An Opportunity for Improvement: Evaluation of Diabetes Technology Education Among Adult Endocrinology Training Programs.
Despite increases in continuous glucose monitor (CGM) and insulin pump use in adults with diabetes, there is room for expansion. Technology adoption may be influenced by the training environment and fellowship education. However, little is known about adult endocrinology trainee comfort with, understanding of, or methods by which trainees receive education about diabetes technology. Mixed methods, sequential explanatory evaluation using survey and semi-structured interviews of endocrinology trainees and fellowship leadership in Accreditation Council for Graduate Medical Education (ACGME)-accredited adult endocrinology fellowship programs to assess trainee and leadership comfort with, perceived knowledge of, and current methods for diabetes technology education. Seventy-seven respondents completed the survey. The majority of training programs have curricula for training on insulin pumps (74%) and CGM (75.3%); 52% of fellows felt curricula are adequate. First- and second-year fellows were more comfortable with CGM than insulin pump use. Only half of third-year fellows felt comfortable with starting insulin pump therapy or recommending insulin dose adjustments based on CGM rate of change arrows. Qualitative interviews identified the importance of both direct instruction and experiential learning in diabetes technology education. Almost half of trainees feel that curricula for learning to use and manage insulin pumps and CGM are inadequate and feel uncomfortable with critical aspects of technology use, demonstrating the need for increased attention to trainee education in the use of diabetes technology. Based on a better understanding of current and preferred methods for instruction, this study provides direction for future development of initiatives to improve fellow education in this field.


Identification of Heterotic Groups and Patterns Based on Genotypic and Phenotypic Characteristics Among Rice Accessions of Diverse Origins.
Identification of the right parental combinations to maximize heterosis is the major goal of hybrid breeding, which could be achieved through identification of heterotic groups. The main objective of this study was to identify promising heterotic groups for future rice breeding programs. A collection of 359 rice genotypes of diverse origins of China and abroad, composed of inbreds, maintainers, restorers, and temperature-sensitive genic male sterile (TGMS) lines were genotyped using 10K SNP chips. The SNP data set was subjected to genomic analyses for estimation of genetic divergence and diversity. Significant variations were observed in the germplasm with the identification of six different genetic groups. These lines were assigned to the genetic groups independent of their origin. Taking an account of commercially used heterotic groups present in each cluster, three cytoplasmic male sterile (CMS) lines and 14 inbred and restorer lines with moderate to high genetic distances selected from five heterotic patterns were crossed and obtained 42 F1 hybrids. A total of 14 hybrids were found with significant maximum mid- and better-parent heterosis, namely, TaifengA × Guang122, TaifengA × Wushansimiao, and TaifengA × Minghui63 for earliness; Guang8A × Huazhan for dwarf stature; and Guang8A × Huanghuzhan-1, TaifengA × Yuexiangzhan, Guang8A × Minhui3301, TianfengA × Guang122, Guang8A × Yahui2115, TianfengA × Huanghuazhan, TianfengA × Minghui63, TianfengA × Minhui3301, TaifengA × Gui99, and Guang8A × Yuenongsimiao for yield and yield-related traits. Mid-parent and better-parent heterotic F1 hybrids were in positive correlation with the genetic distances as that manifested by commercially used heterotic groups, encouraging the use of genotypic data for identification of heterotic groups. Our study provides an informative strategy for the development of early maturing, lodging resistant and high-yielding commercial hybrids and cultivars in future heterosis breeding programs.


Dielectric Polarization and Electrorheological Response of Poly(ethylaniline)-Coated Reduced Graphene Oxide Nanoflakes with Different Reduction Degrees.
We prepared poly(ethylaniline)-coated graphene oxide nanoflakes and then treated them with different concentrations of hydrazine solution to form dielectric composite nanoflakes having different reduction degrees of reduced graphene oxide core and insulating polyethylaniline shell (PEANI/rGO). The morphology of PEANI/rGO was observed by scanning electron microscopy, while the chemical structure was confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectrometer. The influence of reduction degrees on the conductivity, dielectric polarization and electrorheological effect of PEANI/rGO in suspensions was investigated by dielectric spectroscopy and rheological test under electric fields. It shows that the PEANI/rGO has two interfacial polarization processes respectively due to rGO core and PEANI shell. As the number of hydrazine increases, the conductivity and polarization rate of rGO core increase. As a result, the difference between the polarization rate of rGO core and that of the PEANI shell gradually becomes large. This increased difference does not significantly decrease the yield stress but causes the flow instability of PEANI/GO suspensions under the simultaneous action of electric and shear fields.


Production and of monoclonal antibodies to simian immunodeficiency virus envelope glycoproteins.
Eighteen monoclonal antibodies (MAb) to simian immunodeficiency virus (SIV) envelope have been characterized. All MAb were shown to bind to viral antigens on the surface of unfixed SIV-infected cells and to precipitate surface glycoproteins of SIVmac251. In Western blot 11 MAb bound to gp160 and gp120, five bound to gp160 and the transmembrane protein gp41 and two MAb did not react with denatured antigen. Preliminary competition assays identified the existence of six competition groups; two groups were within gp41 and four were within gp120. Of the latter four groups, three contained MAb with neutralizing activity. Two of the neutralizing MAb (KK5 and KK9) did not react with denatured antigen in Western blot suggesting that they may recognize conformational epitopes. Enzyme-linked immunosorbent-assay titres of MAb against SIVmac251 ranged from 10(2.4) to 10(5.6) and although similar titres were obtained with some MAb against other SIV and HIV antigens, the presence of isolate specific and shared group epitopes was demonstrated.


Common and rare variants in patients with early onset drusen maculopathy.
Early onset drusen maculopathy (EODM) can lead to advanced macular degeneration at a young age, affecting quality of life. However, the genetic causes of EODM are not well studied. We performed whole genome sequencing in 49 EODM patients. Common genetic variants were analysed by calculating genetic risk scores based on 52 age-related macular generation (AMD)-associated variants, and we analysed rare variants in candidate genes to identify potential deleterious variants that might contribute to EODM development. We demonstrate that the 52 AMD-associated variants contributed to EODM, especially variants located in the complement pathway. Furthermore, we identified 26 rare genetic variants predicted to be pathogenic based on in silico prediction tools or based on reported pathogenicity in literature. These variants are located predominantly in the complement and lipid metabolism pathways. Last, evaluation of 18 genes causing inherited retinal dystrophies that can mimic AMD characteristics, revealed 11 potential deleterious variants in eight EODM patients. However, phenotypic characteristics did not point towards a retinal dystrophy in these patients. In conclusion, this study reports new insights into rare variants that are potentially involved in EODM development, and which are relevant for future studies unravelling the aetiology of EODM.


Rituals in infection control: what works in the newborn nursery?
Two infection control practices common in the newborn nursery, handwashing and gowning, are compared with regards to historic origins, effectiveness, and extent of practice. The practice of handwashing is the direct result of efforts to prevent puerperal sepsis and has been shown to be effective in reducing neonatal risk of infection. Gowning has evolved from operating room practices and has been shown to be generally ineffective in reducing risk of infant infection. Nevertheless, gowning is practiced extensively and handwashing is often omitted. Such rituals need occasional reexamination so that those practices associated with maximum effectiveness receive appropriate attention.


Localization of one gene for tuberous sclerosis within 9q32-9q34, and further evidence for heterogeneity.
Tuberous sclerosis (TSC) is an autosomal dominant disorder with both neurological and cutaneous manifestations often resulting in significant disability. Although it has been studied clinically and biochemically for many years, the underlying pathophysiology remains unknown. Genetic linkage analysis provides an alternative strategy for understanding the genetic etiology of this disease. Genetic linkage of a gene for TSC to loci in 9q32-9q34 has been reported but has not been a universal finding, since absence of linkage to 9q loci, as well as linkage to loci on 11q, have also been reported. We present here data on 22 families (21 previously unreported) segregating TSC. Our results strongly support a TSC locus in the 9q32-34 region for approximately one-third of families and provide significant evidence for genetic heterogeneity. Application of newly described highly polymorphic dinucleotide repeat marker loci in TSC greatly enhanced the informativeness of our pedigrees and was vital for detecting the heterogeneity. No clear evidence of linkage to chromosome 11q22 markers was found, suggesting that a still unidentified TSC locus elsewhere in the genome may account for the majority of TSC families.


Dendrimer nanotechnology for enhanced formulation and controlled delivery of resveratrol.
In spite of its wide and beneficial pharmacological potential, resveratrol lags behind other compounds because of its comparatively less impressive pharmacokinetic profile. Resveratrol has very low oral bioavailability and, from a formulation perspective, it has low solubility in water, which leads to its poor absorption upon oral administration. Apart from low aqueous solubility, resveratrol has poor metabolic stability and instability at high pH, and is photosensitive. The pharmacokinetic and formulation-related limitations of resveratrol can be controlled by entrapping the small resveratrol molecule inside highly water-soluble poly(amidoamine) dendrimer nanostructures, which provide spherical architecture and polyvalency at the nanoscale level, thus leading to novel features. Dendrimer architecture is used to entrap resveratrol for enhancement of its solubility and stability in aqueous solution; they can be engineered to control pharmacokinetics and targeting for oral, mucosal, transdermal, or parenteral administration. Dendrimers have the potential to work as excipients with multifunctional capability by enhancing solubility, dissolution, stability, permeability, multiple drug/cosmetic entrapment, controlled delivery, bioavailability, and efficacy of drugs.


Simultaneous zinc-finger nuclease editing of the HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection.
HIV-1 entry into CD4(+) T cells requires binding of the virus to CD4 followed by engagement of either the C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor 4 (CXCR4) coreceptor. Pharmacologic blockade or genetic inactivation of either coreceptor protects cells from infection by viruses that exclusively use the targeted coreceptor. We have used zinc-finger nucleases to drive the simultaneous genetic modification of both ccr5 and cxcr4 in primary human CD4(+) T cells. These gene-modified cells proliferated normally and were resistant to both CCR5- and CXCR4-using HIV-1 in vitro. When introduced into a humanized mouse model of HIV-1 infection, these coreceptor negative cells engraft and traffic normally, and are protected from infection with CCR5- and CXCR4-using HIV-1 strains. These data suggest that simultaneous disruption of the HIV coreceptors may provide a useful approach for the long-term, drug-free treatment of established HIV-1 infections.


