Combined hydrogen production and storage with subsequent carbon crystallization.
We provide evidence of low-temperature hydrogen evolution and possible hydrogen trapping in an anthracite coal derivative, formed via reactive ball milling with cyclohexene. No molecular hydrogen is added to the process. Raman-active molecular hydrogen vibrations are apparent in samples at atmospheric conditions (300 K, 1 bar) for samples prepared 1 year previously and stored in ambient air. Hydrogen evolves slowly at room temperature and is accelerated upon sample heating, with a first increase in hydrogen evolution occurring at approximately 60 degrees C. Subsequent chemical modification leads to the observation of crystalline carbons, including nanocrystalline diamond surrounded by graphene ribbons, other sp2-sp3 transition regions, purely graphitic regions, and a previously unidentified crystalline carbon form surrounded by amorphous carbon. The combined evidence for hydrogen trapping and carbon crystallization suggests hydrogen-induced crystallization of the amorphous carbon materials, as metastable hydrogenated carbons formed via the high-energy milling process rearrange into more thermodynamically stable carbon forms and molecular hydrogen.


Pre-post Mixed Methods Study of a Parent and Teen Support Intervention to Prevent Violence Against Adolescents in the Philippines.
This study examines the feasibility of a culturally adapted parenting intervention (MaPa Teens) within the national cash transfer system to reduce violence against adolescents, the first such program in the Philippines. Thirty caregiver-adolescent dyads who were beneficiaries of a government conditional cash transfer program participated in a pilot of a locally adapted version of the Parenting for Lifelong Health for Parents and Teens program. Primary outcomes of reducing child maltreatment and associated risk factors were evaluated using a single-group, pre-post design. Focus group discussions explored the perceptions of participants and facilitators regarding program acceptability and feasibility. Significant and moderate reductions were reported in overall child maltreatment and physical abuse (caregiver and adolescent reports) and in emotional abuse (adolescent report). There were significant reductions in neglect, attitudes supporting punishment, parenting stress, parental and adolescent depressive symptoms, parent-child relationship problems, and significant improvement in parental efficacy in managing child behavior. Adolescents reported reduced behavior problems, risk behavior, and witnessing of family violence. Participants valued learning skills using a collaborative approach, sustained their engagement between sessions through text messages and phone calls, and appreciated the close interaction with caring and skilled facilitators. Program areas of improvement included addressing barriers to attendance, increasing adolescent engagement, and revising the sexual health module. The study provides preliminary support for the effectiveness and feasibility of the program in reducing violence against Filipino adolescents. Findings suggest potential adaptations of the program, and that investment in more rigorous testing using a randomized controlled trial would be worthwhile.


Nutrient and Food Group Intakes of Manitoba Children and Youth: A Population-Based Analysis by Pulse and Soy Consumption Status.
Poor eating habits among children are associated with negative health outcomes. The objective of this study was to use pulse/soy consumption as an indicator to evaluate the eating profile of young Manitobans. Data from the Canadian Community Health Survey Cycle 2.2 were used for analysis and restricted to Manitoba residents aged 2 to 18 years (n = 1840). Consumers were identified as individuals who reported eating at least 1 pulse/soy product during their recall. On any given day, 8.2% of Manitobans reported consumption of pulses/soy. Intakes of fibre, protein, magnesium, and zinc were higher in consumers only when expressed relative to total caloric intake. Consumers also reported increased intakes of meat and alternatives. Total intakes of vitamin D, fibre, and fruit and vegetable consumption were low among all groups. Sodium intakes in both groups were high when compared with levels recommended by health professionals. These results indicate that there are many dietary issues affecting Manitoba children, suggesting the need for more research targeting dietary habits of children and youth, the quality of the food supply, and effective strategies in nutrition education.


Beta-adrenergic blockers in patients with acute myocardial infarction.
Beta-blockers given within the first 24 hours of an acute MI, first as an intravenous bolus followed by oral therapy, have been shown to reduce in-hospital mortality following a myocardial infarction. For the long-term, beta-blockers represent the only documented effective prophylactic treatment for MI patients. The reduction in all-cause mortality is due primarily to a reduction in atherosclerotic cardiovascular deaths, particularly sudden cardiac deaths. This finding is consistent with the experimental observation that beta-blockers raise the threshold for ventricular fibrillation. Indeed, MI patients with complex ventricular arrhythmias respond very favorably to beta-blockers. However, reductions in nonsudden deaths and nonfatal reinfarctions have also been observed, suggesting that the beneficial effects of beta-blockers are not limited to antiarrhythmic effects alone and that these drugs may also have anti-ischemic effects. The prime candidates for beta-blocker therapy are the high-risk MI patients with transient electrical and/or pump complications during the acute phase. If therapy is initiated within hours of an acute infarction, it seems reasonable to continue it after hospital discharge. Evidence from the large, long-term trials suggest that, in the absence of any troublesome adverse reaction and given that most post-MI patients experience ventricular arrhythmias and angina, it seems reasonable not to limit the duration of treatment.


Genetic map of lps3: a new short petiole gene in soybeans.
The short petiole trait is valuable for the development of plant ideotypes with high yield by improving the plant canopy. The soybean breeding line SS98206SP has shown extremely short petioles in the greenhouse and fields. A new single recessive gene designated as lps3 confers the short petiole trait in SS98206SP. The objectives of this study were to map the short petiole gene in SS98206SP with PCR-based markers. In total, 187 F(2) plants and their F(2:3) families from a cross between the short petiole line SS98206SP and the long petiole cultivar 'Taekwang' along with the two parental lines were evaluated for their petiole lengths in a greenhouse. An SSR marker from each 10-cM section of a consensus soybean map was selected for bulked segregant analysis (BSA) to identify the tentative genomic location of the gene. The BSA technique was useful to localize the gene to a genomic region in the soybean linkage group F (chromosome 13). A linkage map with six SSR and two SNP markers flanking the gene was constructed. We positioned the gene between two SSR markers, Sat_234 and Sct_033, at distances of 8.5 and 3.5 cM from the marker, respectively. The makers flanking the gene (lps3) were located within 3-4 cM of the gene. These markers will be useful for maker-assisted selection in the development of new ideotype soybean plants.


Demonstration of vortex-induced beam shaping in seeded second-harmonic generation.
We report the experimental demonstration of a method that allows the simultaneous frequency-doubling and the shaping of a light beam into a variety of patterns. The technique is based on the controllable generation of multiple-vortex patterns in seeded schemes. Our observations were performed under conditions of second-harmonic generation pumped by picosecond pulses at 1055 nm, but the scheme can be extended to all parametric processes.


More effective transposon regulation in fertile, long-lived termite queens than in sterile workers.
Transposable elements (TEs) are mobile genetic sequences, which can cause the accumulation of genomic damage in the lifetime of an organism. The regulation of TEs, for instance via the piRNA-pathway, is an important mechanism to protect the integrity of genomes, especially in the germ-line where mutations can be transmitted to offspring. In eusocial insects, soma and germ-line are divided among worker and reproductive castes, so one may expect caste-specific differences in TE regulation to exist. To test this, we compared whole-genome levels of repeat element transcription in the fat body of female workers, kings and five different queen stages of the higher termite, Macrotermes natalensis. In this species, queens can live over 20 years, maintaining near maximum reproductive output, while sterile workers only live weeks. We found a strong, positive correlation between TE expression and the expression of neighbouring genes in all castes. However, we found substantially higher TE activity in workers than in reproductives. Furthermore, TE expression did not increase with age in queens, despite a sevenfold increase in overall gene expression, due to a significant upregulation of the piRNA-pathway in 20-year-old queens. Our results suggest a caste- and age-specific regulation of the piRNA-pathway has evolved in higher termites that is analogous to germ-line-specific activity in solitary organisms. In the fat body of these termite queens, an important metabolic tissue for maintaining their extreme longevity and reproductive output, an efficient regulation of TEs likely protects genome integrity, thus further promoting reproductive fitness even at high age.


Preparation of biodegradable polylactide microparticles via a biocompatible procedure.
PLA MPs are prepared via a novel and toxic-chemical-free fabrication route using ethyl lactate, a green solvent and FDA-approved aroma. MPs are obtained by a solution jet break-up and solvent displacement method. Adjusting flow parameters allows the tuning of MPs size between 60 and 180 µm, with reduced polydispersity. Morphological analysis shows microporous particles with Janus-like surface. A fluorophore is successfully loaded into the MPs during their formation step. This versatile green solvent-based procedure is proven to be suitable for drug encapsulation and delivery applications. The method may be extended to different droplet generation techniques.


First Report of Downy Mildew Caused by Plasmopara halstedii on Black-eyed Susan (Rudbeckia fulgida cv. 'Goldsturm') in Maryland.
The North American perennial black-eyed Susan (Rudbeckia fulgida cv. Goldsturm) is an important nursery crop, prized by gardeners and landscapers for its persistent bloom and ease of cultivation. In September 2013, disease symptoms characteristic of downy mildew were observed from multiple R. fulgida plants at two commercial nurseries in the Maryland counties of Howard and Anne Arundel. Over 100 R. fulgida were affected by this disease in both nurseries, rendering the plants unmarketable and causing a substantial financial loss. Plants exhibited dark necrotic lesions on the adaxial leaf surface, and sporulating masses of white mycelium on the abaxial leaf surface and on the adaxial in extreme infections. Plants were stunted with a reduced number of blooms. Microscopic visualization showed coenocytic mycelium, hyaline sporangiophores (length 261 to 904 μm; = 557 μm; n = 20) that were straight and monopodially branched at right angles with several terminal branchlets. Sporangia were hyaline, ovoid to elliptical with smooth surfaces ( = 31 × 28 μm; n = 50). Based on morphological data, the organism was identified as Plasmopara halstedii (Farl.) Berl. & De Toni in Sacc (2). Voucher specimens were deposited in the U.S. National Fungus Collections (BPI 892792 to 892794). Molecular identification was conducted by extracting genomic DNA from sporangiophores and mycelium tweezed from the surface of three infected plants, with extractions performed using the QIAGEN Plant DNA kit (QIAGEN, Gaithersburg, MD). The large subunit of the nuclear rDNA was amplified by PCR using primers LROR and LR7 (3) and sequenced bidirectionally. BLASTn searches of NCBI GenBank showed that the resultant rDNA sequences (accessions KF927152 to KF927154) shared 99% nucleotide identity with curated P. halstedii sequences, consistent with morphological identification. To confirm pathogenicity, three 3.78-liter (1 gallon) containerized R. fulgida cv. Goldsturm plants were inoculated with a sporangial suspension of 2.4 × 104 sporangia/ml and sprayed until both the upper and lower surface of the leaves were completely covered. One negative control plant was sprayed with deionized water. Plants were placed in clear plastic bags in a growth chamber (20°C, 12-h photoperiod). Disease symptoms were observed 3 days post inoculation on all plants. The control plant was symptomless. Morphological features of the pathogen on the surface of inoculated plants were identical to those observed from the original infected plants. Although P. halstedii on R. fulgida cv. Goldsturm has been previously reported in Virginia in 2006 and Florida in 2004, to our knowledge, this is the first report on R. fulgida cv. Goldsturm in Maryland (1). Black-eyed Susans are widely distributed throughout Maryland's landscape and are a staple plant for gardeners, nurserymen and landscape professionals. Given the destructive nature of this disease, downy mildew has the potential to cause considerable economic losses to the state's ornamental crop industry. References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases, Syst. Mycol. Microbiol. Lab., ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ , November 18, 2013. (2) P. A. Saccardo. Syllogue Fungorum 7:242, 1888. (3) R. Vilgalys and M. Hester. J. Bacteriol. 172:4238, 1990.


