Stair negotiation in older people: a review.
Locomotion on stairs is among the most challenging and hazardous activities of daily living for older individuals. This is evidenced by the reports that stair falls account for more than 10% of fatal fall accidents. The demands that stairs place on the musculoskeletal and cardiovascular systems are compounded by the need for input from the somatosensory, visual, and vestibular systems at various stages in the task. Many of these collaborating systems deteriorate with aging, thus increasing the difficulty and risk of failure in a task that inherently involves exposure to significant danger. The task itself varies in its degree of challenge depending on many structural and environmental factors that are outside the control of the stair user. This review explores existing literature in the area of stair negotiation by older persons in an effort to define the key factors associated with difficulty and safety on stairs and to interpret these findings in the light of possible interventions that could increase stair safety. Further research is needed to ensure that current recommendations for stair design are suitable for older stair users. A Glossary of Terms is also provided.


Safe, rapid administration of cisplatin in the outpatient clinic.
The records of 147 cancer patients who received at least three courses of cisplatin-containing chemotherapy in the Arizona Cancer Center clinic between 1982 and 1985 were reviewed to determine the safety and tolerance of cisplatin administered in the outpatient setting. Cisplatin was administered at doses of 50-120 mg/m2 every 3-4 weeks. The drug was added to 400 ml of 10% mannitol, was brought up to 1-L volume with normal saline containing 3 g of magnesium sulfate, and was administered iv over 1 hour. An additional liter of normal saline was administered over approximately 1 hour in patients who received cisplatin doses of 70-120 mg/m2. Courses were interrupted if the serum creatinine was greater than 1.5 mg/dl just prior to the next scheduled dose. The median total doses of cisplatin per patient were 487, 595, and 683 mg/m2 and complete plus partial response rates were 64%, 71%, and 78% for those patients who received 50-60, 70-90, and 100-120 mg/m2/course, respectively. Cisplatin-containing therapy was tolerated without evidence of renal failure and with only moderate to severe emesis in 25% of the patients. Calculated creatinine clearances dropped only 4.9%, 13.9%, and 14.9% between Courses 1 and 6 in patients receiving cisplatin doses of 50-60, 70-90, and 100-120 mg/m2, respectively. We conclude that cisplatin doses of 50-120 mg/m2 can be administered safely and with acceptable tolerance in the outpatient setting.


Improving cranial ultrasound scanning strategy in neonates.
Cranial ultrasound scans are undertaken in this tertiary neonatal intensive care unit by the doctors within the department. A quality improvement project was undertaken by means of two PDSA cycles to determine adherence to neonatal cranial ultrasound scanning schedule, assess the quality of scan reporting, and formulate a comprehensive guideline outlining best practice. The baseline measurements assessed 93 scans of preterm infants and 9 of term infants. The results of this prompted intradepartmental education (PDSA cycle 1) then creation and implementation of a documentation template, a local guideline, and education via presentations, posters, and email (PDSA cycle 2). These encompassed 77 preterm and 5 term scans. In our baseline measurements, 52% of preterm infant scans and 44% of term infant scans were performed to schedule. Of premature baby scan reports, 75% had the time documented and 92% the name of the scanning doctor. After implementing changes PDSA cycle 2 data showed that 74% of preterm infant scans and all term infant scans were performed according to schedule, with 100% having the doctor's name and time of scan documented. We successfully introduced a guideline and documentation template, improving performance to schedule and documentation in most areas. It remains an ongoing challenge to adhere to basic standards of documentation; a template can assist in achieving this. Rotating trainees may offer insight into areas that could benefit from quality improvement. This enthusiasm can be successfully harnessed to implement changes to improve quality of patient care.


The relationship between parental fatigue, parenting self-efficacy and behaviour: implications for supporting parents in the early parenting period.
Emerging evidence indicates that parental fatigue is associated with low warmth and increased hostility in parent-child interactions. One possible pathway by which fatigue may impact on parenting behaviour is via parental self-efficacy (PSE), whereby high fatigue may undermine PSE, which is often associated with suboptimal parenting behaviour. The current study sought to explore a model of the relationships between parental fatigue, parenting warmth and hostility, where PSE mediates these relationships and whether the nature of these relationships differ by social or family context. The current sample was drawn from a larger Australian community sample survey on parent well-being and parenting. It consisted of 1143 parents (mothers, n = 1003; fathers, n = 140) of children aged 0-4 years. Path analysis revealed that the relationship between fatigue and parenting warmth and hostility was fully mediated by PSE. These results indicate that fatigue has the potential to negatively influence parenting behaviours that are important for their children's well-being and development, and that fatigue plays a mediating role in this relationship. Implications of the study for psycho-education and interventions targeting the management of parental fatigue are discussed.


Hepatotoxicity Induced by "the 3Ks": Kava, Kratom and Khat.
The 3Ks (kava, kratom and khat) are herbals that can potentially induce liver injuries. On the one hand, growing controversial data have been reported about the hepatotoxicity of kratom, while, on the other hand, even though kava and khat hepatotoxicity has been investigated, the hepatotoxic effects are still not clear. Chronic recreational use of kratom has been associated with rare instances of acute liver injury. Several studies and case reports have suggested that khat is hepatotoxic, leading to deranged liver enzymes and also histopathological evidence of acute hepatocellular degeneration. Numerous reports of severe hepatotoxicity potentially induced by kava have also been highlighted, both in the USA and Europe. The aim of this review is to focus on the different patterns and the mechanisms of hepatotoxicity induced by "the 3Ks", while trying to clarify the numerous aspects that still need to be addressed.


A SpoT polymorphism correlates with chill stress survival and is prevalent in clinical isolates of Campylobacter jejuni.
Resistance of Campylobacter jejuni to environmental stress is regarded as a risk factor for the transmission of C. jejuni from poultry or poultry products to humans. So far, the mechanisms underlying the capacity of C. jejuni to survive environmental stress conditions are not fully understood. In this study, we searched for polymorphisms in C. jejuni genes, potentially involved in resistance to chill stress. To this end, we assessed 3 groups of C. jejuni isolates (clinical, retail chicken meat, and feces) for survival of experimentally induced chill stress. For each isolate we sequenced 3 genes encoding the C. jejuni sigma factors FliA, RpoD, and RpoN as well as the genes for the transcriptional regulator SpoT and the periplasmic protein HtrA. Data suggest a higher prevalence of a specific polymorphism in spoT in clinical isolates compared with poultry meat or farm isolates. Moreover, this genotype correlated with enhanced survival of chill stress. The observation that the prevalence of this SNP is relatively high in clinical isolates, which most likely have been exposed to multiple forms of stress, suggest that this SNP may be a biomarker for enhanced survival of stress.


Tsetse blood-meal sources, endosymbionts and trypanosome-associations in the Maasai Mara National Reserve, a wildlife-human-livestock interface.
African trypanosomiasis (AT) is a neglected disease of both humans and animals caused by Trypanosoma parasites, which are transmitted by obligate hematophagous tsetse flies (Glossina spp.). Knowledge on tsetse fly vertebrate hosts and the influence of tsetse endosymbionts on trypanosome presence, especially in wildlife-human-livestock interfaces, is limited. We identified tsetse species, their blood-meal sources, and correlations between endosymbionts and trypanosome presence in tsetse flies from the trypanosome-endemic Maasai Mara National Reserve (MMNR) in Kenya. Among 1167 tsetse flies (1136 Glossina pallidipes, 31 Glossina swynnertoni) collected from 10 sampling sites, 28 (2.4%) were positive by PCR for trypanosome DNA, most (17/28) being of Trypanosoma vivax species. Blood-meal analyses based on high-resolution melting analysis of vertebrate cytochrome c oxidase 1 and cytochrome b gene PCR products (n = 354) identified humans as the most common vertebrate host (37%), followed by hippopotamus (29.1%), African buffalo (26.3%), elephant (3.39%), and giraffe (0.84%). Flies positive for trypanosome DNA had fed on hippopotamus and buffalo. Tsetse flies were more likely to be positive for trypanosomes if they had the Sodalis glossinidius endosymbiont (P = 0.0002). These findings point to complex interactions of tsetse flies with trypanosomes, endosymbionts, and diverse vertebrate hosts in wildlife ecosystems such as in the MMNR, which should be considered in control programs. These interactions may contribute to the maintenance of tsetse populations and/or persistent circulation of African trypanosomes. Although the African buffalo is a key reservoir of AT, the higher proportion of hippopotamus blood-meals in flies with trypanosome DNA indicates that other wildlife species may be important in AT transmission. No trypanosomes associated with human disease were identified, but the high proportion of human blood-meals identified are indicative of human African trypanosomiasis risk. Our results add to existing data suggesting that Sodalis endosymbionts are associated with increased trypanosome presence in tsetse flies.


Lysosomes in rat thoracic duct lymphocytes.
10 acid hydrolases known to be lysosomal in other tissues were detected in rat thoracic duct lymphocytes (TDL). Except for cathepsin D, all these enzymes occurred in lower levels in TDL than in rat spleen. Fractionation by means of differential centrifugation revealed two types of distribution patterns. Most of the total cathepsin D activity appeared in a high-speed supernatant (S), whereas the other acid hydrolases associated mainly with a high-speed pellet (P). Further studies by isopycnic centrifugation in a sucrose density gradient showed that all the enzymes, including a small portion of cathepsin D, sedimented around a modal density of 1.18. In contrast, most cathepsin D activity was recovered in a soluble, unsedimentable form. These results suggest the presence of two populations of lysosomes. Because the possibility could be excluded that other cell types contaminated the lymphocyte preparations, it is concluded that both lysosomal populations arise from TDL.


Complications related to equipment and technique.
Automated cytapheresis, when performed by experienced operators using modern equipment, is remarkably free of adverse effects. A declining pattern of equipment failure and related problems has been recorded in the 220,000 procedures performed by the American Red Cross in the past 5 years. Other cytapheresis centers report similar findings. Current CBCS are safe and reliable, and defects in plastic disposables, while irritating, result in little danger to the donor. Operator vigilance and careful attention to the details of the procedure can eliminate the majority of serious potential complications that have been encountered to date.


