Behavioral and emotional response of Japanese macaque (Macaca fuscata) mothers after their offspring receive an aggression.
The authors of this study investigated the behavioral and emotional response of female Japanese macaques (Macaca fuscata) to an aggression received by their offspring to evaluate the existence of cognitive empathic responses in a naturalistic setting. After their offspring received an aggression, mothers did not direct increased affiliative contacts to them. The factors likely to affect the degree of distress in the offspring or the perceived risk for the mother failed to appropriately modulate maternal behavior. Finally, mothers did not increase their frequency of scratching (a behavioral indicator of anxiety) after their offspring had received an aggression. The results suggest Japanese macaque mothers may be unable to understand their offspring's need for distress alleviation after the receipt of aggression.


OTA highlight paper predicting future displacement of nonoperatively managed lateral compression sacral fractures: can it be done?
This study was designed to assess the rate of displacement in nondisplaced sacral fractures and to determine if certain fracture patterns are more prone to future displacement. Retrospective. Two Level I trauma centers. Patients consisted of those sustaining a lateral compression pelvic fracture whose age was 17 years or older, had less than 5 mm of initial sacral displacement, were the result of a high-energy mechanism, and had radiographs documenting bony union. By protocol, patients meeting these criteria were mobilized and maintenance of alignment was documented by serial radiographs. All fractures were classified according to the Orthopaedic Trauma Association classification system, the Young and Burgess mechanistic classification system, and to the location of the sacral fracture as described by Denis. In addition, sacral fractures were classified as complete or incomplete. Additionally, the number and location of rami fractures were recorded. Of the initial 117 fractures, 23 were determined to displace and largely consisted of a single fracture pattern. Fractures consisting of a complete sacral fracture combined with bilateral rami fractures displaced at a rate of 68% (15 of 22). In contrast, incomplete sacral fractures with an ipsilateral rami injury had no displaced unions. Incomplete lateral compression sacral fractures that are associated with ipsilateral rami fractures can be treated nonoperatively and are unlikely to displace. In contrast, those with a complete sacral fracture and bilateral rami fractures displace at a significantly greater rate.


[Health in Puerto Rico in the 20th century].
The evolution in physical condition, life expectancy at birth, and access to preventive and curative services rapidly improved the quality of life of Puerto Ricans in the twentieth century. The population quadrupled to almost 4 million inhabitants and the crude mortality rate fell from 38 per thousand in 1900 to 7.7 per thousand in 1997, with its most dramatic change (18.6 to 6.7) occurring from 1941 to 1960. The great promoters of health were the general increase in socioeconomic level, improvements in infrastructure, and vaccines; its great scourges were infectious diseases (from hookworm to AIDS) and social dislocations, such as the war of 1917 (accompanied by epidemics and hunger) or the present war between illicit drug distributors. This article summarizes the events in the century related to health and its political and economic contexts, the developments in public health structures and health care, professional education, volunteer organizations, campaigns against infectious diseases, chronic causes of mortality, and environmental problems. Bringing the capacity to defend public health to the level of sophistication available for clinical care is one of the vital challenges of the twenty-first century for Puerto Rico.


[Expression of the cdx2 gene in benign intestinal-type mucinous ovarian tumors].
Cdx2 gene belongs to the homeobox caudal gene family and it is located, in humans, on the 13q12.3 chromosome; in particular it codifies for a specific nuclear transcription factor which induces intestinal epithelium development, differentiation and preservation. Cdx2 expression in the human embryo can be observed in the intestinal epithelium starting from the sixth week of gestation. In the foetus and in adults it is observed in the whole enteric tube from the duodenum to the anal canal. Because of its organ specificity, cdx2 is an important marker for metastatic neoplastic lesions. Cdx2 is expressed in intestinal metaplasia and it is focally positive in adenocarcinomas of intestinal type of the stomach, pancreas and gall bladder as well as in ovarian mucinous adenocarcinomas. FINALITY OF THE STUDY: The aim of our study is to detect cdx2 positivity, with evaluation of its characteristics and expression, in ovarian mucinous cistoadenomas. We examined cdx2 expression in 50 ovarian mucinous cistoadenomas (mean age between 17 and 85), 19 of which were localised in the right ovary while 31 in the left one. Standard staining techniques (H&E), histochemistry (AB-PAS) ed immunohistochemistry with monoclonal antibodies against cdx2 (Biogenex/Menarini cdx2-88, batch MU3920402XS) were performed on formalin fixed and paraffin embedded material. For each case two samples were analysed. Morphological evaluation of the 50 benign mucinous tumours distinguished 47 of endocervical type and 3 of intestinal type. These data were also confirmed by characterisation of mucin profile by AB-PAS staining. Using anti-cdx2 antibodies tumours of endocervical type were negative, while 3 intestinal type tumours were positive. In particular 2 cases presented diffuse nuclear positivity, while in one positivity was only focal. Until today only two studies deal with cdx2 expression in mucinous ovarian tumours: 5 and 14 cases strong respectively. In the former, cdx2 expression was positive in all cases (100% positivity--5/5), in the latter cdx2 expression was positive in 64% of cases (9/14). In order to explain the lack of consistency in these data one must analyse ovarian mucinous tumours in detail. These neoplasms are divided into two subtypes: endocervical type and intestinal type. Distinction between these two types is near to impossible in malignant tumours, difficult in borderline tumours while it becomes easy in benign ones. Among benign tumours, endocervical type tumours are the majority, while intestinal type are much more infrequent. Our 50 case strong casistic is sufficiently ample to include 3 cases of intestinal type, all of which are cdx2 positive, compared to a complete negativity in the remaining 47 tumours clearly of endocervical type. We believe that the lack of consistency between the aforementioned studies is probably due to the fact that neither work contemplates the subdivision in intestinal and endocervical types. It is hence possible to hypothesise a selective and specific correlation between cdx2 positivity and the intestinal type epithelial component of ovarian tumours.


Long-Term Outcome of Transcutaneous Posterior Tibial Nerve Stimulation in the Treatment of Functional Non-Retentive Fecal Incontinence in Children.
Functional non-retentive fecal incontinence (FNRFI) is a psychologically upsetting and embarrassing issue and affects children's quality of life negatively. Evaluation of the short and long-term effect of Bilateral transcutaneous posterior tibial nerve stimulation (BTPTNS) in the treatment of FNRFI in children and its impact on the quality of life (QoL). Methodology: The current randomized controlled study included 94 Children with FNRFI who were randomly allocated into two equal groups. Group A received BTPTNS and Group B Received Sham BTPTNS. Follow-up was planned for 24 months for manometric findings, incontinence score, Incontinence episodes, and the QoL. The incontinence score was significantly decreases in Group A more than what was reported in Group B at 6, 12, 24 months follow up . In group A 53.2% of the included children who received BTPTNS showed a decrease in the incontinence episodes more than 75% and among them, 23.4% were fully continent. All the QoL domains were significantly improved in Group A after 6, 12, and 24 months when compared with Group B. BTPTNS can be a good modality in the treatment of FNRFI with favorable long-term maintenance of its effect together with a remarkable positive impact on all domains of QoL.


The serial organisation of behaviour by non-human primates; an evaluation of experimental paradigms.
On close examination of research programs which focus, either implicitly or explicitly, on the problem of the organisation of serial order in non-human primates, it is possible to detect some limitations in the paradigms conventionally used. Serial learning studies, which focus on the acquisition of arbitrary lists of unconnected elements point towards a distinction between the representation of ordered series formed by monkeys and pigeons. However, the use of unconnected items prevents an assay of the degree to which primates might be able to impose a structure over the list to be reported. The study of transitive reasoning has been implemented by means of a paradigm where the order of a series is conveyed be presenting a common item in pairs of binary discriminations. Animals tested with this paradigm develop control strategies using more information than that provided by reward contingencies alone. A restriction of this paradigm is that, in its binary form, it does not allow a differentiation between the performance of monkeys and pigeons and even simple models account for a transitive bias in the task. On the basis of these observations it is proposed that novel paradigms which go beyond the binary context, feature multiple connected items, and accord a high degree of spontaneity to the subjects might allow better than traditional ones to uncover qualitative different ways in which different organisms serially organise their behaviour. Some recent research programs based on such rationale, and implemented as search tasks, are then outlined and compared with other approaches to the study of search behaviour. Preliminary results obtained from these studies indicate that the spontaneous serial organisation of multiple connected items might uncover new dimensions of promising comparative relevance.


Community Health Worker Interventions to Improve Glycemic Control in People with Diabetes: A Systematic Review and Meta-Analysis.
We set out to review the efficacy of Community Health Worker (CHW) interventions to improve glycemia in people with diabetes. Data sources included the Cochrane Central Register of Controlled Trials, Medline, clinicaltrials.gov, Google Scholar, and reference lists of previous publications. We reviewed randomized controlled trials (RCTs) that assessed the efficacy of CHW interventions, as compared to usual care, to lower hemoglobin A1c (A1c). Two investigators independently reviewed the RCTs and assessed their quality. Only RCTs with a follow-up of at least 12 months were meta-analyzed. A random effects model was used to estimate, from unadjusted within-group mean reductions, the standardized mean difference (SMD) in A1c achieved by the CHW intervention, beyond usual care. Thirteen RCTs were included in the narrative review, and nine of them, which had at least 12 months of follow-up, were included in the meta-analysis. Publication bias could not be ruled-out due to the small number of trials. Outcome heterogeneity was moderate (I(2)= 37%). The SMD in A1c (95% confidence interval) was 0.21 (0.11-0.32). Meta-regression showed an association between higher baseline A1c and a larger effect size. CHW interventions showed a modest reduction in A1c compared to usual care. A1c reduction was larger in studies with higher mean baseline A1c. Caution is warranted, given the small number of studies.


