Do infants increase the risk of re-emergent infection in households after mass drug administration for trachoma?
Mass treatment with azithromycin for trachoma endemic communities typically excludes infants under age 6 months, whose parents are provided with tubes of tetracycline to administer daily over 4 to 6 weeks. The authors sought to determine whether infants aged <6 months are a source of re-emergent infection in their families after mass treatment in trachoma-endemic communities. In a longitudinal study of all children aged less than 10 years in four communities, the authors identified 91 infants aged <6 months living in 86 of 1241 households. All children aged <ten years in all households were examined for trachoma and ocular infection with C. trachomatis at baseline, and 6 months after mass drug administration. The prevalence of infection at baseline in the infants was 5.9%. At 6 months post mass drug administration, the rate of infection among children older than 6 months and less than 10 years who resided in households with infants was 6.0% compared with 11.1% in children in households without infants (P = 0.18). After adjustment for age, sex, baseline infection status, and treatment, residing in a household with an infant was not associated with infection at 6 months (odds ratio [95% confidence interval] 0.50 [0.20-1.22]). This prospective study did not find evidence that living in a household with an infant increased the risk of infection 6 months post mass drug administration in other children residing in the household.


c-myc amplification is associated with HER2 amplification and closely linked with cell proliferation in tissue microarray of nonselected breast cancers.
C-myc and HER2 amplification were analyzed on 214 consecutive breast cancers by fluorescence in situ hybridization using tissue microarray technology. The frequencies of amplification were 15.4% (33/214) and 23.3% (49/210), respectively. c- myc amplification was significantly associated with HER2 amplification ( P < .001) and closely linked with cell proliferative activity, measured by Ki67 labeling index ( P = .010). In univariate survival analysis, lymph node status, tumor size, and histological grade were significant prognostic factors, but in multivariate analysis, lymph node status was the only significant factor. Patient survival did not differ according to c- myc amplification status, and c- myc amplification showed no significant correlation with clinicopathologic features of the tumors. A strong correlation between c- myc and HER2 amplification and proliferative activity indicates a biological link between these genes in breast cancer cell.


Preference for high status predicts implicit outgroup bias among children from low-status groups.
Whereas members of high-status racial groups show ingroup preference when attitudes are measured implicitly, members of low-status racial groups--both adults and children--typically show no bias, potentially reflecting awareness of the ingroup's low status. We hypothesized that when status differences are especially pronounced, children from low-status groups would show an implicit outgroup bias, the strength of which might relate to attitudes toward status. We tested these predictions among 6- to 11-year-old Black and Coloured (i.e., multiracial) children from South Africa, a country marked by extreme status differentials among racial groups. As a measure of implicit intergroup bias, children (N = 78) completed an Implicit Association Test (IAT), a speeded categorization task that assesses the relative strength of association between 2 target groups (in the present study, either Whites vs. Blacks or Whites vs. Coloureds) and positive vs. negative evaluation. Children also completed explicit (i.e., self-report) measures of attitudes toward racial groups as well as toward rich and poor people (a measure of attitudes toward status). Both groups of children showed an implicit outgroup-favoring (i.e., pro-White) bias, suggesting that children were sensitive to the extent of status differences. The only instance in which implicit pro-White bias did not emerge involved Black children's evaluations of Whites vs. Coloureds, both higher-status outgroups. Explicit preference for high status predicted implicit pro-White bias, particularly when the IAT contrasted 2 outgroups. The impact of status on the development of implicit and explicit intergroup bias is discussed.


Hyper-activation of Aurora kinase a-polo-like kinase 1-FOXM1 axis promotes chronic myeloid leukemia resistance to tyrosine kinase inhibitors.
Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the constitutive tyrosine kinase (TK) activity of the BCR-ABL1 fusion protein. Accordingly, TK inhibitors have drastically changed the disease prognosis. However, persistence of the transformed hematopoiesis even in patients who achieved a complete response to TK inhibitors and the disease relapse upon therapy discontinuation represent a major obstacle to CML cure. Thiostrepton, Danusertib and Volasertib were used to investigate the effects of FOXM1, AKA and Plk1 inhibition in K562-S and K562-R cells. Apoptotic cell death was quantified by annexin V/propidium iodide staining and flow cytometry. Quantitative reverse transcription (RT)-PCR was used to assess BCR-ABL1, FOXM1, PLK1 and AURKA expression. Protein expression and activation was assessed by Western Blotting (WB). Clonogenic assay were performed to confirm K562-R resistance to Imatinib and to evaluate cells sensitivity to the different drugs. Here we proved that BCR-ABL1 TK-dependent hyper-activation of Aurora kinase A (AURKA)-Polo-like kinase 1 (PLK1)-FOXM1 axis is associated with the outcome of Imatinib (IM) resistance in an experimental model (K562 cell line) and bone marrow hematopoietic cells. Notably, such a biomolecular trait was detected in the putative leukemic stem cell (LSC) compartment characterized by a CD34+ phenotype. Constitutive phosphorylation of FOXM1 associated with BCR-ABL1 TK lets FOXM1 binding with β-catenin enables β-catenin nuclear import and recruitment to T cell factor/lymphoid enhancer-binding factor (TCF/LEF) transcription complex, hence supporting leukemic cell proliferation and survival. Lastly, the inhibition of single components of AURKA-PLK1-FOXM1 axis in response to specific drugs raises the expression of growth factor/DNA damage-inducible gene a (GADD45a), a strong inhibitor of AURKA and, as so, a critical component whose induction may mediate the eradication of leukemic clone. Our conclusion is that AURKA, PLK1 and FOXM1 inhibition may be considered as a promising therapeutic approach to cure CML.


Environmental risk analysis for nanomaterials: review and evaluation of frameworks.
In response to the challenges of conducting traditional human health and ecological risk assessment for nanomaterials (NM), a number of alternative frameworks have been proposed for NM risk analysis. This paper evaluates various risk analysis frameworks proposed for NM based on a number of criteria. Among other results, most frameworks were found to be flexible for multiple NM, suitable for multiple decision contexts, included life cycle perspectives and precautionary aspects, transparent and able to include qualitative and quantitative data. Nevertheless, most frameworks were primarily applicable to occupational settings with minor environmental considerations, and most have not been thoroughly tested on a wide range of NM. Care should also be taken when selecting the most appropriate risk analysis strategy for a given risk context. Given this, we recommend a multi-faceted approach to assess the environmental risks of NM as well as increased applications and testing of the proposed frameworks for different NM.


Energetics and structural evolution of Na-Ca exchanged zeolite A during heating.
The properties of zeolite A change significantly upon sodium-calcium exchange. The impact of cation composition on the temperature-induced phase transformations and energetics of Na-Ca exchanged zeolite A was studied systematically using powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and high-temperature oxide melt solution calorimetry. As the temperature increases, the structural evolution of each Na-Ca exchanged zeolite A sample undergoes three distinct stages - dehydration, amorphization, and densification/recrystallization. Initially complete dehydration does not result in framework degradation, but further heating leads to zeolite phase degradation into other aluminosilicate phases. Both amorphization and recrystallization shift to higher temperatures as the calcium content increases. On the other hand, the enthalpies of formation for the high temperature aluminosilicate phases, the amorphous phase (AP) and the dense phase (DP), appear to be a linear function of calcium content (average ionic potential) with diminishing of energetic stability upon increasing the Ca content. 100% Na-A heated at 1200 °C has the most exothermic enthalpy of formation from oxides (-65.87 ± 0.87 kJ mol(-1)- TO2), while 97.9% CaNa-A heated at 945 °C has the least exothermic value (-5.26 ± 0.62 kJ mol(-1)- TO2). For different aluminosilicates with the same chemical composition, the dense phase (DP) assemblage is more stable than the amorphous phase (AP).


