Mechanistic study on the inhibition of Staphylococcus epidermidis biofilm by agrC-specific binding polypeptide.
Considering the wide-spread misuse of antibiotics, the development of new antibacterial drugs may effectively prevent the emergence of antibiotic resistance in bacteria. The understanding of the mechanism underlying the Staphylococcus epidermidis agrC-specific binding polypeptide-mediated inhibition of S. epidermidis biofilm formation may supply ideas for the development of new antibacterial drugs. S. epidermidis cells were cultured with different concentrations (0, 100, 200, 400, 800, and 1,600 µg/mL) of agrC-specific binding polypeptide (N1) and blank (N0). Crystal violet staining was performed to test the formation of biofilms and to determine the best concentration of agrC-specific binding polypeptides, and the bacterial inhibitory concentration was also determined. At different time points (6, 12, 18, 24, and 30 h), XTT assay was used to measure bacterial viability, and the real-time quantitative polymerase chain reaction was performed to measure the expression of atlE, icaA, fbe, and icaR genes. The sulfuric acid-phenol method was used to determine polysaccharide intercellular adhesin (PIA) levels. The biofilm formation ability of S. epidermidis was the lowest after treatment with 800 µg/mL agrC-specific binding polypeptide. After 6 h of culture, agrC-specific binding polypeptide upregulated the expression of atlE, icaA, fbe, and icaR and increased the bacterial viability. However, the polypeptide downregulated the expression of atlE, icaA, fbe, and icaR and inhibited S. epidermidis growth and PIA formation after 12 h of culture. Although agrC-specific binding polypeptide upregulated the expression of atlE, icaA, fbe, and icaR after 18 h, they inhibited bacterial growth and PIA formation. Thus, agrC-specific binding polypeptide could downregulate the expression of atlE, icaA, fbe, and icaR and inhibit PIA formation by S. epidermidis after 12 h, demonstrating its transient inhibitory effects on the biofilm formation ability of S. epidermidis. Its effective concentration was 800 µg/mL.


Phospholipase C delta 1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E-CDK2 activity.
In the present study, we examined the role of PLC delta 1 (phospholipase C delta 1) in the regulation of cellular proliferation. We demonstrate that RNAi (RNA interference)-mediated knockdown of endogenous PLC delta 1, but not PLC beta 3 or PLC epsilon, induces a proliferation defect in Rat-1 and NIH 3T3 fibroblasts. The decreased proliferation was not due to an induction of apoptosis or senescence, but was associated with an approx. 60% inhibition of [(3)H]thymidine incorporation. Analysis of the cell cycle with BrdU (bromodeoxyuridine)/propidium iodide-labelled FACS (fluorescence-activated cell sorting) demonstrated an accumulation of cells in G(0)/G(1)-phase and a corresponding decrease in cells in S-phase. Further examination of the cell cycle after synchronization by serum-starvation demonstrated normal movement through G(1)-phase but delayed entry into S-phase. Consistent with these findings, G(1) cyclin (D2 and D3) and CDK4 (cyclin-dependent kinase 4) levels and associated kinase activity were not affected. However, cyclin E-associated CDK2 activity, responsible for G(1)-to-S-phase progression, was inhibited. This decreased activity was accompanied by unchanged CDK2 protein levels and paradoxically elevated cyclin E and cyclin E-associated CDK2 levels, suggesting inhibition of the cyclin E-CDK2 complex. This inhibition was not due to altered stimulatory or inhibitory phosphorylation of CDK2. However, p27, a Cip/Kip family CKI (CDK inhibitor)-binding partner, was elevated and showed increased association with CDK2 in PLC delta 1-knockdown cells. The result of the present study demonstrate a novel and critical role for PLC delta 1 in cell-cycle progression from G(1)-to-S-phase through regulation of cyclin E-CDK2 activity and p27 levels.


Auxin Metabolism Is Involved in Fruit Set and Early Fruit Development in the Parthenocarpic Tomato "R35-P".
Parthenocarpic tomato can set fruit and develop without pollination and exogenous hormone treatments under unfavorable environmental conditions, which is beneficial to tomato production from late fall to early spring in greenhouses. In this study, the endogenous hormones in the ovaries of the parthenocarpic tomato line "R35-P" (stigma removed or self-pollination) and the non-parthenocarpic tomato line "R35-N" (self-pollination) at four stages between preanthesis and postanthesis investigated, using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A nearly twofold IAA (indoleacetic acid) content was found in "R35-P" rather than in "R35-N" at -2 and 0 days after anthesis (DAA). Except at -2 DAA, a lower ABA (abscisic acid) content was observed in Pe (stigma removed in "R35-P") compared to that in Ps (self-pollination in "R35-P") or CK (self-pollination in "R35-N"). After pollination, although the content of GA1 (gibberellins acid 1) in CK increased, the levels of GAs (gibberellins acids) were notably low. At all four stages, a lower SA (salicylic acid) content was found in Ps and CK than in Pe, while the content and the change trend were similar in Ps and CK. The variation tendencies of JA (jasmonic acid) varied among Pe, Ps, and CK at the studied periods. Furthermore, KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses of transcriptomic data identified 175 differentially expressed genes (DEGs) related to plant hormone signal transduction, including 63 auxin-related genes, 27 abscisic acid-related genes, 22 ethylene-related genes, 16 cytokinin-related genes, 16 salicylic acid-related genes, 14 brassinosteroid-related genes, 13 jasmonic acid-related genes, and 4 gibberellin-related genes at -2 DAA and 0 DAA. Our results suggest that the fate of a fruit set or degeneration occurred before anthesis in tomato. Auxins, whose levels were independent of pollination and fertilization, play prominent roles in controlling a fruit set in "R35-P," and other hormones are integrated in a synergistic or antagonistic way.


Assessment of the quality of cervical mucus among users of the levonorgestrel-releasing intrauterine system at different times of use.
The quality of cervical mucus (CM) among the levonorgestrel-releasing intrauterine system (LNG-IUS) users is controversial. The objectives were to assess CM compared to the levels of oestradiol (E2) and the frequency of cycles with luteal activity among users of the LNG-IUS. In total, 224 LNG-IUS users for between two months and five years were recruited at a Brazilian family planning clinic. For the cross-sectional part of the study, we enrolled 175 LNG-IUS users at 2, 6 12, 24, 36, 48, and 60 months after insertion (25 women in each group), and we performed one evaluation. For the prospective part of the study, we enrolled 49 LNG-IUS users at the same lengths of use after insertion (7 women in each group), and we evaluated these women once a week for five consecutive weeks. . Mean (± SEM) CM scores of all evaluations among women with single and weekly evaluations were between 3.3 ± 0.9 and 8.5 ± 0.3, respectively independently of the length of use of the LNG-IUS. Mean E2 values ranged from 45.5 ± 6.8 to 472.5 ± 34.7 pg/ml and the maximum ovarian follicle diameter on the days of evaluation varied from 14.0 ± 1.3 to 31.2 ± 0.4 mm. The mean CM score of all evaluations, independent of the length of use of the LNG-IUS and normal levels of serum E2, was below 10 was according to the WHO is inadequate for sperm penetration.


One hundred and sixty-three consecutive video thoracoscopic procedures: the Hong Kong experience.
Video-assisted thoracoscopy (VAT) offers a new approach to the diagnosis and treatment of many thoracic conditions. From September 1992 to August 1993, a total of 163 VAT procedures were successfully performed on 108 patients (87 male, 21 female; age range from 12 to 77) which consisted of 42 bleb eliminations and 64 mechanical pleurodesis for spontaneous pneumothorax, 11 wedge resections for pulmonary nodules, three wedge biopsies for diffuse pulmonary infiltrate, four thoracic sympathectomies, resections of two mediastinal masses, three pericardial windows, 10 guided pleural biopsies for undiagnosed effusions, six guided drainage of empyema and haemothorax, 16 staging of intrathoracic tumours and two explorations for penetrating thoracic trauma. There was no procedure-related mortality. Complications included one recurrence for spontaneous pneumothorax, one re-exploration for bleeding (also by VAT approach), one wound infection, and six persistent air leaks for more than 10 days. The median duration of postoperative chest tube drainage was 2 days and the median hospital stay was 4 days. It was concluded that VAT is a safe and effective approach in thoracic surgery and with further refinement in instrumentation even more procedures will be technically feasible. The long-term results of VAT are being awaited in order to define its true merits in thoracic surgery.


Src-protein tyrosine kinases are required for cocaine-induced increase in the expression and function of the NMDA receptor in the ventral tegmental area.
Cocaine-induced long-term potentiation of glutamatergic synapses in the ventral tegmental area (VTA) has been proposed as a key process that contributes to the development of addictive behaviors. In particular, the activation of ionotrophic glutamate NMDA receptor (NMDAR) in the VTA is critical for the initiation of cocaine sensitization. Here we show that application of cocaine both in slices and in vivo induced an increase in tyrosine phosphorylation of the NR2A, but not the NR2B subunit of the NMDAR in juvenile rats. Cocaine induced an increase in the activity of both Fyn and Src kinases, and the Src-protein tyrosine kinase (Src-PTKs) inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), abolished both cocaine-induced increase in tyrosine phosphorylation of the NR2A subunit and the increase in the expression of NR1, NR2A, and NR2B in the VTA. Moreover, cocaine-induced enhancement in NMDAR-mediated excitatory post-synaptic currents was completely abolished by PP2. Taken together, these results suggest that acute cocaine induced an increase in the expression of NMDAR subunits and enhanced tyrosine phosphorylation of NR2A-containing NMDAR through members of the Src-PTKs. This in turn, increased NMDAR-mediated currents in VTA dopamine neurons. These results provide a potential cellular mechanism by which cocaine triggers NMDAR-dependent synaptic plasticity of VTA neurons that may underlie the development of behavioral sensitization.


Diagnostic tools for calculation of glaucoma risk.
Risk calculators may simplify the management of ocular hypertension and glaucoma patients and provide evidence-based treatment. Risk calculators are not new to medicine. Medical providers use risk calculators to guide decision-making for the risk of a chromosomal abnormality in neonates, osteoporosis in postmenopausal women, and cardiovascular disease in adults. This article describes the current knowledge of risk calculators in ophthalmology. Clinicians should recognize that the current risk calculators do not include critical information guiding treatment such as life expectancy and patient's willingness to commit to years of eye drops. Overall, eye-care providers should consider the results of a risk calculator as supplemental information when treating an ocular hypertension or glaucoma patient.