The role of the fetal fibroblast and transforming growth factor-beta in a model of human fetal wound repair.
The fetus heals skin wounds without scar formation. Human fetal skin that is transplanted to a subcutaneous location on an adult athymic mouse and subsequently wounded heals without scar formation, whereas the same fetal skin heals with scar formation when transplanted to a cutaneous location. To characterize the healing process of human fetal skin in these two locations, species-specific human and mouse DNA probes were constructed and used to probe graft wounds under high stringency in situ hybridization conditions. Immunostaining for species-specific fibroblasts, macrophages, and neutrophils was also performed. The cutaneous human fetal graft healed with scar and showed an influx of adult mouse fibroblasts and macrophages. In contrast, subcutaneous human fetal grafts showed exclusively human fetal fibroblasts in the wound environment, an absence of inflammatory cells, and scar-free repair. Thus, the highly organized collagen deposition in scarless human fetal wound repair appears to be intrinsic to the human fetal fibroblast and occurs in the absence of an adult-like inflammatory response. One important cytokine involved in wound repair is transforming growth factor-beta (TGF beta). TGF beta promotes inflammatory cell recruitment and collagen deposition in healing wounds. To determine the role of TGF beta 1 in fetal wound healing, in situ hybridization for TGF beta 1 mRNA expression, immunostaining for TGF beta protein, and species-specific immunohistochemistry for fibroblasts, macrophages, and neutrophils were performed in human adult wounds, fetal wounds, and fetal wounds treated with a TGF beta 1 slow release disk. TGF beta 1 RNA expression and TGF beta protein were found in wounded adult skin. Neither TGF beta 1 mRNA upregulation nor TGF beta protein was detected in human fetal skin after wounding. However, when exogenous TGF beta 1 was added to human fetal skin, induction of TGF beta 1 mRNA expression in human fetal fibroblasts occurred, an adult-like inflammatory response was detected, and the skin healed with scar formation. Thus, non-scarring fetal skin is relatively TGF beta 1 deficient when compared to scarring adult skin. Furthermore, when exogenous TGF beta is added to fetal skin, scarring occurs. TGF beta appears to be an important modulator in scar formation. With a more thorough understanding of scarless repair mechanisms, clinical induction of scarless healing in adults and children soon may be possible.


Senicapoc treatment in COVID-19 patients with severe respiratory insufficiency-A randomized, open-label, phase II trial.
The aim of the current study was to determine if treatment with senicapoc, improves the PaO2 /FiO2 ratio in patients with COVID-19 and severe respiratory insufficiency. Investigator-initiated, randomized, open-label, phase II trial in four intensive care units (ICU) in Denmark. We included patients aged ≥18 years and admitted to an ICU with severe respiratory insufficiency due to COVID-19. The intervention consisted of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 h. Patients in the control group received standard care only. The primary outcome was the PaO2 /FiO2 ratio at 72 h. Twenty patients were randomized to senicapoc and 26 patients to standard care. Important differences existed in patient characteristics at baseline, including more patients being on non-invasive/invasive ventilation in the control group (54% vs. 35%). The median senicapoc concentration at 72 h was 62.1 ng/ml (IQR 46.7-71.2). The primary outcome, PaO2 /FiO2 ratio at 72 h, was significantly lower in the senicapoc group (mean 19.5 kPa, SD 6.6) than in the control group (mean 24.4 kPa, SD 9.2) (mean difference -5.1 kPa [95% CI -10.2, -0.04] p = .05). The 28-day mortality in the senicapoc group was 2/20 (10%) compared with 6/26 (23%) in the control group (OR 0.36 95% CI 0.06-2.07, p = .26). Treatment with senicapoc resulted in a significantly lower PaO2 /FiO2 ratio at 72 h with no differences for other outcomes.


[Antiphospholipid syndrome in Pediatrics: a case report].
The antiphospholipid syndrome is a multisystem autoimmune disease in which autoantibodies against a variety of phospholipids and phospholipid binding proteins are produced. It occurs in 1.8% of the population and only 2% of the cases are pediatric. The spectrum of clinical manifestations is wide from asymptomatic patients to a life-threatening disease like the catastrophic antiphospholipid syndrome. Any organ can be affected. The most frequent manifestations in pediatrics correspond to venous thrombosis in 60% of patients, arterial thrombosis in 32%, hematological disease in 38% (thrombocytopenia, leucopenia), skin alterations in 18% (livedo reticularis, Raynaud's phenomenon) and neurological signs in 16%. We describe the case of a previously healthy 14-year-old female patient diagnosed with antiphospholipid syndrome.


Reactive oxygen species mediate virus-induced STAT activation: role of tyrosine phosphatases.
Respiratory syncytial virus (RSV) is the leading cause of epidemic respiratory tract illness in children in the United States and worldwide. RSV infection of airway epithelial cells induces formation of reactive oxygen species (ROS), whose production mediates the expression of cytokines and chemokines involved the immune/inflammatory responses of the lung. In this study, we have investigated the role of ROS in RSV-induced signal transducers and activators of transcription (STAT) activation and interferon regulatory factor (IRF) gene expression in human airway epithelial cells. Our results indicate that RSV replication induces IRF-1 and -7 gene transcription, a response abrogated by antioxidants. RSV infection induces binding of STAT to the IRF-1 gamma-interferon-activated sequence (GAS) and IRF-7 interferon-stimulated responsive element (ISRE). STAT1 and STAT3 bind IRF-1 GAS, whereas STAT1, STAT2, IRF-1, and IRF-9 bind IRF-7 ISRE. Antioxidant treatment blocks RSV-induced STAT binding to both the IRF-1 GAS and IRF-7 ISRE by inhibition of inducible STAT1 and STAT3 tyrosine phosphorylation, suggesting that RSV-induced ROS formation is required for STAT activation and IRF gene expression. Although protein tyrosine phosphorylation is necessary for RSV-induced STAT activation, Janus kinase and Src kinase activation do not mediate this effect. Instead, RSV infection inhibits intracellular tyrosine phosphatase activity, which is restored by antioxidant treatment. Pharmacological inhibition of tyrosine phosphatases induces STAT activation. Together, these results suggest that modulation of phosphatases could be an important mechanism of virus-induced STAT activation. Treatment of alveolar epithelial cells with the NAD(P)H oxidase inhibitor diphenylene iodonium abolishes RSV-induced STAT activation, indicating that NAD(P)H oxidase-produced ROS are required for downstream activation of the transcription factors IRF and STAT in virus-infected airway epithelial cells.


Formation of dioxins from combustion micropollutants over MSWI fly ash.
Formation of polychlorinated dibenzofurans and dibenzo-p-dioxins (PCDD/Fs) from a model mixture of products of incomplete combustion (PICs) representative of municipal solid waste incineration (MSWI) flue gases, over a fixed bed of MSWI fly ash has been investigated. For comparison, a single model compound (chlorobenzene) was also briefly studied. A newly developed lab-scale system enabled the application of (very) low and stable concentrations of organic substances--of 10(-6) M or less-to approach realistic conditions. Samples taken at several time intervals allowed the observation of changes in rates and patterns due to depletion of the carbon in fly ash. The model flue gas continuously produced PCDDs and PCDFs after the de novo reaction had ceased to occur. Dioxin output levels are comparable to those of "old" MSW incinerators. Replacing the PIC trace constituent phenol by its fully 13C-labeled analogue led to, e.g., PCDD with one labeled ring as prominent product, meaning that the formation is about first order in phenol, contrary to earlier assumptions. The meaning of the results for the formation of dioxins in the MSWI boiler is discussed.


Design of Synthetic Polymer Nanoparticles That Facilitate Resolubilization and Refolding of Aggregated Positively Charged Lysozyme.
Designed polymer hydrogel nanoparticles (NPs) capable of facilitating resolubilization and refolding of an aggregated protein, positively charged lysozyme, are prepared. NPs designed to interact strongly with denatured lysozyme and relatively weakly with native lysozyme, facilitated resolubilization and refolding of aggregated lysozyme. Such NPs could be prepared by copolymerizing optimized combinations and populations of functional monomers. The refolded lysozyme showed native conformation and enzymatic activity. Eleven grams of aggregated protein was refolded by 1 g of NPs. However, NPs having low affinity to denatured lysozyme and NPs having high affinity to both denatured and native lysozyme showed relatively low facilitation activity. Our results suggest a potential strategy for the design of artificial chaperones with high facilitating activity.


Transmitted duplication of 8p23.1-8p23.2 associated with speech delay, autism and learning difficulties.
Duplications of distal 8p with and without significant clinical phenotypes have been reported and are often associated with an unusual degree of structural complexity. Here, we present a duplication of 8p23.1-8p23.2 ascertained in a child with speech delay and a diagnosis of ICD-10 autism. The same duplication was found in his mother who had epilepsy and learning problems. A combination of cytogenetic, FISH, microsatellite, MLPA and oaCGH analysis was used to show that the duplication extended over a minimum of 6.8 Mb between 3 539 893 and 10 323 426 bp. This interval contains 32 novel and 41 known genes, of which only microcephalin (MCPH1) is a plausible candidate gene for autism at present. The distal breakpoint of the duplicated region interrupts the CSMD1 gene in 8p23.2 and the medial breakpoint lies between the MSRA and RP1L1 genes in 8p23.1.An interchromosomal insertion between a normal and polymorphically inverted chromosome 8 is proposed to explain the origin of this duplication. Further mapped imbalances of distal 8p are needed to determine whether the autistic component of the phenotype in this family results from the cumulative imbalance of many genes or dosage imbalance of an individual susceptibility gene.


Vision and reading disability: research problems.
This paper reviews and analyzes the methodological problems of the studies of the relationship of vision and reading disability. Procedures that lead to false positive and false negative findings are discussed. False positive findings can be due to problems in subject selection procedures and criteria, failure to take into account correction of vision problems, use of unselected comparison groups, using unskilled testers, small sample size, and data analysis problems. False negative findings can be due to experimenter expectations, lack of a comparison group, statistical tests and use of clinical samples and failure to rule out competing explanations.


Examining the relations between self-regulation and achievement in third grade students.
Children with stronger self-regulation skills generally demonstrate greater overall success in school both academically and socially. However, there are few valid and reliable measures of self-regulation in middle elementary school. Such a measure could help identify whether a child is truly having difficulties. Thus, the Remembering Rules and Regulation Picture Task (RRRP) was developed. The aim of this study was to develop scoring systems for the RRRP and then to examine the associations between RRRP and independent measures of self-regulation and academic achievement in mathematics and reading. Children (n = 282) from 34 third grade classrooms in Florida participated in this study. Results revealed that the RRRP captured three constructs: working memory, attentional flexibility, and inhibitory control. Hierarchical linear modeling (HLM) demonstrated that the RRRP was significantly and positively associated with other measures of self-regulation. The RRRP was significantly and positively associated with mathematics and reading as well. The RRRP appears to be a promising measure of children's self-regulation skills.


