Re-evaluation of the existing health-based guidance values for copper and exposure assessment from all sources.
Copper is an essential micronutrient and also a regulated product used in organic and in conventional farming pest management. Both deficiency and excessive exposure to copper can have adverse health effects. In this Scientific Opinion, the EFSA 2021 harmonised approach for establishing health-based guidance values (HBGVs) for substances that are regulated products and also nutrients was used to resolve the divergent existing HBGVs for copper. The tightly regulated homeostasis prevents toxicity manifestation in the short term, but the development of chronic copper toxicity is dependent on copper homeostasis and its tissue retention. Evidence from Wilson disease suggests that hepatic retention is indicative of potential future and possibly sudden onset of copper toxicity under conditions of continuous intake. Hence, emphasis was placed on copper retention as an early marker of potential adverse effects. The relationships between (a) chronic copper exposure and its retention in the body, particularly the liver, and (b) hepatic copper concentrations and evidence of toxicity were examined. The Scientific Committee (SC) concludes that no retention of copper is expected to occur with intake of 5 mg/day and established an Acceptable Daily Intake (ADI) of 0.07 mg/kg bw. A refined dietary exposure assessment was performed, assessing contribution from dietary and non-dietary sources. Background copper levels are a significant source of copper. The contribution of copper from its use as plant protection product (PPP), food and feed additives or fertilisers is negligible. The use of copper in fertilisers or PPPs contributes to copper accumulation in soil. Infant formula and follow-on formula are important contributors to dietary exposure of copper in infants and toddlers. Contribution from non-oral sources is negligible. Dietary exposure to total copper does not exceed the HBGV in adolescents, adults, elderly and the very elderly. Neither hepatic copper retention nor adverse effects are expected to occur from the estimated copper exposure in children due to higher nutrient requirements related to growth.


Modeling the dynamics of bivalent histone modifications.
Epigenetic modifications to histones may promote either activation or repression of the transcription of nearby genes. Recent experimental studies show that the promoters of many lineage-control genes in stem cells have "bivalent domains" in which the nucleosomes contain both active (H3K4me3) and repressive (H3K27me3) marks. It is generally agreed that bivalent domains play an important role in stem cell differentiation, but the underlying mechanisms remain unclear. Here we formulate a mathematical model to investigate the dynamic properties of histone modification patterns. We then illustrate that our modeling framework can be used to capture key features of experimentally observed combinatorial chromatin states.


Role of calcium alginate and mannitol in protecting Bifidobacterium.
Fourier transform infrared (FTIR) spectroscopy was carried out to ascertain the mechanism of Ca-alginate and mannitol protection of cell envelope components and secondary proteins of Bifidobacterium animalis subsp. lactis Bb12 after freeze-drying and after 10 weeks of storage at room temperature (25°C) at low water activities (a(w)) of 0.07, 0.1, and 0.2. Preparation of Ca-alginate and Ca-alginate-mannitol as microencapsulants was carried out by dropping an alginate or alginate-mannitol emulsion containing bacteria using a burette into CaCl(2) solution to obtain Ca-alginate beads and Ca-alginate-mannitol beads, respectively. The wet beads were then freeze-dried. The a(w) of freeze-dried beads was then adjusted to 0.07, 0.1, and 0.2 using saturated salt solutions; controls were prepared by keeping Ca-alginate and Ca-alginate-mannitol in aluminum foil without a(w) adjustment. Mannitol in the Ca-alginate system interacted with cell envelopes during freeze-drying and during storage at low a(w)s. In contrast, Ca-alginate protected cell envelopes after freeze-drying but not during 10-week storage. Unlike Ca-alginate, Ca-alginate-mannitol was effective in retarding the changes in secondary proteins during freeze-drying and during 10 weeks of storage at low a(w)s. It appears that Ca-alginate-mannitol is more effective than Ca-alginate in preserving cell envelopes and proteins after freeze-drying and after 10 weeks of storage at room temperature (25°C).


Childhood IQ of parents related to characteristics of their offspring: linking the Scottish Mental Survey 1932 to the Midspan Family Study.
The objective of the study was to investigate the relationship between childhood IQ of parents and characteristics of their adult offspring. It was a prospective family cohort study linked to a mental ability survey of the parents and set in Renfrew and Paisley in Scotland. Participants were 1921-born men and women who took part in the Scottish Mental Survey in 1932 and the Renfrew/Paisley study in the 1970s, and whose offspring took part in the Midspan Family study in 1996. There were 286 offspring from 179 families. Parental IQ was related to some, but not all characteristics of offspring. Greater parental IQ was associated with taller offspring. Parental IQ was inversely related to number of cigarettes smoked by offspring. Higher parental IQ was associated with better education, offspring social class and offspring deprivation category. There were no significant relationships between parental IQ and offspring systolic blood pressure, diastolic blood pressure, cholesterol, glucose, lung function, weight, body mass index, waist hip ratio, housing, alcohol consumption, marital status, car use and exercise. Structural equation modelling showed parental IQ associated with offspring education directly and mediated via parental social class. Offspring education was associated with offspring smoking and social class. The smoking finding may have implications for targeting of health education.


Feroxyhyte nanoflakes coupled to up-converting carbon nanodots: a highly active, magnetically recoverable, Fenton-like photocatalyst in the visible-NIR range.
We demonstrate the enhanced photocatalytic response of a novel Fenton-like heterogeneous catalyst obtained through the assembly of superparamagnetic feroxyhyte nanoflakes synthesized by continuous gas-slug microfluidics and carbon nanodots obtained by pyrolysis from a natural organic source. The novel nanohybrids enable the utilization of the visible and near-infrared ranges due to the active role of the carbon nanodots as up-converting photo-sensitizers. This novel photocatalyst is magnetically recoverable and maintains an excellent response after multiple reutilization cycles. In addition, its synthesis is based on inexpensive and abundant raw materials and its photocatalytic response is evaluated in the presence of energy efficient, affordable light-emitting diodes (LEDs), thereby providing a promising and feasible alternative to the homogeneous Fenton process.


Microfossils in calculus demonstrate consumption of plants and cooked foods in Neanderthal diets (Shanidar III, Iraq; Spy I and II, Belgium).
The nature and causes of the disappearance of Neanderthals and their apparent replacement by modern humans are subjects of considerable debate. Many researchers have proposed biologically or technologically mediated dietary differences between the two groups as one of the fundamental causes of Neanderthal disappearance. Some scenarios have focused on the apparent lack of plant foods in Neanderthal diets. Here we report direct evidence for Neanderthal consumption of a variety of plant foods, in the form of phytoliths and starch grains recovered from dental calculus of Neanderthal skeletons from Shanidar Cave, Iraq, and Spy Cave, Belgium. Some of the plants are typical of recent modern human diets, including date palms (Phoenix spp.), legumes, and grass seeds (Triticeae), whereas others are known to be edible but are not heavily used today. Many of the grass seed starches showed damage that is a distinctive marker of cooking. Our results indicate that in both warm eastern Mediterranean and cold northwestern European climates, and across their latitudinal range, Neanderthals made use of the diverse plant foods available in their local environment and transformed them into more easily digestible foodstuffs in part through cooking them, suggesting an overall sophistication in Neanderthal dietary regimes.


NF-κB mediates the antiproliferative and proapoptotic effects of bergamot juice in HepG2 cells.
Among cancers, hepatocellular carcinoma is one of the commonest worldwide, and its incidence is increasing around the world. A lot of evidence underlines that natural substances usually consumed in the diet can have an important role in the prevention of cancer. In this study we investigated the molecular mechanisms underlying the antiproliferative activity of Citrus bergamia (bergamot) juice (BJ) in human hepatocellular carcinoma HepG2 cells. HepG2 cells were exposed to BJ and then cell proliferation, cell cycle progression, apoptosis and NF-κB nuclear translocation were evaluated. Here we present results demonstrating that BJ reduced the growth rate of human hepatocellular carcinoma HepG2 cells in a time- and concentration-dependent manner, by a mechanism involving the activation of apoptotic machinery via both intrinsic and extrinsic pathways. Moreover, BJ increased expression of P53 and P21 proteins that may be responsible for the HepG2 cell cycle arrest in G2 phase. In addition, BJ reduced NF-κB nuclear translocation. Our data demonstrate the ability of BJ in reducing the growth of HepG2 cells, revealing its mechanism of action and suggesting a promising role as anticancer drugs.


Associations between isozyme phenotypes and environment in the slender wild oat (Avena barbata) in Israel.
Collections from 31 populations of A. barbata from diverse habitats in Israel were assayed electrophoretically for seven enzyme systems. Phenotype frequencies were scored in nine enzyme zones, probably representing 27 loci, to determine isozyme variability within and among populations. Many different isozyme phenotypes were found in all of the populations; also the array of isozyme phenotypes found in each population differed distinctly from that found in each other population. Overlays of phenotypic frequencies on map locations showed that isozyme variability is distributed in mosaic patterns not related to geographical distance. Principal-component and multiple-regression analyses revealed that temperature and moisture-related variables are significantly correlated with particular isozyme phenotypes. Further, the mosaic patterns of isozyme variation were found to correspond closely to mosaic patterns of the habitat. This structuring of the genetic variability into multilocus combinations was attributed to the combined effects of directional and diversifying selection. Comparisons of patterns and extent of genetic variation in Israel and California led to the conclusion that the evolution of 'ecotypes,' each adapted to a specific habitat and marked by a particular set of enzyme alleles, has proceeded further in Israel, where A. barbata is endemic, than in California, where it is a recent introduction.


Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection.
Invariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)-γ and interleukin (IL)-4 ex-vivo enzyme-linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl-ceramide (αGalCer). We found that circulating iNKT cell proportions were significantly higher (P = 0·03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4(+) subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8α and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virus-specific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl-6 (P = 0·0003) and both Bcl-6 and inducible T cell co-stimulator (ICOS) (P = 0·006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4(+) iNKT cells, with reduced expression of CD161 markers.