Deep learning-based pulmonary nodule detection: Effect of slab thickness in maximum intensity projections at the nodule candidate detection stage.
To investigate the effect of the slab thickness in maximum intensity projections (MIPs) on the candidate detection performance of a deep learning-based computer-aided detection (DL-CAD) system for pulmonary nodule detection in CT scans. The public LUNA16 dataset includes 888 CT scans with 1186 nodules annotated by four radiologists. From those scans, MIP images were reconstructed with slab thicknesses of 5 to 50 mm (at 5 mm intervals) and 3 to 13 mm (at 2 mm intervals). The architecture in the nodule candidate detection part of the DL-CAD system was trained separately using MIP images with various slab thicknesses. Based on ten-fold cross-validation, the sensitivity and the F2 score were determined to evaluate the performance of using each slab thickness at the nodule candidate detection stage. The free-response receiver operating characteristic (FROC) curve was used to assess the performance of the whole DL-CAD system that took the results combined from 16 MIP slab thickness settings. At the nodule candidate detection stage, the combination of results from 16 MIP slab thickness settings showed a high sensitivity of 98.0% with 46 false positives (FPs) per scan. Regarding a single MIP slab thickness of 10 mm, the highest sensitivity of 90.0% with 8 FPs/scan was reached before false positive reduction. The sensitivity increased (82.8% to 90.0%) for slab thickness of 1 to 10 mm and decreased (88.7% to 76.6%) for slab thickness of 15-50 mm. The number of FPs was decreasing with increasing slab thickness, but was stable at 5 FPs/scan at a slab thickness of 30 mm or more. After false positive reduction, the DL-CAD system, utilizing 16 MIP slab thickness settings, had the sensitivity of 94.4% with 1 FP/scan. The utilization of multi-MIP images could improve the performance at the nodule candidate detection stage, even for the whole DL-CAD system. For a single slab thickness of 10 mm, the highest sensitivity for pulmonary nodule detection was reached at the nodule candidate detection stage, similar to the slab thickness usually applied by radiologists.


Increased risk of attempted suicide in Australian veterans is associated with total and permanent incapacitation, unemployment and posttraumatic stress disorder severity.
Military veterans have higher rates of suicidality and completed suicides compared to the general population. Previous research has demonstrated suicidal behaviour is higher in US combat veterans who are younger, suffer from posttraumatic stress disorder, depression and anxiety and score lower on measures of health. However, research on predictors of suicide for Australian veterans is limited. The aim of this study was to identify significant demographic and psychological differences between veterans with posttraumatic stress disorder who had attempted suicide and those with posttraumatic stress disorder who had not, as well as determine predictors of suicide attempts within an Australian cohort. A retrospective analysis was conducted on 229 ex-service personnel diagnosed with posttraumatic stress disorder who had attended a Military Service Trauma Recovery Day Program as outpatients at Toowong Private Hospital from 2007 to 2014. Patients completed a battery of mental health self-report questionnaires assessing symptoms of posttraumatic stress disorder, alcohol use, anger, depression, anxiety and quality of life. Demographic information and self-reported history of suicide attempts were also recorded. Results indicated the average age was significantly lower, and the rates of posttraumatic stress disorder, anger, anxiety and depression symptoms were significantly higher in those veterans with history of a suicide attempt. Multivariate logistic regression analyses indicated posttraumatic stress disorder symptom severity, unemployment or total and permanent incapacity pension status significantly predicted suicide attempt history. Among a cohort of Australian veterans with posttraumatic stress disorder, psychopathology severity, unemployment and total and permanent incapacity status are significantly associated with suicidality. This study highlights the importance of early identification of posttraumatic stress disorder and psychopathology, therapeutic and social engagement, and prioritisation of tangible employment options or meaningful and goal-directed activities for veterans deemed unable to work.


Assessment of infant and young child feeding practices among mothers of Paniya tribal children aged 0-23 months in Gudalur Block, Nilgiris District.
Optimal infant and young child feeding practices (IYCFPs), despite being emphasized since 2003, are yet to be met in India. This study assessed these practices and their association with various factors among mothers of children aged 0-23 months in Paniya tribes in Nilgiris, Tamil Nadu. About 89.1% of the infants below six months were timely breastfed and 77.9% of them were exclusively breastfed, respectively. Complementary food was introduced to 25% of infants aged six to eight months. About 27.8% of them received a diverse diet. About 91.7% of them were fed egg and/or flesh food and 37% of them were fed vegetables and fruits. Illiterate mothers and mothers who had a vaginal delivery fed the infant optimally. The adherence to these practices was found to decrease gradually with an increase in the infant's age. The prevalence of IYCFP is higher in the study population compared to the corresponding indicators for the district according to the National Family Health Survey-5.


Effect of Nitrosative Stress on the S-Nitroso-Proteome of Paracoccidioides brasiliensis.
The fungi Paracoccidioides brasiliensis and Paracoccidioides lutzii are the causative agents of paracoccidioidomycosis (PCM), a systemic mycosis endemic to Latin America. This fungus is considered a facultative intracellular pathogen that is able to survive and replicate inside macrophages. The survival of the fungus during infection depends on its adaptability to various conditions, such as nitrosative/oxidative stress produced by the host immune cells, particularly alveolar macrophages. Currently, there is little knowledge about the Paracoccidioides spp. signaling pathways involved in the fungus evasion mechanism of the host defense response. However, it is known that some of these pathways are triggered by reactive oxygen species and reactive nitrogen species (ROS/RNS) produced by host cells. Considering that the effects of NO (nitric oxide) on pathogens are concentration dependent, such effects could alter the redox state of cysteine residues by influencing (activating or inhibiting) a variety of protein functions, notably S-nitrosylation, a highly important NO-dependent posttranslational modification that regulates cellular functions and signaling pathways. It has been demonstrated by our group that P. brasiliensis yeast cells proliferate when exposed to low NO concentrations. Thus, this work investigated the modulation profile of S-nitrosylated proteins of P. brasiliensis, as well as identifying S-nitrosylation sites after treatment with RNS. Through mass spectrometry analysis (LC-MS/MS) and label-free quantification, it was possible to identify 474 proteins in the S-nitrosylated proteome study. With this approach, we observed that proteins treated with NO at low concentrations presented a proliferative response pattern, with several proteins involved in cellular cycle regulation and growth being activated. These proteins appear to play important roles in fungal virulence. On the other hand, fungus stimulated by high NO concentrations exhibited a survival response pattern. Among these S-nitrosylated proteins we identified several potential molecular targets for fungal disease therapy, including cell wall integrity (CWI) pathway, amino acid and folic acid metabolisms. In addition, we detected that the transnitrosylation/denitrosylation redox signaling are preserved in this fungus. Finally, this work may help to uncover the beneficial and antifungal properties of NO in the P. brasiliensis and point to useful targets for the development of antifungal drugs.


An Energy efficient application specific integrated circuit for electrocardiogram feature detection and its potential for ambulatory cardiovascular disease detection.
A novel algorithm based on forward search is developed for real-time electrocardiogram (ECG) signal processing and implemented in application specific integrated circuit (ASIC) for QRS complex related cardiovascular disease diagnosis. The authors have evaluated their algorithm using MIT-BIH database and achieve sensitivity of 99.86% and specificity of 99.93% for QRS complex peak detection. In this Letter, Physionet PTB diagnostic ECG database is used for QRS complex related disease detection. An ASIC for cardiovascular disease detection is fabricated using 130-nm CMOS high-speed process technology. The area of the ASIC is 0.5 mm(2). The power dissipation is 1.73 μW at the operating frequency of 1 kHz with a supply voltage of 0.6 V. The output from the ASIC is fed to their Android application that generates diagnostic report and can be sent to a cardiologist through email. Their ASIC result shows average failed detection rate of 0.16% for six leads data of 290 patients in PTB diagnostic ECG database. They also have implemented a low-leakage version of their ASIC. The ASIC dissipates only 45 pJ with a supply voltage of 0.9 V. Their proposed ASIC is most suitable for energy efficient telemetry cardiovascular disease detection system.


Acoustic radiation force impulse imaging of the liver: measurement of the normal mean values of the shearing wave velocity in a healthy liver.
To find the normal mean values of the liver elasticity/stiffness by Acoustic Radiation Force Impulse (ARFI) Elastography in healthy subjects. This study was conducted on 137 healthy subjects without any known liver pathology or a history of jaundice by using the Siemens Acuson S2000TM Ultrasound machine with a convex probe . A routine ultrasound was also performed in each case, and the subjects with fatty liver changes or any other signs of a chronic liver pathology were excluded. In each subject, 10 measurements were taken and the median value of the 10 measurements was calculated, which was expressed in metres/sec (m/s). The inter quartile range method was used for the interpretation of the data. Only the measurements with an IQR of < 30% and a Success Rate (SR) of >60% were considered. The measurements were taken at 1-2 cm depth from the liver capsule through an intercostal approach, with the subject lying in the decubitus position. The mean ARFI values and the mean values according to the age and gender of the subjects were evaluated. Valid ARFI measurements were taken in 108/137 patients (78.83%). The mean value of the ARFI measurements in the normal individuals was 1.197±0.25 m/s. There were no significant differences between the mean ARFI values in men vs women (1.195±.25 vs. 1.199±0.26m/s, p = 0.939), and also among the different age groups (p>0.05). In our study, the mean liver elasticity value (shearing wave velocity) which was obtained by ARFI in the healthy subjects was 1.197±0.25 m/s.


Molecular biology of Hodgkin's disease.
The mist surrounding the origin and genesis of HRS cells of classical HD is beginning to dissipate. Molecular biological studies of classical HD at the single cell level strongly suggest that the HRS cells in the majority of cases represent a monoclonal outgrowth of late germinal centre B cells that have lost their capacity to express IG through crippling mutations introduced during the germinal centre reaction. Because of the expression of T cell antigens and/or cytotoxic molecules, the HRS cells of a minority of classical HD cases appear to originate from T cells. Under physiological conditions, B cells that are unable to express IG are eliminated by apoptosis. In most B cell derived classical HD cases, the HRS cells have lost their IG gene coding capacity through mutation and should therefore die of apoptosis. Since this usually does not happen, blockade of the apoptotic pathway may be a major event in the pathogenesis of B cell related classical HD. It is tempting to assume that viruses such as EBV, as well as regulator genes that normally monitor the human genome for damaged DNA, such as TP53, might be involved in the postulated hindrance of the apoptotic pathway, leading to the genesis of classical HRS cells.


