A preliminary investigation of materialism and impulsiveness as predictors of technological addictions among young adults.
Background and aims The primary objective of the present research is to investigate the drivers of technological addiction in college students - heavy users of Information and Communication Technology (ICT). The study places cell phone and instant messaging addiction in the broader context of consumption pathologies, investigating the influence of materialism and impulsiveness on these two technologies. Clearly, cell phones serve more than just a utilitarian purpose. Cell phones are used in public and play a vital role in the lives of young adults. The accessibility of new technologies, like cell phones, which have the advantages of portability and an ever increasing array of functions, makes their over-use increasingly likely. Methods College undergraduates (N = 191) from two U.S. universities completed a paper and pencil survey instrument during class. The questionnaire took approximately 15-20 minutes to complete and contained scales that measured materialism, impulsiveness, and mobile phone and instant messaging addiction. Results Factor analysis supported the discriminant validity of Ehrenberg, Juckes, White and Walsh's (2008) Mobile Phone and Instant Messaging Addictive Tendencies Scale. The path model indicates that both materialism and impulsiveness impact the two addictive tendencies, and that materialism's direct impact on these addictions has a noticeably larger effect on cell phone use than instant messaging. Conclusions The present study finds that materialism and impulsiveness drive both a dependence on cell phones and instant messaging. As Griffiths (2012) rightly warns, however, researchers must be aware that one's addiction may not simply be to the cell phone, but to a particular activity or function of the cell phone. The emergence of multi-function smart phones requires that research must dig beneath the technology being used to the activities that draw the user to the particular technology.


Gene expression profiling of long-lived dwarf mice: longevity-associated genes and relationships with diet, gender and aging.
Long-lived strains of dwarf mice carry mutations that suppress growth hormone (GH) and insulin-like growth factor I (IGF-I) signaling. The downstream effects of these endocrine abnormalities, however, are not well understood and it is unclear how these processes interact with aging mechanisms. This study presents a comparative analysis of microarray experiments that have measured hepatic gene expression levels in long-lived strains carrying one of four mutations (Prop1(df/df), Pit1(dw/dw), Ghrhr(lit/lit), GHR-KO) and describes how the effects of these mutations relate to one another at the transcriptional level. Points of overlap with the effects of calorie restriction (CR), CR mimetic compounds, low fat diets, gender dimorphism and aging were also examined. All dwarf mutations had larger and more consistent effects on IGF-I expression than dietary treatments. In comparison to dwarf mutations, however, the transcriptional effects of CR (and some CR mimetics) overlapped more strongly with those of aging. Surprisingly, the Ghrhr(lit/lit) mutation had much larger effects on gene expression than the GHR-KO mutation, even though both mutations affect the same endocrine pathway. Several genes potentially regulated or co-regulated with the IGF-I transcript in liver tissue were identified, including a DNA repair gene (Snm1) that is upregulated in proportion to IGF-I inhibition. A total of 13 genes exhibiting parallel differential expression patterns among all four strains of long-lived dwarf mice were identified, in addition to 30 genes with matching differential expression patterns in multiple long-lived dwarf strains and under CR. Comparative analysis of microarray datasets can identify patterns and consistencies not discernable from any one dataset individually. This study implements new analytical approaches to provide a detailed comparison among the effects of life-extending mutations, dietary treatments, gender and aging. This comparison provides insight into a broad range of issues relevant to the study of mammalian aging. In this context, 43 longevity-associated genes are identified and individual genes with the highest level of support among all microarray experiments are highlighted. These results provide promising targets for future experimental investigation as well as potential clues for understanding the functional basis of lifespan extension in mammalian systems.


Stoichiometry of endothermy: shifting the quest from nitrogen to carbon.
For many animals, notably herbivores, plants are often an inadequate food source given the low content of protein and high content of C-rich material. This conception is mainly based on studies on ectotherms. The validity of this conception for endotherms is unclear given their much higher carbon requirements for maintenance energy metabolism than ectotherms. Applying stoichiometric principles, we hypothesized that endotherms can cope with diets with much higher (metabolizable) carbon to nitrogen ratios than ectotherms. Using empirical data on birds, eutherian mammals, marsupials and reptiles, we compiled and compared measurements and allometric equations for energy metabolism as well as nitrogen requirements. Our analysis supports our hypothesis that plants, and especially their leaves, are generally sufficiently rich in nitrogen to fulfil protein demands in endotherms, at least during maintenance conditions, but less so in ectotherms. This has important implications with respect to community functioning and the evolution of endothermy.


Validation of a brief Multicultural Cognitive Examination (MCE) for evaluation of dementia.
The aims of this study were to present the psychometric properties of a newly designed cognitive screening instrument, the Multicultural Cognitive Examination (MCE), and to compare it with the Rowland Universal Dementia Assessment Scale (RUDAS) in a multicultural population. The study was a Western European cross-sectional multicenter study. The MCE consists of four components evaluating separate cognitive functions and was constructed by adding measures of memory, verbal fluency, and visuospatial function to the RUDAS to create a scale with 0 to 100 points. A total of 66 patients with dementia and 123 cognitively intact participants were included across six memory clinics; 96 had minority ethnic background, and 93 had majority ethnic background. Moderate to large differences were present between patients with dementia and control participants on all MCE components. The MCE significantly improved diagnostic accuracy compared with using the RUDAS alone, with area under the curves of .918, .984, and .991 for the RUDAS, MCE composite, and demographically corrected composite scores, respectively. Diagnostic accuracy of the MCE did not significantly differ between minority and majority ethnic groups. Across MCE subcomponents, patients with Alzheimer's disease (AD) dementia performed significantly poorer on the memory component compared with those with non-AD dementia. The MCE is a brief cross-cultural cognitive screening instrument that expands evaluation of the cognitive functions covered by the RUDAS, does not require any specialized training, and may be useful for classification of mild dementia or dementia subtypes.


Multiple Kernel Learning for Visual Object Recognition: A Review.
Multiple kernel learning (MKL) is a principled approach for selecting and combining kernels for a given recognition task. A number of studies have shown that MKL is a useful tool for object recognition, where each image is represented by multiple sets of features and MKL is applied to combine different feature sets. We review the state-of-the-art for MKL, including different formulations and algorithms for solving the related optimization problems, with the focus on their applications to object recognition. One dilemma faced by practitioners interested in using MKL for object recognition is that different studies often provide conflicting results about the effectiveness and efficiency of MKL. To resolve this, we conduct extensive experiments on standard datasets to evaluate various approaches to MKL for object recognition. We argue that the seemingly contradictory conclusions offered by studies are due to different experimental setups. The conclusions of our study are: (i) given a sufficient number of training examples and feature/kernel types, MKL is more effective for object recognition than simple kernel combination (e.g., choosing the best performing kernel or average of kernels); and (ii) among the various approaches proposed for MKL, the sequential minimal optimization, semi-infinite programming, and level method based ones are computationally most efficient.


A histopathological exploration of the Madurella mycetomatis grain.
Although the Madurella mycetomatis grains seem to interfere with the host defense mechanisms and impede the antifungal drugs penetration, yet their histological features are not fully known and hence this study was set out to determine that. The study included 80 patients with confirmed M. mycetomatis eumycetoma. After informed written consent, surgical biopsies were obtained from the excised tissues during the patients' surgical treatment. All sections were stained with haematoxylin and eosin, Grocott's hexamine silver, Periodic Acid-Schiff's, Masson-Fontana, Perl's Prussian Blue, Von-kossa's, Formalin Inducing Fluorescence and Schmorl's stains. Modified bleaching technique was used. The concentrations of Zinc, Copper, Calcium, Iron, Lead, Cobalt and Nickel were determined by Atomic Absorption Spectrophotometer. The M. Mycetomatis grains appeared to consist of lipid, protein and melanin. The melanin was located on the hyphal wall as thick layers. The Zinc, Copper and Calcium concentrations in the grains were four, six, and sixteen folds higher than in normal tissue respectively, the other metals were found in the same concentrations as in normal tissue. In the grains, calcium was located in the melanin vicinity. From this study, it can be concluded that, the grains contain melanin, heavy metals, proteins, lipids and they contribute in the formation of the grain cement matrix. These elements seem to contribute in the organism pathogenicity and might impede the penetration of various anti-fungal agents.


A phase I clinical trial of Ad5.SSTR/TK.RGD, a novel infectivity-enhanced bicistronic adenovirus, in patients with recurrent gynecologic cancer.
Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and a somatostatin receptor (SSTR) that allows for noninvasive gene transfer imaging. The purpose of this study was to identify the maximum tolerated dose (MTD), toxicities, clinical efficacy, and biologic effects of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Eligible patients were treated intraperitoneally for 3 days with 1 × 10(9) to 1 × 10(12) vp/dose of Ad5.SSTR/TK.RGD followed by intravenous ganciclovir for 14 days. Toxicity and clinical efficacy were assessed using Common Toxicity Criteria (CTC) Adverse Events grading and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Imaging using In-111 pentetreotide was obtained before and after treatment. Tissue samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding, and antibody response. Twelve patients were treated in three cohorts. The most common vector-related clinical toxicities were grade I/II constitutional or pain symptoms, experienced most often in patients treated at the highest dose. MTD was not identified. Five patients showed stable disease; all others experienced progressive disease. One patient with stable disease experienced complete resolution of disease and normalization of CA125 on further follow-up. Imaging detected increased In-111 pentetreotide retention in patients treated at the highest dose. Ancillary studies showed presence of Ad5.SSTR/TK.RGD virus and HSV1-tk expression in ascites samples collected at various time points in most patients treated within the higher dose cohorts. This study shows the safety, potential efficacy, and possible gene transfer imaging capacity of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Further development of this novel gene therapeutic appears to be warranted.


