HIV-1 subtype C reverse transcriptase sequences from drug-naive pregnant women in South Africa.
The HIV-1 reverse transcriptase genes from 37 HIV-1-positive pregnant women attending an antenatal clinical in Soweto, South Africa were sequenced and analyzed for the presence of drug resistance mutations. All women were antiretroviral drug naive, but were being screened as potential participants in clinical trials of antiretroviral drugs aimed at preventing mother-to-child transmission. Sequence analysis revealed that all belonged to HIV-1 subtype C, the predominant subtype among heterosexual populations in South Africa. Twenty-three amino acid loci associated with resistance to zidovudine, lamivudine, didanosine, stavudine, and nevirapine were examined and found not to encode mutations that would confer resistance to these drugs. Polymorphisms at these loci occurred infrequently, with three patients harboring the A98S and V179I polymorphisms. An additional three patients harbored V118I, which can function as an accessory resistance mutation, but in this context is also likely to be a polymorphism. These data show that pregnant women who are candidates for receiving antiretroviral drug therapies do not contain naturally occurring or preexisting drug resistance mutations and that such drug therapies are likely to be highly effective in this setting.


Genome-wide screen of Salmonella genes expressed during infection in pigs, using in vivo expression technology.
Pigs are a food-producing species that readily carry Salmonella but, in the great majority of cases, do not show clinical signs of disease. Little is known about the functions required by Salmonella to be maintained in pigs. We have devised a recombinase-based promoter-trapping strategy to identify genes with elevated expression during pig infection with Salmonella enterica serovar Typhimurium. A total of 55 clones with in vivo-induced promoters were selected from a genomic library of approximately 10,000 random Salmonella DNA fragments fused to the recombinase cre, and the cloned DNA fragments were analyzed by sequencing. Thirty-one genes encoding proteins involved in bacterial adhesion and colonization (including bcfA, hscA, rffG, and yciR), virulence (metL), heat shock (hscA), and a sensor of a two-component regulator (hydH) were identified. Among the 55 clones, 19 were isolated from both the tonsils and the intestine, while 23 were identified only in the intestine and 13 only in tonsils. High temperature and increased osmolarity were identified as environmental signals that induced in vivo-expressed genes, suggesting possible signals for expression.


[Effect of ketamine on global cerebral ischemia].
This review focuses on the significance of S-(+)-ketamine as a neuroprotective agent. Evidence in the literature supporting or contradicting a neuroprotective or even therapeutic role of ketamine in global cerebral ischaemia is critically reviewed, and data from an ongoing study in a rat global cerebral ischaemia model (15 min ischaemia with S(+)-ketamine administered 15 min after reperfusion) are reported. The number of experimental studies available so far limited, however, and therefore results cannot be considered conclusive at the present time. Only at higher ketamine dosages was protection found reliably, especially in models of complete forebrain ischaemia lasting over 10 min. In our own study, only after 90 mg/kg S(+)-ketamine was there significantly better preservation of cortical neurons than without treatment; 30 and 60 mg/kg did not produce this effect.


PERSPECTIVE: THE THEORIES OF FISHER AND WRIGHT IN THE CONTEXT OF METAPOPULATIONS: WHEN NATURE DOES MANY SMALL EXPERIMENTS.
We critically review the two major theories of adaptive evolution developed early in this century, Wright's shifting balance theory and Fisher's large population size theory, in light of novel findings from field observations, laboratory experiments, and theoretical research conducted over the past 15 years. Ecological studies of metapopulations have established that the processes of local extinction and colonization of demes are relatively common in natural populations of many species and theoretical population genetic models have shown that these ecological processes have genetic consequences within and among local demes. Within demes, random genetic drift converts nonadditive genetic variance into additive genetic variance, increasing, rather than limiting, the potential for adaptation to local environments. For this reason, the genetic differences that arise by drift among demes, can be augmented by local selection. The resulting adaptive differences in gene combinations potentially contribute to the genetic origin of new species. These and other recent findings were not discussed by either Wright or Fisher. For example, although Wright emphasized epistatic genetic variance, he did not discuss the conversion process. Similarly, Fisher did not discuss how the average additive effect of a gene varies among demes across a metapopulation whenever there is epistasis. We discuss the implications of such recent findings for the Wright-Fisher controversy and identify some critical open questions that require additional empirical and theoretical study.


Ammonia activates pacC and patulin accumulation in an acidic environment during apple colonization by Penicillium expansum.
Penicillium expansum, the causal agent of blue mould rot, causes severe post-harvest fruit maceration simultaneously with the secretion of d-gluconic acid (GLA) and the mycotoxin patulin in colonized tissue. The factor(s) inducing patulin biosynthesis during colonization of the host acidic environment is unclear. During the colonization of apple fruit in vivo and growth in culture, P. expansum secretes pH-modulating GLA and ammonia. Although patulin and its possible opportunistic precursor GLA accumulate together during fungal development, ammonia is detected on the colonized tissue's leading edge and after extended culture, close to patulin accumulation. Here, we demonstrate ammonia-induced transcript activation of the global pH modulator PacC and patulin accumulation in the presence of GLA by: (i) direct exogenous treatment of P. expansum growing on solid medium; (ii) direct exogenous treatment on colonized apple tissue; (iii) growth under self-ammonia production conditions with limited carbon; and (iv) analysis of the transcriptional response to ammonia of the patulin biosynthesis cluster. Ammonia induced patulin accumulation concurrently with the transcript activation of pacC and patulin biosynthesis cluster genes, indicating the regulatory effect of ammonia on pacC transcript expression under acidic conditions. Electrophoretic mobility shift assays using P. expansum PacC and antibodies to the different cleaved proteins showed that PacC is not protected against proteolytic signalling at pH 4.5 relative to pH 7.0, but NH4 addition did not further enhance its proteolytic cleavage. Ammonia enhanced the activation of palF transcript in the Pal pathway under acidic conditions. Ammonia accumulation in the host environment by the pathogen under acidic pH may be a regulatory cue for pacC activation, towards the accumulation of secondary metabolites, such as patulin.


A qualitative study of the experiences and perceptions of patients with functional motor disorder.
Background: Patients with functional motor disorder are perceived as difficult by health care professionals, but we know very little about the patients' perspective. Understanding the experiences and perceptions of patients could help to improve clinical services and patient outcomes.Purpose: To explore the experiences and perspectives of patients with functional motor disorder using qualitative research methods.Methods: This qualitative study was embedded within a feasibility study of specialist physiotherapy. Eleven patients with functional motor disorder participated in semi-structured qualitative interviews prior to receiving treatment. The interview transcripts were subjected to an inductive thematic analysis.Results: The data were arranged into six themes: (1) the burden of living with functional motor disorder; (2) nobody knew what was wrong; (3) dissatisfaction with psychological explanations; (4) patients feel abandoned; (5) iatrogenic harm; and (6) powerlessness.Discussion and Conclusion: The study participants experienced substantial physical and emotional burdens associated with functional motor disorder. They were generally dissatisfied with psychological explanations for their symptoms and commonly felt misunderstood and abandoned by health care professionals, which appeared to leave them vulnerable to iatrogenic harm. A lack of understanding of functional motor disorder left participants feeling unable to help themselves. This research highlights a number of inadequacies within current clinical services for patients with functional motor disorder.Implications for rehabilitationCareful communication is required to help patients understand and accept the diagnosis of functional motor disorder.It is important to listen to the patient's narrative in order to help them make sense of their illness experience.A nuanced biopsychosocial explanatory model is needed to help patients understand how psychological factors can be relevant to physical symptoms and symptoms that are often perceived to be precipitated by a physical event.A lack of understanding and acceptance of the diagnosis may leave patients vulnerable to iatrogenic harm and powerless to help themselves.


Exploring the relationship between childhood obesity and proximity to the coast: A rural/urban perspective.
Childhood obesity is one of the 21st century's most serious global health challenges. Research suggests that better access to 'greenspace' (e.g. parks) may encourage physical activity and reduce the risk of obesity amongst children. We extend earlier work by considering childhood obesity in relation to proximity to the coast, using data from England's National Child Measurement Programme. Results suggest that although the overall prevalence of childhood obesity is slightly lower at the coast (-0.68% points comparing <1km to >20km, p<0.001), the relationship depends on area type. Specifically, although a coastal proximity gradient (lower obesity rates nearer the coast) was found for rural areas and smaller cities and towns, it was not present among large urban conurbations (interaction p-value<0.001). Coastal environments and access to them are changing in many areas, and research to explore potential impacts on child health is warranted.


Rice Endosperm Protein Improves the Anti-Inflammatory Effects of High-Density Lipoprotein and Produces Lower Atherosclerotic Lesion Accelerated by the Renal Mass Reduction than Casein in a Mouse Model.
Chronic kidney disease (CKD) impairs the anti-inflammatory effects of high-density lipoprotein (HDL) and increases cardiovascular mortality. Though the potential role of dietary interventions to manage HDL is well studied, the clinical trials aimed to increase HDL levels have failed to reduce cardiovascular risk, rendering HDL function to be explored as a more relevant clinical parameter. This study investigates the effects of rice endosperm protein (REP), a plant-based protein, on the anti-inflammatory properties of HDL and renal injury-driven atherosclerosis in comparison with casein, an animal protein. Ten-week-old apolipoprotein E-deficient hyperlipidemic mice underwent uninephrectomy. The mice (n = 6 each) were pair-fed a normal casein-based diet or a REP-based diet (both with 20.0% protein content) for seven weeks. Atherosclerotic lesions were detected by en face Sudan IV staining of the aorta. The number and sizes of the atherosclerotic lesions were significantly lower in the REP-based diet-fed group than the casein-based diet-fed group (p = 0.038). However, the REP-based diet neither elicited an ameliorative effect on kidney function or histology nor impacted the cholesterol profiles. Furthermore, HDL from the REP-based diet-fed mice significantly suppressed the inflammatory cytokine response of human umbilical vein endothelial cells than that from the casein-based diet-fed mice (MCP-1, p = 0.010; IL-6, p = 0.011; IL-1β, p = 0.028). The REP-based diet has a higher potential to lessen the atherosclerotic lesions accelerated by renal mass reduction than a casein-based diet, which could be associated with the anti-inflammatory effects of HDL.