DomArchive: a century of published dominance data.
Dominance behaviours have been collected for many groups of animals since 1922 and serve as a foundation for research on social behaviour and social structure. Despite a wealth of data from the last century of research on dominance hierarchies, these data are only rarely used for comparative insight. Here, we aim to facilitate comparative studies of the structure and function of dominance hierarchies by compiling published dominance interaction datasets from the last 100 years of work. This compiled archive includes 436 datasets from 190 studies of 367 unique groups (mean group size 13.8, s.d. = 13.4) of 135 different species, totalling over 243 000 interactions. These data are presented in an R package alongside relevant metadata and a tool for subsetting the archive based on biological or methodological criteria. In this paper, we explain how to use the archive, discuss potential limitations of the data, and reflect on best practices in publishing dominance data based on our experience in assembling this dataset. This archive will serve as an important resource for future comparative studies and will promote the development of general unifying theories of dominance in behavioural ecology that can be grounded in testing with empirical data. This article is part of the theme issue 'The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies'.


Sexual reproduction of the pentaploid, short-styled Oxalis pes-caprae allows the production of viable offspring.
Reproduction is a key factor for the successful establishment and spread of introduced species. Oxalis pes-caprae is a tristylous species with a self- and morph-incompatibility sexual system that, in the invaded range of the western Mediterranean Basin, has been found to reproduce asexually because only the pentaploid, short-styled morph (5x S-morph) was introduced. The objective of this study was to test the ability of the 5x S-morph of O. pes-caprae to produce viable offspring in the absence of compatible mates, exploring the hypothesis that new morphs could have emerged by sexual reproduction events of the initially introduced morph. Pollen germination, pollen tube development, fruit and seed production, seed germination and offspring ploidy levels were analysed after controlled hand-pollinations to assess self- and morph-incompatibility and production of viable gametes by the 5x S-morph. The self-incompatibility system is still operating, but a partial breakdown in the morph-incompatibility system combined with the production of viable gametes was observed, allowing sexual reproduction of the 5x S-morph in the invaded range. The ability of the 5x S-morph to reproduce sexually may have major consequences for the dynamics of invasive populations of O. pes-caprae and could be one of the factors involved in the occurrence of new floral morphs in this invaded range.


Comprehensive analysis of mitophagy-related genes in NSCLC diagnosis and immune scenery: based on bulk and single-cell RNA sequencing data.
Lung cancer is the main cause of cancer-related deaths, and non-small cell lung cancer (NSCLC) is the most common type. Understanding the potential mechanisms, prognosis, and treatment aspects of NSCLC is essential. This study systematically analyzed the correlation between mitophagy and NSCLC. Six mitophagy-related feature genes (SRC, UBB, PINK1, FUNDC1, MAP1LC3B, and CSNK2A1) were selected through machine learning and used to construct a diagnostic model for NSCLC. These feature genes are closely associated with the occurrence and development of NSCLC. Additionally, NSCLC was divided into two subtypes using unsupervised consensus clustering, and their differences in clinical characteristics, immune infiltration, and immunotherapy were systematically analyzed. Furthermore, the interaction between mitophagy-related genes (MRGs) and immune cells was analyzed using single-cell sequencing data. The findings of this study will contribute to the development of potential diagnostic biomarkers for NSCLC and the advancement of personalized treatment strategies.


Quality choice in Medicaid markets. The case of nursing homes.
This article examines whether private patients, who typically pay a price higher than the Medicaid reimbursement rate, receive the same or higher quality services than Medicaid patients in the same health care facility. Because the mix of patients will affect the firm's cost only when Medicaid and private patients receive different levels of quality, the cost function can be used to test for the presence of quality differences. Estimates of a cost function for Texas nursing home in 1983 indicate that the mix of patients does not affect the firm's cost. Thus, private and Medicaid patients in the same nursing home receive the same level of quality.


Effects of various lighting regimens and pinealectomy on semen production in Romney rams.
Sixteen Romney rams were utilized in a 2 x 2 factorial experiment designed to evaluate the effects on semen production of (i) contrasting lighting regimens, and (ii) pinealectomy or sham-operation. Reversal of the annual photoperiodic cycle advanced the seasonal peak of fructose levels in semen by 4 months and also reduced percentages of unstained and morphologically normal spermatozoa. Pinealectomy abolished this advancement of peak fructose production and reduced overall concentrations and motility of spermatozoa. Moreover, towards the end of the study pinealectomized rams had higher ejaculate volumes than did sham-operated rams. Testicular and accessory sex gland data obtained after the rams were killed showed a marked influence of the lighting regimen: high values from sham-operated rams in short daily photoperiods contrasted with depressed values from those in long daily photoperiods. Pinealectomized rams provided values midway between these extremes, a finding which suggested both anti- and pro-gonadotrophic roles for the pineal gland in rams.


Selective increase of NMDA-sensitive glutamate binding in the striatum of Parkinson's disease, Alzheimer's disease, and mixed Parkinson's disease/Alzheimer's disease patients: an autoradiographic study.
Parkinson's disease (PD) and Alzheimer's disease (AD) may share certain abnormalities since a subset of PD patients suffer from dementia, and some AD individuals show extrapyramidal symptoms. In vitro quantitative autoradiography was used to examine different subtypes of excitatory amino acid (EAA) receptors (NMDA, KA, and AMPA) and dopamine transporter sites in the striatum (caudate, putamen) and nucleus accumbens (NAc) from idiopathic PD, pure AD, and mixed PD/AD patients. PD and AD groups, and to a lesser extent the PD/AD groups, showed substantially increased binding to NMDA receptors in the striatum and NAc. No statistically significant changes in binding to KA and AMPA receptors were found in any patient group. 3H-mazindol binding to dopamine transporter sites was significantly decreased in the striatum and NAc of PD and PD/AD patients, but only in the putamen and NAc of AD patients. The data indicate that (1) the majority of striatal EAA receptors are not located on dopaminergic nigrostriatal nerve terminals, and (2) elevated binding to striatal NMDA receptors correlates with binding to dopamine transporter sites in PD patients, but not in AD and PD/AD individuals. Thus, the mechanisms of NMDA receptor changes in the striatum of AD and PD patients may be different. However, it is postulated that increased binding to NMDA receptors in Parkinson and Alzheimer striatum occurs in response to an insult(s) within the striatothalamocortical circuits and that this may contribute to the clinical similarities described for subsets of PD and AD patients.


The bizarre request for amputation.
Apotemnophilia is a condition where sufferers wish to be an amputee. Currently, belief in the medical profession is that it is part of the spectrum of body dysmorphic disorder and as such patients are denied surgical correction. This can lead sufferers to extreme lengths. Proponents seek to have the disorder reclassified to a body identity integrity disorder such as gender identity disorder. In this way treatment modalities could be reassessed.


Early biological indicators of S-(1,2-dichlorovinyl)-L-cysteine nephrotoxicity in the rabbit.
The progression of changes in rabbit kidney function following dosing with the nephrotoxin S-(1,2-dichlorovinyl)-L-cysteine (DCVC, 20-50 mg/kg) was determined. Proteinuria was observed 0.5-1 hr after administration of DCVC at doses of 20-50 mg/kg. Blood urea nitrogen levels, glomerular filtration rates, urinary glucose excretion, and urine volume were also altered following DCVC dosing; however, these parameters were less sensitive than proteinuria as markers of early renal dysfunction. None of these latter four indicators were affected by low DCVC doses, nor were they altered by high DCVC doses until 1.5-2.5 hr after dosing. Dose-dependent morphological changes to kidney structure were also observed 5 hr after DCVC administration. Low doses caused damage restricted to brush border membranes in the pars recta, while higher doses produced a necrotic lesion encompassing all regions of the proximal tubule. This study indicates that DCVC can cause rapid renal dysfunctional changes which are first detected by elevated urinary protein excretion.


Bilitranslocase localization and function in basolateral plasma membrane of renal proximal tubule in rat.
Bilirubin and phthalein dyes are taken up by the liver via a carrier-mediated mechanism operated at least in part by bilitranslocase (BTL). Because they also undergo renal transport, the presence and function of BTL was investigated in rat renal tubular plasma membrane vesicles. Transport of sulfobromophthalein (BSP) was enriched in basolateral domain of plasma membrane and followed the distribution pattern of Na(+)-K(+)-ATPase but not of gamma-glutamyltransferase. BSP uptake was inhibited by addition of monospecific antibodies raised against hepatic BTL. As in liver vesicles, BSP transport was electrogenic, being greatly accelerated by addition of valinomycin in presence of an inwardly directed K+ gradient. Apparent Km of BSP transport was 17 +/- 2 microM (n = 3 expts), one order of magnitude higher than that measured in liver; however, Vmax was similar to that described in liver vesicles (429 +/- 18 nmol BSP.mg protein-1.min-1, n = 3 expts). Competitive inhibition was observed with both unconjugated bilirubin (Ki, 2.9 +/- 0.2 microM) and rifamycin SV (Ki, 76 +/- 10 microM), known competitors for hepatic BTL-mediated transport of BSP. Immunoblotting studies with anti-BTL monospecific antibodies revealed presence of a single positive band only in basolateral-enriched membrane fraction; its apparent molecular mass was 37 kDa, virtually identical to that of hepatic protein. Immunohistochemistry confined presence of BTL to renal proximal tubules (RPT) We conclude that BTL is present in basolateral plasma membrane of RPT cells. Lower affinity of renal, compared with hepatic protein, for substrates might explain the marginal role of kidney in plasma clearance of bilirubin and cholephilic dyes.


