Acyclic retinoid inhibits functional interaction of transcription factors Krüppel-like factor 5 and retinoic acid receptor-alpha.
We show that transcription factor Krüppel-like factor 5 (KLF5), which is important in cardiovascular remodeling, interacts with retinoic acid receptor-alpha (RARalpha) to regulate downstream gene expression. Here, we investigated whether acyclic retinoid (ACR) regulates KLF5 and inhibits vascular remodeling. Co-immunoprecipitation and pull-down binding assay showed that ACR attenuates functional interaction of KLF5 and RARalpha. ACR affects KLF5 functions by regulating transactivation of platelet-derived growth factor A (PDGF-A) chain. ACR may be a new vascular therapy to target KLF5 in cardiovascular pathology.


Effect of remote ischemic postconditioning during thrombolysis in STEMI.
Remote ischemic postconditioning (RIPC) is suggested to protect the myocardium against ischemia in various settings. However, the effect of RIPC in patients with acute ST-elevation myocardial infarction (STEMI) who undergo thrombolysis has yet to be examined. In this single-center, randomized controlled trial, we examined the effect of RIPC on the resolution of ST-segment elevation (STR) in response to thrombolysis. Patients in the RIPC group had three cycles of 5‑min cuff inflation followed by 5‑min deflation to the upper arm. The study comprised 78 patients (15 women), of whom 41 were randomized to the RIPC group and 37 to the control group. STR occurred in 61% of the patients in the RIPC group, while it was detected only in 35% of controls (p = 0.026). Although STR was more common in the RIPC group, there was no difference in the extent of ΣCK-48 h between the two groups. Furthermore, the length of hospital stay and the frequency of adverse events were similar between the RIPC and control groups. RIPC during thrombolytic therapy in STEMI was associated with a higher frequency of STR. However, it did not affect enzymatic infarct size or the frequency of adverse events. (Clinical trial registration number: IRCT2014011916229N2.).


Metagenomic analysis of the microbiota in the highly compartmented hindguts of six wood- or soil-feeding higher termites.
Termites are important contributors to carbon and nitrogen cycling in tropical ecosystems. Higher termites digest lignocellulose in various stages of humification with the help of an entirely prokaryotic microbiota housed in their compartmented intestinal tract. Previous studies revealed fundamental differences in community structure between compartments, but the functional roles of individual lineages in symbiotic digestion are mostly unknown. Here, we conducted a highly resolved analysis of the gut microbiota in six species of higher termites that feed on plant material at different levels of humification. Combining amplicon sequencing and metagenomics, we assessed similarities in community structure and functional potential between the major hindgut compartments (P1, P3, and P4). Cluster analysis of the relative abundances of orthologous gene clusters (COGs) revealed high similarities among wood- and litter-feeding termites and strong differences to humivorous species. However, abundance estimates of bacterial phyla based on 16S rRNA genes greatly differed from those based on protein-coding genes. Community structure and functional potential of the microbiota in individual gut compartments are clearly driven by the digestive strategy of the host. The metagenomics libraries obtained in this study provide the basis for future studies that elucidate the fundamental differences in the symbiont-mediated breakdown of lignocellulose and humus by termites of different feeding groups. The high proportion of uncultured bacterial lineages in all samples calls for a reference-independent approach for the correct taxonomic assignment of protein-coding genes.


First evidence for phototropin-related blue-light receptors in prokaryotes.
A prokaryotic protein, YtvA from Bacillus subtilis, was found to possess a light, oxygen, voltage (LOV) domain sharing high homology with the photoactive, flavin mononucleotide (FMN)-binding LOV domains of phototropins (phot), blue-light photoreceptors for phototropism in higher plants. Computer-based three-dimensional modeling suggests that YtvA-LOV binds FMN in a similar pocket as phot-LOVs. Recombinant YtvA indeed exhibits the same spectroscopical features and blue-light-induced photochemistry as phot-LOVs, with the reversible formation of a blue-shifted photoproduct, assigned to an FMN-cysteine thiol adduct (Thio383). By means of laser-flash photolysis and time-resolved optoacoustic experiments, we measured the quantum yield of formation for Thio383, Phi(Thio) = 0.49, and the enthalpy change, DeltaH(Thio) = 135 kJ/mol, with respect to the parent state. The formation of Thio383 is accompanied by a considerable volume contraction, DeltaV(Thio) = -13.5 ml/mol. Similar to phot-LOVs, Thio383 is formed from the decay of a red-shifted transient species, T650, within 2 micros. In both YtvA and free FMN, this transient has an enthalpy content of approximately 200 kJ/mol, and its formation is accompanied by a small contraction, DeltaV(T) approximately -1.5 ml/mol, supporting the assignment of T650 to the FMN triplet state, as suggested by spectroscopical evidences. These are the first studies indicating that phototropin-related, blue-light receptors may exist also in prokaryotes, besides constituting a steadily growing family in plants.


A maize-specifically expressed gene cluster in Ustilago maydis.
The corn pathogen Ustilago maydis requires its host plant maize for development and completion of its sexual cycle. We have identified the fungal mig2-1 gene as being specifically expressed during this biotrophic stage. Intriguingly, mig2-1 is part of a gene cluster comprising five highly homologous and similarly regulated genes designated mig2-1 to mig2-5. Deletion analysis of the mig2-1 promoter provides evidence for negative and positive regulation. The predicted polypeptides of all five genes lack significant homologies to known genes but have characteristic N-terminal secretion sequences. The secretion signals of mig2-1 and mig2-5 were shown to be functional, and secretion of a full length Mig2-1-eGFP fusion protein to the extracellular space was demonstrated. The central domains of the Mig2 proteins are highly variable whereas the C-termini are strongly conserved and share a characteristic pattern of eight cysteine residues. The mig2 gene cluster was conserved in a wide collection of U. maydis strains. Interestingly, some U. maydis isolates from South America had lost the mig2-4 gene as a result of a homologous recombination event. Furthermore, the related Ustilago scitaminea strain, which is pathogenic on sugar cane, appears to lack the mig2 cluster. We describe a model of how the mig2 cluster might have evolved and discuss its possible role in governing host interaction.


Epigenetic regulation of the glucose transporter gene Slc2a1 by β-hydroxybutyrate underlies preferential glucose supply to the brain of fasted mice.
We carried out liquid chromatography-tandem mass spectrometry analysis of metabolites in mice. Those metabolome data showed that hepatic glucose content is reduced, but that brain glucose content is unaffected, during fasting, consistent with the priority given to brain glucose consumption during fasting. The molecular mechanisms for this preferential glucose supply to the brain are not fully understood. We also showed that the fasting-induced production of the ketone body β-hydroxybutyrate (β-OHB) enhances expression of the glucose transporter gene Slc2a1 (Glut1) via histone modification. Upon β-OHB treatment, Slc2a1 expression was up-regulated, with a concomitant increase in H3K9 acetylation at the critical cis-regulatory region of the Slc2a1 gene in brain microvascular endothelial cells and NB2a neuronal cells, shown by quantitative PCR analysis and chromatin immunoprecipitation assay. CRISPR/Cas9-mediated disruption of the Hdac2 gene increased Slc2a1 expression, suggesting that it is one of the responsible histone deacetylases (HDACs). These results confirm that β-OHB is a HDAC inhibitor and show that β-OHB plays an important role in fasting-induced epigenetic activation of a glucose transporter gene in the brain.


Temporal Muscle-specific Disuse Atrophy during One Week of Leg Immobilization.
Musculoskeletal injuries necessitate periods of disuse (i.e., limb immobilization) during which rapid skeletal muscle atrophy occurs. The relative susceptibility of different muscles of the thigh to disuse atrophy remains uninvestigated. We assessed muscle disuse atrophy of individual thigh muscles throughout 1 wk of unilateral knee immobilization. Thirteen healthy, young (20.2 ± 0.6 yr) men underwent 7 d of unilateral leg immobilization via knee bracing. Magnetic resonance imaging scans were performed bilaterally prior to, and following 2 and 7 d of immobilization to determine the volume and anatomical cross-sectional area of the individual muscle groups of the upper legs. In contrast to the control leg, total thigh muscle volume had decreased by 1.7% ± 0.3% (P < 0.01) and 5.5% ± 0.6% (P < 0.001) in the immobilized leg after 2 and 7 d of disuse, respectively. Muscle loss was significantly greater in the Musculus quadriceps (day 2; 1.7% ± 0.3% (P < 0.05) and day 7; 6.7% ± 0.6%) when compared with the Musculus hamstrings (day 2; 1.4% ± 0.2% (P < 0.01) and day 7; 3.5% ± 0.3%) after 7 d of disuse (P < 0.001). Individual muscles of the thigh exhibited different atrophy rates with the Musculus vastus lateralis anatomical cross-sectional area showing the greater (2.6% ± 0.4% and 7.2% ± 0.8%), and the Musculus gracilis the lesser (1.1% ± 0.7% and 2.3% ± 1.0%) decline following 2 and 7 d of immobilization, respectively (P < 0.01). Thigh muscle disuse atrophy occurs rapidly and is already evident within 2 d of leg immobilization and progresses at a similar rate over the next 5 d (~0.8% muscle loss per day). M. quadriceps muscle shows more atrophy when compared with the M. hamstrings.


Stereochemical behavior of (77)Se-(1)H spin-spin coupling constants in pyrazolyl-1,3-diselenanes and 1,2-diselenolane.
Conformational study of five derivatives of 2-(pyrazol-4-yl)-1,3-diselenane together with related 1,2-diselenolane in respect to the stereochemical trends of geminal and vicinal (77)Se-(1)H spin-spin coupling constants has been carried out by means of high-level theoretical calculations in combination with experiment. The marked dihedral angle dependences for both types of couplings accounted for the lone pair effect in the case of geminal coupling constants and the Karplus-type relationship for vicinal couplings have been established, which is of major importance for the stereochemical analysis of saturated selenium containing heterocycles.


Glypican-3 is a potential prognostic biomarker for hepatocellular carcinoma after curative resection.
Glypican-3 (GPC3), an oncofetal protein, is overexpressed in hepatocellular carcinoma (HCC). The diagnostic efficacy of GPC3 for HCC has been evaluated intensively in recent years; however, the prognostic value of GPC3 for HCC has not been well clarified. The purpose of this study was to investigate the relationship between GPC3 and postoperative patient survival in a prospective database. GPC3 protein was detected by immunohistochemistry. The relationship between GPC3 expression level and patients' clinicopathologic factors was analyzed. Kaplan-Meier survival analysis was used to calculate patients' survival and was compared by using the log rank test. The Cox regression model was used to identify the risk factors associated with prognosis. GPC3 was expressed in 84% of HCC tissues. GPC3 protein expression was correlated with the number of tumors (P = .015), serum alpha-fetoprotein (AFP) level (P = .011), and TNM stage (P = .006). High GPC3 expression was an independent risk factor for poor postoperative disease-free survival (hazard ratio [HR] = 0.469; 95% confidence interval [CI] 0.303-0.727; P = .001); and overall survival (HR = 0.435; 95% CI, 0.257-0.736; P = .002). Stratification analysis indicated that GPC3 had a good predictive value for tumor recurrence in patients with HCC who have normal serum AFP levels. Also, GPC3 expression status could predict the outcomes of patients with stage I disease. GPC3 is a potential and reliable biomarker for predicting tumor recurrence and overall survival in HCC patients after curative resection.