Tissue microarray-based immunohistochemical study can significantly underestimate the expression of HER2 and progesterone receptor in ductal carcinoma in situ of the breast.
The accuracy of immunohistochemical (IHC) analysis on tissue microarray (TMA)-based studies largely depends on the uniformity of the staining pattern for a given antibody and minimal intratumor heterogeneity of a given tumor. Our study was designed to investigate the concordance of expression in TMA and whole sections of estrogen receptor (ER), progesterone receptor (PR) and HER2 using IHC analysis for ductal carcinoma in situ (DCIS) of the breast. Seventy-five consecutive cases of DCIS were retrieved, reviewed and used to construct the TMA. IHC analysis of the expression of ER, PR, and HER2 were performed on TMA and whole sections of the corresponding cases, and the results were compared. The specificity and sensitivity for TMA-based assays were 87.0, 75.9, 90.6 and 90.4%, and 76.1, 27.3 for ER, PR and HER2, respectively. The concordance and discordance were 89.3, 76.0 and 72.0%, and 6.7, 13.3 and 16.0% for ER, PR, HER2, respectively. The kappa values were 0.83, 0.89 and 0.42 for ER, PR and HER2, respectively. The non-concordance rates were inversely related to core number, with 46.67, 22.67 and 11.56% for one core, two cores, and three cores, respectively, per marker per case (p < 0.001), but not associated with tumor size. Our results showed that the intratumor heterogeneity and the number of cores have a great impact on the results of TMA-based studies. Increasing the number of tissue cores per case may help improve the accuracy and concordance with whole section results. Although TMA remains an effective tool for translational research, we should be cautious in our interpretation of these results.


Alpha-secretase activity of the disintegrin metalloprotease ADAM 10. Influences of domain structure.
Disintegrin metalloproteases from different organisms form the ADAM (a disintegrin and metalloprotease) family. All members display a common domain organization and possess four potential functions: proteolysis, cell adhesion, cell fusion, and cell signaling. Members of the ADAM family are responsible for the proteolytic cleavage of transmembrane proteins and release of their extracellular domain. The proteolytic process is referred to as ectodomain shedding, which is activated by phorbol esters and inhibited by hydroxamic acid-based inhibitors. We have shown that the disintegrin metalloprotease ADAM 10 has both constitutive and regulated alpha-secretase activity. Expression of a dominant negative mutant of ADAM 10 in HEK cells decreases the secretion of APPs alpha. In order to investigate the influence of distinct protein domains of ADAM 10 on alpha-secretase activity, several deletion mutants of ADAM 10 were constructed. Our findings demonstrate that the deletion of the disintegrin domain results in a mutant ADAM 10 with remaining alpha-secretase activity, whereas the deletion of the prodomain destroys the proteolytic activity of ADAM 10.


[Aconite in homeopathic relief of post-operative pain and agitation in children].
Despite the use of modern analgesic methods and an improved use of narcotics, the combination pain-agitation sometimes persists in the recovery-room. Aconit seems to be an appropriate homeopathic treatment in this case. To prescribe it, the following conditions must be combined: violence and suddeness of the stress bringing about intense and anguish. The study included 50 children with such symptoms; it was carried out double-blind, the children being given either placebo or Aconit. Aconit proved to be effective for children's postoperative agitation with 95% good results. It is usually stated in such studies that the placebo effect is high and may reach rates higher than 30%. Aconit is an amazing cure when well prescribed, as much for the speediness of its action as for its efficiency. This remedy has a place in the recovery-room and should be in every physician's emergency case. The fundamental research could specify how the remedy works and may be discover other molecules effective for stress.


Oral protein hydrolysate causes liver glycogen depletion in fasted rats pretreated with glucose.
Studies in rats indicated that the major physiologic stimulus for synthesis of liver glycogen is a rise in the portal glucose concentration after ingestion of a meal. Conversely, glycogen degradation in the liver is stimulated by a rise in portal glucagon concentration. In humans, ingestion of carbohydrate lowers the concentration of circulating glucagon, whereas protein stimulates an increase in peripheral glucagon concentration. Little is known about the effects of these nutrients on glucagon concentrations in the rat. Therefore, we studied the effects of oral protein administration to 24-h-fasted rats pretreated with glucose for 2 h to test the effect of two potent but potentially opposite signals for glycogen metabolism. An increase in liver glycogen concentration was observed in fasted rats given oral glucose, as expected. Removal of glucose by the liver could not account for the glycogen synthesized, indicating that most glycogen formed was derived from gluconeogenesis. In addition, the apparent intracellular and extracellular glucose concentrations were not in equilibrium. A small amount of glucose may have been taken up against a concentration gradient. The portal glucagon was not significantly decreased. Oral protein administration to the rats pretreated with glucose resulted in a rapid and dramatic decrease in liver glycogen concentration. This was associated with an increase in the portal glucagon concentration, no change in insulin concentration, a slight increase in liver cAMP concentration, an increase in the active form of phosphorylase, and a decrease in the active form of synthase. Glycogenolysis could account for the glucose released into the circulation from the liver after protein administration.


Genetic Characterisation of African Swine Fever Virus in Outbreaks in Ha Nam Province, Red River Delta Region of Vietnam, and Activity of Antimicrobial Products Against Virus Infection in Contaminated Feed.
African swine fever (ASF) was officially reported in Vietnam in February 2019 and spread across the whole country, affecting all 63 provinces and cities. In this study, ASF virus (ASFV) VN/Pig/HaNam/2019 (VN/Pig/HN/19) strain was isolated in primary porcine alveolar macrophage (PAM) cells from a sample originating from an outbreak farm in Vietnam's Red River Delta region. The isolate was characterised using the haemadsorption (HAD) test, real-time PCR, and sequencing. The activity of antimicrobial feed products was evaluated via a contaminated ASFV feed assay. Phylogenetic analysis of the viral p72 and EP402R genes placed VN/Pig/HN/19 in genotype II and serogroup 8 and related it closely to Eastern European and Chinese strains. Infectious titres of the virus propagated in primary PAMs were 106 HAD50/ml. Our study reports the activity against ASFV VN/Pig/HN/19 strain of antimicrobial Sal CURB RM E Liquid, F2 Dry and K2 Liquid. Our feed assay findings suggest that the antimicrobial RM E Liquid has a strong effect against ASFV replication. These results suggest that among the Sal CURB products, the antimicrobial RM E Liquid may have the most potential as a mitigant feed additive for ASFV infection. Therefore, further studies on the use of antimicrobial Sal CURB RM E Liquid in vivo are required. Our study demonstrates the threat of ASFV and emphasises the need to control and eradicate it in Vietnam by multiple measures.


Comparative Benefits and Harms of Basal Insulin Analogues for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.
Basal insulin analogues aim for protracted glycemic control with minimal adverse effects. To assess the comparative efficacy and safety of basal insulin analogues for adults with type 2 diabetes mellitus (T2DM). Several databases from inception to April 2018 without language restrictions, ClinicalTrials.gov to April 2018, references of reviews, and meeting abstract books. Randomized trials lasting at least 12 weeks that compared efficacy (change in hemoglobin A1c [HbA1c] level from baseline [primary outcome]; percentage of patients with HbA1c level <7% at end of study and change in body weight [secondary outcomes]) and safety (hypoglycemia) of basal insulin analogues. Two authors independently extracted data and assessed risk of bias for each outcome. All authors evaluated overall confidence in the evidence. Thirty-nine trials (26 195 patients) assessed 10 basal insulin analogues. Low- to very-low-quality evidence indicated that thrice-weekly degludec (Deg-3TW) was inferior to most other regimens for reducing HbA1c level, with mean differences ranging from 0.21% (vs. degludec, 100 U/mL [Deg-100]) to 0.32% (vs. glargine, 300 U/mL [Glar-300]). High- to moderate-quality evidence suggested that detemir had a favorable weight profile versus all comparators, and Glar-300 was associated with less weight gain than glargine, 100 U/mL (Glar-100); Deg-100; degludec, 200 U/mL (Deg-200); Deg-3TW; and LY2963016. Low- and very-low-quality evidence suggested that Deg-100, Deg-200, and Glar-300 were associated with lower incidence of nocturnal hypoglycemia than detemir, Glar-100, LY2963016, and neutral protamine lispro (NPL). Incidence of severe hypoglycemia did not differ among regimens, except NPL, which was associated with increased risk versus Deg-100, detemir, Glar-100, and Glar-300. Results are based mostly on indirect comparisons. Confidence in summary estimates is low or very low due to individual-study limitations, imprecision, or inconsistency. Low-quality evidence suggests that basal insulin analogues for T2DM do not substantially differ in their glucose-lowering effect. Low- and very-low-quality evidence suggests some regimens may be associated with lower risk for nocturnal hypoglycemia (Deg-100, Deg-200, and Glar-300) or less weight gain (detemir and Glar-300). None. (PROSPERO: CRD42016037055).


Investigation of the EVI antibody in parasitic diseases other than American trypanosomiasis. An anti-skeletal muscle antibody in leishmaniasis.
The specificity of a circulating antibody observed in American trypanosomiasis and reacting with endocardium, blood vessels, and the interstitium of striated muscle (EVI factor) was evaluated in the indirect fluorescent antibody test with 60 sera from patients with malaria, leishmaniasis, echinococcosis, amebiasis, African trypanosomiasis, toxoplasmosis, and trichinosis, collected from areas where Chagas' disease is not endemic. Two sera, 1 from a patient with Plasmodium falciparum malaria and 1 from a patient with a relapse pretreatment post kala-azar dermal leishmaniasis, were positive for the EVI factor. In the leishmaniasis group, 3 of 8 sera reacted with 0ovine, murine, and human skeletal muscle. In this reaction, which differs from the EVI test, the sarcolemma and the intracellular structures were stained.


