The GIANT study, a cluster-randomised controlled trial of efficacy of education of doctors about type 2 diabetes mellitus management guidelines in primary care practice.
Primary aim: does general practitioner (GP) education on type 2 diabetes treatment improve HbA1c? Secondary aim: cardiovascular risk factors, hypoglycaemia, treatment intensification, health service utilisation, treatment barriers. 99 Asia-Pacific GPs were cluster-randomised to be educated on regional diabetes management guidelines (intervention) or continue standard care (control). The intervention employed meetings, reminders, medical record summary sheets and patient result cards. Each GP recruited four type 2 diabetic patients, assessed at baseline, 6 and 12 months. The primary outcome was mean change in HbA1c from 0 to 6 months in patients with baseline HbA1c≥6.5%. 361 patients (93%) completed 6 month follow-up. The primary HbA1c outcome was -0.11% (95% CI -0.27, 0.05) with intervention and -0.22% (95% CI -0.39, -0.05) in the control group (p=0.340). The groups did not differ in control of other glycaemic indices, blood pressure or lipids after 6 or 12 months. In those with HbA1c≥9.0%, approximately 50% received intensified treatment by 6 months, and 30% in the final 6 months. GPs identified treatment costs and patient reluctance to use insulin as management barriers. A structured GP education programme did not improve HbA1c in patients with type 2 diabetes.


Etiology of Influenza-Like Illnesses from Sentinel Network Practitioners in Réunion Island, 2011-2012.
In Réunion Island, despite an influenza surveillance established since 1996 by the sentinel general practitioner's network, little is known about the etiology of Influenza like-illness (ILI) that differs from influenza viruses in a tropical area. We set up a retrospective study using nasal swabs collected by sentinel GPs from ILI patients in 2011 and 2012. A total of 250 swabs were randomly selected and analyzed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) including research of 18 viruses and 4 bacteria. We detected respiratory viruses in 169/222 (76.1%) samples, mostly rhinovirus (23.4%), influenza A virus (21.2%), influenza B virus (12.6%), coronavirus (4.9%) and Human metapneumovirus (3.6%). Nine swabs (5.3% of positive swabs) revealed co-infections with two viruses identified, among which six concerned co-infections with influenza viruses. We observed important seasonal differences, with circulation of Human Metapneumoviruses, RSV A and B and coronavirus only during summer; whereas parainfluenza viruses were identified only during winter. In conclusion, this study highlights a substantial circulation of multiple respiratory pathogens in Réunion Island throughout the year. It shows that ILI are not only attributable to influenza and underlines the need for biological surveillance. As the use of multiplex RT-PCR showed its efficacy, it is now used routinely in the surveillance of ILI.


[Disseminated intravascular coagulation in a patient with polyarteritis nodosa and bilateral hypoacusis].
We describe the case of a 44-years-old female patient with a panarteritis nodosa preceded by a rapid progressive bilateral deafness after an acute otitis media. Once on treatment with steroids and cyclophosphamide, she developed a disseminated intravascular coagulation, with a fatal evolution not justifiable by a different cause apart from her main disease.


High-Strength, High-Toughness Aligned Polymer-Based Nanocomposite Reinforced with Ultralow Weight Fraction of Functionalized Nanocellulose.
Multifunctional lightweight, flexible, yet strong polymer-based nanocomposites are highly desired for specific applications. However, the control of orientation and dispersion of reinforcing nanoparticles and the optimization of the interfacial interaction still pose substantial challenges in nanocellulose-reinforced polymer composites. In this study, poly(ethylene glycol) (PEG)-grafted cellulose nanofibers have demonstrated much better dispersion in a poly(lactic acid) (PLA) matrix as compared to unmodified nanocellulose. Through a uniaxial drawing method, aligned PLA/nanocellulose nanocomposites with high strength, high toughness, and unique optical behavior can be obtained. With the incorporation of 0.1 wt % of the PEG-grafted cellulose nanofibers in PLA, the ultimate strength of the aligned nanocomposite reaches 343 MPa, which is significantly higher than that of other aligned PLA-based nanocomposites reported previously. Moreover, its ultimate strength and toughness are enhanced by 39% and 70%, respectively, as compared to the aligned nanocomposite reinforced with unmodified cellulose nanofibers. In addition, the aligned nanocomposite film is highly transparent and possesses an anisotropic light scattering effect, revealing its significant potential for optical applications.


[Specific antibodies and their role in the formation of antidiphtheria immunity].
In human sera, studied with the use of the enzyme immunoassay, antidiphtheria postvaccinal antitoxic IgG and naturally acquired antibacterial IgG, IgM and IgA were detected. In the blood of children and adults aged up to 50 years antitoxic IgG were present at normal and high concentrations. In 50% of children antibacterial IgA were absent, while specific antibacterial IgM could be found at high concentrations. Changes in the content of antibacterial antibodies of different classes in sera were observed with age. More than 90% of adults had antibacterial IgA and IgG at normal and hig concentrations, while the level of IgM decreased. Under the influence of ecological, social, anthropogenic and other environmental factors the optimum levels of specific antibodies were replaced by anomalous ones, which led to an increased number of persons susceptible to diphtheria infection and in the intensity of the circulation of the infective agent. The deficiency of antidiphtheria antibacterial antibodies in the blood determined the necessity of correcting immunity by means of not only toxoid, but also bacterial antigens.


EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer.
EGFR/c-Met activation/amplification and co-expression, mTOR upregulation/activation, and Akt/Wnt signaling upregulation have been individually associated with more aggressive disease and characterized as potential prognostic markers for lung cancer patients. Tumors obtained from 109 participants with stage I-IV non-small cell lung cancer (NSCLC) were studied for EGFR/c-Met co-localization as well as for total and active forms of EGFR, c-Met, mTOR, S6K, beta-catenin, and Axin2. Slides were graded by two independent blinded pathologists using a validated scoring system. Protein expression profile correlations were assessed using Pearson correlation and Spearman's rho. Prognosis was assessed using Kaplan-Meier analysis. Protein expression profile analysis revealed significant correlations between EGFR/p-EGFR (p = 0.0412) and p-mTOR/S6K (p = 0.0044). Co-localization of p-EGFR/p-c-Met was associated with increased p-mTOR (p = 0.0006), S6K (p = 0.0018), and p-S6K (p < 0.0001) expression. In contrast, active beta-catenin was not positively correlated with EGFR/c-Met nor any activated proteins. Axin2, a negative regulator of the Wnt pathway, was correlated with EGFR, p-EGFR, p-mTOR, p-S6K, EGFR/c-Met co-localization, and p-EGFR/p-c-Met co-localization (all p-values <0.03). Kaplan-Meier analysis revealed shorter median survival in participants with high expression of Axin2, total beta-catenin, total/p-S6K, total/p-mTOR, EGFR, and EGFR/c-Met co-localization compared with low expression. After controlling for stage of disease at diagnosis, subjects with late-stage disease demonstrated shorter median survival when exhibiting high co-expression of EGFR/c-Met (8.1 month versus 22.3 month, p = 0.050), mTOR (6.7 month versus 22.3 month, p = 0.002), and p-mTOR (8.1 month versus 25.4 month, p = 0.004) compared with low levels. These findings suggest that increased EGFR/c-Met signaling is correlated with upregulated mTOR/S6K signaling, which may in turn be associated with shorter median survival in late-stage NSCLC.


Reevaluation of the role of progesterone in stimulating sexual receptivity in estrogen-treated gilts.
Three studies were conducted to examine the role of progesterone in stimulating sexual receptivity in estrogen-treated, ovariectomized gilts. Progesterone was administered either before, simultaneously with, or 48 h after estrogen. In each study, gilts were treated with either a suboptimal or an optimal dosage of estradiol benzoate (EB). Progesterone treatment (600 micrograms/kg BW-1 X injection-1) on alternate days for a total of four injections produced serum concentrations of progesterone that were maximal at 9.4 ng/ml and remained greater than 1 ng/ml for 15 d. Estradiol benzoate was administered 22 d after the first of these progesterone injections. When progesterone was administered concurrently with or 48 h after EB, the dosage was 100 micrograms/kg BW and produced a maximal serum progesterone concentration of 1.8 ng/ml 4 h after treatment. Gilts were placed in an evaluation pen with a boar for 5 min on d 3 and 4 after EB treatment. Traits of interest were total number of mounts by the boar, mounts before the gilt showed the immobilization response, proportion of gilts that showed the immobilization response, and latency from entry of the gilt into the evaluation pen until the immobilization response. In none of the three studies did progesterone improve any of the traits of interest. In each study the immobilization response was observed in a higher proportion of gilts treated with the optimal than in those treated with the suboptimal dosage of EB. Latency from entry of gilts into the evaluation pen until the immobilization response was less on d 4 than on d 3 after EB in all studies.(ABSTRACT TRUNCATED AT 250 WORDS)


[Costs and cost-effectiveness of Eptifibatide in the treatment of coronary ischemic syndromes. An analysis based on the PURSUIT study].
We analyzed whether using Eptifibatide plus heparin compared to heparin alone in patients with acute coronary ischemic syndromes is cost saving and/or cost-effective from the perspective of German hospitals. Our analysis is based on the clinical results of the PURSUIT study. We conducted an incremental cost-consequence and cost-effectiveness analysis from the perspective of the admitting hospital. Costs refer to the initial hospitalization following the event. Incremental drug costs are based on a 72 hour infusion of Eptifibatide. Additional costs are analyzed as resulting from the management of complicating myocardial infarctions, including incremental days on the general ward or intensive care unit as well as necessary revascularization procedures. All costs are expressed in EURO (EUR). The estimated costs of managing ischemic complications are based on typical patterns seen in German hospitals. Our estimation of the life-years saved by using Eptifibatide is based on the DEALE method. All calculations are standardized to a hypothetical cohort of 100 treated patients. There are 0.064 saved life-years per patient. Cost-effectiveness of Eptifibatide is EUR 14,464 per life-year saved. Eptifibatide is cost-effective compared to other therapies in the treatment of acute coronary ischemic syndromes. The additional costs of using this substance should be reimbursed to the hospitals.


