New approaches to pharmacosurveillance for monitoring prescription frequency, diversity, and co-prescription in a large sentinel network of companion animal veterinary practices in the United Kingdom, 2014-2016.
Pharmaceutical agents (PAs) are commonly prescribed in companion animal practice in the United Kingdom. However, little is known about PA prescription on a population-level, particularly with respect to PAs authorised for human use alone prescribed via the veterinary cascade; this raises important questions regarding the efficacy and safety of PAs prescribed to companion animals. This study explored new approaches for describing PA prescription, diversity and co-prescription in dogs, cats and rabbits utilising electronic health records (EHRs) from a sentinel network of 457 companion animal-treating veterinary sites throughout the UK over a 2-year period (2014-2016). A novel text mining-based identification and classification methodology was utilised to semi-automatically map practitioner-defined product descriptions recorded in 918,333 EHRs from 413,870 dogs encompassing 1,242,270 prescriptions; 352,730 EHRs from 200,541 cats encompassing 491,554 prescriptions, and 22,526 EHRS from 13,398 rabbits encompassing 18,490 prescriptions respectively. PA prescription as a percentage of booked consultations was 65.4% (95% confidence interval, CI, 64.6-66.3) in dogs; in cats it was 69.1% (95% CI, 67.9-70.2) and in rabbits, 56.3% (95% CI, 54.7-57.8). Vaccines were the most commonly prescribed PAs in all three species, with antibiotics, antimycotics, and parasiticides also commonly prescribed. PA prescription utilising products authorised for human use only (hence, 'human-authorised') comprised 5.1% (95% CI, 4.7-5.5) of total canine prescription events; in cats it was 2.8% (95% CI, 2.6-3.0), and in rabbits, 7.8% (95% CI, 6.5-9.0). The most commonly prescribed human-authorised PA in dogs was metronidazole (antibiotic); in cats and rabbits it was ranitidine (H2 histamine receptor antagonist). Using a new approach utilising the Simpson's Diversity Index (an ecological measure of relative animal, plant etc. species abundance), we identified differences in prescription based on presenting complaint and species, with rabbits generally exposed to a less diverse range of PAs than dogs or cats, potentially reflecting the paucity of authorised PAs for use in rabbits. Finally, through a novel application of network analysis, we demonstrated the existence of three major co-prescription groups (preventive health; treatment of disease, and euthanasia); a trend commonly observed in practice. This study represents the first time PA prescription has been described across all pharmaceutical families in a large population of companion animals, encompassing PAs authorised for both veterinary and human-only use. These data form a baseline against which future studies could be compared, and provides some useful tools for understanding PA comparative efficacy and risks when prescribed in the varied setting of clinical practice.


Systemic immunization with conserved pilus-associated adhesins protects against mucosal infections.
Colonization and infection of the bladder mucosa by Escherichia coli, the major uropathogenic organism, is dependent on the expression of pilus organelles. Type 1 pili are expressed by the majority of E. coli strains derived from patients with cystitis and pyelonephritis. FimH is the adhesin protein located at the distal tip of the heteropolymeric type-1 pilus which mediates binding to bladder cells through mannose receptors. We have shown that humoral antibody raised against two forms of purified FimH adhesin inhibited 94% (49/52) of E. coli UTI clinical isolates from binding to bladder tissue in vitro. Animals immunized with FimH-containing vaccines by a systemic route reduced colonization of the bladder mucosa in vivo in a murine cystitis model by > 99%. IgG antibody to FimH was detected in urinary samples obtained from immunized, protected mice. Passive systemic administration of immune sera from FimH-inoculated mice to naive animals also resulted in reduced colonization of bladder mucosa by uropathogenic E. coli. These studies demonstrate that systemic immunization with an anti-bacterial vaccine targeting a highly conserved adhesin on uropathogenic E. coli can induce IgG-mediated protection at a mucosal surface and may be a means of preventing recurrent and acute infections of the urogenital tract mucosa.


TaxMan: a taxonomic database manager.
Phylogenetic analysis of large, multiple-gene datasets, assembled from public sequence databases, is rapidly becoming a popular way to approach difficult phylogenetic problems. Supermatrices (concatenated multiple sequence alignments of multiple genes) can yield more phylogenetic signal than individual genes. However, manually assembling such datasets for a large taxonomic group is time-consuming and error-prone. Additionally, sequence curation, alignment and assessment of the results of phylogenetic analysis are made particularly difficult by the potential for a given gene in a given species to be unrepresented, or to be represented by multiple or partial sequences. We have developed a software package, TaxMan, that largely automates the processes of sequence acquisition, consensus building, alignment and taxon selection to facilitate this type of phylogenetic study. TaxMan uses freely available tools to allow rapid assembly, storage and analysis of large, aligned DNA and protein sequence datasets for user-defined sets of species and genes. The user provides GenBank format files and a list of gene names and synonyms for the loci to analyse. Sequences are extracted from the GenBank files on the basis of annotation and sequence similarity. Consensus sequences are built automatically. Alignment is carried out (where possible, at the protein level) and aligned sequences are stored in a database. TaxMan can automatically determine the best subset of taxa to examine phylogeny at a given taxonomic level. By using the stored aligned sequences, large concatenated multiple sequence alignments can be generated rapidly for a subset and output in analysis-ready file formats. Trees resulting from phylogenetic analysis can be stored and compared with a reference taxonomy. TaxMan allows rapid automated assembly of a multigene datasets of aligned sequences for large taxonomic groups. By extracting sequences on the basis of both annotation and BLAST similarity, it ensures that all available sequence data can be brought to bear on a phylogenetic problem, but remains fast enough to cope with many thousands of records. By automatically assisting in the selection of the best subset of taxa to address a particular phylogenetic problem, TaxMan greatly speeds up the process of generating multiple sequence alignments for phylogenetic analysis. Our results indicate that an automated phylogenetic workbench can be a useful tool when correctly guided by user knowledge.


Immunization with HER2 extracellular subdomain proteins induces cellular response and tumor growth inhibition in mice.
We investigated cellular and protective immune responses in mice vaccinated with recombinant HER2 extracellular subdomains. Balb/C mice were immunized with recombinant full HER2 extracellular domain and subdomain proteins. Humoral and cellular immune response and antitumor effect was evaluated using a syngeneic mice tumor model. All recombinant proteins induced secretion of IL-4 and particularly IFN-γ and IL-17 cytokines. Challenging of immunized mice with stable 4T1-HER2 transfected cells resulted in partial but significant tumor growth inhibition in all groups of mice particularly those immunized with fHER2-ECD together with CPG. Our results suggest that the recombinant HER2-ECD subdomains induce mainly Th1 and Th17 responses, which seem to contribute to tumor growth inhibition in syngeneic mice.


Recent Progress on Hydrogen Production from Ammonia Decomposition: Technical Roadmap and Catalytic Mechanism.
Ammonia decomposition has attracted significant attention in recent years due to its ability to produce hydrogen without emitting carbon dioxide and the ease of ammonia storage. This paper reviews the recent developments in ammonia decomposition technologies for hydrogen production, focusing on the latest advances in catalytic materials and catalyst design, as well as the research progress in the catalytic reaction mechanism. Additionally, the paper discusses the advantages and disadvantages of each method and the importance of finding non-precious metals to reduce costs and improve efficiency. Overall, this paper provides a valuable reference for further research on ammonia decomposition for hydrogen production.


Intrinsic Properties of Polyelectrolyte Multilayer Membranes: Erasing the Memory of the Interface.
Polyelectrolyte multilayers (PEMUs) are ultrathin membranes made by alternating adsorption of oppositely charged polyelectrolytes on substrates. Although PEMUs have shown exceptional selectivity for certain ion-filtering applications, they usually contain an excess of one of the polyelectrolytes due to the history- and condition-dependent mode of PEMU assembly. This excess charge provides fixed sites for ion exchange, enhancing the concentration of oppositely charged ions. Thus, the ion-permselective properties of PEMUs cannot be compared unless they are assembled under identical conditions. This work demonstrates the enhanced permeability of PEMUs as-made from poly(diallyldimethylammonium) (PDADMA), and poly(styrene sulfonate) (PSS) to ferricyanide as an example of an anion. Annealing by NaCl followed by pairing of excess PDADMA with additional PSS produces an almost stoichiometric film that better reflects the intrinsic transport properties of PEMUs. This pairing, observed in real time using electrochemical methods, occurs at the PEMU/solution interface under countercurrent transport of PSS from solution and excess PDADMA paired with a counterion, termed PDADMA*, from the PEMU bulk. A quantitative comparison of PSS and PDADMA* diffusion reveals the conditions under which PEMU assembly depends on PSS molecular weight and concentration.


Properties of the Temporomandibular Joint in Growing Pigs.
A subset of temporomandibular joint (TMJ) disorders is attributed to joint degeneration. The pig has been considered the preferred in vivo model for the evaluation of potential therapies for TMJ disorders, and practical considerations such as cost and husbandry issues have favored the use of young, skeletally immature animals. However, the effect of growth on the biochemical and biomechanical properties of the TMJ disk and articulating cartilage has not been examined. The present study investigates the effect of age on the biochemical and biomechanical properties of healthy porcine TMJs at 3, 6, and 9 months of age. DNA, hydroxyproline, and glycosaminoglycan (GAG) content were determined and the disks and condyles were tested in uniaxial unconfined stress relaxation compression from 10% to 30% strain. TMJ disks were further assessed with a tensile test to failure technique, which included the ability to test multiple samples from the same region of an individual disk to minimize the intraspecimen variation. No differences in biochemical properties for the disk or compressive properties at 30% stress relaxation in the disk and condylar cartilage were found. In tension, no differences were observed for peak stress and tensile modulus. The collagen content of the condyle was higher at 9 months than 3 months (p < 0.05), and the GAG content was higher at 9 months than 6 months (p < 0.05). There was a trend of increased compressive instantaneous modulus with age. As such, age-matched controls for growing pigs are probably appropriate for most parameters measured.


