Analysis of a coded panel of licensed vaccines by polymerase chain reaction-based reverse transcriptase assays: a collaborative study [seecomments].
A recent publication reporting the presence of low levels of reverse transcriptase (RT) activity in certain vaccines for human use necessitated that regulatory agencies address the issue of whether this RT activity presented a risk to humans. Detection of low levels of RT activity corresponding to fewer than ten virions became possible with the development of highly-sensitive polymerase chain reaction (PCR)-based RT (PBRT) assays. Variations of the PBRT assay were developed in three laboratories. These assays were reported as being at least one million-fold more sensitive than conventional RT assays. To ascertain the sensitivity and reliability of PBRT assays in different laboratories and to determine which vaccine samples possessed RT activity. Coded panels of licensed vaccines together with positive and negative controls was assembled at the Center for Biologics Evaluation and Research (CBER) of the Food and Drug Administration (FDA) and distributed to five cooperating laboratories as well as to our laboratory at CBER. Each laboratory carried out their version of the PBRT assay and submitted the results to the coordinator at CBER. Results of the PBRT analyses carried out in the six laboratories are presented. Five of the six laboratories reported results that were highly consistent. RT activity was detected in live attenuated vaccines that were prepared in chick embryo cells (mumps, measles and yellow fever), but very low or undetectable RT activity was found in vaccines produced in mammalian cells (rabies and rubella). Influenza vaccines from several manufacturers included in the panel displayed the most variability, with different products of this inactivated vaccine having differing amounts of RT activity. Only vaccines produced in chick embryo cells had significant RT activity. Because RT activity was present in the allantoic fluid of uninfected chick embryos and culture medium from chick embryo fibroblasts, the RT activity arises from the cell substrate used for vaccine production. The PBRT assays were reliably able to detect the low levels of RT activity in chicken-derived vaccines.


Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.
Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men.


The effect of playing surface on injury rate: a review of the current literature.
Synthetic playing surfaces are widely used for field and court sports. Artificial turf surfaces are commonly used as an alternative to natural grass, while outdoor surfaces like clay and acrylic are also prevalent. The effect of these synthetic surfaces on injury rates has not been clearly established. The available literature is largely limited to football and soccer data and the majority of studies are short-term. Confounding variables such as climate, player position and footwear, as well as varying definitions of injury, also make it difficult to draw firm conclusions about the general effect of artificial playing surfaces on injury rates. Many peer-reviewed studies cite a higher overall rate of injury on first- and second-generation artificial turf surfaces compared with natural grass. Despite differences in injury type, the rate of injury on third-generation and natural grass surfaces appears to be comparable. It also appears that clay is significantly safer than either grass or hard court tennis surfaces, but this is a conclusion drawn with limited data. Further research investigating overall injury trends as well as sport-specific data is needed to draw more definitive conclusions regarding the effect of artificial playing surfaces on injury rates.


Eradication therapy is effective for Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma.
Mucosa-associated lymphoid tissue (MALT) lymphomas are extra-nodal B-cell lymphomas arising from MALT, and the most commonly affected organ is the stomach. Helicobacter pylori (H. pylori) eradication therapy with proton-pump inhibitors and antibiotics is the first-line therapy for H. pylori-positive gastric MALT lymphomas, but the effectiveness of the therapy for H. pylori-negative gastric MALT lymphomas remains controversial. Hence, we aimed to evaluate the effectiveness of this eradication therapy for H. pylori-negative MALT lymphomas. The H. pylori infection status of 158 gastric MALT lymphoma patients followed in our unit was judged by urea breath test, rapid urease test, histology of the biopsy specimen taken from the stomach during endoscopy, and serum antibody against H. pylori. Seventeen patients that were negative for all four tests and did not have gastric mucosal atrophy were treated with antibiotic eradication therapy. The average age at diagnosis was 56.8 years old (range: 36-73 years), and the median follow-up period after H. pylori eradication in all 17 patients was 5.3 years (range: 0.3-12.7 years). Five patients (29.4%) achieved complete remission (CR) by eradication therapy alone. Comparison between the responding and non-responding patients revealed that the patients endoscopically diagnosed to have a single lesion of gastric MALT lymphoma were seen only in the responding group, whereas all non-responding patients had multiple lesions (P < 0.05). In conclusion, H. pylori eradication therapy achieved a favorable CR rate in H. pylori-negative gastric MALT lymphoma patients and could be considered as a first-line therapy, especially for patients with a single lesion.


Endoscopic Endonasal Transclival Approach versus Dual Transorbital Port Technique for Clip Application to the Posterior Circulation: A Cadaveric Anatomical and Cerebral Circulation Simulation Study.
Purpose Simulation training offers a useful opportunity to appreciate vascular anatomy and develop the technical expertise required to clip intracranial aneurysms of the posterior circulation. Materials and Methods In cadavers, a comparison was made between the endoscopic transclival approach (ETA) alone and a combined multiportal approach using the ETA and a transorbital precaruncular approach (TOPA) to evaluate degrees of freedom, angles of visualization, and ergonomics of aneurysm clip application to the posterior circulation depending on basilar apex position relative to the posterior clinoids. Results ETA alone provided improved access to the posterior circulation when the basilar apex was high riding compared with the posterior clinoids. ETA + TOPA provided a significantly improved functional working area for instruments and visualization of the posterior circulation for a midlevel basilar apex. A single-shaft clip applier provided improved visualization and space for instruments. Proximal and distal vascular control and feasibility of aneurysmal clipping were demonstrated. Conclusions TOPA is a medial orbital approach to the central skull base; a transorbital neuroendoscopic surgery approach. This anatomical simulation provides surgical teams an alternative to the ETA approach alone to address posterior circulation aneurysms, and a means to preoperatively prepare for intraoperative anatomical and surgical instrumentation challenges.


A double-blind, parallel-group, placebo-controlled, multicentre study of acetyl L-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection.
Nucleoside reverse transcriptase inhibitors (NRTIs) disrupt neuronal mitochondrial DNA synthesis, resulting in antiretroviral toxic neuropathy (ATN). Acetyl-L-carnitine (ALCAR) enhances neurotrophic support of sensory neurones, potentially providing symptom relief and nerve regeneration. The objective of the study was to assess the safety and efficacy compared to placebo of intramuscular ALCAR in HIV-positive patients with symptomatic distal symmetrical polyneuropathy. Ninety patients were enrolled and randomized to receive ALCAR [500 mg twice a day (bid); n=43] or placebo (n=47) intramuscularly twice daily for 14 days followed by 42 days of oral ALCAR 1000 mg bid. Assessment of pain was obtained using the Visual Analogue Scale (VAS), Total Symptom Score (TSS), Clinical Global Impression of Change, McGill Pain Questionnaire (MPQ), and the need for rescue analgesics. There was no statistically significant difference in changes in VAS over 14 days between groups for the intent-to-treat (ITT) population, but for the efficacy-evaluable (EE) population ALCAR treatment produced a significantly greater reduction in pain compared with placebo (P=0.022). The proportion of patients with an improvement in TSS over 14 days was greater in the ALCAR group compared with the placebo group, but the differences were not statistically significant. During the open-label phase, patients experienced an improvement in pain, as measured by the VAS, TSS and McGill Pain Questionnaire. ALCAR, administered twice a day intramuscularly to HIV-1-infected patients with symptomatic ATN, significantly reduced weekly mean pain ratings on the VAS compared with placebo. Treatment with oral ALCAR improved symptoms for the patient group as a whole. Intramuscular and oral ALCAR was generally safe and well tolerated.


[Presence and spatio-temporal habitat characterization of Dermatemys mawii (Testudines: Dermatemydidae) in the Grijalva-Usumacinta watershed, Tabasco, Mexico].
The Central American River Turtle (Dermatemys mawii) is an endangered species that has been poorly studied. There are no reports on their population status, habitat condition, and the species distribution area is still unknown. This study analyzes the seasonal and spatial variations of their habitat and the presence/absence of D. mawii in three rivers within the Pantanos de Centla Biosphere Reserve (Tabasco, Mexico). For habitat characterization, natural segmentation of rivers was used and three sites per segment were identified, 9 in each rivers (Grijalva and Usumacinta) and 6 in Tabasquillo. Additionally, the evaluation of 11 environmental variables such as water hydrological, physicochemical characteristics and riparian and hydrophytic vegetation were carried out during two different seasons (dry and rainy). The presence/absence of species was assessed with eight fike nets that were set per segment, with a capture effort of 384 hours per trap. The capture per unit effort (CPUE) was used as an indicator of relative abundance. The results indicated spatio-temporal variations in habitat characteristics and the presence of environmental gradients. The principal components analysis (PCA) applied allowed us to determine that the first three components explained 67.8% of the environmental variability. The species presence was confirmed in all rivers, however significant differences exists in their relative abundance: the highest was registered in the Tabasquillo River where the species was present in both seasons and in all segments. Of the 11 environmental variables analyzed, the gradient, shelter and depth were the most indicative of species presence. The obtained results evidenced the importance of riparian vegetation as habitat for Dermatemys. This represents the first approach towards an action plan for a species and its habitat protection within the Pantanos de Centla Biosphere Reserve.


A wavelet-based multiresolution approach to solve the stereo correspondence problem using mutual information.
In this correspondence, we propose a wavelet-based hierarchical approach using mutual information (MI) to solve the correspondence problem in stereo vision. The correspondence problem involves identifying corresponding pixels between images of a given stereo pair. This results in a disparity map, which is required to extract depth information of the relevant scene. Until recently, mostly correlation-based methods have been used to solve the correspondence problem. However, the performance of correlation-based methods degrades significantly when there is a change in illumination between the two images of the stereo pair. Recent studies indicate MI to be a more robust stereo matching metric for images affected by such radiometric distortions. In this short correspondence paper, we compare the performances of MI and correlation-based metrics for different types of illumination changes between stereo images. MI, as a statistical metric, is computationally more expensive. We propose a wavelet-based hierarchical technique to counter the increase in computational cost and show its effectiveness in stereo matching.