Merkel cell carcinoma: an aggressive malignancy.
Merkel cell carcinoma is a rare and aggressive malignant tumor of the skin. We retrospectively reviewed five patients treated from January 1987 to December 1995. The mean age was 75 years (range, 65-85). There were three primary lesions of the head and neck and two of the extremities. Three were stage II and two were stage III. All primary tumors underwent wide excision with clear margins. Four patients recurred, with a mean time to recurrence of 10 months (range, 2-17). All tumors were positive for immunohistochemical stains (cytokeratin and neuron-specific enolase). Only the two patients who did not have radiotherapy to the primary site had a local recurrence. There was regional recurrence in two of the three patients who had adjuvant radiotherapy to regional lymph nodes. One patient who had a wide excision of the primary lesion, prophylactic lymph node dissection (15 of 34 lymph nodes were positive), and adjuvant chemotherapy is alive and disease free at 23 months. Three patients have died with disease, and two are alive and disease free. Merkel cell carcinoma should be treated aggressively with wide excision of the primary lesion (3-cm margins), and prophylactic lymphadenectomy followed by irradiation to the primary site. If lymph node involvement is detected, then irradiation to the lymph node region must be performed. The role of chemotherapy in this disease is not well defined.


Serum 25-Hydroxyvitamin D Concentrations and Ischemic Stroke and Its Subtypes.
Background and Purpose- Observational studies have reported increased risk of ischemic stroke among individuals with low serum 25-hydroxyvitamin D (S-25OHD) concentrations but uncertainty remains about the causality of this association. We sought to determine whether S-25OHD concentrations are causally associated with ischemic stroke and its subtypes using Mendelian randomization. Methods- We used summary-level data for ischemic stroke (34 217 cases and 404 630 noncases) from the MEGASTROKE consortium. As instruments, we used 6 single nucleotide polymorphisms, explaining 7.5% of the variance in S-25OHD, previously identified to be associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium (n=79 366). The analyses were conducted using the inverse-variance-weighted method and complemented with the weighted median, heterogeneity-penalized, and Mendelian randomization-Egger approaches. Results- Genetically higher S-25OHD concentration was not associated with ischemic stroke. The odds ratios (95% CI) per genetically predicted 1-SD (≈18 nmol/L) increase in S-25OHD concentrations, based on all 6 single nucleotide polymorphisms, were 1.01 (0.94-1.08; P=0.84) for all ischemic stroke, 0.94 (0.80-1.11; P=0.49) for large artery stroke, 0.95 (0.82-1.11; P=0.55) for small vessel stroke, and 1.02 (0.90-1.16; P=0.74) for cardioembolic stroke. The results were similar in sensitivity analyses. Conclusions- These findings provide no support that higher S-25OHD concentrations are causally associated with any ischemic stroke subtype. Thus, vitamin D supplementation will unlikely reduce the risk of ischemic stroke in the general population.


Volumetric Bone Mineral Density and Failure Load of Distal Limbs Predict Incident Clinical Fracture Independent HR-pQCT BMD and Failure Load Predicts Incident Clinical Fracture of FRAX and Clinical Risk Factors Among Older Men.
Our objective was to determine the associations of peripheral bone strength and microarchitecture with incident clinical and major osteoporotic fracture among older men after adjusting for major clinical risk factors. We used a prospective cohort study design with data from 1794 men (mean age 84.4 years) in the Osteoporotic Fractures in Men (MrOS) study. Eligible men attended the year 14 visit, had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal or diaphyseal tibia, DXA measured BMD, and were followed for mean 1.7 years for incident fracture. Failure load was estimated using finite element analysis. We used Cox proportional hazards models with standardized HR-pQCT parameters as exposure variables. Primary outcome was clinical fracture (n = 108). Covariates included either Fracture Risk Assessment Tool (FRAX) major osteoporotic fracture probability calculated with BMD (FRAX-BMD), or individual clinical risk factors (CRF) including age, total hip BMD, race, falls, and prevalent fracture after age 50 years. Lower failure load was associated with higher risk of incident clinical fracture and incident major osteoporotic fracture. For clinical fracture with FRAX-BMD adjustment, the associations ranged from hazard ratio (HR) 1.58 (95% CI, 1.25 to 2.01) to 2.06 (95% CI, 1.60 to 2.66) per SD lower failure load at the diaphyseal tibia and distal radius. These associations were attenuated after adjustment for individual CRFs, but remained significant at the distal sites. Associations of volumetric BMD with these outcomes were similar to those for failure load. At the distal radius, lower trabecular BMD, number, and thickness, and lower cortical BMD, thickness, and area were all associated with higher risk of clinical fracture, but cortical porosity was not. Among community-dwelling older men, HR-pQCT measures including failure load, volumetric BMD, and microstructure parameters at peripheral sites (particularly distal radius) are robust independent predictors of clinical and major osteoporotic fracture. © 2018 American Society for Bone and Mineral Research.


Revealing the pulmonary surfactant corona on silica nanoparticles by cryo-transmission electron microscopy.
When inhaled, nanoparticles (NPs) deposit in alveoli and transit through the pulmonary surfactant (PS), a biofluid made of proteins and phospholipid vesicles. They form a corona reflecting the PS-nanomaterial interaction. Since the corona determines directly the NPs' biological fate, the question of its nature and structure is central. Here, we report on the corona architecture formed after incubation of positive or negative silica particles with Curosurf®, a biomimetic pulmonary surfactant of porcine origin. Using optical, electron and cryo-electron microscopy (cryo-TEM), we determine the pulmonary surfactant corona structure at different scales of observation. Contrary to common belief, the PS corona is not only constituted by phospholipid bilayers surrounding NPs but also by multiple hybrid structures derived from NP-vesicle interaction. Statistical analysis of cryo-TEM images provides interesting highlights about the nature of the corona depending on the particle charge. The influence of Curosurf® pre- or post-treatment is also investigated and demonstrates the need for protocol standardization.


Typing late prehistoric cows and bulls--osteology and genetics of cattle at the Eketorp ringfort on the Öland island in Sweden.
Human management of livestock and the presence of different breeds have been discussed in archaeozoology and animal breeding. Traditionally osteometrics has been the main tool in addressing these questions. We combine osteometrics with molecular sex identifications of 104 of 340 morphometrically analysed bones in order to investigate the use of cattle at the Eketorp ringfort on the Öland island in Sweden. The fort is dated to 300-1220/50 A.D., revealing three different building phases. In order to investigate specific patterns and shifts through time in the use of cattle the genetic data is evaluated in relation to osteometric patterns and occurrence of pathologies on cattle metapodia. Males were genotyped for a Y-chromosomal SNP in UTY19 that separates the two major haplogroups, Y1 and Y2, in taurine cattle. A subset of the samples were also genotyped for one SNP involved in coat coloration (MC1R), one SNP putatively involved in resistance to cattle plague (TLR4), and one SNP in intron 5 of the IGF-1 gene that has been associated to size and reproduction.The results of the molecular analyses confirm that the skeletal assemblage from Eketorp is dominated by skeletal elements from females, which implies that dairying was important. Pathological lesions on the metapodia were classified into two groups; those associated with the use as draught animals and those lesions without a similar aetiology. The results show that while bulls both exhibit draught related lesions and other types of lesions, cows exhibit other types of lesions. Interestingly, a few elements from females exhibit draught related lesions. We conclude that this reflects the different use of adult female and male cattle.Although we note some variation in the use of cattle at Eketorp between Iron Age and Medieval time we have found little evidence for the use of different types of animals for specific purposes. The use of specific (genetic) breeds seems to be a phenomenon that developed later than the Eketorp settlement.


Engineering mammalian chromosomes.
Construction of a mammalian artificial chromosome (MAC) will develop our understanding of the requirements for normal chromosome maintenance, replication and segregation while offering the capacity for introducing genes into cells. Construction of MACs with telomere, centromere and replication function has been approached by two methods. The 'top down' strategy uses artificially induced chromosome truncations as a means to define a minimal chromosome that retains the mitotic properties of a normal chromosome. The 'build up' approach has focused on attempts to assemble MAC vectors containing functionally defined telomere repeats together with candidate centromere and replication origin sequences. Here we report on significant advances in both areas, with particular emphasis on two reports showing that stable, low copy number MACs containing a functional centromere can be produced following transfection of naked DNA into the human HT1080 cell line. One approach used a transfection mixture of cloned synthetic alpha-satellite arrays up to 1 Mb in length and unlinked telomeric DNA, in either the presence or absence of random human genomic DNA fragments. In the second approach, MACs were formed from a defined yeast artificial chromosome (YAC) DNA molecule containing 100 kb of highly homo- geneous alphoid DNA retrofitted with human telomere repeats. These results demonstrate for the first time that alpha-satellite DNA can seed de novo centromeres in human cells, indicating that this repetitive sequence family plays an important role in centromere function. The stability of these MACs suggests that they have potential to be developed as gene delivery vectors.


Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss.
To assess the effectiveness of luteal start vaginal micronized P in a recurrent pregnancy loss (RPL) cohort. Observational cohort study using prospectively collected data. Not applicable. Women seen between 2004 and 2012 with a history of two or more unexplained pregnancy losses <10 weeks in size; endometrial biopsy (EB) performed 9-11 days after LH surge; and one or more subsequent pregnancy(ies). Women were excluded if concomitant findings, such as endometritis, maturation delay, or glandular-stromal dyssynchrony, were identified on EB. Vaginal micronized P was prescribed at a dose of 100-200 mg every 12 hours starting 3 days after LH surge (luteal start) if glandular epithelial nuclear cyclin E (nCyclinE) expression was elevated (>20%) in endometrial glands or empirically despite normal nCyclinE (≤20%). Women with normal nCyclinE (≤20%) who did not receive P were used as controls. Pregnancy success was an ongoing pregnancy >10 weeks in size. One hundred sixteen women met the inclusion criteria, of whom 51% (n = 59) had elevated nCyclinE and 49% (n = 57) had normal nCyclinE. Pregnancy success in the 59 women with elevated nCyclinE significantly improved after intervention: 6% (16/255) in prior pregnancies versus 69% (57/83) in subsequent pregnancies. Pregnancy success in subsequent pregnancies was higher in women prescribed vaginal micronized P compared with controls: 68% (86/126) versus 51% (19/37); odds ratio = 2.1 (95% confidence interval, 1.0-4.4). In this study, we found that the use of luteal start vaginal micronized P was associated with improved pregnancy success in a strictly defined cohort of women with RPL.