Aniticoagulation in patients following prosthetic heart valve replacement.
To identify optimum international normalized ratio (INR) levels and required warfarin doses and anticoagulation-related complications in patients following mechanical prosthetic valve replacement. Five hundred and seven patients were prospectively followed up for 10 years (2008.5 patient-years). Anticoagulation-related complications were classified into hemorrhage and thromboembolism. Two hundred and ninety-two (57.6%) were males and 215 (42.4%) were females with a mean age of 29.5 +/- 11.32 years. A total of 268 (52.9%) patients had mitral, 96 (18.9%) had aortic and mitral, and 76 (15%) had aortic valve replacement (AVR). Valves implanted totaled 345 (68%) ball and cage, 126 (24.9%) bileaflet, and 36 (7.1%) single disc. There were 10,669 total visits, with mean INR 2.6 +/- 0.59 and mean warfarin 5.17 +/- 1.6 mg. Sixty-four (3.2% per patient-years) events occurred during follow-up, of which 23 (1.13% per patient-years) events were due to thromboembolism and 41 (2.04% per patient-years) to bleeding. Atrial fibrillation occurred in 12 (52.4%) patients having thromboembolic events and in 24 (58.5%) suffering from bleeding complications. Among thromboembolic events, valve thrombosis occurred in 9 patients (0.44% per patient-years) and cerebrovascular accidents (CVAs) in 14 (0.69% per patient-years). Atrial fibrillation was present in 7 (77.8%) patients in the valve thrombosis group and in 5 (35.7%) in the CVA group. Of 41 bleeding events, 8 (0.39% per patient-years) were minor episodes, 20 (0.99% per patient-years) were major episodes, and severe hemorrhage occurred in 5 (0.34% per patient-years). Intracranial hemorrhage leading to CVA was seen in 8 patients (0.34% per patient-years). There were 22 (1.1% per patient-years) fatal hemorrhages and 15 (0.74% per patient-years) fatal thromboembolic events. In-hospital mortality was 25 (4.9%), and 62 (12.2%) were late deaths; of these, 37 (7.3%) were anticoagulation related. Anticoagulation for mechanical heart valve replacement can be managed with INR levels of 2-2.5 with acceptable hemorrhagic and thromboembolic events.


Graft-host connections in long-term full-thickness embryonic rabbit retinal transplants.
To establish neuronal connections in the rod and cone pathway between laminated rabbit retinal transplants and the host retina. Fourteen adult rabbits received a complete full-thickness embryonic transplant. After survival times of 3 to 10 months, the retinas were studied under light microscope and with immunohistochemistry. Antibodies against protein kinase C (PKC), parvalbumin, and calbindin were used to label rod bipolar cells, AII amacrine cells, and cone bipolar cells, respectively. The AB5 antibody was used to label ganglion cells. The transplants displayed laminated morphology with layers parallel to the host retinal pigment epithelium. In the oldest specimens (10 months after surgery), laminated layers of graft and host approached each other and almost reconstructed the normal retinal appearance. The ganglion and cone bipolar cells of the host survived well, as was seen with AB5 and calbindin double-labeling. Connections between cone bipolar cells in the graft and ganglion cells in the host were not common. PKC-labeled rod bipolar cells and parvalbumin-labeled AII amacrine cells of host and graft showed sprouting activity directed toward an intermediate plexiform layer located between the graft and host. In specimens double-labeled with PKC and parvalbumin, this intermediate plexiform layer was seen to contain numerous PKC- and parvalbumin-labeled processes. Direct connections between rod bipolar and AII amacrine cells in host and graft were seen in the 10-month specimens. Full-thickness embryonic transplants survive for at least 10 months, and normal laminated morphology develops. Host and graft fuse and together contribute nerve cell processes to an intermediate plexiform layer. Direct graft-host contacts are also present between neuronal types that in the normal retina participate in the rod pathway.


Growth and development of skeletal anomalies in diploid and triploid Atlantic salmon (Salmo salar) fed phosphorus-rich diets with fish meal and hydrolyzed fish protein.
Diploid and triploid Atlantic salmon, Salmo salar were fed high-protein, phosphorus-rich diets (56-60% protein; ca 18g phosphorus kg-1 diet) whilst being reared at low temperature from start-feeding until parr-smolt transformation. Performances of salmon fed diets based on fish meal (STD) or a mix of fishmeal and hydrolysed fish proteins (HFM) as the major protein sources were compared in terms of mortality, diet digestibility, growth and skeletal deformities. Separate groups of diploids and triploids were reared in triplicate tanks (initially 3000 fish per tank; tank biomass ca. 620 g) from 0-2745 degree-days post-start feeding (ddPSF). Growth metrics (weight, length, condition factor) were recorded at ca. 4 week intervals, external signs of deformities to the operculum, jaws and spinal column were examined in parr sampled at 1390 ddPSF, and external signs of deformity and vertebral anomalies (by radiography) were examined in fish sampled at the end of the trial (2745 ddPSF). The triploid salmon generally had a lower mass per unit length, i.e. lower condition factor, throughout the trial, but this did not seem to reflect any consistent dietary or ploidy effects on either dietary digestibility or the growth of the fish. By the end of the trial fish in all treatment groups had achieved a weight of 50+ g, and had completed the parr-smolt transformation. The triploids had slightly, but significantly, fewer vertebrae (Triploids STD 58.74 ± 0.10; HFM 58.68 ± 0.05) than the diploids (Diploids STD 58.97 ± 0.14; HFM 58.89 ± 0.01), and the incidence of skeletal (vertebral) abnormalities was higher in triploids (Triploids STD 31 ± 0.90%; HFM 15 ± 1.44%) than in diploids (Diploids STD 4 ± 0.80%; HFM 4 ± 0.83%). The HFM diet gave a significant reduction in the numbers of triploid salmon with vertebral anomalies in comparison with the triploids fed the STD diet possibly as a result of differences in phosphorus bioavailability between the two diets. Overall, the incidence of skeletal deformities was lower than reported in previous studies (Diploids 20+%, Triploids 40+%), possibly as a result of the combination of rearing at low-temperature and phosphorus-rich diets being used in the present study.


Bestrophin interacts physically and functionally with protein phosphatase 2A.
Bestrophin is a 68-kDa basolateral plasma membrane protein expressed in retinal pigment epithelial cells (RPE). It is encoded by the VMD2 gene, which is mutated in Best macular dystrophy, a disease characterized by a depressed light peak in the electrooculogram. Recently it was proposed that bestrophin is a chloride channel responsible for generating the light peak. To investigate its function further, we immunoaffinity purified a bestrophin complex from RPE lysates and identified bestrophin and the beta-catalytic subunit of protein phosphatase 2A (PP2A) as members of the complex by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Protein-protein interaction between bestrophin and PP2Ac and the structural subunit of PP2A, PR65, was confirmed by reciprocal immunoprecipitation. The C-terminal cytoplasmic domain of bestrophin was sufficient for the interaction with PP2A as demonstrated by a pulldown assay using a fusion of this domain with glutathione S-transferase. Bestrophin was phosphorylated when expressed in RPE-J cells and this phosphorylation was sensitive to okadaic acid. Purified PP2A effectively dephosphorylated bestrophin in vitro. These data suggest that bestrophin is in the signal transduction pathway that modulates the light peak of the electrooculogram, that it is regulated by phosphorylation, and that phosphorylation of bestrophin is in turn regulated by PP2A.


Postcards, green cards and telephone calls: therapeutic contact with individuals following self-harm.
Self-harm is a major public health problem and universal interventions such as contacting individuals by post or telephone following a self-harm episode have received much attention recently. They may also appeal to service providers because of their low cost. However, a widespread introduction of these interventions cannot be justified without a better understanding of whether they work, and if so how.


Disease mapping and regression with count data in the presence of overdispersion and spatial autocorrelation: a Bayesian model averaging approach.
This paper applies the generalised linear model for modelling geographical variation to esophageal cancer incidence data in the Caspian region of Iran. The data have a complex and hierarchical structure that makes them suitable for hierarchical analysis using Bayesian techniques, but with care required to deal with problems arising from counts of events observed in small geographical areas when overdispersion and residual spatial autocorrelation are present. These considerations lead to nine regression models derived from using three probability distributions for count data: Poisson, generalised Poisson and negative binomial, and three different autocorrelation structures. We employ the framework of Bayesian variable selection and a Gibbs sampling based technique to identify significant cancer risk factors. The framework deals with situations where the number of possible models based on different combinations of candidate explanatory variables is large enough such that calculation of posterior probabilities for all models is difficult or infeasible. The evidence from applying the modelling methodology suggests that modelling strategies based on the use of generalised Poisson and negative binomial with spatial autocorrelation work well and provide a robust basis for inference.


THE STRUCTURE OF INSECT FIBRILLAR FLIGHT MUSCLE : A Study Made with Special Reference to the Membrane Systems of the Fiber.
The fine structure of fibrillar flight muscle of the mature adult beetle Tenebrio molitor is described. Although the very high frequency of contraction of fibrillar muscle has previously been in part accounted for as the result of mechanical specialization of the wing-bearing segment rather than of a correspondingly high rate of motor impulse supply, the problem of the nature of the pathway by which excitation is conducted into these large fibers remained. Therefore, particular attention has been given to the disposition and relationships of the plasma membrane and sarcoplasmic reticulum in this tissue. The invading tracheoles draw with them a sheath of plasma membrane from the surface to all depths in the fiber, and it is suggested that these sheaths, together with the extensive tubular arborisations arising from them, reduce the maximum plasma membrane-to-fibril distance from the radius of the fiber to a value of less than 2 micro. The evidence presented here confirms Veratti's contention that in fibrillar muscle the "reticulum" is associated with, though entirely distinct from the fibrils. Unlike other muscles so far examined, these flight muscle fibers contain a plasma membrane reticulum only, but it is possible that elsewhere the general "sarcoplasmic reticulum" includes a component derived from the plasma membrane, likewise acting as the pathway for inward conduction of excitation. Profiles of the internalised plasma membrane in Tenebrio showing the usual triple-layered 25-25-25 A organization are frequently seen, in sections, in close association with isolated vesicles (defined by "simple" 50 A membranes) which are here considered to represent, in vestigial form, the portion of the sarcoplasmic reticulum which in other types of muscle is complex and highly developed. Such associations, in Tenebrio, between these two dissimilar elements are here termed "dyads" and the possible morphological and functional homology between these and the "triads" of other types of fiber is considered.