A Factorial Randomized Controlled Trial of Implementation-Intention-Based Self-Affirmation Interventions: Findings on Depression, Anxiety, and Well-being in Adults With Psoriasis.
This study builds on growing evidence on implementation-intention-based self-affirmation intervention effects on mental health. Using a factorial design, this pre-registered study aimed to further investigate whether (1) strengthening the element of specificity within body-related self-affirming implementation intention (BS-AII) intervention compared to general self-affirming implementation intention (S-AII) would provide greater improvements in mental health outcomes for adults with psoriasis, and (2) whether the addition of a booster component would result in enhancing effectiveness at follow-up. A total of 306 adults with psoriasis were assessed for eligibility and 222 (aged 18-71 years) were randomized and received S-AII, BS-AII, or MGI (mere goal intention-control condition). Within each group, participants were again randomized to booster (B) or no-booster condition in a 3 × 2 factorial design, resulting in six groups: S-AII; S-AII + B; BS-AII; BS-AII + B; MGI; and MGI + B. Data were collected over three-time points, at baseline, 2 weeks post-intervention, and at 1-month later. Three primary outcomes were defined as a reduction of anxiety and depressive symptoms and enhancement of well-being. In terms of secondary outcomes, positive other- and self-directed feelings and also an emotional attitude toward the body were evaluated. To fully estimate intervention effects through intention-to-treat analysis, linear mixed models were used. A significant effect of time was observed, but no evidence of time-by-group interactions and no three-way interactions were detected. Exploratory analyses revealed two significant moderating effects of age and self-esteem, pointing to boundary conditions of the interventions. These findings offer to gain deeper insights on null (or negative) effects also reported in past works and highlight that self-affirmation interventions should be more thoroughly investigated and optimized before they can be broadly implemented in real-life contexts, especially to prevent backfiring and negative-enhancing effects.


Direct association of messenger RNA labeled in the presence of fluoroorotate with membranes of the endoplasmic reticulum in rat liver.
Liver rough endoplasmic reticulum (RER) membranes were isolated from rats given [3H]orotic acid for 48 h (ribosomal RNA [rRNA] label) or for 3 h along with 5-fluoroorotate; this latter procedure permits the labeling of cytoplasmic messenger RNAs (mRNAs) in the absence of rRNA labeling. More than 50% of the labeled mRNA remained attached to membranes of the RER after complete removal of ribosomes with a buffer of high ionic strength in the presence of puromycin. Under similar conditions, membranes retained 40% of their polyadenylate as determined by a [3H]-polyuridylate hybridization assay. Treatment of mRNA-labeled endoplasmic reticulum membranes with pancreatic RNase indicates that the polyadenylate and possibly nonpolyadenylate-pyrimidine portions of the messenger are involved in the binding of mRNA to the membranes. The implication of these results in furthering our understanding of the mechanisms of the translational regulation of genetic expression is discussed.


The prevalence of IgG4-positive plasma cell infiltrates in inflammatory bowel disease patients without autoimmune pancreatitis.
IgG4-related autoimmune disease can exist in other organs even when there is no evidence of autoimmune pancreatitis. The aim of our study was to determine the prevalence of IgG4-positive plasma cells in the histopathological evaluations of colon biopsy specimens in IBD patients. The number of IgG4-positive plasma cells with strong cytoplasmic immunoreactivity was counted in each colon biopsy from inflammatory bowel disease patients who had no evidence of autoimmune pancreatitis. Five high power fields (HPFs) in the highest density plasma cell infiltration area were counted and were then averaged. An average >10 cells/HPF was considered significant for IgG4-related disease. We detected IgG4-positive plasma cell staining in the colon of 21 of 119 patients (17.6%). Of these 21 patients, 5 had elevated serum IgG4 levels (>140 mg/dL). Of the total, 4.2% (5/119) had both IgG4-immunstaining and elevated IgG4 serum levels. The demographic features, disease type and activity, and response to treatment (especially to steroid treatment) were similar between the IgG4-negative and IgG4-positive groups. In our study, 4.2% of patients with the diagnosis of IBD had elevated IgG4 serum levels and significant IGg4 immunostaining. Together, these two parameters indicate the possible diagnosis of an IgG4-related systemic disease.


Gene conversion and hypermutation during diversification of VH sequences in developing splenic germinal centers of immunized rabbits.
The young rabbit appendix and the chicken bursa of Fabricius are primary lymphoid organs where the B cell Ab repertoire develops in germinal centers (GCs) mainly by a gene conversion-like process. In human and mouse, V-gene diversification by somatic hypermutation in GCs of secondary lymphoid organs leads to affinity maturation. We asked whether gene conversion, somatic hypermutation, or both occur in rabbit splenic GCs during responses to the hapten DNP. We determined DNA sequences of rearranged heavy and light chain V region gene segments in single cells from developing DNP-specific GCs after immunization with DNP-bovine gamma-globulin and conclude that the changes at the DNA level that may lead to affinity maturation occur by both gene conversion and hypermutation. Selection was suggested by finding some recurrent amino acid replacements that may contribute increased affinity for antigen in the complementarity-determining region sequences of independently evolved clones, and a narrower range of complementarity-determining region 3 lengths at day 15. Some of the alterations of sequence may also lead to new members of the B cell repertoire in adult rabbits comparable with those produced in gut associated lymphoid tissues of young rabbits.


Design and Development of a Diagnostic System for a Non-Intercepting Direct Measure of the SPIDER Ion Source Beamlet Current.
Stable and uniform beams with low divergence are required in particle accelerators; therefore, beyond the accelerated current, measuring the beam current spatial uniformity and stability over time is necessary to assess the beam performance, since these parameters affect the perveance and thus the beam optics. For high-power beams operating with long pulses, it is convenient to directly measure these current parameters with a non-intercepting system due to the heat management requirement. Such a system needs to be capable of operating in a vacuum in the presence of strong electromagnetic fields and overvoltages, due to electrical breakdowns in the accelerator. Finally, the measure of the beam current needs to be efficiently integrated into a pulse file with the other relevant plant parameters to allow the data analyses required for beam optimization. This paper describes the development, design and commissioning of such a non-intercepting system, the so-called beamlet current monitor (BCM), aimed to directly measure the electric current of a particle beam. In particular, the layout of the system was adapted to the SPIDER experiment, the ion source (IS) prototype of the heating neutral beam injectors (HNB) for the ITER fusion reactor. The diagnostic is suitable to provide the electric current of five beamlets from DC up to 10 MHz.


A comparison of right and left blunt traumatic diaphragmatic rupture.
Since right blunt traumatic diaphragmatic rupture (BTDR) is reported with increasing frequency, BTDR may be a disease in evolution. Data were collected on 59 left, 16 right, and five bilateral BTDRs at a level 1 trauma center. Patients with right BTDR had lower Glasgow Coma Scale (GCS) scores (p < 0.05), were more likely to be initially in hypovolemic shock, and were admitted directly from the field (p < 0.01). Left and right BTDRs were diagnosed from chest films in 37% and 0% of cases, respectively (p < 0.05). Diagnostic peritoneal lavage results were negative in 16% of left and left of 0% of right BTDRs. For right BTDRs, the liver was more likely to be injured (p < 0.001). The mortality rates were similar and ICU and hospital stays, complications, and duration of mechanical ventilation were similar for early survivors with right and left BTDRs. The clinical signs and symptoms, diagnosis, and surgical findings associated with right and left BTDR are different.


Thin-section CT findings of nontuberculous mycobacterial pulmonary diseases: comparison between Mycobacterium avium-intracellulare complex and Mycobacterium abscessus infection.
We aimed to compare the CT findings of nontuberculous mycobacterial pulmonary diseases caused by Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus. Two chest radiologists analyzed retrospectively the thin-section CT findings of 51 patients with MAC and 36 with M. abscessus infection in terms of patterns and forms of lung lesions. No significant difference was found between MAC and M. abscessus infection in the presence of small nodules, tree-in-bud pattern, and bronchiectasis. However, lobar volume decrease (p=0.001), nodule (p=0.018), airspace consolidation (p=0.047) and thin-walled cavity (p=0.009) were more frequently observed in MAC infection. The upper lobe cavitary form was more frequent in the MAC (19 of 51 patients, 37%) group than M. abscessus (5 of 36, 14%) (p=0.029), whereas the nodular bronchiectatic form was more frequent in the M. abscessus group ([29 of 36, 81%] vs. [27 of 51, 53%] in MAC) (p=0.012). In conclusion, there is considerable overlap in common CT findings of MAC and M. abscessus pulmonary infection; however, lobar volume loss, nodule, airspace consolidation, and thin-walled cavity are more frequently seen in MAC than M. abscessus infection.


Effects of age and body mass index on peak-expiratory flow rate in Indian population.
Peak expiratory flow rate (PEFR) is a measure of ventilatory capacity measured by peak flow meter. It is regarded as a basic physiological parameter for the diagnosis, follow up and treatment of patients with respiratory illnesses such as asthma, chronic bronchitis, and emphysema. This study establishes the relationship of PEFR with age and BMI in healthy adult males (N=300) of Kumaon region of Uttarakhand. Overall, the mean PEFR is 478.37±68.14. The age is significantly affecting the PEFR unlike BMI. Age as an independent predictor predicts the 72.3% variability (R2 is 72.3%) in PEFR while BMI > 23 as an independent predictor predicts only 1.4% variability (R2 is 0.014). PEFR declines with advancing age due to degenerative changes in musculoskeletal system leading to decrease in respiratory muscle strength. PEFR shows some decline with high BMI in elderly age group.


[Use of medicines before and during pregnancy: prevalence and associated factors].
This cross-sectional prospective nested cohort study aimed to assess the prevalence of use of medication before and during pregnancy and associated factors in women in a municipality in the countryside of Bahia State, Brazil. Data were collected with a structured questionnaire applied to pregnant women at their prenatal visits at health units. Prevalence rates for use of medication before and during pregnancy were 52.1% and 84.7%, respectively. The following were associated with use of medication before pregnancy: age ≥ 30 years, non-white skin color, first prenatal visit after the 1st trimester, and economic classes C/D/E. There was an increase in medication during pregnancy among women with ≥ 11 years of schooling, women with more than three prenatal visits, and those with some health problem. Pregnant women are exposed to medication before and during pregnancy, notwithstanding the lack of secure information to back the use of medicines during this phase; such use is associated with factors pertaining to prenatal follow-up, suggesting the need for more active participation by pharmacists in orientation and support for rational use of medicines.


