trespin mRNA is expressed in many tissues, including brain, heart, kidney, liver, lung, prostate, skin, spleen, and stomach. FLAG-trespin expressed in HEK293 cells is localized predominantly in the cytoplasm and is not constitutively secreted. The presence of an arginine at the P1 position of trespin's reactive site loop suggests that trespin inhibits trypsin-like proteinases. Accordingly, in vitro transcribed and translated trespin forms detergent-stable and thermostable complexes with plasmin and elastase but not subtilisin A, trypsin, chymotrypsin, thrombin, or papain. Trespin interacts with plasmin at a near 1:1 stoichiometry, and immunopurified mammal-expressed trespin inhibits plasmin in a dose-dependent manner. These data suggest that trespin is a novel and functional member of the rat ov-serpin family.


TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain.
The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by chaperones has not been elucidated, as is the case for other mammalian TRP channels. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain. Antagonism of Sig-1R by progesterone results in the down-regulation of TRPV1 expression in the plasma membrane of sensory neurons and, consequently, a decrease in capsaicin-induced nociceptive responses. This is observed both in males treated with a synthetic antagonist of Sig-1R and in pregnant females where progesterone levels are elevated. This constitutes a previously undescribed mechanism by which TRPV1-dependent nociception and pain can be regulated.


In situ structural characterization of glycerophospholipids and sulfatides in brain tissue using MALDI-MS/MS.
Lipids are major structural components of biomembranes. Negatively charged species such as phosphatidylinositol, phosphatidylserine, sulfatides, and the zwitterionic phosphatidylethanolamines are major components of the cytoplasmic surface of the cellular membrane lipid bilayer and play a key role in several receptors signaling functions. Lipids are not just involved in metabolic and neurological diseases; negatively charged lipids in particular play crucial roles in physiological events such as signal transduction, receptors, and enzymatic activation, as well as storage and release of therapeutic drugs and toxic chemicals in the body. Due to the importance of their role in signaling, the field of lipidomics has rapidly expanded in recent years. In the present study, direct probing of tissue slices with negative ion mode matrix assisted laser desorption/ionization mass spectrometry was employed to profile the distribution of lipids in the brain. In total, 32 lipid species consisting of phosphatidylethanolamines, phosphatidylglycerol, phosphatidylinositols, phosphatidylserines, and sulfatides were assigned. To confirm the structure of lipid species, MALDI-MS/MS analysis was conducted. Product-ion spectra obtained in negative ion mode allow for the assignment of the head groups and the fatty acid chains for the lipid species.


Estrogen and stress interact to regulate the hypothalamic expression of a human proenkephalin promoter-beta-galactosidase fusion gene in a site-specific and sex-specific manner.
Gonadal steroids and physiological stressors affect the regulation of proenkephalin (PPE) gene expression in the paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei. To examine the effects of these modulators at the cellular level, the current study utilized a transgenic mouse line that expresses a human proenkephalin promoter/bacterial beta-galactosidase fusion gene (ENK-1). Previous studies have demonstrated that the regulatory sequences included in this transgene are sufficient to support appropriate transcriptional regulation of the reported gene in the PVN of male ENK-1 mice in response to stress. The present experimental paradigm was designed to examine possible interactions of sex and circulating estrogen levels with the opioid responses to acute systemic stressors, an intraperitoneal injection of hypertonic (1.5 M) or isotonic (0.15 M) saline. Adult ENK-1 mice were gonadally intact, gonadectomized, or 21 days postpartum. Forty-eight hours before perfusion, castrated males and ovariectomized females received either 10 micrograms estradiol benzoate or oil vehicle and 4 animals per group received no further treatment. Six h before perfusion, remaining animals received a single intraperitoneal injection of either hypertonic or isotonic saline. Tissues were sectioned through the hypothalamus and processed for X-gal histochemistry. In the VMH of ovariectomized females that received isotonic saline, estrogen significantly elevated transgene expression. This effect was not seen in females that only received estrogen or in those that received the severe systemic stressor of a injection of hypertonic saline. Estrogen and stress did not interact to elevate transgene expression in the VMH of males. A different pattern of expression was observed in the PVN; injection of hypertonic saline induced transgene expression only in gonadally intact males and in castrated males given estrogen. These findings demonstrate that stress and estrogen have sex-specific and site-specific regulatory effects on the expression of a PPE promoter transgene in hypothalamic neurons.