DNA sequence analysis of Sry alleles (subgenus Mus) implicates misregulation as the cause of C57BL/6J-Y(POS) sex reversal and defines the SRY functional unit.
The Sry (sex determining region, Y chromosome) open reading frame from mice representing four species of the genus Mus was sequenced in an effort to understand the conditional dysfunction of some M. domesticus Sry alleles when present on the C57BL/6J inbred strain genetic background and to delimit the functionally important protein regions. Twenty-two Sry alleles were sequenced, most from wild-derived Y chromosomes, including 11 M. domesticus alleles, seven M. musculus alleles and two alleles each from the related species M. spicilegus and M. spretus. We found that the HMG domain (high mobility group DNA binding domain) and the unique regions are well conserved, while the glutamine repeat cluster (GRC) region is quite variable. No correlation was found between the predicted protein isoforms and the ability of a Sry allele to allow differentiation of ovarian tissue when on the C57BL/6J genetic background, strongly suggesting that the cause of this sex reversal is not the Sry protein itself, but rather the regulation of SRY expression. Furthermore, our interspecies sequence analysis provides compelling evidence that the M. musculus and M. domesticus SRY functional domain is contained in the first 143 amino acids, which includes the HMG domain and adjacent unique region (UR-2).


[Effect of progesterone on theophylline and prolactin stimulated Ca2+ exit from intracellular stores of pig oocytes].
Effect of progesterone on theophylline and prolactin stimulated Ca2+ exit from intracellular stores of pig oocytes was investigated using a fluorescent dye chlortetracycline. It is shown that in progesterone treated oocytes prolactin in concentration 50 ng/ml inhibits Ca2+ exit from intracellular stores of pig oocytes. Theophylline exerts the effect on prolactin Ca2+ exit from intracellular stores of pig oocytes. Employment of protein kinase C inhibitor cancelled inhibitory effect of prolactin and theophylline on Ca2+ exit from intracellular stores of pig oocytes. Ca2+ exit from intracellular stores of pig oocytes caused a joint influence of prolactin and GDP, and that of theophylline and GTP. The influence of protein kinase C inhibitor cancelled the stimulating effect of prolactin and GDP on Ca2+ exit from intracellular stores of pig oocytes also did not render any influence on the action of theophylline and GTP. These data suggest the influence of progesterone on theophylline and prolactin stimulated Ca2+ exit from intracellular stores of pig oocytes.


Paired cloning of the T cell receptor alpha and beta genes from a single T cell without the establishment of a T cell clone.
T cell receptors, which recognize antigen peptides on MHC molecules, are essential probes for the analysis of T cell antigen specificity. The identification of paired T cell receptor (TCR) chains, alpha/beta or gamma/delta, usually requires the establishment of T cell clones, which is not always available. In this study, we tried, as an alternative method, the paired cloning of TCR alpha/beta genes directly from a single T cell. T cells were sorted as a single cell from which RNA was extracted. Then, TCR alpha/beta CDR3 regions were amplified from the single cell-derived cDNA by reverse transcriptase-polymerase chain reaction to determine their sequences. We successfully identified pairs of TCR alpha/beta genes, and reconstructed the TCR molecule by a bacterial expression system. This strategy makes it possible to obtain recombinant TCR molecules from a single T cell without cellular cloning and promotes the investigation of T cell antigen specificity.


The evolution and functional significance of nested gene structures in Drosophila melanogaster.
Nearly 10% of the genes in the genome of Drosophila melanogaster are in nested structures, in which one gene is completely nested within the intron of another gene (nested and including gene, respectively). Even though the coding sequences and untranslated regions of these nested/including gene pairs do not overlap, their intimate structures and the possibility of shared regulatory sequences raise questions about the evolutionary forces governing the origination and subsequent functional and evolutionary impacts of these structures. In this study, we show that nested genes experience weaker evolutionary constraint, have faster rates of protein evolution, and are expressed in fewer tissues than other genes, while including genes show the opposite patterns. Surprisingly, despite completely overlapping with each other, nested and including genes are less likely to display correlated gene expression and biological function than the nearby yet nonoverlapping genes. Interestingly, significantly fewer nested genes are transcribed from the same strand as the including gene. We found that same-strand nested genes are more likely to be single-exon genes. In addition, same-strand including genes are less likely to have known lethal or sterile phenotypes than opposite-strand including genes only when the corresponding nested genes have introns. These results support our hypothesis that selection against potential erroneous mRNA splicing when nested and including genes are on the same strand plays an important role in the evolution of nested gene structures.


A novel algorithm combining finite state method and genetic algorithm for solving crude oil scheduling problem.
A hybrid optimization algorithm combining finite state method (FSM) and genetic algorithm (GA) is proposed to solve the crude oil scheduling problem. The FSM and GA are combined to take the advantage of each method and compensate deficiencies of individual methods. In the proposed algorithm, the finite state method makes up for the weakness of GA which is poor at local searching ability. The heuristic returned by the FSM can guide the GA algorithm towards good solutions. The idea behind this is that we can generate promising substructure or partial solution by using FSM. Furthermore, the FSM can guarantee that the entire solution space is uniformly covered. Therefore, the combination of the two algorithms has better global performance than the existing GA or FSM which is operated individually. Finally, a real-life crude oil scheduling problem from the literature is used for conducting simulation. The experimental results validate that the proposed method outperforms the state-of-art GA method.


Leisure activities and cognitive function in middle age: evidence from the Whitehall II study.
To test the hypothesis of a positive association, independent of social position, between participation in leisure activities and cognitive function in middle age. The nature of this relation is explored by first classifying leisure activities as entailing high or low cognitive effort, and then classifying them as entailing individual or social activities. London based office staff (Whitehall II study) in 20 civil service departments at baseline. Data are from the fifth wave of data collection (phase 5) of a prospective cohort study, collected through clinical examination and a self administered questionnaire. Firstly, hierarchical multiple regression was used to examine age and socioeconomic status (SES) adjusted effect of each leisure activity on cognition. Then structural equation models were used to examine the effects of two categories of leisure activities-activities entailing high or low cognitive effort and social or individual activities. All analyses are cross sectional. There was an age and SES adjusted association between participation in leisure activities and cognitive function. More specifically, leisure activity entailing high cognitive effort or social interaction was associated with better cognitive ability. Participation in cognitively complex or social leisure activities has an independent association with adult cognition, suggesting that seeking mental stimulation may have a beneficial effect on cognition in middle age.


Why do so many Americans oppose the Affordable Care Act?
The Patient Protection and Affordable Care Act (ACA) was passed by a Democratic Congress and signed into law by a Democratic president in 2010. Republican congressmen, governors, and Republican candidates have consistently opposed the ACA and have vowed to repeal it. Polls have consistently shown that it is supported by <50% of Americans. The most important goal of the ACA is to improve the health of Americans by increasing the number covered by health insurance. In the first year of its implementation, more than 10 million citizens gained health insurance. The percentage of Americans without health insurance decreased from 18% in July 2013 to 13.4% in June 2014. In addition, the ACA has eliminated many of the negative features of private insurance such as the denial of coverage for those with "prior conditions." The benefits of Medicare have been enhanced to decrease the cost of prescription drugs and to eliminate co-pays for preventive services. Despite these positive changes, a near majority of Americans still oppose the ACA, even though they approve of most of its features. They oppose the mandate that all Americans must have health insurance (the individual mandate), and they oppose a government role in health care. Yet Medicare, a mandatory insurance for seniors administered by the federal government since 1965, is overwhelmingly approved by the American public. The opposition to a government role in health care is based on the fact that that the vast majority of our citizens do not trust their government. Republicans are much less trusting of the federal government and much less supportive of a government role in health care than Democrats. The overwhelmingly negative TV ads against the ACA by the Republican candidates in the elections of 2012 and 2014 have had a major impact on Americans' views of the ACA. More than 60% of Americans have stated that most of what they know about the ACA came from watching TV. Opposition to a government role in health care and to mandatory health insurance makes it unlikely that the US will be able to insure that all of its citizens have ongoing access to health care in the near future.


Preparing Poly (Lactic-co-Glycolic Acid) (PLGA) Microspheres Containing Lysozyme-Zinc Precipitate Using a Modified Double Emulsion Method.
Lysozyme, as a model protein, was precipitated through the formation of protein-Zn complex to micronize for subsequent encapsulation within poly (lactic-co-glycolic acid) (PLGA) microspheres. Various parameters, including pH, type and concentration of added salts and protein concentration, were modified to optimize the yield of protein complexation and precipitation. The resulting protein particles (lysozyme-Zn complex as a freshly prepared suspension or a freeze-dried solid) were then loaded into PLGA (Resomer(®) 503H) microspheres, using a double emulsion technique and microspheres encapsulation efficiency and their sizes were determined. It was observed that salt type could significantly influence the magnitude of protein complexation. At the same conditions, zinc chloride was found to be more successful in producing pelletizable lysozyme. Generally, higher concentrations of protein solution led also to the higher yields of complexation and at the optimum conditions, the percentage of pelletizable lysozyme reached to 80%. Taking advantage of this procedure, a modified technique for preparation of protein-loaded PLGA microspheres was established, although it is also expected that this technique increases the protein drugs stabilization during the encapsulation process.