Effect of combination therapy of rifampicin and azithromycin on TNF levels during a rat model of chronic osteomyelitis.
The purpose of the present study was to evaluate the combination of azithromycin and rifampicin on experimental chronic osteomyelitis due to Staphylococcus aureus. Alterations in bone bacterial titre, activity of tumour necrosis factor (TNF), a cytokine implicated in inflammation-induced bone pathology, and histopathological changes during infection and following antibiotic treatment were evaluated. Rats were infected with S. aureus by direct tibial inoculation and then randomized 56 days after infection to receive saline treatment or a combination of azithromycin and rifampicin (50 mg/kg po and 25 mg/kg sc respectively) once daily for 21 days. The combination of azithromycin and rifampicin was successful as determined by dramatic reduction in bone bacterial counts (approximately log 4 cfu), but regrowth of the organisms occurred suggesting that the duration of treatment was insufficient. TNF alpha mRNA and TNF activity were constantly elevated by approximately 20- and >200-fold, respectively, and remained elevated irrespective of antimicrobial treatment. Bone histology revealed extensive increase in bone turnover in both the infected and antibiotic treated bones with no difference being observed between the groups. This suggests that, in infected bone, the elevated TNF levels observed may be directly related to the bone pathology and both remain largely unchanged despite potent antibiotic therapy.


High-throughput protoplast transactivation (PTA) system for the analysis of Arabidopsis transcription factor function.
Genomic approaches have generated large Arabidopsis open reading frame (ORF) collections. However, molecular tools are required to characterize this ORFeome functionally. A high-throughput microtiter plate-based protoplast transactivation (PTA) system has been established that can be used in a screening approach to define which transcription factor (TF) regulates a given promoter in planta. Using to this procedure, the transactivation properties of 96 TFs can be analyzed rapidly, making use of promoter:Luciferase (LUC)-reporters and luciferase imaging. Applying GATEWAY® technology, we have established a platform to assay more than 700 Arabidopsis TFs. As a proof-of-principle, the ethylene response factor (ERF) family has been studied to evaluate this system. Importantly, distinct subsets of related ERF factors were found to activate specifically the well described target promoters RD29A and PDF1.2 that are under control of DRE or GCC box cis-elements, respectively. Furthermore, several applications of the PTA system have been demonstrated, such as analysis of transcriptional repressors, salt-inducible gene expression or functional interaction of signaling molecules like kinases and TFs. This novel molecular tool will improve functional studies on transcriptional regulation in plants significantly.


Antioxidants Attenuate Isolation- and L-DOPA-Induced Aggression in Mice.
Aggression is a major hallmark worldwide attributing negative traits in personality. Wide variety of antioxidants is used for the treatment of many ailments. The present study was conducted to evaluate the role of antioxidants such as ascorbic acid (15.42 and 30.84 mg/kg), beta carotene (1.02 and 2.05 mg/kg), vitamin E (2.5 and 5.0 mg/kg), and N-acetyl cysteine (102.85 and 205.70 mg/kg) in the treatment of aggression. Two aggression models (isolation induced aggression model and L-DOPA induced aggression model) were used in the study. Male albino mice (n = 330) were used in the study which were further subdivided into 11 groups (Group I-control, group II-diseased, group III-standard group, group IV-V treated with ascorbic, group VI-VII treated with beta carotene, group VIII-IX treated with vitamin E, group X-XI treated with N-acetyl cysteine for 14 consecutive days). Different biochemical markers (glutathione, superoxide dismutase, and catalase) were determined to evaluate the antioxidant potential in oxidative stress. High dose of vitamin E (5.0 mg/kg) was more effective to reduce the aggression in isolated animals while all other antioxidants produced dose-dependent anti-aggressive effect except N-acetyl cysteine which had marked anti-aggressive effect at low dose (102.75 mg/kg). Low doses of vitamin E (2.5 mg/kg) and N-acetyl cysteine (102.75 mg/kg) and high dose of beta carotene (2.05 mg/kg) were effective to prevent all aggression parameters in acute anti-aggressive activity against L-DOPA induced aggression. However, all test antioxidants were equally effective in chronic anti-aggressive studies against L-DOPA induced aggression. It may be concluded that selected antioxidants can reverse the aggression which is a key symptom of many neurological disorder.


Optimizing the efficacy of epitope-directed DNA vaccination.
An increasing number of clinical trials has been initiated to test the potential of prophylactic or curative vaccination with tumor Ag-encoding DNA vaccines. However, in the past years it has become apparent that for many Ags and in particular for tumor Ags the intracellular processing and presentation are suboptimal. To improve epitope-directed DNA vaccines we have developed a murine model system in which epitope-specific, DNA vaccine-induced T cell immunity can be followed by MHC tetramer technology directly ex vivo. We have used this well-defined model to dissect the parameters that are crucial for the induction of strong cytotoxic T cell immunity using two independent model Ags. These experiments have led to a set of five guidelines for the design of epitope-directed DNA vaccines, indicating that carboxyl-terminal fusion of the epitope to a carrier protein of foreign origin is the most favorable strategy. DNA vaccines that are based on these guidelines induce high-magnitude CD8(+) T cell responses in >95% of vaccinated animals. Moreover, T cell immunity induced by this type of optimized DNA vaccine provides long-term protection against otherwise lethal tumor challenges.


Preclinical evaluation of VIS513, a therapeutic antibody against dengue virus, in non-human primates.
Despite useful in vivo activity, no therapeutic against dengue virus (DENV) has demonstrated efficacy in clinical trials. Herein, we explored dosing and virological endpoints to guide the design of human trials of VIS513, a pan-serotype anti-DENV IgG1 antibody, in non-human primates (NHPs). Dosing VIS513 pre- or post-peak viremia in NHPs neutralized infectious DENV although RNAemia remained detectable post-treatment; differential interaction of human IgGs with macaque Fc-gamma receptors may delay clearance of neutralized DENV. Our findings suggest useful antiviral utility of VIS513 and highlight an important consideration when evaluating virological endpoints of trials for anti-DENV biologics.


Discrimination of soluble and aggregation-prone proteins based on sequence information.
Understanding the factors governing protein solubility is a key to grasp the mechanisms of protein solubility and may provide insight into protein aggregation and misfolding related diseases such as Alzheimer's disease. In this work, we attempt to identify factors important to protein solubility using feature selection. Firstly, we calculate 1438 features including physicochemical properties and statistics for each protein. Random Forest algorithm is used to select the most informative and the minimal subset of features based on their predictive performance. A predictive model is built based on 17 selected features. Compared with previous models, our model achieves better performance with a sensitivity of 0.82, specificity 0.85, ACC 0.84, AUC 0.91 and MCC 0.67. Furthermore, a model using a redundancy-reduced dataset (sequence identity <= 30%) achieves the same performance as the model without redundancy reduction. Our results provide not only a reliable model for predicting protein solubility but also a list of features important to protein solubility. The predictive model is implemented as a freely available web application at .


A network pharmacology technique used to investigate the potential mechanism of Ligustilide's effect on atherosclerosis.
Ligustilide (LIG) is a major active ingredient in traditional Chinese medicines that is also found in plant rhizomes such as carrot, coriander, and others, and it has been demonstrated to have cardiovascular preventive benefits. However, the mechanisms through which LIG protects the cardiovascular and cerebrovascular systems in atherosclerosis (AS) remain unknown. This study was aimed to investigate the mechanisms of LIG in AS utilizing the network pharmacology and molecular docking, and then to validate the putative mechanism through experiments. The network pharmacological analysis indicated that a total of 55 were performed on LIG and AS intersection targets. The genes of LIG and AS intersection targets enriched in the regulation of receptor and enzyme activity, cytokines-related, and transcription factors, indicating that these targets were primarily involved in cell proliferation and migration, regulating cell differentiation and skeletal activities in the development of AS. Finally, molecular docking was used to validate the major targets of LIG and AS intersection targets. Further experiments revealed that LIG may inhibit cell migration induced by AngII by reducing calcium influx, and regulating phenotypic translation-related proteins SM-22α and OPN. The present study investigated the potential targets and signaling pathways of LIG, which provides new insight into its anti-atherosclerosis actions in terms of reducing inflammation, cell proliferation, and migration, and may constitute a novel target for the treatment of AS. PRACTICAL APPLICATIONS: LIG has been shown to have cardiovascular protective benefits, the mechanism by which it protects the cardiovascular and cerebrovascular systems in AS remains unknown. This study uses a holistic network pharmacology strategy to investigate putative treatment pathways and conducts exploratory experimentation. The findings demonstrate that LIG reduces VSMC migration in the treatment of AS, acts as an anti-inflammatory agent, and prevents excessive cell proliferation and migration. Finally, the goal of our research is to uncover the molecular mechanism of LIG's influence on AS. The findings will provide a new research avenue for LIG as well as suggestions for the study of other herbal treatments. These research results will provide a new research direction for LIG and provide guidance for the research of other herbal medicines. This work revealed the multi-component, multi-target, multi-pathway, and multi-disease mechanism of LIG.


Kinetic difference between hydrolyses of gamma-cyclodextrin by human salivary and pancreatic alpha-amylases.
gamma-Cyclodextrin was found to be hydrolyzed by human salivary and pancreatic alpha-amylases (1,4-alpha-D-glucan glucanohydrolase, EC 18.104.22.168) at appreciable rates. The optimum pH for the enzyme reactions at 37 degrees C in the presence of 0.1 M NaCl was at around pH 5, which was remarkably different from the optimum pH (pH 6.9) of the enzymes for starch. The Km value (2.9 mg/ml) of pancreatic alpha-amylase for gamma-cyclodextrin was smaller than that (5.3 mg/ml) of salivary alpha-amylase at pH 5.3, while the V value of the former was 3.7-times larger than that of the latter. The hydrolyses of gamma-cyclodextrin by both enzymes took place via the multiple attack mechanism. The degrees of multiple attack by salivary and pancreatic alpha-amylases for gamma-cyclodextrin at pH 5.3 were 2.0 and 1.1, respectively. The distribution of maltodextrins produced by hydrolysis of gamma-cyclodextrin by salivary alpha-amylase was suggested to be independent of the substrate concentration, while that produced by pancreatic alpha-amylase was presumably dependent on the substrate concentration.