[Significance of the detection of serum specific IgA and IgG antibodies to Chlamydia trachomatis in the epidemiological survey, diagnosis and therapeutic effect on chlamydial infection in women].
In a study to evaluate the epidemiological status of Chlamydia trachomatis (C. trachomatis) infections in the OB/GYN field, we performed an indirect enzyme immune assay, measuring serum specific IgG and IgA. 1) Among 1,812 cases (0-68 years old), antibody positive rates for IgG and IgA were 29.7% and 11.2%, respectively. The first peak was observed in an age group under 1 year old, representing birth canal infections and the second one in a 20-24 age group showed a certain relation to STD. 2) The C. trachomatis IgG and IgA antibody positive rates in the antigen positive group (139 cases) were significantly higher (p less than 0.01) than in the antigen negative group (792 cases). 3) In the antigen positive group (139 cases), the positive IgG rate was high (78.8-90.9%) but it did not show any clear differences among the following groups: PID, cervicitis, pregnancy and infertility. However, the positive IgA rate in peritoneal antigen positive PID showed a significantly higher positive rate (100%) than other groups such as cervicitis (39.4%), pregnancy (37.8%) and infertility (45.5%). 4) Following oral administration of antibiotics, the C. trachomatis antigen became negative in almost all cases, while IgG decreased or became negative only in cases of initial infection. IgA decreased or became negative in the following cases: initial infection, low titer cases before treatment, cases treated many times and comparatively young patients with acute infections. Consequently, the immunoassay of C. trachomatis serum antibody appeared to be valuable for epidemiological surveys, for defermining the status of the infection and the effect of treatment.


Estimation of respiration-induced noise fluctuations from undersampled multislice fMRI data.
Functional MRI time series data are known to be contaminated by highly structured noise due to physiological fluctuations. Significant components of this noise are at frequencies greater than those critically sampled in standard multislice imaging protocols and are therefore aliased into the activation spectrum, compromising the estimation of functional activations and the determination of their significance. However, in this work it is demonstrated that unaliased noise information is available in multislice data, and can be used to estimate and reduce noise due to high-frequency respiratory-related fluctuations. Magn Reson Med 45:635-644, 2001. Published 2001 Wiley-Liss, Inc.


Seasonal and microclimatic effects on leaf beetles (Coleoptera, Chrysomelidae) in a tropical forest fragment in northeastern Mexico.
Leaf beetles (Coleoptera: Chrysomelidae) constitute a family of abundant, diverse, and ecologically important herbivorous insects, due to their high specificity with host plants, a close association with vegetation and a great sensitivity to microclimatic variation (factors that are modified gradually during the rainy and dry seasons). Therefore, the effects of seasonality (rainy and dry seasons) and microclimate on the community attributes of chrysomelids were evaluated in a semideciduous tropical forest fragment of northeastern Mexico. Monthly sampling was conducted, between March 2016 and February 2017, with an entomological sweep net in 18 plots of 20 × 20 m, randomly distributed from 320 to 480 m a.s.l. Seven microclimatic variables were simultaneously recorded during each of the samplings, using a portable weather station. In total, 216 samples were collected at the end of the study, of which 2,103 specimens, six subfamilies, 46 genera, and 71 species were obtained. The subfamily Galerucinae had the highest number of specimens and species in the study area, followed by Cassidinae. Seasonality caused significant changes in the abundance and number of leaf beetle species: highest richness was recorded in the rainy season, with 60 species, while the highest diversity (lowest dominance and highest H' index) was obtained in the dry season. Seasonal inventory completeness of leaf beetles approached (rainy season) or was higher (dry season) than 70%, while the faunistic similarity between seasons was 0.63%. The outlying mean index was significant in both seasons; of the seven microclimatic variables analyzed, only temperature, heat index, evapotranspiration and wind speed were significantly related to changes in abundance of Chrysomelidae. Association between microclimate and leaf beetles was higher in the dry season, with a difference in the value of importance of the abiotic variables. The results indicated that each species exhibited a different response pattern to the microclimate, depending on the season, which suggests that the species may exhibit modifications in their niche requirements according to abiotic conditions. However, the investigations must be replicated in other regions, in order to obtain a better characterization of the seasonal and microclimatic influence on the family Chrysomelidae.


Carpal coalition with radioscaphoid synostosis and hypoplastic thumb.
Carpal coalition is an anomaly that is usually discovered as an incidental finding on roentgenograms. The most common site is between the lunate and the triquetrum, though fusion of almost every combination of carpal bones has been reported. Carpal coalition can be isolated but has also been associated with numerous congenital malformation syndromes. In this article, we report the case of a 12-year-old boy with left-sided asymptomatic fusion of the trapezoid and trapezium, fusion of the radius and scaphoid, and hypoplasia of the thumb.


Steady-state current transfer and scattering theory.
The correspondence between the steady-state theory of current transfer and scattering theory in a system of coupled tight-binding models of one-dimensional wires is explored. For weak interwire coupling both calculations give nearly identical results, except at singular points associated with band edges. The effect of decoherence in each of these models is studied using a generalization of the Liouville-von Neuman equation suitable for steady-state situations. An example of a single impurity model is studied in detail, leading to a lattice model of scattering off target that affects both potential scattering and decoherence. For an impurity level lying inside the energy band, the transmission coefficient diminishes with increasing dephasing rate, while the opposite holds for impurity energy outside the band. The efficiency of current transfer in the coupled wire system decreases with increasing dephasing.


Biochemical sensing by nanofluidic crystal in a confined space.
Electrokinetics at nanoscale has attracted broad attention as a promising conductivity based biochemical sensing principle with a good selectivity. The nanoparticle crystal, formed by self-assembling nanoparticles inside a microstructure, has been utilized to fulfill a nanoscale electrokinetics based biochemical sensing platform, named nanofluidic crystal in our previous works. This paper introduces a novel nanofluidic crystal scheme by packing nanoparticles inside a well-designed confined space to improve the device-to-device readout consistency. A pair of electrodes was patterned at the bottom of this tunnel-shaped confined space for ionic current recording. The readout from different chips (n = 16) varied within 8.4% under the same conditions, which guaranteed a self-calibration-free biochemical sensing. Biotin and Pb(2+) were successfully detected by using nanofluidic crystal devices packed with streptavidin and DNAzyme modified nanoparticles, respectively. The limits of detection (LODs) were both 1 nM. This electrically readable nanofluidic crystal sensing approach may find applications in low cost and fast disease screening in limited resource environments.


Adsorption Media for the Removal of Soluble Phosphorus from Subsurface Drainage Water.
Phosphorus (P) is a valuable, nonrenewable resource in agriculture promoting crop growth. P losses through surface runoff and subsurface drainage discharge beneath the root zone is a loss of investment. P entering surface water contributes to eutrophication of freshwater environments, impacting tourism, human health, environmental safety, and property values. Soluble P (SP) from subsurface drainage is nearly all bioavailable and is a significant contributor to freshwater eutrophication. The research objective was to select phosphorus sorbing media (PSM) best suited for removing SP from subsurface drainage discharge. From the preliminary research and literature, PSM with this potential were steel furnace slag (SFS) and a nano-engineered media (NEM). The PSM were evaluated using typical subsurface drainage P concentrations in column experiments, then with an economic analysis for a study site in Michigan. Both the SFS and generalized NEM (GNEM) removed soluble reactive phosphorus from 0.50 to below 0.05 mg/L in laboratory column experiments. The most cost-effective option from the study site was the use of the SFS, then disposing it each year, costing $906/hectare/year for the case study. GNEM that was regenerated onsite had a very similar cost. The most expensive option was the use of GNEM to remove P, including regeneration at the manufacturer, costing $1641/hectare/year. This study suggests that both SFS and NEM are both suited for treating drainage discharge. The use of SFS was more economical for the study site, but each site needs to be individually considered.


UV Radiation in DNA Damage and Repair Involving DNA-Photolyases and Cryptochromes.
Prolonged exposure to ultraviolet radiation on human skin can lead to mutations in DNA, photoaging, suppression of the immune system, and other damage up to skin cancer (melanoma, basal cell, and squamous cell carcinoma). We reviewed the state of knowledge of the damaging action of UVB and UVA on DNA, and also the mechanisms of DNA repair with the participation of the DNA-photolyase enzyme or of the nucleotide excision repair (NER) system. In the course of evolution, most mammals lost the possibility of DNA photoreparation due to the disappearance of DNA photolyase genes, but they retained closely related cryptochromes that regulate the transcription of the NER system enzymes. We analyze the published relationships between DNA photolyases/cryptochromes and carcinogenesis, as well as their possible role in the prevention and treatment of diseases caused by UV radiation.


Record Low Thermal Conductivity of Polycrystalline Si Nanowire: Breaking the Casimir Limit by Severe Suppression of Propagons.
Thermoelectrics offer an attractive pathway for addressing an important niche in the globally growing landscape of energy demand. Nanoengineering existing low-dimensional thermoelectric materials pertaining to realizing fundamentally low thermal conductivity has emerged as an efficient route to achieve high energy conversion performance for advanced thermoelectrics. In this paper, by performing nonequilibrium and Green-Kubo equilibrium molecular dynamics simulations we report that the thermal conductivity of Si nanowires (NWs) in polycrystalline form can reach a record low value substantially below the Casimir limit, a theory of diffusive boundary limit that regards the direction-averaged mean free path is limited by the characteristic size of the nanostructures. The astonishingly low thermal conductivity of polycrystalline Si NW is 269 and 77 times lower with respect to that of bulk Si and pristine Si NW, respectively, and is even only about one-third of the value of the purely amorphous Si NW at room temperature. By examining the mode level phonon behaviors including phonon group velocities, lifetime, and so forth, we identify the mechanism of breaking the Casimir limit as the strong localization of the middle and high frequency phonon modes, which leads to a prominent decrease of effective mean free path of the heat carriers including both propagons and diffusons. The contribution of the propagons to the overall thermal transport is further quantitatively characterized and is found to be dramatically suppressed in polycrystalline Si NW form as compared with bulk Si, perfect Si NW, and pure amorphous Si NW. Consequently, the diffusons, which transport the heat through overlap with other vibrations, carry the majority of the heat in polycrystalline Si NWs. We also proposed approach of introducing "disorder" in the polycrystalline Si NWs that could eradicate the contribution of propagons to achieve an even lower thermal conductivity than that ever thought possible. Our investigation provides a deep insight into the thermal transport in polycrystalline NWs and offers a promising strategy to construct a new kind of semiconducting thermoelectric NW with high figure of merit.