Missing values in gel-based proteomics.
Gel-based proteomics is a widely applied technique to measure abundances of proteins in various biological systems. Comparison of two or more biological groups involves matching of 2-D gels. Depending on the software, this can result in spots showing missing values on several gels. Most studies ignore this fact or substitute all missing data by zero. Since a couple of years, scientists have realized that this is not the optimal way of analyzing their data and several studies were published presenting methods of imputing missing proteomics data. Most of these methods have already been applied to microarray data before; the phenomenon of missing data is well known in this field, too. With this review, we intend to further raise awareness of the problem of missing values in gel-based proteomics. We summarize reasons for missing values and explore their distribution in data sets. We also provide a comparison and evaluation of hitherto proposed imputation methods for gel-based proteomics data.


The ethics committee of a psychiatric college: its procedures and themes.
Ethics committees (ECs) of medical colleges and other medical associations have become part of their professional experience only in recent years. This is probably attributable to such factors as greater professional accountability and informed consumerism. Relatively little is known about the procedures and agendas of such committees. The aim of the present study was to examine the EC of the Royal Australian and New Zealand College of Psychiatrists, with respect to its practices, in order to learn how a medical college grapples with ethical concerns. Two members of the College's EC, including its foundation chairman, assembled relevant documents, and subjected them to detailed scrutiny. Consensus was used, preceded by independent attempts at categorising these issues covering the period from the EC's inception in 1978 to June, 1995. Three hundred and sixty-seven issues were dealt with by the EC over a 17 year period, covering clinical practice, financial aspects, forensic psychiatry, teaching and research, liaison with other organisations and preparation of guidelines and a code of ethics. An EC can play a vital role in advising its parent body and members in the ethics of day-to-day professional life as well as formulating (and revising) a code of ethics and supplementary ethical guidelines.


Targeted Use of Alcohol-Based Hand Rub on Gloves During Task Dense Periods: One Step Closer to Pathogen Containment by Anesthesia Providers in the Operating Room.
Anesthesia providers' hand hygiene practices in the operating room may contribute to the transmission of bacteria. There is a debate, however, over the best approaches for pathogen containment during task dense periods (induction and extubation) of anesthesia care. A novel approach to reducing pathogen spread during these task dense periods is the use of alcohol-based hand rub on gloves when it may be difficult to either change gloves or clean hands. To evaluate the impact of alcohol-based hand rub on gloves, we estimated perforation rates of 50 gloves that were worn as pairs by volunteers for 2 hours at a time applying alcohol-based hand rub every 15 minutes (total of 8 alcohol-based hand rub applications per pair of gloves). We also identified perforation rates of 50 new, unused gloves. To evaluate the ability to perform routine anesthesia functions, volunteers were asked to pick up a coin from a table top and document whether the gloves felt normal or sticky at each 15-minute period. Fifty new gloves (not exposed to alcohol-based hand rub) were tested for integrity using the Food and Drug Administration-approved process, and one was found to have a microperforation. Of the 50 gloves that had been applied with alcohol-based hand rub 8 times, no microperforations were identified. All volunteers demonstrated tactile competence by picking up a coin from a table top after 8 alcohol-based hand rub applications; in addition, as the number of alcohol-based hand rub applications progressed, the volunteers reported increased stickiness. This study suggests that the use of alcohol-based hand rub on commonly used nitrile examination gloves does not compromise glove integrity or hamper the ability to safely perform routine anesthesia functions.


Comparison of disaturated phosphatidylcholine and fetal lung maturity surfactant/albumin ratio in diabetic and nondiabetic pregnancies.
We studied fetal lung maturity (FLM) by the amniotic fluid surfactant/albumin (FLM S/A) ratio and the disaturated phosphatidylcholine (DSPC) amniotic fluid levels at different gestational ages in diabetic (179 women with type 1 diabetes mellitus antedating pregnancy; infants delivered within 72 hours after amniotic fluid testing for DSPC level and FLM S/A ratio) and nondiabetic pregnancies (2 independent nondiabetic groups, 300 for FLM S/A ratio and 1,231 for DSPC level). The degree of maternal glycemia during gestation was estimated by serial measurements of hemoglobin A1. Multiple regression analyses, including gestational age (GAs) and diabetic status as independent variables and FLM S/A ratio and DSPC level as dependent variables, revealed significant effect from diabetic status and GA for FLM S/A ratio and a significant effect from GA but not from diabetic status for DSPC level. Glucose levels were controlled adequately throughout gestation as reflected by mean total glycated hemoglobin levels. Amniotic fluid levels of DSPC, the major surface tension-lowering component of pulmonary surfactant, are not significantly different between diabetic and nondiabetic pregnancies at different GAs.


Zoledronic acid and survival in patients with metastatic bone disease from lung cancer and elevated markers of osteoclast activity.
Bone metastases from non-small cell lung cancer (NSCLC) are associated with skeletal-related events (SREs) and elevated levels of N-telopeptide of type I collagen (NTX) in some patients. Zoledronic acid (ZOL) reduces SRE risk and NTX levels. To assess effects of baseline variables, including NTX levels (normal = NTX < 64 nmol/mmol creatinine; high = NTX > or = 64 nmol/mmol creatinine), on treatment effects in NSCLC patients, a retrospective analysis was performed in NSCLC patients with bone metastases (N = 382) treated with ZOL or placebo every 3 weeks in a 21-month randomized clinical trial in patients with NSCLC or other solid tumors. Cox proportional hazards models assessed relative risks (RRs) of SREs, bone lesion progression, and death. Multivariate models analyzed covariate effects on survival. For both placebo- and ZOL-treated patients, high baseline NTX correlated with increased SRE risk (p = 0.068 and 0.012, respectively). Although high versus normal baseline NTX correlated with more than twofold increased risks of bone lesion progression and death in the placebo group (p = 0.039 and 0.001, respectively), correlations were weaker in the ZOL group (RR = 1.38; p = 0.0186 and RR = 1.27; p = 0.142, respectively), suggesting an interaction effect of ZOL and baseline NTX. Among patients with high baseline NTX, ZOL significantly reduced the RR of death by 35% versus placebo (p = 0.024). Per multivariate analysis, ZOL treatment (p = 0.005), higher lymphocyte count (p = 0.011), performance status 0 to 1 (p = 0.012), and absence of narcotic use (p = 0.016) correlated with improved survival. This retrospective analysis revealed statistically significant correlations between ZOL and increased survival versus placebo in NSCLC patients and high baseline NTX levels.


Codd's self-replicating computer.
Edgar Codd's 1968 design for a self-replicating cellular automaton has never been implemented. Partly this is due to its enormous size, but we have also identified four problems with the original specification that would prevent it from working. These problems potentially cast doubt on Codd's central assertion, that the eight-state space he presents supports the existence of machines that can act as universal constructors and computers. However, all these problems were found to be correctable, and we present a complete and functioning implementation after making minor changes to the design and transition table. The body of the final machine occupies an area that is 22,254 cells wide and 55,601 cells high, composed of over 45 million nonzero cells in its unsheathed form. The data tape is 208 million cells long, and self-replication is estimated to take at least 1.7 x 10(18) time steps.


Fetal origins of child non-right-handedness and mental health.
Environmental risk during fetal development for non-right-handedness, an index of brain asymmetry, and its relevance for child mental health is not fully understood. A Swedish population-based prospective pregnancy-offspring cohort was followed-up when children were five years old (N = 1714). Prenatal environmental risk exposures were the number of ultrasound examinations and maternal distress during pregnancy. Child mental health, including symptoms of attention deficit hyperactivity disorder (ADHD), language difficulties, and care-seeking for child behavior problems, was assessed via maternal and/or kindergarten teacher's ratings. Prenatal exposure to maternal depressive symptoms and critical life events were associated with increased risk of child non-right-handedness and mixed handedness, after adjustment for parity, maternal age, birth outcomes, infant sex, and parental handedness. No association was found between handedness and number of ultrasound examinations. Non-right and mixed-handedness, rather than left-handedness, were associated with increased risk of language difficulties and particularly with ADHD symptoms, after adjustment for current parental ADHD symptoms, current maternal depressive symptoms, birth outcomes, smoking during pregnancy, depressive symptoms and critical life events. Problems were significant enough to prompt mothers to seek care for children's behavioral problems, and parents were more likely to have received advice from the children's kindergarten teachers to seek care. This study suggests that mixed-handedness, i.e., reflecting atypical brain laterality, can be a marker of both severity of prenatal exposure to maternal distress and of increased risk of ADHD symptoms in childhood. Our results support the idea that the fetal environment plays a role in subsequent child mental health.


Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica.
The inhalation of airborne pollutants, such as asbestos or silica, is linked to inflammation of the lung, fibrosis, and lung cancer. How the presence of pathogenic dust is recognized and how chronic inflammatory diseases are triggered are poorly understood. Here, we show that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin-1beta secretion. Inflammasome activation is triggered by reactive oxygen species, which are generated by a NADPH oxidase upon particle phagocytosis. (NADPH is the reduced form of nicotinamide adenine dinucleotide phosphate.) In a model of asbestos inhalation, Nalp3-/- mice showed diminished recruitment of inflammatory cells to the lungs, paralleled by lower cytokine production. Our findings implicate the Nalp3 inflammasome in particulate matter-related pulmonary diseases and support its role as a major proinflammatory "danger" receptor.