Urethral bulking agents: a retrospective review of primary versus salvage procedure outcomes.
Urethral bulking agents (UBA) have traditionally been offered as salvage procedures for recurrent stress urinary incontinence (SUI). We compare the success of UBA in patients that had undergone a previous procedure for SUI (Salvage-UBA) to the SUI surgery naïve (Primary-UBA). We hypothesised a positive effect in both Primary and Salvage-UBA with potentially poorer rates of response in the salvage group. Retrospective case series of patients having their first UBA (2010-2018). Primary outcome was to assess any difference in patient reported success between groups. Patient-reported improvement was assessed on a 4-point scale: 'cured, improved, no change, worse' and treatment 'success' defined as 'cured' or 'improved'. A multivariate analysis, adjusting for plausible differences between groups, was undertaken in IBM SPSS Statistics (2016). 135 Primary-UBA and 38 Salvage-UBA were performed. Complete follow-up was obtained for 114 patients (66%): 86 Primary and 28 Salvage. Median follow-up time: 33 months. In 2012, 47% (8/17) of all UBA were Salvage-UBA, whilst in 2018, the majority were Primary-UBA (92%, 46/50). Success was not significantly different between Salvage-UBA 75% (21/28) versus Primary-UBA 67% (58/86) (Wald χ2 = 0.687, df = 1, p = 0.407). Top-up rates were similar: 14% (n = 4/28, Salvage-UBA) versus 15% (n = 13/86, Primary-UBA) (χ2 = 0.011, df = 1, p = 0.914). The number of women opting for UBA has increased substantially. No significant differences were noted for success with Salvage-UBA compared to Primary-UBA.


[Fournier gangrene as a rare complication after stapler hemorrhoidectomy. Case report and review of the literature].
Fournier's gangrene is a well known often fatal fasziitis of the pelvic floor following ano-rectal, urologic and gynecologic infections. Although rarely it is described as a complication of operative anal procedures and predisposing factors such as diabetes, alcoholism, immune-defects and consumptive diseases. To our knowledge the described case of a lethal outcome after staplerhemorrhoidectomy is the first one reported in literature.


Cerebral and cerebellar histological changes in the rat animal model of rotenone induced parkinsonism can be ameliorated by bone marrow derived stem cell conditioned media.
Parkinson disease is the second most common neurodegenerative disease affecting elderly patients. It occurs due to the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). We continue our work in this model focusing on other brain areas affected with this disorder; cerebral cortex and cerebellum (areas other than substantia nigra) for better understanding the motor and behavior effect of the Parkinson disease as a forward steep for its treatment and medical control. This work aims to evaluate the therapeutic effect of stem cell-conditioned medium in the Parkinsonism model. In this study, Parkinsonism model was induced in rats by daily subcutaneous injection of 0.5 mg/Kg of rotenone for 28 days. Thirty rats were divided randomly into 3 groups; control, Parkinson, and conditioned medium (CM) treated groups. Cerebral Cortex and Cerebellum were obtained for histological, immunohistochemical and biochemical studies. In the Parkinsonism group, marked histological changes were observed. These findings were nearly ameliorated in CM treated group as confirmed by the biochemical, histological, and immunohistochemical (anti-alpha synculein, anti GFAP and anti nestin) studies. It could be concluded that CM had a good therapeutic effect on Parkinsonism induced damage in both the cerebral cortex and cerebellum.


Comparative analysis of the in vitro cytotoxicity of the dietary biogenic amines tyramine and histamine.
Tyramine and histamine, the most toxic biogenic amines (BA), are often found in high concentrations in certain foods. Prompted by the limited knowledge of BA toxicity, and increasing awareness of the risks associated with high intakes of dietary BA, the in vitro cytotoxicity of tyramine and histamine was investigated. Tyramine and histamine were toxic for HT29 intestinal cell cultures at concentrations commonly found in BA-rich food, as determined by real-time cell analysis. Surprisingly, tyramine had a stronger and more rapid cytotoxic effect than histamine. Their mode of action was also different, while tyramine caused cell necrosis, histamine induced apoptosis. To avoid health risks, the BA content of foods should be reduced and legal limits established for tyramine.


Leaf size and leaf consistence of a riverine forest formation along a climatic gradient.
The riverine forest formation on the levees along the Orange River in South Africa shows a shift in floristic composition as the river traverses various climatic zones on its course through the temperate area in the eastern parts of the subcontinent, the central semi-desert region, and the desert area near the Atlantic in the west. Leaf size classes and leaf consistency types of the woody species in the riverine forest were determined for each community. Analysis of these data revealed a diversification of leaf sizes as the climate changed from temperate to hot and arid and particularly microphylls became relatively less important and were replaced by smaller leaves in the hot areas. In the same direction malacophylls, which are of the "low-cost, quick-profit" strategy type and are well represented in the temperate, frosty areas, disappear and xeromorphic leaves ("high-cost, slow-profit" strategy type) increase in importance. It is suggested that the cooler conditions with higher wind speeds and higher degrees of average air humidity near the Atlantic coast are reflected by an increase in mesophylls which are sclerophyllous as an adaptation to the frequently and rapidly changing temperature conditions here.


Inflammation Perturbs the IL-7 Axis, Promoting Senescence and Exhaustion that Broadly Characterize Immune Failure in Treated HIV Infection.
HIV-infected patients who fail to normalize CD4 T cells despite suppressive antiretroviral therapy have impaired immune homeostasis: diminished naive T-cell numbers, elevated T-cell turnover, senescence, and inflammation. Blood samples from immune failures (n = 60), immune successes (n = 20), and healthy controls (n = 20) were examined for plasma interleukin (IL)-7 levels, for cellular expression of the IL-7Rα chain (CD127), for the exhaustion and senescence markers programed death 1 (PD-1) and CD57, and for the survival factor Bcl2. Because both inflammatory and homeostatic cytokines can induce T-cell cycling, we also examined the effects of these mediators on exhaustion and senescence markers. Plasma levels of IL-7 were elevated and both CD4 and CD8 T-cell CD127 expression was decreased in immune failure. Plasma levels of IL-7 correlated directly with naive CD4 T-cell counts in immune success and inversely with T-cell cycling (Ki67) in healthy controls and immune success, but not in immune failure. CD4 T-cell density of PD-1 was increased and Bcl2+ CD4 T cells were decreased in immune failure but not in immune success, whereas the proportion of T cells expressing CD57 was increased in immune failure. PD-1 and CD57 were induced on CD4 but not CD8 T cells by stimulation in vitro with inflammatory IL-1β or homeostatic (IL-7) cytokines. Perturbation of the IL-7/IL-7 receptor axis, increased T-cell turnover, and increased senescence may reflect dysregulated responses to both homeostatic and inflammatory cytokines in immune failure patients.


The effect of bovine leukemia virus on dairy cow longevity.
Bovine leukemia virus (BLV) is a retrovirus of cattle that infects approximately 45% of all US dairy cattle, with about 90% of US dairy herds having at least one infected animal. Studies have found BLV infection to be associated with multiple measures of decreased immune function, which may explain the observed economic losses from milk production, decreased cow longevity, and predisposition to lymphoma and other diseases. Our objective was to measure the association between BLV infection and cow longevity in dairy cow operations. Ninety-one dairy herds from 9 US states volunteered to participate in this study. Milking dairy cows (n = 3,611) were tested for BLV antibodies using an ELISA milk test, and their presence in the herd was monitored for an average of 29 mo. The survival analysis controlled for herd and lactation number. Cows sold for dairy purposes were excluded, and individual cow results were not shared with producers so as not to influence culling decisions. Overall, 47.1% (1,701/3,611) of cows were BLV-positive by ELISA. The significant hazard ratio of 1.30 indicated that positive cows were 30% more likely than their negative herdmates to die or be culled during the monitoring period. These results are consistent with other studies in finding a negative effect of BLV infection on cow lifespan.


Renal angiomyolipoma: Clinico-pathologic study of 17 cases with emphasis on the epithelioid histology and p53 gene abnormalities.
Epithelioid angiomyolipoma (EAML) is a rare potentially malignant variant of renal angiomyolipoma (RAML). This study aims to determine whether RAML clinico-pathologic and molecular features (i.e. p53 gene abnormalities) differ significantly with regards to its histologic variant or to the presence of an epithelioid component within it. Consecutively resected RAML were reviewed, tumours comprising at least 80% of epithelioid cells were considered as EAML according to the 2016 World Health Organization classification of tumours of the kidney. P53 gene abnormalities were investigated using both immunohistochemical and molecular analysis. A total of 3 EAML among 17 RAML were identified, accounting for 3.9% of the total AML cases. Fatty aspect on imaging was more observed within tumours devoid of an epithelioid component. EAML showed a higher mitotic rate and a stronger p53 staining, no renal poles involvement and was not treated by nephron sparing surgeries. RAML comprising an epithelioid component demonstrated severer nuclear atypia as well as stronger p53 staining. P53 gene sequencing revealed a missense mutation (c.747G > C) in one classic AML harbouring a strong labelling with p53. Strong p53 staining in a RAML, even in the absence of gene mutation, may suggest the presence of an epithelioid component or of a truly EAML. To the best of our knowledge, c.747G > C p53 gene mutation is being reported for the first time in a RAML, although its role in AML pathogenesis is still unknown.


Effects of stop-signal modality on the N2/P3 complex elicited in the stop-signal paradigm.
The principal aim of the present study was to clarify how stop-signal modality affected the speed and efficacy of stopping, using ERP components as converging measures of stop processes. Both performance and ERP latency findings suggested faster processing of stop signals in the auditory than visual version of the stop task. The effects of successful versus unsuccessful stopping on the amplitude and topography of N2/P3 components elicited by the stop signals appeared to be largely independent of the modality of the stop signals. Stop signals elicited a fronto-central N2 that was much larger on unsuccessful than successful stop trials in stimulus-locked waveforms. N2 was followed by a P3 component that showed a fronto-central distribution on successful stop trials. P3 elicited on unsuccessful stop trials showed a posterior-parietal focus, but this topography was manifested more clearly in response-locked than stimulus-locked waveforms. A dipole source analyses confirmed these topographical differences of P3, and further showed that the location of the corresponding dipoles remained largely identical across the visual and auditory versions of the stop-signal task. Taken together, the present findings support the suggestion that ERP components in the stop task reflect endogenous aspects of stop-signal processing, such as effective inhibition of responses on successful stop trials and detection of errors on failed inhibition trials.


