[The relationship between deaths that are avoidable with adequate health care and the implementation of the Unified Health System in Brazil].
To analyze the relationship between the occurrence of deaths that are avoidable with adequate health care and the reorganization of the Brazilian health care system between 1983 and 2002. This ecological study analyzed avoidable mortality in 117 municipalities of Brazil. The causes of death avoidable with adequate health care were grouped into three: (1) ones avoidable through early diagnosis and treatment, (2) ones avoidable with improvements in the quality of treatment and medical care, and (3) ischemic heart disease. To evaluate the association between avoidable mortality and reorganization of the health care system, the period under study was divided into two subperiods: from 1983 through 1992 and from 1993 through 2002 (respectively, before and after approval of the operational guideline that served as the reference for the organization of the Unified Health System (Sistema Unico de Saúde)). A negative binomial regression model that controlled for sex, age, geographic region, and socioeconomic conditions was used for the analysis. During the period analyzed, 1 854 165 individuals between 0 and 74 years old died from avoidable causes in the municipalities studied. The multivariate analysis showed that, for all three groups of avoidable causes, the risk of avoidable mortality was higher in the 1983-1992 subperiod than in the 1993-2002 subperiod. For the entire 1983-2002 period, the risk was higher for males than for females, especially with respect to ischemic heart disease. Younger populations had lower risk. Higher socioeconomic level reduced the risk of death from avoidable causes, except for ischemic heart disease. Our results suggest that in Brazil the decrease in avoidable mortality from the 1983-1992 subperiod to the 1993-2002 subperiod was partially due to the changes in the availability of and access to health services brought about by the reorganization of the Brazilian health care system.


Molecular detection of the oyster parasite Mikrocytos mackini, and a preliminary phylogenetic analysis.
The protistan parasite Mikrocytos mackini, the causative agent of Denman Island disease in the oyster Crassostrea gigas in British Columbia, Canada, is of wide concern because it can infect other oyster species and because its life cycle, mode of transmission, and origins are unknown. PCR and fluorescent in situ hybridization (FISH) assays were developed for M. mackini, the PCR assay was validated against standard histopathological diagnosis, and a preliminary phylogenetic analysis of the M. mackini small-subunit ribosomal RNA gene (SSU rDNA) was undertaken. A PCR designed specifically not to amplify host DNA generated a 544 bp SSU rDNA fragment from M. mackini-infected oysters and enriched M. mackini cell isolates, but not from uninfected control oysters. This fragment was confirmed by FISH to be M. mackini SSU rDNA. A M. mackini-specific PCR was then designed which detected 3 to 4x more M. mackini infections in 1056 wild oysters from Denman Island, British Columbia, than standard histopathology. Mikrocytos mackini prevalence estimates based on both PCR and histopathology increased (PCR from 4.4 to 7.4%, histopathology from 1.2 to 2.1%) when gross lesions were processed in addition to standard samples (i.e. transverse sections for histopathology, left outer palp DNA for PCR). The use of histopathology and tissue imprints plus PCR, and standard samples plus observed gross lesions, represented a 'total evidence' approach that provided the most realistic estimates of the true prevalence of M. mackini. Maximum parsimony and evolutionary distance phylogenetic analyses suggested that M. mackini may be a basal eukaryote, although it is not closely related to other known protistan taxa.


Association of magnetic resonance imaging findings and histologic diagnosis in dogs with nasal disease: 78 cases (2001-2004).
OBJECTIVE-To determine whether magnetic resonance imaging (MRI) features correlated with histologic diagnosis in dogs with nasal disease. DESIGN-Retrospective case series. ANIMALS-78 Dogs undergoing MRI for evaluation of nasal disease. PROCEDURES-Medical records and MRI reports of dogs were reviewed to identify MRI features associated with histologic diagnosis. Features evaluated were presence of a mass effect, frontal sinus involvement, sphenoid sinus involvement, maxillary recess involvement, nasopharyngeal infiltration by soft tissue, nasal turbinate destruction, vomer bone lysis, paranasal bone destruction, cribriform plate erosion, and lesion extent (ie, unilateral vs bilateral). RESULTS-33 Dogs had neoplastic disease, 38 had inflammatory rhinitis, and 7 had fungal rhinitis. Lesion extent was not significantly associated with histologic diagnosis. Absence of a mass effect was significantly associated with inflammatory disease. However, presence of a mass was not specific for neoplasia. In dogs with evidence of a mass on magnetic resonance (MR) images, nasal turbinate destruction, frontal sinus invasion, and maxillary recess invasion were not useful in distinguishing neoplastic from nonneoplastic disease, but cribriform plate erosion, vomer bone lysis, paranasal bone destruction, sphenoid sinus invasion, and nasopharyngeal invasion were. CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that in dogs with nasal disease, the lack of a mass effect on MR images was significantly associated with inflammatory disease. In dogs with a mass effect on MR images, vomer bone lysis, cribriform plate erosion, paranasal bone destruction, sphenoid sinus invasion by a mass, and nasopharyngeal invasion by a mass were significantly associated with a diagnosis of neoplasia.


Intermittent preventive treatment for malaria among children in a refugee camp in Northern Uganda: lessons learned.
Northern Uganda hosts a large population of refugees from South Sudan, and malaria is one of the major health problems in the area. In 2015, intermittent preventive treatment for malaria (IPTc) was implemented in two refugee camps among children aged 6 months to 14 years. Three distributions of dihydroartemisinin-piperaquine (DP) were conducted at 8-week intervals. The first dose was directly administered at IPTc distribution sites and the second and third doses were given to caregivers to administer at home. A multi-faceted evaluation was implemented, including coverage surveys, malaria prevalence surveys, reinforced surveillance, and pharmacovigilance. Programme coverage exceeded 90% during all three distributions with a total of 40,611 participants. Compared to same period during the previous year (only available data), the incidence of malaria in the target populations was reduced (IRR 0.73, 95% CI 0.69-0.77 among children under 5 years old; IRR 0.70, 95% CI 0.67-0.72 among children aged 5-14 years). Among those not targeted for intervention, the incidence between the 2 years increased (IRR 1.49, 95% CI 1.42-1.56). Cross-sectional surveys showed a prevalence of parasitaemia (microscopy or PCR) of 12.9-16.4% (95% CI 12.6-19.3) during the intervention, with the highest prevalence among children aged 5-14 years, but with a large increase 8 weeks after the final distribution. A total of 57 adverse events were reported during the intervention period, including one severe adverse event (death from varicella). Adverse events were of mild to moderate severity, and were mainly dermatologic and gastrointestinal. This is the first documentation of an IPTc programme in a refugee camp. The positive impact of DP on the incidence of malaria, together with its favourable safety profile, should lead to further use of IPTc in similar settings. Expanding coverage groups and decreasing intervals between distributions might provide more benefit, but would need to be balanced with the operational implications of a broader, more frequent distribution schedule.


Advanced LSI-based amperometric sensor array with light-shielding structure for effective removal of photocurrent and mode selectable function for individual operation of 400 electrodes.
We have developed a large-scale integrated (LSI) complementary metal-oxide semiconductor (CMOS)-based amperometric sensor array system called "Bio-LSI" as a platform for electrochemical bio-imaging and multi-point biosensing with 400 measurement points. In this study, we newly developed a Bio-LSI chip with a light-shield structure and a mode-selectable function with the aim of extending the application range of Bio-LSI. The light shield created by the top metal layer of the LSI chip significantly reduces the noise generated by the photocurrent, whose value is less than 1% of the previous Bio-LSI without the light shield. The mode-selectable function enables the individual operation of 400 electrodes in off, electrometer, V1, and V2 mode. The off-mode cuts the electrode from the electric circuit. The electrometer-mode reads out the electrode potential. The V1-mode and the V2-mode set the selected sensor electrode at two different independent voltages and read out the current. We demonstrated the usefulness of the mode-selectable function. First, we displayed a dot picture based on the redox reactions of 2.0 mM ferrocenemethanol at 400 electrodes by applying two different independent voltages using the V1 and V2 modes. Second, we carried out a simultaneous detection of O2 and H2O2 using the V1 and V2 modes. Third, we used the off and V1 modes for the modification of the osmium-polyvinylpyridine gel polymer containing horseradish peroxidase (Os-HRP) at the selected electrodes, which act as sensors for H2O2. These results confirm that the advanced version of Bio-LSI is a promising tool that can be applied to a wide range of analytical fields.


Analysis of existing international policy evidence in public health genomics: mapping exercise.
In the last decades we have seen a constant growth in the fields of science related to the use of genome-based health information. However, there is a gap between basic science research and the Public Health everyday practice. For a successful introduction of genome-based technologies policy actions on the international level are needed. This work represents the initial stage of the PHGEN II (Public Health Genomics European Network II) project. In order to prepare a base for bridging genomics and Public Health, an inventory study of the existing legislative base dealing with controversies of genome-based knowledge was conducted. The work results in the mapping of the most and the least legislatively covered areas and some preliminary conclusions about the existing gaps. The collection of the evidence-based policies was done through the PHGEN II project. The mapping covered the meta-level (international, European general guidelines). The expert opinion of the partners of the project was required to reflect on and grade the collected evidence. AN ANALYSIS OF THE EVIDENCE WAS MADE BY THE AREA OF COVERAGE: using the list of important policy areas for successful introduction of genome-based technologies into Public Health and the Public Health Genomics Wheel (originally Public Health Wheel developed by Institute of Medicine). Severe inequalities in coverage of important issues of Public Health Genomics were found. The most attention was paid to clinical utility and clinical validity of the screening and the protection of human subjects. Important areas such as trade agreements, Public Health Genomics literacy, insurance issues, behaviour modification in response to genomics results etc. were paid less attention to. For the successful adoption of new technologies on the Public Health level the focus should be not only on the translation to clinical practice, but the translation from bench to Public Health policy and back. Coherent and consistent coverage of all aspects of the translation of genome based information and technologies is of outmost importance.