Designing communicating colonies of biomimetic microcapsules.
Using computational modeling, we design colonies of biomimetic microcapsules that exploit chemical mechanisms to communicate and alter their local environment. As a result, these synthetic objects can self-organize into various autonomously moving structures and exhibit ant-like tracking behavior. In the simulations, signaling microcapsules release agonist particles, whereas target microcapsules release antagonist particles and the permeabilities of both capsule types depend on the local particle concentration in the surrounding solution. Additionally, the released nanoscopic particles can bind to the underlying substrate and thereby create adhesion gradients that propel the microcapsules to move. Hydrodynamic interactions and the feedback mechanism provided by the dissolved particles are both necessary to achieve the collective dynamics exhibited by these colonies. Our model provides a platform for integrating both the spatial and temporal behavior of assemblies of "artificial cells," and allows us to design a rich variety of structures capable of exhibiting complex, cooperative behavior. Due to the cell-like attributes of polymeric microcapsules and polymersomes, material systems are available for realizing our predictions.


Usual adult occupation and risk of prostate cancer in West African men: the Ghana Prostate Study.
Established prostate cancer (PCa) risk factors include age, family history of PCa and African ancestry. Studies, mostly among highly screened, predominantly European ancestral populations, suggest that employment in certain occupations (eg, farming, military) may also have an increased risk for PCa. Here, we evaluated the association between usual adult occupation and PCa risk in Ghanaian men, a population with historically low rates of PCa screening. The Ghana Prostate Study is a case-control study of PCa that was conducted from 2004 to 2012 in 749 cases and 964 controls. In-person interviews were conducted to collect information from participants, including longest held job. Industrial hygienists classified job titles into occupational categories. Unconditional logistic regression was used to calculate ORs and 95% CIs for the association between longest held job and PCa risk (overall, aggressive (Gleason≥7)), controlling for potential confounders. Risk was increased among men in management (overall PCa OR=2.2, 95% CI 1.4 to 3.2; aggressive PCa OR=2.2, 95% CI 1.3 to 3.5) and military occupations (overall PCa OR=3.4, 95% CI 1.7 to 7.0; aggressive PCa OR=3.5, 95% CI 1.5 to 8.3). Risks were also elevated for management and military-specific jobs based on 3-digit level Standard Occupational Classification definitions. Sensitivity analyses accounting for access to medical care did not show significant differences. Our study provides some evidence for increased risk of PCa among men in management and military occupations, which is consistent with the published literature. Additional research is needed to clarify the drivers of the associations between these occupations and PCa.


Three siblings with familial non-medullary thyroid carcinoma: a case series.
In 2015, thyroid carcinoma affected approximately 63,000 people in the USA, yet it remains one of the most treatable cancers. It is mainly classified into medullary and non-medullary types. Conventionally, medullary carcinoma was associated with heritability but increasing reports have now begun to associate non-medullary thyroid carcinoma with a genetic predisposition as well. It is important to identify a possible familial association in patients diagnosed with non-medullary thyroid carcinoma because these cancers behave more destructively than would otherwise be expected. Therefore, it is important to aggressively manage such patients and screening of close relatives might be justified. Our case series presents a diagnosis of familial, non-syndromic, non-medullary carcinoma of the thyroid gland in three brothers diagnosed over a span of 6 years. We report the history, signs and symptoms, laboratory results, imaging, and histopathology of the thyroid gland of three Pakistani brothers of 58 years, 55 years, and 52 years from Sindh with non-medullary thyroid carcinoma. Only Patients 1 and 3 had active complaints of swelling and pruritus, respectively, whereas Patient 2 was asymptomatic. Patients 2 and 3 had advanced disease at presentation with lymph node metastasis. All patients underwent a total thyroidectomy with Patients 2 and 3 requiring a neck dissection as well. No previous exposure to radiation was present in any of the patients. Their mother had died from adrenal carcinoma but also had a swelling in the front of her neck which was never investigated. All patients remained stable at follow-up. Non-medullary thyroid carcinoma is classically considered a sporadic condition. Our case report emphasizes a high index of suspicion, a detailed family history, and screening of first degree relatives when evaluating patients with non-medullary thyroid carcinoma to rule out familial cases which might behave more aggressively.


Cannabis use in palliative care - an examination of the evidence and the implications for nurses.
Examine the pharmaceutical qualities of cannabis including a historical overview of cannabis use. Discuss the use of cannabis as a clinical intervention for people experiencing palliative care, including those with life-threatening chronic illness such as multiple sclerosis and motor neurone disease [amyotrophic lateral sclerosis] in the UK. The non-medicinal use of cannabis has been well documented in the media. There is a growing scientific literature on the benefits of cannabis in symptom management in cancer care. Service users, nurses and carers need to be aware of the implications for care and treatment if cannabis is being used medicinally. A comprehensive literature review. Literature searches were made of databases from 1996 using the term cannabis and the combination terms of cannabis and palliative care; symptom management; cancer; oncology; chronic illness; motor neurone disease/amyotrophic lateral sclerosis; and multiple sclerosis. Internet material provided for service users searching for information about the medicinal use of cannabis was also examined. The literature on the use of cannabis in health care repeatedly refers to changes for users that may be equated with improvement in quality of life as an outcome of its use. This has led to increased use of cannabis by these service users. However, the cannabis used is usually obtained illegally and can have consequences for those who choose to use it for its therapeutic value and for nurses who are providing care. Questions and dilemmas are raised concerning the role of the nurse when caring and supporting a person making therapeutic use of cannabis.


Using meiofauna to assess pollutants in freshwater sediments: a microcosm study with cadmium.
The direct and indirect effects of Cd on benthic communities were assessed in a freshwater microcosm study over a period of seven months (218 d). Cadmium was regarded as a model substance to evaluate the usefulness of small-scale laboratory microcosm with microscopic fauna. In particular, effects on the meiofauna community, an ecologically important but rather neglected benthic component, were investigated. In addition, some microfaunal parameters (protozoan abundance and microbial activity) were determined. The sediment was spiked with nominal Cd concentrations of 10, 100, and 1,000 mg/kg dry weight. Because of the strong binding of Cd to sediment particles, measured Cd pore-water concentrations never exceeded 129.5 ± 40.7 µg/L. At 1,000 mg/kg dry weight, the abundances of the two dominant meiofauna taxa, nematodes and oligochaetes, were significantly reduced throughout the present study. Regarding nematodes, species of bacterivorous taxa (Daptonema, Eumonhystera) decreased, whereas species of predacious and omnivorous taxa (Mononchus, Dorylaimus, and Ironus) increased in dominance in microcosms of the highest Cd concentration. Transient effects on microfauna were observed, especially in the first half of the present study, with a reduction in microbial activity and protozoan abundance. However, in microcosms receiving the highest Cd concentration, the abundance of the flagellate Euglena mutabilis increased significantly toward the end of the present study. The results of the present study support the use of small-scale microcosms with natural meiofauna communities as a suitable tool to assess the impact of pollutants in freshwater sediments.


Recapture after exocytosis causes differential retention of protein in granules of bovine chromaffin cells.
After exocytosis, chromaffin granules release essentially all their catecholamines in small fractions of a second, but it is unknown how fast they release stored peptides and proteins. Here we compare the exocytic release of fluorescently labelled neuropeptide Y (NPY) and tissue plasminogen activator from single granules. Exocytosis was tracked by measuring the membrane capacitance, and single granules in live cells were imaged by evanescent field microscopy. Neuropeptide Y left most granules in small fractions of a second, while tissue plasminogen activator remained in open granules for minutes. Taking advantage of the dependence on pH of the fluorescence of green fluorescent protein, we used rhythmic external acidification to determine whether and when granules re-sealed. One-third of them re-sealed within 100 s and retained significant levels of tissue plasminogen activator. Re-sealing accounts for only a fraction of the endocytosis monitored in capacitance measurements. When external [Ca2+] was raised, even neuropeptide Y remained in open granules until they re-sealed. It is concluded that a significant fraction of chromaffin granules re-seal after exocytosis, and retain those proteins that leave granules slowly. We suggest that granules vary the stoichiometry of release by varying both granule re-sealing and the association of proteins with the granule matrix.


Comparison of mental distress in patients with low back pain and a population-based control group measured by Symptoms Check List--A case-referent study.
Mental distress is common in persons experiencing low back pain and who are sick-listed or at risk of being sick-listed. It is, however, not known how mental distress measured by the Symptoms Check List-90 differs between patients with low back pain and the general population. The objective of this study was to compare mental symptoms and distress as measured by the Symptoms Check List-90 in sick-listed or at risk of being sick-listed patients with low back pain with a population-based control group. Mental distress was compared in a group of patients with low back pain (n=770) and a randomly selected population-based reference group (n=909). Established Danish cut-off values for mental distress were used to evaluate the mental distress status in the low back pain and control group and logistic regression was used to calculate odds ratios for the Global Severity Index and the symptom scales of the Symptoms Check List-90 while controlling for baseline demographic differences between the groups. Group mean scores showed that all symptom scales and the Global Severity Index for both sexes were statistically elevated in the low back pain group, except for interpersonal sensitivity in women. When the scores were dichotomized to cases and non-cases of mental distress, a significantly higher prevalence of cases was observed in the low back pain group compared to the reference group on all symptom check list scales, except for paranoid ideation for both sexes and interpersonal sensitivity for women. The biggest between-group difference was observed for the somatization symptom scale. Low back pain patients who are sick-listed or at risk of being sick-listed, are more mentally distressed compared to a randomly selected sample of the general Danish population. Self-reported symptoms of somatization, anxiety, phobic anxiety, obsessive-compulsive, depression and hostility are all more common among patients with low back pain compared to the general population.