Limitation of portal vein embolization for extension of hepatectomy indication in patients with hepatocellular carcinoma.
Although percutaneous trans-hepatic portal vein embolization (PTPE) expands the candidate pool for hepatectomy in patients with hepatobiliary malignancies, the role of PTPE in patients with active hepatitis or cirrhosis has yet to be determined. Records of patients who underwent PTPE of the right portal vein between 1984 and April 2001 were reviewed retrospectively. To determine the indication for PTPE and subsequent hepatectomy, clinical variables, including serum concentrations of hyaluronic acid (HA), procollagen type III peptide (P-III-P), and the 7S domain of type IV collagen (7S-IV), were compared between patients who underwent right hepatectomy (group A; n=44) and the other patients (group B; n=17). The scores for prediction of postoperative liver failure (prediction score) and serum HA and P-III-P concentrations were different in the two groups. Thirteen of 30 patients (43%) whose prediction score was more than 50, the limit of the hepatectomy without PTPE, successfully underwent right hepatectomy following PTPE. The resectability ratios increased to 75% and 100%, when the HA concentration was < or = 100mg/L and the P-III-P concentration < or = 0.7/mL. Serum HA and P-III-P concentrations are useful guidelines for identifying candidates for right hepatectomy following PTPE.


Peppermint as a promising treatment agent in inflammatory conditions: A comprehensive systematic review of literature.
Inflammation, a type of the body's defense against injury or infection, causes many chronic disorders including diabetes, cardiovascular disease, and cancer. Therefore, discovering natural compounds with numerous biological activities for the management of inflammation is highly recommended. Out of natural compounds, peppermint and its main component, menthol, has been suggested to possess antiinflammatory potential. Four databases including Web of Sciences, PubMed, Scopus, and Embase were searched to identify articles about peppermint and its antiinflammatory effects up to March 2023. Out of 3805 records screened, 14 articles met the study criteria. The evidence reviewed here proposed peppermint as an antiinflammatory agent. Peppermint may suppress inflammation by activating the AMP-activated protein kinase/unc-51 like kinase 1/nuclear factor-E2 associated factor 2 autophagy pathway, downregulating extracellular signal-regulated kinase-nuclear factor kappa B and mitogen activated protein kinases pathways, attenuating oxidative stress, suppressing the production of pro-inflammatory mediators and nitric oxide, and inducing the production of antiinflammatory prostaglandins. Due to the promising antiinflammatory effects of peppermint and the lack of human studies in this regard, future randomized clinical trials examining the effects of peppermint on inflammation and its related maladies are warranted.


Radiative flux measurements in the troposphere.
The results of radiative flux-density measurements in the troposphere, made using an especially designed radiometer mounted on a Cessna 402B aircraft, are reported. The radiometer incorporates several well-known principles that result in highly accurate determinations of radiative fluxes in the atmosphere. Heating rates for gases and for aerosols are calculated, using measurements and radiosonde data. Instrument performance is verified by calculating the solar constant at the top of the atmosphere, using the radiative flux densities measured in the troposphere. Total heating rates of 0.175 and 0.377 K h(-1) are determined for hazy and foggy atmospheres, respectively. Aerosol heating rates of 0.065 and 0.235 K h(-1) are deduced from the total heating rates. Environmental noise measurements during data acquisition are presented. The solar constant value of 1387 +/- 21 W m(-2) derived from the experiments agrees within 4% of the standard value.


Left ventricular assist device recovery: does duration of mechanical support matter?
Heart failure is a widespread condition in the United States that is predicted to significantly increase in prevalence in the next decade. Many heart failure patients are given a left ventricular assist device (LVAD) while they wait for a heart transplant, while those that are not able to undergo a heart transplant may be given an LVAD permanently. However, past studies have observed a small subset of heart failure patients that recovered cardiac function of their native heart after being placed on an LVAD. As a result, some patients have been able to have their LVAD explanted and no longer needed a heart transplant. In this review, we analyzed the data of 15 studies that observed recovery of cardiac function in LVAD patients in order to investigate the effects that duration of LVAD support has on patient outcomes. From our review, we identified that there may be negative consequences of prolonged duration of mechanical support such as myocardial atrophy and abnormal calcium cycling as well as circumstances that may allow for a longer duration of LVAD support such as in patients using a continuous-flow LVAD, non-ischemic cardiomyopathy patients, and the specific pharmacological therapy.


Genetic variability of hepatitis C virus in chronically infected patients with viral breakthrough during interferon-ribavirin therapy.
Little is known about hepatitis C virus (HCV) breakthrough during antiviral therapy, although it would help in understanding HCV resistance to current antiviral treatments. To analyse the implication of virological factors and the vigour of humoral immune responses in this phenomenon, we studied nine chronic hepatitis C patients with a viral breakthrough during IFN/ribavirin combination therapy, as well as five responders and five non-responders. The IRES and regions coding for the capsid protein, the PePHD domain of envelope glycoprotein E2 and the NS5A and 5B proteins were amplified by RT-PCR before treatment, before and during breakthrough, and after treatment. The major variant sequence was obtained by direct sequencing. The heterogeneity of quasispecies was studied by SSCP in all patients and sequencing after cloning in seven genotype 1b-infected patients. Humoral responses against HCV epitopes were also analysed. The major sequences of IRES, PePHD, and NS5B remained stable during treatment, regardless of the treatment response. However, the capsid protein and the regions flanking PePHD showed sequence variations in breakthrough patients, although no specific mutation was identified. The variable V3 region of NS5A, but not the PKR-binding domain and the ISDR, seemed to be associated with differences in response to treatment. The analysis of HCV quasispecies revealed no characteristic pattern during treatment in breakthrough patients, whose HCV genome profiles looked most similar to that of non-responders. The humoral response was similar between groups. In conclusion, viral breakthrough does not seem to be due to selection of resistant strains with signature mutations.


Cavitation in medicine.
We generally think of bubbles as benign and harmless and yet they can manifest the most remarkable range of physical effects. Some of those effects are the stuff of our everyday experience as in the tinkling of a brook or the sounds of breaking waves at the beach. But even these mundane effects are examples of the ability of bubbles to gather, focus and radiate energy (acoustic energy in the above examples). In other contexts that focusing of energy can lead to serious technological problems as when cavitation bubbles eat great holes through ships' propeller blades or cause a threat to the integrity of the spillways at the Hoover Dam. In liquid-propelled rocket engines, bubbles pose a danger to the stability of the propulsion system, and in artificial heart valves they can cause serious damage to the red blood cells. In perhaps the most extraordinary example of energy focusing, collapsing cavitation bubbles can emit not only sound, but also light with black body radiation temperatures equal to that of the sun (Brennen 1995 Cavitation and bubble dynamics). But, harnessed carefully, this almost unique ability to focus energy can also be put to remarkably constructive use. Cavitation bubbles are now used in a remarkable range of surgical and medical procedures, for example to emulsify tissue (most commonly in cataract surgery or in lithotripsy procedures for the reduction of kidney and gall stones) or to manipulate the DNA in individual cells. By creating cavitation bubbles non-invasively thereby depositing and focusing energy non-intrusively, one can generate minute incisions or target cancer cells. This paper will begin by briefly reviewing the history of cavitation phenomena and will end with a vision of the new horizons for the amazing cavitation bubble.


Kinetic-Dominated Charging Mechanism within Representative Aqueous Electrolyte-based Electric Double-Layer Capacitors.
The chemical nature of electrolytes has been demonstrated to play a pivotal role in the charge storage of electric double-layer capacitors (EDLCs), whereas primary mechanisms are still partially resolved but controversial. In this work, a systematic exploration into EDL structures and kinetics of representative aqueous electrolytes is performed with numerical simulation and experimental research. Unusually, a novel charging mechanism exclusively predominated by kinetics is recognized, going beyond traditional views of manipulating capacitances preferentially via interfacial structural variations. Specifically, strikingly distinctive EDL structures stimulated by diverse ion sizes, valences, and mixtures manifest a virtually identical EDL capacitance, where the dielectric nature of solvents attenuates ionic effects on electrolyte redistributions, in stark contradiction with solvent-free counterpart and traditional Helmholtz theory. Meanwhile, corresponding kinetics evolve conspicuously with ionic species, intimately correlated with ion-solvent interactions. The achieved mechanisms are subsequently illuminated by electrochemical measurements, highlighting the crucial interplay between ions and solvents in regulating EDLC performances.


The nerve growth factor alters calreticulin translocation from the endoplasmic reticulum to the cell surface and its signaling pathway in epithelial ovarian cancer cells.
Ovarian cancer is the seventh most common cancer among women worldwide, causing approximately 120,000 deaths every year. Immunotherapy, designed to boost the body's natural defenses against cancer, appears to be a promising option against ovarian cancer. Calreticulin (CRT) is an endoplasmic reticulum (ER) resident chaperone that, translocated to the cell membrane after ER stress, allows cancer cells to be recognized by the immune system. The nerve growth factor (NGF) is a pro-angiogenic molecule overexpressed in this cancer. In the present study, we aimed to determine weather NGF has an effect in CRT translocation induced by cytotoxic and ER stress. We treated A2780 ovarian cancer cells with NGF, thapsigargin (Tg), an ER stress inducer and mitoxantrone (Mtx), a chemotherapeutic drug; CRT subcellular localization was analyzed by immunofluorescence followed by confocal microscopy. In order to determine NGF effect on Mtx and Tg-induced CRT translocation from the ER to the cell membrane, cells were preincubated with NGF prior to Mtx or Tg treatment and CRT translocation to the cell surface was determined by flow cytometry. In addition, by western blot analyses, we evaluated proteins associated with the CRT translocation pathway, both in A2780 cells and human ovarian samples. We also measured NGF effect on cell apoptosis induced by Mtx. Our results indicate that Mtx and Tg, but not NGF, induce CRT translocation to the cell membrane. NGF, however, inhibited CRT translocation induced by Mtx, while it had no effect on Tg-induced CRT exposure. NGF also diminished cell death induced by Mtx. NGF effect on CRT translocation could have consequences in immunotherapy, potentially lessening the effectiveness of this type of treatment.