Dopaminergic modulation of phase reversal in desert locusts.
Phenotypic plasticity allows animals to modify their behavior, physiology, and morphology to adapt to environmental change. The global pest, the desert locust, shows two extreme phenotypes; a solitarious phase that is relatively harmless and a gregarious phase that forms swarms and causes extensive agricultural and economic damage. In the field, environmental conditions can drive isolated animals into crowded populations and previous studies have identified the biogenic amine serotonin as a key determinant of this transition. Here we take an integrated approach to investigate the neurochemical, physiological, and behavioral correlates defined by a laboratory based paradigm that mimics facets of swarm break down as gregarious locusts become isolated. Following isolation there was an increased propensity of locusts to avoid conspecifics, and show a reduced locomotion. Changes in choice behavior occurred within 1 h of isolation although isolation-related changes progressed with increased isolation time. Isolation was accompanied by changes in the levels of the biogenic amines dopamine, octopamine, and serotonin within the CNS within 1 h. Dopamine levels were higher in isolated animals and we focused on the role played by this transmitter in synaptic changes that may underpin solitarization. Dopamine reduced synaptic efficacy at a key central synapse between campaniform sensilla (CS) and a fast extensor tibiae motor neuron that is involved in limb movement. We also show that dopamine injection into the haemocoel was sufficient to induce solitarious-like behavior in otherwise gregarious locusts. Further, injection of a dopamine antagonist, fluphenazine, into isolated locusts induced gregarious-like behavior. This highlights that dopaminergic modulation plays an important role in the plasticity underpinning phase transition and sets a context to deepen the understanding of the complementary role that distinct neuromodulators play in polyphenism in locusts.


Directed evolution of Thermotoga neapolitana xylose isomerase: high activity on glucose at low temperature and low pH.
The Thermotoga neapolitana xylose isomerase (TNXI) is extremely thermostable and optimally active at 95 degrees C. Its derivative, TNXI Val185Thr (V185T), is the most active type II xylose isomerase reported, with a catalytic efficiency of 25.1 s(-1) mM(-1) toward glucose at 80 degrees C (pH 7.0). To further optimize TNXI's potential industrial utility, two rounds of random mutagenesis and low temperature/low pH activity screening were performed using the TNXI V185T-encoding gene as the template. Two highly active mutants were obtained, 3A2 (V185T/L282P) and 1F1 (V185T/L282P/F186S). 1F1 was more active than 3A2, which in turn was more active than TNXI V185T at all temperatures and pH values tested. 3A2 and 1F1's high activities at low temperatures were due to significantly lower activation energies (57 and 44 kJ/mol, respectively) than that of TNXI and V185T (87 kJ/mol). Mutation L282P introduced a kink in helix alpha7 of 3A2's (alpha/beta)8 barrel. Surprisingly, this mutation kinetically destabilized 3A2 only at pH 5.5. 1F1 displayed kinetic stability slightly above that of TNXI V185T. In 1F1, mutation F186S creates a cavity that disrupts a four-residue network of aromatic interactions. How the conformation of the neighboring residues is affected by this cavity and how these conformational changes increase 1F1's stability still remain unclear.


Infrared absorption of n-type tensile-strained Ge-on-Si.
We analyze the IR absorption of tensile-strained, n-type Ge for Si-compatible laser applications. A strong intervalley scattering from the indirect L valleys to the direct Γ valley in n+ Ge-on-Si is reported for the first time to our knowledge. The intervalley absorption edge is in good agreement with the theoretical value. On the other hand, we found that the classical λ2-dependent Drude model of intravalley free-carrier absorption (FCA) breaks down at λ<15 μm. A first-principle model has to be employed to reach a good agreement with the experimental data. The intravalley FCA loss is determined to be <20 cm(-1) for n=4×10(19) cm(-3) at λ=1.5-1.7 μm, an order lower than the results from Drude model. The strong L→Γ intervalley scattering favors electronic occupation of the direct Γ valley, thereby enhancing optical gain from the direct gap transition of Ge, while the low intravalley free-electron absorption at lasing wavelengths leads to low optical losses. These two factors explain why the first electrically pumped Ge-on-Si laser achieved a higher net gain than the theoretical prediction using λ2-dependent free-carrier losses of bulk Ge and indicate the great potential for further improvement of Ge-on-Si lasers.


Acute toxic herbal intake in a suicide attempt and fatal refractory ventricular arrhythmia.
This report involves a 54-year-old man who died following refractory ventricular fibrillation after ingestion of a plant in a suicide attempt. Repeated direct-current cardioversions were unsuccessful and no single anti-arrhythmic agent was effective for arrhythmia control. The routine blood toxicological screening was negative. Aconitine, the main toxin of Aconitum napellus was identified using a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The whole blood concentration (24 microg/l) was higher than those reported in other aconitine-related deaths. The patient had found information about the life-threatening nature of such a toxic herb intake on a free medical encyclopedia online.


Spatial whole transcriptome profiling of primary tumor from patients with metastatic prostate cancer.
Prostate cancer (PCa) is a highly heterogeneous disease in terms of its molecular makeup and clinical prognosis. The prostate tumor microenvironment (TME) is hypothesized to play an important role in driving disease aggressiveness, but precise mechanisms remain elusive. In our study, we used spatial transcriptomics to explore for the first time the spatial gene expression heterogeneity within primary prostate tumors from patients with metastatic disease. In total, we analyzed 5459 tissue spots from three PCa patients comprising castration-resistant (CRPC) and neuroendocrine (NEPC) disease stages. Within CRPC, we identified a T cell cluster whose activity might be impaired by nearby regulatory T cells, potentially mediating the aggressive disease phenotype. Moreover, we identified Hallmark signatures of epithelial-mesenchymal transition in a cancer-associated fibroblast (CAF) cluster, indicating the aggressive characteristic of the primary TME leading to metastatic dissemination. Within NEPC, we identified active immune-stroma cross-talk exemplified by significant ligand-receptor interactions between CAFs and M2 macrophages. Further, we identified a malignant cell population that was associated with the down-regulation of an immune-related gene signature. Lower expression of this signature was associated with higher levels of genomic instability in advanced PCa patients (SU2C cohort, n = 99) and poor recurrence free survival in early-stage PCa patients (TCGA cohort, n = 395), suggesting prognostic biomarker potential. Taken together, our study reveals the importance of whole transcriptome profiling at spatial resolution for biomarker discovery and for advancing our understanding of tumor biology.


Coregulation of processing and translation: mature 5' termini of Escherichia coli 23S ribosomal RNA form in polysomes.
In Escherichia coli, the final maturation of rRNA occurs in precursor particles, and recent experiments have suggested that ongoing protein synthesis may somehow be required for maturation to occur. The protein synthesis requirement for the formation of the 5' terminus of 23S rRNA has been clarified in vitro by varying the substrate of the reaction. In cell extracts, pre-23S rRNA in free ribosomes was not matured, but that in polysomes was efficiently processed. The reaction occurred in polysomes without the need for an energy source or other additives required for protein synthesis. Furthermore, when polysomes were dissociated into ribosomal subunits, they were no longer substrates for maturation; but the ribosomes became substrates again when they once more were incubated in the conditions for protein synthesis. All of these results are consistent with the notion that protein synthesis serves to form a polysomal complex that is the true substrate for maturation. Ribosomes in polysomes, possibly in the form of 70S initiation complexes, may more easily adopt a conformation that facilitates maturation cleavage. As a result, the rates of ribosome formation and protein synthesis could be coregulated.


Modality transition on renal replacement therapy and quality of life of patients: a 10-year follow-up cohort study.
Despite advance in renal replacement therapy (RRT), patients with chronic end-stage renal disease (ESRD) face various limitations, and renal transplantation (Tx) is the treatment that impacts most on quality of life (QoL). This study aimed to assess changes in QoL in a cohort of ESRD dialysis patients. Sociodemographic, clinical, nutritional, lifestyle, and QoL data were collected from 712 patients at baseline (time 1) and after 10 years of follow-up (time 2) for patients surviving. The QoL was assessed through the 36-Item Short Form Health Survey (SF-36) and the multiple linear regression model was used to analyze the factors associated with change in QoL. A total of 205 survivors were assessed and distributed into three groups according to current RRT (Dialysis-Dialysis, Dialysis-Tx, and Dialysis-Tx-Dialysis). At time 1, only age was significantly different among groups; at time 2, transplant patients sustained greater social participation, job retention, and improvement in SF-36 scores. The factors associated with change in QoL were more time on dialysis interfering negatively on physical functioning (p = 0.002), role-physical limitations (p = 0.002), general health (p = 0.007), social functioning (p = 0.02), role-emotional (p = 0.003), and physical components ( p = 0.002); non-participation in social groups at times 1 and 2 reducing vitality (p = 0.02) scores; and having work at time 2, increasing vitality (p = 0.02) and mental health (p = 0.02) scores. QoL was shown to be dynamic throughout the years of RRT, transplantation being the treatment with more benefits to the ESRD. More time on dialysis and limited social and occupational routine were associated with a reduction in QoL.


Electrodermal responses to words in chronic low back pain patients: a comparison between pain descriptors, other emotional words, and neutral words.
This study examines the electrodermal reactivity of chronic sufferers to emotional words. The hypothesis that patients are over-sensitive to pain descriptors is tested. Electrodermal activity was recorded in 12 chronic low back pain patients and 12 healthy controls during passive viewing of words on a video monitor. These words were pain descriptors, other emotional words, and neutral words, in a pseudo-randomized order. A jingle was associated with the word occurrence. In chronic low back pain patients, skin conductance responses (SCRs) induced by pain descriptors or other emotional words were larger than SCRs induced by neutral words but they did not differ from each other. Patients presented SCRs, which were both larger and faster than those of controls, including following neutral words. There was no significant effect of word type in controls. Skin conductance level and the number of nonspecific fluctuations were larger in patients as compared with controls. The present electrodermal study suggests that chronic pain is linked to an increased reactivity to a wide range of stimuli. Emotional load amplifies the effect. This leads to recommend broad therapeutic management in chronic sufferers. Contrary to expectation derived from classical conditioning, patients did not prove over-sensitive to pain descriptors. This negative finding is discussed at methodologic, physiologic, and psychologic levels.