Preoperative elective transjugular intrahepatic portosystemic shunt for cirrhotic patients undergoing abdominal surgery.
Despite improvements in the surgical techniques, anesthesia and intensive care, abdominal surgery in patients with cirrhosis remains a challenge. Transjugular intrahepatic portosystemic shunt (TIPS) has been used to manage complications of portal hypertension. Preoperative TIPS (prophylactic) can theoretically improve outcomes in this population. Seven original studies were identified with 24 patients who underwent prophylactic TIPS before abdominal surgery. No perioperative mortality or major abdominal bleeding attributable to portal hypertension was reported for this cohort. One patient had poor wound healing post surgery (4.2%), one had right heart failure (4.2%), and five developed hepatic encephalopathy (20.8%) post surgery. More evidence is needed to optimize the timing of surgery post TIPS and the selection of an appropriate stent size to further decrease the associated morbidity. Overall, the decision for prophylactic TIPS placement for cirrhotic patients undergoing abdominal surgery needs individualization to allow its safe use with concomitant improvement in perioperative morbidity.


Expansion of the global RNA virome reveals diverse clades of bacteriophages.
High-throughput RNA sequencing offers broad opportunities to explore the Earth RNA virome. Mining 5,150 diverse metatranscriptomes uncovered >2.5 million RNA virus contigs. Analysis of >330,000 RNA-dependent RNA polymerases (RdRPs) shows that this expansion corresponds to a 5-fold increase of the known RNA virus diversity. Gene content analysis revealed multiple protein domains previously not found in RNA viruses and implicated in virus-host interactions. Extended RdRP phylogeny supports the monophyly of the five established phyla and reveals two putative additional bacteriophage phyla and numerous putative additional classes and orders. The dramatically expanded phylum Lenarviricota, consisting of bacterial and related eukaryotic viruses, now accounts for a third of the RNA virome. Identification of CRISPR spacer matches and bacteriolytic proteins suggests that subsets of picobirnaviruses and partitiviruses, previously associated with eukaryotes, infect prokaryotic hosts.


Safety and efficacy of co-careldopa as an add-on therapy to occupational and physical therapy in patients after stroke (DARS): a randomised, double-blind, placebo-controlled trial.
Dopamine is a key modulator of striatal function and learning and might improve motor recovery after stroke. Previous small trials of dopamine agonists after stroke provide equivocal evidence of effectiveness on improving motor recovery. We aimed to assess the safety and efficacy of co-careldopa plus routine occupational and physical therapy during early rehabilitation after stroke. This double-blind, multicentre, randomised controlled trial of co-careldopa versus placebo in addition to routine NHS occupational and physical therapy was done at 51 UK NHS acute inpatient stroke rehabilitation services. We recruited patients with new or recurrent clinically diagnosed ischaemic or haemorrhagic (excluding subarachnoid haemorrhage) stroke 5-42 days before randomisation, who were unable to walk 10 m or more, had a score of less than 7 points on the Rivermead Mobility Index, were expected to need rehabilitation, and were able to access rehabilitation after discharge from hospital. Participants were assigned (1:1) using stratified random blocks to receive 6 weeks of oral co-careldopa or matched placebo in addition to routine NHS physiotherapy and occupational therapy. The initial two doses of co-careldopa were 62·5 mg (50 mg of levodopa and 12·5 mg of carbidopa) and the remaining doses were 125 mg (100 mg of levodopa and 25 mg of carbidopa). Participants were required to take a single oral tablet 45-60 min before physiotherapy or occupational therapy session. The primary outcome was ability to walk independently, defined as a Rivermead Mobility Index score of 7 or more, at 8 weeks. Primary and safety analyses were done in the intention-to-treat population. The trial is registered on the ISRCTN registry, number ISRCTN99643613. Between May 30, 2011, and March 28, 2014, of 1574 patients found eligible, 593 (mean age 68·5 years) were randomly assigned to either the co-careldopa group (n=308) or to the placebo group (n=285), on an average 18 days after stroke onset. Primary outcome data were available for all 593 patients. We found no evidence that the ability to walk independently improved with co-careldopa (125 [41%] of 308 patients) compared with placebo (127 [45%] of 285 patients; odds ratio 0·78 [95% CI 0·53-1·15]) at 8 weeks. Mortality at 12 months did not differ between the two groups (22 [7%] vs 17 [6%]). Serious adverse events were largely similar between groups. Vomiting during therapy sessions, after taking the study drug, was the most frequent adverse event and was more frequent in the co-careldopa group than the placebo group (19 [6·2%] vs 9 [3·2%]). Co-careldopa in addition to routine occupational and physical therapy does not seem to improve walking after stroke. Further research might identify subgroups of patients with stroke who could benefit from dopaminergic therapy at different doses or times after stroke with more intensive motor therapy. Medical Research Council.


No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18.
To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). Post hoc analysis of a randomized trial. White AREDS2 participants. AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene-supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction. The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10-5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).


Ecosystem resilience and threshold response in the Galápagos coastal zone.
The Intergovernmental Panel on Climate Change (IPCC) provides a conservative estimate on rates of sea-level rise of 3.8 mm yr(-1) at the end of the 21(st) century, which may have a detrimental effect on ecologically important mangrove ecosystems. Understanding factors influencing the long-term resilience of these communities is critical but poorly understood. We investigate ecological resilience in a coastal mangrove community from the Galápagos Islands over the last 2700 years using three research questions: What are the 'fast and slow' processes operating in the coastal zone? Is there evidence for a threshold response? How can the past inform us about the resilience of the modern system? Palaeoecological methods (AMS radiocarbon dating, stable carbon isotopes (δ(13)C)) were used to reconstruct sedimentation rates and ecological change over the past 2,700 years at Diablas lagoon, Isabela, Galápagos. Bulk geochemical analysis was also used to determine local environmental changes, and salinity was reconstructed using a diatom transfer function. Changes in relative sea level (RSL) were estimated using a glacio-isostatic adjustment model. Non-linear behaviour was observed in the Diablas mangrove ecosystem as it responded to increased salinities following exposure to tidal inundations. A negative feedback was observed which enabled the mangrove canopy to accrete vertically, but disturbances may have opened up the canopy and contributed to an erosion of resilience over time. A combination of drier climatic conditions and a slight fall in RSL then resulted in a threshold response, from a mangrove community to a microbial mat. Palaeoecological records can provide important information on the nature of non-linear behaviour by identifying thresholds within ecological systems, and in outlining responses to 'fast' and 'slow' environmental change between alternative stable states. This study highlights the need to incorporate a long-term ecological perspective when designing strategies for maximizing coastal resilience.


Point of injury tourniquet application during Operation Protective Edge-What do we learn?
Hemorrhage is a leading cause of preventable death on the battlefield. Timely tourniquet application to massively bleeding extremity wounds is critical for casualty survival albeit with reported adverse effects to extremity integrity. The aim of this study was to describe the immediate- and short-term outcomes of point of injury (POI) tourniquet applications during "Operation Protective Edge" (OPE). A case series study regarding tourniquet application at the POI during OPE was collected. The data gathered included reports by medical providers at the POI, aerial and land evacuation vehicles, and receiving hospitals. Variables collected included, the number of tourniquet applications, caregiver level, tourniquet type, limb characters, tourniquet effectiveness, in-hospital procedures, complications, and short-term limb outcome. During OPE, the Israeli Defense Forces Medical Corps treated 704 casualties. Of these, 90 casualties were treated with 119 tourniquets of which 79 survived. Penetrating trauma was the mechanism of injury in 97.8% (88 of 90) of the casualties. Injuries sustained from improvised explosive devices and shrapnel were related to the use of more than one tourniquet per casualty and per limb (p = 0.034). The success rate of the first tourniquet was reported to be 70% (84 of 119), regardless of caregiver level (p = 0.56), tourniquet type (p = 0.16), or limb characters (p = 0.48). Twenty-seven (25.7%) of 105 of the tourniquets were converted to direct pressure dressings enroute to receiving hospitals two of the conversions failed and thus a new tourniquet was applied. Fasciotomy was performed on eight casualties (a single limb in each). Vascular injury was presumed to be the indication for fasciotomy in three of these cases, in the other five limbs (6%, 5 of 85), no vascular involvement was discovered during surgery, and the fasciotomy is suspected as tourniquet related. 7%) 6 of 85) suffered from neurological sequela that could not be explained by their primary injury. Total complication rate was 11.7% (10 of 85) (one patient had both fasciotomy and neural complication without vascular injury). Tourniquet use on the battlefield is a simple method of eliminating preventable death, we believe that clinical practice guidelines should promote liberal use of tourniquets by trained combatants and medical personnel with abilities to convert to direct pressure hemorrhage control when possible since an unjustified tourniquet application risks low rates minor morbidity, whereas a justifiable tourniquet not applied may be lethal. Epidemiologic study, level III; Therapeutic study, level IV.


Undergraduate nursing students' compatibility with the nursing profession.
The high rate of attrition among nursing students has caused some nursing leaders to think about the necessity of considering students' personality during the process of admission into nursing schools. Due to the lack of studies on Iranian nursing students' personality traits, this study was designed to assess freshmen nursing students' personality characteristics and their compatibility with the demands of the nursing profession. A descriptive study was conducted at Tehran and kashan medical universities and one of the branches of Azad University. Convenience sampling was used and 52 freshmen nursing students were assessed using Holland's Vocational Interests Inventory. From the total participants 63.5% were females and 36.5% were males. Based on the Holland's Vocational Interests Inventory 44% did not have appropriate personality characteristics for the nursing profession. 77% of the nursing students participating in the study reported that they lacked information about nursing. It seems that personality tests can help to select the best students for nursing schools from those who show good academic capabilities. This would decrease the rate of attrition and could improve the quality of care.


