Early post-convulsive prolongation of QT time in children.
An important differential diagnosis of seizures in childhood is the long QT syndrome. Childhood epilepsy occurs about 400 times more often than long QT syndrome. We had observed children with slight post-convulsive prolongation of QT time more often than the reported incidence of long QT syndrome. We therefore conducted a prospective study to define the characteristics of post-convulsive prolongation of QT time in children. We investigated 30 consecutive infants and children (3 mo to 14 y) within 2 h after seizures. A follow-up ECG was obtained 1-9 d later. We also obtained ECGs from 30 healthy age- and gender-matched controls. We calculated the QT interval corrected for heart rate (QTc) by Bazett's formula in leads II, V5, V6, QT dispersion and the number of notched T waves. We found a QTc interval of more than 440 ms in one or more leads in the first ECG in seven of 30 infants and children compared to 1 of 30 in the follow-up ECG (p=0.0003) and two of 30 in the healthy controls (p=0.14). Average QTc was higher for all leads in the first ECG. This was statistically significant in leads II (414 vs 402 ms, p=0.008), V5 (416 vs 404 ms, p=0.002) and V6 (415 vs 399 ms, p=0.001). Compared to healthy controls, QT dispersion was slightly larger in the early post-convulsive ECG (36 vs 31 ms, p=0.03). Notched T waves occurred more frequently in the early compared to the late post-convulsive ECGs (p=0.009). Slight to moderate post-convulsive prolongation of the QT interval is not rare but transient in paediatric patients.


Wireless sensing systems in clinical environments: improving the efficiency of the patient monitoring process.
Multiple studies suggest that the level of patient care may decline in the future because of a larger aging population and medical staff shortages. Wireless sensing systems that automate some of the patient monitoring tasks can potentially improve the efficiency of patient workflows, but their efficacy in clinical settings is an open question. This article examines the potential of wireless sensor network (WSN) technologies to improve the efficiency of the patient-monitoring process in clinical environments. MEDiSN, a WSN designed to continuously monitor the vital signs of ambulatory patients, is designed. The usefulness of MEDiSN is validated with test bed experiments and results from a pilot study performed at the Emergency Department, Johns Hopkins Hospital. Promising results indicate that MEDiSN can tolerate high degrees of human mobility, is well received by patients and staff members, and performs well in real clinical environments.


Post-synthetic preparation of Sn-, Ti- and Zr-beta: a facile route to water tolerant, highly active Lewis acidic zeolites.
A two-step procedure for the post-synthetic preparation of Lewis acidic Sn-, Zr- and Ti-zeolite β is reported. Dealumination of a commercially available Al-β zeolite leads to the formation of highly siliceous material containing silanol nests, which can be filled in a second step via the solid-state ion-exchange or impregnation of an appropriate metal precursor. Spectroscopic studies indicate that each metal is subsequently coordinated within the zeolite framework, and that little or no bulk oxides are formed--despite the high metal loadings. The synthesised catalysts demonstrate excellent activity for the isomerisation of glyceraldehyde to dihydroxyacetone, a key model reaction for the upgrading of bio-renewable feedstocks, and the epoxidation of bulky olefins.


Synthesis and Relaxometric Characterization of New Poly[N,N-bis(3-aminopropyl)glycine] (PAPGly) Dendrons Gd-Based Contrast Agents and Their in Vivo Study by Using the Dynamic Contrast-Enhanced MRI Technique at Low Field (1 T).
The synthesis of poly[N,N-bis(3-aminopropyl)glycine] (PAPGly) dendrons Gd-based contrast agents (GdCAs) via an orthogonal protection of the different functional groups and an activation/coupling strategy wherein a specific number of synthetic steps add a generation to the existing dendron has been described. The aim of this protocol is to build up two different generations of dendrons (G-0 or dendron's core, and G-1) with peripheral NH2 groups to conjugate a 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) derivative and afterwards to chelate with Gd3+ paramagnetic ions. These complexes, which have a well-defined molecular weight, are of relevance to MRI as an attempt to gain higher 1 H relaxivity by slowing down the rotation of molecule compared to monomeric Gd(III) complexes used as contrast agents and to increase the number of paramagnetic centers present in one molecular structure. From the study of their water 1 H longitudinal relaxation rate at different magnetic fields (NMRD, Nuclear Magnetic Relaxation Dispersion) and by evaluating the variable temperature 17 O-NMR data we determined the parameters characterizing the water exchange rate and the rotational correlation time of each complex, both affecting 1 H relaxivity. Furthermore, these two novel PAPGly GdCAs were objects of i) an in vivo study to determine their biodistributions in healthy C57 mice at several time points, and ii) the Dynamic Contrast-Enhanced MRI (DCE-MRI) approach to assess their contrast efficiency measured in the tumor region of C57BL/6 mice transplanted subcutaneously with B16-F10 melanoma cells. The aim of the comparison of these two dendrons GdCAs, having different molecular weights (MW), is to understand how MW and relaxivity may influence the contrast enhancement capabilities in vivo at low magnetic field (1 T). Significant contrast enhancement was observed in several organs (vessel, spleen and liver), already at 5 min post-injection, for the investigated CAs. Moreover, these CAs induced a marked contrast enhancement in the tumor region, thanks to the enhanced permeability retention effect of those macromolecular structures.


Do morphological and physiological characteristics of males of the dragonfly Macrothemis imitans determine the winner of territorial contests?
Males of many animal species show intraspecific disputes for mating territories that range from displays without physical contact to physical fights with risk of injury. This variation motivated the proposition of different models that suggest possible rules used by rivals to decide the contest winner. To evaluate those models, it is necessary to identify how males behave during the fight and the individual attributes that determine their fighting ability (resource holding potential). For this, males of the dragonfly Macrothemis imitans (Karsch) (Odonata: Libellulidae) were used to evaluate two hypotheses conditioned on the occurrence of physical contact during the fight: if the contests occur with physical contact, features related to size should determine male resource holding potential, and if males do not exhibit physical contact during the contests, features that confer greater endurance should determine resource holding potential. To assess these hypotheses, we collected males that had ownership of territories (resident males) and males that occupied the territory after we removed the resident males (substitute males). After the capture, the resident and substitute males were transferred to the laboratory for measurements of wing area, dry weight, thoracic muscle mass, and fat content. The results showed that resident males do not differ in any measured trait from substitutes. Because the fights occur with physical contact, it is intriguing that resident males do not possess higher fighting capacity than intruders. Perhaps physical contact does not incur high costs during the fight, and other asymmetries, such as motivation associated with prior residency of the disputed territory, determine the contest winner.


[A pocket pRb mutation induces the increase in its affinity to E2F4 coupled with activation of muscle differentiation].
Co-ordination of proliferation and differentiation in cells committed to muscle fate requires the interaction of the retinoblastoma gene product (pRb) with transcription factors of the E2F family. pRb has different affinities for distinct E2Fs, however, the mechanism involved in pRb-E2Fs interaction has not been completely investigated. We have found that pRb carrying a small deletion at the end of the T antigen binding region (deltaS/N), and unable to interact with large T antigen, could induce acute cell cycle block, stable prolongation of the cell cycle in G0/G1 and G2/M phases and suppression of the growth of tumor cells. The deltaS/N showed increased affinity for E2F4, bound hyperphosphorylated forms of E2F4 and induced its nuclear compartmentalization. The ability of deltaS/N to form complexes with E2F4 on DNA was associated with an increase in formation of "free" E2F4 and transsuppression of the specific reporter through preferential binding to E2F4 but not t o E2F1. Stable expression of deltaS/N in multi-potent fibroblasts promoted early muscle commitment. The results obtained suggest that a mutation in the T antigen binding region may increase in affinity of the pRb for E2F4 combined with activation of muscle differentiation.


Mammalian target of Rapamycin inhibition and mycobacterial survival are uncoupled in murine macrophages.
Autophagy is a cellular response to intracellular pathogens including mycobacteria and is induced by the direct inhibitors of mammalian target of Rapamycin (mTOR), a major negative regulator of autophagy. Autophagy induction by mTOR inhibition (mTOR dependent autophagy), through chemical means or starvation, leads to mycobacterial killing in infected cells. However, previous work by our group has shown that mycobacterial infection of macrophages naturally induces both autophagy and mammalian target of Rapamycin (mTOR) activity (mTOR independent autophagy). In the current work, we further explore the relationship between mTOR activity and mycobacterial killing in macrophages. While low concentrations of the mTOR inhibitors, Rapamycin, Torin 1, and Torin 2, can effectively reduce or block mTOR activity in response to lipopolysaccharides (LPS) or mycobacteria, higher concentrations (10 uM) are required to observe Mycobacterium smegmatis killing. The growth of M. smegmatis was also inhibited by high concentrations of Rapamycin in LC3B and ATG5 deficient bone marrow derived macrophages, suggesting that non-autophagic mechanisms might contribute to killing at high doses. Since mycobacterial killing could be observed only at fairly high concentrations of the mTOR inhibitors, exceeding doses necessary to inhibit mTOR, we hypothesized that high doses of Rapamycin, the most commonly utilized mTOR inhibitor for inducing autophagic killing, may exert a direct bactericidal effect on the mycobacteria. Although a short-term treatment of mycobacteria with Rapamycin did not substantially affect mycobacterial growth, a long-term exposure to Rapamycin could impact mycobacterial growth in vitro in select species. This data, coupled with previous work from our laboratory, further indicates that autophagy induction by mTOR inhibition is an artificial means to increase mycobacterial killing and masks more relevant endogenous autophagic biochemistry that needs to be understood.


Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia.
In order to improve the molecular response rate and prevent resistance to treatment, combination therapy with different dosages of imatinib and cytarabine was studied in newly diagnosed patients with chronic myeloid leukemia in the HOVON-51 study. Having reported feasibility previously, we hereby report the efficacy of escalated imatinib (200 mg, 400 mg, 600 mg or 800 mg) in combination with two cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1 to 7) in 162 patients with chronic myeloid leukemia. With a median follow-up of 55 months, the 5-year cumulative incidences of complete cytogenetic response, major molecular response, and complete molecular response were 89%, 71%, and 53%, respectively. A higher Sokal risk score was inversely associated with complete cytogenetic response (hazard ratio of 0.63; 95% confidence interval, 0.50-0.79, P<0.001). A higher dose of imatinib and a higher dose of cytarabine were associated with increased complete molecular response with hazard ratios of 1.60 (95% confidence interval, 0.96-2.68, P=0.07) and 1.66 (95% confidence interval, 1.02-2.72, P=0.04), respectively. Progression-free survival and overall survival rates at 5 years were 92% and 96%, respectively. Achieving a major molecular response at 1 year was associated with complete absence of progression and a probability of achieving a complete molecular response of 89%. The addition of intravenous cytarabine to imatinib as upfront therapy for patients with chronic myeloid leukemia is associated with a high rate of complete molecular responses (Clinicaltrials.Gov Identifier: NCT00028847).


The struggle for Sunday lunch: gastropolitics in the life of Nelson Mandela.
This paper explores the political, economic, and social life of Nelson Mandela through his food choices from 1918 to the present. A description of the minutiae of one particular 1950s Sunday lunch is used to examine the broader role of first colonial and later apartheid legislation in determining the dietary choices and options of South Africans past and present. How such policies shaped attitudes and access to Nelson Mandela's ancestral Xhosa cuisine is assessed. The long-term cultural, economic, and political impact of a lack of access to core indigenous African ingredients is evaluated. Most of all this paper offers a snapshot portrayal of two families (one white, one black) trying to sustain a normal friendship within a grossly abnormal society.


Lipid Droplet Formation, Their Localization and Dynamics during Leishmania major Macrophage Infection.
Leishmania, the causative agent of vector-borne diseases, known as leishmaniases, is an obligate intracellular parasite within mammalian hosts. The outcome of infection depends largely on the activation status of macrophages, the first line of mammalian defense and the major target cells for parasite replication. Understanding the strategies developed by the parasite to circumvent macrophage defense mechanisms and to survive within those cells help defining novel therapeutic approaches for leishmaniasis. We previously showed the formation of lipid droplets (LDs) in L. major infected macrophages. Here, we provide novel insights on the origin of the formed LDs by determining their cellular distribution and to what extent these high-energy sources are directed to the proximity of Leishmania parasites. We show that the ability of L. major to trigger macrophage LD accumulation is independent of parasite viability and uptake and can also be observed in non-infected cells through paracrine stimuli suggesting that LD formation is from cellular origin. The accumulation of LDs is demonstrated using confocal microscopy and live-cell imagin in parasite-free cytoplasmic region of the host cell, but also promptly recruited to the proximity of Leishmania parasites. Indeed LDs are observed inside parasitophorous vacuole and in parasite cytoplasm suggesting that Leishmania parasites besides producing their own LDs, may take advantage of these high energy sources. Otherwise, these LDs may help cells defending against parasitic infection. These metabolic changes, rising as common features during the last years, occur in host cells infected by a large number of pathogens and seem to play an important role in pathogenesis. Understanding how Leishmania parasites and different pathogens exploit this LD accumulation will help us define the common mechanism used by these different pathogens to manipulate and/or take advantage of this high-energy source.


Sleep Disturbance in Older Patients in the Emergency Department: Prevalence, Predictors and Associated Outcomes.
Impaired sleep is common in hospital. Despite this, little is known about sleep disturbance among older adults attending Emergency Departments (ED), particularly overnight-boarders, those admitted but housed overnight while awaiting a bed. Consecutive, medically-stable patients aged ≥70, admitted through a university hospital ED were evaluated for overnight sleep quality (Richards Campbell Sleep Questionnaire/RCSQ) and baseline sleep (Pittsburgh Sleep Quality Index/PSQI). Additional variables included frailty, functional and cognitive status, trolley location, time in ED and night-time noise levels. Over four-weeks, 152 patients, mean age 80 (± 6.8) years were included; 61% were male. Most (68%) were ED boarders (n = 104) and 43% were frail. The majority (72%) reported impaired sleep quality at baseline (PSQI ≥ 5) and 13% (20/152) had clinical insomnia. The median time spent in ED for boarders was 23 h (Interquartile ± 13). After adjusting for confounders, median RCSQ scores were significantly poorer for ED boarders compared with non-boarders: 22 (± 45) versus 71 (± 34), respectively, (p = 0.003). There was no significant difference in one-year mortality (p = 0.08) length of stay (LOS) (p = 0.84), 30-day (p = 0.73) or 90-day (p = 0.64) readmission rates between boarders and non-boarders. Sleep disturbance is highly prevalent among older adults admitted through ED. ED boarders experienced significantly poorer sleep, without this impacting upon mortality, LOS or re-admission rates.


Severity of combat-related posttraumatic stress disorder versus noncombat-related posttraumatic stress disorder: a community-based study in American Indian and Hispanic veterans.
The goal of the study was to compare severity of combat-related posttraumatic stress disorder (PTSD) versus noncombat-related PTSD in a group known to have high rates of combat-related PTSD. Sample consisted of 255 male American Indian and Hispanic veterans with lifetime PTSD who were contacted in communities in 2 regions of the country. Measures of PTSD severity included current posttraumatic symptoms, remission from lifetime PTSD, lifetime severity of alcohol-drug related problems, and mental health treatment history. Our findings revealed that veterans with combat-related PTSD had more severe posttraumatic symptoms, were less apt to have remitted from PTSD during the last year, and-contrary to expectation-were less apt to have sought mental health treatment since military duty. In conclusion, combat-related PTSD was more severe, as compared with noncombat-related PTSD, in this group, on 2 out of 5 measures. A low rate of mental health treatment since military duty may have contributed to increased symptoms and a lower remission rate.


Risk factors for infection with Toxoplasma gondii for residents and workers on swine farms in Illinois.
Risk factors for Toxoplasma gondii infection in workers and residents of swine farms were studied on 43 farms in Illinois. Blood samples were collected from 174 adults in 1993. The T. gondii seroprevalence was 31%. An interview was conducted with each participant, obtaining information on demographic characteristics and behaviors suspected to affect the risk of T. gondii infection. Factors associated with increased risk of T. gondii seropositivity were a higher number of seropositive cats trapped on the farm, male sex, rearing pigs on pasture, and gardening. Factors associated with a decreased risk were handling of pig feed and presence of cats inside the pig facilities. Thus, infection of cats with T. gondii increased the risk of human infection, and contact with soil was a likely mechanism for transmission. The increased risk of seropositivity in males is attributed to less attention paid to cleanliness in food preparation and eating.


Labor Migration, Drug Trafficking Organizations, and Drug Use: Major Challenges for Transnational Communities in Mexico.
In our article, we present the recent findings of our ethnographic field study on drug use and the emergence of a drug use culture in transnational communities in Mexico. Transnational communities are part of a larger migratory labor circuit that transcends political borders and are not restricted to a single locality. Transnational migrants and returning immigrants link the multiple localities through their social networks. In southern Guanajuato, Mexico, using a transnational migration paradigm, we examined the manner in which transnational migration and drug trafficking organizations are contributing to a growing drug problem in these communities. We found that transnational migrants and returning immigrants, including deported workers, introduce drugs and drug use practices, and contribute to the creation of a drug use culture within the communities. The social conditions in the community that foster and proliferate drug use are many: the erosion of the traditional family, truncated kinship bases, and new social formations. These conditions are all consequences of migration and emigration. Recent drug cartel activities are also contributing to this growing drug problem. The cartels have aggressively targeted these communities because of availability of money, existing drug use, a drug use culture, and the breakdown of traditional deterrents to substance abuse. Although a number of communities in three municipalities were part of our study, we focus on two: Lindavista, a rancho, Progreso, a municipal seat. Our field study in Mexico, one of four sequential ethnographic field studies conducted in Guanajuato and Pennsylvania, was completed over a six month period, from September, 2008, through February, 2009, using traditional ethnography. The four field studies are part of a larger, ongoing, three-year bi-national study on drug use among transnational migrants working in southeastern Pennsylvania. This larger study, near its third and final year, is funded by the National Institute of Drug Abuse.


Ionic sensitivity of baroreceptors.
Baroreceptors respond to distortion of their receptor regions by producing action potentials and, thus, provide information to the central nervous system for cardiovascular control. The mechanisms converting mechanical events to electrical signals are unknown. Since it has not been possible to record a receptor potential in the mechanosensitive terminals, studies rely on interpretation of axonal discharge of baroreceptor endings. In the present study, the ionic sensitivity of in vitro preparations of both low- and high-pressure receptors are compared in studies in which the ionic composition of the extracellular fluid is controlled. The results taken together with previous work suggest uniformity of response to calcium, sodium, and potassium across a variety of cardiovascular receptor types supporting common mechanoelectrical transduction mechanisms. Decreased extracellular sodium produced increased threshold and decreased slopes of pressure-discharge curves for both aortic arch baroreceptors and for low-pressure baroreceptors in the atrium. Results are consistent with data for other mechanoreceptors where it is believed that distortion activates a relatively poorly selective cation-conducting channel through the membrane. As with arterial baroreceptors, increases in external calcium levels caused a decrease in the excitability of atrial baroreceptors. Substitution of half the external calcium with the inorganic calcium channel blocker cobalt failed to alter baroreceptor function. Bay K 8644, a calcium channel agonist of the dihydropyridine class of calcium channel blockers, tended to inhibit baroreceptor discharge with effects consistent with smooth muscle activation within the vessel wall. Several hypotheses of potential underlying mechanisms are discussed. These new experiments are consistent with the results achieved with alterations of ionic calcium and suggest that calcium entry does not play a detectable role in baroreceptor transduction.


