Introducing Mass Communications Strategies to Medical Students: A Novel Short Session for Fourth-Year Students.
The World Health Organization calls on all with quality medical information to share it with the public and combat health misinformation; however, U.S. medical schools do not currently teach students effective communication with lay audiences about health. Most physicians have inadequate training in mass communication strategies. In August 2018, a novel 90-minute class at the University of Minnesota Medical School introduced fourth-year medical students to basic skills for communicating with lay audiences through mass media. Instructors were physicians with experience interacting with the general public via radio, op-ed articles, social media, print media, television, and community and legislative advocacy. After a 20-minute lecture and sharing of instructors' personal experiences, students completed two 30-minute small-group activities. They identified communications objectives and talking points for a health topic, drafting these as Tweets or an op-ed article outline, then presented talking points in a mock press conference with their peers, practicing skills just learned. Pre- and postsurveys documented students' previous engagement and comfort with future engagement with mass media messaging. Over 1 week, 142 students participated in 6 separate classes, and 127 completed both pre- and postsurveys. Before the course, only 6% (7/127) of students had comfortably engaged with social media and 14% (18/127) had engaged with traditional media in their professional roles. After the course, students self-reported an increase in their comfort, perceived ability, and likelihood of using specific communications skills to advocate for their patients (all P < .001). The course will be expanded into a 5-session thread for third- and fourth-year medical students spread over 2 years. This thread will include meeting physicians who engage with lay audiences, identifying best practices for mass health communication, identifying bias and misinformation, "dos and don'ts" of social media, and communication skills for legislative advocacy.


Systemic administration of C-type natriuretic peptide as a novel therapeutic strategy for skeletal dysplasias.
Skeletal dysplasias are a group of genetic disorders characterized by severe impairment of bone growth. Various forms of them add to produce a significant morbidity and mortality, yet no efficient drug therapy has been developed to date. We previously demonstrated that C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, is a potent stimulator of endochondral bone growth. Furthermore, we exhibited that targeted overexpression of a CNP transgene in the growth plate rescued the impaired bone growth observed in a mouse model of achondroplasia (Ach), the most frequent form of human skeletal dysplasias, leading us to propose that CNP may prove to be an effective treatment for this disorder. In the present study, to elucidate whether or not the systemic administration of CNP is a novel drug therapy for skeletal dysplasias, we have investigated the effects of plasma CNP on impaired bone growth in Ach mice that specifically overexpress CNP in the liver under the control of human serum amyloid P component promoter or in those treated with a continuous CNP infusion system. Our results demonstrated that increased plasma CNP from the liver or by iv administration of synthetic CNP-22 rescued the impaired bone growth phenotype of Ach mice without significant adverse effects. These results indicate that treatment with systemic CNP is a potential therapeutic strategy for skeletal dysplasias, including Ach, in humans.


Effects of Paenibacillus xylanexedens on growth performance, intestinal histomorphology, intestinal microflora, and immune response in broiler chickens challenged with Escherichia coli K88.
This study investigated the effects of dietary Paenibacillus xylanexedens ysm1 supplementation on growth performance, intestinal morphology, immune response, and cecal microbiota of broiler chickens challenged with Escherichia coli K88. A total of 320 one-day-old male broiler chicks were randomly allocated to 4 treatments (8 floor pens, 10 birds/pen) including 1) negative control (NC) birds fed a basal diet and not challenged with E. coli K88; 2) positive control (PC) birds fed a basal diet and challenged with of E. coli K88; 3) P. xylanexedens ysm1 treatment (PRO) birds fed a basal diet supplemented with 1 × 109P. xylanexedens ysm1 cfu/kg feed and challenged with E. coli K88; and 4) antibiotic treatment (ANT) birds fed a basal diet supplemented with 20 mg of colistin sulphate/kg of feed and challenged with E. coli K88. The E. coli challenge decreased (P < 0.05) BWG in PC birds compared with the ANT birds on days 21 and 28. The FCR was higher (P < 0.01) in PC birds compared with the NC, PRO, and ANT birds on days 14, 21, and 28. Compared with the NC, PRO, and ANT birds on day 28, PC birds had shorter villi and higher number of goblet cells in both jejunum and ileum (P < 0.001). Irrespective of the dietary treatments, the E. coli challenge reduced the number of PCNA-positive cells in both the jejunum and ileum on day 28. Paenibacillus xylanexedens ysm1 treatment resulted in higher concentration of mucosal sIgA in the jejunum as compared to the other treatment groups on days 14 and 28. The numbers of cecal E. coli were reduced (P = 0.017) in broilers treated with P. xylanexedens ysm1 or antibiotic in comparison with the PC group on day 28. In conclusion, the present study demonstrated that dietary supplementation of this new probiotic bacteria P. xylanexedens ysm1 improved broiler performance by modulating intestinal morphology, enhancing immune response, and reducing the number of E. coli in the cecum.


[The effects of ammonium perchlorate on thyroid function and testis in male rats].
To study the effects of ammonium perchlorate (AP) on the levels of thyroid hormone and the testis function of male rats. Twenty male rats were randomly divided into 4 groups: control group, low, middle and high AP group. The rats were exposed orally to 0, 130, 260 and 520 mg AP/kg a day for 80 days. The levels of thyroid hormone, testosterone in serum and sperm motility were measured and the testis histological change was observed as well. The increase of body weight in high AP group was significantly lower than that in the control group (P < 0.01). The organ coefficients of testis and thyroid in high AP group obviously enhanced, as compared with the control group (P < 0.01). The free thyroxin (FT4) levels of serum in all AP treated groups were significantly lower than that of the control group (P < 0.05). There were no differences of serum FT3 levels between all AP groups and control group, while serum TSH levels in middle and high AP groups decreased significantly, as compared with control group (P < 0.01). In terms of sperm motility, the percentage of Grade A and B sperm in middle and high groups were 12.3% +/- 2.52% and 14.8% +/- 5.93%, 17.7% +/- 4.63%, 15.8% +/- 2.28% respectively, which were significantly lower than that (27.8% +/- 8.70%) in control group (P < 0.01). The percentage of Grade D sperm in middle and high groups were 38.0% +/- 3.61% and 40.0% +/- 8.99%, respectively, which were significantly higher than that (17.0% +/- 5.00%) in control group (P < 0.01). No difference of serum testosterone level between all AP groups and control group was observed. AP can influence the levels of thyroid hormone and reduce the serum FT4 levels in rats. The main toxic effects on male reproductive system may decrease the sperm motility.


Five-year results of Small Incision Lenticule Extraction (ReLEx SMILE).
To evaluate the 5-year results of Refractive Lenticule Extraction (ReLEx) as Small Incision Lenticule Extraction (SMILE) technique for treatment of myopia and myopic astigmatism. In 2008/2009, the worldwide first 91 eyes were treated using a novel surgical technique (SMILE), where a refractive lenticule of intrastromal corneal tissue is removed though a small incision completely eliminating flap-cutting. 56 out of 91 eyes of the original treatment group volunteered for re-examination 5 years after surgery. Uncorrected distance visual acuity and corrected distance visual acuity after 5 years, objective and manifest refractions as well as evaluation of the interface and corneal surface by slit-lamp examination were documented. Late side effects like corneal scars, corneal ectasia, persistent dry eye symptoms or cataract were documented. 5 years postoperatively, no significant change to the 6-month data was found. Spherical equivalent was -0.375 D and therefore close to target refraction (emmetropia). 32 of the 56 eyes had gained 1-2 Snellen lines. There was no loss of 2 or more lines over the 5-year period. Regression in the long term was 0.48 D. This first long-term study demonstrates SMILE to be an effective, stable and safe procedure for treatment of myopia and myopic astigmatism. DE/CA93/KP/07/001. Post-results.


IL-6 may modulate the skeletal response to glucocorticoids during exacerbations of inflammatory bowel disease.
Whether inflammatory cytokines affect the skeletal response to glucocorticoid (GC) treatment is unclear. Our objectives were to (1) identify the cytokine(s) elevated during exacerbations of inflammatory bowel disease (IBD); (2) determine whether the cytokine(s) identified in this way is related to systemic GC sensitivity; and (3) examine whether cytokines and/or measures of GC sensitivity are related to changes in bone formation or resorption following GC therapy. We designed a combined cross-sectional and prospective study, including patients with active (n = 31) and inactive (n = 34) IBD as well as controls (n = 29). We assessed circulating concentrations of cytokines, PINP and betaCTX, as well as GC sensitivity in peripheral blood mononuclear cells. IL-6 was the only cytokine increased in active IBD, 2.35 (2.63) versus 1.64 (1.21) versus 1.31 (2.79) pg/microl active IBD, inactive IBD, and controls, respectively (median [interquartile range]) (P = 0.03, ANOVA). IL-6 was positively related to magnitude of GC sensitivity (beta = 0.02, 95% CI 0.008-0.04, P = 0.005). Following treatment with GC in active IBD, PINP decreased (P < 0.001), whereas betaCTX showed no significant change (P = 0.2). Subsequently, multiple regression analyses revealed that plasma IL-6 concentrations were inversely related to the extent of PINP suppression following GC (beta = 3.3, 95% CI 0.2-6.4, P = 0.04, adjusted for baseline PINP and duration of GC treatment), while no association was observed with GC sensitivity. In conclusion, IL-6 is elevated in active IBD and may protect against GC-induced suppression of bone formation via a mechanism which appears to be independent of systemic GC sensitivity.


Estimating speciation and extinction rates from diversity data and the fossil record.
Understanding the processes that underlie biodiversity requires insight into the evolutionary history of the taxa involved. Accurate estimation of speciation, extinction, and diversification rates is a prerequisite for gaining this insight. Here, we develop a stochastic birth-death model of speciation and extinction that predicts the probability distribution of both extinct and extant numbers of species in a clade. We present two estimation methods based on this model given data on the number of extinct species (from the fossil record) and extant species (from diversity assessments): a multivariate method of moments approach and a maximum-likelihood approach. We show that, except for some special cases, the two estimation methods produce very similar estimates. This is convenient, because the usually preferred maximum-likelihood approach is much more computationally demanding, so the method of moments can serve as a proxy. Furthermore, we introduce a correction for possible bias that can arise by the mere fact that we will normally only consider extant clades. We find that in some cases the bias correction affects the estimates profoundly. Finally, we show how our model can be extended to incorporate incomplete preservation. Preservation rates can, however, not be reliably estimated on the basis of numbers of extant and extinct species alone.