Syndecans promote mycobacterial internalization by lung epithelial cells.
Pulmonary tuberculosis (TB) is an airborne disease caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb). Alveolar epithelial cells and macrophages are the first point of contact for Mtb in the respiratory tract. However, the mechanisms of mycobacterial attachment to, and internalization by, nonprofessional phagocytes, such as epithelial cells, remain incompletely understood. We identified syndecan 4 (Sdc4) as mycobacterial attachment receptor on alveolar epithelial cells. Sdc4 mRNA expression was increased in human and mouse alveolar epithelial cells after mycobacterial infection. Sdc4 knockdown in alveolar epithelial cells or blocking with anti-Sdc4 antibody reduced mycobacterial attachment and internalization. At the molecular level, interactions between epithelial cells and mycobacteria involved host Sdc and the mycobacterial heparin-binding hemagglutinin adhesin. In vivo, Sdc1/Sdc4 double-knockout mice were more resistant to Mtb colonization of the lung. Our work reveals a role for distinct Sdcs in promoting mycobacterial entry into alveolar epithelial cells with impact on outcome of TB disease.


Do assisted living facilities that offer a dementia care program differ from those that do not? A population-level cross-sectional study in Ontario, Canada.
Many residents of assisted living facilities live with dementia, but little is known about the characteristics of assisted living facilities that provide specialized care for older adults who live with dementia. In this study, we identify the characteristics of assisted living facilities that offer a dementia care program, compared to those that do not offer such a program. We conducted a population-level cross-sectional study on all licensed assisted living facilities in Ontario, Canada in 2018 (n = 738). Facility-level characteristics (e.g., resident and suite capacities, etc.) and the provision of the other 12 provincially regulated care services (e.g., pharmacist and medical services, skin and wound care, etc.) attributed to assisted living facilities were examined. Multivariable Poisson regression with robust standard errors was used to model the characteristics of assisted living facilities associated with the provision of a dementia care program. There were 123 assisted living facilities that offered a dementia care program (16.7% versus 83.3% no dementia care). Nearly half of these facilities had a resident capacity exceeding 140 older adults (44.7% versus 21.6% no dementia care) and more than 115 suites (46.3% versus 20.8% no dementia care). All assisted living facilities that offered a dementia care program also offered nursing services, meals, assistance with bathing and hygiene, and administered medications. After adjustment for facility characteristics and other provincially regulated care services, the prevalence of a dementia care program was nearly three times greater in assisted living facilities that offered assistance with feeding (Prevalence Ratio [PR] 2.91, 95% Confidence Interval [CI] 1.98 to 4.29), and almost twice as great among assisted living facilities that offered medical services (PR 1.78, 95% CI 1.00 to 3.17), compared to those that did not. A dementia care program was more prevalent in assisted living facilities that housed many older adults, had many suites, and offered at least five of the other 12 regulated care services. Our findings deepen the understanding of specialized care for dementia in assisted living facilities.


Does hemopericardium after chest trauma mandate sternotomy?
Recently, three patients with hemopericardium after severe chest trauma were successfully managed nonoperatively at our institution. This prompted the question whether these were rare or common events. Therefore, we reviewed our experience with similar injuries to test the hypothesis that trauma-induced hemopericardium mandates sternotomy. Records were retrospectively reviewed for all patients at a Level I trauma center (December 1996 to November 2011) who sustained chest trauma with pericardial window (PCW, n = 377) and/or median sternotomy (n = 110). Fifty-five (15%) patients with positive PCW proceeded to sternotomy. Penetrating injury was the dominant mechanism (n = 49, 89%). Nineteen (35%) were hypotensive on arrival or during initial resuscitation. Most received surgeon-performed focused cardiac ultrasound examinations (n = 43, 78%) with positive results (n = 25, 58%). Ventricular injuries were most common, with equivalent numbers occurring on the right (n = 16, 29%) and left (n = 15, 27%). Six (11%) with positive PCW had isolated pericardial lacerations, but 21 (38%) had no repairable cardiac or great vessel injury. Those with therapeutic versus nontherapeutic sternotomies were similar with respect to age, mechanisms of injury, injury severity scores, presenting laboratory values, resuscitation fluids, and vital signs. Multiple logistic regression revealed that penetrating trauma (odds ratio: 13.3) and hemodynamic instability (odds ratio: 7.8) were independent predictors of therapeutic sternotomy. Hemopericardium per se may be overly sensitive for diagnosing cardiac or great vessel injuries after chest trauma. Some stable blunt or penetrating trauma patients without continuing intrapericardial bleeding had nontherapeutic sternotomies, suggesting that this intervention could be avoided in selected cases. Therapeutic study, level III.


Coinfection with Acanthamoeba and Pseudomonas in contact lens-associated keratitis.
To report coinfection with Acanthamoeba and Pseudomonas aeruginosa in a case with contact lens-associated keratitis. A 20-year-old woman presented to the emergency department of our hospital with a 4-day history of progressively increasing pain, redness, photophobia, mucopurulent discharge, and diminution of vision in her right eye. She was being treated for contact lens-related Pseudomonas keratitis in another hospital before presentation. Gram stain of corneal scrapings revealed gram-negative bacilli. Both Gram stain and 10% KOH wet mount showed the presence of Acanthamoeba cysts. Microbiological cultures obtained from contact lenses and contact lens storage case showed the presence of Pseudomonas aeruginosa and Acanthamoeba. Topical therapy was started in the form of hourly gentamycin 1.3%, cefazolin 5%, chlorhexidine 0.02%, propamidine 0.1%, polymyxin B 30,000 IU eye drops, and neosporin (neomycin, bacitracin, polymyxin) eye ointment four times a day. Symptomatic improvement was observed within 48 hours, along with a decrease in the density of infiltrates and a reduction in the anterior chamber reaction. Repeat corneal scrapings on day 10 showed Acanthamoeba but no bacilli. Progressive resolution of the infiltrate was noted during the next few days. Epithelialization was complete by day 24, following which the amoebicidal therapy was tapered during the next 4 weeks. Complete resolution of keratitis was achieved after 7 weeks of treatment. Both P. aeruginosa and Acanthamoeba are potentially devastating causes of microbial keratitis. Our case highlights the importance of considering the possibility of a concurrent infection in cases with contact lens-related keratitis.


A Qualitative Exploration of the Help-Seeking Behaviors of Students Who Experience Psychological Distress Around Assessment at Medical School.
Medical students are at high risk of experiencing psychological distress at medical school and developing mental ill-health during professional practice. Despite efforts by faculty to raise awareness about this risk, many students choose to suffer in silence in the face of psychological distress. The aim of this study was to explore drivers that prompted help-seeking behavior and barriers that prevented individuals prioritizing their well-being around the time of high-stakes assessment at medical school. Semi-structured interviews were conducted with fifty-seven students who failed high-stakes assessment at two UK medical schools, exploring their experience of academic difficulty and perceptions about causes. A thematic analysis of twenty transcripts that met inclusion criteria was completed to identify key factors that influenced participants' decisions around seeking help for their psychological distress, and in some cases, mental health problems. Twenty participants who specifically described a deterioration in their mental health around the time of assessment were included in this study. Barriers to seeking help in these instances included: normalization of symptoms or situation; failure to recognize a problem existed; fear of stigmatisation; overt symptoms of mental distress; and misconceptions about the true nature of the medical school, for example beliefs about a punitive response from the school if they failed. Drivers for seeking help appropriately included: building trust with someone in order to confide in them later on, and self-awareness about the need to maintain good mental health. There are various drivers and barriers for students' help seeking behaviors when experiencing psychological distress around the time of assessment, particularly self-awareness about the problem and prioritisation of well-being. Students who fail to recognize their own deteriorating mental health are at risk of academic failure and medical schools need to develop strategies to tackle this problem in order to protect these students from harm.


Detecting Membrane Protein-protein Interactions Using the Mammalian Membrane Two-hybrid (MaMTH) Assay.
Protein-protein interactions (PPIs) play an integral role in numerous cellular processes. Membrane protein interactions, in particular, are critical in cellular responses to stresses and stimuli, with dysfunction of these PPIs (e.g., due to aberrant expression and/or mutation of interaction partners) leading to a diverse array of pathological states. Exploration of the interaction space and dynamics of membrane proteins is difficult due to the limitations of current techniques used to study proteins in the biochemically complex environment of biological membranes. In the protocols below, we describe a newly developed membrane protein interaction assay called the Mammalian-Membrane Two-Hybrid (MaMTH), designed specifically for the detection of integral membrane PPIs in the context of living mammalian cells. Prior to using MaMTH, cell lines of interest are genetically modified to encode a reporter of choice. MaMTH "bait" and "prey" constructs of interest are also generated using Gateway cloning technology. The assay is then performed by co-transfection of baits and preys, with bait-prey interaction quantifiably assessed by way of a reporter signal (e.g., light (luciferase), fluorescence (GFP). © 2017 by John Wiley & Sons, Inc.


Cholestatic Pruritus Treatments in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis: A Systematic Literature Review.
We conducted a systematic literature review to understand the evidence supporting treatment decisions for cholestatic pruritus associated with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). Studies that enrolled ≥ 75% participants with PBC or PSC and reported ≥ 1 endpoint(s) related to efficacy, safety, health-related quality of life (HRQoL) or other patient-reported outcomes were included. Bias was assessed using the Cochrane risk of bias tool for randomised controlled trials (RCTs) and the Quality of Cohort studies tool for non-RCTs. Thirty-nine publications were identified, covering 42 studies and six treatment classes (including investigational and approved products): anion-exchange resins, antibiotics (rifampicin/derivatives), opiates, selective serotonin reuptake inhibitors, fibrates, ileal bile acid transporter inhibitors and other agents not categorised in these six classes. Across studies, median sample size was small (n = 18), 20 studies were over 20 years old, 25 followed patients for ≤ 6 weeks, only 25 were RCTs. Pruritus was assessed using several different tools, with inconsistencies in their application. Cholestyramine, considered first-line therapy for moderate-severe cholestatic pruritus, was assessed in six studies (two RCTs) including 56 patients with PBC and 2 with PSC, with evidence of efficacy demonstrated in only three studies, among which, two RCTs were assessed as having a high risk of bias. Findings were similar for other drug classes. There is a lack of consistent and reproducible evidence available on efficacy, impact on HRQoL, and safety of cholestatic pruritus treatments, leaving physicians to rely on clinical experience rather than evidence-based medicine for treatment selection.


Modulation of tRNAAla identity by inorganic pyrophosphatase.
A highly sensitive assay of tRNA aminoacylation was developed that directly measures the fraction of aminoacylated tRNA by following amino acid attachment to the 3'-(32)P-labeled tRNA. When applied to Escherichia coli alanyl-tRNA synthetase, the assay allowed accurate measurement of aminoacylation of the most deleterious mutants of tRNA(Ala). The effect of tRNA(Ala) identity mutations on both aminoacylation efficiency (k(cat)/K(M)) and steady-state level of aminoacyl-tRNA was evaluated in the absence and presence of inorganic pyrophosphatase and elongation factor Tu. Significant levels of aminoacylation were achieved for tRNA mutants even when the k(cat)/K(M) value is reduced by as much as several thousandfold. These results partially reconcile the discrepancy between in vivo and in vitro analysis of tRNA(Ala) identity.