A facile strategy to prepare FeNx decorated PtFe intermetallic with excellent acidic oxygen reduction reaction activity and stability.
The construction of low-Pt-content intermetallic on carbon supports has been verified as a promising method to promote the activity of the oxygen reduction reaction (ORR). In this study, we have developed a simple and effective strategy to obtain a well-designed CNT-PtFe-PPy precursor. This precursor contains modulated Pt- and Fe-based content dispersed in polypyrrole (PPy) chain segments, which are in-situ generated on the templates of carbon nanotubes (CNTs). Subsequent pyrolysis of the CNT-PtFe-PPy precursor produces a CNT-PtFe@FeNC catalyst, which contains both Fe-Nx and PtFe intermetallic active sites. Due to the highly efficient dispersion of active species, the CNT-PtFe@FeNC electrocatalyst displays a 9.5 times higher specific activity (SA) and 8.5 times higher mass activity (MA) than those of a commercial Pt/C catalyst in a 0.1 M HClO4 solution. Additionally, these results, combined with excellent durability (the SA and MA maintained 94 % and 91 % of initial activity after a 10-k cycle accelerated durability test), represent among the best performance achieved so far for Pt-based ORR electrocatalysts. Furthermore, density functional theory (DFT) calculations revealed that the presence of Fe-N4 species reduces the adsorption energy between the PtFe intermetallic compound and OH*, accelerating the ORR process.


Early Influence of Musical Abilities and Working Memory on Speech Imitation Abilities: Study with Pre-School Children.
Musical aptitude and language talent are highly intertwined when it comes to phonetic language ability. Research on pre-school children's musical abilities and foreign language abilities are rare but give further insights into the relationship between language and musical aptitude. We tested pre-school children's abilities to imitate unknown languages, to remember strings of digits, to sing, to discriminate musical statements and their intrinsic (spontaneous) singing behavior ("singing-lovers versus singing nerds"). The findings revealed that having an ear for music is linked to phonetic language abilities. The results of this investigation show that a working memory capacity and phonetic aptitude are linked to high musical perception and production ability already at around the age of 5. This suggests that music and (foreign) language learning capacity may be linked from childhood on. Furthermore, the findings put emphasis on the possibility that early developed abilities may be responsible for individual differences in both linguistic and musical performances.


Activity-related dyspnea is not modified by psychological status in people with COPD, interstitial lung disease or obesity.
Sensory (physiological) and affective (psychological) dimensions of dyspnea have been described but the usefulness of measuring psychological status in addition to ventilatory capacity (spirometry, lung volumes) in the assessment of exertional dyspnea remains controversial. We hypothesized that activity-related dyspnea would not be modified by psychological status. Principal component analysis (PCA) was used to reduce the number of parameters (psychological or functional) to fewer independent dimensions in 328 patients with altered ventilatory capacity: severe obesity (BMI ≥ 35, n = 122), COPD (n = 128) or interstitial lung disease (n = 78). PCA demonstrated that psychological status (Hospital Anxiety-Depression, Fatigue Impact scales) and dyspnea (Medical Research Council [MRC] scale) were independent dimensions. Ventilatory capacity was described by three main dimensions by PCA related to airways, volumes, and their combination (specific airway resistance, FEV(1)/FVC), which were weakly correlated with dyspnea. In conclusion, in patients with COPD, interstitial lung disease or severe obesity, psychological status does not modify activity-related dyspnea rating as evaluated by the MRC scale.


Hexameric immunoglobulin M in humans: desired or unwanted?
Immunoglobulin M (IgM) is the first antibody produced upon infection, and is often suggested as the first line of defense of human immune system. In addition to being present on the surface of naïve B cells as a monomeric molecule, IgM is always secreted as a polymer. The most abundant IgM polymer in humans is pentamer, composed of five monomeric units, joined together by so-called joining or J chain. On the other hand, it is well known that hexameric IgM can be also found in human sera. Its presence is often related to different dissorders (Waldenström's macroglobulinemia, cold agglutinin, and recurrent urinary bacterial infections), although it is believed that small amounts of hexamer are present in normal human sera as well. Unlike pentamer, IgM hexamer contains six monomeric blocks and completely lacks J chain. Although it has been decades since its discovery, the precise function of IgM hexamer is still unknown. Since it was documented that hexamer is very potent in activating complement, it is suggested that its production in humans must be under strict control, and that it is produced in special conditions, when strong activation of complement is absolutely needed. However, the question is whether hexameric IgM is really a secret weapon or just an undesirable molecule in humans. According to structural and known functional characteristics of both pentamers and hexamers of IgM, it can be concluded that hexamers are, in addition to being maybe too reactive to be around, probably not that efficient in protecting us from bacterial and viral infections.


Immunohistochemical localization of S-100 protein in the retina, ciliary body and iris of human fetuses.
The present study deals with the localization and development of S-100 protein-like immunoreactivity in the retina, ciliary body and iris of human fetuses. In the retina, numerous astrocytes, densely distributed in the nerve-fiber layer and ganglion-cell layer, were stained strongly with the S-100 antiserum. The first immunoreactive astrocytes occurred at the posterior pole of the retina and spread gradually outward and toward the ora serrata with increasing age. Müller cells were not immunoreactive for S-100 during development, except in the retina of the latest fetus examined. S-100 immunoreactivity was also found in the nonpigmented ciliary epithelium and posterior epithelium of the iris, both of which are developed from the inner wall of the optic cup. On the other hand, the pigmented epithelium extending from retina to iris, derived from the outer layer of the optic cup, was free of S-100 immunoreactivity.


Survey and mechanism of skin depigmenting and lightening agents.
The type and amount of melanin synthesized by the melanocyte, and its distribution pattern in the surrounding keratinocytes, determines the actual color of the skin. Melanin forms through a series of oxidative reactions involving the amino acid tyrosine in the presence of the enzyme tyrosinase. Tyrosinase catalyses three different reactions in the biosynthetic pathway of melanin in melanocytes: the hydroxylation of tyrosine to l-DOPA and the oxidation of l-DOPA to dopaquinone; furthermore, in humans, dopaquinone is converted by a series of complex reactions to melanin. Among the skin-lightening and depigmenting agents, magnesium-l-ascorbyl-2-phosphate (MAP), hydroxyanisole, N-acetyl-4-S-cysteaminylphenol, arbutin (hydroquinone-beta-d-glucopyranoside) and hydroquinone (HQ) are the most widely prescribed worldwide. However, with reports of potential mutagenicity and epidemics of ochronosis, there has been an increasing impetus to find alternative herbal and pharmaceutical depigmenting agents. A review of the literature reveals that numerous other depigmenting or skin-lightening agents are either in use or in investigational stages. Some of these, such as kojic, glycolic and azelaic acids, are well known to most dermatologists. Others have been discovered and reported in the literature more recently. Several depigmentation and lightening agents are discussed, including their historical background, biochemical characteristics, type of inhibition and activators from various sources. In addition, the clinical importance of mushroom tyrosinase as a recent prospect is discussed in this paper.


Evolving from Morbidity and Mortality to a Case-based Error Reduction Conference: Evidence-based Best Practices from the Council of Emergency Medicine Residency Directors.
Morbidity and mortality conferences are common among emergency medicine residency programs and are an important part of quality improvement initiatives. Here we review the key components of running an effective morbidity and mortality conference with a focus on goals and objectives, case identification and selection, session structure, and case presentation.


Management of venous thromboembolism in athletes.
Venous thromboembolism (VTE) is a common condition with high associated morbidity and mortality. Athletes have unique VTE risk factors compared with the general population, and may have a higher than anticipated risk of thrombosis. Anticoagulant treatment poses additional challenges in athletes, as these individuals usually wish to return to sporting activities without delay. In addition, those athletes who engage in contact sports may have bleeding complications with extended anticoagulation. In this paper, we discuss VTE risk factors in athletes, the impact of exertion on haemostasis, measures which could be adopted to mitigate VTE risks in these highly active individuals and options to deal with bleeding risks from anticoagulation during injury-prone sporting activities.


Improved polymerization activity of Deinococcus geothermalis amylosucrase by semi-rational design: Effect of loop flexibility on the polymerization reaction.
In this study, we improved the polymerization activity of Deinococcus geothermalis amylosucrase (DGAS) via semi-rational design to support increased potential industrial applications. Structural analysis selected three amino acid residues (Pro219, Phe225, and Ala226) in loop 3 of the B domain that were considered to be related to polymerization activity. Various DGAS variants were constructed through site-saturated mutagenesis, from which two mutants (DGAS-P219Y and DGAS-A226N) with increased polymerization activity were selected by fluorescence screening. DGAS-A226N synthesized longer amylose-like polymers from sucrose than those from wild-type (WT) DGAS. A kinetic study of sucrose as a substrate showed that the ratio of polymerization to hydrolysis activity of DGAS-A226N was significantly higher than that of WT DGAS. DGAS-A226N exhibited its highest enzymatic activity at 50 °C; its half-life was 6.8 min at 60 °C, and its melting temperature was 61.16 ± 0.09 °C. Computational simulation analysis of DGAS-A226N indicated that its conformation was more compact than that of WT DGAS, possibly owing to decreased flexibility of loops 2, 3, 4, 7, and 8. Thus, conformational changes in DGAS-A226N allowed the production of longer oligosaccharides, which may support a broader range of industrial application by affording novel or improved product characteristics.


Acute pancreatitis.
In order to recognize acute pancreatitis in the setting of the acute abdomen, the surgeon must be thoroughly familiar with the numerous etiologies of the disease. No specific test is available to diagnose acute pancreatitis. CT scanning is arguably the most useful single tool, but surgical judgment is critical. Most cases of acute pancreatitis resolve spontaneously without sequelae, but the spectrum of the disease also includes highly lethal forms associated with a variety of systemic complications. Operative intervention is indicated when other, more rapidly fatal, abdominal processes cannot be reliably excluded and when local complications develop.