New insights into minor splicing-a transcriptomic analysis of cells derived from TALS patients.
Minor intron splicing plays a central role in human embryonic development and survival. Indeed, biallelic mutations in RNU4ATAC, transcribed into the minor spliceosomal U4atac snRNA, are responsible for three rare autosomal recessive multimalformation disorders named Taybi-Linder (TALS/MOPD1), Roifman (RFMN), and Lowry-Wood (LWS) syndromes, which associate numerous overlapping signs of varying severity. Although RNA-seq experiments have been conducted on a few RFMN patient cells, none have been performed in TALS, and more generally no in-depth transcriptomic analysis of the ∼700 human genes containing a minor (U12-type) intron had been published as yet. We thus sequenced RNA from cells derived from five skin, three amniotic fluid, and one blood biosamples obtained from seven unrelated TALS cases and from age- and sex-matched controls. This allowed us to describe for the first time the mRNA expression and splicing profile of genes containing U12-type introns, in the context of a functional minor spliceosome. Concerning RNU4ATAC-mutated patients, we show that as expected, they display distinct U12-type intron splicing profiles compared to controls, but that rather unexpectedly mRNA expression levels are mostly unchanged. Furthermore, although U12-type intron missplicing concerns most of the expressed U12 genes, the level of U12-type intron retention is surprisingly low in fibroblasts and amniocytes, and much more pronounced in blood cells. Interestingly, we found several occurrences of introns that can be spliced using either U2, U12, or a combination of both types of splice site consensus sequences, with a shift towards splicing using preferentially U2 sites in TALS patients' cells compared to controls.


Quartz crystal microbalance study of protein adsorption kinetics on poly(2-hydroxyethyl methacrylate).
The interaction of macromolecules with artificial biomaterials may lead to potentially serious complications upon implantation into a biological environment. The interaction of one of the most widely used biomaterials, polyHEMA, with lysozyme, bovine serum albumin (BSA), and lactoferrin was investigated using quartz crystal microbalance (QCM). The concentration dependence of adsorption was measured for the aforementioned proteins individually as well as for lysozyme-BSA, and lysozyme-lactoferrin combinations. An extension of Voinova's viscoelastic model to n layers was used to create thickness-time graphs for adsorption. For each of lactoferrin and lysozyme, two distinctly different timescales of adsorption could be differentiated. However, the mechanisms of adsorption appeared to differ between the two. Negative dissipation shifts were measured for low concentrations of lysozyme, trending to positive dissipation at higher concentrations. This suggested that lysozyme was adsorbed initially into the matrix, stiffening the hydrogel, and later onto the surface of polyHEMA. Additionally, trials with commercial no-rub cleaning solutions indicated little added effectiveness over buffer solutions. Mixtures of proteins showed behaviour which differed in some cases from the simple combination of single protein adsorption experiments.


Extensions to Online Feature Selection Using Bagging and Boosting.
Feature subset selection can be used to sieve through large volumes of data and discover the most informative subset of variables for a particular learning problem. Yet, due to memory and other resource constraints (e.g., CPU availability), many of the state-of-the-art feature subset selection methods cannot be extended to high dimensional data, or data sets with an extremely large volume of instances. In this brief, we extend online feature selection (OFS), a recently introduced approach that uses partial feature information, by developing an ensemble of online linear models to make predictions. The OFS approach employs a linear model as the base classifier, which allows the $l_{0}$ -norm of the parameter vector to be constrained to perform feature selection leading to sparse linear models. We demonstrate that the proposed ensemble model typically yields a smaller error rate than any single linear model, while maintaining the same level of sparsity and complexity at the time of testing.


Pyrosequencing analysis yields comprehensive assessment of microbial communities in pilot-scale two-stage membrane biofilm reactors.
We studied the microbial community structure of pilot two-stage membrane biofilm reactors (MBfRs) designed to reduce nitrate (NO3(-)) and perchlorate (ClO4(-)) in contaminated groundwater. The groundwater also contained oxygen (O2) and sulfate (SO4(2-)), which became important electron sinks that affected the NO3(-) and ClO4(-) removal rates. Using pyrosequencing, we elucidated how important phylotypes of each "primary" microbial group, i.e., denitrifying bacteria (DB), perchlorate-reducing bacteria (PRB), and sulfate-reducing bacteria (SRB), responded to changes in electron-acceptor loading. UniFrac, principal coordinate analysis (PCoA), and diversity analyses documented that the microbial community of biofilms sampled when the MBfRs had a high acceptor loading were phylogenetically distant from and less diverse than the microbial community of biofilm samples with lower acceptor loadings. Diminished acceptor loading led to SO4(2-) reduction in the lag MBfR, which allowed Desulfovibrionales (an SRB) and Thiothrichales (sulfur-oxidizers) to thrive through S cycling. As a result of this cooperative relationship, they competed effectively with DB/PRB phylotypes such as Xanthomonadales and Rhodobacterales. Thus, pyrosequencing illustrated that while DB, PRB, and SRB responded predictably to changes in acceptor loading, a decrease in total acceptor loading led to important shifts within the "primary" groups, the onset of other members (e.g., Thiothrichales), and overall greater diversity.


The effectiveness of housing policies in reducing children's lead exposure.
This study evaluated the relation of housing policies to risk of subsequent lead exposure in addresses where lead-poisoned children had lived. Addresses where children with lead poisoning lived between May 1992 and April 1993 were selected from lead screening registries in 2 northeastern states differing in their enforcement of lead poisoning prevention statutes. Blood lead levels of subsequently resident children, exterior condition, tax value, age, and census tract characteristics were collected. The odds of elevated blood lead levels in subsequently resident children were calculated with logistic regression. The risk of identifying 1 or more children with blood lead levels of 10 micrograms/dL or greater was 4 times higher in addresses with limited enforcement. Controlling for major confounders had little effect on the estimate. Enforcement of housing policies interrupts the cycle of repeated lead exposure.


Metabolic changes in deafferented central neurons of an insect, Acheta domesticus. II. Effects on cholinergic binding sites and acetylcholinesterase.
Following the finding that cercal deafferentation of developing giant interneurons in the terminal abdominal ganglion (TG) of the cricket Acheta domesticus reduces TG protein metabolism within target interneuron dendrites and somata (Meyer and Edwards, 1982), it is now shown that deafferentation alters the turnover of three macromolecules associated with cholinergic transmission in the cercal sensory-giant interneuron pathway. The labeled specific ligands 3H-quinuclidinyl benzilate and 125I-alpha-bungarotoxin were used to assay populations of putative TG muscarinic and nicotinic cholinergic receptors, respectively, in control and deafferented groups of ganglia. The AChE activity of TG was also determined by assay and histochemical methods. Long-term deafferentation sustained throughout postembryonic development markedly reduces the densities of both muscarinic and nicotinic binding sites in the TG; short-term deafferentation of adult TG also leads to characteristic alterations in the properties of all three cholinergic markers within several days. Rapid changes seen in adults thus correlate with ultrastructural data demonstrating loss of afferent terminals within hours of sensory appendage removal. We propose that peripheral innervation-dependent regulatory mechanisms operate in both the developing and adult insect nervous system. Such mechanisms may influence transsynaptically the synthesis and turnover of specific macromolecules, some of which may reside on the cell surface of insect central neurons that are part of the cercal sensory-giant interneuron system.


[Pathology of lungs by wounded in the armed conflicts in Northern Caucasus].
According to 7000 patient histories, wounded in armed conflicts in Northern Caucasus, for the last years, is marked a big part of wounds of mild (45.3%) and medium (31.5%) severity. Heavy and extremely heavy wounds marked conformably in 20.8 and 2.4 percents. An acute respiratory distress-syndrome is marked by 32 wounded with heavy and extremely heavy wounds, including 10--with penetrating wound of brainpan, 9--penetrating wound of bosom and tense hemopneumothorax, 11--penetrating wound of abdomen (with deflection of hollow and parenchymal organs), 2--penetrating wound of lower limbs (with firing breakup of long bones and deflections of great vessel), attended by blood loss and shock. Pneumonia was found during first 3 days after the wound by 47%, on 4-7 day--31%, during second week--13%, latter--9%. In 93% of cases pneumonia was marked in combination with traumatic shock. Radiological examining of radiological plays a conclusive account in diagnostics, and according to meanings--computerized tomography. Estimation of function of exterior breathing is also important.


Chondroblastic osteosarcoma: Cytomorphologic characteristics and differential diagnosis on FNA.
Chondroblastic osteosarcoma (COS) is a uniformly fatal bone malignancy if not diagnosed and treated appropriately in a timely manner. Fine-needle aspiration (FNA) of osseous lesions is routinely performed in major medical centers. Appropriate characterization of the tumor will significantly influence patient management and outcomes. A retrospective review of the cytopathology archives of 2 large tertiary care centers for a 15-year period (2001-2015) revealed 17 cases of COS (9 primary, 6 recurrent, and 2 metastatic cases) in 16 patients. Clinical outcome and histopathologic follow-up were reviewed and correlated. There were 9 male and 7 female patients (male-to-female ratio of approximately 1:1), ranging in age from 12 to 70 years (mean age, 29.2 years). The classic locations for osteosarcoma were commonly involved, such as the long bones around the region of the knee in 4 cases and the proximal humerus in 1 case. However, other "nonclassic" sites also were noted to be commonly involved, including the distal tibia or fibula (4 cases), sacroiliac region (4 cases), mandible (3 cases), and skull (1 case). Cytomorphologic characteristics were high cellularity; predominantly discohesive, single cells; small tissue fragments; background osteoid and chondroid matrix; spindled cells and plasmacytoid cells with moderate to abundant basophilic vacuolated cytoplasm and occasional multiple cytoplasmic processes; round to oval nuclei with anisonucleosis; and small to prominent nucleoli. There were scattered binucleated and multinucleated osteoclast-like giant cells. Cases with high-grade morphology demonstrated marked pleomorphism and abundant mitoses. The differential diagnosis of COS includes chondroblastoma, chondrosarcoma, and chondroid chordoma. A definitive diagnosis can be made with clinical and radiological correlation. Cancer Cytopathol 2016;124:493-500. © 2016 American Cancer Society.