Factors associated with the stages of change for dog walking among Japanese dog owners.
There are no previous data on factors at multiple levels associated with the stages of change for dog walking. The current study examined psychosocial and environmental correlates of the stages of change for dog walking among Japanese dog owners. Dog owners (N = 1940) completed a self-administered questionnaire that included items about demographics as well as psychosocial (dog attachment, dog obligation, normative belief, social norm, social support, self-efficacy) and environmental (access to areas, neighborhood safety, enjoyable scenery, frequently observing others dog walking, area where dogs are allowed to be off the lead) factors. MANOVA and discriminant functional analysis were used. The distribution of the dog owners across the stages was as follows: precontemplation (14.7%), contemplation (7.6%), preparation (39.7%), action (2.8%), and maintenance (35.2%). Although differences among the stages were found for all factors in MANOVA, the pattern of distinction among stages differed depending on the factors. Dog obligation and self-efficacy were the best predictors of the stages of change for dog walking. Although psychosocial and environmental correlates differed with the stages, psychosocial factors such as the sense of obligation and self-efficacy in dog walking seem to make relatively stronger contributions to distinctions among the stages.


Playing Tetris decreases drug and other cravings in real world settings.
Most research on cognitive processes in craving has been carried out in the laboratory and focuses on food craving. This study extends laboratory findings to real world settings and cravings for drugs or activities as well as food. Previous laboratory research has found that playing Tetris reduces craving strength. The present study used an ecological momentary assessment protocol in which 31 undergraduate participants carried iPods for a week and were prompted 7 times each day, by SMS message, to use their iPod to report craving. Participants reported craving target and strength (0-100), whether they indulged their previous craving (yes/no), and whether they were under the influence of alcohol (yes/no). Those randomly assigned to the intervention condition (n=15) then played Tetris for 3min and reported their craving again. Those in the monitoring-only control condition (n=16) provided baseline craving data to test if Tetris reduced the incidence and strength of spontaneous cravings across the week. Playing Tetris decreased craving strength for drugs (alcohol, nicotine, caffeine), food and drink, and activities (sex, exercise, gaming), with a mean reduction of 13.9 percentage points, effect size f(2)=0.11. This effect was consistent across the week. This is the first demonstration that visual cognitive interference can be used in the field to reduce cravings for substances and activities other than eating.


Co-expression of a Phanerochaete chrysosporium cellobiohydrolase gene and a Butyrivibrio fibrisolvens endo-beta-1,4-glucanase gene in Saccharomyces cerevisiae.
A cDNA fragment encoding the Phanerochaete chrysosporium cellobiohydrolase (cbh1-4) was amplified and cloned with the aid of the polymerase chain reaction (PCR) technique. The cbh1-4 gene and the Butyrivibrio fibrisolvens endo-beta-1,4-glucanase (end1) gene were successfully expressed in Saccharomyces cerevisiae under the control of the phosphoglycerate kinase-I (PGK1) and alcohol dehydrogenase-II (ADH2) gene promoters and terminators, respectively. The native P. chrysosporium signal sequence mediated secretion of cellobiohydrolase in S. cerevisiae, whereas secretion of the endo-beta-1,4-glucanase was directed by the signal sequence of the yeast mating pheromone alpha-factor (MFalpha1S). These constructs, designated CBH1 and END1, respectively, were expressed separately and jointly in S. cerevisiae. The construction of fur1 ura3 S. cerevisiae strains allowed for the autoselection of these multicopy URA3-based plasmids in rich medium. Enzyme assays confirmed that co-expression of CBH1 and END1 synergistically enhanced cellulose degradation by S. cerevisiae.


Rapid computation of the amplitude and phase of tightly focused optical fields distorted by scattering particles.
We develop an efficient method for accurately calculating the electric field of tightly focused laser beams in the presence of specific configurations of microscopic scatterers. This Huygens-Fresnel wave-based electric field superposition (HF-WEFS) method computes the amplitude and phase of the scattered electric field in excellent agreement with finite difference time-domain (FDTD) solutions of Maxwell's equations. Our HF-WEFS implementation is 2-4 orders of magnitude faster than the FDTD method and enables systematic investigations of the effects of scatterer size and configuration on the focal field. We demonstrate the power of the new HF-WEFS approach by mapping several metrics of focal field distortion as a function of scatterer position. This analysis shows that the maximum focal field distortion occurs for single scatterers placed below the focal plane with an offset from the optical axis. The HF-WEFS method represents an important first step toward the development of a computational model of laser-scanning microscopy of thick cellular/tissue specimens.


Ex vivo mass cytometry analysis reveals a profound myeloid proinflammatory signature in psoriatic arthritis synovial fluid.
A number of immune populations have been implicated in psoriatic arthritis (PsA) pathogenesis. This study used mass cytometry (CyTOF) combined with transcriptomic analysis to generate a high-dimensional dataset of matched PsA synovial fluid (SF) and blood leucocytes, with the aim of identifying cytokine production ex vivo in unstimulated lymphoid and myeloid cells. Fresh SF and paired blood were either fixed or incubated with protein transport inhibitors for 6 hours. Samples were stained with two CyTOF panels: a phenotyping panel and an intracellular panel, including antibodies to both T cell and myeloid cell secreted proteins. Transcriptomic analysis by gene array of key expanded cell populations, single-cell RNA-seq, ELISA and LEGENDplex analysis of PsA SF were also performed. We observed marked changes in the myeloid compartment of PsA SF relative to blood, with expansion of intermediate monocytes, macrophages and dendritic cell populations. Classical monocytes, intermediate monocytes and macrophages spontaneously produced significant levels of the proinflammatory mediators osteopontin and CCL2 in the absence of any in vitro stimulation. By contrast minimal spontaneous cytokine production by T cells was detected. Gene expression analysis showed the genes for osteopontin and CCL2 to be among those most highly upregulated by PsA monocytes/macrophages in SF; and both proteins were elevated in PsA SF. Using multiomic analyses, we have generated a comprehensive cellular map of PsA SF and blood to reveal key expanded myeloid proinflammatory modules in PsA of potential pathogenic and therapeutic importance.


COMAR technical information statement: expert reviews on potential health effects of radiofrequency electromagnetic fields and comments on the bioinitiative report.
The Committee on Man and Radiation (COMAR) is a technical committee of the Engineering in Medicine and Biology Society (EMBS) of the Institute of Electrical and Electronics Engineers (IEEE). Its primary area of interest is biological effects of non-ionizing electromagnetic radiation, including radiofrequency (RF) energy. The public interest in possible health effects attributed to RF energy, such as emitted by mobile phones, wireless telephone base stations, TV and radio broadcasting facilities, Wi-Fi systems and many other sources, has been accompanied by commentary in the media that varies considerably in reliability and usefulness for their audience. The focus of this COMAR Technical Information Statement is to identify quality sources of scientific information on potential health risks from exposure to RF energy. This Statement provides readers with references to expert reports and other reliable sources of information about this topic, most of which are available on the Internet. This report summarizes the conclusions from several major reports and comments on the markedly different conclusions in the BioInitiative Report (abbreviated BIR below). Since appearing on the Internet in August 2007, the BIR has received much media attention but, more recently, has been criticized by several health organizations (see Section titled "Views of health agencies about BIR"). COMAR concludes that the weight of scientific evidence in the RF bioeffects literature does not support the safety limits recommended by the BioInitiative group. For this reason, COMAR recommends that public health officials continue to base their policies on RF safety limits recommended by established and sanctioned international organizations such as the Institute of Electrical and Electronics Engineers International Committee on Electromagnetic Safety and the International Commission on Non-Ionizing Radiation Protection, which is formally related to the World Health Organization.


Pulmonary tuberculosis in outpatients in Sabah, Malaysia: advanced disease but low incidence of HIV co-infection.
Tuberculosis (TB) is generally well controlled in Malaysia, but remains an important problem in the nation's eastern states. In order to better understand factors contributing to high TB rates in the eastern state of Sabah, our aims were to describe characteristics of patients with TB at a large outpatient clinic, and determine the prevalence of HIV co-infection. Additionally, we sought to test sensitivity and specificity of the locally-available point-of-care HIV test kits. We enrolled consenting adults with smear-positive pulmonary TB for a 2-year period at Luyang Clinic, Kota Kinabalu, Malaysia. Participants were questioned about ethnicity, smoking, prior TB, disease duration, symptoms and comorbidities. Chest radiographs were scored using a previously devised tool. HIV was tested after counselling using 2 point-of-care tests for each patient: the test routinely in use at the TB clinic (either Advanced Quality™ Rapid Anti-HIV 1&2, FACTS anti-HIV 1/2 RAPID or HIV (1 + 2) Antibody Colloidal Gold), and a comparator test (Abbott Determine™ HIV-1/2, Inverness Medical). Positive tests were confirmed by enzyme immunoassay (EIA), particle agglutination and line immunoassay. 176 participants were enrolled; 59 (33.5%) were non-Malaysians and 104 (59.1%) were male. Smoking rates were high (81/104 males, 77.9%), most had cavitary disease (51/145, 64.8%), and 81/176 (46.0%) had haemoptysis. The median period of symptoms prior to treatment onset was 8 weeks. Diabetes was present in 12. People with diabetes or other comorbidities had less severe TB, suggesting different healthcare seeking behaviours in this group. All participants consented to HIV testing: three (1.7%) were positive according to Determine™ and EIA, but one of these tested negative on the point-of-care test available at the clinic (Advanced Quality™ Rapid Anti-HIV 1&2). The low number of positive tests and changes in locally-available test type meant that accurate estimates of sensitivity and specificity were not possible. Patients had advanced disease at diagnosis, long diagnostic delays, low HIV co-infection rates, high smoking rates among males, and migrants may be over-represented. These findings provide important insights to guide local TB control efforts. Caution is required in using some point-of-care HIV tests, and ongoing quality control measures are of major importance.


