Serotyping of Haemophilus pleuropneumoniae by rapid slide agglutination and indirect fluorescent antibody tests in swine.
One hundred and forty-one isolates of Haemophilus pleuropneumoniae from Iowa and Illinois swine were characterized morphologically and biochemically and serotyped by rapid slide agglutination (RSA) and indirect fluorescent antibody (IFA) tests. Hyperimmune antisera were produced in rabbits using inactivated whole-cell suspensions of the reference strains for H pleuropneumoniae serotypes 1 to 7 and strain 202, representing the taxon "minor group." Cross testing of the reference strains and reference antisera indicated the antisera to be essentially serotype-specific, although reactivity of some antisera with heterologous strains was observed. Cultures of the 141 isolates formed adherent or smooth colonies or mixtures of these colony forms. Adherent and smooth colony types were found in all serotypes identified. Microscopic and biochemical characteristics of all isolates were typical of those previously described for H pleuropneumoniae. The overall incidence of H pleuropneumoniae serotypes was serotype 5, 55.3%; serotype 1, 34.0%; serotype 7, 7.8%; and nontypeable, 2.8%. Comparing the 2 test procedures, 87.2% of the isolates could be typed by RSA, and 66.0% could be typed by IFA. Cross-reactions between serotype 4 antisera and serotype 5 and 7 isolates were common with the IFA test. The reactions with serotype 7, but not serotype 5, were eliminated by cross adsorption of serotype 4 antisera. There was good correlation between the 2 test procedures, but RSA was judged to be more specific and sensitive than IFA.


Effects of silage protein degradability and fermentation acids on metabolizable protein concentration: a meta-analysis of dairy cow production experiments.
A meta-analysis was conducted using data from dairy cow production studies to evaluate silage metabolizable protein (MP) concentrations. The data consisted of 397 treatment means in 130 comparisons, in which the effects of silage factors (e.g., date of harvest, wilting, silage additives) were investigated. Within a comparison, a fixed amount of the same concentrate was fed. A prerequisite of data to be included in the analysis was that silage dry matter (DM), crude protein (CP), ammonia N, lactic acid (LA), and total acid (TA) concentrations and digestibility were determined. A smaller data set (n = 248) comprised studies in which silage water-soluble N concentration was also analyzed. The supply of MP was estimated as amino acids absorbed from the small intestine using a model with constant values for ruminal effective protein degradability (EPD) and intestinal digestibility of rumen undegraded protein. Microbial protein was calculated on the basis of digestible carbohydrates and rumen degradable protein (RDP). Alternative models were used to estimate microbial protein formation, assuming the energy values of RDP and TA to be equivalent to 1.00, 0.75, 0.50, 0.25, and 0 times that of digestible carbohydrates. Because EPD values are seldom determined in production trials, they were derived using empirical models that estimate them from other feed components. The goodness of fit of models was compared on the basis of root mean squared error (RMSE) of milk protein yield (MPY) predicted from MP supply (adjusted for random study effect) and Akaike's information criterion. Metabolizable protein supply calculated from basal assumptions predicted MPY precisely within a study (RMSE = 16.2 g/d). Variable contribution of RDP to the energy supply for microbial synthesis influenced the precision of MPY prediction very little, but RMSE for MPY increased markedly when the energy supply of rumen microbes was corrected for TA concentration. Using predicted rather than constant EPD values also increased RMSE of MPY prediction. These observations do not mean that the supply of MP from undegraded feed protein is constant. However, it suggests that our current methods overestimate the range in EPD values and that the techniques have so many inherent technical problems that they can mask the true differences between the feeds. Including new elements in feed protein evaluation models may not improve the precision of production response predictions unless the consequent effects on the supply of other nutrients are taken into account.


Building the Powerhouse: What are the Signals Involved in Plant Mitochondrial Biogenesis?
With a central role in respiration and ATP production, regulation of mitochondrial form and function is essential for cell and organism survival. Our understanding of the molecular mechanisms and signaling events underlying plant mitochondrial biogenesis is limited. In a recent paper published in the Journal of Biological Chemistry we have demonstrated aspects of mitochondrial biogenesis that are dependent on an oxygen signal in the monocot model, rice. Specifically, we identified (1) a set of genes encoding mitochondrial components that are responsive to oxygen levels and (2) that a lack of oxygen represses the normal increase in the mitochondrial protein import capacity during germination, and that these changes culminate in a modified mitochondrial proteome and altered respiratory activity. These findings can be combined with an earlier study, which gave insights into the characteristics of promitochondrial structures found in dry seeds and how they change during the germination process. Together they provide evidence for regulation of mitochondrial biogenesis by developmental and environmental cues and transcriptional and post-transcriptional events. This information can be used to build a model of plant mitochondrial biogenesis within the context of seed germination and oxygen availability.


The evolutionary pathways for local adaptation in mountain hares.
Understanding the evolution of local adaptations is a central aim of evolutionary biology and key for the identification of unique populations and lineages of conservation relevance. By combining RAD sequencing and whole-genome sequencing, we identify genetic signatures of local adaptation in mountain hares (Lepus timidus) from isolated and distinctive habitats of its wide distribution: Ireland, the Alps and Fennoscandia. Demographic modelling suggested that the split of these mountain hares occurred around 20 thousand years ago, providing the opportunity to study adaptive evolution over a short timescale. Using genome-wide scans, we identified signatures of extreme differentiation among hares from distinct geographic areas that overlap with area-specific selective sweeps, suggesting targets for local adaptation. Several identified candidate genes are associated with traits related to the uniqueness of the different environments inhabited by the three groups of mountain hares, including coat colour, ability to live at high altitudes and variation in body size. In Irish mountain hares, a variant of ASIP, a gene previously implicated in introgression-driven winter coat colour variation in mountain and snowshoe hares (L. americanus), may underlie brown winter coats, reinforcing the repeated nature of evolution at ASIP moulding adaptive seasonal colouration. Comparative genomic analyses across several hare species suggested that mountain hares' adaptive variants appear predominantly species-specific. However, using coalescent simulations, we also show instances where the candidate adaptive variants have been introduced via introgressive hybridization. Our study shows that standing adaptive variation, including that introgressed from other species, was a crucial component of the post-glacial dynamics of species.


Current practices of physiotherapists in Switzerland regarding fall risk-assessment for community-dwelling older adults: A national cross-sectional survey.
Falls can strongly impact older people's quality of life, health, and lifestyle. Multifactorial assessment can determine an individual's risk of falling as the first step for fall prevention intervention. Physiotherapists have an essential role to play in assessing fall risk by older adults living in the community. In the absence of published data on this topic in Switzerland, this study investigated the current practices of physiotherapists to determine whether those are in line with recommendations. An anonymous cross-sectional survey was undertaken among physiotherapists practising in Switzerland between the 21st of November and the 31st of December 2020. A priori and exploratory hypotheses were tested. Responses to open-ended questions were grouped into themes for analysis. A total of 938 questionnaires from all three language regions of Switzerland was analysed. Participants worked in different settings, with a higher representation of private practice self-employees (56%). Standardised fall risk assessments or instruments were used by 580 (62%) participants, while 235 (25%) preferred subjective assessment of fall risk only. Differences in fall risk assessment were observed according to the workplace setting (adjusted OR 1.93, 95% CI 1.37 to 2.7) and education level (trend test, p<0.001). The standardised assessments most frequently employed were the Berg Balance Scale (58%), the Timed-Up-and-Go (57%) and the Tinetti Balance Assessment tool (47%). Risk factors for falls were frequently queried, particularly history of falls (88%), home hazards (84%), and functional ability (81%). Technical resources (40%), knowledge (30%), and time (22%) were common barriers to implement a systematic fall risk assessment. This study provides an overview of the current practices of physiotherapists in Switzerland in fall risk assessment. There is still room to optimise the standardisation and systematisation of this assessment to implement a best practice strategy and prevent avoidable falls.


Constraints of tolerance: why are desiccation-tolerant organisms so small or rare?
Drying to equilibrium with the air kills nearly all animals and flowering plants, including livestock and crops. This makes drought a key ecological problem for terrestrial life and a major cause of human famine. However, the ability to tolerate complete desiccation is widespread in organisms that are either <5 mm long or found mainly where desiccation-sensitive organisms are scarce. This suggests that there is a trade-off between desiccation tolerance and growth. Recent molecular and biochemical research shows that organisms tolerate desiccation through a set of mechanisms, including sugars that replace water and form glasses, proteins that stabilize macromolecules and membranes, and anti-oxidants that counter damage by reactive oxygen species. These protections are often induced by drying, and some of the genes involved may be homologous in microbes, plants and animals. Understanding how mechanisms of desiccation tolerance may constrain growth might show how to undo the constraint in some economically important macroorganisms and elucidate the much-studied but elusive relationship between tolerance of stress and productivity.


Use of colposcopically directed, four-quadrant cervical biopsy by the colposcopy trainee.
Colposcopically directed cervical biopsies performed by experienced colposcopists have greatly reduced the need for conization of the cervix to evaluate patients with cervical intraepithelial neoplasia (CIN). Because of the subjectivity of the colposcopic technique and variable time required to become skilled, continued reliance on cervical conization is often recommended to validate colposcopic findings for novice colposcopists . We assessed the colposcopic skill of residents in training in obstetrics and gynecology who had received 9-12 months of instruction in colposcopic techniques. Biopsies of each quadrant of the ectocervix were done after the resident recorded his or her colposcopic diagnosis. In 26% of the patients there was overestimation or underestimation of the histologic findings by more than one grade in the cervical quadrant suspected on colposcopy to contain the most advanced CIN lesion. In 30% of patients the histologically most advanced CIN lesion was not identified by the colposcopist . In 11% of patients with histologic findings of CIN both cytology and colposcopy were negative. Only 69% of the histologically confirmed lesions were diagnosed colposcopically by the resident colposcopists . The four-quadrant, colposcopically directed biospy technique is recommended as an effective training method for the beginning colposcopist .