A novel approach for the characterization of tundra wetland regions with C-band SAR satellite data.
A circumpolar representative and consistent wetland map is required for a range of applications ranging from upscaling of carbon fluxes and pools to climate modelling and wildlife habitat assessment. Currently available data sets lack sufficient accuracy and/or thematic detail in many regions of the Arctic. Synthetic aperture radar (SAR) data from satellites have already been shown to be suitable for wetland mapping. Envisat Advanced SAR (ASAR) provides global medium-resolution data which are examined with particular focus on spatial wetness patterns in this study. It was found that winter minimum backscatter values as well as their differences to summer minimum values reflect vegetation physiognomy units of certain wetness regimes. Low winter backscatter values are mostly found in areas vegetated by plant communities typically for wet regions in the tundra biome, due to low roughness and low volume scattering caused by the predominant vegetation. Summer to winter difference backscatter values, which in contrast to the winter values depend almost solely on soil moisture content, show expected higher values for wet regions. While the approach using difference values would seem more reasonable in order to delineate wetness patterns considering its direct link to soil moisture, it was found that a classification of winter minimum backscatter values is more applicable in tundra regions due to its better separability into wetness classes. Previous approaches for wetland detection have investigated the impact of liquid water in the soil on backscatter conditions. In this study the absence of liquid water is utilized. Owing to a lack of comparable regional to circumpolar data with respect to thematic detail, a potential wetland map cannot directly be validated; however, one might claim the validity of such a product by comparison with vegetation maps, which hold some information on the wetness status of certain classes. It was shown that the Envisat ASAR-derived classes are related to wetland classes of conventional vegetation maps, indicating its applicability; 30% of the land area north of the treeline was identified as wetland while conventional maps recorded 1-7%.


Towards new sources of resistance to the currant-lettuce aphid (Nasonovia ribisnigri).
Domesticated lettuce varieties encompass much morphological variation across a range of crop type groups, with large collections of cultivars and landrace accessions maintained in genebanks. Additional variation not captured during domestication, present in ancestral wild relatives, represents a potentially rich source of alleles that can deliver to sustainable crop production. However, these large collections are difficult and costly to screen for many agronomically important traits. In this paper, we describe the generation of a diversity collection of 96 lettuce and wild species accessions that are amenable to routine phenotypic analysis and their genotypic characterization with a panel of 682 newly developed expressed sequence tag (EST)-linked KASP™ single nucleotide polymorphism (SNP) markers that are anchored to the draft Lactuca sativa genome assembly. To exemplify the utility of these resources, we screened the collection for putative sources of resistance to currant-lettuce aphid (Nasonovia ribisnigri) and carried out association analyses to look for potential SNPs linked to resistance.


Case of cryptic malaria.
We report a case of falciparum malaria in a renal transplant patient with no history of foreign travel. Three weeks previously she had been a hospital inpatient with cellulitis and had stayed on the same ward as a man with falciparum malaria acquired in Nigeria. There were no cases of malaria in other patients on the ward at the same time. The parasites from the two cases were genotypically indistinguishable. Despite a thorough investigation, reviewed by an expert external panel, no clear route of infection between the cases was identified. Patients with malaria should be considered highly infectious by the parenteral route. They should be managed with the infection control precautions used for patients with bloodborne virus infections. Our case reinforces the need for high levels of compliance with universal infection control procedures.


Negative refraction at visible frequencies.
Nanofabricated photonic materials offer opportunities for crafting the propagation and dispersion of light in matter. We demonstrate an experimental realization of a two-dimensional negative-index material in the blue-green region of the visible spectrum, substantiated by direct geometric visualization of negative refraction. Negative indices were achieved with the use of an ultrathin Au-Si3N4-Ag waveguide sustaining a surface plasmon polariton mode with antiparallel group and phase velocities. All-angle negative refraction was observed at the interface between this bimetal waveguide and a conventional Ag-Si3N4-Ag slot waveguide. The results may enable the development of practical negative-index optical designs in the visible regime.


Novel low temperature setting nanocrystalline calcium phosphate cements for bone repair: osteoblast cellular response and gene expression studies.
Low temperature setting calcium phosphate cements (CPC) formed from reactive calcium phosphate precursors are receiving great attention in the fields of orthopaedics and tissue engineering. The purpose of this study was to evaluate the mechanical properties and osteocompatibility of a novel calcium deficient hydroxyapatite (CDSHA) with a Ca/P ratio of 1.6 developed in our laboratories and compare it to a previously developed calcium deficient hydroxyapatite (CDHA) with a Ca/P ratio of 1.5. The results demonstrated that the calcium-deficient hydroxyapatites (HA) formed from the CPCs were similar to biological HA at physiological temperature and the elastic moduli of CDHA and CDSHA were found to be 174.42 +/- 20.41 MPa (p < 0.05) and 115.86 +/- 24.8 MPa (p < 0.05), respectively. The surface morphologies of the two calcium deficient HA's formed were identical with a micro/nano porous structure as evidenced from SEM. The cellular proliferation on CDHA, and CDSHA, was comparable to the control, tissue culture polystyrene (TCPS) (p < 0.05). Alkaline phosphatase activity was significantly elevated on CDHA and CDSHA matrices at early time points when compared with the control (TCPS) (p < 0.05). Osteoblast cells gene expression on CDHA, and CDSHA showed type I collagen, alkaline phosphatase, osteocalcin, and osteopontin activity at both 7 and 14 days of culture. Thus, novel calcium-deficient HAs, CDHA, and CDSHA formed at low temperature are promising candidates for orthopaedic applications based on their ability to promote osteoblast cell adhesion and gene expression in vitro.


Structural effects of modified ribonucleotides and magnesium in transfer RNAs.
Modified nucleotides are ubiquitous and important to tRNA structure and function. To understand their effect on tRNA conformation, we performed a series of molecular dynamics simulations on yeast tRNAPhe and tRNAinit, Escherichia coli tRNAinit and HIV tRNALys. Simulations were performed with the wild type modified nucleotides, using the recently developed CHARMM compatible force field parameter set for modified nucleotides (J. Comput. Chem.2016, 37, 896), or with the corresponding unmodified nucleotides, and in the presence or absence of Mg2+. Results showed a stabilizing effect associated with the presence of the modifications and Mg2+ for some important positions, such as modified guanosine in position 37 and dihydrouridines in 16/17 including both structural properties and base interactions. Some other modifications were also found to make subtle contributions to the structural properties of local domains. While we were not able to investigate the effect of adenosine 37 in tRNAinit and limitations were observed in the conformation of E. coli tRNAinit, the presence of the modified nucleotides and of Mg2+ better maintained the structural features and base interactions of the tRNA systems than in their absence indicating the utility of incorporating the modified nucleotides in simulations of tRNA and other RNAs.


Variation in breast cancer hormone receptor and HER2 levels by etiologic factors: a population-based analysis.
Evidence suggests that breast cancer hormone receptor status varies by etiologic factors, but studies have been inconsistent. In a population-based case-control study in Poland that included 2,386 cases and 2,502 controls, we assessed ER-alpha and PR status of tumors based on clinical records according to etiologic exposure data collected via interview. For 842 cancers, we evaluated ER-alpha, ER-beta, PR and HER2 levels by semiquantitative microscopic scoring of immunostained tissue microarrays and a quantitative immunofluorescence method, automated quantitative analysis (AQUAtrade mark). We related marker levels in tumors to etiologic factors, using standard regression models and novel statistical methods, permitting adjustment for both correlated tumor features and exposures. Results obtained with different assays were generally consistent. Receptor levels varied most significantly with body mass index (BMI), a factor that was inversely related to risk among premenopausal women and directly related to risk among postmenopausal women with larger tumors. After adjustment for correlated markers, exposures and pathologic characteristics, PR and HER2 AQUA levels were inversely related to BMI among premenopausal women (p-trend = 0.01, both comparisons), whereas among postmenopausal women, PR levels were associated directly with BMI (p-trend = 0.002). Among postmenopausal women, analyses demonstrated that BMI was related to an interaction of PR and HER2: odds ratio (OR) = 0.86 (95% CI = 0.69-1.07) for low PR and HER2 expression vs. OR = 1.78 (95% CI = 1.25-2.55) for high expression (p-heterogeneity = 0.001). PR and HER2 levels in breast cancer vary by BMI, suggesting a heterogeneous etiology for tumors related to these markers.


How to protect half of Earth to ensure it protects sufficient biodiversity.
It is theoretically possible to protect large fractions of species in relatively small regions. For plants, 85% of species occur entirely within just over a third of the Earth's land surface, carefully optimized to maximize the species captured. Well-known vertebrate taxa show similar patterns. Protecting half of Earth might not be necessary, but would it be sufficient given the current trends of protection? The predilection of national governments is to protect areas that are "wild," that is, typically remote, cold, or arid. Unfortunately, those areas often hold relatively few species. Wild places likely afford the easier opportunities for the future expansion of protected areas, with the expansion into human-dominated landscapes the greater challenge. We identify regions that are not currently protected, but that are wild, and consider which of them hold substantial numbers of especially small-ranged vertebrate species. We assess how successful the strategy of protecting the wilder half of Earth might be in conserving biodiversity. It is far from sufficient. (Protecting large wild places for reasons other than biodiversity protection, such as carbon sequestration and other ecosystem services, might still have importance.) Unexpectedly, we also show that, despite the bias in establishing large protected areas in wild places to date, numerous small protected areas are in biodiverse places. They at least partially protect significant fractions of especially small-ranged species. So, while a preoccupation with protecting large areas for the sake of getting half of Earth might achieve little for biodiversity, there is more progress in protecting high-biodiversity areas than currently appreciated. Continuing to prioritize the right parts of Earth, not just the total area protected, is what matters for biodiversity.