A new pentacyclic cucurbitane glucoside and a new triterpene from the fruits of Gymnopetalum integrifolium.
A new pentacyclic cucurbitane glucoside, named aoibaclyin (1) and a new triterpene (2) have been isolated from the EtOH extract of the fruits of Gymnopetalum integrifolium Kurz (Cucurbitaceae), together with three known compounds, bryoamaride (3), 25-O-acetylbryoamaride (4) and beta-sitosterol 3-O-beta-D-glucopyranoside (5). The structures of these compounds were elucidated by spectroscopic analyses.


Aging and creating families: Never-married heterosexual women over forty.
An examination of women over age forty who had never married was conducted. The women completed a structured questionnaire about their aging and their self-esteem was assessed with a standard measure. The participants were women from across the United States. Descriptive analyses of the data were ordered with ecological systems theory and findings revealed that the women are self-satisfied, socially productive and well adjusted with their single status and that singleness runs in their families. These women have defined what family means for them as they age-family of origin and close friendships. This description may be helpful in understanding this group as a social force and as role models for young women as they age.


Trauma leagues: an alternative way to teach trauma surgery to medical students.
to compare the knowledge of medical students between those who are members of the Trauma League (TL) and those from a non-Trauma League (NTL) group of the Federal University of Espírito Santo (UFES). cross-sectional, analytical and descriptive study. Two knowledge tests, with 30 questions each, were applied to students from 3rd to 12th period, randomly selecting five students per period, with 50 students in the TL group and 50 in NTL. The questionnaire topics were: pre-hospital care, the mnemonic ABCDE trauma sequence, advanced trauma and imaging. The students' performances were evaluated by graduation-period group: basic (3rd-5th period), intermediary/clinical (6th-8th) and internship (9th-12th). in the first test the average accuracy of the TL group was 20.64 ± 3.17, while for the NTL group, it was 14.76 ± 5.28 (p<0.005). In the second test the average accuracy for the TL group was 21.52 ± 3.64, while for the NTL group, the average was 15.36 ± 29.5 (p<0.005). When divided into graduation periods, it was observed that the TL group showed a higher average across all three groups (p<0.05) in both tests. the students who attended the academic league activities have greater knowledge of the issues that are considered relevant to patient trauma care. In all periods of undergraduate academic training, the TL group had greater knowledge of the subject than the NTL group.


C-reactive protein induced activation of MAP-K and RANTES in human renal distal tubular epithelial cells in vitro.
C-reactive protein (CRP) is a component of the acute-phase reaction to inflammation, severe tissue injury, and infection. Investigations have shown that CRP concentration is highly increased in the urine during acute renal graft dysfunction and, therefore, may affect tubular cell metabolism. Nevertheless, no data about the effects of CRP on human renal tubular epithelial cells are available. Human renal distal tubular cells (DTC) were isolated immunomagnetically and cultured. Cells were stimulated with affinity chromatography pure native CRP from human ascites (10 - 0.001 microg/ml). Phosphorylation of MAP-K was assessed by Westernblot analysis. Release of RANTES and interleukin-6 was evaluated with an enzyme immunoassay. Cytotoxic effects of CRP were determined by a commercially available Live/Dead assay and MTT assay. Effects on cell proliferation were analyzed by a fluorimetric assay. Westernblot analysis clearly showed that CRP activates the MAP-K pathway of DTC. CRP upregulated RANTES expression of DTC in a significant and dose-dependent manner. CRP (10 microg/ml) induced a 12.3-fold upregulation, CRP 1 or 0.1 microg/ml induced a 6.3-/2.8-fold RANTES upregulation, respectively. Interleukin-6 synthesis was not influenced. Cytotoxic, proliferative or apoptotic effects were not observed at the concentrations used. We demonstrated an activating effect of CRP on DTC in vitro. In vivo, this effect of CRP might be part of the immune activation cascade during episodes of renal graft rejection or bacterial infections.


Biochemical markers of bone turnover - uses and limitations.
Bone turnover markers of resorption and formation are released during the process of bone remodelling. These markers have been extensively studied in a number of therapeutic trials of osteoporosis during the past decade. This has led to better understanding of their physiology, clinical applications and possible ways to optimize analytical techniques. Bone markers can complement the results of bone mineral density in the management of osteoporosis, but their use in clinical practice is challenged by pre-analytical and analytical variability. This review will discuss different types of bone markers, their limitations, use in different metabolic bone diseases and current recommendations from the International Osteoporosis Foundation and the International Federation of Clinical Chemistry and Laboratory Medicine bone marker standards working group.


Genetic heterogeneity in five captive specific pathogen-free groups of rhesus macaques.
Gene diversity was used to estimate genetic heterogeneity in the founders of five specific pathogen-free (SPF) colonies of rhesus macaques (Macaca mulatta) and ranged from about 0.20 to 0.32. In the founders of three groups at the California Regional Primate Research Center (CRPRC) that have been minimally managed to maintain genetic heterogeneity, gene diversity was about 0.30, approximately the value for that species, and has declined at the rate of only about 2.5% per generation since 1976. Without intervention, less than half the gene diversity in SPF harem groups will remain after 5 generations whereas gene diversity in multimale SPF groups should decline at less than half that rate. The proportion of gene diversity attributable to average differences among the three groups at the CRPRC, indicating the level of genetic subdivision, was lower than that in the founders of all but one of the SPF colonies and actually declined slightly over a 10-year period. Genetic subdivision in SPF colonies consisting of harem breeding groups was about three times that in colonies consisting of multimale breeding groups. The number of male breeders should be increased and variance in male reproductive success should be reduced in all SPF colonies, especially those containing multimale breeding groups. Genetic heterogeneity can most easily be retained, and genetic subdivision prevented, in each breeding group in all SPF colonies by ensuring gene flow among the breeding groups in each colony. Male breeders who exceed the lowest acceptable level of reproductive success in their colony of origin should also be exchanged among different SPF colonies to maximize the effective population size of the breeding groups in all SPF colonies.


De novo generation of a bright blue fluorophore from 2-oxoglutarate in biological samples.
We discovered the generation of a new bright blue fluorophore from a particular type of amine and 2-oxoglutarate (2-OG) under mild conditions without any chemical additives. Two β-aminoethylamine molecules and three 2-OG molecules form an unprecedented 2-pyridone structure with a fused γ-lactam ring (DTPP) via complex reactions including double decarboxylation and quintuple dehydration. The DTPP fluorophore shows a high quantum yield (80%) and photostability. The great potential of the present DTPP generation in the quantitative analysis of 2-OG in biosamples is demonstrated.


Nogo Receptor Signaling Restricts Adult Neural Plasticity by Limiting Synaptic AMPA Receptor Delivery.
Experience-dependent plasticity is limited in the adult brain, and its molecular and cellular mechanisms are poorly understood. Removal of the myelin-inhibiting signaling protein, Nogo receptor (NgR1), restores adult neural plasticity. Here we found that, in NgR1-deficient mice, whisker experience-driven synaptic α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) insertion in the barrel cortex, which is normally complete by 2 weeks after birth, lasts into adulthood. In vivo live imaging by two-photon microscopy revealed more AMPAR on the surface of spines in the adult barrel cortex of NgR1-deficient than on those of wild-type (WT) mice. Furthermore, we observed that whisker stimulation produced new spines in the adult barrel cortex of mutant but not WT mice, and that the newly synthesized spines contained surface AMPAR. These results suggest that Nogo signaling limits plasticity by restricting synaptic AMPAR delivery in coordination with anatomical plasticity.


Photorespiration participates in the assimilation of acetate in Chlorella sorokiniana under high light.
The development of microalgae on an industrial scale largely depends on the economic feasibility of mass production. High light induces productive suspensions during cultivation in a tubular photobioreactor. Herein, we report that high light, which inhibited the growth of Chlorella sorokiniana under autotrophic conditions, enhanced the growth of this alga in the presence of acetate. We compared pigments, proteomics and the metabolic flux ratio in C. sorokiniana cultivated under high light (HL) and under low light (LL) in the presence of acetate. Our results showed that high light induced the synthesis of xanthophyll and suppressed the synthesis of chlorophylls. Acetate in the medium was exhausted much more rapidly in HL than in LL. The data obtained from LC-MS/MS indicated that high light enhanced photorespiration, the Calvin cycle and the glyoxylate cycle of mixotrophic C. sorokiniana. The results of metabolic flux ratio analysis showed that the majority of the assimilated carbon derived from supplemented acetate, and photorespiratory glyoxylate could enter the glyoxylate cycle. Based on these data, we conclude that photorespiration provides glyoxylate to speed up the glyoxylate cycle, and releases acetate-derived CO2 for the Calvin cycle. Thus, photorespiration connects the glyoxylate cycle and the Calvin cycle, and participates in the assimilation of supplemented acetate in C. sorokiniana under high light.


SRSF2 directly inhibits intron splicing to suppresses cassette exon inclusion.
SRSF2, a Serine-Arginine rich (SR) protein, is a splicing activator that mediates exon inclusion and exclusion events equally well. Here we show SRSF2 directly suppresses intron splicing to suppress cassette exon inclusion in SMN premRNA. Through a serial mutagenesis, we demonstrate that a 10 nt RNA sequence surrounding the branch-point (BP), is important for SRSF2-mediated inhibition of cassette exon inclusion through directly interacting with SRSF2. We conclude that SRSF2 inhibits intron splicing to promote exon exclusion. [BMB Reports 2017; 50(8): 423-428].


[Genetic algorithm application to multi-focus patterns of 256-element phased array for focused ultrasound surgery].
The genetic optimal algorithm and sound field calculation approach for the spherical-section phased array are presented in this paper. The in-house manufactured 256-element phased array focused ultrasound surgery system is briefly described. The on-axis single focus and off-axis single focus are simulated along with the axis-symmetric six-focus patter and the axis-asymmetric four-focus pattern using a 256-element phased array and the genetic optimal algorithm and sound field calculation approach. The experimental results of the described 256-element phased array focused ultrasound surgery system acting on organic glass and phantom are also analyzed. The results of the simulations and experiments confirm the applicability of the genetic algorithm and field calculation approaches in accurately steering three dimensional foci and focus.