A systematic review of the worldwide prevalence of survivors of poliomyelitis reported in 31 studies.
Accurate prevalence figures estimating the number of survivors of poliomyelitis (disease causing acute flaccid paralysis) following poliovirus infection are not available. We aim to undertake a systematic review of all literature concerning the prevalence of survivors of poliomyelitis. Electronic databases were searched from 1900 up to May 2016 for peer-reviewed studies using a population-based approach witha defined denominator and some form of diagnostic or clinical verification of polio. Exclusion criteria were any prevalence data that were unable to be extracted or calculated and studies reporting on incidence only. The quality of each included study was assessed using an existing tool modified for use in prevalence studies. Average crude prevalence rates were used to calculate worldwide estimates. Thirty-one studies met criteria with 90% of studies conducted in low-income to lower middle-income countries. Significant variability in the prevalence of survivors of poliomyelitis was revealed, in low- income to lower middle-income (15 per 100 000 in Nigeria to 1733 in India) and upper-middle to high-income countries (24 (Japan) to 380 per 100 000 (Brazil). The total combined prevalence of survivors of poliomyelitis for those studies at low to moderate risk of bias ranged from 165 (high-income countries) to 425 (low-income to lower middle-income countries) per 100 000 person-years. Historical lameness surveys of children predominated, with wide variation in case definition and assessment criteria, and limited relevance to current prevalence given the lack of incidence of poliovirus infection in the ensuing years. These results highlight the need for future epidemiological studies of poliomyelitis to examine nationally representative samples, including all ages and greater focus on high-income countries. Such efforts will improve capacity to provide reliable and more robust worldwide prevalence estimates.


Positional isomers of aspirin are equally potent in inhibiting colon cancer cell growth: differences in mode of cyclooxygenase inhibition.
We compared the differential effects of positional isomers of acetylsalicylic acid (o-ASA, m-ASA, and p-ASA) on cyclooxygenase (COX) inhibition, gastric prostaglandin E2 (PGE2), malondialdehyde, tumor necrosis factor-alpha (TNF-α) levels, superoxide dismutase (SOD) activity, human adenocarcinoma colon cancer cell growth inhibition, cell proliferation, apoptosis, and cell-cycle progression. We also evaluated the gastric toxicity exerted by ASA isomers. All ASA isomers inhibit COX enzymes, but only the o-ASA exerted an irreversible inhibitory profile. We did not observe a significant difference between ASA isomers in their ability to decrease the in vivo synthesis of PGE2 and SOD activity. Furthermore, all isomers increased the levels of gastric and TNF-α when administered orally at equimolar doses. We observed a dose-dependent cell growth inhibitory effect; the order of potency was p-ASA > m-ASA ≈ o-ASA. There was a dose-dependent decrease in cell proliferation and an increase in apoptosis, with a concomitant Go/G1 arrest. The ulcerogenic profile of the three ASA isomers showed a significant difference between o-ASA (aspirin) and its two positional isomers when administered orally at equimolar doses (1 mmol/kg); the ulcer index (UI) for o-ASA indicated extensive mucosal injury (UI = 38), whereas m-ASA and p-ASA produced a significantly decreased toxic response (UI = 12 and 8, respectively) under the same experimental conditions. These results suggest that the three positional isomers of ASA exert practically the same biologic profile in vitro and in vivo but showed different safety profiles. The mechanism of gastric ulcer formation exerted by aspirin and its two isomers warrants a more detailed and thorough investigation.


Associations of cognitive performance with cardiovascular magnetic resonance phenotypes in the UK Biobank.
Existing evidence suggests links between brain and cardiovascular health. We investigated associations between cognitive performance and cardiovascular magnetic resonance (CMR) phenotypes in the UK Biobank, considering a range of potential confounders. We studied 29 763 participants with CMR and cognitive testing, specifically, fluid intelligence (FI, 13 verbal-numeric reasoning questions), and reaction time (RT, a timed pairs matching exercise); both were considered continuous variables for modelling. We included the following CMR metrics: left and right ventricular (LV and RV) volumes in end-diastole and end-systole, LV/RV ejection fractions, LV/RV stroke volumes, LV mass, and aortic distensibility. Multivariable linear regression models were used to estimate the association of each CMR measure with FI and RT, adjusting for age, sex, smoking, education, deprivation, diabetes, hypertension, high cholesterol, prior myocardial infarction, alcohol intake, and exercise level. We report standardized beta-coefficients, 95% confidence intervals, and P-values adjusted for multiple testing. In this predominantly healthy cohort (average age 63.0 ± 7.5 years), better cognitive performance (higher FI, lower RT) was associated with larger LV/RV volumes, higher LV/RV stroke volumes, greater LV mass, and greater aortic distensibility in fully adjusted models. There was some evidence of non-linearity in the relationship between FI and LV end-systolic volume, with reversal of the direction of association at very high volumes. Associations were consistent for men and women and in different ages. Better cognitive performance is associated with CMR measures likely representing a healthier cardiovascular phenotype. These relationships remained significant after adjustment for a range of cardiometabolic, lifestyle, and demographic factors, suggesting possible involvement of alternative disease mechanisms.


High Blood Glucose Levels Correlate with Tumor Malignancy in Colorectal Cancer Patients.
BACKGROUND Research shows that type 2 diabetes mellitus (T2DM) affects the risk and prognosis of colorectal cancer (CRC). Here, we conducted a retrospective study to investigate whether the clinicopathological features of CRC patients correlate with their blood glucose levels. MATERIAL AND METHODS We enrolled 391 CRC patients hospitalized in our center between 2008 and 2013. Data of their first fasting plasma glucose (FPG) and 2-h postprandial glucose (2hPPG) level after admission, their clinicopathological features, and survival were collected. The correlations between blood glucose level and clinicopathological features were analyzed by Pearson chi-square analysis. Patient survival was analyzed by Kaplan-Meier and Cox-regression analysis. RESULTS There were 116 out of the 391 CRC patients who had high blood glucose level (H-G group, 29.67%), among which 58 (14.83%), 18 (4.60%), and 40 (10.23%) were diabetes mellitus (DM), impaired glucose tolerance (IGT), and impaired fasting glucose (IFG), respectively, while 275 (70.33%) patients had normal glucose level (N-G group). Compared with the N-G group, patients in the H-G group had larger tumor diameters and lower tumor differentiation (p<0.05). A higher ratio of patients in the H-G group also had more advanced TNM staging and more ulcerative CRC gross type (p<0.05). No significant difference was observed in patient overall survival among different glucose groups. No effect of insulin therapy on CRC development and patient survival was observed. CONCLUSIONS Blood glucose level in CRC patients correlates significantly with local tumor malignancy, but no significant effect on distant metastasis and patient overall survival was observed.


Hinge Region in DNA Packaging Terminase pUL15 of Herpes Simplex Virus: A Potential Allosteric Target for Antiviral Drugs.
Approximately 80% of adults are infected with a member of the herpesviridae family. Herpesviruses establish life-long latent infections within neurons, which may reactivate into lytic infections due to stress or immune suppression. There are nine human herpesviruses (HHV) posing health concerns from benign conditions to life threatening encephalitis, including cancers associated with viral infections. The current treatment options for most HHV conditions mainly include several nucleoside and nucleotide analogs targeting viral DNA polymerase. Although these drugs help manage infections, their common mechanism of action may lead to the development of drug resistance, which is particularly devastating in immunocompromised patients. Therefore, new classes of drugs directed against novel targets in HHVs are necessary to alleviate this issue. We analyzed the conservation rates of all proteins in herpes simplex virus 1 (HHV-1), a representative of the HHV family and one of the most common viruses infecting the human population. Furthermore, we generated a full-length structure model of the most conserved HHV-1 protein, the DNA packaging terminase pUL15. A series of computational analyses were performed on the model to identify ATP and DNA binding sites and characterize the dynamics of the protein. Our study indicates that proteins involved in HHV-1 DNA packaging and cleavage are amongst the most conserved gene products of HHVs. Since the packaging protein pUL15 is the most conserved among all HHV-1 gene products, the virus will have a lower chance of developing resistance to small molecules targeting pUL15. A subsequent analysis of the structure of pUL15 revealed distinct ATP and DNA binding domains and the elastic network model identifies a functionally important hinge region between the two domains of pUL15. The atomic information on the active and allosteric sites in the ATP- and DNA-bound model of pUL15 presented in this study can inform the structure-based drug discovery of a new class of drugs to treat a wide range of HHVs.


Molecular Characterization of Arginine Kinases in the Soybean Cyst Nematode (Heterodera glycines).
Arginine kinase (AK) is a phosphagen kinase that plays a key role in energy mobilization in invertebrates. Alignment of expressed sequence tags (ESTs) for soybean cyst nematode (SCN) (Heterodera glycines) produced two separate contiguous sequences (contigs) and three singletons encoding peptides with high similarity to AKs. One contig, Hg-AK1, had 244 ESTs in the alignment whereas the other, Hg-AK2, had only three; nonetheless, the consensus sequence for Hg-AK1 was missing much of the 5' end. Polymerase chain reaction (PCR) was used to prepare clones that were then sequenced to obtain full-length sequences for both Hg-AK1 and Hg-AK2. Hg-AK1 has an open reading frame of 1080 nucleotides (nt) encoding a protein of 360 amino acids (aa) with a predicted molecular weight of 40 kDa. The open reading frame for Hg-AK2 is 1221 nt, 407 aa, and 46 kDa with a 71% aa identity with Hg-AK1. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) indicated that Hg-AK1 and Hg-AK2 are expressed constitutively throughout the SCN life cycle. Phylogenetic analysis of peptide sequences for near full-length nematode contigs and other AKs in the Swisspro database indicates that the nematode AKs evolved from a single gene after divergence of insects and nematodes.


