Single-dose intravenous nefopam on postoperative catheter-related bladder discomfort in patients undergoing transurethral resection of prostate: a randomized, double-blind placebo-controlled trial.
Transurethral resection of prostate (TURP) with postoperative catheter traction can lead to significant catheter-related bladder discomfort (CRBD). This condition causes many postoperative complications and low patient satisfaction. This study aimed to evaluate the effectiveness of preoperative single-dose intravenous nefopam on the incidence and severity of CRBD and its adverse effects. This randomized, controlled, double-blind study included patients who underwent TURP under spinal anesthesia with postoperative urinary catheter traction. Patients were allocated into nefopam (NF) and normal saline (NS) groups. Twenty mg of nefopam in normal saline solution (NSS) 100 mL or NSS 100 mL were given intravenously before TURP. The primary outcome was the incidence of CRBD. Seventy-three patients were randomized into NF (n = 37) and NS (n = 36) groups. There were 35 and 33 patients in the NF and NS groups, respectively, in the final analysis. The incidences of CRBD were 45.71% and 84.85% in the NF and NS groups at 6 h after operation, respectively, OR 0.54 (95% CI 0.36, 0.73), while before the end of catheter traction, the corresponding incidences were 37.14% and 75.76%, respectively, OR 0.49 (95% CI 0.28, 0.84). The CRBD scores were statistically significantly lower in the NF group at both time points. Morphine consumptions and adverse effects were not different between groups. Patient satisfaction was higher in the NF group. Single-dose nefopam significantly reduced the incidence and severity of CRBD in patients undergoing TURP with urinary catheter traction at 6 h after the procedure and before the end of catheter traction without increasing the adverse effects.


Diffusion tensor imaging of the human optic nerve using a non-CPMG fast spin echo sequence.
To investigate the diffusion tensor properties of the human optic nerve in vivo using a non-Carr-Purcell-Meiboom-Gill (CPMG) fast spin echo (FSE) sequence. This non-CPMG FSE sequence, which is based on a quadratic phase modulation of the refocusing pulses, allows diffusion measures to be acquired with full signal and without artifacts from geometric distortions due to magnetic field inhomogeneities, which are among the main problems encountered in the orbital area. Good-quality images were obtained at a resolution of 0.94 x 0.94 x 3 mm. The mean diffusivity (MD) and fractional anisotropy (FA) were respectively 1.1 +/- 0.2 x 10(-3) mm(2)/second and 0.49 +/- 0.06, reflecting the optic nerve anisotropy. This non-CPMG-FSE sequence provides reliable diffusion-weighted images of the human optic nerve. This approach could potentially improve the diagnosis and management of optic nerve diseases or compression, such as optic neuritis, orbit tumors, and muscle hypertrophy.


Examining the impact of a tutoring program implemented with community support on math proficiency and growth.
The current study evaluated the impact of a math tutoring program delivered in 20 schools to students in 4th through 8th grades by community members over one academic year. Students were randomly assigned to treatment and control groups. Multi-level linear and generalized linear mixed models were used to evaluate group differences in post-test scores and the probability of attaining the spring proficiency benchmark on two increasingly distal measures of math achievement. Intent-to-treat analyses identified higher achievement scores among students assigned to treatment on a measure of fact fluency and a computer adaptive measure of overall math achievement. Students assigned to treatment also had a higher probability of reaching grade-level benchmarks on the computer adaptive test. No statistically significant effects were observed on a state proficiency test. Implications for significant and null findings are discussed within the context of intervention content and delivery.


Comparative efficacy and safety of injection therapies for knee osteoarthritis: A protocol for systematic review and Bayesian network meta analysis.
There are many injection methods for the treatment of knee osteoarthritis, but there is no comprehensive comparison, based on the fixed effect model. According to the retrieval strategy, we searched randomized controlled trials (RCTs) randomly from PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure (CNKI), Wanfang Database from their inceptions to August 2020, and 2 members of us selected literatures and extracted data independently. Methodological quality was assessed by using the Cochrane bias risk tool, and meta-analysis was performed by using the Stat.14.0. This study will evaluate the effectiveness and safety of different injectable drugs for the treatment of knee osteoarthritis and rank the efficacies of drugs, then to determine the optimal treatment. This study will provide evidence for the choice of injection therapy for knee osteoarthritis. INPLASY202080099.


The evolution of Ericaceae flowers and their pollination syndromes at a global scale.
Floral evolution in large clades is difficult to study not only because of the number of species involved, but also because they often are geographically widespread and include a diversity of outcrossing pollination systems. The cosmopolitan blueberry family (Ericaceae) is one such example, most notably pollinated by bees and multiple clades of nectarivorous birds. We combined data on floral traits, pollination ecology, and geography with a comprehensive phylogeny to examine the structuring of floral diversity across pollination systems and continents. We focused on ornithophilous systems to test the hypothesis that some Old World Ericaceae were pollinated by now-extinct hummingbirds. Despite some support for floral differentiation at a continental scale, we found a large amount of variability within and among landmasses, due to both phylogenetic conservatism and parallel evolution. We found support for floral differentiation in anther and corolla traits across pollination systems, including among different ornithophilous systems. Corolla traits show inconclusive evidence that some Old World Ericaceae were pollinated by hummingbirds, while anther traits show stronger evidence. Some major shifts in floral traits are associated with changes in pollination system, but shifts within bee systems are likely also important. Studying the floral evolution of large, morphologically diverse, and widespread clades is feasible. We demonstrate that continent-specific radiations have led to widespread parallel evolution of floral morphology. We show that traits outside of the perianth may hold important clues to the ecological history of lineages.


Managing your energy levels when you're struggling.
Living with chronic illness means living with limits to what you can do on any given day. It also means that Claire Hodgson - cofounder of British Veterinary Chronic Illness Support (BVCIS) - has any number of 'energy-saving life hacks' to share with fellow vets, as she tells Claire Read.


A posterior versus anterior surgical approach in combination with debridement, interbody autografting and instrumentation for thoracic and lumbar tuberculosis.
The purpose of this study was to compare posterior and anterior surgical approach in combination with debridement, interbody autografting and instrumentation for thoracic and lumbar tuberculosis. These approaches were compared in terms of the operation duration, intraoperative blood loss, bony fusion, intraoperative and postoperative complications, neurological status and the angle of kyphosis. Forty-seven patients with thoracic and lumbar tuberculosis who underwent either the posterior or the anterior approach in combination with debridement, interbody autografting and instrumentation from January 2004 to March 2010 were reviewed retrospectively. In group A (n = 25), the posterior approach was combined with debridement, interbody autografting and instrumentation. In group B (n = 22), the anterior approach was performed in addition to debridement, interbody autografting and instrumentation. All cases were followed up for 12-62 months. There was no statistically significant difference between groups in terms of the operation duration, intraoperative blood loss, bony fusion, intraoperative and postoperative complications, neurological status and the angle of kyphosis (p > 0.05). Good clinical outcomes were achieved in both groups. The posterior approach combined with debridement, interbody autografting and instrumentation is an alternative procedure to treat thoracic and lumbar tuberculosis. The posterior approach is sufficient for lesion debridement. In addition, the posterior approach can maintain spinal stabilisation and prevent loss of corrected vertebral alignment as effectively as the anterior approach.


Manipulation of the fractured nose using topical local anaesthesia.
Simple fracture of the nasal bone can be reduced under local or general anaesthesia. A combination of topical anaesthetic (EMLA cream) and cocainization of the nasal mucosa was used successfully in manipulation of fractured nasal bones in twelve patients without discomfort.


Inflammatory myofibroblastic tumours of the spleen and liver.
Inflammatory myofibroblastic tumour (IMT) is a rare neoplasm. Generally, these lesions have a benign behaviour, but the possibility of malignant transformation exists. We report the rare case of a 43-year-old woman with metachronous IMTs in the spleen and the liver. The patient was treated with laparoscopic splenectomy and partial hepatectomy. The patient recovered uneventfully. This case emphasizes the difficulties in diagnosis and the possibility of a metachronous occurrence.


The Prognostic Significance of Postoperative Adjuvant Chemotherapy in the Population Aged 75 Years and Older with Stage II-III Colorectal Cancer: A Retrospective Multi-Center Cohort Study.
It is common for elderly patients to be underrepresented in clinical trials for cancer, which can result in a lack of efficacy data and unclear criteria to guide treatment decisions for clinical doctors. Therefore, one of the common challenges in oncology treatment is determining the extent to which patients aged 75 and older have benefited from postoperative chemotherapy. The study aimed to explore the effect of adjuvant chemotherapy (AC) on 3-year recurrence-free survival (RFS) after curative resection in patients aged 75 years and older with stage II-III colorectal cancer (CRC). The retrospective cohort analysis was performed on patients with stage II-III CRC who received curative resection at three cancer centers in China between 2008 and 2017. Kaplan-Meier curves and Multivariable Cox regression models were used to analyze the impact of AC on RFS in patients. Finally, propensity-score matching was used to reduce selection bias and confounding factors in patients aged 75 years and older with stage II-III CRC. A total of 2885 patients were included (1729 (59.9%) male; 1312 (61.5%) received AC). The pre-matching cohort was comprised of 151 patients aged 75 years and older (median age (IQR)77.00 (76.00, 79.00); 97 (64.2%) male, 51 (72.9%) received AC). Age (P=0.001), postoperative carcinoembryonic antigen (CEA)(P=0.02) level were associated with prognosis. But AC was not associated with 3-year RFS (HR, 1.27; 95% CI, 0.80-2.0; log-rank P=0.37). After a predisposition 1: 1 match (with or without AC, n = 42), AC remains uncorrelated with 3-year RFS (HR, 1.39; 95% CI, 0.52-3.70; log-rank P=0.66). Patients over the age of 75 with stage II-III CRC who receive AC or do not face the same risk of postoperative recurrence. As a result, patients with stage II-III postoperative adjuvant chemotherapy can make an informed decision regarding whether they want to undergo chemotherapy based on their age and reduce the unnecessary side effects of chemotherapy.


Hydrophobic moeties in recombinant proteins are crucial to generate efficient saponin-based vaccine against Apicomplexan Babesia divergens.
Throughout Europe, bovine babesiosis is mainly caused by Babesia divergens, an Apicomplexan parasite transmitted by tick bites. The intra-erythrocytic development of B. divergens merozoites leads to haemolytic anaemia, and bovine babesiosis is responsible for economic losses in the agro-business industry. A totally efficient recombinant vaccine based on the merozoite surface protein Bd37 and saponin QuilA was recently described. In the present study we determined that protective immunity elicited by the Bd37 recombinant protein was related to the presence of hydrophobic residues in the protein. Using polymeric fusion of Bd37 as well as cell-free in vitro protein expression, we successfully expressed recombinant proteins containing hydrophobic sequences without the need of GST fusion. We used different hydrophobic sequences and different recombinant Bd37 proteins to demonstrate that antigen hydrophobicity affects the immune system, turning an inefficient protein into a 100% protective vaccine. Some hypotheses about the hydrophobic effect and its potential application to other parasitic protozoa vaccine are also discussed.