Spatial distribution of tropospheric ozone in national parks of California: interpretation of passive-sampler data.
The National Park Service (NPS) has tested and used passive ozone samplers for several years to get baseline values for parks and to determine the spatial variability within parks. Experience has shown that the Ogawa passive samplers can provide +/-10% accuracy when used with a quality assurance program consisting of blanks, duplicates, collocated instrumentation, and a standard operating procedure that carefully guides site operators. Although the passive device does not meet EPA criteria as a certified method (mainly, that hourly values be measured), it does provide seasonal summed values of ozone. The seasonal ozone concentrations from the passive devices can be compared to other monitoring to determine baseline values, trends, and spatial variations. This point is illustrated with some kriged interpolation maps of ozone statistics. Passive ozone samplers were used to get elevational gradients and spatial distributions of ozone within a park. This was done in varying degrees at Mount Rainier, Olympic, Sequoia-Kings Canyon, Yosemite, Joshua Tree, Rocky Mountain, and Great Smoky Mountains national parks. The ozone has been found to vary by factors of 2 and 3 within a park when average ozone is compared between locations. Specific examples of the spatial distributions of ozone in three parks within California are given using interpolation maps. Positive aspects and limitations of the passive sampling approach are presented.


Role of ocular involvement in the prediction of visual development and clinical prognosis in Aicardi syndrome.
This study was undertaken to document visual function and acuity in patients with Aicardi syndrome, and to determine whether there is any relation between ocular features of the syndrome exhibited at birth and later visual function. Fourteen patients with Aicardi syndrome, all examined and followed by the same ophthalmologist, were reviewed between 1975 and 1992 and their ocular characteristics and visual acuity described. It was hypothesised that larger lacunae may be associated with poorer clinical outcome and therefore the relation between these two variables was investigated. Visual acuity as documented by Snellen, Sheridan-Gardner, preferential looking, or pattern visual evoked potential tests was in the normal to low normal range in six eyes of four patients. Visual function correlated significantly with macular appearance. Good visual function was preserved if the fovea appeared normal on funduscopic examination and was uninvolved by lacunae. The size of the largest chorioretinal lacuna also correlated significantly with clinical outcome: patients with large lacunae were more likely to be immobile and to have no language skills. It was concluded that good visual function in patients with Aicardi syndrome may be anticipated if the fovea is normal. Although many patients have severe psychomotor retardation, the presence of predominantly small chorioretinal lacunae may indicate a better prognosis for mobility and language development.


Long-term association between seizure outcome and depression after resective epilepsy surgery.
This study explored the association between long-term epilepsy surgery outcome and changes in depressive symptoms. Adults were enrolled between 1996 and 2001 in a multicenter prospective study to evaluate outcomes of resective epilepsy surgery. The extent of depressive symptoms and depression case status (none, mild, or moderate/severe) were assessed using the Beck Depression Inventory (BDI) preoperatively and 3, 12, 24, 48, and 60 months postoperatively. A mixed-model repeated-measures analysis was performed, adjusting for covariates of seizure location, gender, age, race, education, and seizure control. Of the total 373 subjects, 256 were evaluated at baseline and 5 years after surgery. At baseline, 164 (64.1%) were not depressed, 34 (13.3%) were mildly depressed, and 58 (22.7%) had moderate to severe depression. After 5 years, 198 (77.3%) were not depressed, 20 (7.8%) were mildly depressed, and 38 (14.8%) were moderately to severely depressed. Five years after surgery, the reduction in mean change from baseline in BDI score was greater in subjects with excellent seizure control than in the fair and poor seizure control groups (p = 0.0006 and p = 0.02 respectively). Those with good seizure control had a greater reduction in BDI score than the poor seizure control group (p = 0.02) and borderline significant reduction compared with the fair seizure control group (p = 0.055). Although study participants had initial improvement in depressive symptoms, on average, after resective surgery, only patients with good or excellent seizure control had sustained long-term improvement in mood.


Gd2(MoO4)3:Er(3+) nanophosphors for an enhancement of silicon solar-cell near-infrared response.
In an attempt to take full advantage of near-infrared part of the solar spectrum, Gd(2)(MoO(4))(3):Er(3+) nanophosphors have been proposed as potential luminescent materials to enhance the response of the silicon solar-cell. Upon excitation with low-energy near-infrared photons, intense upconverted emissions at 545, 665, 800, and 980 nm, for which energies higher than the bandgap of silicon solar-cell, have been achieved with conversion efficiencies of 0.12%, 0.05%, 0.83%, and 1.35%, respectively. Development of nanophosphors for photovoltaic purposes could open up an approach in achieving high-efficiency silicon-based solar-cell by means of the up-conversion of the sub-bandgap near-infrared part of the solar spectrum (E < 1.12 eV) to visible/near-infrared photons.


Antiplatelet and lipid-lowering therapies for the secondary prevention of cardiovascular disease: are we doing enough?
To evaluate whether current recommendations with respect to the treatment of dyslipidemias and the use of antiplatelet agents are being applied in the secondary prevention of cardiovascular disease in primary care settings. Descriptive study based on data from the FAMUS (FAmily Medicine, Université de Sherbrooke) primary care register. Two-hundred and thirty-three physicians participating in the FAMUS project contributed information from nonpregnant patients over 20 years of age consulting for a periodic health examination between 1992 and 1996. Data from patients in secondary prevention (those with or having had angina, a previous myocardial infarction, bypass surgery, coronary angioplasty or peripheral vascular disease) were extracted and analyzed. Of the 52,505 patients in the register, 4315 (8%) were identified as being in secondary prevention. Overall, 53% were noted as receiving an antiplatelet agent while 4% were taking warfarin therapy. Only 64% (2780) had a complete lipid profile on record while 38% were being treated with a hypolipidemic agent. In the treated group, only 30% had a low density lipoprotein cholesterol level below 3.0 mmol/L compared with 22% in the untreated group. A large number of patients identified as being in secondary prevention were not screened for dyslipidemias, and, of those who were, the majority were undertreated according to current recommendations. Antiplatelet agents were more widely prescribed but potentially underused.


Epigenetic Dysregulation in the Prefrontal Cortex of Suicide Completers.
The epigenome is thought to mediate between genes and the environment, particularly in response to adverse life experiences. Similar to other psychiatric diseases, the suicide liability of an individual appears to be influenced by many genetic factors of small effect size as well as by environmental stressors. To identify epigenetic marks associated with suicide, which is considered the endpoint of complex gene-environment interactions, we compared the cortex DNA methylation patterns of 6 suicide completers versus 6 non-psychiatric sudden-death controls, using Illumina 450K methylation arrays. Consistent with a multifactorial disease model, we found DNA methylation changes in a large number of genes, but no changes with large effects reaching genome-wide significance. Global methylation of all analyzed CpG sites was significantly (0.25 percentage point) lower in suicide than in control brains, whereas the vast majority (97%) of the top 1,000 differentially methylated regions (DMRs) were higher methylated (0.6 percentage point) in suicide brains. Annotation analysis of the top 1,000 DMRs revealed an enrichment of differentially methylated promoters in functional categories associated with transcription and expression in the brain. In addition, we performed a comprehensive literature research to identify suicide genes that have been replicated in independent genetic association, brain methylation and/or expression studies. Although, in general, there was no significant overlap between different published data sets or between our top 1,000 DMRs and published data sets, our methylation screen strengthens a number of candidate genes (APLP2, BDNF, HTR1A, NUAK1, PHACTR3, MSMP, SLC6A4, SYN2, and SYNE2) and supports a role for epigenetics in the pathophysiology of suicide.


Barriers to timely disclosure of HIV serostatus: A qualitative study at care and treatment centers in Dar es Salaam, Tanzania.
Disclosure of Human Immunodeficiency Virus (HIV) status is important to prevent the spread of HIV and maintain the health of people living with HIV, their spouses, and the community. Despite the benefits of disclosure, many people living with HIV delay disclosing their status to those close to them thereby increasing the risk for disease transmission. This study aimed to determine the barriers to timely disclosure of HIV serostatus for people living with HIV in Dar es Salaam, Tanzania, and identify what motivated disclosure. A qualitative descriptive study using in-depth individual interviews was conducted with10 participants attending HIV care and treatment centers in Dar es Salaam. The participants were people living with HIV who had delayed disclosing their serostatus for more than one month after diagnosis. Data was analyzed using qualitative content analysis. Three categories emerged from the analysis: Barriers hindering timely disclosure, motivation for disclosure of serostatus, and consequences of delayed disclosure. Barriers to timely disclosure included denial of one's status, the fear of stigmatization, fear of being separated or divorced, the need to protect loved ones, and lack of adequate knowledge about the disease. Reasons that motivated disclosure included gaining social support, preventing disease transmission and wanting to be at peace. Timely disclosure is hindered by stigma because HIV is negatively perceived by the public. People living with HIV prefer not to disclose to avoid the negative consequences of disclosure, especially because of fear of being discriminated against and losing their social status, which plays a major role in social status in Tanzania. Trust and adequate counseling from health care workers helps prompt disclosure.


Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications.
Gastric inhibitory polypeptide (GIP) is a physiological gut peptide secreted from the intestinal K-cells with well documented insulin-releasing actions. However, the GIP receptor is widely distributed in peripheral organs, including the pancreas, gut, adipose tissue, heart, adrenal cortex and brain, suggesting that it may have other functions. The presence of functional GIP receptors on adipocytes and the key role played by GIP in lipid metabolism and fat deposition suggest a possible beneficial effect of compromised GIP action in obesity and insulin resistance. Several key observations in animal models of obesity-related diabetes with chemically or genetically mediated biological GIP deficiency support this concept. Thus, obese diabetic animals with compromised GIP action due to peptide-based GIP receptor antagonists, small molecular weight GIP receptor antagonists, vaccination against GIP, genetic knockout of GIP receptor or targeted K-cell destruction are protected against obesity and associated metabolic disturbances. In addition, by causing preferential oxidation of fat, blockade of GIP signalling clears triacylglycerol deposits from liver and muscle, thereby restoring mechanisms for suppression of hepatic glucose output and improving insulin sensitivity. Emerging evidence also suggests that rapid cure of diabetes in grossly obese patients undergoing bypass surgery is mediated, in part, by surgical removal of GIP-secreting K-cells in the upper small intestine.


