Improved non-redundant species screening panels for benchmarking the performance of new investigational antibacterial candidates against Category A and B priority pathogens.
NIAID has a programme for testing drug candidates against biodefense and emerging bacterial pathogens that uses defined strain panels consisting of standard laboratory reference strains and strains of clinical origin. The current studies were performed to assess the activity of standard-of-care drugs, determine benchmark criteria for new investigational antibacterial candidate prioritization and identify reduced non-redundant strain panels for candidate performance classification. The susceptibilities of each strain in the screening panels to 40 standard-of-care drugs and clinical drug combinations were determined by percentage growth inhibition using multiple concentrations, a method commonly used in efficient high-throughput screening efforts. The drug susceptibility of each strain was categorized based on interpretive criteria to benchmark the activity of each standard-of-care drug and drug combination, followed by confirmation of select active drugs. Exact match and clustering analyses defined focused non-redundant species and pan-species screening panels. This process revealed a broad spectrum of susceptibilities among strains in each species, with important differences between the standard laboratory reference strains and strains of clinical origin. Exact match and clustering analyses identified subsets of non-redundant strains that can more efficiently classify drug activity resulting in individual species screening panels, a pan-species screening panel and a pan-species maximum resistance panel. This study resulted in improved non-redundant species screening panels for benchmarking the performance of new investigational antibacterial candidates with the greatest potential for efficacy against clinically relevant Category A and B priority and emerging pathogens.


Molecular characterization of enterococci harboring genotype and phenotype incongruence related to glycopeptide resistance isolated in Brazilian hospitals.
Three Enterococcus faecalis and one Enterococcus faecium strains were characterized by plasmid profile, pulsed-field gel electrophoresis (PFGE) and determination of antimicrobial minimal inhibitory concentrations. VanA elements were characterized by Long PCR, overlapping PCR and DNA sequencing. Enterococcal strains showed resistance to vancomycin and harbored the vanA gene, and three these were teicoplanin susceptible while one showed intermediate resistance to teicoplanin. Two E. faecalis strains showed indistinguishable PFGE profile while the third was unrelated. E. faecalis strains showed a deletion in the right terminal region of the Tn1546-like element. The E. faecium strain showed an insertion element in the vanXY intergenic region. Mutations in VanA elements were not found. Rearrangements in the VanA element could be responsible for incongruities in genotype and phenotype in these strains.


Silicone implant incompatibility syndrome (SIIS) in a 57-year-old woman with unilateral silicone breast implant.
Since the 1960s, silicone implants have been used for breast augmentations, both cosmetically and in reconstructive surgery. Tissue exposed to silicone can react with multiple adverse advents. Autoimmune/inflammatory syndrome induced by adjuvants due to silicone exposure from ruptured silicone implants can lead to different interstitial lung manifestations predominantly with granuloma evolvement, leading to the so-called silicone implant incompatibility syndrome (SIIS). This case describes a 57-year-old woman with multiple lung infiltrations and a left-sided breast implant. The implant had been replaced twice, once due to implant rupture 36 years ago. The nodular infiltrates could not be related to infection, malignancy, interstitial lung disease, vasculitis or connective tissue disorder, and it was concluded that the nodular infiltrations were of inflammatory origin due to an autoimmune response secondary to the silicone implants (SIIS). After explantation, the patient's symptoms subsided and her physical condition has remarkably improved.


Elevations of serum cancer biomarkers correlate with severity of COVID-19.
In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 vs 46.5 ± 14.7 pmol/L; P < .001), cytokeratin-19 fragment (CYFRA21-1) (2.2 ± 0.9 vs 1.9 ± 0.8 μg/L; P < .001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 vs 2.1 ± 1.2 μg/L; P < .001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 vs 10.5 ± 4.6 μg/L; P < .001), and 153 (14.4 ± 8.9 vs 10.1 ± 4.4 μg/L; P < .001) in COVID-19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21-1, and CA125: P < .001; CEA and CA153: P < .01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID-19 as compared with mild and severe cases and normal controls (P < .01). There were positive associations between levels of C-reactive protein and levels of HE4 (R = .631; P < .001), CYFRA21-1 (R = .431; P < .001), CEA (R = .316; P < .001), SCC (R = .351; P < .001), CA153 (R = .359; P < .001) and CA125 (R = .223; P = .031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19.


Iododeoxyuridine radiosensitization of human glioblastoma cells exposed to acute and chronic gamma irradiation: mechanistic implications and clinical relevance.
Iododeoxyuridine (IdUrd) is a recognized sensitizer of sparsely and some densely ionizing radiations. The mechanism of sensitization remains uncertain. Sensitization is likely to involve increased production of DNA damage and/or inhibition of DNA damage repair. To test these possibilities, we have characterized acute and chronic radiosensitization, and the sublethal damage repair capacity of two human glioblastoma cell lines, with or without clinically relevant concentrations of IdUrd. Exponentially growing human glioblastoma cell lines, G18 and U251, were irradiated with acute (1.4 Gy/min) and chronic (20, 40, and 80 cGy/hr) cobalt 60 exposures in the presence and absence of 0 to 10 microM IdUrd. Clonogenic survival was determined. Sensitizer enhancement ratios and global survival curve comparisons were determined with and without IdUrd. Repair half-times for chronic exposures with and without IdUrd were calculated. Split-dose recovery following acute fractions of 5 Gy separated by 0, 0.5, 1, 2, and 5 hours was evaluated. Following acute exposure, a sensitizer enhancement ratio at 10% survival of 1.85 and 1.75 was observed at concentrations of 10 microM IdUrd for the G18 and U251 cell lines, respectively. A global comparison of the survival curves similarly revealed significant sensitization at 10 microM IdUrd. Sensitizer enhancement ratios and global comparisons of the chronic exposures showed significant sensitization in the presence of 2 microM IdUrd for both lines. No significant interaction between dose rate and IdUrd effect could be shown using a global comparison. Repair half-times for chronic exposures were similar in the presence or absence of IdUrd. Both cell lines demonstrate capacity for sublethal damage repair in the presence of 2 microM IdUrd in split-dose experiments. The results of the chronic clonogenic and split-dose studies suggest that increased DNA damage production contributes to the mechanism of IdUrd radio-sensitization, perhaps more so than repair inhibition. A capacity for sublethal damage repair is not necessarily a prerequisite for sensitization. IdUrd remains an attractive sensitizer of ionizing irradiation delivered at high or low dose rates, particularly for actively growing tumors located in quiescent normal tissues.


Overexpression of SGLT2 in the kidney of a P. gingivalis LPS-induced diabetic nephropathy mouse model.
The overexpression of sodium-glucose cotransporter 2 (SGLT2) in diabetic kidneys has been reported. It has also been established that the diabetic glomerular endothelium expresses the toll-like receptors TLR2 and TLR4. The present study aims to examine the renal SGLT2 induction by the TLR2/4 ligand Porphyromonas (P.) gingivalis lipopolysaccharide (Pg-LPS) in mouse diabetic nephropathy. Immunohistochemical study and tissue RT-PCR analyses were performed on mouse kidneys in streptozotocin (STZ)-induced diabetic ICR mice (STZ-ICR), in healthy ICR mice administered Pg-LPS (LPS-ICR), and in diabetic ICR mouse kidneys with Pg-LPS-induced nephropathy (LPS-STZ). In the quantitative analysis of blood sugar levels, the mean time to reach 600 mg/dl was shorter in the LPS-STZ than in the STZ-ICR kidneys. The rise in blood glucose levels was significantly steeper in the LPS-STZ than in the STZ-ICR kidneys. According to these data the LPS-STZ model suggests a marked glucose intolerance. The expression of SGLT2 was significantly stronger in the whole of the renal parenchyma of the LPS-STZ than in the LPS-ICR or in the STZ-ICR. The expression of SGLT2 was observed both in the renal tubules and around the renal tubules, and in the glomeruli of the LPS-STZ kidneys. In the analysis by tissue real-time PCR and cell ELISA, the expression of the SGLT2 gene and protein was significantly stronger in the LPS-STZ than in the LPS-ICR or in the STZ-ICR. There were no differences in the renal SGLT2 production in the LPS-ICR and the STZ-ICR kidneys. Abnormally high renal expression of SGLT2 occurs in diabetic kidneys with P. gingivalis LPS. Periodontitis may be an exacerbating factor in diabetic nephropathy as well as in diabetes.


The effect of bladder outlet obstruction treatment on ultrasound-determined bladder wall thickness.
Detrusor hypertrophy associated with bladder outlet obstruction can be imaged on suprapubic ultrasound, and bladder mass can be quantified from the evaluation of bladder wall thickness and bladder volume. Bladder wall hypertrophy has been found to be correlated with detrusor function. Independent studies have shown that surgical treatment of benign prostatic obstruction results in a significant decrease of bladder mass. Preliminary data suggest the possibility that medical treatment with alpha-adrenergic antagonists might also produce a reduction of bladder wall hypertrophy, although confirmation is still awaited. The development of dedicated automated ultrasound systems for the evaluation of bladder mass might result in the use of such parameters in clinical trials of treatment for benign prostatic hyperplasia and ultimately in daily urologic practice.


Primary graft dysfunction in heart transplantation.
Primary graft dysfunction (PGD) is common early postheart transplantation; however, use of standardized definitions remains inconsistent. This review focuses on understanding the incidence, classification, risk factors, and management of PGD. The incidence and mortality of PGD in heart transplant varies considerably in the published literature ranging from 1.0% to 31% and 3% to 75%, respectively. There is also considerable variation in management strategies with current data favoring early intervention. PGD in heart transplantation remains a challenging problem associated with significant mortality and morbidity. There is need for a consistent and accessible definition to better define associated risk factors and optimize management strategies.