Factors affecting efficacy of oral trimeprazine sedation for dental procedures in children: A retrospective study.
To investigate the influence of factors such as age, gender and pre-operative behavior rating on the outcome of sedation using oral trimeprazine during dental treatment of children. Records of children who received dental treatment under sedation with oral trimeprazine between 2000 and 2007 were reviewed and the following data were obtained: age and weight of patient at the time of treatment, gender, behavior classification prior to sedation, dose of medication used, efficacy of sedation and treatment accomplished. Descriptive statistics, cross-tabulations and χ (2) analysis were done. Forty-eight sedation sessions met the inclusive criteria for children whose mean age was 4.92 (SD 1.65, range 3.0-8.0) years and mean weight was 18.23 (SD 4.82, range: 12.0-31.0) kg. Overall, 54.2% (26/48) of the sedations were rated successful, 20.8% (10/48) were partially successful and 25.0% (12/48) not successful. Younger children 3-5 years, and those with only negative pre-operative behavior rating had more successful sedation sessions than older, 6-8 years or children with definitely negative pre-operative behavior rating (X (2) = 8.165, p = .017) and (X (2) = 17.258, p = .001), respectively. Variables such as patient's age and pre-operative behavior but not gender and type of treatment could predict outcome of dental sedation using trimeprazine in children.


A rat model of HTLV-I infection: development of chronic progressive myeloneuropathy in seropositive WKAH rats and related apoptosis.
In seropositive HTLV-I carrier rats of the WKAH strain inoculated with 2 x 10(7) MT-2 cells at 3-6 months of age, chronic progressive myeloneuropathy, tentatively designated as HTLV-I-associated myelopathy (HAM) rat disease, occurred when the rats were 19-23 months old. Clinical and pathological findings were basically identical to those of seronegative HAM rats of the same strain neonatally inoculated with MT-2 cells. It appears that a high dose of MT-2 cells (10(8) cells) is more effective for the induction and acceleration of HAM rat disease. Seronegative and seropositive carriers of other strains (F344, ACI, and LEW), WKAH rats inoculated with HUT-78 (a human T cell line without HTLV-I infection), and untreated WKAH rats at comparable ages did not develop HAM rat disease, thereby indicating that development of this disease is caused by HTLV-I infection and is under strict genetic restriction of the host strain. Chronological examination of HAM rat disease induced by 10(7) MT-2 inoculation into newborn rats showed that the spinal cord lesion began to develop by 12 months of age. T cells were absent in the affected spinal cord throughout the disease process. There was morphological evidence of apoptotic death of oligodendrocytes in the affected spinal cord. Apoptosis was also confirmed by the specific nick end labeling of the nuclear fragmentation in situ, and the apoptotic oligodendrocytes confined to the demyelinating foci, and the number of apoptotic cells positively correlated with severity of the spinal cord lesion.(ABSTRACT TRUNCATED AT 250 WORDS)


Phacoemulsification and intraocular lens implantation for angle closure glaucoma after the relief of pupillary block.
We studied the surgical outcomes of phacoemulsification and intraocular lens (IOL) implantation for cataract and/or uncontrolled intraocular pressure (IOP) in eyes with angle closure glaucoma. Department of Ophthalmology, National Nagasaki Medical Center, Nagasaki, Japan. Eighteen eyes from 15 patients after laser iridotomy (17 eyes) or peripheral iridectomy (1 eye) had undergone surgery and were studied. We used an iris retractor in 7 eyes due to insufficient mydriasis and a capsular tension ring in 2 eyes due to phacodonesis during the operation. The patients were followed up for at least 6 months (13.8 +/- 7.2 months; range: 6-36 months). The mean IOP significantly decreased from 17.4 +/- 8.1 to 13.5 +/- 3.3 mm Hg at 6 months after surgery. The IOP was below 21 mm Hg in all eyes. The visual acuity was not worsened in any eyes and became better than 2 Snellen lines in 14 eyes. The corneal endothelial cell count decreased from 2,365 +/- 517 to 1,960 +/- 661/mm2 (18.3 +/- 17.2%). Phacoemulsification and IOL implantation is useful in IOP control for angle closure glaucoma after relief of pupillary block. However, we should take care of operative complications because of a shallow anterior chamber, poor mydriasis and zonular weakness.


Simulation of forced convection in a channel with nanofluid by the lattice Boltzmann method.
This paper presents a numerical study of the thermal performance of fins mounted on the bottom wall of a horizontal channel and cooled with either pure water or an Al2O3-water nanofluid. The bottom wall of the channel is heated at a constant temperature and cooled by mixed convection of laminar flow at a relatively low temperature. The results of the numerical simulation indicate that the heat transfer rate of fins is significantly affected by the Reynolds number (Re) and the thermal conductivity of the fins. The influence of the solid volume fraction on the increase of heat transfer is more noticeable at higher values of the Re.


Effect of reduced temperature on glycoprotein (Ig, HLA) processing and transport in lymphoid cells.
Secretion of Igs and surface expression of HLA antigens was examined in lymphoid cells as a function of temp. Upon reducing the temp from 37 to 20 degrees C a progressive decrease in the secretion of Ig and surface expression of HLA antigens was noted. When the status of the oligosaccharides present on these glycoproteins was examined, conversion of high-mannose [endo-beta-N-acetylglucosaminidase-(Endo H) sensitive] to complex-type (Endo H resistant) oligosaccharides diminished with decreasing temp. At no time was an accumulation of Endo H resistant glycoproteins seen intracellularly. These results show that the phenomenon observed for synthesis and intracellular transport of viral glycoproteins in epithelial cells at reduced temp, namely intracellular accumulation of viral glycoproteins carrying complex sugar moieties, does not necessarily apply to glycoprotein transport in lymphoid cells. A difference in subcellular organization of epithelial and lymphoid cells may be responsible for this discrepancy.


Simultaneous monitoring the real and imaginary parts of the analyte refractive index using liquid-core photonic bandgap Bragg fibers.
We demonstrate simultaneous monitoring of the real and imaginary parts of the liquid analyte refractive index by using a hollow-core Bragg fiber. We apply this two-channel fiber sensor to monitor concentrations of various commercial cooling oils. The sensor operates using spectral monitoring of the fiber bandgap center wavelength, as well as monitoring of the fiber transmission amplitude at mid-bandgap position. The sensitivity of the fiber sensor to changes in the real part of the core refractive index is found to be 1460nm/Refractive index unit (RIU). By using spectral modality and effective medium theory, we determine the concentrations of the two commercial fluids from the measured refractive indices with an accuracy of ~0.57% for both low- and high-loss oils. Moreover, using an amplitude-based detection modality allows determination of the oil concentration with accuracy of ~1.64% for low-loss oils and ~2.81% for the high-loss oils.


Statistical analysis of fluctuations in red grouse bag data.
Serial correlations were performed on grouse bag data spanning periods of 40 to 100 years and taken from throughout the British Isles, to test for the presence of cyclical fluctuations. Six of the fourteen series analysed showed clear evidence of a 6-year cycle in bag numbers. Four of the remaining series produced correlograms suggestive of cycles of other lengths. Only four of the series analysed showed no evidence of cyclicity.


2',6'-Dimethylazobenzene as an efficient and thermo-stable photo-regulator for the photoregulation of DNA hybridization.
The introduction of methyl groups into two ortho positions (2' and 6' positions) of the same benzene ring in an azobenzene remarkably raised both its photoregulation ability and the thermal stability of the cis-form.


Computed tomography of bladder malakoplakia.
The CT findings in a case of malakoplakia involving the bladder and retroperitoneum are described.


Cooperative interaction between Cra and Fnr in the regulation of the cydAB operon of Escherichia coli.
In vivo and in vitro experiments are reported demonstrating that the catabolite repressor-activator (Cra) protein (formerly designated FruR) regulates expression of the cydAB operon of Escherichia coli encoding cytochrome d oxidase. The Fnr protein is required for Cra-mediated transcriptional control, but the ArcA protein antagonizes the response to Cra. The results establish that Fnr, ArcA, and Cra exert their effects in an interdependent fashion.


Influence of prismatic effect due to decentration of optical center in ophthalmic lens.
Induced prismatic effects due to poor fitting spectacle frames is a common problem, seen in most of the spectacle wearers and this improper fitting is often due to optical center demarcation on lenses and this error causes asthenopic symptoms and diplopia. However, these errors are most common in developing countries due to lack of awareness, hence a standardized regulation is required. The current study aimed to estimate the amount of prismatic effect that is induced due to the decentration of an optical center in ophthalmic lens. A quantitative cross-sectional study was conducted in single vision spectacle wearers (N = 120) with a mean age of 25 ± 5 years. The pupillometric evaluation was performed to mark the pupil center on the spectacle lens. A lensometry evaluation was done to mark the optic center of the spectacle lens. A comparison was made to note whether the optic center is aligned with pupillary center. Objective assessment was performed through Prentice's rule (P = cF) and subjective symptoms were assessed through a validated visual comfort questionnaire. In this sample, around 57% of the individual with single vision glasses were not looking through the optic center and experiencing induced prismatic effect of -0.7 to 0.6 prism diopter, with mean decentration of 3.5 mm. Forty percent of the individuals with misaligned optic center showed asthenopic symptoms and visual discomfort. Optometrist should check quality of dispensing and visual performance before handing over the newly dispensed glasses to the patients.


Mortality patterns in a population living near a copper smelter.
An attempt to investigate the effects of pollution by a copper smelter on an adjacent community was carried out by studying the mortality patterns in Rouyn-Noranda, Province of Quebec, compared to the mortality in Val d'Or (a control community of the same area) and the whole province, during the period 1965-1974. The study shows, in Rouyn-Noranda, an excess of deaths by lung cancer, chronic respiratory diseases, and diseases of the digestive system among men and this excess remains even after adjustment for occupational exposure and could not be attributed to smoking habits either. Among women, deaths by endocrine and metabolic diseases and chronic respiratory diseases are in excess in Rouyn-Noranda.


Thoracic and abdominal aortic alterations in dogs affected with systemic hypertension.
Aortic remodeling is the consequence of untreated systemic hypertension along with aortic dilatation as a marker for target organ damage in human literature. Therefore, the present study was planned to detect the changes in aorta at the level of aortic root via echocardiography, thoracic descending aorta via radiography and abdominal aorta via ultrasonography in healthy (n = 46), diseased normotensive (n = 20) and systemically hypertensive dogs (n = 60). The aortic root dimensions were measured at the level of aortic annulus, sinus of valsalva, sino-tubular junction and proximal ascending aorta via left ventricular outflow tract view of echocardiography. The thoracic descending aorta was subjectively assessed for any disparity in size and shape of aorta via lateral and dorso-ventral view of chest radiography. The abdominal aorta was assessed via left and right paralumbar window for calculating the aortic elasticity along with aortic and caudal venacaval dimensions to calculate the aortic-caval ratio. The aortic root measurements were dilated (p < 0.001) in systemically hypertensive dogs with a positive correlation (p < 0.001) with systolic blood pressure (BP). Thoracic descending aorta was also (p < 0.05) altered in the size and shape (undulation) of systemically hypertensive dogs. Abdominal aorta was markedly stiffened with reduced elasticity (p < 0.05) along with dilatation (p < 0.01) in hypertensive dogs. Also, there was a positive correlation (p < 0.001) of aortic diameters and aortic-caval ratio and negative correlation (p < 0.001) of aortic elasticity with systolic BP. Therefore, it was concluded that aorta could be considered as an important target organ damage of systemic hypertension in dogs.