Population structure in a continuously distributed coastal marine species, the harbor porpoise, based on microhaplotypes derived from poor-quality samples.
Harbor porpoise in the North Pacific are found in coastal waters from southern California to Japan, but population structure is poorly known outside of a few local areas. We used multiplexed amplicon sequencing of 292 loci and genotyped clusters of single nucleotide polymoirphisms as microhaplotypes (N = 271 samples) in addition to mitochondrial (mtDNA) sequence data (N = 413 samples) to examine the genetic structure from samples collected along the Pacific coast and inland waterways from California to southern British Columbia. We confirmed an overall pattern of strong isolation-by-distance, suggesting that individual dispersal is restricted. We also found evidence of regions where genetic differences are larger than expected based on geographical distance alone, implying current or historical barriers to gene flow. In particular, the southernmost population in California is genetically distinct (FST = 0.02 [microhaplotypes]; 0.31 [mtDNA]), with both reduced genetic variability and high frequency of an otherwise rare mtDNA haplotype. At the northern end of our study range, we found significant genetic differentiation of samples from the Strait of Georgia, previously identified as a potential biogeographical boundary or secondary contact zone between harbor porpoise populations. Association of microhaplotypes with remotely sensed environmental variables indicated potential local adaptation, especially at the southern end of the species' range. These results inform conservation and management for this nearshore species, illustrate the value of genomic methods for detecting patterns of genetic structure within a continuously distributed marine species, and highlight the power of microhaplotype genotyping for detecting genetic structure in harbor porpoises despite reliance on poor-quality samples.


Reconstruction in head-and-neck cancers - analysis of the learning curve.
Oral cancers are some of the most common cancers in India. Most patients present with locally advanced disease requiring extensive resection resulting in large defects. Reconstruction of these defects plays a major role in restoring form and function to these patients, as well as enabling the delivery of adjuvant therapy on time. The aim of this study was to analyze the learning curve involved in microvascular surgery. A retrospective analysis of the case records of all patients of oral cancers, who underwent resection and reconstruction between January 2008 and December 2012 at our institute, was done. Demographic, clinical, and pathological data were collected and analyzed. Statistical analysis was done using the SPSS software. The operative time and the postoperative ventilation (7.8 h and 3.7 days, respectively) were significantly higher than those for pedicled flaps (3.6 h and 1.4 days, respectively). Both these variables reached statistical significance with P < 0.05 and < 0.04. The hospital stay was also statistically significantly longer for patients who underwent free-flap reconstruction (17.9 days vs. 7.9 days; P < 0.05). The number of reexplorations were higher in the free-flap group (31), when compared to the pedicled flap group (9). However, partial flap loss was higher in the pedicled flap subset when compared to the free-flap group. The complications significantly dropped after the performance of 30-40 free flaps. There is a steep learning curve in microvascular surgery, but the cosmetic and functional outcomes outweigh the complications.


Spatial patterns of air pollutants and social groups: a distributive environmental justice study in the phoenix metropolitan region of USA.
Quantifying spatial distribution patterns of air pollutants is imperative to understand environmental justice issues. Here we present a landscape-based hierarchical approach in which air pollution variables are regressed against population demographics on multiple spatiotemporal scales. Using this approach, we investigated the potential problem of distributive environmental justice in the Phoenix metropolitan region, focusing on ambient ozone and particulate matter. Pollution surfaces (maps) are evaluated against the demographics of class, age, race (African American, Native American), and ethnicity (Hispanic). A hierarchical multiple regression method is used to detect distributive environmental justice relationships. Our results show that significant relationships exist between the dependent and independent variables, signifying possible environmental inequity. Although changing spatiotemporal scales only altered the overall direction of these relationships in a few instances, it did cause the relationship to become nonsignificant in many cases. Several consistent patterns emerged: people aged 17 and under were significant predictors for ambient ozone and particulate matter, but people 65 and older were only predictors for ambient particulate matter. African Americans were strong predictors for ambient particulate matter, while Native Americans were strong predictors for ambient ozone. Hispanics had a strong negative correlation with ambient ozone, but a less consistent positive relationship with ambient particulate matter. Given the legacy conditions endured by minority racial and ethnic groups, and the relative lack of mobility of all the groups, our findings suggest the existence of environmental inequities in the Phoenix metropolitan region. The methodology developed in this study is generalizable with other pollutants to provide a multi-scaled perspective of environmental justice issues.


Assembly of the mitochondrial system. Purification of a mitochondrial product of the ATPase.
A low-molecular-weight protein synthesized in yeast mitochondria was purified. The protein was identified as a component of the rutamycin-sensitive ATPase. The amino-acid composition of the purified protein shows an extremely large preponderance of nonpolar residues, which may account for its solubility in chloroform-methanol. Indirect evidence suggests that this component is involved in the conferral of rutamycin sensitivity and may also have a function in the assembly of the ATPase complex.


Current issues in diagnostic breast pathology.
On behalf of the NHS Breast Screening Programme Pathology Coordinating Group we present recommendations for terminology and diagnostic criteria for a number of key areas of practice in breast pathology where terminology can be confusing and where accurate communication will ensure appropriate clinical management. These recommendations cover columnar cell lesions and the spectrum of changes that can be seen in these epithelial proliferations, lobular neoplasia, micrometastases and isolated tumour cells in axillary lymph nodes, the use of basal/myoepithelial markers in diagnostic practice and oestrogen receptor testing in ductal carcinoma in situ.


Fire injury reduces inducible defenses of lodgepole pine against Mountain pine beetle.
We examined the effect of wildfire injury on lodgepole pine chemical defenses against mountain pine beetle. We compared the constitutive phloem chemistry among uninjured, lightly-, moderately-, and severely-injured trees, and the induced chemistry elicited by simulated beetle attack, among these same categories. We also compared the entry rates of caged female beetles into trees of these categories. The volatiles we studied included thirteen monoterpene hydrocarbons, four allylic monoterpene alcohols, one ester, and one phenyl propanoid, of which the monoterpene hydrocarbons always comprised 96% or more of the total. Fire injury reduced the total concentration of these compounds in the induced but not constitutive phloem tissue of lodgepole pines. Fire injury also affected the relative composition of some volatiles in both induced and constitutive phloem. For example, increased fire injury reduced 4-allylanisole, a host compound that inhibits mountain pine beetle aggregation. Increased fire injury also increased (-) α-pinene, which can serve as precursor of pheromone communication. However, it also reduced myrcene and terpinolene, which can serve as stimulants and synergists of pheromone communication. Beetle entry did not show statistical differences among fire injury categories, although there was a trend to increased entry with fire injury. These results suggest that the reduced ability of trees to mobilize induced chemical defenses is an important mechanism behind the higher incidence of attack on fire-injured trees in the field. Future studies should concentrate on whether beetles that enter fire-injured trees are more likely to elicit aggregation, based on the differences we observed in volatile composition.


Selective sweep probabilities in spatially expanding populations.
Evolution during range expansions is an important feature of many biological systems including tumours, microbial communities, and invasive species. A selective sweep is a fundamental process, in which an advantageous mutation evades clonal interference and spreads through the population to fixation. However, most theoretical investigations of selective sweeps have assumed constant population size or have ignored spatial structure. Here we use mathematical modelling and analysis to investigate selective sweep probabilities in populations that grow with constant radial expansion speed. We derive probability distributions for the arrival time and location of the first surviving mutant and hence find simple approximate and exact expressions for selective sweep probabilities in one, two and three dimensions, which are independent of mutation rate. Namely, the selective sweep probability is approximately (1 -c wt / c m ) d , where c wt and c m are the wildtype and mutant radial expansion speeds, and d is the spatial dimension. Using agent-based simulations, we show that our analytical results accurately predict selective sweep frequencies in the two-dimensional spatial Moran process. We further compare our results with those obtained for alternative growth laws. Parameterizing our model for human tumours, we find that selective sweeps are predicted to be rare except during very early solid tumour growth, thus providing a general, pan-cancer explanation for findings from recent sequencing studies.


Vaccination of pediatric nurses with live attenuated cytomegalovirus.
Congenital cytomegalovirus (CMV) infections contribute considerably to morbidity and mortality among infants in the United States. In a preliminary study aimed at protecting fetuses from congenital disease we evaluated Towne 125-strain CMV vaccine in ten female pediatric nurses of childbearing age. The women were seen 2, 4, 8, 12, 26, 39, and 52 weeks after vaccination; specimens were obtained for routine laboratory testing, virus isolation, cell-mediated immunity testing, and serologic examination (complement fixation, anticomplement immunofluorescence [ACIF], and neutralization). Local but not systemic reactions were observed in all subjects. Serologic responses appeared at two to four weeks and peaked at four to eight weeks. Mean titers were highest in the ACIF test. A cell-mediated immune response, as assayed by lymphocyte proliferation, was observed in all women, and in most there was a biphasic pattern. Towne 125-strain CMV vaccine seems to be safe and immunogenic in women of childbearing age.


iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data.
RNA-seq is widely used for transcriptomic profiling, but the bioinformatics analysis of resultant data can be time-consuming and challenging, especially for biologists. We aim to streamline the bioinformatic analyses of gene-level data by developing a user-friendly, interactive web application for exploratory data analysis, differential expression, and pathway analysis. iDEP (integrated Differential Expression and Pathway analysis) seamlessly connects 63 R/Bioconductor packages, 2 web services, and comprehensive annotation and pathway databases for 220 plant and animal species. The workflow can be reproduced by downloading customized R code and related pathway files. As an example, we analyzed an RNA-Seq dataset of lung fibroblasts with Hoxa1 knockdown and revealed the possible roles of SP1 and E2F1 and their target genes, including microRNAs, in blocking G1/S transition. In another example, our analysis shows that in mouse B cells without functional p53, ionizing radiation activates the MYC pathway and its downstream genes involved in cell proliferation, ribosome biogenesis, and non-coding RNA metabolism. In wildtype B cells, radiation induces p53-mediated apoptosis and DNA repair while suppressing the target genes of MYC and E2F1, and leads to growth and cell cycle arrest. iDEP helps unveil the multifaceted functions of p53 and the possible involvement of several microRNAs such as miR-92a, miR-504, and miR-30a. In both examples, we validated known molecular pathways and generated novel, testable hypotheses. Combining comprehensive analytic functionalities with massive annotation databases, iDEP ( http://ge-lab.org/idep/ ) enables biologists to easily translate transcriptomic and proteomic data into actionable insights.