Relation of circulating PCSK9 concentration to fibrinogen in patients with stable coronary artery disease.
Both proprotein convertase subtilisin/kexin type 9 (PCSK9) and fibrinogen have been established as novel markers for atherosclerotic diseases. However, no data are available regarding the relationship between circulating PCSK9 and fibrinogen concentration up to now. To explore the potential link of the circulating PCSK9 concentration to fibrinogen in patients with stable coronary artery disease (CAD). We studied 219 eligible consecutive patients with angiographically proven stable CAD. Baseline clinical and laboratory data were collected. Plasma PCSK9 concentration was measured by enzyme-linked immunosorbent assay. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate, D-dimer, and albumin were also measured in all subjects as inflammatory markers. The relation of the circulating PCSK9 concentration to fibrinogen was evaluated. The data indicated that the patients with high PCSK9 concentration tended to have higher fibrinogen levels according to PCSK9 tertiles (P = .037). Spearman correlation analysis revealed a positive relation between plasma PCSK9 concentration and fibrinogen (r = 0.211, P = .002). Additionally, the circulating PCSK9 concentration also correlated positively with total cholesterol, low-density lipoprotein cholesterol, and hs-CRP levels (r = 0.333, P < .001; r = 0.302, P < .001; r = 0.153, P = .023, respectively). In the stepwise multivariate regression analysis, the association between PCSK9 and fibrinogen remained significant (β = 0.168, P = .011) after adjustment for conventional cardiovascular risk factors including lipid profiles, hs-CRP, and D-dimer. The present study first demonstrated that the circulating PCSK9 concentration was positively associated with fibrinogen in patients with stable CAD, suggesting that the interactions of PCSK9 and fibrinogen in the status of atherosclerosis may need further investigation.


leptin b and its regeneration enhancer illustrate the regenerative features of zebrafish hearts.
Zebrafish possess a remarkable regenerative capacity, which is mediated by the induction of various genes upon injury. Injury-dependent transcription is governed by the tissue regeneration enhancer elements (TREEs). Here, we utilized leptin b (lepb), an injury-specific factor, and its TREE to dissect heterogeneity of noncardiomyocytes (CMs) in regenerating hearts. Our single-cell RNA sequencing (scRNA-seq) analysis demonstrated that the endothelium/endocardium(EC) is activated to induce distinct subpopulations upon injury. We demonstrated that lepb can be utilized as a regeneration-specific marker to subset injury-activated ECs. lepb+ ECs robustly induce pro-regenerative factors, implicating lepb+ ECs as a signaling center to interact with other cardiac cells. Our scRNA-seq analysis identified that lepb is also produced by subpopulation of epicardium (Epi) and epicardium-derived cells (EPDCs). To determine whether lepb labels injury-emerging non-CM cells, we tested the activity of lepb-linked regeneration enhancer (LEN) with chromatin accessibility profiles and transgenic lines. While nondetectable in uninjured hearts, LEN directs EC and Epi/EPDC expression upon injury. The endogenous LEN activity was assessed using LEN deletion lines, demonstrating that LEN deletion abolished injury-dependent expression of lepb, but not other nearby genes. Our integrative analyses identify regeneration-emerging cell-types and factors, leading to the discovery of regenerative features of hearts.


A review of coronavirus infection in the central nervous system of cats and mice.
Feline infectious peritonitis (FIP) is a common cause of death in cats. Management of this disease has been hampered by difficulties identifying the infection and determining the immunological status of affected cats and by high variability in the clinical, pathological, and immunological characteristics of affected cats. Neurological FIP, which is much more homogeneous than systemic effusive or noneffusive FIP, appears to be a good model for establishing the basic features of FIP immunopathogenesis. Very little information is available about the immunopathogenesis of neurologic FIP, and it is reasonable to use research from the well-characterized mouse hepatitis virus (MHV) immune-mediated encephalitis system, as a template for FIP investigation, and to contrast findings from the MHV model with those of FIP. It is expected that the immunopathogenic mechanisms will have important similarities. Such comparative research may lead to better understanding of FIP immunopathogenesis and rational prospects for management of this frustrating disease.


The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis.
Patients with familial adenomatous polyposis have a nearly 100 percent risk of colorectal cancer. In this disease, the chemopreventive effects of nonsteroidal antiinflammatory drugs may be related to their inhibition of cyclooxygenase-2. We studied the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on colorectal polyps in patients with familial adenomatous polyposis. In a double-blind, placebo-controlled study, we randomly assigned 77 patients to treatment with celecoxib (100 or 400 mg twice daily) or placebo for six months. Patients underwent endoscopy at the beginning and end of the study. We determined the number and size of polyps from photographs and videotapes; the response to treatment was expressed as the mean percent change from base line. At base line, the mean (+/-SD) number of polyps in focal areas where polyps were counted was 15.5+/-13.4 in the 15 patients assigned to placebo, 11.5+/-8.5 in the 32 patients assigned to 100 mg of celecoxib twice a day, and 12.3+/-8.2 in the 30 patients assigned to 400 mg of celecoxib twice a day (P=0.66 for the comparison among groups). After six months, the patients receiving 400 mg of celecoxib twice a day had a 28.0 percent reduction in the mean number of colorectal polyps (P=0.003 for the comparison with placebo) and a 30.7 percent reduction in the polyp burden (the sum of polyp diameters) (P=0.001), as compared with reductions of 4.5 and 4.9 percent, respectively, in the placebo group. The improvement in the extent of colorectal polyposis in the group receiving 400 mg twice a day was confirmed by a panel of endoscopists who reviewed the videotapes. The reductions in the group receiving 100 mg of celecoxib twice a day were 11.9 percent (P=0.33 for the comparison with placebo) and 14.6 percent (P=0.09), respectively. The incidence of adverse events was similar among the groups. In patients with familial adenomatous polyposis, six months of twice-daily treatment with 400 mg of celecoxib, a cyclooxygenase-2 inhibitor, leads to a significant reduction in the number of colorectal polyps.


The toboggan sun.
Special variants of the Novaya Zemlya effect may arise from localized temperature inversions that follow the height profile of hills or mountains. Rather than following its natural path, the rising or setting Sun may, under such circumstances, appear to slide along a distant mountain slope. We found early observations of this effect in the literature by Willem Barents (1597) and by Captain Scott and H. G. Ponting (1911). We show recent photographic material of the effect and present ray-tracing calculations to explain its essentials.


Chiral differentiation of d- and l-alanine by permethylated β-cyclodextrin: IRMPD spectroscopy and DFT methods.
The gaseous chiral differentiation of alanine by permethylated β-cyclodextrin was studied using IRMPD spectroscopy and density functional theory calculations. The protonated non-covalent complexes of permethylated β-cyclodextrin and d- or l-alanine were mass-selected and investigated by IR laser pulses in the wavelength region of 2650-3800 cm-1. The remarkably different features of the IRMPD spectra for d- and l-alanine are described, and their origin is elucidated by quantum chemical calculations. We show that the differentiation of the experimentally observed spectral features is the result of different local interactions of d- and l-alanine with permethylated β-cyclodextrin. We also assign the extremely high-frequency (>3700 cm-1) bands in the observed spectra to the stretch motions of completely isolated alanine -OH groups.


Antibody neutralization of neurite growth inhibitors from oligodendrocytes results in expanded pattern of postnatally sprouting retinocollicular axons.
After early postnatal ablation of one superior colliculus together with the ipsilateral eye in Syrian hamsters, retinofugal fibers abnormally cross the tectal midline and innervate the remaining superior colliculus. The fibers of this aberrant decussation are confined mainly to the superficial gray layer, with little ingrowth or termination in the deeper stratum opticum; laterally, most termination is in the superficial part of the superficial gray. Establishment of this abnormal pattern is temporally correlated with the appearance of oligodendrocytes at progressively more superficial locations in the colliculus. Oligodendrocytes express, on their surface, molecules that are inhibitory to neurite growth. This raises the possibility that their differential distribution in the superior colliculus during growth of retinal fibers is causally involved in the generation of the observed termination pattern. We tested this hypothesis by applying the monoclonal antibody IN-1, which neutralizes this inhibitory activity, during the time of postnatal fiber growth and terminal arbor formation. We found that in the presence of IN-1, but not a control antibody, recrossing retinofugal fibers, observed at postnatal day 12, traverse the stratum opticum as well as the superficial gray, with greater depth of termination in superficial gray and stratum opticum. This pattern resembles that of the normal contralateral retinotectal projection. The results indicate that neurite growth inhibitors expressed by oligodendrocytes are responsible for restricting the innervation of a target area in postnatal plasticity.