Cellular differentiation in response to nutrient availability: The repressor of meiosis, Rme1p, positively regulates invasive growth in Saccharomyces cerevisiae.
In the yeast Saccharomyces cerevisiae, the transition from a nutrient-rich to a nutrient-limited growth medium typically leads to the implementation of a cellular adaptation program that results in invasive growth and/or the formation of pseudohyphae. Complete depletion of essential nutrients, on the other hand, leads either to entry into a nonbudding, metabolically quiescent state referred to as G0 in haploid strains or to meiosis and sporulation in diploids. Entry into meiosis is repressed by the transcriptional regulator Rme1p, a zinc-finger-containing DNA-binding protein. In this article, we show that Rme1p positively regulates invasive growth and starch metabolism in both haploid and diploid strains by directly modifying the transcription of the FLO11 (also known as MUC1) and STA2 genes, which encode a cell wall-associated protein essential for invasive growth and a starch-degrading glucoamylase, respectively. Genetic evidence suggests that Rme1p functions independently of identified signaling modules that regulate invasive growth and of other transcription factors that regulate FLO11 and that the activation of FLO11 is dependent on the presence of a promoter sequence that shows significant homology to identified Rme1p response elements (RREs). The data suggest that Rme1p functions as a central switch between different cellular differentiation pathways.


Circular Bivalent Aptamers Enable in Vivo Stability and Recognition.
Aptamers are powerful candidates for molecular imaging and targeted therapy of cancer based on such appealing features as high binding affinity, high specificity, site-specific modification and rapid tumor penetration. However, aptamers are susceptible to plasma exonucleases in vivo. This seriously affects their in vivo applications. To overcome this key limitation, we herein report the design and development of circular bivalent aptamers. Systematic studies reveal that cyclization of aptamers can improve thermal stability, nuclease resistance and binding affinity. In vivo fluorescence imaging further validates the efficient accumulation and retention of circular bivalent aptamers in tumors compared to "mono-aptamers". Therefore, this study provides a simple and efficient strategy to boost in vivo aptamer applications in cancer diagnosis and therapy.


Post-mortem 1.5T MR quantification of regular anatomical brain structures.
Recently, post-mortem MR quantification has been introduced to the field of post-mortem magnetic resonance imaging. By usage of a particular MR quantification sequence, T1 and T2 relaxation times and proton density (PD) of tissues and organs can be quantified simultaneously. The aim of the present basic research study was to assess the quantitative T1, T2, and PD values of regular anatomical brain structures for a 1.5T application and to correlate the assessed values with corpse temperatures. In a prospective study, 30 forensic cases were MR-scanned with a quantification sequence prior to autopsy. Body temperature was assessed during MR scans. In synthetically calculated T1, T2, and PD-weighted images, quantitative T1, T2 (both in ms) and PD (in %) values of anatomical structures of cerebrum (Group 1: frontal gray matter, frontal white matter, thalamus, internal capsule, caudate nucleus, putamen, and globus pallidus) and brainstem/cerebellum (Group 2: cerebral crus, substantia nigra, red nucleus, pons, cerebellar hemisphere, and superior cerebellar peduncle) were assessed. The investigated brain structures of cerebrum and brainstem/cerebellum could be characterized and differentiated based on a combination of their quantitative T1, T2, and PD values. MANOVA testing verified significant differences between the investigated anatomical brain structures among each other in Group 1 and Group 2 based on their quantitative values. Temperature dependence was observed mainly for T1 values, which were slightly increasing with rising temperature in the investigated brain structures in both groups. The results provide a base for future computer-aided diagnosis of brain pathologies and lesions in post-mortem magnetic resonance imaging.


Quantitative trait loci associated with elevated thyroid-stimulating hormone in the Wistar-Kyoto rat.
Thyroid hormones are essential for the regulation of developmental and physiological processes. The genetic factors underlying naturally occurring variability in mammalian thyroid function are, however, only partially understood. Genetic control of thyroid function can be studied with animal models such as the inbred Wistar-Kyoto (WKY) rat strain. Previous studies established that WKY rats have elevated TSH, slightly elevated total T3, and normal total T4 levels compared with Wistar controls. The present study confirmed a persistent 24-h elevation of TSH in WKY rats compared with the Fisher 344 (F344) rat, another inbred strain. Acute T3 challenge (25 microg/100 g body weight ip) suppressed serum TSH and T4 levels in both strains. Quantitative trait locus analysis of elevated TSH in a reciprocally bred WKY x F344 F2 population identified one highly significant locus on chromosome 6 (LOD=11.7, TSH-1) and one suggestive locus on chromosome 5 (LOD=2.3, TSH-2). The confidence interval of TSH-1 contains the TSH receptor and type 2 deiodinase genes, and TSH-2 contains the type 1 deiodinase gene. The WKY alleles of each gene contain sequence alterations, but additional studies are indicated to identify the specific gene or genes responsible for altered regulation of the thyroid axis. These findings suggest that one or more genetic alterations within the TSH-1 locus significantly contribute to the altered thyroid function tests of the WKY rat.


Gender differences in the variables of exercise treadmill test in type 2 diabetes mellitus.
Exercise capacity, like some other variables of exercise stress test, is a strong predictor of cardiovascular and overall mortality. Many confounding factors, including gender, have been found to affect exercise capacity. This study evaluated whether exercise capacity differs in age-matched type 2 diabetic Nigerian men and their women counterparts and the hemodynamic variables of exercise treadmill test that correlate with exercise capacity in them. A total of 61 type 2 diabetics (male = 34; female = 27) aged 30 to 60 years who were recruited through the Medical Out-patient Department of OAUTHC, Ile Ife, Nigeria, underwent symptom-limited maximal treadmill exercise using Bruce protocol. Patients had comparable clinical and demographic patterns. There was no gender difference in the chronotropic response to exercise. Males had faster heart rate recovery (HRR) than females. Though both sexes had similar resting systolic blood pressure (SBP), males had significantly higher peak SBP than females (216.2 ± 23.7 mmHg vs 203.3 ± 21.7 mmHg; P = 0.03). Exercise capacity was significantly higher in males (7.5 ± 2.0 METs) than females (6.4 ± 1.5 METs); P = 0.01. Significant correlates of exercise capacity in both sexes were fasting plasma glucose, resting diastolic blood pressure, Duke Treadmill Score, and HRR. Majority of the patients were in moderate DUKE risk subgroup and there was no statistically significant difference between males and females in this regard. Gender difference occurs in the exercise capacity of diabetic patients and the factors associated with this disparity may be related to gender differences in resting heart rate and HRR, both reflecting a withdrawal of vagal tone.


Autopsy demonstration of intramyocardial polymer gel emboli associated with a giant-cell reaction following cardiac catheterization: a case report.
Foreign body type granulomatous vasculitis has been reported in blood vessels of the brain, lungs, and skin of the foot following intravascular instrumentation with devices coated with hydrophilic polymer gel. We report a case of intramyocardial polymer gel emboli associated with granulomatous vasculitis following cardiac catheterization. Autopsy observations in a 77-year-old woman are presented. The patient experienced an acute myocardial infarction requiring catheterization and coronary stenting. The patient returned with a pseudoaneurysm at the site of catheterization and shortly after suffered a fatal arrhythmia. Microscopically, multiple small vessels within the myocardium were noted to contain a basophilic, amorphous, focally lamellated, focally granular material. A granulomatous inflammatory response was noted in the vessels containing the foreign material. Our case is the first to our knowledge to document intramyocardial vessel gel emboli following a cardiac catheterization with stenting. Although the microscopic finding of emboli within vessels does not seem to be the immediate cause of death in our case, it is highly possible that it contributed to the patient's demise.


Skin cancer and arsenical intoxication from well water.
A case of acute arsenical intoxication arising from ingested well water containing only 1.2 ppm of arsenic is reported. After a latent period of 14 years, multiple cutaneous basal cell carcinomas developed. The water was analyzed for a variety of other trace elements and compounds and no evidence for the existence of other carcinogens was found. This study strengthens the concept that arsenic is a carcinogen. The role of a possible selenium deficiency is also discussed.


A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle.
Epidemiological studies showed that chronic caffeine intake decreased the risk of type 2 diabetes. Previously, we described that chronic caffeine intake prevents and reverses insulin resistance induced by hypercaloric diets and aging, in rats. Caffeine has several cellular mechanisms of action, being the antagonism of adenosine receptors the only attained with human coffee consumption. Here, we investigated the subtypes of adenosine receptors involved on the effects of chronic caffeine intake on insulin sensitivity and the mechanisms and sex differences behind this effect. Experiments were performed in male and female Wistar rats fed either a chow or high-sucrose (HSu) diet (35% of sucrose in drinking water) during 28 days, to induce insulin resistance. In the last 15 days of diet the animals were submitted to DPCPX (A1 antagonist, 0.4 mg/kg), SCH58261 (A2A antagonist, 0.5 mg/kg), or MRS1754 (A2B antagonist, 9.5 μg/kg) administration. Insulin sensitivity, fasting glycaemia, blood pressure, catecholamines, and fat depots were assessed. Expression of A1, A2A, A2B adenosine receptors and protein involved in insulin signaling pathways were evaluated in the liver, skeletal muscle, and visceral adipose tissue. UCP1 expression was measured in adipose tissue. Paradoxically, SCH58261 and MRS1754 decreased insulin sensitivity in control animals, whereas they both improved insulin response in HSu diet animals. DPCPX did not alter significantly insulin sensitivity in control or HSu animals, but reversed the increase in total and visceral fat induced by the HSu diet. In skeletal muscle, A1, A2A, and A2B adenosine receptor expression were increased in HSu group, an effect that was restored by SCH58261 and MRS1754. In the liver, A1, A2A expression was increased in HSu group, while A2B expression was decreased, being this last effect reversed by administration of MRS1754. In adipose tissue, A1 and A2A block upregulated the expression of these receptors. A2 adenosine antagonists restored impaired insulin signaling in the skeletal muscle of HSu rats, but did not affect liver or adipose insulin signaling. Our results show that adenosine receptors exert opposite effects on insulin sensitivity, in control and insulin resistant states and strongly suggest that A2 adenosine receptors in the skeletal muscle are the majors responsible for whole-body insulin sensitivity.