Control of homeostatic proliferation by regulatory T cells.
Homeostatic proliferation of T cells leads to the generation of effector/memory cells, which have the potential to cause harm to the host. The role of Tregs in the control of homeostatic proliferation is unclear. In this study we utilized mice that either harbor or lack Tregs as recipients of monoclonal or polyclonal T cells. We observed that while Tregs completely prevented cell division of T cells displaying low affinity for self ligands, they had a less marked, albeit significant, effect on cell cycle entry of T cells displaying higher affinity. The presence of Tregs resulted in a lower accumulation of T cells, enhanced apoptosis, and impaired differentiation to a cytokine-producing state. We conclude that Tregs play a major role in the control of homeostatic proliferation.


Structural and antigenic heterogeneity of lipopolysaccharides of Campylobacter jejuni and Campylobacter coli.
The techniques of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, silver staining, and immunoblotting were used to analyze the lipopolysaccharide (LPS) structure of 20 strains of Campylobacter jejuni and 4 strains of Campylobacter coli belonging to more than 22 thermostable serotypes. The LPSs of all strains examined were shown to be of a low-molecular-weight type, and these low-molecular-weight LPSs conferred heat-stable serospecificity. High-molecular-weight banding observed with both in vivo LPS in proteinase K digests of whole cell lysates and purified LPS was shown to be due to the ready ability of Campylobacter lipopolysaccharide to form aggregates rather than to the presence of O polysaccharide chains. Purified LPSs from two strains of C. jejuni were also subjected to gross chemical analysis. The high-lipid A to low-neutral sugar ratio of both LPSs was typical of LPSs lacking O polysaccharide chains.


Dual-time-point FDG PET/CT imaging in prosthetic heart valve endocarditis.
FDG PET/CT has been of increasing interest in the diagnostic workup of prosthetic heart valve endocarditis (PVE). Some reports advocate later imaging time points to improve the diagnostic accuracy for PVE. In this study, we compared standard and late FDG PET/CT images in patients with a clinical suspicion of PVE. Fourteen scans in 13 patients referred for FDG PET/CT for suspicion of PVE performed at standard (60 min post injection) and late (150 min post injection) time points were scored based on visual interpretation and semi-quantitatively with SUVmax and target-to-background ratio (TBR, defined as [SUVmax valve/SUVmean blood pool]). Final diagnosis was based on surgical findings in all cases of infection (n = 6) and unremarkable follow-up in all others (n = 8). Late images were more prone to false positive interpretation for both visual and semi-quantitative analyses. Visual analysis of the standard images yielded 1 false negative and 1 false positive result. On the late images, no scans were false negative but 5 scans were false positive. Late FDG PET/CT imaging for PVE seems prone to false positive results. Therefore, late imaging should be interpreted with caution.


Comparative analysis: effects of positive and negative lateral acceleration on isometric fatigue in the forearm.
The purpose of this investigation was to determine the difference, if any, produced by +/- Gy acceleration on forearm fatigue. The Dynamic Environment Simulator (DES) at the USAF Aerospace Medical Research Laboratory was used to create a lateral acceleration environment. The experiment was designed to measure the forearm strength, endurance, recovery from fatigue, and surface electrical activity of six subjects during +/- 2 Gy acceleration. isometric performance was degraded during -2 Gy acceleration compared to + 2 Gy acceleration. The percentage drop in center frequency of the EMG signal was determined to be unreliable as a fatigue index during lateral acceleration. When head and shoulder restraints were used during lateral maneuvers, they were a factor in pilot performance, with + 2 Gy being superior to -2 Gy. This study suggested a way of analyzing the EMG signals that may permit quantification of isometric fatigue during lateral acceleration.


Systematic Review and Meta-Analysis on Human African Trypanocide Resistance.
Background Human African trypanocide resistance (HATr) is a challenge for the eradication of Human African Trypansomiaisis (HAT) following the widespread emergence of increased monotherapy drug treatment failures against Trypanosoma brucei gambiense and T. b. rhodesiense that are associated with changes in pathogen receptors. Methods: Electronic searches of 12 databases and 3 Google search websites for human African trypanocide resistance were performed using a keyword search criterion applied to both laboratory and clinical studies. Fifty-one publications were identified and included in this study using the PRISMA checklist. Data were analyzed using RevMan and random effect sizes were computed for the statistics at the 95% confidence interval. Results: Pentamidine/melarsoprol/nifurtimox cross-resistance is associated with loss of the T. brucei adenosine transporter 1/purine 2 gene (TbAT1/P2), aquaglyceroporins (TbAQP) 2 and 3, followed by the high affinity pentamidine melarsoprol transporter (HAPT) 1. In addition, the loss of the amino acid transporter (AAT) 6 is associated with eflornithine resistance. Nifurtimox/eflornithine combination therapy resistance is associated with AAT6 and nitroreductase loss, and high resistance and parasite regrowth is responsible for treatment relapse. In clinical studies, the TbAT1 proportion of total random effects was 68% (95% CI: 38.0−91.6); I2 = 96.99% (95% CI: 94.6−98.3). Treatment failure rates were highest with melarsoprol followed by eflornithine at 41.49% (95% CI: 24.94−59.09) and 6.56% (3.06−11.25) respectively. HATr-resistant phenotypes used in most laboratory experiments demonstrated significantly higher pentamidine resistance than other trypanocides. Conclusion: The emergence of drug resistance across the spectrum of trypanocidal agents that are used to treat HAT is a major threat to the global WHO target to eliminate HAT by 2030. T. brucei strains were largely resistant to diamidines and the use of high trypanocide concentrations in clinical studies have proved fatal in humans. Studies to develop novel chemotherapeutical agents and identify alternative protein targets could help to reduce the emergence and spread of HATr.


Optimizing differential equations to fit data and predict outcomes.
Many scientific problems focus on observed patterns of change or on how to design a system to achieve particular dynamics. Those problems often require fitting differential equation models to target trajectories. Fitting such models can be difficult because each evaluation of the fit must calculate the distance between the model and target patterns at numerous points along a trajectory. The gradient of the fit with respect to the model parameters can be challenging to compute. Recent technical advances in automatic differentiation through numerical differential equation solvers potentially change the fitting process into a relatively easy problem, opening up new possibilities to study dynamics. However, application of the new tools to real data may fail to achieve a good fit. This article illustrates how to overcome a variety of common challenges, using the classic ecological data for oscillations in hare and lynx populations. Models include simple ordinary differential equations (ODEs) and neural ordinary differential equations (NODEs), which use artificial neural networks to estimate the derivatives of differential equation systems. Comparing the fits obtained with ODEs versus NODEs, representing small and large parameter spaces, and changing the number of variable dimensions provide insight into the geometry of the observed and model trajectories. To analyze the quality of the models for predicting future observations, a Bayesian-inspired preconditioned stochastic gradient Langevin dynamics (pSGLD) calculation of the posterior distribution of predicted model trajectories clarifies the tendency for various models to underfit or overfit the data. Coupling fitted differential equation systems with pSGLD sampling provides a powerful way to study the properties of optimization surfaces, raising an analogy with mutation-selection dynamics on fitness landscapes.


An unusual late manifestation of a Salmonella typhi infection.
We report the case history of a patient in whom we diagnosed purulent lymphadenitis due to Salmonella typhi, a late complication of a febris typhoidea that occurred 11 yr previously. We also review the literature concerning complications of Salmonella infections, and particularly discuss their hematogenous spread and lodgment.


Impact of a hospital-wide antibiotic restriction policy program on the resistance rates of nosocomial Gram-negative bacteria.
To evaluate the impact of an antibiotic restriction policy on antibiotic consumption and Gram-negative resistance rates, in an environment of antibiotic overconsumption and increasing resistance rates for nosocomial pathogens. The study was a 'before and after' trial of 18-month duration; the antibiotic restriction policy program was implemented in 1998-2000 and was based on a government program addressed by the Ministry of Health to public hospitals on a national basis. This included prescribing of all newer antibiotics on an order form, auditing of the order forms and consultation with infectious diseases (ID) specialists, dispensing of treatment and prophylaxis guidelines, feedback, and face-to-face education. Antibiotic consumption and Gram-negative resistance rates were recorded before and after the intervention. Despite the addition of a new 40-bed ID department in the hospital during the 'after' period, the consumption of restricted antibiotics was significantly reduced by 42% (and their cost by 31%). Gram-negative resistance rates for Pseudomonas, Klebsiella, and Enterobacter, serving as index microorganisms for Gram-negative nosocomial pathogens, were significantly reduced during the 'after' period, even against antibiotics for which there was an increase in consumption. Multidisciplinary restriction programs can reduce antibiotic consumption and Gram-negative resistance rates in the hospital setting.


Predictive value of vascular calcification identified in 4D planning CT of lung cancer patients treated with stereotactic body radiation therapy.
The aim was to identify vascular calcification in 4DCT scan of lung cancer patients and establish the association between overall survival (OS) and vascular calcification, as surrogate for vascular health. Vascular calcification within the thoracic cavity were segmented in 334 lung cancer patients treated with stereotactic body radiation therapy (SBRT). This has been done automatically on 4D planning CT and average reconstruction scans. Correlation between cardiac comorbidity and calcification volumes was evaluated for patients with recorded Adult Co-Morbidity Evaluation (n = 303). Associations between the identified calcifications and OS were further investigated. The volume of calcification from the average scan was significantly lower than from each phase (p < 0.001). The highest level of correlations between cardiac comorbidity and volume of the calcifications were found for one phase representing inhale and two phases representing exhale with the least motion blurring due to respiration (p < 0.005). The volume of the calcifications was subsequently averaged over these three phases. The average of calcification volumes over the three phases (denoted by inhale-exhale) showed the highest likelihood in univariate analysis and was chosen as vascular calcification measure. Cox-model suggested that tumor volume (Hazard Ratio [HR] = 1.46, p < 0.01) and inhale-exhale volume (HR = 1.05, p < 0.05) are independent factors predicting OS after adjusting for age, sex, and performance status. It was feasible to use. It 4DCT scan for identifying thoracic calcifications in lung cancer patients treated with SBRT. Calcification volumes from inhale-exhale phases had the highest correlation with overall cardiac comorbidity and the average of the calcification volume obtained from these phases was an independent predictive factor for OS.