[The surface phenotype and enzymatic cytochemical markers of B cells during pokeweed mitogen activation].
Methods of monoclonal antibodies, cytochemistry and rosette formation have been used to study antigens, receptors and enzymatic activity of peripheral blood lymphocytes during pokeweed mitogen-stimulation. After 18-20 hours in mitogen-stimulated cultures there is a decrease in number of T-lymphocytes that express CD7, CD5, CD4, CD8 antigens and of E-receptors and cells with the local activities of acid phosphatase and acid non-specific esterase. The number of lymphocytes with E37-, FcM- and M-receptors and of cells with granular PAS-reaction increased. Blast cells were revealed after 40-48 hours. Approximately 50% blast cells forming E37-rosettes and expressing CD7, CD5, CD2 antigens were characterized by the local activities of the above enzymes. The blasts did not express FcG-, FcM-, C3- or M-receptors. Cells like those at the Hodgkin disease and the "hand mirror" type cells were established on days 3-4. The number of lymphocytes with plasmatization was seen to increase by day 7.


In vivo EIS characterization of tumour tissue properties is dominated by excess extracellular fluid.
Electrical impedance spectroscopy (EIS) is a non-ionizing, non-invasive technique which can be used to detect the presence of malignant tumours based on their electrical properties. Although it has been suggested that the edema which accompanies tumours strongly influences EIS tumour characterization, such information has not, until now, been documented in the literature. Growing intramuscular rodent tumours were imaged using magnetic resonance imaging (MRI) and EIS at several time points post-tumour implantation. The amount of edema associated with the tumours was calculated from the MRI images. Electrical parameters (resistivity, permittivity, fluid index ratio and peak frequency) were extracted from the EIS spectra. Taken together, the resulting electrical parameters strongly indicate that edema is the dominating pathological feature in EIS characterization and can at times conceal the presence of the tumour. Receiver operating characteristic analysis supports these findings.


One-year open-label safety evaluation of the fixed combination of ibuprofen and famotidine with a prospective analysis of dyspepsia.
To assess the long-term safety of the single-tablet combination of ibuprofen 800 mg and famotidine 26.6 mg. A phase 3b open-label study (NCT00984815) was conducted in 86 adults requiring daily non-steroidal anti-inflammatory drug (NSAID) administration for ≥12 months. The combination tablet of ibuprofen/famotidine was self-administered orally three times daily for up to 54 consecutive weeks. Adverse events (AEs) were collected beginning at the first dose and continued through completion (54 weeks). The Severity of Dyspepsia Assessment (SODA) questionnaire was completed by patients to assess tolerability. Most patients (65%) finished the trial, with 76% contributing data at 6 months, and 21% withdrew due to adverse effects. Overall and gastrointestinal AE discontinuation rates (21% and 13%, respectively) were lower than that previously reported with ibuprofen 2400 mg given alone. Each of the SODA subscale scores demonstrated improvement by week 6 and improved statistically significantly at week 24 and week 54. Of the cardiovascular AEs, hypertension was reported most frequently (9/86, 9.3%), with 3.5% determined to be drug related. Twelve serious AEs were reported by 9 of 86 (10%) patients; two were considered possibly related to the study medication (unstable angina and gastric ulcer). There were no reports of serious gastrointestinal or CV complications. Most AEs were mild or moderate in severity and not considered drug related. These data, together with previously reported findings of a significant decrease in upper gastrointestinal endoscopic ulcer rate at 6 months, support the overall safety, compliance, and tolerability of this single-tablet formulation.


Sidedness of ceramide-phosphoethanolamine synthesis on rat liver and brain microsomal membranes.
Phosphatidylethanolamine:ceramide-ethanolamine-phosphotransferase catalyzes the synthesis of ceramide-phosphoethanolamine, a sphingomyelin analogue. Its localization was studied in rat liver and brain microsomes. After testing the integrity and the sidedness of microsomal vesicles, trypsin treatment of intact or deoxycholate-disrupted microsomes made it possible to conclude that both the transferase and the ceramide-phosphoethanolamine are located in the cisternal leaflet of the membrane bilayer. Using trinitrobenzenesulfonic acid as a probe, no trace of newly synthesized ceramide-phosphoethanolamine was detectable on the cytoplasmic side of the microsomes.


[The cell morphology of peritoneal exudate in the course of bacterial peritonitis (experimental animal studies)].
According to diagnosis of the liquor cerebrospinalis in inflammatory diseases of the central nervous system there shall be demonstrated a method to support diagnosis and control of an efficient therapy of diffuse bacterial peritonitis. Mice were infected intraperitoneal with Escherichia coli suspension without complement. At intervals of 12 hours there was carried out a peritoneal lavage. The peritoneal lavage fluid was given into the sedimentary chamber according to Sayk. The sediment was coloured according to Pappenheim and differentiated under microscope. With help of the described method it is possible to take valuable informations about inflammation in peritoneal cavity by means of cellular composition of the peritoneal fluid in different times post infection. Of greatest importance is the number of polymorphonuclear cells in the exudate.


The roles of Ca2+ and adenosine 3',5'-monophosphate in the regulation of progesterone production by human placental tissue.
The effects of Ca2+ and cAMP on progesterone production by placental tissue were studied. Term placentas obtained from normal pregnant women were perfused with sterile saline to remove blood, and the minced trophoblastic tissue was incubated in vitro. The rate of progesterone secretion by the trophoblastic tissue was 47.5 +/- 5.0 (+/- SE) ng/mg cell protein X h (control) at 450 micrograms low density lipoprotein/mL. The rates of progesterone production and cAMP accumulation were accelerated 3.0- and 1.7-fold, respectively, by 10(-5) M terbutaline, and the terbutaline effect was blocked by the addition of 50 microM N-(6-aminohexyl)5-chloro-1-naphthalenesulfonamide (W-7) or 50 microM trifluoperazine. Whereas progesterone secretion by placental explants cultured in medium containing low density lipoprotein with 1 microM A23187 (calcium ionophore) reached a rate of 128.5 +/- 8.5 ng/mg cell protein X h, incubation of placental explants with A23187 caused a highly significant, dose-related decrease in terbutaline-stimulated cAMP accumulation in the presence of 3-isobutyl-1-methylxanthine, a phosphodiesterase inhibitor. Inhibition by A23187 was Ca2+ dependent, since incubation in a Ca2+-free medium with EGTA blocked its effect. Intracellular Ca2+ is apparently necessary for placental progesterone production; enhancement of progesterone production by beta2-stimulation is mediated by intracellular Ca2+ and cAMP.


Thinking upstream: the roles of international health and drug policies in public health responses to chemsex.
Chemsex is a growing public health concern in urban centres, and few interventions exist to mitigate the significant sexual, drug-related, and social harms potentially experienced by people who participate in chemsex. In much of the world, these immediate harms are further compounded by the criminalisation and stigmatisation of both homosexuality and drug use, preventing participants fully engaging with treatment services or provision of health care. Gay, bisexual and other men who have sex with men participating in chemsex fall between the traditional definitions of key populations and consequently are poorly provided for by existing drug and sexual health frameworks. Aetiologically complex issues such as chemsex require multifaceted interventions that may fall outside conventional frameworks. Existing interventions have been designed and implemented at the local level. The use of international policy to mitigate these structural barriers, however, has largely been ignored. International policy is broad in nature and its implementation is, in principle, binding for member states. We believe that despite its low international prevalence, international policy can be of use in improving the lives of people who participate in chemsex. Through stimulating a much-needed debate on the interplay between sex and drugs within global health and harm reduction frameworks, this paper aims to address the paucity of substantial discussion surrounding the applicability of international language to chemsex. We analyse international policy aimed at addressing HIV, illicit drugs, harm reduction, and development, and make recommendations for both national advocacy, and advocates working to alter the positions of member states internationally.


Bone marrow examination: for metastatic tumor: aspirate and biopsy.
A 6-year experience with bone marrow aspirates and biopsies (96 cases) positive for metastatic carcinoma is reviewed. Marrow examination detected secondary carcinoma in 58 cases (60%) despite negative roentgenographic and/or bone scan examinations. Breast carcinoma was the most frequent primary site. The bone marrow biopsy was superior to the aspirate in finding carcinoma (97% vs. 72%). However, in an occasional case, tumor was found only in aspirate preparations. Both procedures should be considered complementary and are recommended in the marrow evaluation of patients with carcinoma.


New surfaces stabilized by adsorbate-induced faceting.
Faceting is a form of self-assembly of single-crystal surfaces at the nanometer-scale in which an initially planar surface converts to a 'hill-and-valley' structure, exposing new faces of low-index surfaces. Our recent studies revealed that, upon annealing in O(2), three-sided nanoscale pyramids form on Ir(210) exposing smooth {311} and partially restructured (110) faces. Through a combination of scanning tunneling microscopy and density functional theory, we identify this structure to be a stepped double-missing-row reconstruction, which is only stable on nanopyramidal facets, not on a planar Ir(110) surface. This faceting-enabled stabilization of a hitherto unstable surface points to a new approach to prepare nanoscale model catalysts for structure-sensitivity studies in heterogeneous (electro-)catalysis with high selectivity and reactivity.


Implementation of an open adoption research data management system for clinical studies.
Research institutions need to manage multiple studies with individual data sets, processing rules and different permissions. So far, there is no standard technology that provides an easy to use environment to create databases and user interfaces for clinical trials or research studies. Therefore various software solutions are being used-from custom software, explicitly designed for a specific study, to cost intensive commercial Clinical Trial Management Systems (CTMS) up to very basic approaches with self-designed Microsoft® databases. The technology applied to conduct those studies varies tremendously from study to study, making it difficult to evaluate data across various studies (meta-analysis) and keeping a defined level of quality in database design, data processing, displaying and exporting. Furthermore, the systems being used to collect study data are often operated redundantly to systems used in patient care. As a consequence the data collection in studies is inefficient and data quality may suffer from unsynchronized datasets, non-normalized database scenarios and manually executed data transfers. With OpenCampus Research we implemented an open adoption software (OAS) solution on an open source basis, which provides a standard environment for state-of-the-art research database management at low cost.