Ca2+-dependent phosphorylation of tyrosine hydroxylase in PC12 cells.
Ca2+-dependent protein phosphorylation has been detected in numerous tissues and may mediate some of the effects of hormones and other extracellular stimuli on cell function. In this paper we demonstrate that a Ca2+/calmodulin-dependent protein kinase similar to the enzyme previously purified and characterized from rat brain is present in PC12, a rat pheochromocytoma cell line. We show that Ca2+ influx elicited by various forms of cell stimulation leads to increased 32P incorporation into tyrosine hydroxylase (TH), a major phosphoprotein in these cells. Several other unidentified proteins are either phosphorylated or dephosphorylated as a result of Ca2+ influx. Acetylcholine stimulates TH phosphorylation by activation of nicotinic receptors. K+-induced depolarization stimulates TH phosphorylation in a Ca2+-dependent manner, presumably by opening voltage-dependent Ca2+ channels. Ca2+ influx that results from the direct effects of the ionophore A23187 also leads to TH phosphorylation. Phosphorylation of TH is accompanied by an activation of the enzyme. These Ca2+-dependent effects are independent of cyclic AMP and thus implicate a Ca2+-dependent protein kinase as a mediator of both hormonal and electrical stimulation of PC12 cells.


Evidence towards the role of arylamine N-acetyltransferase in Mycobacterium smegmatis and development of a specific antiserum against the homologous enzyme of Mycobacterium tuberculosis.
Arylamine N-acetyltransferase (NAT) in humans inactivates the anti-tubercular drug isoniazid (INH). Homologues of human NAT are present in Mycobacterium tuberculosis and Mycobacterium smegmatis, where they can acetylate, and hence inactivate, INH. The in vivo role of mycobacterial NAT is not known but heterologous expression of the M. tuberculosis gene increases the INH resistance. The 0.85 kb nat gene is part of a gene cluster in M. smegmatis. The gene is transcribed as a large, 7.5 kb mRNA as demonstrated by Northern analysis. A nat knockout strain of M. smegmatis was generated by targeted disruption. The new strain was confirmed to be devoid of NAT activity. The growth of the knockout strain is considerably delayed compared with the wild-type, due to an extended lag phase. The knockout mutant has an increased sensitivity to INH as would be predicted. The NATs from M. smegmatis and M. tuberculosis have a high degree of homology, except in the region of the C terminus. A specific polyclonal antiserum raised against recombinant NAT protein from M. tuberculosis is described that recognizes a stretch of about twenty residues within the C terminus of M. tuberculosis NAT. This highly specific antiserum will enable comparison of nat expression between isolates of M. tuberculosis.


Endoplasmic reticulum membrane localization of Rce1p and Ste24p, yeast proteases involved in carboxyl-terminal CAAX protein processing and amino-terminal a-factor cleavage.
Proteins terminating in the CAAX motif, for example Ras and the yeast a-factor mating pheromone, are prenylated, trimmed of their last three amino acids, and carboxyl-methylated. The enzymes that mediate these activities, collectively referred to as CAAX processing components, have been identified genetically in Saccharomyces cerevisiae. Whereas the Ram1p/Ram2p prenyltransferase is a cytosolic soluble enzyme, sequence analysis predicts that the other CAAX processing components, the Rce1p and Ste24p proteases and the Ste14p methyltransferase, contain multiple membrane spans. To determine the intracellular site(s) at which CAAX processing occurs, we have examined the localization of the CAAX proteases Rce1p and Ste24p by subcellular fractionation and indirect immunofluorescence. We find that both of these proteases are associated with the endoplasmic reticulum (ER) membrane. In addition to having a role in CAAX processing, the Ste24p protease catalyzes the first of two cleavage steps that remove the amino-terminal extension from the a-factor precursor, suggesting that the first amino-terminal processing step of a-factor maturation also occurs at the ER membrane. The ER localization of Ste24p is consistent with the presence of a carboxyl-terminal dilysine ER retrieval motif, although we find that mutation of this motif does not result in mislocalization of Ste24p. Because the ER is not the ultimate destination for a-factor or most CAAX proteins, our results imply that a mechanism must exist for the intracellular routing of CAAX proteins from the ER membrane to other cellular sites.


In vivo X-ray fluorescence of lead in bone.
The in vivo measurement of lead in bone by K X-ray fluorescence (K XRF) is becoming an increasingly widely utilized technique for assessing long-term lead dosimetry. Several groups have already reported the development of in vivo measurement systems, the majority adopting the 109Cd/backscatter K XRF technique because of its substantial advantages in terms of a robust measurement, lower detection limit (compared with 57Co/90 degrees), absence of the need for sedation of younger subjects, and lower effective (radiation) dose when calculated according to the most recent guidelines. The advantages of the 109Cd system are primarily a consequence of the physics principles of the technique. The apparatus of each XRF technique is transportable, facilitating easy establishment of mobile laboratory facilities. More research is needed to substantiate claims made for particular XRF technologies, but both L and K XRF techniques provide the possibility of improved understanding of the body's handling of the ubiquitous toxin lead.


Factors associated with requesting and receiving euthanasia: a nationwide mortality follow-back study with a focus on patients with psychiatric disorders, dementia, or an accumulation of health problems related to old age.
Recently, euthanasia and assisted suicide (EAS) in patients with psychiatric disorders, dementia, or an accumulation of health problems has taken a prominent place in the public debate. However, limited is known about this practice. The purpose of this study was threefold: to estimate the frequency of requesting and receiving EAS among people with (also) a psychiatric disorder, dementia, or an accumulation of health problems; to explore reasons for physicians to grant or refuse a request; and to describe differences in characteristics, including the presence of psychiatric disorders, dementia, and accumulation of health problems, between patients who did and did not request EAS and between patients whose request was or was not granted. A nationwide cross-sectional survey study was performed. A stratified sample of death certificates of patients who died between 1 August and 1 December 2015 was drawn from the central death registry of Statistics Netherlands. Questionnaires were sent to the certifying physician (n = 9351, response 78%). Only deceased patients aged ≥ 17 years and who died a non-sudden death were included in the analyses (n = 5361). The frequency of euthanasia requests among deceased people who died non-suddenly and with (also) a psychiatric disorder (11.4%), dementia (2.1%), or an accumulation of health problems (8.0%) varied. Factors positively associated with requesting euthanasia were age (< 80 years), ethnicity (Dutch/Western), cause of death (cancer), attending physician (general practitioner), and involvement of a pain specialist or psychiatrist. Cause of death (neurological disorders, another cause) and attending physician (general practitioner) were also positively associated with receiving euthanasia. Psychiatric disorders, dementia, and/or an accumulation of health problems were negatively associated with both requesting and receiving euthanasia. EAS in deceased patients with psychiatric disorders, dementia, and/or an accumulation of health problems is relatively rare. Partly, this can be explained by the belief that the due care criteria cannot be met. Another explanation is that patients with these conditions are less likely to request EAS.


A biomechanical study of two methods of internal fixation of unstable fractures of the femoral neck. A preliminary study.
A model of an unstable femoral neck fracture was used in this study to compare the axial and torsional displacement obtained when the neck was fixed by a compression hip screw (CHS) and side plate, or three Knowles pins. Six paired, embalmed femora were mounted on a special, custom-made jig that grasped the femoral head and shaft securely. A standardized osteotomy was made with an oscillating saw, bisecting the distance between the lower cartilaginous portion of the femoral head and the intertrochanteric line. A 5-mm thick slice of bone was excised from the posteromedial quadrant of the distal fragment. The right or left femur in each pair was then randomly assigned to internal fixation with either three Knowles pins or a keyed CHS plus a 130 degrees four-hole side plate. After potting of the specimens and application of rosette strain gauges, axial displacements were measured during the application of in-plane and out-of-plane compressive loads. The resistance to torsion was also determined. There were no statistical differences between the two devices for compressive or torsional loading using this model.


Investigating longitudinal changes to frontal cortico-striatal tracts in Huntington's disease: the IMAGE-HD study.
The striatum is the principal site of disease pathology in Huntington's disease and contains neural connections to numerous cortical brain regions. Studies examining abnormalities to neural connections find that white matter integrity is compromised in HD; however, further regional, and longitudinal investigation is required. This paper is the first longitudinal investigation into region-based white-matter integrity changes in Huntington's Disease. The aim of this study was to better understand how disease progression impacts white matter tracts connecting the striatum to the prefrontal and motor cortical regions in HD. We used existing neuroimaging data from IMAGE-HD, comprised of 25 pre-symptomatic, 27 symptomatic, and 25 healthy controls at three separate time points (baseline, 18-months, 30-months). Fractional anisotropy, axial diffusivity and radial diffusivity were derived as measures of white matter microstructure. The anatomical regions of interest were identified using the Desikan-Killiany brain atlas. A Group by Time repeated measures ANCOVA was conducted for each tract of interest and for each measure. We found significantly lower fractional anisotropy and significantly higher radial diffusivity in the symptomatic group, compared to both the pre-symptomatic group and controls (the latter two groups did not differ from each other), in the rostral middle frontal and superior frontal tracts; as well as significantly higher axial diffusivity in the rostral middle tracts only. We did not find a Group by Time interaction for any of the white matter integrity measures. These findings demonstrate that whilst the microstructure of white matter tracts, extending from the striatum to these regions of interest, are compromised during the symptomatic stages of Huntington's disease, 36-month follow-up did not show progressive changes in these measures. Additionally, no correlations were found between clinical measures and tractography changes, indicating further investigations into the relationship between tractography changes and clinical symptoms in Huntington's disease are required.


Incidence of HIV and sexually transmitted infections and risk factors for acquisition among young methamphetamine users in northern Thailand.
Southeast Asia is experiencing an epidemic of methamphetamine use, a drug associated with risky sexual behaviors, putting a large segment of the population at increased risk for sexually transmitted infections (STIs) and HIV and in need of prevention efforts. Incidence estimates of STIs are rare in Southeast Asia, especially among newer risk groups. We enrolled methamphetamine users aged 18 to 25 years in a 12-month randomized behavioral intervention trial in Chiang Mai, Thailand in 2005. Behavioral questionnaires were administered at visits every 3 months, and biologic specimens were collected at baseline and 12 months to test for common STIs (chlamydia, gonorrhea, HSV-2, and HIV). Poisson regression with robust variance was used to determine risk factors for incident STIs. Overall, 12.7% of 519 participants acquired at least 1 STI. Chlamydia was the most common (10.6%), followed by HSV-2 (4.0%), gonorrhea (2.9%), and HIV (0.6%). Risk factors for both men and women included self-reported incarceration and having a casual sex partner during follow-up, and having a prevalent STI at baseline. Additionally, among women, having 2 or more heterosexual partners, and among men, having a greater frequency of drunkenness were risk factors for STI acquisition. Although HIV incidence is low in this population, incidence of other STIs is high compared with previous studies of young Thai adults. Risk factors for acquisition emphasize the need for new prevention strategies targeted toward current populations at risk.