Nitrosation, nitration, and autoxidation of the selective estrogen receptor modulator raloxifene by nitric oxide, peroxynitrite, and reactive nitrogen/oxygen species.
The regulation of estrogenic and antiestrogenic effects by selective estrogen receptor modulators (SERMs) provides the basis for use in long-term therapy in cancer chemoprevention and postmenopausal osteoporosis. However, the evidence for carcinogenic properties within this class requires study of potential pathways of toxicity. There is strong evidence for the elevation of cellular levels of NO in tissue treated with SERMs, including the benzothiophene derivative, raloxifene, in part via up-regulation of nitric oxide synthases. Therefore, the reactions of 17beta-estradiol (E(2)), raloxifene, and an isomer with NO, peroxynitrite, and reactive nitrogen/oxygen species (RNOS) generated from NO(2)(-)/H(2)O(2) systems were examined. Peroxynitrite from bolus injection or slow release from higher concentrations of 3-morpholinosydnonimine (SIN-1) reacted with the benzothiophenes and E(2) to give aromatic ring nitration, whereas peroxynitrite, produced from the slow decomposition of lower concentrations of SIN-1, was relatively unreactive toward E(2) and yielded oxidation and nitrosation products with raloxifene and its isomer. The oxidation and nitrosation products formed were characterized as a dimer and quinone oxime derivative. Interestingly, the reaction of the benzothiophenes with NO in aerobic solution efficiently generated the same oxidation products. Stable quinone oximes are not unprecedented but have not been previously reported as products of RNOS-mediated metabolism. The reaction of glutathione (GSH) with the quinone oxime gave both GSH adducts from Michael addition and reduction to the corresponding o-aminophenol. The ready autoxidation of raloxifene, observed in the presence of NO, is the first such observation on the reactivity of SERMs and is potentially a general phenomenon of significance to SERM chemical toxicology.


Sports psychiatry: mental health and mental disorders in athletes and exercise treatment of mental disorders.
Sports psychiatry has developed for the past 3 decades as an emerging field within psychiatry and sports medicine. An International society has been established in 1994 and also national interest groups were implemented, mostly within the national organizations for psychiatry, some also containing the topic of exercise treatment of mental disorders. Where are we now 30 years later? We systematically but also selectively review the medical literature on exercise, sport, psychiatry, mental health and mental disorders and related topics. The number of publications in the field has increased exponentially. Most topics keep remaining on the agenda, e.g., head trauma and concussion, drug abuse and doping, performance enhancement, overtraining, ADHD or eating disorders. Supported by the growing literature, evidence-based recommendations have become available now in many clinical areas. A relatively new phenomenon is muscle dysmorphia, observed in weightlifters, bodybuilders but also in college students and gym users. Further, sports therapy of mental disorders has been studied by more and more high-quality randomized controlled clinical trials. Mostly as a complementary treatment, however, for some disorders already with a 1a evidence level, e.g., depression, dementia or MCI but also post-traumatic stress disorder. Being grown up and accepted nowadays, sports psychiatry still represents a fast-developing field. The reverse side of the coin, sport therapy of mental disorders has received a scientific basis now. Who else than sports psychiatry could advance sport therapy of mental disorders? We need this enthusiasm for sports and psychiatry for our patients with mental disorders and it is time now for a broadening of the scope. Optimized psychiatric prevention and treatment of athletes and ideal sport-related support for individuals with mental disorders should be our main purpose and goal.


A Comparative Study of Dermatoscopic Features of Melasma and Hori's Nevus in Asian Patients.
Dermatoscopy is a noninvasive diagnostic tool for pigmented lesions. However, data regarding dermatoscopic features in melasma and Hori's nevus, which are commonly found in Asian populations, are still lacking. In addition, melasma coexisting with Hori's nevus presents a particular diagnostic challenge and they generally require different treatments. We sought to describe the dermatoscopic features of melasma and Hori's nevus and to establish diagnostic clues for each condition. Fifty patients with melasma and 46 patients with Hori's nevus were enrolled in the study. Dermatoscopic pictures were taken with Dermlite DL200 HR (3Gen, San Juan Capistrano, Califorinia) and evaluated by two blinded board-certified dermatologists. The dermatoscopic features more prominently seen in melasma compared to Hori's nevus include light brown pigmentation (98% vs. 10.9%, P<0.001), regular pigment network (38% vs. 2.2%, P<0.001), irregular pigment network (98% vs. 63%, P<0.001), arcuate structure (68% vs. 13%, P<0.001), circles (48% vs. 10.9%, P<0.001), sparing of follicles and sweat gland openings (98% vs. 4.3%, P<0.001), and telangiectasias (52% vs. 19.6%, P=0.001). In contrast, the common features of Hori's nevus include blue-brown or grey pigmentation (63% vs. 0%, P=0.001) and speckled homogenous pattern (52.2% vs. 0%, P<0.001). Dermatoscopy is a useful diagnostic tool for distinguishing between melasma and Hori's nevus. In patients with coexistence of both conditions, dermatoscopy can be used to confirm the diagnosis and aid the proper treatment.


Phenotyping of Silique Morphology in Oilseed Rape Using Skeletonization with Hierarchical Segmentation.
Silique morphology is an important trait that determines the yield output of oilseed rape (Brassica napus L.). Segmenting siliques and quantifying traits are challenging because of the complicated structure of an oilseed rape plant at the reproductive stage. This study aims to develop an accurate method in which a skeletonization algorithm was combined with the hierarchical segmentation (SHS) algorithm to separate siliques from the whole plant using 3-dimensional (3D) point clouds. We combined the L1-median skeleton with the random sample consensus for iteratively extracting skeleton points and optimized the skeleton based on information such as distance, angle, and direction from neighborhood points. Density-based spatial clustering of applications with noise and weighted unidirectional graph were used to achieve hierarchical segmentation of siliques. Using the SHS, we quantified the silique number (SN), silique length (SL), and silique volume (SV) automatically based on the geometric rules. The proposed method was tested with the oilseed rape plants at the mature stage grown in a greenhouse and field. We found that our method showed good performance in silique segmentation and phenotypic extraction with R 2 values of 0.922 and 0.934 for SN and total SL, respectively. Additionally, SN, total SL, and total SV had the statistical significance of correlations with the yield of a plant, with R values of 0.935, 0.916, and 0.897, respectively. Overall, the SHS algorithm is accurate, efficient, and robust for the segmentation of siliques and extraction of silique morphological parameters, which is promising for high-throughput silique phenotyping in oilseed rape breeding.


Total hip replacement for acetabular fractures. Results in 121 patients operated between 1983 and 2003.
Total hip replacement has an important role in the treatment of acetabular fractures. Immediate total hip arthroplasty is only indicated for some rare cases but late reconstruction is performed more frequently and may follow failed non-operative or operative treatment of the original acetabular fracture. The purpose of this study is to determine the results of the use of total hip replacement for the treatment of acetabular fractures and to compare the results of the early and late reconstruction group. 121 acetabular fractures treated with total hip arthroplasty between 1983 and 2003 at the University Hospitals Gasthuisberg in Leuven, Belgium were retrospectively studied. The patients were divided into two groups. In the "early reconstruction group" total hip arthroplasty was performed as primary treatment of the acetabular fracture. In the "late reconstruction group": total hip arthroplasty was performed following failed operative or non-operative treatment of the acetabular fracture. The indications for total hip arthroplasty and the surgical technique in both the early and late reconstruction group were compared. Secondly, complications were reviewed in both groups and a functional scoring system was applied for each patient. Primarily there was a significant difference in the age of the patient population of each group with a predominance for older patients in the early reconstruction group. Secondly, less revisions were performed in the early reconstruction group: 8% compared to 22% in the late reconstruction group. The results obtained in our patient groups were compared to the results found in literature by a Medline search. In general, our results were comparable to the results found in literature but a remarkable difference was found between different authors. Total hip replacement for acetabular fractures is rarely indicated in the acute phase. After failed treatment of an acetabular fracture, total hip replacement has to be considered as a salvage procedure. In both cases, one may not forget total hip arthroplasty is a severe intervention associated with a high number of complications.


Reactive Pendant Mn═O in a Synthetic Structural Model of a Proposed S4 State in the Photosynthetic Oxygen Evolving Complex.
The molecular mechanism of the Oxygen Evolving Center of photosystem II has been under debate for decades. One frequently cited proposal is the nucleophilic attack by water hydroxide on a pendant Mn═O moiety, though no chemical example of this reactivity at a manganese cubane cluster has been reported. We describe here the preparation, characterization, and a reactivity study of a synthetic manganese cubane cluster with a pendant manganese-oxo moiety. Reaction of this cluster with alkenes results in oxygen and hydrogen atom transfer reactions to form alcohol- and ketone-based oxygen-containing products. Nitrene transfer from core imides is negligible. The inorganic product is a cluster identical to the precursor, but with the pendant Mn═O moiety replaced by a hydrogen abstracted from the organic substrate, and is isolated in quantitative yield. 18O and 2H isotopic labeling studies confirm the transfer of atoms between the cluster and the organic substrate. The results suggest that the core cubane structure of this model compound remains intact, and that the pendant Mn═O moiety is preferentially reactive.


[Human factor in concern to occupational safety].
The article deals with results of studies covering safety problems in connection with human factor. The authors presented risks and their sources classification, models of risky behavior exemplified by actual and potential workers.


Establishing the validity of a spiritual distress scale for cancer patients hospitalized in southern Taiwan.
The present study was conducted to establish the validity of the spiritual distress scale (SDS), a scale developed as part of a qualitative study in which 20 cancer patients were interviewed about spiritual needs in 2003-2004. The SDS has four domains: relationship with self, relationship with others, relationship with God, and attitude towards death A measurement study was conducted whereby 85 patients completed the SDS during their hospitalization in the oncology unit of a medical centre in southern Taiwan. The SDS, including four domains of sub-scales, was broader than other spiritual scales in the literature that only contained one or two domains and focused on the health area. The SDS has established the adequate content and construct validity. Further training of nurses for assessing spiritual distress of cancer patients using the SDS would be recommended for future study. The established content and construct validity of the SDS could be applied in oncology for nurses to assess spiritual distress of cancer patients.