Controllable high-performance liquid marble micromixer.
A liquid marble is a liquid droplet coated with a shell of microparticles. Liquid marbles have served as a unique microreactor for chemical reactions and cell culture. Mixing is an essential task for liquid marbles as a microreactor. However, the potential of liquid marble-based microreactors is significantly limited due to the lack of effective mixing strategies. Most mixing strategies used manual and contact-based actuation schemes. This paper reports the development of a manipulation scheme that induces fluid motion into a liquid marble, leading to enhanced mixing. By inducing rotation on a horizontal axis, we significantly increased the mixing rate by 27.6 times compared to a non-actuated liquid marble and reduced the reaction time by more than 10 times. The proposed method provides a simple, continuous, precise, and controllable high-performance mixing strategy on a liquid marble platform.


Evolutionary shifts in habitat aridity predict evaporative water loss across squamate reptiles.
Aridity is an important determinant of species distributions, shaping both ecological and evolutionary diversity. Lizards and snakes are often abundant in deserts, suggesting a high potential for adaptation or acclimation to arid habitats. However, phylogenetic evidence indicates that squamate diversity in deserts may be more strongly tied to speciation within arid habitats than to convergent evolution following repeated colonization from mesic habitats. To assess the frequency of evolutionary transitions in habitat aridity while simultaneously testing for associated changes in water-balance physiology, we analyzed estimates of total evaporative water loss (EWL) for 120 squamate species inhabiting arid, semiarid, or mesic habitats. Phylogenetic reconstructions revealed that evolutionary transitions to and from semiarid habitats were much more common than those between arid and mesic extremes. Species from mesic habitats exhibited significantly higher EWL than those from arid habitats, while species from semiarid habitats had intermediate EWL. Phylogenetic comparative methods confirmed this association between habitat aridity and EWL despite phylogenetic signal in each. Thus, the historical colonization of arid habitats by squamates is repeatedly associated with adaptive changes in EWL. This physiological convergence, which may reflect both phenotypic plasticity and genetic adaptation, has likely contributed to the success of squamates in arid environments.


rpS6 regulates blood-testis barrier dynamics through Akt-mediated effects on MMP-9.
Mammalian target of rapamycin complex 1 (mTORC1) is an emerging regulator of blood-tissue barriers that utilizes ribosomal protein S6 (rpS6) as the downstream signaling molecule. To explore the role of rpS6 in blood-testis barrier (BTB) function, a constitutively active quadruple rpS6 phosphomimetic mutant was constructed in mammalian expression vector and overexpressed in Sertoli cells cultured in vitro that mimicked the BTB in vivo. Using this quadruple phosphomimetic mutant, phosphorylated (p)-rpS6 was shown to disrupt IGF-1/insulin signaling, thereby abolishing Akt phosphorylation, which led to an induction of MMP-9. This increase in MMP-9 secretion perturbed the Sertoli cell tight junction permeability barrier by proteolysis-mediated downregulation of tight junction proteins at the BTB. These findings were confirmed by the use of a specific MMP-9 inhibitor that blocked the disruption of the tight junction permeability barrier by the rpS6 mutant. Additionally, RNA interference (RNAi)-mediated Akt silencing was able to mimic the results of rpS6 mutant overexpression in Sertoli cells, further confirming this p-rpS6-Akt-MMP-9 signaling pathway. In conclusion, these data support a new concept of mTORC1-mediated BTB regulation, that is possibly also applicable to other blood-tissue barriers.


Nonlinear mode-coupling for passive mode-locking: application of waveguide arrays, dual-core fibers, and/or fiber arrays.
A detailed analysis of mode-locking is presented in which the nonlinear mode-coupling behavior in a waveguide array, dual-core fiber, and/or fiber array is used to achieve stable and robust passive modelocking. By using the discrete, nearest-neighbor spatial coupling of these nonlinear mode-coupling devices, low-intensity light can be transferred to the neighboring waveguides and ejected (attenuated) from the laser cavity. In contrast, higher intensity light is self-focused in the launch waveguide and remains largely unaffected. This nonlinear effect, which is a discrete Kerr lens effect, leads to the temporal intensity discrimination required in the laser cavity for mode-locking. Numerical studies of this pulse shaping mechanism show that using current waveguide arrays, fiber-arrays, or dual-core fibers in conjunction with standard optical fiber technology, stable and robustmode-locked soliton-like pulses are produced.


Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP).
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling genetic disorder of progressive heterotopic ossification (HO). The single-arm, open-label, phase 3 MOVE trial (NCT03312634) assessed efficacy and safety of palovarotene, a selective retinoic acid receptor gamma agonist, in patients with FOP. Findings were compared with FOP natural history study (NHS; NCT02322255) participants untreated beyond standard of care. Patients aged ≥4 years received palovarotene once daily (chronic: 5 mg; flare-up: 20 mg for 4 weeks, then 10 mg for ≥8 weeks; weight-adjusted if skeletally immature). The primary endpoint was annualized change in new HO volume versus NHS participants (by low-dose whole-body computed tomography [WBCT]), analyzed using a Bayesian compound Poisson model (BcPM) with square-root transformation. Twelve-month interim analyses met futility criteria; dosing was paused. An independent Data Monitoring Committee recommended trial continuation. Post hoc 18-month interim analyses utilized BcPM with square-root transformation and HO data collapsed to equalize MOVE and NHS visit schedules, BcPM without transformation, and weighted linear mixed-effects (wLME) models, alongside prespecified analysis. Safety was assessed throughout. Eighteen-month interim analyses included 97 MOVE and 101 NHS individuals with post-baseline WBCT. BcPM analyses without transformation showed 99.4% probability of any reduction in new HO with palovarotene versus NHS participants (with transformation: 65.4%). Mean annualized new HO volume was 60% lower in MOVE versus the NHS. wLME results were similar (54% reduction fitted; nominal p = 0.039). All palovarotene-treated patients reported ≥1 adverse event (AE); 97.0% reported ≥1 retinoid-associated AE; 29.3% reported ≥1 serious AE, including premature physeal closure (PPC)/epiphyseal disorder in 21/57 (36.8%) patients aged <14 years. Post hoc computational analyses using WBCT showed decreased vertebral bone mineral density, content, and strength, and increased vertebral fracture risk in palovarotene-treated patients. Thus, post hoc analyses showed evidence for efficacy of palovarotene in reducing new HO in FOP, but high risk of PPC in skeletally immature patients. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Brief measure for screening complicated grief: reliability and discriminant validity.
Complicated grief, which is often under-recognized and under-treated, can lead to substantial impairment in functioning. The Brief Grief Questionnaire (BGQ) is a 5-item self-report or interview instrument for screening complicated grief. Although investigations with help-seeking samples suggest that the BGQ is valid and reliable, it has not been validated in a broader population. A questionnaire was mailed to a randomly selected sample (n = 5000) residing in one of 4 areas of Japan. The BCQ was examined for responders who were bereaved more than 6 months and less than 10 years (n = 915). Non-specific psychological distress was assessed with the K6 screening scale. Multiple group confirmatory factor analysis supported a uni-dimensional factor structure and the invariance of parameters across gender and age. Cronbach's alpha was sufficiently high (alpha = .75) to confirm internal consistency. Average Variance Extracted (0.39) was higher than the shared covariance (0.14) between BGQ and K6, suggesting discriminant validity. The results of this study support the reliability and validity of the BGQ in the Japanese population. Future studies should examine predictive validity by using structured interviews or more detailed scales for complicated grief.


[Potential hazard of zoonotic parasites present in canine feces in Puerto Escondido, Oaxaca].
To estimate the zoonotic parasites prevalence in feral dog feces in Puerto Escondido. The fecalism frecuency was estimated in ten zones. To identify the parasites parasitological flotation and direct smear methods were used. The parasitic prevalence was estimated in the canine feces. All the zones presented canine fecalism. The parasitic prevalence in the feces was 73.33%. The parasites with the highest prevalence were Toxocara canis (47.78%), Ancylostoma caninum (17.88%), and Dipylidium caninum (13.89%). Canine fecalism comes from strayed and owned dogs. 66.66% of the parasites found in the dog feces are zoonotics. The factors associated to this problem are the suburban habitat, waste mishandling and nil tenure of stray dogs.


Random networks of single-walled carbon nanotubes promote mesenchymal stem cell's proliferation and differentiation.
Studies on the interaction of cells with single-walled carbon nanotubes (SWCNTs) have been receiving increasing attention owing to their potential for various cellular applications. In this report, we investigated the interactions between biological cells and nanostructured SWCNTs films and focused on how morphological structures of SWCNT films affected cellular behavior such as cell proliferation and differentiation. One directionally aligned SWCNT Langmuir-Blodgett (LB) film and random network SWCNT film were fabricated by LB and vacuum filteration methods, respectively. We demonstrate that our SWCNT LB and network film based scaffolds do not show any cytotoxicity, while on the other hand, these scaffolds promote differentiation property of rat mesenchymal stem cells (rMSCs) when compared with that on conventional tissue culture polystyrene substrates. Especially, the SWCNT network film with average thickness and roughness values of 95 ± 5 and 9.81 nm, respectively, demonstrated faster growth rate and higher cell thickness for rMSCs. These results suggest that systematic manipulation of the thickness, roughness, and directional alignment of SWCNT films would provide the convenient strategy for controlling the growth and maintenance of the differentiation property of stem cells. The SWCNT film could be an alternative culture substrate for various stem cells, which often require close control of the growth and differentiation properties.


Advances in efficient extraction of essential oils from spices and its application in food industry: A critical review.
With the increase of people's awareness of food safety, it is crucial to find natural and green antimicrobial agents to replace traditional antimicrobial agents. Essential oils of spices (SEOs) are low toxicity or nontoxic, which exhibited antioxidants and antimicrobial activity according to many in vitro and in situ experiments. Spices are widely available and low cost as a plant raw material for the extraction of SEOs. This review summarized highly efficient extraction techniques for SEOs, such as physical field assisted extraction technology, supercritical fluid extraction, and biological-based techniques. Furthermore, purification of SEOs and components were also recapitulated. Purification techniques of SEOs improve their utilization value due to the increased content of bioactive components. Finally, the review concentrated on the applications of SEOs in food industry, including food preservation, food active packaging by means of films or coatings, antioxidant properties. In addition, addressing the problem of unstability of SEOs and its role to inhibit the pathogenic bacteria, the encapsulation of SEOs for use in the food industrial sectors reduces the safety risk to human health.