Use of fast-sequence spine MRI in pediatric patients.
The immediate and long-term risk of anesthesia in the pediatric population is controversial. Traditional spine MRI protocols require the patient to remain still during the examination, and in young children this frequently results in the need for sedation administration. The authors' goal was to develop an abbreviated spine MRI protocol to reduce sedation administration in young patients undergoing spine MRI. After IRB approval, the medical records of all pediatric patients who underwent a fast spine MRI protocol between 2017 and 2019 were reviewed. The protocol consisted of T2-weighted half-Fourier acquisition single-shot turbo spin echo, T1-weighted turbo spin echo, and T2-weighted STIR sequences acquired in the sagittal plane. The total acquisition time was 2 minutes with no single sequence acquisition longer than 60 seconds. Interpretability of the scans was assessed in accordance with the radiology report in conjunction with the neurosurgeon's clinical notes. A total of 47 fast spine MRI sessions were performed in 45 patients. The median age at the time of the MRI was 2.4 years (25th-75th quartile, 1.1-4.3 years; range 0.16-18.58 years). The most common indication for imaging was to rule out or follow a known syrinx (n = 30), followed by the need to rule out or follow known spinal dysraphism (n = 22). There were no uninterpretable or unusable scans. Eight of 47 scans were noted to have moderate motion artifact limitations with respect to the quality of the scan. Seven patients underwent a subsequent MRI with a sedated standard spine protocol within 1 year from the fast scan, which confirmed the findings on the fast MRI protocol with no new findings identified. The authors report the first pediatric series of a fast spine MRI protocol for use in young patients. The protocol does not require sedation and is able to identify and monitor syrinx, spinal dysraphism, and potentially other intraspinal anomalies.


Sextant Biopsy-Based Criteria for Clinically Insignificant Prostate Cancer Are Also Valid for the 12-Core Prostate Biopsy Scheme: A Multicenter Study of Urooncology Association, Turkey.
Epstein criteria based on sextant biopsy are assumed to be valid for 12-core biopsies. However, very scarce information is present in the current literature to support this view. To investigate the validity of Epstein criteria for clinically insignificant prostate cancer (PCa) in a cohort of the currently utilized 12-core prostate biopsy (TRUS-Bx) scheme in patients with low-risk and intermediate-risk PCa. Pathological findings were separately evaluated in the areas matching the sextant biopsy (6-core paramedian) scheme and in all 12-core schemes. Patients were divided into 2 groups according to the final pathology report of RP as true clinically significant PCa (sPCa) and insignificant PCa (insPCa) groups. Predictive factors (including Epstein criteria) and cutoff values for the presence of insPCa were separately evaluated for 6- and 12-core TRUS-Bx schemes. Then, different predictive models based on Epstein criteria with or without additional biopsy findings were created. A total of 442 patients were evaluated. PSA density, biopsy GS, percentage of tumor and number of positive cores, PNI, and HG-PIN were independent predictive factors for insPCa in both TRUS-Bx schemes. For the 12-core scheme, the best cutoff values of tumor percentage and number of positive cores were found to be ≤50% (OR: 3.662) and 1.5 cores (OR: 2.194), respectively. The best predictive model was found to be that which added 3 additional factors (PNI and HG-PIN absence and number of positive cores) to Epstein criteria (OR: 6.041). Using a cutoff value of "1" for the number of positive biopsy cores and absence of biopsy PNI and HG-PIN findings can be more useful for improving the prediction model of the Epstein criteria in the 12-core biopsy scheme.


Prevalence of Meeting Physical Activity, Screen-Time, and Sleep Guidelines Among Children and Adolescents With and Without Visual Impairments in the United States.
The purpose of this study was to compare the degree to which children and adolescents with and without visual impairments (VIs) met national physical activity, screen-time, and sleep guidelines. This observational, cross-sectional analysis of the 2016 National Survey of Children's Health focused on children (age 6-12 yr) and adolescents (age 13-17 yr) with and without VIs. The sample included 241 (weighted n = 472,127) and 17,610 (weighted n = 28,249,833) children, and 255 (weighted n = 505,401) and 17,417 (weighted n = 20,071,557) adolescents with and without VIs, respectively. Chi-square statistics were computed to examine the degree to which participants with and without VIs met health-behavior guidelines. Children (p = .02) with VIs were less likely to meet screen-time guidelines, but adolescents with VIs were not (p = .87). VI status was not associated with the likelihood of meeting physical activity or sleep guidelines (p < .05). Low numbers of children and adolescents with and without VIs meeting health-behavior guidelines warrant targeted interventions aimed at enhancing engagement.


Phosphorylation of CREB affects its binding to high and low affinity sites: implications for cAMP induced gene transcription.
Cyclic AMP treatment of hepatoma cells leads to increased protein binding at the cyclic AMP response element (CRE) of the tyrosine aminotransferase (TAT) gene in vivo, as revealed by genomic footprinting, whereas no increase is observed at the CRE of the phosphoenolpyruvate carboxykinase (PEPCK) gene. Several criteria establish that the 43 kDa CREB protein is interacting with both of these sites. Two classes of CRE with different affinity for CREB are described. One class, including the TATCRE, is characterized by asymmetric and weak binding sites (CGTCA), whereas the second class containing symmetrical TGACGTCA sites shows a much higher binding affinity for CREB. Both classes show an increase in binding after phosphorylation of CREB by protein kinase A (PKA). An in vivo phosphorylation-dependent change in binding of CREB increases the occupancy of weak binding sites used for transactivation, such as the TATCRE, while high affinity sites may have constitutive binding of transcriptionally active and inactive CREB dimers, as demonstrated by in vivo footprinting at the PEPCK CRE. Thus, lower basal level and higher relative stimulation of transcription by cyclic AMP through low affinity CREs should result, allowing finely tuned control of gene activation.


The hydrochemistry of groundwater in the Densu River Basin, Ghana.
Hydrochemical analyses of groundwater samples were used to establish the hydrochemistry of groundwater in the Densu River Basin. The groundwater was weakly acidic, moderately mineralized, fresh to brackish with conductivity ranging from of 96.6 microS cm(-1) in the North to 10,070 microS cm( - 1) in the South. Densu River basin have special economic significance, representing the countries greatest hydrostructure with freshwater. Chemical constituents are generally low in the North and high in the South. The order of relative abundance of major cations in the groundwater is Na+>Ca2+>Mg2+>K+ while that of anions is Cl->HCO3->SO4(2-)>NO3-. Four main chemical water types were delineated in the Basin. These include Ca-Mg-HCO3, Mg-Ca-Cl, Na-Cl, and mixed waters in which neither a particular cation nor anion dominates. Silicate weathering and ion exchange are probably the main processes through which major ions enter the groundwater system. Anthropogenic activities were found to have greatly impacted negatively on the quality of the groundwater.


Tissue-specific expression of a FMR1/beta-galactosidase fusion gene in transgenic mice.
Fragile X syndrome is one of the most common genetic causes of mental retardation, yet the mechanisms controlling expression of the fragile X mental retardation gene FMR1 are poorly understood. To identify sequences regulating FMR1 transcription, transgenic mouse lines were established using a fusion gene consisting of an E.coli beta-galactosidase reporter gene (lacZ) linked to a 2.8 kb fragment spanning the 5'-region of FMR1. Five transgenic mouse lines showed lacZ expression in brain, in particular in neurons of the hippocampus and the granular layer of the cerebellum. Expression of the reporter gene was also detected in Leydig cells and spermatogonia in the testis, in many epithelia of adult mice, and in the two other steroidogenic cell types, adrenal cortex cells and ovarian follicle cells. Embryonic tissues which showed strong activity of the reporter gene included the telencephalon, the genital ridge, and the notochord. This expression pattern closely resembles the endogenous one, indicating that the 5' FMR1 gene promoter region used in this study contains most cis-acting elements regulating FMR1 transcription.