Forging a unique nursing partnership with China.
When members of a London nursing faculty forged a learning partnership with a Chinese counterpart they likely did not expect to be discussing the benefits of using Florence Nightingale lamps to decorate hospital walls. But there is nothing ordinary about the collaboration between King's College London and Nanjing Health School.


[Advanced autonomic cardiovascular denervation of diabetic etiology. Presentation of a case].
"Functional" total cardiac denervation due to diabetic autonomic neuropathy, is relatively rare. Sympathetic and parasympathetic fibers differ in the frequency with which they are damaged, with preference of parasympathetic abnormality. We report a diabetic patient who presented cardiac denervation with fixed heart rate at rest (95 beats for minute), severe orthostatic hypotension and cardiovascular abnormalities such as absence of reactions to physiological and pharmacological stimuli, sympathetic and parasympathetic. To the best of our knowledge our patient is the third such case in the literature.


Displacement in urban areas: new challenges, new partnerships.
Rapid urbanisation is a key characteristic of the modern world, interacting with and reinforcing other global mega trends, including armed conflict, climate change, crime, environmental degradation, financial and economic instability, food shortages, underemployment, volatile commodity prices, and weak governance. Displaced people also are affected by and engaged in the process of urbanisation. Increasingly, refugees, returnees, and internally displaced persons (IDPs) are to be found not in camps or among host communities in rural areas, but in the towns and cities of developing and middle-income countries. The arrival and long-term settlement of displaced populations in urban areas needs to be better anticipated, understood, and planned for, with a particular emphasis on the establishment of new partnerships. Humanitarian actors can no longer liaise only with national governments; they must also develop urgently closer working relationships with mayors and municipal authorities, service providers, urban police forces, and, most importantly, the representatives of both displaced and resident communities. This requires linking up with those development actors that have established such partnerships already.


Urinary excretion of chlorpheniramine and its metabolites in children.
The pharmacokinetics and urinary excretion of chlorpheniramine were studied in 11 patients, aged 6-16 years, with allergic rhinitis. In these children, chlorpheniramine had a mean elimination half-life of 13.1 +/- 6.6 h, a mean clearance rate of 7.23 +/- 3.16 mL/min/kg, and a mean apparent volume of distribution of 7.0 +/- 2.8 L/kg. Over 48 h, the recovery in urine was as follows: chlorpheniramine, 11.3 +/- 6.7%; demethylchlorpheniramine , 23.3 +/- 11.1%; and didemethylchlorpheniramine , 9.6 +/- 9.4%. Urine flow rate and urine pH were uncontrolled and ranged from 2.2 to 113.3 mL/h and 5.1-7.9, respectively, over the 48-h period. In some children urine flow rate and pH were constant, while in others there was great variability. When drug and metabolite excretion rates versus both urine flow rates and pH values were analyzed by multiple linear regression, the results were significantly better (p less than or equal to 0.05) than when each factor was analyzed independently. The excretion rate of chlorpheniramine and its two demethylated metabolites decreased as urine pH increased and urine flow rate decreased. This information must be considered in future pharmacokinetic studies of this drug.


Enhancing the Overall Performances of Blue Light-Emitting Electrochemical Cells by Using an Electron-Injecting/Transporting Ionic Additive.
Light-emitting electrochemical cells (LECs) have emerged as a promising emissive thin-film technology for next-generation solid-state lighting. However, blue LECs show low performances, which has remained a bottleneck for the fabrication of white LECs for lighting applications. Here, we demonstrate a remarkable enhancement of overall device performance for blue LECs by using an electron-injecting/transporting ionic additive, that is, [Zn(bpy)3](PF6)2 (bpy is 2.2'-bipyridine, PF6- is hexafluorophosphate). It is revealed that adding [Zn(bpy)3](PF6)2 into the active layers of blue LECs accelerates the device response, simultaneously enhances the brightness and efficiency, reduces the efficiency roll-offs, significantly improves the blue color stability upon the continuous electrical operation, and enhances the device operational stability at optimized conditions. The remarkable enhancement of the overall device performance upon adding [Zn(bpy)3](PF6)2 results from facilitated electron injection/transport and thus more balanced electron-hole recombination and more centered recombination zone, as well as the reduction of phosphorescence concentration quenching in the LECs. The work demonstrates for the first time that the use of electron-injecting/transporting ionic additives such as [Zn(bpy)3](PF6)2 is a facile yet effective strategy to remarkably boost the overall performances of blue LECs.


The Candida glabrata putative sterol transporter gene CgAUS1 protects cells against azoles in the presence of serum.
The uptake of endogenous sterol from serum may allow Candida glabrata to survive azole treatment. This study aims to determine the contribution of a sterol transporter that alters fluconazole sensitivity in the presence of serum. Bioinformatic analysis predicted CgAUS1 as the C. glabrata orthologue of the Saccharomyces cerevisiae transporters AUS1 and PDR11. To investigate whether the CgAUS1 gene has sterol transporter activity, we investigated the effects of an AUS1 deletion on the growth of a tetracycline-regulatable ERG9 strain (tet-ERG9aus1), wherein ERG9 expression is turned off giving rise to a sterol requirement. Tetracycline-dependent repression of CgAUS1 in the tet-AUS1 strain was used to determine the fluconazole susceptibility of CgAUS1 in the presence and absence of serum. The tetracycline-treated tet-ERG9aus1 strain failed to grow in the presence of serum, whereas the parental tet-ERG9AUS1 strain grew by incorporating sterol from exogenously supplied serum. Serum cholesterol protected cells against the antifungal effects of fluconazole and this protection was lost by repressing CgAUS1 gene expression. Furthermore, such protection was also observed during itraconazole treatment, but not observed in cells treated with non-azole antifungals. CgAUS1 appears to function as a sterol transporter that may contribute to lower azole susceptibility in the presence of serum and to protect C. glabrata against azole toxicity in vivo.


[Clinical and therapeutic approach of the borderline patient in psychiatric clinic (author's transl)].
The author summarises the evolution of the borderline concept in the literature. He emphasizes the specificity of the pathological objectal relation and the lack of development of the ego in the separation-individualisation phase. The clinical approach of the borderline patient shows the lability of interpersonal relations of the borderline patient and the presence of a variable and polymorphic symptomatology. The author gives some considerations which are essential in undertaking a treatment with the borderline patient during a brief hospitalisation in a psychiatric service. This type of treatment is based on an early clinical diagnosis, a homogenous, logical and adequate attitude of the therapeutic team, the organisation of an adequate therapeutic team where the patient can learn to accept his own pathological findings and the initiation of an individual psychotherapy.


[Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group].
A randomized study of mitomycin C (MMC)+5-FU [control group] vs MMC+5-FU+lentinan (LNT) [LNT group] was conducted in order to evaluate the effect of LNT against advanced gastric and colorectal cancers by the envelope method in 166 patients, comprising of 115 cases of gastric cancer and 51 cases of colorectal cancer. Significant increases were observed in the survival rates for the LNT group (p less than 0.05) for both patients with gastric and colorectal cancer. No significant difference was observed in response rates between the aforesaid two groups, though the response rate in the LNT group was slightly higher than the control group. These results suggest that LNT in combination with anticancer drugs prolong the survival time of patients with advanced gastric and colorectal cancer.


Ixazomib with cyclophosphamide and dexamethasone in relapsed or refractory myeloma: MUKeight phase II randomised controlled trial results.
The all-oral combination of ixazomib, cyclophosphamide, and dexamethasone (ICD) is well tolerated and effective in newly diagnosed and relapsed multiple myeloma (MM). We carried out MUKeight, a randomised, controlled, open, parallel group, multi-centre phase II trial in patients with relapsed MM after prior treatment with thalidomide, lenalidomide, and a proteasome inhibitor (ISRCTN58227268), with the primary objective to test whether ICD has improved clinical activity compared to cyclophosphamide and dexamethasone (CD) in terms of progression-free survival (PFS). Between January 2016 and December 2018, 112 participants were randomised between ICD (n = 58) and CD (n = 54) in 33 UK centres. Patients had a median age of 70 years and had received a median of four prior lines of therapy. 74% were classed as frail. Median PFS in the ICD arm was 5.6 months, compared to 6.7 months with CD (hazard ratio (HR) = 1.21, 80% CI 0.9-1.6, p = 0.3634). Response rates and overall survival were not significantly different between ICD and CD. Dose modifications or omissions, and serious adverse events (SAEs), occurred more often in the ICD arm. In summary, the addition of ixazomib to cyclophosphamide and dexamethasone did not improve outcomes in the comparatively frail patients enroled in the MUKeight trial.


Disease-modifying anti-rheumatic drug therapy. An expensive therapy despite inexpensive drugs.
In a study of the costs for drug therapy, 81 patients with rheumatoid arthritis taking parenteral gold, penicillamine or chloroquine were included. The patients were assessed for costs, directly and indirectly caused by the therapy, during a 12-week period. The three therapy groups were comparable in terms of number of patients, sex, age and duration of disease. There were substantial differences in costs for therapy between the three disease-modifying anti-rheumatic drugs. Treatment with parenteral gold gave the highest cost, 2.2 times that of chloroquine and 1.4 times the cost of penicillamine. The cost for the antirheumatic drug constituted a minor part of the total cost (4.4-15.4%). The need for patient visits for treatment and safety controls was a major factor in the overall cost.