The epidural blood patch--current practices and concerns.
Post dural puncture headache is a common sequelae of spinal and, sometimes, epidural anesthesia. Since 1960, the practice of placing autologous blood into the epidural space to treat spinal headache has been used with great success. The blood patch can provide immediate symptom relief from spinal headache and repair of the CSF leak, which is the basic mechanism of post dural puncture headache. Discrepancies exist in the literature and in today's common practice regarding technique and timing for this treatment. This is a procedure not without complications and requires caution. Contained herein are recommendations for safe and effective use of the epidural blood patch. Following these procedures, anesthetists will likely see an 85% to 98% immediate cure rate for post dural puncture headache with the fewest possible complications.


Radiation Dose Reduction by Indication-Directed Focused z-Direction Coverage for Neck CT.
The American College of Radiology-American Society of Neuroradiology-Society for Pediatric Radiology Practice Parameter for a neck CT suggests that coverage should be from the sella to the aortic arch. It also recommends using CT scans judiciously to achieve the clinical objective. Our purpose was to analyze the potential dose reduction by decreasing the scan length of a neck CT and to assess for any clinically relevant information that might be missed from this modified approach. This retrospective study included 126 children who underwent a neck CT between August 1, 2013, and September 30, 2014. Alteration of the scan length for the modified CT was suggested on the topographic image on the basis of the indication of the study, with the reader blinded to the images and the report. The CT dose index volume of the original scan was multiplied by the new scan length to calculate the dose-length product of the modified study. The effective dose was calculated for the original and modified studies by using age-based conversion factors from the American Association of Physicists in Medicine Report No. 96. Decreasing the scan length resulted in an average estimated dose reduction of 47%. The average reduction in scan length was 10.4 cm, decreasing the overall coverage by 48%. The change in scan length did not result in any missed findings that altered management. Of the 27 abscesses in this study, none extended to the mediastinum. All of the lesions in question were completely covered. Decreasing the scan length of a neck CT according to the indication provides a significant savings in radiation dose, while not altering diagnostic ability or management.


In vitro fermentation assay on the bifidogenic effect of steviol glycosides of Stevia rebaudiana plant for the development of dietetic novel products.
The relationship between excessive sugar consumption and many diseases such as dental caries, obesity, diabetes and coronary heart has been increasing in recent years. In this study, utilization of natural sugar replacer steviol glycosides and bifidogenic effect by Bifidobacterium animalis subsp. lactis was assayed in vitro model system. The basal medium (non-carbohydrate containing MRS, Man, Rogosa and Sharpe Agar) were supplemented with 0.025% and 1% stevia, 0.025% stevia + 1% inulin, %1 stevia + 1% inulin. The medium which contained no carbohydrate was designated as negative control, whereas the medium containing 1% glucose or inulin were evaluated as positive and evaluated on the 0, 12, 24, 36 and 48 h of fermentation. Steviol glycosides in both system significantly stimulated the growth of Bifidobacterium animalis subsp. lactis to varying degrees with highest prebiotic activity score, short chain fatty acid production and growth parameters as much as glucose and prebiotic inulin. The viability of the probiotic bacteria was determined within the bio-therapeutic level with potential prebiotic effects depending on the probiotic bacterial strain growing and the type of carbohydrate source utilized. In the study, stevia at lower concentration showed a higher growth rate of with inulin. In conclusion, stevia can be used as functional ingredients for the modulation of the gut microbiota and design of synbiotic systems as a prebiotic substrate and sugar substitute.


Short tools to assess young children's dietary intake: a systematic review focusing on application to dietary index research.
Dietary indices evaluate diet quality, usually based on current dietary guidelines. Indices can therefore contribute to our understanding of early-life obesity-risk dietary behaviours. Yet indices are commonly applied to dietary data collected by onerous methods (e.g., recalls or records). Short dietary assessment instruments are an attractive alternative to collect data from which to derive an index score. A systematic review of studies published before April 2013 was conducted to identify short (≤50 items) tools that measure whole-of-diet intake of young children (birth-five years) and are applicable to dietary indices, in particular screening obesogenic dietary behaviours. The search identified 3686 papers of which 16, reporting on 15 tools (n = 7, infants and toddlers birth-24 months; n = 8, preschoolers 2-5 years), met the inclusion criteria. Most tools were food frequency questionnaires (n = 14), with one innovative dietary questionnaire identified. Seven were tested for validity or reliability, and one was tested for both. Six tools (n = 2, infants and toddlers; n = 4, preschoolers) are applicable for use with current dietary indices, five of which screen obesogenic dietary behaviours. Given the limited number of brief, valid and reliable dietary assessment tools for young children to which an index can be applied, future short tool development is warranted, particularly for screening obesogenic dietary behaviours.


Cloning, sequencing and expression of the gene encoding the coenzyme B12-dependent 2-methyleneglutarate mutase from Clostridium barkeri in Escherichia coli.
The coenzyme B12 (adenosylcobalamin)-dependent 2-methyleneglutarate mutase catalyses the carbon skeleton rearrangement of 2-methyleneglutarate to (R)-3-methylitaconate in the fermentation of nicotinic acid by the strict anaerobic bacterium Clostridium barkeri. (a) The mgm gene encoding 2-methyleneglutarate mutase was cloned and its nucleotide sequence was determined. The deduced amino acid sequence revealed a 66.8-kDa protein of 614 amino acids. It shows significant similarity in its C-terminal part to that of other cobamide-dependent enzymes. Probably, this is the coenzyme-binding region. (b) The mgm gene from C. barkeri was expressed in Escherichia coli as was shown by SDS/PAGE and Western-blot analysis with rabbit antiserum directed against the native mutase. (c) Cell-free extracts from E. coli carrying the mgm gene showed 2-methyleneglutarate mutase activity that was strictly dependent on the addition of coenzyme B12. Experiments are presented which suggest that the expression product is an apoenzyme.


Single-dose immunization with virus replicon particles confers rapid robust protection against Rift Valley fever virus challenge.
Rift Valley fever virus (RVFV) causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. The potential for RVFV introduction outside the area of endemicity highlights the need for fast-acting, safe, and efficacious vaccines. Here, we demonstrate a robust system for the reverse genetics generation of a RVF virus replicon particle (VRP(RVF)) vaccine candidate. Using a mouse model, we show that VRP(RVF) immunization provides the optimal balance of safety and single-dose robust efficacy. VRP(RVF) can actively synthesize viral RNA and proteins but lacks structural glycoprotein genes, preventing spread within immunized individuals and reducing the risk of vaccine-induced pathogenicity. VRP(RVF) proved to be completely safe following intracranial inoculation of suckling mice, a stringent test of vaccine safety. Single-dose subcutaneous immunization with VRP(RVF), although it is highly attenuated, completely protected mice against a virulent RVFV challenge dose which was 100,000-fold greater than the 50% lethal dose (LD(50)). Robust protection from lethal challenge was observed by 24 h postvaccination, with 100% protection induced in as little as 96 h. We show that a single subcutaneous VRP(RVF) immunization initiated a systemic antiviral state followed by an enhanced adaptive response. These data contrast sharply with the much-reduced survivability and immune responses observed among animals immunized with nonreplicating viral particles, indicating that replication, even if confined to the initially infected cells, contributes substantially to protective efficacy at early and late time points postimmunization. These data demonstrate that replicon vaccines successfully bridge the gap between safety and efficacy and provide insights into the kinetics of antiviral protection from RVFV infection.


Class I-restricted CTL induction by mucosal immunization with naked DNA encoding measles virus haemagglutinin.
We have investigated the class I-restricted CTL response specific for measles virus haemagglutinin (HA) in the spleens of mice immunized by various mucosal routes with a DNA plasmid carrying the HA gene (pV1j-HA). A single immunization with recombinant DNA injected in the buccal mucosa induced an HA-specific CTL response. Similarly, nasal immunization with the DNA vaccine induced primary CTLs against measles virus HA. Booster immunization did not enhance the CTL activity. Oral or intrajejunal immunization with the plasmid induced a CTL response of lower magnitude. However, this could be potentiated by co-administration of the mucosal adjuvant cholera toxin or cationic lipids (DOTAP). These data show that a CTL response can be generated by mucosal vaccination using DNA vaccines.


A theory of planned behavior-based structural model for breast-feeding.
Breast-feeding is the recommended method of infant feeding because it is clearly associated with health benefits for infants and their mothers. Yet, many women who initiate breast-feeding fail to meet their own personal goals or recommended standards for duration of breast-feeding. To refine a Theory of Planned Behavior (TPB)-based structural model for explaining variability in breast-feeding intention and duration. The study design was prospective, multicorrelational, and longitudinal. Out of the total sample of 635 women, 602 mothers of healthy, full-term infants provided complete datasets over the entire course of their breast-feeding experience and these datasets were used in the modeling analyses. Simultaneous multisample analysis of covariance structures was used to develop the model. The resulting TPB for Breast-Feeding (TPB-BrF) describes the rational, motivational processes of the original TPB, but reconfigures the relationships among them, for homemakers (TPB-BrF/H), women employed half-time or less (TPB-BrF/EL), and women employed more than half-time (TPB-BrF/EM). Mothers' early postpartum ratings of adequacy of milk supply and stimulus conditions of maternal education and breast-feeding knowledge were included in the TPB-BrF to better explain breast-feeding outcomes. Model complexity increased with employment effort. The TPB-BrF is a comprehensive, theoretically based, empirically verified model that can serve as a useful heuristic for understanding the personal motivational components of breast-feeding behavior.