Sex- and Gamete-Specific Patterns of X Chromosome Segregation in a Trioecious Nematode.
Three key steps in meiosis allow diploid organisms to produce haploid gametes: (1) homologous chromosomes (homologs) pair and undergo crossovers; (2) homologs segregate to opposite poles; and (3) sister chromatids segregate to opposite poles. The XX/XO sex determination system found in many nematodes [1] facilitates the study of meiosis because variation is easily recognized [2-4]. Here we show that meiotic segregation of X chromosomes in the trioecious nematode Auanema rhodensis [5] varies according to sex (hermaphrodite, female, or male) and type of gametogenesis (oogenesis or spermatogenesis). In this species, XO males exclusively produce X-bearing sperm [6, 7]. The unpaired X precociously separates into sister chromatids, which co-segregate with the autosome set to generate a functional haplo-X sperm. The other set of autosomes is discarded into a residual body. Here we explore the X chromosome behavior in female and hermaphrodite meioses. Whereas X chromosomes segregate following the canonical pattern during XX female oogenesis to yield haplo-X oocytes, during XX hermaphrodite oogenesis they segregate to the first polar body to yield nullo-X oocytes. Thus, crosses between XX hermaphrodites and males yield exclusively male progeny. During hermaphrodite spermatogenesis, the sister chromatids of the X chromosomes separate during meiosis I, and homologous X chromatids segregate to the functional sperm to create diplo-X sperm. Given these intra-species, intra-individual, and intra-gametogenesis variations in the meiotic program, A. rhodensis is an ideal model for studying the plasticity of meiosis and how it can be modulated.


Reductions in plasma prolactin during acute erythropoietin administration.
The presence of erythropoietin (EPO) and its receptors in several central nervous system regions indicates additional functions beside its hematopoietic role. Preclinical data suggest that it may slow down the process of neuronal loss, and that EPO may cause dopamine release, and thus influence hormone release, especially prolactin. This possibility has not yet been studied in humans. During a clinical trial on possible protective effects in patients with amyotrophic lateral sclerosis (ALS), we studied the acute effects of EPO administration on prolactin, the release of which is under tonic inhibition of hypothalamic-pituitary dopaminergic activity. Prolactin as well as EPO levels were estimated in blood samples taken every 30 min over 2 hours after administration of 3000 IU EPO i.v. in seven male and four female patients with ALS. The baseline PRL levels of the 11 patients were all within normal range (4.5-10.5 ng/ml). EPO administration caused a significant reduction in prolactin levels, maximal at 60 min after administration. Reductions in PRL were not related to EPO dose (IU per kg body weight), or to duration of illness. The findings indicate that EPO promotes dopamine release in humans, and is consistent with preclinical data showing that EPO releases dopamine from rat striatal slices. Previous reports showed that dopaminergic neurons express EPO receptors, which exert a facilitating action on dopamine release, and the present data indicate that this may hold true in humans.


The mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus).
We report the first two complete mitochondrial genome sequences of the thylacine (Thylacinus cynocephalus), or so-called Tasmanian tiger, extinct since 1936. The thylacine's phylogenetic position within australidelphian marsupials has long been debated, and here we provide strong support for the thylacine's basal position in Dasyuromorphia, aided by mitochondrial genome sequence that we generated from the extant numbat (Myrmecobius fasciatus). Surprisingly, both of our thylacine sequences differ by 11%-15% from putative thylacine mitochondrial genes in GenBank, with one of our samples originating from a direct offspring of the previously sequenced individual. Our data sample each mitochondrial nucleotide an average of 50 times, thereby providing the first high-fidelity reference sequence for thylacine population genetics. Our two sequences differ in only five nucleotides out of 15,452, hinting at a very low genetic diversity shortly before extinction. Despite the samples' heavy contamination with bacterial and human DNA and their temperate storage history, we estimate that as much as one-third of the total DNA in each sample is from the thylacine. The microbial content of the two thylacine samples was subjected to metagenomic analysis, and showed striking differences between a wild-captured individual and a born-in-captivity one. This study therefore adds to the growing evidence that extensive sequencing of museum collections is both feasible and desirable, and can yield complete genomes.


The effects of untreated bednets on malaria infection and morbidity on the Kenyan coast.
A study was conducted in order to determine whether children that slept under untreated bednets were protected against both malaria infection and clinical disease compared with children not sleeping under bednets. The study was conducted in Kilifi District, Kenya, during the malaria season (June-August, 2000) and involved 416 children aged < or = 10 years. Data collected from a cross-sectional survey showed evidence of protection against malaria infection among children sleeping under untreated bednets in good condition compared with those not using nets (adjusted odds ratio [AOR] = 0.4, 95% CI 0.22-0.72, P = 0.002). There was no evidence of a protective effect against infection when comparing those that used untreated bednets that were worn and those not using nets (AOR = 0.75, 95% CI 0.34-1.63, P = 0.47). When these same children were followed-up during the malaria season, there was evidence of a lower rate of clinical malaria among those that used untreated nets in good condition (adjusted incidence rate ratio = 0.65, 95% CI 0.45-0.94, P = 0.022), while the rate of clinical malaria among those that used untreated bednets that were worn was similar to that of those that did not use bednets. In the face of persistent failure of communities to take up net retreatment, there is hope that untreated nets will offer some protection against malaria infection and disease compared with not using nets at all.


Real-world palbociclib dosing patterns and implications for drug costs in the treatment of HR+/HER2- metastatic breast cancer.
This study described real-world palbociclib dosing patterns and associated impacts on treatment costs for HR+/HER2- metastatic breast cancer (mBC) in the US. Postmenopausal women with HR+/HER2- mBC who initiated palbociclib-based therapy (initiation date = index date) between 02/03/2015 (palbociclib approval) and 02/29/2016, and continuous quarterly activity 1 year before and 6 months after the index date, were identified in the Symphony Health Solutions database. Rates of 1) dose reduction (≥25 mg dose decrease/daily), and 2) reduction or interruption (>60 day gap in continuous drug supply) were assessed using Kaplan-Meier analyses. Drug wastage cost was estimated based on overlapping days between two prescription fills: the last original dose fill and the first reduced dose fill. 1,242 patients initiated palbociclib-based therapy (mean age = 62.7 years, median follow-up = 8.7 months). During the 12-month post-index period, across the first four lines, dose reduction rates were 31.9-33.7% and dose reduction/interruption rates were 63.5-80.9%. A total of 411 (33.1%) patients changed dose, among whom 128 (31.1%) experienced prescription fill overlap (average = 11.1 days). Mean potential drug wastage cost among patients with fill overlap was $5,471. Most patients receiving palbociclib experienced dose reduction or interruption early in treatment; the associated drug wastage may lead to considerable costs.


Estrogenic Endocrine Disrupting Chemicals Influencing NRF1 Regulated Gene Networks in the Development of Complex Human Brain Diseases.
During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese. Also we discuss the brain health effects associated from exposure to EEDs including the promotion of neurodegeneration, protection against neurodegeneration, and involvement in various neurological deficits; changes in rearing behavior, locomotion, anxiety, learning difficulties, memory issues, and neuronal abnormalities. The effects of EEDs on the brain are varied during the entire life span and far-reaching with many different mechanisms. To understand endocrine disrupting chemicals mechanisms, we use bioinformatics, molecular, and epidemiologic approaches. Through those approaches, we learn how the effects of EEDs on the brain go beyond known mechanism to disrupt the circulatory and neural estrogen function and estrogen-mediated signaling. Effects on EEDs-modified estrogen and nuclear respiratory factor 1 (NRF1) signaling genes with exposure to natural estrogen, pharmacological estrogen-ethinyl estradiol, PCBs, phthalates, BPA, and metalloestrogens are presented here. Bioinformatics analysis of gene-EEDs interactions and brain disease associations identified hundreds of genes that were altered by exposure to estrogen, phthalate, PCBs, BPA or metalloestrogens. Many genes modified by EEDs are common targets of both 17 β-estradiol (E2) and NRF1. Some of these genes are involved with brain diseases, such as Alzheimer's Disease (AD), Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis, Autism Spectrum Disorder, and Brain Neoplasms. For example, the search of enriched pathways showed that top ten E2 interacting genes in AD-APOE, APP, ATP5A1, CALM1, CASP3, GSK3B, IL1B, MAPT, PSEN2 and TNF-underlie the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) AD pathway. With AD, the six E2-responsive genes are NRF1 target genes: APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1. These genes are also responsive to the following EEDs: ethinyl estradiol (APBB2, DPYSL2, EIF2S1, ENO1, MAPT, and PAXIP1), BPA (APBB2, EIF2S1, ENO1, MAPT, and PAXIP1), dibutyl phthalate (DPYSL2, EIF2S1, and ENO1), diethylhexyl phthalate (DPYSL2 and MAPT). To validate findings from Comparative Toxicogenomics Database (CTD) curated data, we used Bayesian network (BN) analysis on microarray data of AD patients. We observed that both gender and NRF1 were associated with AD. The female NRF1 gene network is completely different from male human AD patients. AD-associated NRF1 target genes-APLP1, APP, GRIN1, GRIN2B, MAPT, PSEN2, PEN2, and IDE-are also regulated by E2. NRF1 regulates targets genes with diverse functions, including cell growth, apoptosis/autophagy, mitochondrial biogenesis, genomic instability, neurogenesis, neuroplasticity, synaptogenesis, and senescence. By activating or repressing the genes involved in cell proliferation, growth suppression, DNA damage/repair, apoptosis/autophagy, angiogenesis, estrogen signaling, neurogenesis, synaptogenesis, and senescence, and inducing a wide range of DNA damage, genomic instability and DNA methylation and transcriptional repression, NRF1 may act as a major regulator of EEDs-induced brain health deficits. In summary, estrogenic endocrine disrupting chemicals-modified genes in brain health deficits are part of both estrogen and NRF1 signaling pathways. Our findings suggest that in addition to estrogen signaling, EEDs influencing NRF1 regulated communities of genes across genomic and epigenomic multiple networks may contribute in the development of complex chronic human brain health disorders.