Current Approaches for Phenotyping as a Target for Precision Medicine in COPD Management.
The study of airway diseases continues to present several challenges for modern medicine. The different disease presentations with variables and overlapping features may result in a real challenge for the clinician. In this context, the concept of precision medicine has started to emerge in order to give answers to some of these challenges from a diagnostic and therapeutic point of view. The main reasons to target for precision medicine in chronic obstructive pulmonary disease (COPD) include that there is variability in the clinical presentation, there is no correlation between the different clinical variables at the patient level, there are a number of relevant clinical variables associated with outcomes, we do have specific therapies for specific patient types, and that there is variability in the clinical response to different therapies. To bring precision medicine into clinical practice several approaches have been used, including the use of independent variables to identify subjects, the use of multidimensional indexes, the so-called clinical phenotypes, and the approximation by the so-called treatable traits. All these approaches have their strengths and weaknesses which are reviewed in the present document. Although there is no universally accepted proposal, the available initiatives provide us with a framework on which to start working and move toward precision medicine in COPD, with the ultimate goal of bringing the best possible medicine to each patient in particular.


The High Stakes of Outsourcing in Health Care.
Outsourcing in health care has become increasingly common as health system administrators seek to enhance profitability and efficiency while maintaining clinical excellence. When clinical services are outsourced, however, the outsourcing organization relinquishes control over its most important service value: high-quality patient care. Farming out work to an external service provider can have many unintended results, including inconsistencies in standards of care; harmful medical errors; declines in patient and employee satisfaction; and damage to clinicians' morale and income, and to the health organization's culture, reputation, and long-term financial performance. Research on outsourcing in the areas of emergency medicine, radiology, laboratory services, and environmental services provides concerning evidence of potentially large downsides when outsourcing is driven by short-term cost concerns or is planned without diligently considering all of the ramifications of not keeping key clinical and nonclinical services in-house. To better equip health system leaders for decision-making about outsourcing, we examine this body of literature, identify common pitfalls of outsourcing in specific clinical and nonclinical health services and scenarios, explore alternatives to outsourcing, and consider how outsourcing (when necessary) can be done in a strategic manner that does not compromise the values of the organization and its commitment to patients.


Reduced frequency of pulsatile luteinizing hormone secretion in the luteal phase of the rhesus monkey. Involvement of endogenous opiates.
Pulsatile secretion of LH in women has been shown to vary during the menstrual cycle. LH pulse frequency during the luteal phase is markedly reduced compared to that in the follicular phase. The objectives of the present study were to determine if similar changes in pulsatile LH secretion occur in the monkey, and whether endogenous opiates are involved in producing these changes. In order to document if LH pulse frequency is reduced in the nonhuman primate luteal phase, serial blood samples were collected from 10 rhesus monkeys at 15-min intervals for 6 h at 3 different times of the luteal phase (early, mid-, and late). This pattern of secretion was contrasted to that observed during the ensuing early follicular phase. LH pulse frequency during the luteal phase was significantly reduced compared to the early follicular phase. Mean pulse frequency (+/- SE) was 0.84 +/- 0.16 pulses/6 h in the luteal phase vs. 2.99 +/- 0.58 pulses/6 h in the early follicular phase. When endogenous opioid activity was blocked during the luteal phase by a 5-h continuous infusion of naloxone (2 mg/h), an opiate antagonist, LH pulse frequency was increased to 2.48 +/- 0.25 pulses/5 h. This frequency was markedly different from the frequency of 0.85 +/- 0.17 pulses/5 h observed in the control period which immediately preceeded the naloxone infusion. The mean amplitude of the LH pulses in the luteal phase, which was significantly greater than that observed in the early follicular phase (20.9 +/- 1.9 ng/ml and 11.7 +/- 0.3 ng/ml) was not affected by naloxone (23.5 +/- 2.4 ng/ml vs. 25.3 +/- 1.9 ng/ml). Infusion of naloxone for longer periods (9 h) in 3 additional monkeys caused an increase in LH pulse frequency which was maintained in 2 of the monkeys, whereas the third animal exhibited only an acute response (a single pulse). These results indicate that the reduction in LH pulse frequency that occurs in the luteal phase of the rhesus menstrual cycle is an event in which endogenous opiates participate. Our previous finding that beta-endorphin release from neurons in the median eminence is stimulated during the luteal phase of the monkey, together with the present results, suggest that beta-endorphin functions as a modulator of pulsatile LH secretion in the primate menstrual cycle.


Initial injectable therapy in type 2 diabetes: Key considerations when choosing between glucagon-like peptide 1 receptor agonists and insulin.
Managing type 2 diabetes is complex and necessitates careful consideration of patient factors such as engagement in self-care, comorbidities and costs. Since type 2 diabetes is a progressive disease, many patients will require injectable agents, usually insulin. Recent ADA-EASD guidelines recommend glucagon-like peptide 1 receptor agonists (GLP-1 RAs) as first injectable therapy in most cases. The basis for this recommendation is the similar glycemic efficacy of GLP-1 RAs and insulin, but with GLP-1 RAs promoting weight loss instead of weight gain, at lower hypoglycemia risk, and with cardiovascular benefits in patients with pre-existing cardiovascular disease. GLP-1 RAs also reduce burden of glucose self-monitoring. However, tolerability and costs are important considerations, and notably, rates of drug discontinuation are often higher for GLP-1 RAs than basal insulin. To minimize risk of gastrointestinal symptoms patients should be started on lowest doses of GLP-1 RAs and up-titrated slowly. Overall healthcare costs may be lower with GLP-1 RAs compared to insulin. Though patient-level costs may still be prohibitive, GLP-1 RAs can replace 50-80 units of insulin daily and reduce costs associated with glucose self-monitoring. Decisions regarding initiating injectable therapy should be individualized. This review provides a framework to guide decision-making in the real-world setting.


An alternative technique for downsizing a modified Blalock-Taussig shunt.
An alternative surgical approach for downsizing an existed modified Blalock-Taussig shunt is described as a reoperation in a hemodynamically unstable patient. This method was selected in order to minimize the surgical manipulations in the setting of a critically ill infant.


HIV-1 Transmission, Replication Fitness and Disease Progression.
Upon transmission, human immunodeficiency virus type 1 (HIV-1) establishes infection of the lymphatic reservoir, leading to profound depletion of the memory CD4(+) T cell population, despite the induction of the adaptive immune response. The rapid evolution and association of viral variants having distinct characteristics with different stages of infection, the level of viral burden, and rate of disease progression suggest a role for viral variants in this process. Here, we review the literature on HIV-1 variants and disease and discuss the importance of viral fitness for transmission and disease.


Stimulation of replication efficiency of a chromatin template by chromosomal protein HMG-17.
The effect of chromosomal protein HMG-17 on the replication of a chromatin template was studied with minichromosomes containing the SV40 origin of replication. The minichromosomes were assembled from M13 DNA in Xenopus egg extracts in either the absence or presence of HMG-17. Structural data show that HMG-17 was efficiently incorporated into the chromatin and induced an extended chromatin structure. Using an in vitro SV40 replication system, we find that minichromosomes containing HMG-17 replicate with higher efficiency than minichromosomes deficient of HMG-17. The replicational potential of chromatin was enhanced only when HMG-17 was incorporated into the template during, but not after, chromatin assembly. HMG-17 stimulated replication only from a chromatin template, but not from protein-free DNA. Thus, HMG-17 protein enhances the rate of replication of a chromatin template by unfolding the higher order chromatin structure and increasing the accessibility of target sequences to components of the replication machinery.


1,2-dinitroguanidine.
The title compound, CH(3)N(5)O(4), is almost planar, and the conformation is fixed by two intramolecular N-H...O hydrogen bonds. Owing to the delocalization of pi-electron density over the whole molecule, there is through-conjugation, with the C-N, N-N and N-O bond lengths having values intermediate between those typical for the corresponding single and double bonds.


Ethical dilemmas in the treatment of adolescent gang members.
Therapists treating adolescent gang members face unique ethical dilemmas. These dilemmas arise from clinical issues that inevitably emerge in the treatment of this population. Clinical issues related to the adolescent gang member having great difficulty trusting, having experienced and observed much violence, and usually having participated in criminal activities are central to the treatment process. In this article I discuss the ethical problems that subsequently emerge: maintaining confidentiality, discharging one's duty to warn or protect, and imposing one's personal values. Suggestions for future research are offered.


A live-virus "suicide" vaccine for human immunodeficiency virus.
A vaccine that uses a live, attenuated human immunodeficiency virus (HIV) may offer the best hope of a vaccine against acquired immunodeficiency syndrome (AIDS). A recent improvement should increase the safety of the live-virus approach: a "suicide gene" inserted into the viral RNA, which causes infected cells to die when treated with ganciclovir. We envision using this strategy not only to prevent AIDS, but also to treat it.


The influence of histologic type on survival in early extranodal non-Hodgkin's lymphoma in head and neck.
Since the Rappaport classification provides little information for the prognosis of extranodal non-Hodgkin's lymphoma (NHL), the Kiel classification was used for 71 patients with head and neck extranodal NHL, stages IE and IIE. The ratios of low grade malignancy ( LGM ) and high grade malignancy ( HGM ) were about 60 and 40%, respectively. The lesions comprised 37 non-thyroid lymphomas and 34 thyroid lymphomas. 8 cases of thyroid NHL did not fit into a rigid classification scheme, and were separatively analyzed. In the whole group of patients and the subset of 37 patients with non-thyroid NHL, the 5-year survival rates for LGM were significantly better than for HGM . LGM showed a more favorable prognosis than HGM in 26 patients with thyroid NHL, but the difference was not statistically significant. 8 cases of thyroid NHL showed diffuse proliferation of centrocytes or centroblasts in which various numbers of nodules consisting of large centroblasts and centrocytes with high mitotic activity were scattered. The cases behaved as HGM . From these findings, we suggest that the Kiel classification in extranodal NHL is helpful.


The monosomy 7 clone in interphase and metaphase cell population: a combined chromosome and primed in situ labeling study.
Loss of a chromosome 7 is associated with a poor prognosis in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Some studies have shown higher frequencies of monosomy 7 (-7) in dividing than nondividing myeloid cells, which might indicate that -7 confers a proliferative advantage on the host cell. As other groups have not been able to confirm this, we compared the -7 frequencies in bone marrow metaphases as studied with conventional cytogenetics and in interphase cells using primed in situ (PRINS) labeling. We found significantly higher -7 frequencies in metaphase than in interphase cells irrespective of diagnosis and presence or absence of additional chromosome aberrations. Further, we found a significant correlation between the -7 percentages in resting and dividing cells. Finally, as our material showed a clear male preponderance, Mitelman's Catalog of Chromosome Aberrations in Cancer was searched for -7. Of 815 cases with AML or MDS, 491 (60.3%) were found to be men. To our knowledge, this is the first observation of a clear deviation from the 1:1 sex ratio in -7 patients.