How equitable are the distributions of the physical activity and accessibility benefits of bicycle infrastructure?
Cycling for transport provides many health and social benefits - including physical activity and independent access to jobs, education, social opportunities, health care and other services (accessibility). However, some population groups have less opportunity to reach everyday destinations, and public transport stops, by bicycle - owing in part to their greater aversion to riding amongst motor vehicle traffic. Health equity can therefore be improved by providing separated cycleway networks that give more people the opportunity to access places by bicycle using traffic-free routes. The aim of this study was to assess the health equity benefits of two bicycle infrastructure development scenarios - a single cycleway, and a complete network of cycleways - by examining the distributions of physical activity and accessibility benefits across gender, age and income groups. Travel survey data collected from residents in Sydney (Australia) were used to train a predictive transport mode choice model, which was then used to forecast the impact of the two intervention scenarios on transport mode choice, physical activity and accessibility. The latter was measured using a utility-based measure derived from the mode choice model. The distributions of the forecast physical activity and accessibility benefits were then calculated across gender, age and income groups. The modelled physical activity and accessibility measures improve in both intervention scenarios. However, in the single cycleway scenario, the benefits are greatest for the male, high-income and older age groups. In the complete network scenario, the benefits are more equally distributed. Forecast increases in cycling time are largely offset by decreases in walking time - though the latter is typically low-intensity physical activity, which confers a lesser health benefit than moderate-intensity cycling. Separated cycleway infrastructure can be used to improve health equity by providing greater opportunities for transport cycling in population groups more averse to riding amongst motor vehicle traffic. Disparities in the opportunity to access services and economic/social activities by bicycle - and incorporate more physical activity into everyday travel - could be addressed with connected, traffic-free cycleway networks that cater to people of all genders, ages and incomes.


Biochemical heterogeneity of skeletal-muscle microsomal membranes. Membrane origin, membrane specificity and fibre types.
1. Microsomes were isolated from rabbit fast-twitch and slow-twitch muscle and were separated into heavy and light fractions by centrifugation in a linear (0.3-2m) sucrose density gradient. The membrane origin of microsomal vesicles was investigated by studying biochemical markers of the sarcoplasmic-reticulum membranes and of surface and T-tubular membranes, as well as their freeze-fracture properties. 2. Polyacrylamide-gel electrophoresis showed differences in the Ca(2+)-dependent ATPase/calsequestrin ratio between heavy and light fractions, which were apparently consistent with their respective origin from cisternal and longitudinal sarcoplasmic reticulum, as well as unrelated differences, such as peptides specific to slow-muscle microsomes (mol.wts. 76000, 60000, 56000 and 45000). 3. Freeze-fracture electron microscopy of muscle microsomes demonstrated that vesicles truly derived from the sarcoplasmic reticulum, with an average density of 9nm particles on the concave face of about 3000/mum(2) for both fast and slow muscle, were admixed with vesicles with particle densities below 1000/mum(2). 4. As determined in the light fractions, the sarcoplasmic-reticulum vesicles accounted for 84% and 57% of the total number of microsomal vesicles, for fast and slow muscle respectively. These values agreed closely with the percentage values of Ca(2+)-dependent ATPase protein obtained by gel densitometry. 5. The T-tubular origin of vesicles with a smooth concave fracture face in slow-muscle microsomes is supported by their relative high content in total phospholipid and cholesterol, compared with the microsomes of fast muscle, and by other correlative data, such as the presence of (Na(+)+K(+))-dependent ATPase activity and of low amounts of Na(+)-dependent membrane phosphorylation. 6. Among intrinsic sarcoplasmic-reticulum membrane proteins, a proteolipid of mol.wt. 12000 is shown to be identical in the microsomes of both fast and slow muscle and the Ca(2+)-dependent ATPase to be antigenically and catalytically different, though electrophoretically homogeneous. 7. Basal Mg(2+)-activated ATPase activity was found to be high in light microsomes from slow muscle, but its identification with an enzyme different from the Ca(2+)-dependent ATPase is still not conclusive. 8. Enzyme proteins that are suggested to be specific to slow-muscle longitudinal sarcoplasmic reticulum are the flavoprotein NADH:cytochrome b(5) reductase (mol.wt. 32000), cytochrome b(5) (mol.wt. 17000) and the stearoyl-CoA desaturase, though essentially by criteria of plausibility.


The English national cohort study of flooding and health: cross-sectional analysis of mental health outcomes at year one.
In winter 2013/14 there was widespread flooding in England. Previous studies have described an increased prevalence of psychological morbidity six months after flooding. Disruption to essential services may increase morbidity however there have been no studies examining whether those experiencing disruption but not directly flooded are affected. The National Study of Flooding and Health was established in order to investigate the longer-term impact of flooding and related disruptions on mental health and wellbeing. In year one we conducted a cross sectional analysis of people living in neighbourhoods affected by flooding between 1 December 2013 and 31 March 2014. 8761 households were invited to participate. Participants were categorised according to exposure as flooded, disrupted by flooding or unaffected. We used validated instruments to screen for probable psychological morbidity, the Patient Health Questionnaire (PHQ 2), Generalised Anxiety Disorder scale (GAD-2) and Post Traumatic Stress Disorder (PTSD) checklist (PCL-6). We calculated prevalence and odds ratios for each outcome by exposure group relative to unaffected participants, adjusting for confounders. 2126 people (23%) responded. The prevalence of psychological morbidity was elevated amongst flooded participants ([n = 622] depression 20.1%, anxiety 28.3%, PTSD 36.2%) and disrupted participants ([n = 1099] depression 9.6%, anxiety 10.7% PTSD 15.2%). Flooding was associated with higher odds of all outcomes (adjusted odds ratios (aORs), 95% CIs for depression 5.91 (3.91-10.99), anxiety 6.50 (3.77-11.24), PTSD 7.19 (4.33-11.93)). Flooded participants who reported domestic utilities disruption had higher odds of all outcomes than other flooded participants, (aORs, depression 6.19 (3.30-11.59), anxiety 6.64 (3.84-11.48), PTSD 7.27 (4.39-12.03) aORs without such disruption, depression, 3.14 (1.17-8.39), anxiety 3.45 (1.45-8.22), PTSD 2.90 (1.25-6.73)). Increased floodwater depth was significantly associated with higher odds of each outcome. Disruption without flooding was associated with borderline higher odds of anxiety (aOR 1.61 (0.94-2.77)) and higher odds of PTSD 2.06 (1.27-3.35)) compared with unaffected participants. Disruption to health/social care and work/education was also associated with higher odds of psychological morbidity. This study provides an insight into the impact of flooding on mental health, suggesting that the impacts of flooding are large, prolonged and extend beyond just those whose homes are flooded.


[Contribution of gastroscopy with aimed biopsy to the diagnosis of early gastric cancer].
Gastroscopy was carried out in 320 patients with gastric cancer. In 35 instances, the tumour was located in the mucosa or barely extended into the submucosa. Diagnostic corroboration was obtained by means of biopsies conducted during the examination. Gastric fibroscopy can now offer early diagnosis of carcinoma of the stomach. A barium meal often fails to reveal these lesions, especially in the initial stages, nor can it indicate whether an ulcer is benign or a tumour. The fact that biopsy can be performed at the same time is of fundamental importance in determing whether medical or surgical management should be chosen.


The effect of inhibitors of mitochondrial energy production on hepatic glutathione, UDP-glucuronic acid, and adenosine 3'-phosphate-5'-phosphosulfate concentrations.
The hepatic conjugation of xenobiotics with sulfate, glucuronic acid, and glutathione is decreased in vitro by compounds that impair cellular energy production. The proposed mechanism is that depletion of ATP in metabolically compromised cells causes a decreased synthesis of the co-substrates, adenosine 3'-phosphate 5'-phosphosulfate (PAPS), UDP-glucuronic acid, and glutathione. This proposal was examined in vivo by quantitating hepatic adenine nucleotides and co-substrates in rats treated with the following inhibitors of mitochondrial ATP production: rotenone, antimycin A, carbonyl cyanide m-chlorophenylhydrazone, and 2,4-dinitrophenol. Hepatic ATP levels 30 min after administration of the inhibitors were about 30% of control. Hepatic energy charge (ATP + 0.5 X ADP)/(ATP + ADP + AMP) was significantly reduced by each inhibitor. Unexpectedly, UDP-glucuronic acid, PAPS, and glutathione concentrations were not reduced at 30 or 60 min after administration of the inhibitors. Thus, it does not appear possible to deplete hepatic ATP in vivo by means of mitochondrial inhibitors to the extent necessary to affect basal levels of UDP-glucuronic acid, PAPS, and glutathione. PAPS levels increased after administration of 2,4-dinitrophenol. This was shown to be a property shared with phenolic inhibitors of phenol sulfotransferase.


Photodynamic therapy: shedding light on the biochemical pathways regulating porphyrin-mediated cell death.
Photodynamic therapy (PDT) is a clinically approved treatment for the ocular condition age-related macular degeneration, and certain types of cancer. PDT is also under investigation for other ocular, as well as, immune-mediated and cardiovascular indications. PDT is a two step procedure. In the first step, the photosensitizer, usually a porphyrin derivative, is administered and taken up by cells. The second step involves activation of the photosensitizer with a specific wavelength of visible light. Exposure to light of an activating wavelength generates reactive oxygen species within cells containing photosensitizer. PDT with porphyrin photosensitizers induces rapid apoptotic cell death, an event which may be attributed to the close association of these compounds with mitochondria. Thus, PDT is an attractive method to treat ailments such as cancer, viral infections, autoimmune disorders and certain cardiovascular diseases in which the apoptotic program may be compromised. The present review examines the cellular events triggered at lethal and sublethal PDT doses and their relationship to the subsequent effects exerted upon cells.


Cellulosome gene cluster analysis for gauging the diversity of the ruminal cellulolytic bacterium Ruminococcus flavefaciens.
Ruminococcus flavefaciens is a vital cellulosome-producing fibrolytic rumen bacterium. The arrangement of the cellulosomal scaffoldin gene cluster (scaC-scaA-scaB-cttA-scaE) is conserved in two R. flavefaciens strains (17 and FD-1). Sequence analysis revealed a high mosaic conservation of the intergenic regions in the two strains that contrasted sharply with the divergence of the structural sca gene sequences. Based on the conserved intergenic regions, we designed PCR primers in order to examine the sca gene cluster in additional R. flavefaciens strains (C94, B34b, C1a and JM1). Using these conserved and/or degenerate primers, the scaC, scaA and scaB genes were amplified in all six strains, while the entire sca gene cluster and the proximal genes cttA and scaE were successfully amplified in four of the strains (17, FD-1, C94 and JM1). The sequencing of scaA and scaC genes in all the strains yielded additional insight into the variability of the structural genes with regard to the number and type of cohesin modules contained in a conserved molecular skeleton. Moreover, the scaC gene, being short and variable, appears to be a promising functional phylotyping target for metagenomic population studies of R. flavefaciens in the rumen as a function of the individual host animal.