Making medicinal chemistry more effective--application of Lean Sigma to improve processes, speed and quality.
The pharmaceutical industry, particularly the small molecule domain, faces unprecedented challenges of escalating costs, high attrition as well as increasing competitive pressure from other companies and from new treatment modes such as biological products. In other industries, process improvement approaches, such as Lean Sigma, have delivered benefits in speed, quality and cost of delivery. Examining the medicinal chemistry contributions to the iterative improvement process of design-make-test-analyse from a Lean Sigma perspective revealed that major improvements could be made. Thus, the cycle times of synthesis, as well as compound analysis and purification, were reduced dramatically. Improvements focused on team, rather than individual, performance. These new ways of working have consequences for staff engagement, goals, rewards and motivation, which are also discussed.


[Temporo-mandibular joint pain dysfunction syndrome in children].
Otalgia is a common symptom in children. Otological examination usually reveals a local pathology as the causative agent. However, it does occur that otoscopy reveals normal ear drums and canals. The otologist must then review the causes of referred otalgia. We know that the ear is a nervous crossroad: vagus, trigeminal and third cervical nerve. The most common causes of referred otalgia are the teeth, the sinus, the mouth, the pharynx, and the larynx. If none of these factors is involved, one must then think about the painful temporomandibular dysfunction syndrome.


Distal Val346Ile mutation in inducible NO synthase promotes substrate-dependent NO confinement.
The function of inducible NO synthase (WT iNOS) depends on the release of NO from the ferric heme before the enzyme is reduced. Key parameters controlling ligand dynamics include the distal and proximal heme pocket amino acids, as well as the inner solvent molecules. In this work, we tested how a point mutation in the distal heme side of WT iNOS affected the geminate rebinding of NO by ultrafast kinetics and molecular dynamics simulations. The mutation sequestered much of the photodissociated NO close to the heme compared to WT iNOS, with a main picosecond phase accounting for 78% of the rebinding to the arginine-bound Val346Ile protein. Consequently, the probability of NO release from Val346Ile decreased as compared to that from WT iNOS, provided the substrate binding site is filled. These data are rationalized by a steric effect of the Ile methyl group inducing events mediated by the substrate, transmitted via the propionates to the NO and the protein. This model is consistent with the role of the H-bonding network involving the heme, the substrate, and the BH4 cofactor in controlling NO release, with a key role of the heme propionates [Gautier et al. (2006) Nitric Oxide 15, 312]. These data support the effect of Val346Ile mutation in decreasing NO release and slowing down NO synthesis compared to WT iNOS determined by single turnover catalysis [Wang et al. (2004) J. Biol. Chem. 279, 19018].


Human prion protein sequence elements impede cross-species chronic wasting disease transmission.
Chronic wasting disease (CWD) is a fatal prion disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165-175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165-175) that exactly matches that of elk PrP. Compared with transgenic mice expressing unaltered human PrP, mice expressing the human-elk chimeric PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to human Creutzfeldt-Jakob disease prions. A systematic in vitro survey of amino acid differences between humans and cervids identified two additional residues that impacted CWD conversion of human PrP. This work identifies amino acids that constitute a substantial structural barrier for CWD transmission to humans and helps illuminate the molecular requirements for cross-species prion transmission.


Structural and functional changes with depth in microbial communities in a tropical Malaysian peat swamp forest.
Tropical peat swamp forests are important and endangered ecosystems, although little is known of their microbial diversity and ecology. We used molecular and enzymatic techniques to examine patterns in prokaryotic community structure and overall microbial activity at 0-, 10-, 20-, and 50-cm depths in sediments in a peat swamp forest in Malaysia. Denaturing gradient gel electrophoresis profiles of amplified 16S ribosomal ribonucleic acid (rRNA) gene fragments showed that different depths harbored different bacterial assemblages and that Archaea appeared to be limited to the deeper samples. Cloning and sequencing of longer 16S rRNA gene fragments suggested reduced microbial diversity in the deeper samples compared to the surface. Bacterial clone libraries were largely dominated by ribotypes affiliated with the Acidobacteria, which accounted for at least 27-54% of the sequences obtained. All of the sequenced representatives from the archaeal clone libraries were Crenarchaeota. Activities of microbial extracellular enzymes involved in carbon, nitrogen, and phosphorus cycling declined appreciably with depth, the only exception being peroxidase. These results show that tropical peat swamp forests are unusual systems with microbial assemblages dominated by members of the Acidobacteria and Crenarchaeota. Microbial communities show clear changes with depth, and most microbial activity is likely confined to populations in the upper few centimeters, the site of new leaf litter fall, rather than the deeper, older, peat layers.


Accurate interaction energies of hydrogen-bonded nucleic acid base pairs.
Hydrogen-bonded nucleic acids base pairs substantially contribute to the structure and stability of nucleic acids. The study presents reference ab initio structures and interaction energies of selected base pairs with binding energies ranging from -5 to -47 kcal/mol. The molecular structures are obtained using the RI-MP2 (resolution of identity MP2) method with extended cc-pVTZ basis set of atomic orbitals. The RI-MP2 method provides results essentially identical with the standard MP2 method. The interaction energies are calculated using the Complete Basis Set (CBS) extrapolation at the RI-MP2 level. For some base pairs, Coupled-Cluster corrections with inclusion of noniterative triple contributions (CCSD(T)) are given. The calculations are compared with selected medium quality methods. The PW91 DFT functional with the 6-31G basis set matches well the RI-MP2/CBS absolute interaction energies and reproduces the relative values of base pairing energies with a maximum relative error of 2.6 kcal/mol when applied with Becke3LYP-optimized geometries. The Becke3LYP DFT functional underestimates the interaction energies by few kcal/mol with relative error of 2.2 kcal/mol. Very good performance of nonpolarizable Cornell et al. force field is confirmed and this indirectly supports the view that H-bonded base pairs are primarily stabilized by electrostatic interactions.


Unpacking Healthcare Professionals' Work to Achieve Coherence in the Healthcare Journey of Elderly Patients: An Interview Study.
Today, seamless, person-centered healthcare is emphasized when dealing with elderly patients with comprehensive needs. Studies have uncovered a complex healthcare terrain. Despite a great deal of effort on the part of policy makers and healthcare providers, the work healthcare professionals undertake to develop seamless healthcare is still unclear. Therefore, the aim of this study was to uncover the work that healthcare professionals undertake to achieve coherent and comprehensive healthcare for elderly patients with multiple health problems during their journey through the complex healthcare terrain. This study has an explorative design with individual interviews. Twenty-five healthcare professionals from primary and specialist care agreed to participate. A thematic analysis method was employed. The analyses revealed three central themes in the healthcare professionals' work to build coherence in the patients' care trajectory: Working to manage a patient's illness trajectory during the course of the patient's life, working to achieve a comprehensive overall picture, and considering multiple options in a "patchwork" terrain. Healthcare professionals have a common understanding that hospital stays are a short part of the elderly person's journey in the healthcare system. In the comprehensive work to obtain the overall picture of the illness trajectory within the patient's life story, healthcare professionals emphasized the importance of working in an interdisciplinary manner. Interprofessional consulting and collaboration should be strengthened to build coherence in the older patient's complex care trajectory.


In Vitro Antibacterial, Antioxidant, Anticholinesterase, and Antidiabetic Activities and Chemical Composition of Salvia balansae.
Salvia balansae de Noé (S. balansae) (Lamiaceae) is known to be an important plant used in folk medicine as an herbal remedy in Algeria. The purpose of the present study was to demonstrate the phytochemical composition, antioxidant activities, enzyme inhibitory activities, and antimicrobial activities of S. balansae extracts. A methanolic extract and a petroleum ether extract from the aerial parts of the plant were assessed for their chemical composition. HPLC-MS and HPLC-DAD assessed the content of phenols, GC-MS the fatty acid composition, and ICP-MS the mineral profiles of the plant. Additionally, we evaluated the bioactivities of S. balansae extracts by the DPPH, ABTS, and CUPRAC assays, including the antioxidant potential against AChE, BChE, α-amylase, and α-glucosidase for enzyme inhibition. The antibacterial and antifungal activities of the methanolic extract were determined by the disc diffusion test against several strains of bacteria and yeasts. Our findings revealed that the aerial parts of S. balansae were rich in phytochemical components and contained large amounts of minerals. Quantitative analysis of phenolic compounds by HPLC-DAD revealed the presence of 12 compounds in three major classes, flavonoids, hydroxycinnamic acid, and phenolic acid derivatives, with 0.61, 0.45, and 0.29 mg/g of extract, respectively. Nine phenolic constituents were quantified by HPLC-MS analysis; catechin (72.5%) was the main compound, followed by myricetin (21.7%). The fatty acid composition of the S. balansae petroleum ether extract by GC-MS analysis was quantified. Seventeen compounds, including palmitic acid, were identified as the major fatty acids. The antioxidant activity of the S. balansae extracts was measured by three different methods: the methanol extract provided better results than the petroleum ether extract, and interesting values were noted for the DPPH, ABTS, and CUPRAC assays of 242.7 ± 7.44, 124.1 ± 9.70, and 222.9 ± 6.05 µg/mL, respectively. The enzyme inhibition activity of the plant could not be determined. The antimicrobial results of the methanolic extract obtained from the disc diffusion method, followed by measurements of MIC, MBC, and MFC against several bacteria and yeasts, indicated that S. balansae exhibited noticeable antimicrobial and antifungal activities. These results provided new data about the main phenolic compounds and biological activities of extracts of the aerial parts of S. balansae, which might be an alternative source for synthetic bioactive compounds.