[Pregnancy in obese patients: which risks is it necessary to fear?].
To evaluate the deleterious effects of maternal obesity on obstetrical complications and neonatal outcomes. Historical cohort study including all patients delivered in our maternity between 1st January 2002 and 31st December 2004. Intra uterine death and fetal loss before 22 weeks were excluded. Women were categorized by the Body Mass Index: less than 25, between 25 and 30, and more than 30. Maternal data, obstetrical complications, labor and its complications, and neonatal outcomes were studied. During these 3 years, 23.5% (1336/5686) of patients were overweight and 7.5% (425/5686) were obese. Obstetrical pathologies (gestational diabetes mellitus, hypertension, preeclampsia and fetal macrosomia) and labour induction were more significantly frequent in obese patients (P < 0.01). We noted twice more caesarean sections during labour in obese patients. The rate of artificial placental delivery was significantly higher in obese patients (P < 0.01). Obese patients with prior caesarean sections had a rate of vaginal delivery significantly lower than non obese patients with prior C-sections (23.6 vs 43.8%; P < 0.01). Mean children birth weight was significantly higher in obese patients (3305 vs 3181 g; P < 0.01) with no impact on Apgar score. Our study confirms that obesity is responsible for major obstetrical complications, for what should no doubt be considered as high risk pregnancies. Our practices must take these complications into account by ensuring an adapted and early management in order to improve maternal and neonatal issues.


Effects of anticholinergic treatment on the cardiac and respiratory systems in dogs sedated with medetomidine.
Alpha 2-adrenergic agonists are often used for sedation and, or, analgesia in dogs, but they are often associated with bradycardia and in some animals with atrioventricular heart block. In this study, atropine or glycopyrrolate either helped to maintain the heart rates or were effective in increasing reduced heart rates of dogs treated with medetomidine. In the process, however, cardiac dysrhythmias often developed. These dysrhythmias were predominantly associated with the combined responses to the medetomidine and the anticholinergic agent because there were no significant changes in respiratory function. A reduced blood oxygen content or increased blood carbon dioxide can contribute to cardiac irritability. Atropine and glycopyrrolate were more effective in preventing bradycardia and had less undesirable side effects when they were given before the administration of medetomidine.


VEGF-ablation therapy reduces drug delivery and therapeutic response in ECM-dense tumors.
The inadequate transport of drugs into the tumor tissue caused by its abnormal vasculature is a major obstacle to the treatment of cancer. Anti-vascular endothelial growth factor (anti-VEGF) drugs can cause phenotypic alteration and maturation of the tumor's vasculature. However, whether this consistently improves delivery and subsequent response to therapy is still controversial. Clinical results indicate that not all patients benefit from antiangiogenic treatment, necessitating the development of criteria to predict the effect of these agents in individual tumors. We demonstrate that, in anti-VEGF-refractory murine tumors, vascular changes after VEGF ablation result in reduced delivery leading to therapeutic failure. In these tumors, the impaired response after anti-VEGF treatment is directly linked to strong deposition of fibrillar extracellular matrix (ECM) components and high expression of lysyl oxidases. The resulting condensed, highly crosslinked ECM impeded drug permeation, protecting tumor cells from exposure to small-molecule drugs. The reduced vascular density after anti-VEGF treatment further decreased delivery in these tumors, an effect not compensated by the improved vessel quality. Pharmacological inhibition of lysyl oxidases improved drug delivery in various tumor models and reversed the negative effect of VEGF ablation on drug delivery and therapeutic response in anti-VEGF-resistant tumors. In conclusion, the vascular changes after anti-VEGF therapy can have a context-dependent negative impact on overall therapeutic efficacy. A determining factor is the tumor ECM, which strongly influences the effect of anti-VEGF therapy. Our results reveal the prospect to revert a possible negative effect and to potentiate responsiveness to antiangiogenic therapy by concomitantly targeting ECM-modifying enzymes.


[Psychiatry and philosophy: a paradigm of scientific knowledge unity].
Considering the potential unification of philosophic and scientific research methods, on the basis of Popper's theory, a relevant question about the indifference of the method towards the object-event. This work illustrates the Popper-Hempel nomological-inferential model and provides a description of the relationship between psychiatry and bioethics as an example of the unity of science.


The National Cholesterol Education Program - Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes.
The clinical value of metabolic syndrome is uncertain. Thus, we examined cardiovascular disease (CVD) and diabetes risk prediction by the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATPIII), International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome. We analyzed the risks associated with metabolic syndrome, the NCEP multiple risk factor categories, and 2-h glucose values in the San Antonio Heart Study (n = 2,559; age range 25-64 years; 7.4 years of follow-up). Both ATPIII metabolic syndrome plus age > or = 45 years (odds ratio 9.25 [95% CI 4.85-17.7]) and multiple (two or more) risk factors plus a 10-year coronary heart disease (CHD) risk of 10-20% (11.9 [6.00-23.6]) had similar CVD risk in men without CHD, as well as CHD risk equivalents. In women counterparts, multiple (two or more) risk factors plus a 10-year CHD risk of 10-20% was infrequent (10 of 1,254). However, either a 10-year CHD risk of 5-20% (7.72 [3.42-17.4]) or ATPIII metabolic syndrome plus age > or = 55 years (4.98 [2.08-12.0]) predicted CVD. ATPIII metabolic syndrome increased the area under the receiver operating characteristic curve of a model containing age, sex, ethnic origin, family history of diabetes, and 2-h and fasting glucose values (0.857 vs. 0.842, P = 0.013). All three metabolic syndrome definitions imparted similar CVD and diabetes risks. Metabolic syndrome is associated with a significant CVD risk, particularly in men aged > or = 45 years and women aged > or = 55 years. The metabolic syndrome predicts diabetes beyond glucose intolerance alone.


[Ad-hVEGF165 reverses homocysteine-induced endothelial dysfunction by regulating nitric oxide system].
To investigate the therapeutic effect of Ad-hVEGF165 on the endothelial cells dysfunction induced by homocysteine (Hcy) and related molecular mechanisms. Human umbilical vein endothelial cells CRL-1730 were treated with Hcy at different concentrations (0, 0.05, 1.00 mmol/L) for 24 h. The same concentration of Hcy, Ad-Track and Ad-hVEGF165 were added to the cells in the following groups: blank group, Hcy0.05 group, Hcy1.00 group, Ad-Track group, Hcy0.05+Ad-Track group, Hcy1.00+Ad-Track group, Ad-hVEGF165 group, Hcy0.05+Ad-hVEGF165 group, Hcy1.00+ Ad-hVEGF165 group for 48 h. The mRNA and protein expressions of eNOS and DDAH2 were detected by real-time PCR and Western blot. The correlations of mRNA and protein expressions between endothelial nitric oxide synthase (eNOS) and dimethylarginine dimthylaminohydrolase (DDAH)2 were evaluated by Pearson correlation analysis. Compared with blank group and Ad-hVEGF165 group, the mRNA and protein expressions of eNOS were decreased in Hcy0.05 group and Hcy0.05+Ad-hVEGF165 group (both P < 0.05), and the mRNA and protein expressions of DDAH2 in cells treated with 0.05 mmol/L and 1.00 mmol/L Hcy were reduced as well (all P < 0.05). DDAH2 mRNA and protein expression are increased (all P < 0.05) in Ad-hVEGF165 group compared with the blank group and Ad-Track, Hcy0.05 + Ad-hVEGF165 and Hcy0.05 group compared with Hcy0.05+Ad-Track group, Hcy1.00+Ad-hVEGF165 and Hcy1.00 group compared with Hcy1.00+Ad-Track group. The mRNA and protein expressions of eNOS and DDAH2 were uncorrelated under the effect of Hcy (r = 0.057 and 0.449, both P > 0.05) and VEGF (r = 0.284 and 0.432, both P > 0.05). Recombinant adenovirus Ad-hVEGF165 could reverse Hcy-induced endothelial cells dysfunction via upregulating the expressions of eNOS and DDAH2.


Spin-electricity conversion induced by spin injection into topological insulators.
We report successful spin injection into the surface states of topological insulators by using a spin pumping technique. By measuring the voltage that shows up across the samples as a result of spin pumping, we demonstrate that a spin-electricity conversion effect takes place in the surface states of bulk-insulating topological insulators Bi(1.5)Sb(0.5)Te(1.7)Se(1.3) and Sn-doped Bi(2)Te(2)Se. In this process, the injected spins are converted into a charge current along the Hall direction due to the spin-momentum locking on the surface state.


Pregnane X receptor modulates the inflammatory response in primary cultures of hepatocytes.
Bacterial sepsis is characterized by a rapid increase in the expression of inflammatory mediators to initiate the acute phase response in liver. Inflammatory mediator release is counterbalanced by the coordinated expression of anti-inflammatory molecules such as interleukin 1 receptor antagonist (IL1-Ra) through time. This study determined whether activation of pregnane X receptor (PXR, NR1I2) alters the lipopolysaccharide (LPS)-inducible gene expression program in primary cultures of hepatocytes (PCHs). Preactivation of PXR for 24 hours in PCHs isolated from wild-type mice suppressed the subsequent LPS-inducible expression of the key inflammatory mediators interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNFα) but not in PCHs isolated from Pxr-null (PXR-knockout [KO]) mice. Basal expression of key inflammatory cytokines was elevated in PCHs from PXR-KO mice. Stimulation of PCHs from PXR-KO mice with LPS alone produced enhanced levels of IL-1β when compared with wild-type mice. Experiments performed using PCHs from both humanized-PXR transgenic mice as well as human donors indicate that prolonged activation of PXR produces an increased secretion of IL1-Ra from cells through time. Our data reveal a working model that describes a pivotal role for PXR in both inhibiting as well as in resolving the inflammatory response in hepatocytes. Understanding the molecular details of how PXR is converted from a positive regulator of drug-metabolizing enzymes into a transcriptional suppressor of inflammation in liver will provide new pharmacologic strategies for modulating inflammatory-related diseases in the liver and intestine.