Virucidal activity of oral, hand, and surface disinfectants against respiratory syncytial virus.
Respiratory syncytial virus (RSV) is known as a major cause of respiratory tract infection in adults and children. Human-to-human transmission occurs via droplets as well as direct and indirect contact (e.g. contaminated surfaces or hands of medical staff). Therefore, applicable hygiene measures and knowledge about viral inactivation are of utmost importance. To elucidate the disinfection profile of RSV. The study evaluated the virucidal efficacy of oral rinses specifically designed for children, World Health Organization (WHO)-recommended hand-rub formulations, and ethanol, as well as 2-propanol against RSV in a quantitative suspension test (EN14476). The stability of RSV on stainless steel discs was assessed and its inactivation by different surface disinfectants (EN16777) investigated. All tested oral rinses except one reduced infectious viral titres to the lower limit of quantification. The two WHO-recommended hand-rub formulations as well as 30% ethanol and 2-propanol completely abolished the detection of infectious virus. Infectious RSV was recovered after several days on stainless steel discs. However, RSV was efficiently inactivated by all tested surface disinfectants based on alcohol, aldehyde, or hydrogen peroxide. Oral rinses, all tested hand-rub formulations as well as surface inactivation reagents were sufficient for RSV inactivation in vitro.


The effects of several diphosphonates on murine bone marrow proliferation.
Six diphosphonates were examined for their ability to alter proliferative responses of mouse bone marrow cells to recombinant human M-CSF and recombinant murine GM-CSF. Risedronate ([2-(3-pyridinyl)-ethylidene] hydroxy bisphosphonic acid) added to in vitro cultures at 10 microM, suppressed the response to M-CSF by 58%, but had no significant effect on GM-CSF-induced proliferation. Ethane-1-hydroxy-1,1-bisphosphonic acid (EHDP), dichloromethylene bisphosphonic acid (Cl2MBP), 3-amino-1-hydroxy-propylidene-1,1-bisphosphonic acid (APD), (4-chlorophenyl)-thiomethylene bisphosphonic acid (tiludronate) and (cycloheptylamino)-methylene bisphosphonic acid (YM-175) had no significant effect. Treatment of mice for 5 or 14 days with 200 mg/kg/day p.o., Cl2MBP or 3 mg/kg/day p.o. of risedronate failed to inhibit M-CSF- or GM-CSF-induced proliferation by recovered bone marrow cells. Addition of Cl2MBP or risedronate in vitro to these cells did not reveal any change in sensitivity to CSFs as a result of exposure to diphosphonate in vivo.


Sickle cell anaemia: diagnosis and care in a Nigerian health centre.
A study of 156 cases of SS and SC disease diagnosed at Igbo-Ora between 1962 and 1975 is described. In 1971 haemoglobin electrophoresis was introduced for all previously untested patients with a PCV of less than 30 and/or a clinical suspicion of SS or SC. Following this, the total known cases of SS and SC disease rose from nine to 156 in four years. The new cases diagnosed within one year of birth rose from zero before 1971 to 10 in 1974. This is 25% of all expected cases. The percentage of cases diagnosed within one calendar year of detecting anaemia (PCV less than 30) rose from 0 to 94%. It is concluded that haemoglobin electrophoresis is of great value in improving early diagnosis in peripheral clinics. Ways of further improving the early diagnosis and management of SS and SC disease in peripheral clinics is discussed.


Characterization of phospholipase A activity of beta1-bungarotoxin from Bungarus multicinctus venom. II. Identification of the histidine residue of beta1-bungarotoxin modified by p-bromophenacyl bromide.
beta1-Bungarotoxin modified with p-bromophenacyl bromide (BPB) was reduced and carboxymethylated, and the resulting two constituent RCM-polypeptide chains (the RCM-A and B chains) were separated. The RCM-A chain was found to be modified by BPB by measuring its UV absorption spectrum and was shown to have lost one histidine residue by analyzing its amino acid composition. To determine the location of the modified histidine residue in the A chain of the toxin, the RCM-A chain was digested with TPCK-trypsin, and the resulting peptides were fractionated by gel filtration followed by DEAE-cellulose chromatography. The modified residue was finally identified as histidine-48 in the A chain by Edman degradation and from the amino acid composition of the BPB-modified peptide. The amino acid sequence around the modified histidine residue in the A chain is highly homologous with those of porcine pancreas phospholipase A2 and presynaptic toxin, notexin. We conclude that histidine-48 in the A chain participates in the phospholipase A activity of beta1-bungarotoxin.


[Acute ethanol intoxication among children and adolescents in Hamburg, Germany].
By using an anonymous postcard reporting system, data of n=358 children, adolescents, and young adults who were treated in 26 emergency departments because of acute alcohol intoxication were collected. The aim of this study was to estimate the prevalence of acute alcohol intoxications in Hamburg, compare these data with the official hospital diagnosis register, and analyze the circumstances that led to the intoxication. A total of 358 cases were reported by the postcard system. Age ranged from 11-21 years, with 64.5% being 14-17 years old. Data were collected in the municipal area of Hamburg during the calendar year of 2008. The percentage of female patients was 65.6% in the age group from 11-17 years and decreased in the age group of patients being 18 years and older. A vast majority of patients were admitted by ambulance and were reported as being a"first offender". On average, male patients showed a higher level of blood alcohol when being admitted (2.02 ‰) than female patients (1.76 ‰). The older the age group, the higher the blood alcohol level. Among drinking circumstances, the situation"drank together with friends" was most frequently reported. In comparison with the official hospital diagnosis register, prevalence was 31.6% higher. This could mean that the prevalence reported in the official hospital diagnosis register is an underestimation of the actual case numbers.


Design, synthesis, and anticancer evaluation of benzophenone derivatives bearing naphthalene moiety as novel tubulin polymerization inhibitors.
A series of benzophenone derivatives bearing naphthalene moiety were designed, synthesized, characterized by 1H NMR, 13C NMR, and HRMS and evaluated for their antiproliferative activity against human breast cancer cell line (MCF-7). Most of the tested derivatives showed good to moderate cytotoxicity against MCF-7 cell line. Among them, compound 4u (IC50 = 1.47 ± 0.14 μM) was found to be the most active compound, which is more active than the standard drug cisplatin (IC50 = 15.24 ± 1.27 μM). In vitro tubulin polymerization inhibition assay, EBI competition assay, cell cycle analysis, and cell apoptosis assay identified that compound 4u was a new tubulin polymerization inhibitor by targeting the colchicine binding site. Besides, molecular docking study showed that compound 4u has high binding affinities with the colchicine binding site of tubulin through hydrogen bond, cation-π, and hydrophobic interaction.


Disseminated fusariosis and hematologic malignancies, a still devastating association. Report of three new cases.
Fungi of the genus Fusarium are primarily plant pathogens and saprobes that produce disseminated infections in immunologically deficient humans. After aspergillosis, disseminated fusariosis is the second most common cause of invasive infection by filamentous fungi in patients with hematologic malignancies or those undergoing transplants of hematopoietic progenitors. Disseminated fusariosis (DF) is considered an extremely rare infection and has reached a stable incidence rate, but its high mortality rate and the lack of an optimal management protocol have raised increasing interest in this mycosis. We present three cases of DF produced by Fusarium oxysporum species complex, Fusarium solani species complex and the highly unusual Fusarium dimerum in patients with advanced hematological malignancies diagnosed in our hospital between 2007 and 2011. The species level identification of the Fusarium isolates was established by sequencing their TEF1 gene. The isolates showed low susceptibility to most of the antifungal agents analyzed, except that observed for F. dimerum to amphotericin B (AmB) and terbinafine, and F. oxysporum species complex to AmB. Interestingly, the strain of F. solani species complex exhibited high MIC values for AmB and voriconazole, notwithstanding these drugs were used for treatment with good results. Other relevant aspects to be considered in the treatment of DF are surgically cleaning foci of infection, withdrawing presumably contaminated catheters and recovery from neutropenia. The prevention of infection in colonized patients, the maintenance of a high level of diagnostic suspicion for early diagnosis, and the combined, vigorous and prolonged use of L-AmB and voriconazole are essential to decrease the mortality rate of this devastating infection.


Pseudaptinus (Thalpius) nobilis Liebke, new to the United States, and a key to the species of subgenus Thalpius LeConte in North America, including Mexico (Coleoptera, Carabidae, Zuphiini).
The Mexican carabid species Pseudaptinus (Thalpius) nobilis Liebke is documented from the United States for the first time based on two specimens captured in southeastern Texas. A new taxonomic key distinguishes the 10 members of subgenus Thalpius known in North America, including Mexico. Pseudaptinus (Thalpius) dorsalis, which is found to be highly variable in its dorsal coloration, is compared to similar Pseudaptinus (Thalpius) hoegei. Geographic ranges are extended for several species.


Multifocal early gastric cancer in a patient with atrophic gastritis and pernicious anemia.
Pernicious anemia (PA) caused by vitamin B12 deficiency is associated with Autoimmune Metaplastic Atrophic Gastritis (AMAG). Patients with AMAG have threefold risk of the development of gastric cancer. We describe a case of a 66 year old man with a history of PA and atrophic antral-corpus gastritis. After endoscopic and chromoendoscopic evaluation the patient was treated with subtotal gastrectomy plus D2 lymphadenectomy. The tumor was diagnosed as Stage Ia; pT1a pN0 pM0 G2 with multiple foci of high grade dysplasia and intramucosal adenocarcinoma. Multifocal Early Gastric Cancer can be a problem for minimally invasive treatment such as endoscopic excision. Surgical management where it is not possible Endoscopic Mucosal Resection or Submucosal Resection (EMR/ESD) should include D1 or more type of lymphadenectomy because of the risk of nodes metastases. The chromoendoscopic evaluation may be helpful in the preoperative work-up and during the follow-up period. Multidisciplinary approach is very important to reduce the under-treatment risk in multifocal early gastric cancer. Further studies will be needed to evaluate the safety of Subtotal vs Total Gastrectomy in this kind of disease.