Transcriptomes of MPO-Deficient Patients with Generalized Pustular Psoriasis Reveals Expansion of CD4+ Cytotoxic T Cells and an Involvement of the Complement System.
Generalized pustular psoriasis is a severe psoriatic subtype characterized by epidermal neutrophil infiltration. Although variants in IL36RN and MPO have been shown to affect immune cells, a systematic analysis of neutrophils and PBMC subsets and their differential gene expression dependent on MPO genotypes was not performed yet. We assessed the transcriptomes of MPO-deficient patients using single-cell RNA sequencing of PBMCs and RNA sequencing of neutrophils in a stable disease state. Cell-type annotation by multimodal reference mapping of single-cell RNA-sequencing data was verified by flow cytometry of surface and intracellular markers; the proportions of CD4+ cytotoxic T lymphocytes and other CD4+ effector cells were increased in generalized pustular psoriasis, whereas the frequencies of naïve CD4+ T cells were significantly lower. The expression of FGFBP2 marking CD4+ cytotoxic T lymphocytes and CD8+ effector memory T cells was elevated in patients with generalized pustular psoriasis with disease-contributing variants compared with that in noncarriers (P = 0.0015). In neutrophils, differentially expressed genes were significantly enriched in genes of the classical complement activation pathway. Future studies assessing affected cell types and pathways will show their contribution to generalized pustular psoriasis's pathogenesis and indicate whether findings can be transferred to the acute epidermal situation and whether depletion or inactivation of CD4+ cytotoxic T lymphocytes may be a reasonable therapeutic approach.


Stable and efficient immobilization technique of aldolase under consecutive microwave irradiation at low temperature.
To establish a stable and efficient immobilization technique under microwave irradiation, a focused microwave reaction system was used, where the temperature was set appropriately in the microwave system and cooling module to produce consecutive microwave irradiation. 2-Deoxy-D-ribose-5-phosphate aldolase (DERA) was rapidly and efficiently immobilized in mesocellular siliceous foams (MCFs) under microwave irradiation. When the output power in the microwave system was set to 30 W, after 3 min, 88.4% of the enzyme protein was coupled to the wall of the support pores and the specific activity of the immobilized enzyme was 2.24 U mg(-1), 149.2% higher than that of the free enzyme and 157.0% higher than that of the non-microwave-assisted immobilized enzyme. In catalysis, microwave-assisted immobilized DERA tolerated a wider range of both pH and temperature than other DERA preparations. The thermal and storage stabilities were also significantly improved. This focused; microwave-assisted immobilization technique has proven to be simple, stable and highly efficient. This technique could also be applied to other enzyme immobilizations.


Cognitive and emotional functions of the teleost fish cerebellum.
Increasing experimental and neuropsychological evidence indicates that the cerebellum of humans and other mammals, traditionally associated with motor control, is implicated in a variety of cognitive and emotional functions. For example, the cerebellum has been identified as an essential structure in different learning processes, ranging from simple forms of associative, sensory-motor learning and emotional conditioning, to more complex, higher-order processes such as spatial cognition. Although neuroanatomical and neurophysiological data indicate that the organization of the cerebellum is notably well conserved in vertebrates, little is actually known about the cerebellar contribution to processes besides the motor domain in non-mammals. In this work, we analyzed the involvement of the teleost fish cerebellum on classical conditioning of motor and emotional responses and on spatial cognition. Cerebellum lesions in goldfish impair the classical conditioning of a simple eye-retraction response analogous to the eyeblink conditioning described in mammals. Single unit extracellular electrophysiological recording and cytochrome oxidase histochemistry also reveal the involvement of the teleost fish cerebellum in classical conditioning. Autonomic emotional responses (e.g., heart rate classical conditioning) are also impaired by cerebellum lesions in goldfish. Furthermore, goldfish with cerebellum lesions present a severe impairment in spatial cognition. In contrast, cerebellum lesions do not produce any observable motor deficit as indicated by the swimming activity or obstacle avoidance and do not interfere with the occurrence of unconditioned motor or emotional responses. These data indicate that the functional involvement of the teleost cerebellum in learning and memory is strikingly similar to mammals and suggest that the cognitive and emotional functions of the cerebellum may have evolved early in vertebrate evolution, having been conserved along the phylogenetic history of the extant vertebrate groups.


Acral malignant melanoma; emphasis on the primary metastasis and the usefulness of preoperative ultrasound for sentinel lymph node metastasis.
This study aimed to evaluate the most common primary metastatic location of acral malignant melanoma and to evaluate the usefulness of preoperative ultrasound for sentinel lymph node metastasis. Ninety-eight Korean acral malignant melanoma patients were enrolled. Acral malignant melanoma was present in 76 lower limbs and in 22 upper limbs. The most common origin location was the sole (33.7%). The most common location of primary metastasis was loco-regional recurrence (22/34, 64.7%). The sensitivity, specificity, positive predictive value, and negative predictive value of preoperative sentinel lymph node ultrasound was 29.1%, 94.6%, 63.6%, and 80.5%, respectively. We postulate the unusefulness of preoperative ultrasound for sentinel lymph node metastasis in acral malignant melanoma.


Suppression of BMX-ARHGAP fusion gene inhibits epithelial-mesenchymal transition in gastric cancer cells via RhoA-mediated blockade of JAK/STAT axis.
Gastric cancer (GC) is one of the main causes of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) is an important biological process involving the process by which malignant tumor cells obtain the ability of migration, invasion, resistance of apoptosis, and degradation in the extracellular matrix. The current study aimed at investigating whether bone marrow X kinase Rho GTPase activating protein 12 (BMX-ARHGAP) fusion gene affects GC. First, short hairpin RNA (shRNA) against BMX-ARHGAP or BMX-ARHGAP were introduced to treat SGC-7901 cells with the highest BMX-ARHGAP among the five GC cell lines (SGC-7901, MKN-45, NCI-N87, SNU-5, and AGS). Next, cell vitality, drug resistance, migration, and invasion of SGC-7901 cells, activities of Rho and JAK/STAT axis, as well as EMT and lymph node metastasis (LNM) were evaluated. The survival rate of the mice was then determined through the transfection of the specific pathogen-free NOD-SCID mice with treated SGC-7901 cells. The results showed that BMX-ARHGAP expression was associated with the infiltration degree of GC tumor and poor prognosis for patients with GC. BMX-ARHGAP silencing was found to play an inhibitory role in the Rho and JAK/STAT axis to reduce cell vitality, drug resistance, migration and invasion, reverse EMT process, as well as inhibit LNM. BMX-ARHGAP overexpression was observed to have induced effects on GC cells as opposed to those inhibited by BMX-ARHGAP silencing. The survival rate of mice was increased after transfection with silenced BMX-ARHGAP. These findings provided evidence that the suppression of BMX-ARHGAP resulted in the inhibition of RhoA to restraint the development of GC cells by blocking the JAK/STAT axis.


The Role of Different Alkali Metals in the A15Tl27 Type Structure and the Synthesis and X-ray Structure Analysis of a New Substitutional Variant Cs14.53Tl28.4.
Alkali metal thallides have been known since the report of E. Zintl on NaTl in 1932. Subsequently, binary and ternary thallides of alkali metals have been characterized. At an alkali metal proportion of approximately 33% (A:Tl~1:2, A = alkali metal), three different unique type structures are reported: K49Tl108, Rb17Tl41 and A15Tl27 (A = Rb, Cs). Whereas Rb17Tl41 and K49Tl108 feature a three-dimensional sublattice of Tl atoms, the A15Tl27 structure type includes isolated Tl11 clusters as well as two-dimensional Tl-layers. This unique arrangement is only known so far when the heavier alkali metals Rb and Cs are included. In our contribution, we present single-crystal X-ray structure analyses of new ternary and quaternary compounds of the A15Tl27 type structure, which include different amounts of potassium. The crystal structures allow for the discussion of the favored alkali metal for each of the four Wyckoff positions and clearly demonstrate alkali metal dependent site preferences. Thereby, the compound Cs2.27K12.73Tl27 unambiguously proves the possibility of a potassium-rich A15Tl27 phase, even though a small amount of cesium appears to be needed for the stabilization of the latter structure type. Furthermore, we also present two compounds that show an embedding of Tl instead of alkali metal into the two-dimensional substructure, being equivalent to the formal oxidation of the latter. Cs14.53Tl28.4 represents the binary compound with the so far largest proportion of incorporated Tl in the structure type A15Tl27.


Testing the clockface model of amphibian limb regeneration.
Contrary to the predictions of the clockface model, rotating a regenerate by 90 degrees produces duplications identical to those resulting from 180 degrees axial reversals. Exchanging regenerates between arms indicates the presence of 2 determined transverse axes.


Is There a Role for [18F]FDG PET-CT in Staging MALT Lymphoma?
The role of 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography-computed tomography (PET-CT) in assessing mucosa-associated lymphoid tissue (MALT) lymphoma is debatable. We retrospectively explored the role of [18F]FDG PET-CT in staging and predicting progression-free-survival (PFS) of patients with newly-diagnosed MALT lymphoma. Sixty-six studies were included. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were documented in the "hottest" extranodal and nodal lesions. Extranodal lesions and accompanying nodal disease were detected on PET in 38/66 (57.6%) and 13/66 (19.7%) studies, respectively. Detection rate of extranodal lesions differed significantly between those located in tissues with high/heterogeneous (e.g., stomach) vs low/homogenous (e.g., subcutaneous-tissue, lung) physiologic [18F]FDG-uptake (40.4% vs. 100%, p < 0.01). Nodal lesions had significantly lower SUVmax, MTV and TLG compared with extrandodal lesions in the same patients. Detection and [18F]FDG-avidity of extranodal lesions were higher in patients with advanced, bulky disease and concomitant marrow/nodal involvement. Increased SUVmax of extranodal lesions predicted shorter PFS (HR 1.10, 95% CI 1.01-1.19, p = 0.02). Higher SUVmax and TLG showed trends towards shorter PFS in patients with localized disease. In conclusion, detection rate of extranodal MALT lymphoma lesions located in tissues with low/homogeneous physiologic [18F]FDG-uptake is excellent on [18F]FDG PET-CT. When detected, SUVmax of extranodal lesions may predict PFS.