Simultaneous occurrence of internal capsule infarct and cerebellar haemorrhage in a patient with hemiplegia.
A 68-year-old woman with hypertension with no history of cerebrovascular events presented with a left-sided hemiplegia which had developed acutely 2 days ago. She was not on maintenance therapy with antiplatelets or anticoagulants. A CT scan showed acute ischaemic infarction of the right internal capsule and cerebellar haemorrhage. Cardiac evaluation was normal. Doppler ultrasonography of the extracranial carotid and vertebral arteries showed diffuse arteriosclerotic changes, but did not reveal any haemodynamic occlusion. The simultaneous development of dual strokes was considered to be an extension of the same arteriosclerotic process to the intracranial carotid and basilar arteries.


Prevention of relapsing backache.
The condition of non-specific back pain is characterized by high prevalence, non satisfactory therapeutic options and severe socioeconomic consequences. Therefore prevention seems an attractive option to downsize the problem. However, the construction of effective preventive measures is complicated by the obscure aetiology of the condition, the multidimensionality of risk and prognostic factors (bio psychosocial model!) and the variability of its natural as well as clinical course. This led to the development of a wide variety of preventive measures: e. g. exercise programs, educational measures (including back school), ergonomic modification of the work environment, mechanical supports (e. g. back belts) as well as multidisciplinary interventions. For two reasons the workplace seems to be a suitable setting for prevention. First, because a number of strong risk factors are associated with working conditions and second, because it allows addressing a large proportion of the adult population. Against this background the assessment at hand sets out to answer the following questions: What is the amount and methodological quality of the available scientific literature on the effectiveness of back pain prevention in the workplace environment? What are effective measures for the prevention of back pain and its consequences in the workplace environment and how effective are they? Is back pain prevention in the workplace environment cost-effective? Is there a need for more research? As primary outcomes for effectiveness the assessment will focus on time lost from work and the frequency and duration of episodes with back pain. The preventive measures assessed belong to the following categories: exercise programs, educational and information measures, multidimensional interventions, back belts, lifting teams and ergonomic interventions. The assessment is based on a systematic review of the published literature according to the methodological requirements of DAHTA. Proceedings of the electronic literature searches are documented in the appendix. In addition references of review articles were searched. Methodological quality of publications (systematic reviews, HTA reports) was assessed using the checklists developed by the German Scientific Working Group for Technology Assessment in Health Care (GSWGTAHC) or with the Jadad-Score (controlled trials) respectively. Due to the large number of relevant publications the assessment is mainly based on data reported by systematic reviews and supplemented by the results of newer trials. A separate economic assessment was not performed because of the low amount of available data. An assessment of ethical, legal and social impact was omitted due to resource constraints. For preventive interventions based on exercise programs most of the analysed trials demonstrate some effectiveness. Due to the heterogeneity of the programs it is not possible to conclude whether positive effects are associated with a special type, duration or intensity of exercise. For purely educational measures or information strategies applied in a workplace setting the available trials were not able to demonstrate effectiveness. Back school programs, which in addition to theoretical instructions offer intensive exercising may in the short term, be successful in reducing the incidence of new episodes of back pain. Some trials in high risk groups demonstrate effectiveness of multidimensional interventions on time lost from work. These programs include education and exercise as well as cognitive behavioural interventions to change pain perception. The assessment of the benefits of back belts for the prevention of back pain is based on results of high quality efficacy as well as effectiveness trials. Their results imply for the otherwise healthy working population no protective effect of back belts on time lost from work due to back pain, on the incidence of painful episodes or on days with impairment by back pain. So far there are no data from controlled trials that demonstrate the effectiveness of "lifting teams" in nursing care to prevent back pain or its consequences. However, results from uncontrolled pilot studies indicate a potential for effectiveness. Among "ergonomic interventions" three different approaches have to be distinguished: interventions addressing changes of the workplace setting, interventions addressing the individual's behaviour and combined interventions. Studies evaluating the effectiveness of setting interventions (modification of the physical workplace environment, changes of production processes, organisational changes) yield no dependable results. This conclusion is not based on indifferent trial results but rather on the lack of methodologically sound studies. Results from studies on ergonomic interventions addressing the individual confirm the conclusions drawn for exercise and educational measures. The most marked results are found in trials that examine the effectiveness of combined interventions in high risk groups and contain a strong participatory component. Hardly any of the trials studying the effects of ergonomic interventions satisfied methodological quality criteria that are accepted standard for clinical or public health intervention studies. There were no data allowing firm conclusions on the cost-effectiveness of interventions from any of the categories. The significance of the results of the assessment at hand is strongly limited by the comprehensiveness of the questions addressed. Reviewing the literature on the basis of (even systematic) review articles impairs the differentiated examination of the role of target groups, program contents, application and duration, effect sizes and context factors. While the methodological quality of the review articles is quite high, the quality of individual trials (even those included in the review papers) is highly variable. While most trials examining preventive interventions addressed at individuals satisfy at least some methodological requirements many studies dealing with setting interventions do not. In conclusion, sound scientific evidence for the effectiveness and cost-effectiveness of back pain prevention in the workplace environment is still quite scarce. Further research should include: The development of interventions guided by the bio psychosocial model of back pain aetiology that combines individual prevention as well as measures addressing the workplace environment.The integration of results from basic ergonomic research into prevention concepts and the conduct of trials focussing outcomes with relevance to health.at the workplace setting. The conduct of qualitative studies to identify factors that impair the effectiveness of prevention programs (e. g. motivation, compliance, people skills).The integration of cost-effectiveness evaluations into all interventional studies.


A tale of two cases: urging caution in the prosecution of HIV non-disclosure.
Two provincial Courts of Appeal have recently released unanimous decisions that clarify the law regarding the obligation imposed upon people living with HIV to disclose their HIV status prior to sexual relations. The decision of the Manitoba Court of Appeal in R v. Mabior and of the Quebec Court of Appeal in R c. D.C. must be seen against a background of increasing criminal prosecutions in Canada of people with HIV who allegedly do not disclose their HIV status to sexual partners. Since the first HIV non-disclosure prosecution in 1989, there have been over 120 prosecutions. A high proportion of accused has either pleaded guilty to, or been convicted at trial, of serious criminal offences, often resulting in harsh sentences and sex offender registration. In the majority of convictions, there was no transmission of HIV to the complainant.


Runx2 is a novel regulator of mammary epithelial cell fate in development and breast cancer.
Regulators of differentiated cell fate can offer targets for managing cancer development and progression. Here, we identify Runx2 as a new regulator of epithelial cell fate in mammary gland development and breast cancer. Runx2 is expressed in the epithelium of pregnant mice in a strict temporally and hormonally regulated manner. During pregnancy, Runx2 genetic deletion impaired alveolar differentiation in a manner that disrupted alveolar progenitor cell populations. Conversely, exogenous transgenic expression of Runx2 in mammary epithelial cells blocked milk production, suggesting that the decrease in endogenous Runx2 observed late in pregnancy is necessary for full differentiation. In addition, overexpression of Runx2 drove epithelial-to-mesenchymal transition-like changes in normal mammary epithelial cells, whereas Runx2 deletion in basal breast cancer cells inhibited cellular phenotypes associated with tumorigenesis. Notably, loss of Runx2 expression increased tumor latency and enhanced overall survival in a mouse model of breast cancer, with Runx2-deficient tumors exhibiting reduced cell proliferation. Together, our results establish a previously unreported function for Runx2 in breast cancer that may offer a novel generalized route for therapeutic interventions. Cancer Res; 74(18); 5277-86. ©2014 AACR.


Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells.
Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5x10(10) viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases.


Real-world performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions.
About 3 million surgical pigmented skin lesion biopsies are performed each year in the USA alone to diagnose fewer than 200 000 new cases of invasive melanoma and melanoma in situ using the current standard of care that includes visual assessment and histopathology. A recently described noninvasive adhesive patch-based gene expression rule-out test [pigmented lesion assay (PLA)] may be helpful in identifying high-risk pigmented skin lesions to aid with surgical biopsy decisions. The main objective of this utility study was to determine the real-world clinical performance of PLA use and assess how the PLA changes physician behavior in an observational cohort analysis of 381 patients assessed with the PLA. All (100%) of 51 PLA(+) test results were clinically managed with surgical biopsy. Of these, 19 (37%) were melanomas, corresponding to a number needed to biopsy of 2.7 and a biopsy ratio of 1.7. All melanomas were histopathologically classified as melanoma in situ or stage 1. Nearly all (99%) of 330 PLA(-) test results were clinically managed with surveillance. None of the three follow-up biopsies performed in the following 3-6 months, were diagnosed as melanoma histopathologically. The estimated sensitivity and specificity of the PLA from these data sets are 95 and 91%, respectively. Overall, 93% of PLA results positive for both LINC00518 and PRAME were diagnosed histopathologically as melanoma. PRAME-only and LINC00518-only lesions were melanomas histopathologically in 50 and 7%, respectively. The PLA alters clinical management of pigmented lesions and shows high clinical performance. The likelihood of positive histopathologic diagnosis of melanoma is higher in PLA results that are positive for both LINC00518 and PRAME.