Streptomyces wuyuanensis sp. nov., an actinomycete from soil.
A novel actinomycete, strain FX61(T), was isolated from a saline sample collected from the Inner Mongolian Autonomous Region in China and subjected to a taxonomic study using a polyphasic approach. The predominant menaquinones were MK-9(H6), MK-9(H8) and MK-9(H4). The major fatty acids were iso-C16 : 0, anteiso-C15 : 0, iso-C15 : 0, iso-C16 : 1 H, C16 : 0, iso-C14 : 0 and anteiso-C17 : 0. The phospholipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, two phosphatidylinositol mannosides and an unidentified phospholipid. The G+C content of the genomic DNA was 72 mol%. The 16S rRNA gene sequence of the isolate had greater than 98 % similarity with those of Streptomyces griseoincarnatus ATCC 23623(T) (98.2 %), Streptomyces labedae DSM 41446(T) (98.2 %), Streptomyces variabilis ATCC 19815(T) (98.2 %), Streptomyces erythrogriseus ATCC 27427(T) (98.2 %), Streptomyces matensis ATCC 23935(T) (98.2 %), Streptomyces althioticus ATCC 19724(T) (98.2 %) and Streptomyces luteosporeus ATCC 33049(T) (98.0 %), showing that the novel strain should be assigned to the genus Streptomyces. DNA-DNA hybridizations with the seven above-mentioned members of the genus Streptomyces showed 29.8, 28.5, 27.0, 25.5, 25.0, 23.5 and 22.0 % relatedness, respectively. On the basis of the phenotypic characteristics and genotypic distinctiveness, strain FX61(T) should be classified as a novel species of the genus Streptomyces, for which the name Streptomyces wuyuanensis sp. nov. is proposed. The type strain is FX61(T) (= CGMCC 4.7042(T) = KCTC 29112(T)).


Enzyme immunoassay of testosterone, 17beta-estradiol, and progesterone in perspiration and urine of preadolescents and young adults: exceptional levels in men's axillary perspiration.
Enzyme immunoassays for testosterone, 17beta-estradiol, and progesterone were validated for human facial and axillary perspiration and compared to levels in urine. In study 1, these assays were applied to samples from preadolescent girls and boys and young women and men. Men's axillary perspiration contained substantially higher levels of steroids than seen in other substrates from men or in any sample from women, boys, and girls. Male axillary steroid levels were very variable across individuals, and on average they exceeded levels in facial perspiration by 90-fold for testosterone and 45-fold for estradiol. Men's urinary testosterone also exceeded urinary levels of the other subjects. In study 2, axillary perspiration, urine, and saliva were collected from young men. Substantial axillary levels of testosterone and estradiol were again observed. Correlations of the same hormone among the different substrates were generally very low, except for a small correlation between estradiol levels measured in axillary perspiration and urine in study 2. High unconjugated steroid content in men's axillary excretions could, if absorbed by women during intimacy, be implicated in pheromonal activity.


Sickle cell chronic lung disease among young adult Nigerians.
Sickle cell chronic lung disease (SCLD) is often underappreciated by health care providers because its exact prevalence and methods of diagnosis have not been well studied. To describe the pattern of SCLD among young adult Nigerians with sickle cell anaemia (SCA).its exact prevalence and methods of diagnosis have not been well studied. To describe the pattern of SCLD among young adult Nigerians with sickle cell anaemia (SCA). Ninety (43 males and 47 females) patients with SCA who were selected by balloting and 90 (54 males and 36 females) healthy subjects with normal adult haemoglobin were studied. Their ventilatory function test (spirometry and peak expiratory flow rates), radiological and electocardiographic parameters were obtained and analyzed for SCLD. Seventeen (18.9%) of the patients had SCLD. Majority (94.1%) of them were in stage1 disease, 5.9% in stage two, and none in the more advanced stages3 and 4. The number of patients with SCLD increased with increasing age. SCLD was associated with more than five previous hospital admissions: 82.4%, (OR of 10.02; CI:4.51 to 22.22) and presence of symptoms suggesting previous acute chest syndrome: dyspnoea in 58.8% (OR of 33.33, CI 7.39 to 150.30); chest pain in 94.1%, (OR of 81.33, CI 9.83 to 672.85); and cough in 47.1%, (OR of 64.00, CI 7.15 to 572.60). SCLD may not be a rare event in Nigeria. Therefore efforts should be made to diagnose it in the early asymptomatic stage so as to offer effective intervention therapy to halt progression to the more disabling advanced stages.


Subcellular distribution of calmodulin and its binding proteins within the rat submandibular gland.
The involvement of calmodulin (CaM) in rat submandibular gland mucin secretion was investigated in vitro using a dispersed cell preparation. The CaM antagonist trifluoperazine (TFP) inhibited mucin secretion in response to both isoproterenol and dibutyryladenosine 3',5'-cyclic monophosphate. The inhibitory concentrations of TFP were between 10 and 100 microM. One millimolar TFP was toxic to submandibular cells and resulted in decreased levels of cellular ATP and a significant release of lactate dehydrogenase. Determination of CaM levels via radioimmunoassay within various subcellular fractions indicated that the majority of the CaM within the rat submandibular cell was located within the cytoplasm. CaM binding proteins were also identified within these subcellular fractions utilizing a gel overlay procedure. The two major, specific CaM binding proteins present within rat submandibular cells were a 59-kDa cytosolic protein and a 47-kDa membrane-associated protein.


Sequence Variation of Epstein-Barr Virus: Viral Types, Geography, Codon Usage, and Diseases.
One hundred thirty-eight new Epstein-Barr virus (EBV) genome sequences have been determined. One hundred twenty-five of these and 116 from previous reports were combined to produce a multiple-sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type 2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 single-nucleotide polymorphisms (SNPs) at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART microRNA region of the genome was present in 21 EBV strains. EBV from saliva of U.S. patients with chronic active EBV infection aligned with the wild-type EBV genome with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases from both Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes, and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious mononucleosis and posttransplant lymphoproliferative disease. It contributes to several types of cancer, including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. EBV genome variation is important because some of the diseases associated with EBV have very different incidences in different populations and geographic regions, and differences in the EBV genome might contribute to these diseases. Some specific EBV genome alterations that appear to be significant in EBV-associated cancers are already known, and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets.


Peripheral neuropathy due to gasoline sniffing - A case report.
A case of polyneuropathy in a 14-year-old boy, a chronic gasoline sniffer, is reported. Clinical and electromyographic examination showed a symmetrical motor involvement, mainly distally and in the lower limbs. A sural nerve biopsy showed only slight changes, both of axonal and demyelinating type. The role of gasoline toxic substances in the etiology of this rare polyneuropathy is discussed.


The complete amino acid sequence of human complement factor H.
The complete amino acid sequence of the human complement system regulatory protein, factor H, has been derived from sequencing three overlapping cDNA clones. The sequence consists of 1213 amino acids arranged in 20 homologous units, each about 60 amino acids long, and an 18-residue leader sequence. The 60-amino-acid-long repetitive units are homologous with those found in a large number of other complement and non-complement proteins. Two basic C-terminal residues, deduced from the cDNA sequence, are absent from factor H isolated from outdated plasma. A tyrosine/histidine polymorphism was observed within the seventh homologous repeat unit of factor H. This is likely to represent a difference between the two major allelic variants of factor H. The nature of the cDNA clones indicates that there is likely to be an alternative splicing mechanism, resulting in the formation of at least two species of factor H mRNA.


[Reflexotherapy and evidence-based medicine].
Assessment of the role and place of nontraditional methods of treatment and reflexotherapy, widely applied in hospitals is presented in the article. Besides, we become alerted regarding not serious approach of some scientists and health service managers to reflexotherapy as a whole and to one of its methods acupuncture.


The nucleocapsid of Berne virus.
In Berne virus-infected cells and in gradient-purified virions two major proteins with mol. wt. of 20K and 22K were detected. The 22K species is thought to represent the main envelope polypeptide; in infectious culture media it was present in a low envelope polypeptide; in infectious culture media it was present in a low density substructure which could be quantitatively converted into slowly sedimenting material by detergent treatment. The 20K polypeptide (accounting for about 80% of the 14C-amino acid label in the virion) was phosphorylated, occurred in an intracellular substructure of higher density than the virion (rho = 1.36 g/ml in CsCl) and was the only viral protein possessing RNA-binding properties; it was recognized preferentially by heterologous animal sera in immune precipitation. The 20K species is therefore identified as the main capsid protein. Two additional polypeptides (19K and 17K) were regularly detected in extracts of infected cells; they appeared to share oligopeptides with the 20K protein and are interpreted as being proteolytic cleavage products. The nucleocapsid of Berne virus was visualized after ether treatment as a flexible bacilliform structure with conspicuous transverse striation. Demonstration of a 20K nucleocapsid protein further supports the authors' proposal that Berne virus is a representative of a new family of enveloped RNA viruses (Toroviridae).


Ring of negative charge in BK channels facilitates block by intracellular Mg2+ and polyamines through electrostatics.
Intracellular Mg2+ and natural polyamines block outward currents in BK channels in a highly voltage-dependent manner. Here we investigate the contribution of the ring of eight negatively charged residues (4 x E321/E324) at the entrance to the inner vestibule of BK channels to this block. Channels with or without (E321N/E324N) the ring of negative charge were expressed in oocytes and unitary currents were recorded from inside-out patches over a range of intracellular Mg2+ and polyamine concentrations. Removing the ring of charge greatly decreased the block, increasing K(B)(ap) (0 mV) for Mg2+ block from 48.3 +/- 3.0 to 143 +/- 8 mM, and for spermine block from 8.0 +/- 1.0 to 721 +/- 9 mM (150 mM symmetrical KCl). Polyamines with fewer amine groups blocked less: putrescine < spermidine < spermine. An equation that combined an empirical Hill function for block together with a Boltzmann function for the voltage dependence of K(B)(ap) described the voltage and concentration dependence of the block for channels with and without the ring of charge. The Hill coefficients for these descriptions were <1 for both Mg2+ and spermine block, and were unchanged by removing the ring of charge. When KCl(i) was increased from 150 mM to 3 M, the ring of charge no longer facilitated block, Mg2+ block was reduced, spermine block became negligible, and the Hill coefficients became approximately 1.0. BK channels in cell-attached oocyte patches displayed inward rectification, which was reduced for channels without the ring of charge. Taken together, these observations suggest that the ring of negative charge facilitates block through a preferential electrostatic attraction of Mg2+ and polyamine over K+. This preferential attraction of multivalent blockers over monovalent K+ would decrease the K+ available at the inner vestibule to carry outward current in the presence of Mg2+ or polyamines, while increasing the concentration of blocker available to enter and block the conduction pathway.