Luminescence properties of different Eu sites in LiMgPO4:Eu(2+), Eu(3+).
The effect of temperature on the luminescence properties of LiMgPO4 doped with Eu(3+) and Eu(2+) are presented. Depending on the excitation wavelength, luminescence spectra consist of two distinct broad emission bands peaking at 380 nm and 490 nm related to 4f(6)5d(1) → 4f(7) ((8)S7/2) luminescence of Eu(2+) and to europium-trapped exciton, respectively, and/or several sharp lines between the 580 nm and 710 nm region, ascribed to the (5)D0 → (7)FJ (J = 0, 1, 2, 3 and 4) transitions in Eu(3+). To explain all the features of the Eu(2+) and Eu(3+) luminescence we discussed the existence of two different Eu sites substituting for Li(+), with short and long distance compensation. The evident effect of increasing the intensity of the Eu(2+) luminescence with increasing temperature was observed. It was considered that the charge compensation mechanism for Eu(3+) and Li(+) as well as Eu(2+) replacing Li(+) in the LiMgPO4 is a long distance compensation that allows for the existence of some of the europium ions either as Eu(3+) at low temperature or as Eu(2+) at high temperature. We concluded that Eu(2+) in the Li(+) site with long distance compensation yields only 4f(6)5d(1) → 4f(7) luminescence, whereas Eu(2+) in the Li(+) site with short distance compensation yields 4f(6)5d(1) → 4f(7) luminescence and europium-trapped exciton emission.


Treatment of visceral leishmaniasis in Kenya by aminosidine alone or combined with sodium stibogluconate.
The treatment of leishmaniasis, as currently conducted in Kenya with sodium stibogluconate, is unsatisfactory as it is expensive, resistance and relapses may occur, and major adverse effects have been reported. Recently, aminosidine (paromomycin) sulphate has shown good antileishmanial activity on its own as well as synergism with pentavalent antimony, administered concurrently. The present study was designed to assess the effectiveness of parenteral aminosidine, alone or combined with sodium stibogluconate, in visceral leishmaniasis, compared to treatment by stibogluconate alone. 53 patients were allocated to the 3 therapeutic regimes. The presenting signs and symptoms of leishmaniasis were those commonly seen in the visceral form of the disease, particularly in Kenya. At termination, clinical cures were achieved in all 53 patients with no difference between treatment groups. Spleen aspirates revealed the best parasitological results in patients receiving the combined treatment, with only 13% failures (partial cures + relapses), as opposed to 21% failures with aminosidine alone and 45% with stibogluconate alone. Treatment with aminosidine alone was the cheapest and safest regime.


Imaging-based chemical screening reveals activity-dependent neural differentiation of pluripotent stem cells.
Mammalian pluripotent stem cells (PSCs) represent an important venue for understanding basic principles regulating tissue-specific differentiation and discovering new tools that may facilitate clinical applications. Mechanisms that direct neural differentiation of PSCs involve growth factor signaling and transcription regulation. However, it is unknown whether and how electrical activity influences this process. Here we report a high throughput imaging-based screen, which uncovers that selamectin, an anti-helminthic therapeutic compound with reported activity on invertebrate glutamate-gated chloride channels, promotes neural differentiation of PSCs. We show that selamectin's pro-neurogenic activity is mediated by γ2-containing GABAA receptors in subsets of neural rosette progenitors, accompanied by increased proneural and lineage-specific transcription factor expression and cell cycle exit. In vivo, selamectin promotes neurogenesis in developing zebrafish. Our results establish a chemical screening platform that reveals activity-dependent neural differentiation from PSCs. Compounds identified in this and future screening might prove therapeutically beneficial for treating neurodevelopmental or neurodegenerative disorders. DOI:http://dx.doi.org/10.7554/eLife.00508.001.


Heterogeneity of intestinal receptors for Escherichia coli heat-stable enterotoxin.
The structure of rat intestinal cell receptors for Escherichia coli heat-stable enterotoxin (ST) was investigated by affinity cross-linking to 125I-ST and analysis by denaturing gel electrophoresis. Cross-linking of labeled toxin to intestinal membranes and analysis by nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed five specifically labeled proteins with molecular masses of 160, 136, 78, 71, and 56 (kilodaltons) kDa. Exhaustive reduction of these samples resulted in a similar pattern of labeling. Affinity-labeled proteins were further analyzed by nonreducing SDS-PAGE, reduction of the resulting separated proteins, and further separation by SDS-PAGE in the presence of beta-mercaptoethanol. Thus, the 160-kDa band on nonreducing gels consisted of two different receptors: a 160-kDa polypeptide not further reducible and one composed of at least two subunits, one of which was the 78-kDa subunit. Similarly, the 136-kDa band on nonreducing gels consisted of a 136-kDa polypeptide not further reducible and one composed of at least two subunits, one of which was the 71-kDa subunit. The 78-, 71-, and 56-kDa subunits were not further reducible. These data suggest heterogeneity of the ST receptor subunit structure and organization in rat intestinal epithelia.


GP speciality training in areas of deprivation: factors influencing engagement. A qualitative study.
GP training practices are less likely to be situated in areas of deprivation; little is known about GP views of postgraduate training in such areas. To explore the views of GPs working in deprived areas about GP speciality training (GPST). Qualitative in-depth interviews with GPs working in practices in deprived areas in Scotland. Ten in-depth interviews were conducted with GPs in training and non-training practices, to explore views on training. Interviews were audiotaped and transcribed verbatim, and inductive thematic analysis was undertaken. The importance of producing 'well-rounded' GPs who are able to work in a variety of environments was highlighted. Trainees need exposure to the specific challenges of deprived contexts (such as early multimorbidity, child protection, and addiction) and the benefit of this for trainees was thought to be invaluable. GPs identified many perceived barriers and benefits to training, some generic but some - such as inspiring the next generation (benefit) or overwhelming workload (barrier) - may be more relevant in areas of high deprivation. Overwhelming workload was the main reason for not becoming a training practice, though some would consider it if supported to develop a training culture. All the GPs, including non-trainers, were involved in optional activities which were felt to be important for resilience. GPs in areas of deprivation highlighted specific skills that could be gained by undertaking at least a part placement in deprived areas, with different skills likely to be gained from affluent areas. National education bodies should consider GP training rotations ensure a variety of training environments.


Mycoviruses as Triggers and Targets of RNA Silencing in White Mold Fungus Sclerotinia sclerotiorum.
This study aimed to demonstrate the existence of antiviral RNA silencing mechanisms in Sclerotinia sclerotiorum by infecting wild-type and RNA-silencing-deficient strains of the fungus with an RNA virus and a DNA virus. Key silencing-related genes were disrupted to dissect the RNA silencing pathway. Specifically, dicer genes (dcl-1, dcl-2, and both dcl-1/dcl-2) were displaced by selective marker(s). Disruption mutants were then compared for changes in phenotype, virulence, and susceptibility to virus infections. Wild-type and mutant strains were transfected with a single-stranded RNA virus, SsHV2-L, and copies of a single-stranded DNA mycovirus, SsHADV-1, as a synthetic virus constructed in this study. Disruption of dcl-1 or dcl-2 resulted in no changes in phenotype compared to wild-type S. sclerotiorum; however, the double dicer mutant strain exhibited significantly slower growth. Furthermore, the Δdcl-1/dcl-2 double mutant, which was slow growing without virus infection, exhibited much more severe debilitation following virus infections including phenotypic changes such as slower growth, reduced pigmentation, and delayed sclerotial formation. These phenotypic changes were absent in the single mutants, Δdcl-1 and Δdcl-2. Complementation of a single dicer in the double disruption mutant reversed viral susceptibility to the wild-type state. Virus-derived small RNAs were accumulated from virus-infected wild-type strains with strand bias towards the negative sense. The findings of these studies indicate that S. sclerotiorum has robust RNA silencing mechanisms that process both DNA and RNA mycoviruses and that, when both dicers are silenced, invasive nucleic acids can greatly debilitate the virulence of this fungus.


Why people refuse to make tradeoffs in person tradeoff elicitations: a matter of perspective?
Person tradeoff (PTO) elicitations assess people's values for health states by asking them to compare the value of treatment programs. For example, people might be asked how many patients need to be cured of health condition X to equal the benefit of curing 100 people of condition Y. However, when faced with PTO elicitations, people frequently refuse to make quantifiable tradeoffs, exhibiting 2 kinds of refusals: 1) They say that 2 treatment programs have equal value, that curing 100 of X is just as good as curing 100 of Y, even if X is a less serious condition than Y, or 2) they say that the 2 programs are incomparable, that millions of people need to be cured of X to be as good as curing 100 of Y. The authors explore whether people would be more willing to make tradeoffs if the focus was changed from trading off groups of patients to choosing the best decision or evaluating treatment benefits. . Two randomized trials used diverse samples (N=2400) via the Internet to test for the effect of perspective on refusal rates. The authors predicted that perspectives that removed people from decision-making roles would increase their willingness make tradeoffs. Contrary to expectations, refusal rates increased when people were removed from decision-making roles. In fact, the more pressure put on people to make a decision, the less likely they were to refuse to make tradeoffs. To reduce PTO refusals, it is best to adopt a decision-maker perspective.


Red cell N5-methyltetrahydrofolate concentrations and C677T methylenetetrahydrofolate reductase genotype in patients with stroke.
To investigate the relation between total red cell folate, red cell N(5)-methyltetrahydrofolate (N(5)MTHF) concentrations, and N(5)N(10)-methylenetetrahydrofolate reductase (MTHFR) genotypes in stroke. The study comprised 120 consecutive patients presenting to hospital with acute stroke. Multivitamin supplement use was recorded. Serum and red cell folate were measured by microbiological assays using Lactobacillus casei and Enterococcus faecalis, and by the DPC-BioMediq Immulite 2000 analyser. Total plasma homocysteine (tHcy), serum cobalamin, and serum vitamin B(6) were measured and the C677T MTHFR genotype determined. There were no significant differences in blood tHcy or vitamin concentrations according to MTHFR genotype in the overall patient cohort. However, when patients taking vitamins were excluded, total red cell folate and red cell N(5)MTHF were significantly lower in patients with the TT genotype compared with CT or CC genotypes. In the overall cohort, irrespective of genotype, red cell folate was significantly lower when assayed microbiologically than with the Immulite assay. This discrepancy remained after exclusion of patients taking vitamins. Total red cell folate and red cell N(5)MTHF are significantly lower in stroke patients with the TT compared with the CT and TT MTHFR genotypes, particularly those not taking vitamin supplements. Microbiological assays that measure biologically active folates provide substantially lower estimates of folate than the Immulite assay. Because folate is a key determinant of blood homocysteine values, these findings may impact on the interpretation of the strength and independence of the association between raised blood concentrations of homocysteine and atherothrombosis risk reported in most epidemiological studies.