The Prevalence and Predictors of Iron Deficiency Anemia among Rural Infants in Nablus Governorate.
Iron deficiency anemia (IDA) in infants and young children remains a significant public health problem in most developing countries. IDA had short and long-term adverse impacts on infants' health and development. We aimed to assess the frequency of IDA and associated risk factors among infants aged between 9-12 months in rural areas of Nablus Governorate. A cross-sectional study. The study was conducted between Jan and Mar 2015. A random sample of 654 infants aged 9-12 months were selected from thirty villages in Nablus Governorate, Central Highlands of the West Bank, north of Jerusalem. Data were collected using pre-designed structured interviewing questionnaire, complete blood count analysis and anthropometric measurements were done. The prevalence of anemia and IDA among infants was 34.6%, and 32.6%, respectively. Predictors of IDA were increased in infants' age OR=1.19 (95% CI: 1.02, 1.40), maternal anemia during the third trimester OR=2.39 (95% CI: 1.55, 3.71), birth spacing less than three years OR=2.86 (95%CI: 1.58, 5.18), exclusive breastfeeding during the first six months OR=2.40 (95% CI: 1.46, 3.95), early OR=1.64 (95%CI: 1.03, 2.613) and late introduction of complementary feeding OR=2.26 (95% CI: 1.27, 4.05), and non-compliance to iron supplement in the correct frequency and duration during pregnancy OR=1.81 (95% CI: 1.19, 2.75). Different dietary and non-dietary risk factors for IDA should be considered for any intervention aimed to reduce the prevalence of IDA among infants.


Lifetime and current mood and anxiety disorders in short-term and long-term abstinent alcoholics.
A high prevalence of comorbid mood and anxiety disorders has been demonstrated in alcoholics. We examined lifetime and current mood and anxiety diagnoses and symptoms in long-term (mean 7.6 years; n = 110) and short-term (mean 10.1 weeks; n = 101) abstinent alcoholics (LTAA and STAA) and nonsubstance abusing controls (NSAC; n = 82). All alcoholics met DSM-IV lifetime alcohol dependence criteria. About half of each alcoholic group had lifetime drug dependence. Alcohol use was assessed using timeline follow-back methodology, and drug and alcohol use disorders were diagnosed using the AUDADIS-IV. Lifetime and current mood and anxiety disorder diagnoses and symptom counts were gathered using the computerized Diagnostic Interview Schedule. Over 60% of STAA and LTAA had a lifetime internalizing diagnosis versus about 15% of NSAC, with no difference between STAA and LTAA. The group effect on lifetime diagnoses was independent of comorbid drug dependence or gender and was of comparable size for mood and anxiety disorders. Current diagnoses showed a similar pattern, except that STAA had more current mood diagnoses than LTAA. Excluding individuals with lifetime internalizing diagnoses, alcoholics still had more mood and anxiety symptoms than controls. (i) The presence of a lifetime mood or anxiety diagnosis or of a current anxiety diagnosis did not differ between STAA and LTAA, suggesting that such diagnoses do not impact one's ability to achieve or maintain abstinence. (ii) Prevalence of mood and anxiety diagnoses was unaffected by presence of a comorbid substance use disorder, and (iii) excluding individuals with a mood or anxiety diagnosis does not eliminate mood and anxiety symptom count differences between groups.


Data quality evaluation for observational multiple sclerosis registries.
Objective and reproducible evaluation of data quality is of paramount importance for studies of 'real-world' observational data. Here, we summarise a standardised data quality, density and generalisability process implemented by MSBase, a global multiple sclerosis (MS) cohort study. Error rate, data density score and generalisability score were developed using all 35,869 patients enrolled in MSBase as of November 2015. The data density score was calculated across six domains (follow-up, demography, visits, MS relapses, paraclinical data and therapy) and emphasised data completeness. The error rate evaluated syntactic accuracy and consistency of data. The generalisability score evaluated believability of the demographic and treatment information. Correlations among the three scores and the number of patients per centre were evaluated. Errors were identified at the median rate of 3 per 100 patient-years. The generalisability score indicated the samples' representativeness of the known MS epidemiology. Moderate correlation between the density and generalisability scores (ρ = 0.58) and a weak correlation between the error rate and the other two scores (ρ = -0.32 to -0.33) were observed. The generalisability score was strongly correlated with centre size (ρ = 0.79). The implemented scores enable objective evaluation of the quality of observational MS data, with an impact on the design of future analyses.


Oxygen-induced dynamics of nitrous oxide in water and off-gas during the treatment of digester supernatant.
Nitrous oxide (N(2)O) is a potent greenhouse gas and of special concern in wastewater treatment. It is formed in biological wastewater treatment under both aerobic and anaerobic conditions. A major reason for high N(2)O emissions is low oxygen concentration during nitrification. In this full-scale study of N(2)O emissions from a sequencing batch reactor for treating digester supernatant, the oxygen concentration was reduced stepwise to investigate how N(2)O emissions were influenced. N(2)O concentrations were measured online in water and off-gas. A distinct relationship was found between low oxygen concentration and high N(2)O emissions. N(2)O was formed in water during both nitrification and denitrification. Decreased oxygen concentration during nitrification led to increased nitrite concentration, which in turn led to increased N(2)O concentration in the subsequent denitrification phase. When the nitrification resumed, accumulated N(2)O was stripped off to the atmosphere. Very high concentrations of N(2)O, over 56,000 ppmv, were measured in the off-gas. Furthermore, the maximum amount of N(2)O emitted during one cycle corresponded to 107.6% of the total nitrogen load (21.9% of total nitrogen present in the bulk liquid at the beginning of the cycle). This is among the highest emission levels ever measured from a full-scale municipal plant for digester supernatant.


Cellular functions of Ufd2 and Ufd3 in proteasomal protein degradation depend on Cdc48 binding.
The chaperone-related AAA ATPase Cdc48 (p97/VCP in higher eukaryotes) segregates ubiquitylated proteins for subsequent degradation by the 26S proteasome or for nonproteolytic fates. The specific outcome of Cdc48 activity is controlled by the evolutionary conserved cofactors Ufd2 and Ufd3, which antagonistically regulate the substrates' ubiquitylation states. In contrast to the interaction of Ufd3 and Cdc48, the interaction between the ubiquitin chain elongating enzyme Ufd2 and Cdc48 has not been precisely mapped. Consequently, it is still unknown whether physiological functions of Ufd2 in fact require Cdc48 binding. Here, we show that Ufd2 binds to the C-terminal tail of Cdc48, unlike the human Ufd2 homologue E4B, which interacts with the N domain of p97. The binding sites for Ufd2 and Ufd3 on Cdc48 overlap and depend critically on the conserved residue Y834 but are not identical. Saccharomyces cerevisiae cdc48 mutants altered in residue Y834 or lacking the C-terminal tail are viable and exhibit normal growth. Importantly, however, loss of Ufd2 and Ufd3 binding in these mutants phenocopies defects of Δufd2 and Δufd3 mutants in the ubiquitin fusion degradation (UFD) and Ole1 fatty acid desaturase activation (OLE) pathways. These results indicate that key cellular functions of Ufd2 and Ufd3 in proteasomal protein degradation require their interaction with Cdc48.


Antidepressant-like effect of saponins extracted from Chaihu-jia-longgu-muli-tang and its possible mechanism.
In this study, we investigated the antidepressant-like effect of saponins (SCLM) extracted from a traditional Chinese medicine, Chaihu-jia-longgu-muli-tang (CLM), in mice and rats using the tail suspension test (TST) and forced swimming test (FST). Subchronic administration of 100 and 200 mg/kg (p.o.) SCLM for 7 days reduced immobility time in the TST and FST in mice and also decreased immobility time at 70 and 140 mg/kg (p.o.) in the FST in rats. The results also showed that the anti-immobility activity of SCLM in these two tests is dose-dependent, without accompanying significant effects on locomotor activity. In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactic dehydrogenase (LDH) assays showed that 25, 50 and 100 microg/ml SCLM or 10 microM fluoxetine (FLU), protected PC12 cells from the lesion induced by 10 microM corticosterone (Cort) treatment for 48 h. In the fura-2/AM (acetoxymethyl ester) labeling assay, 50 and 100 microg/ml SCLM, 10 microM FLU attenuated the intracellular Ca2+ overloading induced by 200 microM Cort treatment for 48 h in PC12 cells. Using RT-PCR, the mRNA level of nerve growth factor (NGF) was also detected. Treatment with SCLM (50, 100 microg/ml) for 48 h elevated the NGF mRNA expression in PC12 cells. In summary, these results suggest that SCLM possesses an antidepressant-like activity in behavioral models that might be mediated via the cytoprotective action shown in PC12 cells.


Progress in self-healing hydrogels assembled by host-guest interactions: preparation and biomedical applications.
Self-healing is one of the most fundamental properties of living tissues that allows them to withstand repeated damage. Self-healing hydrogels, which can spontaneously recover themselves after being ruptured, result in enhanced lifetimes for materials and open up a fascinating direction in materials science. Host-guest interactions have been widely used in the construction of self-healing hydrogels. We have emphasized the preparation and biomedical applications of self-healing hydrogels assembled by host-guest interactions, focusing on hosts of cyclodextrins and cucurbit[n]urils with various guests and tailored structures. The applications of self-healing hydrogels in biomedical fields such as drug delivery, encapsulation of cells and tissue engineering and 3D printing as well as interfacial adhesion were also summarized. At the end of this review, we propose the current challenges and future perspectives in this developing area.