Dual orexin receptor antagonist 12 inhibits expression of proteins in neurons and glia implicated in peripheral and central sensitization.
Sensitization and activation of trigeminal nociceptors is implicated in prevalent and debilitating orofacial pain conditions including temporomandibular joint (TMJ) disorders. Orexins are excitatory neuropeptides that function to regulate many physiological processes and are reported to modulate nociception. To determine the role of orexins in an inflammatory model of trigeminal activation, the effects of a dual orexin receptor antagonist (DORA-12) on levels of proteins that promote peripheral and central sensitization and changes in nocifensive responses were investigated. In adult male Sprague-Dawley rats, mRNA for orexin receptor 1 (OX₁R) and receptor 2 (OX₂R) were detected in trigeminal ganglia and spinal trigeminal nucleus (STN). OX₁R immunoreactivity was localized primarily in neuronal cell bodies in the V3 region of the ganglion and in laminas I-II of the STN. Animals injected bilaterally with complete Freund's adjuvant (CFA) in the TMJ capsule exhibited increased expression of P-p38, P-ERK, and lba1 in trigeminal ganglia and P-ERK and lba1 in the STN at 2 days post injection. However, levels of each of these proteins in rats receiving daily oral DORA-12 were inhibited to near basal levels. Similarly, administration of DORA-12 on days 3 and 4 post CFA injection in the TMJ effectively inhibited the prolonged stimulated expression of protein kinase A, NFkB, and Iba1 in the STN on day 5 post injection. While injection of CFA mediated a nocifensive response to mechanical stimulation of the orofacial region at 2h and 3 and 5 days post injection, treatment with DORA-12 suppressed the nocifensive response on day 5. Somewhat surprisingly, nocifensive responses were again observed on day 10 post CFA stimulation in the absence of daily DORA-12 administration. Our results provide evidence that DORA-12 can inhibit CFA-induced stimulation of trigeminal sensory neurons by inhibiting expression of proteins associated with sensitization of peripheral and central neurons and nociception.


Caudate volumes in public transportation workers exposed to trauma in the Stockholm train system.
The caudate nucleus is a structure implicated in the neural circuitry of psychological responses to trauma. This study aimed to quantify the volume of the caudate in persons exposed to trauma. Thirty-six subjects under 65 were recruited from transport workers in Stockholm who reported having been unintentionally responsible for a person-under-the-train accident or among employees having experienced an assault in their work (1999-2001) between 3 months and 6 years before MRI scanning. In those exposed to the trauma, a DSM-IV diagnosis of post-traumatic stress disorder (PTSD) was made by an independent psychiatrist, with subjects being classified as PTSD or no PTSD. MRI data were analyzed blindly to all clinical information by an experienced rater using a standardized manual tracing protocol to quantify the volume of the caudate. Within-group comparisons of PTSD (n=19) and no PTSD (n=17) found the right caudate nucleus to be significantly (9%) larger than the left: a right hemisphere baseline asymmetry. A multivariate analysis of covariance (MANCOVA) was conducted to assess the volume of the caudate nucleus (right and left) in relation to the diagnosis of no PTSD (n=17) or PTSD (n=19). After adjustment for the covariates (age, sex, intracranial volume, years since trauma, and number of trauma episodes), there was a significant difference in raw right caudate nucleus volume between subjects with PTSD compared with those without PTSD. Volume of the left caudate nucleus was not significantly different between the PTSD and no PTSD groups. The right caudate volume in the PTSD group was 9% greater compared with the no PTSD group. There is a larger right hemisphere volume of the caudate within those exposed to trauma with active PTSD compared with those without PTSD, superimposed upon a baseline caudate asymmetry.


Nature-Inspired, 3D Origami Solar Steam Generator toward Near Full Utilization of Solar Energy.
Solar steam generation, due to its capability of producing clean water directly by solar energy, is emerging as a promising eco-friendly and energy-efficient technology to address global challenges of water crisis and energy shortage. Although diverse materials and architectures have been explored to improve solar energy utilization, high efficiency in solar steam generation could be accomplished only with external optical and thermal management. For the first time, we report a deployable, three-dimensional (3D) origami-based solar steam generator capable of near full utilization of solar energy. This auxetic platform is designed based on Miura-ori tessellation and is able to efficiently recover radiative and convective heat loss as well as to trap solar energy via its periodic concavity pattern. The 3D solar steam generator device with a nanocarbon composite of graphene oxide and carbon nanotubes being photothermal component in this work shows a very strong dependence between its solar energy efficiency and surface areal density. The device yields an extraordinary solar energy efficiency close to 100% under 1 sun illumination at a highly folded configuration. The 3D origami device can withstand a great number of folding and unfolding cycles and shows unimpaired solar steam generation performances. The unique structural feature of the 3D origami structure offers a new insight into the future development of highly efficient and easily deployable solar steam generator.


Rex1/Zfp42 as an epigenetic regulator for genomic imprinting.
Zfp42/Rex1 (reduced expression gene 1) is a well-known stem-cell marker that has been duplicated from YY1 in the eutherian lineage. In the current study, we characterized the in vivo roles of Rex1 using a mutant mouse line disrupting its transcription. In contrast to the ubiquitous expression of YY1, Rex1 is expressed only during spermatogenesis and early embryogenesis and also in a very limited area of the placenta. Yet, the gene dosage of Rex1 is very critical for the survival of the late-stage embryos and neonates. This delayed phenotypic consequence suggests potential roles for Rex1 in establishing and maintaining unknown epigenetic modifications. Consistently, Rex1-null blastocysts display hypermethylation in the differentially methylated regions (DMRs) of Peg3 and Gnas imprinted domains, which are known to contain YY1 binding sites. Further analyses confirmed in vivo binding of Rex1 only to the unmethylated allele of these two regions. Thus, Rex1 may function as a protector for these DMRs against DNA methylation. Overall, the functional connection of Rex1 to genomic imprinting represents another case where newly made genes have co-evolved with lineage-specific phenomena.


Effects of CSFs in preleukemia.
Based on pre-clinical and in vitro studies demonstrating enhanced granulocytic proliferation and differentiation induced by granulocyte-monocyte and granulocyte-colony stimulating factors (GM-CSF and G-CSF), these recombinant human hormones have been used to treat cytopenic patients with preleukemia [i.e., myelodysplastic syndromes (MDS)]. To date, five studies have been reported using GM-CSF short-term (generally 7-14 days, x 1-5 courses). Thirty-eight of 45 treated patients had improvements in neutrophil counts, 14 had increased reticulocyte counts with three of these individuals having decreased RBC transfusion requirements, and eight had transient increases in platelets. In 12 patients an increase in marrow and/or peripheral blood blasts was noted. Seven patients progressed to acute myeloid leukemia (AML), particularly patients with greater than 15% marrow blasts. In a longer term study, five patients received GM-CSF for 2 to 9 weeks, although only one individual maintained increased neutrophil counts, one developed antibodies to GM-CSF and one evolved into AML. Eighteen patients have been treated for 2 months with G-CSF, 16 of whom had normalization of neutrophil counts with improved marrow maturation, five had increased reticulocyte counts with three having decreased transfusion requirements, no substantial changes in platelet counts were noted. Eleven patients have received maintenance therapy with G-CSF for 6-16 months, ten had persistent increases in neutrophil counts with enhanced marrow myeloid maturation and five had increased reticulocytes. Decreased infectious episodes were notedat times of neutrophil improvements. Four of the 18 individuals have subsequently developed AML after 6-16 months.(ABSTRACT TRUNCATED AT 250 WORDS)


Interactions among chronic and acute impacts on coral recruits: the importance of size-escape thresholds.
Newly settled recruits typically suffer high mortality from disturbances, but rapid growth reduces their mortality once size-escape thresholds are attained. Ocean acidification (OA) reduces the growth of recruiting benthic invertebrates, yet no direct effects on survivorship have been demonstrated. We tested whether the reduced growth of coral recruits caused by OA would increase their mortality by prolonging their vulnerability to an acute disturbance: fish herbivory on surrounding algal turf. After two months' growth in ambient or elevated CO2 levels, the linear extension and calcification of coral (Acropora millepora) recruits decreased as CO2 partial pressure (pCO2) increased. When recruits were subjected to incidental fish grazing, their mortality was inversely size dependent. However, we also found an additive effect of pCO2 such that recruit mortality was higher under elevated pCO2 irrespective of size. Compared to ambient conditions, coral recruits needed to double their size at the highest pCO2 to escape incidental grazing mortality. This general trend was observed with three groups of predators (blenny, surgeonfish, and parrotfish), although the magnitude of the fish treatment varied among species. Our study demonstrates the importance of size-escape thresholds in early recruit survival and how OA can shift these thresholds, potentially intensifying population bottlenecks in benthic invertebrate recruitment.