Development of new glass composite membranes and their properties for low temperature H2/O2 fuel cells.
A new glass electrolyte formed by constant amounts of titanium oxide (TiO2) and various amount of phosphotungstic acid (PWA) doped P2O5-SiO2 is prepared using the sol-gel process. The structural formation is confirmed by Fourier infrared spectroscopy (FTIR) and from thermogravimetric and differential thermal analysis (TG/DTA) measurements, the glasses display good thermal stability. Further characterisation is undertaken by N2 adsorption/desorption measurements, proton conductivity and hydrogen permeability analyses and a H2/O2 fuel cell test is also performed. The glass materials with large pores and specific surface area are suitable for use as the electrolyte in H2/O2 fuel cells. The effect of TiO2 processing with constant amount of PWA in phosphosilicate glasses, is investigated and discussed. The hydrogen permeability is 1.57x10(-11) mol cm(-1) s(-1) Pa(-1) at 110 degrees C for 0.8 mm thick glass; a power density of 46.3 mW cm(-2) at 125 mA cm(-2) and a current density of 175 mA cm(-2) is obtained (T=28 degrees C, relative humidity).


Green growth strategies in Asia: unleashing the heterogeneous asymmetry of ICT capital, financial fragility, environmental policy stringency, and education.
Financial fragility, ICT capital, environmental policy stringency, and education are the main factors that have also gained popularity regarding their impact on green growth. This study examines the impact of financial fragility, ICT capital, environmental policy stringency, and education on green growth. For analyzing the short- and long-run estimates, we have applied the panel QARDL model. The results of the panel QARDL model highlight that the estimates of non-performing bank loans and bank costs are negatively significant in both the short and long run, implying that financial fragility hurts green growth in the short and long run. Similarly, the estimated coefficients of the internet (mobile) and education estimates are positively significant in the short and long run, confirming that ICT capital and education are causing green growth, while environmental policy stringency promotes green growth only in the long run. Regarding the asymmetric effects of all the factors on green growth, the Wald test only confirms asymmetric effects in the long run. The study offers several significant recommendations for sustainable green development policies.


Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype.
Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If iAs methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago.


Combination of tenofovir and lamivudine versus tenofovir after lamivudine failure for therapy of hepatitis B in HIV-coinfection.
At present sequential monotherapy for chronic hepatitis B with hepatitis B virus (HBV)-polymerase inhibitors is clinical practice. It is unknown to date whether combination therapy with lamivudine plus tenofovir could be superior to sequential therapy with tenofovir after the occurrence of lamivudine resistance. We conducted a multicenter, 1: 2 matched pair analysis comparing patients with HBV/HIV-coinfection starting an antiretroviral regimen including tenofovir plus lamivudine with patients who had highly replicative, lamivudine resistant HBe-antigen positive chronic hepatitis B and started with tenofovir as the only active HBV polymerase inhibitor subsequent to lamivudine. At baseline patients on tenofovir plus lamivudine (n = 25) had a median HBV DNA of 5.9 x 10(7) copies/ml compared to 1.37 x 10(8) copies/ml in the tenofovir arm (n = 50; P = 0.32). A sustained undetectable HBV DNA < 1000 copies/ml was achieved in 19/25 (76%) patients on tenofovir plus lamivudine and in 42/50 (84%) on tenofovir (P = 0.53). A loss of HBe-antigen was observed in 9/25 (36%) patients on tenofovir plus lamivudine and in 12/50 (24%) patients on tenofovir (P = 0.29). HBs-antigen loss was found in 1/25 (4%) and 3/50 (6%) patients. In this cohort of HBV/HIV-coinfected individuals, full HBV DNA suppression was achieved in the majority of patients independent of treatment allocation. Loss of HBe- and HBs-antigen was not different between the two study arms. Over a median treatment period of 116 weeks tenofovir was as effective as tenofovir plus lamivudine. Longer treatment periods may be needed to evaluate potential benefits of first-line combination therapy for chronic hepatitis B.


Protein inhibitor of activated STAT 4 (PIAS4) regulates pro-inflammatory transcription in hepatocytes by repressing SIRT1.
Excessive nutrition promotes the pathogenesis of non-alcoholic steatohepatitis (NASH), characterized by the accumulation of pro-inflammation mediators in the liver. In the present study we investigated the regulation of pro-inflammatory transcription in hepatocytes by protein inhibitor of activated STAT 4 (PIAS4) in this process and the underlying mechanisms. We report that expression of the class III deacetylase SIRT1 was down-regulated in the livers of NASH mice accompanied by a simultaneous increase in the expression and binding activity of PIAS4. Exposure to high glucose stimulated the expression PIAS4 in cultured hepatocytes paralleling SIRT1 repression. Estrogen, a known NASH-protective hormone, ameliorated SIRT1 trans-repression by targeting PIAS4. Over-expression of PIAS4 enhanced, while PIAS4 knockdown alleviated, repression of SIRT1 transcription by high glucose. Lentiviral delivery of short hairpin RNA (shRNA) targeting PIAS4 attenuated hepatic inflammation in NASH mice by restoring SIRT1 expression. Mechanistically, PIAS4 promoted NF-κB-mediated pro-inflammatory transcription in a SIRT1 dependent manner. In conclusion, our study indicates that PIAS4 mediated SIRT1 repression in response to nutrient surplus contributes to the pathogenesis of NASH. Therefore, targeting PIAS4 might provide novel therapeutic strategies in the intervention of NASH.


Strengthened removal of emerging contaminants over S/Fe codoped activated carbon fabricated by a mild one-step thermal transformation scheme.
Thermal transformation of carbonized materials to functional activated carbon (AC) is a simplified, economical and eco-friendly strategy, which has great potential in the practical applications of water purification. Herein, a S/Fe codoped activated carbon (S/Fe@AC) with only 0.90 wt% S and 0.76 wt% Fe was creatively fabricated by one synchronous method of physical activation, carbothermal reduction and sulfidation in the solid phase. The formed iron sulfide shell significantly enhances the antioxidation ability of nanoscale zero-valent iron (NZVI, >180 d) and dramatically improves the hydrophobicity of the composite. Meanwhile, the doped thiophenic S in AC enhances the hydrophobicity and increases the specific surface area to 1194.14 m2 g-1. Incorporating with AC in turn greatly strengthens the dispersibility and stability of sulfurized NZVI particles. Compared to NZVI@AC, AC and NZVI, the removal capacity of S/Fe@AC for the representative hydrophobic contaminant-triclosan (TCS) increases to 519.68 mg g-1 by 66.60%, 78.60% and 981.21%, respectively, outperforming most of the previously reported materials. The strong hydrophobic and π-π interactions, and weak hydrogen bonding and electrostatic repulsion are responsible for the excellent removal performance for TCS. More importantly, the improved chemical property (29.38%) of the composite caused by the doped S/Fe has a greater effect on TCS removal compared with the changed physical structure (14.56%). Furthermore, the stable S/Fe@AC shows strong anti-interference capability and exceptional regenerability. These intriguing discoveries provide new insights into the design of advanced and sustainable adsorbing materials for emerging contaminants.


ERβ1: characterization, prognosis, and evaluation of treatment strategies in ERα-positive and -negative breast cancer.
The role and clinical value of ERβ1 expression is controversial and recent data demonstrates that many ERβ antibodies are insensitive and/or non-specific. Therefore, we sought to comprehensively characterize ERβ1 expression across all sub-types of breast cancer using a validated antibody and determine the roles of this receptor in mediating response to multiple forms of endocrine therapy both in the presence and absence of ERα expression. Nuclear and cytoplasmic expression patterns of ERβ1 were analyzed in three patient cohorts, including a retrospective analysis of a prospective adjuvant tamoxifen study and a triple negative breast cancer cohort. To investigate the utility of therapeutically targeting ERβ1, we generated multiple ERβ1 expressing cell model systems and determined their proliferative responses following anti-estrogenic or ERβ-specific agonist exposure. Nuclear ERβ1 was shown to be expressed across all major sub-types of breast cancer, including 25% of triple negative breast cancers and 33% of ER-positive tumors, and was associated with significantly improved outcomes in ERα-positive tamoxifen-treated patients. In agreement with these observations, ERβ1 expression sensitized ERα-positive breast cancer cells to the anti-cancer effects of selective estrogen receptor modulators (SERMs). However, in the absence of ERα expression, ERβ-specific agonists potently inhibited cell proliferation rates while anti-estrogenic therapies were ineffective. Using a validated antibody, we have confirmed that nuclear ERβ1 expression is commonly present in breast cancer and is prognostic in tamoxifen-treated patients. Using multiple breast cancer cell lines, ERβ appears to be a novel therapeutic target. However, the efficacy of SERMs and ERβ-specific agonists differ as a function of ERα expression.


Using simulation to teach child injury prevention to mothers recovering from substance abuse.
A paucity of literature regarding strategies for injury prevention in children for mothers with substance abuse exists. Substance abuse propagates distractions such as inattention; therefore, these mothers should be targeted for injury prevention education. A quasi-experimental design compared the results of traditional classroom teaching with an innovative home hazard simulation activity to teach injury prevention to mothers recovering from substance abuse. Study results identified a need to employ multiple modalities when teaching injury prevention. Information obtained from this research suggests a need for continued study and adaptation of current teaching strategies for injury prevention education in other high-risk populations.


Moisture content prediction in poultry litter using artificial intelligence techniques and Monte Carlo simulation to determine the economic yield from energy use.
The objective of this study is to determine the economic return of poultry litter combustion in boilers to produce bioenergy (thermal and electrical), as this biomass has a high-energy potential due to its component elements, using fuzzy logic to predict moisture and identify the high-impact variables. This is carried out using a proposed 7-stage methodology, which includes a statistical analysis of agricultural systems and practices to identify activities contributing to moisture in poultry litter (for example, broiler chicken management, number of air extractors, and avian population density), and thereby reduce moisture to increase the yield of the combustion process. Estimates of poultry litter production and heating value are made based on 4 different moisture content percentages (scenarios of 25%, 30%, 35%, and 40%), and then a risk analysis is proposed using the Monte Carlo simulation to select the best investment alternative and to estimate the environmental impact for greenhouse gas mitigation. The results show that dry poultry litter (25%) is slightly better for combustion, generating 3.20% more energy. Reducing moisture from 40% to 25% involves considerable economic investment due to the purchase of equipment to reduce moisture; thus, when calculating financial indicators, the 40% scenario is the most attractive, as it is the current scenario. Thus, this methodology proposes a technology approach based on the use of advanced tools to predict moisture and representation of the system (Monte Carlo simulation), where the variability and uncertainty of the system are accurately represented. Therefore, this methodology is considered generic for any bioenergy generation system and not just for the poultry sector, whether it uses combustion or another type of technology.