Premorbid social underachievement in schizophrenia. Results from the Camberwell Collaborative Psychosis Study.
In an investigation of the timing and precursors of social decline in schizophrenia and affective psychosis, 195 subjects from the Camberwell Collaborative Psychosis Study were currently of lower social class than were their fathers. A comparison between father's occupation and proband's best premorbid occupational level indicated underachievement confined to DSM-III schizophrenia, there being no such effect in affective psychosis. Decline in social status following onset of psychosis, analysed by comparing best premorbid occupation with current occupation, was marked in both schizophrenia and affective psychosis, indicating a non-specific effect. Schizophrenic patients who failed to achieve their fathers' social status had poorer educational qualifications than those who equalled or bettered their paternal social class, despite similar premorbid IQ (NART) scores and age at onset of psychosis. These results indicate that schizophrenia may be manifest before the onset of psychosis, and lend weight to the notion of a developmental origin to this disorder.


An innovative approach to supporting hospitalist physicians towards academic success.
Academic hospitalist physicians face significant challenges that may threaten their chances for successful and timely promotions, such as heavy clinical workloads, limited training in research, and relatively few experienced mentors in their field. The appreciable growth of hospital medicine groups in recent years, as has occurred at our institution, compounds the predicament by diluting the limited resources that are available to support these physicians. A needs assessment was followed by the development of specific objectives for the division and for individual members of the division related to academic success. The resulting 3-pronged strategy to support the academic success of our group was based on securing strong mentorship, investing requisite resources, and committing to recruit fellowship-trained new faculty. To date, the initiative has resulted in an increased number of peer-reviewed publication and grants, as well as national leadership roles for division members.


Heterogeneity of the developmental patterns of neurotrophin protein levels among neocortical areas of macaque monkeys.
Based on morphological and physiological characteristics, the mammalian neocortex is divided into various neocortical areas and its diversity is prominent in the primates including humans. These neocortical areas are constructed during development, but the details of the developmental events remain unclear, especially at the molecular level. We measured the mRNA and protein levels of neurotrophins in various neocortical areas of developing rhesus monkeys. The expression patterns of both the neurotrophin-3 (NT-3) mRNA and the protein showed area differences. In the sensory and motor areas, NT-3 mRNA and protein levels had started to decline by a week after birth. In contrast, the levels declined after the third postnatal week in the association neocortical areas. The level of brain-derived neurotrophic factor (BDNF) protein changed in an area-dependent manner during development, but that of mRNA did not. The decline of the BDNF protein level started earlier in the sensory and motor neocortical areas than in the association neocortical areas, suggesting that sensory and motor neocortical areas develop earlier than the association areas in terms of the developmental changes in neurotrophins.


Spitz nevus and its histologic simulators.
Spitz nevi continue to pose a considerable diagnostic challenge to the histopathologist. Key features of Spitz nevus and its variants are discussed and contrasted with the telltale signs of malignancy of "Spitzoid" melanomas. The importance of the histologic features of the deep, rather than superficial, part of the lesions is emphasized.


Multi-clone infections and the impact of intraspecific competition on trematode colonies with a division of labour.
A division of labour occurs in colonies of the trematode Philophthalmus sp. within their first intermediate hosts. Two castes exist: one which reproduces and one which does not reproduce. It has been hypothesized that the benefit of the non-reproductive caste is in competitive interactions. Evidence for this from past experiments with Philophthalmus sp. colonies has been contradictory: the non-reproductive caste appears to benefit the colony in some way but not necessarily by combating interspecific competitors. The aims of this study were to consider intraspecific competition as a possible cause of the division of labour in Philophthalmus sp. colonies. Results show that mixed genotype infections occur in Philophthalmus sp. infected hosts and thus intraspecific competition is likely. Furthermore, the total number of individuals per colony is reduced in mixed genotype infections, indicating that intraspecific competition reduces colony fitness. However, the results do not indicate that the division of labour in Philophthalmus sp. plays a role in competitive interactions as the ratio of small, non-reproductive to large, reproductive individuals is unaffected by the presence of intraspecific competition. This is the first study to identify and quantify intraspecific competition in Philophthalmus sp., and to assess its selective role in this species' division of labour.


Treatment for primary HIV infection: projecting outcomes of immediate, interrupted, or delayed therapy.
With limited data available on the optimal treatment of primary HIV infection, disease modeling can be used to project clinical outcomes and inform decision makers. The authors developed a simulation model to evaluate the clinical outcomes and life expectancy projections for three primary HIV infection treatment strategies: 1) continuous antiretroviral therapy (ART) initiated at CD4 count <350 cells/mm(3); 2) continuous ART initiated immediately on diagnosis of primary HIV infection; and 3) ART initiated on diagnosis followed by structured treatment interruption. Projected life expectancies for the three strategies were 23.92, 24.46, and 26.07 years, respectively. The impact of key variables was assessed in sensitivity analysis, with the structured treatment interruption strategy remaining the most effective over a broad range of inputs. The immunologic benefit associated with immediate therapy and the potential for antiretroviral resistance due to structured treatment interruption have the most important impact on the optimal strategy. Based on current data, immediate treatment on diagnosis of primary HIV infection followed by structured treatment interruption will likely yield the best outcome. These results can assist decision makers and those planning clinical trials in defining evidence-based performance measures for primary HIV infection treatment and future trials.


Effects of thiopental and halothane on spontaneous contractile activity induced in isolated ventricular muscles of the rabbit.
To see if the known properties of thiopental of reducing Ca2+ and K+ fluxes across the myocardial sarcolemma account for its arrhythmogenic action, we have evaluated the effect of the anesthetic on spontaneous contractile activity induced in isolated rabbit papillary muscles. Thiopental (20 mg/l) prolonged the duration of sustained automaticity induced by stimulation at 1-2 Hz in the presence of 1 mumol/l isoproterenol. Thiopental (10, 20 mg/l) shortened the delay before the onset of Ba(2+)-induced automaticity, which involves a decrease in a K+ current. The minimum concentration of Ba2+ required to induce automaticity was lowered by thiopental. Whether spontaneous activities were induced by high frequency stimulation in the presence of isoproterenol or by Ba2+, thiopental lowered the frequency of spontaneous beats. Thus, thiopental appears to have both arrhythmogenic and antiarrhythmic actions, and the former may be unmasked when catecholamines counteract the latter by increasing Ca2+ influx. Like thiopental, halothane (1.0%) decreased the frequency and force of Ba(2+)-induced automatic beats but, unlike thiopental, prolonged the delay before the onset of Ba(2+)-induced automaticity, indicating that halothane acts as a purely antiarrhythmic agent in this type of automaticity.


Socioeconomic factors related to leprosy: an integrative literature review.
To investigate in the literature the relation of socioeconomic factors in the incidence of the disease and other outcomes related to leprosy. Integrative review conducted in Lilacs, Medline, Scopus databases and SciELO online library with studies from 2000 to 2016. 32 studies were included. Only studies that analyzed statistical associations of socioeconomic factors and outcomes related to leprosy were selected. Leprosy is greatly affected by the social context in which the patient is inserted, the chances of exposure to illness are the result of a set of not only individual aspects, but also of contexts or collective conditions. It is imperative for Nursing, as an essential part of the multiprofessional team entrusted with the care and surveillance of the disease, to recognize these factors to predict unfavorable outcomes and to develop new practices capable of reducing inequities.


Insulin activation of cyclic AMP phosphodiesterase in intact ureteral segments.
Low doses of insulin (0.1-50 nM) when presented to intact ureteral segments increase cyclic AMP (cAMP) phosphodiesterase (PDE) activity in subsequently isolated supernatant and particulate fractions. The stimulation of cAMP PDE occurs within 5 to 10 min of the introduction of insulin. When cyclic GMP or high concentrations of cAMP (greater than 5 microM) are used as substrate, insulin does not increase PDE activity. Although the insulin-increased cAMP PDE exhibits the same sensitivity as control PDE from untreated preparations to isobutylmethyl xanthine, a nonspecific PDE inhibitor, and M & B 22,948, a relatively selective cyclic GMP PDE inhibitor, differences in the degree of inhibition of PDE activity are seen in the insulin-treated and untreated preparations with the low Km cAMP PDE inhibitors Ro20-1724, rolipram, amrinone and milrinone and with cyclic GMP. Pertussis toxin, which modifies GTP regulatory proteins of the adenylate cyclase enzyme and the photoreceptor PDE, blocks cAMP PDE activation by insulin.


Cross-cultural similarities and differences in the theoretical predictors of cyberbullying perpetration: Results from a seven-country study.
The Barlett Gentile cyberbullying model (BGCM) posits that correlated anonymity perceptions and the belief in the irrelevance of muscularity for online bullying (BIMOB) predict positive cyberbullying attitudes to predict subsequent cyberbullying perpetration. Much research has shown the BGCM to be the only published theory that differentiates traditional and cyberbullying while validly predicting cyberbullying. So far, however, the cross-cultural ubiquity has gone understudied. Thus, 1,592 adult participants across seven countries (USA, Australia, Brazil, China, Germany, Japan, and Singapore) completed measures germane to the BGCM. Supporting the BGCM, the variables were significantly correlated for the entire sample, participants from independent cultures, and participants from interdependent cultures. However, the relationship between BIMOB and positive cyberbullying attitudes as well as the relationship between positive cyberbullying attitudes and cyberbullying perpetration were stronger for independent cultures. These results suggest that the BGCM postulates are mostly universal, but several relations appear to be culturally different. Theoretical implications are discussed.