Inhaled molecular hydrogen reduces hippocampal neuroinflammation, glial reactivity and ameliorates memory impairment during systemic inflammation.
Sepsis is associated with numerous physiological and biochemical abnormalities that result in a life-threatening condition. The involvement of the Central Nervous System (CNS) during sepsis has received considerable attention, especially the hippocampus which plays a key role in the learning and memory processes. The increased interest in this limbic region during systemic inflammation (SI) is related to the number of sepsis survivor patients who have cognitive impairments. A single injection of lipopolysaccharide (LPS)-induced systemic inflammation is the most commonly used murine endotoxemia model because it replicates several pathophysiological changes observed in severe sepsis. Molecular hydrogen (H2) has been used as an anti-inflammatory therapeutic strategy to prevent neuroinflammation. However, the mechanisms by which inhaled H2 mitigate memory loss during SI remains unknown. To understand how H2 acts in the hippocampus, the current study focused on specific mechanisms that may be involved in reducing neuroinflammation in rats during SI. We hypothesized that inhaled H2 decreases LPS-induced hippocampal pro-inflammatory cytokines surges and this effect is associated with reduced memory loss. Using different and integrative approaches, i.e., from hippocampal cells electrophysiology to animal behavior, we report that inhaled H2 decreased LPS-induced peripheral and hippocampal inflammation, decreased microglial and astrocytic activation, lessen memory loss without affecting long-term potentiation (LTP). To our knowledge, this is the first evidence showing that inhaled H2 reduces hippocampal microglial and glial cells inflammation, which may be associated with a reduced memory impairment induced by SI.


When does activating diversity alleviate, when does it increase intergroup bias? An ingroup projection perspective.
The question how intergroup bias can be alleviated is of much theoretical and practical interest. Whereas diversity training and the multiculturalism ideology are two approaches prominent in practice, most theoretical models on reducing intergroup bias are based on social-identity theory and self-categorization theory. This social-identity perspective assumes that similar processes lead to intergroup bias in very different intergroup contexts if people identify with the respective social groups. A recent prominent model based on these theories is the ingroup-projection model. As this model assumes, an ingroup's norms and standards are applied to outgroups included in a common superordinate category (this is called ingroup projection). Intergroup bias results because the outgroup fulfils these norms and standards less than the ingroup. Importantly, if the diversity of the superordinate category is induced as the norm, ingroup projection and thus intergroup bias should be reduced. The present research delineates and tests how general this process is. We propose that ingroup prototypicality is not only an outcome variable, as the ingroup-projection model originally assumes, but can also be an important moderator. We hypothesize that for members considering their ingroup highly prototypical ("pars pro toto", large majorities), the superordinate group's diversity may question their ingroup's position and thus elicit threat and intergroup bias. In contrast, for members who consider their group as less prototypical (one among several, or "una inter pares" groups), activating diversity should, as originally assumed in the ingroup-projection model, reduce intergroup bias. Three experiments (total N = 345) supported these predictions in the contexts of groups defined by gender or nationality. Taken together, the ingroup-projection model can explain under which conditions activating superordinate-category diversity induces tolerance, and when it may backfire. We discuss in how far the ingroup-projection model can integrate conflicting findings on the multiculturalism ideology.


Possible involvement of phospholipase A2 in A23187-induced histamine release from purified rat mast cells.
A23187-induced histamine release from purified rat mast cells is accompanied by degradation of mast cell phosphatidylcholine. When inhibitors of histamine release such as ethacrynic acid, eicosatetraynoic acid and phenylmethylsulfonylfluoride are added to the mast cell system, the phosphatidylcholine hydrolysis is inhibited along with the release of histamine. A simultaneous striking increase in prostaglandin D2 synthesis by the A23187-treated mast cells suggests that the degradation of phosphatidylcholine is associated with the activation of phospholipase A2. Arachidonic acid, one of the major products formed as a result of this activation, inhibits A23187 and antigen-induced histamine release when added 5 min prior to the histamine release inducers. Lysophosphatidylcholine, the other major product, demonstrates a biphasic effect, stimulating histamine release at low concentrations and inhibiting release at slightly higher concentrations. These findings suggest a histamine release regulating function for arachidonic acid and lysophosphatidylcholine.


Low thoracic muscle mass index on computed tomography predicts adverse outcomes following lobectomy via thoracotomy for lung cancer.
The aim of this study was to determine whether the preoperative thoracic muscle mass is associated with postoperative outcomes in patients undergoing lobectomy via thoracotomy for lung cancer. Consecutive patients undergoing lobectomy were retrospectively reviewed. The thoracic muscle mass index (TMMI) was obtained at the level of the fifth thoracic vertebra on preoperative thoracic computed tomography (CT). Patients were analysed comparatively by being dividing into low and high muscle index groups by the median of sex-specific TMMI. The primary outcomes were the incidence of any or postoperative pulmonary complications. The secondary outcomes were postoperative intensive care unit (ICU) admission, length of stay (LOS) in the ICU, total hospital LOS, readmission and mortality. The study population consisted of 120 patients (63.6 ± 9.8 years; 74% male). Each groups included 60 patients. Major complications occurred in 28.3% (34/120) and readmission in 18.3% (22/120) of patients. The adjusted multivariable analysis showed that each unit increase in TMMI (cm2/m2) was independently associated with the rates of less any complications [odds ratio (OR) 0.92, P = 0.014], pulmonary complications (OR 0.27, P = 0.019), ICU admission (OR 0.76, P = 0.031), hospitalization for >6 days (OR 0.90, P = 0.008) and readmission (OR 0.93, P = 0.029). Low TMMI obtained from the preoperative thoracic CT is an independent predictor of postoperative adverse outcomes in patients following lobectomy via thoracotomy for lung cancer. TMMI measurements may contribute to the development of preoperative risk stratification studies in the future.


A mathematical model to estimate cholesterylester transfer protein (CETP) triglycerides flux in human plasma.
Cholesterylester transfer protein (CETP) modulates the composition of various lipoproteins associated with cardiovascular disease. Despite its central role in lipoprotein metabolism, its mode of action is still not fully understood. Here we present a simple way to estimate CETP-mediated lipid fluxes between different lipoprotein fractions. The model derived adequately describes the observed findings, especially regarding low- and high dense lipoproteins (LDL and HDL), delivering correlation coefficients of R2 = 0.567 (p < 0.001) and R2 = 0.466 (p < 0.001), respectively. These estimated fluxes correlate best among all other measured concentrations and 'lipid per lipoprotein' ratios to the observed fluxes. Our model approach is independent of CETP-action's exact mechanistic mode. It is simple and easy to apply, and may be a useful tool in revealing CETP's ambiguous role in lipid metabolism. The model mirrors a diffusion-like exchange of triglycerides between lipoproteins. Cholesteryl ester and triglyceride concentrations measured in HDL, LDL and VLDL are sufficient to apply the model on a plasma sample.


The role of vitamin K in vascular calcification of patients with chronic kidney disease.
Patients with chronic kidney disease (CKD) are prone to vascular calcification. Pathogenetic mechanisms of vascular calcifications have been broadly studied and discussed such as the role of hyperphosphatemia, hypercalcemia, parathormone, and vitamin D. In recent years, new insights have been gained pointing to vitamin K as a main actor. It has been discovered that vitamin K is an essential cofactor for the activation of matrix Gla protein (MGP), a calcification inhibitor in the vessel wall. Patients with CKD often suffer from vitamin K deficiency, resulting in low active MGP and eventually a lack of inhibition of vascular calcification. Vitamin K supplementation and switching warfarin to new oral anticoagulants are potential treatments. In addition, MGP may have a role as a non-invasive biomarker for vascular calcification.


Relationship Between Fluoroquinolone Structure and Neurotoxicity Revealed by Zebrafish Neurobehavior.
Central nervous system side effects are one of the most frequently reported adverse reactions of fluoroquinolones (FQs). However, the mechanism is not fully understood. In this study, zebrafish ( Danio rerio) were used as a model system. We quantified neurobehavior by recording indicators with automated video-tracking and used liquid chromatography-tandem mass spectrometry to detect drug absorption in vivo. We studied embryotoxicity and effects on zebrafish locomotor activity of 17 typical FQs. In addition, we calculated the stable conformation of typical FQs in aqueous conditions. The relationships between structure, neurotoxicity, and embryotoxicity were analyzed. The results indicate: (1) The effects of FQs on zebrafish neurobehavior can be divided into four categories. Type I has no significant influence on locomotor activity. Type II suppresses locomotor activity. Type III inhibits at low concentration and stimulates at high concentration. Type IV stimulates and then suppresses (biphasic response). (2) Structural modifications of FQs can change toxicity properties in zebrafish. Cleavage of the C-7 piperazinyl structure decreases neurotoxicity but enhances embryotoxicity. The C-3 decarboxyl formation and 5-NH2 derivatives might enhance embryotoxicity and neurotoxicity. (3) There are two toxic functional groups. The piperazinyl structure at position C-7 (toxic functional group I) can cause primary reactions which may be by the inhibition of γ-aminobutyric acid receptors, and the nucleus containing a carboxyl group at position 3 (toxic functional group II) might cause a reaction secondary to the effect of toxic functional group I and reverse its effects.


Impact of expansion of telemedicine screening for retinopathy of prematurity in India.
The purpose of this study is to estimate the unknown burden of retinopathy of prematurity (ROP) blindness from nine states of India using demographic, incidence and treatment data from an ongoing statewide ROP program in Karnataka called the Karnataka Internet Assisted Diagnosis of ROP (KIDROP) and to calculate the fiscal quantum of preventable blindness in these states. The KIDROP model is an ongoing tele-ROP service providing screening and treatment for ROP in Karnataka since 2008. Using this index strategy, an impact assessment in nine other states was constructed, the number of potential blind babies enumerated, the fiscal quantum of blindness prevented in blind person-years (BPYs), and the increase in burden with improving survival and institutional deliveries calculated. The total population in the ten study states is 681.5 million. The eligible babies for ROP screening annually are 467,664. The number of babies admitted to neonatal units is 188,561 of which 160,277 are likely to survive and require screening. Based on KIDROP data, ROP would develop in 35,886 of these infants, and 1281 babies would require treatment annually. The fiscal quantum of BPY saved in these ten states is USD 108.4 million annually, with a further increase of USD 106.8 million with improving infant survival and higher admission rates for delivery. A KIDROP like model can provide ROP screening in low-resource settings, remote centers, and regions with few ROP specialists. Expanding the model to other states with similar demographics can prevent over USD 100 million of blindness burden annually.


Antiproliferative and apoptosis inducing effects of the methanolic extract of Centaurea hermannii in human cervical cancer cell line.
We investigated the antiproliferative and apoptosis inducing effects of a methanolic extract of Centaurea hermannii in Vero and HeLa cell lines. Both cell lines also were treated with doxorubicin. Antiproliferative effects were assessed by MTT assay and cell index parameters were determined using the xCELLigence real time cell analysis system (RTCA). The IC50, the half maximal inhibitory concentration, and selectivity index (SI) values for doxorubicin and the C. hermannii extract were determined for both cell lines. At 48 h culture, the C. hermannii extract exhibited a potent cytotoxic effect in HeLa cells. Our MTT findings were consistent with morphological evaluation and analysis by the xCELLigence RTCA. The apoptosis inducing effect of the C. hermannii extract in HeLa cells was determined by flow cytometry; caspases 3, 7 and 9 activation assays; and quantitative reverse transcription polymerase chain reaction analysis. Our findings suggest that components of C. hermannii extract should be investigated as possible anticancer drugs.