A new fast-ion D(alpha) diagnostic for DIII-D.
The fast-ion D(alpha) (FIDA) technique is a charge-exchange recombination spectroscopy measurement that exploits the large Doppler shift of Balmer-alpha light from energetic hydrogenic atoms to infer the fast-ion density. Operational experience with the first dedicated FIDA diagnostic on DIII-D is guiding the design of the second-generation instrument. In the first instrument, dynamic changes in background light associated with plasma instabilities usually dominate measurement uncertainties. Accordingly, the design of the new instrument minimizes scattering of cold D(alpha) light while monitoring its level. The first instrument uses a vertical view to avoid bright interference from the injected-neutral beams. The sightline of the new instrument includes a toroidal component but only measures blueshifted fast-ion light that is Doppler shifted away from the redshifted light of the injected neutrals. The new views are more sensitive to fast ions that circulate in the direction of the plasma current and less sensitive to the trapped-ion and countercirculating populations. Details of the design criteria and solutions are presented.


Sequential synthesis of (E)-alpha,beta-unsaturated primary amides with complete stereoselectivity.
A novel, efficient, and totally stereoselective synthesis of (E)-alpha,beta-unsaturated primary amides is reported. This process is consistent with a SmI(2)-mediated sequential reaction of an unmasked samarium chloroacetamide enolate with an aldehyde, followed by a beta-elimination to produce (E)-alpha,beta-unsaturated primary amides in good yields.


A comparison of the academic impact of plastic surgery units in the United Kingdom and Ireland using bibliometric analysis.
Academic output is just one aspect of a successful career as a plastic surgeon. However, for those with a strong interest in academia, the academic output of a department will likely be a key factor when deciding how to rank jobs. The aim of this study was to quantify and rank the academic output of plastic surgery units across the UK and Ireland. The Institute for Scientific Information (ISI) Web of Science Bibliometric analysis tool was used to collate cumulative (1950-2016), 10 year (2006-2016) and 3 years (2013-2015) research output data for plastic surgery units in the UK and Ireland. Sixty-six plastic surgery units were identified. Departments were ranked for each time period according to the number of papers produced, number of citations (Nc) and h-index (a measure of the impact of scientific output). The top 3 departments for number of papers in the last 10 years were The Royal Free Hospital, London (226) Broomfield Hospital, Chelmsford (218), and Morriston Hospital and Swansea (188). The top 3 for h-number were The Royal Free Hospital (21) Wythenshawe Hospital, Manchester (18) and Morriston Hospital (17). Academic output varies across plastic surgery units in the UK and Ireland. A number of departments have consistently maintained high academic outputs across the years and will be of interest to surgeons hoping to pursue a career in academia.


Probes of spin conservation in heavy metal reactions: experimental and theoretical studies of the reactions of Re+ with H2, D2, and HD.
A guided ion beam tandem mass spectrometer is used to examine the kinetic energy dependence of reactions of the third-row transition metal cation, Re(+), with molecular hydrogen and its isotopologues. A flow tube ion source produces Re(+) in its (7)S(3) electronic ground state. Reaction with H(2), D(2), and HD forms Re H(+)(Re D(+)) in endothermic processes. Modeling of the endothermic reaction cross sections yields the 0 K bond dissociation energy of D(0)(Re(+)-H)=2.29+/-0.07 eV (221+/-6 kJ/mol). The experimental thermochemistry is consistent with ab initio calculations, performed here and in the literature. Theory also provides the electronic structures of these species and is used to examine the reactive potential energy surfaces. Results from reactions with HD provide insight into the reaction mechanisms and indicate that the late metal ion, Re(+), reacts largely via a statistical mechanism. This is consistent with the potential energy surfaces which locate a stable Re H(2) (+)((5)B(2)) complex. Results for this third-row transition metal system are compared with the first-row congener (Mn(+)) and found to have much higher reactivity towards dihydrogen and stronger M(+)-H bonds. These differences can be attributed to efficient coupling among surfaces of different spin along with lanthanide contraction and relativistic effects.