Acute brachial diplegia due to Lyme disease.
to describe acute brachial diplegia as the initial manifestation of Lyme disease. bilateral, predominantly motor, cervical radiculoplexus neuropathy, the "dangling arm syndrome," has not been reported as a complication of acute Lyme infection. retrospective series of 5 patients from 2 tertiary neuromuscular centers. there were 4 men and 1 woman with an average age of 69 years. One recalled a tick bite, and preceding constitutional symptoms included headache (2) and fever, arthralgias, and fatigue in 1 patient each. Proximal arm weakness and acute pain developed within 3 weeks from onset; pain was bilateral in 3 patients and unilateral in 2 patients, and was described as severe throbbing. Arm weakness was bilateral at onset in 3 patients, and right sided in 2 patients followed by spread to the left arm within days. All the patients had weakness in the deltoid and biceps that was 3/5 or less (Medical Research Council scale), with variable weakness of the triceps and wrist extensors; 1 patient had a flail right arm and moderate (4/5) weakness of the proximal left arm muscles. Light touch was normal in the regions of weakness, and 1 patient had mildly reduced pin sensation over the forearm. Serum IgM Lyme titers were elevated in all the patients and were detected in the cerebrospinal fluid in 4 tested patients. The cerebrospinal fluid protein ranged between 135 and 176 mg/dL with lymphocytic pleocytosis (range, 42 to 270 cells). Electrodiagnostic studies showed normal median and ulnar motor potentials with asymmetrically reduced sensory amplitudes in the median (4), ulnar (3), and radial, and lateral antebrachial cutaneous potentials in 1 patient each. Two patients had acute denervation in the cervical or proximal arm muscles. There was full recovery after antibiotic therapy in 4 patients and considerable improvement in 1 patient after 2 months. acute brachial diplegia is a rare manifestation of acute Lyme infection and responds promptly to antibiotic therapy.


Prion proteins: physiological functions and role in neurological disorders.
Stanley Prusiner was the first to promote the concept of misfolded proteins as a cause for neurological disease. It has since been shown by him and other investigators that the scrapie isoform of prion protein (PrP(Sc)) functions as an infectious agent in numerous human and non-human disorders of the central nervous system (CNS). Interestingly, other organ systems appear to be less affected, and do not appear to lead to major co-morbidities. The physiological function of the endogenous cellular form of the prion protein (PrP(C)) is much less clear. It is intriguing that PrP(c) is expressed on most tissues in mammals, suggesting not only biological functions outside the CNS, but also a role other than the propagation of its misfolded isotype. In this review, we summarize accumulating in vitro and in vivo evidence regarding the physiological functions of PrP(C) in the nervous system, as well as in lymphoid organs.


Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis.
Rheumatoid arthritis is associated with increased cardiovascular mortality and morbidity. To assess the effect of severe extra-articular rheumatoid arthritis (ExRA) manifestations on the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis. Patients with ExRA (n = 81) according to predefined criteria and controls (n = 184) without evidence of extra-articular disease were identified from a large research database of patients with rheumatoid arthritis. In a structured review of the medical records, the occurrence and the date of onset of clinically diagnosed CVD events were noted. Cox proportional hazards models were used to estimate the effect of ExRA on the risk of first ever CVD events after the diagnosis of rheumatoid arthritis. ExRA manifestations were modelled as time-dependent covariates, with adjustment for age, sex and smoking at the diagnosis of rheumatoid arthritis. Onset of erosive disease and rheumatoid factor seropositivity were entered as time-dependent variables. Patients were followed until onset of CVD, death or loss to follow-up. ExRA was associated with a significantly increased risk of first ever CVD events (p<0.001), and also with an increased risk of new-onset coronary artery disease, adjusted for age, sex and smoking (hazard ratio (HR): 3.16; 95% confidence interval (95% CI: 1.58 to 6.33). The association between ExRA and any first ever CVD event remained significant when controlling for age, sex, smoking, rheumatoid factor and erosive disease (HR: 3.25; 95% CI: 1.59 to 6.64). Severe ExRA manifestations are associated with an increased risk of CVD events in patients with rheumatoid arthritis. This association is not due to differences in age, sex, smoking, rheumatoid factor or erosive joint damage. It is suggested that systemic extra-articular disease is a major determinant of cardiovascular morbidity in rheumatoid arthritis.


Diode-end-pumped continuously tunable single frequency Tm, Ho:LLF laser at 2.06 μm.
We report on a laser diode-end-pumped continuously tunable single frequency Tm, Ho:LLF laser near room temperature. For transmission of 5%, the maximum single frequency output power of 221 mW at 2064.4 nm was obtained by using two uncoated etalons. The single frequency Tm, Ho:LLF laser operated on the fundamental transverse mode with an M2 factor of 1.13, and the output frequency could be tuned continuously near 1.5 GHz by angle tuning only of the 1 mm thick etalon. Furthermore, the influence of output coupler transmission on the laser performance was also investigated. The single frequency laser can be used as a seed laser for coherent Doppler lidar and differential absorption lidar systems.


Low Diastolic Blood Pressure and Cognitive Decline in Korean Elderly People: The Korean Longitudinal Study on Cognitive Aging and Dementia.
Cardiovascular diseases are representative risk factors for the onset of cognitive decline. The purpose of this study was to confirm the relationship between diastolic blood pressure and cognitive function in elderly people in Korea. Data from subjects who were enrolled in the prospective Korean Longitudinal Study on Cognitive Aging and Dementia were used in this study. Data from 701 subjects whose diastolic blood pressure range did not change (≤79 mm Hg or ≥80 mm Hg) over 2 years were analyzed. To analyze the differences in cognitive function between the groups at the 2-year follow-up, an analysis of covariance was performed with covariates, which were significantly different between the two groups, and the baseline cognitive function. Significant differences were observed between the two groups, and the mean scores on the constructional praxis (η2=0.010) and word list recall tests (η2=0.018) in the diastolic blood pressure ≥80 mm Hg group were higher than those in the diastolic blood pressure ≤79 mm Hg group at the 2-year follow-up. These results indicate that maintaining a DBP below 79 mm Hg presents a greater risk of cognitive decline in Korean elderly people.


Effects of ecological engineered oxygenation on the bacterial community structure in an anoxic fjord in western Sweden.
Oxygen-depleted bodies of water are becoming increasingly common in marine ecosystems. Solutions to reverse this trend are needed and under development, for example, by the Baltic deep-water OXygenation (BOX) project. In the framework of this project, the Swedish Byfjord was chosen for a pilot study, investigating the effects of an engineered oxygenation on long-term anoxic bottom waters. The strong stratification of the water column of the Byfjord was broken up by pumping surface water into the deeper layers, triggering several inflows of oxygen-rich water and increasing oxygen levels in the lower water column and the benthic zone up to 110 μmol l(-1).We used molecular ecologic methods to study changes in bacterial community structure in response to the oxygenation in the Byfjord. Water column samples from before, during and after the oxygenation as well as from two nearby control fjords were analyzed. Our results showed a strong shift in bacterial community composition when the bottom water in the Byfjord became oxic. Initially dominant indicator species for oxygen minimum zones such as members of the SUP05 clade declined in abundance during the oxygenation event and nearly vanished after the oxygenation was accomplished. In contrast, aerobic species like SAR11 that initially were restricted to surface waters could later be detected deep into the water column. Overall, the bacterial community in the formerly anoxic bottom waters changed to a community structure similar to those found in oxic waters, showing that an engineered oxygenation of a large body of anoxic marine water is possible and emulates that of a natural oxygenation event.


Overview on the endoscopic treatment for obesity: A review.
Obesity rates have increased, and so has the need for more specific treatments. This trend has raised interest in non-surgical weight loss techniques that are novel, safe, and straightforward. Thus, the present review describes the endoscopic bariatric treatment for obesity, its most recent supporting data, the questions it raises, and its future directions. Various endoscopic bariatric therapies for weight reduction, such as intragastric balloons (IGBs), aspiration therapy (AT), small bowel endoscopy, endoscopic sleeve gastroplasty, endoluminal procedures, malabsorption endoscopic procedures, and methods of regulating gastric emptying, were explored through literature sourced from different databases. IGBs, AT, and small bowel endoscopy have short-term effects with a possibility of weight regain. Minor adverse events have occurred; however, all procedures reduce weight. Vomiting and nausea are common side effects, although serious complications have also been observed.


Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid.
Huntington's disease (HD) is an autosomal dominant neurological disorder characterized by progressive chorea, cognitive impairment and emotional disturbance. The disease usually occurs in midlife and symptoms progress inexorably to mental and physical incapacitation. It has been postulated that an excitotoxin is involved in the pathogenesis of HD. Schwarcz and colleagues have shown that quinolinic acid (QA) can produce axon-sparing lesions similar to those observed in HD. The lesions result in a depletion of neurotransmitters contained within striatal spiny neurones, for example gamma-aminobutyric acid (GABA), while dopamine is unaffected. Recently, we and others have demonstrated that in HD striatum there is a paradoxical 3-5-fold increase in both somatostatin and neuropeptide Y which is attributable to selective preservation of a subclass of striatal aspiny neurones in which these peptides are co-localized. In the present study we demonstrate that lesions due to quinolinic acid closely resemble those of HD as they result in marked depletions of both GABA and substance P, with selective sparing of somatostatin/neuropeptide Y neurones. Lesions produced by kainic acid (KA), ibotenic acid (IA) and N-methyl-D-aspartate (MeAsp) were unlike those produced by QA, as they affected all cell types without sparing somatostatin/neuropeptide Y neurones. These results suggest that QA or a similar compound could be responsible for neuronal degeneration in HD.


Cost-Effectiveness of Dengue Vaccination Programs in Brazil.
AbstractThe first approved dengue vaccine, CYD-TDV, a chimeric, live-attenuated, tetravalent dengue virus vaccine, was recently licensed in 13 countries, including Brazil. In light of recent vaccine approval, we modeled the cost-effectiveness of potential vaccination policies mathematically based on data from recent vaccine efficacy trials that indicated that vaccine efficacy was lower in seronegative individuals than in seropositive individuals. In our analysis, we investigated several vaccination programs, including routine vaccination, with various vaccine coverage levels and those with and without large catch-up campaigns. As it is unclear whether the vaccine protects against infection or just against disease, our model incorporated both direct and indirect effects of vaccination. We found that in the presence of vaccine-induced indirect protection, the cost-effectiveness of dengue vaccination decreased with increasing vaccine coverage levels because the marginal returns of herd immunity decreases with vaccine coverage. All routine dengue vaccination programs that we considered were cost-effective, reducing dengue incidence significantly. Specifically, a routine dengue vaccination of 9-year-olds would be cost-effective when the cost of vaccination per individual is less than $262. Furthermore, the combination of routine vaccination and large catch-up campaigns resulted in a greater reduction of dengue burden (by up to 93%) than routine vaccination alone, making it a cost-effective intervention as long as the cost per course of vaccination is $255 or less. Our results show that dengue vaccination would be cost-effective in Brazil even with a relatively low vaccine efficacy in seronegative individuals.