Controversies Regarding Ovarian Suppression and Infertility in Early Stage Breast Cancer.
A common side effect of chemotherapy in breast cancer is early menopause in premenopausal patients, which is mainly a result of an indirect form of ovarian ablation, and is associated with substantial impairment of quality of life. Suppressing the production of ovarian estrogen has been shown to reduce the recurrence of hormone receptor-positive early breast cancer in premenopausal women, but whether it has an added advantage over tamoxifen is being discussed. Types of permanent ablation of the ovarian function include surgical oophorectomy and radiation-induced ovarian failure. Both are associated with similar response rates in hormone receptor-positive metastatic breast cancer. Medical castration with luteinizing hormone-releasing hormone analogs (LHRHa) has the benefit of being a reversible approach. Another advantage that premenopausal patients who wish to reduce the risk of developing premature ovarian insufficiency induced by chemotherapy may be offered LHRHa irrespective of whether they desire pregnancy and their age at diagnosis. This also helps reduce the risk of menopausal signs and symptoms as well as the loss of bone density in the long-term, which are primary concerns for women. This is of utmost importance to premenopausal women who do not want to conceive after treatment or are not candidates for fertility preservation strategies because of age. It should be emphasized that for women who are interested in fertility preservation, gamete cryopreservation remains the first option, and LHRHa is not an alternative. During chemotherapy, however, temporary ovarian suppression with LHRHa may be given to women who either have no access to a fertility clinic or who have declined chemotherapy or have contraindications.


The effect of feedback on pathway transient response.
The effect of variation of the rate of input of material on the transient behaviour of metabolic pathways is examined. This reveals the existence of three transient times which make up the overall pathway transient. Two of these have been described previously and represent the times required for the accumulation of the free intermediate pool and the pool of enzyme-bound intermediate. They are state functions and as such are independent of the way in which the steady state was reached. The third is attributable to the variation in the rate of input of material to the pathway. It is dependent on three further factors. These are (a) the time required for the initial enzyme to reach its own steady state, (b) substrate depletion and (c) feedback. The description of the transient is: (Formula: see text) where V0 represents the rate of input and Vss represents the steady-state flux. The transient time associated with the transition between steady-states is shown to be a simple function of the transients for the establishment of each steady state from rest and may be expressed as: tau = tau b-Va/Vb . tau a where Va and Vb refer to the fluxes in the two steady states and tau a and tau b represent the transient times for the establishment of each of the steady-states from rest. The total pathway transient may now be completely defined as: (formula: see text) where summation over all intermediates, I, is implied. The significance of this to the analysis of pathway behaviour is discussed with more general examples of pathway transient analysis.


The post-carpal tunnel syndrome. Causes and prevention.
Even after opening the carpal tunnel for median nerve compression 25 percent of patients have persistent symptoms, the so-called post-carpal tunnel syndrome. Analysis of 135 median nerve decompressions carried out for primary carpal tunnel syndrome showed flexor tenosynovitis in the flexor sheaths of the fingers and operation scarring to be the main causes. A different local pathology in the hand can also be responsible for the symptoms, and it is important to diagnose such conditions before median nerve decompression so that correction can be performed simultaneously. This is demonstrated in a series of 31 patients.


A peptide of SPARC interferes with the interaction between caspase8 and Bcl2 to resensitize chemoresistant tumors and enhance their regression in vivo.
SPARC, a matricellular protein with tumor suppressor properties in certain human cancers, was initially identified in a genome-wide analysis of differentially expressed genes in chemotherapy resistance. Its exciting new role as a potential chemosensitizer arises from its ability to augment the apoptotic cascade, although the exact mechanisms are unclear. This study further examines the mechanism by which SPARC may be promoting apoptosis and identifies a smaller peptide analogue with greater chemosensitizing and tumor-regressing properties than the native protein. We examined the possibility that the apoptosis-enhancing activity of SPARC could reside within one of its three biological domains (N-terminus (NT), the follistatin-like (FS), or extracellular (EC) domains), and identified the N-terminus as the region with its chemosensitizing properties. These results were not only confirmed by studies utilizing stable cell lines overexpressing the different domains of SPARC, but as well, with a synthetic 51-aa peptide spanning the NT-domain. It revealed that the NT-domain induced a significantly greater reduction in cell viability than SPARC, and that it enhanced the apoptotic cascade via its activation of caspase 8. Moreover, in chemotherapy resistant human colon, breast and pancreatic cancer cells, its chemosensitizing properties also depended on its ability to dissociate Bcl2 from caspase 8. These observations translated to clinically significant findings in that, in-vivo, mouse tumor xenografts overexpressing the NT-domain of SPARC had significantly greater sensitivity to chemotherapy and tumor regression, even when compared to the highly-sensitive SPARC-overexpressing tumors. Our results identified an interplay between the NT-domain, Bcl2 and caspase 8 that helps augment apoptosis and as a consequence, a tumor's response to therapy. This NT-domain of SPARC and its 51-aa peptide are highly efficacious in modulating and enhancing apoptosis, thereby conferring greater chemosensitivity to resistant tumors. Our findings provide additional insight into mechanisms involved in chemotherapy resistance and a potential novel therapeutic that specifically targets this devastating phenomenon.


A 54-year-old Philippine sailor with fever and jaundice.
A 54-year-old man presented with fever, vomiting, jaundice and conjunctival injection. These clinical signs, together with the presence of mild inflammation, hepatitis and severe acute kidney injury, lead to the suspicion of leptospirosis. Infection was serologically confirmed and treatment with ceftriaxone and intermittent haemodialysis was followed by rapid clinical and biochemical recovery. Worldwide, leptospirosis is an emerging pathogen as a result of overpopulation and flooding, but due to increasing tourism also in other regions. In Belgium, clinicians must be aware of endemic as well as imported cases of leptospirosis and differentiate them from hantavirus infections. Leptospirosis is a zoonosis that is transmitted through the urine of chronically colonized animals, mainly rats. Infection can be asymptomatic, present as a mild inflammatory syndrome or cause a severe icterohaemorrhagic disease with multiple organ failure and a high mortality rate. Initial serological diagnosis requires confirmation with a microscopic agglutination assay in a reference laboratory. Treatment is mainly supportive. Antibiotics are often used although mild acute infection often is self-limiting and there is uncertainty about the influence of antibiotic therapy on the duration of fever or mortality. In general, patients fully recover with no remaining organ damage.


[Prognostic Value of Morphology and Hans Classification in Diffuse Large B Cell Lymphoma].
To investigate the prognostic value of morphology and Hans classification in diffuse large B cell lymphoma(DLBCL). Clinical data of 249 patients diagnosed with DLBCL in our hospital and Hangzhou Xixi hospital during Jan 2006 to Dec 2016 were analyzed retrospectively. These patients were classified into 3 groups: immunoblastic variant(IB) group, centroblastic variant(CB) group and others group according to the cell morphology. And DLBCL was also divided into GCB(germinal center B-cell-like)or non-GCB(non-germinal center B-cell-like) group by analyzing the expression of CD10, BCL6 and MUM1 (GCB: CD10 +,BCL6+-,MUM1+-/CD10-,BCL6+,MUM1-;non-GCB:CD10-,BCL6-,MUM1+-/CD10-,BCL6+,MUM1+). The univariate analysis displayed that the age,LDH level,IPI,IB,non-GCB,B-symptoms and rituximab all could influence the OS and EFS, the CR rate of CB subtype patients was significantly higher than that of the patients with IB subtype (68.3% vs 38.9%)(P=0.02). IB subtype was the in dependent prognostic factor for both EFS and OS in the whole study. In multivariate analysis, IPI and IB were the independent prognostic factors for OS and EFS. IB subtype was also an independent prognostic factor in EFS and OS with or without rituximab. The expression of BCL2 and BCL6 was related with prognosis in R-CHOP, but not in CHOP treated patients. Other markers (CD5, CD10, IRF4/MUM1, HLA-DR and Ki-67 proliferation index) were not of the significant prognostic value for DLBCL. When accepted rituximab, the GCB and non-GCB were not different significantly for prognosis. However, the non-GCB group showed a poor prognosis without using rituximab (EFS P=0.020;OS P=0.020). Multivariate Cox models showed that OS and EFS were not significantly different between GCB and non-GCB group, however, the IB subtype had a very significantly poor prognosis in OS and EFS (P=0.001, P=0.002). When the analysis was restricted to DLBCL with CB morphology only, no prognostic value was observed in Hans classification. The subtype of immunoblast is a major risk factor in patients treated with CHOP or R-CHOP. There is a significant association between the Hans classification and the morphologic subclassification. Results of this study have supplemented the data for the prognostic factor of DLBCL and demonstrated that the cytomorphologic diagnosis can be reproducible.


Distilling Heterogeneity among Children with Disruptive Behavior: Associations between Symptom Patterns and Social Functioning.
Children with disruptive behavior (DB) are a heterogeneous group who exhibit several characteristics that may contribute to poor social functioning. The present study identified profiles of reactive aggression, proactive aggression, callous-unemotional (CU) traits, and prosocial behavior in a sample of children with DB. Associations with social functioning (social interaction, social status) were then examined, along with sex differences in profile membership. Parent ratings of 304 clinic-referred children ages 6-12 years with DB were analyzed using latent profile analysis. Five profiles were identified: 1) Moderate prosocial behavior, reactive aggression, and CU, and low proactive aggression (labelled Moderate); 2) Relatively high prosocial behavior and low reactive and proactive aggression and CU traits (Prosocial); 3) High prosocial behavior and reactive aggression, moderate proactive aggression, and low-moderate CU (Reactive-Prosocial); 4) Low prosocial behavior, high CU, high-moderate reactive aggression, and low-moderate proactive aggression (Reactive-CU); and 5) Low prosocial behavior and high reactive and proactive aggression and CU (Aggressive-CU). Profiles characterized by CU traits, reactive aggression, and low prosocial behavior were associated with the most problematic parent-rated social interaction and social status. The results highlight the need to differentiate profiles of psychopathology in children with DB to better address factors most associated with social functioning.