Magnetic studies of ferrofluid-modified microbial cells.
Microbial cells (Kluyveromyces fragilis and Chlorella vulgaris) efficiently interacted with maghemite nanoparticles stabilized as low-pH ionic magnetic fluid, leading to the formation of magnetically labeled cells. This simple procedure allows to use the prepared materials as new cheap and easy to get magnetic affinity adsorbents to the removal of water-soluble dyes from polluted water sources using magnetic separation techniques. Magnetically modified cells were investigated by means of electron spin resonance spectroscopy and conventional magnetic methods over the temperature range 4-300 K. The magnetic behavior of these materials was dominated by the superparamagnetic relaxation of isolated single domain maghemite particles although a little amount of agglomerates was also present on the cell surface. However, these agglomerates were sufficiently small to show at static conditions the superparamagnetic behavior at room temperature. Therefore, the ferrofluid-modified microbial cells represent new interesting magnetic affinity adsorbents which could be applied for large-scale magnetic separation processes.


Calcium, Iron, and Zinc Bioaccessibilities of Australian Sweet Lupin (Lupinus angustifolius L.) Cultivars.
In this study, we aimed to determine the effect of the cultivar and dehulling on calcium, iron, and zinc bioaccessibilities of Australian sweet lupin (ASL). Ten ASL cultivars grown in 2011, 2012, and 2013 in Western Australia were used for the study. The bioaccessibilities of calcium, iron, and zinc in whole seed and dehulled lupin samples were determined using a dialysability method. The cultivar had significant effects on calcium, iron, and zinc contents and their bioaccessibilities. Average bioaccessibilities of 6% for calcium, 17% for iron, and 9% for zinc were found for whole seeds. Dehulled ASL had average calcium, iron, and zinc bioaccessibilities of 11%, 21%, and 12%, respectively. Compared to some other pulses, ASL had better iron bioaccessibility and poorer calcium and zinc bioaccessibilities. Dehulling increased calcium bioaccessibilities of almost all lupin cultivars. The effect of dehulling on iron and zinc bioaccessibilities depends on the ASL cultivar.


Electrical stimulation in the lateral hypothalamus in rats in the activity-based anorexia model.
One quarter of patients with anorexia nervosa have a poor outcome and continue to suffer chronically or die. Electrical brain stimulation may be of therapeutic benefit in some of these patients; however, the brain target for inducing symptom relief is unknown. In this study, the authors evaluated the effects of acute and chronic electrical stimulation in the lateral hypothalamus on food intake, locomotor activity, and survival time in rats in an activity-based anorexia model. In an acute experiment, the authors electrically stimulated at 100 Hz and 0, 25, 50 and 75% of the maximal stimulation amplitude (that is, the amplitude leading to severe side effects) in the lateral hypothalamus on consecutive days during 4 test sessions in 10 rats and evaluated food intake and locomotor activity. In a chronic experiment, they compared food intake, wheel revolutions, and survival time between 6 rats that underwent electrical stimulation in the lateral hypothalamus (50% of maximal stimulation amplitude) and 8 rats that did not undergo stimulation. In the acute experiment, overall electrical stimulation (25, 50, and 75% combined) and stimulation at 75% of the maximal stimulation amplitude significantly decreased the locomotor activity. However, if the authors omitted results of 1 rat, in which the electrode tip was not located in the lateral hypothalamus on one side but rather in the supraoptic chiasm, the remaining results did not yield significance. No other differences were observed. When the findings of the current study are extrapolated to patients with anorexia nervosa, the authors do not expect major effects on symptoms with electrical stimulation at high frequency in the lateral hypothalamus.