[Variability in outpatient resource use in mental health services for children and adolescents].
To assess possible variability in the therapeutic approaches provided to patients aged less than 18 years old in community mental health centres (CMHC) in terms of the number of visits and length of treatment. An observational, analytical, prospective, longitudinal study was performed in a clinical cohort of 298 subjects attending the CMHC of Leganés and Fuenlabrada (Madrid) for the first time. The median number of visits per patient was six in Leganés and three in Fuenlabrada (p < 0.001). The mean length of treatment was more than twice as long in Leganés (276 days) than in Fuenlabrada (119 days) (p < 0.001). Stratified analysis showed that the treatments provided in Fuenlabrada involved fewer visits, irrespective of the health professional in charge (psychiatrist or psychologist), the treatment modality prescribed (individual psychotherapy, other psychotherapies or no explicit treatment prescribed), or whether the patient abandoned treatment or the discharge was agreed. Similar results were found for the length of treatment. The different clinical styles illustrate the difficulty of developing useful risk adjustment systems in mental health. The differences in resource consumption and costs cannot easily be attributed to patient-related variables, but are due rather to the intervention provided, which depends on the staff.


Magnetic Resonance Biomarkers in Neonatal Encephalopathy (MARBLE): a prospective multicountry study.
Despite cooling, adverse outcomes are seen in up to half of the surviving infants after neonatal encephalopathy. A number of novel adjunct drug therapies with cooling have been shown to be highly neuroprotective in animal studies, and are currently awaiting clinical translation. Rigorous evaluation of these therapies in phase II trials using surrogate MR biomarkers may speed up their bench to bedside translation. A recent systematic review of single-centre studies has suggested that MR spectroscopy biomarkers offer the best promise; however, the prognostic accuracy of these biomarkers in cooled encephalopathic babies in a multicentre setting using different MR scan makers is not known. The MR scanners (3 T; Philips, Siemens, GE) in all the participating sites will be harmonised using phantom experiments and healthy adult volunteers before the start of the study. We will then recruit 180 encephalopathic infants treated with whole body cooling from the participating centres. MRI and spectroscopy will be performed within 2 weeks of birth. Neurodevelopmental outcomes will be assessed at 18-24 months of age. Agreement between MR cerebral biomarkers and neurodevelopmental outcome will be reported. The sample size is calculated using the 'rule of 10', generally used to calculate the sample size requirements for developing prognostic models. Considering 9 parameters, we require 9×10 adverse events, which suggest that a total sample size of 180 is required. Human Research Ethics Committee approvals have been received from Brent Research Ethics Committee (London), and from Imperial College London (Sponsor). We will submit the results of the study to relevant journals and offer national and international presentations. Clinical Trials.gov Number: NCT01309711.


No effect of ambient odor on the affective appraisal of a desktop virtual environment with signs of disorder.
Desktop virtual environments (VEs) are increasingly deployed to study the effects of environmental qualities and interventions on human behavior and safety related concerns in built environments. For these applications it is essential that users appraise the affective qualities of the VE similar to those of its real world counterpart. Previous studies have shown that factors like simulated lighting, sound and dynamic elements all contribute to the affective appraisal of a desktop VE. Since ambient odor is known to affect the affective appraisal of real environments, and has been shown to increase the sense of presence in immersive VEs, it may also be an effective tool to tune the affective appraisal of desktop VEs. This study investigated if exposure to ambient odor can modulate the affective appraisal of a desktop VE with signs of public disorder. Participants explored a desktop VE representing a suburban neighborhood with signs of public disorder (neglect, vandalism and crime), while being exposed to either room air or subliminal levels of unpleasant (tar) or pleasant (cut grass) ambient odor. Whenever they encountered signs of disorder they reported their safety related concerns and associated affective feelings. Signs of crime in the desktop VE were associated with negative affective feelings and concerns for personal safety and personal property. However, there was no significant difference between reported safety related concerns and affective connotations in the control (no-odor) and in each of the two ambient odor conditions. Ambient odor did not affect safety related concerns and affective connotations associated with signs of disorder in the desktop VE. Thus, semantic congruency between ambient odor and a desktop VE may not be sufficient to influence its affective appraisal, and a more realistic simulation in which simulated objects appear to emit scents may be required to achieve this goal.


Medication-related osteonecrosis of the jaws (MRONJ) and quality of life evaluation: a pilot study.
MRONJ (medication related osteonecrosis of the jaws) is a well-known side effect of certain drugs, which are used to influence bone metabolism for the cure of osteo-metabolic or cancer diseases. The aim of this study is to assess the quality of life (QOL) under a physical and mental point of view in patients affected by MRONJ compared with the general population. The study has been accomplished through the administration of the SF-12 questionnaire: 30 patients of the MRONJ group were evaluated. Significant differences based on the level of education and age of the subjects, on the location and finally on the stage of necrosis of the jaw have been identified. In this pilot study the test sample shows how MRONJ can aggravate the conditions of patients, above all under a physical point of view. Prevention of MRONJ and its symptoms as dysphagia, oral pain, immunological compromission and the need of frequent antibiotic therapies is a crucial part of modern oral pathology and dentistry, above all for oncologic patients who already have a general decrease of physical and mental activities, leading to a poor quality of life.


Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case-control study.
To assess the relationship between maternal clinical chorioamnionitis and neonatal outcome in preterm very-low birthweight (VLBW) infants. An observational case-control study was conducted in the Neonatology Services of 12 acute-care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (< or =1500 g) infants born to a mother with clinical chorioamnionitis were enrolled. Controls were infants without chorioamnionitis matched by gestational age who were born immediately after each index case. There were 165 cases and 163 controls. A significantly higher percentage of cases than controls required intubation (53% vs. 35.8%), had normal intrauterine growth (98.1% vs. 84.7%), were born in a tertiary center (inborn) (95.1% vs. 89.1%), from single gestations (76.4% vs. 65.6%) and vaginal delivery (47.3% vs. 33.3%), showed a lower Apgar score at 5 min, and presented a higher rate of early-onset sepsis (10.4% vs. 1.2%). Older maternal age (32.5 vs. 30.8 years), premature labor (67.3% vs. 25.8%), premature rupture of membranes (61.3% vs. 25.8%), and antibiotic treatment (88.5% vs. 52.3%) were significantly more frequent among cases than controls. After controlling by gestational age, maternal chorioamnionitis was associated with neonatal depression and early sepsis but not with other prematurity-related complications.


Newer generation antidepressants for depressive disorders in children and adolescents.
Depressive disorders are common in young people and are associated with significant negative impacts. Newer generation antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are often used, however evidence of their effectiveness in children and adolescents is not clear. Furthermore, there have been warnings against their use in this population due to concerns about increased risk of suicidal ideation and behaviour. To determine the efficacy and adverse outcomes, including definitive suicidal behaviour and suicidal ideation, of newer generation antidepressants compared with placebo in the treatment of depressive disorders in children and adolescents. For this update of the review, we searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to October 2011. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 -), MEDLINE (1950 -) and PsycINFO (1967 -). We searched clinical trial registries and pharmaceutical company websites. We checked reference lists of included trials and other reviews, and sent letters to key researchers and the pharmaceutical companies of included trials from January to August 2011. Published and unpublished randomised controlled trials (RCTs), cross-over trials and cluster trials comparing a newer generation antidepressant with a placebo in children and adolescents aged 6 to 18 years old and diagnosed with a depressive disorder were eligible for inclusion. In this update, we amended the selection criteria to include newer generation antidepressants rather than SSRIs only. Two or three review authors selected the trials, assessed their quality, and extracted trial and outcome data. We used a random-effects meta-analysis. We used risk ratio (RR) to summarise dichotomous outcomes and mean difference (MD) to summarise continuous measures. Nineteen trials of a range of newer antidepressants compared with placebo, containing 3335 participants, were included. The trials excluded young people at high risk of suicide and many co-morbid conditions and the participants are likely to be less unwell than those seen in clinical practice. We judged none of these trials to be at low risk of bias, with limited information about many aspects of risk of bias, high drop out rates and issues regarding measurement instruments and the clinical usefulness of outcomes, which were often variously defined across trials. Overall, there was evidence that those treated with an antidepressant had lower depression severity scores and higher rates of response/remission than those on placebo. However, the size of these effects was small with a reduction in depression symptoms of 3.51 on a scale from 17 to 113 (14 trials; N = 2490; MD -3.51; 95% confidence interval (CI) -4.55 to -2.47). Remission rates increased from 380 per 1000 to 448 per 1000 for those treated with an antidepressant. There was evidence of an increased risk (58%) of suicide-related outcome for those on antidepressants compared with a placebo (17 trials; N = 3229; RR 1.58; 95% CI 1.02 to 2.45). This equates to an increased risk in a group with a median baseline risk from 25 in 1000 to 40 in 1000. Where rates of adverse events were reported, this was higher for those prescribed an antidepressant. There was no evidence that the magnitude of intervention effects (compared with placebo) were modified by individual drug class. Caution is required in interpreting the results given the methodological limitations of the included trials in terms of internal and external validity. Further, the size and clinical meaningfulness of statistically significant results are uncertain. However, given the risks of untreated depression in terms of completed suicide and impacts on functioning, if a decision to use medication is agreed, then fluoxetine might be the medication of first choice given guideline recommendations. Clinicians need to keep in mind that there is evidence of an increased risk of suicide-related outcomes in those treated with antidepressant medications.


Admissions of patients with alcohol intoxication in the Emergency Department: a growing phenomenon.
To investigate the change over time in the number of ED admissions with positive blood alcohol concentration (BAC) and to evaluate predictors of BAC level. We conducted a single site retrospective study at the ED of a tertiary referral hospital (western part of Switzerland) and obtained all the BAC performed from 2002 to 2011. We determined the proportion of ED admissions with positive BAC (number of positive BAC/number of admissions). Regression models assessed trends in the proportion of admissions with positive BAC and the predictors of BAC level among patients with positive BAC. A total of 319,489 admissions were recorded and 20,021 BAC tests were performed, of which 14,359 were positive, divided 34.5% female and 65.5% male. The mean (SD) age was 41.7(16.8), and the mean BAC was 2.12(1.04) permille (g of ethanol/liter of blood). An increase in the number of positive BAC was observed, from 756 in 2002 to 1,819 in 2011. The total number of admissions also increased but less: 1.2 versus 2.4 times more admissions with positive BAC. Being male was independently associated with a higher (+0.19 permille) BAC, as was each passing year (+0.03). A significant quadratic association with age indicated a maximum BAC at age 53. We observed an increase in the percentage of admissions with positive BAC that was not limited to younger individuals. Given the potential consequences of alcohol intoxication, and the large burden imposed on ED teams, communities should be encouraged to take measures aimed at reducing alcohol intoxication.


Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress.
alpha-Lipoic acid (LA), a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. Aside from its enzymatic role, in vitro and in vivo studies suggest that LA also acts as a powerful micronutrient with diverse pharmacologic and antioxidant properties. Pharmacologically, LA improves glycemic control, polyneuropathies associated with diabetes mellitus, and effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, LA directly terminates free radicals, chelates transition metal ions (e.g. iron and copper), increases cytosolic glutathione and vitamin C levels and prevents toxicities associated with their loss. These diverse actions suggest that LA acts by multiple mechanisms both physiologically and pharmacologically, many of which are only now being explored. Herein, we review the known biochemical properties of LA with particular reference to how LA may be an effective agent to ameliorate certain pathophysiologies of many chronic diseases.


Challenges in Antibody Development against Tn and Sialyl-Tn Antigens.
The carbohydrate antigens Tn and sialyl-Tn (STn) are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment.


Human lung macrophage-derived histamine-releasing activity is due to IgE-dependent factors.
Human lung macrophages obtained from surgical specimens spontaneously secreted a factor(s) (which we term macrophage factor) during 24-hr culture that induced calcium-dependent histamine release from human basophils and lung mast cells. Macrophage factor induced noncytotoxic histamine release from purified (85%) basophils. The kinetics of release were relatively slow and similar to that of anti-IgE. We performed a series of experiments to test the IgE dependence of macrophage factor-induced release. Preincubation of basophils with anti-IgE in calcium-free medium resulted in complete desensitization to macrophage factor-induced histamine release (i.e., when calcium and macrophage factor were added to the basophils, no histamine release occurred), and preincubation with macrophage factor in calcium-free medium resulted in partial desensitization to anti-IgE-induced histamine release. Pretreatment of basophils with pH 3.9 lactic acid buffer, which dissociates basophil IgE from its receptors, markedly reduced the capacity of basophils to release histamine in response to macrophage factor. Basophils that were incubated with IgE myeloma (but not with IgG) after lactic acid treatment partially or completely regained their capacity to release histamine in response to macrophage factor. Fluid-phase IgE myeloma (15 micrograms/ml) (but not IgG) inhibited basophil histamine release induced by two macrophage-derived supernatants, whereas IgE myeloma (200 micrograms/ml) did not inhibit release due to other supernatants. IgE-affinity columns removed the histamine-releasing activity of five macrophage-derived supernatants, and IgG-affinity columns had similar effects. However, neither affinity column removed the histamine-releasing activity of three other macrophage-derived supernatants. On Sephadex G-75 chromatography, nearly all of the histamine-releasing activity migrated as single peak with an apparent m.w. of 18,000. These results suggest that, although macrophage factor are heterogeneous, they are related, as they are a IgE-dependent factors that induce histamine release by interacting with cell surface IgE. These macrophage factors may be responsible for stimulation of basophil/mast cell mediator release in chronic allergic reactions.


DNase hypersensitive sites and association with multiple sclerosis.
Genome-wide association studies (GWASs) have shown that approximately 60 genetic variants influence the risk of developing multiple sclerosis (MS). Our aim was to identify the cell types in which these variants are active. We used available data on MS-associated single nucleotide polymorphisms (SNPs) and deoxyribonuclease I hypersensitive sites (DHSs) from 112 different cell types. Genomic intervals were tested for overlap using the Genomic Hyperbrowser. The expression profile of the genes located nearby MS-associated SNPs was assessed using the software GRAIL (Gene Relationships Across Implicated Loci). Genomic regions associated with MS were significantly enriched for a number of immune DHSs and in particular T helper (Th) 1, Th17, CD8+ cytotoxic T cells, CD19+ B cells and CD56+ natural killer (NK) cells (enrichment = 2.34, 2.19, 2.27, 2.05 and 1.95, respectively; P < 0.0001 for all of them). Similar results were obtained when genomic regions with suggestive association with MS and additional immune-mediated traits were investigated. Several new candidate MS-associated genes located within regions of suggestive association were identified by GRAIL (CARD11, FCRL2, CHST12, SYK, TCF7, SOCS1, NFKBIZ and NPAS1). Genetic data indicate that Th1, Th17, cytotoxic T, B and NK cells play a prominent role in the etiology of MS. Regions with confirmed and suggestive association have a similar immunological profile, indicating that many SNPs truly influencing the risk of MS actually fail to reach genome-wide significance. Finally, similar cell types are involved in the etiology of other immune-mediated diseases.


Baltic Sea nutrient reductions--what should we aim for?
Nutrient load reductions are needed to improve the state of the Baltic Sea, but it is still under debate how they should be implemented. In this paper, we use data from an environmental valuation study conducted in all nine Baltic Sea states to investigate public preferences of relevance to three of the involved decision-dimensions: First, the roles of nitrogen versus phosphorus reductions causing different eutrophication effects; second, the role of time - the lag between actions to reduce nutrient loads and perceived improvements; and third; the spatial dimension and the roles of actions targeting the coastal and open sea environment and different sub-basins. Our findings indicate that respondents view and value the Baltic Sea environment as a whole, and are not focussed only on their local sea area, or a particular aspect of water quality. We argue that public preferences concerning these three perspectives should be one of the factors guiding marine policy. This requires considering the entire range of eutrophication effects, in coastal and open sea areas, and including long-term and short-term measures.


Patients' visual experience during phacoemulsification cataract surgery and associated fear.
Data from several published studies indicate that patients undergoing phacoemulsification cataract surgery can experience a variety of visual sensations which can result in fear. This phenomenon has not been studied in Pakistan to-date. We examined the visual experience and its associated fear among patients undergoing phacoemulsification cataract surgery under topical anaesthesia. This cross-sectional study was carried out in Aga Khan University Hospital, a tertiary care hospital, in Karachi, Pakistan from August 2010 to July 2011. Adults >18 years of age scheduled to undergo cataract surgery (phacoemulsification with intraocular lens implantation) under topical anaesthesia by a single surgeon were included. A structured questionnaire was used to collect data on socio-demographics, intraoperative visual experiences and subsequent reaction to these sensations. Participants were asked if they experienced visual sensations such as colours, shapes and movements during surgery. Moreover, they were asked if they developed fear due to these sensations. Fifty three patients (mean age: 60.4 ± 12.4 years) were enrolled. Thirty (56.6%) of them were men and 23 (43.4%) were women. All of them reported having experienced visual sensations during surgery, the most common being light perception (100%), different colours (77.4%), movements of instruments or surgeon's hands (37.7%) and different shapes (7.5%) such as circles, clouds and patches. The most common colours perceived included white (46.2%), blue (35.8%), red (30.2%) and yellow (30.2%). One out of every four (26.4%) participants reported having developed fear due to these visual sensations. Only 4 (7.5%) reported having received preoperative counselling regarding such sensations. Patients in our study experienced a variety of visual sensations during cataract surgery under topical anaesthesia. The prevalence of frightening visual sensations is higher than that reported in all previous published studies on the subject and needs to be addressed through targeted interventions.


Exposure of infants to outdoor and indoor air pollution in low-income urban areas - a case study of Delhi.
Indoor air pollution is potentially a very serious environmental and public health problem in India. In poor communities, with the continuing trend in biofuel combustion coupled with deteriorating housing conditions, the problem will remain for some time to come. While to some extent the problem has been studied in rural areas, there is a dearth of reliable data and knowledge about the situation in urban slum areas. The microenvironmental model was used for assessing daily-integrated exposure of infants and women to respirable suspended particulates (RSP) in two slums of Delhi - one in an area of high outdoor pollution and the other in a less polluted area. The study confirmed that indoor concentrations of RSP during cooking in kerosene-using houses are lesser than that in wood-using houses. However, the exposure due to cooking was not significantly different across the two groups. This was because, perhaps due to socioeconomic reasons, kerosene-using women were found to cook for longer durations, cook inside more often, and that infants in such houses stayed in the kitchen for longer durations. It was observed that indoor background levels during the day and at nighttime can be exceedingly high. We speculate that this may have been due to resuspension of dust, infiltration, unknown sources, or a combination of these factors. The outdoor RSP levels measured just outside the houses (near ambient) were not correlated with indoor background levels and were higher than those reported by the ambient air quality monitoring network at the corresponding stations. More importantly, the outdoor levels measured in this study not only underestimated the daily-integrated exposure, but were also poorly correlated with it.


Improving health service delivery for women with diabetes in pregnancy in remote Australia: survey of care in the Northern Territory Diabetes in Pregnancy Partnership.
In the Northern Territory (NT), 38% of 3500 births each year are to Indigenous women, 80% of whom live in regional and remote areas. Compared with the general Australian population, rates of pre-existing type 2 diabetes in pregnancy are 10-fold higher and rates of gestational diabetes are 1.5-fold higher among Indigenous women. Current practices in screening for diabetes in pregnancy in remote Australia are not known. To assess current health service delivery for NT women with diabetes in pregnancy (DIP) by surveying healthcare professionals' views and practices in DIP screening and management. A cross-sectional survey of NT healthcare professionals providing clinical care for women with DIP was conducted based on pre-identified themes of communication, care-coordination, education, orientation and guidelines, logistics and access, and information technology. Of the 116 responders to the survey, 78% were primary healthcare professionals, 32% midwives and 25% general practitioners. High staff turnover was evident: of Central Australian professionals, only 33% (urban) and 18% (regional/remote) had been in their current position over 5 years. DIP screening was conducted at first antenatal visit by 66% and at 24-28-week gestation by 81%. Only 50% of respondents agreed that most women at their health service received appropriate care for DIP, and 41% of primary care practitioners were neutral or not confident in their skills to manage DIP. It is promising that many healthcare professionals report following new guidelines in conducting early pregnancy screening for DIP in high risk women. Several challenges were identified in healthcare delivery to a high risk population in remote Australia.