Functional movement ScreenTM--normative values in healthy distance runners.
Recreational runners have an estimated overuse injury incidence rate of up to 79% and 90% for marathoners. A pre-participation screening tool that can identify risk for injury may help reduce overuse injury in runners. The Functional Movement Screen (FMS(TM)) is a reliable clinical tool used with athletes to help predict injury. To date, the FMS(TM) has not been used with endurance athletes. The purpose of this article is to establish normative FMS(TM) values for distance runners. 45 healthy runners performed the FMS(TM). Descriptive statistics were calculated; independent t-tests were performed to examine the effect of gender, experience and injury on scores. A Chi-square test was used to evaluate whether significant differences in scores exist for any component of the FMS(TM). The mean FMS(TM) score was 13.13±1.8. No significant differences in FMS(TM) scores were found between novice and experienced runners (p=0.71) or runners with a history of injury and those without (p=0.20). While male and female runners did not differ significantly in their total FMS(TM) score (p=0.65), significant differences were found in the deep squat (p<0.05), trunk stability push-up (p<0.001) and active straight leg raise components (p=0.002). This study provides normative values for FMS(TM) scores when testing uninjured distance runners.


Improvement in Dissolution Rate of Cefuroxime Axetil by using Poloxamer 188 and Neusilin US2.
A combination of fusion and surface adsorption techniques was used to enhance the dissolution rate of cefuroxime axetil. Solid dispersions of cefuroxime axetil were prepared by two methods, namely fusion method using poloxamer 188 alone and combination of poloxamer 188 and Neusilin US2 by fusion and surface adsorption method. Solid dispersions were evaluated for solubility, phase solubility, flowability, compressibility, Kawakita analysis, Fourier transform-infrared spectra, differential scanning calorimetry, powder X-ray diffraction study, in vitro drug release, and stability study. Solubility studies showed 12- and 14-fold increase in solubility for solid dispersions by fusion method, and fusion and surface adsorption method, respectively. Phase solubility studies showed negative ΔG (0) tr values for poloxamer 188 at various concentrations (0, 0.25, 0.5, 0.75 and 1%) indicating spontaneous nature of solubilisation. Fourier transform-infrared spectra and differential scanning calorimetry spectra showed that drug and excipients are compatible with each other. Powder X-ray diffraction study studies indicated that presence of Neusilin US2 is less likely to promote the reversion of the amorphous cefuroxime axetil to crystalline state. in vitro dissolution studies, T50% and mean dissolution time have shown better dissolution rate for solid dispersions by fusion and surface adsorption method. Cefuroxime axetil release at 15 min (Q15) and DE15 exhibited 23- and 20-fold improvement in dissolution rate. The optimized solid dispersion formulation was stable for 6 months of stability study as per ICH guidelines. The stability was ascertained from drug content, in vitro dissolution, Fourier transform-infrared spectra and differential scanning calorimetry study. Hence, this combined approach of fusion and surface adsorption can be used successfully to improve the dissolution rate of poorly soluble biopharmaceutical classification system class II drug cefuroxime axetil.


Modular microfluidics for point-of-care protein purifications.
Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured to suit a variety of fluidic operations or biochemical processes. We demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.


A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence.
Kratom (Mitragyna speciosa) has been used for medicinal and recreational purposes. It has reported analgesic, euphoric and antitussive effects via its action as an agonist at opioid receptors. It is illegal in many countries including Thailand, Malaysia, Myanmar, South Korea and Australia; however, it remains legal or uncontrolled in the UK and USA, where it is easily available over the Internet. We describe a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. He demonstrated dependence on kratom with withdrawal symptoms consisting of anxiety, restlessness, tremor, sweating and cravings for the substance. A reducing regime of dihydrocodeine and lofexidine proved effective in treating subjective and objective measures of opioid-like withdrawal phenomena, and withdrawal was relatively short and benign. There are only few reports in the literature of supervised detoxification and drug treatment for kratom dependence. Our observations support the idea that kratom dependence syndrome is due to short-acting opioid receptor agonist activity, and suggest that dihydrocodeine and lofexidine are effective in supporting detoxification.


Association Between Postpartum Breast Cancer Diagnosis and Metastasis and the Clinical Features Underlying Risk.
In women 45 years or younger, breast cancer diagnosis after childbirth increases the risk for metastasis and death, yet limited data exist to define this window of risk and associated prognostic factors. To assess the window of elevated risk for metastasis following a postpartum breast cancer (PPBC) diagnosis and whether clinical prognostic factors are associated with the increased risk. This multicenter cohort study conducted using cases from the Colorado Young Women's Breast Cancer Cohort diagnosed between January 1, 1981, and December 31, 2014, included 701 women 45 years or younger with stage I to III invasive breast cancer for whom parity data, including time of last childbirth, were available. Data analysis was conducted from July 1 to September 30, 2017. This study involved a tertiary care academic hospital-based breast center and its regional affiliates with cases from the greater Rocky Mountain region. Primary exposures were prior childbirth or no childbirth, time between most recent childbirth and breast cancer diagnosis, and time between breast cancer diagnosis and metastasis. The primary outcome was distant metastasis-free survival. A total of 701 women 45 years or younger from the greater Rocky Mountain states region were included in the analysis; mean (SD) age at diagnosis was 37.9 (5.1) years. Breast cancer diagnosis within 10 years after parturition was associated with elevated risk for metastasis, particularly in women with stage I or II disease. In addition, women with PPBC diagnosed within 10 years of a completed pregnancy that was estrogen receptor-positive showed distant metastasis-free survival similar to that of nulliparous patients with estrogen receptor-negative cancer, and women with estrogen receptor-negative PPBC had further reduced metastasis-free survival. Moreover, women with PPBC had increased lymphovascular invasion and lymph node involvement. In addition, tumor-associated Ki67 positivity identified 129 patients with luminal B cancer in the cohort that, independent of parity status, had poorer prognosis compared with patients with luminal A cancer, although it did not reach statistical significance. Diagnosis of PPBC within 10 years post partum appears to be associated with an increased risk for metastasis. This increased risk was highest in stages I and II cancer at diagnosis and present in both patients with estrogen receptor-positive and estrogen receptor-negative cancer, persisting in estrogen receptor-positive cases for up to 15 years after diagnosis. Postpartum breast cancer diagnoses were not associated with increased Ki67 index but were associated with increased lymphovascular invasion and lymph node involvement compared with breast cancer in nulliparous patients.


Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results.
Nilotinib (Tasigna) is a potent and selective BCR-ABL inhibitor approved for use in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CML-CP) and in patients with CML-CP and accelerated phase (CML-AP) who are resistant to or intolerant of imatinib. Patients with CML-AP (N = 137) with at least 24 months of follow-up or who discontinued early were evaluated to determine the efficacy and tolerability of nilotinib. The majority (55%) of patients achieved a confirmed hematologic response, and 31% attained a confirmed complete hematologic response on nilotinib treatment. Overall, 32% of patients achieved major cytogenetic responses (MCyR), with most being complete cytogenetic responses. Responses were durable, with 66% of patients maintaining MCyR at 24 months. The estimated overall and progression-free survival rates at 24 months were 70% and 33%, respectively. Grade 3/4 neutropenia and thrombocytopenia were each observed in 42% of patients. Non-hematologic adverse events were mostly mild to moderate; the safety profile of nilotinib has not changed with longer follow-up. In all, 20 (15%) patients remained on study at data cutoff. In summary, nilotinib has a manageable safety profile, and can provide favorable long-term outcomes in the pretreated CML-AP patient population for whom treatment options are limited.


Post-outbreak serological screening for SARS-CoV-2 infection in healthcare workers at a Swedish University Hospital.
Nosocomial outbreaks of coronavirus disease 2019 (COVID-19) can have devastating consequences from both a resource cost and patient healthcare perspective. Relying on reverse transcription-polymerase chain reaction (RT-PCR) for identifying infected individuals may result in missed cases. Screening for antibodies after an outbreak can help to find missed cases and better illuminate routes of transmission. In this study, we present the results of a serological screening of the healthcare workers (HCWs) on a ward for infectious diseases in Sweden with a point-of-care antibody test 8 weeks after an outbreak of COVID-19. In all, 107/123 (87%) of HCWs who were tested with RT-PCR in the outbreak investigation participated in this study on seroprevalence. Participants were also asked to fill out a questionnaire entailing epidemiological data. The cohort was stratified by RT-PCR result and the resulting groups were compared to each other. Six (8%) HCWs who were tested RT-PCR negative during the outbreak investigation had developed specific IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These HCWs had all worked shifts with colleagues who later were tested RT-PCR positive during the outbreak. Our results indicate that a serological follow-up screening after an outbreak may be used as a complement to virus detection in an outbreak situation. However, immunoglobulin (Ig) G-detection should also be performed at the start of an outbreak, to facilitate interpretation of the results.


Cost-effectiveness of full and partial opioid agonists for opioid use disorder in outpatient settings: United States healthcare sector perspective.
Studies show that medications for opioid use disorder (MOUD) reduce illicit opioid use, emergency healthcare services, opioid-related overdose, and death. However, few studies have investigated the long-term cost-effectiveness of MOUD in office-based opioid treatment (OBOT) and opioid treatment program (OTP) settings. We aimed to estimate the cost, utility, quality-adjusted life years gained (QALYs), and incremental cost-effectiveness ratios (ICERs) of three MOUD compared to each other and counseling without medication from a US healthcare sector perspective. Our study developed a Markov model to conduct a cost-effectiveness analysis of counseling and three MOUD in the OBOT and OTP settings: sublingual buprenorphine/naloxone (BUPNX), buprenorphine extended-release (XR-BUP) injection, and oral methadone. The model included five health states representing combinations of receiving or off treatment while either using or not actively using illicit opioids, and death. The cycle length was one month; the time-horizon was 10 years. The study obtained model inputs from systematic reviews of published literature and public data. 3 % annual discount rate was applied to cost and utility calculation. The primary outcomes included total costs, life-years (LYs), QALYs, and ICERs. We also conducted scenario analysis using a hypothetical OBOT outpatient setting with methadone. In the base-case OBOT setting, the total costs and QALYs, respectively, were counseling $22,848, 5.60; BUPNX $29,875, 5.82; and XR-BUP $63,936, 5.87. ICERs were $32,345/QALY (BUPNX vs counseling) and $625,858/QALY (XR-BUP vs BUPNX). In the OTP setting, the total costs of counseling, methadone, BUPNX, and XR-BUP were $20,124, $27,000, $33,500, and $75,272, respectively. QALYs of methadone were 5.86. QALYs of counseling, BUPNX, and XR-BUP remained the same as the OBOT setting. Incremental ICERs were $26,714/QALY (methadone vs counseling) and $3,337,623/QALY (XR-BUP vs methadone). BUPNX was dominated by methadone. In the scenario analysis, BUPNX was also dominated by methadone. Outpatient MOUD resulted in important gains in quality of life and life expectancy. In both OBOT and OTP settings, XR-BUP was not cost-effective. BUPNX was cost-effective in the OBOT setting, while it was dominated by methadone in the OTP setting. The cost-effectiveness of BUPNX and XR-BUP could be enhanced if the costs of these medications were reduced.