Socioeconomic Predictors of the Employment of Migrant Care Workers by Italian Families Assisting Older Alzheimer's Disease Patients: Evidence From the Up-Tech Study.
The availability of family caregivers of older people is decreasing in Italy as the number of migrant care workers (MCWs) hired by families increases. There is little evidence on the influence of socioeconomic factors in the employment of MCWs. We analyzed baseline data from 438 older people with moderate Alzheimer's disease (AD), and their family caregivers enrolled in the Up-Tech trial. We used bivariate analysis and multilevel regressions to investigate the association between independent variables-education, social class, and the availability of a care allowance-and three outcomes-employment of a MCW, hours of care provided by the primary family caregiver, and by the family network (primary and other family caregivers). The availability of a care allowance and the educational level were independently associated with employing MCWs. A significant interaction between education and care allowance was found, suggesting that more educated families are more likely to spend the care allowance to hire a MCW. Socioeconomic inequalities negatively influenced access both to private care and to care allowance, leading disadvantaged families to directly provide more assistance to AD patients. Care allowance entitlement needs to be reformed in Italy and in countries with similar long-term care and migration systems.


Traditional Applications of Tannin Rich Extracts Supported by Scientific Data: Chemical Composition, Bioavailability and Bioaccessibility.
Tannins are polyphenolic compounds historically utilized in textile and adhesive industries, but also in traditional human and animal medicines or foodstuffs. Since 20th-century, advances in analytical chemistry have allowed disclosure of the chemical nature of these molecules. The chemical profile of extracts obtained from previously selected species was investigated to try to establish a bridge between traditional background and scientific data. The study of the chemical composition of these extracts has permitted us to correlate the presence of tannins and other related molecules with the effectiveness of their apparent uses. The revision of traditional knowledge paired with scientific evidence may provide a supporting background on their use and the basis for developing innovative pharmacology and food applications based on formulations using natural sources of tannins. This traditional-scientific approach can result useful due to the raising consumers' demand for natural products in markets, to which tannin-rich extracts may pose an attractive alternative. Therefore, it is of interest to back traditional applications with accurate data while meeting consumer's acceptance. In this review, several species known to contain high amounts of tannins have been selected as a starting point to establish a correlation between their alleged traditional use, tannins content and composition and potential bioaccessibility.


Sequential formation of ion pairs during activation of a sodium channel voltage sensor.
Electrical signaling in biology depends upon a unique electromechanical transduction process mediated by the S4 segments of voltage-gated ion channels. These transmembrane segments are driven outward by the force of the electric field on positively charged amino acid residues termed "gating charges," which are positioned at three-residue intervals in the S4 transmembrane segment, and this movement is coupled to opening of the pore. Here, we use the disulfide-locking method to demonstrate sequential ion pair formation between the fourth gating charge in the S4 segment (R4) and two acidic residues in the S2 segment during activation. R4 interacts first with E70 at the intracellular end of the S2 segment and then with D60 near the extracellular end. Analysis with the Rosetta Membrane method reveals the 3-D structures of the gating pore as these ion pairs are formed sequentially to catalyze the S4 transmembrane movement required for voltage-dependent activation. Our results directly demonstrate sequential ion pair formation that is an essential feature of the sliding helix model of voltage sensor function but is not compatible with the other widely discussed gating models.


Knowledge and practice of emergency contraception among female undergraduates in South eastern Nigeria.
Unintended pregnancy remains a major challenge to the reproductive health of women especially in the developing countries. It is a major reason for unsafe abortion, a major contributor to maternal mortality. This study was designed to assess the knowledge and practice of emergency contraception among female non-medical undergraduates. In this cross sectional observational study, 675 female non medical undergraduates were interviewed using pretested semi structured questionnaire to assess their knowledge and experience with emergency contraception. Data was analysed using SPSS version 17 (SPSS, Chicago, IL, USA). Data were presented as percentages and tables. Associaton between variables was tested using the χ(2) test. Only 51.6% (348/675) of the respondents reported knowledge of emergency contraception. Being sexually active, use of regular family planning methods and having an extra risk for unintended pregnancy were factors that significantly influenced knowledge. Only 45.7% (159/348) knew the correct methods (Postinor-2, combined oral contraceptive and intra uterine contraceptive device), 37.9% (132/348) practiced any method with about half of them using the correct methods. There is poor basic knowledge of emergency contraception among these female undergraduates in south eastern Nigeria. A sizeable number of them depend on unconventional methods for emergency contraception. We recommend the introduction of formal lessons on emergency contraception and other reproductive health issues into the Nigerian undergraduate curriculum.


Reduced argininosuccinate synthetase is a predictive biomarker for the development of pulmonary metastasis in patients with osteosarcoma.
Pulmonary metastasis is the most significant prognostic determinant for osteosarcoma, but methods for its prediction and treatment have not been established. Using oligonucleotide microarrays, we compared the global gene expression of biopsy samples between seven osteosarcoma patients who developed pulmonary metastasis within 4 years after neoadjuvant chemotherapy and curative resection, and 12 patients who did not relapse. We identified argininosuccinate synthetase (ASS) as a gene differentially expressed with the highest statistical significance (Welch's t test, P = 2.2 x 10(-5)). Immunohistochemical analysis of an independent cohort of 62 osteosarcoma cases confirmed that reduced expression of ASS protein was significantly correlated with the development of pulmonary metastasis after surgery (log-rank test, P < 0.05). Cox regression analysis revealed that ASS was the sole significant predictive factor (P = 0.039; hazard ratio, 0.319; 95% confidence interval, 0.108-0.945). ASS is one of the enzymes required for the production of a nonessential amino acid, arginine. We showed that osteosarcoma cells lacking ASS expression were auxotrophic for arginine and underwent G(0)-G(1) arrest in arginine-free medium, suggesting that an arginine deprivation therapy could be effective in patients with osteosarcoma. Recently, phase I and II clinical trials in patients with melanoma and hepatocellular carcinoma have shown the safety and efficacy of plasma arginine depletion by stabilized arginine deiminase. Our data indicate that in patients with osteosarcoma, reduced expression of ASS is not only a novel predictive biomarker for the development of metastasis, but also a potential target for pharmacologic intervention.


Voltage waveform effects on output and penetration of W- and Mo-anode mammographic tubes.
The output and half-value thickness (HVT) for arbitrary voltage waveforms can be calculated if the variation of both quantities with voltage is known under constant-potential (ripple-free) conditions. An apparatus to study this variation is described. It permits measurements of output and HVT with a Si(Li) spectrometer under conditions equivalent to constant-potential operation; it uses mechanical or electronic gating to limit observations to constant-potential operation; it uses mechanical or electronic gating to limit observations to short periods near the peaks of a sinusoidal waveform. For W anodes both HVT and output are found to follow simple power laws, while polynomial functions of voltage are needed for Mo anodes. Calculations based on these data agree well with experiments in which various ripples are simulated by altering the gating interval. For Mo anodes, the output increases as the ripple decreases, but the HVT changes very little. For W anodes both quantities decrease when the ripple increases. The implications in mammography are briefly discussed.


Conserved role for the Drosophila Pax6 homolog Eyeless in differentiation and function of insulin-producing neurons.
Insulin/insulin-like growth factor (IGF) signaling constitutes an evolutionarily conserved pathway that controls growth, energy homeostasis, and longevity. In Drosophila melanogaster, key components of this pathway are the insulin-like peptides (Dilps). The major source of Dilps is a cluster of large neurons in the brain, the insulin-producing cells (IPCs). The genetic control of IPC development and function is poorly understood. Here, we demonstrate that the Pax6 homolog Eyeless is required in the IPCs to control their differentiation and function. Loss of eyeless results in phenotypes associated with loss of insulin signaling, including decreased animal size and increased carbohydrate levels in larval hemolymph. We show that mutations in eyeless lead to defective differentiation and morphologically abnormal IPCs. We also demonstrate that Eyeless controls IPC function by the direct transcriptional control of one of the major Dilps, dilp5. We propose that Eyeless has an evolutionarily conserved role in IPCs with remarkable similarities to the role of vertebrate Pax6 in beta cells of the pancreas.


Reliability of a brief intercept survey for trail use behaviors.
This study assessed test-retest reliability of an interviewer-administered trail survey. An intercept survey was conducted with adults using 2 paved trails in Indiana and South Carolina (N = 295; mean age = 46.9 +/- 18 y). The survey included items on frequency and duration of trail use for recreation and transportation, other patterns of trail use, and sociodemographic characteristics. Fifty-five adults completed the survey twice (2-16 d apart; mean = 7.4 +/- 2.6 d). Test-retest reliability was assessed with Spearman rank correlation coefficients, Kappa coefficients, and percent agreement. Kappa coefficients and percent agreement for 9 categorical items ranged from 0.65 to 0.96 and from 64.0% to 98.2%, respectively. Among these items, the lowest Kappas were found for perceived safety (0.65) and reported duration of visits for recreational purposes (0.67). Spearman rank correlation coefficients for travel distance to and on the trail and frequency of trail use during the past 7 days and past 4 weeks ranged from 0.62 to 0.93. Though further assessments of this survey with different populations and types of trails may be warranted, its overall high reliability indicates it can be used by researchers and practitioners in its current form.


Larch arabinogalactan.
Larch arabinogalactan is a polysaccharide powder derived from the wood of the larch tree (Larix species) and comprised of approximately 98 percent arabinogalactan. Arabinogalactans are found in a variety of plants but are more abundant in the Larix genus, primarily Larix occidentalis (Western Larch). The Western Larch is unique among pines in that it loses its needles in the fall. Western Larch is also known as Mountain Larch or Western Tamarack and is native to the Pacific and Inland Northwest United States as well as parts of British Columbia, Canada. Larch arabinogalactan is approved by the U.S. Food and Drug Administration (FDA) as a source of dietary fiber, but also has potential therapeutic benefits as an immune stimulating agent and cancer protocol adjunct.