Standard set of health outcome measures for older persons.
The International Consortium for Health Outcomes Measurement (ICHOM) was founded in 2012 to propose consensus-based measurement tools and documentation for different conditions and populations.This article describes how the ICHOM Older Person Working Group followed a consensus-driven modified Delphi technique to develop multiple global outcome measures in older persons. The standard set of outcome measures developed by this group will support the ability of healthcare systems to improve their care pathways and quality of care. An additional benefit will be the opportunity to compare variations in outcomes which encourages and supports learning between different health care systems that drives quality improvement. These outcome measures were not developed for use in research. They are aimed at non researchers in healthcare provision and those who pay for these services. A modified Delphi technique utilising a value based healthcare framework was applied by an international panel to arrive at consensus decisions.To inform the panel meetings, information was sought from literature reviews, longitudinal ageing surveys and a focus group. The outcome measures developed and recommended were participation in decision making, autonomy and control, mood and emotional health, loneliness and isolation, pain, activities of daily living, frailty, time spent in hospital, overall survival, carer burden, polypharmacy, falls and place of death mapped to a three tier value based healthcare framework. The first global health standard set of outcome measures in older persons has been developed to enable health care systems improve the quality of care provided to older persons.


Evaluation of Lactobacillus spp. and yeast based probiotic (Lavipan) supplementation for the reduction of Salmonella Enteritidis after infection of broiler chickens.
The number of human cases of salmonellosis in the EU was 94,625 in 2015. Considering the source of these infections, Salmonella spp. was most frequently detected in broiler chicken meat and Salmonella Enteritidis (SE) was the most commonly reported serovar. The efficacy of probiotics in limiting Salmonella spp. infection in poultry has been demonstrated in numerous papers. The administration of probiotics at the level of primary production reduces the risk of contamination of poultry food products with Salmonella spp. A study was carried out in order to determine the potential for reducing the Salmonella spp. population in broiler chickens with the use of the Lavipan (JHJ, Poland) probiotic that comprised selected stains of lactic acid bacteria and Saccharomyces cervisae. Salmonella spp.-free broiler chickens were divided into two groups and received the same feed with (group L) or without (group C) the probiotic throughout the experiment. All day-old chickens were infected per os with SE. Samples of cecum content were collected 2, 4, and 6 weeks after SE infection and pectoral muscles were collected 6 weeks following SE infection for the evaluation of the SE population number. Serum samples for serological examinations were collected 6 weeks after infection. Six weeks after infection, the number of SE-positive cecal samples was lower in the L group (12.5% positive) in comparison to the C group (87.5%). Similar results were demonstrated for the muscle samples (25% in contrast to 87.5%). At the same time, in both cases, the SE CFU/g was significantly lower in the L group. The results of our study indicate that Lavipan was capable of reducing the population of SE in the gastrointestinal tract, which eventually improved the hygienic parameters of the pectoral muscles. Four weeks after infection, SE was not detected in any of the experimental groups. In both groups, no specific anti-SE antibodies were detected.


Status of Cassava Begomoviruses and Their New Natural Hosts in Nigeria.
A diagnostic survey was conducted in 2002-03 to determine the status of cassava mosaic begomoviruses in Nigeria and to ascertain if the virulent Ugandan variant of East African cassava mosaic virus (EACMV-Ug2) was present. Of the 418 farms visited, 48% had cassava with moderately severe or severe symptoms, whereas 52% had cassava with mild symptoms. These distributions were at random. Of the 1,397 cassava leaf samples examined, 1,106 had symptoms. In polymerase chain reaction tests, 74.1% of the symptom-bearing samples tested positive for African cassava mosaic virus (ACMV) alone, 0.3% for EACMV alone, 24.4% for mixed infections by the two viruses, and 1.2% did not react with any of the primers used. The two viruses also were detected in 32% of the 291 symptomless plants and in the whitefly vector samples. EACMV-Ug2, Indian cassava mosaic virus, and South African cassava mosaic virus were not detected in any of the whitefly or leaf samples. Most farms had ACMV in single infection as well as in mixed infections with EACMV. Most doubly infected plants showed severe symptoms. Two biological variants of ACMV were identified based on symptom expression on cassava in the field. ACMV and EACMV were detected in the leguminous plant Senna occidentalis (L.) Link and the weed Combretum confertum Lams.; these are new natural hosts of the viruses. Although the virulent EACMV-Ug2 was not detected, the occurrence of variants of ACMV and a high proportion of mixed infections by ACMV and EACMV, which could result in recombination events such as the one that produced EACMV-Ug2, demands appropriate measures to safeguard cassava production in Nigeria.


Holographic interferometry using anisotropic self-diffraction in Bi(12)SiO(20).
Anisotropic self-diffraction in photorefractive Bi(12)SiO(20) crystals is applied to the investigation of dynamic holographic recording through the diffusion process. Specific attention is paid to optimization of experimental parameters for real-time holographic interferometry. The resultant interferometer is applied to obtain both timeaverage and double-exposure interferograms of vibrating and displaced structures.


How Diverse Detrital Environments Influence Nutrient Stoichiometry between Males and Females of the Co-Occurring Container Mosquitoes Aedes albopictus, Ae. aegypti, and Culex quinquefasciatus.
Allocation patterns of carbon and nitrogen in animals are influenced by food quality and quantity, as well as by inherent metabolic and physiological constraints within organisms. Whole body stoichiometry also may vary between the sexes who differ in development rates and reproductive allocation patterns. In aquatic containers, such as tree holes and tires, detrital inputs, which vary in amounts of carbon and nitrogen, form the basis of the mosquito-dominated food web. Differences in development times and mass between male and female mosquitoes may be the result of different reproductive constraints, which could also influence patterns of nutrient allocation. We examined development time, survival, and adult mass for males and females of three co-occurring species, Aedes albopictus, Ae. aegypti, and Culex quinquefasciatus, across environments with different ratios of animal and leaf detritus. We quantified the contribution of detritus to biomass using stable isotope analysis and measured tissue carbon and nitrogen concentrations among species and between the sexes. Development times were shorter and adults were heavier for Aedes in animal versus leaf-only environments, whereas Culex development times were invariant across detritus types. Aedes displayed similar survival across detritus types whereas C. quinquefasciatus showed decreased survival with increasing leaf detritus. All species had lower values of 15N and 13C in leaf-only detritus compared to animal, however, Aedes generally had lower tissue nitrogen compared to C. quinquefasciatus. There were no differences in the C:N ratio between male and female Aedes, however, Aedes were different than C. quinquefasciatus adults, with male C. quinquefasciatus significantly higher than females. Culex quinquefasciatus was homeostatic across detrital environments. These results allow us to hypothesize an underlying stoichiometric explanation for the variation in performance of different container species under similar detrital environments, and if supported may assist in explaining the production of vector populations in nature.


Disrupted neural activity patterns to novelty and effort in young adult APOE-e4 carriers performing a subsequent memory task.
The APOE e4 allele has been linked to poorer cognitive aging and enhanced dementia risk. Previous imaging studies have used subsequent memory paradigms to probe hippocampal function in e4 carriers across the age range, and evidence suggests a pattern of hippocampal overactivation in young adult e4 carriers. In this study, we employed a word-based subsequent memory task under fMRI; pupillometry data were also acquired as an index of cognitive effort. Participants (26 non-e4 carriers and 28 e4 carriers) performed an incidental encoding task (presented as word categorization), followed by a surprise old/new recognition task after a 40 minute delay. In e4 carriers only, subsequently remembered words were linked to increased hippocampal activity. Across all participants, increased pupil diameter differentiated subsequently remembered from forgotten words, and neural activity covaried with pupil diameter in cuneus and precuneus. These effects were weaker in e4 carriers, and e4 carriers did not show greater pupil diameter to remembered words. In the recognition phase, genotype status also modulated hippocampal activity: here, however, e4 carriers failed to show the conventional pattern of greater hippocampal activity to novel words. Overall, neural activity changes were unstable in e4 carriers, failed to respond to novelty, and did not link strongly to cognitive effort, as indexed by pupil diameter. This provides further evidence of abnormal hippocampal recruitment in young adult e4 carriers, manifesting as both up and downregulation of neural activity, in the absence of behavioral performance differences.


Toxoplasma gondii clonal strains all inhibit STAT1 transcriptional activity but polymorphic effectors differentially modulate IFNγ induced gene expression and STAT1 phosphorylation.
Host defense against the parasite Toxoplasma gondii requires the cytokine interferon-gamma (IFNγ). However, Toxoplasma inhibits the host cell transcriptional response to IFNγ, which is thought to allow the parasite to establish a chronic infection. It is not known whether all strains of Toxoplasma block IFNγ-responsive transcription equally and whether this inhibition occurs solely through the modulation of STAT1 activity or whether other transcription factors are involved. We find that strains from three North American/European clonal lineages of Toxoplasma, types I, II, and III, can differentially modulate specific aspects of IFNγ signaling through the polymorphic effector proteins ROP16 and GRA15. STAT1 tyrosine phosphorylation is activated in the absence of IFNγ by the Toxoplasma kinase ROP16, but this ROP16-activated STAT1 is not transcriptionally active. Many genes induced by STAT1 can also be controlled by other transcription factors and therefore using these genes as specific readouts to determine Toxoplasma inhibition of STAT1 activity might be inappropriate. Indeed, GRA15 and ROP16 modulate the expression of subsets of IFNγ responsive genes through activation of the NF-κB/IRF1 and STAT3/6 transcription factors, respectively. However, using a stable STAT1-specific reporter cell line we show that strains from the type I, II, and III clonal lineages equally inhibit STAT1 transcriptional activity. Furthermore, all three of the clonal lineages significantly inhibit global IFNγ induced gene expression.