A picture is worth a thousand words.
The diagnosis of weight faltering can be challenging and often controversial. The determination should be made based on careful evaluation of growth parameters, including longitudinal patterns plotted on age- and gender-appropriate growth charts. For children with suspected or diagnosed weight faltering, the initial work-up should be limited, with laboratory tests and studies directed by findings on history and physical examination. Treatment should include nutritional counselling, familial support, and close outpatient follow-up. Hospitalisation may be useful in some cases but should not be used routinely to assist in the diagnostic work-up. Patients with limited response to these interventions may require further evaluation.


Susceptibility of nucleotide-binding oligomerization domain 2 mutations to Whipple's disease.
Whipple's disease (WD) results from infection of the bacteria Tropheryma whipplei (TW). This disease is characterized by macrophage infiltration of intestinal mucosa and primarily affects Caucasian males. Genetic studies of host susceptibility are scarce. Nucleotide-binding oligomerization domain containing protein 2 (NOD2) is an innate immune sensor, resides mainly in monocytes/macrophages and contributes to defense against infection and inflammatory regulation. NOD2 mutations are associated with autoinflammatory diseases. We report the association of NOD2 mutations with TW and WD for the first time. A multicenter, retrospective study of three patients with WD was conducted. Patients received extensive multidisciplinary evaluations and were cared for by the authors. NOD2 and its association with infection and inflammation were schematically represented. All patients were Caucasian men and presented with years of autoinflammatory phenotypes, including recurrent fever, rash, inflammatory arthritis, gastrointestinal symptoms, and elevated inflammatory markers. All patients underwent molecular testing using a gene panel for periodic fever syndromes and were identified to carry NOD2 mutations associated with NOD2-associated autoinflammatory disease. Despite initially negative gastrointestinal evaluations, repeat endoscopy with duodenal tissue biopsy ultimately confirmed WD. After initial ceftriaxone and maintenance with doxycycline and/or hydroxychloroquine, symptoms were largely controlled, though mild relapses occurred in follow up. Both NOD2 and TW/WD are intensively involved in monocytes/macrophages. WD is regarded as a macrophage disease. NOD2 leucin rich repeat-associated mutations in monocytes/macrophages cause functional impairment of these cells and consequently may make the host susceptible for TW infection and WD, especially in the setting of immunosuppression.


Midazolams cardiac depressant effects and their lack of reversal by flumazenil in isolated rabbit hearts.
Midazolam is known to cause a dose-dependent increase and decrease in the contractile force of the myocardium. Whether flumazenil can reverse these effects of midazolam remains unclear. In this study, we determined the cardiac effects of midazolam and the counter effect of flumazenil on midazolam-induced myocardial depression in isolated rabbit hearts. Rabbit hearts were isolated and perfused using the Langendorff technique, and left ventricle pressure and heart rate were measured by a pressure transducer in the left ventricle. One set of hearts were perfused with increasing concentrations of midazolam for 10 min, another set were perfused with concomitant midazolam and flumazenil. Concentrations of 5, 10, 20 and 50 microM midazolam decreased left ventricle pressure significantly (P < 0.01, P < 0.05, P < 0.01, P < 0.01, respectively). Heart rates decreased with concentrations of 10, 20 and 50 microM midazolam (P < 0.01, P < 0.01, P < 0.05, respectively). Flumazenil had no effect on the midazolam-induced decrease in left ventricle pressure and heart rate. Midazolam decreased the cardiac contractile force and heart rate of isolated rabbit hearts in a concentration-dependent manner. The failure of flumazenil to reverse these effects suggest that this cardiac depressant effect of midazolam is not mediated through peripheral benzodiazepine receptors.