Quantitative microscopy in studies of intrauterine growth retardation.
In the past, the detection of fetal damage has tended to be restricted to the naked eye identification of major malformations, with the period of organ maturation being relatively neglected. Increasingly, however, unbiased design-based stereology is being used in developmental toxicological studies. In the field of intrauterine growth retardation, such methods are capable of providing new insights into fetal vulnerability during critical periods in organogenesis, with consequences for both post-natal and adult disease.


Bedaquiline containing triple combination powder for inhalation to treat drug-resistant tuberculosis.
Drug-resistant tuberculosis (DR-TB) is an emerging health problem, challenging the effective control of global TB. Current treatment of DR-TB includes administration of multiple anti-TB drugs via oral and parenteral routes for a duration of 20-28 months. High systemic exposure, side effects and lengthy treatment time are problems affecting current treatment. The success rate of current lengthy treatment regimens is generally <50%. Bedaquiline, a new anti-TB drug is synergistic with pyrazinamide and in combination with moxifloxacin accelerates sputum-culture conversion. Therefore, a triple combination of these drugs may have the potential to shorten the treatment time and improve treatment success. Additionally, inhalation of these drugs in combination may be advantageous due to the direct delivery to the lungs, possibly reducing systemic exposure. This study aimed to develop an inhalable triple combination powder of bedaquiline, moxifloxacin and pyrazinamide and study their physicochemical properties and safety. An inhalable (aerodynamic diameter: ≤2.4 µm) triple combination powder of bedaquiline, moxifloxacin and pyrazinamide with 20% w/w of L-leucine was prepared using a Buchi Mini Spray-Dryer. Combination powder consisted of spherical and porous particles. In vitro aerosolization (fine particle fraction, FPF) determined using a next generation impactor (NGI) showed improved FPF as a combination powder (>75.0%) when compared to single drug-only formulations (<45.0%). The powder was non-toxic to A549 and Calu-3 cells up to 100 µg/mL and stable at 30 ± 2% RH and ambient room temperature during one-month storage. This is the first study reporting the development of inhalable triple combination powder of bedaquiline, moxifloxacin and pyrazinamide with high aerosolization efficiency. The improved aerosolization may help to deliver a high dose of these drugs to treat drug-resistant tuberculosis.


LC-DAD-MS Phenolic Characterisation of Six Invasive Plant Species in Croatia and Determination of Their Antimicrobial and Cytotoxic Activity.
Invasive plants' phytochemicals are important for their invasiveness, enabling them to spread in new environments. However, these chemicals could offer many pharmaceutical compounds or active ingredients for herbal preparations. This study provides the first LC-MS phytochemical screening of six invasive alien plant species (IAPS) in the Istria region (Croatia): Ailanthus altissima, Ambrosia artemisiifolia, Conyza canadensis, Dittrichia viscosa, Erigeron annuus, and Xanthium strumarium. The study aims to identify and quantify the phenolic content of their leaf extracts and assess their antimicrobial and cytotoxic potential. A total of 32 species-specific compounds were recorded. Neochlorogenic, chlorogenic, and 5-p-coumaroylquinic acids, quercetin-3-glucoside, and kaempferol hexoside were detected in all the tested IAPS. Hydroxycinnamic acid derivatives were the main components in all the tested IAPS, except in E. annuus, where flavanones dominated with a share of 70%. X. strumarium extract had the best activity against the tested bacteria, with an average MIC value of 0.11 mg/mL, while A. altissima and X. strumarium extracts had the best activity against the tested fungi, with an average MIC value of 0.21 mg/mL in both cases. All the plant extracts studied, except X. strumarium, were less cytotoxic than the positive control. The results provided additional information on the phytochemical properties of IAPS and their potential for use as antimicrobial agents.


Changes in body composition and leptin levels during growth hormone (GH) treatment in short children with various GH secretory capacities.
The aim of this study was to follow changes in body composition, estimated by dual-energy X-ray absorptiometry (DXA), in relation to changes in leptin during the first year of GH therapy in order to test the hypothesis that leptin is a metabolic signal involved in the regulation of GH secretion in children. In total, 33 prepubertal children were investigated. Their mean (S.D.) chronological age at the start of GH treatment was 11.5 (1.6) years, and their mean height was -2.33 (0.38) S.D. scores (SDS). GH was administered subcutaneously at a daily dose of 0.1 (n=26) or 0.2 (n=7) IU/kg body weight. Ten children were in the Swedish National Registry for children with GH deficiency, and twenty-three children were involved in trials of GH treatment for idiopathic short stature. Spontaneous 24-h GH secretion was studied in 32 of the children. In the 24-h GH profiles, the maximum level of GH was determined and the secretion rate estimated by deconvolution analysis (GHt). Serum leptin levels were measured at the start of GH treatment and after 10 and 30 days and 3, 6 and 12 months of treatment. Body composition measurements, by DXA, were performed at baseline and 12 months after the onset of GH treatment. After 12 months of GH treatment, mean height increased from -2.33 to -1.73 SDS and total body fat decreased significantly by 3.0 (3.3)%. Serum leptin levels were decreased significantly at all time points studied compared with baseline. There was a significant correlation between the change in total body fat and the change in serum leptin levels during the 12 months of GH treatment, whereas the leptin concentration per unit fat mass did not change. In a multiple stepwise linear regression analysis with 12 month change in leptin levels as the dependent variable, the percentage change in fat over 12 months, the baseline fat mass (%) of body mass and GHt accounted for 24.0%, 11.5% and 12.2% of the variability respectively. There are significant correlations between changes in leptin and fat and endogenous GH secretion in short children with various GH secretory capacities. Leptin may be the messenger by which the adipose tissue affects hypothalamic regulation of GH secretion.


Luminescent cyanometallates based on phenylpyridine-Ir(III) units: solvatochromism, metallochromism, and energy-transfer in Ir/Ln and Ir/Re complexes.
[Ir(ppy)(2)(CN)(2)](-) (ppy = anion of 2-phenylpyridine) and some substituted derivatives have been investigated for their ability to interact with additional metal cations, both in solution and the solid state, via the externally-directed cyanide lone pairs, and to act as energy-donors in the resulting assemblies. [Ir(ppy)(2)(CN)(2)](-) is slightly solvatochromic, showing a blue-shift of the lowest energy absorption manifold in water compared to organic solvents, and the solubilised (t)Bu-substituted analogue [Ir((t)Buppy)(2)(CN)(2)](-) [(t)Buppy = anion of 2-(4-(t)Bu-phenyl)pyridine] is also metallochromic with coordination of the cyanide lone pairs to two M(II) cations in MeCN (M = Ba, Zn) resulting in blue-shifts of the lowest-energy absorption and emission maxima. These effects are however modest because of (i) the presence of only two cyanide groups, and (ii) the fact that the lowest-energy excited state has a substantial (3)LC component and is therefore not purely charge-transfer in nature. Crystallisation of [Ir(ppy)(2)(CN)(2)](-) as its (PPN)(+) salt in the presence of excess of lanthanide(III) salts leads to formation of assemblies based on Ir-CN-Ln bonds, which generate in the solid state either Ir(2)Ln(2)(μ-CN)(4) square assemblies or linear trinuclear species with Ir-CN-Ln-NC-Ir cores. In the Ir(2)Eu(2)(μ-CN)(4) and Ir(2)Nd(2)(μ-CN)(4) complexes the Ir-based emission is substantially quenched due to energy-transfer to lower-lying f-f states of these lanthanide ions. In addition reaction of [Ir(F(2)ppy)(2)(CN)(2)](-) [F(2)ppy = cyclometallating anion of 2-(2,4-difluorophenyl)pyridine] with [Re(phen)(CO)(3)(MeCN)][PF(6)] in solution affords dinuclear IrRe and trinuclear IrRe(2) species in which {Re(phen)(CO)(3)} units are attached to the N-donor termini of one or both of the cyanide groups; these complexes have been structurally characterised and display quantitative Ir→Re energy-transfer, showing luminescence only from the Re(I) terminus on excitation of the Ir(III) unit.


Structural basis for Ca2+-induced activation and dimerization of estrogen receptor α by calmodulin.
The estrogen receptor α (ER-α) regulates expression of target genes implicated in development, metabolism, and breast cancer. Calcium-dependent regulation of ER-α is critical for activating gene expression and is controlled by calmodulin (CaM). Here, we present the NMR structures for the two lobes of CaM each bound to a localized region of ER-α (residues 287-305). A model of the complete CaM·ER-α complex was constructed by combining these two structures with additional data. The two lobes of CaM both compete for binding at the same site on ER-α (residues 292, 296, 299, 302, and 303), which explains why full-length CaM binds two molecules of ER-α in a 1:2 complex and stabilizes ER-α dimerization. Exposed glutamate residues in CaM (Glu(11), Glu(14), Glu(84), and Glu(87)) form salt bridges with key lysine residues in ER-α (Lys(299), Lys(302), and Lys(303)), which are likely to prevent ubiquitination at these sites and inhibit degradation of ER-α. Mutants of ER-α at the CaM-binding site (W292A and K299A) weaken binding to CaM, and I298E/K299D disrupts estrogen-induced transcription. CaM facilitates dimerization of ER-α in the absence of estrogen, and stimulation of ER-α by either Ca(2+) and/or estrogen may serve to regulate transcription in a combinatorial fashion.


Intensity effect on latency and interval of human BAER.
Intensity effect on wave latency and interval (IPI) in brainstem auditory evoked responses (BAER) from birth to adulthood was investigated. The L-I functions were slightly steeper in younger groups than in older groups, which was associated with age-related difference in the absolute latencies. Wave I latency in most age groups exhibited two "transitional" responses: one at 70 dB HL or, sometimes, at 60 dB HL and the other mostly at 20 dB HL. As click intensity decreased, the I-III IPI tended to decrease slightly while the III-V IPI tended to increase slightly in most age groups. Since the I-V IPI was constant at various intensities which could be attributed to a slight change in the morphology of wave III with altering intensity.