Chromosomal replicases as asymmetric dimers: studies of subunit arrangement and functional consequences.
Studies of the DNA polymerase III holoenzyme of Escherichia coli support a model in which both the leading and lagging strand polymerases are held together in a complex with the replicative helicase and priming activities, allowing two identical alpha catalytic subunits to assume different functions on the two strands of the replication fork. Creation of distinct functions for each of the two polymerases within the holoenzyme depends on the asymmetric character of the entire complex. The asymmetry of the holoenzyme is created by the DnaX complex, a heptamer that includes tau and gamma products of the dnaX gene. tau and gamma perform unique functions in the DnaX complex, and the interaction between alpha and tau appears to dictate the catalytic subunit's role in the replicative reaction. This review considers the properties of the DnaX complex including both tau and gamma, with the goal of understanding the properties of the replicase and its function in vivo. Recent studies in eukaryotic and other prokaryotic systems suggest that an asymmetric dimeric replicase may be universal. The leading and lagging strand polymerases may be distinct in some systems. For example, Pol e and Pol delta may function as distinct leading and lagging strand polymerases in eukaryotes, and PolC and DnaE may function as distinct leading and lagging strand polymerases in low GC content Gram-positive bacteria.


IAPP aggregation and cellular toxicity are inhibited by 1,2,3,4,6-penta-O-galloyl-β-D-glucose.
The polyphenol, 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) has been found to exhibit a host of positive pharmacologic activities, including anti-cancer and anti-diabetic. Little is known about the mode of action of PGG in yielding these positive activities. We show here that PGG is a potent inhibitor of IAPP (islet amyloid polypeptide, amylin) aggregation. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the toxic effects of IAPP oligomeric intermediates. Equal molar ratios of PGG to IAPP substantially reduced the ability of IAPP to bind thioflavin T. Atomic force microscopy revealed that PGG prevented amyloid-based fiber formation under rigorous conditions conducive to forming IAPP aggregates. PGG was also found to protect PC12 rat cells from toxic IAPP. PGG was compared to the known amyloid inhibitors (and structural relatives); tannic acid and gallic acid. In every test, PGG was far superior to tannic and gallic acids at inhibiting amyloid aggregation. These results indicate that PGG is a potent inhibitor of IAPP amyloid aggregation and a potential lead molecule for development of an amyloid inhibiting therapeutic.


Trends of mortality attributable to child and maternal undernutrition, overweight/obesity and dietary risk factors of non-communicable diseases in sub-Saharan Africa, 1990-2015: findings from the Global Burden of Disease Study 2015.
To assess trends of mortality attributable to child and maternal undernutrition (CMU), overweight/obesity and dietary risks of non-communicable diseases (NCD) in sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD) Study 2015. For each risk factor, a systematic review of data was used to compute the exposure level and the effect size. A Bayesian hierarchical meta-regression analysis was used to estimate the exposure level of the risk factors by age, sex, geography and year. The burden of all-cause mortality attributable to CMU, fourteen dietary risk factors (eight diets, five nutrients and fibre intake) and overweight/obesity was estimated. Sub-Saharan Africa.ParticipantsAll age groups and both sexes. In 2015, CMU, overweight/obesity and dietary risks of NCD accounted for 826204 (95 % uncertainty interval (UI) 737346, 923789), 266768 (95 % UI 189051, 353096) and 558578 (95 % UI 453433, 680197) deaths, respectively, representing 10·3 % (95 % UI 9·1, 11·6 %), 3·3 % (95 % UI 2·4, 4·4 %) and 7·0 % (95 % UI 5·8, 8·3 %) of all-cause mortality. While the age-standardized proportion of all-cause mortality accounted for by CMU decreased by 55·2 % between 1990 and 2015 in SSA, it increased by 63·3 and 17·2 % for overweight/obesity and dietary risks of NCD, respectively. The increasing burden of diet- and obesity-related diseases and the reduction of mortality attributable to CMU indicate that SSA is undergoing a rapid nutritional transition. To tackle the impact in SSA, interventions and international development agendas should also target dietary risks associated with NCD and overweight/obesity.


Acoustic startle evokes bilaterally synchronous oscillatory EMG activity in the healthy human.
Despite animal evidence that the reticulospinal system is of major importance to movement, this motor pathway has remained relatively inaccessible to experimentation in the human. Consequently, little is known about its function in health and disease. Here, we use the acoustic startle response to demonstrate that one type of reticulospinal activity in the human is associated with a characteristic pattern of bilateral synchronization between motor units. Surface electromyography (EMG) was recorded from upper limb muscles in 15 healthy subjects during the reflex startle to unexpected acoustic stimulation, voluntary movements mimicking the startle and during sustained voluntary tonic contraction. Frequency analysis demonstrated autospectral peaks at approximately 14 Hz in deltoid and biceps muscles only during the startle reflex. Similarly, coherence spectra of the EMG recorded between homologous proximal upper limb muscles demonstrated a peak centered approximately 12-16 Hz during reflex startles. Coherence in the 10- to 20-Hz band was significantly greater in the startle reflex than during voluntary sham startles or voluntary tonic contraction for deltoid, but not first dorsal interosseous, muscles. The coherence at 10-20 Hz between EMGs from homologous muscles represents a potential surrogate measure of reticulospinal activity that may be useful in determining the contribution of the reticulospinal system to different types of movement in health and disease.


Do plans and execution agree in a humanitarian medical mission?
There is a significant need for orthopaedic care in developing countries. For the past 10 years, the United States Army has supported annual orthopaedic hand surgery humanitarian missions to Honduras. The goal of this article is to compare the premission planning to the realities of mission execution to provide a template for future missions. Premission planning began 1 year before the mission. Based on previous missions, supplies were brought for 50 surgical cases. The mission began with 1 preoperative clinic day followed by 8 operative days and 1 postoperative clinic day. Of the 99 prescreened patients, 65 were indicated for surgery. A total of 58 surgeries were performed using innovative methods to stretch available supplies. A multidisciplinary and multination concerted effort is required for a successful humanitarian medical mission. A premission plan is critical prior to arrival and a contingency plan must be in place for missing mission-critical items.


Roles of glutamine synthetase inhibition in epilepsy.
Glutamine synthetase (GS, E.C. 220.127.116.11) is a ubiquitous and highly compartmentalized enzyme that is critically involved in several metabolic pathways in the brain, including the glutamine-glutamate-GABA cycle and detoxification of ammonia. GS is normally localized to the cytoplasm of most astrocytes, with elevated concentrations of the enzyme being present in perivascular endfeet and in processes close to excitatory synapses. Interestingly, an increasing number of studies have indicated that the expression, distribution, or activity of brain GS is altered in several brain disorders, including Alzheimer's disease, schizophrenia, depression, suicidality, and mesial temporal lobe epilepsy (MTLE). Although the metabolic and functional sequelae of brain GS perturbations are not fully understood, it is likely that a deficiency in brain GS will have a significant biological impact due to the critical metabolic role of the enzyme. Furthermore, it is possible that restoration of GS in astrocytes lacking the enzyme could constitute a novel and highly specific therapy for these disorders. The goals of this review are to summarize key features of mammalian GS under normal conditions, and discuss the consequences of GS deficiency in brain disorders, specifically MTLE.


Challenges of ecological monitoring: estimating population abundance from sparse trap counts.
Ecological monitoring aims to provide estimates of pest species abundance-this information being then used for making decisions about means of control. For invertebrate species, population size estimates are often based on trap counts which provide the value of the population density at the traps' location. However, the use of traps in large numbers is problematic as it is costly and may also be disruptive to agricultural procedures. Therefore, the challenge is to obtain a reliable population size estimate from sparse spatial data. The approach we develop in this paper is based on the ideas of numerical integration on a coarse grid. We investigate several methods of numerical integration in order to understand how badly the lack of spatial data can affect the accuracy of results. We first test our approach on simulation data mimicking spatial population distributions of different complexity. We show that, rather counterintuitively, a robust estimate of the population size can be obtained from just a few traps, even when the population distribution has a highly complicated spatial structure. We obtain an estimate of the minimum number of traps required to calculate the population size with good accuracy. We then apply our approach to field data to confirm that the number of trap/sampling locations can be much fewer than has been used in many monitoring programmes. We also show that the accuracy of our approach is greater that that of the statistical method commonly used in field studies. Finally, we discuss the implications of our findings for ecological monitoring practice and show that the use of trap numbers 'smaller than minimum' may still be possible but it would result in a paradigm shift: the population size estimates should be treated probabilistically and the arising uncertainty may introduce additional risk in decision-making.


Effects of whole-body vibration on postural balance and proprioception in healthy young and elderly subjects: a randomized cross-over study.
The aim of this paper was to investigate the effects of the whole-body vibration (WBV) intervention on neuromuscular performances in both young and elderly healthy subjects, taking into consideration the recommendations of the international standard for such exposure. Two groups of healthy subjects (9 young and 18 elderly) received the intervention while standing on a side-alternating platform, during two exposure periods of 8 weeks each separated by a washout period of 8 weeks between those periods. The intervention (with or without exposure to vibration) was administered twice a week. Vibration was produced at 20 Hz with an unweighted acceleration of 11.2 m/s2 rms in the first 4 weeks, and 22.3 m/s2 rms, in the last 4 weeks. Blood pressure, heart rate, single leg stance time with closed eyes (SSCE), postural stability parameters and knee joint position sense were measured before and after intervention and were compared. In the young group, the post-intervention measurement values did not differ from the corresponding pre-intervention values. In the elderly group, SSCE at the right side significantly increased (P<0.014) after vibration intervention. The lateral sway (X-axis locus length) of postural stability parameter after WBV intervention tended to decrease in the elderly group (P=0.078). However, in both groups, pre- and post-intervention values of knee joint position sense were not significantly different. The used level of vibration showed some improvements in postural balance among the elderly. However, an effective level of vibration exposure should be decided for this purpose, considering the recommendations of the relevant standards.