Double-Winged 3-Hydroxypyrimidine-2,4-diones: Potent and Selective Inhibition against HIV-1 RNase H with Significant Antiviral Activity.
Human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated ribonuclease H (RNase H) remains the only virally encoded enzymatic function yet to be exploited as an antiviral target. One of the possible challenges may be that targeting HIV RNase H is confronted with a steep substrate barrier. We have previously reported a 3-hydroxypyrimidine-2,4-dione (HPD) subtype that potently and selectively inhibited RNase H without inhibiting HIV in cell culture. We report herein a critical redesign of the HPD chemotype featuring an additional wing at the C5 position that led to drastically improved RNase H inhibition and significant antiviral activity. Structure-activity relationship (SAR) concerning primarily the length and flexibility of the two wings revealed important structural features that dictate the potency and selectivity of RNase H inhibition as well as the observed antiviral activity. Our current medicinal chemistry data also revealed that the RNase H biochemical inhibition largely correlated the antiviral activity.


The influence of breed and sex on the incidence of mortalities and skin tears in broiler carcasses.
The effects of nutrition, breed and sex on the incidence of mortalities and of skin tears on broiler carcasses were studied. Both sexes of 2 breeds, Hubbard and Ross, were given 4 dietary treatments consisting of a normal level of vitamin and mineral premix plus 300 ppm furazolidone, twice normal premix inclusion level plus 300 ppm furazolidone, a normal level of vitamin and mineral premix, and twice normal mineral premix inclusion level. A coccidiostat containing the active ingredient halofuginone was included at 6 ppm, twice the recommended dosage. Starter, grower and finisher diets were fed respectively up to Day 20, Day 30 and Day 48. Group growth performances, mortalities and the incidence of torn skin were monitored on both the live birds and carcasses. The effect of the different nutritional treatments on skin tears was not significant (P = 0.9533), as was the breed effect (P = 0.0547). However, the effect of sex was significant (P = 0.0044), the incidence in hens being higher. Mortalities among the Hubbard were significantly greater than among the Ross (P = 0.0001). Hens showed a slightly higher mortality rate than roosters, tending towards significance at the 5% level (P = 0.0554).


Correction of temporo-masseteric contour deformity using the dual paddle thoracodorsal artery perforator adiposal flap.
In cases of facial asymmetry with denervation atrophy of the masticatory muscles associated with head and neck tumors involving the trigeminal nerve, facial contour depression occurs selectively over the temple and masseteric area, separated by an uninvolved area over the zygomatic arch. The authors developed a new thoracodorsal artery perforator flap with two separate adiposal paddles based on their own perforators from the same mother vessel, the thoracodorsal vessel. Nearly normal temporo-masseteric contour was achieved in two patients. By freely positioning two adiposal paddles supplied by independent perforators based on the same vessel, separate non-contiguous regions of the face could be reconstructed correctly with one microvascular anastomosis in a single-stage operation, without the need for a secondary procedure to reduce the bulk over the zygomatic arch.


A highly sensitive radioreceptor assay for atrial natriuretic peptide in rat plasma.
To enable serial measurements of plasma atrial natriuretic peptide (ANP) concentrations in the rat, a microradioreceptor assay (RRA) for this hormone was developed. Glomerular microsomes bearing ANP receptors were used to bind ANP. The smallest quantity of ANP detectable by this method was 0.2 fmol/sample. By contrast, a radioimmunoassay for ANP was sensitive to 2.4 fmol/sample. The intra- and interassay coefficients of variation for the RRA were 4.1 and 11.6%, respectively. Recovery of 10, 20, 50, and 100 pM synthetic ANP added to unextracted rat plasma was essentially 100%. Biologically inactive, synthetic amino- and carboxy-terminal ANP fragments added to rat plasma were not detected. Plasma ANP was stable when measured four consecutive times at 90-min intervals in 10 fasting rats. In a separate group of rats, fasting plasma ANP levels averaged 34 +/- 3 and rose to 57 +/- 5 pM in the postprandial state (P less than 0.001), whereas levels in fasting time controls remained constant. It is concluded that the RRA for ANP described here detects ANP in microliter quantities of unextracted rat plasma. Thus serial measurements of ANP concentrations can be undertaken in rats without inducing major changes in the volume status.


Angiosarcoma of Anterior Mandibular Gingiva Showing Recurrence - A Case Report with Immunohistochemistry.
Angiosarcomas of oral cavity and salivary gland represent 1% of all cases reported in the literature and are therefore considered as extremely rare. To the best of our knowledge very few cases of angiosarcomas involving mandibular gingiva have been reported previously. Here, we report a case of angiosarcoma occurring in the gingiva with review of literature on clinical features. A 30-year-old female patient presented with a complaint of a small growing mass in relation to lower front teeth. Intraoral examination revealed a soft sessile growth arising from the labial gingiva in relation to 31 and 41 on the labial aspect extending distally to 32. The lesion was locally excised. Histolopathological analysis showed that the tumour was composed of spindle shaped to polygonal cells with hyperchromatic nuclei, conspicuous nucleoli and intracytoplasmic vacuoles, mitotic figure were also scattered. Immunohistochemical staining revealed that the tumour cells was positive for factor VIII-related antigen, CD31 and CD34. An excisional biopsy showed a diagnosis of angiosarcoma. After two months patient reported back with the same chief complaint. This present case is a 17(th) case report of angiosarcoma arising in anterior mandiblular gingiva.


Fetal cell microchimerism in human cancers.
The transfer of fetal cells into the maternal circulation occurs normally during pregnancy and the post-partum persistence of these cells in the maternal blood and tissues, known as fetal cell microchimerism, has been clearly demonstrated. However, the long-term consequences of this phenomenon are only beginning to be appreciated. In particular, whether microchimerism could be involved in the carcinogenetic process or whether fetal microchimeric cells could be able to differentiate in host tissues, participating in the maternal response to injury, is still matter of study. In this review, the possible role and the consequences of fetal cell microchimerism, as emerged from studies in animal models and in women with different types of cancer, will be presented.


A Single-Nucleotide Polymorphism in 3'-Untranslated Region of Endothelin-1 Reduces Risk of Dementia After Ischemic Stroke.
BACKGROUND Ischemic stroke is widely recognized as a major health problem and social burden worldwide, and it usually leads to dementia. In this study, we aimed to better understand the pathogenesis in the development of dementia following ischemic stroke. MATERIAL AND METHODS We exploited miRNA database to search for the target for miR-125a and validated the found target using luciferase assay. Further, we performed real-time PCR and Western blot analysis to examine the expression of miR-125a and its target in the tissue samples. In addition, a polymorphism was genotyped and its association with post-stroke dementia was analyzed. RESULTS We identified enthothelin-1 (ET-1) as a target of miR-125a, and this relationship was validated using luciferase assay. Furthermore, transfection of miR-125a inhibitor substantially upregulated the expression of ET-1, while miR-125a and ET-1 siRNA caused downregulation of ET-1 in endothelial cells. In addition, we found that a polymorphism (rs12976445) interferes with the expression of miR-125a, which in turn caused an increase in the expression of ET-1 in human endothelial cells. Logistic regression analysis showed that rs12976445 is significantly associated with the risk of dementia after ischemic stroke. CONCLUSIONS Our study demonstrated the pathogenesis mechanism during the development of dementia after ischemic stroke by investigating the relationship between miR-125a and its target ET-1, promising a potential pathological solution for post-stroke dementia in the future.


Elevated International Normalized Ratio values in a patient receiving warfarin and ceftaroline.
The case of a patient whose International Normalized Ratio (INR) became elevated due to a probable interaction between ceftaroline and warfarin is reported. A 65-year-old African-American man developed an INR of >18.0 after completing 12 days of ceftaroline therapy for the treatment of cellulitis while taking warfarin therapy. The patient was on warfarin due to his history of deep vein thrombosis of a lower extremity and pulmonary embolism, and his INR was consistently therapeutic for approximately 2 years before ceftaroline therapy. The patient reported no known drug allergies, had no history of adverse drug reactions, and had no recent changes in medications or diet. Phytonadione was administered, and the patient's INR began to decrease, returning to a therapeutic range of 2.30 after approximately 48 hours, at which time warfarin was restarted. After six days of hospitalization, the patient was discharged on his previous regimen of warfarin 7.5 mg orally once daily, with a therapeutic INR of 2.11. His cellulitis had resolved, so no further antibiotic therapy was warranted. To determine the likelihood of the drug interaction between warfarin and ceftaroline in this patient, the Drug Interaction Probability Scale of Horn and colleagues was applied and yielded a score of 6, indicating a probable likelihood of an interaction. Rechallenge was not attempted, as the patient's cellulitis had resolved and there were no evident signs or symptoms of infection. A 65-year-old man experienced an increase in INR values after the addition of ceftaroline to his medication regimen.


MR Image Reconstruction Using Deep Density Priors.
Algorithms for magnetic resonance (MR) image reconstruction from undersampled measurements exploit prior information to compensate for missing k-space data. Deep learning (DL) provides a powerful framework for extracting such information from existing image datasets, through learning, and then using it for reconstruction. Leveraging this, recent methods employed DL to learn mappings from undersampled to fully sampled images using paired datasets, including undersampled and corresponding fully sampled images, integrating prior knowledge implicitly. In this letter, we propose an alternative approach that learns the probability distribution of fully sampled MR images using unsupervised DL, specifically variational autoencoders (VAE), and use this as an explicit prior term in reconstruction, completely decoupling the encoding operation from the prior. The resulting reconstruction algorithm enjoys a powerful image prior to compensate for missing k-space data without requiring paired datasets for training nor being prone to associated sensitivities, such as deviations in undersampling patterns used in training and test time or coil settings. We evaluated the proposed method with T1 weighted images from a publicly available dataset, multi-coil complex images acquired from healthy volunteers ( N=8 ), and images with white matter lesions. The proposed algorithm, using the VAE prior, produced visually high quality reconstructions and achieved low RMSE values, outperforming most of the alternative methods on the same dataset. On multi-coil complex data, the algorithm yielded accurate magnitude and phase reconstruction results. In the experiments on images with white matter lesions, the method faithfully reconstructed the lesions.