EQ-5D Utilities in Chronic Spontaneous/Idiopathic Urticaria.
To obtain utility estimates suitable for use in economic models for chronic spontaneous (idiopathic) urticaria (CSU). Patient-level data from three randomized clinical trials-ASTERIA I, ASTERIA II and GLACIAL-were analysed. Health states were derived from the Urticaria Activity Score over 7 days (UAS7); higher scores denote greater activity. The health state score ranges were urticaria free: 0; well-controlled urticaria: 1-6; mild urticaria: 7-15; moderate urticaria: 16-27; and severe urticaria: 28-42. The mean EQ-5D utilities were calculated for each health state. A mixed model was used to predict the EQ-5D according to UAS7 health states in a pooled data set containing all treatment arms and time points from the three trials. Pooled trial data were validated through visual comparisons and interaction terms. Fixed and random effects for trials and patients were included, along with the following covariates: UAS7 health state at baseline (moderate or severe); presence of angioedema at baseline and during follow-up; duration of CSU; number of previous CSU medications; visit; current treatment; and patient age and sex. There was a consistent improvement in EQ-5D utilities as urticaria activity decreased. The mean utilities ranged from 0.710 (severe urticaria) to 0.780 (moderate urticaria), 0.829 (mild urticaria), 0.862 (well-controlled urticaria) and 0.894 (urticaria free). Sensitivity and subgroup analyses confirmed the robustness of the results. The results suggest that EQ-5D utility scores increase with decreasing urticaria activity. EQ-5D utility scores enable the health-related quality of life of CSU patients to be compared with that of patients with other diseases.


SCCT curriculum guidelines for general (level 1) cardiovascular CT training.
The Society of Cardiovascular Computed Tomography has developed general (level 1) cardiovascular CT (CCT) training guidelines for radiology resident and cardiology fellow education. As CCT use has expanded over the past decade, it is essential to incorporate such training in both diagnostic radiology residency programs and cardiology fellowship programs. This curriculum will ensure residents and fellows-in-training obtain a fundamental understanding of CCT to stay current in the evolving landscape of cardiovascular imaging and know how and when to use CCT. The curriculum will also help narrow the present knowledge and training gap that exists for CCT between different programs and may encourage trainees to pursue additional training in advanced cardiovascular imaging.


Primary and secondary transcriptional effects in the developing human Down syndrome brain and heart.
Down syndrome, caused by trisomic chromosome 21, is the leading genetic cause of mental retardation. Recent studies demonstrated that dosage-dependent increases in chromosome 21 gene expression occur in trisomy 21. However, it is unclear whether the entire transcriptome is disrupted, or whether there is a more restricted increase in the expression of those genes assigned to chromosome 21. Also, the statistical significance of differentially expressed genes in human Down syndrome tissues has not been reported. We measured levels of transcripts in human fetal cerebellum and heart tissues using DNA microarrays and demonstrated a dosage-dependent increase in transcription across different tissue/cell types as a result of trisomy 21. Moreover, by having a larger sample size, combining the data from four different tissue and cell types, and using an ANOVA approach, we identified individual genes with significantly altered expression in trisomy 21, some of which showed this dysregulation in a tissue-specific manner. We validated our microarray data by over 5,600 quantitative real-time PCRs on 28 genes assigned to chromosome 21 and other chromosomes. Gene expression values from chromosome 21, but not from other chromosomes, accurately classified trisomy 21 from euploid samples. Our data also indicated functional groups that might be perturbed in trisomy 21. In Down syndrome, there is a primary transcriptional effect of disruption of chromosome 21 gene expression, without a pervasive secondary effect on the remaining transcriptome. The identification of dysregulated genes and pathways suggests molecular changes that may underlie the Down syndrome phenotypes.


The damaging punch.
The mechanical properties of a boxing punch have been determined using several techniques. The results are consistent with the medical consequences of boxing discussed in the report of the Board of Science and Education Working Party on boxing. Data were gathered from a world ranked British professional heavyweight, Frank Bruno, as he punched an instrumented, padded target mass suspended as a ballistic pendulum. Within 0.1 s of the start the punch had travelled 0.49 m and attained a velocity on impact of 8.9 m/s. The peak force on impact of 4096N (0.4 ton), attained within 14 ms of contact, represents a blow to the human head of up to 6320N (0.63 ton). The transmitted impulse generated an acceleration of 520 m/s2 (53 g) in the target head. For comparison an equivalent blow would be delivered by a padded wooden mallet with a mass of 6 kg (13 lbs) if swung at 20 mph.


NK1 receptor antagonists as a new treatment for corneal neovascularization.
To determine whether the inhibition of Substance P (SP) activity can reduce corneal neovascularization (CNV) by means of local administration of high-affinity, competitive, tachykinin 1 receptor (NK1R) antagonists Lanepitant and Befetupitant. We performed a safety and efficacy study by using (1) two different C57BL/6 mouse models of CNV: alkali burn and sutures; (2) different concentrations; and (3) different routes of administration: topical or subconjunctival. Clinical examination endpoints, SP levels, CNV index, and leukocyte infiltration were measured. Substance P increased after injury in the corneal epithelium of both CNV models, and later in the suture model. Topical Lanepitant was nontoxic to the ocular surface and effective in reducing hemangiogenesis and lymphangiogenesis, corneal SP levels, and leukocyte infiltration, as soon as 4 days later in the alkali burn model. Topical Lanepitant, up to 7 days, was ineffective in the suture model. However, subconjunctival Lanepitant was effective in reducing lymphatic CNV, leukocyte infiltration, and SP levels in the suture model, after 10 days. Additionally, in the alkali burn model, subconjunctival Lanepitant significantly reduced blood CNV, corneal perforation rate, opacity, and leukocyte infiltration, and improved tear secretion. Finally, topical application of Befetupitant reduced CNV in the alkali burn model but was toxic owing to the vehicle (dimethyl sulfoxide [DMSO]); hence, Befetupitant was not tested in the suture model. The NK1R antagonist Lanepitant is safe for the ocular surface and effective in reducing both corneal hemangiogenesis and lymphangiogenesis, and leukocyte infiltration. We suggest that inhibition of NK1R may represent an adjunctive tool in the treatment of CNV.


The importance of microhabitat for biodiversity sampling.
Responses to microhabitat are often neglected when ecologists sample animal indicator groups. Microhabitats may be particularly influential in non-passive biodiversity sampling methods, such as baited traps or light traps, and for certain taxonomic groups which respond to fine scale environmental variation, such as insects. Here we test the effects of microhabitat on measures of species diversity, guild structure and biomass of dung beetles, a widely used ecological indicator taxon. We demonstrate that choice of trap placement influences dung beetle functional guild structure and species diversity. We found that locally measured environmental variables were unable to fully explain trap-based differences in species diversity metrics or microhabitat specialism of functional guilds. To compare the effects of habitat degradation on biodiversity across multiple sites, sampling protocols must be standardized and scale-relevant. Our work highlights the importance of considering microhabitat scale responses of indicator taxa and designing robust sampling protocols which account for variation in microhabitats during trap placement. We suggest that this can be achieved either through standardization of microhabitat or through better efforts to record relevant environmental variables that can be incorporated into analyses to account for microhabitat effects. This is especially important when rapidly assessing the consequences of human activity on biodiversity loss and associated ecosystem function and services.


Regional myocardial substrate uptake in hypertensive rats: a quantitative autoradiographic measurement.
Severe hypertension causes global and regional changes in myocardial perfusion and substrate utilization. Regional perfusion and fatty acid utilization were evaluated by dual-tracer autoradiography in normotensive and hypertensive rats of the Dahl strain. The regional distributions of perfusion and fatty acid utilization were homogeneous in normotensive rats. Severe hypertension was associated with a homogeneous pattern of regional perfusion, but fatty acid utilization was focally decreased in the free wall of the left ventricle. The decrease in fatty acid uptake was associated with a concomitant increase in glucose utilization. These findings suggest that severe hypertension is associated with uniform myocardial perfusion and focal alterations in the substrates used for the performance of myocardial work.


The internal representation of spectral contrast in hearing-impaired listeners.
Abnormal frequency resolution associated with sensorineural hearing impairment produces a smearing of spectral detail in the internal representation of complex acoustic stimuli. As a result, listeners with hearing loss may have difficulty locating spectral peaks (e.g., vowel formants) within stimuli which cue their identity. This study examined the relationship between frequency separation of peaks in a complex spectrum and the degree of spectral contrast preserved in the internal representations in normal and impaired auditory systems. Hearing-impaired and normal-hearing subjects discriminated a flat-spectrum bandpass stimulus from a stimulus containing a sinusoidal ripple across its frequency range. The peak-to-valley amplitude (in dB) necessary for detection of the ripple was measured for ripple frequencies ranging from 1 to 9 cycles/oct. Auditory filter characteristics were also measured at 1 and 3 kHz in order to examine the internal representations of the stimuli after cochlear processing. There were clear differences between groups in both auditory filter characteristics and spectral contrast detection. However, the amount of contrast in the internal representations predicted from these measurements was nearly the same for all subjects, suggesting that the reduced frequency resolution of the hearing-impaired group was largely responsible for differences in required peak-to-valley amplitude in the input spectra. Further, for all subjects, there was a trade-off between the absolute level of internal contrast necessary for ripple detection and the number of samples of this contrast available to the listener.