Interstitial cells of the heart valves possess characteristics similar to smooth muscle cells.
Interstitial cells of heart atrioventricular and sigmoid valves were examined in several laboratory animals (rabbit, hamster, rat, and mouse) and in humans. These cells constitute a large fraction of the total cell population of the valve; in mouse atrioventricular valves, they amount to approximately 30% of the volumetric density. By their ultrastructural features and functional properties, valvular interstitial cells are intermediate between fibroblasts and vascular smooth muscle cells. Like fibroblasts, valvular interstitial cells lack a basal lamina establishing direct and extensive contacts with collagen fibers, elastin microfibrils, and proteoglycans of the matrix. The cells have numerous slender and long processes, connected to one another, forming a complex cellular framework spanning the entire valve. Similar to smooth muscle cells, valvular interstitial cells are extensively coupled by communicating junctions as shown by thin sections, freeze-fracture, lanthanum staining, and carboxyfluorescein microinjection. The cells contain numerous bundles of actin filaments, which are decorated by the S1 fragment of heavy meromyosin. Valvular interstitial cells also express cyclic guanosine-monophosphate-dependent protein kinase, as detected by immunofluorescence and immunoperoxidase histochemistry. Motor nerve endings are located closely apposed to valvular interstitial cells: structurally most of them appear to be of the adrenergic type. Valvular interstitial cells contract on epinephrine or angiotensin II stimulation as shown both in culture and in situ (valvular strips). Taken together these observations suggest that VIC may have contractile properties, which can account for a controlled tonus, actively correlated with the cyclically changing forces acting on valves during diastole and systole.


Effect of irrigation of the nose with isotonic salt solution on adult patients with chronic paranasal sinus disease.
In a prospective, randomized, controlled, double-blind trial we compared the effectiveness of endonasal irrigations with Ems salt solution to that with sodium chloride solution in the treatment of adult patients with chronic paranasal sinus disease. Subjects (n = 40) were randomly allocated to treatment either with isotonic Ems salt solution or with isotonic sodium chloride solution. The treatment consisted of endonasal irrigation twice daily and additional nasal spray as required. Nasal endoscopy, plain radiography of the paranasal sinuses, olfactometry, anterior rhinomanometry, and a saccharin-clearance test were carried out on days 1 and 7. Patients recorded rating scales of general discomfort, nasal airway obstruction, agreeableness of the irrigation, duration of improved nasal resistance after each irrigation, and the amount of additional nasal spray in a diary. Nasal air flow was not improved significantly. Subjective complaints, endonasal endoscopy, and radiography results revealed a significant improvement in both groups (P = 0.0001). In comparison, the two groups were not significantly different in outcome. Endonasal irrigations with salt solutions are effective in the treatment of chronic sinusitis, and a significant difference between Ems salt and sodium chloride was not observed.


Temporally structured metapopulation dynamics and persistence of influenza A H3N2 virus in humans.
Populations of seasonal influenza virus experience strong annual bottlenecks that pose a considerable extinction risk. It has been suggested that an influenza source population located in tropical Southeast or East Asia seeds annual temperate epidemics. Here we investigate the seasonal dynamics and migration patterns of influenza A H3N2 virus by analysis of virus samples obtained from 2003 to 2006 from Australia, Europe, Japan, New York, New Zealand, Southeast Asia, and newly sequenced viruses from Hong Kong. In contrast to annual temperate epidemics, relatively low levels of relative genetic diversity and no seasonal fluctuations characterized virus populations in tropical Southeast Asia and Hong Kong. Bayesian phylogeographic analysis using discrete temporal and spatial characters reveal high rates of viral migration between urban centers tested. Although the virus population that migrated between Southeast Asia and Hong Kong persisted through time, this was dependent on virus input from temperate regions and these tropical regions did not maintain a source for annual H3N2 influenza epidemics. We further show that multiple lineages may seed annual influenza epidemics, and that each region may function as a potential source population. We therefore propose that the global persistence of H3N2 influenza A virus is the result of a migrating metapopulation in which multiple different localities may seed seasonal epidemics in temperate regions in a given year. Such complex global migration dynamics may confound control efforts and contribute to the emergence and spread of antigenic variants and drug-resistant viruses.


A genetic analysis of the alpha-glycerophosphate oxidase locus in Drosophila melanogaster.
The gene for alpha-glycerophosphate oxidase, the nuclear encoded mitochondrial enzyme of the alpha-glycerophosphate cycle (alpha GP); has been mapped in Drosophila melanogaster. Several interstitial deficiencies in region 50c-53AB of chromosome 2R were used to localize the structural gene to 52D2-5. In addition, mutations of alpha GPO were generated; alpha GPO mutants are viable yet flightless. Interactions of alpha GPO with alpha-glycerophosphate dehydrogenase (alpha GPDH), the cytoplasmic enzyme of the alpha GP cycle, were investigated through the synthesis of a series of alpha GPDHnull-alpha GPOnull double mutants. Of the six double null mutants constructed, four alpha GPDH-alpha GPO double nulls are viable and flightless. Two double mutants, however, exhibit an allelic-dependent synthetic lethal phenotype.


Sleep spindle and slow wave frequency reflect motor skill performance in primary school-age children.
The role of sleep in the enhancement of motor skills has been studied extensively in adults. We aimed to determine involvement of sleep and characteristics of spindles and slow waves in a motor skill in children. We hypothesized sleep-dependence of skill enhancement and an association of interindividual differences in skill and sleep characteristics. 30 children (19 females, 10.7 ± 0.8 years of age; mean ± SD) performed finger sequence tapping tasks in a repeated-measures design spanning 4 days including 1 polysomnography (PSG) night. Initial and delayed performance were assessed over 12 h of wake; 12 h with sleep; and 24 h with wake and sleep. For the 12 h with sleep, children were assigned to one of three conditions: modulation of slow waves and spindles was attempted using acoustic perturbation, and compared to yoked and no-sound control conditions. Mixed effect regression models evaluated the association of sleep, its macrostructure and spindles and slow wave parameters with initial and delayed speed and accuracy. Children enhance their accuracy only over an interval with sleep. Unlike previously reported in adults, children enhance their speed independent of sleep, a capacity that may to be lost in adulthood. Individual differences in the dominant frequency of spindles and slow waves were predictive for performance: children performed better if they had less slow spindles, more fast spindles and faster slow waves. On the other hand, overnight enhancement of accuracy was most pronounced in children with more slow spindles and slower slow waves, i.e., the ones with an initial lower performance. Associations of spindle and slow wave characteristics with initial performance may confound interpretation of their involvement in overnight enhancement. Slower frequencies of characteristic sleep events may mark slower learning and immaturity of networks involved in motor skills.


Ammonia and bicarbonate transport by thick ascending limb of rat kidney.
Ammonia and bicarbonate transport by the thick ascending limb of rat kidney was studied to determine whether this segment contributes to the regulation of renal ammonia and net acid excretion. Cortical and medullary thick ascending limbs were perfused in vitro at 1.0-1.5 nl X min-1 X mm-1 with HCO3-buffered solutions. There was no significant net fluid transport. With 4 mM ammonia in bath and perfusate, transepithelial voltage averaged 6-9 mV, lumen positive, and did not differ between the two segments. The mean ammonia concentration in collected tubule fluid was 2.8 mM with cortical segments and 2.3 mM with medullary segments, indicating net absorption of ammonia. Furosemide (10(-4) M) in the perfusate eliminated ammonia absorption in medullary thick ascending limbs and converted net absorption to net secretion in cortical thick ascending limbs. Furosemide reduced transepithelial voltage to near zero in every tubule. Cortical and medullary thick ascending limbs also absorbed bicarbonate, indicating that their tubule fluid was acidified relative to the bath. Therefore, absorption of ammonia could not have occurred by nonionic diffusion. The absorption most likely was due to direct transport of NH4+. The possible mechanisms involved are discussed, and it is proposed that absorption of ammonia by thick ascending limbs provides a source for its accumulation in the renal medulla and secretion into the collecting ducts.


Carnosic acid regulates cell proliferation and invasion in chronic myeloid leukemia cancer cells via suppressing microRNA-708.
Carnosic acid (CA) is an important polyphenol mainly isolated from the famous spice and the medicinal plant Rosmarinus officinalis. CA has been shown to exhibit tremendous pharmacological properties which include, but are not limited to, anticancer, antioxidant and anti-inflammatory activities. The current study was designed to evaluate the anticancer effects of CA against chronic myeloid leukemia (CML) which is one of the rare but deadly malignancies both in men and women. CML KBM-7 cell line was used in this study. Cell viability was assessed by MTT assay. Apoptosis was detected by DAPI and annexin V/PI staining, cell cycle analysis by flow cytometry and cell invasion by Boyden chamber assay. The microRNA-780 expression was determined by quantitative RT-PCR. Our results indicated that CA exhibits significant anticancer activity on CML KBM-7 cells with an IC50 of 25 μM. The anticancer activity was due to induction of apoptosis and cell cycle arrest. Moreover, it was observed that CA inhibits the proliferation and invasion of CML KBM-7 cells which could mainly be due to downregulation of microRNA- 780 expression as indicated by the quantitative RT-PCR analysis. Taken together, we propose that carnosic acid could prove a potential lead compound in the treatment of CML and deserves further in vitro as well as in vivo study.


Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.
To compare outcomes of bone marrow transplants for leukemia from HLA-identical siblings, haploidentical HLA-mismatched relatives, and HLA-matched and mismatched unrelated donors. A total of 2,055 recipients of allogeneic bone marrow transplants for chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the study. Transplants were performed between 1985 and 1991 and reported to the International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA-matched (n = 383) or mismatched for one HLA-A, -B, or -DR antigen (n = 108). HLA typing was performed using serologic techniques. Transplant-related mortality was significantly higher after alternative donor transplants than after HLA-identical sibling transplants. Among patients with early leukemia (CML in chronic phase or acute leukemia in first remission), 3-year transplant-related mortality (+/-SE) was 21% +/- 2% after HLA-identical sibling transplants and greater than 50% after all types of alternative donor transplants studied. Among patients with early leukemia, relative risks of treatment failure (inverse of leukemia-free survival), using HLA-identical sibling transplants as the reference group, were 2.43 (P < .0001) with 1-HLA-antigen-mismatched related donors, 3.79 (P < .0001) with 2-HLA-antigen-mismatched related donors, 2.11 (P < .0001) with HLA-matched unrelated donors, and 3.33 (P < .0001) with 1-HLA-antigen-mismatched unrelated donors. For patients with more advanced leukemia, differences in treatment failure were less striking: 1-HLA-antigen-mismatched relatives, 1.22 (P = not significant [NS]); 2-HLA-antigen-mismatched relatives, 1.81 (P < .0001); HLA-matched unrelated donors, 1.39 (P = .002); and 1-HLA-antigen-mismatched unrelated donors, 1.63 (P = .002). Although transplants from alternative donors are effective in some patients with leukemia, treatment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor-recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This difference is less in advanced leukemia.