Early goal-directed therapy in severe sepsis and septic shock: insights and comparisons to ProCESS, ProMISe, and ARISE.
Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.


Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life.
An increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma. Follow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge. Increased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO. Severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling.


Assessing and managing all aspects of migraine: migraine attacks, migraine-related functional impairment, common comorbidities, and quality of life.
Migraine can be characterized as a chronic disorder with episodic attacks and the potential for progression to chronic migraine. We conducted a PubMed literature search (January 1, 1970 through May 31, 2008) for studies on the impact of migraine, including disability, health-related quality of life (HRQoL), comorbidities, and instruments used by health care professionals to treat patients with migraine. Numerous studies have shown that migraine substantially impairs a person's functions during attacks and diminishes HRQoL during and between attacks. Despite its impact, migraine remains underestimated, underdiagnosed, and undertreated. Several tools are available to help physicians assess the impact of migraine on the daily activities and HRQoL of their patients, such as the 36-Item Short-Form Health Survey and the Headache Impact Test. Improving communication during the office visit through active listening, use of open-ended questions, and use of the "ask-tell-ask" strategy can also help in assessing migraine-related impairment. Together, these tools and communication techniques can lead to a more complete assessment of how migraine affects patients' lives and can aid in the development of the optimal treatment plan for each patient. Both pharmacotherapy (acute and preventive treatment strategies) and nonpharmacological therapies play important roles in the management of migraine.


[The Turkish Adult Risk Factor survey 2009: similar cardiovascular mortality in rural and urban areas].
We analyzed 2009 survey of the Turkish Adult Risk Factor (TARF) Study to assess the distribution of all-cause and cardiovascular mortality in urban and rural areas and sex-specific coronary mortality in the age-bracket of 45 to 74 years. The Marmara and Middle East regions have been surveyed every odd year in the TARF Study. In 2009, 1,655 participants were surveyed. Information on the mode of death was obtained from first-degree relatives and/or health personnel of local heath office; 960 participants underwent physical examination and ECG recording, and 572 subjects were evaluated on the basis of information obtained regarding health status. In the survey, 23 men and 20 women were ascertained to have died. Twenty-one deaths were attributed to coronary disease and four deaths to cerebrovascular events. Assessment of the entire cohort in the age bracket of 45-74 years after a 19-year follow-up disclosed a high coronary mortality with 7.5 per 1000 person-years in men and 3.9 in women. In a Cox regression analysis comprising 405 deaths (235 cardiovascular) and over 24,000 person-year follow-up, age-adjusted cardiovascular mortality was similar in rural and urban participants. All-cause mortality was higher in females living in urban areas than those living in rural areas (HR 1.41; 95% CI 1.02-1.96). Cardiovascular mortality both in absolute terms and as a share of overall mortality persists to be high among Turkish adults, with similar rates in urban and rural areas. Age-adjusted all-cause mortality rate is higher among urban versus rural women.


Mitotic chromosome size scaling in Xenopus.
As rapid divisions without growth generate progressively smaller cells within an embryo, mitotic chromosomes must also decrease in size to permit their proper segregation, but this scaling phenomenon is poorly understood. We demonstrated previously that nuclear and spindle size scale between egg extracts of the related frog species Xenopus tropicalis and Xenopus laevis, but show here that dimensions of isolated mitotic sperm chromosomes do not differ. This is consistent with the hypothesis that chromosome scaling does not occur in early embryonic development when cell and spindles sizes are large and anaphase B segregates chromosomes long distances. To recapitulate chromosome scaling during development, we combined nuclei isolated from different stage Xenopus laevis embryos with metaphase-arrested egg extracts. Mitotic chromosomes derived from nuclei of cleaving embryos through the blastula stage were similar in size to replicated sperm chromosomes, but decreased in area approximately 50% by the neurula stage, reproducing the trend in size changes observed in fixed embryos. Allowing G2 nuclei to swell in interphase prior to mitotic condensation did not increase mitotic chromosome size, but progression through a full cell cycle in egg extract did, suggesting that epigenetic mechanisms determining chromosome size can be altered during DNA replication. Comparison of different sized mitotic chromosomes assembled in vitro provides a tractable system to elucidate underlying molecular mechanisms.


Production diversification, dietary diversity and consumption seasonality: panel data evidence from Nigeria.
Despite some improvements towards reducing hunger, malnutrition remains to be a crucial challenge in the developing world. The objective of this paper is to analyze the interplay between production diversity and dietary diversity across different seasons in rural Nigeria. The paper also investigates the relationship across different income quantiles. The study uses the Living Standards Measurement Study - Integrated Surveys on Agriculture (LSMS-ISA) dataset of the World Bank. We use two rounds of survey data (2010 and 2012) from Nigeria. Data were collected in two visits: at post-planting (from September to November), and at post-harvesting (from February to April). We analyze the relationship between production diversity and dietary diversity using different panel data regression tools. In post-harvest season, an increase in farm production diversification is associated with an increase with dietary diversity. On the other hand, production diversification does not have a significant contribution to the dietary diversity at post-planting. The analysis reveals that production diversification leads to better diet diversity for households in the second and third income quantiles. Seasonal variation on the contribution of production diversification on dietary diversity in rural Nigeria calls for the role of seasonally targeted policies. A higher propensity of households in the poorest quantile for malnutrition irrespective of the season suggests the need for targeted and continuous public health and nutrition interventions.


Personal and ethnic identity in Swedish adolescents and emerging adults.
The chapter describes empirical evidence about identity development in Swedish adolescents and emerging adults and highlights cultural and contextual influences that may be specific to coming of age in Sweden. Broad trends in identity options are evident in the lives of many youth living in Sweden. Although research on identity and diversity is in its infancy in Sweden, due at least in part to its tradition of longitudinal research, its contribution to understanding advances in adolescent-parent and peer relations, and its contributions to developmental interactionist metatheories of human development, the country has the potential to forge a new generation of identity research that takes into account the ongoing process of person-environment interactions.


Genoprotective Capacity of Alternatively Cultivated Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), Basidiocarps.
Ganoderma lucidum is traditionally used in Eastern medicine to preserve vitality, promote longevity, and treat disease. It possesses immunomodulatory, antitumor, antimicrobial, and antiaging activities, among others, but one of the most important is its antioxidant property, which is the basis for other effects, because free radicals trigger many diseases. The substrate commonly used for commercial cultivation of G. lucidum is not environmentally friendly nor economically justified, so there is a need to find new alternative substrates. The aim of this study was to analyze the effect of substrate composition on the bioactivity of G. lucidum basidiocarps. G. lucidum was cultivated on 2 different substrates: (1) a mixture of wheat straw, grapevine branches, and wheat bran, and (2) wheat straw. Commercial fruiting bodies, cultivated on oak sawdust, were used as the control. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, total phenols, and flavonoid content were determined spectrophotometrically to define the antioxidative potential of basidiocarp extracts. The comet test was performed to detect the degree of DNA damage in the cells that were exposed to G. lucidum extracts before and after the effect of oxidants. Higher antioxidative potential was observed for the extract of G. lucidum basidiocarps cultivated on wheat straw compared with that from the mixed substrate and especially with commercial ones. The alternatively cultivated basidiocarps also showed stronger antigenotoxic potential compared with commercial ones. The study showed that fruiting bodies produced on wheat straw, one of the most accessible and cheapest crop residues, are more potent antioxidant and antigenotoxic agents than commercially cultivated ones.


Mode-based microparticle conveyor belt in air-filled hollow-core photonic crystal fiber.
We show how microparticles can be moved over long distances and precisely positioned in a low-loss air-filled hollow-core photonic crystal fiber using a coherent superposition of two co-propagating spatial modes, balanced by a backward-propagating fundamental mode. This creates a series of trapping positions spaced by half the beat-length between the forward-propagating modes (typically a fraction of a millimeter). The system allows a trapped microparticle to be moved along the fiber by continuously tuning the relative phase between the two forward-propagating modes. This mode-based optical conveyor belt combines long-range transport of microparticles with a positional accuracy of 1 µm. The technique also has potential uses in waveguide-based optofluidic systems.


Hydrocephalus in 389 patients with aneurysm-associated subarachnoid hemorrhage.
Subarachnoid hemorrhage (SAH) often leads to hydrocephalus, which is commonly treated by placement of a ventriculoperitoneal (VP) shunt. There is controversy over which factors affect the need for such treatment. In this study, data were prospectively collected from 389 consecutive patients who presented with an aneurysm-associated SAH at a single center. External ventricular drainage placement was performed as part of the treatment for acute hydrocephalus, and VP shunts were placed in patients with chronic hydrocephalus. The data were retrospectively analyzed using two-sample t-tests, Fisher's exact test and logistic regression analysis. Overall, shunt dependency occurred in 91 of the 389 patients (23.4%). Using logistic regression analysis, two factors were found to be significantly associated with VP shunt placement: an initial Glasgow Coma Scale (GCS) score of 8-14 (8-14 versus 3-7, p = 0.016; 15 versus 3-7, p = 0.55); and aneurysm coiling (p = 0.017). Patients with an initial GCS score of 8-14 after aneurysm-associated SAH had a 2.5-fold higher risk of receiving a VP shunt than those with a GCS score of 3-7. Those with a GCS of 15 had a 50% lower risk of becoming shunt dependent than did the subgroup with a GCS score of 8-14. To clarify and strengthen these observations, prospective, randomized trials are needed.