Neural reprogramming in retinal degeneration.
Early visual defects in degenerative diseases such as retinitis pigmentosa (RP) may arise from phased remodeling of the neural retina. The authors sought to explore the functional expression of ionotropic (iGluR) and group 3, type 6 metabotropic (mGluR6) glutamate receptors in late-stage photoreceptor degeneration. Excitation mapping with organic cations and computational molecular phenotyping were used to determine whether retinal neurons displayed functional glutamate receptor signaling in rodent models of retinal degeneration and a sample of human RP. After photoreceptor loss in rodent models of RP, bipolar cells lose mGluR6 and iGluR glutamate-activated currents, whereas amacrine and ganglion cells retain iGluR-mediated responsivity. Paradoxically, amacrine and ganglion cells show spontaneous iGluR signals in vivo even though bipolar cells lack glutamate-coupled depolarization mechanisms. Cone survival can rescue iGluR expression by OFF bipolar cells. In a case of human RP with cone sparing, iGluR signaling appeared intact, but the number of bipolar cells expressing functional iGluRs was double that of normal retina. RP triggers permanent loss of bipolar cell glutamate receptor expression, though spontaneous iGluR-mediated signaling by amacrine and ganglion cells implies that such truncated bipolar cells still release glutamate in response to some nonglutamatergic depolarization. Focal cone-sparing can preserve iGluR display by nearby bipolar cells, which may facilitate late RP photoreceptor transplantation attempts. An instance of human RP provides evidence that rod bipolar cell dendrite switching likely triggers new gene expression patterns and may impair cone pathway function.


The tissue-specific nuclear matrix protein, NMP-2, is a member of the AML/CBF/PEBP2/runt domain transcription factor family: interactions with the osteocalcin gene promoter.
The nuclear matrix protein, NMP-2, was originally identified as an osteoblast-specific DNA-binding complex localized exclusively to the nuclear matrix. NMP-2 was shown to recognize two binding sites, site A (nt-605 to -599) and site B (nt -441 to -435), in the rat bone-specific osteocalcin gene promoter. This study shows that the NMP-2 binding sites A and B as well as a third NMP-2 binding site (nt -135 to -130) constitute a consensus sequence, ATGCTGGT, and represent an AML-1 recognition motif. AML-1 is a member of the AML transcription factor family which is associated with acute myelogenous leukemia and binds to the sequence TGCTGGT via its DNA-binding runt domain. Electrophoretic mobility shift assays reveal that a component of NMP-2 is a member of the AML/PEBP2/runt domain transcription factor family based on cross-competition with AML-1 consensus oligonucleotide. Limited immunoreactivity of NMP-2 with a polyclonal N-terminal AML-1 antibody and inability of the AML-1 partner protein CBF-beta to form complexes with NMP-2 indicate that NMP-2 is not identical to AML-1 but represents a variant AML/PEBP2/runt domain protein. Western and Northern blots reveal the presence of multiple AML-related proteins and AML-1 transcripts in several osseous cell lines. Furthermore, our results indicate that AML family members may selectively partition between nuclear matrix and nonmatrix compartments. Because proteins that contain a runt domain are implicated in tissue-specific transcriptional regulation, our results support the concept that the nuclear matrix mediates osteoblast-specific expression of the osteocalcin gene.


Intracellular lumen formation in Drosophila proceeds via a novel subcellular compartment.
Cellular tubes have diverse morphologies, including multicellular, unicellular and subcellular architectures. Subcellular tubes are found prominently within the vertebrate vasculature, the insect breathing system and the nematode excretory apparatus, but how such tubes form is poorly understood. To characterize the cellular mechanisms of subcellular tube formation, we have refined methods of high pressure freezing/freeze substitution to prepare Drosophila larvae for transmission electron microscopic (TEM) analysis. Using our methods, we have found that subcellular tube formation may proceed through a previously undescribed multimembrane intermediate composed of vesicles bound within a novel subcellular compartment. We have also developed correlative light/TEM procedures to identify labeled cells in TEM-fixed larval samples. Using this technique, we have found that Vacuolar ATPase (V-ATPase) and the V-ATPase regulator Rabconnectin-3 are required for subcellular tube formation, probably in a step resolving the intermediate compartment into a mature lumen. In general, our ultrastructural analysis methods could be useful for a wide range of cellular investigations in Drosophila larvae.


CALCIFICATION OF THE BREAST FOLLOWING A TYPHOID ABSCESS.
1. In a patient with typhoid fever, who had taken, during eleven days, 132 grammes of lactate of calcium by the mouth, as well as 5 grammes of chloride of calcium subcutaneously, there developed, eleven days after the subcutaneous infusion, a large abscess of the breast from which Bacillus typhosus and Staphylococcus aureus were obtained on culture. The abscess was opened and the wound packed with iodoform gauze. Eleven days later a deposit of calcium appeared in the granulation tissue bordering the wound. This rapidly increased until the rim of the opening and the lining granulation tissue were converted into a hard, calcareous mass. A number of nodules of an apparently similar character appeared in other parts of the breast. 2. A month later the iodoform packing was removed and the patient was put on a carbohydrate free diet. This was continued for twenty-four of the next thirty-six days. Under this treatment the abscess almost entirely healed with complete disappearance of the deposit of calcium. 3. Studies of the intake and output of calcium showed that, during three days under a diet of milk and eggs there was a material calcium retention ((I).346 grammes) : (b) That during two periods amounting to three weeks in all, under a carbohydrate free diet, there was an excess of Ca elimination over the intake of 3.672 grammes, (c) That during ten days following the last carbohydrate free period, under a normal diet, there was a retention of calcium amounting to 0.602 gramme. 4. The disappearance of calcium from the breast was associated in time with the carbohydrate free diet and the excessive elimination of calcium. 3. Under the carbohydrate free diet acetone and diacetic acid appeared on two occasions in the urine, but were not accompanied by any increase in the elimination of calcium. 6. With regard to the cause of the calcification, we cannot speak with certainty. The remarkable association of the deposition of calcium at the seat of an injection of calcium chloride in an individual who had been receiving large quantities of lactate of calcium by the mouth-a deposition occurring in tissues which were in direct connection with or in the immediate neighborhood of a dressing containing iodoform, a poison which in certain animals produces degenerative changes in the kidneys and liver which are peculiarly prone to calcification, is striking and worthy of note. 7. In how far the decalcification of the affected area may have been due to the carbohydrate free regime with the consequent excess in calcium elimination, it is impossible, on the basis of a single case, to say. The coincidence in time of the disappearance of calcium from the breast with this treatment is, however, remarkable and extremely suggestive.


Spatial guidance of choice behavior in the radial-arm maze.
In 6 experiments, the performance of male rats in a 12-arm radial maze was examined. The focus of study was the extent to which the spatial location of individual baited maze arms was determined before the rat was exposed to the extramaze visual cues corresponding to the arm, and thereby guided the rat toward the location of baited arms. Such spatial guidance of choice behavior implies a spatially organized cognitive representation of maze arms (i.e., a cognitive map). A higher level of spatial guidance was found when visual access to extramaze cues was restricted than when it was unrestricted. There was no evidence of a difference between the level of spatial guidance in the context of working memory performance and reference memory performance. Some evidence that intramaze cues contributed to microchoice guidance was found. However, spatial guidance, under at least some conditions, is best explained in terms of cognitive mapping.


PAX6 dosage effects on corneal development, growth, and wound healing.
The requirement for correct dosage of the transcription factor Pax6 during corneal growth and development was investigated using the Pax6-overexpressing (PAX77) transgenic mouse. Transgenics had a microcornea phenotype due to failure of postnatal growth, associated with reduction in the number of cells layers in the corneal epithelium. Cell cycle progression was monitored using bromodeoxyuridine, p63, cyclin E, and phosphohistone-3 labeling: proliferation rates were higher in PAX77+ than wild-type, without a concomitant increase in apoptosis. Hence, failure of proliferation did not underlie microcornea. PAX77+ corneal epithelia had reduced levels of cytokeratin-12, and exhibited severe wound healing delay that, in contrast to Pax6+/- mice, could not be modulated by exogenous growth factors. PAX77+ lenses showed partial failure of lens fiber differentiation. The data demonstrate that anterior eye development is very sensitive to Pax6 dosage. Although there are similarities between the eye phenotype of Pax6 heterozygotes and overexpressing mice, there are also striking differences. Developmental


Characterization of monoclonal antibodies against rabbit CD44: evidence of a role for CD44 in modulating synoviocyte metabolism.
The CD44 adhesion receptor is a hyaluronan-binding cell surface glycoprotein whose major isoform is a 95 kDa molecule with a wide tissue distribution. We have characterized two MAbs, W4/86 and RPN3/24, by immunochemistry, flow cytometry and fluorescence staining and demonstrated that they recognize the rabbit CD44 molecule. The results show that CD44 in the rabbit has a similar molecular size and cell distribution to human CD44. These antibodies have demonstrated for the first time, the presence of CD44 on synoviocytes. Preincubation of the rabbit synovial cell line HIG-82 with W4/86 inhibited its synthesis of PGE2 in response to autocrine synovial cytokines. These results indicate that the CD44 molecule may help to modulate synoviocyte metabolism.