Clinical trial of intramuscular anti-snake venom administration as a first aid measure in the field in the management of Russell's viper bite patients.
Efficacy of intramuscular anti-snake venom administration immediately after bite as a first aid measure in the field followed by standard hospital management versus standard hospital management alone in the therapy of Russell's viper bite patients was studied. There was a definite reduction in the number of patients with systemic envenomation, complications following disseminated intravascular coagulation and in fatality rate of Russell's viper bite victims who had received first aid intramuscular anti-snake venom prior to hospitalization when compared with those who had not.


Fragility and basic process energies in vitrifying systems.
The concept of 'fragility' constitutes a central point of the glass transition science serving as the 'universal' metric linking previtreous dynamics of qualitatively distinct systems. Finding the fundamental meaning of fragility is the 'condicio sine qua' for reaching the long expected conceptual breakthrough in this domain. This report shows that fragility is determined by the ratio between two fundamental process energies, viz. the activation enthalpy and activation energy. The reasoning, avoiding any underlying physical model, is supported by the experimental evidence ranging from low molecular weight liquids and polymers to plastic crystals and liquid crystals. All these lead to the new general scaling plot for dynamics of arbitrary glass former. The limited adequacy of broadly used so far semi-empirical relationships between fragility and the activation energy is shown. Results presented remain valid for an arbitrary complex system and collective phenomena if their dynamics is described by the general super-Arrhenius relation.


Fisetin inhibits IL-31 production in stimulated human mast cells: Possibilities of fisetin being exploited to treat histamine-independent pruritus.
Interleukin-31 (IL-31) is a recently discovered cytokine that is tightly linked to the pathogenesis of pruritus seen in atopic dermatitis. Flavonoids, like fisetin, are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. the present study sought to investigate whether fisetin modulates IL-31 and histamine release in human mast cells (HMC-1). HMC-1 cells were pretreated with fisetin at various doses and stimulated with phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PI) for different time intervals. We evaluated IL-31 production and histamine release and signaling mechanism of the action of fisetin on IL-31 production. We also investigated the effects of fisetin on scratching behaviors in mice. Fisetin decreased PI-stimulated mRNA expression and production of IL-31 in HMC-1 cells. Fisetin inhibited PI-induced phosphorylation of mitogen-activated protein kinases that further suppressed nuclear factor (NF-κB) activation and translocation to the nucleus through the inhibition of IκB-α phosphorylation. Fisetin also prevented mast cell release of histamine in HMC-1 cells. Mice in-vivo studies show that fisetin reduced scratching behaviors in mice. These pharmacological actions of fisetin provide new suggestions that fisetin can be of potential use for the treatment of pruritus that cannot be treated with histamine receptor blockers alone.


Effects of different levels of intravenous alpha-linolenic acid and supplemental breast milk on red blood cell docosahexaenoic acid in very low birth-weight infants.
Preterm infants weighing less than 1,500 g were started on total parenteral nutrition (TPN) if unable to tolerate full enteral feedings. They were randomly assigned to receive intravenous lipids containing either 4.2 or 9.0% alpha-linolenic acid to assess the effect on red blood cell (RBC) phospholipid polyenoic fatty acid composition, particularly docosahexaenoic acid (22:6n3) (DHA). DHA ultimately comes from alpha-linolenic acid (18:3n3), although there is evidence in human preterm infants that they require preformed DHA. After 1 week of TPN, infants were started on gradually increasing amounts of enteral feeding, breast milk, if elected by mothers, or premature milk formula (Preemie Enfamil). RBC phospholipid fatty acids were measured weekly. Results were evaluated comparing samples from week 1 and week 6. Supplying 9% alpha-linolenic acid in intravenous lipids did not prevent a fall in DHA by 6 weeks; however, infants receiving breast-milk feeding did not have a significant decrease in DHA. Studies are needed to evaluate supplying DHA in intravenous lipids.


Protective Effect of Patchouli Alcohol Against High-Fat Diet Induced Hepatic Steatosis by Alleviating Endoplasmic Reticulum Stress and Regulating VLDL Metabolism in Rats.
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic hepatic disorder worldwide. The earliest stage of NAFLD is simple steatosis, which is characterized by the accumulation of triglycerides in hepatocytes. Inhibition of steatosis is a potential treatment for NAFLD. Patchouli alcohol (PA) is an active component of Pogostemon cablin (Blanco) Benth. (Labiatae), which is a medicinal food in Asia countries and proved to possess hepatoprotective effect. This research aimed to investigate the effectiveness of PA against high fat diet (HFD)-induced hepatic steatosis in rats. In this study, male Sprague Dawley rats were fed a HFD for 4 weeks to induce NAFLD. Oral administration with PA significantly reduced pathological severity of steatosis in HFD-fed rats. It was associated with suppressing endoplasmic reticulum (ER) stress and regulating very low-density lipoprotein (VLDL) metabolism. Our data showed that PA treatment effectively attenuated ER stress by inhibiting the activation of protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), and activating transcription factor 6 (ATF6). Moreover, PA decreased hepatic VLDL uptake by suppressing very low-density lipoprotein receptor (VLDLR) expression. It also restored VLDL synthesis and export by increasing apolipoprotein B100 (apoB 100) secretion and microsomal triglyceride-transfer protein (MTP) activity. Taken together, PA exerted a protective effect on the treatment of NAFLD in HFD-fed rats and may be potential therapeutic agent acting on hepatic steatosis.


Fragile XE: an important differential diagnosis.
Fragile X is a common cause of mental retardation in boys that can also affect girls. We present the case of a 21-year-old woman with Fragile X E (FRAXE) with learning difficulty, behavioural problems and epilepsy. Her diagnosis was made after investigations spanning several years, highlighting the importance of considering FRAXE and the benefits of reviewing genetic test results in the light of advancing technology.


Syncope in adolescents.
Syncope is common in adolescents. It is usually attributable to simple faint, but the differential diagnosis includes other, less common disorders, such as migraine, epilepsy, hyperventilation, hysteria and cardiac dysrhythmia or outflow obstruction. The patient's feelings immediately before and after the syncopal episode will help the physician determine the cause. An observer's description of the event may also be helpful. Laboratory evaluation is seldom necessary.


Induction of immunity in mice to Fasciola hepatica with a Fasciola/Schistosoma cross-reactive defined immunity antigen.
The paradox of schistosomiasis is that infection confers immunity to its host, yet immunization with subcellular antigens of the parasite does not, in general, induce protective immunity. Infection or immunization with subcellular antigens of Fasciola hepatica confers high levels of immunity to a challenge infection with another trematode, Schistosoma mansoni. We have isolated by antibody affinity chromatography a Fasciola hepatica/Schistoma mansoni cross-reactive antigen, designated FhSmIII(M), and also have shown that this antigen confers immunity in mice to a challenge infection with S. mansoni. This antigen was compared with a crude F. hepatica worm extract (FhWWE) as to its ability to induce an IgG antibody response in mice, and to determine whether it had a protective effect in mice to a challenge infection with F. hepatica metacercariae. Mice immunized with FhSmIII(M) or FhWWE, and subsequently infected with F. hepatica, developed higher IgG antibody levels to FhSmIII(M), as measured by ELISA, than F. hepatica-infected controls. Mice immunized with FhWWE did not develop significant levels of resistance to challenge with F. hepatica metacercariae. Mice immunized with FhSmIII(M) and infected with F. hepatica metacercariae developed 69%-78% less worms than controls. An F. hepatica/S. mansoni cross-reactive, cross-protective defined immunity antigen confers in mice significant levels of protection to a challenge infection with F. hepatica.


Wide-area measurement-based supervision of the cerebral venous hemodynamic in a novel rat model.
Traumatic brain injury (TBI) includes primary and secondary injuries, while monitoring intracranial pressure (ICP) and cerebral blood flow (CBF) is conducive to improve the prognosis of patients. However, the function of cerebral venous in this process is still unclear. An acute epidural hematoma (AEDH) model was developed by placing a controllable micro balloon in the right epidural space of a rat. The laser speckle contrast imaging (LSCI) system was used to observe CBF in real time, while ICP was monitored simultaneously. And the stability of this model was examined by magnetic resonance imaging (MRI). The blood perfusion rate (BPR) of venous was significantly negatively correlated with ICP. In the 100 μ L group, the ipsilateral cerebral venous and microcirculation blood flow significantly decreased. According to the gross observations and pathological results, ischemic brain injury was the most serious on this condition. Modeling method is relatively simple, which effectively reduces the cost. The volume of the micro balloon is adjusted to simulate the volume of different size of hematomas. In addition, LSCI, as an advanced blood flow monitoring technology, has high sensitivity to detect subtle changes in CBF. This study successfully developed a stable and reproducible AEDH rat model. Based on this model, it is preliminarily demonstrated that local intracranial hypertension can cause cerebral venous return restriction, which is an indispensable factor leading to the aggravation of secondary brain injury.