Pain and labor outcomes: A longitudinal study of adults with cerebral palsy in Sweden.
Pain is a global health concern with substantial societal costs and limits the activity participation of individuals. The prevalence of pain is estimated to be high among individuals with cerebral palsy (CP). To estimate the association between pain and labor outcomes for adults with CP in Sweden. A longitudinal cohort study based on data from Swedish population-based administrative registers of 6899 individuals (53,657 person-years) with CP aged 20-64 years. Individual fixed effects regression models were used to analyze the association between pain and labor outcomes (employment and earnings from employment), as well as potential pathways through which pain might affect employment and earnings. Pain was associated with adverse outcomes varying across severity, corresponding to a reduction of 7-12% in employment and 2-8% in earnings if employed. Pain might affect employment and earnings through increased likelihood of both sickness leave and early retirement. Pain management could potentially be important to improve labor outcomes for adults with CP, in addition to improving the quality of life.


Neural remodeling in retinal degeneration.
Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in phase 1 or 2 in some animal models, but depletion of all neuronal classes is evident in phase 3. As remodeling progresses over months and years, more neurons are lost and patches of the ganglion cell layer can become depleted. Some survivor neurons of all classes elaborate new neurites, many of which form fascicles that travel hundreds of microns through the retina, often beneath the distal glial seal. These and other processes form new synaptic microneuromas in the remnant inner nuclear layer as well as cryptic connections throughout the retina. Remodeling activity peaks at mid-phase 3, where neuronal somas actively migrate on glial surfaces. Some amacrine and bipolar cells move into the former ganglion cell layer while other amacrine cells are everted through the inner nuclear layer to the glial seal. Remodeled retinas engage in anomalous self-signaling via rewired circuits that might not support vision even if they could be driven anew by cellular or bionic agents. We propose that survivor neurons actively seek excitation as sources of homeostatic Ca(2+) fluxes. In late phase 3, neuron loss continues and the retina becomes increasingly glial in composition. Retinal remodeling is not plasticity, but represents the invocation of mechanisms resembling developmental and CNS plasticities. Together, neuronal remodeling and the formation of the glial seal may abrogate many cellular and bionic rescue strategies. However, survivor neurons appear to be stable, healthy, active cells and given the evidence of their reactivity to deafferentation, it may be possible to influence their emergent rewiring and migration habits.


In vitro toxicity of polymorphonuclear neutrophils to rat hepatocytes: evidence for a proteinase-mediated mechanism.
Human polymorphonuclear neutrophils, when exposed to soluble or particulate stimuli, can destroy various types of cells. The aim of this study was to investigate their toxicity against hepatocytes. Human polymorphonuclear neutrophils were incubated in basal conditions and after stimulation with 5 mg per ml opsonized zymosan in the presence of rat hepatocytes isolated by collagenase digestion. Cytotoxicity was quantified by the percentage of ALT activity released by hepatocytes in culture medium. Whereas unstimulated neutrophils exhibited only minor effects, opsonized zymosan-stimulated neutrophils induced, after 16 hr incubation, a 24.0 +/- 4.1% (mean +/- 1 S.E.) ALT activity release at a neutrophil/hepatocyte ratio of 5, and a 51.7 +/- 6.8% ALT activity release at a ratio of 20. At this ratio of 20, the ALT activity release was 9.0% at 1 hr and 24.0% at 4 hr. Three proteinase inhibitors (i.e., soybean trypsin inhibitor, alpha 1-proteinase inhibitor and fetal calf serum) decrease cytotoxicity by 78, 76 and 78%, respectively. The protective effect of proteinase inhibitors was not due to a nonspecific effect of proteins, since bovine serum albumin did not decrease the toxicity of stimulated polymorphonuclear cells. The supernatant of stimulated neutrophils was also found to be toxic against hepatocytes, and again, this effect was inhibited by soybean trypsin inhibitor, alpha 1-proteinase inhibitor and fetal calf serum. Finally, the role of proteinases was supported by the demonstration of a cytotoxic effect of two purified proteinases: porcine pancreatic elastase and human neutrophil cathepsin G. The toxicity of these proteinases was also markedly reduced by the specific inhibitors used in the study.(ABSTRACT TRUNCATED AT 250 WORDS)


Foraging behavior of specialist and generalist caterpillars on plantain (Plantago lanceolata) altered by predatory stinkbugs.
To examine the effects of predators and plant genotype on the behavior, patterns of herbivory, growth and survivorship of caterpillars, we used an experimental garden in which we contrasted two hostplant genotypes of plantain (Plantago lanceolata), two kinds of herbivores (specialist Junonia coenia vs. generalist Pyrrharctia isabella) and two levels of caterpillar predation (with and without Podisus maculiventris stinkbugs). Each of the replicate plots per treatment contained two plants of the same genotype. The stinkbugs reduced the survivorship of the specialist caterpillars but not that of the generalists, which reflects the differences in predatoravoidance behaviors of these species. Nonetheless, the stinkbugs influenced the behavior of both caterpillar species. When stinkbugs were present, both specialist and generalist caterpillars were less likely to be found on the plant upon which they were initially placed (="initial" plant), and they were more likely to be off both plants within the plot than larvae in the absence of predators. Consequently in the presence of the stinkbug predators, the proportion of the "initial" plants consumed was less than in the absence of the predators. Plant genotype influenced plant size and the proportion of individual plants eaten, but it did not affect larval location on the plots. Neither presence of predators nor plant genotype had an effect on relative growth rate of the caterpillars.


Matrix Metalloproteinases and Their Inhibitors in Chronic Obstructive Pulmonary Disease.
Chronic obstructive pulmonary disease (COPD) is characterised by irreversible airflow limitation associated with chronic inflammation. Matrix metalloproteinases (MMPs) are proteolytic enzymes that contribute to the inflammatory response in COPD and degrade extracellular matrix components. Their enzymatic activity is inhibited by a four-member family of tissue inhibitors of metalloproteinases (TIMPs). In COPD, the MMP/TIMP network, mainly MMP-9, has been repeatedly observed to be dysregulated at both the local (lung) and systemic levels. Here, we review the findings reported in numerous cross-sectional studies with our primary focus on longitudinal observations in human COPD studies. The data from longitudinal prospective studies on the MMP/TIMP network may lead to the introduction of novel prognostic biomarkers into clinical management of COPD. We address the relationship between the systemic and local lung MMP/TIMP network in COPD patients and briefly describe the involvement of microRNAs. Finally, the role of the MMP/TIMP network in COPD treatment is discussed.


Pharmacokinetics, pharmacodynamics, safety and tolerability of FTP-198, a novel, selective Autotaxin inhibitor, in healthy subjects: A phase I randomized placebo-controlled trial.
Autotaxin (ATX) and lysophosphatidic acid (LPA) play an important role in pathogenesis of idiopathic pulmonary fibrosis (IPF). FTP-198 is an oral, novel and selective ATX inhibitor indicated for treating IPF. The study aimed to investigate the pharmacokinetics, pharmacodynamics, safety and tolerability of FTP-198 in healthy subjects. A single-center, randomized, double-blind, placebo-controlled, single ascending-dose Phase I study was performed. Pharmacokinetics, pharmacodynamics, food effect on pharmacokinetics, elimination, safety and tolerability of FTP-198 were evaluated. A total of 30 subjects were enrolled and completed the study. After oral administration of single ascending-dose of 100 mg, 300 mg and 400 mg FTP-198 under fasted condition, FTP-198 was absorbed with median time to reach peak concentration (Tmax) of 1.75, 2.75 and 3.5 h, respectively and eliminated with mean elimination half-life (t1/2) of 8.77, 10.58 and 10.57 h, respectively. Peak concentration (Cmax), plasma area under concentration-time curve from time 0 to the last measurable concentration (AUC0-t) and to infinity (AUC0-∞) increased in dose-proportional manner for 100 mg to 400 mg FTP-198. Food intake slightly increased the Cmax, AUC0-t and AUC0-∞ and prolonged Tmax, but not affecting t1/2 of FTP-198 compared with fasted state. The pharmacodynamic biomarker plasma lysophosphatidic acid (LPA) 18:2 decreased significantly for 100 mg to 400 mg FTP-198, with inhibition rate from baseline reaching approximately 80% at 24 h post dosing, and higher dose of FTP-198 increased the time to maintain inhibitory plateau. FTP-198 was eliminated from the body almost with no unchanged drug excreted in urine and a small amount of unchanged drug detected in feces of human. Moreover, FTP-198 exhibited favorable safety and tolerability in healthy subjects. Pharmacokinetics, pharmacodynamics, safety and tolerability of FTP-198 support further subsequent clinical development of FTP -198 in IPF patients.


Aqueous Zinc-Tellurium Batteries with Ultraflat Discharge Plateau and High Volumetric Capacity.
Traditional aqueous zinc-ion batteries (ZIBs) based on ion-intercalation or surface redox behaviors at the cathode side suffer severely from an unsatisfactory specific capacity and unstable output potential. Herein, these issues are applied to a conversion-type zinc-tellurium (Zn-Te) battery. Typically, this battery works based on a two-step solid-to-solid conversion with the successive formation of zinc ditelluride (ZnTe2 ) and zinc telluride (ZnTe). It delivers an ultrahigh volumetric capacity of 2619 mAh cm-3 (419 mAh g-1 ), 74.1% of which is from the first conversion (Te to ZnTe2 ) with an ultraflat discharge plateau. Though reported first in a challenging aqueous environment, this Zn-Te battery demonstrates an excellent capacity retention of >82.8% after 500 cycles, which results from the elimination of the notorious "shuttle effect" due to the solid-to-solid conversion behaviors. In addition, a quasi-solid-state Zn-Te battery is also fabricated, exhibiting superior flexibility, robustness, and good electrochemical performance. This work develops a novel cathode material based on conversion-type ion-storage mechanism. The system is attractive due to its ultrastable energy output, which is rarely reported for ZIBs.


Nano- and microparticles as adjuvants in vaccine design: success and failure is related to host natural antibodies.
Bovine serum albumin (BSA) and the surface A-layer protein (AP) of an atypical strain of fish bacterial pathogen Aeromonas salmonicida were covalently linked with polymeric nano- and microparticles, and antigenicity of the resulted conjugates was compared in mice and goldfish. Distinct albeit different levels of natural BSA and AP antibodies were present in both animal species. Significant stimulation of the anti-AP antibody response in mice strikingly contrasted to unresponsiveness or even suppression in fish. The results negatively correlate with the levels of respective natural antibodies in the host and are discussed in context of problems related to fish vaccination. The work reinforces the instructive role of natural antibodies in adaptive immune response.