Absence of a signature of aqueous I(2P(1/2)) after 200-nm photodetachment of I-(aq).
Ultrafast pump-broadband probe spectroscopy was used to study the transient photoproducts following 200-nm photodetachment of I(-)(aq). Resonant detachment at 200 nm in the second charge-transfer-to-solvent (CTTS) band of I(-)(aq) is expected to produce an electron and iodine in its spin-orbit excited state, I*((2)P(1/2)). The transients in solution following photodetachment were probed from 200 to 620 nm. Along with strong absorption in the visible region due to solvated electrons and a strong bleach of the I(-)(aq) ground-state absorption, a weaker transient absorption near 260 nm was observed that is consistent with a previously assigned ground-state I((2)P(3/2)) charge-transfer band. However, no evidence was found for an equivalent I*(aq) charge-transfer absorption, and I((2)P(3/2)) was produced within the instrument response. This suggests either that I* is electronically relaxed in less than 300 fs or that excitation in the second CTTS band does not in fact lead to I*. The consequences for previous experimental work where I*(aq) production has been postulated, as well as for halogen electron ejection mechanisms, are discussed. In addition, the broad spectral coverage of this study reveals in the bleach recovery the rapid cooling of the solvent surrounding the re-formed iodide after geminate recombination of the iodine with the solvated electron.


Factors influencing Chinese college students' preferences for mental health professionals.
Transition from high school to college can be particularly difficult and stressful for Chinese college students because of parent expectations. The purpose of this study was to examine therapist variables influencing Chinese college students' preferences for mental health professionals using conjoint analysis. Two hundred fifty-eight community college students in Hong Kong were asked to rate the profile of 55 mental health professionals representing a combination of therapist characteristics (i.e., gender, age, race/ethnicity, professional background, and training institutions) from the most to least preferred therapist from whom to seek psychological counselling. Results indicated that students' preference formation was based largely on professional background and training institution of the mental health professionals. Clinical psychologists and clinical social workers were preferred over educational psychologists (school psychologists), counsellors, and psychiatrists. Mental health professionals who received training from more prestigious schools were preferred over those trained at less prestigious schools. Understanding clients' preference formation for choosing mental health professionals could be the first step to gain insights for developing effective educational and outreach strategies to promote help seeking behavior and mental health service utilization among Chinese college students.


Simultaneous genotyping of sex and kappa-casein of bovine in vitro fertilized embryos by the PCR technique.
Sex and the kappa-casein genotype of in vitro produced cattle demiembryos was identified by simultaneous PCR-genotyping using polymorphic sites in ZFY/ZFX and kappa-casein genes. We obtained PCR products of 530 bp (kappa-casein) and of 445/447 bp (sex). Sex and the two kappa-casein alleles could be identified after digestion of the PCR products with Pstl and simultaneous separation of the restriction fragments on one step, allowing a rapid and efficient analyses of embryos.


Imitation: a mechanism of play behavior.
Imitation, as a critical mechanism of play behavior, is a primary learning process in child development that has received scant attention in therapists' work with children. The purpose of this study is to conceptualize a system of imitation for occupational therapy within the framework of play behavior, and to analyze this process by using system categories. A case is presented to show how the imitation process can be specifically analyzed and influenced. The imitation process, when applied in clinical practice, could broaden the perspective of existing clinical interventions with children.


The need for closer control of warfarin therapy.
Warfarin therapy is associated with a variety of haemorrhagic complications. We report a representative series of six cases of warfarin-induced bleeding in non-cerebral sites admitted to one unit. In all of these cases, there was inadequate control of anticoagulation, resulting in major morbidity and one death. In particular, closer attention must be paid to the indications for and duration of warfarin treatment.