Molecular dating of phylogenies by likelihood methods: a comparison of models and a new information criterion.
Dating the divergence in a phylogenetic tree is a fundamental step in evolutionary analysis. Some extensions and improvements of the penalised likelihood method originally presented by Sanderson are introduced. The improvements are the introduction of alternative models, including one with non-correlated rates of molecular substitution ("relaxed" model), a completely reworked fitting algorithm that considers the high-dimensionality of the optimisation problem, and the development of a new information criterion for model selection in the presence of a penalised term. It is also shown that the strict clock model is a special case of the present approach. An extensive simulation study was conducted to assess the statistical performance of these improvements. Overall, the different estimators studied here appeared as unbiased though their variance varied depending on the fitted and the simulated models and on the number of calibration points. The strict clock model gave good estimates of branch lengths even in the presence of heterogeneous substitution rates. The correlated model gave the best estimates of substitution rates whatever the model used to simulate the data. These results, which are certainly the first from an extensive simulation study of a molecular dating method, call for more comparison with alternative methods, as well as further work on the developments introduced here.


Transmission of stimulus-locked responses in two coupled phase oscillators.
A model of two n:m coupled phase oscillators is studied, where both oscillators are subject to random forces, but only one oscillator is repetitively stimulated with a pulsatile stimulus. The focus of the paper is on transmission of transient responses as well as transient synchronization and desynchronization, which are stimulus locked, i.e., tightly time locked to the stimulus. A bistability or multistability of stable synchronized states of the two-phase oscillators (modulo 2pi ) occurs due to the n:m coupling. Accordingly, after stimulation the two oscillators may tend to qualitatively different stable states, which leads to a cross-trial (CT) response clustering (i.e., a switching between qualitatively different poststimulus responses across trials) of either one of the oscillators or both. A stochastic CT phase resetting analysis allows one to detect such transient responses and provides a reliable estimation of the transmission time. In contrast, CT averaging (averaging over an ensemble of responses), CT standard deviation, and CT cross correlation fail in studying the transmission of such stimulus-locked responses, even in the simpler case of 1:1 coupling. In particular, even though being used as golden standard for the analysis of evoked responses in medicine and neuroscience, CT averaging typically causes severe artifacts and misinterpretations.


Clustering biological annotations and gene expression data to identify putatively co-regulated biological processes.
Functional profiling is a key step of microarray gene expression data analysis. Identifying co-regulated biological processes could help for better understanding of underlying biological interactions within the studied biological frame. We present herein an original approach designed to search for putatively co-regulated biological processes sharing a significant number of co-expressed genes. An R language implementation named "FunCluster" was built and tested on two gene expression data sets. A discriminatory functional analysis of the first data set, related to experiments performed on separated adipocytes and stroma vascular fraction cells of human white adipose tissue, highlighted the prevalent role of nonadipose cells in the synthesis of inflammatory and immunity molecules in human adiposity. On the second data set, resulting from a model investigating insulin coordinated regulation of gene expression in human skeletal muscle, FunCluster analysis spotlighted novel functional classes of putatively co-regulated biological processes related to protein metabolism and the regulation of muscular contraction. Supplementary information about the FunCluster tool is available on-line at http://corneliu.henegar.info/FunCluster.htm.


Examination of Anterior Leaflet Pseudoprolapse Causing Severe Mitral Regurgitation and Its Ideal Surgical Procedure.
The aim of this study is to evaluate severe mitral regurgitation caused by so called atrial leaflet "pseudoprolapse" and verify the effect of simple annular stabilization. One-hundred-twenty-two patients underwent surgery for severe mitral regurgitation at our institute between January 2015 to July 2018. Of those, 32 cases diagnosed as anterior leaflet prolapse that underwent mitral repair were analyzed. Ten cases with pseudoprolapse, which is defined as anterior leaflet prolapse without dropping into the left atrium beyond the annular line causing eccentric regurgitation flow directed to the posterior atrium, were classified as the Pseudoprolapse Group. The other 22 cases had obvious anterior leaflet prolapse dropping into the left atrium; these cases were classified as the True Prolapse Group. We compared clinical findings between the 2 groups and reviewed pseudoprolapse cases. Patients in the Pseudoprolapse Group had lower ejection fraction and lower regurgitation volume than those in the True Prolapse Group. A2 lesion as main inflow of regurgitation was more included in the Pseudoprolapse Group. All but one patient in the Pseudoprolapse Group received only simple annuloplasty, and all patients in the True Prolapse Group received leaflet repair and annuloplasty. In both groups, mid-term regurgitation grade and the reoperation rate were satisfactory. In the Pseudoprolapse Group, 6 cases were clarified as atrial functional mitral regurgitation, and 4 cases were considered to have focal posterior leaflet tethering. Pseudoprolapse cases could be characterized by low ejection fraction, low regurgitation volume, and A2 prolapse. For most cases with pseudoprolapse, simple annuloplasty may be enough, however further study is needed.


Role of calcium in signal transduction during the hypersensitive response caused by basidiospore-derived infection of the cowpea rust fungus
The hypersensitive response (HR) of disease-resistant plant cells to fungal invasion is a rapid cell death that has some features in common with programmed cell death (apoptosis) in animals. We investigated the role of cytosolic free calcium ([Ca2+]i) in the HR of cowpea to the cowpea rust fungus. By using confocal laser scanning microscopy in conjunction with a calcium reporter dye, we found a slow, prolonged elevation of [Ca2+]i in epidermal cells of resistant but not susceptible plants as the fungus grew through the cell wall. [Ca2+]i levels declined to normal levels as the fungus entered and grew within the cell lumen. This elevation was related to the stage of fungal growth and not to the speed of initiation of subsequent cell death. Elevated [Ca2+]i levels also represent the first sign of the HR detectable in this cowpea-cowpea rust fungus system. The increase in [Ca2+]i was prevented by calcium channnel inhibitors. This effect was consistent with pharmacological tests in which these inhibitors delayed the HR. The data suggest that elevation of [Ca2+]i is involved in signal transduction leading to the HR during rust fungal infection.


Experimental ulcerative herpetic keratitis. III. Evaluation of hyperimmune gammaglobulin therapy.
The value of hyperimmune gammaglobulin (HGG) therapy in ulcerative herpetic keratitis was assessed in rabbits. HGG treated of early disease in normal rabbits was very effective, producing a 10-fold rise in the virus concentration needed to infect 50% of sites (CID50) and an 88% inhibition of ulceration after 2 days. The efficacy of the gammaglobulin preparations tested depended on their anti-HSV antibody content. Established disease was considerably less responsive to HGG therapy. No conclusive effect of HGG therapy could be demonstrated in rabbits with a previous HSV skin infection ('immunised'). Corticosteroid-induced geographic ulceration in immunised rabbits was not prevented by concurrent HGG therapy. The findings indicate that HGG is unlikely to represent a useful therapy for ulcerative herpetic keratitis but that it may be valuable in primary disease and in long-term prophylaxis.


Reaction dynamics of carbon-bearing radicals in circumstellar envelopes of carbon stars.
Crossed molecular beams experiments on dicarbon molecules, C2(X1sigmag+/a3piu), with unsaturated hydrocarbons acetylene (C2H2(X1sigmag+), ethylene (C2H4(X1Ag)), methylacetylene (CH3CCH(X1A1)), and allene (H2CCCH2 (X1A1)) were carried out at 18 collision energies between 10.6 and 50.3 kJ mol(-1) utilizing a universal crossed beams machine to untangle the reaction dynamics forming hydrogen deficient hydrocarbon radicals in circumstellar envelopes of carbons stars and in cold molecular clouds. We find that all reactions proceed without the entrance barrier through indirect (complex forming) scattering dynamics. Each bimolecular collision is initiated by an addition of the dicarbon molecule to the pi bond of the unsaturated hydrocarbon molecule yielding initially acyclic (triplet) and three- or four-membered cyclic collision complexes (triplet and singlet surface). On the singlet surface, the cyclic structures isomerize to form eventually diacetylene (HCCCCH; C2/C2H2), butatriene (H2CCCCH2; C2/C2H4), methyldiacetylene (CH3CCCCH; C2/CH3CCH), and pentatetraene (H2CCCCCH2; C2/H2CCCH2) intermediates. The latter were found to decompose via atomic hydrogen loss yielding the buta-1,3-diynyl [C4H(X2sigma+) HCCCC], 1-butene-3-yne-2-yl [i-C4H3(X2A') H2CCCCH], penta-2,4-diynyl-1 [C5H3(X2B1) HCCCCCH2], and penta-1,4-diynyl-3 radical [C5H3(X2B1) HCCCHCCH] under single collision conditions. The underlying characteristics of these dicarbon versus atomic hydrogen replacement pathways (indirect scattering dynamics; no entrance barrier; isomerization barriers below the energy of the separated reactants; exoergic reactions) suggest the enormous potential of the dicarbon plus unsaturated hydrocarbon reaction class to form highly hydrogen-deficient carbonaceous molecules in cold molecular clouds and in circumstellar envelopes of carbon stars. The studies therefore present an important advancement in establishing a comprehensive database of reaction intermediates and products involved in bimolecular collisions of dicarbon molecules with unsaturated hydrocarbons which can be utilized in refined astrochemical models and also in future searches of hitherto unidentified interstellar molecules. Implications of these experiments to understand related combustion processes are also addressed.