A proteomic approach for the discovery of early detection markers of hepatocellular carcinoma.
Individuals chronically infected with hepatitis B or C virus (HBV, HCV) are at high risk for the development of hepatocellular carcinoma (HCC), with disease progression occurring relentlessly over many years. The diagnosis of HCC usually occurs at late stages in the disease when there are few effective treatment options and the prognosis for patients with HCC is very poor. The long latency period, together with clearly identified at risk populations, provide opportunities for earlier detection that will allow more timely and effective treatment of this devastating cancer. We are using a proteomic approach to test the hypothesis that changes in the amount of certain serum polypeptides, or changes in their post-translational modifications, can be used to predict the onset of HCC. Advances in the standardization of two dimensional gel electrophoresis (2DE) coupled with computerized image analysis now permit the reproducible resolution of thousands of polypeptides per run. Serum polypeptides from individuals at different stages in the disease continuum are being resolved by 2DE to identify those that change with disease progression. Polypeptides found by this method can be further characterized by mass spectrometry. In addition, the potential for changes in the glycan structure of certain polypeptides to serve as a marker for disease progression can be explored. The proteomic approach is expected to liberate us from the need to "cherry pick" or guess the best biomarkers and let the data tell us which are the best indicators of disease. Information may also be gleaned about the pathobiology of the disease process.


Cognitive Interventions and Nutritional Supplements (The CINS Trial): A Randomized Controlled, Multicenter Trial Comparing a Brief Intervention With Additional Cognitive Behavioral Therapy, Seal Oil, and Soy Oil for Sick-Listed Low Back Pain Patients.
A randomized controlled trial. The aim of this study was to evaluate whether a tailored and manualized cognitive behavior therapy (CBT) or nutritional supplements of seal oil and soy oil had any additional benefits over a brief cognitive intervention (BI) on return to work (RTW). Brief intervention programs are clinically beneficial and cost-effective for patients with low back pain (LBP). CBT is recommended for LBP, but evidence on RTW is lacking. Seal oil has previously been shown to have a possible effect on muscle pain, but no randomized controlled trials have so far been carried out in LBP patients. Four hundred thirteen adults aged 18 to 60 years were included. Participants were sick-listed 2 to 10 months due to LBP. Main outcome was objectively ascertained work participation at 12-month follow-up. Participants were randomly assigned to BI (n = 100), BI and CBT (n = 103), BI and seal oil (n = 105), or BI and soy oil (n = 105). BI is a two-session cognitive, clinical examination program followed by two booster sessions, while the CBT program is a tailored, individual, seven-session manual-based treatment. At 12-month follow-up, 60% of the participants in the BI group, 50% in the BI and CBT group, 51% in the BI and seal oil group, and 53% in the BI and soy oil group showed reduced sick leave from baseline, and had either partly or fully RTW. The differences between the groups were not statistically significant (χ = 2.54, P = 0.47). There were no significant differences between the treatment groups at any of the other follow-up assessments either, except for a significantly lower sick leave rate in the BI group than the other groups during the first 3 months of follow-up (χ = 9.50, P = 0.02). CBT and seal oil had no additional benefits over a brief cognitive intervention on sick leave. The brief cognitive intervention alone was superior in facilitating a fast RTW. 2.


Center-surround velocity-based segmentation: Speed, eccentricity, and timing of visual stimuli interact to determine interocular dominance.
We used a novel method to capture the spatial dominance pattern of competing motion fields at rivalry onset. When rivaling velocities were different, the participants reported center-surround segmentation: The slower stimuli often dominated in the center while faster motion persisted along the borders. The size of the central static/slow field scaled with the stimulus size. The central dominance was time-locked to the static stimulus onset but was disrupted if the dynamic stimulus was presented later. We then used the same stimuli as masks in an interocular suppression paradigm. The local suppression strengths were probed with targets at different eccentricities. Consistent with the center-surround segmentation, target speed and location interacted with mask velocities. Specifically, suppression power of the slower masks was nonhomogenous with eccentricity, providing a potential explanation for center-surround velocity-based segmentation. This interaction of speed, eccentricity, and timing has implications for motion processing and interocular suppression. The influence of different masks on which target features get suppressed predicts that some "unconscious effects" are not generalizable across masks and, thus, need to be replicated under various masking conditions.


Relationship between mass transfer coefficient and liquid flow velocity in heterogenous biofilms using microelectrodes and confocal microscopy.
The relationship between local mass transfer coefficient and fluid velocity in heterogenous biofilms was investigated by combining microelectrodes and confocal scanning laser microscopy (CSLM). The biofilms were grown for up to 7 days and consisted of cell clusters separated by interstitial channels. Mass transfer coefficient depth profiles were measured at specific locations in the cell clusters and channels at average flow velocities of 2.3 and 4.0 cm/s. Liquid flow velocity profiles were measured in the same locations using a particle tracking technique. The velocity profiles showed that flow in the open channel was laminar. There was no flow at the top surface of the biofilm cell clusters but the mass transfer coefficient was 0.01 cm/s. At the same depth in a biofilm channel, the flow velocity was 0.3 cm/s and the mass transfer coefficient was 0.017 cm/s. The mass transfer coefficient profiles in the channels were not influenced by the surrounding cell clusters. Local flow velocities were correlated with local mass transfer coefficients using a semi-theoretical mass transfer equation. The relationship between the Sherwood number (Sh,) the Reynolds number (Re,) and the Schmidt number (Sc) was found using the experimental data to find the dimensionless empirical constants (n1, n2, and m) in the equation Sh = n(1) + n(2)Re(m) Sc(1/3). The values of the constants ranged from 1.45 to 2.0 for n(1), 0.22 to 0.28 for n(2), and 0.21 to 0.60 for m. These values were similar to literature values for mass transfer in porous media. The Sherwood number for the entire flow cell was 10 when the bulk flow velocity was 2.3 cm/s and 11 when the bulk flow velocity was 4.0 cm/s. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 681-688, 1997.


Effect of therapeutic footwear on foot reulceration in patients with diabetes: a randomized controlled trial.
Many people with diabetes experience lower-limb ulcers. Footwear has been implicated as a primary cause of foot ulcers, yet research is limited on the efficacy of shoe and insert combinations to prevent reulceration. To determine whether extra-depth and -width therapeutic shoes used with 2 types of inserts reduce reulceration in diabetic individuals with a history of foot ulcer. Randomized clinical trial of 400 diabetes patients with history of foot ulcer in 2 Washington State health care organizations who did not require custom shoes for foot deformity and were enrolled between August 1997 and December 1998 and followed up for 2 years. Data collected at regular intervals documented physical, foot, and diabetes characteristics; footwear use; foot lesions; and ulcers. Participants were randomly assigned to receive 3 pairs of therapeutic shoes and 3 pairs of customized medium-density cork inserts with a neoprene closed-cell cover (n = 121); to receive 3 pairs of therapeutic shoes and 3 pairs of prefabricated, tapered polyurethane inserts with a brushed nylon cover (n = 119); or to wear their usual footwear (controls; n = 160). Foot reulceration, compared among the 3 groups. Two-year cumulative reulceration incidence across the 3 groups was low: 15% in the cork-insert group, 14% in the prefabricated-insert group, and 17% in controls. In the intent-to-treat analysis, patients assigned to therapeutic shoes did not have a significantly lower risk of reulceration compared with controls (risk ratio [RR] for the cork-insert group, 0.88; 95% confidence interval [CI], 0.51-1.52 and RR the for prefabricated-insert group, 0.85; 95% CI, 0.48-1.48). All ulcer episodes in patients assigned to therapeutic shoes and 88% wearing nonstudy shoes occurred in patients with foot insensitivity. This study of persons without severe foot deformity does not provide evidence to support widespread dispensing of therapeutic shoes and inserts to diabetic patients with a history of foot ulcer. Study shoes and custom cork or preformed polyurethane inserts conferred no significant ulcer reduction compared with control footwear. This study suggests that careful attention to foot care by health care professionals may be more important than therapeutic footwear but does not negate the possibility that special footwear is beneficial in persons with diabetes who do not receive such close attention to foot care by their health care providers or in individuals with severe foot deformities.


Pure sensory stroke due to bilateral basal ganglion hemorrhage: a case report.
Bilateral simultaneous hypertensive intracerebral hemorrhages are extremely rare. The predisposing factors and pathophysiological mechanisms leading to the development of this picture are not well known. Possible mechanisms of simultaneous multiple hemorrhages include concomitant primary hemorrhages in two or more regions, or development of a second hemorrhage in another region shortly after the primary hemorrhage. The etiology of the cases presenting with bilateral simultaneous basal ganglion hemorrhage include migraine, lightning stroke, hyperglycemic hyperosmolar coma, hypertension and diabetic ketoacidosis coma. Bilateral simultaneous hemorrhage has a poor prognosis. The case of bilateral simultaneous intracerebral hemorrhage presented here had a good clinical course similar to a pure sensorial stroke.


Adult lymphomas in Lagos Nigeria: a fourteen year study.
we present a 14 year retrospective histopathological study of 92 cases of adult lymphomas in Lagos. The aim is to document the histologic types, age and sex distribution. The materials consisted of slides and paraffin embedded blocks of all cases of lymphoma in adults above the age of 16 years seen between 1991 and 2004 at the Morbid Anatomy Department of Lagos University Teaching Hospital Idi-Araba Lagos. Of ninety two cases of lymphoma studied, male and female patients accounted for 59(64%) and 33(36%) cases respectively, giving a M: F ratio of 1.8:1. The most frequently biopsied site is the cervical lymph node. Non-Hodgkin's lymphoma (NHL) which accounted for 60 cases occurred most frequently in the 46-55 years age group and gives a male: female ratio of 2:1. Intermediate grade, high grade and low grade variants of NHLs accounted for 39%, 34% and 27% respectively. Hodgkin's lymphoma mostly affected patients of younger age group, 25-35 years with a M:F ratio of 1.7:1. Mixed cellularity 17 (55%) was the commonest subtype of Hodgkin's lymphoma. Non-Hodgkin's lymphoma is commoner than Hodgkin's lymphoma. The age and sex distribution agrees with reports from other parts of Nigeria and Africa with minimal variations.