Teen Pregnancy Risk Factors Among Young Women of Diverse Sexual Orientations.
Young women who are sexual minorities (eg, bisexual and lesbian) are approximately twice as likely as those who are heterosexual to have a teen pregnancy. Therefore, we hypothesized that risk factors for teen pregnancy would vary across sexual orientation groups and that other potential risk factors exist that are unique to sexual minorities. We used multivariable log-binomial models gathered from 7120 young women in the longitudinal cohort known as the Growing Up Today Study to examine the following potential teen pregnancy risk factors: childhood maltreatment, bullying victimization and perpetration, and gender nonconformity. Among sexual minorities, we also examined the following: sexual minority developmental milestones, sexual orientation-related stress, sexual minority outness, and lesbian, gay, and bisexual social activity involvement. Childhood maltreatment and bullying were significant teen pregnancy risk factors among all participants. After adjusting for childhood maltreatment and bullying, the sexual orientation-related teen pregnancy disparities were attenuated; these risk factors explained 45% of the disparity. Among sexual minorities, reaching sexual minority developmental milestones earlier was also associated with an increased teen pregnancy risk. The higher teen pregnancy prevalence among sexual minorities compared with heterosexuals in this cohort was partially explained by childhood maltreatment and bullying, which may, in part, stem from sexual orientation-related discrimination. Teen pregnancy prevention efforts that are focused on risk factors more common among young women who are sexual minorities (eg, childhood maltreatment, bullying) can help to reduce the existing sexual orientation-related teen pregnancy disparity.


Similarities and differences in altitudinal versus latitudinal variation for morphological traits in Drosophila melanogaster.
Understanding how natural environments shape phenotypic variation is a major aim in evolutionary biology. Here, we have examined clinal, likely genetically based variation in morphology among 19 populations of the fruit fly (Drosophila melanogaster) from Africa and Europe, spanning a range from sea level to 3000 m altitude and including locations approximating the southern and northern range limit. We were interested in testing whether latitude and altitude have similar phenotypic effects, as has often been postulated. Both latitude and altitude were positively correlated with wing area, ovariole number, and cell number. In contrast, latitude and altitude had opposite effects on the ratio between ovariole number and body size, which was negatively correlated with egg production rate per ovariole. We also used transgenic manipulation to examine how increased cell number affects morphology and found that larger transgenic flies, due to a higher number of cells, had more ovarioles, larger wings, and, unlike flies from natural populations, increased wing loading. Clinal patterns in morphology are thus not a simple function of changes in body size; instead, each trait might be subject to different selection pressures. Together, our results provide compelling evidence for profound similarities as well as differences between phenotypic effects of latitude and altitude.


In-vitro and in-vivo antivenin activity of 2-[2-(5,5,8a-trimethyl-2-methylene-decahydro-naphthalen-1-yl)-ethylidene]-succinaldehyde against Ophiophagus hannah venom.
Curcuma zedoaroides A. Chaveerach & T. Tanee, locally known as Wan-Paya-Ngoo-Tua-Mia, is commonly used in the North-Eastern part of Thailand as a 'snakebite antidote'. The aim of this study was to isolate the active compound from the rhizome of C. zedoaroides, to determine its structure and to assess its antagonistic activity in vitro and in vivo against King cobra venom. The active compound was obtained from C. zedoaroides by extraction with acetone followed by purification using column chromatography; its X-ray structure was determined. Its inhibition of venom lethality was studied in vitro in rat phrenic nerve-hemidiaphragms and in vivo in mice. The acetone extract of the Curcuma rhizomes contained a C20 dialdehyde, [2-(5,5,8a-trimethyl-2-methylene-decahydro-naphthalen-1-yl)-ethylidene]-succinaldehyde, as the major component. The isolated curcuma dialdehyde was found active in vitro and in vivo for antivenin activity against the King cobra venom. Using isolated rat phrenic nerve-hemidiaphragm preparations, a significant antagonistic effect on the inhibition of neuromuscular transmission was observed in vitro. Inhibition on muscle contraction, produced by the 4 microg/ml venom, was reversed by 2-16 microg/ml of Curcuma dialdehyde in organ bath preparations over a period of 2 h. Mice intraperitoneally injected with 0.75 mg/kg venom and dialdehyde at 100 mg/kg had a significantly increased survival time. Injection of Curcuma dialdehyde (100 mg/kg) 30 min before the subcutaneous injection of the venom resulted in a 100% survival time after 2 h compared with 0% for the control group. The in vitro and in vivo evaluation confirmed the medicinal use of traditional snake plants against snakebites. The bioactivity is linked to an isolated molecule and not a result of synergistic effects of a mixture. The active compound was isolated and the structure fully elucidated, including its stereochemistry. This dialdehyde is a versatile chemical building block and can be easily obtained from this plant source.


Exercise intervention studies in patients with peripheral neuropathy: a systematic review.
Peripheral neuropathies (PNPs) encompass a large group of disorders of heterogeneous origin which can manifest themselves with sensory and/or motor deficits depending on the predominantly affected nerve fiber modality. It represents a highly prevalent disease group which can be associated with significant disability and poor recovery. Exercise has the potential to improve side effects of PNP. Our objective in this systematic review was to analyze exercise interventions for neuropathic patients in order to evaluate the possible benefits of exercise. Three independent reviewers used PubMed, MEDPILOT (MEDLINE), Cochrane, and relevant reference lists to obtain the data. Relevant studies were graded according to the Oxford Levels of Evidence. Eighteen studies (ten randomized controlled trials and eight controlled clinical trials) met all inclusion criteria. Three (diabetic) studies were ranked very high quality [1b (A)], nine high quality (four diabetes, one cancer, four others) [2b (B)], while six (four diabetes, two others) showed low quality (4/C). Current data suggests that exercise is a feasible, safe, and promising supportive measure for neuropathic patients. This is best documented for patients with diabetic peripheral neuropathy (DPN), suggesting that endurance training has the potential to prevent the onset of and reduce the progression of DPN. In general, balance exercises showed the highest effect on the motor as well as sensory symptoms in all types of PNP. Overall, balance training appears to be the most effective exercise intervention. Studies focusing exclusively on strength, or a combination of endurance and strength, appear to have a lower impact. For metabolically-induced neuropathies, endurance training also plays an important role. Further research with high methodological quality needs to be conducted in order to establish evidence-based clinical recommendations for neuropathic patients.


Molecular snapshot of Mycobacterium tuberculosis population structure and drug-resistance in Kyrgyzstan.
Kyrgyzstan is a post-Soviet country in Central Asia marked with high incidence and mortality rates of tuberculosis (TB). The present study provided first assessment of Mycobacterium tuberculosis population structure and drug-resistance in civilian population here. The collection included 103 M. tuberculosis DNA samples subjected to the analysis of rifampin and isoniazid resistance mutations and spoligotyping. The major spoligotype-defined families were Beijing (n = 62), T (n = 14), LAM (n = 9), Ural-2 (n = 6) and Ural-1 (n = 3). Genotypically, 20 isolates were RIF-resistant, 28 were INH-resistant, 17 were multidrug-resistant. Drug resistant isolates were more prevalent among Beijing than non-Beijing groups (P = 0.03). The predominance of the mainly "Russian" spoligotypes among the non-Beijing strains (LAM-RUS and Ural-1) in this study along with previously demonstrated prevalence of the Russia-specific subtype of the Beijing family in Kyrgyz prison (Mokrousov et al., 2009) suggest that the current population structure of M. tuberculosis in Kyrgyzstan has been mainly formed within the course of the 20th century when the country was a part of the Russian Empire and Soviet Union. On the other hand, a prevalence of the Asia-specific Ural-2 type in the oldest age group (68-85 years old; P < 0.0001) may present a heritage of the more distant historical events. In summary, we suggest: (i) a clear shift of the local M. tuberculosis population structure during the last 100 years and (ii) a critical impact of the Beijing genotype on the current situation with drug resistant TB in Kyrgyzstan.


Role of infectious agents in systemic rheumatic diseases.
The relationship between infection and autoimmunity has been increasingly defined over the last twenty years or so. It is now quite clear that, in genetically susceptible individuals, environmental factors (mainly infections) play a critical role in the pathogenesis of autoimmune diseases. It is believed that infections contribute to the maturation of the immune system from the innate to adoptive phases, and that bacterial and viral infections are arthritogenic stimulants leading to various rheumatic conditions. A failure to isolate these microorganisms is probably due to the action of the immune system, but often casts doubt on their role in the pathogenesis of autoimmune diseases. Among bacteria, Helicobacter pylori has been associated with diseases such as autoimmune gastritis, Sjögren's syndrome, atherosclerosis, immune thrombocytopenia purpura, inflammatory bowel diseases and autoimmune pancreatitis, in each of which it seems to play a pathogenatic, but it has also been suggested that it may help to protect against the development of autoimmune gastritis, multiple sclerosis, systemic lupus erythemathosus and inflammatory bowel diseases. Infectious agents may play a dual role in the etiopathogenesis of antiphospholipid syndrome (APS): they may be the initial trigger of the production of antibodies cross-reacting with beta 2 glycoprotein I (Beta2GPI) and infectious peptides, and also induce an inflammatory response. According to the two-hit theory, pathogenetic anti-Beta2GPI antibodies act as the first hit whereas inflammatory responses may represent the second hit The slowly growing Propionibacterium acnes may be involved in the etiopathogenesis of SAPHO syndrome non-specific activation of cell-mediated immunity. Its ability to persist in bone lesions in a form that is incompatible with culturing suggests the possibility an arthritis that is secondary to a "persistent" infection.


[Current biological markers of cutaneous melanoma progression].
Melanoma is the most agressive skin cancer in humans. The most important prognostic factors are the histological features of the tumor, while the clinical ones play a secondary role. Melanoma progression is characterized by the metastatic process which directly threatens the patients life. Unfortunately, routine imaging methods cannot estimate early enough this metastatic risk. Are biologic markers of cancer progression more efficient than those applied in everyday practice? Are they able to evaluate the metastatic risk and thus help the therapeutic strategy? In this review, we analysed the analytical and the clinical aspects of biologic markers of cutaneous melanoma currently available or in development. At the present time it is very difficult to distinguish one single marker of melanoma progression in the blood which correlates with the stage and the prognosis of melanoma. The most specific and sensitive enough are the melanoma associated antigens protein S-100, MIA (melanoma inhibiting activity) and the melanin precursors 5-S-cysteinyldopa and the ratio L-dopa/L-tyrosine. Tyrosinase mRNA remains the best target for the detection of circulating metastatic melanoma cells by RT-PCR. Simultaneous detection of several markers might be useful if they are carefully selected. Despite the progress in the field, more clinical studies should be performed for the development of new techniques or improvements of the existing ones for the follow-up of cutaneous melanoma.