Isolation and characterization of the tax protein of HTLV-I.
The transactivator protein tax of the human T-cell leukemia virus type I, HTLV-I, is responsible for transactivation of gene expression of viral and cellular genes and is involved in the onset of adult T-cell leukemia, ATL. Genetic deletion studies have implicated a region of the HTLV-I LTR designated as tax-acceptor region, TAR, which is the target of the tax protein. Using antibodies against a tax carboxyterminal synthetic decapeptide the tax protein was purified from an HTLV-I immortalized human T-lymphocyte cell line by immunoaffinity chromatography. The tax protein, purified to apparent homogeneity binds to double-stranded DNA irrespective of its origin from either a nuclear or cytoplasmic fraction of the HTLV-I immortalized cell-line - both of which harbor similar quantities of tax protein. The tax protein binds less to single-stranded DNA and not to single-stranded RNA in vitro. It also binds to DNA-cellulose and heparin-Sepharose. Nuclease treatment of isolated nuclei does not release the tax protein under conditions which release known DNA-binding proteins, such as the myb protein. Transactivation by the tax protein presumably involves host-cell factors, since it does not recognize specific DNA sequences.


Purification of rabbit kidney cytokinase and a comparison of its properties with human urokinase.
1. The cytokinase (tissue activator of plasminogen) content of several mammalian tissues was evaluated by a quantitative casein hydrolysis method. 2. An alkaline (pH10.5) extraction of cytokinase from rabbit kidney lysosome-microsome fraction, followed by chromatography on DEAE-cellulose at pH7.6 with stepwise or linear increase in concentration of phosphate buffer, gave an 86-fold purification of the enzyme. The purified material was non-proteolytic against casein and heated fibrin and was freeze-dried without significant loss of activity or solubility. 3. Cytokinase is a protein with E(0.1%) (1cm.)=0.87 at 280mmu, and does not possess sufficient hexose or sialic acid to be classified as a glycoprotein. It has S(20,w) 2.9-3.1s and molecular weight 50000 when measured on a calibrated Sephadex G-100 column. It has an isoelectric point between pH8 and pH9, and is maximally active and stable at pH8.5. It is inactivated by heat at 78 degrees . 4. Cytokinase and human urokinase have the same K(m) value and are inhibited in a partially competitive manner by in-aminohexanoic acid and aminomethylcyclohexanecarboxylic acid. They are also inhibited by cysteine and arginine, but are unaffected by iodoacetamide and p-chloromercuribenzoate. 5. On the basis of this and other evidence it is suggested that rabbit kidney cytokinase and human urokinase are similar, if not identical, enzymes.


Gender differences in the risk of depressive disorders following the loss of a young child: a nationwide population-based longitudinal study.
Losing a child to death is one of the most stressful life events experienced in adulthood. The aim of the current study is to investigate parental risk of seeking treatment for major depression disorders (MDD) after a child's death and to explore whether such connection may operate differentially by parents' prior medical condition. We studied a retrospective cohort of 7245 parents (2987 mothers and 4258 fathers) identified in the National Health Insurance Research Database of Taiwan (NHIRD) who had lost a child with age between 1 and 12 years. For comparison, the parents of 1:4 birth year- and gender-matched non-deceased children were retrieved (16,512 mothers and 17,753 fathers). Gender-specific Cox regression analyses were performed to estimate risk. Nearly 5.0% and 2.4% of bereaved mothers and fathers sought treatment for MDD within three years after a child's death, significantly higher than 0.8% and 0.5% in the non-bereaved parents. With covariate adjustment, the hazard ratio (HR) for maternal and paternal seeking treatment for MDD was estimated 4.71 (95% confidence interval [CI]: 3.35-6.64) and 1.93 (95% CI: 1.27-2.95), respectively. The increased risk of MDD varied by prior disease history; specifically, the increased risk of seeking treatment for MDD was especially prominent for those without chronic physical condition (CPC) (e.g., mothers with CPC: aHR = 2.38, 95% CI: 1.56-3.65 vs. no CPC: aHR = 9.55, 95% CI: 6.17-14.79). After the death of a child, parental elevated risk of MDD was especially prominent for the women and those without prior medical condition. Effective strategies addressing bereavement may require family-based, integrated physical and mental healthcare and even extended counseling service.