Genes preserved in relatives.
The genes of an individual are said to be preserved in his relatives if they possess, collectively, all copies of his genes. We present a method for computing the probability that an individual's genes are preserved in his relatives. Using this method, we compute gene preservation probabilities (up to three linked loci) for a variety of relationships for humans and for haplodiploid species. The results suggest that some widely held notions in ethology and sociobiology seem to be questionable. From the gene preservation viewpoint, two brothers are far from enough to justify the sacrifice of one's own life, because the probability that an individual's genes are preserved in his two siblings is dismally small. The precise probability that an individual's genes are all preserved in a group of his relatives depends on the precise specification of the pedigree structure. We also demonstrate that, for a hymenopteran female, there is no practical difference, in terms of gene preservation probability, between helping her sisters to breed and breeding her own offspring. In fact, since the genes of her sister will be either lost or preserved in her nieces/nephews, it is more appropriate to compare the probability of preserving her genes through her own offspring with that through her nieces/nephews. We show that her chance of preserving all her genes is much higher if she chooses to breed her own offspring instead of helping her sister.


Comparison of long-term clinical and radiographic outcomes between alternative-level and all-level fixation unilateral open-door laminoplasty.
Titanium mini-plate has been used in unilateral open-door laminoplasty to maintain the open angle of laminae. Previously, both all-level fixation (C3-C7) and alternative-level (C3, C5, C7) unilateral open-door laminoplasty have been proven to have satisfactory clinical outcomes. However, whether they could achieve similar long-term clinical and radiographic efficacy is still questionable. To compare the long-term clinical and radiological outcomes between alternative-level and all-level fixation unilateral open-door laminoplasty with a mini-plate fixation system. Retrospective comparative study. Ninety-one patients who underwent unilateral open-door laminoplasty. Clinical results including Japanese Orthopedic Association score, Visual Analogue Score, Neck Dysfunction Index score. Radiographic results including cervical curvature index, cervical range of motion, and the spinal canal expansive parameters, including anteroposterior diameter, Pavlov's ratio, and open angle. Between April 2007 and June 2011, 91 patients with minimum 7-year postoperative follow-up were included. Thirty-eight underwent alternative-level fixation (group A) and 53 underwent all-level fixation (group B). Demographic data, including age, gender, operative time, blood loss, and cost, were collected and compared between the two groups. Clinical and radiographic data were obtained preoperatively, at 3 and 6 months and 1 and 3 years postoperatively, as well as at final follow-up. The difference between the two groups and between different time points within one group was compared. Both groups obtained satisfactory clinical outcomes till the final follow-up. No statistic difference was found in Japanese Orthopedic Association, Visual Analogue Score, and Neck Dysfunction Index between the two groups throughout the whole follow-up. Both groups maintained APD and Pavlov's ratio well till follow-up. However, statistic difference was found in the open angle between two groups at final follow-up (34.17±2.75° vs. 36.19±1.80°, p<.05). When we subdivided the cervical segments in group A, we found the mini-plate segments showed maintenance in open angle but a 4.52° decrease in suture segments. The mean cost in group B (17,669.82±1,157.65 $) was significantly higher than in group A (11,452.19±871.07 $; p<.05). Despite a difference in the maintenance of open angle, both fixation methods achieved satisfactory clinical outcomes. We believe alternative-level fixation is also a safe, effective, and economical fixation method.


The clinical assessment of chronic pain in rheumatic disease: evaluating the use of two instruments.
Health care professionals are becoming increasingly aware of the complex nature of chronic pain. Measurement instruments are needed which will assist in better understanding the patient's response to the pain. The McGill Pain Questionnaire (MPQ) and an expanded version useful in comprehensive clinical assessment, the McGill Comprehensive Pain Questionnaire (MCPQ), are currently-available tools for assessing chronic pain. The major purposes of this study were to test the discriminant and concurrent validity of the MPQ and to describe the major responses of the person with rheumatic disease to chronic pain using both instruments. Two sample groups were used: (1) 30 patients with chronic pain related to rheumatic disease, and (2) 30 patients with acute pain related to a surgical procedure. The MPQ's Affective Subscale discriminated between acute and chronic pain, and its Present Pain Intensity (PPI) Scale correlated moderately with the Visual Analogue Scale (VAS), another commonly-used scale for measuring pain intensity. While the MCPQ was useful in describing the patient's response to chronic pain, administration was time-consuming, and its open-ended format makes validity and reliability testing impossible. The information gained through the use of the MCPQ was helpful in determining what living with chronic pain means to the individual. Such information should be useful in the future development of a valid and reliable instrument for more efficiently measuring the chronic pain experience. Such an instrument would be useful in coordination with the MPQ which focuses on pain description.


The molecular mechanism and potential role of heat shock-induced p53 protein accumulation.
Workers who are exposed to extreme heat or work in hot environments may be at risk of heat stress. Exposure to extreme heat can result in occupational illnesses and injuries. On the other hand, local and regional heat therapy has been used for the treatment of some cancers, such as liver cancer, lung cancer, and kidney cancer. Although heat stress has been shown to induce the accumulation of p53 protein, a key regulator of cell cycle, apoptosis, DNA repair, and autophagy, how it regulates p53 protein accumulation and what the p53 targets are remain unclear. Here, we show that, among various genotoxic stresses, including ionizing radiation (IR) and ultraviolet (UV) radiation, heat stress contributes significantly to increase p53 protein levels in normal liver cells and liver cancer cells. Heat stress did not increase p53 mRNA expression as well as p53 promoter activity. However, heat stress enhanced the half-life of p53 protein. Moreover, heat stress increased the expression of puma and light chain 3 (LC-3), which are associated with the apoptotic and autophagic function of p53, respectively, whereas it did not change the expression of the cell cycle regulators p21, 14-3-3δ, and GADD45α, suggesting that heat-triggered alteration of p53 selectively modulates the downstream targets of p53. Our study provides a novel mechanism by which heat shock stimulates p53 protein accumulation, which is different from common DNA damages, such as IR and UV, and also provides new molecular basis for heat injuries or heat therapy.


High efficiency quantum cascade laser frequency comb.
An efficient mid-infrared frequency comb source is of great interest to high speed, high resolution spectroscopy and metrology. Here we demonstrate a mid-IR quantum cascade laser frequency comb with a high power output and narrow beatnote linewidth at room temperature. The active region was designed with a strong-coupling between the injector and the upper lasing level for high internal quantum efficiency and a broadband gain. The group velocity dispersion was engineered for efficient, broadband mode-locking via four wave mixing. The comb device exhibits a narrow intermode beatnote linewidth of 50.5 Hz and a maximum wall-plug efficiency of 6.5% covering a spectral coverage of 110 cm-1 at λ ~ 8 μm. The efficiency is improved by a factor of 6 compared with previous demonstrations. The high power efficiency and narrow beatnote linewidth will greatly expand the applications of quantum cascade laser frequency combs including high-precision remote sensing and spectroscopy.


Varietal turn-over and their effect on yield and food security - Evidence from 20 years of household surveys in Kenya.
Agricultural technology is key to food security in SSA, but new maize varieties are not able to replace the old, trusted ones. This study uses data from four representative household surveys conducted in Kenya over 21 years, to show that younger maize varieties have a clear, although limited, effect on yield (4 kg/ha/year controlling for fertilizer) and food security. Unfortunately, this is not sufficient to entice farmers to adopt them, and adoption rates have barely increased despite the market liberalization that brought many private seed companies and their varieties in the market, as the parastatal Kenya Seed Company continues to dominate the market. As a result, in combination with low fertilizer use, yields have stagnated for the last three decennia.


Short and long-term prospects for consumption of fish.
If real prices for fish remain at the levels they had attained by 1999, in the year 2050 demand for fish and shellfish as food could be of the order of 270 million tons (live weight equivalent) per year. If producers were able to supply these quantities consumption would rise by 176% over this 50-year period. To meet the demand supply would have to expand at the rate of 2.1% annually; but, a review of the pattern of population growth--and of historical patterns of increases in per capita consumption of fish--shows that annual growth in the volume of fish demanded is likely to be largest in the coming two decades, and then to taper off. Will producers be able to deliver? It is clear that wild marine stocks at present harvested by capture fishermen cannot support fisheries that would yield much more than 100 million tons per year and of this amount a significant proportion will continue to be used for fish meal and oil production. The question therefore narrows down to: can aquaculture, or non-traditional marine species, supply the required amounts? The historical context of supply is considerably different from that which has prevailed during the past 30 years. At that time the growing demand in OECD countries was met partly through imports of fish produced in the seas and lakes of developing countries. During coming decades the increased demand in developing countries must be met essentially through their own resources. In fact, in poor countries it seems unlikely that supply will respond to demand unless they experience economic growth.


Experimenting with distributed approaches - Case study: A 'national-level' distributed dialogue on bioenergy in the United Kingdom.
An emerging thread in the public participation debate is the need for innovative and more experimental forms of dialogue to address weaknesses of previous structured deliberative methods. This research note discusses an experiment with a distributed approach to dialogue, which used bioenergy as a case study. We discuss the potential of the model to attract a variety of publics and views and to inform policy. This is done with a view to refining future dialogues and increasing the involvement of scientists and other practitioners at the science-policy interface.


Uptake of formative feedback: perspective from a transnational education cohort.
An important aspect of teaching and learning is the student's response to and enaction of formative feedback. Few studies have examined how students interpret the formative feedback provided by tutors and translate these into action. In order to understand this better, we carried out a retrospective analysis of student responses to iterative formative feedback. The context of the present study is an extracurricular project where undergraduate biomedical science students on a transnational education programme competed in an extracurricular, cross-disciplinary video competition. Based on detailed analysis of provided feedback and subsequent enaction of the feedback, we found that students were active participants in the feedback process, engaged with the meaningful feedback critically, and incorporated the relevant changes to improve the final output. In this article, we will give our perspectives on how students understand, process and act on feedback, and also examine the features of the feedback that elicited these responses from students.