[The effect of psychoeducation on quality of life in depressive disorders - results of an evaluation study in Graz].
This study aimed to evaluate the effect of psychoeducation (PE) on quality of life in depressive patients at the Department of Psychiatry, University of Medicine of Graz. We tested 49 depressive patients who participated in 9 PE group sessions at twice weekly intervals. Psychometric observer-rating and self-rating scales were conducted before and after PE completion. Our evaluation study found significant improvement in mental health status, life satisfaction, psychopathology, specific knowledge about depression and compliance. Using multiple regression analyses, we identified variables predicting a more favourable outcome in the participating patients. The vast majority of our sample would highly recommend PE to other depressive patients, and found an increase in knowledge about depression to be supportive. Our results with PE for depressive patients are encouraging, but the inclusion of appropriate control groups needs to be considered in forthcoming studies. Future research should also focus on comparison studies of PE in depressive patients with PE in schizophrenic patients, particularly as PE has proven to be an effective treatment in schizophrenia.


How the components of speaking rate influence perception of phonetic segments.
In two studies we investigated the way in which the components of speaking rate, articulation rate and pause rate, combine to influence processing of the silence-duration cue for the voicing distinction in medial stop consonants. First, we replicated the finding that the articulation rate of a carrier sentence, that is, the rate at which the speech itself is produced, influences how the duration information is used to assign voicing values. Second, and more importantly, the assignment of voicing values was also influenced by the pause rate of the sentence. Thus, the listener adjusts for both articulation rate and pause rate when processing the phonetically relevant information. Finally, the two rate components did not function in an equivalent manner, since changes in articulation rate had considerably more effect on phonetic judgments than did changes in pause rate. Alternative explanations fo the relative weighting of the two variables are discussed.


Molecular cloning of antisense transcripts of the mouse Xist gene.
Prior to X-inactivation, Xist is transcribed in unstable form. The initiation of X-inactivation is associated with the appearance of stable Xist transcripts which coat the X chromosome to be inactivated. Using strand specific RT-PCR analysis of the 5' region of Xist, we have detected antisense transcripts (Xist AS) in undifferentiated embryonic stem (ES) cells, but not in female somatic cells. Screening of a female ES cell cDNA library allowed us to isolate one poly(A)-tailed cDNA clone corresponding to this RNA. 5' RACE analysis showed that XistAS and the P1 sense product of Xist overlap by at least 707 bp. Expression of XistAS was also detected in early mouse embryos before random X-inactivation in the epiblast lineage. Although XistAS is low in abundance, it may be involved in destabilizing Xist mRNA in undifferentiated ES cells.


[Clinical observation on combined acupuncture and moxibustion therapy for treatment of 160 cases of polyneuritis].
To observe clinical therapeutic effect of combined acupuncture and moxibustion therapy on polyneuritis. One hundred and sixty cases were treated with combined scalp acupuncture, body acupuncture (stimulating root of nerve as main), cupping and pricking at segmental root of nerve, and electric hot moxibustion, and their therapeutic effects were observed. One hundred and thirty-eight cases were cured (86.3%) and the total effective rate was 100.0%. The average recovery time for clinical symptoms was 12.81 days, the average recovery time for nervous system signs was 19.76 days, the average recovery time for recovery of ocular muscular dyskinesia was 15.14 days. There was significant therapeutic effect for improvement of simple symptoms, with significant differences when the first and second therapeutic courses compared with that before treatment (P < 0.01). The combined acupuncture and moxibustion therapy has a definite therapeutic effect on polyneuritis.


Cellular reactivity to mechanical axonal injury in an organotypic in vitro model of neurotrauma.
An in vitro model of traumatic brain injury is described that is based on organotypic cocultures (OTCs) of rat neocortex and thalamus connected by reciprocal axonal projections. Localized mechanical compression of this projection was inflicted with a mechanical device, and the effects on cell viability, axonal morphology, and protein expression levels were analyzed. Within 24 h after insult, major cell damage occurred in infragranular cortical layers containing the corticothalamic projection neurons and in thalamic regions adjacent to the mechanical impact as was assessed through the use of the vital stain Syto 21, and propidium iodide labeling. A small, but significant number of calretinin-positive interneurons in cortical and thalamic areas displayed symptoms of injury. Axonal elements, as revealed by neurofilament (NF-H/M) immunohistochemistry, in the corticothalamic transition zone displayed pathomorphological changes, such as axonal bulbs and swellings, already 4 h after insult. Densitometric analysis revealed that MAP-2a,b expression was not significantly changed within 4 h after injury. A significant reduction in MAP-2a,b amount was evident at 20 h after injury in thalamus (by 31.6%) and cortex (by 30%) maintained for 12 days in vitro (DIV), but not in OTCs aged 20 DIV. The axonally localized form MAP-2c significantly increased in cortex of 12-DIV OTCs at 4 and 20 h after insult (65.6% and 33.4%, respectively). MAP-2c levels in cortex of 20 DIV initially increased by 47.7% and declined below control values 20 h after injury. Thalamic areas revealed a delay in MAP-2c reactivity, in that expression was significantly elevated only at 20 h after injury (by 84.4% in 12-DIV and by 39.6% in 20-DIV OTCs, respectively). These data may reflect the regenerative ability of juvenile, but not of older neurons in response to mechanical axonal injury.


How Germ Cells Determine Their Own Sexual Fate in Mice.
Whether to produce sperm or eggs is the most basic and important choice from the perspective of germ cell development and differentiation. However, the induction mechanism has not received much attention until relatively recently. This is because the issue of sexual differentiation has generally been considered a theme of somatic cells to make a testis or ovary. Basically, the sex of individual somatic cells and germ cells matches. Therefore, the sex of germ cells is thought to follow the sex of somatic cells once determined. However, researchers realized that a big, open question remained: What somatic cell signals actually induce the sexual differentiation of germ cells and what is the sex determinant in germ cells? In vitro experiments demonstrated that 2 somatic signals (BMP and RA) act directly on germ cells to induce oogonia. Therefore, these 2 signals may be referred to as oogonia inducers. From the viewpoint of germ cells, an independent experiment identified SMAD4 and STRA8, which are directly downstream of BMP and RA, respectively, acting in germ cells as female determinants. However, what about male? If these factors are female determinants, their absence may result in the induction of spermatogonia. This may be true in vivo because germ cells enter a male pathway if they do not receive these signals even in the ovary. However, this has not been confirmed in an in vitro culture system. There should be signals required for germ cells to enter a male pathway. The important message is that although testis-specific factors secreted from the testis are considered to include male-inducing factors for germ cells, this may not be the case, and the male-inducing factor, if it exists, also exists in the ovary.


The Community Follow-up Project (CFUP).
The Community Follow-up Project (CFUP) is a project where medical students choose a hospital in-ward patient during their clinical ward-based attachments and follow-up this patient's progress after discharge from the hospital. The students do a series of home visits and also accompany their patients for some of their follow-ups at the hospital, government clinics, general practitioners' clinics and even to the palliative care or social welfare centres. The students assess the physical, psychological and social impact of the illness on the patient, family and community. By following their patients from the time their patients were in the hospital and back to their homes and community, the students are able to understand in depth the problems faced by patients, the importance of communication skills in educating patients on their illness and the importance of good communication between primary, secondary and tertiary care.


Unveiling the role of network and systems biology in drug discovery.
Network and systems biology offer a novel way of approaching drug discovery by developing models that consider the global physiological environment of protein targets, and the effects of modifying them, without losing the key molecular details. Here we review some recent advances in network and systems biology applied to human health, and discuss how they can have a big impact on some of the most interesting areas of drug discovery. In particular, we claim that network biology will play a central part in the development of novel polypharmacology strategies to fight complex multifactorial diseases, where efficacious therapies will need to center on altering entire pathways rather than single proteins. We briefly present new developments in the two areas where we believe network and system biology strategies are more likely to have an immediate contribution: predictive toxicology and drug repurposing.


Studies on the effect of the axial magnetic field on the x-ray bremsstrahlung in a 2.45 GHz permanent magnet microwave ion source.
A compact microwave ion source has been designed and developed for operation at a frequency of 2.45 GHz. The axial magnetic field is based on two permanent magnet rings, operating in the "off-resonance" mode and is tunable by moving the permanent magnets. In order to understand the electron energy distribution function, x-ray bremsstrahlung has been measured in the axial direction. Simulation studies on the x-ray bremsstrahlung have been carried out to compare with the experimental results. The effect of the axial magnetic field with respect to the microwave launching position and the position of the extraction electrode on the x-ray bremsstrahlung have been studied.


Protective effect of BP 2-94, a histamine H3-receptor agonist prodrug, in a model of carbon tetrachloride-induced hepatotoxicity in rats.
BP 2-94 is a prodrug of the H3-receptor agonist (R)-alpha-methylhistamine [(R)-alpha-MeHA]. BP 2-94 displayed anti-inflammatory, antinociceptive and ulcero-protective properties in experimental animals. The aim of the present study was to investigate the effect of BP 2-94 in a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. In order to investigate the effect of BP 2-94 it was applied to rats either alone (20, 40 and 60 micromol kg(-1), 4 days) or as a pretreatment (20, 40 and 60 micromol kg(-1), 4 days) before the application of CCl4 (0,2 ml kg(-1), 2 days). BP 2-94 in the tested doses did not cause significant changes in the plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities and the liver microscopic appearance was normal. Hepatocyte damage, as evident by local areas of liver necrosis and elevated levels of plasma AST and ALT, occurred in rats following acute exposure to CCl4 (0,2 ml kg(-1), 2 days). BP 2-94 applied as a pretreatment dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities in response to CCl4. BP 2-94 had a hepatoprotective effect in a model of CCl4-induced toxicity in rats. This effect might be due the H3-agonistic activity of its active metabolite (R)-alpha-MeHA.


Transcutaneous partial pressure of oxygen after surgical wounds.
Transcutaneous partial pressure of oxygen (TcPO2) predicts wound healing in critical ischemia. However, no studies have controlled for the effect of wounds on TcPO2. In this study, in 24 hip or knee arthroplasty cases without vascular disease, TcPO2 was measured preoperatively at the incision site, contralaterally, and at a reference site on the chest wall. The measurements were repeated at 2 days and 2 months postoperatively and compared. TcPO2, normal preoperatively, decreased at all sites on the second postoperative day (p < 0.001), with a trend toward a greater decrease at the wound (p = 0.09). All wounds healed, and TcPO2 returned to baseline at all sites 2 months postoperatively. In conclusion, acute surgical wounds are associated with a significant and widespread decrease in cutaneous TcPO2 in the setting of normal arterial perfusion. This decrease is likely multifactorial and deserves further investigation.