[Comparative characteristic of lactate dehydrogenase properties from the white muscles and liver of goldfish (Carassius auratus L.)].
Lactate dehydrogenase (LDH) from the liver and white muscles of the gold fish Carassius auratus was partially purified by differential precipitation with ammonium sulfate. The enzyme from the liver had relatively low Vmax--1.85 +/- 0.31 U/mg protein, the muscle enzyme--3.74 +/- 0.27 U/mg protein. LDH from the liver was less sensitive to substrate inhibition (I50 - 9.92 +/- 1.09 mM) compared to white muscles isozyme (I50 - 5.87 +/- 1.39 mM). The studied isozymes had pH-dependencies with pH optima at 7.0-8.0 and 7.25-8.75 for LDH from the white muscle and liver, respectively. In this work the inactivation of partially purified LDH in the system free radicals oxidations Fe2+/H2O2 has been conducted. During incubation for 5 min of both isozymes with H2O2 (10-50 mM) and FeSO4 (20-500 microM), approximately 50% of their initial activities were lost. The level of enzyme inactivation increased with the increase of iron ion and hydrogen peroxide concentrations. During incubation in the presence of 20 microM FeSO4 and 10 mM H2O2 for 60 min white muscles isozyme lost 44% while liver isozyme--26%, independent of buffer which was used.


Description of Actinomycetospora chibensis sp. nov., Actinomycetospora chlora sp. nov., Actinomycetospora cinnamomea sp. nov., Actinomycetospora corticicola sp. nov., Actinomycetospora lutea sp. nov., Actinomycetospora straminea sp. nov. and Actinomycetospora succinea sp. nov. and emended description of the genus Actinomycetospora.
Eight actinomycete strains that form bud-like spore chains were isolated from various samples collected in Japan. Phylogenetically, the isolates formed a single clade with the type strain of Actinomycetospora chiangmaiensis according to 16S rRNA gene sequence analysis. The isolates contained meso-diaminopimelic acid, d-glutamic acid and d- and l- alanine in the cell-wall peptidoglycan, arabinose and galactose as characteristic sugars, phosphatidylcholine and phosphatidylethanolamine as diagnostic phospholipids, MK-8(H(4)) as the predominant isoprenoid quinone, iso-C(16 : 0) as the major cellular fatty acid and DNA G+C contents of 72-74 mol%. Actinomycetospora chiangmaiensis, the type species of the genus Actinomycetospora, was also found to contain MK-8(H(4)) predominantly in our study, although it was earlier reported to contain MK-9(H(4)) as the predominant isoprenoid quinone. On the basis of the morphological, physiological, chemotaxonomic, phylogenetic and DNA-DNA hybridization data, we concluded that the isolates can be accommodated in the genus Actinomycetospora with emendation of the description of the genus and are assigned to the following seven novel species: Actinomycetospora chibensis sp. nov. (type strain TT04-21(T) = NBRC 103694(T) = KACC 14256(T)), Actinomycetospora chlora sp. nov. (type strain TT07I-57(T) = NBRC 105900(T) = KACC 14252(T)), Actinomycetospora cinnamomea sp. nov. (type strain IY07-53(T) = NBRC 105527(T) = KACC 14250(T)), Actinomycetospora corticicola sp. nov. (type strain 014-5(T) = NBRC 103689(T) = KACC 14253(T)), Actinomycetospora lutea sp. nov. (type strain TT00-04(T) = NBRC 103690(T) = KACC 14254(T)), Actinomycetospora straminea sp. nov. (type strain IY07-55(T) = NBRC 105528(T) = KACC 14251(T)) and Actinomycetospora succinea sp. nov. (type strain TT00-49(T) = NBRC 103691(T) = KACC 14255(T)).


The possible role of esRAGE and sRAGE in the natural history of diabetic nephropathy in childhood.
The advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p = 0.0004, r = -0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy.


Interference induced in GL-V3 monkey kidney cells by rabies virus strains.
Resistance to superinfection with vesicular stomatitis virus (VSV) occurred in GL-V3 monkey kidney cells infected with the CVS-11, Pitman Moore, LEP Flury, but not the ERA strain of rabies virus. Specific immunofluorescent staining of intracellular rabies antigen showed that the number and size of fluorescent foci increased after the onset of interference, and that this was paralleled by increasing yields of infectious virus. Although CVS-11 and ERA differed in their ability to induce interference, the virus yields from monolayers infected with either strain were similar. Interference apparently had no effect on the replication or dissemination of the inducing virus, and seems unrelated to the long incubation period or aberrant forms of infection in vivo.


Midgut-enriched receptor protein tyrosine phosphatase PTP52F is required for Drosophila development during larva-pupa transition.
To date our understanding of Drosophila receptor protein tyrosine phosphatases (R-PTPs) in the regulation of signal transduction is limited. Of the seven R-PTPs identified in flies, six are involved in the axon guidance that occurs during embryogenesis. However, whether and how R-PTPs may control key steps of Drosophila development is not clear. In this study we investigated the potential role of Drosophila R-PTPs in developmental processes outside the neuronal system and beyond the embryogenesis stage. Through systematic data mining of available microarray databases, we found the mRNA level of PTP52F to be highly enriched in the midgut of flies at the larva-pupa transition. This finding was confirmed by gut tissue staining with a specific antibody. The unique spatiotemporal expression of PTP52F suggests that it is possibly involved in regulating metamorphosis during the transformation from larva to pupa. To test this hypothesis, we employed RNA interference to examine the defects of transgenic flies. We found that ablation of endogenous PTP52F led to high lethality characterized by the pharate adult phenotype, occurring due to post pupal eclosion failure. These results show that PTP52F plays an indispensable role during the larva-pupa transition. We also found that PTP52F could be reclassified as a member of the subtype R3 PTPs instead of as an unclassified R-PTP without a human ortholog, as suggested previously. Together, these findings suggest that Drosophila R-PTPs may control metamorphosis and other biological processes beyond our current knowledge.


Diagnostic value of LncRNA-MEG3 as a serum biomarker in patients with hepatitis B complicated with liver fibrosis.
The aim of this work was to explore whether lncRNA-MEG3 could serve as a serum biomarker for diagnosing chronic hepatitis B (CHB) and improve the early diagnostic and treatment efficacies. Serum level of lncRNA-MEG3 in CHB patients and healthy controls was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Subsequently, CHB patients were divided into HBeAg-positive group and HBeAg-negative group based on the infection condition of hepatitis B virus. Correlation analyses were conducted to investigate the relationship between lncRNA-MEG3 level and HBV. Correlation between serum level of lncRNA-MEG3 and liver fibrosis was also analyzed. Survival analyses were performed to elucidate whether lncRNA-MEG3 could be served as a serum biomarker for diagnosing CHB combined with liver fibrosis. Expression levels of lncRNA-MEG3, α-SMA, and COL1A1 in mouse hepatic stellate cells (HSCs) were detected. Serum level of lncRNA-MEG3 was lower in CHB patients compared with that of healthy controls, which was negatively correlated to liver fibrotic degree. Survival analyses showed that serum level of lncRNA-MEG3 exerts significant diagnostic value on the liver fibrotic degree in CHB patients. ROC (receiver operating curve) results showed the AUC was 0.9395, the sensitivity was 100%, and the specificity was 78.13% in comparing the serum level of lncRNA-MEG3 between CHB patients with liver fibrosis and healthy controls. Further analyses showed that serum level of lncRNA-MEG3 was negatively correlated to levels of α-SMA and COL1A1. However, no significant correlations were found among the serum level of lncRNA-MEG3, HBV, hepatic inflammation and liver function. In vitro experiments showed that lncRNA-MEG3 expression was gradually decreased, whereas expression levels of α-SMA and COL1A1 in HSCs were gradually increased in a time-dependent manner. Serum level of lncRNA-MEG3 is lowly expressed in CHB patients, which is negatively correlated to the liver fibrotic degree. LncRNA-MEG3 may serve as a diagnostic biomarker for CHB.


Associations of regrets and coping strategies with job satisfaction and turnover intention: international prospective cohort study of novice healthcare professionals.
(1) To assess the associations of care-related regrets with job satisfaction and turnover intention; and (2) to examine whether these associations are partially mediated by coping strategies. Data came from ICARUS, a prospective international cohort study of novice healthcare professionals working in acute care hospitals and clinics from various countries (e.g., Australia, Austria, Botswana, Canada, Denmark, France, Haiti, Ireland, Kenya, the United Kingdom and United States). Care-related regrets (number of regrets and regret intensity), coping strategies, job satisfaction and turnover intention were assessed weekly for 1 year. 229 young healthcare professionals (2387 observations) were included in the analysis. For a given week, experiencing a larger number of care-related regrets was associated with decreased job satisfaction, and experiencing more intense care-related regrets was associated with increased turnover intention. These associations were partially mediated by coping strategies. Maladaptive emotion-focused strategies were associated with decreased job satisfaction and increased turnover intention, whereas adaptive problem-focused strategies showed the opposite pattern. Our results revealed that care-related regrets and maladaptive coping strategies are associated with job dissatisfaction and the intention to quit patient care. Helping healthcare professionals to cope with these emotional experiences seems essential to prevent early job quitting. &nbsp.


Photosynthetic pigments in acid mine drainage: Seasonal patterns and associations with stressful abiotic characteristics.
Acid mine drainage represents an extreme type of water pollution. The environments develop especial hydrochemical and ecological characteristics, such as high concentrations of acidity and low biodiversity, with dominance of acidophilic organisms. Ecological criteria are assuming increasing relevance for assessing water quality, including in acid mine drainage-affected systems. Photosynthetic pigments, like chlorophyll, could be considered in this context as they are generally used to estimate phytoplankton biomass. The present work was focused on acid mine drainage and their relationships with chlorophyll a. It was developed in the historic mine of São Domingos (Iberian Pyrite Belt, SW Europe). The methodological approach comprised two sampling campaigns (October and February) to represent seasonal behaviour. The diversity of hydrological conditions was also considered through sampling sites established in the pit lake, acidic lagoons and affected stream. Hydrochemistry and chlorophyll a were analysed. The obtained results revealed very low pH values, with a minimum of 2.1. In general, hydrochemistry indicates higher concentrations of pollutants in summer. One of the sampling point, located in an acidic lagoon, stood out by highest concentrations, presenting maximum of sulfate (6564 mg/L), As (6.26 mg/L), and metals like Al (675 mg/L), Cd (1,30 mg/L), Zn (199 mg/L). These highest concentrations coincided with the maximum concentration of chlorophyll a (113 μg/L). The results suggested that the more contaminated the environment, more chlorophyll a was produced. Factor analyses emphasised the relationships between acid drainage properties and the photosynthetic activity, indicating a strong pH dependency of chlorophyll a production.