Glycoconjugates of Trypanosoma cruzi: a 74 kD antigen of trypomastigotes specifically reacts with lytic anti-alpha-galactosyl antibodies from patients with chronic Chagas disease.
Protective, lytic antibodies are believed to be correlated with active Trypanosoma cruzi infection. In patients with chronic infection, antibodies lysing trypomastigote forms recognize chiefly alpha-galactosyl structures at the parasite surface. The target molecules on cell-derived trypomastigotes that react with anti-alpha-galactosyl antibodies (anti-Gal) from patients with chronic Chagas disease were investigated. Glycoconjugates were isolated from trypomastigotes and shown to absorb purified Chagasic (Ch) anti-Gel effectively as well as lytic antibodies from Ch sera. Active fractions were F2 (74 kD and 95.6 kD) and F3 (120-200 kD). A differential reactivity with antibodies from untreated Ch patients (trypanolytic) and from treated, presumably cured, individuals (not trypanolytic) was evident using F2 and F3 antigenic fractions. No cross-reactivity with heterologous sera (other infections) was observed. The F2 glycoconjugate (mostly 74 kD) can be used in the diagnosis of active Chagas infection, replacing the quantitative determination of complement-mediated lysis. With the present sample of patients' sera and normal human sera, it showed 100% sensitivity and specificity.


Vasodilator monotherapy in the treatment of hypertension: comparative efficacy and safety of pinacidil, a potassium channel opener, and prazosin.
We compared antihypertensive effects of monotherapy with pinacidil (N = 197) or prazosin (N = 204) in a randomized, parallel, double-blind dose-titration study in which hydrochlorothiazide or propranolol could be added for adverse events or lack of efficacy. Pinacidil (12.5 to 75 mg b.i.d.) was a more potent vasodilator, producing a mean decrease in supine diastolic blood pressure (baseline = 102 to 103 +/- 9 mm Hg) of 18.8 +/- 10.0 (SD) mm Hg compared with 15.5 +/- 9.2 mm Hg with prazosin (1 to 10 mg b.i.d.; p less than 0.001). Patients responding to each drug had similar average blood pressure levels during 12-hour monitoring (137/85 mm Hg). More patients taking pinacidil required hydrochlorothiazide for edema (p = 0.008) and more taking prazosin required hydrochlorothiazide and propranolol for lack of efficacy (p less than 0.001). Tachycardia (15% to 20%) and palpitation (13% to 15%) were frequent events with both drugs. Edema (38.2% vs 22.3%) was more frequent with pinacidil (p less than 0.001) and postural hypotension (4.7% vs 1.0%) and asthenia (20.2% vs 13.2%) were more frequent with prazosin (p = 0.025; 0.062). No significant laboratory toxicity was noted. In conclusion, both pinacidil and prazosin are effective as monotherapy for hypertension. Monotherapy with pinacidil is limited by adverse events related to vasodilatation and monotherapy with prazosin is limited by lack of efficacy.


[The comparative characteristics of the clinico-physiological action of electromagnetic radiation in the milli- and nanometer ranges in hypertension].
The sinocarotid zone (SCZ) of 127 patients with essential hypertension (EH) stage I and II was exposed to electromagnetic millimetric and nanometric waves. Differentiated indications for laser and short-wave-frequency therapy on SCZ in EH have been formulated basing on the postexposure changes in blood pressure, main complaints, central and cerebral hemodynamics, lipid metabolism, blood coagulation.


Utilization of naproxen by Amycolatopsis sp. Poz 14 and detection of the enzymes involved in the degradation metabolic pathway.
The pollution of aquatic environments by drugs is a problem for which scarce research has been conducted in regards of their removal. Amycolatopsis sp. Poz 14 presents the ability to biotransformation naphthalene at high efficiency, therefore, in this work this bacterium was proposed as an assimilator of naproxen and carbamazepine. Growth curves at different concentrations of naproxen and carbamazepine showed that Amycolatopsis sp. Poz 14 is able to utilize these drugs at a concentration of 50 mg L-1 as a source of carbon and energy. At higher concentrations, the bacterial growth was inhibited. The transformation kinetics of naproxen showed the total elimination of the compound in 18 days, but carbamazepine was only eliminated in 19.9%. The supplementation with cometabolites such as yeast extract and naphthalene (structure similar to naproxen) at 50 mg L-1, showed that the yeast extract shortened the naproxen elimination to 6 days and reached a higher global consumption rate compared to the naphthalene cometabolite. The biotransformation of carbamazepine was not improved by the addition of cometabolites. The partial sequencing of the genome of Amycolatopsis sp. Poz 14 detected genes encoding putative enzymes for the degradation of cyclic aromatic compounds and the activities of aromatic monooxygenase, catechol 1,2-dioxygenase and gentisate 1,2-dioxygenase exhibited their involving in the naproxen biodegradation. The HPLC-MS analysis detected the 5-methoxysalicylic acid at the end of the biotransformation kinetics. This work demonstrates that Amycolatopsis sp. Poz 14 utilizes naproxen and transforms it to 5-methoxysalicylic acid which is the initial compound for the catechol and gentisic acid metabolic pathway.


Outcome of BEAM-autologous and BEAM-alemtuzumab allogeneic transplantation in relapsed advanced stage follicular lymphoma.
The role of haematopoietic stem cell transplantation (HSCT) in relapsed follicular lymphoma remains controversial. This study analysed 126 patients with relapsed, advanced stage follicular lymphoma who received BEAM (BCNU [carmustine], cytarabine, etoposide, melphalan)-alemtuzumab allogeneic HSCT (BEAM-allo) (n = 44) or BEAM-autologous HSCT (BEAM-auto) (n = 82). The BEAM-allo group had a younger median age (48 years vs. 56 years, P < 0.001) but received a higher median number of therapies pretransplant (P = 0.015) compared with the BEAM-auto group. There was a higher non-relapse mortality (NRM) in the BEAM-allo group compared with the BEAM-auto group at 1 year (20% vs. 2%, P = 0.001). Older age and heavily pretreated patients were associated with a higher NRM and poorer survival in the BEAM-allo group. There was, however, a significantly lower relapse rate (20% vs. 43%, P = 0.01) at 3 years with BEAM-alemtuzumab, with no relapses after 2 years, compared with a continued pattern of relapse in the autologous group. No difference in overall survival (OS) (P = 0.99) or disease-free survival (DFS) (P = 0.90) was identified at 3 years, whereas a plateau in OS and DFS with crossing of the survival curves in favour of BEAM-allo group was observed. Furthermore, the ability to re-induce remissions with donor leucocytes provides additional benefit in favour of allogeneic HSCT.


[Transparietal needle biopsy of pulmonary lesions with an image intensification system. Apropos of 82 biopsies].
We report the results of 82 needle biopsies of pulmonary nodules, using a fine screw needle. Owing to the very small diameter of the needle (0.8 mm), very few complications were observed (minor pneumothorax 13%, major pneumothorax 2.5%). The screw needle provided samples adequate for both cytological and histological examination. Forty-eight out of 53 cancers were diagnosed by this method (sensitivity 83%, specificity 100%).


Percutaneous thrombin injection of a femoral artery pseudoaneurysm with simultaneous venous balloon occlusion of a communicating arteriovenous fistula.
An 82-year-old woman developed acute occlusion of her right coronary artery. She underwent percutaneous coronary stent placement and aortic balloon pump installation. In the postprocedural period, she developed a common femoral artery pseudoaneurysm (PSA) that communicated with the common femoral vein via an arteriovenous fistula (AVF). After unsuccessful ultrasound-guided compression, ultrasound-guided thrombin injection of the PSA was performed, with simultaneous balloon occlusion of the common femoral vein at the level of the AVF. There was complete thrombosis of the PSA and AVF.


Diphenyl diselenide modulates oxLDL-induced cytotoxicity in macrophage by improving the redox signaling.
It has been reported that oxidized LDLs (oxLDL) are involved in the pathogenesis of atherosclerosis, and that macrophages as well as other cells of the arterial wall can oxidize LDL in vitro, depending on the balance between intracellular prooxidant generation and antioxidant defense efficiency. Because of their potential beneficial role in preventing atherosclerosis and other oxidative stress-related diseases, organoselenium compounds such as diphenyl diselenide (PhSe)2, are receiving increased attention. In the present work, we investigated the mechanisms underlying the protective effect exerted by (PhSe)2 on oxLDL-mediated effects in murine J774 macrophage-like cells. (PhSe)2 pretreatment reduced atherogenic signaling triggered by oxLDL in macrophages in vitro, namely: ROS generation, disturbance of NO homeostasis, activation of matrix metalloproteinase, foam cell formation, and mitochondrial dysfunction. Moreover, the redox signaling effects of (PhSe)2 presented herein were accompanied by a downregulation of NF-κB-binding activity. The relatively strong performance of (PhSe)2 makes it an ideal candidate for further, expanded trials as a new generation of antioxidants for preventing atherosclerotic lesion.


Performance validation of chromogenic coliform agar for the enumeration of Escherichia coli and coliform bacteria.
The performance of chromogenic coliform agar (CCA) for the enumeration of Escherichia coli and coliform bacteria was validated according to ENV ISO 13843 using pure cultures and naturally contaminated water samples. The results indicate that for the detection of E. coli and coliform bacteria, respectively, the method is sensitive (94 and 91%), specific (97 and 94%), selective (selectivity -0·78 and -0·32) and efficient (96 and 92%). Relative recovery of E. coli and coliform bacteria on CCA in comparison with tryptone soy agar (TSA) was good (104 and 94% in mean, >80 and >70% in all cases), and repeatability and reproducibility were sufficient. The linear working range was defined for 10-100 total target colonies per 47-mm membrane filter. A high precision of the method was confirmed by low overdispersion in comparison with Poisson distribution. The robustness of the method with respect to the variable incubation time of 21 ± 3 h was found to be low, because an incidental increase in presumptive colonies especially between 18 and 21 h was observed. In conclusion, the CCA method was proved as a reliable method for the quantification of E. coli and coliform bacteria. The international standard for the detection and enumeration of E. coli and coliform bacteria by membrane filtration (ISO 9308-1) is currently under revision and will be published in 2014. In the new standard, lactose-triphenyl tetrazolium chloride (TTC) agar will be replaced by a CCA. A performance validation of this revised method according to ENV ISO 13843 is presented in this study to determine fundamental data on its applicability and to provide reference data for secondary validation by users of this method.