Doppler spectral estimation using time-frequency distributions.
The time-frequency distribution (TFD) of Doppler blood flow signals is usually obtained using the spectrogram, which requires signal stationarity and is known to produce large estimation variance. This paper examines four alternative, nonstationary spectral estimators: a smoothed pseudo-Wigner distribution (SPWD), the Choi-Williams distribution (CWD), the Bessel distribution (BD), and the novel, adaptive constant-Q distribution (AQD) for their applicability to Doppler ultrasound. A synthetic Doppler signal, simulating the nonaxial and pulsatile flow of the common carotid artery, was used for quantitative comparisons at different signal-to-noise-ratios (SNR) of 0, 10, 20, and 30 dB as well as noise free. The cross-correlation (rho) and the root-mean-square-error (RMSE) were calculated after log-compression for each technique and SNR relative to the theoretical distribution. The AQD consistently had the lowest RMSE (< or =53.7%) and the highest rho (> or =0.889) of all the TFDs, irrespective of the SNR. The SPWD performed better than the spectrogram, which performed better than the BD and the CWD. Qualitative comparisons were carried out using in vivo data acquired with a 10 MHz ultrasound cuff transducer positioned around the distal aorta of a rabbit. In vivo, the AQD was considered best with respect to background noise and internal gray scale features; it was rated second (after the spectrogram) in depicting the spectral envelope. The AQD performed better as a Doppler spectral estimator than the traditional spectrogram and the other TFDs under the conditions studied here.


Antibody fragments: hope and hype.
The antibody molecule is modular and separate domains can be extracted through biochemical or genetic means. It is clear from review of the literature that a wave of novel, antigen-specific molecular forms may soon enter clinical evaluation. This report examines the developmental histories of therapeutics derived from antigen-specific fragments of antibodies produced by recombinant processes. Three general types of fragments were observed, antigen-binding fragments (Fab), single chain variable fragments (scFv) and "third generation" (3G), each representing a successive wave of antibody fragment technology. In parallel, drug developers have explored multi-specificity and conjugation with exogenous functional moieties in all three fragment types. Despite high hopes and an active pipeline, enthusiasm for differentiating performance of fragments should, perhaps, be tempered as there are yet few data that suggest these molecules have distinct clinical properties due only to their size.


A putative tRNATrp gene cloned from Dictyostelium discoideum: its nucleotide sequence and association with repetitive deoxyribonucleic acid.
Using a total tRNA population labeled with 32P, we have cloned a number of tRNA genes from Dictyostelium discoideum. A partial sequence of a cloned 1250-base-pair DNA insert, pDT-513, revealed the occurrence of a putative tRNATrp gene. In addition to the cloverleaf secondary structure, the tRNATrp gene contained all of the invariant and semiinvariant residues found in most tRNA sequences and has a 13-base-pair intron which is located one base removed from the 3' residue of the anticodon. The genomic distribution of the tRNA gene and its flanking sequences was examined via Southern annealing experiments. The structural gene is represented on at least six EcoRI fragments in the D. discoideum genome. Sequences flanking the 5' terminus of the cloned gene are repeated many times in the genome while the sequence flanking the 3' terminus of the pDT-513 DNA insert structural tRNA gene is present only once in the genome.


Widal test in diagnosis of typhoid fever in Turkey.
We studied the value of the Widal tube agglutination test for the diagnosis of typhoid fever. The subjects were all adults >18 years of age and were divided into four groups: (i) 317 healthy blood donor controls, (ii) 31 bacteriologically confirmed patients with Salmonella enterica serotype Typhi, (iii) 21 patients with a clinical diagnosis of typhoid fever, and (iv) 41 febrile nontyphoid patients. Blood donor controls were screened with a slide agglutination test for the Salmonella enterica serotype Typhi O and H antigens, and positives were then tested with the Widal test. Acute- and convalescent-phase sera from patients in groups 2, 3, and 4 were obtained 7 to 10 days apart and tested by the Widal test. Using a cutoff of >or = 1/200 for the O antigen test performed on acute-phase serum gave a sensitivity of 52% and a specificity of 88% with a positive predictive value (PPV) of 76% and a negative predictive value (NPV) of 71%. This increased to 90% sensitivity and specificity with a PPV of 88% and an NPV of 93% when the convalescent-phase serum was tested. We concluded that O and H agglutinin titers of > or = 1/200 are of diagnostic significance. The Widal test is easy, inexpensive, and relatively noninvasive. It can be of diagnostic value when blood cultures are not available or practical. The results must be interpreted cautiously because of the low sensitivity of the test. The Widal test done on convalescent-phase serum gave more-reliable results with higher specificity and sensitivity.


A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes: design and methodology [ISRCTN78467674].
Age-related macular disease is the leading cause of blind registration in the developed world. One aetiological hypothesis involves oxidation, and the intrinsic vulnerability of the retina to damage via this process. This has prompted interest in the role of antioxidants, particularly the carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye disease. The aim of this randomised controlled trial is to determine the effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc, and copper on measures of visual function in people with and without age-related macular disease. Outcome measures are distance and near visual acuity, contrast sensitivity, colour vision, macular visual field, glare recovery, and fundus photography. Randomisation is achieved via a random number generator, and masking achieved by third party coding of the active and placebo containers. Data collection will take place at nine and 18 months, and statistical analysis will employ Student's t test. A paucity of treatment modalities for age-related macular disease has prompted research into the development of prevention strategies. A positive effect on normals may be indicative of a role of nutritional supplementation in preventing or delaying onset of the condition. An observed benefit in the age-related macular disease group may indicate a potential role of supplementation in prevention of progression, or even a degree reversal of the visual effects caused by this condition.


Development of de novo urge incontinence in women post sling: the role of preoperative urodynamics in assessing the risk.
The study was undertaken to investigate if there are specific identifiable risk factors on the preoperative history or urodynamics testing associated with an increased risk for the development of symptoms of de novo urge urinary incontinence after a minimally invasive sling procedure. Two hundred eighty-one women who had undergone minimally invasive sling surgery for stress urinary incontinence between January 2000 and December 2003 were identified. The records of 92 patients were included in this review. Twenty-five patients (27%) reported urge urinary incontinence on postoperative questioning. Clinical and urodynamic parameters were correlated with the development of de novo urge urinary incontinence. Preoperative history parameters were not predictive of the increased risk of de novo urge urinary incontinence, with the exception of increased preoperative daytime frequency (OR 3.3 (1.2, 9.1)). Of 16 women whose detrusor pressure during the filling phase of cystometry exceeded 15 cm H(2)O, de novo urge urinary incontinence developed in 9 (56%) vs. 16 (21%) of 76 women, whose detrusor pressure was < or = 15 cm H(2)O (OR 4.6 (1.4, 15.0)). Directed patient history is only minimally helpful in the identification of women at increased risk for the development of de novo urge urinary incontinence, with the exception of the complaint of increased daytime frequency. Women with elevated detrusor pressure during the filling phase of cystometry were more likely to develop urge urinary incontinence postoperatively. Therefore, we suggest that preoperative urodynamic evaluation, and specifically detrusor pressure > 15 cm H(2)O may help identify patients at increased risk of developing de novo urge urinary incontinence following the minimally invasive sling procedure.


The effect of bleaching agents on the color stability of ceromer and porcelain restorative materials in vitro.
The aim of this in vitro study was to determine the color changes of five different restorative materials after exposing these materials to two different home bleaching agents. This study applied bleaching agents to an ultralow-fusing porcelain, a low-fusing porcelain, two types of heat-pressed glass ceramics, and a ceromer. A total of 24 disc-shaped specimens were fabricated (with a diameter of 10 mm and a thickness of 2 mm) from each material (n=12). The initial color measurements were taken with a spectrophotometer. The first set of specimens were bleached with 10% hydrogen peroxide (HP) for one hour daily for 10 days. The other set of specimens were bleached with 10% carbamide peroxide (CP) bleaching gel for eight hours daily for 14 days. Data were analyzed with the one-way analysis of variance and Kruskal-Wallis statistical test. The difference in the prebleaching and postbleaching color of each material was considered to be statistically significant at p < 0.05. The study found a statistically significant difference among the color changes of the test groups after exposing them to both bleaching agents (p<0.05). Appreciable color change was observed in the Estenia (ΔE=3.99) specimens that were bleached with the HP, and noticeable color changes were observed in the Estenia (ΔE=1.89) and IPS Empress 2 (ΔE=1.66) groups when they were treated with the CP. Restorations (especially polymer-containing restorative materials) should be protected before any bleaching procedure due to the high risk of color change.


Abnormal contractility in human heart myofibrils from patients with dilated cardiomyopathy due to mutations in TTN and contractile protein genes.
Dilated cardiomyopathy (DCM) is an important cause of heart failure. Single gene mutations in at least 50 genes have been proposed to account for 25-50% of DCM cases and up to 25% of inherited DCM has been attributed to truncating mutations in the sarcomeric structural protein titin (TTNtv). Whilst the primary molecular mechanism of some DCM-associated mutations in the contractile apparatus has been studied in vitro and in transgenic mice, the contractile defect in human heart muscle has not been studied. In this study we isolated cardiac myofibrils from 3 TTNtv mutants, and 3 with contractile protein mutations (TNNI3 K36Q, TNNC1 G159D and MYH7 E1426K) and measured their contractility and passive stiffness in comparison with donor heart muscle as a control. We found that the three contractile protein mutations but not the TTNtv mutations had faster relaxation kinetics. Passive stiffness was reduced about 38% in all the DCM mutant samples. However, there was no change in maximum force or the titin N2BA/N2B isoform ratio and there was no titin haploinsufficiency. The decrease in myofibril passive stiffness was a common feature in all hearts with DCM-associated mutations and may be causative of DCM.


Beef up your discharge planning processes, experts recommend.
The Centers for Medicare & Medicaid Services is increasing its emphasis on discharge planning and has developed a worksheet for surveyors to use to determine if hospitals are in compliance with the Conditions of Participation. Hospitals must have discharge policies and procedures in writing and must be able to show that they are following them. Discharge planning assessments should be comprehensive and include the patient's psychosocial needs as well as medical needs and should take into consideration whether patients can safely go back to their previous setting. Communication with post-acute providers is essential to create smooth transitions and identify any gaps in information.


Osteoarthritis of the hip in patients under 60 years of age. A study of the importance of pain at rest as an indication for intertrochanteric osteotomy.
Pain at rest with osteoarthritis of the hip may be due to increased intraosseous blood pressure, which falls immediately after an intertrochanteric osteotomy. Eighty-five consecutive hips from patients under 60 years of age at the time of operation were studied in order to evaluate if pain at rest was an indication for intertrochanteric osteotomy. Patients who operatively were predominantly in pain at rest had a significantly better prognosis than patients with a predominantly weight-bearing pain (P less than 0.05). Intertrochanteric osteotomy reduced pain for the group of patients with predominant pain at rest (n = 50) by 81%, 66%, and 56% at 5, 10, and 15 years respectively. In the group where weight-bearing pain was predominant (n = 35), the operation was a success in only 39% at 5 years and after.