Interactions between Escherichia coli arginyl-tRNA synthetase and its substrates.
Interactions between Escherichia coli arginyl-tRNA synthetase and its substrates were extensively studied and distinctly demonstrated. Various approaches such as equilibrium dialysis, fluorescence titration, and substrate protection against heat inactivation of the enzyme were used for these studies. In the absence of other substrates, the equilibrium dissociation constants for arginine, ATP, and the cognate tRNA were about 70 microM, 0.85 mM, and 0.45 microM, respectively, at pH 7.5, in Tris buffer. The binding of arginine to the enzyme was affected neither by the presence of tRNA nor by the presence of ATP but was considerably enhanced when ATP and tRNA were both present at saturating concentrations. The dissociation constant in this case (about 16 microM) was very close to the Km (12 microM) for arginine during aminoacylation. The binding of ATP (the equilibrium dissociation constant KD approximately 0.85 mM) was not affected by the presence of arginine but was depressed in the presence of tRNA (KD became 3 mM). Arginyl-tRNA showed a dissociation constant of (4-5) X 10(-7) M which was not affected by the presence of a single other substrate. Possible explanations for the high Km for tRNA in the aminoacylation are discussed. Our results indicated pronounced interactions between substrates mediated by the enzyme under catalytic conditions. Periodate oxidation did not alter the tRNA binding to the enzyme. The oxidized tRNA still afforded protection against heat inactivation of the enzyme.


pMH11, A tool for gene disruption and expression analysis in Azorhizobium caulinodans.
Tools for mutagenesis and expression analyses are needed to study the role of bacterial genes. Here, we report the construction of pMH11, a small, mobilizable plasmid that replicates in Escherichia coli, but not in Azorhizobium caulinodans, a nodulating microsymbiont of Sesbania rostrata, and that contains a unique BamHI restriction site upstream of a promoterless lacZ gene. pMH11 and two derivatives with the multiple cloning site of pBluescript (KS(II)) are useful for mutagenesis by gene disruption and for expression analyses after selection for cointegration by kanamycin resistance. Weakly constitutive promoter activity from the vector allowed transcription of genes downstream of the integration site, so that no polar effects were caused by gene disruption.


Promotion of fracture healing by conjugated linoleic acid in rats.
The ability of fracture healing in Tibetans is significantly superior to Chinese Hans, which may attribute to factors from diet, altitude to physical conditions. Conjugated linoleic acid (CLA) is an important ingredient in Tibetan diet, playing a role in antioxidation, antiatherosclerosis, and decrease in body fat accumulation. Methods: This study further quantified CLA effect in fracture healing in rats using combined structural evaluation (X-ray and micro-computed tomography), biomechanical test, and histological examination. CLA could promote fracture healing with quicker development of trabecular connection, network and thickening and were more active at the stage of bony union and remodeling. The load to failure could reach 78.12 ± 10.03 N, 41.4% stronger than the control by week 6 ( p = 0.0209). CLA improved the quality and mechanical strength of fracture healing in rats callus. The information may offer insight in development of new therapeutic strategies of fracture healing for general populations beyond Tibetans.


Sugarcane DIRIGENT and O-methyltransferase promoters confer stem-regulated gene expression in diverse monocots.
Transcription profiling analysis identified Saccharum hybrid DIRIGENT (SHDIR16) and Omicron-Methyltransferase (SHOMT), putative defense and fiber biosynthesis-related genes that are highly expressed in the stem of sugarcane, a major sucrose accumulator and biomass producer. Promoters (Pro) of these genes were isolated and fused to the beta-glucuronidase (GUS) reporter gene. Transient and stable transgene expression analyses showed that both Pro( DIR16 ):GUS and Pro( OMT ):GUS retain the expression characteristics of their respective endogenous genes in sugarcane and function in orthologous monocot species, including rice, maize and sorghum. Furthermore, both promoters conferred stem-regulated expression, which was further enhanced in the stem and induced in the leaf and root by salicylic acid, jasmonic acid and methyl jasmonate, key regulators of biotic and abiotic stresses. Pro( DIR16 ) and Pro( OMT ) will enable functional gene analysis in monocots, and will facilitate engineering monocots for improved carbon metabolism, enhanced stress tolerance and bioenergy production.


Familial hyperproinsulinemia. Two cohorts secreting indistinguishable type II intermediates of proinsulin conversion.
Familial hyperproinsulinemia, a hereditary syndrome in which individuals secrete high amounts of 9,000-mol wt proinsulin-like material, has been identified in two unrelated cohorts. Separate analysis of the material from each of the two cohorts had suggested that the proinsulin-like peptide was a conversion intermediate in which the C-peptide remained attached to the insulin B-chain in one case, whereas it was a conversion intermediate in which the C-peptide remained attached to the insulin A-chain in the other. To reinvestigate this apparent discrepancy, we have now used chemical, biochemical, immunochemical, and physical techniques to compare in parallel the structures of the immunoaffinity chromatography-purified, proinsulin-like peptides isolated from the serum of members of both families. Our results show that affected individuals in both cohorts secrete two-chained intermediates of proinsulin conversion in which the COOH-terminus of the C-peptide is extended by the insulin A-chain and from which the insulin B-chain is released by oxidative sulfitolysis. Analysis of the conversion intermediates by reverse-phase high-performance liquid chromatography using two different buffer systems showed that the proinsulin-related peptides from both families elute at a single position very near that of the normal intermediate des-Arg31, Arg32-proinsulin. Further, treatment of these peptides with acetic anhydride prevented trypsin-catalyzed cleavage of the C-peptide from the insulin A-chain, a result demonstrating the presence of Lys64 and the absence of Arg65 in both abnormal forms. We conclude that individuals from both cohorts with familial hyperproinsulinemia secret very similar or identical intermediates of proinsulin conversion in which the C-peptide remains attached to the insulin A chain and in which Arg65 has been replaced by another amino acid residue.


Blau syndrome-associated Nod2 mutation alters expression of full-length NOD2 and limits responses to muramyl dipeptide in knock-in mice.
The biochemical mechanism by which mutations in nucleotide-binding oligomerization domain containing 2 (NOD2) cause Blau syndrome is unknown. Several studies have examined the effect of mutations associated with Blau syndrome in vitro, but none has looked at the implication of the mutations in vivo. To test the hypothesis that mutated NOD2 causes alterations in signaling pathways downstream of NOD2, we created a Nod2 knock-in mouse carrying the most common mutation seen in Blau syndrome, R314Q (corresponding to R334Q in humans). The endogenous regulatory elements of mouse Nod2 were unaltered. R314Q mice showed reduced cytokine production in response to i.p. and intravitreal muramyl dipeptide (MDP). Macrophages from R314Q mice showed reduced NF-κB and IL-6 responses, blunted phosphorylation of MAPKs, and deficient ubiquitination of receptor-interacting protein 2 in response to MDP. R314Q mice expressed a truncated 80-kDa form of NOD2 that was most likely generated by a posttranslational event because there was no evidence for a stop codon or alternative splicing event. Human macrophages from two patients with Blau syndrome also showed a reduction of both cytokine production and phosphorylation of p38 in response to MDP, indicating that both R314Q mice and cells from patients with Blau syndrome show reduced responses to MDP. These data indicate that the R314Q mutation when studied with the Nod2 endogenous regulatory elements left intact is associated with marked structural and biochemical changes that are significantly different from those observed from studies of the mutation using overexpression, transient transfection systems.


Prevalence of gestational diabetes mellitus and associated risk factors in pregnant Chinese women: a cross-sectional study in Huangdao, Qingdao, China.
This study explored the prevalence of gestational diabetes mellitus (GDM) in Chinese pregnant women and identified risk factors for GDM after the implementation of the universal two-child policy. On the basis of income and population, we randomly selected three hospitals through stratified and cluster sampling. From January 1 to July 31, 2016, 4959 women who had been registered within 12 weeks of gestation received a 75-g 2-h oral glucose tolerance test (OGTT) at 24-28 gestational weeks. International Association of Diabetes and Pregnancy Study Group criteria were used for the diagnosis of GDM. The OGTT was positive in 1080 (21.8%; 1080/4959) women, who were then diagnosed as having GDM on the basis of their results. GDM was positively associated with the following factors: advanced maternal age (p<0.001; adjusted odds ratio [OR]=4.88; 95% confidence interval [CI]=2.38-10.0, pre-pregnancy body mass index overweight (OR=2.44, 95% CI=1.78-3.34)/obesity (OR=10.9, 95% CI=6-19.6; p<0.001), paternal history of diabetes (p=0.003; OR=2.54, 95% CI=1.38-4.67), and maternal history of diabetes (p<0.001; OR=3.6, 95% CI=2.16-5.98). Qingdao has an exceptionally high estimated prevalence of GDM. Widely recognized risk factors for GDM were advanced age, pre-pregnancy overweight/obesity, and a family history of diabetes in first-degree relatives. More options to prevent and manage GDM must be explored.


Records in fractal stochastic processes.
The record statistics in stationary and non-stationary fractal time series is studied extensively. By calculating various concepts in record dynamics, we find some interesting results. In stationary fractional Gaussian noises, we observe a universal behavior for the whole range of Hurst exponents. However, for non-stationary fractional Brownian motions, the record dynamics is crucially dependent on the memory, which plays the role of a non-stationarity index, here. Indeed, the deviation from the results of the stationary case increases by increasing the Hurst exponent in fractional Brownian motions. We demonstrate that the memory governs the dynamics of the records as long as it causes non-stationarity in fractal stochastic processes; otherwise, it has no impact on the record statistics.


[Annular erythema in childhood--a new eosinophilic dermatosis].
Annular erythema of infancy is a rare and little-known entity. Since its initial description by Peterson and Jarratt in 1981 only 4 further cases have been reported. We present the first case in the German literature. A 4-year-old boy developed non-itching erythematous papules on the trunk which evolved into annular and gyrate erythemas within weeks. The condition showed a relapsing course with disease-free intervals of several months duration. There were no general complaints. Laboratory investigations including detailed serological tests for infectious diseases were normal. Histopathology showed a striking eosinophilic inflammatory infiltrate predominantly in perivascular areas, without peripheral blood eosinophilia. The clinical differential diagnosis of annular erythema of infancy includes erythema annulare centrifugum, while microscopically one must exclude eosinophilic cellulitis (Wells' syndrome). The etiology is unknown and there is no effective therapy. In our case, as well as in all previously published cases, the disease resolved spontaneously. Therefore, it may be considered benign and self-limited.