Aging increases Nepsilon-(carboxymethyl)lysine and caloric restriction decreases Nepsilon-(carboxyethyl)lysine and Nepsilon-(malondialdehyde)lysine in rat heart mitochondrial proteins.
The present investigation studies the effect of aging, short-term and long-term caloric restriction on four different markers of oxidative, glycoxidative or lipoxidative damage to heart mitochondrial proteins: protein carbonyls (measured by ELISA); Nepsilon-(carboxyethyl)lysine (CEL), Nepsilon-(carboxymethyl)lysine (CML), and Nepsilon-(malondialdehyde)lysine (MDA-lys) measured by gas chromatography/mass spectrometry. Aging increased the steady state level of CML in rat heart mitochondria without changing the levels of the other three markers of protein damage. Short-term caloric restriction (six weeks) did not change any of the parameters measured. However, long-term (one year) caloric restriction decreased CEL and MDA-lys in heart mitochondria and did not change protein carbonyls and CML levels. The decrease in MDA-lys was not due to changes in the sensitivity of mitochondrial lipids to peroxidation since the measurements of the fatty acid composition showed that the total number of fatty acid double bonds was not changed by caloric restriction. The decrease in CEL and MDA-lys in caloric restriction agrees with the previously and consistently described finding that caloric restriction agrees with the previously and consistently described finding that caloric restriction lowers the rate of generation of reactive oxygen species (ROS) in rodent heart mitochondria, although in the case of CEL a caloric restriction-induced lowering of glycaemia can also be involved. The CEL and MDA-lys results support the notion that caloric restriction decreases oxidative stress-derived damage to heart mitochondrial proteins.


Pyridoxine-responsive hyper-beta-alaninemia associated with Cohen's syndrome.
We report intermittent seizures, lethargy, and Cohen's syndrome in a 4-year-old girl with hyper-beta-alaninemia and a partial deficiency of beta-alanyl-alpha-ketoglutarate transaminase (AKT). To examine the role of beta-alanine (beta ALA) in cellular metabolism, we cultured her skin fibroblasts in medium containing increasing amounts of beta ALA. At concentrations of 10 to 25 mM, beta ALA caused more than a 50% reduction in the growth of her cells compared with normal control skin fibroblasts. The addition of 0.1 mM of pyridoxine to the culture medium abolished these toxic effects and increased her skin fibroblast AKT enzyme activity more than twofold. During a 2-year period of clinical observation, there were no further episodes of seizures or somnolence in our patient while she received oral pyridoxine therapy.


Evaluation of Cyanea capillata Sting Management Protocols Using Ex Vivo and In Vitro Envenomation Models.
Lion's mane jellyfish (Cyanea capillata) stings cause severe pain and can lead to dangerous systemic effects, including Irukandji-like syndrome. As is the case for most cnidarian stings, recommended medical protocols in response to such stings lack rigorous scientific support. In this study, we sought to evaluate potential first aid care protocols using previously described envenomation models that allow for direct measurements of venom activity. We found that seawater rinsing, the most commonly recommended method of tentacle removal for this species, induced significant increases in venom delivery, while rinsing with vinegar or Sting No More® Spray did not. Post-sting temperature treatments affected sting severity, with 40 min of hot-pack treatment reducing lysis of sheep's blood (in agar plates), a direct representation of venom load, by over 90%. Ice pack treatment had no effect on sting severity. These results indicate that sting management protocols for Cyanea need to be revised immediately to discontinue rinsing with seawater and include the use of heat treatment.


Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective.
The retinal pigment epithelium (RPE) performs a range of necessary functions within the neural layers of the retina and helps ensure vision. The regulation of pro-oxidative and antioxidant processes is the basis for maintaining RPE homeostasis and preventing retinal degenerative processes. Long-term stable changes in the redox balance under the influence of endogenous or exogenous factors can lead to oxidative stress (OS) and the development of a number of retinal pathologies associated with RPE dysfunction, and can eventually lead to vision loss. Reparative autophagy, ubiquitin-proteasome utilization, the repair of damaged proteins, and the maintenance of their conformational structure are important interrelated mechanisms of the endogenous defense system that protects against oxidative damage. Antioxidant protection of RPE cells is realized as a result of the activity of specific transcription factors, a large group of enzymes, chaperone proteins, etc., which form many signaling pathways in the RPE and the retina. Here, we discuss the role of the key components of the antioxidant defense system (ADS) in the cellular response of the RPE against OS. Understanding the role and interactions of OS mediators and the components of the ADS contributes to the formation of ideas about the subtle mechanisms in the regulation of RPE cellular functions and prospects for experimental approaches to restore RPE functions.


Psychological response to amputation as a function of age and time since amputation.
Much of what is known about the psychological response to amputation is derived from studies of veterans. Most recent amputees come from a different group; they are typically older and have experienced medical problems prior to their amputation. In order to investigate the effects of age and time since amputation on psychological response, 66 amputees were assessed by the Symptom Checklist-90, Beck Depression Inventory and interviewed. When classified by time since amputation and by age, the results indicate that older amputees exhibited less depression and fewer psychological symptoms: in contrast, younger amputees evidenced increased depression and psychological symptomatology the longer the time since their amputation.


Right Heart Transvalvular Embolus with High Risk Pulmonary Embolism in a Recently Hospitalized Patient: A Case Report of a Therapeutic Challenge.
Thrombus-in-transit is not uncommon in pulmonary embolism but Right Heart Transvalvular Embolus (RHTVE) complicating this is rare. A 54-year-old obese male with recent hospitalization presented with severe dyspnea and collapse. Initial investigations revealed elevated d-dimer and troponin. CTA showed saddle pulmonary embolus and bedside echocardiogram revealed right ventricular (RV) pressure overload and dilatation (RV > 41 mm), McConnell's sign, and mobile echodensity attached to tricuspid valve. Patient was immediately resuscitated and promptly transferred for surgical embolectomy under cardiopulmonary bypass. A long segment of embolus traversing through the tricuspid valve and extensive bilateral pulmonary artery embolus were removed. IVC filter was placed for a persistent right lower extremity DVT. Hypercoagulable work-up was negative. Patient continued to do well after discharge on Coumadin. Open embolectomy offers great promises where there is no consensus in optimal management approach in such patients. Bedside echocardiogram is vital in risk stratification and deciding choice of advanced PE treatment.


Utility of olfactory identification test for diagnosing Chinese patients with Alzheimer's disease.
The present study examined the utility of two tests, the olfactory identification test and the olfactory threshold test, in detecting dementia of the Alzheimer's type in Chinese patients in Hong Kong. The olfactory identification test developed by Murphy, Anderson, and Markinson (1994) was utilized with some modifications of odor stimuli suitable for the Chinese culture. Results showed that patients with Alzheimer's disease (AD) identified significantly fewer odors and had significantly higher olfactory threshold than their age- and education-matched normal control subjects. With the cut-off point of 5 identified odors (out of 6), the olfactory identification test yielded a sensitivity of 83% in discriminating AD patients from normal controls which was consistent with that reported by Morgan, Nordin, and Murphy (1995). Thus, the present results suggested that the olfactory identification test could be applied cross-culturally for identifying patients with dementia of the Alzheimer's type.


A preliminary study on screening prevalence of pervasive developmental disorder in schoolchildren in Iran.
To study prevalence rates of pervasive developmental disorder (PDD) symptoms and differences between subtypes in school age Iranian children. A random sample of 2,000 school age children from both genders was selected. A parent-completed, DSM-IV-referenced rating scale of PDD symptoms was used. About 1.9% of the sample obtained screening cutoff scores for probable autistic disorder and 0.5 for probable asperger's disorder. The rate of probable PDD was not more in girls than the boys. The rate of suspected cases of PDD in Iran is very high and probable autistic disorder is not gender related. It shows the need for more consideration of PDD in the mental health programs planning.


Expression and purification of isotopically labeled peptide inhibitors and substrates of cAMP-dependant protein kinase A for NMR analysis.
Extensive X-ray crystallographic studies carried out on the catalytic-subunit of protein kinase A (PKA-C) enabled the atomic characterization of inhibitor and/or substrate peptide analogues trapped at its active site. Yet, the structural and dynamic transitions of these peptides from the free to the bound state are missing. These conformational transitions are central to understanding molecular recognition and the enzymatic cycle. NMR spectroscopy allows one to study these phenomena under functionally relevant conditions. However, the amounts of isotopically labeled peptides required for this technique present prohibitive costs for solid-phase peptide synthesis. To enable NMR studies, we have optimized both expression and purification of isotopically enriched substrate/inhibitor peptides using a recombinant fusion protein system. Three of these peptides correspond to the cytoplasmic regions of the wild-type and lethal mutants of the membrane protein phospholamban, while the fourth peptide correspond to the binding epitope of the heat-stable protein kinase inhibitor (PKI(5-24)). The target peptides were fused to the maltose binding protein (MBP), which is further purified using a His(6) tag approach. This convenient protocol allows for the purification of milligram amounts of peptides necessary for NMR analysis.


RNA-binding protein is involved in aggregation of light neurofilament protein and is implicated in the pathogenesis of motor neuron degeneration.
Abnormal protein aggregation is emerging as a common theme in the pathogenesis of neurodegenerative disease. Our previous studies have shown that overexpression of untranslated light neurofilament (NF-L) RNA causes motor neuron degeneration in transgenic mice, leads to accumulation of ubiquitinated aggregates in degenerating cultured motor neurons and triggers aggregation of NF-L protein and co-aggregation of mutant SOD1 protein in neuronal cells. Here, we report that p190RhoGEF, an RNA-binding protein that binds to a destabilizing element in NF-L mRNA, is involved in aggregation of NF-L protein and is implicated in the pathogenesis of motor neuron degeneration. We show that p190RhoGEF co-aggregates with unassembled NF-L protein and that co-aggregation is associated with down-regulation of parent NF-L mRNA in neuronal cells. Co-expression of NF-M increases NF assembly and reduces RNA-triggered aggregation as well as loss of solubility of NF-L protein. siRNA-induced down-regulation of p190RhoGEF not only reduces aggregation and promotes assembly of NF-L and NF-M, but also causes reversal of aggregation and recovery of NF assembly in transfected cells. Examination of transgenic models of motor neuron disease shows that prominent aggregates of p190RhoGEF and NF-L and down-regulation of NF-L expression occur in degenerating motor neurons of mice expressing untranslated NF-L RNA or a G93A mutant SOD1 transgene. Moreover, aggregates of p190RhoGEF and NF-L appear as early pathological changes in presymptomatic G93A mutant SOD1 transgenic mice. Together, the findings indicate that p190RhoGEF is involved in aggregation of NF-L protein and support a working hypothesis that aggregation of p190RhoGEF and NF-L is an upstream event triggering neurotoxicity in motor neuron disease.