Algorithm for optimal dialysis access timing.
Acute initiation of dialysis is associated with increased morbidity due to access and uremia complications. It is frequent despite early referral and regular out-patient control. We studied factors associated with end-stage renal disease (ESRD) progression in order to optimize the timing of dialysis access (DA). In a retrospective longitudinal study (Study 1), the biochemical and clinical course of 255 dialysis and 64 predialysis patients was registered to determine factors associated with dialysis-free survival (DFS). On the basis of these results an algorithm was developed to predict timely DA, defined as >6 weeks and <26 weeks before dialysis initiation, with too late placement weighted twice as harmful as too early. The algorithm was validated in a prospective study (Study 2) of 150 dialysis and 28 predialysis patients. Acute dialysis was associated with increased 90-day hospitalization (17.9 vs. 9.0 days) and mortality (14% vs. 6%). P-creatinine and p-urea were poor indicators of DFS. At any level of p-creatinine, DFS was shorter with lower creatinine clearance and vice versa. Patients with systemic renal disease had a significantly shorter DFS than primary renal disease, due to faster GFR loss and earlier dialysis initiation. Short DFS was seen with hypoalbuminemia and cachexia; these patients were recommended early DA. The following algorithm was used to time DA (units: 1iM and ml/min/1.73 m2): P-Creatinine - 50 x GFR + (100 if Systemic Renal Disease) >200. Use of the algorithm was associated with earlier dialysis placement and a fall in acute dialysis requirements from 50% to 23%. The incidence of too early DA was unchanged (7% vs. 9%), and was due to algorithm non-application. The algorithm failed to predict imminent dialysis in 10% of cases, primarily due to acute exacerbation of stable uremia. Dialysis initiation was advanced by approximately one month. A predialysis program based on early dialysis planning and GFR-based DA timing may reduce the requirement for acute dialysis initiation and patient morbidity and mortality, at the cost of slightly earlier dialysis initiation.


Double free gracilis muscle transfer after complete brachial plexus injury: First Canadian experience.
Traumatic brachial plexus root avulsions are devastating injuries, and are complex and challenging to reconstruct. Double free muscle transfer using the gracilis muscles is a potentially effective method of restoring upper extremity function. The authors report on the first two patients treated using this technique in Canada. Both sustained traumatic brachial plexus root avulsion injuries resulting in a flail arm. In the first step of this two-stage procedure, a gracilis muscle was transferred to restore elbow flexion, and wrist and digit extension. Months later, the transfer of the second gracilis muscle was performed to enhance elbow flexion and to enable wrist and digit flexion. Postoperatively, both patients achieved Medical Research Council grade 4 elbow flexion, functional handgrip and were able to return to gainful employment. Patient satisfaction was high and active range of motion improved substantially. The authors' experience supports the use of this technique following severe brachial plexus injury.


[Healthcare associated infection: emerging problem in a neurology department].
Healthcare-associated infection (HAI) is, nowadays, a serious problem, contributing a lot to the burden of the hospital stays. Its impact is really huge and the study of these matters is taking a growing interest. To compare, in terms of HAI, the current Neurology Department (localized inside the building of Hospital Geral) and the oldest one, which was far away from the institutional campus. To identify difficulties regarding the management of HAI, trying to propose measures for quality improvement. We revised the clinical files of the patients with HAI documented by culture, on a homologue period of 6 months. Variables like more frequently isolated microorganisms, antibiotics sensibilities, patients' comorbidities, treatment adequacy and duration of hospitalization were analyzed. In the oldest Department, 23 patients were identified, 8 men (mean +/- 2SD: 80.4 +/- 9.04 years old) and 15 women (77.3 +/- 21.28 years old), with positive microbiological studies (51). Ischemic stroke caused 73.9% of these hospitalizations. Escherichia coli - EC - (27%), methicillin-resistant Staphylococcus aureus - MRSA - (22%) and Klebsiella pneumoniae - KP - (10%) were the most frequently identified microorganisms in the biological samples studied (sputum, urine, blood, urethral exudate and eschar). Amoxicillin/clavulanic acid was the most empirically used antibiotic (only effective on 37% of the cases, according to the sensibility tests). Hospitalizations had an average of 22 days and 1.3 antibiotics per patient were used. At discharge, Rankin had a mode of 5. In the current Department, 46 patients were studied, 22 men (76.4 +/- 22.6 years old) and 24 women (74.1 +/- 32.6 years old), having 119 positive cultures. Again, ischemic stroke caused the majority of the admissions (52.2%). MRSA (26%), Pseudomonas aeruginosa - PA - (17%) and EC (17%) were the most prevalent pathogens (the same biological products were studied, plus lingual exudates and central venous catheter tips). Ciprofloxacin was the most used antibiotic (suitable on 75% of the cases). Internments had an average of 24.3 days and, this time, 2.5 antibiotics were used per patient, by mean. At discharge, Rankin evaluation had again a mode of 5. Despite the taken measures and change in facilities, HAI had really increased in the Neurology Department. Since human resources are the same, we think are important, as possible aggravating conditions, space restriction and ward sharing with patients of other medical specialities, as it happens in the current Department. More aggressive pathogens require a rapid and comprehensive intervention, in order to minimize its impact on daily clinical practice and in the management of hospital stays.


[Role of IL-6 in regulation of inflammation and stem cell differentiation in CNS trauma].
Interleukin-6 (IL-6) has been demonstrated to play a pivotal role in CNS trauma as a proinflammatory cytokine which regulates inflammatory response. Not only being a mediator of inflammation, but IL-6 induces neural stem/progenitor cells to undergo astrocytic differentiation selectively in the injured CNS. These effects are considered to coordinate to prevent the CNS repair after traumatic injury. Consistently, we previously reported that the administration of anti-IL-6 receptor antibody (MR16-1) immediately after spinal cord injury in mice decreased the number of invading inflammatory cells and the severity of connective tissue scar formation, and led to improved functional recovery. These findings suggest that neutralization of IL-6 signaling in the acute phase of SCI will be beneficial for CNS repair. A critical merit of this anti-IL-6 receptor antibody is that humanized antibody to human IL-6 receptor (MRA; Atlizumab) has already been reshaped. However, there are several studies which show beneficial aspects of IL-6 signaling in the pathology of CNS trauma. Further investigation of the mechanisms how MR16-1 reduces tissue damage should be required for clinical application.


Diet-induced hyperhomocysteinemia increases amyloid-beta formation and deposition in a mouse model of Alzheimer's disease.
Hyperhomocysteinemia (HHcy) has been recognized as a risk factor for developing Alzheimer's disease (AD). However, its underlying molecular mechanisms are still elusive. Here we show that HHcy induces an elevation of amyloid beta (Abeta) levels and deposition, as well as behavioral impairments, in a mouse model of AD-like amyloidosis, the Tg2576 mice. This elevation is not associated with significant change of the steady state levels of the Abeta precursor protein (APP), beta- or alpha-secretase pathways, nor with the Abeta catabolic pathways. By contrast, HHcy significantly reduces glycogen synthase kinase 3 (GSK3) Ser21/9 phosphorylation, but not total GSK3 protein levels. Similar results are obtained in brains homogenates from a genetic mouse model of HHcy. In vitro studies show that homocysteine increases Abeta formation, reduces phosphorylated GSK3 levels, without changes in total APP and its metabolism, and these effects are prevented by selective GSK3 inhibition. Overall, these data support a potential link between GSK3 and the pro-amyloidotic effect of HHcy in vivo and in vitro.


An evaluation of several methods for computing lingual coarticulatory resistance using ultrasound.
The paper evaluates the efficiency of six computation methods in distinguishing lingual coarticulatory resistance among consonants and vowels using ultrasound data. This research goal is tested on a corpus of symmetrical vowel-consonant-vowel sequences composed of 10 consonants and five vowels produced by five Catalan speakers. Results show that, while the coarticulatory resistance hierarchies obtained by all methods conform largely to the predictions of the degree of articulatory constraint model of coarticulation, some (i.e., area of the articulatory zone, mean point-by-point coefficient of variation, and mean nearest neighbour distance) are somewhat more highly predictive than others (i.e., locus equation, mutual information, and highest point of the tongue dorsum). Methods differ mostly regarding the classification of consonants exhibiting intermediate degrees of coarticulatory resistance due to the way the methods have been designed. The implications of these findings for research on dialectal variation are discussed.


Molecular cloning and characterization of a mitochondrial peroxisome proliferator-induced acyl-CoA thioesterase from rat liver.
We have previously reported the purification and characterization of the peroxisome proliferator-induced very-long-chain acyl-CoA thioesterase (MTE-I) from rat liver mitochondria [L.T. Svensson, S.E. H. Alexson and J.K. Hiltunen (1995) J. Biol. Chem. 270, 12177-12183]. Here we describe the cloning of the corresponding cDNA. One full-length clone was isolated that contained an open reading frame of 1359 bp encoding a polypeptide with a calculated molecular mass of 49707 Da. The deduced amino acid sequence contains a putative mitochondrial leader peptide of 42 residues. Expression of the cDNA in Chinese hamster ovary cells, followed by immunofluorescence, immunoelectron microscopy and Western blot analyses, showed that the product was targeted to mitochondria and processed to a mature protein of 45 kDa, which is similar to the molecular mass of the protein isolated from rat liver mitochondria. The recombinant enzyme showed the same acyl-CoA chain-length specificity as the isolated rat liver enzyme. Sequence analysis showed no similarity to known esterases, but a high degree (approx. 40%) of identity with bile acid-CoA:amino acid N-acyltransferase cloned from human and rat liver. A putative active-site serine motif (Gly-Xaa-Ser-Xaa-Gly) of several carboxylesterases and lipases was identified. Western and Northern blot analyses showed that MTE-I is constitutively expressed in heart and is strongly induced in liver by feeding rats with di(2-ethylhexyl)phthalate, a peroxisome proliferator, suggesting a role for the enzyme in lipid metabolism.