Regulatory Connections between Iron and Glucose Metabolism.
Iron is essential for energy metabolism, and states of iron deficiency or excess are detrimental for organisms and cells. Therefore, iron and carbohydrate metabolism are tightly regulated. Serum iron and glucose levels are subjected to hormonal regulation by hepcidin and insulin, respectively. Hepcidin is a liver-derived peptide hormone that inactivates the iron exporter ferroportin in target cells, thereby limiting iron efflux to the bloodstream. Insulin is a protein hormone secreted from pancreatic β-cells that stimulates glucose uptake and metabolism via insulin receptor signaling. There is increasing evidence that systemic, but also cellular iron and glucose metabolic pathways are interconnected. This review article presents relevant data derived primarily from mouse models and biochemical studies. In addition, it discusses iron and glucose metabolism in the context of human disease.


Immersive virtual reality improves movement patterns in patients after ACL reconstruction: implications for enhanced criteria-based return-to-sport rehabilitation.
The purpose of this study was to evaluate the influence of immersion in a virtual reality environment on knee biomechanics in patients after ACL reconstruction (ACLR). It was hypothesized that virtual reality techniques aimed to change attentional focus would influence altered knee flexion angle, knee extension moment and peak vertical ground reaction force (vGRF) in patients following ACLR. Twenty athletes following ACLR and 20 healthy controls (CTRL) performed a step-down task in both a non-virtual reality environment and a virtual reality environment displaying a pedestrian traffic scene. A motion analysis system and force plates were used to measure kinematics and kinetics during a step-down task to analyse each single-leg landing. A significant main effect was found for environment for knee flexion excursion (P = n.s.). Significant interaction differences were found between environment and groups for vGRF (P = 0.004), knee moment (P < 0.001), knee angle at peak vGRF (P = 0.01) and knee flexion excursion (P = 0.03). There was larger effect of virtual reality environment on knee biomechanics in patients after ACLR compared with controls. Patients after ACLR immersed in virtual reality environment demonstrated knee joint biomechanics that approximate those of CTRL. The results of this study indicate that a realistic virtual reality scenario may distract patients after ACLR from conscious motor control. Application of clinically available technology may aid in current rehabilitation programmes to target altered movement patterns after ACLR. Diagnostic study, Level III.


Regulation of NOTCH signaling by RAB7 and RAB8 requires carboxyl methylation by ICMT.
Isoprenylcysteine carboxyl methyltransferase (ICMT) methylesterifies C-terminal prenylcysteine residues of CaaX proteins and some RAB GTPases. Deficiency of either ICMT or NOTCH1 accelerates pancreatic neoplasia in Pdx1-Cre;LSL-KrasG12D mice, suggesting that ICMT is required for NOTCH signaling. We used Drosophila melanogaster wing vein and scutellar bristle development to screen Rab proteins predicted to be substrates for ICMT (ste14 in flies). We identified Rab7 and Rab8 as ICMT substrates that when silenced phenocopy ste14 deficiency. ICMT, RAB7, and RAB8 were all required for efficient NOTCH1 signaling in mammalian cells. Overexpression of RAB8 rescued NOTCH activation after ICMT knockdown both in U2OS cells expressing NOTCH1 and in fly wing vein development. ICMT deficiency induced mislocalization of GFP-RAB7 and GFP-RAB8 from endomembrane to cytosol, enhanced binding to RABGDI, and decreased GTP loading of RAB7 and RAB8. Deficiency of ICMT, RAB7, or RAB8 led to mislocalization and diminished processing of NOTCH1-GFP. Thus, NOTCH signaling requires ICMT in part because it requires methylated RAB7 and RAB8.


Collagen metabolism and tooth eruption: the effects of sodium morrhuate infusions on premolar eruption in dogs.
To test the essential contribution to tooth eruption of the known high level of collagen metabolism in the periodontal ligament, we have infused the crypts of erupting premolars in dogs with sodium morrhuate, a compound known to reduce production, hydroxyproline content and maturation of collagen. Infusions of sodium morrhuate early or later in eruption for more than half the period of eruption had no effect on the process evaluated radiographically and clinically. These data, considered together with other studies, suggest that collagen metabolism per se plays no essential role in tooth eruption.


[Monocentric two-year results after phakic posterior chamber lens (PRL) implantation in myopic patients].
Some refractive procedures such as PRK or LASIK are limited by factors, including high myopia, hyperopia, or a thin cornea. For these cases, phakic intraocular lenses have been developed. Previous models have been associated with various complications, however. In order to minimize risks involved, a new phakic posterior chamber lens (PRL, IOLTECH) has been developed. Recent data suggest a considerably lower complication rate. Our two-year results are presented. The implanted lens (PRL) is a very thin foldable lens made of highly refractive silicone. The design allows floating of the lens and avoids contact to the natural lens. It is not fixed in the ciliary sulcus. Up to now, we have implanted this lens into 56 myopic eyes of 31 patients. Preoperative refraction was within a range of -8.5 to -21.25 D (spherical equivalent = S.E). Best corrected preoperative visual acuity was between 0.3 and 1.0. Postoperative follow-up was up to 3.5 years. In this study 44 eyes with at least 2 years follow-up were included. Postoperative refraction was + 0.25 to - 1.0 D (SE, one patient with intended postoperative myopia). Far visual acuity without correction was 0.4 to 1.25, far visual acuity with best correction was 0.6 to 1.25. Two cataract formations were observed, one lens had to be removed due to repeated decentration. The PRL lens seems to be a promising choice for refractive surgery in myopic patients unfit for corneal surgery, although more results, especially long-term follow-ups are needed.


Exposure of Children to Ultrafine Particles in Primary Schools in Portugal.
Children spend a large part of their time at schools, which might be reflected as chronic exposure. Ultrafine particles (UFP) are generally associated with a more severe toxicity compared to fine and coarse particles, due to their ability to penetrate cell membranes. In addition, children tend to be more susceptible to UFP-mediated toxicity compared to adults, due to various factors including undeveloped immune and respiratory systems and inhalation rates. Thus, the purpose of this study was to determine indoor UFP number concentrations in Portuguese primary schools. Ultrafine particles were sampled between January and March 2014 in 10 public primary schools (35 classrooms) located in Porto, Portugal. Overall, the average indoor UFP number concentrations were not significantly different from outdoor concentrations (8.69 × 10(3) vs. 9.25 × 10(3) pt/cm(3), respectively; considering 6.5 h of indoor occupancy). Classrooms with distinct characteristics showed different trends of indoor UFP concentrations. The levels of carbon dioxide were negatively correlated with indoor UFP concentrations. Occupational density was significantly and positively correlated with UFP concentrations. Although the obtained results need to be interpreted with caution since there are no guidelines for UFP levels, special attention needs to be given to source control strategies in order to reduce major particle emissions and ensure good indoor air quality.


Effect of NXY-059 on secondary mitochondrial dysfunction after transient focal ischemia; comparison with cyclosporin A.
The free radical trapping agents NXY-059 and alpha-phenyl-N-tert.-butylnitrone (PBN) markedly reduce infarct volume, even when given 1 or 3 h after the start of recirculation, following 2 h of middle cerebral artery (MCA) occlusion in rats. Their anti-ischemic effects are shared by the two immunosuppressants cyclosporin A (CsA) and FK506. Interestingly, CsA causes an additional reduction in infarct volume when given after only 5 min of recirculation, possibly reflecting blockade of a mitochondrial permeability transition (MPT) pore. PBN, CsA and FK506 are known to ameliorate the secondary dysfunction of mitochondrial function, as assessed in vitro, which occurs during the first 4-6 h of recirculation. The present experiments were undertaken to assess whether NXY-059 reduces tissue damage by acting directly on mitochondrial membranes, and provided that this is the case, if blockade of an MPT is involved. The results were compared to those of CsA, which thus served as a reference compound. NXY-059 was given i.v. after 5 min and 1 h, and CsA after 5 min of recirculation. Both NXY-059 and CsA reduced infarct volumes to about 30% of control, prevented the secondary decline in mitochondrial respiratory function during recirculation, and reduced the mitochondrial release of cytochrome c after 6 and 24 h of recirculation. However, NXY-059 failed to block the effect of Ca(2+) on mitochondrial swelling in vitro, as CsA did. Furthermore, NXY-059, given after 5 min of recirculation, did not reproduce the effects of CsA. The results thus suggest that NXY-059 exerts its effects on mitochondria by indirect mechanisms.


Sedative Effect of Sophora flavescens and Matrine.
The present study investigated the sedative effects of Sophora flavescens (SF) and its bioactive compound, matrine through performing locomotor activity test and the electroencephalography (EEG) analysis in the rat. The underlying neural mechanism of their beneficial effects was determined by assessing c-Fos immunoreactivity and serotonin (5-HT) in the brain utilizing immunohistochemical method and enzyme-linked immunosorbent assay. The results showed that SF and matrine administration had an effect on normalization of caffeine-induced hyperactivity and promoting a shift toward non-rapid eye movement (NREM) sleep. c-Fos-immunoreactivity and 5-HT level in the ventrolateral preoptic nucleus (VLPO), a sleep promoting region, were increased in the both SF and matrine-injected groups. In conclusion, SF and its bioactive compound, matrine alleviated caffeine-induced hyperactivity and promoted NREM sleep by activating VLPO neurons and modulating serotonergic transmission. It is suggested that SF might be a useful natural alternatives for hypnotic medicine.


m6A RNA modification modulates PI3K/Akt/mTOR signal pathway in Gastrointestinal Cancer.
Rationale: Methylation at the N6 position of adenosine (m6A) is the most prevalent RNA modification within protein-coding mRNAs in mammals, and it is a reversible modification with various important biological functions. The formation and function of m6A are regulated by methyltransferases (writers), demethylases (erasers), and special binding proteins (readers) as key factors. However, the underlying modification mechanisms of m6A in gastrointestinal (GI) cancer remain unclear. Here, we performed comprehensive molecular profiling of the nine known m6A writer, eraser, and reader proteins in GI cancer. Methods: Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were used. Gene alteration and pathway analysis were done in cBioportal. The protein network of m6A regulators and its related pathway members was analyzed in STRING online platform. Phylogenetic tree was constructed in MEGA7. m6A modification sites were predicted by SRAMP. m6A related SNPs were analyzed by m6ASNP. The modulation of m6A on its related pathway members was validated by m6A-seq, real-time PCR and phosphor-MAPK array. Results: We found that m6A regulators were mostly upregulated in GI cancer and their differential expression significantly influenced the overall survival of patients with GI cancer. The phosphatidylinositol-3-kinase (PI3K)/Akt and mammalian target of rapamycin (mTOR) signaling pathways were found to be potentially affected by m6A modification in most human cancers, including GI cancer, which was further verified by m6A-Seq and phospho-MAPK array. Conclusions: Our findings suggest that m6A RNA modification has a fundamental role in the regulation of PI3K/Akt and mTOR signaling pathway function in cancer.