On Functions Computed on Trees.
Any function can be constructed using a hierarchy of simpler functions through compositions. Such a hierarchy can be characterized by a binary rooted tree. Each node of this tree is associated with a function that takes as inputs two numbers from its children and produces one output. Since thinking about functions in terms of computation graphs is becoming popular, we may want to know which functions can be implemented on a given tree. Here, we describe a set of necessary constraints in the form of a system of nonlinear partial differential equations that must be satisfied. Moreover, we prove that these conditions are sufficient in contexts of analytic and bit-valued functions. In the latter case, we explicitly enumerate discrete functions and observe that there are relatively few. Our point of view allows us to compare different neural network architectures in regard to their function spaces. Our work connects the structure of computation graphs with the functions they can implement and has potential applications to neuroscience and computer science.


Nurse Stress Scale (NSS): Reliability and validity of the Turkish version.
This study aims to conduct the reliability and validity study of the Turkish version of the Nurse Stress Scale (NSS), which determines the job stress of nurses. The sample of the methodological study consisted of 349 nurses. The factor load of the scale was in the appropriate range (0.32-0.79), Cronbach's α was determined as .928, and the item total score correlations ranged between 0.418 and 0.662. The test-retest reliability coefficient was determined to be r = .859. The Turkish version of the NSS was evaluated and it was found that it could be used as a valid and reliable measurement tool in Turkish nurses. Health care service providers can use NSS to determine the work stress of nurses.


Functional or Nonfunctional Cusps Preservation for Molars Restored with Indirect Composite or Glass-Ceramic Onlays: 3D FEA Study.
Evidence regarding the effect of the onlay preparation design for different CAD/CAM restorative materials considering the preservation of cusps is lacking. Molars were 3D-modeled in four preparation designs for onlay restoration: traditional design with functional cusp coverage (TFC), non-retentive design with functional cusp coverage (NFC), traditional design with non-functional cusp coverage (TNFC) and non-retentive design with non-functional cusp coverage (NNFC). The restorations were simulated with two CAD/CAM restorative materials: LD-lithium disilicate (IPS e.max CAD) and RC-resin composite (GrandioBloc). A 100 N axial load was applied to the occlusal surface, simulating the centric contact point. Von Mises (VM) and maximum principal (Pmax) stress were evaluated for restorations, cement layer and dental substrate. The non-retentive preparation design reduced the stress concentration in the tooth structure in comparison to the conventional retentive design. For LD onlays, the stress distribution on the restoration intaglio surface showed that the preparation design, as well as the prepared cusp, influenced the stress magnitude. The non-retentive preparation design provided better load distribution in both restorative materials and more advantageous for molar structure. The resin composite restoration on thenon-functional cusp is recommended when the functional cusp is preserved in order to associate conservative dentistry and low-stress magnitude.


Depression during menopausal transition: a review of treatment strategies and pathophysiological correlates.
It has long been recognized that women are at a higher risk than men to develop depression and that such risk is particularly associated with reproductive cycle events. Recent long-term, prospective studies have demonstrated that the transition to menopause is associated with higher risk for new onset and recurrent depression. A number of biological and environmental factors are independent predictors for depression in this population, including the presence of hot flushes, sleep disturbance, history of severe premenstrual syndrome or postpartum blues, ethnicity, history of stressful life events, past history of depression, body mass index, socioeconomic status and the use of hormones and antidepressants. Accumulated evidence suggests that ovarian hormones modulate serotonin and noradrenaline neurotransmission, a process that may be associated with underlying pathophysiological processes involved in the emergence of depressive symptoms during periods of hormonal fluctuation in biologically predisposed subpopulations. Transdermal estradiol and serotonergic and noradrenergic antidepressants are efficacious in the treatment of depression and vasomotor symptoms in symptomatic, midlife women. The identification of individuals whom might be at a higher risk for depression during menopausal transition could guide preventive strategies for this population.


Differences in movement limitations in different low back pain severity in functional tests using an RGB-D camera.
Low back pain (LBP) can lead to motor control disturbance which can be one of the causes of reoccurrence of the complaint. It is important to improve our knowledge of movement related disturbances during assessment in LBP and to classify patients according to the severity. The aim of this study is to present differences in kinematic variables using a RGB-D camera in order to classify LBP patients with different severity. A cross-sectional study was carried out. Subjects with non-specific subacute and chronic LBP were screened 6 weeks following an episode. Functional tests were bending trunk test, sock test and sit to stand test. Participants performed as many repetitions as possible during 30 s for each functional test. Angular displacement, velocity and acceleration, linear acceleration, time and repetitions were analysed. Participants were divided into two groups to determine their different LBP severity with a k-means clusters according to the results obtained in Roland Morris questionnaire (RMQ). Comparing different severity groups based on RMQ score (high impact = 17.15, low impact = 7.47), bending trunk test obtained significative differences in linear acceleration (p = 0.002-0.01). The differences of total linear acceleration during the Sit to Stand test were significative (p = 0.004-0.02). Sock test showed not significative differences between groups (p > 0.05). Linear acceleration variables during Sit to Stand test and Bending trunk test were significatively different between the different severity groups. RGB-D camera system and functional tests can detect kinematic differences in different type of LBP according to the functionality. Trial registration: ClinicalTrials.gov NCT03293095 "Functional Task Kinematic in Musculoskeletal Pathology" September 26, 2017.


Alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a systematic review of published studies.
Alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) has emerged as a lesser invasive alternative to surgical myectomy over the past decade. The purpose of this study is to analyze all the published literature on outcomes and complications after ASA. MEDLINE and PubMed were searched for all available published literature on ASA (June 1996-June 2005) using the terms hypertrophic obstructive cardiomyopathy (HOCM), alcohol septal ablation for hypertrophic obstructive cardiomyopathy, alcohol septal ablation for HOCM, alcohol septal ablation (ASA), transcoronary alcohol septal ablation for hypertrophic obstructive cardiomyopathy (TASH), transcoronary alcohol septal ablation for HOCM, nonsurgical septal reduction therapy (NSRT), and percutaneous transcoronary septal myocardial ablation (PTSMA). A total of 42 published studies (2,959 patients) were analyzed. Mean age was 53.5 (35.4-72) years with a mean male to female ratio of 1.17. Mean follow-up was 12.7 +/- 0.3 months (1.5-43.2). Absolute ethanol (3 mL) was injected in 1.2 septal perforator arteries. On average, serum CK peaked at 964 units. At 12 months, there was a sustained decrease in resting and provoked LVOT gradient (65.3-15.8 and 125.4-31.5 mmHg, respectively) accompanied by reduction in basal septal diameter (20.9-13.9 mm), improvement in NYHA Class (2.9-1.2), and increase in exercise capacity (325.3-437.5 seconds). Early mortality (within 30 days) was 1.5% (0.0-5.0%) and late mortality (beyond 30 days) was 0.5% (0.0-9.3%). Other complications include ventricular fibrillation (2.2%), LAD dissection (1.8%), complete heart block requiring permanent pacemaker (10.5%), and pericardial effusion (0.6%). A repeat ASA was performed on 6.6% of patients and 1.9% of patients underwent surgical myomectomy with resolution of symptoms. Literature to date suggests that ASA results in acute and intermediate-term favorable clinical and echocardiographic outcomes. A randomized controlled trial is needed to compare ASA and myomectomy in order to determine which technique provides maximal benefit.


Notched Belly Grain 4, a Novel Allele of Dwarf 11, Regulates Grain Shape and Seed Germination in Rice (Oryza sativa L.).
Notched belly grain (NBG) is a type of deformed grain shape that has been associated with inferior appearance and tastes in rice. NBG is coordinated by both environments and genetics. In this study, we report on the first map-based cloning of an NBG gene on chromosome 4, denoted NBG4, which is a novel allele of Dwarf 11 encoding a cytochrome P450 (CYP724B1) involved in brassinosteroid (BR) biosynthesis. A 10-bp deletion in the 7th exon knocked down the level of the NBG4 transcript and shifted the reading frame of the resulting protein. In addition to the dwarf and clustered panicle as previously reported in the allelic mutants, nbg4 grains also displayed retarded germination and NBG due to the physical constraint of deformed hulls caused by abnormal hull elongation. NBG4 is constitutively expressed with the highest level of expression in immature inflorescences. In all, 2294 genes were differentially expressed in nbg4 and wild-type (WT), and evidence is presented that NBG4 regulates OsPPS-2, OsPRA2, OsYUCCA1, sped1-D, and Dwarf that play critical roles in determining plant architecture, panicle development, and seed germination. This study demonstrated that NBG4 is a key node in the brassinosteroid-mediated regulation of rice grain shape.


A multicenter observational survey of management strategies in 442 pregnancies with suspected placenta accreta spectrum.
Management options for women with placenta accreta spectrum (PAS) comprise termination of pregnancy before the viable gestational age, leaving the placenta in situ for subsequent reabsorption of the placenta or delayed hysterectomy, manual removal of placenta after vaginal delivery or during cesarean section, focal resection of the affected uterine wall, and peripartum hysterectomy. The aim of this observational study was to describe actual clinical management and outcomes in PAS in a large international cohort. Data from women in 15 referral centers of the International Society of PAS (IS-PAS) were analyzed and correlated with the clinical classification of the IS-PAS: From Grade 1 (no PAS) to Grade 6 (invasion into pelvic organs other than the bladder). PAS was usually diagnosed antenatally and the operators performing ultrasound rated the likelihood of PAS on a Likert scale of 1 to 10. In total, 442 women were registered in the database. No maternal deaths occurred. Mean blood loss was 2600 mL (range 150-20 000 mL). Placenta previa was present in 375 (84.8%) women and there was a history of a previous cesarean in 329 (74.4%) women. The PAS likelihood score was strongly correlated with the PAS grade (P < .001). The mode of delivery in the majority of women (n = 252, 57.0%) was cesarean hysterectomy, with a repeat laparotomy in 20 (7.9%) due to complications. In 48 women (10.8%), the placenta was intentionally left in situ, of those, 20 (41.7%) had a delayed hysterectomy. In 26 women (5.9%), focal resection was performed. Termination of pregnancy was performed in 9 (2.0%), of whom 5 had fetal abnormalities. The placenta could be removed in 90 women (20.4%) at cesarean, and in 17 (3.9%) after vaginal delivery indicating mild or no PAS. In 34 women (7.7%) with an antenatal diagnosis of PAS, the placenta spontaneously separated (false positives). We found lower blood loss (P < .002) in 2018-2019 compared with 2009-2017, suggesting a positive learning curve. In referral centers, the most common management for severe PAS was cesarean hysterectomy, followed by leaving the placenta in situ and focal resection. Prenatal diagnosis correlated with clinical PAS grade. No maternal deaths occurred.