Changes in prevalence of prescription opioid abuse after introduction of an abuse-deterrent opioid formulation.
The reformulation of oxycodone hydrochloride controlled-release (CR) tablets in August 2010 created a natural experiment at a national scale, providing an opportunity to evaluate patterns of abuse of prescription opioids and other drugs before and after introduction of this abuse-deterrent formulation (ADF). Observational, cross-sectional study Sentinel sample of adults assessed for substance abuse treatment within the NAVIPPRO® surveillance system Two hundred thirty-two thousand and eight hundred seventy-four adults at 437 facilities during January 1, 2008 through December 31, 2011. Time-series analysis using logistic regression to estimate quarterly prevalence of past 30-day abuse (adjusted for covariates and prescription volume) and changes in abuse pre-and post-ADF introduction. Increases in abuse prevalence occurred for all prescription opioids as a class and for extended-release (ER) opioids. Significantly greater abuse of ER oxymorphone and buprenorphine occurred in the post-ADF period (relative risk [RR] = 2.91, 95% confidence interval [CI] = 2.59-3.27 and RR = 1.85, 95% CI = 1.74-1.96). Increases in abuse for these two compounds were significant among groups who reported abuse via preferential routes of administration (oral only, snorting only, injection only) post-ADF introduction. Replacement of a widely prescribed opioid formulation known for its abuse potential alone may have had little impact on overall rates of prescription opioids as a class. However, changes in abuse levels of certain opioids coinciding with ADF introduction suggest possible switching of abuse among this study sample to specific long-acting opioid analgesics. Additional follow-up studies will be important to monitor changing abuse patterns and their public health impact as new opioid formulations are developed and introduced to market.


Hospitalization before and after mini-gastric bypass surgery.
The mini-gastric bypass (MGB) was developed to address some of the limitations of the Roux-en-Y gastric bypass ("RNY"). The RNY has recently been reported to increase the need for hospitalization for complications after RNY surgery. To determine the rates and indications for inpatient hospital use before and after MGB in comparison to similar rates in RNY. The study is a self reported retrospective study of patients from across the United States receiving MGB in Centers for Excellence in Laparoscopic Obesity Surgery ("CELOS") hospitals from 2000 to 2005. Complications and hospitalization in the year before and in the 1 to 5 years after MGB. 1069 patients who underwent MGB were selected for study. The rate of hospitalization in the year following MGB was 67% of the rate in the year preceding MGB (11% vs. 17%, P<0.001). The most common reasons for admission prior to MGB were general medical problems (38%) obstetric and Gynecological issues (36%), orthopedic problems (16%), gallbladder surgery (9%) and renal stones in 2%. The most common reasons for hospital admission after MGB were complications from surgery (29%), gallbladder surgery (20%), renal stones (14%), plastic surgery procedures (11%), appendectomy (9%), Gynecologic issues (9%) and orthopedic problems (6%). Thus while MGB complications made up a third of hospital readmissions following MGB surgery the over all hospitalization rates declined significantly. Previous studies have demonstrated that hospitalization after RNY gastric bypass increases remarkably (20% per year). The present study shows that hospitalization following MGB instead of rising, as reported with RNY, decreases by a third. The MGB has been shown to be a short, safe successful weight loss surgery in previous work. The present study supports the MGB as a low risk procedure that decreases the need for hospitalization.


Progress on ternary oxide-based photoanodes for use in photoelectrochemical cells for solar water splitting.
Solar water splitting using photoelectrochemical cells (PECs) has emerged as one of the most promising routes to produce hydrogen as a clean and renewable fuel source. Among various semiconductors that have been considered as photoelectrodes for use in PECs, oxide-based photoanodes are particularly attractive because of their stability in aqueous media in addition to inexpensive and facile processing compared to other types of semiconductors. However, they typically suffer from poor charge carrier separation and transport. In the past few years, there has been tremendous progress in developing ternary oxide-based photoelectrodes, specifically, photoanodes. The use of ternary oxides provides more opportunities to tune the composition and electronic structure of the photoelectrode compared to binary oxides, thus providing more freedom to tune the photoelectrochemical properties. In this article, we outline the important characteristics to analyze when evaluating photoanodes and review the major recent progress made on the development of ternary oxide-based photoanodes. For each system, we highlight the favorable and unfavorable features and summarize the strategies utilized to address the challenges associated with each material. Finally, by combining our analyses of all the photoanodes surveyed in this review, we provide possible future research directions for each compound and an outlook for constructing more efficient oxide-based PECs. Overall, this review will provide a critical overview of current ternary oxide-based photoanodes and will serve as a platform for the design of future oxide-based PECs.


Noma in Laos: stigma of severe poverty in rural Asia.
Noma, or cancrum oris, is a debilitating necrotizing ulcerative stomatitis that destroys the mouth and face. It usually starts in early childhood and is associated with severe poverty, malnutrition, and infections. It is most frequently described from sub-Saharan Africa but is under-reported. There have been very few reports from Asia. We describe the clinical and social features of a series of 12 patients with noma from remote poor villages in rural Lao People's Democratic Republic (Laos). Noma is an ominous stigma of severe poverty and the description of this disease emphasizes the importance of poverty reduction and nutritional improvement in Lao development. In the meantime, more awareness of the problem and the importance of early therapy in acute noma by primary health care workers may reduce mortality and prevent progression to severe disfigurement.


Concerted regulation of low density lipoprotein receptor gene expression by follicle-stimulating hormone and insulin-like growth factor I in porcine granulosa cells: promoter activation, messenger ribonucleic acid stability, and sterol feedback.
Insulin-like growth factor I (IGF-I) and the gonadotropin, FSH, can synergize to stimulate progesterone production in primary cultures of maturing granulosa cells. These trophic hormones increase low density lipoprotein (LDL) receptor binding and internalization, and the utilization of LDL-borne cholesterol by granulosa cells. To determine whether and how IGF-I and FSH control the genomic expression of the LDL receptor, we evaluated their individual and concerted effects on LDL receptor messenger RNA (mRNA) accumulation, stability, and gene promoter activity in first passage monolayer (serum-free) cultures of porcine granulosa cells. Ribonuclease protection assays revealed that LDL receptor mRNA accumulation was increased by human recombinant IGF-I (100 ng/ml), FSH (25 ng/ml NIDDK oFSH-20), or their combination by 2.2-, 2.6-, and 4.6-fold, respectively (P < 0.01). Hormonally stimulated LDL receptor mRNA accumulation was suppressed by 54-75% by the concurrent addition of LDL substrate (50 microg/ml). The combination of FSH and IGF-I significantly prolonged the message half-life, even in the presence of LDL. Using a combination of rapid amplification of cDNA 5'-ends, PCR with adapter-ligated genomic DNA, Southern hybridization, and DNA sequencing, we isolated 1076 bp of the porcine LDL receptor gene upstream of the coding region. In transient transfection assays, with a pLDLR1076/luciferase plasmid construct, FSH, FSH plus IGF-I, or 8-bromo-cAMP (1 mM) treatment (but not IGF-I alone) increased luciferase reporter gene activity by 10- to 23-fold in porcine granulosa cells. Over time in serum-free culture, the basal activity of the LDL receptor gene promoter increased and eventually surpassed hormone-stimulated effects, but was suppressed by LDL substrate (by 75%) at 24 h. The foregoing stimulatory hormone effects and sterol repression were localized to a 116-bp region in the porcine promoter between -255 and -139 upstream of the translational start site. We conclude that the combination of FSH and IGF-I can induce accumulation of LDL receptor mRNA in cultured granulosa cells even in the presence of sterol negative feedback and can do so mechanistically by a combination of promoter activation and increased mRNA stability.


Mother and child interactions about the mother's breast cancer: an interview study.
To describe mothers' reported methods of interacting with the mothers' school-age children about their breast cancer. Qualitative. 19 mothers newly diagnosed with breast cancer. Mothers received treatment for their illness in the Pacific Northwest. Mothers had at least one child between 7 and 12 years old at the time of diagnosis. Case-intensive, in-home, semistructured interviews were audiotaped, transcribed, and inductively coded into four conceptual domains and 16 categories of behavioral strategies used by the mothers to interact with their children about the breast cancer. Behavioral strategies used by mothers when interacting with the children about the breast cancer and when providing children with support. Mothers used a number of methods to bring children into the mothers' breast cancer experience. The conceptual domains included talking about the breast cancer, explaining treatment and care, providing experiences, and doing things to help children cope. The dominant pattern in the interview data was for mothers to assume a teacher/educator role with the children about the cancer, not an interactive, emotive-expressive parenting role. Most mothers used technical biomedical language; did not give evidence of systematically checking on the children's understanding of what they were told; did not elicit the children's concerns; and exposed the children to emotionally laden or potentially frightening images, words, or experiences. Programs and materials need to be developed that help mothers work from a model of parenting that includes developmentally appropriate language, facilitates the children's expression of questions and feelings, links the mothers with the children's understanding of the illness, and assists the children to better manage what is happening related to the breast cancer.


Clinical decision making in a high-risk primary care environment: a qualitative study in the UK.
Examine clinical reasoning and decision making in an out of hours (OOH) primary care setting to gain insights into how general practitioners (GPs) make clinical decisions and manage risk in this environment. Semi-structured interviews using open-ended questions. A 2-month qualitative interview study conducted in Oxfordshire, UK. 21 GPs working in OOH primary care. The most powerful themes to emerge related to dealing with urgent potentially high-risk cases, keeping patients safe and responding to their needs, while trying to keep patients out of hospital and the concept of 'fire fighting'. There were a number of well-defined characteristics that GPs reported making presentations easy or difficult to deal with. Severely ill patients were straightforward, while the older people, with complex multisystem diseases, were often difficult. GPs stopped collecting clinical information and came to clinical decisions when high-risk disease and severe illness requiring hospital attention has been excluded; they had responded directly to the patient's needs and there was a reliable safety net in place. Learning points that GPs identified as important for trainees in the OOH setting included the importance of developing rapport in spite of time pressures, learning to deal with uncertainty and learning about common presentations with a focus on critical cues to exclude severe illness. The findings support suggestions that improvements in primary care OOH could be achieved by including automated and regular timely feedback system for GPs and individual peer and expert clinician support for GPs with regular meetings to discuss recent cases. In addition, trainee support and mentoring to focus on clinical skills, knowledge and risk management issues specific to OOH is currently required. Investigating the stopping rules used for diagnostic closure may provide new insights into the root causes of clinical error in such a high-risk setting.