Differential effects on enzyme stability and kinetic parameters of mutants related to human triosephosphate isomerase deficiency.
Human triosephosphate isomerase (TIM) deficiency is a very rare disease, but there are several mutations reported to be causing the illness. In this work, we produced nine recombinant human triosephosphate isomerases which have the mutations reported to produce TIM deficiency. These enzymes were characterized biophysically and biochemically to determine their kinetic and stability parameters, and also to substitute TIM activity in supporting the growth of an Escherichia coli strain lacking the tim gene. Our results allowed us to rate the deleteriousness of the human TIM mutants based on the type and severity of the alterations observed, to classify four "unknown severity mutants" with altered residues in positions 62, 72, 122 and 154 and to explain in structural terms the mutation V231M, the most affected mutant from the kinetic point of view and the only homozygous mutation reported besides E104D.


Maternal work outside the home and its effect on women and their families.
Up to 65% of American women work outside the home in paid employment, thus it is essential to examine the effect of that employment on the health of both women and their families. Employed women of all ages and occupations have a lower mortality rate and better reported and perceived health than women who do not work outside the home. The incidence of cardiovascular disease in women has not increased because of their increased participation in the work force. For hypertension, for psychological health, and for the incidence of coronary heart disease, women's emotional response to work is more important in predicting ill health than work itself. Working does not worsen women's health during pregnancy, and perinatal outcome may be improved for employed mothers. Middle-aged women who work have better measures of psychological and physical well-being. Employment seems to ahve a beneficial effect on the woman's family as well; more employed women confide in their husbands and report helpful or supportive responses from them. Multiple studies found no difference in many psychological and educational characteristics between children of working and nonworking mothers. One difference discovered was that children of working mothers are less likely to believe in "traditional" sex roles. There is no age group for which the employment of the mother is harmful, and at many ages if employment resulted in better maternal well-being, there is a definite gain for the children. More important than work itself is the mother's satisfaction with work, child care arrangements, and the home situation.(ABSTRACT TRUNCATED AT 250 WORDS)


Targeting and regulation of the HER-2/neu oncogene promoter with bis-peptide nucleic acids.
Antigene oligonucleotides have the potential to regulate gene expression through site-specific DNA binding. However, in vivo applications have been hindered by inefficient cellular uptake, degradation, and strand displacement. Peptide nucleic acids (PNAs) address several of these problems, as they are resistant to degradation and bind DNA with high affinity. We designed two cationic pyrimidine bis-PNAs (cpy-PNAs) to target the polypurine tract of the HER-2/neu promoter and compared them to an unmodified phosphodiester triplex-forming oligonucleotide (TFO1) and a TFO-nitrogen mustard conjugate (TFO2). PNA1 contains a + 2 charge and bound two adjacent 9-bp target sequences with high affinity and specificity, but only at low pH. PNA2 contains a +5 charge and bound one 11-bp target with high affinity up to pH 7.4, but with lower specificity. The PNA:DNA:PNA triplex formed by these cpy-bis-PNAs presented a stable barrier to DNA polymerase extension. The cpy-bis-PNAs and the TFO-alkylator conjugate prevented HER-2/neu transcription in a reporter gene assay (TFO2 = PNA1 > PNA2 >> TFO1). Both PNAs and TFOs were effective at binding the target sequence in naked genomic DNA, but only the TFO-alkylator (TFO2) and the more cationic PNA (PNA2) were detected at the endogenous HER-2/neu promoter in permeabilized cells. This work demonstrates the potential for preventing HER-2/neu gene expression with cpy-bis-PNAs in tumor cells.


Organization of afferent input to subdivisions of area 8 in the rhesus monkey.
The sources of ipsilateral afferents to subdivisions of one frontal eye field (Walker, '40a area 8) were studied with horseradish peroxidase (HRP) in macaque monkeys. There were major differences in the distribution of cells projecting to the caudal and rostral parts of area 8. The majority (53%) of labeled cortical cells projecting to caudal regions were in visual association areas, and an additional 23% were in the ventral bank of the intraparietal sulcus, where neurons may have predominantly visual and visuomotor properties. In contrast, rostral area 8 had a much lower percentage of its cortical input originating in visual association areas (5%) or in the ventral bank of the intraparietal sulcus (8%). After HRP injection in this rostral part, 21% of labeled cells were in auditory association areas and 13% in paralimbic regions, whereas labeling in these two types of cortex was negligible after HRP administration to caudal parts of area 8. The percentage of cells in other association regions (portions of the banks of the superior temporal sulcus, dorsolateral parietal, medial parietal, and prefrontal cortices) was higher in the rostral (53%) than in the caudal case (21%). The results suggest that caudal area 8 may be involved in head and eye movements in response to visual stimuli, while its anterior subdivisions may be involved in directing the head and eyes in response to auditory stimuli. Furthermore, limbic input may also be relevant to the neural processing occurring in rostral frontal eye fields, perhaps by directing attention toward motivationally relevant stimuli.


Optimization of factors affecting the rooting of pine wilt disease resistant Masson pine (Pinus massoniana) stem cuttings.
Pine wilt disease (PWD) is a devastating disease affecting trees belonging to the genus Pinus. To control the spread of PWD in the Masson pine forest in China, PWD resistant Masson pine clones have been selected by the Anhui Academy of Forestry. However, because Masson pine is a difficult-to-root species, producing seedlings is challenging, especially from trees older than 5 years of age, which impedes the application of PWD resistant clones. In this study, we investigated the factors affecting rooting of PWD resistant clones and established a cheap, reliable, and simple method that promotes rooting. We tested the effects of three management methods, four substrates, two cutting materials, two cutting treatments, and three collection times on the rooting of cuttings obtained from 9-year-old PWD resistant clones. Rooting was observed only in stem cuttings treated with the full-light automatic spray management method. Additionally, stem cuttings showed a significantly higher rooting rate and root quality than needles cuttings. Compared with other substrates, stem cuttings planted in perlite produced the longest adventitious root and the highest total root length and lateral root number. Moreover, stem cuttings of PWD resistant clones collected in May showed a significantly higher rooting rate and root quality than those collected in June and July. Moreover, stem cuttings prepared with a horizontal cut while retaining the needles showed significantly higher rooting rate and root quality than those prepared with a diagonal cut while partly removing the needles. This study promotes the reproduction of seedlings of PWD-resistant Masson pine clones which helps control the spread of PWD, meanwhile, provides a technical reference for the propagation of mature pine trees via cuttings.


Family burden after traumatic brain injury in children.
Traumatic brain injury has a substantial impact on caregivers. This study describes the burden experienced by caregivers of children with traumatic brain injury and examines the relationship between child functioning and family burden during the first year after injury. Children aged 5 to 15 years hospitalized for traumatic brain injury at 4 participating trauma centers were eligible. Caregivers completed baseline and 3- and 12-month telephone interviews measuring the child's health-related quality of life using the Pediatric Quality of Life Inventory. The emotional impact scale of the Child Health Questionnaire was used to identify caregivers with substantial distress, including general worry or interference with family routine. Caregiver perceptions of whether health care needs were met or unmet and days missed from work were also measured. A total of 330 subjects enrolled; follow-up was conducted with 312 at 3 months and 288 at 12 months. Most subjects were white (68%) and male (69%). Abnormal Pediatric Quality of Life Inventory subscores were related to substantial caregiver burden (either general worry or interference in routine). These abnormalities were reported by >75% of patients at 3 months and persisted to 1 year in some patients. Parental perception of unmet health care needs was strongly related to family burden outcomes, with up to 69% of this subset of parents reporting substantial worry, and nearly one quarter reporting interference with daily routine/concentration 1 year after injury. Child dysfunction predicted parental burden at 3 and 12 months. Burden was greater when health care need was unmet. Abnormalities on the Pediatric Quality of Life Inventory predicted the amount of work missed by parents, especially in the presence of unmet needs. Caregivers are more likely to report family burden problems when child functioning is poorer and health care needs are unmet. Improved identification and provision of services is a potentially modifiable factor that may decrease family burden after pediatric traumatic brain injury.


High-Quality Transmission of Cardiotocogram and Fetal Information Using a 5G System: Pilot Experiment.
A cardiotocogram (CTG) is a device used to perceive the status of a fetus in utero in real time. There are a few reports of its use at home or during emergency transport. The aim of this study was to test whether CTG and other perinatal information can be transmitted accurately using an experimental station with a 5G transmission system. In the research institute, real-time fetal heart rate waveform data from the CTG device, high-definition video ultrasound images of the fetus, and high-definition video taken with a video camera on a single line were transmitted by 5G radio waves from the transmitting station to the receiving station. All data were proven to be transmitted with a minimum delay of less than 1 second. The CTG waveform image quality was not inferior, and there was no interruption in transmission. Images of the transmitted ultrasound examination and video movie were fine and smooth. CTG and other information about the fetuses and pregnant women were successfully transmitted by a 5G system. This finding will lead to prompt and accurate medical treatment and improve the prognosis of newborns.


First-event or marginal estimation of cause-specific hazards for analysing correlated multivariate failure-time data?
In the analysis of multivariate failure-time data, the effect of a treatment or an exposure on the hazard of each failure type is sometimes evaluated using only the information on the first event that occurs in every individual, ignoring all events that follow. A Cox proportional hazards model may be fitted to such data, yielding a cause-specific hazard ratio (HR) estimate of the exposure for each failure type conditional on surviving all other failure types. However, such an estimate would not fully utilize all the available information on event times. Alternatively, a marginal approach may be implemented to model the time distribution of each failure type beyond the subject's first failure to (any) second and later failures. We investigate the performance of these two approaches by simulating positive and negative correlated event times from exponential distributions. Surprisingly, our results suggest that the first-event-only method (when multiple failures are possible) performs as well as the marginal method in most practical situations. Generally, for a modest sample size of 400, it is possible to achieve at least 85 per cent coverage of the true marginal HR with the first-event method. Although the coverage is poor for a correlation of 0.7 and beyond, such a high correlation between competing event times may be biologically rather implausible.