[Cardiotropic effects of luliberin. Effects of luliberin on the activities of phosphorylase A and ornithine decarboxylase and concentration of 3', 5'-AMP].
The level of luliberin, the luteinizing hormone-releasing hormone (LH-RH), and the possibility of the hormonal control of metabolic and biosynthetic processes in the heart were studied. It was shown that the rat heart contains a factor, which is immunochemically and chromatographically related to LH-RH (19--46 picograms per organ). Intraperitoneal injection of LH-RH increases the activities of phosphorylase A and ornithine decarboxylase and the concentration of 3',5'-AMP and potentiates the stimulating effect of adrenaline on ornithine decarboxylase.


Transvaginal sonographic features of peritoneal carcinomatosis.
Peritoneal carcinomatosis involves the dissemination of intra-abdominal tumor tissue often associated with gynecological malignancies. The objective of this study was to describe the transvaginal sonographic appearance of this condition. The data of 60 patients with surgically and histologically proven peritoneal carcinomatosis were analyzed. Transvaginal sonograms performed within 7 days of admission to the operating theater were re-evaluated in order to identify the sonographic features associated with peritoneal carcinomatosis. Carcinomatosis was revealed in 53/60 cases (88%) by the presence of hypoechoic nodules attached to the peritoneum and visible on transvaginal sonography (TVS). The pouch of Douglas was the site most frequently involved. Power Doppler sonography showed the presence of blood vessels in 48 (91%) of these metastases. Ascites was found in 50 (83%) women. An adnexal mass suggestive of being the primary tumor was present in only 41 women (68%). Peritoneal carcinomatosis has typical features on TVS and, in the vast majority of cases, its genital origin can be correctly hypothesized. Power Doppler sonography strengthens the diagnosis by showing vascularity of the peritoneal implants. In a patient with a known pelvic malignancy or whenever peritoneal carcinomatosis is suspected, TVS can give useful information in order to better assess the presence and extension of metastatic nodules within the abdominal cavity.


Treatment of multiple myeloma according to the extension of the disease: a prospective, randomised study comparing a less with a more aggressive cystostatic policy. Cooperative Group of Study and Treatment of Multiple Myeloma.
The purpose of the study was to ascertain whether the prognostic significance of staging in multiple myeloma (MM) is influenced by the aggressiveness of effective induction treatment and/or by continuing or discontinuing maintenance chemotherapy. Patients with untreated stage I MM (defined according to Durie and Salmon) were randomised between being followed without cytostatics until the disease progressed and receiving six courses of melphalan and prednisone (MP-P) just after diagnosis; stage II patients were uniformly treated with MPH-P and stage III patients were randomised between MPH-P and four courses of combination chemotherapy with Peptichemio, vincristine and prednisone (PTC-VCR-P). Within each stage, responsive patients were randomised between receiving additional therapy only until maximal tumour reduction was reached (plateau phase) and continuing induction therapy indefinitely until relapse. With resistant, progressive or relapsing disease, patients originally treated with MPH-P for induction received combination chemotherapy and vice versa. The overall first response rate was 43.8% (42.2% in 206 stage I, II and III patients treated with MPH-P and 48.0% in 75 stage III patients treated with combination chemotherapy, P = NS). Combination chemotherapy was more myelotoxic than MPH-P and, in particular, caused more non-haematological side-effects. Both the less and the more aggressive induction policies gave the same disease control. Progression of disease was statistically similar in stage I patients who were initially left untreated and in t hose who received MPH-P just after diagnosis; median duration of first response was similar in stage III patients receiving MPH-P and in those on combination chemotherapy. In all stages, discontinuing or continuing maintenance did not alter the median duration of first response. The overall second response rate was 28.5% (34.0% to MPH-P and 25.3% to combination chemotherapy, P = NS). Median survival was greater than 78 months in stage I, was 46.3 months in stage II and was 24.3 months in stage III patients, still independent of both induction and post-induction policies. In MM, the significance of staging for survival is independent of both the aggressiveness of induction and of continuing or discontinuing maintenance chemotherapy after the maximal tumor reduction has been achieved. Both MPH-P and and the association of PTC, VCR and P are effective in inducing first response and also second response in patients failing on the alternative regimen, but PTC-VCR-P causes more side effects. Thus, the overwhelming majority of patients with MM can safely be given MPH-P as first therapy, and this treatment may be delayed in early diseases.


High power and low critical current density spin transfer torque nano-oscillators using MgO barriers with intermediate thickness.
Reported steady-state microwave emission in magnetic tunnel junction (MTJ)-based spin transfer torque nano-oscillators (STNOs) relies mostly on very thin insulating barriers [resulting in a resistance × area product (R × A) of ~1 Ωμm2] that can sustain large current densities and thus trigger large orbit magnetic dynamics. Apart from the low R × A requirement, the role of the tunnel barrier in the dynamics has so far been largely overlooked, in comparison to the magnetic configuration of STNOs. In this report, STNOs with an in-plane magnetized homogeneous free layer configuration are used to probe the role of the tunnel barrier in the dynamics. In this type of STNOs, the RF modes are in the GHz region with integrated matched output powers (P out ) in the range of 1-40 nW. Here, P o u t values up to 200 nW are reported using thicker insulating barriers for junctions with R × A values ranging from 7.5 to 12.5 Ωμm2, without compromising the ability to trigger self-sustained oscillations and without any noticeable degradation of the signal linewidth (Γ). Furthermore, a decrease of two orders of magnitude in the critical current density for spin transfer torque induced dynamics (J STT ) was observed, without any further change in the magnetic configuration.


Chain elongation process for caproate production using lactate as electron donor in Megasphaera hexanoica.
Megasphaera hexnaoica is anaerobic bacteria who has well running reverse β-oxidation pathway. In previous study, the strain showed excellent production of medium chain carboxylic acids (MCCAs) using fructose as electron donor. In this study, chain elongation process study using lactate instead of fructose was conducted in M. hexnaoica fermentation. It was found that M. hexanoica can use lactate as electron donor in chain elongation process. 8.9 g/L caproate production was achieved in fermentation using lactate as sole electron donor. Compare to fructose condition, lactate as electron donor showed more than 3 times higher specific titer and specific productivity. In addition, when fructose and lactate were used as electron donor simultaneously, further improvement of MCCAs production was observed to achieve maximum caproate productivity of 20.9 g/L/day. Utilization of lactate as electron donor in M. hexanoica showed potential opportunity in chain elongation process.


Development of a pathogenesis-based therapy for peeling skin syndrome type 1.
Peeling skin syndrome type 1 (PSS1) is a rare and severe autosomal recessive form of congenital ichthyosis. Patients are affected by pronounced erythroderma accompanied by pruritus and superficial generalized peeling of the skin. The disease is caused by nonsense mutations or complete deletion of the CDSN gene encoding for corneodesmosin (CDSN). PSS1 severely impairs quality of life and therapeutic approaches are totally unsatisfactory. The objective of this study was to develop the first steps towards a specific protein replacement therapy for CDSN deficiency. Using this approach, we aimed to restore the lack of CDSN and improve cell-cell cohesion in the transition area of the stratum granulosum (SG) to the stratum corneum. Human CDSN was recombinantly expressed in Escherichia coli. A liposome-based carrier system, prepared with a cationic lipopeptide to mediate the transport to the outer membrane of keratinocytes, was developed. This formulation was chosen for CDSN delivery into the skin. The liposomal carrier system was characterized with respect to size, stability and toxicity. Furthermore, the interaction with primary keratinocytes and human epidermal equivalents was investigated. The liposomes showed an accumulation at the membranes of keratinocytes. CDSN-deficient epidermal equivalents that were treated with liposomal encapsulated CDSN demonstrated presence of CDSN in the SG. Finally, the penetration assay and histological examinations revealed an improved epidermal integrity for CDSN-deficient epidermal equivalents, if they were treated with liposomal encapsulated CDSN. This study presents the first preclinical in vitro experiments for a future specific protein replacement therapy for patients affected by PSS1.


Effect of microwave disinfection on the hardness and adhesion of two resilient liners.
Microwave irradiation has been suggested for denture disinfection. However, the effect of this procedure on the hardness and bond strength between resilient liners and denture base acrylic resin is not known. This study evaluated the effect of water storage time and microwave disinfection on the hardness and peel bond strength of 2 silicone resilient lining materials to a heat-polymerized acrylic resin. Acrylic resin (Lucitone 199) specimens (75 x 10 x 3 mm) were stored in water at 37 degrees C (2 or 30 days) before bonding (n = 160). The resilient lining materials (GC Reline Extra Soft and Dentusil) were bonded to the denture base and divided into the following 4 groups (n = 10): Tests performed immediately after bonding (control); specimens immersed in water (200 mL) and irradiated twice, with 650 W for 6 minutes; specimens irradiated daily for 7 total cycles of disinfection; specimens immersed in water (37 degrees C) for 7 days. Specimens were submitted to a 180-degree peel test (at a crosshead speed of 10 mm/min) and the failure values (MPa) and mode of failure were recorded. Pretreatment and posttreatment hardness measurements (Shore A) of the resilient materials were also performed. Three-way analysis of variance, followed by the Tukey HSD test, was performed (alpha = .05). The analysis revealed that, for all conditions, the mean failure strengths of GC Reline Extra Soft (0.95-1.19 MPa) were significantly higher ( P < .001) than those of Dentusil (0.45-0.50 MPa). The adhesion of the liners was not adversely affected by water storage time of Lucitone 199 or microwave disinfection. All peel test failures were cohesive. There was a small but significant difference ( P < .001) between the pretreatment (34.33 Shore A) and posttreatment (38.69 Shore A) hardness measurements. Microwave disinfection did not compromise the hardness of either resilient liners or their adhesion to the denture base resin Lucitone 199.


Effect of dairy consumption on weight and body composition in adults: a systematic review and meta-analysis of randomized controlled clinical trials.
Although several observational and experimental studies have investigated the effect of dairy consumption on weight and body composition, results are inconsistent. This systematic review and meta-analysis was conducted to summarize the published evidence from randomized controlled clinical trials (RCTs) regarding the effect of dairy consumption on weight, body fat mass, lean mass and waist circumference (WC) in adults. PubMed, ISI Web of Science, SCOPUS, Science Direct and EMBASE were searched from January 1960 to October 2011 for relevant English and non-English publications. Sixteen studies were selected for the systematic review and fourteen studies were included in meta-analysis. Our search led to 14, 12, 6 and 8 eligible RCTs that had data on weight, body fat mass, lean mass and WC, respectively. Overall, mean difference for the effect of dairy on body weight was -0.61 kg (95% confidence interval (CI): -1.29, 0.07, P=0.08). Increased dairy intake resulted in 0.72 kg (95% CI: -1.29, -0.14, P=0.01) greater reduction in fat mass, 0.58 kg (95% CI: 0.18, 0.99, P<0.01) gain in lean mass and 2.19 cm (95% CI: -3.42, -0.96, P-value <0.001) further reduction in WC than that in controls. Subgroup analysis revealed that increasing dairy intake without energy restriction in both intervention and control groups does not significantly affect weight, body fat mass, lean mass and WC; consumption of high-dairy weight loss diets led to 1.29 kg (95% CI: -1.98, -0.6, P<0.001) greater weight loss, 1.11 kg (95% CI: -1.75, -0.47, P=0.001) greater reduction in body fat mass, 0.72 kg (95% CI: 0.12, 1.32, P=0.02) gain in body lean mass and 2.43 cm (95% CI: -3.42, -1.44, P<0.001) additional reduction in WC compared with controls. Increased dairy consumption without energy restriction might not lead to a significant change in weight or body composition; whereas inclusion of dairy products in energy-restricted weight loss diets significantly affects weight, body fat mass, lean mass and WC compared with that in the usual weight loss diets.