Morphologic alterations observed during experimental ischemia of the equine large colon.
Morphologic changes that develop sequentially in the large colon during experimentally induced ischemia were documented in 14 halothane-anesthetized horses. Colonic ischemia was induced by 4 types of vascular occlusion, 24 cm proximal and distal to the pelvic flexure. The effect of transmural (colonic wall) vascular compression combined with either venous occlusion (3 horses, group A) or venous and arterial occlusion (3 horses, group B) of the colonic vessels was studied for 1, 2, and 6 hours of occlusion. Also observed was the effect of reperfusion for 0.5 hour after release of the clamps for the 1- and 2-hour occlusions and for 1 hour after release of the clamps for the 6-hour occlusion. Effects of occluding only the colonic veins (4 horses, group C), or the colonic veins and arteries (4 horses, group D) were studied for 0.5, 1, 1.5, and 2 hours of occlusion and during reperfusion for 0.5 hour. Full-thickness intestinal biopsy specimens were obtained from the antimesenteric border of the pelvic flexure at 0, 0.25, 0.5, 0.75, 1, 1.5, and 2 hours during occlusion and at 0.5 hour after release of vascular occlusion. Biopsy specimens were obtained at hourly intervals from the 2 horses in which 6-hour occlusion was performed and at 1 hour after release of vascular occlusion. Macroscopic changes (serosal color, mucosal color, serum leakage) in the colon were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)


Vascular risk factors in late onset mania.
Previous researches have suggested that late onset mania is a distinct subtype associated with medical and neurological disorders. Few studies, however, have focused on vascular risk factors. Records of 366 bipolar patients were reviewed and age of first psychiatric hospitalization determined. Late-onset cases were determined empirically from a distribution histogram. Late onset cases were matched to early onset cases and histories of vascular disease/risks and current cholesterol levels compared. The distribution of age of first psychiatric hospitalization was bimodal with an intermode at age 47. Using that threshold, 6.3% of the cohort was classified as having late onset mania. Vascular risks factors were greater and current cholesterol levels higher in the late onset group. Late onset mania is associated with greater vascular risk factors. The bimodal appearance of age of first psychiatric hospitalization in this study provides further support of late onset mania as a distinct manic subtype with possibly a different, vascular aetiology. Control of these vascular risks may impact on the incidence of late onset mania, as well as on its clinical management.


Epidermal thickness measurements in vaginal intraepithelial neoplasia. A basis for optimal CO2 laser vaporization.
The current management of vaginal intraepithelial neoplasia (VAIN) often involves the use of laser vaporization. A study was performed to measure the epithelial thickness in both premenopausal and postmenopausal women with various grades of VAIN to determine the optimum depth of tissue destruction if laser vaporization is used for therapy. Hematoxylin and eosin-stained tissue sections were examined with light microscopy and measurements made with a calibrated micrometer. Sixty-three biopsies from 56 patients were studied. Patients' ages ranged from 22 to 84 years, with a mean of 56. Thirty-six had a prior history of cervical neoplasia. Thirty-nine patients (70%) had VAIN III, 10 had VAIN II, and the remaining 7 patients had VAIN I lesions. The involved epithelium varied from 0.10 to 1.4 mm in thickness, with a mean of 0.46. Noninvolved vaginal epithelium varied in thickness from 0.10 to 0.70 mm, with a mean of 0.28. Koilocytosis was noted in only 9 of the 63 biopsy specimens. In comparing the thickness of involved epithelium in a given patient to that of an adjacent area of normal-appearing epithelium, the epithelium containing VAIN tended to be thicker. The recommended depth of epithelial destruction with laser vaporization in the literature varies widely and appears to have largely an empiric basis. Our study attempted to provide a scientific basis for laser destruction of these lesions. The results obtained indicate that epithelial destruction to a depth of 1.5 mm, including the zone of thermal necrosis, should be sufficient to destroy epithelium containing VAIN without damage to surrounding structures.


A rare case of dependence on pemoline.
This is the first case to report about a patient dependent on the dopaminergic CNS-stimulant pemoline. Throughout the treatment of adult attention-deficit hyperactivity disorder (ADHD) with pemoline mental (e.g. craving, loss of control) and physical symptoms (e.g. tolerance, withdrawal symptoms) appeared that fulfill the DSM-IV or ICD-10 criteria for dependence on psychostimulants. However, the dependence was regarded not to be induced by pemoline itself because the patient was prone to irregular and reinforced intake of amphetamines since her adolescence. Therefore, this case confirms the experience that in the treatment of ADHD the high risk to develop a dependence on psychostimulants is combined with a history of stimulant abuse.


Sex-ratio dependent execution of queens in polygynous colonies of the ant Formica exsecta.
Formica exsecta has become an important model system for studying intraspecific variation in sex ratios. Patterns of sex allocation in polygynous (multiple queen per nest) populations of F. exsecta are generally consistent with the queen-replenishment hypothesis. This hypothesis states that colonies produce gynes (reproductive females) in order to increase queen number and enhance colony survival and/or productivity when the number of resident queens is low. However, the small proportion of colonies that raise gynes produce more than necessary for simple queen replenishment. It has been hypothesized that excess production of gynes may occur to reduce the frequency of accepting foreign unrelated gynes into the colony when workers cannot distinguish nestmate from non-nestmate queens. This explanation for excess gynes requires weak or no aggression between non-nestmates and is expected to lead to the selective execution of new queens by colonies that do not invest in the production of gynes. Experimental studies where gynes were introduced into natal and foreign colonies indeed suggested that polygynous populations of F. exsecta have a poor nestmate recognition system. Although gynes were significantly more likely to be accepted in their parental colony compared to another foreign female-producing colony, the difference was small. Moreover, encounters between workers from different colonies within the population showed very little aggression and were no more aggressive than encounters between nestmates, again suggesting a weak capacity for nestmate recognition. Our experiment also showed that colonies that produced only males executed most of the gynes that were experimentally introduced into the colony, whereas female-producing colonies accepted most gynes. This is consistent with ants using a simple rule of thumb to decrease parasitism by unrelated queens, whereby colonies selectively destroy gynes whenever gynes are not produced in the colonies.


Traumatic rupture of the diaphragm.
Diaphragmatic rupture following trauma is often an associated and missed injury. The diagnosis is difficult, so is usually made intraoperatively. Twenty-one patients with traumatic rupture of the diaphragm (TRD) who presented between 1995 and 1998 were retrospectively analysed: 12 had penetrating injuries and nine had blunt injuries. Right-sided defects exceeded left (12 vs 9). Only seven patients had signs and symptoms directly referrable to rupture of the diaphragm. All patients were operated on through a midline laparotomy. Diaphragmatic hernia was seen in six patients (28.5%); 20 (95%) patients had concomitant injuries. The liver was the most commonly injured organ (10 patients). The aim of this study was to report our experiences with TRD and review the literature. We conclude that correct preoperative diagnosis of TRD needs a high index of suspicion. It can be diagnosed intraoperatively by explorative laparotomy. Most ruptures can be repaired by the abdominal approach.


Smoking worsens the prognosis in multiple sclerosis.
To estimate the effect of smoking on the risk for progression in multiple sclerosis (MS). Self-reported data were used on smoking habits in 122 incident cases with disability assessments made after a median of 6 years disease duration. Ever smokers were more likely to have progressive disease compared with never smokers (P < 0.01). This was most pronounced in ever smokers with early smoking debut (< or = 15 years of age) for whom progressive disease was significantly more likely and occurred at an earlier age, compared with those with later smoking debut (P < 0.01 for both) or never smokers (P < 0.01 for both). Earlys moking start also predisposed to a progressive disease from onset when compared with never smokers (P = 0.012). A multivariate Cox regression analysis of sex, age at disease onset (above vs. under median) and smoking (ever vs. never) status showed that cases with late disease onset had three times higher risk and ever smokers had twice as high a risk for progression. Past smoking is associated with a worsened prognosis in MS. The negative effect from smoking is most obvious in ever smokers with early smoking debut, which also affects MS phenotype significantly.


Rapid antigen detection testing in diagnosing group A beta-hemolytic streptococcal pharyngitis.
The purpose of this study was to determine the accuracy of diagnosing group A beta-hemolytic streptococci (GABHS) with rapid antigen testing compared with throat culture methods commonly used. Two separate studies were conducted. Initially, 182 patients with acute pharyngitis had both throat culture (sheep blood agar or Strep Select Agar) and rapid antigen detection screening tests (Directigen1-2-3 Group A Strep) performed. For the second study, a rapid antigen detection test (Directigen1-2-3 Group A Strep) was obtained from 614 patients. All subjects who screened negative (n = 469) received a throat culture. All subjects who screened positive (n = 145) were treated with antibiotics, and 31 of these patients received a throat culture. Statistical analyses included calculating sensitivity, specificity, positive and negative predictive values, and prevalence. For the initial 182 patients, the prevalence of GABHS was 12 percent. Sensitivity was 95.45 percent, specificity was 96.25 percent, positive predictive value was 77.78 percent, and negative predictive value was 99.35 percent. In the second group of subjects, four false-negatives were present (negative predictive value = 99.18 percent). Results of these pilot studies indicate that an extremely low percentage (< 1 percent) of subjects with GABHS escaped detection with our rapid screening test methods. These results conflict with results from previous investigations, which have reported relatively low specificity and sensitivity of rapid antigen detection tests when compared with throat cultures. Results from this study support treatment protocols based on a rapid screening test as a single diagnostic test.


Cardiac transcription factor Nkx2.5 is downregulated under excessive O-GlcNAcylation condition.
Post-translational modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) is linked the development of diabetic cardiomyopathy. We investigated whether Nkx2.5 protein, a cardiac transcription factor, is regulated by O-GlcNAc. Recombinant Nkx2.5 (myc-Nkx2.5) proteins were reduced by treatment with the O-GlcNAcase inhibitors STZ and O-(2-acetamido-2-deoxy-D-glucopyroanosylidene)-amino-N-phenylcarbamate; PUGNAC) as well as the overexpression of recombinant O-GlcNAc transferase (OGT-flag). Co-immunoprecipitation analysis revealed that myc-Nkx2.5 and OGT-flag proteins interacted and myc-Nkx2.5 proteins were modified by O-GlcNAc. In addition, Nkx2.5 proteins were reduced in the heart tissue of streptozotocin (STZ)-induced diabetic mice and O-GlcNAc modification of Nkx2.5 protein increased in diabetic heart tissue compared with non-diabetic heart. Thus, excessive O-GlcNAcylation causes downregulation of Nkx2.5, which may be an underlying contributing factor for the development of diabetic cardiomyopathy.