Ecological Importance of Cross-Feeding of the Intermediate Metabolite 1,2-Propanediol between Bacterial Gut Symbionts.
Cross-feeding based on the metabolite 1,2-propanediol has been proposed to have an important role in the establishment of trophic interactions among gut symbionts, but its ecological importance has not been empirically established. Here, we show that in vitro growth of Lactobacillus reuteri (syn. Limosilactobacillus reuteri) ATCC PTA 6475 is enhanced through 1,2-propanediol produced by Bifidobacterium breve UCC2003 and Escherichia coli MG1655 from the metabolization of fucose and rhamnose, respectively. Work with isogenic mutants showed that the trophic interaction is dependent on the pduCDE operon in L. reuteri, which encodes the ability to use 1,2-propanediol, and the l-fucose permease (fucP) gene in B. breve, which is required for 1,2-propanediol formation from fucose. Experiments in gnotobiotic mice revealed that, although the pduCDE operon bestows a fitness burden on L. reuteri ATCC PTA 6475 in the mouse digestive tract, the ecological performance of the strain was enhanced in the presence of B. breve UCC2003 and the mucus-degrading species Bifidobacterium bifidum The use of the respective pduCDE and fucP mutants of L. reuteri and B. breve in the mouse experiments indicated that the trophic interaction was specifically based on 1,2-propanediol. Overall, our work established the ecological importance of cross-feeding relationships based on 1,2-propanediol for the fitness of a bacterial symbiont in the vertebrate gut.IMPORTANCE Through experiments in gnotobiotic mice that employed isogenic mutants of bacterial strains that produce (Bifidobacterium breve) and utilize (Lactobacillus reuteri) 1,2-propanediol, this study provides mechanistic insight into the ecological ramifications of a trophic interaction between gut symbionts. The findings improve our understanding on how cross-feeding influences the competitive fitness of L. reuteri in the vertebrate gut and revealed a putative selective force that shaped the evolution of the species. The findings are relevant since they provide a basis to design rational microbial-based strategies to modulate gut ecosystems, which could employ mixtures of bacterial strains that establish trophic interactions or a personalized approach based on the ability of a resident microbiota to provide resources for the incoming microbe.


Occupational goals of mothers of children with disabilities: influence of temporal, social, and emotional contexts.
The purpose of this study was to describe the occupational concerns and goals of mothers who care for children with disabilities. Retrospective data collected from 38 mothers of children with disabilities using the Canadian Occupational Performance Measure (COPM) were analyzed qualitatively. Six themes emerged: (I) doing and being alone: taking care of my own health and well-being; (II) doing and being with others: expanding my social life; (III) improving my child's quality of life; (IV) household management: organizing time and resources; (V) balancing work, home, and community responsibilities; and (VI) sharing the workload. Overarching patterns in the data suggested that the occupational performance of mothers of children with disabilities is constrained by time, overlaid by difficult emotions, and involves a desire for increased social contact. Qualitative analysis of data from the COPM may provide insight into contextual factors that affect occupational performance as well as signaling point of entry for therapists to facilitate client-centered occupational goals.


[Orientational, conformational stability and surface potential of immunoglobulins in monomolecular layers].
Orientation, resistance to surface denaturation and surface potential of bovine and horse immunoglobulin G (IgG) and also of pig IgG-antibodies against DNP and DNS groups on the surface of NaCl solutions of various concentrations have been studied by monomolecular layer method. High conformational stability of IgG molecules of all the species was confirmed. At the surface of NaCl solutions with concentrations 0.15--0.5 M immunoglobulins of all species from monolayers consisting of practically non-unfolded molecules with such an orientation, that all the fragments of IgG molecule are located horizontally. Beyond the limits of this native structure stability zone the rate of surface denaturation is directly proportional to NaCl concentration in the solution. The values of surface potentials of all immunoglobulins under study are close to each other and change little with the surface denaturation.


Molecular dynamics simulations of protein folding from the transition state.
Putative transition-state ensemble (TSE) conformations of src SH3 were identified by monitoring the deviation from the experimental phi values along molecular dynamics (MD) simulations of unfolding. Sixty MD trajectories (for a total of about 7 micros) were then started from the putative TSE. About one-half of the 60 runs reached the folded state while unfolding was observed in the remaining half of the runs. This result validates phi-value analysis as an approach to obtain structural information on the transition state. It also demonstrates that an atomic resolution description of the TSE can be extracted from MD simulations. All conformations in the TSE have the central three-stranded beta-sheet formed in agreement with experimental data. An elongation of strand beta 2 as well as non-native side-chain interactions between the diverging turn and the distal hairpin are observed. The simulation results indicate that the tight packing of the side chains between the diverging turn and the distal hairpin is a necessary condition for rapid folding. Contacts between residues in the most structured element of the TSE, the central beta-sheet, are kinetically more important than those between the N- and C-terminal strands.


Mechanisms of electron-transfer oxidation of NADH analogues and chemiluminescence. Detection of the keto and enol radical cations.
The radical cation of an NADH analogue (BNAH: 1-benzyl-1,4-dihydronicotinamide) has been successfully detected as the transient absorption and ESR spectra in the thermal electron transfer from BNAH to Fe(bpy)(3)(3+) (bpy = 2,2'-bipyridine) and Ru(bpy)(3)(3+). The ESR spectra of the radical cations of BNAH and the dideuterated compound (BNAH-4,4'-d(2)) indicate that the observed radical cation is the keto form rather than the enol form in the tautomerization. The deprotonation rate and the kinetic isotope effects of the keto form of BNAH(*)(+) were determined from the kinetic analysis of the electron-transfer reactions. In the case of electron transfer from BNAH to Ru(bpy)(3)(3+), the chemiluminescence due to Ru(bpy)(3)(2+) was observed in the second electron-transfer step from BNA(*), produced by the deprotonation of the keto form of BNAH(*)(+), to Ru(bpy)(3)(3+). The observation of chemiluminescence due to Ru(bpy)(3)(2+) provides compelling evidence that the Marcus inverted region is observed even for such an intermolecular electron-transfer reaction. When BNAH is replaced by 4-tert-butylated BNAH (4-t-BuBNAH), no chemiluminescence due to Ru(bpy)(3)(2+) has been observed in the electron transfer from 4-t-BuBNAH to Ru(bpy)(3)(3+). This is ascribed to the facile C-C bond cleavage in 4-t-BuBNAH(*)(+). In the laser flash photolysis of a deaerated MeCN solution of BNAH and CHBr(3), the transient absorption spectrum of the enol form of BNAH(*)(+) was detected instead of the keto form of BNAH(*)(+), and the enol form was tautomerized to the keto form. The rate of intramolecular proton transfer in the enol form to produce the keto form of BNAH(*)(+) was determined from the decay of the absorption band due to the enol form and the rise in the absorption band due to the keto form. The kinetic isotope effects were observed for the intramolecular proton-transfer process in the keto form to produce the enol form.


Moderate red wine consumption and cardiovascular disease risk: beyond the "French paradox".
The term FRENCH PARADOX was coined in 1992 to describe the relatively low incidence of cardiovascular disease in the French population, despite a relatively high dietary intake of saturated fats, and potentially attributable to the consumption of red wine. After nearly 20 years, several studies have investigated the fascinating, overwhelmingly positive biological and clinical associations of red wine consumption with cardiovascular disease and mortality. Light to moderate intake of red wine produces a kaleidoscope of potentially beneficial effects that target all phases of the atherosclerotic process, from atherogenesis (early plaque development and growth) to vessel occlusion (flow-mediated dilatation, thrombosis). Such beneficial effects involve cellular signaling mechanisms, interactions at the genomic level, and biochemical modifications of cellular and plasma components. Red wine components, especially alcohol, resveratrol, and other polyphenolic compounds, may decrease oxidative stress, enhance cholesterol efflux from vessel walls (mainly by increasing levels of high-density lipoprotein cholesterol), and inhibit lipoproteins oxidation, macrophage cholesterol accumulation, and foam-cell formation. These components may also increase nitric oxide bioavailability, thereby antagonizing the development of endothelial dysfunction, decrease blood viscosity, improve insulin sensitivity, counteract platelet hyperactivity, inhibit platelet adhesion to fibrinogen-coated surfaces, and decrease plasma levels of von Willebrand factor, fibrinogen, and coagulation factor VII. Light to moderate red wine consumption is also associated with a favorable genetic modulation of fibrinolytic proteins, ultimately increasing the surface-localized endothelial cell fibrinolysis. Overall, therefore, the "French paradox" may have its basis within a milieu containing several key molecules, so that favorable cardiovascular benefits might be primarily attributable to combined, additive, or perhaps synergistic effects of alcohol and other wine components on atherogenesis, coagulation, and fibrinolysis. Conversely, chronic heavy alcohol consumption and binge drinking are associated with increased risk of cardiovascular events. In conclusion, although mounting evidence strongly supports beneficial cardiovascular effects of moderate red wine consumption (one to two drinks per day; 10-30 g alcohol) in most populations, clinical advice to abstainers to initiate daily alcohol consumption has not yet been substantiated in the literature and must be considered with caution on an individual basis.


Halogen bonding, chalcogen bonding, pnictogen bonding, tetrel bonding: origins, current status and discussion.
The role of the closing lecture in a Faraday Discussion is to summarise the contributions made to the Discussion over the course of the meeting and in so doing capture the main themes that have arisen. This article is based upon my Closing Remarks Lecture at the 203rd Faraday Discussion meeting on Halogen Bonding in Supramolecular and Solid State Chemistry, held in Ottawa, Canada, on 10-12th July, 2017. The Discussion included papers on fundamentals and applications of halogen bonding in the solid state and solution phase. Analogous interactions involving main group elements outside group 17 were also examined. In the closing lecture and in this article these contributions have been grouped into the four themes: (a) fundamentals, (b) beyond the halogen bond, (c) characterisation, and (d) applications. The lecture and paper also include a short reflection on past work that has a bearing on the Discussion.