Efficacy of a 1 day Rifaximin and Metronidazole Regimen and Mechanical Bowel Preparation for Preventing Surgical Site Infection in Minimally Invasive Colorectal Cancer Surgery: A Prospective Observational Study.
A combination of oral antibiotics and mechanical bowel preparation is recommended for patients scheduled to undergo elective colorectal surgery on the basis of recent large trials that have reported the superiority of this approach in preventing surgical site infections (SSIs). However, there are no standard recommendations for this approach. Therefore, in this study, we evaluated the efficacy of rifaximin and metronidazole and mechanical bowel preparation for preventing SSIs in cases of minimally invasive surgery for colorectal cancer. This single-arm prospective observational study included 256 individuals. The primary end point was the rate of SSI. Rifaximin 400 mg and metronidazole 500 mg were administered twice daily (10 am and 10 pm), and mechanical bowel preparation was administered the day before the operation. After excluding 15 patients, 241 were enrolled. No adverse event occurred following the administration of oral antibiotics and mechanical bowel preparation; there was 100% compliance. The total SSI rate was 2.9%; the rates of incisional and organ/space SSIs were 1.2% and 1.7%, respectively. All patients were treated conservatively. Univariate analyses revealed preoperative anemia, hypoalbuminemia, and transfusion and postoperative transfusion were significantly associated with SSIs. A 1 day rifaximin and metronidazole regimen with mechanical bowel preparation for elective minimally invasive surgery for colorectal cancer was associated with a favorable SSI rate of 2.9%, safety, and high compliance. This approach is appropriate for inclusion in the current guidelines for perioperative management of patients scheduled to undergo minimally invasive surgery for colorectal cancer.


A lipid A-associated protein of Porphyromonas gingivalis, derived from the haemagglutinating domain of the RI protease gene family, is a potent stimulator of interleukin 6 synthesis.
There is evidence that the lipid A-associated proteins (LAPs) of enteric bacteria can induce the synthesis of interleukin 1 (IL-1) and therefore may be important virulence factors. Porphyromonas gingivalis is now recognized as a major pathogen in the chronic inflammatory periodontal diseases and it has previously been reported that a crude LAP fraction from this organism could induce IL-1 and interleukin 6 (IL-6) synthesis. In the present study the chemical and biological properties of the LAPs of this bacterium have been further characterized. Analysis by SDS-PAGE has shown that the LAPs comprise nine proteins of molecular masses 81, 68, 48, 47, 28, 25, 20, 17 and 16 kDa. These LAPs, at concentrations as low as 100 ng ml(-1), were shown to stimulate human gingival fibroblasts, human peripheral blood mononuclear cells and whole human blood to produce the pro-inflammatory cytokine IL-6. The cytokine-inducing activity of the LAPs was reduced after heat-inactivation and trypsinization, suggesting that the activity was not due to contaminating LPS. To establish which proteins in this mixture were the active cytokine inducers, the LAPs were separated by electrophoresis on polyacrylamide gels. The majority of the activity was associated with the 17 kDa LAP. N-terminal sequence analysis demonstrated that this protein was homologous to an internal region of a conserved adhesin domain contained within a family of P. gingivalis extracellular proteins including the RI protease, Lys-gingipain, porphypain and haemagglutinin A. In addition to a role in adherence, the adhesin domain(s) of these proteins may also have cytokine-inducing properties. Furthermore, it has also been shown that the previously observed degradation of cytokines by P. gingivalis may be attributable to the catalytic domain of the RI protease. Thus, different domains within the same molecule appear to have opposing actions on pro-inflammatory cytokine levels and the balance between these two activities may influence the cytokine status of the periodontium in patients with the common chronic inflammatory conditions known as the periodontal diseases.


Association between pet ownership and cardiovascular risks and mortality: a systematic review and meta-analysis.
: The aim of the study was to determine the association between pet ownership and cardiovascular risk factors and mortality. Electronic search was conducted through nine databases including PubMed for relevant publications reporting cardiovascular events and mortality among pet owners. Meta-analysis was used to pool the results. Of a total of 2818 reports screened, 26 studies were included in our systematic review and meta-analysis. Higher survival rate was observed in the pet owners group after pooling nonadjusted and adjusted hazard ratios for cardiovascular mortality at 0.73 [95% confidence interval (CI) 0.62-0.86] and 0.81 (0.68-0.97), respectively. A similar trend was observed for the pooled nonadjusted hazard ratio for overall mortality 0.73 (0.62-0.87) but not the adjusted hazard ratio 0.40 (0.04-3.78). Cat owners have a reduction in cardiovascular mortality but not overall mortality after pooling the adjusted hazard ratio 0.79 (0.63-0.99) and 1.04 (0.90-1.21), respectively. However, no significant association between dog owners and survival rate was observed for overall and cardiovascular-specific mortality. Pet owners had significantly lower heart rate (mean difference 95% CI: -2.32 (-3.07 to -1.57), mean arterial pressure -2.60 (-4.25 to -0.95) and SBP -1.69 (-3.06 to -0.31) but not DBP -0.23 (-1.05 to 0.60). No significant difference was observed between pet owners and nonpet owners in prevalence of hypertension. Our study draws attention to the beneficial effects of the human--pet bond; therefore, we recommend pet acquisition for better cardiovascular outcomes after controlling for zoonotics and pet-induced allergies.


Detection, typing, and subtyping of enteric adenoviruses 40 and 41 from fecal samples and observation of changing incidences of infections with these types and subtypes.
Monoclonal antibody (MAb) preparations specific for the enteric adenoviruses of subgenus F (AdF) were generated and evaluated as typing reagents in virus neutralization tests and enzyme-linked immunosorbent assays (ELISAs). A panel of 11 genome types of adenovirus 40 (Ad40), 24 genome types of Ad41, and 47 adenovirus prototype strains was used to determine the specificities of the MAbs in the two assays. In this way two MAbs, MAb 40-1 (anti-Ad40) and MAb 41-1 (anti-Ad41) were selected. These two MAbs showed strict type specificity in both assays. A third MAb reacted in an ELISA with all 47 human adenovirus types. With two other MAbs, three antigenic subtypes of Ad41 could be distinguished by their reactivities in virus neutralization tests and ELISAs. On the basis of the five selected MAbs, a sensitive ELISA system was developed for the direct detection and simultaneous typing and subtyping of Ad40 and Ad41 present in stool specimens. The five MAbs were also used to study the epidemiology of infections with Ad40 and Ad41 in The Netherlands in the period 1981 through 1989. It was shown that there were no significant fluctuations in the annual incidence of the cluster of enteric adenoviruses as a whole. This cluster should therefore be considered to belong to the "endemic" rather than the "epidemic" adenoviruses. The relative incidence of Ad40 infections compared with that of Ad41 infections changed considerably during the period studied; the proportion of Ad41 infections rose from about 30% in 1981 to about 95% in 1986, after which it stabilized at 90 to 95%. The proportion of one of the subtypes of Ad41 (Ad41 subtype M3) increased from about 40 to 80% in the same period.


Chronic low dose Adderall XR down-regulates cfos expression in infantile and prepubertal rat striatum and cortex.
We previously reported that treatment of prepubertal male rats with low, injected or oral, doses of methylphenidate stimulated cfos, fosB and arc expression in many areas of the developing brain. In the present study our objective was to determine whether the widely prescribed psychostimulant Adderall XR (ADD) exerted similar effects in infantile and prepubertal rat brain. We report here, for the first time, that low threshold doses of oral ADD, an extended-release mixture of amphetamine salts, now routinely used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), also increased cfos expression in infantile (postnatal day 10; PD10) and prepubertal (PD24) rat brain. These threshold doses were correlated with blood levels of amphetamine determined by liquid chromatography-mass spectrometry. Moreover, we observed that chronic treatment with oral ADD (1.6 mg/kg; x 14 days) not only significantly down-regulated cfos expression following a final challenge dose of ADD in prepubertal (PD24) rat striatum and cortex, quantified in terms of FOS immunoreactivity (FOS-ir), but did so at a daily dose that was without effect with methylphenidate (MPH); that is a much higher oral dose of MPH (7.5 mg/kg; x 14 days) failed to induce down-regulation of cfos expression. Similar experiments in infantile rats (PD10), but using a threshold injected dose of ADD (1.25 mg/kg sc) also significantly reduced striatal and cingulate cortical FOS-ir. An additional finding in the prepubertal rats was that oral ADD-induced FOS-ir was observed in the cerebral cortex following doses lower than the threshold dose necessary to increase FOS-ir in the striatum. This was not the case in the PD10 rats. In conclusion, our efforts to calibrate biological responses, such as immediate early gene expression, to clinically relevant blood levels of stimulants confirmed that expression of cfos is very sensitive to repeated low doses of Adderall XR. It is now feasible to examine whether other genes are also affected in these young rats and if the changes we report are reversible. The implications of such studies should be relevant to the putative effects of psychostimulant treatment of very young children.


Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial.
To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962. Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2-81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8-10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4-10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI -3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001). Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients. National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.


"SDM:HOSP"- a generic model for hospital-based implementation of shared decision making.
Shared decision making (SDM) is a core element in the meeting between patient and healthcare professionals, but has proved difficult to implement and sustain in routine clinical practice. One of five Danish regions set out to succeed and to develop a model that ensures lasting SDM based on learnings from large-scale real-world implementation initiatives that go beyond the 'barriers' and 'facilitators' research approach. This paper describes this process and development of a generic implementation model, SDM:HOSP. This project was carried out in the Region of Southern Denmark with five major hospital units. Based on existing theory of SDM, SDM implementation, implementation science and improvement methodology, a process of four phases were described; development of conceptual elements, field-testing, evaluation, and development of the final implementation model. The conceptual elements developed aimed to prepare leaders, train SDM teachers, teach clinicians to perform SDM, support development of patient decision aids, and support systematic planning, execution and follow-up. Field testing was done including continuous participant evaluations and an overall evaluation after one year. Data from field testing and learnings from the implementation process, illustrated the need for a dynamic and easy adjustable model. The final SDM:HOSP model included four themes; i)Training of Leaders, ii) Training of Teachers and Clinicians, iii) Decision Helper, and iv) 'Process', each with details in three levels, 1) shared elements, 2) recommendations, and 3) local adaption. A feasible and acceptable model for implementation of SDM across hospitals and departments that accounts for different organizations and cultures was developed. The overall design can easily be adapted to other organizations and can be adjusted to fit the specific organization and culture. The results from the ongoing and overall evaluation suggest promising avenues for future work in further testing and research of the usability of the model.