[Desmin filaments and their disorganization associated with myofibrillar myopathies].
Desmin, the muscle-specific intermediate filament protein, is one of the earliest markers expressed in all muscle tissues during development. It forms a three-dimensional scaffold around the myofibril Z-disc and connects the entire contractile apparatus to the subsarcolemmal cytoskeleton, the nuclei and other cytoplasmic organelles. Desmin is essential for tensile strength and muscle integrity. In humans, disorganization of the desmin network is associated with cardiac and/or skeletal myopathies characterized by accumulation of desmin-containing aggregates in the cells. Currently, 49 mutations have been identified in desmin gene. The majority of these mutations alter desmin filament assembly process through different molecular mechanisms and also its interaction with its protein partners. Here, we will give an overview of desmin network organization as well as the impact of desmin mutations on this process. Furthermore, we will discuss the different molecular mechanisms implicated in perturbation of the desmin filament assembly process.


CDF/LIF selectively increases c-fos and jun-B transcripts in sympathetic neurons.
We recently demonstrated that the neuronal cholinergic differentiation factor (CDF) which switches the neurotransmitter phenotype of cultured sympathetic neurons from noradrenergic to cholinergic is identical to leukemia inhibitory factor (LIF). To elucidate some of the initial events leading to the phenotypic switch, the effects of CDF/LIF on the mRNA levels of several immediate early genes were examined in cultured neonatal rat sympathetic neurons. c-fos and jun-B were induced within 30 min of addition of CDF/LIF. In contrast, no effect on the expression of c-myc, fra-1, v-jun or actin mRNA was detected at this time. Thus, CDF/LIF may induce the expression of particular immediate early genes prior to its positive and negative effects on neurotransmitter and neuropeptide gene expression.


The impact of child, family, and professional support characteristics on the quality of life in families of young children with disabilities.
Families of young children with disabilities are faced with ongoing challenges that impact various aspects of family life. Given the increasing emphasis on promoting positive outcomes in these families, the overall aim of the current study was to examine the contribution of child, family, and support characteristics to the quality of life in families of young children with disabilities. The sample was recruited from several early childhood intervention programs within metropolitan Melbourne, Australia, and consisted of 64 families of children aged between 3 and 5 years with a developmental delay or disability. As a whole, parental perceptions and experiences of family-centred professional support was one of the strongest predictors of family quality of life. The perceived intensity of child behavioural problems as well as support from extended family members also accounted for a significant proportion of unique variance in predicting quality of family life. The current findings provide further evidence for the importance of a family-focused approach to intervention that acknowledges and provides support that is tailored to the unique needs of each individual family. The practical implications of these results as well as directions for future research are discussed.


Effects of magnesium deficiency on the photosynthesis and respiration of leaves of sugar beet.
The effects of Mg deficiency on the photosynthesis and respiration of sugar beets (Beta vulgaris L. cv. F58-554H1) were studied by withholding Mg from the culture solution and by following changes in CO(2) and water vapor exchange of attached leaves. Leaf blade Mg concentration decreased from about 1200 to less than 200 meq kg(-1) dry matter without change in the rate of photosynthetic CO(2) uptake per unit leaf area, while from 200 to 50 meq kg(-1) the rate decreased to one-third. Rates of photorespiratory evolution of CO(2) into CO(2)-free air responded to Mg like those of photosynthetic CO(2) uptake, the rates decreasing to one-half, below 200 meq kg(-1). Respiratory CO(2) evolution in the dark increased almost 2-fold in low Mg leaves. Magnesium deficiency had less effect on leaf (mainly stomatal) diffusion resistance (r(1)) than on mesophyll resistance (r(m)); in Mg-deficient plants r(m) increased from 2.9 to 7.1 sec cm(-1), whereas r(1) became significantly greater than the control value only in the most severe instances of Mg deficiency.


Infantile spasms associated with a histamine H1 antagonist.
Some anti-allergic agents act as histamine H1 antagonists and induce seizure discharges in epileptic patients. Of these agents, ketotifen has an especially potent effect. We have experienced 2 cases of 4-month-old boys who developed infantile spasms 8 to 10 days after ketotifen administration. They showed almost the same clinical course with regard to their age, the interval between ketotifen administration and the onset of seizures, their symptoms and EEG abnormalities. These cases suggest that the administration of ketotifen to young infants may be hazardous with regard to inducing infantile spasms.


Filarial Lymphedema Patients Are Characterized by Exhausted CD4+ T Cells.
Worldwide, more than 200 million people are infected with filariae which can cause severe symptoms leading to reduced quality of life and contribute to disability-adjusted life years (DALYs). In particular, lymphatic filariasis (LF) caused by Wuchereria bancrofti can lead to lymphedema (LE) and consequently presents a serious health problem. To understand why only a fraction of the infected individuals develop pathology, it is essential to understand how filariae regulate host immunity. The central role of T cells for immunity against filariae has been shown in several studies. However, there is little knowledge about T cell exhaustion, which causes T cell dysfunction and impaired immune responses, in this group of individuals. Recently, we showed that LE patients from Ghana harbor distinct patterns of exhausted effector and memory CD8+ T cell subsets. Based on these findings, we now characterized CD4+ T cell subsets from the same Ghanaian patient cohort by analyzing distinct markers within a 13-colour flow cytometry panel. We revealed that LE patients had increased frequencies of CD4+ T cells expressing exhaustion-associated receptors such as KLRG-1, TIM-3 and PD-1 compared to healthy endemic normal and W. bancrofti-infected individuals. Moreover, CD4+ T cells in LE patients were characterized by distinct co-expression patterns of inhibitory receptors. Collectively with the previous findings on CD8+ T cell exhaustion patterns, the data shown here demonstrates that filarial LE patients harbor distinct subsets of exhausted T cells. Thus, T cell exhaustion patterns in LE patients need attention especially in regards to susceptibility of concomitant infections and should be taken into consideration for LE management measures.


High-dose chemotherapy in adult acute myeloid leukemia: rationale and results.
Preclinical studies and retrospective evaluations of clinical trials of a number of cytotoxic drugs have provided a rationale for the use of high doses of chemotherapy in adults with acute myeloid leukemia (AML). To maximize cure and remission rates at an acceptable cost in toxicity, many schedules and combinations of dose-intensive chemotherapy have been tested in recent years in patients with de novo disease, cytosine arabinoside (Ara-C) being the most extensively evaluated drug. In this article we review the principal results of both randomized and non-controlled studies. Our analysis indicates that high-dose Ara-C (HIDAC) used during induction results is no substantial benefit relative to conventional doses of drug. On the other hand, consolidation with HIDAC is a major advance in the treatment of this disease. In fact, in individuals less than 60 years of age and a favorable or intermediate-risk karyotype, HIDAC-based regimens have resulted in survival estimates comparable to those of autologous or allogeneic bone marrow transplantation. Yet, the role of HIDAC is irrelevant in younger individuals with an unfavorable cytogenetic pattern and detrimental in patients greater than 60 years of age. Since recently new cytotoxic agents have expanded the armamentarium of antileukemic drugs, well conducted randomized trials of dose intensive chemotherapy still need to be performed to optimize schedules and combinations of drugs in patients with AML.


Do interventions to improve adherence to antiretroviral therapy recognise diversity? A systematic review.
People living with HIV (PLWH) are often culturally and linguistically diverse populations; these differences are associated with differing barriers to antiretroviral therapy (ART) adherence. Cultural competence measures the extent to which trial design recognises this diversity. This systematic review aimed to determine whether adherence trial participants represent the diversity of PLWH. Randomised Controlled Trials in Organisation for Economic Co-operation and Development countries to improve ART adherence were eligible. We searched MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews. For all included trials, we searched for their development, testing and evaluation studies. We compared trial participant characteristics with nationally reported PLWH data. We appraised trial cultural competence against ten criteria; scoring each criterion as 0, 1 or 2 indicating cultural blindness, pre-competence or competence respectively. For 80 included trials, a further 13 studies presenting development/testing/evaluation data for the included trials were identified. Only one of the 80 included studies reported trial participants representative of the country's population of PLWH. The median (IQ) cultural competence score was 2.5 (1.0, 4.0) out of 20. HIV adherence trial participants are not reflective of the population with HIV, which may be due to limited adoption of culturally competent research methods.


Inhibition of Salmonella enterica biofilm formation using small-molecule adenosine mimetics.
Biofilms have been widely implicated in chronic infections and environmental persistence of Salmonella enterica, facilitating enhanced colonization of surfaces and increasing the ability of the bacteria to be transmitted to new hosts. Salmonella enterica serovar Typhi biofilm formation on gallstones from humans and mice enhances gallbladder colonization and bacterial shedding, while Salmonella enterica serovar Typhimurium biofilms facilitate long-term persistence in a number of environments important to food, medical, and farming industries. Salmonella regulates expression of many virulence- and biofilm-related processes using kinase-driven pathways. Kinases play pivotal roles in phosphorylation and energy transfer in cellular processes and possess an ATP-binding pocket required for their functions. Many other cellular proteins also require ATP for their activity. Here we test the hypothesis that pharmacological interference with ATP-requiring enzymes utilizing adenosine mimetic compounds would decrease or inhibit bacterial biofilm formation. Through the screening of a 3,000-member ATP mimetic library, we identified a single compound (compound 7955004) capable of significantly reducing biofilm formation by S. Typhimurium and S. Typhi. The compound was not bactericidal or bacteriostatic toward S. Typhimurium or cytotoxic to mammalian cells. An ATP-Sepharose affinity matrix technique was used to discover potential protein-binding targets of the compound and identified GroEL and DeoD. Compound 7955004 was screened against other known biofilm-forming bacterial species and was found to potently inhibit biofilms of Acinetobacter baumannii as well. The identification of a lead compound with biofilm-inhibiting capabilities toward Salmonella provides a potential new avenue of therapeutic intervention against Salmonella biofilm formation, with applicability to biofilms of other bacterial pathogens.