Solid state and dissolution rate characterization of co-ground mixtures of nifedipine and hydrophilic carriers.
Co-ground powders of the poorly water-soluble drug nifedipine and a hydrophilic carrier, [partially hydrolyzed gelatin (PHG), polyvinylpyrrolidone (PVP), sodium dodecyl sulfate (SDS), hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), urea or Pluronic F108] were prepared in order to improve the dissolution rate of nifedipine. The effects of type of grinding equipment, grinding time, and type of hydrophilic carrier on the crystallinity of nifedipine (x-ray diffraction and differential scanning calorimetry) on the interaction between drug and carriers (differential scanning calorimetry), on the particle size and appearance (scanning electron microscopy), on the wettability (contact angle measurements), and on the drug release were investigated. Grinding nifedipine together with these carriers improved the dissolution rate. PHG-ground mixtures resulted in the fastest dissolution rate followed by PVP, SDS, HPMC, Pluronic, urea, and PEG. This effect was not only due to particle size reduction, which increased in the order PHG<PEG=SDS<Pluronic<drug<urea<HPMC<PVP, but also resulted from the ability of some carriers (PVP and HPMC) to prevent reaggregation of the finely divided drug particles. PVP, HPMC, and PHG formed a powder with amorphous drug. The carriers improved the wettability of the ground products in the order HPMC<drug<urea<PVP<SDS<PHG<PEG<Pluronic. Differential scanning calorimetry (DSC) measurements gave valuable information about the nature of drug crystallinity and the interactions with the carriers within the ground mixtures.


Negative to positive lymph node ratio is a superior predictor than traditional lymph node status in stage III colorectal cancer.
Negative lymph node counts has recently attracted attention as a prognostic indicator in colorectal cancer (CRC). But little is known about prognostic significance of negative to positive lymph node ratio (NPR) in CRC. Our aim was to determine impact of NPR on oncological outcomes in patients with stage III CRC. This retrospective study included 2,256 patients with stage III CRC under curative resection at Fudan university Shanghai cancer center. Kaplan-Meier methods and multivariable Cox regression models were built for the analysis of survival outcomes and risk factors. Accuracy of the NPR was assessed with the Harrell's concordance-index(C-index).X-tile program identified 2.38 or 0.55/2.38 as the optimal cutoff value for NPR to divide the cohort into high/low risk or high/middle/low risk subsets in terms of CRC cause specific survival (CCSS). In a multivariate analysis, NPR was significant independent prognostic factors for CCSS (P<0.05), notably, N classification was not an independently prognostic factor (P>0.05).Further analysis found NPR could give detailed prognostic classification for both N1 and N2 stage (P<0.05). Interestingly, patients in N2+ NPR >2.38 stage have similar survival outcome with N1+ NPR >2.38 stage (χ2=0.030, P=0.863), and better than those at N1+ NPR ≤2.38 and N2+ NPR ≤2.38 stage (P<0.001). The TNNPRM stage was more accurate for predicting CCSS (C-index = 0.659) than current TNM stage system(C-index = 0.628) (P<0.001). Collectively, NPR was an independent prognostic factor for stage III CRC patients, it could provide more accurate prognostic information than the current node stage system.


Education of physicians in the sexually transmitted diseases in the United Kingdom.
Undergraduate and postgraduate training in sexually transmitted diseases and genitourinary medicine in the UK is described. The course for overseas postgraduate students is briefly described. It is noted that once funds are available it has been agreed to establish a professorial chair of venereology at the Middlesex Hospital Medical School. This will be a major advance and is the most desirable goal to aim at in the encouragement of education in STD for the next few years.


Experiences of over-the-counter codeine misusers and accounts of recovery: A qualitative study in Tasmania, Australia.
There is international concern about misuse of over-the-counter (OTC) codeine, yet few studies have reported the perspectives of misusers themselves. This study explored the experience of OTC codeine misuse and recovery in Tasmania, Australia. Semi-structured telephone interviews were conducted with 15 self-identified long-term users of OTC codeine. The interview guide prompted responses about reasons for codeine use, positive and negative impacts, recovery, identity and codeine accessibility. Transcripts were analysed abductively using qualitative content analysis. Categories that emerged from misuser accounts were aligned to three broad temporal phases: (i) transition to misuse; (ii) growing awareness; and (iii) towards recovery. Salient features of the misuse experience included: initial use for the self-treatment of physical pain; ongoing use to self-medicate physical pain, stress or mental health conditions; a perception of safety of OTC codeine; an insidious transition from use to misuse; growing awareness of a problem over time; support provided by family, friends and the internet; recovery through self-change; and recognition that recovery is an ongoing process. Knowledge and understanding of the experience of OTC codeine misuse and recovery is critical to inform and tailor approaches to prevention and intervention. The findings suggest that strategies to improve the management of pain, stress and mental health, raise self-awareness of problematic use and potential for self-change, and increase social and web-based supports, should be considered when designing health policy initiatives that aim to reduce misuse.


[Catheter Isolation of Pulmonary Veins in a Patient With Paroxysmal Atrial Fibrillation After Repair of Interventricular Septum With a Xeno-Pericardial Patch].
Catheter radiofrequency ablation of focal atrial fibrillation was successfully performed in a patient after closure of interventricular septal defect with a xeno-pericardial patch and plastic of tricuspid valve. The case demonstrates feasibility of carrying out such interventions under intracardiac echocardiographic guidance in patients with disturbed anatomy and complicated access to the left atrium.


Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases.
The importance of histone methylation in gene regulation was suggested over 40 years ago. Yet, the dynamic nature of this histone modification was recognized only recently, with the discovery of the first histone demethylase nearly five years ago. Since then, our insight into the mechanisms, structures, and macromolecular complexes of these enzymes has grown exponentially. Overall, the evidence strongly supports a key role for histone demethylases in eukaryotic transcription and other chromatin-dependent processes. Here, we examine these and related facets of histone demethylases discovered to date, focusing on their biochemistry, structure, and enzymology.


Hemispheric asymmetry for global and local processing: language is less important than one might think.
There have been consistent findings of hemispheric asymmetry in global/local processing, in both neurological patients and the neurologically normal. However, with one exception, these studies have used purely linguistic stimuli (letters made up of letters). The present study investigates lateral asymmetry for processing of global/local objects with less "linguistic" properties (e.g., letters made up of shapes, and shapes made up of letters) using a change detection paradigm. In each case the classic pattern of hemispheric asymmetry was found. These results are discussed in the context of the relative importance of hemispheric asymmetry for both global/local and linguistic information.


[Treatment of spasmodic torticollis by differentiation of symptoms and signs].
Spasmodic torticollis belongs to local dysmyotonia and it is a difficult and complicated disease with unknown pathogenic factor. The clinical effects of medication and operation on it are not satisfactory and there is not a safe and effective therapy for this disease at home and abroad. The authors apply flexibly the theory of treatment based on syndrome differentiation and fully exert the advantages of TCM to analyze the disease from pathogenic factor, disease and syndrome, pathogenesis and so on, and originally create acupuncture at "Wu Xin Xue" for treatment of this disease with Kaiqiao Shunjin method (resuscitation and regulating muscle) as main, clinically attaining satisfactory therapeutic effect.


Purification and characterization of surface-associated proteins from adult Haemonchus contortus.
Extrinsic radioiodination experiments have shown that male and female adults of Haemonchus contortus (BPL strain) express a stage-specific set of surface-associated proteins with apparent molecular mass values of 30, 58, 81, and 143 kDa. A quantitatively different pattern of iodinated surface proteins is expressed by adults of the PPR strain of H. contortus, whereas the pattern of iodinated proteins expressed by Haemonchus similis is qualitatively distinct (38, 68, and 121 kDa). The 58-, 81-, and 143-kDa proteins of the BPL strain are glycosylated, whereas the 30-kDa protein is not. The binding of wheat germ agglutinin to the surface glycoproteins was inhibited by the trimer of N-acetylglucosamine (N,N,N-triacetylchitotroise) but not by the monosaccharide, indicating the presence of chitin-like homopolymers. The carbohydrate portion of the 58-kDa protein is N-linked and accounts for 30% of its apparent mass. Under nonreducing conditions, the 58-kDa glycoprotein forms a high molecular mass polymer that is unable to penetrate a 10% acrylamide gel. The 143- and 81-kDa surface glycoproteins were not hydrolyzed by either N- or O-glycanase, indicating unusual modifications to the saccharide-linkage and rendering it resistant to glycosidase digestion. The 30-, 58-, and 143-kDa purified surface proteins produced distinct peptide maps with Staphylococcus aureus V8 protease.


An assessment of hypercapnia-induced elevations in regional cerebral perfusion during combined orthostatic and heat stresses.
We investigated that the effects of hypercapnia-induced elevations in cerebral perfusion during a heat stress on global cerebrovascular responses to an orthostatic challenge. Seven volunteers completed a progressive lower-body negative pressure (LBNP) challenge to presyncope during heat stress, with or without breathing a hypercapnic gas mixture. Administration of the hypercapnic gas mixture increased the partial pressure of end-tidal CO2 greater than pre-heat stress alone, and increased both internal carotid artery (ICA) and vertebral artery (VA) blood flows (P < 0.05). During LBNP, both ICA and VA blood flows with the hypercapnic gas mixture remained elevated relative to the control trial (P < 0.05). However, at the end of LBNP due to pre-syncopal symptoms, both ICA and VA blood flows decreased to similar levels between trials. These findings suggest that hypercapnia-induced cerebral vasodilation is insufficient to maintain cerebral perfusion at the end of LBNP due to pre-syncope in either the anterior or posterior vascular beds.


Prosthecobacter fluviatilis sp. nov., which lacks the bacterial tubulin btubA and btubB genes.
Leptothrix cholodnii is a sheathed bacterium often found in metal-rich and oligotrophic aquatic environments. A bacterial strain that is able to degrade the NaOH-treated sheath of L. cholodnii was isolated. The isolate was a Gram-negative, aerobic and prosthecate bacterium. The optimum growth temperature and pH were 30 degrees C and pH 7.0, respectively. The DNA G+C content was 62.9 mol%. The major respiratory quinone was MK-6. A phylogenetic analysis based on the 16S rRNA gene indicated that the isolate is a member of the genus Prosthecobacter. The nearest relative was the type strain of Prosthecobacter vanneervenii, with a similarity of 97.1 %. However, the isolate does not possess the bacterial tubulin genes, btubA and btubB, unique to known species of the genus Prosthecobacter. It is proposed that the isolate represents a novel species, Prosthecobacter fluviatilis sp. nov. The type strain is HAQ-1(T) (=JCM 14805(T) =KACC 12649(T) =KCTC 22182(T)).