Monitoring the therapeutic efficacy of CA4P in the rabbit VX2 liver tumor using dynamic contrast-enhanced MRI.
The present work aims to evaluate whether dynamic contrast-enhanced magnetic resonance Imaging (DCE-MRI) can monitor non-invasively the blocking effect on microvessels of the Combretastatin-A4-phosphate (CA4P) and assess the therapeutic efficacy. Forty rabbits were implanted the VX2 tumors specimens. Two weeks later, serial MRI (T1 weighted image, T2 weighted image and DCE) were performed at 0 h, 4 h, 24 h, 3 d and 7 d after CA4P (10 mg/kg) or saline treatment. The parameters of DCE (Ktrans, Kep, Ve and iAUC60) of enhancement tumor portions were measured. Then all the tumor samples were stained to count microvessel density (MVD). At last, two-way repeated measures ANOVA was used to analyze the difference between and within groups. The correlation between the Ktrans, Kep, Ve, iAUC60 and MVD was analyzed by using the Pearson correlation analysis and Spearman's rank correlation. The Ktrans and iAUC60 in the CA4P group were lower than the values of the control group at 4 h after treatment, which have significant differences (D-value: -0.133 min-1, 95%CI: -0.169~-0.097 min-1,F = 59.109, p < 0.001 for Ktrans; D-value: -10.533 mmol/sec, 95%CI: -17.147~-3.919 mmol/sec,F = 11.110, and p = 0.003 for iAUC60). In the CA4P group, the Ktrans and iAUC60 reached the minimum values at 4 h. There were significant differences between 4 h and other different time points of the Ktrans and iAUC60 in the treatment group (all p < 0.01). The parameters Ktrans (r = 0.532, P = 0.016 and r = 0.681, P = 0.001, respectively) and iAUC60 (r = 0.580, P = 0.007 and r = 0.568, P = 0.009, respectively) of 7 days showed correlation with MVD in both groups, while Kep and Ve did not show correlation with MVD (P > 0.05). The blocking effect of microvessels after CA4P treatment can be evaluated by DCE-MRI, and the parameters of quantitative Ktrans and semi- quantitative iAUC60 can assess the change of the tumor angiogenesis noninvasively.


CD18-dependent leukocyte adherence and vascular injury in pig cerebral circulation after ischemia.
Recent accumulating evidence indicates that leukocytes contribute importantly to ischemic brain injury. Although large numbers of leukocytes are present in the ischemic territory of reperfused brain 24-48 h after the ischemic insult, little is known of the acute inflammatory response to cerebral ischemia, particularly regarding the time course and magnitude of leukocyte adherence to cerebrovascular endothelium and the functional consequences of such adherence. To study these issues, we developed an epifluorescence videomicroscopy system for observing and quantifying the dynamic behavior of rhodamine-labeled leukocytes in the cerebrovascular microcirculation. Anesthetized piglets equipped with closed cranial windows were used in these investigations. During the initial 2 h of reperfusion after 9 min of asphyxia (n = 6), a marked, progressive increase in adherent leukocytes was noted in cerebral postcapillary venules that was significantly greater in magnitude than that seen in nonasphyxic, time-matched controls (n = 8). A similar response was observed after complete global ischemia of 10 min duration. A significant increase in sodium fluorescein permeability was also measured at 2 h of reperfusion in asphyxic animals. Pretreating a separate asphyxic animal group (n = 7) with a monoclonal antibody to the leukocyte adhesion glycoprotein complex CD11/CD18 severely attenuated both leukocyte adherence and the increase in vascular permeability. These results provide evidence that adherent leukocytes contribute to disruption of endothelial integrity during early reperfusion after global ischemic insults, the inhibition of which may reduce the vasogenic edema that occurs early during reperfusion after birth asphyxia, stroke, and cardiac arrest.


Clinical evaluation of the Humphrey automatic refractor.
A new automatic objective refractor was used on healthy adults. In the absence of cycloplegic drugs, spherocylindrical objective refractions performed with the instrument provided 20/20 acuity 96% as often as with standard subjective techniques. No instrument-induced accommodations effects were seen. One hundred percent of instrument spherical findings were repeatable within 0.50 diopters; all cylindrical findings were repeatable within 0.37 D. This result represents a higher level of repeatability than that reported for standard subjective refraction under clinical conditions. In the absence of cycloplegic drugs, the correlation coefficient between the instrument's findings and standard subjective spherical findings was .97 v .98 between two practitioners' subjective refractions. The average difference between cylindrical findings of the instrument and those of an experienced practitioner was 0.04 D larger than the average difference seen between two practitioners using subjective techniques.


Characteristics and trends of newly diagnosed HIV-infections, 2000-2004.
To describe the characteristics and trends of newly diagnosed HIV-infections. We analysed all newly diagnosed HIV-infections among residents of the Canary Islands, Ceuta, La Rioja, Navarre and the Basque Country (Spain) between 2000 and 2004. In total, 1,807 HIV-infections -74.4 per million inhabitants, per year- were diagnosed. The heterosexual transmission category was the most frequent (48.6%), followed by that of homo/bisexual men (23.0%) and injecting drug users (IDU) (22.5%). From 2000 to 2004, the rate of new diagnoses of HIV infection decreased by 29.8% (p < 0.0001). The rate of diagnoses of infections acquired by IDU diminished by 58.5% (p < 0.0001), and the rate of infections associated with homo/bisexual practices in men descended by 33.9% (p = 0.0318). Nevertheless, the rate of diagnoses of infections by heterosexual transmission has not undergone significant changes. In the period 2002-2004, 28.7% of cases were diagnosed in foreigners, but the rate of diagnoses in the population of non-Spanish origin diminished by 24% (p = 0.0534). 39.7% of HIV diagnoses were delayed (with CD4 < 200 cells/microlitre or coinciding with the diagnosis of AIDS). This situation was less frequent in women (odds ratio = 0.5; p < 0.001) and increased with age amongst people over 30. The proportion of delayed diagnoses reached a maximum in 2001 (47.5%) and then declined until 2004 (38.6%; p = 0.022). Although none of the analysed indicators evolved unfavourably, it is important to insist on the prevention of sexual transmission, the early diagnosis of HIV infection, and the need to adapt preventive activities and focus them on people from other countries.


Collective In-Plane Molecular Rotator Based on Dibromoiodomesitylene π-Stacks.
Interest in artificial solid-state molecular rotator systems is growing as they enable systems to be designed for achieving specific physical functions. The phase transition behavior of four halomesitylene crystals indicated dynamic in-plane molecular rotator characteristics in dibromoiodomesitylene, tribromomesitylene, and dibromomesitylene crystals. Such molecular rotation in diiodomesitylene crystals was suppressed by effective I···I intermolecular interactions. The in-plane molecular rotation accompanied by a change in dipole moment resulted in dielectric phase transitions in polar dibromoiodomesitylene and dibromomesitylene crystals. No dielectric anomaly was observed for the in-plane molecular rotation of tribromomesitylene in the absence of this dipole moment change. Typical antiferroelectric-paraelectric phase transitions were observed in the dibromomesitylene crystal, whereas the dielectric anomaly of dibromoiodomesitylene crystals was associated with the collective in-plane molecular rotation of polar π-molecules in the π-stack. We found that the single-rope-like collective in-plane molecular rotator was dominated by intermolecular I···I interactions along the π-stacking column of polar dibromoiodomesitylene.


A prospective study of bilateral inguinal hernia repair.
A prospective study of outcome after inguinal hernia repair in patients undergoing simultaneous repair of bilateral hernias (n = 31), sequential repair of bilateral hernias (n = 5), and unilateral hernia repair (n = 75) is reported. There were no differences in wound complications, post-operative respiratory complications, or other adverse effects in the three groups. Operating time was similar in the unilateral and bilateral simultaneous repairs (median 55 min), but was longer (100 min) for the combination of two sequential repairs. Hospital stay was shortest for patients undergoing unilateral repair (2 days) but was less with bilateral simultaneous repair (4 days) than after two sequential repairs (total of 6 days). There were 12 (11%) wound complications of which five (5%) were infections. There was no difference in complication rate between unilateral and bilateral hernia repair. Postoperative recovery was assessed prospectively and was recorded at 1 month. There was no difference between unilateral and bilateral simultaneous repairs in the number of days before the patient was able to climb stairs easily, drive a car or return to work. The duration of the requirement for analgesia was similar in each group. We conclude that bilateral simultaneous hernia repair can be carried out with no greater morbidity than a unilateral repair, and the return to normal activity is as rapid. Bilateral hernias should be repaired simultaneously rather than sequentially.


Pathobiology of ALK+ anaplastic large-cell lymphoma.
Anaplastic large-cell lymphoma (ALCL) was initially recognized on the basis of morphologic features and the consistent expression of CD30. It then became evident that the majority of these tumors are derived from lymphoid cells of T or null immunophenotype. The subsequent finding that t(2;5)(p23;q35) occurs in 40% to 60% of ALCL patients established a distinct clinicopathologic entity. This chromosomal translocation induces the formation of the chimeric protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which possesses significant oncogenic potential resulting from the constitutive activation of the tyrosine kinase ALK. In addition to its specific pathophysiologic events, NPM-ALK-expressing lymphoma presents with consistent clinical manifestations. Only 13 years after the identification of NPM-ALK, tremendous progress has been made in our understanding of this molecule because of the relentless efforts of multiple investigators who have dissected its biologic roles using in vitro and in vivo experimental models. Several upstream modulators, cross-reacting oncogenes, and downstream effectors of NPM-ALK have been identified and characterized. Understanding these interacting oncogenic systems is expected to facilitate the design of new therapeutic strategies and agents. In this review, we briefly discuss ALCL and focus on NPM-ALK.