Psychosocial considerations in occupational therapy treatment for adults with acquired brain injury: a survey.
ABSTRACT The psychosocial factors of coping, locus of control, and self-efficacy have been shown to be associated positively with real-world outcomes following acquired brain injury (ABI), although to our knowledge there are no studies investigating whether occupational therapists address these factors in practice. This study used on-line survey methodology to investigate whether Canadian occupational therapists working in ABI rehabilitation were addressing these factors in their practice. Of 151 respondents, the majority reported being able to explain the factors to clients and that they and/or their team members were incorporating them into clinical practice. Participants also provided examples that were analyzed for common themes. The majority of examples of how these factors were incorporated into practice were implicit in nature. Further education regarding these factors may be warranted as only 25% of the respondents reported learning about these factors in their occupational therapy education.


Recognition of foldback DNA by the human DNA (cytosine-5-)-methyltransferase.
In order to specify the recognition requirements of the human DNA (cytosine-5-)-methyltransferase, two isomeric 48mers were synthesized so as to link a long block of DNA with a shorter complementary block of DNA through a tether consisting of five thymidine residues. These isomeric foldback molecules, differing only in the location of the 5-methyldeoxycytosine, were shown to be unimolecular, to contain a region of duplex DNA, and to contain a region of single-stranded DNA. When used as substrates for the DNA methyltransferase, only one of the isomers was methylated. A comparison of the structures of the two isomers allows us to begin to define the potential sites of interaction between the enzyme and the three nucleotides forming a structural motif consisting of 5-methyldeoxycytosine, its base-paired deoxyguanosine, and a deoxycytosine 5' to the paired deoxyguanosine.


Testing GSTP1 genotypes and haplotypes interactions in Slovenian post-/pre-menopausal women: novel involvement of glutathione S-transferases in bone remodeling process.
Osteoporosis (OP) is an age-related disease associated with increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense system, such as low activity of glutathione S-transferase (GST) family. The enzyme activity of the member of GSTs, GSTP1, depends on gene polymorphisms such as: Ala114Val and Ile105Val. The aim of this study was to evaluate the association between genetic polymorphisms of the GSTP1 gene and BMD variation and biochemical bone remodeling markers in 523 Slovenian pre- and post-menopausal women. Observational pilot study in a representative cohort of Slovenian patients with adjustment for potential confounders (age, height, weight, years since menopause, smoking status and glucocorticoid use) using univariate one-way and two-way analyses. Ala114Val and Ile105Val polymorphisms genotypes of GSTP1 gene, bone mineral density (BMD) values of total hip (_th), femoral neck (_fn) and lumbar spine (_ls), plasma osteocalcin (OC), serum bone alkaline phosphatase (BALP), free soluble RANKL and serum osteoprotegerin (sOPG) concentrations were determined. Our results show that the Ala114Val heterozygotes are (borderline) significantly associated with higher concentrations of pOC (p=0.052) and decreased BMD_fn values (p=0.053) and the same trend is shown for BMD_th and BMD_ls values in osteopenic postmenopausal women. Furthermore, significantly higher concentrations of pOC were determined among Val allele carriers of Ile105Val gene polymorphism (p=0.037) and in carriers with the absent 114Ala-105Ile haplotype combination, again in osteopenic post-menopausal women. In addition, in pre-menopausal women the significant associations between sOPG and Ala114Val genotypes subgroups and between sBALP and Ile105Val genotypes subgroups, alone or in combination with Ala114Val, were determined (0.032, 0.026 and 0.008, respectively). Since significant associations existed in Ala114Val genotype and 114Ala-105Ile haplotype subgroups, these variations can be useful for determining low BMD and high pOC risk in postmenopausal women.


Determination of the toxicologically relevant arsenic content in urine.
A combination of the flow injection technique with hydride AAS for the detection of the toxicologically relevant arsenic sum parameters offers the following advantages: Automated sample preparation Detection of arsenic as As(III), As(V), mono- and dimethyl arsinic acid (MMA and DMA) Good accuracy and precision Very good detection limits Simple calibration against aqueous As3+ solutions.


Analyzing Twitter as a Platform for Alzheimer-Related Dementia Awareness: Thematic Analyses of Tweets.
Dementia is a prevalent disorder among adults and often subjects an individual and his or her family. Social media websites may serve as a platform to raise awareness for dementia and allow researchers to explore health-related data. The objective of this study was to utilize Twitter, a social media website, to examine the content and location of tweets containing the keyword "dementia" to better understand the reasons why individuals discuss dementia. We adopted an approach that analyzed user location, user category, and tweet content subcategories to classify large publicly available datasets. A total of 398 tweets were collected using the Twitter search application programming interface with the keyword "dementia," circulated between January and February 2018. Twitter users were categorized into 4 categories: general public, health care field, advocacy organization, and public broadcasting. Tweets posted by "general public" users were further subcategorized into 5 categories: mental health advocate, affected persons, stigmatization, marketing, and other. Placement into the categories was done through thematic analysis. A total of 398 tweets were written by 359 different screen names from 28 different countries. The largest number of Twitter users were from the United States and the United Kingdom. Within the United States, the largest number of users were from California and Texas. The majority (281/398, 70.6%) of Twitter users were categorized into the "general public" category. Content analysis of tweets from the "general public" category revealed stigmatization (113/281, 40.2%) and mental health advocacy (102/281, 36.3%) as the most common themes. Among tweets from California and Texas, California had more stigmatization tweets, while Texas had more mental health advocacy tweets. Themes from the content of tweets highlight the mixture of the political climate and the supportive network present on Twitter. The ability to use Twitter to combat stigma and raise awareness of mental health indicates the benefits that can potentially be facilitated via the platform, but negative stigmatizing tweets may interfere with the effectiveness of this social support.


Consumer interpretation of ramipril and clopidogrel medication risk information - implications for risk communication strategies.
Side effects and side-effect risk information can be provided using written medicine information. However, challenges exist in effectively communicating this information to consumers. This study aimed to explore broad consumer profiles relevant to ramipril and clopidogrel side-effect risk information interpretation. Three focus groups were conducted (n=18 consumers) exploring consumer perspectives, understanding and treatment decision making in response to ramipril and clopidogrel written medicine information leaflets containing side effects and side-effect risk information. All discussions were audio recorded, transcribed verbatim, and analyzed to explore consumer profiles pertaining to side-effect risk appraisal. Three consumer profiles emerged: glass half-empty, glass half-full, and middle-of-the-road consumers, highlighting the influence of perceived individual susceptibility, interpretation of side-effect risk information, and interindividual differences, on consumers' understanding of side-effect risk information. All profiles emphasized the importance of gaining an understanding of individual side-effect risk when taking medicines. Written side-effect risk information is not interpreted uniformly by consumers. Consumers formulated their own construct of individual susceptibility to side effects. Health care professionals should consider how consumers interpret side-effect risk information and its impact on medication use. Existing risk communication strategies should be evaluated in light of these profiles to determine their effectiveness in conveying information.


Leukocyte depleted, unscreened blood products give a low risk for CMV infection and disease in CMV seronegative allogeneic stem cell transplant recipients with seronegative stem cell donors.
Leukocyte depletion (LD) by blood product filtration has been shown to be similarly effective to the use of screened, CMV seronegative blood products to prevent CMV disease in CMV seronegative allogeneic stem cell transplant (SCT) patients with CMV seronegative donors. The aim of this retrospective study was to determine the risk for development of CMV infection requiring preemptive therapy and for CMV disease if unscreened products treated by prestorage LD is used. Forty-nine consecutive patients transplanted after June 1995 were included. As a control group, 33 patients transplanted from January 1992 to June 1995 in whom a combination of CMV seronegative and LD blood products were given. All patients were monitored weekly by a leukocyte-based PCR for CMV DNA detection. Preemptive therapy was initiated after two consecutively positive tests. No patient developed CMV disease in either group. CMV DNA was detected in 6/49 (p = NS) in the study group and in 3/33 patients in the historical control group. Two patients in the study group were given preemptive therapy compared to one patient in the control group. This study suggests that the risk for CMV disease and the need for preemptive therapy against CMV is low in CMV seronegative allogeneic SCT patients receiving grafts from CMV seronegative stem cell donors receiving LD blood products. Thus, this strategy can be safely used together with PCR monitoring and preemptive therapy.


Community health orientation, community-based quality improvement, and health promotion services in hospitals.
The objective of the study presented in this article was to examine the relationship between hospital community orientation and the provision of health promotion services. The study used data from the 2000 American Hospital Association survey and the 2000 Area Resource File to examine acute care hospitals throughout the United States. The study was a cross-sectional multiple regression analysis. Hospital community orientation was measured by two independent variables: (1) community health orientation and (2) community-based quality orientation. Health promotion services were represented by two dependent variables: (1) hospital-based health promotion services and (2) collaborative health promotion services. Organizational control variables included bed-size code, not-for-profit ownership, network participation, and joint venture/alliance membership. Environmental control variables included the proportion of population over age 65, the percentage of population below the poverty level, the square root of the proportion of Medicaid inpatient revenue, the presence of state community benefit laws/guidelines, a Herfindahl-Hirschman Index of level of competition, and an index of managed care influence. Results of regression analyses showed that community health and community-based quality orientations were positively and significantly related to both the direct provision of health promotion services by hospitals and the collaborative provision of health promotion services through systems, joint ventures, and networks. The study concludes that a community health orientation and a community-based quality orientation lead to greater provision of health promotion services.