Identification and Development of a New Positron Emission Tomography Ligand 4-(2-Fluoro-4-[11C]methoxyphenyl)-5-((1-methyl-1H-pyrazol-3-yl)methoxy)picolinamide for Imaging Metabotropic Glutamate Receptor Subtype 2 (mGlu2).
Metabotropic glutamate receptor 2 (mGlu2) is a known target for treating several central nervous system (CNS) disorders. To develop a viable positron emission tomography (PET) ligand for mGlu2, we identified new candidates 5a-i that are potent negative allosteric modulators (NAMs) of mGlu2. Among these candidates, 4-(2-fluoro-4-methoxyphenyl)-5-((1-methyl-1H-pyrazol-3-yl)methoxy)picolinamide (5i, also named as [11C]MG2-1812) exhibited high potency, high subtype selectivity, and favorable lipophilicity. Compound 5i was labeled with positron-emitting carbon-11 (11C) to obtain [11C]5i in high radiochemical yield and high molar activity by O-[11C]methylation of the phenol precursor 12 with [11C]CH3I. In vitro autoradiography with [11C]5i showed heterogeneous radioactive accumulation in the brain tissue sections, ranked in the order: cortex > striatum > hippocampus > cerebellum ≫ thalamus > pons. PET study of [11C]5i indicated in vivo specific binding of mGlu2 in the rat brain. Based on the [11C]5i scaffold, further optimization for new candidates is underway to identify a more suitable ligand for imaging mGlu2.


Neuroprotective Effects of Astaxanthin in Oxygen-Glucose Deprivation in SH-SY5Y Cells and Global Cerebral Ischemia in Rat.
Astaxanthin (ATX), a naturally occurring carotenoid pigment, is a powerful biological antioxidant. In the present study, we investigated whether ATX pharmacologically offers neuroprotection against oxidative stress by cerebral ischemia. We found that the neuroprotective efficacy of ATX at the dose of 30 mg/kg (n = 8) was 59.5% compared with the control group (n = 3). In order to make clear the mechanism of ATX neuroprotection, the up-regulation inducible nitric oxide synthase (iNOS) and heat shock proteins (HSPs) together with the oxygen glucose deprivation (OGD) in SH-SY5Y cells were also investigated. The induction of various factors involved in oxidative stress processes such as iNOS was suppressed by the treatment of ATX at 25 and 50 µM after OGD-induced oxidative stress. In addition, Western blots showed that ATX elevated of heme oxygenase-1 (HO-1; Hsp32) and Hsp70 protein levels in in vitro. These results suggest that the neuroprotective effects of ATX were related to anti-oxidant activities in global ischemia.


Gene activation in response to neural induction.
In order to study the molecular processes involved in the final steps of neural induction, we are investigating the transcriptional regulation of the Xenopus laevis neural cell adhesion molecule (NCAM) gene. NCAM is expressed very early during neural development and its expression is dependent on neural induction signals. Using microinjection of reporter gene constructions into fertilized frog eggs, we have shown that cloned copies of the NCAM promoter respond appropriately to neural induction signals. Examination of the Xenopus NCAM promoter reveals a number of potential regulatory elements. We have directed our attention to a small region of the promoter that is highly conserved over large evolutionary distances. This region contains an enhancer, the OZ element, and also a silencer element, the N-box. We have purified DNA DNA proteins that interact specifically with both the OZ enhancer and the N-box silencer sequences. A model suggesting a role for these regulatory factors during neural induction is presented.


Molecular mass ranges of coal tar pitch fractions by mass spectrometry and size-exclusion chromatography.
A coal tar pitch was fractionated by solvent solubility into heptane-solubles, heptane-insoluble/toluene-solubles (asphaltenes), and toluene-insolubles (preasphaltenes). The aim of the work was to compare the mass ranges of the different fractions by several different techniques. Thermogravimetric analysis, size-exclusion chromatography (SEC) and UV-fluorescence spectroscopy showed distinct differences between the three fractions in terms of volatility, molecular size ranges and the aromatic chromophore sizes present. The mass spectrometric methods used were gas chromatography/mass spectrometry (GC/MS), pyrolysis/GC/MS, electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS) and laser desorption time-of-flight mass spectrometry (LD-TOFMS). The first three techniques gave good mass spectra only for the heptane-soluble fraction. Only LDMS gave signals from the toluene-insolubles, indicating that the molecules were too involatile for GC and too complex to pyrolyze into small molecules during pyrolysis/GC/MS. ESI-FTICRMS gave no signal for toluene-insolubles probably because the fraction was insoluble in the methanol or acetonitrile, water and formic acid mixture used as solvent to the ESI source. LDMS was able to generate ions from each of the fractions. Fractionation of complex samples is necessary to separate smaller molecules to allow the use of higher laser fluences for the larger molecules and suppress the formation of ionized molecular clusters. The upper mass limit of the pitch was determined as between 5000 and 10,000 u. The pitch asphaltenes showed a peak of maximum intensity in the LDMS spectra at around m/z 400, in broad agreement with the estimate from SEC. The mass ranges of the toluene-insoluble fraction found by LDMS and SEC (400-10,000 u with maximum intensity around 2000 u by LDMS and 100-9320 u with maximum intensity around 740 u by SEC) are higher than those for the asphaltene fraction (200-4000 u with maximum intensity around 400 u by LDMS and 100-2680 u with maximum intensity around 286 u by SEC) and greater than values considered appropriate for petroleum asphaltenes (300-1200 u with maximum intensity near 700 u).


Trends of fatal road traffic injuries in Iran (2004-2011).
Road traffic injuries (RTIs) leading to death need the most essential concern for low, middle and high income societies. Mortality rate due to traffic injuries is considerable in Iran particularly during the last decade along with the industrialization process. The present study considered the trend of traffic injuries leading to death in Iran for a period of seven-years which started from March 2004 to March 2011. The formal merged Iranian database provided by the Ministry of Roads, the Legal Medicine Organization, the Traffic Police (NAJA), and the Ministry of Health covering 146, 269 deaths due to traffic injuries between 2004 and 2011 was analyzed. The time series method was carried out to determine the death trends of RTIs in the whole country. The Poisson regression model was used to estimate the changes in the frequency of events over time adjusting for associated known risk factors. The SARIMA (0, 1, 1)×(0, 1, 1)12 model was used for fitting to the time series of death rate. The death rate due to RTIs in Iran has statistically declined from 38 in 2004 to 31 per 100,000 populations in 2011. Based on the number of vehicles, the mortality rate has also declined from 38 to 12 cases per 10,000 vehicles from 2004 to 2011 respectively. However, the mortality rate was increased from 51 to 65 cases per 1000 accidents from 2004 to March 2011 respectively. Despite minor variations in mortality trends of RTIs in Iran according to different criteria, an annual average of 21,000 deaths is considerable and needs serious attentions. Modification of traffic laws, enhancement of police controls, improving transport infrastructure, holding education courses for drivers and providing optimal healthcare services are recommended.


Comparing ELISA and surface plasmon resonance for assessing clinical immunogenicity of panitumumab.
Evaluation of the immunogenicity of panitumumab, a fully human anti-epidermal growth factor receptor mAb approved for use in colorectal cancer patients, led to the development of two separate immunoassays for the detection of anti-panitumumab Abs. The first immunoassay used a bridging ELISA capable of detecting 10 ng/ml positive control anti-panitumumab Ab. The ELISA incorporated an acid dissociation step to reduce drug interference and tolerated the presence of approximately 100-fold molar excess of drug. During eight clinical trials, the ELISA detected developing Ab responses in 2 of 612 (0.3%) subjects. In one of the ELISA positive subjects, neutralizing Abs were detected using an epidermal growth factor receptor phosphorylation bioassay. The second immunoassay used a Biacore biosensor immunoassay format capable of detecting 1 mug/ml positive control Ab while tolerating the presence of equal molar amounts of drug. Although less sensitive and less tolerant to competing drug in the assay, the Biacore assay detected developing Ab responses in 25 of the 604 (4.1%) subjects. Additionally, the Biacore assay identified eight subjects who developed neutralizing Abs. Mouse mAbs with affinities ranging from 1.1 x 10(-6) to 8.4 x 10(-10) M were used to characterize both assay types. The ELISA was more sensitive for the detection of higher affinity mAbs and detected high-affinity mAbs in the presence of higher molar ratio of drug to mAb. The Biacore assay was more sensitive for detection of lower affinity mAbs and detected low affinity Abs in the presence of higher molar ratios of drug to mAb.


Artificial hairy surfaces with a nearly perfect hydrophobic response.
A nearly perfect hydrophobic interface by dint of mimicking hairs of arthropods was achieved for the first time. These Gamma-shape artificial hairs were made via a membrane casting technique on polypropylene substrates. This extreme hydrophobicity merely arises from microstructure modification, and no further chemical treatments are needed. The ultralow adhesion to water droplets was evaluated through video assessment, and it is believed to be attributed to the mechanical response of the artificial hairs. The principle of this fabrication technique is accessible and is expected to be compatible with large-area fabrication of superhydrophobic interfaces.


The future of allied health in the health promotion/disease prevention movement.
Although allied health was not included in the earliest stages of the health promotion/disease prevention movement, it now has a unique opportunity to assume a leadership position. To a great extent, realization of that potential will depend on the individual and collective efforts of the American Society of Allied Health Professions (ASAHP) and its constituencies, allied health educational institutions, professional associations, and individual professionals.


A combination of NaCl and urea enhances survival of IMCD cells to hyperosmolality.
Physiological adaptation to the hyperosmolar milieu of the renal medulla involves a complex series of signaling and gene expression events in which NaCl and urea activate different cellular processes. In the present study, we evaluated the effects of NaCl and urea, individually and in combination, on the viability of murine inner medullary collecting duct (mIMCD3) cells. Exposure to hyperosmolar NaCl or urea caused comparable dose- and time-dependent decreases in cell viability, such that 700 mosmol/kgH2O killed >90% of the cells within 24 h. In both cases, cell death was an apoptotic event. For NaCl, loss of viability at 24 h paralleled decreases in RNA and protein synthesis at 4h, whereas lethal doses of urea had little or no effect on these biosynthetic processes. Cell cycle analysis showed both solutes caused a slowing of the G2/M phase. Surprisingly, cells exposed to a combination of NaCl + urea were significantly more osmotolerant such that 40% survived 900 mosmol/kgH2O. Madin-Darby canine kidney cells but not human umbilical vein endothelial cells also exhibited a similar osmotolerance response. Enhanced survival was not associated with a restoration of normal biosynthetic rates or cell cycle progression. However, the combination of NaCl + urea resulted in a shift in Hsp70 expression that appeared to correlate with survival. In conclusion, hyperosmolar NaCl and urea activate independent and complementary cellular programs that confer enhanced osmotolerance to renal medullary epithelial cells.