Challenges, Solutions, and Quality Metrics of Personal Genome Assembly in Advancing Precision Medicine.
Even though each of us shares more than 99% of the DNA sequences in our genome, there are millions of sequence codes or structure in small regions that differ between individuals, giving us different characteristics of appearance or responsiveness to medical treatments. Currently, genetic variants in diseased tissues, such as tumors, are uncovered by exploring the differences between the reference genome and the sequences detected in the diseased tissue. However, the public reference genome was derived with the DNA from multiple individuals. As a result of this, the reference genome is incomplete and may misrepresent the sequence variants of the general population. The more reliable solution is to compare sequences of diseased tissue with its own genome sequence derived from tissue in a normal state. As the price to sequence the human genome has dropped dramatically to around $1000, it shows a promising future of documenting the personal genome for every individual. However, de novo assembly of individual genomes at an affordable cost is still challenging. Thus, till now, only a few human genomes have been fully assembled. In this review, we introduce the history of human genome sequencing and the evolution of sequencing platforms, from Sanger sequencing to emerging "third generation sequencing" technologies. We present the currently available de novo assembly and post-assembly software packages for human genome assembly and their requirements for computational infrastructures. We recommend that a combined hybrid assembly with long and short reads would be a promising way to generate good quality human genome assemblies and specify parameters for the quality assessment of assembly outcomes. We provide a perspective view of the benefit of using personal genomes as references and suggestions for obtaining a quality personal genome. Finally, we discuss the usage of the personal genome in aiding vaccine design and development, monitoring host immune-response, tailoring drug therapy and detecting tumors. We believe the precision medicine would largely benefit from bioinformatics solutions, particularly for personal genome assembly.


Coccidioidomycosis in the acquired immunodeficiency syndrome.
Of 27 patients with the acquired immunodeficiency syndrome (AIDS) in Tucson, Arizona, 7 had concurrent coccidioidomycosis. Early manifestations of infection in 6 patients included diffuse nodular pulmonary infiltrates and Coccidioides immitis in many extrathoracic sites. By comparison, a retrospective review of the cases of 300 patients hospitalized with coccidioidal infection identified only 13 patients without AIDS who had the same extent of infection, and only 3 of these patients had no immunosuppressing conditions. Antibodies for coccidioidal antigens at serum dilutions as high as 1:2048 were detected in 5 of the 7 patients with AIDS. Six had temporary responses to amphotericin B treatment, taken both alone and combined with ketoconazole, but all died within 14 months of their diagnosis of coccidioidomycosis. Because annual rates of coccidioidal infection in the Tucson area are 4% or less, the rate of 27% that we calculated, based on 7 patients having the infection during 26 years of risk for AIDS, suggests frequent reactivation of the infection or enhanced susceptibility to endemic exposure in persons with AIDS.


Incongruent patterns of local and global genome size evolution in cotton.
Genome sizes in plants vary over several orders of magnitude, reflecting a combination of differentially acting local and global forces such as biases in indel accumulation and transposable element proliferation or removal. To gain insight into the relative role of these and other forces, approximately 105 kb of contiguous sequence surrounding the cellulose synthase gene CesA1 was compared for the two coresident genomes (AT and DT) of the allopolyploid cotton species, Gossypium hirsutum. These two genomes differ approximately twofold in size, having diverged from a common ancestor approximately 5-10 million years ago (Mya) and been reunited in the same nucleus at the time of polyploid formation, approximately 1-2 Mya. Gene content, order, and spacing are largely conserved between the two genomes, although a few transposable elements and a single cpDNA fragment distinguish the two homoeologs. Sequence conservation is high in both intergenic and genic regions, with 14 conserved genes detected in both genomes yielding a density of 1 gene every 7.5 kb. In contrast to the twofold overall difference in DNA content, no disparity in size was observed for this 105-kb region, and 555 indels were detected that distinguish the two homoeologous BACs, approximately equally distributed between AT and DT in number and aggregate size. The data demonstrate that genome size evolution at this phylogenetic scale is not primarily caused by mechanisms that operate uniformly across different genomic regions and components; instead, the twofold overall difference in DNA content must reflect locally operating forces between gene islands or in largely gene-free regions.


Bronchiectasis Rheumatoid Overlap Syndrome Is an Independent Risk Factor for Mortality in Patients With Bronchiectasis: A Multicenter Cohort Study.
This study assessed if bronchiectasis (BR) and rheumatoid arthritis (RA), when manifesting as an overlap syndrome (BROS), were associated with worse outcomes than other BR etiologies applying the Bronchiectasis Severity Index (BSI). Data were collected from the BSI databases of 1,716 adult patients with BR across six centers: Edinburgh, United Kingdom (608 patients); Dundee, United Kingdom (n = 286); Leuven, Belgium (n = 253); Monza, Italy (n = 201); Galway, Ireland (n = 242); and Newcastle, United Kingdom (n = 126). Patients were categorized as having BROS (those with RA and BR without interstitial lung disease), idiopathic BR, bronchiectasis-COPD overlap syndrome (BCOS), and "other" BR etiologies. Mortality rates, hospitalization, and exacerbation frequency were recorded. A total of 147 patients with BROS (8.5% of the cohort) were identified. There was a statistically significant relationship between BROS and mortality, although this relationship was not associated with higher rates of BR exacerbations or BR-related hospitalizations. The mortality rate over a mean of 48 months was 9.3% for idiopathic BR, 8.6% in patients with other causes of BR, 18% for RA, and 28.5% for BCOS. Mortality was statistically higher in patients with BROS and BCOS compared with those with all other etiologies. The BSI scores were statistically but not clinically significantly higher in those with BROS compared with those with idiopathic BR (BSI mean, 7.7 vs 7.1, respectively; P < .05). Patients with BCOS had significantly higher BSI scores (mean, 10.4), Pseudomonas aeruginosa colonization rates (24%), and previous hospitalization rates (58%). Both the BROS and BCOS groups have an excess of mortality. The mechanisms for this finding may be complex, but these data emphasize that these subgroups require additional study to understand this excess mortality.


De novo designed proteins from a library of artificial sequences function in Escherichia coli and enable cell growth.
A central challenge of synthetic biology is to enable the growth of living systems using parts that are not derived from nature, but designed and synthesized in the laboratory. As an initial step toward achieving this goal, we probed the ability of a collection of >10(6) de novo designed proteins to provide biological functions necessary to sustain cell growth. Our collection of proteins was drawn from a combinatorial library of 102-residue sequences, designed by binary patterning of polar and nonpolar residues to fold into stable 4-helix bundles. We probed the capacity of proteins from this library to function in vivo by testing their abilities to rescue 27 different knockout strains of Escherichia coli, each deleted for a conditionally essential gene. Four different strains--ΔserB, ΔgltA, ΔilvA, and Δfes--were rescued by specific sequences from our library. Further experiments demonstrated that a strain simultaneously deleted for all four genes was rescued by co-expression of four novel sequences. Thus, cells deleted for ∼0.1% of the E. coli genome (and ∼1% of the genes required for growth under nutrient-poor conditions) can be sustained by sequences designed de novo.


Protein phosphatase 2A dephosphorylation of phosphoserine 112 plays the gatekeeper role for BAD-mediated apoptosis.
BAD, a proapoptotic molecule of the BCL2 family, is regulated by reversible phosphorylation. During survival, BAD is sequestered by 14-3-3 through serine 136 phosphorylation and is dissociated from BCL-X(L) through serine 155 phosphorylation. We report that phosphoserine 112 (pSer112) dephosphorylation functions as a gatekeeper for BAD-mediated apoptosis. During apoptosis, dephosphorylation of pSer112 preceded pSer136 dephosphorylation. Dephosphorylation of pSer112 accelerated dephosphorylation of pSer136, and inhibition of pSer112 dephosphorylation prevented pSer136 dephosphorylation, indicating that dephosphorylation of pSer112 is required for dephosphorylation of pSer136. Protein phosphatase 2A (PP2A) is the major pSer112 phosphatase. PP2A competed with 14-3-3 for BAD binding, and survival factor withdrawal enhanced PP2A association with BAD. Dephosphorylation of the critical residue, pSer136, could only be blocked by inhibition of all known subfamilies of serine/threonine phosphatases, suggesting that multiple phosphatases are involved in pSer136 dephosphorylation. Inhibition of PP2A rescued FL5.12 cells from apoptosis, demonstrating a physiologic role for PP2A-mediated pSer112 dephosphorylation. Thus, PP2A dephosphorylation of pSer112 is the key initiating event regulating the activation of BAD during interleukin-3 withdrawal-induced apoptosis.