Traumatic brain injury-needs and treatment options in the chronic phase: Study protocol for a randomized controlled community-based intervention.
Traumatic brain injury (TBI) is often associated with life-long medical, cognitive, emotional, and behavioral changes. Although long-lasting disabilities are expected, research on effective treatment options in the chronic phase of TBI is scarce. This study protocol describes a randomized controlled trial (RCT) aimed at evaluating the effectiveness of a goal-oriented and community-based intervention for increasing community integration, quality of life, and functional independence in the chronic phase of complicated mild to severe TBI. Participants will be recruited from Oslo University Hospital, Norway. Patients aged 18-72 years living at home with MRI/CT-verified intracranial abnormalities, a TBI diagnosis, a time since injury of ≥ 2 years, and who experience either current TBI-related problems or restrictions in community integration will be included. The 120 participants will be randomized 1:1 to either (a) an intervention group, which will receive an in-home intervention program over 4 months, or (b) a control group receiving standard care in the municipalities. The intervention will consist of six home visits and two telephone contacts with a rehabilitation professional. A SMART-goal approach will be adopted to target the individual's self-reported TBI difficulties in everyday life. Primary outcomes will be self-reported quality of life and participation. Secondary outcomes include symptom burden, emotional functioning, and clinician-assessed global outcome and need for rehabilitation services. Outcomes will be evaluated at baseline and 4-5 and 12 months after baseline. Caregiver burden and general health will be assessed in participating family members. Goal attainment and acceptability will be evaluated in the intervention group. A process evaluation will be carried out to evaluate protocol adherence, and a cost-effectiveness analysis will be applied if the intervention is found to be effective. The current study provides an innovative approach to rehabilitation in the chronic phase of TBI evaluated using an RCT design that may inform treatment planning, health policies, and coordination of patient care. Further, the study may demonstrate new modes of establishing collaboration and knowledge transition between specialized rehabilitation facilities and local rehabilitation services that may improve patient outcomes. ClinicalTrials.gov, NCT03545594. Registered on June 4th, 2018.


Anticonvulsants in the treatment of aggression in the demented elderly: an update.
Complex psychopathological and behavioral symptoms, such as delusions and aggression against care providers, are often the primary cause of acute hospital admissions of elderly patients to emergency units and psychiatric departments. This issue resembles an interdisciplinary clinically highly relevant diagnostic and therapeutic challenge across many medical subjects and general practice. At least 50% of the dramatically growing number of patients with dementia exerts aggressive and agitated symptoms during the course of clinical progression, particularly at moderate clinical severity. Commonly used rating scales for agitation and aggression are reviewed and discussed. Furthermore, we focus in this article on benefits and limitations of all available data of anticonvulsants published in this specific indication, such as valproate, carbamazepine, oxcarbazepine, lamotrigine, gabapentin and topiramate. To date, most positive and robust data are available for carbamazepine, however, pharmacokinetic interactions with secondary enzyme induction limit its use. Controlled data of valproate do not seem to support the use in this population. For oxcarbazepine only one controlled but negative trial is available. Positive small series and case reports have been reported for lamotrigine, gabapentin and topiramate. So far, data of anticonvulsants in demented patients with behavioral disturbances are not convincing. Controlled clinical trials using specific, valid and psychometrically sound instruments of newer anticonvulsants with a better tolerability profile are mandatory to verify whether they can contribute as treatment option in this indication.


Folate for depressive disorders.
There are a number of effective interventions for the treatment of depression. It is possible that the efficacy of these treatments will be improved further by the use of adjunctive therapies such as folate. 1. To determine the effectiveness of folate in the treatment of depression 2. To determine the adverse effects and acceptability of treatment with folate. The Cochrane Controlled Trials Register (CCTR), and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR) incorporating results of group searches of EMBASE, MEDLINE, LILACS, CINAHL, PSYNDEX and PsycLIT were searched. Reference lists of relevant papers and major textbooks of affective disorder were checked. Experts in the field and pharmaceutical companies were contacted regarding unpublished material. All randomised controlled trials that compared treatment with folic acid or 5'-methyltetrahydrofolic acid to an alternative treatment, whether another antidepressant medication or placebo, for patients with a diagnosis of depressive disorder (diagnosed according to explicit criteria). Data were independently extracted from the original reports by two reviewers. Statistical analysis was conducted using Review Manager version 4.1. Three trials involving 247 people were included. Two studies involving 151 people assessed the use of folate in addition to other treatment, and found that adding folate reduced Hamilton Depression Rating Scale scores on average by a further 2.65 points (95% confidence interval 0.38 to 4.93). Fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at ten weeks (relative risk (RR) 0.47, 95% CI 0.24 to 0.92) The number needed to treat with folate for one additional person to experience a 50% reduction on this scale was 5 (95% confidence interval 4 to 33). One study involving 96 people assessed the use of folate instead of the antidepressant trazodone and did not find a significant benefit from the use of folate. The trials identified did not find evidence of any problems with the acceptability or safety of folate. The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.


Congenital rubella syndrome surveillance as a platform for surveillance of other congenital infections, Peru, 2004-2007.
Rubella during pregnancy can cause serious fetal abnormalities and death. Peru has had integrated measles/rubella surveillance since 2000 but did not implement congenital rubella syndrome (CRS) surveillance until 2004, in accordance with the Pan American Health Organization recommendations for rubella elimination. The article describes the experience from the CRS sentinel surveillance system in Peru. Peru has maintained a national sentinel surveillance system for reporting confirmed and suspected CRS cases since 2004. A surveillance protocol was implemented with standardized case definitions and instruments in the selected sentinel sites. Each sentinel site completes their case investigations and report forms and sends the reports to the Health Region Epidemiology Department, which forwards the data to the national Epidemiology Department. CRS surveillance data were analyzed for the period 2004-2007. During the period 2004-2007, 16 health facilities, which are located in 9 of the 33 health regions, representing the 3 main geographical areas (coast, mountain, and jungle), were included as sentinel sites for the CRS surveillance. A total of 2061 suspected CRS cases were reported to the system. Of these, 11 were classified as CRS and 23 as congenital rubella infection. Factors significantly associated with rubella vertical transmission were: (1) in the mother, maternal history of rash during pregnancy (odds ratio [OR], 12.0; 95% confidence interval [CI], 3.8-37.8); (2) and in the infant, pigmentary retinopathy (OR, 18.4; 95% CI, 3.2-104.6), purpura (OR, 14.7; 95% CI, 2.8-78.3), and developmental delay (OR, 4.4; 95% CI, 1.75-11.1). The surveillance system has been able to identify rubella vertical transmission, reinforcing the evidence that rubella was a public health problem in Peru. This system may serve as a platform to implement surveillance for other congenital infections in Peru.


[Natural and photo-induced aging of the skin: the three dimensional culture approach].
Human skin is a complex multifunctional organ which covers and surrounds the whole body ensuring a key function of protection against external injuries. Because of this unique situation, aging of skin is the result of both extrinsic factors-mostly sun exposure leading to photoaging- and intrinsic factors assumed to represent chronological aging. Studies of such complex phenomena on human volunteers is questionable and classical cultures of skin cells are not close enough to in vivo physiological conditions. However it is possible to address these questions by reconstructing human skin in vitro with both a living dermal equivalent defined as a fibroblast-contracted collagen gel (Bell et al., 1979) and a fully differentiated epidermis characterized by horny layers (Asselineau et al., 1985).


Speed choice and mental workload of elderly cyclists on e-bikes in simple and complex traffic situations: a field experiment.
To study the speed choice and mental workload of elderly cyclists on electrical assisted bicycles (e-bikes) in simple and complex traffic situations compared to these on conventional bicycles, a field experiment was conducted using two instrumented bicycles. These bicycles were identical except for the electric pedal support system. Two groups were compared: elderly cyclists (65 years of age and older) and a reference group of cyclists in middle adulthood (between 30 and 45 years of age). Participants rode a fixed route with a length of approximately 3.5 km on both bicycles in counterbalanced order. The route consisted of secluded bicycle paths and roads in a residential area where cyclist have to share the road with motorized traffic. The straight sections on secluded bicycle paths were classified as simple traffic situations and the intersections in the residential area where participants had to turn left, as complex traffic situations. Speed and mental workload were measured. For the assessment of mental workload the peripheral detection task (PDT) was applied. In simple traffic situations the elderly cyclists rode an average 3.6 km/h faster on the e-bike than on the conventional bicycle. However, in complex traffic situations they rode an average only 1.7 km/h faster on the e-bike than on the conventional bicycle. Except for the fact that the cyclists in middle adulthood rode an average approximately 2.6 km/h faster on both bicycle types and in both traffic conditions, their speed patterns were very similar. The speed of the elderly cyclists on an e-bike was approximately the speed of the cyclists in middle adulthood on a conventional bicycle. For the elderly cyclist and the cyclists in middle adulthood, mental workload did not differ between bicycle type. For both groups, the mental workload was higher in complex traffic situations than in simple traffic situations. Mental workload of the elderly cyclists was somewhat higher than the mental workload of the cyclists in middle adulthood. The relatively high speed of the elderly cyclists on e-bikes in complex traffic situations and their relatively high mental workload in these situations may increase the accident risk of elderly cyclist when they ride on an e-bike.