Bioelectrical impedance: from theories to applications.
Total body bioelectrical impedance is a measure for total body water. From total body water the fat free mass and, by difference with body weight, the fat mass (body fat percent) can be calculated. Prediction formulas for body fat percent based on impedance assume a constant hydration of the fat free mass, an assumption that might be violated in individuals, thus resulting in biased individual predictions. The electrical properties of the human body depend on water distribution between extra- and intra-cellular space and also on geometrical water distribution. In addition, body build factors also influence total or segmental impedance values. As body build and water distribution can differ between populations, impedance formulas aiming to quantify water compartments or body fat percent should also be population specific. In addition other factors like body position, skin and/or body temperature and osmotic values of the body fluids have an impact on the measured impedance values. This, together with likely disturbances in body water distribution in patients, makes the quantitative use of impedance in clinical practice difficult and prone to misinterpretations. For the prediction of body fat percent in populations, the method can be suitable. But, as there are differences in body build between (ethnic) population groups, for example in relative leg length and in slenderness, it is likely that that prediction formulas have different bias across ethnic groups. This means that for meaningful comparisons between population groups, formulas have to be validated in these groups.


Deep organ space infection after emergency bowel resection and anastomosis: The anatomic site does not matter.
Deep organ space infection (DOSI) is a serious complication after emergency bowel resection and anastomosis. The aim of this study was to identify the incidence and risk factors for the development of DOSI. National Surgical Quality Improvement Program database study including patients who underwent large bowel or small bowel resection and primary anastomosis. The incidence, outcomes, and risk factors for DOSI were evaluated using univariate and multivariate analyses. A total of 87,562 patients underwent small bowel, large bowel, or rectal resection and anastomosis. Of these, 14,942 (17.1%) underwent emergency operations and formed the study population. The overall mortality rate in emergency operations was 12.5%, and the rate of DOSI was 5.6%. A total of 18.0% required ventilatory support in more than 48 hours, and 16.0% required reoperation. Predictors of DOSI included age, steroid use, sepsis or septic shock on admission, severe wound contamination, and advanced American Society of Anesthesiologists classification. The anatomic location of resection and anastomosis was not significantly associated with DOSI. Patients undergoing emergency bowel resection and anastomosis have a high mortality, risk of DOSI, and systemic complications. Independent predictors of DOSI include wound and American Society of Anesthesiologists classification, sepsis or septic shock on admission, and steroid use. The anatomic location of resection and anastomosis was not significantly associated with DOSI. Epidemiologic/prognostic study, level III.


Thickness dependence of amplified spontaneous emission in low-absorbing organic waveguides.
The effect of varying film thickness (h) on the amplified spontaneous emission (ASE) properties of 0.5 wt.% perylenediimide-doped polystyrene waveguides is reported. The threshold dependence on h, not previously investigated in detail, is analyzed in terms of the film absorption and photoluminescence, the confinement of the fundamental waveguide mode (TE0), and the presence of high-order modes. For h<400 nm and down to 150 nm, the ASE wavelength blueshifts, while the linewidth and threshold increase. The detrimental ASE operation in very thin films is due to the low absorption as well as to the poor confinement of the TE0 mode.


Complexation, Stabilization, and UV Photolysis of Extracellular and Surface-Bound Glucosidase and Alkaline Phosphatase: Implications for Biofilm Microbiota.
Biofilm-produced and commercially-purified a- and b-glucosidase and alkaline phosphatase were subjected to different spectral portions of natural and artificial light and exposed to various humic substances to elucidate their impact on enzyme activities. Photochemical degradation of all enzymes occurred under different portions of the light spectrum. UVB irradiance produced the greatest overall photochemical degradation of enzymes, with significant rates occurring with UVA and PAR irradiance. The complexation of enzymes with humic substances resulted in inhibition, stabilization, and photochemical protection of the enzyme. Inhibition of enzyme activity occurred via reductions in overall enzyme activity in the presence of humic substances. However, humic-enzyme complexation also resulted in stabilization by restricting enzyme degradation while retaining high activities. Enzymes exposed to natural and artificial light sources had significantly lower reductions in enzyme activities in the presence of humic substances, which indicates that humic-enzyme complexes may protect enzymes from light-induced photochemical degradation. Bacterial surface-bound a- and b-glucosidase activities were significantly reduced in the presence of humic substances. Photosynthetically induced pH changes within biofilm communities can cause large reductions in a- and b-glucosidase activities while enhancing the hydrolytic activity of alkaline phosphatase.


Pharmacokinetics of two multiple-dosing regimens of D0870 in human immunodeficiency virus-positive patients: a phase I study.
D0870 is a triazole with a broad antifungal spectrum, and it has been shown to have both in vitro and in vivo activities against wild-type and fluconazole-resistant strains of Candida albicans. Twenty-two human immunodeficiency virus (HIV)-positive male subjects were enrolled in an open, nonrandomized trial investigating the pharmacokinetics of two different dosing regimens of D0870 and assessing the safety of multiple oral doses of D0870 in HIV-positive subjects and their ability to tolerate multiple oral doses. Nine subjects received an initial loading dose of 50 mg, followed by four once-daily maintenance doses of 10 mg. A further nine subjects received an initial 200-mg loading dose followed by four daily maintenance doses of 25 mg. All subjects were fasting. A single loading dose of 50 mg of D0870 resulted in a mean maximum concentration in serum (Cmax) of 107 +/- 32 ng/ml. Concentrations in plasma were maintained by the 10-mg once-daily dosing regimen as seen by the similar values of the area under the concentration-time curve from 0 to 24 h following dosing on days 1 and 5 and a mean accumulation ratio close to unity (0.90). The terminal plasma half-life of D0870 in plasma following dosing on day 5 ranged from 23 to 85 h (mean, 49 h). A single loading dose of 200 mg of D0870 resulted in a Cmax of 431 +/- 186 ng/ml. Concentrations in plasma were again maintained by the 25-mg daily dosing regimen, with the mean accumulation ratio being close to unity (1.17). The terminal half-life of D0870 in plasma following dosing on day 5 of phase II of the study ranged from 34 to 137 h (mean, 71 h). In addition, the concentrations achieved in the plasma of these HIV-positive subjects were similar to the values predicted from simulations based on data derived from normal, healthy subjects. D0870 was well tolerated. No serious adverse events were experienced during the course of the study, and all volunteers completed the trial. A total of 15 adverse events were reported, but none were considered to be related to the administration of D0870 and all had resolved by the end of the trial. No changes in the hematology, clinical chemistry, or urinalysis parameters were considered to be related to dosing with D0870. No clinically significant changes in the electrocardiogram parameters were noted during the trial. The data generated in this trial support further investigation of these regimens with HIV-positive subjects with fluconazole-susceptible or -resistant oropharyngeal candidosis.


Multiple layers of regulation influence cell integrity control by the PKC ortholog Pck2 in fission yeast.
The fission yeast protein kinase C (PKC) ortholog Pck2 controls cell wall synthesis and is a major upstream activator of the cell integrity pathway (CIP) and its core component, the MAP kinase Pmk1 (also known as Spm1), in response to environmental stimuli. We show that in vivo phosphorylation of Pck2 at the conserved T842 activation loop during growth and in response to different stresses is mediated by the phosphoinositide-dependent kinase (PDK) ortholog Ksg1 and an autophosphorylation mechanism. However, T842 phosphorylation is not essential for Pmk1 activation, and putative phosphorylation at T846 might play an additional role in Pck2 catalytic activation and downstream signaling. These events, together with turn motif autophosphorylation at T984 and binding to small GTPases Rho1 and/or Rho2, stabilize Pck2 and render it competent to exert its biological functions. Remarkably, the target of rapamycin complex 2 (TORC2) does not participate in the catalytic activation of Pck2, but instead contributes to de novo Pck2 synthesis, which is essential to activate the CIP in response to cell wall damage or glucose exhaustion. These results unveil a novel mechanism whereby TOR regulates PKC function at a translational level, and they add a new regulatory layer to MAPK signaling cascades.


A comparison of continuous video-EEG monitoring and 30-minute EEG in an ICU.
To determine whether there is added benefit in detecting electrographic abnormalities from 16-24 hours of continuous video-EEG in adult medical/surgical ICU patients, compared to a 30-minute EEG. This was a prospectively enroled non-randomized study of 130 consecutive ICU patients for whom EEG was requested. For 117 patients, a 30-minute EEG was requested for altered mental state and/or suspected seizures; 83 patients continued with continuous video-EEG for 16-24 hours and 34 patients had only the 30-minute EEG. For 13 patients with prior seizures, continuous video-EEG was requested and was carried out for 16-24 hours. We gathered EEG data prospectively, and reviewed the medical records retrospectively to assess the impact of continuous video-EEG. A total of 83 continuous video-EEG recordings were performed for 16-24 hours beyond 30 minutes of routine EEG. All were slow, and 34% showed epileptiform findings in the first 30 minutes, including 2% with seizures. Over 16-24 hours, 14% developed new or additional epileptiform abnormalities, including 6% with seizures. In 8%, treatment was changed based on continuous video-EEG. Among the 34 EEGs limited to 30 minutes, almost all were slow and 18% showed epileptiform activity, including 3% with seizures. Among the 13 patients with known seizures, continuous video-EEG was slow in all and 69% had epileptiform abnormalities in the first 30 minutes, including 31% with seizures. An additional 8% developed epileptiform abnormalities over 16-24 hours. In 46%, treatment was changed based on continuous video-EEG. This study indicates that if continuous video-EEG is not available, a 30-minute EEG in the ICU has a substantial diagnostic yield and will lead to the detection of the majority of epileptiform abnormalities. In a small percentage of patients, continuous video-EEG will lead to the detection of additional epileptiform abnormalities. In a sub-population, with a history of seizures prior to the initiation of EEG recording, the benefits of continuous video-EEG in monitoring seizure activity and influencing treatment may be greater.


[Surgical treatment of patients with hilar cholangiocarcinoma in a single center].
Objective: To study the experience of preoperative evaluation, surgical planning and postoperative treatment of hilar cholangiocarcinoma (HCC) in our center. Method: The clinical data of 70 patients with HCC who underwent resection at the First Affiliated Hospital of Bengbu Medical College, from January 2011 to December 2017 were analyzed retrospectively. The treatment experience of HCC from the aspects of preoperative evaluation and treatment, surgical methods, postoperative recovery and prognosis were discussed. Results: The accurate evaluation of HCC by three-dimensional visualization technology was beneficial to the formulation of surgical plan preoperatively. Extended hemihepatectomy or combined resection of caudate lobe or portal vein was effective for type Ⅲ-Ⅳ HCC. The R0 resection rate was 93% (53/57). Postoperative pathology showed that high/middle/low differentiated adenocarcinoma of 21/30/16, adenoma in 2 cases, inflammatory lesion in 1 case. The 1/3/5-year overall survival rates of patients with adenocarcinoma after chemotherapy were 87%(60/69)/47.0%(31/66)/30.2%(19/63) respectively. Conclusion: HCC patients who under radical surgery after preoperative evaluation and postoperative chemotherapy can obtain a good prognosis. Expanding hepatectomy can improve R0 resection rate and prognosis in patients with type Ⅲ-Ⅳ HCC.