Omission of dysphagia therapies in hospital discharge communications.
Despite the wide implementation of dysphagia therapies, it is unclear whether these therapies are successfully communicated beyond the inpatient setting. The aim of this study was to examine the rate of dysphagia recommendation omissions in hospital discharge summaries for high-risk subacute care (i.e., skilled nursing facility, rehabilitation, long-term care) populations. We performed a retrospective cohort study that included all stroke and hip fracture patients billed for inpatient dysphagia evaluations by speech-language pathologists (SLPs) and discharged to subacute care from 2003 through 2005 from a single large academic medical center (N=187). Dysphagia recommendations from final SLP hospital notes and from hospital (physician) discharge summaries were abstracted, coded, and compared for each patient. Recommendation categories included dietary (food and liquid), postural/compensatory techniques (e.g., chin tuck), rehabilitation (e.g., exercise), meal pacing (e.g., small bites), medication delivery (e.g., crush pills), and provider/supervision (e.g., 1-to-1 assist). Forty-five percent of discharge summaries omitted all SLP dysphagia recommendations. Forty-seven percent (88/186) of patients with SLP dietary recommendations, 82% (93/114) with postural, 100% (16/16) with rehabilitation, 90% (69/77) with meal pacing, 95% (21/22) with medication, and 79% (96/122) with provider/supervision recommendations had these recommendations completely omitted from their discharge summaries. Discharge summaries omitted all categories of SLP recommendations at notably high rates. Improved post-hospital communication strategies are needed for discharges to subacute care.


Hepatic retinoid levels in seven fish species (teleosts) from a tropical coastal lagoon receiving effluents from iron-ore mining and processing.
The present study was undertaken to investigate the possible effects of Fe and trace element exposure on hepatic levels of retinoids in seven fish species. Concentrations of retinoids were measured in fish collected from a coastal lagoon in Brazil that receives effluents from an iron-ore mining and processing plant. Fish from nearby coastal lagoons were also included to assess possible differences related to chemical exposure. Results indicated considerable differences in hepatic retinoid composition among the various species investigated. The most striking differences were in retinol and derivative-specific profiles and in didehydro retinol and derivative-specific profiles. The Perciformes species Geophagus brasiliensis, Tilapia rendalli, Mugil liza, and Cichla ocellaris and the Characiforme Hoplias malabaricus were characterized as retinol and derivative-specific, while the Siluriformes species Hoplosternum littorale and Rhamdia quelen were didehydro retinol and derivative-specific fish species. A negative association was observed between Al, Pb, As, and Cd and hepatic didehydro retinoid levels. Fish with higher levels of hepatic Fe, Cu, and Zn showed unexpectedly significant positive correlations with increased hepatic retinol levels. This finding, associated with the positive relationships between retinol and retinyl palmitate with lipid peroxidation, may suggest that vitamin A is mobilized from other tissues to increase hepatic antioxidant levels for protection against oxidative damage. These data show significant but dissimilar associations between trace element exposure and hepatic retinoid levels in fish species exposed to iron-ore mining and processing effluents, without apparent major impacts on fish health and condition.


Case report: ICF-level changes in a preschooler after constraint-induced movement therapy.
The authors examined changes associated with constraint-induced movement therapy (CIMT) provided to a preschool-aged child with right spastic hemiplegia. This case study design used a 2-week pretest measure baseline period, 2 weeks of CIMT, and postmeasures at 1 week and 3 months. Measures were chosen to document changes at the different levels of International Classification of Functioning, Disability and Health (ICF), including the Canadian Occupational Performance Measure (COPM), Pediatric Evaluation of Disability Inventory (PEDI) Self-Care Section, Melbourne Assessment of Unilateral Upper Limb Function, and grip and pinch strength. Results showed increases on COPM-identified goals of increased independence with bilateral hand play and participation in gross motor play with friends. Changes were also documented in self-care, arm function, and grip strength. Another unexpected association reported by parents and professionals was increased speech intelligibility. Potential implications of implementing CIMT with young children are presented.


ADP receptors: inhibitory strategies for antiplatelet therapy.
The interaction of adenosine-5'-diphosphate (ADP) with its platelet receptors (P2Y(1) and P2Y(12)) plays a very important role in thrombogenesis. The thienopyridine ticlopidine was the first specific antagonist of the platelet P2Y(12) ADP receptor to be tested in randomized clinical trials for the prevention of arterial thrombotic events. Although ticlopidine reduces the incidence of vascular events in patients at risk, it also unfortunately has some significant drawbacks: a relatively high incidence of toxic effects, which may be fatal in some cases; delayed onset of action; and a high interindividual variability in response. A second thienopyridine, clopidogrel, has superseded ticlopidine, because it is also an efficacious antithrombotic drug and is less toxic than ticlopidine. However, clopidogrel is not completely free from faults: severe toxic effects, albeit occurring much less frequently than with ticlopidine, may still complicate its administration to patients; the onset of pharmacologic action can be accelerated by the use of large loading doses, but may still not be optimal; the high interpatient variability in response remains an important issue. These concerns justify the continued search for agents that can further improve the clinical outcome of patients with atherosclerosis through greater efficacy and/or safety. A new thienopyridyl compound, prasugrel, which is characterized by higher potency and faster onset of action compared with clopidogrel, is currently under clinical evaluation. Two direct and reversible P2Y(12) antagonists, cangrelor and AZD6140, feature very rapid onset and reversal of platelet inhibition, which make them attractive alternatives to thienopyridines, especially when rapid inhibition of platelet aggregation or its quick reversal are required. Along with new the P2Y(12) antagonists, inhibitors of the other platelet receptor for ADP, the antagonists P2Y(1), are under development and may prove to be effective antithrombotic agents.


Engagement intervention versus treatment as usual for young adults with serious mental illness: a randomized pilot trial.
Young adults have elevated rates of mental health disorders, yet they often do not receive consistent care. The challenge of continuing to engage young adults has been pervasive worldwide. Few engagement interventions have been designed for young adults with serious mental illness. Just Do You is a theoretically guided engagement intervention. It uses innovative modalities (i.e., technology, expressive arts activities, narrative expression, mentoring) to engage participants in conversations about services and how they work, while simultaneously orienting them to treatment. This pilot and feasibility study utilizes a hybrid research design, examining feasibility, acceptability, and preliminary impact, alongside implementation. The study combines qualitative methods, a small pilot randomized trial, and a small cost-benefit analysis. Respondents are clinic staff and young adults who have made initial contact with the Personalized Recovery Oriented Services (PROS) program. Quantitative survey data are collected at baseline, 2 weeks (post-intervention), 1 month, and 3 months. The assessments focus on measuring feasibility, acceptability, engagement, and mental health outcomes. Medical record extraction will be used to triangulate self-report data. We will conduct single degree of freedom contrasts to examine whether Just Do You leads to improved outcomes relative to Treatment-As-Usual using robust regression for each outcome measure. We will examine whether changes in the proposed mediating variables occur across groups using a similar contrast strategy. In addition, we will use structural equation modeling to examine the contribution of mediators to ultimate outcomes. Finally, we will use constant comparison coding techniques for qualitative analyses. The aim of this study is to examine the feasibility of a young adult engagement meta-intervention through an intensive preliminary pilot trial, learning through collaboration with stakeholders. Just Do You has the potential to fill a gap in the service system for young adults with serious mental illnesses, improving the seemingly intractable problem of disengagement. The program uses culturally responsive strategies, is recovery-oriented, and builds upon the best evidence to date. Our efforts align with local and national health care reform efforts embedding people with lived experience. This trial was registered with ClinicalTrials.gov (Identifier: NCT03423212) on April 18, 2018, as Protocol Record R34 MH111861-01, New York University, as the Just Do You Program for Young Adults with Serious Mental Illness.


Hope as determinant for psychiatric morbidity in family caregivers of advanced cancer patients.
Home care of advanced cancer patients often has adverse effects on physical and mental health of family caregivers. Little is known about the long-term effects of continuous caregiving on mental health as compared with the effects of bereavement. The objectives of this study were to describe the course of psychiatric morbidity in family caregivers over time, to identify the impact of the patients' death on caregivers, and to explore possible predictor variables for psychiatric morbidity. This multi-institutional, prospective study included 80 family caregivers of 80 advanced cancer patients for baseline and 9 months follow-up assessment. Possible psychiatric disorders (ie, depression, anxiety, posttraumatic stress disorder, and alcohol abuse/dependence) as well as potentially predictive factors (ie, sociodemographic factors, burden, hope, and coping mechanisms) were assessed. Follow-up assessment was conducted on average 9.2 months (±2.9) after baseline assessment. Prevalence rates of anxiety and posttraumatic stress disorder decreased significantly over time, whereas depression and alcoholism remained stable. Bereavement was experienced by 53% of caregivers in the follow-up period. The patients' death had no influence on psychiatric morbidity at follow-up. Predictors for the development of a psychiatric disorder varied according to condition, with hope and emotion-oriented coping identified as important influences, especially for anxiety and depression. Family caregivers with certain psychiatric disorders might need targeted psychosocial support to ensure their mental well-being and prevent long-term disability. Supporting hope and functional coping strategies early after the patient's diagnosis might limit development and extent of psychiatric morbidity.


Sieve tube geometry in relation to phloem flow.
Sieve elements are one of the least understood cell types in plants. Translocation velocities and volume flow to supply sinks with photoassimilates greatly depend on the geometry of the microfluidic sieve tube system and especially on the anatomy of sieve plates and sieve plate pores. Several models for phloem translocation have been developed, but appropriate data on the geometry of pores, plates, sieve elements, and flow parameters are lacking. We developed a method to clear cells from cytoplasmic constituents to image cell walls by scanning electron microscopy. This method allows high-resolution measurements of sieve element and sieve plate geometries. Sieve tube-specific conductivity and its reduction by callose deposition after injury was calculated for green bean (Phaseolus vulgaris), bamboo (Phyllostachys nuda), squash (Cucurbita maxima), castor bean (Ricinus communis), and tomato (Solanum lycopersicum). Phloem sap velocity measurements by magnetic resonance imaging velocimetry indicate that higher conductivity is not accompanied by a higher velocity. Studies on the temporal development of callose show that small sieve plate pores might be occluded by callose within minutes, but plants containing sieve tubes with large pores need additional mechanisms.