Chip-integrated metasurface for versatile and multi-wavelength control of light couplings with independent phase and arbitrary polarization.
While metasurfaces are now widely considered in free-space optics, their potential for coupling and tailoring guided waves is not fully explored. Here we transfer the Jones matrix method to target versatile on-chip coupling using metasurface-patterned photonic waveguides around the telecommunication wavelength of 1.55 μm, which can accommodate both propagation and Pancharatnam-Berry phase metasurfaces for guided waves. One can either encode two arbitrary and independent phase profiles to any pair of orthogonal polarizations or deploy complete control over both the phase and polarization of coupled modes. A set of design scenarios synergizing silicon nanoantennas and low-loss silicon-nitride waveguides are proposed, including directional couplers with mode-selectivity and polarization splitters with directionality ranging from 10 to 20 dB. Furthermore, our optimization method can be further extended to cover multiple working wavelengths. Exemplary on-chip color routers are also numerically demonstrated. This chip-integrated metasurface platform further translates the concept of a metasurface into photonic integrated circuits, serving as a positive paradigm for versatile and complete control over waveguide optical signals and motivating chip-scale applications such as polarization/wavelength demultiplexers, optical switches, and multifunctional mode converters.


[Mechanism of action and exogenous supplementation of vitamin D in Crohn's disease].
Vitamin D can not only regulate calcium and phosphorus metabolism, but also exert an immunoregulatory effect. Vitamin D deficiency is common in patients with Crohn's disease (CD). Studies have shown that vitamin D is associated with CD and other autoimmune diseases and can improve the condition of patients with CD and promote their recovery by regulating intestinal immunity, repairing the intestinal mucosal barrier, inhibiting intestinal fibrosis, enhancing the response to infliximab, and regulating intestinal microbiota. Exogenous vitamin D supplementation can induce disease remission while increasing the serum level of vitamin D. However, only a few randomized, double-blind, and placebo-controlled trials have investigated the therapeutic effect of vitamin D in CD, and the optimal form of vitamin D supplementation, the specific dosage of vitamin D supplementation, and the optimal serum maintenance concentration of vitamin D remain to be clarified. This article mainly discusses the mechanism of action of vitamin D in CD and the beneficial effect of exogenous vitamin D supplementation on CD.


Biopesticides in India: technology and sustainability linkages.
Despite enhancing the crop yields, the so called green revolution (GR) has proven unsuccessful in assuring long term agricultural sustainability. The methods used for productivity enhancement during GR have not only proven to be problematic but have also resulted in deterioration of soil quality and several other issues related to ecosystems and health issues. The damage was mainly caused by the indiscriminate use of chemical fertilizers and insecticides. Various types of pesticides, are now known to be causing huge problems in the agro-ecosystems. In such a situation, where chemicals have caused or are causing irreversible impacts on agroecosystems, the use of biopesticides has emerged as a sustainable alternative leading to safe organic farming. At the global level, environmentally benign nature and target-specificity of biopesticides are gaining wide popularity. However, in developing countries like India usage of biopesticides is still minuscule in comparison to conventional chemical pesticides. Although the Indian government has encouraged the use of biopesticides by placing them into many of the agricultural schemes, at the grassroots level, biopesticides are facing many challenges. The lower adaptability and declining interest of farmers towards biopesticides have become a matter of concern. However, technological challenges related to production, manufacture and application in agroecosystems have also raised a question on their long-term sustainability. The main objective of this review is to highlight the developing trend in the field of biocontrol products in India. Apart from this, the review also focuses on the technological perspectives that are required for the long-term sustainability of biological control products in Indian agriculture and market.


High frequency of activated NKp46(+) natural killer cells in patients with new diagnosed of latent autoimmune diabetes in adults.
To determine the potential association of different subsets of NK cells with the development of latent autoimmune diabetes of adults (LADA) in patients. The frequency of different subsets of NK and NKT cells, including IFN-γ(+) and CD107a(+) NK and NKT cells, in 27 patients with newly diagnosed LADA and 20 healthy controls (HC) were determined by flow cytometry. The concentrations of serum autoantibodies against GAD65 were measured by direct radioligand assay. The potential association of the frequency of NK cells with clinical measures was analyzed. In comparison with that in the HC, significantly higher frequency of peripheral blood NK and NKp46(+) NK cells, but lower frequency of KIR3DL1(+) NK cells were detected in patients with newly diagnosed LADA (p < 0.0001, p < 0.0001, p = 0.0039, respectively). The percentages of inducible IFN-γ(+) NK cells were significantly higher in the LADA patients than that in the HC (p < 0.0001). Moreover, the percentages of NKp46(+) NK cells were negatively correlated with the levels of fasting plasma C-peptide in patients (R = -0.4877, p = 0.0099). There was no significant difference in the frequency of spontaneous and inducible CD107a(+) between patients and controls. Our data indicate a higher frequency of activated NKp46(+) NK cells may be associated with the development of LADA in humans.


Isolation of Cryptococcus neoformans var. neoformans from pigeon droppings collected throughout Turkey.
The six hundred and thirty-four samples of pigeon droppings were collected throughout Turkey, from 54 of 80 provinces. Cryptococcus neoformans was isolated from 29 (4.6%, overall) of 634 samples and 29 isolates were from 18 provinces. Interestingly, 16 (88.9%) of these provinces occur on the three different coastlines of Turkey, therefore the ecological role of a humid climate was speculated. Almost all isolates [28/29] were recovered from samples collected from roofs (n=14) and dovecotes (n=14). All isolates were found to be C. neoformans var. neoformans.


Testicular cancer risk and maternal parity: a population-based cohort study.
The aim was to study, in a population-based cohort design, whether first-born sons run a higher risk of testicular cancer than later born sons; to investigate whether this difference in risk was affected by birth cohort, age of the son, maternal age, interval to previous delivery and other reproductive factors; and, finally, to evaluate to what extent changes in women's parity over time might explain the increasing incidence of testicular cancer. By using data from the Civil Registration System, a database was established of all women born in Denmark since 1935 and all their children alive in 1968 or born later. Sons with testicular cancer were identified in the Danish Cancer Registry. Among 1015994 sons followed for 15981 967 person-years, 626 developed testicular cancer (443 non-seminomas, 183 seminomas). Later born sons had a decreased risk of testicular cancer (RR = 0.80, 95% CI = 0.67-0.95) compared with first-born sons. The RR was 0.79 (95% CI = 0.64-0.98) for non-seminomas and 0.81 (95% CI = 0.58-1.13) for seminomas. There was no association between testicular cancer risk and overall parity of the mother, maternal or paternal age at the birth of the son, or maternal age at first birth. The decreased risk of testicular cancer among later born sons was not modified by age, birth cohort, interval to the previous birth, sex of the first-born child, or maternal age at birth of the son or at first birth. The increased proportion of first-borns from birth cohort 1946 to birth cohort 1969 only explained around 3% of an approximated two-fold increase in incidence between the cohorts. Our data document a distinctly higher risk of testicular cancer in first-born compared with later born sons and suggest that the most likely explanation should be sought among exposures in utero. The increase in the proportion of first-borns in the population has only contributed marginally to the increase in testicular cancer incidence.


Stratified medicine: drugs meet genetics.
It is well recognised that genetic factors play a major role in the development of respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, whilst extensive data exist on diseases caused primarily by single gene defects, such as α1-antitrypsin deficiency, the genetic factors responsible for the development of complex disease are only now being defined. Once the gene(s) responsible for the heritable element of disease risk are known, the next step is to identify the mechanisms underlying the pathophysiological effects of the causal mutations in these genes. This process can be time consuming, but allows a full understanding of the mechanisms underlying disease development to be obtained. This knowledge can then potentially be used to stratify patient groups within (or even across) disease boundaries and then to target therapy more effectively.


Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice.
The atheroprotective effects of estrogen in women are well recognized, but the underlying mechanisms responsible are not well understood. Blood vessel cells express the classic estrogen receptor, ER alpha (ref. 2-6), and are directly affected by estrogen, which inhibits the development of atherosclerotic and injury-induced vascular lesions. We have generated mice in which the ER alpha gene is disrupted and have used a mouse model of carotid arterial injury to compare the effects of estrogen on wild-type and estrogen receptor-deficient mice. Increases in vascular medial area and smooth muscle cell proliferation were quantified following vascular injury in ovariectomized mice treated with vehicle or with physiologic levels of 17 beta-estradiol. Surprisingly, in both wild-type and estrogen receptor-deficient mice, 17 beta-estradiol markedly inhibited to the same degree all measures of vascular injury. These data demonstrate that estrogen inhibits vascular by a novel mechanism that is independent of the classic estrogen receptor, ER alpha.


Locally advanced tonsillar squamous cell carcinoma: Treatment approach revisited.
The purpose of this study was to review the treatment policy for locally advanced stage III and IV squamous cell carcinoma (SCC) of the tonsil at the Princess Alexandra Hospital Head and Neck Unit, Brisbane, Australia. The records of 148 patients with curable stage III and IV SCC of the tonsil were reviewed from the years 1992 to 2004 inclusive. During this period, patients were treated with surgery and postoperative radiotherapy and only offered definitive radiation if they were medically or surgically inoperable. There were 102 patients treated with surgery +/- postoperative radiotherapy (group 1) and 46 patients treated with definitive radiotherapy +/- chemotherapy (group 2). The endpoints of locoregional control (LRC), disease specific survival (DSS), and overall survival (OS) were studied and prognostic factors were investigated with univariate and multivariate analyses. The 5-year OS, DSS, and LRC were 57%, 69%, and 84%, respectively. Univariate analyses showed that patients in group 1 had a superior OS (69% vs. 41%, P = .007), a trend toward improvement in LRC (88% vs. 73%, P = .08), and a nonsignificant improvement in DSS (75% vs. 56%, P = .14). There was a greater percentage of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 or less in group 1, suggesting selection bias toward the surgical group. Multivariate analyses, which adjusted for known prognostic factors, showed that treatment group was significant for OS but not for LRC or DSS. Surgery and postoperative radiotherapy continues to provide a superior outcome in locally advanced tonsil SCC in patients with surgically resectable disease, good ECOG performance status, and medically operable.