The morbidity and outcome of patients with Guillain-Barré syndrome admitted to the intensive care unit.
One third of patients with Guillain-Barré syndrome (GBS) require admission to the intensive care unit (ICU), associated with significant risk of morbidity, mortality, and incomplete recovery. 76 adult patients with GBS admitted to the ICU at a regional referral center over a 20-year period were studied. We determined the frequency, nature, and predictors of complications they experienced while in the ICU; this morbidity was related to long-term functional recovery and time to regain independent ambulation, extracted from longitudinal follow-up data. ICU stay was a median 21 days and mechanical ventilation (MV) was required in 78% (median duration 28 days). Two-thirds suffered at least one major complication, most commonly pneumonia (54%). Morbidity was strongly associated with MV and male sex. Mortality occurred in only 5 patients (6.5%). Over an average 3 years follow-up, recovery of independent ambulation was seen in 75%, with advanced age being the most powerful predictor of poor outcome. Prolonged MV and severe axonal loss did not preclude a favorable recovery. Time to ambulate was a median 198 days, although recovery could occur as late as ten years after onset; slower recovery was associated with ICU complications, prolonged MV, and early axonal abnormalities. Although patients with GBS suffer significant morbidity during protracted ICU stays, with meticulous supportive care, many make gratifying functional recoveries. In severely afflicted patients, this may only be appreciated after extended follow-up.


Dietary soy protein isolate modifies hepatic retinoic acid receptor-beta proteins and inhibits their DNA binding activity in rats.
Retinoic acid receptors (RAR) belong to the same nuclear receptor superfamily as thyroid hormone receptors (TR) that were previously shown to be modulated by dietary soy protein isolate (SPI). This study has examined the effect of dietary SPI and isoflavones (ISF) on hepatic RAR gene expression and DNA binding activity. In Expt. 1, Sprague-Dawley rats were fed diets containing 20% casein or 20% alcohol-washed SPI in the absence or presence of increasing amounts of ISF (5-1250 mg/kg diet) for 70, 190, or 310 d. In Expt. 2, weanling Sprague-Dawley rats were fed diets containing 20% casein with or without supplemental ISF (50 mg/kg diet) or increasing amounts of alcohol-washed SPI (5, 10, and 20%) for 90 d. Intake of soy proteins significantly elevated hepatic RARbeta2 protein content dose-dependently compared with a casein diet, whereas supplemental ISF had no consistent effect. Neither RARbeta protein in the other tissues measured nor the other RAR (RARalpha and RARgamma) in the liver were affected by dietary SPI, indicating a tissue and isoform-specific effect of SPI. RARbeta2 mRNA abundances were not different between dietary groups except that its expression was markedly suppressed in male rats fed SPI for 310 d. DNA binding activity of nuclear RARbeta was significantly attenuated and the isoelectric points of RARbeta2 were shifted by dietary SPI. Overall, these results show for the first time, to our knowledge, that dietary soy proteins affect hepatic RARbeta2 protein content and RARbeta DNA binding activity, which may contribute to the suppression of retinoid-induced hypertriglyceridemia by SPI as reported.


[Pressure load of the temporomandibular joint--an experimental study].
In the connection with the pathogenesis and therapy of the diseases of the temporo- mandibulare joint it is of interest, if and in what kind of extent the joint is pressure burden. For examining this problem photoelastic investigations on a lower jaw model were performed. According to the opening angle, burden height and attack point of the burden, pressure strengths of 90-270 N were ascertained on the proc. condylaris , when a pure rotation-movement was performed.


Gene expression signature of obesity in monozygotic twins.
Observational studies suggest that obesity might have a Mendelian origin, but it is not clear if gene expression patterns observed in obese subjects are secondary to genetic traits or not. Here we test a transcriptomic signature of obesity previously identified by our group on a large cohort of twin subjects (TwinsUK). The results show that the signature correlates strongly both with body mass index (BMI) and fat mass. Moreover, in paired transcriptomes of monozygotic twins, changes in signature correlate with changes in BMI and fat mass. We also identify a set of deregulated pathways involved in obesity, from inflammation to metabolism, and show that their pathway deregulation score is strongly correlated with BMI variations in pairs of identical twins. Taken together, our results strongly indicate that alterations in gene expression observed in obese subjects are not due to their genetic background, and should therefore primarily be associated with environment and lifestyle.


[Chemical constituents of Gekko swinhonis].
To study the chemical constituents of Gekko swinhonis. The compounds were isolated and purified by several column chromatographic methods with silica gel, ODS, Sephadex LH-20 and preparative HPLC, Their structures were identified by physicochemical properties and spectral data. Thirteen compounds were isolated and elucidated as cyclo-(Pro-Leu) (1), cyclo-(Ala-Pro) (2),cyclo-(Gly-Pro) (3),cyclo-(Ala-Val) (4),6-amino-9-beta-D-ribofuranosyl-9H-purine (5), uridine (6), thymidine (7),hypoxanthine-9-beta-D-ribofuranosid (8),L-phenylalanine (9),5alpha-cholest-3,6-dione (10),cholesterol (11), 1-O-hexadecanolenin (12),octadecanoic acid (13),respectively. All compounds were isolated from G. swinhonis for the first time.


Efficacy of butylscopolamine for the treatment of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study.
Catheter-related bladder discomfort (CRBD) secondary to intraoperative catheterization of urinary bladder is one of the most distressing symptoms during recovery from anaesthesia. Butylscopolamine, a peripheral antimuscarinic agent, is effective for relieving the pain, which is because of smooth muscle contraction. The aim of this study was to assess the efficacy and safety profiles of butylscopolamine in treating CRBD after urological surgeries. Adult male patients undergoing urological surgery requiring urinary bladder catheterization intraoperatively were enrolled. Induction and maintenance of anaesthesia were standardized. Patients were randomized into two groups after complaining of CRBD in the post-anaesthesia care unit. The control group (n=29) received normal saline and the butylscopolamine group (n=28) was administered butylscopolamine 20 mg i.v. The severity of CRBD, postoperative pain, and adverse effects were assessed at baseline, 20 min, 1, 2, and 6 h after administration of the study drug. The severity of CRBD observed in the butylscopolamine group was significantly lower than that of the control group at 1, 2, and 6 h after administration of the study drug [59 (12), 50 (16), 40 (21) in the control group vs 41 (22), 32 (25), 23 (18) in the butylscopolamine group, P<0.01]. Rescue analgesics were required less in the butylscopolamine group than in the control group (P=0.001). Adverse events were comparable between the two groups. Butylscopolamine 20 mg administered i.v. after complaining CRBD during recovery reduced both the severity of CRBD and the need for rescue analgesics without adverse effects in patients undergoing urologic surgeries.


Length requirements for tRNA-specific enzymes and cleavage specificity at the 3' end of turnip yellow mosaic virus RNA.
This paper describes the minimum length of the turnip yellow mosaic virus (TYMV) RNA necessary to fulfill the tRNA-like properties of the viral RNA: 50 to 75 nucleotides and 86 nucleotides from the 3' end of TYMV RNA are sufficient for adenylation and valylation respectively by the Escherichia coli system. The size of the tRNA-like fragments obtained in vitro in the presence of an E. coli, a reticulocyte or a chinese cabbage leaf extract has also been determined. Among the major fragments liberated from the 3' end of TYMV RNA by the three systems are fragments of 117 and 112 nucleotides. In addition, the E. coli extract liberates fragments of 139 and 61 nucleotides, and the reticulocyte lysate fragments of 109, 94, 84, 73 and 46 nucleotides. The cleavage of the viral RNA by several systems in vitro to yield RNA fragments encompassing the tRNA-like sequence suggests that such fragments might also be liberated in vivo.


Radioprotective agents for radiation therapy: future trends.
Only two radioprotective compounds, amifostine and palifermin, currently have the US FDA approval for use in radiation therapy. However, several agents have been reported that show therapeutic promise. Many of these agents are free radical scavengers/antioxidants. Superoxide dismutase and superoxide dismutase mimetics, nitroxides and dietary antioxidants are all being investigated. Recently, alternative strategies of drug development have been evolving, which focus on targeting the series of cellular insult recognition/repair responses initiated following radiation. These agents, which include cytokines/growth factors, angiotensin-converting enzyme inhibitors and apoptotic modulators, show promise of having significant impact on the mitigation of radiation injury. Herein, we review current literature on the development of radioprotectors with emphasis on compounds with proven or potential usefulness in radiation therapy.


Reliability of an Integrated Ultrasound and Stereophotogrammetric System for Lower Limb Anatomical Characterisation.
Lower extremity analysis for preoperative total knee and hip arthroplasty routines can increase surgery success rate and hence reduce associated costs. Current tools are limited by being invasive, limited to supine analysis, or too expensive. This study aimed to propose and validate a device, OrthoPilot®, based on the combined use of a stereophotogrammetric and ultrasound system which can in vivo and noninvasively measure varus/valgus, flexion/extension, femur and tibia torsion, and femur and tibia lengths. A phantom was measured by four operators to determine the resolution of the system. Interoperator variability was measured on three operators who measured the above six variables on both legs of three subjects in standing and supine positions. Intraoperator variability was assessed on data from three repeats from 9 subjects (18 legs). All 6 variables were reliably detected on a phantom, with a resolution of 1 mm and 0.5°. Inter- and intraoperator consistency was observed for varus/valgus, flexion/extension, and length measurements on the healthy subjects in standing and supine positions (all ICC > 0.93). For torsion measurements, there was a considerable variation. The proposed system, when used on healthy subjects, allowed reliable measurements of key parameters for preoperative procedures in both supine and standing positions. Accuracy testing and further validation on patient populations will be the next step toward its clinical adoption.


A laccase-catalysed tyrosine click reaction.
A laccase-catalysed tyrosine click reaction proceeded between the tyrosine modification reagent N-methyl luminol and tyrosine residues in peptides/proteins. Laccase-catalysed tyrosine-specific modification under mild reaction conditions (shaking at 37 °C) was more efficient than previously reported tyrosine click reactions using hemin, horseradish peroxidase (HRP) or electrochemistry.