Whole-Genome Analysis of Diversity and SNP-Major Gene Association in Peach Germplasm.
Peach was domesticated in China more than four millennia ago and from there it spread world-wide. Since the middle of the last century, peach breeding programs have been very dynamic generating hundreds of new commercial varieties, however, in most cases such varieties derive from a limited collection of parental lines (founders). This is one reason for the observed low levels of variability of the commercial gene pool, implying that knowledge of the extent and distribution of genetic variability in peach is critical to allow the choice of adequate parents to confer enhanced productivity, adaptation and quality to improved varieties. With this aim we genotyped 1,580 peach accessions (including a few closely related Prunus species) maintained and phenotyped in five germplasm collections (four European and one Chinese) with the International Peach SNP Consortium 9K SNP peach array. The study of population structure revealed the subdivision of the panel in three main populations, one mainly made up of Occidental varieties from breeding programs (POP1OCB), one of Occidental landraces (POP2OCT) and the third of Oriental accessions (POP3OR). Analysis of linkage disequilibrium (LD) identified differential patterns of genome-wide LD blocks in each of the populations. Phenotypic data for seven monogenic traits were integrated in a genome-wide association study (GWAS). The significantly associated SNPs were always in the regions predicted by linkage analysis, forming haplotypes of markers. These diagnostic haplotypes could be used for marker-assisted selection (MAS) in modern breeding programs.


Edge method for on-orbit defocus assessment.
In the earth observation domain, two classes of sensors may be distinguished: a class for which sensor performances are driven by radiometric accuracy of the images and a class for which sensor performances are driven by spatial resolution. In this latter case, as spatial resolution depends on the triplet constituted by the Ground Sampling Distance (GSD), Modulation Transfer Function (MTF), and Signal to Noise Ratio (SNR), refocusing, acting as an MTF improvement, is very important. Refocusing is not difficult by itself as far as the on-board mechanism is reliable. The difficulty is on the defocus assessment side. Some methods such as those used for the SPOT family rely on the ability of the satellite to image the same landscape with two focusing positions. This can be done with a bi-sensor configuration, with adequate focal plane, or with the satellite agility. A new generation of refocusing mechanism will be taken aboard Pleiades. As the speed of this mechanism will be much slower than the speed of the older generation, it won't be possible, despite the agility of the satellite, to image the same landscape with two focusing positions on the same orbit. That's why methods relying on MTF measurement with edge method have been studied. This paper describes the methods and the work done to assess the defocus measurement accuracy in the Pleiades context.


A grammar of action generates predictions in skilled musicians.
The present study investigates shared representations of syntactic knowledge in music and action. We examined whether expectancy violations in musical harmonic sequences are also perceived as violations of the movement sequences necessary to produce them. Pianists imitated silent videos showing one hand playing chord sequences on a muted keyboard. Results indicate that, despite the absence of auditory feedback, imitation of a chord is fastest when it is congruent with the preceding harmonic context. This suggests that the harmonic rules implied by observed actions induce expectations that influence action execution. As evidence that these predictions are derived at a high representational level, imitation was more accurate for harmonically incongruent chords than for congruent chords executed with unconventional fingering. The magnitude of the effects of context and goal prioritization increased with musical training. Thus, musical training may lead to a domain-general representation of musical grammar, i.e., to a grammar of action.


Characterization of family IV UDG from Aeropyrum pernix and its application in hot-start PCR by family B DNA polymerase.
Recombinant uracil-DNA glycosylase (UDG) from Aeropyrum pernix (A. pernix) was expressed in E. coli. The biochemical characteristics of A. pernix UDG (ApeUDG) were studied using oligonucleotides carrying a deoxyuracil (dU) base. The optimal temperature range and pH value for dU removal by ApeUDG were 55-65°C and pH 9.0, respectively. The removal of dU was inhibited by the divalent ions of Zn, Cu, Co, Ni, and Mn, as well as a high concentration of NaCl. The opposite base in the complementary strand affected the dU removal by ApeUDG as follows: U/C≈U/G>U/T≈U/AP≈U/->U/U≈U/I>U/A. The phosphorothioate around dU strongly inhibited dU removal by ApeUDG. Based on the above biochemical characteristics and the conservation of amino acid residues, ApeUDG was determined to belong to the IV UDG family. ApeUDG increased the yield of PCR by Pfu DNA polymerase via the removal of dU in amplified DNA. Using the dU-carrying oligonucleotide as an inhibitor and ApeUDG as an activator of Pfu DNA polymerase, the yield of undesired DNA fragments, such as primer-dimer, was significantly decreased, and the yield of the PCR target fragment was increased. This strategy, which aims to amplify the target gene with high specificity and yield, can be applied to all family B DNA polymerases.


Long-term effectiveness of health coaching in rehabilitation and prevention: A systematic review.
This systematic review aims to evaluate the long-term effectiveness of health coaching interventions in rehabilitation and prevention. Databases and a manual search were used to identify randomized controlled trials (RCTs) in English through to June 2015. Studies were included if: (1) the target population were people of employment age, (2) the intervention addressed either people suffering from a diagnosed disease or healthy people, (3) the intervention included health coaching to influence health-related outcomes and/or processes and (4) the study had a follow-up of at least 24 weeks after the end of the intervention period. Out of 90 RCTs, 14 studies were selected using the inclusion criteria: seven were designed for the rehabilitative setting and seven for the preventive setting. Three studies of each setting found statistically significant long-term effectiveness. The high number of studies evaluating health coaching underlines the relevance of this approach. Despite the increasing popularity of health coaching, a research gap exists in regard to its long-term effectiveness. It is of utmost importance to consider the sustainability already during planning of health coaching interventions. The involvement of the target group and the setting seems to be a promising strategy.


Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials.
Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, myocardial infarction, stroke, heart failure, need for revascularization, nephropathy, and diabetes and its complications. Although angiotensin-II receptor blockers (ARBs) have been less extensively evaluated, theoretically they may have "protective" effects similar to those of ACE inhibitors, but with better tolerability. Currently, there is uncertainty about the role of ARBs when used alone or in combination with an ACE inhibitor in high-risk populations with controlled hypertension. Primary objectives of the ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) are to determine if the combination of the ARB telmisartan and the ACE inhibitor ramipril is more effective than ramipril alone, and if telmisartan is at least as effective as ramipril. The Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) will determine if telmisartan is superior to placebo in patients who are intolerant of ACE inhibitors. The primary outcome for both trials is the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. High-risk patients with coronary, peripheral, or cerebrovascular disease or diabetes with end-organ damage are being recruited and followed for 3.5 to 5.5 years in 2 parallel, randomized, double-blind clinical trials. Recruitment from 730 centers in 40 countries for ONTARGET (n = 25,620) was completed in July 2003. For TRANSCEND, 5776 patients (out of a projected total of 6000) have been recruited (by May 10, 2004). Baseline patient characteristics are comparable to the Heart Outcomes Prevention Evaluation (HOPE) trial, the basis of the design of the current study, confirming that patients are at high-risk.


NHC adducts of tantalum amidohalides: the first example of NHC abnormally coordinated to an early transition metal.
The reaction of Ta(NMe2)5 with NHC·HBF4 (NHC = IMes and SIMes) leads to new carbene adducts of the mixed TaV amidofluoride, [(NHC)TaF3(NMe2)2]. On the contrary, the reaction of Ta(NMe2)5 with IMes·HCl gives a complex mixture, where [(aIMes)TaCl2(NMe2)3] is identified as one of the products. This is the first example of abnormal NHC coordination to an early transition metal.


Intratumoral CD56bright natural killer cells are associated with improved survival in bladder cancer.
Natural killer (NK) cells are effective at killing tumors in a non-MHC restricted manner and are emerging targets for cancer therapy but their importance in bladder cancer (BC) is poorly defined. NK cells are commonly subdivided into populations based on relative surface expression of CD56. Two major subsets are CD56bright and CD56dim NK cells. The prevalence of intratumoral lymphocytes was examined via flow cytometric analysis of bladder tissue from a local cohort of patients with non-invasive and invasive BC (n=28). The association of NK cell subsets with cancer-specific survival (CSS) and overall survival (OS) was examined in 50 patients with BC using Cox regression. Fluorescence-activated cell sorting (FACS) of intratumoral lymphocytes isolated CD56 NK cell subsets were used for examination of function, including cytokine production and in vitro cytotoxicity. NK cells predominated among bladder intratumoral lymphocytes. Intratumoral CD56bright NK cells showed increased cytokine production and cytotoxicity compared to their CD56dim counterparts and were associated with improved CSS and OS independent of pathologic tumor stage. On the other hand, CD56dim NK cells were not associated with improved outcomes but were associated with higher pathologic stage. NK cells are frequent among intratumoral lymphocytes in BC. Bladder intratumoral CD56bright NK cells are functional and prognostically relevant whereas CD56dim NK cells are dysfunctional and prevalent in higher stage tumors. Thus, CD56bright NK cells are promising targets in BC.