Plasma levels of TNF-alpha soluble receptors correlate with outcome in human falciparum malaria.
Plasma from immune (residents of malaria infested areas) and non immune (European travellers) patients suffering from cerebral malaria, severe or mild, was analyzed for the presence of soluble tumor necrosis factor receptors. On admission of the subjects, sTNF-R55 and sTNF-R75 levels were significantly elevated in all groups and correlated with TNF-alpha. Except for sTNF-R55 whose levels were higher in severe than in mild malaria, no correlation was observed between soluble receptors and clinical status. Nevertheless, sTNF-R55 and sTNF-R75 were significantly more elevated in patients who died (10.7 +/- 2.3 ng/ml and 94.9 +/- 31 ng/ml, respectively) than in those surviving (5.5 +/- 0.4 ng/ml and 37.4 +/- 5.4 ng/ml respectively). A marked correlation was observed between soluble receptors levels and some biological markers of gravity like creatinine, urea, and bilirubin. In 13 non immune patients, circulating soluble receptors levels decreased significantly after 7 days when clinical and biological malaria features had disappeared, but TNFsR75 remained above normal levels. After a fortnight of treatment in 17 immune patients, sTNF-R55 and sTNF-R75 remained elevated. However, the ratios of TNF-alpha/s TNF-R55 and 75 were not higher in the cases of cerebral malaria or fatal outcome. Further studies are required to determine if elevated levels of sTNF-R55 and sTNF-R75 are beneficial, due to the inhibition of TNF-alpha or whether they are detrimental since they stabilize this deleterious cytokine.


Effect of fibroin sponge coating on in vivo performance of knitted silk small diameter vascular grafts.
Vascular grafts under 5 mm or less in diameter are not developed due to a problem caused by early thrombus formation, neointimal hyperplasia, etc. Bombyx mori silk fibroin (SF) which has biodegradability and tissue infiltration is focused as tube and coating material of vascular grafts. Coating is an important factor to maintain the strength of the anastomotic region of vascular grafts, and to prevent the blood leak from the vascular grafts after implantation. Therefore, in this research, we focused on the SF concentration of the coating solution, and tissue infiltration and remodeling were compared among each SF concentration. Silk poly (-ethylene) glycol diglycidyl ether (PGDE) coating with concentrations of 1.0%, 2.5%, 5.0%, and 7.5% SF were applied for the double-raschel knitted small-sized vessel with 1.5 mm diameter and 1cm in length. The grafts were implanted in the rat abdominal aorta and removed after 3 weeks or 3 months. Vascular grafts patency was monitored by ultrasound, and morphological evaluation was performed by histopathological examination. SF concentration had no significant effects on the patency rate. However, tissue infiltration was significantly higher in the sample of 2.5% SF in 3 weeks, and 1.0% and 2.5% SF in 3 months. Also, in comparison of length inside of the graft, stenosis were not found in 3 weeks, however, found with 5.0% and 7.5% in 3 months. From these results, it is clear that 2.5% SF coating is the most suitable concentration, based on the characteristics of less stenosis, early tissue infiltration, and less neointimal hyperplasia.


Localization of beta-adrenergic receptors on differentiated cells of the central nervous system in culture.
Hypothalamic neurons and cortical protoplasmic (type 1) astrocytes in dissociated cultures of rat brain express binding sites for antibodies specific for epitopes related to the beta-adrenergic receptor. Undifferentiated glial progenitor cells of the rat optic nerve do not detectably bind these antibodies, but both of the progeny [oligodendroglia and process-bearing (type 2) astrocytes] express immunologically identified beta-adrenergic receptors. Levels of receptor expression are variable: not all cells of each type express receptors nor is expression uniform on a given cell. The data suggest that cells of the central nervous system express beta-adrenergic receptors but that levels of expression may be determined by the differentiated state of the cells.


The state of school health: a Bay of Plenty study.
A health survey was carried out on 131 primary school children in the Bay of Plenty. Ninety children had no health defect. Inadequate hearing was the commonest defect and was more prevalent in Maoris. In all 55 health defects were found of which 18 were newly detected. There was a total absence of iron deficiency anaemia.


If nursing associates are here to stay, get involved.
Like the idea or not - and professional opinion appears to be divided - nursing associates are coming. It was announced last week that about 1,000 students will be enrolled on courses next year, before starting work at a selection of test sites that are yet to be identified.


Interaction of P-fimbriated Escherichia coli with human meconium.
The ability of Escherichia coli with different receptor specificities to interact with meconium was studied. E. coli strains expressing P-fimbriae, specific for Gal alpha 1-4Gal beta-containing receptors, were agglutinated by meconium at high titres. This reaction was inhibited by globotetraosylceramide. The attachment of P-fimbriated E. coli to human colonic epithelial cells of the HT-29 cell line was inhibited by meconium. Some type 1 fimbriated strains were agglutinated by meconium, but the agglutination was rarely blocked by methyl alpha-D-mannoside. The attachment by type 1 fimbriated strains to HT-29 cells was reduced by meconium only in some cases. These results suggest that meconium interacts with the P-fimbriae of E. coli, in a way that may influence bacterial colonization of the neonatal intestine.


Imaging and histological appearance of pleomorphic hyalinizing angiectatic tumors: A case series and literature review.
Pleomorphic hyalinizing angiectatic tumors (PHATs) are rare mesenchymal soft tissue tumors of uncertain lineage and intermediate malignancy. The present study assesses two cases of PHAT and discusses the histological and immunophenotypical features, as well as the imaging appearance of these tumors on ultrasound, computed tomography (CT), magnetic resonance imaging and positron emission tomography/CT scans. The current study also reviews the literature and discusses the clinical management of these tumors. Wide local excision with tumor free margins is the current recommended treatment for PHAT. Surgical excision may be combined with low-dose radiation to reduce the risk of local recurrence. Patients should be followed up with serial imaging, as PHAT lesions tend to recur locally.


Early diagnosis of invasive candidiasis and rapid evaluation of antifungal therapy by combined use of conventional chromogenic limulus test and a newly developed endotoxin specific assay.
Since beta-1,3-glucan is a common component of fungal cell wall, its detection might be useful in diagnosing invasive candidiasis. Not only endotoxin but beta-1,3-glucan activates proclotting enzyme contained in a conventional chromogenic limulus test (CCLT). Endotoxin activates this enzyme through factor C, while the beta-1,3-glucan activates through factor G. Since endotoxin specific test (EST) contains factor C, endotoxin would be quantified. By subtracting EST value from CCLT value, beta-1,3-glucan would be quantified. We named this value Fungal Index (FI), and examined if it actually reflects the candidal infection. Ninety-two patients were tested for CCLT and EST prospectively. FI increased significantly in candidal infection (p less than 0.05) but remained low in GNR infection. Moreover, FI increased proportionally to the severity of candidal infection. Elevated FI decreased when antifungal therapy was successful. Thus FI was a useful index not only in the diagnosis of invasive candidiasis but also in the evaluation of antifungal therapy.


Leptin and Adiponectin in the HIV Associated Metabolic Syndrome: Physiologic and Therapeutic Implications.
Leptin and adiponectin represent two newly discovered adipose tissue derived hormones with important roles in energy homeostasis and insulin resistance. Their interrelations with the manifestations of the HIV associated metabolic syndrome and specific somatomorphic changes i.e. fat redistribution is reviewed. A synopsis of published studies is presented and the potential role of leptin and adiponectin is discussed. We have described an association of the HIV metabolic syndrome with a state of reduced insulin sensitivity due to adiponectin deficiency. The metabolic syndrome is also accompanied by leptin deficiency in lipoatrophic subjects and possibly by a leptin resistance state in lipohypertrophic patients. Adiponectin and / or leptin therapy in a manner similar to other leptin deficiency states may assist in the future management of such patients.


The Drive For Self-Assertion And The Reality Principle In A Patient With Malignant Pleural Mesothelioma: The History of Giulia.
Life in a contaminated environment is often marked by a cumulative psychological trauma that exhibits a variety of social-environmental aspects. This is why I suggested a psychotherapeutic group intervention for the population of Casale Monferrato, a municipality in Northern Italy that is sadly renowned for asbestos-related events and the high mortality rate of its inhabitants. Groupality appears to show the point of contact between psyche and soma, while also promoting the birth of a more realistic approach to the various levels of suffering and their configuration. The multifamily approach seemed to be the most adequate to elaborate the feelings of rage and fear that are concurrent with the aerial contagion. In the "long wave" of group work we have learned to work with participants as well as with empty chairs, the ghosts of the dead: live traces in the mind. Whereas the mind recovers the possibility of entering into a dialogue with the feelings connected to the trauma, without bypassing them towards actions that are apparently more assertive of one's sense of Ego, the will of conciliation can reactivate a thought that is oriented towards the plane of reality.


Optimising diagnostics to discriminate complicated from uncomplicated appendicitis: a prospective cohort study protocol.
Growing evidence is showing that complicated and uncomplicated appendicitis are two different entities that may be treated differently. A correct diagnosis of the type of appendicitis is therefore essential. The Scoring system of Appendicitis Severity (SAS) combines clinical, laboratory and imaging findings. The SAS rules out complicated appendicitis in 95% (negative predictive value, NPV) and detects 95% (sensitivity) of patients with complicated appendicitis in adults suspected of acute appendicitis. However, this scoring system has not yet been validated externally. In this study, we aim to provide a prospective external validation of the SAS in a new cohort of patients with clinical suspicion of appendicitis. We will optimise the score when necessary. The SAS will be validated in 795 consecutive adult patients diagnosed with acute appendicitis confirmed by imaging. Data will be collected prospectively in multiple centres. The predicted diagnosis based on the SAS score will be compared with the combined surgical and histological diagnosis. Diagnostic accuracy for ruling out complicated appendicitis will be calculated. If the SAS does not reach a sensitivity and NPV of 95% in its present form, the score will be optimised. After optimisation, a second external validation will be performed in a new group of 328 patients. Furthermore, the diagnostic accuracy of the clinical perspective of the treating physician for differentiation between uncomplicated and complicated appendicitis and the patient's preferences for different treatment options will be assessed. Ethical approval was granted by the Amsterdam UMC Medical Ethics Committee (reference W19_416 # 19.483). Because of the observational nature of this study, the study does not fall under the scope of the Medical Research Involving Human Subjects Act. Results will be presented in peer-reviewed journals. This protocol is submitted for publication before analysis of the results.