[High-conflict-divorce and personality disorder].
We tried to identify clues related to personality disorders - especially related to borderline personality--in parents of high-conflict divorce. We compared n = 34 high-conflict clients of psychological counselling to n = 45 clients not related to high-conflict divorce. Parents of high-conflict divorce did not show significantly more hints related to personality disorder. Parents who live separated scored higher than parents living together. Extreme-group-analyses over all clients revealed in 20% definitely evidence of personality disorders or very low resiliency. Psychological counselling in the realm of Child care units also addresses clients who rate themselves as seriously impaired or non-resilient.


Smartphone-Based Electrocardiographic and Cardiac Implantable Electronic Device Monitoring.
The field of arrhythmia monitoring is changing rapidly. The rapid advent of technology in combination with marked improvements in cellular communication and an increased desire by patients to be actively engaged in their care has ushered in a new era of clinical care. Today, physicians need to think about their patients outside the traditional in-office setting. Two technologies that embody this changing landscape are smartphone-based electrocardiographic (ECG) monitors and remote monitoring of cardiac implantable electronic devices (CIEDs). Smartphone-based ECG monitors allow the patient to assume a greater stake in their own care. They purchase the monitor, couple it to their smartphone, own it forever, and can capture a representative ECG whenever they want to assess symptoms. The physician needs to accept that this approach is vastly different from the use of standard ambulatory external ECG monitors that have been used for years in clinical practice. A similar paradigm shift is underway with respect to the care of the CIED patient. Remote follow-up was once considered an acceptable alternative to in-office calendar-based follow-up of CIEDs. Today, guidelines recommend remote monitoring to be the preferred method for device follow-up. Remote monitoring is tailor-made for the current evolution to a value-based healthcare system, having been demonstrated to reduce scheduled office visits, hospital admissions, and mortality. It is now time to educate patients and physicians on the value of remote monitoring and to ensure that clinical practices develop the infrastructure needed to enroll, monitor, and manage their patients.


Analysis of pesticide residues in lettuce by large volume-difficult matrix introduction-gas chromatography-time of flight-mass spectrometry (LV-DMI-GC-TOF-MS).
A multi-residue method is described that eliminates the need for a clean-up step and thus allows the rapid determination of pesticides in crude extracts of lettuce. Samples were extracted with a mixture of ethyl acetate, Na2SO4 and NaHCO3 and the crude extracts analysed directly using large volume-difficult matrix introduction (LV-DMI) in combination with gas chromatography-time of flight-mass spectrometry (GC-TOF-MS). The LV-DMI procedure described was evaluated for the analysis of dimethoate, pyrimethanil, chlorothalonil, vinclozolin, furalaxyl and oxadixyl. Satisfactory response was obtained at the lowest calibrated level (LCL) of 0.0025 microg ml(-1), with good linearity over the range 0.0025-0.5 microg ml(-1) (0.005-1.0 mg kg(-1) equivalent). Average recoveries between 73 and 118% were obtained at the 0.01-0.5 mg kg(-1) levels with RSD values < or = 13%.


A technique for making porcelain facings.
New improved refractory die materials are now being introduced onto the UK market which make it possible to construct porcelain facings and inlays directly onto refractory dies. From previous experience with several refractory die facing systems, it was decided that the Flexo-Ceram system should be used. This is because the porcelain is matched to the full Vita shade range and the materials are relatively easy to handle.


In vivo Studies on Antidiabetic Plants Used in South African Herbal Medicine.
Diabetes is one of the most common metabolic disorders worldwide. It is a major health problem with its frequency increasing every day in most countries. The disease is generally believed to be incurable; and the few orthodox drugs available to manage the disease are not readily affordable to the poor. Based on the historical success of natural products as antidiabetic agents and the ever increasing need for new antidiabetics, a number of South African medicinal plants have been evaluated for their antidiabetic properties. In this article, we review the major studies conducted based on ethnobotanical surveys carried out between 2005 and 2008 in South Africa on plants that are traditionally used for the treatment of diabetes. Overall, the results of the studies conducted confirmed the potential of South African medicinal plants in antidiabetic drug discovery and identified a number of promising taxa for further in vivo investigation as plant-based antidiabetic agents.


Surgical treatment of obesity.
Thirty-two patients, 28 women and 4 men aged from 17 to 57 years were treated surgically for obesity. Their body weight ranged from 90 to 184 kg, with an excess weight from 42% to 180%. In 6 cases the Salmon operation and in 26 the Payne-de Wind operation were performed. Two patients died. In the remaining cases the postoperative course was uneventful and relatively mild. The longest follow-up period was 22 months. Weight loss rate was highest in the first period after the operation and the monthly rate of the weight loss in the first year after the operation was 3.5 to 6 kg. Diarrhea disappeared usually after 4 months. In some patients a transient fall in serum potassium and calcium level was observed. Other favorable results included a significant fall in the serum levels of cholesterol and beta-lipoproteins and improved value of BSP retention test. The condition of the patients is good and they have returned to work.


Dietary Practice among the Patients with End Stage Renal Disease undergoing Maintenance Haemodialysis.
Several studies on the nutritional status of chronic kidney disease patients living on haemodialysis revealed high prevalence of malnutrition (18-94%). A hospital-based study in Nepal revealed 66.7% mild to moderately malnourished and National Kidney Center reported common protein-energy malnutrition problem among haemodialysis patients. As almost all patients undergoing maintenance haemodialysis looked malnourished, this study was carried out to explore prevailing dietary knowledge and practice of the patients. A descriptive cross-sectional survey of 471 patients undergoing haemodialysis from June 2015 to July in 2015 was carried out. After stratification through a systematic random sampling method, 40 (67%) patients from National Kidney Center and 20 (33%) from Bir Hospital were selected, interviewed face to face by using structured questionnaire. Ethical and institutional approval and patients' consent were obtained. The level of knowledge score found to be medium and practice score was even low. Seventy percent knew about renal diet but only 36 (60%) believed in it. After having kidney disease 42 (70%) had changed their dietary practice. Surprisingly, 38 (63.3%) said they ate the food what the other member in their family ate. Considerable limited knowledge (medium) and practices (low) scores were found. Had they have taken adequate dietician's support, they might have taken right kind and right amounts of foods and benefitted in controlling potassium, phosphate and protein at the recommended level. Plant-based diet could assist in end stage renal disease in a number of ways: an edge of protection against diet cost, reduce inter-related co-morbidities or complications (hypertension and diabetes).


Anorectal malignant melanomas: experience of Uludag University.
Anorectal melanomas represent a group of mucosal melanomas with unknown etiology and poor prognosis. The lesions can be misdiagnosed as hemorrhoids during clinical examination. We reviewed the morphological and clinical features of 14 anorectal melanomas, and discuss the treatment modalities of this entity. Fourteen patients who were diagnosed with anorectal malignant melanoma between 1997 and 2004 were evaluated with regard to age, sex, size, morphology, lymph node or distant metastasis, treatment modality and survival. Eight patients were female and six were male, and their mean age was 58 years. The size of melanoma ranged from 3 cm to 8 cm. Pathological evaluation revealed epithelioid and spindle cell type tumor in seven and two patients, respectively, whereas, in the remaining seven patients, the tumor was composed of both types. Pigmentation was apparent in all tumors. There was lymph node metastasis in 11 patients and distant metastasis in all patients. Eleven patients underwent abdominoperineal resection and three were treated by local excision. Mean survival was 8.7 months. Prognosis of anorectal melanoma remains poor. Awareness of the diverse clinicopathological features of these lesions, both on the part of the clinicians and pathologists, is crucial for their early detection and proper treatment.


Immobilization of laccase in alginate-gelatin mixed gel and decolorization of synthetic dyes.
Alginate-gelatin mixed gel was applied to immobilized laccase for decolorization of some synthetic dyes including crystal violet. The immobilization procedure was accomplished by adding alginate to a gelatin solution containing the enzyme and the subsequent dropwise addition of the mixture into a stirred CaCl(2) solution. The obtained data showed that both immobilized and free enzymes acted optimally at 50°C for removal of crystal violet, but the entrapped enzyme showed higher thermal stability compared to the free enzyme. The immobilized enzyme represented optimum decolorization at pH 8. Reusability of the entrapped laccase was also studied and the results showed that ca. 85% activity was retained after five successive cycles. The best removal condition was applied for decolorization of seven other synthetic dyes. Results showed that the maximum and minimum dye removal was related to amido black 10B and eosin, respectively.


The Snail protein family regulates neuroblast expression of inscuteable and string, genes involved in asymmetry and cell division in Drosophila.
Delaminated neuroblasts in Drosophila function as stem cells during embryonic central nervous system development. They go through repeated asymmetric divisions to generate multiple ganglion mother cells, which divide only once more to produce postmitotic neurons. Snail, a zinc-finger transcriptional repressor, is a pan-neural protein, based on its extensive expression in neuroblasts. Previous results have demonstrated that Snail and related proteins, Worniu and Escargot, have redundant and essential functions in the nervous system. We show that the Snail family of proteins control central nervous system development by regulating genes involved in asymmetry and cell division of neuroblasts. In mutant embryos that have the three genes deleted, the expression of inscuteable is significantly lowered, while the expression of other genes that participate in asymmetric division, including miranda, staufen and prospero, appears normal. The deletion mutants also have much reduced expression of string, suggesting that a key component that drives neuroblast cell division is abnormal. Consistent with the gene expression defects, the mutant embryos lose the asymmetric localization of prospero RNA in neuroblasts and lose the staining of Prospero protein that is normally present in ganglion mother cells. Simultaneous expression of inscuteable and string in the snail family deletion mutant efficiently restores Prospero expression in ganglion mother cells, demonstrating that the two genes are key targets of Snail in neuroblasts. Mutation of the dCtBP co-repressor interaction motifs in the Snail protein leads to reduction of the Snail function in central nervous system. These results suggest that the Snail family of proteins control both asymmetry and cell division of neuroblasts by activating, probably indirectly, the expression of inscuteable and string.