Long-term redox conditions in a landfill-leachate-contaminated groundwater.
Indicators of redox conditions; oxygen, sulphate, nitrate, ammonium, iron and manganese, and in addition, bicarbonate and total organic carbon were studied in groundwater samples contaminated by leachate emanating from Revdalen Landfill (Norway). Based on these variables, the study aimed to deduce the redox conditions in the aquifer. Literature on landfill leachate contamination of confined aquifers is scarce and to the best of our knowledge, this study, which describes long-term analysis of redox chemistry, is the first of its kind in such an environment. Groundwater samples were monitored for a period of 24 years, enabling us to describe redox conditions on both short-term and long-term bases. Levels of measured parameters in the contaminated aquifer varied spatially and with time, but were generally elevated except oxygen; pH (4.9-8.8), oxygen (0-11.3 mg/L), sulphate (0-28 mg/L), nitrate (0-16 mg N/L), ammonium (0.02-40 mg/L), iron (0-99 mg/L), manganese (0.06-16 mg/L), bicarbonate (22-616 mg/L) and total organic carbon (1.3-47 mg/L). From the result, levels of iron, manganese, nitrate and ammonium violated the Norwegian drinking water norms. However, iron, ammonium, total organic carbon and bicarbonate showed strong attenuation along the groundwater flow path. By contrast, oxygen, nitrate and sulphate increased farther out in the plume. The redox conditions that developed in the aquifer were similar to those previously reported for phreatic aquifers, structuring by proximity to the landfill as sulphate-reducing, iron-reducing, manganese-reducing, nitrate-reducing, and finally aerobic condition. Eventually, there was an apparent breakdown of this system due to ecosystem shift in the landfill when leachable reduced ions were depleted and the landfill became aerobic. Overall, the redox framework provided remarkable attenuation to contaminants, and thus prevented potential degradation of ecological health due to the landfill leachate.


Enhancement of in vitro transcription of human c-myc correlates with the binding of phosphorylated protein factors from HeLa cell extract.
Hela cell extract overphosphorylated with endogenous protein kinases was used for in vitro transcription of human c-myc DNA. The activation of transcription initiated from P1, P1a and P2 cap-sites was observed. Three phosphoproteins of 70, 35 and 23 kDa are found, whose binding to DNA correlates with activation of c-myc transcription. Sites of binding of these proteins to DNA are located.


Components of the kallikrein-kinin system in urine.
The excretion of kallikrein in urine varies, but the pathophysiologic implications are not clear. To help clarify the role of the urinary kallikrein-kinin system, we have begun to define components of the system as they occur in urine. To minimize artifacts which may arise through extensive purification procedures, we studied urinary protein concentrates prepared by ultrafiltration. The concentrates were separated by chromatography on Sephacryl. Urine contains abundant kininase activity, but in strongly inhibited forms. Kininase II is separable into at least two forms. Another major kininase can hydrolyze benzoyl-Pro-Phe-Arg and is inhibited by arginine but not by BPP9a or SQ 14,225. Its molecular weight is approximately 63,000. A third kininase, not inhibited by BPP9a, is excluded from Sephacryl. Human urine appears to contain only one kallikrein-like enzyme (MW 45,000). In addition, urine contains a protein (MW approximately 80,000) which reacts with trypsin to release bradykinin and which inhibits the hydrolysis of Pro-Phe-Arg-[3H]anilide by urinary kallikrein. Thus, in addition to kallikrein and kinins, urine contains kininogen and at least three kininase enzymes. Urinary ultrafiltrate contains an inhibitory substance (approximately MW 400).


Phenotypic characterization of resident macrophages in submandibular salivary glands of normal and isoproterenol-treated rats.
Macrophages exert a major effect in the stimulation of lymphocytes and the modulation of immunological responses. To determine the presence and phenotypic distribution of the resident cells of the mononuclear phagocyte system in submandibular glands, frozen sections were prepared from five normal rats, and from six rats treated with 20 mg/kg isoproterenol/day for 10 days. A panel of six monoclonal antibodies was used to identify membrane markers associated primarily with circulatory monocytes (ED1), mature tissue macrophages (ED2), lymphoid macrophages (ED3), Ia antigen (OX6), CD5-positive T lymphocytes (OX19) and rat B lymphocytes (OX33). Cells identified by each monoclonal antibody were quantified by averaging the number of positive cells in 10 consecutive random high-power fields. ED2 cells (165 cells/field) were predominant in normal rat submandibular gland, followed by lower numbers of OX6-positive cells (18 cells/field). Cells positive for the remaining markers were also present in smaller amounts. In submandibular glands, treatment of rats with isoproterenol resulted in an increase in ED1-positive cells (from 2 to 39 cells/field), but also in substantial decreases in the number of cells positive for the remaining cell markers. B cells were not detected in any of the submandibular glands examined. These data suggest that isoproterenol induces a mild inflammatory response within rat submandibular glands that is not observed in normal glands. This results in an increase in the relative number of infiltrating monocytes compared to the number of more mature tissue macrophages.


Regulation of ketogenesis by epinephrine and norepinephrine in the overnight-fasted, conscious dog.
The effects on ketogenesis and lipolysis of a norepinephrine (0.04 microgram/kg-min), epinephrine (0.04 microgram/kg-min), or saline infusion were examined in the overnight-fasted, conscious dog. Plasma insulin and glucagon levels were maintained constant by means of a somatostatin infusion (0.8 microgram/kg-min) and intraportal replacement infusions of insulin and glucagon. In saline-infused dogs, plasma epinephrine (62 +/- 8 pg/ml), norepinephrine (92 +/- 29 pg/ml), blood glycerol (87 +/- 10 microM), and plasma nonesterified fatty acid (NEFA) (0.82 +/- 0.17 mM) levels did not change. Total blood ketone body levels tended to rise (62 +/- 10 to 83 +/- 11 microM) by 3 h as did total ketone body production (1.5 +/- 0.4 to 2.2 +/- 0.4 mumol/kg-min) over the same time interval. Norepinephrine infusion to produce plasma levels of 447 +/- 86 pg/ml caused a sustained 50% rise in glycerol levels (66 +/- 17 to 99 +/- 15 mumol/L, P less than 0.05) and 53% rise in nonesterified fatty acids (0.53 +/- 0.07 to 0.81 +/- 0.15 mumol/L, P less than 0.05). Total ketone body levels rose by 43% (51 +/- 8 to 73 +/- 10 mumol/L) and ketone body production rose by a similar proportion (1.5 +/- 0.2 to 2.2 +/- 0.3 mumol/kg-min), changes that did not differ significantly from control animals. A similar increment in plasma epinephrine levels (75 +/- 15 to 475 +/- 60 pg/ml) caused glycerol levels to rise by 82% (105 +/- 23 to 191 +/- 26 mumol/L) in 30 min, but this rise was not sustained and the level fell to 146 +/- 14 mumol/L by 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)


Patient and Provider Perceptions About Communication After Bariatric Surgery: A Qualitative Analysis.
Communication between patients and providers can strongly influence patient behavior after surgery. The objective of this study was to assess patient and provider perceptions of how communication affected weight-related behaviors after bariatric surgery. Semistructured interviews with bariatric surgery patients and providers were conducted from April-November 2020. Patients who had Medicaid within 3 y of surgery were defined as socioeconomically disadvantaged. Interview guides were derived from Andersen's Behavioral Model of Health Services and Torain's Framework for Surgical Disparities. Participants described postoperative experiences regarding diet, physical activity, and follow-up care. A codebook was developed deductively based on the two theories. Directed content analysis identified themes pertaining to patient-provider communication. Forty-five participants were interviewed, including 24 patients (83% female; 79% White), six primary care providers, four health psychologists, five registered dietitians, and six bariatric surgeons. Four themes regarding communication emerged: (1) Patients experiencing weight regain did not want to follow-up with providers to discuss their weight; (2) Patients from socioeconomically disadvantaged backgrounds had less trust and required more rapport-building from providers to enhance trust; (3) Patients felt that providers did not get to know them personally, which was perceived as a lack of personalized communication; and (4) Providers often changed their language to be simpler, so patients could understand them. Patient-provider communication after bariatric surgery is essential, but perceptions about the elements of communication differ between patients and providers. Reassuring patients who have attained less weight loss than expected and establishing trust with socioeconomically vulnerable patients could strengthen care after bariatric surgery.


Evaluation of patient effective dose from sentinel lymph node lymphoscintigraphy in breast cancer: a phantom study with SPECT/CT and ICRP-103 recommendations.
To evaluate the effective dose delivered to patients undergoing sentinel lymph node (SLN) lymphoscintigraphy by taking into account both the transmission dose using the CT component of a SPECT/CT system and the (99m)Tc internal emission dose. An adult female humanoid phantom and a set of thermoluminescent dosimeters were used in dose measurement from the CT transmission irradiation. The choice of measurement organs in the humanoid was guided by the recommendations described in the International Commission on Radiological Protection report number 103 (ICRP-103). The effective doses due to (99m)Tc internal emission source were re-calculated from measurement data reported in our previous study on the same subject with the use of tissue weighting factors of ICRP-103. CT transmission dose is the main contribution to the patient total effective dose for both 1-day and 2-day lymphoscintigraphy protocols and for different surgical procedures. Patients undergoing SLN lymphoscintigraphy receive about the same amount of total effective dose of about 3mSv for both 1-day and 2-day protocol, regardless of whether the tissues containing radioactivity would be excised at surgery or not. Although the total effective dose from using SPECT/CT is equivalent to the annual natural background radiation of about 3mSv, nuclear medicine physicians should be aware of the increase in effective dose for SLN lymphoscintigraphy using hybrid imaging technique of SPECT/CT when compared to conventional planar (57)Co flood source for transmission scan. Results from the current study provide update information in radiation exposure to patients undergoing SLN lymphoscintigraphy with the use of SPECT/CT.


Cell proliferation is influenced by bulbectomy and normalized by imipramine treatment in a region-specific manner.
Growing evidence indicates that alterations of neuroplasticity may contribute to the pathophysiology of depression. In contrast, various antidepressants increase adult hippocampal neurogenesis and block the effects of stress. These findings result in the 'neurogenesis hypothesis of depression'. The present study seeks to determine out whether cell proliferation is altered in the hippocampus, subventricular zone (SVZ), and basolateral amygdala of adult rats exposed to bilateral olfactory bulbectomy, another established model of depression and, if so, how imipramine effects bulbectomy-induced changes of cell genesis. Bulbectomy results in a significant reduction of cell proliferation in the hippocampus and SVZ, an effect that is normalized by subchronic doses of imipramine. Moreover, an increase in cell genesis in the basolateral amygdala, which is not affected by imipramine, is demonstrated. TUNEL staining indicates an enhanced apoptosis after bulbectomy in the SVZ that cannot be reduced by imipramine. Cell death rates in the hippocampus and amygdala are not affected by bulbectomy. The opposing effects of bulbectomy and imipramine treatment in the hippocampus and amygdala demonstrate that these structures of the limbic system, both integrated in emotional processing, react quite differently with regard to neuroplasticity. Further to this, we discuss a possible link between the pathogenesis of depression and changed neuronal plasticity in the SVZ.