Capillary electrophoresis-based immunoassays: principles and quantitative applications.
The use of CE as a tool to conduct immunoassays has been an area of increasing interest over the last decade. This approach combines the efficiency, small sample requirements, and relatively high speed of CE with the selectivity of antibodies as binding agents. This review examines the various assay formats and detection modes that have been reported for these assays, along with some representative applications. Most CE immunoassays in the past have employed homogeneous methods in which the sample and reagents are allowed to react in solution. These homogeneous methods have been conducted as both competitive binding immunoassays and as noncompetitive binding immunoassays. Fluorescent labels are most commonly used for detection in these assays, but enzyme labels have also been utilized for such work. Some additional work has been performed in CE immunoassays with heterogeneous methods in which either antibodies or an analog of the analyte is immobilized to a solid support. These heterogeneous methods can be used for the selective isolation of analytes prior to their separation by CE or to remove a given species from a sample/reagent mixture prior to analysis by CE. These CE immunoassays can be used with a variety of detection modes, such as fluorescence, UV/Vis absorbance, chemiluminescence, electrochemical measurements, MS, and surface plasmon resonance.


Interaction of phagocytes with filamentous fungi.
Phagocytosis of conidia by macrophages and destruction of hyphae by neutrophils are key processes in the defense against infections caused by filamentous fungi. Impairment in phagocytic function leads to increased susceptibility for an infection with Aspergillus species. The fact that a Th1-based immune response to an infection with Aspergillus species results in an improved prognosis for survival underlines the importance of the phagocytic response. Recognition of conidia by macrophages occurs after shedding of the hydrophobic rodlet layer during swelling and germination. Whereas Aspergillus conidia are killed by various immune effector cells, hyphae are in particular targeted and killed by neutrophils. Moreover, both conidia and hyphae are trapped in neutrophil extracellular traps (NETs) that form a containment to localize the infection and to prevent systemic spreading of the fungus in the host. In addition, A. fumigatus interferes with the innate immunity, with both the complement system and defense mechanisms of phagocytes, thereby evading at least in part the innate immune system.


Inhibition of anandamide hydrolysis by cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester (URB597) reverses abuse-related behavioral and neurochemical effects of nicotine in rats.
Emerging evidence suggests that the rewarding, abuse-related effects of nicotine are modulated by the endocannabinoid system of the brain. For example, pharmacological blockade or genetic deletion of cannabinoid CB(1) receptors can reduce or eliminate many abuse-related behavioral and neurochemical effects of nicotine. Furthermore, doses of Delta(9)-tetrahydrocannabinol and nicotine that are ineffective when given alone can induce conditioned place preference when given together. These previous studies have used systemically administered CB(1) receptor agonists and antagonists and gene deletion techniques, which affect cannabinoid CB(1) receptors throughout the brain. A more functionally selective way to alter endocannabinoid activity is to inhibit fatty acid amide hydrolase (FAAH), thereby magnifying and prolonging the effects of the endocannabinoid anandamide only when and where it is synthesized and released on demand. Here, we combined behavioral and neurochemical approaches to evaluate whether the FAAH inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-3-yl ester) could alter the abuse-related effects of nicotine in rats. We found that URB597, at a dose (0.3 mg/kg) that had no behavioral effects by itself, prevented development of nicotine-induced conditioned place preference (CPP) and acquisition of nicotine self-administration. URB597 also reduced nicotine-induced reinstatement in both CPP and self-administration models of relapse. Furthermore, in vivo microdialysis showed that URB597 reduced nicotine-induced dopamine elevations in the nucleus accumbens shell, the terminal area of the brain's mesolimbic reward system. These findings suggest that FAAH inhibition can counteract the addictive properties of nicotine and that FAAH may serve as a new target for development of medications for treatment of tobacco dependence.


Daily Associations between Child and Parent Psychological Factors and Home Opioid Use in Youth with Sickle Cell Disease.
Opioid analgesics are frequently used in the home setting to manage episodic pain in youth with sickle cell disease (SCD). Given the risk of adverse side effects, including constipation and sedation, understanding factors associated with at-home opioid use is important for maximizing pain relief while minimizing negative side effects. The present study aimed to evaluate the relationship between individual psychological factors (pain catastrophizing and negative affect), caregiver psychological factors (catastrophizing about child's pain and caregiver negative affect), and home opioid use in youth with SCD. Youth with SCD (n = 32) and a caregiver (n = 28) recruited during a routine outpatient hematology visit completed electronic 14 day diaries assessing pain, opioid use, and psychological factors. Approximately 28% of youth (n = 9) reported pain ≥50% of diary days and a third of youth (n = 11, 34%) used opioid analgesics at least one of the diary days. The number of days opioid analgesics were used ranged from 0 to 7 (50% of diary days). Results from generalized linear mixed models indicated greater child negative affect accounted for increased odds of opioid use on a given day when accounting for pain intensity. Greater caregiver catastrophizing about children's pain was also associated with increased odds of children's opioid use. Child and parent psychological factors relate to child opioid use at home for SCD-related pain. Future research is warranted in larger samples to identify targets for interventions to enhance pain management while reducing opioid-related risk and side effects.


Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer.
We have previously shown that miR-486-5p is one of the most downregulated micro RNAs in lung cancer. The objective of the study was to investigate the role of miR-486-5p in the progression and metastasis of non-small-cell lung cancer (NSCLC). We evaluated miR-486-5p expression status on 76 frozen and 33 formalin-fixed paraffin-embedded tissues of NSCLC by quantitative reverse transcriptase PCR to determine its clinicopathologic significance. We then performed function analysis of miR-486-5p to determine its potential roles on cancer cell migration and invasion in vitro and metastasis in vivo. We also investigated the target genes of miR-486-5p in lung tumorigenesis. miR-486-5p expression level was significantly lower in lung tumors compared with their corresponding normal tissues (P<0.0001), and associated with stage (P=0.0001) and lymph node metastasis of NSCLC (P=0.0019). Forced expression of miR-486-5p inhibited NSCLC cell migration and invasion in vitro and metastasis in mice by inhibiting cell proliferation. Furthermore, ectopic expression of miR-486-5p in cancer cells reduced ARHGAP5 expression level, whereas miR-486-5p silencing increased its expression. Luciferase assay demonstrated that miR-486-5p could directly bind to the 3'-untranslated region of ARHGAP5. The expression level of miR-486-5p was inversely correlated with that of ARHGAP5 in lung tumor tissues (P=0.0156). Reduced expression of ARHGAP5 considerably inhibited lung cancer cell migration and invasion, resembling that of miR-486-5p overexpression. miR-486-5p may act as a tumor-suppressor contributing to the progression and metastasis of NSCLC by targeting ARHGAP5. miR-486-5p would provide potential diagnostic and therapeutic targets for the disease.


Decreased exposure to sunitinib due to concomitant administration of ifosfamide: results of a phase I and pharmacokinetic study on the combination of sunitinib and ifosfamide in patients with advanced solid malignancies.
This study aimed to define the maximally tolerated dose (MTD) of sunitinib combined with two different infusion schedules of ifosfamide. Patients with advanced solid tumours, good performance score, good organ function, and no standard therapy available were eligible. Continuous once daily sunitinib, in escalating doses per cohort, was combined with ifosfamide, 9 g m(-2) for 3 days or 6 g m(-2) for 5 days, administered every 3 weeks. Pharmacokinetic (PK) and pharmacodynamic (PD) assessments were performed. With growth-factor support, the MTD of sunitinib combined with either ifosfamide schedule was 12.5 mg in 32 patients enrolled. Neutropenia-related adverse events were dose-limiting toxicities. Sunitinib did not affect ifosfamide PK. Ifosfamide significantly decreased exposure to sunitinib and increased exposure to its metabolite, SU12662. No consistent changes in PD parameters were observed. With growth-factor support, the MTD of sunitinib with both ifosfamide schedules was 12.5 mg. Ifosfamide produced decreased sunitinib blood levels because of CYP3A induction. As PK interactions cannot explain the relatively low sunitinib doses that can be combined with ifosfamide, synergy in toxicity is likely. Whether this also holds true for anti-tumour activity needs to be further explored.


Structure and Computational Basis for Backbone Rearrangement in Marine Oxasqualenoids.
Six novel oxasqualenoids (polyether triterpenes) were isolated from the red alga Laurencia viridis. Laurokanols A-E (1-5) comprise an unreported tricyclic core with a [6,6]-spiroketal system. Yucatecone (6) shows a biogenetically intriguing epimerization at C14. Quantum mechanical calculations were used to corroborate their structures and to explain key steps involved in the biogenetic mechanisms proposed for the formation of oxasqualenoids.


Antidepressant treatment and adherence to combination antiretroviral therapy among patients with AIDS and diagnosed depression.
The prevalence of depression is elevated among HIV-infected individuals and there is evidence that depression exerts a negative impact on HIV medication adherence. Merged HIV/AIDS surveillance data and Medicaid claims data from January 1996 to December 1998 were used to identify AIDS-infected patients with diagnosed depression, and filled prescriptions were used to identify their antidepressant use, and highly active antiretroviral therapy (HAART). Chi-square tests and robust logistic regressions were used to examine antidepressant use after HAART initiation, and a person-month approach was used to estimate the association between antidepressant treatment and adherence to HAART after its initiation. Of the 406 AIDS-infected patients diagnosed with depression who initiated HAART during this period, 81% (N = 329) were treated with an antidepressant. The HAART adherence rate was low overall. After HAART initiation; only 63% of the person-months had a prescription for it. However, use of an antidepressant in the prior month was significantly associated with HAART in the current month. After controlling for other factors, the odds of current-month HAART adherence were increased by almost 30% for those with antidepressant use in the prior month (Adjusted OR = 1.28, 95% CI [1.16, 1.41]). While the HAART adherence rate was low among patients with AIDS diagnosed with depression, prior month's antidepressant use increases odds of adherence. Unmeasured factors may influence the reported association between antidepressant use and HAART adherence, but our findings point to the need to investigate directly the impact of antidepressant therapy on HAART adherence found among patients with AIDS and depression.