Travel restrictions and infectious disease outbreaks.
A key purpose of the International Health Regulations (IHR) is to prevent unwarranted interruptions to trade and travel during large and/or transnational infectious disease outbreaks. Nevertheless, such outbreaks continue to disrupt the travel industry. This aspect of the IHR has received little attention in the academic literature despite its considerable impact on affected States and commercial activity. This article outlines the challenges and gaps in knowledge regarding the relationship between outbreaks and the travel sector and discusses the opportunities for further research and policy work to overcome these challenges. We conducted a literature review on the relationship between outbreaks and travel restrictions, with a particular focus on the 2014-16 Ebola epidemic in West Africa. This review was complemented by an expert roundtable at Chatham House and further supported by case studies and qualitative interviews. Numerous travel stakeholders are affected by, and affect, large-scale infectious disease outbreaks. These stakeholders react in different ways: peer pressure plays an important role for both governments and the travel sector, and the reactions of the media and public influence and are influenced by these stakeholders. While various data sources on travel are available, and World Health Organization is mandated to work with States, there is no recognized coordinating body to disseminate timely, consistent, reliable and authoritative information and best practices to all stakeholders. This article highlights the interdependent relationship between various travel stakeholders. The reasons for interruption of travel during the 2014-16 Ebola outbreak were complex, with decisions by States only partly contributing to the cessation. Decisions by non-state actors, particularly the travel industry itself, contributed significantly and were based on a variety of factors. Further research, analysis and policy development are required to mitigate the health and economic consequences of infectious disease outbreaks. Any further research will also need to take account of COVID-19 travel-related issues.


[Capabilities of telemedicine in conditions of self-contained shipping].
Was analyzed a capability of effectuating of telemedicine between a ship in automized navigation and specialists of board medical service using different variants of technical supporting and communication channels. During trial session of telemedicine was effectuated fibergastroduodenoscopy in operation room of cruiser, situated near a quay. Then session was effectuated when the ship was in sea. Was made a conclusion that effectuating sessions of telemedicine of physicians of board medical service and physicians of a ship in automized navigation is capable and advisable, but variants of technical realization need a development.


Transthoracic hilar and mediastinal biopsy.
Transthoracic needle biopsy (TNB) of the mediastinum is an accurate, safe, and cost-effective diagnostic tool for the evaluation of mediastinal masses and lymphadenopathy. The technique is most useful in the staging of carcinoma, where it serves as a less expensive and minimally invasive alternative to mediastinoscopy for establishing unresectability. With recent advances in immunohistochemical and core-biopsy techniques, TNB has become more accurate for establishing the initial diagnosis of lymphoma and for confirming recurrent disease. Core-needle biopsy has improved the accuracy of TNB and is particularly useful when fine-needle aspiration fails to yield a specific diagnosis, or when lymphoma or a noncarcinomatous lesion is suspected.


Auditory mechanics in the grig (Cyphoderris monstrosa): tympanal travelling waves and frequency discrimination as a precursor to inner ear tonotopy.
Ensiferan orthopterans offer a key study system for acoustic communication and the process of insect hearing. Cyphoderris monstrosa (Hagloidea) belongs to a relict ensiferan family and is often used for evolutionary comparisons between bushcrickets (Tettigoniidae) and their ancestors. Understanding how this species processes sound is therefore vital to reconstructing the evolutionary history of ensiferan hearing. Previous investigations have found a mismatch in the ear of this species, whereby neurophysiological and tympanal tuning does not match the conspecific communication frequency. However, the role of the whole tympanum in signal reception remains unknown. Using laser Doppler vibrometry, we show that the tympana are tonotopic, with higher frequencies being received more distally. The tympana use two key modalities to mechanically separate sounds into two auditory receptor populations. Frequencies below approximately 8 kHz generate a basic resonant mode in the proximal end of the tympanum, whereas frequencies above approximately 8 kHz generate travelling waves in the distal region. Micro-CT imaging of the ear and the presented data suggest that this tonotopy of the tympana drive the tonotopic mechanotransduction of the crista acustica (CA). This mechanism represents a functional intermediate between simple tuned tympana and the complex tonotopy of the bushcricket CA.


Closed-loop stable control of two deformable mirrors for compensation of amplitude and phase fluctuations.
A method for closed-loop stable control of two deformable mirrors for compensation of both amplitude and phase fluctuations is described. A generic implementation is described as well as an implementation that integrates the concept behind a point diffraction interferometer with a two-deformable-mirror system. The relationship of the closed-loop control algorithm to previously developed open-loop iterative algorithms is described. Simulation results are presented that indicate that the system is stable and provides superior performance over that of a single-deformable-mirror system. The impact of finite servo bandwidth on control of two deformable mirrors is evaluated by means of wave optical simulation, and it is found that to achieve a performance improvement attributable to compensation of amplitude fluctuations, the bandwidth of the two-deformable-mirror system must be at least twice the Greenwood frequency.


Gastrostomy, esophagitis, and gastrointestinal bleeding in older adults.
Percutaneous endoscopic gastrostomy tubes (PEG) are commonly used in older adults with dysphagia and poor nutrition. The association of PEG with upper gastrointestinal bleeding (UGIB) and role of gastroesophageal reflux disease (GERD) in relation to UGIB in patients with PEG are not well known. We conducted a retrospective analysis of older patients with PEG, hospitalized for UGIB, during a 1-year period between 1997 and 1998. The study was performed in a university teaching hospital involving residents from long-term care facilities (LTCF) of the Bronx. A total of 38 patients with PEG were admitted for UGIB; 28 were evaluated with upper endoscopy. The mean age of the group who underwent endoscopy was 83.4 +/- 9.2 years, with 18 females and 10 males. In the same group, 13 patients were on H2 blockers and 4 patients used nonsteroidal antiinflammatory drugs before hospitalization. None of the residents were on proton pump inhibitors. The most common upper endoscopic findings were esophagitis, either alone (11 patients) or in association with other lesions (10 patients). Esophagitis predominantly involved the lower third of the esophagus. Other significant findings on endoscopy were gastric and duodenal ulcers, gastritis, and gastric erosions either alone or in combinations. Esophagitis is a common occurrence and a significant contributor for UGIB in patients with PEG. Use of H2 blockers does not appear to be an effective preventive measure for UGIB in these patients.


TACI mutations and disease susceptibility in patients with common variable immunodeficiency.
The most prevalent primary immunodeficiency is common variable immunodeficiency (CVID). Mutations have been described in four genes, ICOS, CD19, BAFF-R and TNFRSF13B (encoding TACI), together associated with 10-15% of CVID cases. We investigated a family with CVID and identified the heterozygous C104R TNFRSF13B mutation in two of the three index-children with CVID, a mother with selective immunoglobulin A deficiency, a mother with recurrent infections and a healthy grandfather. Remarkably, we did not find the TNFRSF13B mutation in the third index-child with CVID, despite his hypogammaglobulinaemia and decreased response to unconjugated pneumococcal vaccine. This family illustrates that TNFRSF13B mutations induce disease susceptibility rather than cause disease directly. Apparently, other genetic or environmental factors, still to be identified, contributed to the development of CVID in this family. Consequently, TNFRSF13B mutations must be interpreted with caution in the clinical setting.


Familial aggregation of coronary artery calcium in families with type 2 diabetes.
Type 2 diabetes is widely recognized as a major risk factor for atherosclerotic cardiovascular disease, including subclinical atherosclerosis as measured by noninvasive procedures. However, the role of genetic factors that contribute to various measures of subclinical atherosclerosis is largely unknown. We hypothesize that subclinical atherosclerosis, measured as coronary artery calcification (CAC), will be extensive in individuals with type 2 diabetes and that its presence depends on both genetic and environmental factors. The genetic factors should result in the familial aggregation of CAC. To determine the extent of familial aggregation of CAC in the presence of type 2 diabetes, we studied 122 individuals with type 2 diabetes (mean age 60 years) and 13 individuals without diabetes in 56 families. CAC was measured by fast-gated helical computed tomography. Other measured factors included blood pressure, body size, lipids, HbA1c, and self-reported medical history. To test for an association between CAC and these factors while accounting for the potential familial correlation of CAC, generalized estimating equations were used. CAC was detectable in 80% of individuals with diabetes (median score 84, range 0-5,776). Extent of CAC, adjusted for age, was positively associated with male sex (P = 0.0003), reduced HDL (P = 0.02), albumin-to-creatinine ratio (P = 0.008), and cigarette pack-years (P = 0.03). CAC was also positively associated with a history of angina, myocardial infarction, stroke, and vascular procedures (all P < 0.01). HbA1c and fasting glucose were positively, but nonsignificantly, associated with the extent of CAC (P = 0.14 and 0.08, respectively). CAC, adjusted for age, sex, race, and diabetes status, was heritable (h2 = 0.50; P = 0.009). In multivariate analysis with additional adjustment for HDL, BMI, hypertension, and smoking, h2 = 0.40 (P = 0.038). These results suggest that strong (independent) genetic factors as well as environmental factors contribute to the variance of CAC in individuals with type 2 diabetes. In these data, CAC seems heritable and may serve as an important feature in designing studies to map genes contributing to both atherosclerosis and type 2 diabetes.


Occurrence of spontaneous tumours of the renal proximal tubules in oscars Astronotus ocellatus.
This report describes the occurrence of renal papillary cystic adenomas and adenocarcinomas in oscars Astronotus ocellatus Cuvier, 1829. Samples from 5 oscars with abdominal swelling were collected between 1996 and 2004 and compared to a published case from the USA. Macroscopically, all cases revealed a large, well-demarcated, greyish-brown nodular mass in a retroperitoneal position within the body cavity, and originating from the posterior kidney. Histologically, these neoplasms were composed of epithelial cells, which were arranged in papillary cystic tubular structures and partly covered by cilia. In this study, microscopic and ultrastructural examination confirmed that the origin of the neoplasm was the proximal tubules of the kidney.