Interaction and interdependent packaging of tegument protein UL11 and glycoprotein e of herpes simplex virus.
The UL11 tegument protein of herpes simplex virus plays a critical role in the secondary envelopment; however, the mechanistic details remain elusive. Here, we report a new function of UL11 in the budding process in which it directs efficient acquisition of glycoprotein E (gE) via a direct interaction. In vitro binding assays showed that the interaction required only the first 28, membrane-proximal residues of the cytoplasmic tail of gE, and the C-terminal 26 residues of UL11. A second, weaker binding site was also found in the N-terminal half of UL11. The significance of the gE-UL11 interaction was subsequently investigated with viral deletion mutants. In the absence of the gE tail, virion packaging of UL11, but not other tegument proteins such as VP22 and VP16, was reduced by at least 80%. Reciprocally, wild-type gE packaging was also drastically reduced by about 87% in the absence of UL11, and this defect could be rescued in trans by expressing U(L)11 at the U(L)35 locus. Surprisingly, a mutant that lacks the C-terminal gE-binding site of UL11 packaged nearly normal amounts of gE despite its strong interaction with the gE tail in vitro, indicating that the interaction with the UL11 N terminus may be important. Mutagenesis studies of the UL11 N terminus revealed that the association of UL11 with membrane was not required for this function. In contrast, the UL11 acidic cluster motif was found to be critical for gE packaging and was not replaceable with foreign acidic clusters. Together, these results highlight an important role of UL11 in the acquisition of glycoprotein-enriched lipid bilayers, and the findings may also have important implications for the role of UL11 in gE-mediated cell-to-cell spread.


A randomized controlled trial comparing the quadhelix and the expansion arch for the correction of crossbite.
To compare the use of the quadhelix and the expansion arch for the correction of crossbite. A prospective randomized clinical trial supported by preliminary laboratory measurements. The null hypothesis was that there was no difference in the clinical effectiveness of the two expansion devices in terms of crossbite correction. Queen's Hospital, Burton on Trent and The University of Birmingham, School of Dentistry. The first 60 patients on the orthodontic waiting list at Queen's Hospital who required expansion of the maxillary arch as part of the treatment plan were allocated to be treated with either a quadhelix or an expansion arch by random allocation. Twenty-eight and 27 members of each respective group completed the study. Commercial quadhelix arches (3M Unitek) and custom-made expansion arches The force produced by the type of expansion arches used in the study was measured in the laboratory to be 1.8 N at 10 mm of expansion. Quadhelix arches of sizes 2 and 3 were found to produce equivalent forces at 5 and 7 mm of expansion respectively. Either expansion device was fitted to the 60 participants according to random allocation and expanded by the standard amount. Intermolar and intercanine expansion was measured after 4, 8 and 12 weeks. Patient opinion was assessed by using a questionnaire. The quadhelix and the expansion arch were equally effective in producing expansion (p>0.05). After 12 weeks, the two types of archwire had produced mean intermolar expansions of 4.54 and 5.09 mm and intercanine expansions of 1.41 and 2.12 mm, respectively. Both types of arch were reported as uncomfortable by a majority of patients, the quadhelix affected mainly the tongue and the expansion arch the cheeks. The appearance of the quadhelix was disliked by 25% of participants, while 70% disliked the expansion arch. The null hypothesis was confirmed. However, the expansion arch had several advantages that made it a cheap alternative to the quadhelix for crossbite expansion, because it can be made and fitted at the chairside.


Isoflavone formononetin from red propolis acts as a fungicide against Candida sp.
A bioassay-guided fractionation of two samples of Brazilian red propolis (from Igarassu, PE, Brazil, hereinafter propolis 1 and 2) was conducted in order to determine the components responsible for its antimicrobial activity, especially against Candida spp. Samples of both the crude powdered resin and the crude ethanolic extract of propolis from both locations inhibited the growth of all 12 tested Candida strains, with a minimum inhibitory concentration of 256μg/mL. The hexane, acetate and methanol fractions of propolis 1 also inhibited all strains with minimum inhibitory concentration values ranging from 128 to 512μg/mL for the six bacteria tested and from 32 to 1024μg/mL for the yeasts. Similarly, hexane and acetate fractions of propolis sample 2 inhibited all microorganisms tested, with minimum inhibitory concentration values of 512μg/mL for bacteria and 32μg/mL for yeasts. The extracts were analyzed by HPLC and their phenolic profile allowed us to identify and quantitate one phenolic acid and seven flavonoids in the crude ethanolic extract. Formononetin and pinocembrin were the major constituents amongst the identified compounds. Formononetin was detected in all extracts and fractions tested, except for the methanolic fraction of sample 2. The isolated isoflavone formononetin inhibited the growth of all the microorganisms tested, with a minimum inhibitory concentration of 200μg/mL for the six bacteria strains tested and 25μg/mL for the six yeasts. Formononetin also exhibited fungicidal activity against five of the six yeasts tested. Taken together our results demonstrate that the isoflavone formononetin is implicated in the reported antimicrobial activity of red propolis.


[THC-carbonic acid determination in serum with fluorescence polarization immunoassay (FPIA, TDX) and GCMS].
The Urine-Immuno-Assay (Abbot, TDX) for Cannabis you may also use for the investigation of blood or serum. First the protein is precipitated by Metanol. The solvent is removed by a gentle stream of nitrogen and the solution reconstituted with Phosphat-Buffer. You may handle this solution like urine. Confirmation analysis is made by GCMS after extraction using C-18-extraction tubes and derivation with a proper reagent. Detection limit is about 10 ng/ml. You need only 0.3 ml Serum.


Subjective awareness of ultrasound expertise development: individual experience as a determinant of overconfidence.
Medical decision-making requires years of experience in order to develop an adequate level of competence to successfully engage in safe practice. While diagnostic and technical skills are essential, an awareness of the extent and limits of our own knowledge and skills is critical. The present study examines clinicians' subjective awareness in a diagnostic cardiac ultrasound task. Clinicians answered diagnostic and treatment related questions for a range of pathologies. Following these questions, clinicians indicated their level of confidence in their response. A comparison of response accuracy and confidence revealed that clinicians were generally overconfident in their responses. Critically, we observed that a clinician's overconfidence was negatively correlated with prior experience: clinicians that had more prior experience expressed less overconfidence in their performance such that some clinicians were in fact underconfident. We discuss the implications for training in medical education and decision-making.


Cerebrospinal fluid exposure of efavirenz and its major metabolites when dosed at 400 mg and 600 mg once daily: a randomized controlled trial.
The optimal penetration of antiretroviral agents into the central nervous system may be a balance between providing adequate drug exposure to inhibit human immunodeficiency virus (HIV) replication while avoiding concentrations associated with neuronal toxicities. Cerebrospinal fluid (CSF) exposure of efavirenz and the metabolites 7-hydroxy (7OH) and 8-hydroxy (8OH) efavirenz were assessed after at least 12 weeks of therapy in HIV-infected subjects randomized to commence antiretroviral regimens containing efavirenz at either 400 mg or 600 mg once daily. Of 28 subjects (14 and 14 on efavirenz 400 mg and 600 mg, respectively), CSF HIV RNA was undetectable in all. Geometric mean CSF efavirenz, 7OH-, and 8OH-efavirenz concentrations (with 90% confidence intervals [CIs]) for the 400-mg and 600-mg dosing groups were 16.5 (13-21) and 19.5 (15-25) ng/mL; 0.6 (.4-.9) and 0.6 (.4-1) ng/mL; and 5.1 (4.0-6.4) and 3.1 (2.1-4.4) ng/mL, respectively. Efavirenz concentration in CSF was >0.51 ng/mL (proposed CSF 50% maximal inhibitory concentration for wild-type virus) in all subjects, and 8OH-efavirenz concentration in CSF was >3.3 ng/mL (a proposed toxicity threshold) in 11 of 14 and 7 of 14 subjects randomized to the 400 mg and 600 mg doses of efavirenz, respectively. Whereas CSF efavirenz concentration was significantly associated with plasma concentration (P < .001) and cytochrome P450 2B6 genotype (CSF efavirenz GG to GT/TT geometric mean ratio, 0.56 [90% CI, .42-.74]), CSF 8OH-efavirenz concentration was not (P = .242 for association and CSF 8OH-efavirenz GG to GT/TT geometric mean ratio, 1.52 [90% CI, .97-2.36]). With both doses of efavirenz studied, CSF concentrations were considered adequate to inhibit HIV replication, although concentrations of 8OH-efavirenz were greater than those reportedly associated with neuronal toxicity. CSF exposure of 8OH-efavirenz was not dependent on plasma exposure and, as we postulate, may be subject to saturable pharmacokinetic effects. NCT01011413.


Seasonal structure and dynamics of sarcosaprophagous fauna on pig carrion in a rural area of Cordoba (Argentina): their importance in forensic science.
Four experiments, one in each season, were carried out during 2004 in a rural area of Córdoba, central Argentina. Two pigs (Sus scrofa L.), weighing approximately 8 kg each, were used in each of the four experiments. The animals were killed by a sharp blow to the head and immediately placed in an appropriate arthropod trap. One pig was placed in the shade and the other under direct sunlight. This research was conducted to determine the seasonal structure and dynamics of arthropods that constitute the sarcosaprophagous community in a given area of the central region of Argentina. The decomposition process was divided into five stages: fresh, bloated, decay, advanced decay and dry. The duration of each stage varied in different seasons, showing that the temperature and humidity are the most important variables that influence this process. A total of 51,500 adults and 36,909 immature were collected. More than 80% of the specimens collected belong to Insecta, and within this, Diptera were the most abundant order. The flies were mainly represented by adults and immature of the following species: Chrysomya albiceps (Wiedemann) (Calliphoridae), Musca domestica Linnaeus (Muscidae) and Fannia femoralis (Stein) (Fanniidae). Coleoptera were mainly represented by adults and immature of the species Creophilus maxillosus (Linnaeus) (Staphylinidae) and Dermestes maculatus (Geer) (Dermestidae). More than 50% of hymenopteran fauna collected belong to Formicidae. The trophic levels associated with the decomposition of the remains included five categories: necrophagous, parasites and predators of the necrophagous species, omnivores, opportunists and adventives. During faunal succession a strong dominance of the necrophagous species of the family Calliphoridae and Muscidae was observed, mainly during the early stages of decay process in all seasons.