Test-dependent changes in nociception after administration of the putative serotonin antagonist metitepin in mice.
Intraperitoneal administration of the putative serotonin receptor antagonist metitepin (0.06-1.0 mg/kg) in mice induced dose-dependent antinociception in the increasing temperature hot-plate test and the formalin test, but elicited hyperalgesia in the tail-flick test. Reduced motor activity was observed after injection of the largest dose of metitepin, but did not influence the behavioural responses in the tests. Selective lesions of ascending serotonergic pathways induced by administration of the neurotoxin p-chloroamphetamine 5 and 6 days before testing (40 mg/kg each day) did not directly affect the responsiveness in any of the tests but enhanced the metitepin-induced antinociception in the hot-plate and formalin tests. The hyperalgesia in the tail-flick test was not affected by the lesions. The results suggest that metitepin may alter nociception in mice by exhibiting both agonist and antagonist properties on central serotonergic receptors.


Rates, Risks, and Time to Fracture in Patients Undergoing Laparoscopic Vertical Sleeve Gastrectomy versus Roux-en-Y Gastric Bypass.
To assess the rates, risks, and time to fracture in patients undergoing laparoscopic vertical sleeve gastrectomy (VSG) versus those undergoing Roux-en-Y gastric bypass (RYGB). Metabolic and bariatric surgery has been implicated in significant bone loss and may increase fracture risk. Preoperative patient characteristics that might impact fracture risk and the time to fractures have not been established. Furthermore, the patient characteristics that might impact fracture risk and the time to fractures by surgical approach are unknown. This population-based retrospective cohort analysis used Humana claims data from January 1, 2007 to March 31, 2017, and included 4073 patients undergoing laparoscopic RYGB and VSG as a first surgical intervention for weight loss. The primary outcomes were the incidence of fractures (Humeral, Radial or Ulnar, Pelvic, Hip, and Vertebral) within 48 months after laparoscopic VSG versus RYGB and days to these fractures. An analysis of total fractures (odds ratio [OR] 0.53; 95% confidence interval [CI], 0.38-0.73), vertebral fractures (OR 0.61; 95% CI, 0.38-0.99), hip fractures (OR 0.36; 95% CI, 0.15-0.84), and humeral fractures (OR 0.44; 95% CI, 0.22-0.90) demonstrated a reduction in fracture risk in patients undergoing VSG versus RYGB. Furthermore, postmenopausal status was independently associated with increased odds of total fractures and hip fractures (OR 2.18; 95% CI, 1.06-4.50; OR 5.83; 95% CI, 1.16-29.27; respectively). Likewise, osteoporosis at the time of surgery was associated with increased odds of total fractures (OR 1.61; 95% CI, 1.09-2.37), vertebral fractures (OR 2.01; 95% CI, 1.19-3.39), and hip fractures (OR 2.38; 95% CI, 1.19-4.77). Except for a significantly decreased odds of vertebral fractures in osteoporotic patients undergoing VSG versus RYGB (OR 0.41; 95% CI, 0.18-0.95), osteoporotic or postmenopausal status at the time of surgery was not found to increase odds of fracture depending on surgical intervention. However, time to fracture (total) and for all site-specific fractures, except for pelvic fractures, was significantly reduced in postmenopausal women undergoing RYGB versus VSG. Time to fracture (total) and for all site-specific fractures except pelvic and radial or ulnar fractures was significantly reduced in osteoporotic patients undergoing RYGB versus VSG. Though bariatric surgery is associated with several health-related benefits, increased fracture risk is an important factor to discuss with patients undergoing bariatric surgery. Bariatric surgery strategy, RYGB versus VSG, carries a differential risk of fracture, with RYGB carrying a higher risk of fracture and decreased time to fracture. Furthermore, patients who are postmenopausal or osteoporotic at the time of surgery carry an increased risk of total fractures, independent of bariatric surgery strategy. Being mindful of patient-specific fracture risk after bariatric surgery may help anticipate, identify, and prevent fractures.


Highly regio-, chemo- and diastereoselective synthesis of oxa-bridged spirocycles: a novel observation of reverse selectivity.
The reverse regio- and diastereoselectivities are observed between the reactions involving 5- and 6-membered-ring cyclic carbonyl ylide dipoles with alpha-methylene ketones. A mild catalytic route to synthesize spirocyclic systems with high regio-, chemo- and diastereoselectivities is described.


Serum proteins in prostatic cancer. V. Alterations in immunoglobulins and clinical responsiveness following cryoprostatectomy.
Levels of the three major serum immunoglobulins (G, A, M) were quantitated prior to and up to 2 weeks following each of two independent freezing treatments of the primary prostatic tumour in 4 patients undergoing remission or healing of their metastatic lesions. Cyclical alterations in the level of IgG accompanied by moderate alterations in the level of IgA were noted post-operatively. Most striking was an almost twofold increase in the level of IgM in 3 of the 4 patients evaluated. While possibly a non-specific association, observations of increased levels of IgG and IgM following cryotherapy may represent an active immunologic response by the host to prostatic tissue (tumour?)-specific or tumour-associated antigen(s) in the form of 'blocking' factor(s) or cytotoxic antibody.


Beneficial effects of candesartan, an angiotensin-blocking agent, on compensated alcoholic liver fibrosis - a randomized open-label controlled study.
Recent studies have shown that the renin-angiotensin system is implicated in hepatic fibrogenesis in vitro and in vivo. However, no study was done in humans with alcoholic liver disease. To investigate the antifibrotic effect of angiotensin II type 1 receptor (AT1-R) blocking agents (ARB) in patients with alcoholic liver disease. The primary outcome was improvement in patients' histological features. Eighty-five patients with compensated alcoholic liver fibrosis (≥ F2) which was confirmed by baseline liver biopsy were randomized (intention-to-treat (ITT)) to receive either ARB, candesartan (8 mg/day) with ursodeoxycholic acid (UDCA) (600 mg/day) (n = 42) or UDCA alone (n = 43) as control for 6 months and follow-up liver biopsies were conducted. According to the Laennec fibrosis system, candesartan showed significantly higher rates of histological improvements (ITT, 33.3% vs. 11.6%, P = 0.020). In addition, the fibrosis score was significantly reduced from 3.4 ± 1.4 to 3.1 ± 1.5 (P = 0.005) in the candesartan group. Candesartan also reduced the area of fibrosis and α-smooth muscle actin positive from 11.3 ± 6.0 to 8.3 ± 4.7 and 28.7 ± 10.5 to 23.9 ± 10.3 (%), and the hydroxyproline levels (μg/g liver tissue) from 7.8 ± 2.4 to 6.3 ± 1.7 respectively (P < 0.05). In addition, the relative expression of transforming growth factor-β1(TGF-β1), collagen-1, AT1-R, tissue inhibitor of metalloproteinase 1 (TIMP-1), metalloproteinases2 (MMP2), Rac1 and p22phox by real-time RT-PCR decreased in the candesartan group (P < 0.05). Mean arterial blood pressure in the candesartan group decreased mildly but significantly (P < 0.001). No significant complications and side effects were observed during the present study. Administration of ARB in compensated alcoholic liver disease induces improvement of fibrosis in histological and quantitative measurements.


Global bibliometric meta-analytic assessment of research trends on microbial chlorine resistance in drinking water/water treatment systems.
Chlorine is the commonest and cheapest disinfectant used in drinking water and wastewater treatment at household, municipal and industrial levels. However, the uprising of microbial chlorine resistance (MCR) pose critical public health hazard concerns; because, its potentiate exposure to difficult-to-treat resistant pathogens. Therefore, this study aimed at evaluating the burden of MCR in drinking water/wastewater treatment and distribution systems (DWWTDS) via science mapping of research productivity (authors, countries, institutions), thematic conceptual framework, disciplines, research networks and associated intellectual landscape. MCR data were mined from Scopus and Web of Science based on optimized algorithms with the root key term "chlorine* resistant*'' and analysed for pre-set indicator variables. Results revealed 1127 documents from 442 journals and 1430% average growth rate (AGR) of research articles from 2017 to 2019 on MCR. Country-wise, the USA (n = 299), China (n = 119), and Japan (n = 43) ranked in the 1st, 2nd, and 3rd positions respectively, among the top participating countries in MCR research. MCR research had considerable performance in public health and sustainable concern subjects namely, Environmental Sciences & Ecology, Engineering, Microbiology, Water Resources, Biotechnology & Applied Microbiology, Food Science & Technology, Public, Environ & Occupational Health, Chemistry, Infectious Diseases, and Marine & Freshwater Biology; and with noticeable AGR in Environmental Sciences & Ecology (330%) and Infectious Diseases (130%). The study found biofilm-related thrusts (n = 90, 270% AGR) as main research hotspots on MCR. Overall, the study identified and discussed four important thematic areas of public health challenges in MCR that could promote increasing waterborne diseases due to (re)emerging pathogens, enteric viruses and dissemination in DWWTDS. In conclusion, this study provides comprehensive overview of the growing burden of MCR in DWWTDS and standout as a primer of information for researchers on MCR. It recommends direct, intentional and integrated research priorities on MCR to overcome accompanying public health and environmental threats. In addition, chlorine resistance in waterborne fungi have not received research attention. Research activities related to fungal chlorine resistance will be an invaluable future direction in DWWTDS and guide against exposure to waterborne pathogenic fungi and mycotoxins. It is unknown whether chlorine resistance can be acquired by horizontal gene transfer in microorganisms and future research should elucidate this important thrust.


MicroRNA-4656 is a prognostic factor and tumor suppressor in human pancreatic cancer through a downstream target of TrkA.
In the present study, we investigated the expression profile and functional mechanism of microRNA-4656 in human pancreatic cancer (PC). MiR-4656 expression in PC tumors was examined using a quantitative reverse transcriptase-polymerase chain reaction in 134 patients. Associations between tumorous miR-4656 expression and clinicopathological parameters of patients, as well as overall survival, were analyzed. MiR-4656 expression was also examined in PC in vitro cell lines. In Capan-1 and AsPC-1 PC cells, lentivirus-induced miR-4656 overexpression or downregulation was applied to investigate its functional regulations on PC in vitro proliferation and invasion, as well as in vivo transplant growth. The association of miR-4656 and its downstream target, the tropomyosin receptor kinase A (TrkA) gene, was investigated in both cell line and clinical pancreatic tumors. In miR-4656-overerxpressed PC cells, TrkA was overexpressed with the aim of investigating its role in miR-4656-induced functional regulation in PC. MiR-4656 was downregulated in PC. Low tumorous miR-4656 expression was associated with a poor prognosis and overall survival of patients. MiR-4656 was also found to be downregulated in PC cell lines. MiR-4656 overexpression in Capan-1 and AsPC-1 cells significantly inhibited cancer proliferation and invasion in vitro, as well as explant growth in vivo, whereas miR-4656 downregulation had no effect on cancer development. The TrkA gene was directly bound by miR-4656, and reversely expressed in PC tumors as miR-4656. TrkA overexpression reversed the inhibitory effect of miR-4656-overexpression on PC proliferation and invasion. MiR-4656 is expressed to a low extent and is a potential biomarker in PC. Overexpressing miR-4656 has tumor suppressive effects on PC development both in vitro and in vivo, likely through its downstream target of the TrkA gene.