Emerging and Diverse Functions of the EphA2 Noncanonical Pathway in Cancer Progression.
Erythropoietin-producing hepatocellular receptor A2 (EphA2) receptor tyrosine kinase controls multiple physiological processes to maintain homeostasis in normal cells. In many types of solid tumors, it has been reported that EphA2 is overexpressed and plays a critical role in oncogenic signaling. However, in recent years, the opposing functions of EphA2 have been explained by the canonical and noncanonical signaling pathways. Ligand- and tyrosine kinase-dependent EphA2 activation (the canonical pathway) inhibits cancer cell proliferation and motility. In contrast, ligand- and tyrosine kinase-independent EphA2 signaling (the noncanonical pathway) promotes tumor survival and metastasis and controls acquired drug resistance and maintenance of cancer stem cell-like properties. Evidence has accumulated showing that the EphA2 noncanonical pathway is mainly regulated by inflammatory cytokines and growth factors via phosphorylation at Ser-897 in the intracellular C-tail region via some serine/threonine kinases, including p90 ribosomal S6 kinase. In this review, we focus on the regulation of Ser-897 phosphorylation and its functional importance in tumor malignancy and discuss future therapeutic targeting.


Both insulin and epidermal growth factor stimulate lipogenesis and acetyl-CoA carboxylase activity in isolated adipocytes. Importance of homogenization procedure in avoiding artefacts in acetyl-CoA carboxylase assay.
Epidermal growth factor (EGF) stimulates lipogenesis by 3-4-fold in isolated adipocytes, with a half-maximal effect at 10 nM-EGF. In the same batches of cells insulin stimulated lipogenesis by 15-fold. Freezing and prolonged homogenization of adipocytes results in release of large quantities of pyruvate carboxylase from broken mitochondria, and sufficient pyruvate can be carried through into assays for this enzyme to cause significant interference with assays of acetyl-CoA carboxylase in crude adipocyte extracts. This may account for the high amount of citrate-independent acetyl-CoA carboxylase activity reported to be present in adipocyte extracts in some previous publications. This problem may be eliminated by homogenizing very briefly without freezing. By using the modified homogenization procedure, EGF treatment of adipocytes was shown to produce an effect on acetyl-CoA carboxylase activity almost identical with that of insulin. Both messengers increase Vmax. without significant effect on the Ka for the allosteric activator, citrate.


COVID-19 quarantine measures are associated with negative social impacts and compromised follow-up care in patients with inflammatory bowel disease in Brazil.
COVID-19 has affected the entire world. We aimed to determine the impact of COVID-19 containment measures on the daily life and follow up of patients with inflammatory bowel disease (IBD). During May 2020, we evaluated 179 (79.6%) patients with Crohn's disease (CD) and 46 (20.4%) with ulcerative colitis (UC) by telephone, using a structured questionnaire to gather information on social impact and IBD follow up. Some kind of social distancing measure was reported by 95.6% of our patients, self-quarantine (64.9%) being the most frequent. Depressive mood was the most prevalent social impact (80.2%), followed by anxiety/fear of death (58.2%), insomnia (51.4%), daily activity impairment (48%), sexual dysfunction (46.2%), and productivity impairment (44%). The results were similar when we compared patients with active disease to those in remission and patients with UC to those with CD. Analysis of IBD follow up showed that 83.1% of all patients missed an IBD medical appointment, 45.5% of the patients missed laboratory tests, 41.3% missed the national flu vaccination program, 31.3% missed any radiologic exam, 17.3% missed colonoscopy, and 16.9% failed to obtain biologic therapy prescriptions. Biologics were discontinued by 28.4% of the patients. UC patients had higher rates of missed vaccination than CD patients (56.5% vs. 37.4%, P=0.02) and more failures to obtain a biologic prescription (28.3% vs. 14.0%, P=0.02). Our study reveals alarming social impacts and declining follow-up care for IBD patients during the COVID-19 outbreak. These findings may have implications for disease control in the near future.


Firearm-related hospitalization and risk for subsequent violent injury, death, or crime perpetration: a cohort study.
Risk for violent victimization or crime perpetration after firearm-related hospitalization (FRH) must be determined to inform the need for future interventions. To compare the risk for subsequent violent injury, death, or crime perpetration among patients with an FRH, those hospitalized for noninjury reasons, and the general population. Retrospective cohort study. All hospitals in Washington. Patients with an FRH and a random sample of those with a non-injury-related hospitalization in 2006 to 2007 (index hospitalization). Primary outcomes included subsequent FRH, firearm-related death, and the combined outcome of firearm- or violence-related arrest ascertained through 2011. Among patients with an index FRH (n = 613), rates of subsequent FRH, firearm-related death, and firearm- or violence-related arrest were 329 (95% CI, 142 to 649), 100 (CI, 21 to 293), and 4221 (CI, 3352 to 5246) per 100 000 person-years, respectively. Compared with the general population, standardized incidence ratios among patients with an index FRH were 30.1 (CI, 14.9 to 61.0) for a subsequent FRH and 7.3 (CI, 2.4 to 22.9) for firearm-related death. In survival analyses that accounted for competing risks, patients with an index FRH were at greater risk for subsequent FRH (subhazard ratio [sHR], 21.2 [CI, 7.0 to 64.0]), firearm-related death (sHR, 4.3 [CI, 1.3 to 14.1]), and firearm- or violence-related arrest (sHR, 2.7 [CI, 2.0 to 3.5]) than those with a non-injury-related index hospitalization. Lack of information on whether patients continued to reside in Washington during follow-up may have introduced outcome misclassification. Hospitalization for a firearm-related injury is associated with a heightened risk for subsequent violent victimization or crime perpetration. Further research at the intersection of clinical care, the criminal justice system, and public health to evaluate the effectiveness of interventions delivered to survivors of firearm-related injury is warranted. Seattle City Council and University of Washington Royalty Research Fund.


Flavobacterium tagetis sp. nov., a novel urea-hydrolysing bacterium isolated from the roots of Tagetes patula.
A Gram-stain-negative, rod-shaped, motile by gliding, non-sporulating and strictly aerobic bacterium, designated strain GN10T, was isolated from the roots of Tagetes patula, collected from the garden of Dongguk University, Goyang, Republic of Korea. The cells could grow at 10-42 °C and at pH 5.5-9.0. Strain GN10T was sensitive to NaCl and tolerated up to 4 % NaCl (w/v). Comparative analysis of 16S rRNA gene sequences revealed the highest similarities to Flavobacterium tistrianum GB 56.1T (98.9 %), Flavobacterium sharifuzzamanii A7.6T (98.6 %), Flavobacterium zhairuonense A5.7T (98.3 %) and Flavobacterium anhuiense D3T (98 %). Phylogenetic analysis showed that strain GN10T clustered within the genus Flavobacterium and formed a monophyletic cluster with its close relative members. The average nucleotide identity and digital DNA-DNA hybridization values between strain GN10T and related species belonging to the genus Flavobacterium were well below the standard threshold for prokaryotic species delineation. The DNA G+C content of strain GN10T was 33.6 mol%. The predominant cellular fatty acids (>10 %) were identified as iso-C15 : 0, C16 : 0 and summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c). Strain GN10T contained menaquinone 6 as the major respiratory quinone. The major polar lipids were phosphatidylethanolamine, three unidentified aminoglycolipids, two unidentified glycolipids, one unidentified phosphoglycolipid and five unidentified lipids. Urease is a nickel-containing enzyme found in archaea, bacteria, plants and unicellular eukaryotes. It serves as a virulence factor and is responsible for pathogenesis in humans and animals. Here, we describe a novel urease-hydrolysing bacterium, strain GN10T. The urease activity of this strain may serve as an indicator of pathogenic potential and drug resistance, which may facilitate the development of many diseases. The results of physiological and biochemical tests allowed the genotypic and phenotypic differentiation of strain GN10T from its closely related members and considered to represent novel species in the genus Flavobacterium, for which the name Flavobacterium tagetis (GN10T=KCTC 82695T=NBRC 114841T) is proposed.


High Intensity Interval Training for Maximizing Health Outcomes.
Regular physical activity and exercise training are important actions to improve cardiorespiratory fitness and maintain health throughout life. There is solid evidence that exercise is an effective preventative strategy against at least 25 medical conditions, including cardiovascular disease, stroke, hypertension, colon and breast cancer, and type 2 diabetes. Traditionally, endurance exercise training (ET) to improve health related outcomes has consisted of low- to moderate ET intensity. However, a growing body of evidence suggests that higher exercise intensities may be superior to moderate intensity for maximizing health outcomes. The primary objective of this review is to discuss how aerobic high-intensity interval training (HIIT) as compared to moderate continuous training may maximize outcomes, and to provide practical advices for successful clinical and home-based HIIT.


Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene.
Cranioectodermal dysplasia (CED) is a disorder characterized by craniofacial, skeletal, and ectodermal abnormalities. Most cases reported to date are sporadic, but a few familial cases support an autosomal-recessive inheritance pattern. Aiming at the elucidation of the genetic basis of CED, we collected 13 patients with CED symptoms from 12 independent families. In one family with consanguineous parents two siblings were affected, permitting linkage analysis and homozygosity mapping. This revealed a single region of homozygosity with a significant LOD score (3.57) on chromosome 3q21-3q24. By sequencing candidate genes from this interval we found a homozygous missense mutation in the IFT122 (WDR10) gene that cosegregated with the disease. Examination of IFT122 in our patient cohort revealed one additional homozygous missense change in the patient from a second consanguineous family. In addition, we found compound heterozygosity for a donor splice-site change and a missense change in one sporadic patient. All mutations were absent in 340 control chromosomes. Because IFT122 plays an important role in the assembly and maintenance of eukaryotic cilia, we investigated patient fibroblasts and found significantly reduced frequency and length of primary cilia as compared to controls. Furthermore, we transiently knocked down ift122 in zebrafish embryos and observed the typical phenotype found in other models of ciliopathies. Because not all of our patients harbored mutations in IFT122, CED seems to be genetically heterogeneous. Still, by identifying CED as a ciliary disorder, our study suggests that the causative mutations in the unresolved cases most likely affect primary cilia function too.