[Studies on small thyroid carcinoma in dialysis patients with hyperparathyroidism].
For twenty long-term hemodialysis patients with medically uncontrolled hyperparathyroidism, subtotal parathyroidectomy (PTX) was performed and histological examination was done for 17 out of them, suspected of thyroid disease from operative findings. Thyroid carcinomas were found in 5 out of 17 patients by biopsied specimens of thyroids. Histological findings of carcinomas were follicular (2 cases) and papillary types (3 cases). In all cases, carcinomas were in occult state and the sizes of carcinomas of 4 cases were small being a diameter less than 10 mm. Among others, findings of follicular adenoma (2 cases) and chronic thyroiditis (1 case) were obtained. The incidence rate of thyroid carcinoma in this report seemed to be rather high as the incidence diagnosed from biopsied specimen at operation. Several factors such as immunological incompetence accompanied by renal failure, metabolic abnormalities of cells induced by parathyroid dysfunction and accelerated aging are considered to be involved as a cause of increased incidence of thyroid carcinoma in hemodialysis patients with hyperparathyroidism.


Chromosome 5 harbors two independent deletion hotspots at 5q13 and 5q21 that characterize biologically different subsets of aggressive prostate cancer.
Deletion of chromosome 5q is common in prostate cancer and is linked to aggressive disease. Most previous studies focused on 5q21 where CHD1 is located, but deletion of mapping studies has identified a second deletion hotspot at 5q13. To clarify the prevalence and clinical relevance of 5q13 deletions and to determine the relative importance of 5q13 and 5q21 abnormalities, a tissue microarray containing samples from 12 427 prostate cancers was analyzed by fluorescence in situ hybridization. Deletion of 5q13 and 5q21 was found in 13.5% and 10%, respectively, of 7932 successfully analyzed cancers. Deletion was restricted to 5q13 in 49.4% and to 5q21 in 32.0% of cancers with a 5q deletion. Only 18.6% of 5q-deleted cancers had deletions of both loci. Both 5q13 and 5q21 deletions were significantly linked to advanced tumor stage, high Gleason grade, nodal metastasis and early biochemical recurrence (P < .005 each). Cancers with co-deletion of 5q13 and 5q21 had a worse prognosis than cancers with isolated 5q13 or 5q21 deletion (P = .0080). Comparison with TMPRSS2:ERG fusion status revealed that 5q21 deletions were tightly linked to ERG negativity (P < .0001) while 5q13 deletions were unrelated to the ERG status. In summary, 5q13 deletion and 5q21 deletion are common, but independent genomic alterations with different functional effects lead to aggressive prostate cancer.


Handwashing and antiseptic-containing soaps in hospital.
Two aspects of handwashing in hospital were considered. A study was carried out to examine the contamination of bar soap and containers, and the use of antiseptic soaps in reducing the resident flora of the skin. Swabs were collected from soap dishes on six wards and from a bacteriology laboratory on four consecutive days. The unmedicated bar soap was replaced by bar soap containing 2.5% povidone-iodine, and further swabs were collected over a period of seven days. Ninety-two isolates from 48 samples were obtained when unmedicated bar soap was used, and nine isolates from 42 samples when povidone-iodine (Betadine) soap was substituted. The number of organisms recovered when povidone-iodine soap was used was much reduced, and Pseudomonas spp were recovered in low numbers on only one occasion. Six laboratory workers took part in a study to compare bar soap with other agents-povidone-iodine soap, povidone-iodine surgical scrub, povidone-iodine alcoholic solution, chlorhexidine surgical scrub, and alcoholic chlorhexidine. Samples were collected after standard washes and after surgical gloves had been worn for 90 minutes. The effect of multiple washes was assessed by samples collected after six washes with the agent under study (three per day) followed by 90 minutes wearing surgical gloves. The average percentage reduction in normal flora obtained indicated that alcoholic chlorhexidine was superior to the other agents.


What stops practitioners discussing medication breaks in children and adolescents with ADHD? Identifying barriers through theory-driven qualitative research.
National and international guidelines on the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents call for annual reviews to assess continuing need for medication by considering brief periods without medication, referred to as 'Drug holidays'. However, drug holidays are reactively initiated by families, or recommended by practitioners if growth has been suppressed by medication rather than proactively to check the need. There is little evidence of planned, practitioner-initiated drug holidays from methylphenidate. The aim of this study was to identify what stops practitioners from routinely discussing planned drug holidays from methylphenidate with children, adolescents, and their parents. Practitioners involved in shared-care prescribing for children and adolescents with ADHD in one UK County were included. Interviews with 8 general practitioners (GPs) and 8 Child and Adolescent Mental Health Service (CAMHS) practitioners were conducted. Transcripts were analysed qualitatively against the components of the Capability-Opportunity-Motivation-Behaviour (COM-B) model. Possible interventions for increasing prescribers' engagement with planned drug holidays were considered in response. Multiple barriers to practitioner engagement in planned drug holidays from methylphenidate were identified. Capability, in terms of knowledge and skills, was not a barrier identified for CAMHS practitioners but was for GPs. Opportunity was a main barrier for both groups, who reported lack of time and the absence of educational material about drug holidays. Motivation was more complex to define, with CAMHS practitioners questioning the need for drug holidays and GPs being more accepting due to worries about long-term medication side effects as well as cost savings. 'Education' and 'enablement' interventions were identified as key activities targeting all three components, which could feasibly increase uptake of practitioner-initiated planned drug holidays from methylphenidate. The application of the COM-B system identified a number of key barriers to practitioner engagement with drug holidays in children and adolescents with ADHD. Accordingly, a number of interventions could be developed to facilitate change. For example, educating and training GPs about ADHD management and drug holidays, and developing a decision aid to help families make informed decisions about whether or not to implement drug holidays could be used.


Genetic rescue of an insular population of large mammals.
Natural populations worldwide are increasingly fragmented by habitat loss. Isolation at small population size is thought to reduce individual and population fitness via inbreeding depression. However, little is known about the time-scale over which adverse genetic effects may develop in natural populations or the number and types of traits likely to be affected. The benefits of restoring gene flow to isolates are therefore also largely unknown. In contrast, the potential costs of migration (e.g. disease spread) are readily apparent. Management for ecological connectivity has therefore been controversial and sometimes avoided. Using pedigree and life-history data collected during 25 years of study, we evaluated genetic decline and rescue in a population of bighorn sheep founded by 12 individuals in 1922 and isolated at an average size of 42 animals for 10-12 generations. Immigration was restored experimentally, beginning in 1985. We detected marked improvements in reproduction, survival and five fitness-related traits among descendants of the 15 recent migrants. Trait values were increased by 23-257% in maximally outbred individuals. This is the first demonstration, to our knowledge, of increased male and female fitness attributable to outbreeding realized in a fully competitive natural setting. Our findings suggest that genetic principles deserve broader recognition as practical management tools with near-term consequences for large-mammal conservation.


Streetlife and delinquency.
The correlation between class and delinquency often observed in areal studies and assumed in prominent sociological theories is elusive in studies of individuals commonly used to test these theories. A restricted conceptualization of class in terms of parental origins and the concentration of self-report survey designs on adolescents in school have removed from this area of research street youth who were once central to classic studies of delinquency. We argue that street youth experience current class conditions that cause serious delinquency, and that life on the street is an important intervening variable that transmits indirect effects of control and strain theory variables, including parental class origins. Data gathered from nearly 1000 Toronto school and street youth are analyzed with important implications for the conceptualization of class and delinquency, testing and integrating sociological theories of delinquency, the measurement of delinquency, and the use of cross-sectional and longitudinal research designs. Our findings especially encourage incorporation of street-based samples into research on class-based aspects of theories of delinquency.


Risk factors for immune checkpoint inhibitor-related pneumonitis in non-small cell lung cancer.
Immune checkpoint inhibitors (ICIs) have led to dramatic improvements in survival a subset of patients with non-small cell lung cancer (NSCLC); however, they have been shown to cause life-threatening toxicity such as immune checkpoint inhibitor-related pneumonitis (CIP). Our previous studies have shown that chronic obstructive pulmonary disease (COPD) and circulating cytokines are associated with clinical outcomes in NSCLC patients receiving ICIs. However, the relationship between these factors and the development of CIP is unclear. In this study, we retrospectively assessed NSCLC patients receiving ICIs to identify CIP risk factors. This retrospective cohort study reviewed medical records of NSCLC patients receiving ICIs targeting programmed cell death 1 (PD-1) or its ligand PD-L1 between March 2017 and December 2020 at Zhongshan Hospital Fudan University. CIP was diagnosed by the treating investigator. Clinical characteristics and baseline plasma cytokines were collected. Logistic regression was used to compare clinical characteristics and circulating cytokine levels between patients with and without CIP to identify CIP risk factors. Of 164 NSCLC patients who received ICIs, CIP developed in 20 cases (12.2%). The presence of COPD [odds ratio (OR), 7.194; 95% confidence interval (CI): 1.130 to 45.798; P=0.037] and PD-L1 expression of ≥50% (OR, 7.184; 95% CI: 1.154 to 44.721; P=0.035) were independently associated with a higher incidence of CIP, whereas a higher baseline level of interleukin-8 (IL-8) was associated with a lower incidence of CIP (OR, 0.758; 95% CI: 0.587 to 0.978; P=0.033). The independent risk factors from final multivariate analysis were incorporated into a nomogram to predict the incidence of CIP. The nomogram model receiver operating characteristic (ROC) curve had a good predictive accuracy of 0.883 (95% CI: 0.806 to 0.959). Increased risk of CIP independently associated with history of COPD, tumor PD-L1 expression ≥50%, and low baseline IL-8 level. The nomogram may hold promise for CIP risk assessment in the administration of ICIs.


Sub-femtosecond timing jitter, all-fiber, CNT-mode-locked Er-laser at telecom wavelength.
We demonstrate a 490-attosecond timing jitter (integration bandwidth: 10 kHz - 39.4 MHz) optical pulse train from a 78.7-MHz repetition rate, all-fiber soliton Er laser mode-locked by a fiber tapered carbon nanotube saturable absorber (ft-CNT-SA). To achieve this jitter performance, we searched for a net cavity dispersion condition where the Gordon-Haus jitter is minimized while maintaining stable soliton mode-locking. Our result shows that optical pulse trains with well below a femtosecond timing jitter can be generated from a self-starting and robust all-fiber laser operating at telecom wavelength.