Strengthened Surface Modification for High-Performance Inorganic Perovskite Solar Cells with 21.3% Efficiency.
Metal halide inorganic perovskites show excellent thermal stability compared to organic-inorganic perovskites. However, the performance of inorganic perovskite solar cells (PSCs) is far from theoretical values, together with unsatisfactory stability, mainly due to the poor interfacial properties. In this work, a facial but effective method is reported to realize high-performance inorganic PSCs by post-modifying the perovskite surface with 2-thiophene ethylamine (TEA). It is found that amine group from TEA can favorably interact with the undercoordinated Pb2+ via Lewis acid-based coordination, while thiophene ring with electron-rich sulfur assists such interaction by functioning as an electron donor. The synergetic interaction allows TEA to passivate perovskite film defects more efficiently, as compared to phenethylamine (PEA) with less electron-donating ability. Moreover, perovskite valence band is slightly upward shift to match with hole transport material and facilitate hole transfer. These combinations result in a reduced non-radiative charge recombination and improved charge carrier lifetime. Consequently, PSCs with TEA modification shows a drastic improvement of VOC by 54 mV, yielding a champion PCE of 21.3%, much higher than the control PSCs (19.3%), along with improved ambient stability. This work demonstrates that surface modifier with an electron-rich moiety is critical for achieving efficient and stable inorganic PSCs.


Effect of spark plasma sintering on plasma electrolytic oxidation coatings on gas-atomized Mg-Zn-Y alloy containing nano-sized powders.
Mg-1.0wt%Zn-2.0wt%Y alloy powders were produced by gas atomization, and subsequently sintered by spark plasma sintering (SPS). The SPSed Mg-1.0wt%Zn-2.0wt%Y alloy, which showed a microstructure of well-bonded grains containing nano-sized powders of approximately 100 nm in diameter, was coated by a plasma electrolytic oxidation (PEO) method. Microstructure, mechanical properties and corrosion properties of PEO coatings were investigated and compared to those of normally sintered Mg-1.0wt%Zn-2.0wt%Y and cast Mg-1.0wt%Zn alloys. All coatings consisted of MgO and Mg2SiO4. The micro-hardness and friction coefficient of coatings on the SPSed Mg-1.0wt%Zn-2.0wt%Y alloy were higher than those on normally sintered Mg-1.0wt%Zn-2.0wt%Y and cast Mg-l.0wt%Zn alloys. However, the corrosion resistance in 3.5% NaCl solution for the SPSed Mg-1.0wt%Zn-2.0wt%Y alloy was between that for normally sintered Mg-1.0wt%Zn-2.0wt%Y alloy and cast Mg-1.0wt%Zn alloy.


Epidemiology and Financial Burden of Musculoskeletal Injuries as the Leading Health Problem in the Military.
Musculoskeletal injuries (MSIs) have direct impact on occupational readiness and task performance in military populations. Until this date, no epidemiologic data have been published concerning MSI incidence in the Netherlands Armed Forces (NAF). The aim of this study was to assess the MSI incidence and related costs in the NAF. In this descriptive epidemiologic study, we collected injury surveillance data from the electronic patient records of multiple military units of the NAF. Using data of all new consultations with a military physician from January 1, 2014 to December 31, 2016, we calculated MSI incidence rates per 100 person-years, with a 95% confidence interval (CI). Physician care costs were determined based on the number of physician consults and the charge per appointment. We used two methods to determine productivity costs; the top-down microcosting method and the friction cost method. Our study sample included 22% (n = 8,847) of the total NAF population of 2016 (n =40,178). In this sample, consultations of MSIs accounted for 23.2% (n = 7,815) of all new consultations (n = 33,666). MSI incidence rates per unit ranged from 12.5 to53.3 per 100 person-years. In the total sample, MSI incidence rates were highest in the back (6.73, 95% CI 6.39-7.10), knee (5.04, 95% CI 4.74-5.35), and foot (4.79, 95% CI 4.50-5.10). The estimated costs for physician visits for MSIs in our sample were €0.69 million. Limited duty days accounted for €1.10 million productivity costs using top-down microcosting method. Our study provided evidence that MSIs result in substantial financial burden. Injuries of the back, knee, and foot account for the majority of demands on curative care for MSIs.