The evolution of epilepsy surgery.
This review traces the evolution of epilepsy surgery from its early beginnings in the 20th century with the development of neurophysiology, and later the identification of pathology in surgical specimens, to the tremendous boost given by direct brain imaging in the late 20th century. This resulted in the sophisticated methods of presurgical investigation, surgical techniques, and postsurgery care available from the millennium. In parallel, functional surgery, which modifies the nervous system's behaviour, available throughout, has attained a greater place by the use of stimulation.


Parasite strain specificity of precursor cytotoxic T cells in individual animals correlates with cross-protection in cattle challenged with Theileria parva.
Class I major histocompatibility complex-restricted parasite-specific cytotoxic T lymphocytes (CTL) are known to be a major component of the bovine immune response to the protozoan parasite Theileria parva, but formal proof for their role in protection of cattle against infection with T. parva has been lacking. Animals immunized with one stock of T. parva show variations in the degree of protection against heterologous challenge and also in the parasite strain specificity of their CTL responses. The present study investigated the relationship of strain specificity of CTL responses and cross-protection in an effort to verify the role of CTL in protection. The parasite strain specificity of the CTL responses generated in 23 cattle immunized with either of two immunologically distinct parasite populations was examined, and the susceptibility of individual cattle to challenge with the heterologous parasite population was determined. The frequency of stock-specific or cross-reactive CTL precursor cells (CTLp) in individual animals was measured by a limiting-dilution microassay. A proportion of animals immunized with either parasite exhibited cross-reactive CTLp, whereas CTLp detected in the remaining animals were specific for the homologous parasite. On challenge with the heterologous stock, those animals with cross-reactive CTLp were solidly protected while those with strain-specific CTLp showed moderate to severe reactions, although many of them recovered. The finding of a close association between strain specificity of the CTL response and protection against challenge provides strong evidence that CTL are important in mediating immunity.


A Randomized Controlled Trial to Improve the Success of Women Assistant Professors.
Given the persistent disparity in the advancement of women compared with men faculty in academic medicine, it is critical to develop effective interventions to enhance women's careers. We carried out a cluster-randomized, multifaceted intervention to improve the success of women assistant professors at a research-intensive medical school. Twenty-seven departments/divisions were randomly assigned to intervention or control groups. The three-tiered intervention included components that were aimed at (1) the professional development of women assistant professors, (2) changes at the department/division level through faculty-led task forces, and (3) engagement of institutional leaders. Generalized linear models were used to test associations between assignment and outcomes, adjusting for correlations induced by the clustered design. Academic productivity and work self-efficacy improved significantly over the 3-year trial in both intervention and control groups, but the improvements did not differ between the groups. Average hours worked per week declined significantly more for faculty in the intervention group as compared with the control group (-3.82 vs. -1.39 hours, respectively, p = 0.006). The PhD faculty in the intervention group published significantly more than PhD controls; however, no differences were observed between MDs in the intervention group and MDs in the control group. Significant improvements in academic productivity and work self-efficacy occurred in both intervention and control groups, potentially due to school-wide intervention effects. A greater decline in work hours in the intervention group despite similar increases in academic productivity may reflect learning to "work smarter" or reveal efficiencies brought about as a result of the multifaceted intervention. The intervention appeared to benefit the academic productivity of faculty with PhDs, but not MDs, suggesting that interventions should be more intense or tailored to specific faculty groups.


Circumvention of acquired resistance to doxorubicin in K562 human leukemia cells by oxatomide.
We studied the effect of oxatomide, an antiallergic drug, on the resistance of K562 cells to doxorubicin. Oxatomide synergistically potentiated the cytotoxicity of doxorubicin in doxorubicin-resistant K562 cells (K562/DXR) at a concentration of 1-10 microM, but had hardly any synergistic effect on the parental cell line (K562) at the same concentration. Oxatomide inhibit P-glycoprotein pump-efflux activity and the binding of [3H]-azidopine to the cell-surface protein P-glycoprotein, in a dose-related manner. These results indicate that oxatomide reverses the multidrug-resistance phenotype through direct interaction with P-glycoprotein.


High levels of dietary advanced glycation end products transform low-density lipoprotein into a potent redox-sensitive mitogen-activated protein kinase stimulant in diabetic patients.
LDL modification by endogenous advanced glycation end products (AGEs) is thought to contribute to cardiovascular disease of diabetes. It remains unclear, however, whether exogenous (diet-derived) AGEs influence glycoxidation and endothelial cell toxicity of diabetic LDL. Twenty-four diabetic subjects were randomized to either a standard diet (here called high-AGE, HAGE) or a diet 5-fold lower in AGE (LAGE diet) for 6 weeks. LDL pooled from patients on HAGE diet (Db-HAGE-LDL) was more glycated than LDL from the LAGE diet group (Db-LAGE-LDL) (192 versus 92 AGE U/mg apolipoprotein B) and more oxidized (5.7 versus 1.5 nmol malondialdehyde/mg lipoprotein). When added to human endothelial cells (ECV 304 or human umbilical vein endothelial cells), Db-HAGE-LDL promoted marked ERK1/2 phosphorylation (pERK1/2) (5.5- to 10-fold of control) in a time- and dose-dependent manner compared with Db-LAGE-LDL or native LDL. In addition, Db-HAGE-LDL stimulated NF-kappaB activity significantly in ECV 304 and human umbilical vein endothelial cells (2.3-fold above baseline) in a manner inhibitable by a MEK inhibitor PD98059 (10 micromol/L), the antioxidant N-acetyl-l-cysteine, NAC (30 mmol/L), and the NADPH oxidase inhibitor DPI (20 micromol/L). In contrast to Db-LAGE-LD and native LDL, Db-HAGE-LDL induced significant soluble vascular cell adhesion molecule-1 production (2.3-fold), which was blocked by PD98059, NAC, and DPI. Exposure to daily dietary glycoxidants enhances LDL-induced vascular toxicity via redox-sensitive mitogen-activated protein kinase activation. This can be prevented by dietary AGE restriction.


Using homology modeling to interrogate binding affinity in neutralization of ricin toxin by a family of single domain antibodies.
In this report we investigated, within a group of closely related single domain camelid antibodies (VH Hs), the relationship between binding affinity and neutralizing activity as it pertains to ricin, a fast-acting toxin and biothreat agent. The V1C7-like VH Hs (V1C7, V2B9, V2E8, and V5C1) are similar in amino acid sequence, but differ in their binding affinities and toxin-neutralizing activities. Using the X-ray crystal structure of V1C7 in complex with ricin's enzymatic subunit (RTA) as a template, Rosetta-based homology modeling coupled with energetic decomposition led us to predict that a single pairwise interaction between Arg29 on V5C1 and Glu67 on RTA was responsible for the difference in ricin toxin binding affinity between V1C7, a weak neutralizer, and V5C1, a moderate neutralizer. This prediction was borne out experimentally: substitution of Arg for Gly at position 29 enhanced V1C7's binding affinity for ricin, whereas the reverse (ie, Gly for Arg at position 29) diminished V5C1's binding affinity by >10 fold. As expected, the V5C1R29G mutant was largely devoid of toxin-neutralizing activity (TNA). However, the TNA of the V1C7G29R mutant was not correspondingly improved, indicating that in the V1C7 family binding affinity alone does not account for differences in antibody function. V1C7 and V5C1, as well as their respective point mutants, recognized indistinguishable epitopes on RTA, at least at the level of sensitivity afforded by hydrogen-deuterium mass spectrometry. The results of this study have implications for engineering therapeutic antibodies because they demonstrate that even subtle differences in epitope specificity can account for important differences in antibody function.


The TGF-beta superfamily and its roles in the human ovary and placenta.
The transforming growth factor-beta (TGF-beta) superfamily consists of a large group of growth and differentiation factors, such as TGF-betas, activins, inhibins, growth and differentiation factors (GDFs), and bone morphogenetic proteins (BMPs). These molecules act through specific receptor complexes that are composed of type I and type II serine/threonine receptor kinases. The receptor kinases subsequently activate Smad proteins, which then propagate the signals into the nucleus to regulate target gene expression. Several ligands in this family, such as TGF-betas, activins, inhibins, BMP-15, and GDF-9, play important roles in regulating human ovarian functions, including follicle development and maturation. Activin and TGF-beta are also involved in regulating placental development and functions. Abnormal expression or function of these ligands has been found in several pathological conditions. This review summarizes the role of the TGF-beta superfamily in human ovarian and placental regulation and function, and the potential clinical implications.


Elimination of levofloxacin in critically ill patients with renal failure: influence of continuous veno-venous hemofiltration.
Pharmacokinetic data on levofloxacin in critically ill patients are sparse and conflicting. Aim of the study was to assess the clearance of levofloxacin in critically ill patients treated with continuous veno-venous hemofiltration (CVVH). Pharmacokinetics of levofloxacin were studied in 11 critically ill patients. Four patients were treated with CVVH because of renal failure, 4 patients had moderately impaired renal function but were not on hemofiltration, and 3 patients had approximately normal renal function. Patients received 0.5 g levofloxacin infused over 0.5 hours. Plasma levels of levofloxacin were determined by HPLC and pharmacokinetic parameters were calculated using a non-compartmental model. Levofloxacin clearance in critically ill patients with approximately normal renal function was similar to that in healthy subjects. In critically ill patients with impaired renal function not on CVVH, mean half-life was prolonged by a factor of about 3 (20-25 hours). The mean residence time and the volume of distribution were also increased. In renal failure treated with CVVH, a wide variability in pharmacokinetics was seen. The half-life was about 30 hours and the mean levofloxacin clearance was raised by a factor of 2. The area under the concentration-time curve was reduced by hemofiltration, while the volume of distribution was increased. There was a positive correlation between blood flow through the hemofilter and levofloxacin clearance. Variable amounts of the drug were recovered from the hemofilter. Most plasma levels, however, were in the therapeutic range and drug accumulation to toxic plasma concentrations was not observed in renal failure patients undergoing CVVH and receiving single daily administration of 0.5 g of levofloxacin i.v. During CVVH using polysulfone membrane hemofilters, plasma concentrations of levofloxacin are not easily predictable. Levofloxacin clearance may be affected by binding to secondary membranes formed in hemofilters during CVVH and blood flow rates have a significant impact on the pharmacokinetics of levofloxacin.