[Palliative embolization of kidney tumors using iodol-marked Ethibloc].
In 59 patients having non-operable malignant renal tumours, palliative trans-catheter embolization was performed. In 42 of them follow-up observations were realized over 18 months. The average survival rate was then 43% of cases. Local tumour growth was documented in 9 patients (23%) due to recanalization of the embolized arteries (13%) and to non-occluded collateral vessels (10%). The choice of suitable embolizing materials mainly influences the therapeutic result: Oily contrast labeled amino-acid Ethibloc is considered to be the material of choice for safe application and reliable vascular distribution causing persisting occlusion of the renal arteries.


Longitudinal optical coherence tomography angiography (OCT-A) in a patient with radiation retinopathy following plaque brachytherapy for uveal melanoma.
Patients with choroidal melanoma treated with brachytherapy lose vision over time due to radiation retinopathy and optic neuropathy. Newer imaging modalities such as optical coherence tomography angiography (OCT-A) may provide further insight into the ultrastructural vascular changes that occur over time. We studied the progressive OCT-A derived reduction in capillary density that occurred in the macula and juxtapapillary region of a patient treated with plaque brachytherapy for posterior uveal melanoma. A patient with medium-sized choroidal melanoma in the inferonasal mid-periphery of the right eye was followed with OCT-A imaging in addition to standard imaging (color fundus photography, standardized echography, OCT) over a four-year time period following brachytherapy. Images were analyzed to measure vascular density in nine discrete areas of the macula at each time point as a function of region-specific radiation dose. OCT-A over time showed focal capillary loss and enlargement of the foveal avascular zone in addition to vascular re-modeling. These changes progressed over time despite improvement in the clinical markers of radiation retinopathy (cotton wool spots, retinal hemorrhages). Radiation dose significantly correlated with rate of reduction in vascular density assessed within 9 square sectors of the macula, and was greatest in sectors closest to the plaque, which had received the highest radiation dose. There was no change in the choriocapillaris flow area over time. The patient developed cystoid macular edema, but maintained 20/30 vision. Longitudinal OCT-A demonstrates the microvascular changes that occur in response to radiation over time. Identification of these features may help define therapeutic windows to prevent vision loss associated with radiation retinopathy and optic neuropathy. Ongoing studies will describe a larger cohort of patients followed with this modality over time.


In vitro study of P-glycoprotein induction as an antidotal pathway to prevent cytotoxicity in Caco-2 cells.
The Caco-2 cell line is a reliable in vitro model for predicting drug intestinal absorption and P-glycoprotein (P-gp)-mediated excretion in humans. Recent in vivo studies suggested the induction of P-gp as a cellular protection tool against paraquat poisoning, through the increase in its pulmonary and intestinal excretion. Thus, the aim of the present work was to evaluate P-gp expression and activity in Caco-2 cells exposed to doxorubicin (a known P-gp inducer) and to correlate these changes with paraquat toxic effects. Cytotoxicity of doxorubicin (0-100 μM) and paraquat (0-1,000 μM) was evaluated for a maximum period of 96 h. In doxorubicin-exposed cells, P-gp expression and transport activity were evaluated by flow cytometry, using a fluorescein isothiocyanate-conjugated antibody and the P-gp fluorescent subtract rhodamine 123, respectively. A significant increase in P-gp expression was observed as soon as 6 h after exposure to 5 μM doxorubicin. P-gp activity also increased after 6 h, but only at higher doxorubicin concentrations (over 50 μM). Paraquat (0-5,000 μM) cytotoxicity was then evaluated with or without previous exposure of the cells to doxorubicin (5-100 μM, a concentration range causing both an increase in P-gp expression and activity). Under P-gp induction, a significant reduction in paraquat cytotoxicity was observed. Furthermore, when these cells were incubated with a specific P-gp inhibitor (UIC2 antibody) the doxorubicin protective effects were blocked, confirming the involvement of P-gp in the reduction in paraquat cytotoxicity. In conclusion, the human Caco-2 cell line model can be used for the study of P-gp induction as an antidotal pathway against substrates of this transporter system.


Synthesis of L-enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides.
L-Enantiomers of 4'-thioarabinofuranosyl pyrimidine nucleosides were synthesized from D-xylose. Methyl 2,3,5-tri-O-benzyl-D-xylofuranoside 6 was converted to the corresponding xylitol 7, which was treated with MsCl and then Na2S to give 1,4-anhydro-L-4-thioarabitol 8. As previously reported, Pummerer rearrangement of 8 followed by glycosylation with a silylated thymine and N4-acetylcytosine derivative and deprotection gave the corresponding alpha- and beta-L-4'-thioarabinofuranosyl pyrimidine nucleosides.


ZNT-1 Expression Reduction Enhances Free Zinc Accumulation in Astrocytes After Ischemic Stroke.
Excess intracellular zinc has been implicated in ischemic brain cell death. We previously reported that extracellular zinc increases intracellular free zinc level only in hypoxic astrocytes but not in normoxia astrocytes. However, the underlying mechanisms remain to be elucidated. Zinc transporters ZnTs and ZIPs mediate intracellular zinc efflux and extracellular zinc influx. In the present study, we determined the effect of hypoxia/reoxygenation on ZnT-1 and ZIP-1. Hypoxia/reoxygenation did not change the ZIP-1 level in astrocytes. Remarkably, hypoxia/reoxygenation dramatically decreased ZnT-1 expression, which can be difficult to reverse by the addition of extracellular zinc, although extracellular zinc treatment significantly increased ZnT-1 level at normoxia. These results suggest that hypoxia/reoxygenation blocked zinc efflux, whereas zinc influx may be at a similar level to that in normoxia, providing a novel mechanism for intracellular free zinc accumulation after ischemic stroke.


SagS and its unorthodox contributions to Pseudomonas aeruginosa biofilm development.
The Pseudomonas aeruginosa orphan sensor SagS (PA2824) was initially reported as one of three orphan sensor kinases capable of activating HptB, a component of the HptB signaling pathway that intersects with the Gac/Rsm signaling pathway and fine-tunes P. aeruginosa motility and pathogenesis. Since then, this orphan sensor has been reported to be involved in other, unorthodox signaling pathways serving additional functions. The present review is aimed at summarizing the various functions of SagS, with an emphasis on its toggle or dual switch functions, and highlighting the role of SagS as a hub at which the various signaling pathways intersect, to regulate the transition from the planktonic to the sessile mode of growth, as well as the transition of surface-associated cells to a drug tolerant state.


Structural basis of degradation signal recognition by SspB, a specificity-enhancing factor for the ClpXP proteolytic machine.
In prokaryotes, incomplete or misfolded polypeptides emanating from a stalled ribosome are marked for degradation by the addition of an 11 residue peptide (AANDENYALAA) to their C terminus. Substrates containing this conserved degradation signal, the SsrA tag, are targeted to specific proteases including ClpXP and ClpAP. SspB was originally characterized as a stringent starvation protein and has been found to bind specifically to SsrA-tagged proteins and to enhance recognition of these proteins by the ClpXP degradation machine. Here, we report the crystal structures of SspB alone and in complex with an SsrA peptide. Unexpectedly, SspB exhibits a fold found in Sm-family RNA binding proteins. The dimeric SspB structures explain the key determinants for recognition of the SsrA tag and define a hydrophobic channel that may bind unfolded substrates.


Improved palliation of a respiratory-esophageal fistula with a cuffed esophageal prosthesis.
We report a case in which a traditional prosthesis failed to seal a malignant respiratory-esophageal fistula. Removal of the prosthesis and replacement with a new type with an inflatable cuff provided palliation, and allowed the patient to leave the hospital. The cuffed prosthesis provides a custom fit which should seal fistulous tracts of any shape or size, without causing tissue necrosis.


Nitrergic neurons in the spinal cord of the bottlenose Dolphin (Tursiops truncatus).
Nitric oxide (NO) is a freely diffusible gaseous neurotransmitter generated by a selected population of neurons and acts as a paracrine molecule in the nervous system. NO is synthesized from l-arginine by means of the neuronal nitric oxide synthase (nNOS), an enzyme requiring nicotine adenine dinucleotide phosphate (NADPH) as cofactor. In this study, we used histochemical and immunohistochemical techniques to investigate the distribution of NADPH-diaphorase (NADPH-d) and nNOS in the spinal cord of the bottlenose dolphin (Tursiops truncatus). Cells with a fusiform-shaped somata were numerous in the laminae I and II. The intermediolateral horn showed darkly-stained cells with a multipolar morphology. Neurons with a multipolar or fusiform morphology were observed in the ventral horn. Multipolar and fusiform neurons were the most common cell types in lamina X. Nitrergic fibers were numerous especially in the dorsal and intermediolateral horns. The presence of nitrergic cells and fibers in different laminae of the spinal cord suggests that NO may be involved in spinal sensory and visceral circuitries, and potentially contribute to the regulation of the complex retia mirabilia.


Prion protein immunohistochemistry in Creutzfeldt-Jakob disease.
Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy characterized clinically by dementia, myoclonus and, in some cases, periodic triphasic EEG-patterns. Neuropathologically the main features are spongiform change, astrocytosis, neuronal cell loss and, in a small percent of cases, amyloid plaques. Prion protein immunohistochemistry is used for definitive diagnosis of these diseases. In our study we present different immunostaining patterns in light microscopy using anti prion protein, and with immunogold labelling for ultrastructural localization of prion protein. Our results demonstrate the clinicopathological heterogeneity of Creutzfeldt-Jakob disease and reveal the role of the endosomal-lysosomal system in the pathogenesis.