The effects of a low-fat/high-fiber diet on sex hormone levels and menstrual cycling in premenopausal women: a 12-month randomized trial (the diet and hormone study).
Reduction of cumulative exposure to endogenous ovarian steroid hormones is a postulated method for reducing the risk of carcinoma of the breast and other malignancies. Although there are data from trials evaluating the effect of low-fat and high-fiber diets on sex hormone levels in premenopausal women, to the authors' knowledge none of these trials has combined a relatively large number of participants, follow-up of > 2-3 months, parallel controls receiving a usual diet, and careful timing of blood sampling within the menstrual cycle. A total of 213 healthy women, ages 20-40 years, were randomly assigned to follow their usual diet or to adopt an isocaloric diet with goals of 20% calories as fat, total fiber of 25 g/day, and at least 8 fruit or vegetable servings per day. Serum levels of total estradiol (E2), sex hormone-binding globulin (SHBG), non-SHBG-bound estradiol (NSBE2), SHBG, and progesterone were evaluated during a menstrual cycle at baseline, and at 4 cycles (C4) and 12 cycles (C12) after the start of the intervention. Serum was collected during each test cycle 7-9 days after the detection of an luteinizing hormone peak in the urine. One hundred eighty-nine women provided serum at C4 and 176 women at C12. Serum E2 decreased by an average of 7.5% or 7.8 pg/mL (95% confidence interval [95% CI], -16.0-0.04) at C12 in the intervention group, versus a decrease of 0.9% or 0.9 pg/mL (95% CI, -9.5-7.7) in the control group (the P value for the difference between the treatment groups was 0.25). Results for NSBE2 were very similar to those for total estradiol. There were no material effects found to result from intervention with regard to SHBG or progesterone. The results did not differ by baseline age, body mass index, or baseline hormone level above or below the median, and were not likely to be affected by weight change, which amounted to a mean loss of only 0.23 kg in the diet group versus a gain of 0.17 kg in the control group. The decrease in serum E2 associated with intervention was not greater when subjects were stratified by self-reported adherence to the dietary goals. The results of the current study suggest that the effects of this isocaloric low-fat, high-fiber diet pattern on circulating ovarian steroids were modest or nonexistent. However, the observed 7.5% reduction in estradiol could have biologic significance if it persisted over many years. Moreover, underestimation of the true dietary effect could have occurred because of incomplete adherence to assigned diets. Weight loss and weight control through midlife could be a more effective and feasible approach to dietary intervention in reducing the risk of breast carcinoma.


Influence of protein-protein interactions on the cellular localization of cytochrome P450.
Microsomal CYPs are integral membrane proteins that are localized in the endoplasmic reticulum (ER), which is critical for their function. CYPs are co-translationally inserted into the rough ER membrane and are then either directly retained in the smooth ER or retained by a retrieval mechanism or targeted for ER-associated degradation. Protein-protein interactions are likely to be important for proper cellular targeting of CYPs. Progress in understanding the mechanisms of cellular targeting and ER retention of CYPs is reviewed with emphasis on the role of protein-protein interactions. Possible mechanisms of direct retention are the incorporation of CYPs into an immobile complex in the ER membrane, homooligomerization that prevents inclusion in transport vesicles, exclusion of CYP monomers from transport vesicles or targeting of CYPs to an ER subdomain away from sites of transport vesicle formation. Degradation of CYPs occurs either by lysosomal mechanisms or by the ubiquitin-proteasomal pathway. The scope of this review includes studies published in the research literature that have defined the targeting of CYPs to the ER, the retention of CYPs in the ER and the degradation of CYPs. Targeting of CYPs to the ER is well understood and involves signal recognition particle-mediated delivery to the sec61 complex. The mechanism of ER retention of CYPs remains unclear, but self-oligomerization or binding to large immobile networks do not underlie ER retention of CYPs. An ER retention 'receptor' remains elusive, but BAP31 is important for the proper cellular localization of CYPs and Dap1p is a CYP-binding protein that is a candidate for such a receptor. Identification of protein binding partners of CYPs will be critical to understanding the mechanism of ER retention.


Health care workers as second victims of medical errors.
"Second victims" are health care providers who are involved with patient adverse events and who subsequently have difficulty coping with their emotions. Growing attention is being paid to making system improvements to create safer health care and to the appropriate handling of patients and families harmed during the provision of medical care. In contrast, there has been little attention to helping health care workers cope with adverse events. The aim of the study was to emphasize the importance of support structures for second victims in the handling of patient adverse events and in building a culture of safety within hospitals. A survey was administered to health care workers who participated in a patient safety meeting. The total number of registered participants was 350 individuals from various professions and different institutions within Johns Hopkins Medicine. The first part of the survey was paper-based and the second was administered online. The survey results reflected a need in "second victim" support strategies within health care organizations. Overall, informal emotional support and peer support were among the most requested and most useful strategies. When there is a serious patient adverse event, there are always second victims who are health care workers. The Johns Hopkins Hospital has established a "Second Victims" Work Group that will develop support strategies, particularly a peer-support program, for health care professionals within the system.


Rational use of cholinesterase activity testing in pesticide poisoning.
The use of acetylcholinesterase (AChE) activity testing in pesticide poisoning often falls on family physicians when evaluating a suspected poisoning or when monitoring the health of pesticide applicators. A review of the literature and consideration of three illustrative cases shows misunderstandings in the pathophysiology of the enzyme and in procedures for effective testing and monitoring of AChE levels. The physiologic characteristics of acetylcholine neurotransmission are described and related to carbamate and organophosphate poisoning. Pre-exposure monitoring is described using the California plan. A 23 percent variance in AChE levels exists among normal patients. It is necessary, therefore, to establish baseline levels to overcome individual variance. The practice of measuring of AChE levels in acute poisoning is limited. In employees who have been monitored and for whom baseline AChE levels have been established, a diagnosis of poisoning can be made by comparing postexposure AChE levels with baseline levels. If there is no baseline level recorded, and if the offending chemical is in question, the clinician must base treatment on the clinical signs and symptoms.


Usefulness of Crossword Puzzles in Helping First-Year BVSc Students Learn Veterinary Terminology.
Appropriate terminology is essential for successful communication among health professionals. However, students have traditionally been encouraged to learn terminology by rote memorization and recall, strategies that students try to avoid. The use of crossword puzzles as a learning tool has been evaluated in other education disciplines, but not for terminology related to veterinary science. Hence, the objective of this study was to test whether crossword puzzles might be an effective aid to learning veterinary terminology. Forty-two first-year students enrolled in a Bachelor of Veterinary Science program were randomly divided into two groups and their previous knowledge of veterinary terms tested. One group received a list of 30 terms with their definitions. The other group received the same list plus six specially designed puzzles incorporating these 30 terms. After 50 minutes, both groups completed a post-intervention test and the results were compared statistically. The results showed that the students using the crossword puzzles performed better in the post-intervention test, correctly retaining more terms than the students using only rote learning. In addition, qualitative data, gathered through an electronic survey and focus group discussions, revealed a positive attitude among students toward the use of crossword puzzles.


Light adaptation in turtle cones. Testing and analysis of a model for phototransduction.
Light adaptation in cones was characterized by measuring the changes in temporal frequency responses to sinusoidal modulation of light around various mean levels spanning a range of four log units. We have shown previously that some aspects of cone adaptation behavior can be accounted for by a biochemical kinetic model for phototransduction in which adaptation is mediated largely by a sigmoidal dependence of guanylate cyclase activity on the concentration of free cytoplasmic Ca2+, ([Ca2+]i) (Sneyd and Tranchina, 1989). Here we extend the model by incorporating electrogenic Na+/K+ exchange, and the model is put to further tests by simulating experiments in the literature. It accounts for (a) speeding up of the impulse response, transition from monophasic to biphasic waveform, and improvement in contrast sensitivity with increasing background light level, I0; (b) linearity of the response to moderate modulations around I0; (c) shift of the intensity-response function (linear vs. log coordinates) with change in I0 (Normann and Perlman, 1979); the dark-adapted curve adheres closely to the Naka-Rushton equation; (d) steepening of the sensitivity vs. I0 function with [Ca2+]i fixed at its dark level, [Ca2+]i dark; (Matthews et al., 1988, 1990); (e) steepening of the steady-state intensity-response function when [Ca2+]i is held fixed at its dark level (Matthews et al., 1988; 1990); (f) shifting of a steep template saturation curve for normalized photocurrent vs. light-step intensity when the response is measured at fixed times and [Ca2+]i is held fixed at [Ca2+]i dark (Nakatani and Yau, 1988). Furthermore, the predicted dependence of guanylate cyclase activity on [Ca2+] closely matches a cooperative inhibition equation suggested by the experimental results of Koch and Stryer (1988) on cyclase activity in bovine rods. Finally, the model predicts that some changes in response kinetics with background light will still be present, even when [Ca2+]i is held fixed at [Ca2]i dark.


Comparison of Quality Characteristics and Palatability between Sous-Vide Cooked Pork Loin Patties with Different Searing Treatments.
This study compared the quality, cooking, textural, and palatability characteristics between sous-vide (SV) cooked pork loin patties with different searing treatments (ST). Before SV cooking, STs were conducted on each side of the pork loin patties for 0 (control) to 120 s (ST120), and all patties were then cooked using an SV cooker at 75°C for 120 min. Noticeable differences were observed in quality properties between the groups. The seared SV loin patties exhibited lower lightness and higher browning index values compared to the unseared SV loin patties (p<0.001). Cooking loss gradually increased with increasing ST times, and the control group had a lower percentage compared to the ST60 group (19.5 vs. 25.7%, p<0.001). Changes in cooking properties were associated with the extent of ST, and the ST groups exhibited a higher hardness value compared to the control group (p<0.001). Regarding palatability, loin patties from the control group scored lower in appearance acceptability compared to patties from the ST groups (p<0.05) due to extent of browning on the surface. Moreover, the ST groups did exhibit a higher flavor intensity compared to the control group, but no differences were observed in tenderness and juiciness scores between the control and ST60 groups. Due to these results, the ST60 group exhibited a greater score in overall acceptability compared to the other groups except for the ST90 group. Therefore, an additional ST before SV cooking can achieve a more appealing appearance and palatability as well as to enhance the availability of pork loin.