The role of state public health agencies in addressing less prevalent chronic conditions.
State-based chronic disease programs typically focus on the most prevalent chronic conditions, such as cancer, diabetes, and cardiovascular disease, but interest in less prevalent chronic conditions (LPCCs), such as epilepsy, is growing. In our study, we examined the perceived roles of state health departments in addressing LPCCs and used this information to develop recommendations for state health departments that are considering developing LPCCs programs. We also compared the identified state health department roles for LPCCs with roles related to healthy aging, as well as to the essential elements of existing state-based chronic disease programs, to determine whether future LPCCs programs would have any unique requirements. Participants used concept-mapping techniques to generate a set of 100 statements on steps that state health departments could take to address LPCCs. The participants sorted and rated each statement according to importance and feasibility. We used a sequence of multivariate statistical analyses to generate a series of maps, or clusters, and rating graphics. We reviewed the findings and produced recommendations for state health departments. We used a similar process to examine roles of state health departments in addressing healthy aging. The participants grouped the LPCCs statements into nine clusters, which they rated as moderately feasible and important. The healthy aging statements were grouped into eight clusters. Clusters for LPCCs and healthy aging were similar. We also compared LPCCs clusters and the essential elements of existing state-based chronic disease programs and found that they were similar. The similarities between LPCCs clusters and essential elements of existing state-based chronic disease programs highlight an important point. State health departments that are considering establishing LPCCs programs should use strategies that have already been used by other public health agencies to develop chronic disease prevention and control programs.


Factors affecting bubble size in ionic liquids.
This study reports on understanding the formation of bubbles in ionic liquids (ILs), with a view to utilising ILs more efficiently in gas capture processes. In particular, the impact of the IL structure on the bubble sizes obtained has been determined in order to obtain design principles for the ionic liquids utilised. 11 ILs were used in this study with a range of physico-chemical properties in order to determine parametrically the impact on bubble size due to the liquid properties and chemical moieties present. The results suggest the bubble size observed is dictated by the strength of interaction between the cation and anion of the IL and, therefore, the mass transport within the system. This bubble size - ILs structure-physical property relationship has been illustrated using a series of QSPR correlations. A predictive model based only on the sigma profiles of the anions and cations has been developed which shows the best correlation without the need to incorporate the physico-chemical properties of the liquids. Depending on the IL, selected mean bubble sizes observed were between 56.1 and 766.9 μm demonstrating that microbubbles can be produced in the IL allowing the potential for enhanced mass transport and absorption kinetics in these systems.


Overweight and obesity in young adult women: A matter of health or appearance? The Tromsø study: Fit futures.
With the increasing number of overweight and obese people, there is a growing public health concern and focus on body size and lifestyle issues, especially in the media. Young adult women comprise a vulnerable group regarding issues of weight balance and appearance. The aim of the study was to examine the experiences of young women on how this focus influences their attitudes concerning weight changes, appearance, and health. We conducted 12 interviews with young women from two different weight groups about the attention on overweight issues. The results from the in-depth interviews were scrutinized through content analyses. The main findings indicate that young women experience a considerable focus on overweight issues with a trend towards appearance rather than health. Overweight and obesity are sensitive topics, and participants expressed strong views on the cultural definitions of normal body size and appearance. The squeeze between cultural norms and young women's perceptions of their own body and health was described as a possible negative factor influencing well-being as well as motivation for lifestyle changes. A more relaxed focus on overweight issues and especially on appearance is necessary when addressing weight-balance issues and lifestyle changes in young adult women.


Emotions and Instructed Language Learning: Proposing a Second Language Emotions and Positive Psychology Model.
Although emotion research and positive psychology (PP) have recently gained strong momentum in the field of second language acquisition (SLA), theoretical models linking language emotion and PP research, which offer insights for both research and intervention practice are lacking. To address this gap, the present article first introduces the origin, concept, and research around PP. Next, it summarizes recent research on PP and emotions in SLA. Finally, by triangulating emotion theories and research in the fields of psychology, education, and SLA, we propose a new model, which merges the three pillars of PP (positive institutions, positive characteristics, and positive emotions) with the antecedents, outcomes, and interventions of second language (L2) emotions (the L2EPP model). The value of the model to L2 pedagogy and research is highlighted in the context of the importance of integrating PP into the area of emotions and instructed SLA.


Academic global surgical competencies: A modified Delphi consensus study.
Academic global surgery is a rapidly growing field that aims to improve access to safe surgical care worldwide. However, no universally accepted competencies exist to inform this developing field. A consensus-based approach, with input from a diverse group of experts, is needed to identify essential competencies that will lead to standardization in this field. A task force was set up using snowball sampling to recruit a broad group of content and context experts in global surgical and perioperative care. A draft set of competencies was revised through the modified Delphi process with two rounds of anonymous input. A threshold of 80% consensus was used to determine whether a competency or sub-competency learning objective was relevant to the skillset needed within academic global surgery and perioperative care. A diverse task force recruited experts from 22 countries to participate in both rounds of the Delphi process. Of the n = 59 respondents completing both rounds of iterative polling, 63% were from low- or middle-income countries. After two rounds of anonymous feedback, participants reached consensus on nine core competencies and 31 sub-competency objectives. The greatest consensus pertained to competency in ethics and professionalism in global surgery (100%) with emphasis on justice, equity, and decolonization across multiple competencies. This Delphi process, with input from experts worldwide, identified nine competencies which can be used to develop standardized academic global surgery and perioperative care curricula worldwide. Further work needs to be done to validate these competencies and establish assessments to ensure that they are taught effectively.


Effectiveness of a back school program in the application of body mechanics principles.
Low back pain is one of the most frequent work related injuries in all occupations. Back school programs are therapeutic interventions directed towards treatment, prevention and rehabilitation of backaches. The purpose of this study was to (1) evaluate the test-retest reliability of the modified version of the Body Mechanics Evaluation Checklist (BMEC) and (2) examine the effectiveness of a back school program in terms of application of body mechanics during a lifting task. A sample of 12 participants from a public corporation in Puerto Rico was selected to participate in a back school program. The modified and translated version of the American Back School Posttest and the modified version of the Body Mechanics Evaluation Checklist were used to evaluate the theoretical and practical component of the back school program. The test-retest reliability of the BMEC was obtained through the intraclass correlation coefficient (ICC [3,1]). For pre/post assessment, a single factor repeated measures MANOVA was conducted to asses the effect of the intervention. The test-retest reliability of the modified version of the BMEC was 0.84. The single factor repeated measures MANOVA revealed significant differences between pre-test and post-test (p < .0001) scores. This study demonstrated that the modified version of the BMEC is a reliable instrument to evaluate a lifting activity. It was also demonstrated that the back school program served as an effective educational intervention that promotes short-term changes in the body mechanics of back-injured working adults in Puerto Rico.


Prenatal undernutrition and leukocyte telomere length in late adulthood: the Dutch famine birth cohort study.
Energy restriction in prenatal life has detrimental effects on later life health and longevity. Studies in rats have shown that the shortening of telomeres in key tissues plays an important role in this association. The aim of the current study was to investigate leukocyte telomere length in relation to prenatal famine exposure. The Dutch famine birth cohort consists of 2414 term singleton men and women who were born between 1943 and 1947 in Amsterdam around the time of the famine. At a mean age of 68 y, telomere length and the percentage of short telomeres was assessed in a subsample of 131 cohort members, of whom 45 were born before the famine (control), 41 were exposed to famine during early gestation, and 45 were conceived after the famine (control). Median telomere length was determined in peripheral blood leukocytes by a high-throughput quantitative fluorescent in situ hybridization-based technology. Leukocyte telomere length and the percentage of short telomeres did not differ between those exposed to famine during early gestation and those unexposed during gestation. A lower socioeconomic status at birth, frequent consumption of alcohol (specifically consumption of spirits), a history of cancer, and a lower self-reported health status were significantly associated with shorter leukocyte telomere length (all P ≤ 0.03). Currently having a job was significantly associated with a smaller percentage of short telomeres (P = 0.04). The results of the current study suggest that prenatal exposure to famine is not associated with the shortening of telomeres in peripheral blood leukocytes at age 68 y.


HOW I DID IT....THE CEO OF ATHENAHEALTH on ON THE ROLE OF ANGER IN STARTING NEW BUSINESSES.
As a boy, Bush watched Emergency! on television and was captivated by the romance and seeming magic of saving lives. As an adult, he found the reality of medicine to be very different: There wasn't much humanity in the way health care was actually delivered. Believing that he'd be daunted by the course work required for a medical degree, he decided to take an entrepreneurial route to improving the system. His first sense of the opportunity came while he was driving an ambulance in New Orleans one summer during college. Some patients with chronic disease who couldn't afford their medicines would repeatedly call the ambulance to take them to a hospital where they could be stabilized. What if the ambulance itself were outfitted with treatments for the five most common chronic diseases and carried EMTs who were trained to use them? Those patients could be treated in place, at a radically lower cost than what the hospital would charge. That idea didn't work out, and Bush moved on to think about a network of maternity clinics. He and Todd Park drew up a business plan at Harvard Business School--one that was "unbelievably complicated to execute and very risky." But in the process of pursuing it, they created websites for the paperwork with rules that prevented mistakes. That was the seed for athenahealth, which today supports electronic medical records and a suite of practice management and care coordination services, leaving doctors free to spend more time with their patients.