Potential of using real-time PCR-based detection of spoilage yeast in fruit juice--a preliminary study.
A real-time PCR system was used to differentiate between the common spoilage yeasts, Zygosaccharomyces bailii, Zygosaccharomyces rouxii, Candida krusei, Rhodotorula glutinis and Saccharomyces cerevisiae, based on melting peak Tm analysis of the 5.8S rDNA subunit and the adjacent ITS2 region of these yeasts. By using the real-time PCR system and by targeting the citrate synthase (cs 1) gene of C. krusei, it was possible to develop a sensitive detection system to both identify and quantitate the level of C. krusei growth in an artificially contaminated apple juice sample.


The Effect of Bariatric Surgery on Irisin Level: a Systematic Review and Meta-analysis.
This systematic analysis and meta-analysis aimed to assess changes in the plasma levels of irisin after bariatric surgery. Search strategy, study screening, and data gathering were all conducted using a checklist and the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Two researchers independently extracted the data, and a third person was included to resolve disagreements. The results illustrated no statistical difference between before and after surgery irisin plasma levels (P = 0.216, 95% CI = -1.812-0.410, SMD = -0.701, I-squared = 94.9%). BMI exhibited a meaningful decline after surgery compared to preoperative values (SMD = -3.09, 95% CI = -4.59--1.59, I-squared = 95.5%, P<0.05). According to our analysis, it can be concluded that irisin plasma levels are not significantly influenced by bariatric surgery.


A population pharmacokinetic model for R- and S-citalopram and desmethylcitalopram in Alzheimer's disease patients with agitation.
The citalopram for Alzheimer's disease trial evaluated citalopram for the management for agitation in Alzheimer's disease patients. Sparse data was available from this elderly patient population. A nonlinear mixed effects population pharmacokinetic modeling approach was used to describe the pharmacokinetics of R- and S-citalopram and their primary metabolite (desmethylcitalopram). A structural model with 4 compartments (one compartment/compound) with linear oral absorption and elimination described the data adequately. Overall, the model showed that clearance of the R-enantiomer was slower than the clearance of the S-enantiomer. Without accounting for any patient-specific covariates, the population estimate of the metabolic clearance of citalopram was 8.6 (R-citalopram) and 14 L/h (S-citalopram). The population estimate of the clearance of desmethylcitalopram was 23.8 (R-Dcit) and 38.5 L/h (S-Dcit). Several patient-specific covariates were found to have a significant effect on the pharmacokinetics of R,S-citalopram and desmethylcitalopram. A significant difference in the metabolic clearance of R-citalopram between males and females (13 vs 9.05 L/h) was identified in this analysis. Both R- and S-citalopram metabolic clearance decreased with age. Additionally, consistent with literature reports S-citalopram metabolic clearance increased with increasing body weight and was significantly influenced by CYPC19 genotype, with a difference of 5.8 L/h between extensive/rapid and intermediate/poor metabolizers. R,S-desmethylcitalopram clearance increased with increasing body weight. This model may allow for the opportunity to delineate the effect of R- and S-citalopram on pharmacodynamics outcomes related to the management of agitation in Alzheimer's disease.


Concept of "awake venovenous extracorporeal membrane oxygenation" in pediatric patients awaiting lung transplantation.
In patients awaiting LuTx, MV and ECMO are often the last ways to create a bridge to LuTx. Both interventions are associated with a poor posttransplant outcome and survival rate. To improve the results of these patients, new "bridging-strategies" are necessary. Recent reports demonstrate promising results for the concept of "awake ECMO" in adult patients. To date, no data on this approach in pediatric patients have been available. We therefore describe the use of VV-ECMO as a treatment strategy for RF in awake pediatric patients. It presents our experiences with the first three children treated using this new concept. Mean amount of time on ECMO was 44 days (range, 11.5-109 days). Two patients were successfully bridged to their LuTx. Both are still alive without any recurrences (24 and three months following LuTx). One patient died before a further LuTx after 109 days on ECMO due to adenoviral infection. Although reintubation was necessary in two patients, and total time being awake while on ECMO was <50%, we conclude that the concept of "awake VV-ECMO" is feasible for the treatment of RF and can be used as a "bridging therapy" to LuTx.


Effect of Welsh Onion on Taste Components and Sensory Characteristics of Porcine Bone Soup.
To investigate the effect of welsh onion on taste components and sensory characteristics in porcine bone soup, the stewing condition was as follows: the material-liquid ratio (m/V) was 1:1, the stewing time was 5.0 h, and the ratio of welsh onion was 2.5%. Then, the content of taste components was measured. The content of free amino acids in porcine bone soup with welsh onion (PWS) was higher than the sum of welsh onion soup (WS) and porcine bone soup (PS); particularly, the umami amino acids increased by 35.73% compared with PS. Significant increases in four organic acids (lactic acid, pyroglutamic acid, citric acid and ascorbic acid), two 5'-nucleotides (5'-AMP and 5'-GMP) and three mineral elements (K, Ca and Mg) were observed in PWS. Compared with PS, the equivalent umami concentration (EUC) value was increased from 79.09 to 106.47 mg MSG/100 g in PWS, which was due to the high content of umami amino acids and the synergistic effect with 5'-nucleotides. The results of the sensory analysis indicated a certain enhancement of umami taste in PWS, and the sweet and salty tastes were also increased with the addition of welsh onion. The correlation analysis was consistent with the variation of the components tested above.


Evaluating Data Product Exposure Metrics for Use in Epidemiologic Studies of Dust Storms.
Dust storms are increasing in frequency and correlate with adverse health outcomes but remain understudied in the United States (U.S.), partially due to the limited spatio-temporal coverage, resolution, and accuracy of current data sets. In this work, dust-related metrics from four public areal data products were compared to a monitor-based "gold standard" dust data set. The data products included the National Weather Service (NWS) storm event database, the Modern-Era Retrospective analysis for Research and Applications-Version 2, the EPA's Air QUAlity TimE Series (EQUATES) Project using the Community Multiscale Air Quality Modeling System (CMAQ), and the Copernicus Atmosphere Monitoring Service global reanalysis product. California, Nevada, Utah, and Arizona, which account for most dust storms reported in the U.S., were examined. Dichotomous and continuous metrics based on reported dust storms, particulate matter concentrations (PM10 and PM2.5), and aerosol-type variables were extracted or derived from the data products. Associations between these metrics and a validated dust storm detection method utilizing Interagency Monitoring of Protected Visual Environments monitors were estimated via quasi-binomial regression. In general, metrics from CAMS yielded the strongest associations with the "gold standard," followed by the NWS storm database metric. Dust aerosol (0.9-20 μm) mixing ratio, vertically integrated mass of dust aerosol (9-20 μm), and dust aerosol optical depth at 550 nm from CAMS generated the highest standardized odds ratios among all metrics. Future work will apply machine-learning methods to the best-performing metrics to create a public dust storm database suitable for long-term epidemiologic studies.


Persistent inequality: evolution of psychosocial exposures at work among the salaried population in Spain between 2005 and 2016.
To assess the prevalence of poor mental health and of exposure to psychosocial risks among the working population in Spain in 2005, 2010 and 2016; to analyse the associations between workplace psychosocial exposures and mental health problems according to gender and occupation. Three representative samples of the Spanish working population were analysed, in 2005 (n = 7,023), 2010 (n = 4,979), and 2016 (n = 1,807). Prevalence ratios between mental health and the five dimensions - job demands, job control, social support, employment insecurity and insecurity over working conditions-were estimated using multilevel mixed-effects Poisson regressions. All the analyses were separated by gender and occupation. In 2016, there were improvements in job control, job demands and social support, and deteriorations in employment insecurity and insecurity over working conditions. The risk of poor mental health among manual workers rose if they were exposed to high demands, low social support and high employment insecurity; among non-manual workers, the risk increased if they were exposed to high demands, low control, low social support and high insecurity over working conditions. There were no differences according to gender. The new findings shed light on the evolution of the working conditions and health of the wage-earning population in Spain over the last 11 years. The stratification by gender and occupational group is relevant, since it allows a detailed analysis of the social disparities in the associations between psychosocial risks and mental health. The most vulnerable groups can be identified and preventive measures developed at source.


[Combined manifestations of natural foci in the territory of the Vologda province].
Based on epizootological and epidemiological investigations in the Vologda province since 1958 till 2000, the combined territorial and temporal manifestations of natural foci of diseases was revealed. A natural focus occupies a complex of biotopes, and in different time the focus is activated in different areas, such as a river plain, marsh, meadow-field, and forest. Most commonly an activation of the natural focus appears in a border zone of three biotopes, namely, a forest, meadow-field, and river plain. A dependence of activation of various natural foci upon local climate conditions and fluctuations of micromammalian host number are considered.


Identification case of evidence in timber tracing of Pinus radiate, using high-resolution melting (HRM) analysis.
Fast, accurate detection of plant species and their hybrids using molecular tools will facilitate assessment and monitoring of timber tracing evidence. In this study the origin of unknown pine samples is determined for a case of timber theft in the region of Araucania southern Chile. We evaluate the utility of the trnL marker region for species identification applied to pine wood based on High Resolution Melting. This efficient tracing methods can be incorporated into forestry applications such as certification of origin. The object of this work was genotype identification using high-resolution melting (HRM) and trnL approaches for Pinus radiata (Don) in timber tracing evidence. Our results indicate that trnL is a very sensitive marker for delimiting species and HRM analysis was used successfully for genotyping Pinus samples for timber tracing purposes. Genotyping samples by HRM analysis with the trnL1 approach allowed us to differentiate two wood samples from the Pinaceae family: Pinus radiata (Don) and Pseudotsuga menziesii (Mirb.) Franco. The same approach with Pinus trnL wood was not able to discriminate between samples of Pinus radiata, indicating that the samples were genetically indistinguishable, possibly because they have the same genotype at this locus. Timber tracing with HRM analysis is expected to contribute to future forest certification schemes, control of illegal trading, and molecular traceability of Pinus spp.


Sex steroids in the female zebrafish (Danio rerio). Effects of cyproterone acetate and leachate-contaminated sediment extract.
In Molnbyggen, a leachate-contaminated lake in Sweden, effects on the reproductive system of perch included a decreased frequency of sexually mature female perch, reduced gonadosomatic index and decreased plasma levels of androstenedione and testosterone, but the contaminants responsible for these effects have not yet been identified. A biomarker-directed fractionation approach could be used to narrow the search for the compound(s) responsible for the adverse effects in Molnbyggen female perch. Thus, it is important to develop and test a suitable biomarker, which can be used in this type of approach. We evaluated if decreased concentrations of sex steroids could work as an in vivo end-point in female zebrafish fed an organic extract of bottom sediments from Molnbyggen. The responsiveness of zebrafish to endocrine alteration was evaluated using a positive control substance, cyproterone acetate (CA), which is known to inhibit steroid biosynthesis. After the 21-day exposure period the concentrations of testosterone (T) and estradiol (E2) were successfully determined by HRGC/HRMS in whole-body homogenates of individual fish. Median T concentrations were 1.7pmol/g fish in controls and were decreased after exposure both to CA (0.55pmol/g fish) and Molnbyggen sediment extract (1.2-1.3pmol/g fish). Median E2 concentrations were 5.3pmol/g fish in controls and were decreased after CA exposure (2.3pmol/g fish) and after exposure to Molnbyggen sediment extract (4.0-4.5pmol/g fish). This suggests that sex steroid concentrations in zebrafish are responsive to endocrine alteration and indicates that compounds with endocrine altering potency are present in Molnbyggen sediments.