Identification of Rare Variants in ATP8B4 as a Risk Factor for Systemic Sclerosis by Whole-Exome Sequencing.
To determine the contribution of rare variants as genetic modifiers of the expressivity, penetrance, and severity of systemic sclerosis (SSc). We performed whole-exome sequencing of 78 European American patients with SSc, including 35 patients without pulmonary arterial hypertension (PAH) and 43 patients with PAH. Association testing of case-control probability for rare variants was performed using the unified sequence kernel association test with optimal kernel weighting and small sample adjustment by comparing all SSc patients with a reference population of 3,179 controls from the Exome Sequencing Project 5,500 exome data set. Replication genotyping was performed in an independent sample of 3,263 patients (415 patients with SSc and 2,848 controls). We conducted expression profiling of messenger RNA from 61 SSc patients (19 without PAH and 42 with PAH) and 41 corresponding controls. The ATP8B4 gene was associated with a significant increase in the risk of SSc (P = 2.77 × 10(-7)). Among the 64 ATP8B4 variants tested, a single missense variant, c.1308C>G (F436L, rs55687265), provided the most compelling evidence of association (P = 9.35 × 10(-10), odds ratio [OR] 6.11), which was confirmed in the replication cohort (P = 0.012, OR 1.86) and meta-analysis (P = 1.92 × 10(-7), OR 2.5). Genes involved in E3 ubiquitin-protein ligase complex (ASB10) and cyclic nucleotide gated channelopathies (CNGB3) as well as HLA-DRB5 and HSPB2 (heat-shock protein 27) provided additional evidence of association (P < 10(-5)). Differential ATP8B4 expression was observed among the SSc patients compared to the controls (P = 0.0005). ATP8B4 may represent a putative genetic risk factor for SSc and pulmonary vascular complications.


Vibrational circular dichroism spectroscopy study of paroxetine and femoxetine precursors.
The solution structures of (3R,4S)- and (3S,4R)- 4-(4-fluorophenyl)-3-hydroxylmethyl- 1-methylpiperidine, which are intermediates in the synthesis of the two pharmaceuticals paroxetine and femoxetine, were studied by vibrational circular dichroism (VCD) spectroscopy. In addition, six derivatives with different substituents attached to the C3 atom were prepared and their VCD and absorption spectra discussed with the aid of ab initio simulations. The VCD spectra were found to be sensitive to the geometry changes. In addition, a subtle variation caused by intermolecular aggregation was apparent in the spectra. The VCD technique can be applied for structural analysis of chiral pharmaceuticals in solutions.


New Genetic Insights into Pearl Millet Diversity As Revealed by Characterization of Early- and Late-Flowering Landraces from Senegal.
Pearl millet (Pennisetum glaucum (L.) R. Br.) is a staple food and a drought-tolerant cereal well adapted to Sub-Saharan Africa agro-ecosystems. An important diversity of pearl millet landraces has been widely conserved by farmers and therefore could help copping with climate changes and contribute to future food security. Hence, characterizing its genetic diversity and population structure can contribute to better assist breeding programs for a sustainable agricultural productivity enhancement. Toward this goal, a comprehensive panel of 404 accessions were used that correspond to 12 improved varieties, 306 early flowering and 86 late-flowering cultivated landraces from Senegal. Twelve highly polymorphic SSR markers were used to study diversity and population structure. Two genes, PgMADS11 and PgPHYC, were genotyped to assess their association to flowering phenotypic difference in landraces. Results indicate a large diversity and untapped potential of Senegalese pearl millet germplasm as well as a genetic differentiation between early- and late-flowering landraces. Further, a fine-scale genetic difference of PgPHYC and PgMADS11 (SNP and indel, respectively) and co-variation of their alleles with flowering time were found among landraces. These findings highlight new genetic insights of pearl millet useful to define heterotic populations for breeding, genomic association panel, or crosses for trait-specific mapping.


Spinal Epidural Hematoma Related to Vertebral Fracture in an Atypical Rigid Diffuse Idiopathic Skeletal Hyperostosis: A Case Report.
Spinal epidural hematoma (SEH) is a rare disease that causes cord compression and neurologic deficit. Spontaneous SEH is related to minor trauma, bleeding disorders, and anticoagulant medications. Posttraumatic SEH has been associated with low-energy spine hyperextension injuries in patients with ankylosing spinal disorders such as ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis (DISH). A variant named atypical DISH-like with SEH is reported. To describe the management, diagnosis, and treatment of an unusual SEH case in a patient causing delayed neurologic deficit with rigid atypical DISH-like spine. An elderly woman with prior antiplatelet therapy presented with delayed neurological deficit suffering trauma after falling. Computed tomography (CT) imaging studies reveal hyperextension fracture pattern and signs mimic DISH missed on standard X-ray images. Magnetic resonance (MR) study demonstrates posterior epidural mass compatible with SEH in thoracic spine with cord compression. Using a midline posterior approach, an urgent intervention and a left multiple partial unilateral decompressive laminectomy at T4-T7 and a long instrumented fusion at T3-T9 were performed for achieving spinal stability and neurological improvement, both of which were observed. Patients with rigid spine who sustain low-energy injuries may be prone to have a fracture and epidural hematoma, especially if they take anticoagulant medications. Imaging studies including MR and CT scans should be reviewed carefully to rule out any occult fracture. Urgent or early surgical hematoma drainage and instrumented fusion must be performed to achieve stability and functional recovery.


Gold Raspberry-Like Colloidosomes Prepared at the Water-Nitromethane Interface.
In this study, we propose a simple shake-flask method to produce micron-size colloidosomes from a liquid-liquid interface functionalized with a gold nanoparticle (AuNP) film. A step-by-step extraction process of an organic phase partially miscible with water led to the formation of raspberry-like structures covered and protected by a gold nanofilm. The distinctive feature of the prepared colloidosomes is a very thin shell consisting of small AuNPs of 12 or 38 nm in diameter instead of several hundred nanometers reported previously. The interesting and remarkable property of the proposed approach is their reversibility: the colloidosomes may be easily transformed back to a nanofilm state simply by adding pure organic solvent. The obtained colloidosomes have a broadband absorbance spectrum, which makes them of great interest in applications such as photothermal therapy, surface-enhanced Raman spectroscopy studies, and microreactor vesicles for interfacial electrocatalysis.


Study on the Fabrication of Super-Hydrophobic Surface on Inconel Alloy via Nanosecond Laser Ablation.
Nanosecond laser ablated metallic surfaces showed initial super-hydrophilicity, and then experienced gradual wettability conversion to super-hydrophobicity with the increase of exposing time to ambient air. Due to the presence of hierarchical structures and change of surface chemistry, the laser-induced Inconel alloy surfaces showed a stable apparent contact angle beyond 150° over 30-day air exposure. The wetting states were proposed to elucidate the initial super-hydrophilicity and the final super-hydrophobicity. The basic fundaments behind the wettability conversion was explored by analyzing surface chemistry using X-ray photoelectron spectroscopy (XPS). The results indicated that the origins of super-hydrophobicity were identified as the increase of carbon content and the dominance of C⁻C(H) functional group. The C⁻C(H) bond with excellent nonpolarity derived from the chemisorbed airborne hydrocarbons, which resulted in dramatic reduction of surface-free-energy. This study confirmed that the surface chemistry is not the only factor to determine surface super-hydrophobicity. The laser-induced super-hydrophobicity was attributed to the synergistic effect of surface topography and surface chemical compositions. In this work, the corresponding chemical reaction was particularly described to discuss how the airborne hydrocarbons were attached onto the laser ablated surfaces, which reveals the generation mechanism of air-exposed super-hydrophobic surfaces.


Immunophenotypic profile predictive of KIT activating mutations in AML1-ETO leukemia.
Translocation (8; 21)/AML1-ETO is considered a favorable cytogenetic abnormality in acute myeloid leukemia (AML). However, associated KIT activating mutations confer poor outcome. The immunophenotype associated with KIT mutations in AML1-ETO has not previously been elucidated. We retrospectively reviewed the immunophenotype by flow cytometry of 56 cases of AML with t(8; 21) and compared them with 100 cases of AML without t(8; 21). In 21 t(8; 21) cases, we sought KIT mutations by direct sequencing. Although CD19 and CD56 were aberrantly expressed in 42 (75%) of 56 and 46 (82%) of 56 cases, respectively, with t(8; 21), these markers were only expressed in 4% and 25%, respectively, without t(8; 21) (P < .001). However, the 5 KIT-mutated cases (D816H, 3; D816Y, 1; and N822K, 1) of t(8; 21) AML had diminished CD19 expression (P = .04) with definite CD56 expression (P = .30) on myeloid blasts. Our study suggests that KIT activating mutations in AML with t(8; 21) are associated with diminished CD 19 and positive CD56 expression on leukemic blasts and, thus, can be phenotypically distinguished from AML1-ETO leukemias without KIT mutations.


Nutritional indexes of clients in a maternity and infant care project. II. Dietary, anthropometric, and hematologic indexes of pregnant women and their infants.
Low intakes by 198 pregnant women of milk, fruit, and vegetables are reported: consumption of meat and bread and cereals was satisfactory. However, mean hemoglobin and hematocrit values were within acceptable ranges for these women, indicating that supplementation apparently compensated in part for poor dietary habits. Protein intake of the infants of these mothers was above recommendations, the advisability of which is questioned. Height and weight of the male and female infants at birth were above and below the 10th percentile, respectively. By the age of four months, however, all infants were equal to or above this level. Mean hemoglobin levels were above acceptable levels.