A randomised controlled trial on suture materials for skin closure at caesarean section: Do wound infection rates differ?
Objective.The aim of this study was to determine wound complication rates following the use of suture materials and staples for skin closure at caesarean section (CS). A randomised, controlled, prospective study was undertaken. Results. A total of 1 100 women was assigned randomly into 3 groups: polyglycolic acid (PGA) suture group (N=361), skin staple (SS) group (N=373) and nylon suture group (N=366). The overall wound infection rate was 7%. There was no difference in respect of number of patients, age, parity and gestation between the study groups. Those who had nylon sutures as opposed to PGA sutures were 9.5 times more likely to experience wound infection (p=0.055). Women who had SS were at 6.93 times higher risk of wound infection than those who had PGA sutures (p=0.014). Other factors influencing wound infection rates included: rupture of membranes >12 hours were 13.7 times (95% confidence interval (CI) 3.9 - 47.9, p<0.0001) more likely to have wound infection than those with rupture of membranes <12 hours. For every 1-minute increase of surgery duration, the risk of infection increased 1.094 times (95% CI 1.046 - 1.145; p<0.0001). HIV-infected women were 53.4% less likely to develop wound infection than their uninfected counterparts (odds ratio 0.466, 95% CI 0.238 - 0.913; p=0.026). As the time period of observation increased from baseline to day 3 and from day 3 to day 10, wound infection risk increased by 35 times (95% CI 8.155 - 150.868; p<0.001). Conclusion.The use of SS for CS wound closure is associated with a significantly greater risk of wound infections. SS for wound closure at CS is not recommended for use in South African district hospitals.


Perforation of the colon in renal homograft recipients. A report of 11 cases and a review of the literature.
Colon perforation in renal transplant recipients is a potentially lethal condition that is amenable to appropriate medical and surgical treatment. The 11 cases seen at the Cleveland Clinic (incidence 1.1% of all renal transplant patients) and previous reports in the literature have been reviewed. The pathogenesis is related to a high incidence of diverticular disease in patients with polycystic kidneys and/or chronic renal failure, the effects of long-term immunosuppression, and the transplant procedure itself. The high mortality of this condition (61% overall) is related to the effects of immunosuppression on the response to sepsis and the surgical procedure used. Mortality has fallen from 88% (1970-1974) to 53% (1975-1979), and there are indications that it is continuing to fall. All four cases operated on here since 1980 have survived, giving a total operative mortality of 2/6, and all have maintained excellent allograft function. A high clinical index of suspicion, prompt exteriorization of the perforated colon, reduction of immunosuppression to minimal levels, and effective antibiotic coverage have all contributed to the declining mortality.


Analysis of crystallin-crystallin interactions by surface plasmon resonance.
The mechanism of aggregation and insolubilization of lens proteins was examined based on the kinetics of crystallin-crystallin interaction determined by the surface plasmon resonance method on a BlAcore system. Lens proteins are composed mainly of three types crystallins, alpha-, beta-, and gamma-crystallin. The present study indicated that alpha-crystallin shows marked self-interaction. Furthermore, this interaction was shown to be due to alphaA-crystallin, which is a subunit of alpha-crystallin. It was also clarified that this mutual interaction of aA-crystallin decreases abruptly after the age of 20 years. On the other hand, it was assumed that alphaB-crystallin, the other subunit of alpha-crystallin, may play an important role in interactions with beta- and gamma-crystallin, while a-crystallin shows chaperone-like activity. Based on the present results, alphaA- and betaB-crystallin may play different roles when alpha-crystallin displays chaperone-like activity, and also that the decreased chaperone-like activity of a-crystallin may finally result in cataract formation following aggregation and insolubilization of lens proteins.


Point of no return for improvement of cartilage quality indicated by dGEMRIC before and after weight loss in patients with knee osteoarthritis: a cohort study.
Background It has been demonstrated that weight loss improves symptoms in obese subjects with knee osteoarthritis (KOA). A parallel change in cartilage morphology remains to be demonstrated. Purpose To demonstrate a parallel change in cartilage morphology. Material and Methods Obese patients with KOA were examined before and after weight loss over 16 weeks. Target knee joints were radiographically assessed by the Kellgren/Lawrence grading (KLG) system. Patients with KLG-1 and 2 changes in the lateral compartment were included. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was performed using intra-articular contrast. Results Nine patients with lateral KLG-1 and ten patients with lateral KLG-2 were studied. There were no group differences regarding the lateral compartment baseline dGEMRIC T1 values: median = 497 ms (KLG-1) and 533 ms (KLG-2) ( P = 0.12), or regarding reduction in body mass index (BMI) after 16 weeks: 12.8% versus 11.4% ( P = 0.74). In the KLG-1 group, several cases of increased dGEMRIC T1 values were seen and median value decreased significantly less than in KLG-2 group (15 ms versus 41 ms, P = 0.03) after weight loss. Conclusion Improvement of cartilage quality, assessed with dGEMRIC, after weight loss might be possible in early stage KOA (KLG-1), but not in later stage KOA (KLG-2). The results may suggest a point of no return for improvement of cartilage quality that should be tested in larger trials.


Psycho-educational and social interventions provided for orphans and vulnerable children at a community-based organisation in Soweto, South Africa.
This qualitative study explored the psycho-educational and social interventions provided for orphans and vulnerable children (OVC) in a community-based organisation (CBO) in Soweto, South Africa. The study involved 12 OVC (males = 40%, and females = 60%; aged 10 to 18 years). Data was collected using individual interviews, focus group discussions, and autobiographies. The thematically analysed data revealed that the OVC received psychological interventions through mentorship and peer-group support in the CBO. Educational interventions included the provision of school uniforms and educational materials, as well as sponsorship of tuition, sports and excursion fees. Academic track records presented a challenge, however, which was attributed to the enormous numbers of OVC under the care of the CBO. It was further established that social interventions were addressed by empowering the OVC with life skills and providing economic support for their families, specifically to pay rent and provide meals. The major contributions of this study are to note the importance of the CBO in addressing issues related to the lack of counselling, the stigmatisation of OVC by community members and the need for empowerment of their families by providing income-generating activities. The information obtained is useful in opening up avenues for interested parties to further explore the effectiveness of these psycho-educational and social interventions in improving the lives of OVC in society.


System size dependence of the diffusion coefficient in a simple liquid.
An equation to estimate the system size dependence of the self-diffusion coefficient of a tagged particle moving in a simple fluid is given using linear-response theory and linearized hydrodynamics. Estimates made by the equation are compared with the results of the molecular dynamics simulation for a hard-sphere fluid at two densities, rhosigma(3) approximately 0.88 and 0.47, where sigma is the hard-sphere diameter. Good agreement between theory and simulation is obtained at the higher density. At the lower density, the agreement becomes poorer, but it is improved by taking into account the diffusion effect of the tagged particle. The equation gives the same diffusion coefficient for the infinite system as that obtained by taking into account the long-time tail contribution of the velocity autocorrelation function [B. J. Alder, D. M. Gass, and T. E. Wainwright, J. Chem. Phys. 53, 3813 (1970)]. When the tagged particle has a larger mass than the fluid particles, the equation presented here gives the better estimates. It is confirmed by the molecular dynamics calculation.


Divergent neuropeptide evolutionary drifts between American and Australian marsupials.
Present-day marsupials, which are supposed to have arisen from a single stem diverging from the placental stem some 130 million years ago, exist only in the American and Australian continents. Comparison of the homologous genes and their protein products, which evolved under different environmental conditions, may provide arguments for either selective or neutral evolution. In contrast to Australian Macropodidae, which have peculiar neurohypophysial peptides, namely mesotocin and two pressor peptides, lysine vasopressin and phenypressin, the South American oppossum, Didelphis marsupialis, has oxytocin, lysine vasopressin, and arginine vasopressin. Because placental mammals have oxytocin and usually arginine vasopressin, and nonmammalian tetrapods have mesotocin and arginine vasotocin, it is assumed that (1) selective change of arginine vasotocin into arginine vasopressin occurred in mammalian ancestors and a subsequent gene duplication in the marsupial line gave rise to two pressor peptides with divergent neutral drifts in American and Australian groups, and (2) mesotocin of nonmammalian tetrapods has been preserved in Australian marsupials and reclaimed for milk-ejecting function whereas it has been converted into oxytocin in South American oppossums. The change of mesotocin into oxytocin seems neutral rather than selective.


Domains of retinoid signalling and neurectodermal expression of zebrafish otx1 and goosecoid are mutually exclusive.
Retinoid signalling plays an important role in embryonic pattern formation. Excess of retinoic acid during gastrulation results in axial defects in vertebrate embryos, suggesting that retinoids are involved in early anteroposterior patterning. To study retinoid signalling in zebrafish embryos, we developed a novel method to detect endogenous retinoids in situ in embryos, using a fusion protein of the ligand inducible transactivation domain of a retinoic acid receptor and a heterologous DNA binding domain. Using this method, we show that retinoid signalling is localized in zebrafish embryos in the region of the embryonic shield, and towards the end of gastrulation in a posterior dorsal domain. To investigate the relationships between the spatial distribution of retinoid signalling and the regulation of retinoid target genes, we studied the downregulation by retinoic acid of two genes expressed in anterior regions of the embryo, goosecoid and otx1. These experiments show that expression of both genes is strongly downregulated in the anterior neurectoderm of zebrafish embryos treated with retinoic acid, whereas mesendodermal expression is only mildly affected. Interestingly, a significant downregulation of goosecoid expression by retinoic acid was observed only during midgastrulation but not in earlier stages. In agreement with these results, spatial expression of goosecoid and otx1 does not overlap with the region of retinoid signalling in the late gastrula. Our data support the hypothesis that a localized retinoid signal is involved in axial patterning during early development, at least in part through the repression of anterior genes in posterior regions of the embryo. Furthermore, our data suggest that the action of retinoids is spatially as well as temporally regulated in the developing embryo.


Notch signaling regulates neuroepithelial stem cell maintenance and neuroblast formation in Drosophila optic lobe development.
Notch signaling mediates multiple developmental decisions in Drosophila. In this study, we have examined the role of Notch signaling in Drosophila larval optic lobe development. Loss of function in Notch or its ligand Delta leads to loss of the lamina and a smaller medulla. The neuroepithelial cells in the optic lobe in Notch or Delta mutant brains do not expand but instead differentiate prematurely into medulla neuroblasts, which lead to premature neurogenesis in the medulla. Clonal analyses of loss-of-function alleles for the pathway components, including N, Dl, Su(H), and E(spl)-C, indicate that the Delta/Notch/Su(H) pathway is required for both maintaining the neuroepithelial stem cells and inhibiting medulla neuroblast formation while E(spl)-C is only required for some aspects of the inhibition of medulla neuroblast formation. Conversely, Notch pathway overactivation promotes neuroepithelial cell expansion while suppressing medulla neuroblast formation and neurogenesis; numb loss of function mimics Notch overactivation, suggesting that Numb may inhibit Notch signaling activity in the optic lobe neuroepithelial cells. Thus, our results show that Notch signaling plays a dual role in optic lobe development, by maintaining the neuroepithelial stem cells and promoting their expansion while inhibiting their differentiation into medulla neuroblasts. These roles of Notch signaling are strikingly similar to those of the JAK/STAT pathway in optic lobe development, raising the possibility that these pathways may collaborate to control neuroepithelial stem cell maintenance and expansion, and their differentiation into the progenitor cells.