Protein kinase C-mediated phosphorylation and calmodulin binding of recombinant myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein.
The myristoylated alanine-rich C kinase substrate (MARCKS) and the MARCKS-related protein (MRP) are members of a distinct family of protein kinase C (PKC) substrates that also bind calmodulin in a manner regulated by phosphorylation by PKC. The kinetics of PKC-mediated phosphorylation and the calmodulin binding properties of intact, recombinant MARCKS and MRP were investigated and compared with previous studies of synthetic peptides spanning the PKC phosphorylation site/calmodulin binding domains (PSCBD) of these proteins. Both MARCKS and MRP were high affinity substrates for the catalytic fragment of PKC, and their phosphorylation occurred with positive cooperativity (MARCKS: S0.5 = 100 nM, KH = 1.43; MRP: S0.5 = 238 nM, KH = 1.72). These affinities are similar to the values determined from studies of their respective PSCBD peptides. Two-dimensional mapping of MRP and its synthetic PSCBD peptide yielded identical patterns of tryptic phosphopeptides, indicating that, as in the case of MARCKS, all of the PKC phosphorylation sites in MRP lie within the 24-amino acid PSCBD. Sequence analysis of tryptic phosphopeptides revealed that the first and third, but not the second, serines in the MRP PSCBD were phosphorylated by PKC. Both MARCKS and MRP bound dansyl-calmodulin with high affinity, with a Kapp of 4.6 and 9.5 nM, respectively. Phosphorylation of MARCKS and MRP by PKC disrupted the protein-calmodulin complexes, with half-lives of 4.0 and 3.5 min, respectively. These studies suggest that intact, recombinant MARCKS and MRP are accurately modeled by their synthetic PSCBD peptides with respect to PKC phosphorylation kinetics and their phosphorylation-dependent calmodulin binding properties.


Human growth hormone in urine: development of an ultrasensitive radiometric assay.
An immunoradiometric assay for human growth hormone (HGH) has been developed which has a detection limit of 1 ng/l and can measure HGH in unextracted urine from normal children and adults. The assay is based on a two-step procedure, using a solid-phase goat-anti-HGH immunosorbent for immunoextraction and [125I]-labeled monoclonal HGH-antibody for detection and quantification. The assay is not affected by urea, NaCl or changes of pH from 5-8. The mean urine HGH concentration in normal children is 6.78 +/- 7.6 (SD) pg/ml, in patients with HGH-deficiency 1.3 +/- 0.9 pg/ml which increases to 11.7 +/- 13.4 pg/ml on the day of growth hormone injection.


A 79-Year-Old Man With Recurrent Respiratory and Constitutional Symptoms, Elevated Acute Phase Reactants, and Pancytopenia.
A 79-year-old man was examined because of recurrent dyspnea and constitutional symptoms that included malaise, fatigue, fevers, and arthralgias over the past 7 years. He was a nonsmoker who was a retired farmer. Elevated levels of acute phase reactants and C-reactive protein and a high erythrocyte sedimentation rate were noted often in his health records. However, an extensive rheumatologic evaluation, which included serologic studies (antinuclear antibodies, cyclic citrullinated peptide antibodies, antineutrophil cytoplasmic antibodies) and temporal artery biopsy, had not shown an identifiable autoimmune disease. The patient had been treated intermittently with prednisone, with partial symptomatic improvement. Various cytopenias had been present over the preceding years; however, three bone marrow biopsy specimens showed moderately hypercellular bone marrow with no diagnostic findings.


Role of G308 promoter variant of tumor necrosis factor alpha gene on weight loss and metabolic parameters after a high monounsaturated versus a high polyunsaturated fat hypocaloric diets.
The aim of our study was to investigate the influence of G-308 promoter variant of the tumor necrosis factor (TNF) alpha gene on metabolic changes and weight loss secondary to a high monounsaturated fat vs a high polyunsaturated fat hypocaloric diet in obese subjects. A sample of 261 obese subjects were enrolled in a consecutive prospective way, from May 2011 to July 2012 in a tertiary hospital. In the basal visit, patients were randomly allocated during 3 months to Diet M (high monounsaturated fat hypocaloric diet) and Diet P (high polyunsaturated fat hypocaloric diet). One hundred and ninety seven patients (73.2%) had the genotype G-308G and 64 (26.8%) patients had the genotype G-308A. There were no significant differences between the effects (on weight, body mass index (BMI), waist circumference, fat mass) in either genotype group with both diets. With the diet type P and in genotype G-308G, glucose levels (-6.7(22.1)mg/dl vs -3.7(2.2)mg/dl: p = 0.02), HOMA-R (-0.6(2.1)units vs -0.26(3.1)units: p = 0.01), insulin levels (-1.7(6.6)UI/L vs -0.6(7.1)UI/L: p = 0.009), total cholesterol levels (-15.3(31.1)mg/dl vs -8.4(22.1)mg/dl: p = 0.01), LDL cholesterol levels (-10.7(28.1)mg/dl vs -3.8(21.1)mg/dl: p = 0.008) and triglycerides (-12.1(52.1)mg/dl vs -6.6(43.1)mg/dl: p = 0.02) decreased. Carriers of the G-308G promoter variant of TNF alpha gene have a better metabolic response than A-308 obese with a high polyunsaturated fat hypocaloric diet.


Intensive care unit variables and outcome after pediatric traumatic brain injury: a retrospective study of survivors.
Traumatic brain injury is a leading cause of death and disability in children. Hypotension has been associated with poor survival and outcome in children after traumatic brain injury, but the effect of acute hypertension is less certain. The objective was to obtain acute physiologic variables during the early hospitalization period in a cohort of children prospectively enrolled in another study. Retrospective chart reviews. University-affiliated pediatric rehabilitation center. Fifty-seven survivors, 5-17 yrs of age, admitted for rehabilitation between 1992 and 1995 after sustaining a traumatic brain injury. Standard of care. Outcomes were assessed at 1 yr postinjury through cognitive testing of the child and parent interview of the child's global functional skills. Cognitive outcome was measured using the Performance IQ from the Wechsler Intelligence Scale for Children, Third Edition. Overall functional outcome was assessed using the Disability Rating Scale. This study suggests that early markers of secondary injury after moderate to severe traumatic brain injury in children may be predictive of long-term outcome. This study reinforces the need for longer term, systematic, and more precise measurements of outcomes in children with traumatic brain injury and prospective studies to examine the predictive value of acute management variables on multiple types of outcomes after traumatic brain injury in children.


New in-situ synthetized hydrogel composite based on alginate and brushite as a potential pH sensitive drug delivery system.
A Series of in-situ alginate-brushite (Alg-Bru) hydrogel composites were fabricated to optimize release profile of ibuprofen (Ibu) and to avoid burst releases associated with the pure form of the hydrogels. The Bru crystals were synthetized and dispersed during the crosslinking process of Alg matrix. The beads with different formulations were subject to various characterization tests such as X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), dynamic mechanical analysis (DMA), and swelling. In addition, the entrapment Efficiency (%EE) and drug release profile were obtained to investigate the impacts of initial concentration of Alg and content of Bru on these parameters. FTIR and XRD outcomes confirmed the successful fabricating of Alg-Bru composite as well as the loading of Ibu. Besides, the results showed that the presence of Bru within Alg matrix restricted polymer chain movement, improved mechanical properties, and decreased swelling ratio. Although the presence of Bru crystals did not improve%EE, they optimized the release profile in a more gradual manner.


Preoperative estimation of operative risk in liver surgery, with special reference to functional reserve of the remnant liver following major hepatic resection.
Hepatic functional reserve was evaluated in 76 patients with known liver, biliary tract or pancreas diseases using kinetic analysis of removal of indocyanine green (ICG) with special reference to maximal removal rate (Rmax). In surgery other than hepatectomy, if ICG Rmax is below 0.4 mg/kg/min the operative risk should be considered high. In hepatic surgery, even if ICG Rmax is above 0.4 mg/kg/min the operative risk was high and it should be required to be above 1.0 mg/kg/min for extended lobectomy or hepatectomy. Furthermore, prior to hepatectomy the functional reserve of the remnant liver was estimated from an effective liver volume rate, calculated from the rate of uptake of radioisotope as measured by on-line computer system, and ICG Rmax. The functional reserve of the remnant liver was compared with the operative results, such as morbidity or mortality for each patient. When ICG Rmax of the remnant liver was below 0.4 mg/kg/min the prognosis was poor in hepatic surgery, because of there were three postoperative death and seven complications such as ascites or liver failure in the ten cases. On the other hand, when above 0.4 mg/kg/min, the prognosis was good without any postoperative death or complications in the twelve cases of hepatic surgery, as the completely same results for general surgery, in which it is as well when ICG Rmax of whole liver is above 0.4 mg/kg/min.


Evaluation of protective shielding thickness for diagnostic radiology rooms: theory and computer simulation.
This work presents the development and evaluation using modern techniques to calculate radiation protection barriers in clinical radiographic facilities. Our methodology uses realistic primary and scattered spectra. The primary spectra were computer simulated using a waveform generalization and a semiempirical model (the Tucker-Barnes-Chakraborty model). The scattered spectra were obtained from published data. An analytical function was used to produce attenuation curves from polychromatic radiation for specified kVp, waveform, and filtration. The results of this analytical function are given in ambient dose equivalent units. The attenuation curves were obtained by application of Archer's model to computer simulation data. The parameters for the best fit to the model using primary and secondary radiation data from different radiographic procedures were determined. They resulted in an optimized model for shielding calculation for any radiographic room. The shielding costs were about 50% lower than those calculated using the traditional method based on Report No. 49 of the National Council on Radiation Protection and Measurements.


[Minimally invasive interventions in emergency large bowel surgery].
The current trends in the treatment of various surgical diseases of large bowel using minimally invasive operations are reviewed in the manuscript. It is shown that laparoscopy is currently possible in most cases for urgent large bowel diseases.