The Significance of Ion Conduction in a Hybrid Organic-Inorganic Lead-Iodide-Based Perovskite Photosensitizer.
The success of perovskite solar cells has sparked enormous excitement in the photovoltaic community not only because of unexpectedly high efficiencies but also because of the future potential ascribed to such crystalline absorber materials. Far from being exhaustively studied in terms of solid-state properties, these materials surprised by anomalies such as a huge apparent low-frequency dielectric constant and pronounced hysteretic current-voltage behavior. Here we show that methylammonium (but also formamidinium) iodoplumbates are mixed conductors with a large fraction of ion conduction because of iodine ions. In particular, we measure and model the stoichiometric polarization caused by the mixed conduction and demonstrate that the above anomalies can be explained by the build-up of stoichiometric gradients as a consequence of ion blocking interfaces. These findings provide insight into electrical charge transport in the hybrid organic-inorganic lead halide solar cells as well as into new possibilities of improving the photovoltaic performance by controlling the ionic disorder.


Molecular structure, infrared spectra, photochemistry, and thermal properties of 1-methylhydantoin.
The structural, vibrational, and photochemical study of 1-methylhydantoin (1-MH, C4H6N2O2) was undertaken by matrix isolation infrared spectroscopy (in argon matrix; 10 K), complemented by quantum chemical calculations performed at the DFT(B3LYP)/6-311++G(d,p) level of approximation. The theoretical calculations yielded the Cs symmetry structure, with planar heavy atom skeleton, as the minimum energy structure on the potential energy surface of the molecule. The electronic structure of this minimum energy structure of 1-MH was then studied in detail by means of the natural bond orbital (NBO) and atoms in molecules (AIM) approaches, allowing for the elucidation of specific characteristics of the molecule's σ and π electronic systems. The infrared spectrum of the matrix-isolated 1-MH was fully assigned, also with the help of the theoretically predicted spectrum of the compound, and its UV-induced unimolecular photochemistry (λ ≥ 230 nm) was investigated. The compound was found to fragment to CO, isocyanic acid, methylenimine, and N-methyl-methylenimine. Finally, a thermal behavior investigation on 1-MH samples was carried out using infrared spectroscopy (10 K until melting), differential scanning calorimetry and polarized light thermal microscopy. A new polymorph of 1-MH was identified. The IR spectra of the different observed phases were recorded and interpreted.


Short- and long-term outcomes of kidney donors: a report from Tunisia.
Kidney transplantation remains the best treatment option of end-stage renal disease. Kidney donations are of particular interest with the currently increasing practice of living-donor transplantation. The purpose of this study was to analyze retrospectively the general health status as well as renal and cardiovascular consequences of living-related kidney donation. A total of 549 living-related kidney donors had donated their kidneys between 1986 and 2007. We attempted to contact all donors to determine short- and long-term outcome following kidney donation. All kidney donors who responded underwent detailed clinical and biochemical evaluation. The data were compared with age-matched health tables of the Tunisian general population. In all, 284 donors (52%) had a complete evaluation. They included 117 men and 167 women with a mean age of 42 ± 12 years. The major peri-operative complications that occurred in these donors included four cases of pneumothorax, six cases of surgical site infection, one case of phlebitis and one case of pulmonary embolism. None of the study cases died. The median length of hospital stay after donor nephrectomy was 6.5 days (range: 3-28 days). The median follow-up period was eight years. The mean creatinine clearance after donation was 90.4 ± 25 mL/min in men and 81.5 ± 27.2 mL/min in women. Proteinuria was >300 mg/24 h in 17 cases (5.9%). Fifty-eight (20.4%) donors became hypertensive and 19.6% of the men and 37.2% of the women became obese. Diabetes mellitus developed in 24 (8.4%), and was more common in patients who had significant weight gain. Our study suggests that kidney donors have minimal adverse effects on overall health status. Regular follow-up identifies at-risk populations and potentially modifiable factors. Creation of a national registry of living donors and their monitoring are an absolute necessity.


Effects of exposure to carbon disulphide on low density lipoprotein cholesterol concentration and diastolic blood pressure.
The relation of carbon disulphide (CS2) exposure to risk factors for ischaemic heart disease was recently examined using data from a 1979 cross sectional study of 410 male textile workers, of whom 165 were exposed and 245 were unexposed to CS2. Average eight hour CS2 exposure concentrations ranged from 0.6 to 11.8 ppm by job title category among the exposed workers. A significant and positive linear trend in low density lipoprotein cholesterol concentration (LDLc) and diastolic blood pressure with increasing CS2 exposure was found after adjustment for potential confounders. When exposure was examined as a categorical variable (none, low, moderate, and high), the high exposure group had an adjusted mean LDLc that was 0.32 mmol/l greater than the non-exposed group (p = 0.02), and an adjusted mean diastolic blood pressure that was 3.16 mm Hg greater than the non-exposed group (p = 0.09). The effect of CS2 on diastolic blood pressure was strengthened in analyses limited to exposed workers: the high exposure group had an adjusted mean diastolic blood pressure that was 5 mm Hg greater than that of the low exposed group (p = 0.03). Triglyceride, high density lipoprotein cholesterol, and fasting glucose concentration, and systolic blood pressure were not affected by exposure. Blood lead concentration was positively associated with systolic and diastolic blood pressure. The results indicate that relatively modest exposure to CS2 may raise LDLc concentration and diastolic blood pressure and suggest mechanisms by which exposure to CS2 may influence risk of ischaemic heart disease. Also the results provide further support for the hypothesis of a possible association between blood lead concentration and blood pressure.


IMDB network revisited: unveiling fractal and modular properties from a typical small-world network.
We study a subset of the movie collaboration network, http://www.imdb.com, where only adult movies are included. We show that there are many benefits in using such a network, which can serve as a prototype for studying social interactions. We find that the strength of links, i.e., how many times two actors have collaborated with each other, is an important factor that can significantly influence the network topology. We see that when we link all actors in the same movie with each other, the network becomes small-world, lacking a proper modular structure. On the other hand, by imposing a threshold on the minimum number of links two actors should have to be in our studied subset, the network topology becomes naturally fractal. This occurs due to a large number of meaningless links, namely, links connecting actors that did not actually interact. We focus our analysis on the fractal and modular properties of this resulting network, and show that the renormalization group analysis can characterize the self-similar structure of these networks.


Immigrants with dementia in Swedish residential care: an exploratory study of the experiences of their family members and Nursing staff.
Worldwide, there is a growing population of older people who develop dementia in a country other than that of their origin. When their dementia has reached an advanced stage, residential care is most often needed. People with dementia in Sweden are often cared for in group homes. For immigrants, this may mean a linguistically challenging care environment for both healthcare staff and the patients' family members. The aim of this study was to explore and describe the experiences of family members and professional caregivers regarding the care provided to immigrants with dementia in group homes in Sweden. An exploratory, descriptive study with a qualitative approach was chosen. In-depth semi-structured interviews were conducted with nine professional caregivers and five family members of people with dementia with Finnish, Estonian, Hungarian and Ingrian backgrounds; all were chosen purposefully. All people with dementia had lost their Swedish language skills as their second language. The data was analysed using qualitative content analysis. Three main categories and seven subcategories were identified. The first main category: A new living situation comprised the subcategories: adjusting to new living arrangements and expectations regarding activities and traditional food at the group home, the second main category: Challenges in communication with the subcategories: limited communication between the immigrant with dementia and the Swedish-speaking nursing staff and the consequences of linguistic misunderstandings and nuanced communication in a common language and the third main category: The role of the family member at the group home with the subcategories: a link to the healthy life story of the family member with dementia and an expert and interpreter for the nursing staff. The family member played a crucial role in the lives of immigrants with dementia living in a group home by facilitating communication between the nursing staff and the PWD and also by making it possible for PWD to access the cultural activities they wanted and which professional caregivers were either not able to recognise as needed or could not deliver.


Basal muscle intracellular amino acid kinetics in women and men.
Sexual dimorphism in skeletal muscle mass is apparent, with men having more muscle mass and larger individual muscle cells. However, no sex-based differences have been detected in blood forearm phenylalanine turnover, although whole body leucine oxidation has been reported to be greater in men than in women. We hypothesized that sex differences in intracellular amino acid turnover may account for these discrepancies, with men having a higher intracellular turnover than women. We studied young, healthy women (women, n = 8) and men (men, n = 10) following an overnight fast. Phenylalanine, leucine, and alanine muscle intracellular kinetics were assessed using stable isotope methodologies, femoral arteriovenous blood sampling, and muscle biopsies. Muscle intracellular amino acid kinetics were reported relative to both leg volume and lean leg mass because of sex differences in leg volume and in muscle and fat distribution. When expressed per leg volume (nmol.min(-1).100 ml leg volume(-1)), phenylalanine net balance (women: -16 +/- 4, men: -31 +/- 5), release from proteolysis in the blood (women: 46 +/- 9, men: 75 +/- 10) and intracellular availability (women: 149 +/- 23, men: 241 +/- 35), and alanine production, utilization, and intracellular availability were higher in men (P < 0.05). However, when the kinetic parameters were normalized per unit of lean leg mass, all differences disappeared. Muscle fractional synthetic rate was also not different between women and men. We conclude that there are no sex-based differences in basal muscle intracellular amino acid turnover when the data are normalized by lean mass. It remains to be determined if there are sex differences in intracellular amino acid metabolism following anabolic or catabolic stimuli.


The impact of ambient temperature on the incidence of urolithiasis: a systematic review and meta-analysis.
Objective This review aimed to confirm the association between ambient temperature and incidence of urolithiasis and evaluate the impact thereof. Methods A systematic literature review was performed up to September 2019 using multiple databases. The effect of temperature on urolithiasis risk was assessed using risk ratio (RR). Pearson correlation coefficient (Pearson's r) was used to evaluate the linear association between ambient temperature and urolithiasis incidence. The non-linear association between climatic temperature and the urolithiasis incidence was also evaluated. Results Twenty-four studies related to the temperature and urolithiasis risk in 14 different countries or regions of five continent involving over 2.5 million cases were included in the meta-analysis. High climatic or workplace temperature was a significant risk factor of urolithiasis. The weighted correlation coefficient (Pearson's r) of monthly temperature and urolithiasis risk was 0.49 [95% confidence interval (CI) 0.40-0.57], a moderate correlation (0.4<r<0.6). According to non-linear models, as the daily temperature increases by 5 °C, the risk of urolithiasis will increase by 10% (95% CI 8-11%). Conclusion Both workplace and climatic temperatures are related to the incidence of urolithiasis. Public health intervention strategies need to be developed to prevent those in high-risk districts or occupations from being exposed to high ambient temperature.


Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung.
Distal lung epithelium is maintained by proliferation of alveolar type II (AT2) cells and, for some daughter AT2 cells, transdifferentiation into alveolar type I (AT1) cells. We investigated if subpopulations of alveolar epithelial cells (AEC) exist that represent various stages in transdifferentiation from AT2 to AT1 cell phenotypes in normal adult lung and if they can be identified using combinations of cell-specific markers. Immunofluorescence microscopy showed that, in distal rat and mouse lungs, ∼ 20-30% of NKX2.1(+) (or thyroid transcription factor 1(+)) cells did not colocalize with pro-surfactant protein C (pro-SP-C), a highly specific AT2 cell marker. In distal rat lung, NKX2.1(+) cells coexpressed either pro-SP-C or the AT1 cell marker homeodomain only protein x (HOPX). Not all HOPX(+) cells colocalize with the AT1 cell marker aquaporin 5 (AQP5), and some AQP5(+) cells were NKX2.1(+). HOPX was expressed earlier than AQP5 during transdifferentiation in rat AEC primary culture, with robust expression of both by day 7. We speculate that NKX2.1 and pro-SP-C colocalize in AT2 cells, NKX2.1 and HOPX or AQP5 colocalize in intermediate or transitional cells, and HOPX and AQP5 are expressed without NKX2.1 in AT1 cells. These findings suggest marked heterogeneity among cells previously identified as exclusively AT1 or AT2 cells, implying the presence of subpopulations of intermediate or transitional AEC in normal adult lung.


Proteome dynamics in complex organisms: using stable isotopes to monitor individual protein turnover rates.
The complete definition of changes in a proteome requires information about dynamics and specifically the rate at which the individual proteins are turned over intracellularly. Whilst this can be achieved in single-cell culture using stable isotope precursors, it is more challenging to develop methods for intact animals. In this study, we show how dietary administration of stable isotope-labelled amino acids can obtain information on the relative rates of synthesis and degradation of individual proteins in a proteome. The pattern of stable isotope-labelling in tryptic peptides can be deconstructed to yield a highly reliable measure of the isotope abundance of the precursor pool, a parameter that is often difficult to acquire. We demonstrate this approach using chickens fed a semisynthetic diet containing [(2)H(8)]valine at a calculated relative isotope abundance (RIA) of 0.5. When the labelling pattern of gel-resolved muscle proteins was analyzed, the intracellular precursor isotope abundance was 0.35, consistent with dilution of the amino acid precursor pool with unlabelled amino acids derived from degradation of pre-existing proteins. However, the RIA was stable over an extended labelling window, and permitted calculation of the rates of synthesis and degradation of individual proteins isolated by gel electrophoresis. For the first time, it is feasible to contemplate the analysis of turnover of individual proteins in intact animals.


Raymond Pearl and the shaping of human biology.
Raymond Pearl (1879-1940) was a significant figure in the field of biology. He founded the journal Human Biology and almost single-handedly promoted and established the scientific discipline of human biology. His scientific versatility was one of his most important features during the first four decades of the 20th century, and he played a major role in developing the fields of biodemography, human population biology, human life-cycle and life span approaches, fertility, growth, the biology of longevity and senescence, and mortality. He was one of the earliest biologists to combine biometric analyses and experimental studies to explore the dimensions of human biology. Pearl also was broadly educated in the arts, music, literature, history, the classics, and science. His writing was sophisticated and often witty, and his views were sometimes provocative and controversial. His network of colleagues and friends among the literary and science worlds was substantial. The following biographical memoir of Raymond Pearl is designed to commemorate the 80th anniversary of the founding of his journal Human Biology and is a tribute to this great scientist. Pearl's sudden death at age 61 truncated a scientific career that was one of the most productive of the 20th century.


The language profile of posterior cortical atrophy.
Posterior cortical atrophy (PCA) is typically considered to be a visual syndrome, primarily characterised by progressive impairment of visuoperceptual and visuospatial skills. However, patients commonly describe early difficulties with word retrieval. This paper details the first systematic analysis of linguistic function in PCA. Characterising and quantifying the aphasia associated with PCA is important for clarifying diagnostic and selection criteria for clinical and research studies. 15 patients with PCA, seven patients with logopenic/phonological aphasia (LPA) and 18 age matched healthy participants completed a detailed battery of linguistic tests evaluating auditory input processing, repetition and working memory, lexical and grammatical comprehension, single word retrieval and fluency, and spontaneous speech. Relative to healthy controls, PCA patients exhibited language impairments across all of the domains examined, but with anomia, reduced phonemic fluency and slowed speech rate the most prominent deficits. PCA performance most closely resembled that of LPA patients on tests of auditory input processing, repetition and digit span, but was relatively stronger on tasks of comprehension and spontaneous speech. The study demonstrates that in addition to the well reported degradation of vision, literacy and numeracy, PCA is characterised by progressive oral language dysfunction with prominent word retrieval difficulties. Overlap in the linguistic profiles of PCA and LPA, which are both most commonly caused by Alzheimer's disease, further emphasises the notion of a phenotypic continuum between typical and atypical manifestations of the disease. Clarifying the boundaries between Alzheimer's disease phenotypes has important implications for diagnosis, clinical trial recruitment and investigations into biological factors driving phenotypic heterogeneity in Alzheimer's disease. Rehabilitation strategies to ameliorate the phonological deficit in PCA are required.


Acremonium kiliense infection in a child with chronic granulomatous disease.
Infection by unusual microorganisms can be one of the clinical manifestations of primary immunodeficiency (PID). We report on a four-month-old child with pneumonia caused by the fungus Acremonium kiliense as the first clinical manifestation of chronic granulomatous disease. We emphasize the importance of an active search for unusual organisms in immunodeficient patients, and a precise diagnosis and early institution of specific treatment against such microorganisms for the reduction of the morbidity and mortality of these patients.


Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy: A randomized controlled trial. rhNGF Clinical Investigator Group.
Nerve growth factor is a neurotrophic factor that promotes the survival of small fiber sensory neurons and sympathetic neurons in the peripheral nervous system. Recombinant human nerve growth factor (rhNGF) has demonstrated efficacy as treatment for peripheral neuropathy in experimental models and phase 2 clinical trials. To evaluate the efficacy and safety of a 12-month regimen of rhNGF in patients with diabetic polyneuropathy. Randomized, double-blind, placebo-controlled phase 3 trial conducted from July 1997 through May 1999. Eighty-four outpatient centers throughout the United States. A total of 1019 men and women aged 18 to 74 years with either type 1 or type 2 diabetes and a sensory polyneuropathy attributable to diabetes. Patients were randomly assigned to receive either rhNGF, 0.1 microg/kg (n = 504), or placebo (n = 515) by subcutaneous injection 3 times per week for 48 weeks. Patients were assessed at baseline, 12 weeks, 24 weeks, and 48 weeks. The primary outcome measure was a change in neuropathy between baseline and week 48, demonstrated by the Neuropathy Impairment Score for the Lower Limbs, compared between the 2 groups. Secondary outcome measures included quantitative sensory tests using the CASE IV System, the Neuropathy Symptom and Change questionnaire, the Patient Benefit Questionnaire (PBQ), and a global symptom assessment, as well as nerve conduction studies and occurrence of new plantar foot ulcers. Patients also were evaluated for presence of adverse events. Among patients who received rhNGF, 418 (83%) completed the regimen compared with 461 (90%) who received placebo. Administration of rhNGF was safe, with few adverse events attributed to treatment apart from injection site pain/hyperalgesia and other pain syndromes. However, neither the primary end point (P =.25) nor most of the secondary end points demonstrated a significant benefit of rhNGF. Exceptions were the global symptom assessment (P =.03) and 2 of 32 comparisons within the PBQ, which showed a modest but significant benefit of rhNGF (P =.05 for severity of pain in the legs and P =.003 for 6-month symptoms in the feet and legs). Unlike previous phase 2 trials, this phase 3 clinical trial failed to demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy. JAMA. 2000;284:2215-2221.


Determination of Antiproliferative Activities of Volatile Contents and HPLC Profiles of Dicranum scoparium (Dicranaceae, Bryophyta).
The aim of this study was to examine the anticancer activities and phytochemical profiles of Dicranum scoparium against HeLa cell lines. The bio-guided fractionation studies of dichloromethane extract have high antiproliferative activities. Fractions 7, 9, 19, 20 are rich source of unsaturated fatty acids, and- in the case of Fr-19 may improve the antiproliferative activities as well as increase the unsaturated fatty acid content. The effect of proliferative activities in hexane extract can be attributed to the saturated fatty acid composition of D. scoparium. The Fr-9 exhibited strong antiproliferative activity at concentrations of 100 and 50 μg mL(-1) compared to 5-FU. The fractions of 7, 9, 19 and 20 from dichloromethane extracts exhibited antiproliferative activities at a concentration of 100 μg mL(-1). The HPLC-TOF/MS studies gave nine compounds from the most active fraction of dichloromethane at concentrations of 250 and 100 μg mL(-1). The lower activities were obtained from the fractions including steroid derivatives.