[Similarity of natriuretic action and qualitative differences of the hydrouretic action of 1-deamino-arginine-vasotocin and furosemide in rats].
Injections of furosemide at a dose of 0.3 micromol per 100 g body weight or 1-deamino-arginine-vasotocin (1dAVT) at a dose of 0.05 nmol per 100 g body weight induced nearly equal increase in urinary sodium excretion: up to 406 +/- 20 and 405 +/- 23 micromol/2 h, respectively. Increase in urinary sodium excretion after injection of 1d-AVT was followed by enhancement of solute free water reabsorption from -0.51 +/- 0.05 to -2.75 +/- 0.11 ml/2 h (p < 0.05). On the contrary, furosemide injection induced a significant decrease in solute free water reabsorption to -0.19 +/- 0.06 ml/2 h (p < 0.05) and led to the appearance of solute free water in urine during peak of diuretic reaction. These data for the first time show that furosemide not only decreases sodium reabsorption, but also blocks some componentin molecular mechanism of vasopressin-dependent increase of the osmotic permeability of water.


Anti-hypercholesterolemic impacts of barley and date palm fruits on the ovary of Wistar albino rats and their offspring.
A high cholesterol diet is related to ovarian dysfunction and infertility which has been increased among young ages consuming processed food products. The present study was conducted to evaluate the role of a high cholesterol diet on the ovaries of young female rats via assessments of histopathology, immunohistochemistry, oxidative stress and apoptic markers. Also, mating of hypercholesterolemic female rats was carried out to measure the fertility and numbers of their offspring. At the same time, phytotherapy was carried out through supplementing the diet with barley and/ or date palm fruits (10%) during the experiment to assess the phyto-therapeutic impacts in attenuation of drastic hypercholesterolemic effects. Hypercholesterolemic diet-fed rats exhibited damage of the ovarian follicles and increased follicular atresia. Furthermore, expression of cleaved caspase-3 was upregulated, while PCNA was downregulated in granulosa, theca and stroma cells. Hypercholesterolemic female rats showed marked depletion of antioxidative enzymes, increased lipid peroxidation and apoptotic markers. Alterations to the female serum hormones were detected. Offspring maternally fed on hypercholesterolemic diet showed a significant decrease of body weight and altered sex ratio. However, concomitant supplementation of barley and or date fruits to hypercholesterolemic groups revealed marked improvement of ovarian structure and function. On the basis of these evidences, it is believed that the enhanced synergistic effects of barley and/or date palm fruits in the amelioration of ovarian structure and functions were elicited by the potential antioxidant activity of their phytomicronutrients, polyphenols, β-glucan and trace elements. These materials scavenge free radicals from inflamed cells that can be used to establish an effective and novel therapeutic strategy for activating ovarian cell regeneration.


Mycobacterial antibody levels and immune restoration disease in HIV patients treated in South East Asia.
Immune restoration disease (IRD) associated with Mycobacterium tuberculosis parallels the reconstitution of a pathogen-specific Th1 response. However, it is not clear whether humoral responses to M. tuberculosis antigens also rise, or whether antibody levels predict IRD. Here, humoral immunity to M. tuberculosis antigens was investigated in four Asian cohorts. Plasma samples were obtained from longitudinal prospective studies of HIV patients beginning antiretroviral therapy (ART) in New Delhi (India), Kuala Lumpur (Malaysia), Jakarta (Indonesia) and Phnom Penh (Cambodia). IgG antibodies to purified protein derivative, lipoarabinomannan and 38-kDa antigens of M. tuberculosis were quantitated using in-house ELISAs. IRD was defined as exacerbated symptoms of tuberculosis in patients on anti-tuberculosis therapy or a novel presentation of tuberculosis on ART. Pre-ART IgG levels to purified protein derivative, lipoarabinomannan and 38-kDa antigen were similar in the IRD and control groups from each site. Compared with non-IRD controls, a higher proportion of IRD patients had elevated IgG levels to lipoarabinomannan (defined as a greater than twofold increase) over 12 weeks of ART. However, this trend was not significant for the other antigens and longitudinal analyses did not reveal clear rises in antibody levels at the time of IRD. Levels of antibody to mycobacterial antigens do not predict IRD, but levels of antibody reactive with lipoarabinomannan rise during an IRD in some patients.


Are Past Adverse Pregnancy Outcomes Associated with Maternal Anxiety and Depressive Symptoms in a Sample of Currently Pregnant Women?
There has been a great deal of concern about the mental health of women whose pregnancies involve miscarriage, termination of a pregnancy (ToP), child death or where a child has been given up for adoption. Despite this concern there has been remarkably little population-based research which has addressed the long-term consequences of pregnancy loss and child death. This study investigated the maternal mental health consequences of women whose pregnancies involve miscarriage, ToP, child death or where a child has been given up for adoption at two different time points, adjusting for socio-demographic characteristics and baseline mental health. The Mater-University of Queensland Study of Pregnancy is a prospective pre-birth cohort study. Women were recruited early in pregnancy over the period 1981 to 1983 at their first antenatal clinic visit (FCV). Women were interviewed again at the 14-year follow-up. Data from 4403 mothers were analysed using maternal reports of a prior history of giving a child up for adoption, miscarriage, ToP, and neonatal, infant and/or child deaths. Symptoms of maternal anxiety and depression were measured at FCV and the 14-year follow-up using the Delusions-Symptoms-States Inventory. We carried out logistic regression analysis using Stata 13. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to display the findings. A prior miscarriage was associated with anxiety (adjusted OR (AOR) = 1.30; 95% CI: 1.10-1.66) and depressive (AOR = 1.70; 95% CI: 1.21-2.39) symptoms at the 14-year follow-up. Having had a neonatal, infant and/or child deaths was associated with symptoms of depression at 14-year follow-up (AOR = 2.12; 95% CI: 1.06-4.25). The period after a child loss which involves a new pregnancy may be associated with relatively good mental health despite the fact that some mothers have experienced previous adverse pregnancy outcomes.


A Qualitative Study on Nudging and Palliative Care: "An Attractive but Misleading Concept".
The debate about the ethical decision-making process in the healthcare context has been enriched with a theory called "nudging", which has been defined as the framing of information that can significantly influence behaviour without restricting choice. The literature shows very limited data on the opinion and experience of palliative care healthcare professionals on the use of nudging techniques in their care setting. The aim of this study is to explore the beliefs of experienced palliative care professionals towards nudging. We performed a qualitative study using textual data collected through a focus group. It was audio-recorded, and the transcripts were subjected to a thematic analysis. It was performed within an oncological research hospital with a small and multidisciplinary group of healthcare professionals specialised in PC. Participants reported two overarching positions grounded in two main themes: (1) translating nudging in the PC setting and (2) towards a neutral space. The participants found few justifications for the use of nudging in the PC field, even if it can be very attractive and reassuring. Participants also expressed concerns about the excessive risk of developing pure paternalism.


Radiofrequency energy: applications and basic science.
Interest in using radiofrequency energy devices in orthopedics has been growing recently. The basic science of this intervention is similar to that of laser energy application and involves the heating of tissue. Collagen responds characteristically to heat--it becomes denatured, and its configuration becomes disorganized. Thus, this application of heat can be used to shorten collagenous soft tissue. Radiofrequency energy can also be used at higher parameters for tissue ablation. Although early clinical trials have shown promising results for many applications, long-term study is needed.


Complement activation during liver transplantation-special emphasis on patients with atypical hemolytic uremic syndrome.
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy often caused by mutations in complement factor H (CFH), the main regulator of alternative complement pathway. Because CFH is produced mainly by the liver, combined liver-kidney transplantation is a reasonable option in treatment of patients with severe aHUS. We studied complement activation by monitoring activation markers during liver transplantation in two aHUS patients treated extensively with plasma exchange and nine other liver transplantation patients. After the reperfusion, a clear increase in all the activation markers except C4d was observed indicating that the activation occurs mainly through the alternative pathway. Concentration of SC5b-9 was higher in the hepatic than the portal vein indicating complement activation in the graft. Preoperatively and early during the operation, the aHUS patients showed highest C3d concentrations but otherwise their activation markers were similar to the other patients. In the other patients, correlation was found between perioperative SC5b-9 concentration and postoperative alanine aminotransferase and histological changes. This study explains why supply of normal CFH by extensive plasma exchange is beneficial before combined liver-kidney transplantation of aHUS patients. Also the results suggest that perioperative inhibition of the terminal complement cascade might be beneficial if enhanced complement activation is expected.


Antimüllerian hormone as predictor of reproductive outcome in subfertile women with elevated basal follicle-stimulating hormone levels: a follow-up study.
To investigate the role of serum antimüllerian hormone (AMH) as a predictor of live birth and reproductive stage in subfertile women with elevated basal FSH levels. A prospective observational cohort study conducted between February 2005 and June 2009. Tertiary fertility center. Subfertile women with [1] a regular menstrual cycle (mean cycle length 25-35 days); [2] basal FSH concentrations ≥12.3 IU/L; and [3] younger than 40 years (n = 96). None. Live birth and reproductive stage according to the Stages of Reproductive Aging Workshop. A cumulative live birth rate of 63.5% was observed during a median follow-up of 3.3 years (n = 85). The AMH level was significantly associated with live birth. There was evidence of a nonlinear prediction pattern, with an increase in chances of live birth until an AMH level of 1 μg/L. Other ovarian reserve tests and chronological age appeared of limited value in predicting live birth. In addition, AMH was significantly associated with the timing of reproductive stages (n = 68) (i.e., the occurrence of menopausal transition or menopause during follow-up). The present findings suggest applicability of AMH determination as a marker for actual fertility in subfertile women with elevated basal FSH levels.