Working shifts and mental health--findings from the British Household Panel Survey (1995-2005).
Our objective was to examine the impact of shift work on mental health at the population level. We expected that this impact would depend on duration of exposure, type of shift work, and gender. We analyzed longitudinal data (1995-2005) from the British Household Panel Survey. From the 2005 wave, we selected a subsample of people aged 21-73 years who had been followed annually from 1995 to 2005. We used responses in 2005 to the General Health Questionnaire (GHQ, 12-item) and self-reported anxiety/depression as dependent variables. Controlling for age, marital status, education, number of years working in six occupational categories (1995-2005), and baseline mental health, we performed nested logistic regression models to examine the effect of the duration of night work and varied shift patterns on mental health for men and women. Undertaking night work for > or =4 years in men was associated with an increased risk of having a GHQ score reflecting mental ill health and reporting anxiety/depression [odds ratios (OR) 2.58, 95% confidence interval (95% CI) 1.22-5.48; OR 6.08, 95% CI 2.06-17.92, respectively]. Women were significantly more likely to report anxiety/depression (OR 2.58, 95% CI 1.53-4.35 ) and to have a GHQ score reflecting mental ill health (OR 4.17, 95% CI 1.45-11.98), after working varied shift patterns for 2-3 years, and >/=4 years, respectively. Different types of shift work had a differential impact on mental health, but this impact varied according to gender. Women's mental health was more adversely affected by varied shift patterns, while night work had a greater negative impact on men's mental health.


Stability of stored canine plasma for hemostasis testing.
A review of the literature revealed limited information about the stability of samples for coagulation testing in dogs. The aim of this study was to evaluate the stability of individual coagulation factors, clotting times, and other parameters of hemostasis in stored canine plasma. Citrated plasma samples were obtained from 21 dogs. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and factor I, II, V, VII, VIII, IX, X, XI, and XII activities were measured on an automated coagulation analyzer with commercially available reagents. Antithrombin (AT) activity and D-dimer concentration were measured on an automated chemistry analyzer using validated kits. Samples were analyzed within 1 hour after collection (initial analysis) and once daily for 2 or 4 consecutive days following storage at room temperature (RT) or 4 degrees C, respectively. Storage time at either temperature did not have any effect on PT, factor II, V, VII, X, or XII activities, D-dimer concentration, or AT activity. In contrast, aPTT was significantly prolonged after 72 and 96 hours at 4 degrees C; fibrinogen concentration was decreased after 48 hours at RT; the activities of factors VIII and IX were decreased after 48, 72, and 96 hours at 4 degrees C; and factor XI activity was decreased after 72 hours at 4 degrees C. Results suggest that storage of canine plasma for 2 days at RT does not have a significant effect on hemostasis test results with the exception of a slight decrease in fibrinogen concentration. In contrast, aPTT and factors VIII, IX, and XI were unstable in refrigerated plasma after 48 or 72 hours of storage.


Detection of and intervention for excessive alcohol and tobacco use among adult hospital in-patients.
Early detection and intervention for alcohol problems have been shown to reduce subsequent health consequences. However, the extent to which these practices have been implemented is unclear. The study assessed among hospital in-patients (1) the prevalence of at-risk drinking and smoking, (2) current practice in detection and intervention for at-risk drinking and smoking and (3) self-reported effect of any intervention. A brief self-administered questionnaire was administered to adult in-patients addressing alcohol use [Alcohol Use Disorders Identification Test (AUDIT) questionnaire], smoking and self-reported effect of any recent intervention for drinking or smoking. The participant's smoking status and alcohol use as recorded by medical and nursing staff was compared to self-reports. Of 448 in-patients, 50% (226) participated in the study; 38% (170) were ineligible and 12% (52) refused. Participants were aged 61.3 (+/-18.9) years. A higher number of problem drinkers (11.9% vs. 3.5%, p < 0.0001) and current smokers (17.3% vs. 9.3%, p < 0.0001) were identified by the questionnaire compared to the medical records. Hospital staff quantified smoking more consistently than alcohol (54% vs. 42%, p = 0.02). Of those who recalled an intervention, 19% of drinkers and 27% of smokers said they had stopped drinking or smoking for a period since that intervention. Further improvement is required in the rates of detection and interventions for alcohol use disorders and smoking in the hospital setting.


The administration of dextrose during in-hospital cardiac arrest is associated with increased mortality and neurologic morbidity.
Dextrose may be used during cardiac arrest resuscitation to prevent or reverse hypoglycemia. However, the incidence of dextrose administration during cardiac arrest and the association of dextrose administration with survival and other outcomes are unknown. We used the Get With The Guidelines®-Resuscitation national registry to identify adult patients with an in-hospital cardiac arrest between the years 2000 and 2010. To assess the adjusted effects of dextrose administration on survival, we used multivariable regression models with adjustment for multiple patient, event, and hospital characteristics. We performed additional analyses to examine the effects of dextrose on neurological outcome and return of spontaneous circulation. Among the 100,029 patients included in our study, 4,189 (4.2%) received dextrose during cardiac arrest resuscitation. The rate of dextrose administration increased during the study period (odds ratio 1.11, 95% confidence interval (CI) 1.09-1.12 per year, P <0.001). Patients who received dextrose during resuscitation had lower rates of survival compared with patients who did not receive dextrose (relative risk 0.88, 95% CI 0.80-0.98, P = 0.02). Administration of dextrose was associated with worse neurological outcome (relative risk 0.88, 95% CI 0.79-0.99, P = 0.03) but an increased chance of return of spontaneous circulation (relative risk 1.07, 95% CI 1.04-1.10, P <0.001). In this dataset, the administration of dextrose during resuscitation in patients with in-hospital cardiac arrest was found to be associated with a significantly decreased chance of survival and a decreased chance of good neurological outcome.


Extraterrestrial life detection based on oxygen isotope exchange reactions.
A method is described for detecting extraterrestrial life, based on catalysis of isotopic oxygen exchange between water and oxygen-containing anions such as phosphate, nitrate, or sulfate. This catalytic activity appears to be unique to living systems. Its applicability requires very few assumptions concerning the chemical nature of "life." Data obtained so far indicate that the experiment is sound and technically feasible.


Predicting Bleeding Events in Anticoagulated Patients With Atrial Fibrillation: A Comparison Between the HAS-BLED and GARFIELD-AF Bleeding Scores.
Background Patients with atrial fibrillation (AF) treated with oral anticoagulants may be exposed to an increased risk of bleeding events. The HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INRs, Elderly, Drugs or alcohol) score is a simple, well-established, clinical bleeding-risk prediction score. Recently, a new algorithm-based score was proposed, the GARFIELD-AF (Global Anticoagulant in the Field-AF) bleeding score. We compared HAS-BLED and GARFIELD-AF scores in predicting adjudicated bleeding events in a clinical trial cohort of patients with AF taking anticoagulants, in the first external comparative validation of both scores. Methods and Results We analyzed patients from the SPORTIF (Stroke Prevention Using an Oral Thrombin Inhibitor in Patients With AF) III and V trials. All patients assigned to the warfarin arm with information to calculate the scores were considered. Outcomes were major, major/clinically relevant nonmajor, and any bleeding. A total of 3550 warfarin-treated patients were available for analysis. Of these patients, 2519 (71.0%) had a HAS-BLED score ≥3, whereas based on GARFIELD-AF median value, 2056 (57.9%) were categorized as "high score." Both HAS-BLED and GARFIELD-AF C-indexes showed modest predictive value (C-index [95% confidence interval] for major bleeding, 0.58 [0.56-0.60] and 0.56 [0.54-0.57], respectively); however, GARFIELD-AF was not predictive of any bleeding. The GARFIELD-AF bleeding score had a significantly lower sensitivity and a negative reclassification for any bleeding compared with HAS-BLED, assessed by integrated discrimination improvement and net reclassification improvement (both P<0.001). HAS-BLED showed a 5% net benefit for any bleeding occurrence. Conclusions The algorithm-based GARFIELD-AF bleeding score did not show any significant improvement in major and major/clinically relevant nonmajor prediction compared with the simple HAS-BLED score. For clinical usefulness in prediction of any bleeding, the HAS-BLED score showed a significant net benefit compared with the GARFIELD-AF.


Regulation of the hyaluronan system in ovine endometrium by ovarian steroids.
In this study, we investigated steroid regulation of the hyaluronan (HA) system in ovine endometrium including HA synthases (HAS), hyaluronidases, and HA receptor-CD44 using 30 adult Welsh Mountain ewes. Eight ewes were kept intact and synchronized to estrous (day 0). Intact ewes were killed on day 9 (luteal phase; LUT; n=5) and day 16 (follicular phase; FOL; n=3). The remaining ewes (n=22) were ovariectomized and then treated (i.m.) with vehicle (n=6) or progesterone (n=8) for 10 days, or estrogen and progesterone for 3 days followed by 7 days of progesterone alone (n=8). Estradiol and progesterone concentrations in plasma correlated with the stage of estrous or steroid treatment. Our results showed trends (P<0.1) and statistically significant effects (P<0.05, by t-test) indicating that LUT had lower HAS1 and HAS2 and higher HAS3 and CD44 mRNA expression compared with FOL. This was reflected in immunostaining of the corresponding HAS proteins. Similarly, in ovariectomized ewes, progesterone decreased HAS1 and HAS2 and increased HAS3 and CD44, whereas estradiol tended to increase HAS2 and decrease CD44. Sometimes, HAS mRNA expression did not follow the same trend observed in the intact animals or the protein expression. HA and its associated genes and receptors were regulated by the steroids. In conclusion, these results show that the level of HA production and the molecular weight of HA in the endometrium are regulated by ovarian steroids through differential expression of different HAS both at the gene and at the protein levels.


The use of Tiemann tip catheters for male intermittent self-catheterisation.
Male catheterisation can be difficult to perform, especially in patients with an enlarged prostate gland or other potentially obstructive conditions in the lower urinary tract. Repeated and unsuccessful catheterisations, as well as causing trauma, pain and distress, can cause other conditions such as urethral strictures and 'false passages' (when the catheter is pushed through the urethral wall instead of passing down the urethra), which then require more costly interventions to correct. With an increasingly ageing population these complications are expected to rise, putting added strain on an already stretched health service. This article discusses the use of the Coudé (or Tiemann) tip catheter in patients presenting with these challenging catheterisations and, in particular, male patients performing intermittent self-catheterisation. Device design can help overcome obstructive difficulties, making catheterisation easier, less traumatic and more comfortable for the patient. A survey of 200 nurses working in the urology and continence field was undertaken to understand their awareness and usage of Coudé/Tiemann tip catheters in practice. It was found that many nurses and doctors were unaware of this type of catheter and its advantages and therefore did not use or offer it as an alternative to the more commonly used straight-tipped catheter. In the vast majority of cases when Tiemann tip catheters were used this occurred after failure with a straight-tipped catheter, or they were used with patients with benign prostatic hyperplasia or other potentially obstructive conditions. In many cases, the catheterisation was consultant initiated, despite the fact that intermittent self-catheterisation is instigated and taught mainly by nurses. This survey highlighted the need for better education for nurses and doctors in assessing the alternative catheter tips available to ensure successful catheterisation on first attempt.