Itraconazole in chronic cavitary pulmonary aspergillosis: a randomised controlled trial and systematic review of literature.
Patients with aspergilloma can be safely managed with supportive therapy in absence of massive haemoptysis. We hypothesised that chronic cavitary pulmonary aspergillosis (CCPA) could also be managed on similar grounds. The aim of this prospective, randomised controlled trial was to evaluate the efficacy and safety of itraconazole in CCPA. Consecutive patients of CCPA with presence of chronic pulmonary/systemic symptoms; and pulmonary cavities; and presence of Aspergillus (immunological or microbiological) were randomised to receive either supportive treatment alone or itraconazole 400 mg daily for 6 months plus supportive therapy. Response was assessed clinically, radiologically and overall after 6 months therapy. A total of 31 patients (mean age, 37 years) were randomised to itraconazole (n = 17) or the control (n = 14) group. The number of patients showing overall response was significantly higher in the itraconazole group (76.5%) vs. the control (35.7%) group (P = 0.02). The numbers of patients demonstrating clinical or radiological response were also significantly higher in the itraconazole group (P = 0.016 and 0.01 respectively). Adverse events were noted in eight patients in the itraconazole group, however, none was serious or led to discontinuation of the study drug. Itraconazole was found to be superior to standard supportive treatment alone in stabilising cases of CCPA. (clinicaltrials.gov; NCT01259336).


Off-axis holographic laser speckle contrast imaging of blood vessels in tissues.
Laser speckle contrast imaging (LSCI) has become one of the most common tools for functional imaging in tissues. Incomplete theoretical description and sophisticated interpretation of measurement results are completely sidelined by a low-cost and simple hardware, fastness, consistent results, and repeatability. In addition to the relatively low measuring volume with around 700 ?? ? m of the probing depth for the visible spectral range of illumination, there is no depth selectivity in conventional LSCI configuration; furthermore, in a case of high NA objective, the actual penetration depth of light in tissues is greater than depth of field (DOF) of an imaging system. Thus, the information about these out-of-focus regions persists in the recorded frames but cannot be retrieved due to intensity-based registration method. We propose a simple modification of LSCI system based on the off-axis holography to introduce after-registration refocusing ability to overcome both depth-selectivity and DOF problems as well as to get the potential possibility of producing a cross-section view of the specimen.


Role of HRB in clathrin-dependent endocytosis.
Human immunodeficiency virus Rev-binding protein (HRB), also called human Rev-interacting protein (hRIP) or Rev/Rex activation domain binding (RAB) is a partner of the tyrosine kinase substrate EPS15, and it has been recovered in the AP-2 interactome. EPS15 and AP-2 are involved in endocytosis, but the function of HRB in this process is still unknown. Here we identified HRB as a partner of the vesicular SNARE tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP, also called VAMP7) in yeast two-hybrid screens and using biochemical assays. In HeLa cells, HRB localized both in the nucleus and in the cytoplasm. In the cytoplasm, HRB colocalized with clathrin-, AP-2-, EPS15-, and transferrin receptor-containing vesicles. We did not see significant colocalization between HRB and TI-VAMP in HeLa cells, and we saw partial colocalization with green fluorescent protein-TI-VAMP in stably expressing Madin-Darby canine kidney cells. Nevertheless using a pHLuorin-tagged TI-VAMP construct, we found that HRB and TI-VAMP colocalize close to the plasma membrane after 5 min of anti-green fluorescent protein antibody uptake. These results suggest that TI-VAMP and HRB may interact only during the early stages of endocytosis. Furthermore uptake experiments followed by fluorescence-activated cell sorting showed that the endocytosis of fluorescent transferrin and pHLuorin-TI-VAMP is strongly reduced in HRB knockdown cells. Altogether these results suggest that HRB is involved in clathrin-dependent endocytosis and recruits TI-VAMP in this process.


SPECT/CT evaluation of unusual physiologic radioiodine biodistributions: pearls and pitfalls in image interpretation.
Radioiodine imaging has a well-established role in depicting metastatic disease after thyroidectomy in patients with well-differentiated thyroid cancer. Uptake of radioiodine in thyroid metastases depends on expression of sodium-iodide symporter (NIS) by tumor tissues. However, because radioiodine may also accumulate in normal structures and tissues, it is important to distinguish physiologic radioiodine activity from metastatic disease. Furthermore, secretions that contain radioiodine may also simulate pathologic uptake. A spectrum of physiologic distributions, normal variants, and benign mimics of disease have been described in the literature; yet, even when armed with a comprehensive knowledge of these patterns, interpreting radiologists and nuclear physicians may still encounter diagnostic uncertainty. Single-photon emission computed tomography (SPECT) with integrated computed tomography (CT) is a novel technology that, when applied to diagnostic iodine 123 or iodine 131 ((131)I) radioiodine scintigraphy, may accurately localize and help distinguish benign mimics of disease, with the potential to alter the management plan. SPECT/CT is increasingly being used with radioiodine scintigraphy to evaluate patients with thyroid cancer and shows promise for improving imaging specificity and reducing false-positive results.


[Endoscopic surgery in neoplasms of the upper digestive tract].
Endoscopic surgery has been performed since 1987 when in France the first laparoscopic cholecystectomy was done. Since then it has evolved and found a place in surgical practice. In the field of surgical oncology it has allowed the diagnosis, staging, resection and palliation of a great variety of neoplasms. evaluate usefulness and recent advances of endoscopic surgery in neoplasms of the upper digestive tract, applied specifically to the esophagus and stomach. We did a review of the medical literature using Medline data base (Pubmed). All series of cases, cohort and controlled studies published between January 1995 and April 2003 were included. For esophageal carcinoma as well as for gastric carcinoma, endoscopic surgery is used as a complement for computed tomography and endoscopic ultrasound to define clinical stage, increasing sensibility to detect metastatic disease. Techniques of endoscopic or video assisted esophageal transhiatal and thoracoscopic resection have been described, as well as Japanese studies including radical gastric resections in early gastric cancer with multiple advantages. There are also several developing possibilities of palliative endoscopic or video assisted treatment which are discussed in this article. Usefulness of endoscopic surgery in staging gastric and esophageal carcinoma is proven. Nevertheless oncologic endoscopic resections are still experimental and the advantages between these and open surgery are still to be shown with prospective randomized trials.


Classification of transmission risk in the national HIV/AIDS surveillance system.
Risk behavior information is essential for allocating resources and developing effective HIV prevention strategies. Over time, transmission risk information on HIV/AIDS cases has been less likely to be reported to the national surveillance system. The Centers for Disease Control and Prevention (CDC) invited approximately 30 experts in HIV/AIDS and behavioral research from state and local health departments, academia, community-based organizations, and the CDC to participate in a consultation in December 2001 to generate ideas on how best to deal with the lack of risk data. The group was charged with providing recommendations on methods for classifying and reporting risk information and for identifying methods and sources for improving ascertainment of transmission risk behaviors for individuals infected with HIV. This report describes the recommendations and the effects of implementing such recommended procedures on the national HIV/AIDS surveillance database.


Distinct mechanisms of alpha 5beta 1 integrin activation by Ha-Ras and R-Ras.
To investigate the possible roles of the Ras/Rho family members in the inside-out signals to activate integrins, we examined the ability of Ras/Rho small GTPases to stimulate avidity of alpha(5)beta(1) (VLA-5) to fibronectin in bone marrow-derived mast cells. We found that both Ha-Ras(Val-12) and R-Ras(Val-38) had strong stimulatory effects on adhesion and ligand binding activity of VLA-5 to fibronectin. However, only Ha-Ras(Val-12)-, but not R-Ras(Val-38)-induced adhesion was inhibited by wortmannin, which suggests that Ha-Ras(Val-12) is dependent on phosphatidylinositol (PI) 3-kinase on adhesion whereas R-Ras(Val-38) has another PI 3-kinase independent pathway to induce adhesion. The effector loop mutant Ha-Ras(Val-12)E37G, but not Y40C retained the ability to stimulate adhesion of mast cells to fibronectin. Consistently, PI 3-kinase p110delta, predominantly expressed in mast cells, interacted with Ha-Ras(Val-12) E37G, but not Y40C, which was also correlated with the levels of Akt phosphorylation in mast cells. Furthermore, marked adhesion was induced by a membrane-targeted version of p110delta. These results indicate that Ha-Ras(Val-12) activated VLA-5 through PI 3-kinase p110delta. The mutational effects of the R-Ras effector loop region on adhesion were not correlated with PI 3-kinase activities, consistent with our contention that R-Ras has a distinct pathway to modulate avidity of VLA-5.


Affinity purification and characterization of a G-protein coupled receptor, Saccharomyces cerevisiae Ste2p.
We present an example of expression and purification of a biologically active G-protein coupled receptor (GPCR) from yeast. An expression vector was constructed to encode the Saccharomyces cerevisiae GPCR alpha-factor receptor (Ste2p, the STE2 gene product) containing a 9-amino acid sequence of rhodopsin that served as an epitope/affinity tag. In the construct, two glycosylation sites and two cysteine residues were removed to aid future structural and functional studies. The receptor was expressed in yeast cells and was detected as a single band in a western blot indicating the absence of glycosylation. Ligand binding and signaling assays of the epitope-tagged, mutated receptor showed it maintained the full wild-type biological activity. For extraction of Ste2p, yeast membranes were solubilized with 0.5% n-dodecyl maltoside (DM). Approximately 120 microg of purified alpha-factor receptor was obtained per liter of culture by single-step affinity chromatography using a monoclonal antibody to the rhodopsin epitope. The binding affinity (K(d)) of the purified alpha-factor receptor in DM micelles was 28 nM as compared to K(d)=12.7 nM for Ste2p in cell membranes, and approximately 40% of the purified receptor was correctly folded as judged by ligand saturation binding. About 50% of the receptor sequence was retrieved from MALDI-TOF and nanospray mass spectrometry after CNBr digestion of the purified receptor. The methods described will enable structural studies of the alpha-factor receptor and may provide an efficient technique to purify other GPCRs that have been functionally expressed in yeast.