Non-technical skills learning in healthcare through simulation education: integrating the SECTORS learning model and complexity theory.
Recent works have reported the SECTORS model for non-technical skills learning in healthcare. The TINSELS programme applied this model, together with complexity theory, to guide the design and piloting of a non-technical skills based simulation training programme in the context of medicines safety. The SECTORS model defined learning outcomes. Complexity Theory led to a simulation intervention that employed authentic multi-professional learner teams, included planned and unplanned disturbances from the norm and used a staged debrief to encourage peer observation and learning. Assessment videos of non-technical skills in each learning outcome were produced and viewed as part of a Non-Technical Skills Observation Test (NOTSOT) both preintervention and postintervention. Learner observations were assessed by two researchers and statistical difference investigated using a student's t test. The resultant intervention is described and available from the authors. Eighteen participants were recruited from a range of inter-professional groups and were split into two cohorts. There was a statistically significant improvement (p=0.0314) between the Mean (SD) scores for the NOTSOT pre course 13.9 (2.32) and postcourse 16.42 (3.45). An original, theoretically underpinned, multiprofessional, simulation based training programme has been produced by the integration of the SECTORS model for non-technical skills learning the complexity theory. This pilot work suggests the resultant intervention can enhance non-technical skills.


Four fibroblast tropomyosin isoforms are expressed from the rat alpha-tropomyosin gene via alternative RNA splicing and the use of two promoters.
cDNA clones encoding four rat tropomyosin isoforms, termed TM-2, TM-3, TM-5a, and TM-5b, were isolated and characterized. All are derived from the alpha-tropomyosin gene via alternative RNA processing and the use of two alternate promoters. The cDNA sequences predict that TM-2 and TM-3 both contain 284 amino acids and differ from each other only at an internal region of the protein from amino acids 189 through 213, due to alternative splicing of exons 6a and 6b. TM-5a and TM-5b both contain 248 amino acids and differ from each other only at an internal exon encoding amino acids 153 through 177, also due to alternative splicing of exons 6a and 6b. The differences in the amino acid sequence encoded by these alternate exons affects the theoretical actin-binding pattern of the tropomyosins, such that TM-5b is expected to bind actin with greater affinity than TM-5a. TM-2 and TM-3 are transcribed from the upstream promoter, and TM-5a and TM-5b are transcribed from an internal promoter. In addition, all four isoforms contain the identical COOH-terminal coding region. RNA protection analyses revealed that the mRNA for each isoform is expressed in a number of different tissues and cell types, although the expression of some isoforms is restricted to particular cell types. Furthermore, the expression of mRNA encoding these isoforms was found to be altered in a number of different virally transformed cell lines. The changes in the expression of tropomyosin mRNAs in transformed cells reflect changes in the relative use of the two promoters, as well as the relative use of alternatively spliced exons 6a and 6b.


Auditory evoked visual awareness following sudden ocular blindness: an EEG and TMS investigation.
Neurophysiological and neuroanatomical studies have provoked controversy about whether the visual cortex may be more modifiable than previously believed. Auditory processing is enhanced in blind compared to sighted people, and the enhancement might reflect encroachment of auditory transmission onto visual cortex. To address this issue, we recorded the auditory event-related potentials (ERPs) correlated with auditory related paradoxical visual awareness in a subject with traumatic total late-onset blindness. We found that (1) there was auditory related brain activity over the occipital visual scalp regions starting from a very early stage (< 80 ms) and (2) this occipital activity was significantly different between "visually aware" and "visually unaware" responses in the P1 (40-80 ms) component following meaningful stimuli. There was also a significant difference between responses with and without visual awareness in the N1 (100-120 ms) component following either tones or meaningful stimuli. The phosphenes accompanying auditory stimuli in the ERP experiment were always perceived to be directly in front of the subject and this was reproduced by transcranial magnetic stimulation over the blind primary visual cortex and by sudden sounds delivered to the side or behind the subject. The TMS induced phosphenes were restricted to the central part of the space and were, at least qualitatively, the same as those induced by sounds. The results are clear evidence that human perceptual functions can be reorganized after sudden, late-onset, total ocular blindness.


Lived experiences of a community regarding its involvement in a university community-based education programme.
Community involvement is one of the crucial principles in the implementation of successful community-based education programmes. However, a gap continues to exist between the rhetoric of this principle and the reality of involving or engaging communities in the education of health professionals. This study investigated the experiences of a community regarding its involvement in a community-based education programme offered by a university nursing school in Durban, South Africa. An interpretive existentialist-phenomenological design was employed for its richness in extracting human experiences. Individual interviews were held with school teachers and coordinators from non-government organisations, whilst focus groups were used for school children and community health workers. Although focus group discussions are not well suited for phenomenological studies, they can promote active participation and reduce possible intimidation by providing support through group interaction. Analysis of data was guided by Schweitzer's model for analysing phenomenological data. Themes that emerged from the data include: (1) Community experience of unmet expectations; (2) Benefits to the community from its involvement in the University Nursing School community-based education programme; (3) Existing partnership between the community and the university; (4) Sharing in the case-based learning activities; (5) Awareness of available services, human rights and self-reliance. The researched community indeed benefited in its participation in the University Nursing School (UNS) CBE programme. However, there is a need to improve the communication between partners to make the partnership more sustainable through close relationships and interaction. There is also a need for further research on related aspects of the community's involvement.


A disease-specific activity index for Wegener's granulomatosis: modification of the Birmingham Vasculitis Activity Score. International Network for the Study of the Systemic Vasculitides (INSSYS).
To refine and validate the Birmingham Vasculitis Activity Score (BVAS) as a disease-specific activity index for Wegener's granulomatosis (WG). Sixteen members of the International Network for the Study of the Systemic Vasculitides (INSSYS) revised the BVAS, with 3 goals: to reduce the redundancy of some component items, to enhance its ability to capture important disease manifestations specific to WG, and to streamline the instrument for use in clinical research. We defined the items and weighted them empirically as either minor (e.g., nasal crusting = 1 point) or major (e.g., alveolar hemorrhage = 3 points). We then validated the new, disease-specific BVAS/WG in 2 simulation exercises and a clinical case series that involved 117 patients with WG. We removed 38 items from the original BVAS, revised 9 items, and added 7 new items. Correlations between the scores on the BVAS/WG and the physician's global assessment (PGA) of disease activity were high, even when patients in remission were excluded. In the clinical case series, Spearman's rank correlation coefficient between the BVAS/WG and the PGA was r = 0.81 (95% confidence interval 0.73-0.87). The interobserver reliability using intraclass (within-case) correlation coefficients in the 2 simulation exercises was r = 0.93 for the BVAS/WG and r = 0.88 for the PGA in the first and r = 0.91 for the BVAS/WG and r = 0.88 for the PGA in the second. There was no significant observer effect in the scoring of the BVAS/WG or the PGA. The discriminant validity of the BVAS/WG was good: r = 0.73 (95% confidence interval 0.43-0.83). The BVAS/WG is a valid, disease-specific activity index for WG. Tested in simulation exercises and in actual patients, the BVAS/WG correlates well with the PGA, is sensitive to change, and has good inter- and intraobserver reliability. The INSSYS will use the BVAS/WG to assess the primary outcome in a phase II/III trial of etanercept in WG.


Gene expression profiles in Atlantic salmon adipose-derived stromo-vascular fraction during differentiation into adipocytes.
Excessive fat deposition is one of the largest problems faced by salmon aquaculture industries, leading to production losses due to high volume of adipose tissue offal. In addition, increased lipid accumulation may impose considerable stress on adipocytes leading to adipocyte activation and production and secretion of inflammatory mediators, as observed in mammals. Microarray and qPCR analyses were performed to follow transcriptome changes during adipogenesis in the primary culture of adipose stromo-vascular fraction (aSVF) of Atlantic salmon. Cellular heterogeneity decreased by confluence as evidenced by the down-regulation of markers of osteo/chondrogenic, myogenic, immune and vasculature lineages. Transgelin (TAGLN), a marker of the multipotent pericyte, was prominently expressed around confluence while adipogenic PPARgamma was up-regulated already in subconfluent cells. Proliferative activity and subsequent cell cycle arrest were reflected in the fluctuations of pro- and anti-mitotic regulators. Marked regulation of genes involved in lipid and glucose metabolism and pathways producing NADPH and glycerol-3-phosphate (G3P) was seen during the terminal differentiation, also characterised by diverse stress responses. Activation of the glutathione and thioredoxin antioxidant systems and changes in the iron metabolism suggested the need for protection against oxidative stress. Signs of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) occured in parallel with the increased lipid droplet (LD) formation and production of secretory proteins (adipsin, visfatin). The UPR markers XBP1 and ATF6 were induced together with genes involved in ubiquitin-proteasome and lysosomal proteolysis. Concurrently, translation was suppressed as evidenced by the down-regulation of genes encoding elongation factors and components of the ribosomal machinery. Notably, expression changes of a panel of genes that belong to different immune pathways were seen throughout adipogenesis. The induction of AP1 (Jun, Fos), which is a master regulator of stress responses, culminated by the end of adipogenesis, concurrent with the maximal observed lipid deposition. Our data point to an intimate relationship between metabolic regulation and immune responses in white adipocytes of a cold-blooded vertebrate. Stress imposed on adipocytes by LD formation and expansion is prominently reflected in the ER compartment and the activated UPR response could have an important role at visceral obesity in fish.


Recovering the absolute phase maps of two fringe patterns with selected frequencies.
Phase unwrapping is an important and challenging issue in fringe pattern profilometry. In this Letter we propose an approach to recover absolute phase maps of two fringe patterns with selected frequencies. Compared to existing temporal multiple frequency algorithms, the two frequencies in our proposed algorithm can be high enough and thus enable efficient and accurate recovery of absolute phase maps. Experiment results are presented to confirm the effectiveness of the proposed technique.