High-Throughput Screening Approach for Identifying Compounds That Inhibit Nonhomologous End Joining.
DNA double-strand breaks (DSBs) are repaired primarily by homologous recombination (HR) or nonhomologous end joining (NHEJ). Compounds that modulate HR have shown promise as cancer therapeutics. The V(D)J recombination reaction, which assembles antigen receptor genes in lymphocytes, is initiated by the introduction of DNA DSBs at two recombining gene segments by the RAG endonuclease, followed by the NHEJ-mediated repair of these DSBs. Here, using HyperCyt automated flow cytometry, we develop a robust high-throughput screening (HTS) assay for NHEJ that utilizes engineered pre-B-cell lines where the V(D)J recombination reaction can be induced and monitored at a single-cell level. This approach, novel in processing four 384-well plates at a time in parallel, was used to screen the National Cancer Institute NeXT library to identify compounds that inhibit V(D)J recombination and NHEJ. Assessment of cell light scattering characteristics at the primary HTS stage (83,536 compounds) enabled elimination of 60% of apparent hits as false positives. Although all the active compounds that we identified had an inhibitory effect on RAG cleavage, we have established this as an approach that could identify compounds that inhibit RAG cleavage or NHEJ using new chemical libraries.


Generation of two induced pluripotent stem cell lines from a 33-year-old central core disease patient with a heterozygous dominant c.14145_14156delCTACTGGGACA (p.Asn4715_Asp4718del) deletion in the RYR1 gene.
Central core disease (CCD) is a congenital disorder that results in hypotonia, delayed motor development, and areas of reduced oxidative activity in the muscle fibre. Two induced pluripotent stem cell (iPSC) lines were generated from the lymphoblastoid cells of a 33-year-old male with CCD, caused by a previously unreported dominant c.14145_14156delCTACTGGGACA (p.Asn4715_Asp4718del) deletion in the RYR1 gene. Both lines demonstrated typical morphology, pluripotency, trilineage differentiation, and had a normal karyotype. As the first published iPSC model of CCD caused by an RYR1 variant these lines are a potential resource for further investigation of RYR1-related myopathies in a human context.


Tanzanian malignant lymphomas: WHO classification, presentation, ploidy, proliferation and HIV/EBV association.
In Tanzania, the International Working Formulation [WF] rather than the WHO Classification is still being used in diagnosing malignant lymphomas (ML) and the biological characterization including the HIV/EBV association is sketchy, thus restraining comparison, prognostication and application of established therapeutic protocols. Archival, diagnostic ML biopsies (N = 336), available sera (N = 35) screened by ELISA for HIV antibodies and corresponding clinical/histological reports at Muhimbili National Hospital (MNH) in Tanzania between 1996 and 2006 were retrieved and evaluated. A fraction (N = 174) were analyzed by histopathology and immunohistochemistry (IHC). Selected biopsies were characterized by flow-cytometry (FC) for DNA ploidy (N = 60) and some by in-situ hybridization (ISH) for EBV-encoded RNA (EBER, N = 37). A third (38.8%, 109/281) of the ML patients with available clinical information had extranodal disease presentation. A total of 158 out of 174 biopsies selected for immunophenotyping were confirmed to be ML which were mostly (84. 8%, 134/158) non-Hodgkin lymphoma (NHL). Most (83.6%, 112/134) of NHL were B-cell lymphomas (BCL) (CD20+), of which 50.9%, (57/112) were diffuse large B-cell (DLBCL). Out of the 158 confirmed MLs, 22 (13.9%) were T-cell [CD3+] lymphomas (TCL) and 24 (15.2%) were Hodgkin lymphomas (HL) [CD30+]. Furthermore, out of the 60 FC analyzed ML cases, 27 (M:F ratio 2:1) were DLBCL, a slight majority (55.6%, 15/27) with activated B-cell like (ABC) and 45% (12/27) with germinal center B-cell like (GCB) immunophenotype. Overall, 40% (24/60) ML were aneuploid mostly (63.0%, 17/27) the DLBCL and TCL (54.5%, 6/11). DNA index (DI) of FC-analyzed ML ranged from 1.103-2.407 (median = 1.51) and most (75.0%) aneuploid cases showed high (>40%) cell proliferation by Ki-67 reactivity. The majority (51.4%, 19/37) of EBER ISH analyzed lymphoma biopsies were positive. Of the serologically tested MLs, 40.0% (14/35) were HIV positive, mostly with high (> or =40.0%) Ki-67 reactivity. According to the 2001 WHO Classification, most subtypes are represented in Tanzanian ML. Extranodal presentation was common among MNH lymphoma patients who also showed high aneuploidy, tumor proliferation (KI-67) and EBER positivity. DLBCL was frequent and phenotype heterogeneity appeared similar to observations in Western countries suggesting applicability of established intervention approaches. HIV was apparently associated with high ML cell proliferation but extended studies are needed to clarify this.


Application of "omics" to prion biomarker discovery.
The advent of genomics and proteomics has been a catalyst for the discovery of biomarkers able to discriminate biological processes such as the pathogenesis of complex diseases. Prompt detection of prion diseases is particularly desirable given their transmissibility, which is responsible for a number of human health risks stemming from exogenous sources of prion protein. Diagnosis relies on the ability to detect the biomarker PrP(Sc), a pathological isoform of the host protein PrP(C), which is an essential component of the infectious prion. Immunochemical detection of PrP(Sc) is specific and sensitive enough for antemortem testing of brain tissue, however, this is not the case in accessible biological fluids or for the detection of recently identified novel prions with unique biochemical properties. A complementary approach to the detection of PrP(Sc) itself is to identify alternative, "surrogate" gene or protein biomarkers indicative of disease. Biomarkers are also useful to track the progress of disease, especially important in the assessment of therapies, or to identify individuals "at risk". In this review we provide perspective on current progress and pitfalls in the use of "omics" technologies to screen body fluids and tissues for biomarker discovery in prion diseases.


GSTT1 is deregulated in left colon tumors.
Our aim was to determine GSTT1 expression levels in left colon tumors and paired normal tissue in order to identify specific alterations in GSTT1 mRNA levels. Alterations in GSTT1 expression in twenty-four left- sided colon tumors and paired cancer free tissue were determined by qRT-PCR. Significant fold changes were determined with t-test. When compared with cancer free tissue, left colon cancers showed a significant decrease in GSTT1 expression. However, GSTT1 mRNA levels among different grades increased gradually in correlation with tumor grade. Our results suggest that downregulation of GSTT1 in left-sided colon cancers is an early event and is reversed with cancer progression, probably due to cellular defense mechanisms as a response to changes in the microenvironment.


Spillovers and vulnerability: the case of community uninsurance.
This paper studies the uninsured as a vulnerable population. We contend that reducing the size of the uninsured population yields important spillover benefits to the insured population, benefits that go beyond a lower charity care burden. Evidence presented in this paper reinforces studies in the literature that show that problems of health services quality and access facing insured people increase when the proportion of uninsured people in their local communities is greater. The size of such spillover benefits is reduced if the local market is large enough to be segmented based on insurance status.


[The modern treatment of colorectal cancer. Present and future].
The modern treatment of colorectal cancer. Present and future. Fluorouracyl has been the mainstay of treatment for colorectal cancer for decades. The addition of folinic acid to 5FU, the use of infusional, rather than bolus 5FU, and the combination of new active agents such as irinotecan and oxaliplatin with 5FU/LV have each led to increase in effectivity. Oral formulations of fluoropyrimidines can replace the infusional 5FU therapy with better convenience. The authors review the current progress with the use of novel molecular targeted therapies that are tumor specific with better toxicity profile than chemotherapy. The integration of the new biological response modifier therapeutic possibilities in the chemotherapy protocols may result prolongation in survival, in metastatic patients the presently 2 years survival will approach 3 years. Combining these drugs with chemotherapeutics in the adjuvant setting we hope to raise further the presently achieved 78% of 3 years disease free survival by oxaliplatin plus 5FU therapy. As the variation of agents has been increased, choosing the most effective treatment strategy has become increasingly complex.


JAK inhibitors in autoinflammation.
Interferonopathies are a subset of autoinflammatory disorders with a prominent type I IFN gene signature. Treatment of these patients has been challenging, given the lack of response to common autoinflammatory therapeutics including IL-1 and TNF blockade. JAK inhibitors (Jakinibs) are a family of small-molecule inhibitors that target the JAK/STAT signaling pathway and have shown clinical efficacy, with FDA and European Medicines Agency (EMA) approval for arthritic and myeloproliferative syndromes. Sanchez and colleagues repurposed baricitinib to establish a significant role for JAK inhibition as a novel therapy for patients with interferonopathies, demonstrating the power of translational rare disease research with lifesaving effects.


The restorative effects of pulsed infrared light therapy on significant loss of peripheral protective sensation in patients with long-term type 1 and type 2 diabetes mellitus.
Pulsed infrared light therapy (PILT) has been shown to increase peripheral sensation in diabetic patients with diabetic peripheral neuropathy (DPN). However, most studies last for very short periods, with the subjects receiving only 6-20 treatments. The purpose of this study was to evaluate the effectiveness of an eight-week course of PILT in reversing long-standing, profound DPN in patients with type 1 and type 2 diabetes. Twenty-two subjects with a diagnosis of type 1 (n=2) or type 2 (n=20) diabetes participated in the study. PILT was administered to one foot chosen at random with the other foot serving as a within-subject control (no treatment). Patients underwent 24 treatments (3 times/week, for eight weeks) for 30 min per treatment. Changes in peripheral protective sensation (PPS) were measured using Semmes-Weinstein monofilaments (SWM) ranging from 3.7 to 6.48. PILT improved PPS even in patients with long-standing chronic neuropathies whose initial pre-study sensation was not measurable with a 200-g SWM. PILT significantly improves PPS. While the exact mechanism of action is not understood, infrared light may improve peripheral neuropathies by improving foot perfusion by stimulating nitric oxide production.