Signature of prognostic epithelial-mesenchymal transition related long noncoding RNAs (ERLs) in hepatocellular carcinoma.
Reliable biomarkers are of great significance for the treatment and diagnosis of hepatocellular carcinoma (HCC). This study identified potential prognostic epithelial-mesenchymal transition related lncRNAs (ERLs) by the cancer genome atlas (TCGA) database and bioinformatics.The differential expression of long noncoding RNA (lncRNA) was obtained by analyzing the lncRNA data of 370 HCC samples in TCGA. Then, Pearson correlation analysis was carried out with EMT related genes (ERGs) from molecular signatures database. Combined with the univariate Cox expression analysis of the total survival rate of hepatocellular carcinoma (HCC) patients, the prognostic ERLs were obtained. Then use "step" function to select the optimal combination of constructing multivariate Cox expression model. The expression levels of ERLs in HCC samples were verified by real-time quantitative polymerase chain reaction.Finally, we identified 5 prognostic ERLs (AC023157.3, AC099850.3, AL031985.3, AL365203.2, CYTOR). The model showed that these prognostic markers were reliable independent predictors of risk factors (P value <.0001, hazard ratio [HR] = 2.400, 95% confidence interval [CI] = 1.667-3.454 for OS). In the time-dependent receiver operating characteristic analysis, this prognostic marker is a good predictor of HCC survival (area under the curve of 1 year, 2 years, 3 years, and 5 years are 0.754, 0.720, 0.704, and 0.662 respectively). We analyzed the correlation of clinical characteristics of these prognostic markers, and the results show that this prognostic marker is an independent factor that can predict the prognosis of HCC more accurately. In addition, by matching with the Molecular Signatures Database, we obtained 18 ERLs, and then constructed the HCC prognosis model and clinical feature correlation analysis using 5 prognostic ERLs. The results show that these prognostic markers have reliable independent predictive value. Bioinformatics analysis showed that these prognostic markers were involved in the regulation of EMT and related functions of tumor occurrence and migration.Five prognostic types of ERLs identified in this study can be used as potential biomarkers to predict the prognosis of HCC.


Anti-Remodeling Cardiac Therapy in Patients With Duchenne Muscular Dystrophy, Meta-Analysis Study.
Background: Almost all Duchenne muscular dystrophy (DMD) patients that reach their 30s present cardiomyopathy. As a result, this population remains under-treated. There is no sufficient proof of the efficacy of anti-remodeling cardiac therapy for DMD cardiomyopathy (DMDCM). We aim to assess the efficacy of anti-remodeling cardiac therapy for DMDCM by using meta-analysis. Methods: PubMed (MEDLINE), Embase, and Cochrane library were searched through January 2021. Randomized control trials, case-control studies, and observational studies that reported assessments of cardiovascular outcomes and death of participants using angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid-receptor antagonists and Ivabradine, were included. The primary outcome was total mortality. Secondary outcomes included changes in left ventricular ejection fraction (LVEF), serum natriuretic peptide levels (BNP), and heart rate (HR). Data were extracted for eligibility by two independent reviewers. Random-effects meta-analysis was used to pool results. Results: Twelve studies with 439 patients were included in our meta-analysis. Treated patients have lower HR, mean difference of -17 beats per minute (CI [-25]-[-9], p < 0.01). The LVEF was improved in treated patients, with a mean difference of LVEF of 3.77% (CI 0.44-7.12, p < 0.03). Although mortality rates did not reach statistical significance there was a trend for total mortality reduction (hazard ratio 0.36, CI (0.1-1.25), p = 0.107) and for BNP reduction (SSMD: 0.141, CI ([-0.19]-[0.47]), p = 0.3). Conclusion: Pharmacologic treatment for DMDCM patients is associated with decreased HR and improved LVEF. Therefore, DMDCM patients may benefit from implementing guideline therapy for HF.


Making a difference as a nurse consultant.
The nurse consultant role has existed for a decade. The five components of the role--professional leadership, service development, research, education and training, and expert practice--are discussed in relation to Aileen Fraser's work with older people in Bristol. Ms Fraser explains how she has identified gaps in services and developed new policies to improve practice on safeguarding vulnerable adults. She also discusses how she has been influenced by good practice she witnessed on a study tour in the United States.


Decomposition of lignin from sugar cane bagasse during ozonation process monitored by optical and mass spectrometries.
Mass spectrometry was used to monitor neutral chemical species from sugar cane bagasse that could volatilize during the bagasse ozonation process. Lignin fragments and some radicals liberated by direct ozone reaction with the biomass structure were detected. Ozone density was monitored during the ozonation by optical absorption spectroscopy. The optical results indicated that the ozone interaction with the bagasse material was better for bagasse particle sizes less than or equal to 0.5 mm. Both techniques have shown that the best condition for the ozone diffusion in the bagasse was at 50% of its moisture content. In addition, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were employed to analyze the lignin bond disruptions and morphology changes of the bagasse surface that occurred due to the ozonolysis reactions as well. Appropriate chemical characterization of the lignin content in bagasse before and after its ozonation was also carried out.


Potassium and diuretic-induced ventricular arrhythmias in ambulatory hypertensive patients.
We studied 17 hypertensive men to determine the relationship of diuretic-induced hypokalemia to ventricular ectopic activity ( VEA ). Blood values and 24-hour ambulatory ECG monitoring were done at baseline, after diuretic and after serum potassium normalization. Two subgroups of patients were identified: group A patients were older (63.0 vs. 53.8 years) and had clinical evidence of organic heart disease compared to group B. Group A had increased frequency and complexity of VEA with diuretic which reverted to baseline after potassium normalization. Group B had no changes. Serum and intra-red blood cell potassium decrements were equal in both groups. We conclude that clinical in addition to laboratory observation should be used to identify those hypertensive patients most susceptible to diuretic-induced VEA and their serum potassium level should be normalized in order to minimize this complication.


Effect of soy fiber and soy protein on cholesterol metabolism and atherosclerosis in rabbits.
The effect of dietary fiber isolated from dehulled, defatted soybean seeds on cholesterol (CHOL) metabolism and atherosclerosis in rabbits was studied alone and in combination with isolated soy protein (ISP). Soy fiber (SF) contains both cellulosic and non-cellulosic dietary fiber. Based on the official AOAC method, soy fibers contains 75% total dietary fiber. Rabbits at 6 months of age were randomly assigned to 1 of 4 dietary treatments. All rabbits received either a casein or ISP-based diet with cellulose or SF as the only dietary fiber source for 36 weeks. Fasting blood samples and feces were collected and analyzed for lipids from individual rabbits. The entire aorta was removed and fixed, and sudanophilic stained lesions were examined visually. Rabbits consuming the SF and/or ISP diets had lower plasma CHOL levels and lower incidence of atherosclerotic lesions relative to the rabbits fed the casein-based cellulose diets. Rabbits consuming the SF and/or ISP diets also had a lower CHOL content in their liver and heart. Rabbits fed ISP-based diets had consistently increased fecal bile acid excretion, whereas rabbits fed diets containing SF had increased fecal and cholesterol concentration. These results suggest a complementary role for SF and ISP in preventing atherosclerosis in rabbits.


The history and present status of moral insanity.
Psychiatric taxonomies, always a little uncertain, are most confused and illogical when they endeavour to encompass the moral and legal aspects of human behaviour. The concept of moral insanity represented a step backwards when it came into being, but it has persisted for a century and a half, changing only its title. Its creation and its subsequent history exemplify some of the common errors in psychiatric theorising.


Analysis of Renal Artery Stenosis in Patients with Heart Failure: A RASHEF Study.
Previous data are controversial about the association of renal artery stenosis (RAS) with clinical outcome in patients with heart failure. Definition of RAS in previous studies might not be appropriate. By definition of RAS with renal duplex sonography, we investigated the association of RAS with clinical outcome in patients with heart failure. In this retrospective study, we identified 164 patients with heart failure (New York Heart Association classification ≥II; left ventricular ejection fraction <50%) who had received renal duplex sonography during hospital stay. RAS was defined as renal-aortic ratio ≥3.5 or a peak systolic velocity ≥200 cm/s (or both), or occlusion of the renal artery. Categorical data of patients were compared using the Chi-square test or Fisher's exact test. Cox proportional hazards regression modeling technique was used to investigate the prognostic significance of possible predictors. Finally, 143 patients were enrolled. Median follow-up time was 32 months (1-53 months). Twenty-two patients were diagnosed as RAS by renal duplex sonography, including 13 unilateral RAS (3 left RAS, 10 right RAS) and 9 bilateral RAS. There were more all-cause mortality and cardiovascular death in patients with RAS than patients without RAS. By multivariate analysis, RAS was a significant predictor for all-cause death and cardiovascular death (hazard ratio [HR] = 4.155, 95% confidence interval [CI]: 1.546-11.164, P = 0.005; and HR = 3.483, 95% CI: 1.200-10.104, P = 0.022, respectively). As for composite endpoint events, including death, nonfatal myocardial infarction, ischemic stroke or intracranial hemorrhage, rehospitalization for cardiac failure, and renal replacement therapy, only angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker was significant predictor. RAS was not a significant predictor for composite endpoint events. Our data suggested that RAS is associated with a poorer clinical outcome in patients with heart failure.


Postbiotic activities of lactobacilli-derived factors.
Probiotics are alive nonpathogenic microorganisms present in the gut microbiota that confer benefits to the host for his health. They act through molecular and cellular mechanisms that contrast pathogen bacteria adhesion, enhance innate immunity, decrease pathogen-induced inflammation, and promote intestinal epithelial cell survival, barrier function, and protective responses. Some of these beneficial effects result to be determined by secreted probiotic-derived factors that recently have been identified as "postbiotic" mediators. They have been reported for several probiotic strains but most available literature concerns Lactobacilli. In this review, we focus on the reported actions of several secretory products of different Lactobacillus species highlighting the available mechanistic data. The identification of soluble factors mediating the beneficial effects of probiotics may present an opportunity not only to understand their fine mechanisms of action, but also to develop effective pharmacological strategies that could integrate the action of treatments with live bacteria.


[Methologic contribution to blood transfusion materials surveillance].
To reduce seriousness and frequency of iatrogenic risk implies prevention policies and efficient operational systems for vigilance. This risk management implies definition of precise organizations and procedures able to locate and to notify quickly undesirable events. This is the case about single use medical devices (SUMD) used in blood transfusion. This article is a contribution to the organisation of the implemented material vigilance in blood transfusion, collectively carried out with actors concerned (users, manufacturers, National Commission for Material Vigilance). It presents a lot of tools and methods to favour practices harmonization, as well as preventive a curative (specifications before purchase, main part of the quality contract between customer and supplier; internal control plan; index for medical device used in transfusion; illustrated glossaries for three main families of medical devices; index about symptomatic events; definitions of seriousness levels with their operational consequences; methods to manage a single use medical device judged as defective; tool for the review of incidents according to reference and batch). Then, the management of incidents about SUMD is presented within a material vigilance system integrated into the quality system of the institution, for user as for manufacturer. This is done in a chronological order with successively description of the incident, the assessment of the impact, the management of the associated risk, the periodical review of incidents and management of matters in dispute.