Radiation-sensitizing effect of low-concentration docetaxel on human esophageal squamous cell carcinoma cell lines.
Esophageal squamous cell carcinoma (ESCC) is more sensitive to radiation and chemotherapy than other cancers of the digestive system, and combined modality therapy may represent a promising treatment method. The radiation-sensitizing effect of docetaxel on ESCC cell lines was investigated. A colony formation assay was performed in which ESCC cell lines (TE2, TE3) and A431 were exposed to docetaxel (from 1.0×10(-11) to 10(-7) M) for 3 h to determine the concentration of docetaxel that was not able to kill individual cells (i.e., the non-cytocidal concentration). Individual cell lines were then exposed to the non-cytocidal concentration of docetaxel prior to, during, and after irradiation to determine whether the timing of docetaxel administration affected cell survival. In addition, flow-cytometry was performed, and the cell cycle was examined prior to and after docetaxel exposure to assess the mechanism of docetaxel as a radiation sensitizer. Docetaxel exhibited a concentration-dependent cytocidal effect, with a different IC(50) for each cell type. Almost no cytocidal effect was observed at the following docetaxel concentrations: A431, ≤1.0×10(-10) M; TE-2 and TE-3, ≤1.0×10(-9) M. Concurrent treatment with docetaxel and radiation tended to decrease cell survival in all the cell lines compared with docetaxel or radiation alone. Cell survival was lowest when the cells were treated using X-ray irradiation after docetaxel exposure (p<0.05). Flow cytometry revealed that in all three cell lines, docetaxel exposure increased the G2/M cell fraction with a higher increase in the cell line that exhibited the highest radiosensitivity. This study demonstrated that the administration of docetaxel at a non-cytocidal concentration prior to radiotherapy produced a synergistic cell-killing effect in SCC cell lines.


A single gonadotropin alpha-subunit gene in normal tissue and tumor-derived cell lines.
The structure of gene sequences coding for the mRNA of human chorionic gonadotropin (hCG) alpha-subunit was investigated by Southern blot analysis of genomic DNAs using a cloned, full length cDNA probe. While four hormones, lutropin, follitropin, thyrotropin, and choriogonadotropin, have homologous alpha-subunits, only one gene that bears hCG-alpha sequences could be detected per haploid complement. The structure of this single gonadotropin alpha-subunit gene, which contains intervening sequences, is the same in DNA from first trimester and term placentae. However polymorphism was observed for the presence of a HindIII site and of an Eco RI site in the gene's 3' flanking sequences. The organization of hCG-alpha sequences in several trophoblastic and nontrophoblastic tumor cell lines, which produce hCG subunits, was also examined. In each, the same gene copy number and structure were seen as in normal tissue. Thus, the characteristics of ectopic alpha-subunit expression in these cells seem not to be determined by DNA rearrangements.


Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study.
There are few data on the epidemiology and outcomes of influenza infection in recipients of solid-organ transplants. We aimed to establish the outcomes of pandemic influenza A H1N1 and factors leading to severe disease in a cohort of patients who had received transplants. We did a multicentre cohort study of adults and children who had received organ transplants with microbiological confirmation of influenza A infection from April to December, 2009. Centres were identified through the American Society of Transplantation Influenza Collaborative Study Group. Demographics, clinical presentation, treatment, and outcomes were assessed. Severity of disease was measured by admission to hospital and intensive care units (ICUs). The data were analysed with descriptive statistics. Proportions were compared by use of chi(2) tests. We used univariate analysis to identify factors leading to pneumonia, admission to hospital, and admission to an ICU. Multivariate analysis was done by use of a stepwise logistic regression model. We analysed deaths with Kaplan-Meier survival analysis. We assessed 237 cases of medically attended influenza A H1N1 reported from 26 transplant centres during the study period. Transplant types included kidney, liver, heart, lung, and others. Both adults (154 patients; median age 47 years) and children (83; 9 years) were assessed. Median time from transplant was 3.6 years. 167 (71%) of 237 patients were admitted to hospital. Data on complications were available for 230 patients; 73 (32%) had pneumonia, 37 (16%) were admitted to ICUs, and ten (4%) died. Antiviral treatment was used in 223 (94%) patients (primarily oseltamivir monotherapy). Seven (8%) patients given antiviral drugs within 48 h of symptom onset were admitted to an ICU compared with 28 (22.4%) given antivirals later (p=0.007). Children who received transplants were less likely to present with pneumonia than adults, but rates of admission to hospital and ICU were similar. Influenza A H1N1 caused substantial morbidity in recipients of solid-organ transplants during the 2009-10 pandemic. Starting antiviral therapy early is associated with clinical benefit as measured by need for ICU admission and mechanical ventilation. None.


Differences in Pes Planus and Pes Cavus subtalar eversion/inversion before and after prolonged running, using a two-dimensional digital analysis.
In sports, there is a constant discussion about the hyper-pronation and supination of the foot during loading and its relation to injuries or discomfort. The purpose of the present study was to investigate the possible differences in the subtalar joint in the midstance phase of running, between individuals with Pes Planus and Pes Cavus, after 5 min and 45 min of running. Thirty-four subjects, meeting the requirements for Pes Planus (30 feet) and Pes Cavus (35 feet), according to the criteria for Medial Longitudinal Arch-angle, were included in the study. The calcaneal vertical angle, representing the eversion/inversion of the subtalar joint, was measured using with two-dimensional digital analysis and Dartfish Software with the subjects running barefoot on a treadmill, before and after 45 min of outside running wearing shoes. Both individuals with Pes Cavus and Pes Planus showed a significant increase in the calcaneal eversion (P<0.05) after 45 min of running. Between the groups, there was a significantly greater eversion of the Pes Planus, on the right foot, after 45 min of running (P<0.05) compared to the Pes Cavus. The effect of fatigue evident in the present study suggests that further biomechanical research should be considered when exposing the foot to the repetitive nature of running, conditions most likely responsible for the overrepresented overuse injuries among runners.


An assessment of the so called point of reversibility of dementia syndrome in making an effective prognosis for continued use of medication.
An effort to share our many years of clinical experience. To predict the effectiveness of medication in advanced phases of dementia in the light of pharmaceutical economics and to find the most suitable alternative treatments. Use of 3 commonly available geriatric tests Mini-Mental State Examination (MMSE), Activity of Daily Living (ADL) and Instrumental Activity of Daily Living (IADL). Threshold values of these tests, after mathematical transformation to comparable values, enables calculation of the hypothetical Point of Reversibility Pr found on the range here called MEKO. Estimated values of SD can be used to choose the most effective medical treatment. Beyond the upper threshold of S(D), on the basis of the above mentioned method, continued medication is of dubious value.


Dabigatran Versus Rivaroxaban for Secondary Stroke Prevention in Patients with Atrial Fibrillation Rehabilitated in Skilled Nursing Facilities.
Thromboembolic and bleeding risk are elevated in older patients with atrial fibrillation and prior stroke. We compared dabigatran with rivaroxaban for secondary prevention in a national population after skilled nursing facility (SNF) discharge. Medicare fee-for-service beneficiaries aged ≥ 65 years with atrial fibrillation hospitalized for ischemic stroke (November 2011-October 2013) and subsequently admitted to an SNF were studied. Dabigatran (n = 332) and rivaroxaban users (n = 378) were compared in a retrospective, active comparator, new-user cohort. The index medication claim occurred within 120 days after hospital discharge and exposure continued until a 14-day treatment gap ('as treated'). The primary net clinical benefit outcome was the time to recurrent stroke, transient ischemic attack, intracranial hemorrhage, extracranial bleed, myocardial infarction, venous thromboembolism, or death. All-cause mortality was evaluated separately as a secondary outcome. Multivariable adjusted Cox models stratified by dosage estimated hazard ratios (aHR). Among those receiving low dosages, the crude composite event rate was 40.4/100 person-years among dabigatran users and 33.7/100 person-years among rivaroxaban users. The composite outcome [aHR 1.48; 95% confidence interval (CI) 0.87-2.51] and all-cause mortality (aHR 1.67; 95% CI 0.84-3.31) rates were higher among low-dose dabigatran users. For those receiving standard doses, the crude composite event rates were 19.5/100 person-years for dabigatran users and 37.1/100 person-years for rivaroxaban users. Although no difference in mortality was observed, the composite outcome rate was lower among standard-dose dabigatran users (aHR 0.65; 95% CI 0.36-1.15). In older adults treated with direct-acting oral anticoagulants after ischemic stroke, outcome rates varied considerably by drug and dosage.


[Dependent individuals classification based on the 1999 Disabilities, Impairments and Health Status Survey].
In order to move to a system in which formal medical-social care is a priority, in which the institutions play a greater role, it is advisable to analyze the different actual situations of those individuals who are dependent. The objective of this study consists of classifying the dependent Spanish population into different groups, each of their own distinguishing characteristics. The data from the Disabilities, Deficiencies and Health Status Survey (Spanish National Institute of Statistics, 1999) related to the non-institionalized population over 6 years of age. Groups are configured using multivariate analysis techniques in terms of the age, sex, daily living activity-related disabilities, the severity thereof and the number of hours of care per week. Nine statistically heterogeneous profiles were obtained. In the first three, with 341,262 individuals (24.5% of the total dependent population), the individuals in question were under 60 years of age. With the exception of one group, females were predominant (61% males), falling within the 13-36 age range. In the group least affected by lack of self-sufficiency (136,240 individuals), solely 26% of those comprising this group had problems getting around (maximum degree of severity in 7%), regarding care, 25% (maximum degree of severity in 10%) and only 32% need more than 15 hours of care per week. Most thereof (74%) are females within the 82-90 age range. The dependent Spanish population is revealed to be in different situations related to different categories in terms of age, sex, number and severity of the daily living activities affected. The different assessments of the severity related to said categories, employing both the Spanish National Institute of Statistics maximum severity criterion as well as another alternative criterion which implements the degree of severity of all of the daily living activities, not only the maximum, confirm the nine groups found to be different from one another.