Pressure Injury Knowledge in Critical Care Nurses.
The purpose of this study was to identify pressure injury knowledge in critical care nurses related to prevention and staging following multimodal education initiatives. Postintervention descriptive study. The sample comprised 32 RNs employed in medical intensive care/coronary intensive care or surgical intensive care units. The study setting was a 237-bed Veterans Affairs acute care hospital in the Midwestern United States. Critical care RNs were asked to participate in this project over a 3-week period following a multimodal 2-year education initiative. Nurses completed the paper version of the 72-item Pieper-Zulkowski Pressure Ulcer Knowledge Test (PZ-PUKT) to determine pressure injury knowledge level. Calculated mean cumulative scores and subscores for items related to prevention and staging, respectively. Pearson correlations were used to examine associations between nursing staff characteristics and the PZ-PUKT prevention and staging scores. The cumulative score on the PZ-PUKT was 51.66 (72%); nurses with 5 to 10 years' experience had a higher mean score than nurses with experiences of 20 years or more (mean ± SD = 54.25 ± 4.37 vs 49.5 ± 7.12), but the difference was not statistically significant. Nurses scored higher on the staging system-related items as compared to the prevention-related items (81% vs 70%). Nurses achieved higher staging subscale scores if they were younger (r =-0.41, P < .05), had less experience (r =-0.43, P < .05), and if they worked in the medical intensive care unit (r = 0.37, P < .05). Study findings indicate gaps in knowledge related to pressure injury practice; participants had greater knowledge of staging rather than prevention. Cumulative and subscale findings can be used to direct educational efforts needed to improve and maintain an effective pressure injury prevention program.


Toxoplasma gondii antigenuria in patients with acquired immune deficiency syndrome.
A longitudinal study was performed with sera and urine of patients with acquired immune deficiency syndrome (AIDS), taken before, during and after clinically Toxoplasma infection. The tested patients were followed for an average of two years. The titres of the specific IgG and IgM antibodies were measured by an indirect fluorescent antibody test (IFAT), and the appearance of circulating antigens of T. gondii was determined in 36 urine samples of 13 patients with neurotoxoplasmosis by means of the coagglutination test. The presence of T. gondii antigens in the urine of AIDS patients by this test was correlated with the immunoblot technique, with clinical symptoms and also with pathological findings. Our results indicate that the detection of T. gondii antigens in the urine of AIDS patients can be regarded as a rapid and efficient method for the diagnosis of acute toxoplasmosis.


Differential regulation of Toll-like receptor 4 gene expression in renal cells by angiotensin II: dependency on AP1 and PU.1 transcriptional sites.
Toll-like receptor 4 (TLR4) is involved in the sensing of lipopolysaccharide and, therefore, plays a central role in innate immune responses to gram-negative bacteria. Interestingly, TLR4 expression occurs within the kidney. We have previously demonstrated that angiotensin II (ANG II) upregulates TLR4 expression on mesangial cells. However, the factors controlling transcriptional activation of the Tlr4 gene in mesangial cells are not known, and the specificity of this response for other renal cells is unclear. Cultured murine proximal tubular cells (mouse cortical tubule cell line; MCT cells), murine mesangial cells (MMCs), and murine podocytes were treated with ANG II. The expression of ANG II receptor mRNA and TLR4 mRNA and protein was determined by polymerase chain reaction and Western blotting. The transcriptional activity of wild-type and mutant mouse TLR4 promoter reporter constructs was determined upon transient transfection of the three cell types. Although MMCs, podocytes, and syngeneic proximal MCT cells similarly expressed ANG II receptors, ANG II stimulated TLR4 mRNA and protein expression in MMCs and podocytes only. A mouse TLR4 promoter construct (-518/+129), previously shown to contain all important transcriptional regulatory elements in various cell types, was activated by ANG II in MMCs and podocytes, but not in MCT cells. Mutation of a proximal PU.1-binding consensus site or an AP1 site abolished ANG-II-mediated transcriptional activation of the TLR4 promoter. Finally, basal transcription of the Tlr4 gene depended in all three cell lines on an intact AP1 site and additionally on the proximal PU.1 site in MMCs. ANG II stimulates TLR4 transcription through AP1 and PU.1 sites in a cell-specific manner. Since the intrarenal ANG II concentrations are enhanced in many pathophysiological situations, ANG-II-stimulated transcription of TLR4 on MMCs and podocytes may contribute to renal inflammation.


Gemfibrozil, a lipid-lowering drug, upregulates IL-1 receptor antagonist in mouse cortical neurons: implications for neuronal self-defense.
Chronic inflammation is becoming a hallmark of several neurodegenerative disorders and accordingly, IL-1β, a proinflammatory cytokine, is implicated in the pathogenesis of neurodegenerative diseases. Although IL-1β binds to its high-affinity receptor, IL-1R, and upregulates proinflammatory signaling pathways, IL-1R antagonist (IL-1Ra) adheres to the same receptor and inhibits proinflammatory cell signaling. Therefore, upregulation of IL-1Ra is considered important in attenuating inflammation. The present study underlines a novel application of gemfibrozil (gem), a Food and Drug Administration-approved lipid-lowering drug, in increasing the expression of IL-1Ra in primary mouse and human neurons. Gem alone induced an early and pronounced increase in the expression of IL-1Ra in primary mouse cortical neurons. Activation of type IA p110α PI3K and Akt by gem and abrogation of gem-induced upregulation of IL-1Ra by inhibitors of PI3K and Akt indicate a role of the PI3K-Akt pathway in the upregulation of IL-1Ra. Gem also induced the activation of CREB via the PI3K-Akt pathway, and small interfering RNA attenuation of CREB abolished the gem-mediated increase in IL-1Ra. Furthermore, gem was able to protect neurons from IL-1β insult. However, small interfering RNA knockdown of neuronal IL-1Ra abrogated the protective effect of gem against IL-1β, suggesting that this drug increases the defense mechanism of cortical neurons via upregulation of IL-1Ra. Taken together, these results highlight the importance of the PI3K-Akt-CREB pathway in mediating gem-induced upregulation of IL-1Ra in neurons and suggest gem as a possible therapeutic treatment for propagating neuronal self-defense in neuroinflammatory and neurodegenerative disorders.


Principal Component Analysis for Gaussian Process Posteriors.
This letter proposes an extension of principal component analysis for gaussian process (GP) posteriors, denoted by GP-PCA. Since GP-PCA estimates a low-dimensional space of GP posteriors, it can be used for metalearning, a framework for improving the performance of target tasks by estimating a structure of a set of tasks. The issue is how to define a structure of a set of GPs with an infinite-dimensional parameter, such as coordinate system and a divergence. In this study, we reduce the infiniteness of GP to the finite-dimensional case under the information geometrical framework by considering a space of GP posteriors that have the same prior. In addition, we propose an approximation method of GP-PCA based on variational inference and demonstrate the effectiveness of GP-PCA as meta-learning through experiments.


The impact of asthma exacerbations and preventive strategies.
To review the pathophysiologic mechanisms underlying asthma exacerbations, the impact of exacerbations, and both current and future treatment strategies to establish asthma control and reduce the risk of future exacerbations. Relevant adult data were identified via PubMed, with additional references obtained by reviewing bibliographies from selected articles. Asthma exacerbations or 'attacks' are acute episodes of progressive worsening of symptoms which occur in patients with all degrees of asthma severity and are an important cause of morbidity and mortality. For patients, these asthma attacks constitute a considerable part of the disease burden in terms of both personal suffering and economic impact. Exacerbations are characterized in part by decreases in expiratory flow or lung function. The pathophysiologic mechanism underlying these changes is likely to be different depending on the specific asthma phenotype. Asthma exacerbations are commonly initiated by upper respiratory tract infections and/or environmental allergens, although there are other known factors which increase the risk of a patient developing exacerbations, such as cigarette smoking. Establishing asthma control and reducing the risk of future exacerbations is the main goal of asthma treatment. Inhaled corticosteroids alone or in combination with long-acting β2-agonists, in addition to other step-up strategies such as leukotriene receptor antagonists and theophylline, are recommended. The anti-immunoglobulin E monoclonal antibody omalizumab should also be considered in difficult-to-treat allergic asthma. Despite the currently available treatments, many patients with asthma remain symptomatic and experience exacerbations regardless of disease severity. New therapies, including long-acting anticholinergics, anti-cytokines, and chemoattractant receptor-homologous molecules, are under investigation with some promising results. In addition to increased education and use of self-management plans, these novel therapies are essential to help improve asthma control and reduce exacerbation risk.


Clinicopathological analysis and risk factors of advanced colorectal neoplasms incidentally detected by 18F-FDG PET-CT.
As the clinical use of fluorine-18-fluorodeoxyglucose PET-computed tomography (F-FDG PET-CT) has increased, the incidental finding of F-FDG uptake with subsequent diagnosis of advanced neoplasm at colorectum has increased. The aim of this study is to analyze the characteristics and risk factors of advanced colorectal neoplasm incidentally detected by F-FDG PET-CT. Patients who underwent colonoscopy because of an incidental finding of F-FDG uptake at the colorectum from January 2006 to January 2015 at Yeungnam University Hospital were reviewed retrospectively. Advanced neoplasm was defined as adenoma of at least 10 mm, adenoma with serrated or villous component, high-grade dysplasia, and adenocarcinoma. Of the 19 798 candidates, 180 patients with incidental colorectal F-FDG uptake were included in this study. The indications of PET-CT were metastasis work-up, health screening, and others. The male to female ratio was 1.6 : 1 and the mean age was 62.7±11.4 years. A total of 156 lesions were detected in the colorectum and 86 (47.8%) were diagnosed as advanced neoplasms. Of the 86 patients with advanced neoplasms, 34 (39.5%) underwent an operation, 34 (39.5%) underwent endoscopic resection, and 18 (20.9%) underwent chemotherapy or conservative treatments. In univariate analysis, age of 62.5 years or older, carcinoembryonic antigen (CEA) of at least 3.4 ng/ml, maximum standardized uptake value (SUVmax) of at least 8.0, hypertension, F-FDG uptake on the rectosigmoid, and PET-CT for metastasis work-up showed a significant association with advanced neoplasm. In multivariate analysis, CEA (P=0.028), SUVmax (P<0.001) and an indication of PET-CT for metastasis work-up (P=0.008) were independent predictors of advanced neoplasm. Colonoscopy should be recommended in case of F-FDG uptake at the colorectum, particularly in patients with CEA of at least 3.4 ng/ml, SUVmax of at least 8.0, or metastasis work-up of malignancy.