The impact of cataract surgery on glaucoma care.
To summarize the effects of cataract surgery on the management of glaucoma, in terms of the effect on both the intraocular pressure (IOP) and postoperative diagnostic as well as therapeutic considerations. Recent evidence corroborates prior data demonstrating significant and sustained IOP reduction after cataract extraction, particularly in closed-angle variants of glaucoma, but also in individuals with open-angle glaucoma or ocular hypertension. Performing cataract surgery after trabeculectomy increases the odds of filtration failure with the likelihood of this adverse effect being inversely proportional to the duration between the glaucoma and cataract procedures. Although cataract has a significant effect on the results of visual field testing, the Visual Field Index may be less influenced than other parameters such as the mean and pattern deviation. The accuracy of time-domain ocular coherence tomography and spectral-domain ocular coherence tomography are also negatively impacted by cataract. Considering cataract surgery as an IOP-lowering procedure may be appropriate in select patients. Performing cataract extraction prior to glaucoma surgery has numerous benefits. The sequence of the procedures performed has implications in terms of complications, surgical success, and diagnostics. Reestablishing perimetric and structural baselines with imaging modalities is appropriate after cataract surgery is performed in glaucoma patients.


Lung squamous cell carcinoma mRNA expression subtypes are reproducible, clinically important, and correspond to normal cell types.
Lung squamous cell carcinoma (SCC) is clinically and genetically heterogeneous, and current diagnostic practices do not adequately substratify this heterogeneity. A robust, biologically based SCC subclassification may describe this variability and lead to more precise patient prognosis and management. We sought to determine if SCC mRNA expression subtypes exist, are reproducible across multiple patient cohorts, and are clinically relevant. Subtypes were detected by unsupervised consensus clustering in five published discovery cohorts of mRNA microarrays, totaling 382 SCC patients. An independent validation cohort of 56 SCC patients was collected and assayed by microarrays. A nearest-centroid subtype predictor was built using discovery cohorts. Validation cohort subtypes were predicted and evaluated for confirmation. Subtype survival outcome, clinical covariates, and biological processes were compared by statistical and bioinformatic methods. Four lung SCC mRNA expression subtypes, named primitive, classical, secretory, and basal, were detected and independently validated (P < 0.001). The primitive subtype had the worst survival outcome (P < 0.05) and is an independent predictor of survival (P < 0.05). Tumor differentiation and patient sex were associated with subtype. The expression profiles of the subtypes contained distinct biological processes (primitive: proliferation; classical: xenobiotic metabolism; secretory: immune response; basal: cell adhesion) and suggested distinct pharmacologic interventions. Comparison with lung model systems revealed distinct subtype to cell type correspondence. Lung SCC consists of four mRNA expression subtypes that have different survival outcomes, patient populations, and biological processes. The subtypes stratify patients for more precise prognosis and targeted research.


The influence of integrated tuberculosis and human immunodeficiency virus service delivery on patient outcomes.
Public health clinics in Cape Town, South Africa. To examine the influence of integrated tuberculosis (TB) and human immunodeficiency virus (HIV) service delivery on mortality, TB cure and successful treatment completion and loss to follow-up of TB-HIV co-infected patients on concurrent anti-tuberculosis and antiretroviral treatment (ART). A survey instrument was used to measure the degree to which TB and HIV services were jointly delivered, and patient data were collected retrospectively from clinic sites and the Department of Health. Six domains measuring integrated TB and HIV service delivery were modelled to assess their relationship with patient outcomes. Two domains, integrated TB and ART service delivery and the delivery of TB and HIV care by one clinical team, were associated with lowered odds of death. Care by the same clinical team was also associated with reduced loss to follow-up. Overall, these findings show that the organization and delivery of health services are important factors that influence health outcomes. These findings strongly support efforts by local governments to integrate TB and ART services, and may help to alleviate concerns that restructuring of TB programs could have a negative impact on long-standing gains.


Analysis Of The KLIC-score; An Outcome Predictor Tool For Prosthetic Joint Infections Treated With Debridement, Antibiotics And Implant Retention.
Background: Debridement, antibiotics and implant retention (DAIR) forms the primary treatment modality for early prosthetic joint infection (PJI). The KLIC score has been proposed as a risk stratification tool for use in predicting outcome of prosthetic knee infections. Our aim was to determine the accuracy of this scoring system at an independent tertiary PJI centre in a typical DAIR population. Methods: Between 2008 and 2015, patients with infected knee prostheses treated with DAIR were identified. The patient notes and blood tests were reviewed retrospectively and the 'KLIC-score' was calculated and correlated with outcome. The end point for early failure was defined as: 1) the need for unscheduled surgery, 2) infection-related death ≤12 months from debridement or 3) the need for suppressive antibiotic treatment. Results: 59 patients received DAIR procedures for knee PJI. Treatment was successful in 41 patients (69%) with early failure in 18 patients (31%). Patients deemed high-risk (KLIC-score ≥7) had notably higher failure rates (60%) than those scoring <7 (28%). No relationship can be drawn between KLIC-scores of <7 and failure rates. Conclusions: The KLIC-score applied retrospectively was able to predict patients with the highest risk of early failure but provides little information in patients with scores of <7.


Predictors of long-term opioid use among patients with painful lumbar spine conditions.
Our objective was to assess predictors of self-reported opioid use among patients with back pain due to lumbar disc herniation or spinal stenosis. Data were from the Spine Patient Outcomes Research Trial (SPORT), a multi-site observational study and randomized trial. We examined characteristics shown or hypothesized to be associated with opioid use. Using generalized estimating equations, we modeled associations of each potential predictor with opioid use at 12 and 24 months. At baseline, 42% of participants reported opioid use. Of these participants, 25% reported continued use at 12 months and 21% reported use at 24 months. In adjusted models, smoking (RR = 1.9, P < .001 at 12 months; RR = 1.5, P = .043 at 24 months) and nonsurgical treatment (RR = 1.7, P < .001 at 12 months; RR = 1.8, P = .003 at 24 months) predicted long-term opioid continuation. Among participants not using opioids at baseline, incident use was reported by 8% at 12 months and 7% at 24 months. We found no significant predictors of incident use at 12 or 24 months in the main models. In conclusion, nonsurgical treatment and smoking independently predicted long-term continued opioid use. To our knowledge, this is the first longitudinal study to assess predictors of long-term and incident opioid use among patients with lumbar spine conditions. This longitudinal study of patients with disc herniation or spinal stenosis found that nonsurgical treatment and smoking predicted long-term self-reported opioid use. The greater risk of opioid continuation with nonsurgical therapy may be helpful in decision-making about treatment. The relationship between opioid use, smoking, and other substance use deserves further study.


Play Within the Pre-registration Children's Nursing Curriculum Within the United Kingdom: A Content Analysis of Programme Specifications.
To determine the number of programme specifications which cite play within the curriculum and in what context. Play is an essential part of childhood. Therefore we might expect nurses caring for children to be trained in how to facilitate play within their clinical areas. Programme specifications provide information on course aims, the intended learning outcomes and what the learner is expected to achieve. Inductive qualitative content analysis. Only 13% (seven out of 54) programme specifications published by Higher Education Institutions cite play. Where play is mentioned there is a clear link made to use play as a communication tool. Also distraction figured prominently within the same sentence as play, despite these two terms being quite distinct. The availability of the programme specifications was also noted with 49% (28 out of 57) were easily accessible from the university web sites. A further 16% (9 out of 57) provided web links when access was requested. 35% were not publicly accessible without requesting access. Three Universities declined to be involved. It is clear that even if play is embedded within the child field nursing curriculum, it is not clearly stated as a priority within 87% of universities programme specifications which make no mention of it. If play is not part of programme specifications its importance could be lost to educators already delivering a full curriculum. Nurses could be qualifying with little or no knowledge around their role in facilitating play for their patients.


Protection from 1,1-dichloroethylene-induced Clara cell injury by diallyl sulfone, a derivative of garlic.
Bronchiolar Clara cell damage ensues after treatment of mice with 1,1-dichloroethylene (DCE). The cytotoxicity is mediated by CYP2E1, a cytochrome P450 isozyme that is highly localized in the Clara cells. Bioactivation of DCE produces the primary metabolites 2,2-dichloroacetaldehyde, which hydrolyzes to the acetal, and DCE epoxide, which reacts with glutathione to form the conjugates 2-(S-glutathionyl) acetyl glutathione [B] and 2-S-glutathionyl acetate [C]. In this study, we investigated the potential of diallyl sulfone (DASO2) to inhibit CYP2E1, to suppress the bioactivation of DCE to reactive intermediates and to abrogate DCE-induced Clara cell cytotoxicity. Our results showed that treatment of mice with DASO2 (100 mg/kg p.o.) produced decreases in CYP2E1-dependent p-nitrophenol hydroxylation that were apparent at 1 h. Enzyme activity plummeted to about 20% of the control by 2 h and remained at this low level from 3 to 8 h. Recovery of activity was evident at 16 h and returned to the control level by 24 h. Immunoreactivity of the CYP2E1 protein was decreased in immunoblots of lung microsomes from DASO2-treated mice. Treatment with DASO2 did not cause any structural alterations in lung tissue; in contrast, treatment with DCE (75 mg/kg) produced Clara cell damage. This lesion was not manifested in mice treated with DASO2 in conjunction with DCE. The lack of cytotoxicity observed in vivo correlated with a reduction of about 45% in the levels of both the acetal and the DCE epoxide-derived conjugates [B] and [C] in vitro. These results demonstrated that DASO2 significantly inhibited the CYP2E1 enzyme, decreased the production of DCE metabolites and protected Clara cells from DCE-induced cytotoxicity.