Two Cases of Fulminant Hepatic Failure from Amanita phalloides Poisoning Treated Additively by Homeopathy.
Intoxication with Amanita phalloides is associated with high morbidity and mortality. Treatment therapies include general support, toxin elimination, pharmacotherapy with agents such as the hepatoprotective agent silibinin, and, in extreme states, liver transplantation. Despite these therapeutic interventions, mortality remains relatively high. We present reports of 2 patients with severe hepatic failure following intoxication with Amanita phalloides. Both patients were admitted to the intensive care unit; 1 patient suffered from hepatic failure solely, and the second patient experienced severe 5-organ failure. In addition to conventional intensive care treatment, both patients were treated additively with classical homeopathy. The 2 patients survived without any residual pathological sequelae. Based on the 2 cases, including 1 extreme situation, we suggest that adjunctive homeopathic treatment has a role in the treatment of acute Amanita phalloides-induced toxicity following mushroom poisoning. Additional studies may clarify a more precise dosing regimen, standardization, and better acceptance of homeopathic medicine in the intensive care setting.


Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis. A risk to patients and health care workers.
To determine the factors associated with the development of multidrug-resistant tuberculosis among patients at a New York City Hospital and to investigate possible nosocomial transmission. A retrospective case-control study and tuberculin skin test survey. Twenty-three patients with tuberculosis whose isolates were resistant to at least isoniazid and rifampin (case patients) were compared with patients with tuberculosis whose isolates were susceptible to all agents tested (controls). Tuberculin skin test conversion rates were compared among health care workers assigned to wards where patients with tuberculosis were frequently or rarely admitted. A large, teaching hospital in New York City. Mycobacterium tuberculosis isolates from case patients and controls were typed by restriction fragment length polymorphism analysis. Case patients were younger (median age, 34 compared with 42 years; P = 0.006), more likely to be seropositive for HIV (21 of 23 compared with 11 of 23 patients; odds ratio, 11.5; 95% CI, 1.9 to 117), and more likely to have had a previous hospital admission within 7 months before the onset of tuberculosis (19 of 23 compared with 5 of 23 patients; odds ratio, 17.1; CI, 3.3 to 97), particularly on one ward (12 of 23 compared with 0 of 23 patients; odds ratio, undefined; P = 0.002). Health care workers assigned to wards housing case patients were more likely to have tuberculin skin test conversions than were health care workers assigned to other wards (11 of 32 compared with 1 of 47 health care workers; P less than 0.001). Few (6 of 23) case patients were placed in acid-fast bacilli isolation, and no rooms tested had negative pressure. Of 16 available multidrug-resistant isolates obtained from case patients, 14 had identical banding patterns by restriction fragment length polymorphism analysis. In contrast, M. tuberculosis isolates from controls with drug-susceptible tuberculosis had patterns distinct from each other and from those of case patients. These data suggest nosocomial transmission of multidrug-resistant tuberculosis occurred from patient to patient and from patient to health care worker and underscore the need for effective acid-fast bacilli isolation facilities and adherence to published infection control guidelines in health care institutions.


Protective Role of L-3-n-Butylphthalide in Cognitive Function and Dysthymic Disorders in Mouse With Chronic Epilepsy.
Epilepsy is a common neurological disease with recurrent seizures and neurobehavioral comorbidities, including cognitive impairment and psychiatric disorders. Recent studies suggest that L-3-n-butylphthalide (NBP), an extract from the seeds of Apium graveolens Linn. (Chinese celery), ameliorates cognitive dysfunction in ischemia and/or Alzheimer's disease animal models. However, little is known about the role of NBP in epilepsy and the associated comorbidities. Here, using a pilocarpine-induced chronic epileptic mouse model, we found that NBP supplement not only alleviated seizure severity and abnormal electroencephalogram, but also rescued cognitive and emotional impairments in these epileptic mice. The possible underlying mechanisms may be associated with the protective role of NBP in reducing neuronal loss and in restoring the expression of neural synaptic proteins such as postsynaptic density protein 95 (PSD95) and glutamic acid decarboxylase 65/67 (GAD65/67). In addition, NBP treatment increased the transcription of neuroprotective factors, brain-derived neurotrophic factor and Klotho. These findings suggest that NBP treatment may be a potential strategy for ameliorating epileptogenesis and the comorbidities of cognitive and psychological impairments.


Modification of myocardial substrate use as a therapy for heart failure.
Despite advances in treatment, chronic heart failure is still associated with significant morbidity and a poor prognosis. The scope for further advances based on additional neurohumoral blockade is small. Effective adjunctive therapies acting via a different cellular mechanism would, therefore, be attractive. Energetic impairment seems to contribute to the pathogenesis of heart failure. The findings from several studies have shown that the so-called metabolic agents could have potential as adjunctive therapies in heart failure. These agents cause a shift in the substrate used by the heart away from free fatty acids, the oxidation of which normally provides around 70% of the energy needed, towards glucose. The oxygen cost of energy generation is lessened when glucose is used as the substrate. In this review we aim to draw attention to the metabolic alteration in heart failure and we present evidence supporting the use of metabolic therapy in heart failure.


An RNA stem-loop structure directs hepatitis B virus genomic RNA encapsidation.
Selective encapsidation of hepatitis B virus (HBV) genomic RNA within cytoplasmic core particles requires recognition of the cis-encapsidation signal, (termed epsilon) located at the 5' end of genomic RNA. By transfecting plasmids expressing chimeric RNAs bearing HBV sequences fused to lacZ, we have mapped the minimal region of epsilon to the 5' 94 nucleotides (nt) of genomic RNA. Enzymatic probing of the RNA secondary structure in this region (by using either in vitro transcripts or RNA extracted from HBV core particles) reveals a stem-loop structure containing a lower stem, a 6-nt bulge, an upper stem with a single unpaired U residue, and a 6-nt loop. The functional role of this structure in encapsidation was explored by examining the effects of mutations in epsilon on encapsidation of RNA in vivo. These studies reveal that (i) in the lower stem, base pairing but not specific primary sequence is required for function; (ii) there is no requirement for base pairing in the lower portion of the upper stem, but base pairing elsewhere in this stem contributes to packaging efficiency; (iii) the presence of the 6-nt bulge, but not its primary sequence, is important for function; and (iv) specific nucleotide sequences in the loop and in regions of the upper stem are critical for RNA encapsidation.


Pre-dispersal seed predation in Primula veris: among-population variation in damage intensity and selection on flower number.
The geographic mosaic theory of co-evolution states that evolution of interactions is driven by geographical variation in interactions between species. We investigated whether the intensity of pre-dispersal seed predation differed among nine Primula veris populations over 5 years, and whether such differences lead to geographical variation in selection on flower number. Seed predation intensity differed significantly among years and populations, and it increased with canopy closure and decreased with the density of the field layer vegetation. Individuals in open habitats also produced the highest number of flowers. Moreover, the phenotypic selection on flower number differed among years and populations. In populations of closed habitats, with high seed predation pressure, the increased number of flowers was often correlated with an increased number of damaged capsules. However, an increased flower number did not result in fewer intact fruits due to seed predation in any population.


Vision-based tracking system for augmented reality to localize recurrent laryngeal nerve during robotic thyroid surgery.
We adopted a vision-based tracking system for augmented reality (AR), and evaluated whether it helped surgeons to localize the recurrent laryngeal nerve (RLN) during robotic thyroid surgery. We constructed an AR image of the trachea, common carotid artery, and RLN using CT images. During surgery, an AR image of the trachea and common carotid artery were overlaid on the physical structures after they were exposed. The vision-based tracking system was activated so that the AR image of the RLN followed the camera movement. After identifying the RLN, the distance between the AR image of the RLN and the actual RLN was measured. Eleven RLNs (9 right, 4 left) were tested. The mean distance between the RLN AR image and the actual RLN was 1.9 ± 1.5 mm (range 0.5 to 3.7). RLN localization using AR and vision-based tracking system was successfully applied during robotic thyroidectomy. There were no cases of RLN palsy. This technique may allow surgeons to identify hidden anatomical structures during robotic surgery.


Guidelines for Infection Control in the Urological Field, including Urinary Tract Management (revised second edition).
The Committee for the Development of Guidelines for Infection Control in the Urological Field, including Urinary Tract Management of the Japanese Urological Association, together with its systematic review team and external reviewers, have prepared a set of practice guidelines, an abridged version of which is published herein. These guidelines cover the following topics: (i) foundations of infection control, standard precautions, route-specific precautions, and occupational infection control (including vaccines); (ii) the relationship between urologists and infection control; (iii) infection control in urological wards and outpatient clinics; (iv) response to hepatitis B virus reactivation; (v) infection control in urological procedures and examinations; (vi) prevention of infections occurring in conjunction with medical procedures and examinations; (vii) responses to urinary tract tuberculosis and bacillus Calmette-Guérin; (viii) aseptic handling, cleaning, disinfection, and sterilization of urinary tract endoscopes (principles of endoscope manipulation, endoscope lumen cleaning, and disinfection); (ix) infection control in the operating room (principles of hand washing, preoperative rubbing methods, etc.); (x) prevention of needlestick and blood/bodily fluid exposure and response to accidental exposure; (xi) urinary catheter-associated urinary tract infection and purple urinary bag syndrome; and (xii) urinary catheter-associated urinary tract infections in conjunction with home care. In addressing these topics, the relevant medical literature was searched to the extent possible, and content was prepared for the purpose of providing useful information for clinical practice.