Three-dimensional structural analysis of fibronectin heparin-binding domain mutations.
Using recombinant fibronectin proteins containing the V region and two point mutations in the high-affinity heparin-binding domain, we previously showed that these domains modulate tumor cell invasion as well as proteinase expression and apoptosis in human fibroblasts. Structurally, the wildtype counterparts to these two point mutations, together with four other discontinuous, positively charged residues, form a cationic cradle in domain III-13 of fibronectin that binds heparin. We constructed a three-dimensional model of this cationic cradle and determined whether the two engineered point mutations in the heparin-binding domain would alter this cradle conformation, thus explaining the altered cell behavior. Our model of fibronectin domain III-13 was generated from a template of the three-dimensional structure of a homologous (25% identity) domain, III-3, from tenascin. The amino acid sequences of III-13 that differed from tenascin III-3 were replaced, and side chains for positively charged arginines 6 and 7 were substituted with uncharged threonines. The model revealed that the two mutated threonine residues were solvent accessible, readily accommodated as part of an antiparallel beta strand, and remained part of the three-dimensional cradle. These models suggest that the two point mutations in the heparin-binding domain of fibronectin III-13 alter cell function probably through changes in charge and not through changes in the conformational structure of the cationic cradle. J. Cell. Biochem. Suppl. 36: 156-161, 2001.


Partners in defense, vitamin E and vitamin C.
In addition to the enzymic mechanism of free-radical removal, essential nutrients that can scavenge free radicals, such as vitamins E and C, constitute a strong line of defense in retarding free radical induced cellular damage. Distinct pathways for the repair of oxidized vitamin E in human cells have been recently identified. Within 0.5 min after the addition of arachidonic acid to a human platelet homogenate, over half of the platelet vitamin E and added arachidonate were metabolized by platelet cyclooxygenase and lipoxygenase pathways. After adding nordihydroguaiaretic acid, a lipoxygenase inhibitor and a strong reductant, over 60% of the oxidized vitamin E was regenerated. To test other physiological, water-soluble reductants that may help regenerate vitamin E, eicosatetraynoic acid, a lipoxygenase inhibitor that is not an antioxidant, was used. In this system, both ascorbate and glutathione provided significant vitamin E regeneration. Kinetic analysis and studies of vitamin E regeneration in a protein-denaturing system revealed that ascorbate regenerates vitamin E by a nonenzymic mechanism, whereas glutathione regenerates vitamin E enzymatically. These studies suggest that significant interaction occurs between water- and lipid-soluble molecules at the membrane-cytosol interface and that vitamin C may function in vivo to repair the membrane-bound oxidized vitamin E.


[Environmental pollution with heavy metals at carrier rockets fall areas].
Based on hygienic monitoring, the authors evaluated environmental pollution with heavy metals at carrier rockets fall places and determined actual chemical load on environment.


Are patients with acute leukaemia, alive and well 2 years post bone marrow transplantation cured? A European survey. Acute Leukaemia Working Party of the European Group for Bone Marrow Transplantation (EBMT).
We investigated the occurrence of late events (beyond 2 years) in patients with acute leukaemia who received an allogeneic (BMT) (n = 1059), or an autologous bone marrow transplantation (ABMT) (n = 656) in Europe during the period from January 1979 to December 1990. Patients with no recurrence of leukaemia at 2 years had overall 82% chance of being alive in complete remission at 9 years following transplantation regardless of the nature of the leukaemia, the status at transplant, and the type of transplant. The incidence of late relapses continuously decreased with time. The latest relapses in acute myelogenous leukaemia (AML) were observed following BMT at 6.6 years in a patient transplanted in first remission (CR1) and at 3.7 years in a patient transplanted in second remission (CR2), and following ABMT at 6 years and 5.1 years respectively. The latest relapses in acute lymphoblastic leukaemia (ALL) were observed following BMT at 4 years in a patient transplanted in first remission (CR1) and at 6.8 years in a patient transplanted in second remission (CR2), and following ABMT at 5.3 years and 4.5 years respectively. Several factors predictive for late relapse or death were identified. Patients allografted experienced a lower frequency of late relapse than patients autografted. Of the numerous other prognostic factors studied, female sex in AML, the use of total body irradiation (TBI) in ALL and status in CR1, rather than CR2-3, for both ALL and AML allografted were correlated with a lower relapse incidence. The use of TBI in ALL was also associated with a better LFS and survival. The absence of acute graft-versus-host disease (GVHD) in allografted AML correlated with better LFS and better survival, but had no influence on the relapse incidence. This study indicates that patients alive and well at 2 years post transplant have a very high probability of being cured, but the possibility of late relapse still remains.


Changes in NGF/c-Fos double staining in the structures of the limbic system in juvenile and aged rats exposed to forced swim test.
This study aimed to investigate the influence of acute (a single 15 min) and chronic (15 min daily for 21 days) exposure to forced swim (FS) test on nerve growth factor (NGF)/c-Fos cells in hypothalamic paraventricular (PV) and supraoptic (SO) nuclei, the central (CeA) and medial (MeA) amygdaloid nuclei and CA3-hippocampus in juvenile (P28) and aged (P360) rats. The double-immunofluorescence (-ir) method was used to detect NGF-ir and c-Fos-ir cells. The amount of NGF/c-Fosir cells in relation to all NGF-ir cells is shown as a percentage. In the acute FS test an increase in NGF/c-Fos-ir cells (P<.05) was observed in all studied structures of juvenile rats and in the PV and SO of the aged individuals. After chronic FS stress, the NGF/c-Fos-ir ratio remained unaltered (except in the SO) in P28, but it increased (P<.05) in all investigated regions in P360 compared with the controls. The findings may reflect the state of molecular plasticity within the limbic hypothalamicpituitary- adrenocortical (HPA) axis in both age groups, yet the phenomenon of habituation in NGF/c-Fos-ir after chronic FS exposure was observed only in juvenile animals.


Orthopaedic injuries in children with nonaccidental trauma: demographics and incidence from the 2000 kids' inpatient database.
The purpose of this study was to examine the demographic and injury characteristics of children hospitalized with nonaccidental trauma as a causative factor using a large national database. Of the nearly 2.5 million cases in the database, 1794 (0.1%) were identified through diagnostic coding of abuse. Both sexes were equally represented, and two thirds had Medicaid as their primary payer. About one half of the children were younger than 1 year, but all ages were represented. The most common orthopaedic injuries were fractures of the femur or humerus, and most of those fractures occurred in children younger than 2 years. The most common nonorthopaedic injuries were contusions and brain injuries, with or without skull fracture, and 62 (3.5%) of the abused children died; almost all deaths were associated with brain trauma. Nearly one half of the abused hospitalized children between the ages of 3 and 20 years had a concomitant psychiatric or neurological condition. These data provide the orthopaedic surgeon with additional information to assist in identification of potential cases of nonaccidental trauma. In addition to presence of long bone fractures in infants and toddlers, older children with concomitant psychiatric or neurological conditions presenting with nonaccidental injuries should be assessed for possible abuse.


Current perioperative management of anticoagulant and antiplatelet use in neuroendovascular therapy: analysis of JR-NET1 and 2.
To evaluate current perioperative antithrombotic management in neuroendovascular therapy in Japan, we analyzed perioperative anticoagulant and antiplatelet use in various procedures and examined their relationships with periprocedural adverse events. Patient's data from nationwide surveys administered by the Japanese Registry of Neuroendovascular Therapy (JR-NET) between January 2005 and December 2007 (JR-NET1) and January 2008 and December 2009 (JR-NET2) were retrospectively analyzed. Compared to JR-NET1, the frequency of perioperative antiplatelet therapy and dual or triple therapy were increased for either aneurysm coiling and percutaneous transluminal angioplasty or stenting in JR-NET2. Although ischemic complications were significantly decreased (4.2% vs. 2.1%, p<0.001), hemorrhagic complications (2.1% vs. 5.3%, p<0.001), severe adverse events (1.5% vs. 2.1%, p<0.001), and total perioperative complications (8.3% vs. 10.3%, p<0.001) were significantly increased in JR-NET2. The rate of hemorrhagic complications was significantly higher in patients with triple or more perioperative antiplatelet therapy (preoperative: 5.3% vs. 9.2%, p<0.0001, postoperative: 5.7% vs. 12.7%, p<0.0001). Perioperative antithrombotic therapy was performed more frequently and intensively in neuroendovascular therapy in Japan. While ischemic complications were decreased, hemorrhagic complications and severe adverse events were increased. These results suggest that intensive antithrombotic therapy has a potential risk of hemorrhagic complications for Japanese patients.


Operational research within a Global Fund supported tuberculosis project in India: why, how and its contribution towards change in policy and practice.
The Global Fund encourages operational research (OR) in all its grants; however very few reports describe this aspect. In India, Project Axshya was supported by a Global Fund grant to improve the reach and visibility of the government Tuberculosis (TB) services among marginalised and vulnerable communities. OR was incorporated to build research capacity of professionals working with the national TB programme and to generate evidence to inform policies and practices. To describe how Project Axshya facilitated building OR capacity within the country, helped in addressing several TB control priority research questions, documented project activities and their outcomes, and influenced policy and practice. From September 2010 to September 2016, three key OR-related activities were implemented. First, practical output-oriented modular training courses were conducted (n = 3) to build research capacity of personnel involved in the TB programme, co-facilitated by The Union, in collaboration with the national TB programme, WHO country office and CDC, Atlanta. Second, two large-scale Knowledge, Attitude and Practice (KAP) surveys were conducted at baseline and mid-project to assess the changes pertaining to TB knowledge, attitudes and practices among the general population, TB patients and health care providers over the project period. Third, studies were conducted to describe the project's core activities and outcomes. In the training courses, 44 participant teams were supported to develop research protocols on topics of national priority, resulting in 28 peer-reviewed scientific publications. The KAP surveys and description of project activities resulted in 14 peer-reviewed publications. Of the published papers at least 12 have influenced change in policy or practice. OR within a Global Fund supported TB project has resulted in building OR capacity, facilitating research in areas of national priority and influencing policy and practice. We believe this experience will provide guidance for undertaking OR in Global Fund projects.