Identification of the pharmacogenetic determinants of alfentanil metabolism: cytochrome P-450 3A4. An explanation of the variable elimination clearance.
There is considerable variability in the elimination clearance of the opioid analgesic alfentanil. It has been shown previously that alfentanil clearance is independent of the polymorphic debrisoquine hydroxylase (P-450 2D6), and it is therefore of interest to identify the human cytochrome P-450 enzymes involved in noralfentanil formation, the primary reaction involved in the oxidative N-dealkylation at the piperidine nitrogen. Purified human P-450 3A4 showed appreciable catalytic activity, and yeast recombinant P-450 3A4 also showed alfentanil oxidation activity. When microsomes prepared from different human liver samples were compared, noralfentanil formation activity was well correlated (r = 0.95,P less than 0.005) with nifedipine oxidation (a P-450 3A4 marker) but not with markers of other P-450s, including phenacetin O-deethylation (P-450 1A2), chlorzoxazone 6-hydroxylation (P-450 2E1), and (S)-mephenytoin 4'-hydroxylation (a P-450 2C enzyme). Using antibodies that recognize specific human P-450 enzymes (immunoinhibition techniques), it was possible to demonstrate that anti-P-450 3A4 nearly completely inhibited alfentanil oxidation activity in the human liver microsomes, but no other antibodies showed a measurable inhibitory effect. Selective chemical inhibitors of P-450 3A4, gestodene and troleandomycin, inhibited as much as 90% of the microsomal noralfentanil formation activity, but other chemical inhibitors did not show a detectable inhibitory effect. 7,8-Benzoflavone inhibited as much as 90% of the alfentanil oxidation activity of the microsomal or reconstituted P-450 3A4 system. This work indicates that P-450 3A4 contributes significantly to human liver microsomal alfentanil oxidation, whereas P-450 2D6 does not contribute.(ABSTRACT TRUNCATED AT 250 WORDS)


Structural characterization and promoter analysis of human potassium channel Kv8.1 (KCNV1) gene.
The voltage-gated K(+) channel (Kv) family comprises four subfamilies: Kv1, Kv2, Kv3 and Kv4. Kv6, Kv7, Kv8 and Kv9 subfamilies have also recently been reported. The gene for Kv8.1 (KCNV1) maps onto chromosome 8q23.3, a locus for benign adult familial myoclonic epilepsy. Despite sequence identity with other K(+) channel genes, KCNV1 does not display K(+) channel activity when expressed in Xenopus oocytes, instead inhibiting activity of Kv2 and Kv3 channels. The present study investigated the molecular structure of KCNV1. In silico analysis detected a new 5' noncoding exon, which extended the reported cDNA sequence to approximately 600 bp. A promoter motif was found only in the upstream region of the newly detected exon 1. To determine the transcriptional mechanism of KCNV1, we generated a series of deletion mutants and random mutants, and examined promoter activities using the luciferase system. Three Sp1 motifs were found to be active in the core promoter sequence, spanning from nt -1350 to -911 (A of the ATG initiation codon was counted as +1). At least two additional sequences were detected as essential elements for promoter activity. A possible alternative 3' end was also detected at 280 bp downstream from the reported 3' end. These results provide useful information in developing KCNV1 screening for epileptic disease.


Generation of adrenergic and cholinergic potentials in sympathetic ganglion cells.
Norepinephrine elicited a hyperpolarizing response, and acetylcholine (during nicotinic blockade) elicited a depolarizing one. Both responses showed no increase in membrane conductance. The norepinephrine response was suppressed by initial depolarization; the acetylcholine response (frog cells); by hyperpolarization. These neurotransmitters apparently can activate electrogenic mechanisms which do not involve movement of ions down their electrochemical gradients.


Implementing and revitalizing the Baby-Friendly Hospital Initiative.
The Baby-Friendly Hospital Initiative (BFHI) was launched in the 1990s by the World Health Organization (WHO) and UNICEF as a global effort with hospitals, health services, and parents to ensure babies are breastfed for the best start in life. It is one of the Operational Targets of the Global Strategy for Infant and Young Child Feeding endorsed in 2002 by the Fifty-Fifth World Health Assembly and the UNICEF Executive Board. After about 18 years, great progress has been made, and most countries have breastfeeding authorities or BFHI coordinating groups. The BFHI has led to increased rates of exclusive breastfeeding, which are reflected in improved health and survival. Based on this progress, the Initiative was streamlined according to the experience of the countries and materials were revised. The new package consolidated all WHO and UNICEF materials into one package, reflected new research and experience, revisited the criteria used for the BFHI in light of HIV/ AIDS, reinforced the International Code of Marketing of Breast-Milk Substitutes, provided modules for mother-friendly care, and gave more guidance for monitoring and reassessment. WHO and partners will continue to give support to BFHI implementation as one essential effort contributing to achievement of the Millennium Development Goals.


Non-host volatile blend optimization for forest protection against the European spruce bark beetle, Ips typographus.
Conifer feeding bark beetles (Coleoptera, Curculionidae, Scolytinae) pose a serious economic threat to forest production. Volatiles released by non-host angiosperm plants (so called non-host volatiles, NHV) have been shown to reduce the risk of attack by many bark beetle species, including the European spruce bark beetle, Ips typographus. However, the most active blend for I. typographus, containing three green leaf volatiles (GLVs) in addition to the key compounds trans-conophthorin (tC) and verbenone, has been considered too expensive for use in large-scale management. To lower the cost and improve the applicability of NHV, we aim to simplify the blend without compromising its anti-attractant potency. Since the key compound tC is expensive in pure form, we also tested a crude version: technical grade trans-conophthorin (T-tC). In another attempt to find a more cost effective substitute for tC, we evaluated a more readily synthesized analog: dehydro-conophthorin (DHC). Our results showed that 1-hexanol alone could replace the three-component GLV blend containing 1-hexanol, (3Z)-hexen-1-ol, and (2E)-hexen-1-ol. Furthermore, the release rate of tC could be reduced from 5 mg/day to 0.5 mg/day in a blend with 1-hexanol and (-)-verbenone without compromising the anti-attractant activity. We further show that T-tC was comparable with tC, whereas DHC was a less effective anti-attractant. DHC also elicited weaker physiological responses in the tC-responding olfactory receptor neuron class, providing a likely mechanistic explanation for its weaker anti-attractive effect. Our results suggest a blend consisting of (-)-verbenone, 1-hexanol and technical trans-conophthorin as a cost-efficient anti-attractant for forest protection against I. typographus.


Seroprevalence and risk factors for Toxoplasma infection in pregnant women in Jordan.
To determine the seroprevalence and risk factors for toxoplasmosis among pregnant women in Jordan, sera from 280 pregnant women were tested during the period January 2000-May 2001. Blood samples were taken after the first antenatal visit. Serum was separated and tested for Toxoplasma IgG antibodies using an indirect fluorescent antibody. Seroprevalence gradually increased with age, from 31.7% at 15-24 years to 90.0% at 35-45 years. Regression analysis showed that seroprevalence of toxoplasmosis is positively correlated with age and residence. Consumption of undercooked meat and contact with soil were significant risk factors.


Comparison of automated Difco ESP blood culture system with biphasic BBL Septi-Chek system for detection of bloodstream infections in pediatric patients.
We compared the Difco ESP 384 blood culture system with the pediatric Septi-Chek system for the detection of bloodstream infections in pediatric patients. A total of 10,762 blood culture sets included an ESP aerobic bottle and a Septi-Chek bottle. From these cultures, a total of 278 organisms classified as probable pathogens were isolated, including 237 from ESP bottles and 221 from Septi-Chek bottles. This difference was not statistically significant. More organisms classified as possible contaminants were also isolated from ESP bottles (for ESP, 480 bottles; for Septi-Chek, 418 bottles; P < 0.01). The time to detection was shorter for probable pathogens isolated from ESP bottles (median times for organisms isolated from both systems: ESP, 14.0 h; Septi-Chek, 34.5 h; P < 0.001). The proportions of all probable pathogens detected by 24 and 48 h after inoculation were 78 and 96%, respectively, for ESP compared with 31 and 74%, respectively, for Septi-Chek. The time to final identification was also shorter for organisms grown in ESP bottles (median times for organisms isolated from both systems: ESP, 48.8 h; Septi-Chek, 58.5 h; P < or = 0.001). A subset of 4,442 cultures also included an ESP anaerobic bottle in addition to an ESP aerobic bottle and a Septi-Chek bottle. There were no significant differences in the recovery of probable pathogens by any of the possible two bottle combinations, but five anaerobic pathogens were recovered only in the anaerobic bottle. We conclude that the ESP 384 is an excellent system for culturing pediatric blood samples and that it provides for the very rapid detection of bloodstream pathogens.


Practical fluorescence detection of acrolein in human plasma via a two-step tethering approach.
Acrolein, a cytotoxic α,β-unsaturated aldehyde and disease biomarker, was determined in plasma by means of a novel tethering strategy using Michael addition of the compound to a fluorescent dye, followed by immobilization of the product on microbeads via the aldehyde moiety. Elevation of blood acrolein was detected in mice treated with an anticancer agent cyclophosphamide, which releases acrolein upon activation. This method should be suitable for high-throughput diagnostic and clinical application.


Transfusion-associated iron overload as an adverse risk factor for transplantation outcome in patients undergoing reduced-intensity stem cell transplantation for myeloid malignancies.
Transfusion-associated iron overload could be an important risk factor in myeloablative hematopoietic stem cell transplantation. However, few studies have evaluated the effect of iron overload in reduced-intensity stem cell transplantation (RIST). We evaluated 38 patients with myeloid malignancies, 16 with and 22 without iron overload, who received RIST. We used pretransplant serum ferritin as a marker of iron overload. There was a positive correlation between the number of transfused packed red blood cells and pretransplant serum ferritin levels (21.5 units and 1,578.7 microg/l in the iron overload group vs. 12 units and 739.3 microg/l in the iron non-overload group; p <0.01). Engraftment day and chimerism analysis were not affected by iron overload (p = 0.71 and 0.47, respectively). There were no differences in treatment-related mortality (p = 0.94), veno-occlusive disease (p = 0.99), acute and chronic graft versus host disease (p = 0.58 and 0.99, respectively) according to iron overload. There was a significant difference in disease-free and overall survival (35.8 and 27% in the iron overload group vs. 80.6 and 54.6% in the iron non-overload group; p = 0.01 and 0.03, respectively). We conclude that transfusion-associated iron overload is an adverse risk factor in RIST for myeloid malignancies. The clinical outcomes according to iron overload in RIST were different in myeloablative hematopoietic stem cell transplantation. A serial follow-up of serum ferritin level and judicious iron chelation therapy will be needed to manage the side effect of iron overload in RIST and improve transplantation outcomes.