A pseudogene homologous to mouse transplantation antigens: transplantation antigens are encoded by eight exons that correlate with protein domains.
We have isolated about 30 to 40 different BALB/c mouse sperm DNA genomic clones that hybridize to cDNA clones encoding proteins homologous to transplantation antigens. One of these clones (27.1) was selected for sequence because it was polymorphic in Southern blot analysis of the DNAs from BALB/c and CBA mice. A fragment of 5.7 kilobases of this clone was completely sequenced and found to contain a pseudogene whose sequence is highly homologous to the sequences of known transplantation antigens. Pseudogene 27.1 is split into eight exons that correlate with the structurally defined protein domains of transplantation antigens. Using Southern blot hybridization on the DNAs of different inbred mouse strains, we mapped the pseudogene to the Qa-2,3 region, a part of the Tla complex on chromosome 17 that is adjacent to the major histocompatibility complex. The Qa2,3 region encodes lymphoid differentiation antigens homologous to the transplantation antigens in size, in peptide map profiles and in their association with beta2-microglobulin. These mapping studies suggest that gene 27.1 may be a pseudogene for eigher a Qa antigen or an as yet undefined transplantation antigen. Accordingly, we may have isolate genes encoding lymphoid differentiation antigens of the Tla complex as well as those encoding transplantation antigens among the 30 to 40 different genomic clones isolated from our sperm library.


Evaluation of a machine learning capability for a clinical decision support system to enhance antimicrobial stewardship programs.
Antimicrobial stewardship programs have been shown to limit the inappropriate use of antimicrobials. Hospitals are increasingly relying on clinical decision support systems to assist in the demanding prescription reviewing process. In previous work, we have reported on an emerging clinical decision support system for antimicrobial stewardship that can learn new rules supervised by user feedback. In this paper, we report on the evaluation of this system. The evaluated system uses a knowledge base coupled with a supervised learning module that extracts classification rules for inappropriate antimicrobial prescriptions using past recommendations for dose and dosing frequency adjustments, discontinuation of therapy, early switch from intravenous to oral therapy, and redundant antimicrobial spectrum. Over five weeks, the learning module was deployed alongside the baseline system to prospectively evaluate its ability to discover rules that complement the existing knowledge base for identifying inappropriate prescriptions of piperacillin-tazobactam, a frequently used antimicrobial. The antimicrobial stewardship pharmacists reviewed 374 prescriptions, of which 209 (56% of 374) were identified as inappropriate leading to 43 recommendations to optimize prescriptions. The baseline system combined with the learning module triggered alerts in 270 prescriptions with a positive predictive value of identifying inappropriate prescriptions of 74%. Of these, 240 reviewed prescriptions were identified by the alerts of the baseline system with a positive predictive value of 82% and 105 reviewed prescriptions were identified by the alerts of the learning module with a positive predictive value of 62%. The combined system triggered alerts for all 43 recommendations, resulting in a rate of actionable alerts of 16% (43 recommendations of 270 reviewed alerts); the baseline system triggered alerts for 38 interventions, resulting in a rate of actionable alerts of 16% (38 of 240 reviewed alerts); and the learning module triggered alerts for 17 interventions, resulting in a rate of actionable alerts of 16% (17 of 105 reviewed alerts). The learning module triggered alerts for every inappropriate prescription missed by the knowledge base of the baseline system (n=5). The learning module was able to extract clinically relevant rules for multiple types of antimicrobial alerts. The learned rules were shown to extend the knowledge base of the baseline system by identifying pharmacist interventions that were missed by the baseline system. The learned rules identified inappropriate prescribing practices that were not supported by local experts and were missing from its knowledge base. However, combining the baseline system and the learning module increased the number of false positives.


Age-related changes in the human nigrostriatal dopaminergic system.
A deficiency of dopamine in the striatum may contribute to the decline in motor function associated with aging. We examined the effect of aging on the densities of the D1 and D2 dopamine receptors, their high-agonist affinity sites, and the dopamine uptake sites in postmortem human putamen (n = 32; age range, 19-88 years). With aging a steady decrease was seen in dopamine uptake sites (p less than 0.001), confirming previous morphometric and biochemical data of an age-related loss of nigrostriatal axons. In contrast, the concentrations of the D1 and D2 dopamine receptors and their high-agonist affinity sites, which are believed to represent the functionally active receptors, were not affected by the aging process. These results may have implications for the pharmacological treatment of the age-related decline in motor function.


Affective meanings of 1,469 Bengali concepts.
This article provides semantic differential ratings of 1,469 concepts in Bengali, a language spoken by about 250 million individuals in eastern India and Bangladesh. These data were collected from 20 male and 20 female Calcutta respondents who rated stimuli on three culturally universal affective dimensions: evaluation-potency-activity (EPA). This study employs pan-respondent component analyses as a means of examining the respondents' usage of the standard EPA scales. The pan-respondent component analyses indicate that some respondents used the rating scales in unexpected ways, recording their feelings about one component of concepts' EPA with ratings on a scale intended to measure a different dimension. When scores were based only on respondents who used the scales appropriately, several interesting patterns were found. For respondents of both genders, potency scores have a curvilinear relation with evaluation, such that very good and very bad concepts are mostly seen as very potent, whereas evaluatively neutral concepts are seen as somewhat impotent or just slightly potent. A moderate linear correlation exists between activity and evaluation, and a modest positive relation exists between potency and activity. Gender correlations are high on evaluation, .93, but much lower for potency scores, with a correlation of .55, and even lower for activity, .30. In this article we examine several explanations for why scales denoting potency and activity were reinterpreted as indicating goodness by certain respondents, and consider the matter of including data collected from respondents who used scales in this way.


An overview of lung transplantation in Korea.
Lung transplantation (LTx) is the only option for end-stage lung disease refractory to medical treatment. The program was slow to start in Korea; the first LTx was performed in July 1996. By October 2007, 25 lung and 7 heart-lung transplantations have been performed at 5 institutes, with the majority being performed at one center. The aim of this study was to improve the survival rate following LTx by analyzing the operative procedure and its complications. We performed a retrospective review of the medical records of 18 patients who underwent lung and heart-lung transplantations from July 1996 to October 2007 at a single institute. Operative mortality was excluded from the analysis of early and late complications. There were 12 males and 6 females of mean age 46.2 +/- 11.5 years (range, 25-63 years). The indications for transplantation included pulmonary emphysema (n = 6), idiopathic pulmonary fibrosis (n = 3), lymphangioleiomyomatosis (n = 3), Eisenmenger's syndrome (n = 2), bronchiectasis (n = 2), primary pulmonary hypertension (n = 1), and primary graft dysfunction after a single lung transplantation (SLT; n = 1). Operations consisted of SLTs in 9 patients, bilateral sequential single lung transplantations (BSSLTs) in 8 patients, and a heart-lung transplantation (HLT) in 1 patient. Early complications were bleeding necessitating rethoracotomy, severe reperfusion injury, seizure, prolonged airleak, chylothorax, and pulmonary artery stenosis. Late complications consisted of cytomegalovirus infection, pulmonary tuberculosis, posttransplantation lymphoproliferative disease, gastric ulcer perforation, pneumothorax, chylothorax, empyema, and aspergillosis. There were 5 operative deaths due to intraoperative bleeding (n = 1), acute graft dysfunction (n = 2), and multiorgan failure (n = 2). Excluding the operative mortality, the mean survival period was 18.5 +/- 23.7 months (range, 3-87 months). Clinical experience in recent years may have reduced complication rates and led to prolonged survival. Increasing the candidate list through better results and raising awareness of the LTx program is necessary to move forward with thoracic transplantation in Korea.


[Advances in surgical techniques and results of radical cystectomies for bladder cancer. 106 patients].
Retrospective analysis of result of radical cystectomy at Cochin Hospital. We report the results of a 106 patients series treated by radical cystectomy for bladder carcinoma after a 5-year period follow-up. The extent of the tumour invasion according to pathological analysis was: pT1 or less: 26%, pT2 and pT3a: 33%, pT3b and over: 41%. Morbidity rate was 19% with a 7.5% reintervention rate. Long term complication rate was 31%, concerning essentially ureteral stenosis. A local recurrence or distant metastasis occurred in 35% of patients. Local recurrence rate was 10.7%. Cancer specific survival rates were 88%, 81% and 42% for pT1, pT2-pT3a, and pT3b patients respectively. The present results confirm that radical cystectomy is the most effective curative treatment for invasive bladder carcinoma.


Anemia prevalence, severity and associated factors among children aged 6-71 months in rural Hunan Province, China: a community-based cross-sectional study.
In recent 10 years, with the rapid socioeconomic development and the extensive implementation of children nutrition improvement projects, the previous epidemiological data cannot reflect the actual level of anemia among children in China, especially in rural areas. Therefore, this study analyzed the prevalence, severity and associated factors of anemia among children aged 6-71 months in rural Hunan Province. A community-based cross-sectional study was conducted. Through multistage stratified cluster sampling, 5229 children aged 6 to 71 months and their caregivers were randomly selected from 72 villages across 24 towns in 12 counties from rural Hunan. The demographic characteristics of children and their caregivers, feeding practice, nutritional status of children, caregivers' anemia-related feeding knowledge, and gestational conditions of mothers were acquired by using a unified questionnaire. Peripheral blood from the left-hand middle fingertip was sampled from each child, and hemoglobin concentration was measured using a HemoCue301 portable hemoglobin analyzer (Sweden). Associated factors analyses involving overall anemia and anemia severities were conducted on multivariate logistic regression models. The overall anemia prevalence was 8.8%, and the prevalence of mild, moderate and severe anemia was 6.3, 2.5 and 0.1%, respectively. Children age groups of 6-11 months, 12-23 months and 36-47 months, exclusive breast-feeding within 6 months after birth, and maternal moderate/severe anemia were significantly associated with an increased risk of overall anemia in children. Children age groups of 6-11 months and 12-23 months were significantly associated with an increased risk of mild anemia in children. Children age groups of 6-11 months, 12-23 months and 36-47 months, low caregivers' anemia-related feeding knowledge level, and maternal moderate/severe anemia were significantly associated with an increased risk of moderate/severe anemia in children. Children who underwent regular physical examination were less likely to have moderate/severe anemia. The common protective factor for overall, mild and moderate/severe anemia in children was high family income. The anemia status of preschool children in rural Hunan Province was a mild public health problem and associated with children age group, feeding practice, regular physical examination, family income, caregivers' anemia-related feeding knowledge level, and maternal moderate/severe anemia.