Palladium-Catalyzed β-C(sp3)-H Arylation of Silyl Prop-1-en-1-ol Ethers with Aryl Halides: Entry to α,β-Unsaturated Ketones.
A palladium(0)-catalyzed β-C(sp3)-H arylation of silyl prop-1-en-1-ol ethers with aryl halides for the synthesis of α,β-unsaturated ketones is presented. In contrast to the reported β-C(sp3)-H arylation of ketones, the chemoselectivity of this current method relies on the Pd(0) catalytic systems and reaction temperatures: While using the Pd(dba)2/DavePhos/KF system at 80 °C resulted in β-C(sp3)-H monoarylation to produce β-monoarylated α,β-unsaturated ketones, harnessing the Pd(OAc)2/t-Bu XPhos/K2HPO4 system at 110 °C induced β-C(sp3)-H diarylation to afford β,β-diarylated α,β-unsaturated ketones. The method provides a versatile route that uses readily available ketone-derivatized α-nonsubstituted silyl prop-1-en-1-ol ethers as the alkene sources and is characterized by a good functional group compatibility, a broad substrate scope, and an excellent selectivity.


Subdural empyema in chronic suppurative otitis media: a rarely encountered complication.
Here the authors describe the case of a 23-year-old young woman with life-threatening focal suppurative intracranial collection with brain compression secondary to long forgotten chronic suppurative otitis media. With the development and availability of broad-spectrum antibiotics and their timely usage, cases of suppurative otitis media are a rarity in the current times.


Cytotoxic, antibacterial and antioxidant activities of extracts of the bark of Melia azedarach (China Berry).
Nature provides a variety of drugs and medicinal agents derived from plants. This study was conducted to determine antimicrobial, antioxidant and cytotoxic activities of extracts of Melia azedarach bark with methanol/water (9:1 v/v), chloroform, butanol, hexane, water and ethyl acetate. For the determination of the antimicrobial activities, the agar well diffusion method was employed. Cytotoxicity was studied by brine shrimp lethality assay; antioxidant activities were measured using 1,1-diphenyl-2-picrylhydrazyl. The chloroform extract was active against Enterobacter aerogenes and Proteus mirabilis, the ethyl acetate extract had highest antibacterial spectrum against Pseudomonas aeruginosa, the n-hexane extract had highest inhibition against E. aerogenes, the aqueous extract showed highest activities against P. mirabilis, the butanol fraction showed highest activities against E. aerogenes and the methanolic extract was highly active against P. mirabilis.


Functional connectivity analysis in EEG source space: The choice of method.
Functional connectivity (FC) is among the most informative features derived from EEG. However, the most straightforward sensor-space analysis of FC is unreliable owing to volume conductance effects. An alternative-source-space analysis of FC-is optimal for high- and mid-density EEG (hdEEG, mdEEG); however, it is questionable for widely used low-density EEG (ldEEG) because of inadequate surface sampling. Here, using simulations, we investigate the performance of the two source FC methods, the inverse-based source FC (ISFC) and the cortical partial coherence (CPC). To examine the effects of localization errors of the inverse method on the FC estimation, we simulated an oscillatory source with varying locations and SNRs. To compare the FC estimations by the two methods, we simulated two synchronized sources with varying between-source distance and SNR. The simulations were implemented for hdEEG, mdEEG, and ldEEG. We showed that the performance of both methods deteriorates for deep sources owing to their inaccurate localization and smoothing. The accuracy of both methods improves with the increasing between-source distance. The best ISFC performance was achieved using hd/mdEEG, while the best CPC performance was observed with ldEEG. In conclusion, with hdEEG, ISFC outperforms CPC and therefore should be the preferred method. In the studies based on ldEEG, the CPC is a method of choice.


Identification and characterization of mutations underlying Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA).
Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA; MPS IIIA) is caused by a deficiency of the lysosomal enzyme haparan N-sulphatase (NS). The genomic DNA segments of the NS gene from two Chinese patients with MPS IIIA were amplified by polymerase chain reaction, followed by DNA sequencing to study the molecular lesions. Four mutations (i.e. N42K, D235N, P293S and R377C) and five polymorphisms (i.e. IVS2-72A --> G, IVS2-26T --> C, IVS5+17C --> T, IVS5-37GC --> CTGT and R456H) were identified. Transfection of COS-7 cells with cDNA mutagenized to the corresponding mutations did not yield active enzyme, demonstrating the deleterious nature of the mutations. Western blot analysis revealed a 62-kDa precursor and 56-kDa mature forms for cells transfected with wild-type and polymorphic R456H enzymes. For cells transfected with mutant enzymes, the reduction in precursor and mature forms suggests an increased degradation of the mutant enzymes. The polymorphic DNA haplotype of the NS gene was analysed in 52 unrelated subjects. All five polymorphisms were in Hardy-Weinberg equilibrium. The strong non-random association among the five polymorphisms suggests little or no recombination in the NS gene.


Melatonin promotes adventitious root regeneration in in vitro shoot tip explants of the commercial sweet cherry rootstocks CAB-6P (Prunus cerasus L.), Gisela 6 (P. cerasus × P. canescens), and MxM 60 (P. avium × P. mahaleb).
The objectives of this study were to test the effects of melatonin (N-acetyl-5-methoxytryptamine), a natural compound of edible plants on the rooting of certain commercial sweet cherry rootstocks. Shoot tip explants from previous in vitro cultures of the cherry rootstocks CAB-6P (Prunus cerasus L.), Gisela 6 (P. cerasus × P. canescens), and M × M 60 (P. avium × P. mahaleb) were included in the experiment. The effect of indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA) alone or in combination with melatonin was tested concerning their rooting potential. Seven concentrations of melatonin (0, 0.05, 0.1, 0.5, 1, 5, and 10 μM) alone or in combination with 5.71 μM of IAA or 4.92 μM of IBA were tested. For each rootstock, 21 treatments were included. The explants were grown in glass tubes containing 10 mL of substrate. The parameters measured include rooting percentage, number of roots per rooted explant, root length, and callus formation. The data presented in this study show that melatonin has a rooting promoting effect at a low concentration but a growth inhibitory effect at high concentrations. In the absence of auxin, 1 μM melatonin had auxinic response concerning the number and length of roots, but 10 μM melatonin was inhibitory to rooting in all the tested rootstocks. The final conclusion of this experiment is that exogenously applied melatonin acted as a rooting promoter and its action was similar to that of IAA.


Postcardiotomy syndrome following transvenous pacemaker insertion.
We describe a case of postcardiotomy syndrome following permanent pacemaker insertion. A 79-year-old woman presented with complete heart block. Following temporary pacing, a dual chamber permanent pacemaker was inserted. Two weeks later she developed fevers and malaise with an acute rise in inflammatory markers. After systemic infection had been carefully excluded, she was commenced on prednisolone with immediate benefit. Prednisolone was withdrawn over 2 months without recurrence of symptoms. Although the postcardiotomy syndrome is rare following transvenous pacemaker insertion it should be considered in the differential diagnosis of fevers and malaise after implantation.


Three-dimensional morphology of GaP-GaAs nanowires revealed by transmission electron microscopy tomography.
We have investigated the morphology of heterostructured GaP-GaAs nanowires grown by metal-organic vapor-phase epitaxy as a function of growth temperature and V/III precursor ratio. The study of heterostructured nanowires with transmission electron microscopy tomography allowed the three-dimensional morphology to be resolved, and discrimination between the effect of axial (core) and radial (shell) growth on the morphology. A temperature- and precursor-dependent structure diagram for the GaP nanowire core morphology and the evolution of the different types of side facets during GaAs and GaP shell growth were constituted.


Nipple aspirate fluid expression of urokinase-type plasminogen activator, plasminogen activator inhibitor-1, and urokinase-type plasminogen activator receptor predicts breast cancer diagnosis and advanced disease.
Tumor expression of urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA receptor (uPAR) are breast cancer prognostic factors. Less is known about their usefulness in breast cancer diagnosis. Nipple aspirate fluid (NAF) is secreted into the breast duct and collected noninvasively, making it potentially useful both in breast cancer diagnosis and prognosis. We determined the association of uPA, PAI-1, and uPAR levels in NAF with breast cancer (1) detection and (2) advanced disease. A total of 88 NAF specimens were collected from women with or without breast cancer, and uPA, PAI-1, and uPAR expression were measured by enzyme-linked immunosorbent assay. uPA and uPAR were independent predictors of cancer presence; uPAR was also an independent predictor of advanced disease stage. Higher PAI-1 expression in breast cancer that was found with univariate analysis was not observed after logistic regression was applied. NAF evaluation of uPA, uPAR, and, perhaps, PAI-1 (significant only in univariate analysis) may provide useful breast cancer diagnostic and prognostic information.


MiR-199a-5p suppresses non-small cell lung cancer via targeting MAP3K11.
MicroRNAs (miRNAs) comprise a class of short, non-coding RNAs that directly target 3'UTR of mRNA, causing subsequent degradation or suppression of translation. Here, we verified that miR-199a-5p was significantly down-regulated in mouse NSCLC tissues and human patient samples. To further study the function of miR-199a-5p, lentivirus system was adopted to construct stably over-expressing miR-199a-5p A549, SPC-A1 and H1299 cell lines. Then, miR-199a-5p played a tumor suppression role via directly targeting MAP3K11 gene in non-small cell lung cancer (NSCLC). Elevated miR-199a-5p suppressed cell proliferation and arrested cell cycle in G1 phase. We found that MAP3K11 was negatively correlated with miR-199a-5p in NSCLC patient tissues and mouse xenograft tumors. Our results suggest that miR-199a-5p together with its target gene MAP3K11 is a key factor and constitutes a complicated regulation network in NSCLC.