Effectiveness of platinum-based chemotherapy among elderly patients with advanced ovarian cancer.
Platinum-based chemotherapy is the standard of care for women with advanced ovarian cancer based on the results of randomized trials. We previously showed that only about half of women over the age of 65 years with this disease received platinum-based chemotherapy, and that the likelihood of receiving it decreases with age. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify women diagnosed from 1/1/92 to 12/31/96 with stage III or IV ovarian cancer who survived > or =120 days beyond diagnosis, and were > or =65 years of age. Cox proportional hazards models and propensity scores were used to control for known predictors of receiving treatment and to estimate the relative effectiveness of different platinum-based regimens. Of the 1759 patients in the sample who met our eligibility criteria, 53% received platinum-based therapy. For this sample, the Cox proportional hazard ratio was 0.72 (95% CI, 0.62-0.91) for mortality associated with the use of any platinum-based therapy, and 0.59 (95% CI, 0.45-0.76) for combination platinum/paclitaxel therapy. Similar results were obtained using propensity score modeling. In this population-based study, we found that only about half of women with advanced ovarian cancer over age 65 were treated with platinum-based chemotherapy; however, survival improved by 38% in treated women, similar to the benefits described in randomized controlled trials among younger patients, and were greatest when platinum was combined with paclitaxel. An effort to increase the utilization of platinum combination therapy among older patients with advanced ovarian cancer is justified.


Influence of wastewater disinfection on densities of culturable fecal indicator bacteria and genetic markers.
The US Environmental Protection Agency has proposed the use of quantitative polymerase chain reaction (qPCR) as a rapid alternative analytical method for monitoring recreational water quality at beaches. For qPCR to be considered for other Clean Water Act purposes, such as inclusion in discharge permits and use in Total Maximum Daily Load calculations, it is necessary to understand how qPCR detectable genetic markers are influenced by wastewater disinfection. This study investigated genetic markers for Escherichia coli, Enterococcus, Clostridium spp., Bacteroides, total Bacteroidales, as well as the human-associated Bacteroides markers, HF183 and HumM2, to determine which, if any, were influenced by disinfection (chlorination or ultraviolet light) of effluents from secondary wastewater treatment in different seasons. The effects of disinfection on culturable enterococci, E. coli, Bacteroides, and C. perfringens were also compared to their associated genetic markers. Disinfection of secondary treatment effluents significantly reduced culturable fecal indicator bacteria (FIB) but not genetic marker densities. No significant differences were observed in the responses of FIB culture and genetic marker densities to type of disinfection (chlorination vs UV) or season. Results of this study provide evidence that qPCR may not be suitable for monitoring efficacy of wastewater disinfection on the inactivation of bacterial pathogens.


Pharmacokinetic and safety study of subcutaneously administered weekly ING-1, a human engineere monoclonal antibody targeting human EpCAM, in patients with advanced solid tumors.
ING-1 is a high-affinity, human engineeredtrade mark monoclonal antibody that recognizes a 40 kilodalton epithelial cell adhesion molecule (EpCAM) glycoprotein that is expressed in high levels on most adenocarcinomas and is an attractive target for immunotherapy. ING-1 was administered subcutaneously weekly at doses between 0.1 and 2 mg/kg/week. Pharmacokinetic samples were drawn during weeks 1 and 6. Fourteen patients with advanced refractory cancer received a median of 6 (range 1-9) doses of ING-1. At 1 mg/kg, a 62-year-old man with colon cancer developed reversible grade 3 pancreatitis after the third dose. His plasma ING-1 levels were similar to the other two patients dosed at 1 mg/kg. Two patients dosed at 0.6 mg/kg experienced stable disease at 6 weeks. Peak drug levels increased with dose and time, suggesting drug accumulation with repeated dosing. Low human anti-human antibody response was noted in three of the 13 patients assessed and was directed towards the variable region of ING-1. Weekly ING-1 administered subcutaneously was well tolerated at 0.6 mg/kg/week and further experience at this dose is warranted to demonstrate safety. The risk of pancreatitis and the marginal anti-tumor effect may preclude further monotherapy studies; however, combination studies with chemotherapy are warranted.


Carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long-term outcomes.
Carbamazepine (CBZ) has been used in the treatment of bipolar disorder, both in acute mania and maintenance therapy, since the early 1970s. Here, we report a follow-up study of CBZ-treated bipolar patients in the Taipei City Psychiatric Centre. Bipolar patients diagnosed according to the DSM-IV system and treated with CBZ at the Taipei City Psychiatric Centre had their charts reviewed to evaluate the efficacy and side effects of this medication during an average follow-up period of 10 years. A total of 129 bipolar patients (45 males, mean age: 45.7 ± 10.9 year) were included in the analysis of CBZ efficacy used alone (n = 63) or as an add-on after lithium (n = 50) or valproic acid (n = 11), or the both of them (n = 5). The mean age of disease onset was 24.6 ± 9.5 years. The mean duration of CBZ use was 10.4 ± 5.2 year. The mean dose used was 571.3 ± 212.6 mg/day with a mean plasma level of 7.8 ± 5.9 μg/mL. Mean body weight increased from 62.0 ± 13.4 kg to 66.7 ± 13.1 kg during treatment. The frequencies of admission per year before and after CBZ treatment were 0.33 ± 0.46 and 0.14 ± 0.30, respectively. The most common side effects targeted the central nervous system (24%), including dizziness, ataxia and cognitive impairment. Other common side effects were gastrointestinal disturbances (3.6%), tremor (3.6%), skin rash (2.9%), and blurred vision (2.9%). Eighty-eight patients (68.2%) were taking antipsychotics concomitantly. Ninety-six patients (74.4%) needed to use benzodiazepines concomitantly. Sixty-three (48.8%) patients had zero episodes in a 10-year follow-up period, compared to all patients having episodes prior to treatment. Using variable analysis, we found better response to CBZ in males than in females. CBZ is efficacious in the maintenance treatment of bipolar disorder in naturalistic clinical practice, either as monotherapy or in combination with other medications. CBZ is well tolerated by most patients in this patient group.


Risk for incident diabetes mellitus following initiation of second-generation antipsychotics among Medicaid-enrolled youths.
Second-generation antipsychotics (SGAs) have increasingly been prescribed to Medicaid-enrolled children, either singly or in a medication combination. Although metabolic adverse effects have been linked to SGA use in youths, estimating the risk for type 2 diabetes mellitus, a rarer outcome, has been challenging. To determine whether SGA initiation was associated with an increased risk for incident type 2 diabetes mellitus. Secondary analyses examined the risk associated with multiple-drug regimens, including stimulants and antidepressants, as well as individual SGAs. Retrospective national cohort study of Medicaid-enrolled youths between January 2003 and December 2007. In this observational study using national Medicaid Analytic eXtract data files, initiators and noninitiators of SGAs were identified in each month. Included in this study were US youths aged 10 to 18 years with a mental health diagnosis and enrolled in a Medicaid fee-for-service arrangement during the study. Those with chronic steroid exposure, a diagnosis of diabetes mellitus, or SGA use during a 1-year look-back period were ineligible. The mean follow-up time for all participants was 17.2 months. Youths were followed up until diagnosis of diabetes mellitus or end of follow-up owing to censoring caused by the transition into a Medicaid managed care arrangement or Medicaid ineligibility (the end of available data). Propensity weights were developed to balance observed demographic and clinical characteristics between exposure groups. Discrete failure time models were fitted using weighted logistic regression to estimate the risk for incident diabetes mellitus between initiators and noninitiators. A filled SGA prescription. Incident type 2 diabetes mellitus identified through visit and pharmacy claims during the observation period. Among 107,551 SGA initiators and 1,221,434 noninitiators, the risk for incident diabetes mellitus was increased among initiators (odds ratio [OR], 1.51; 95% CI, 1.35-1.69; P < .001). Compared with youths initiating only SGAs, the risk was higher among SGA initiators who used antidepressants concomitantly at the time of SGA initiation (OR, 1.54; 95% CI, 1.17-2.03; P = .002) but was not significantly different for SGA initiators who were concomitantly using stimulants. As compared with a reference group of risperidone initiators, the risk was higher among those initiating ziprasidone (OR, 1.61; 95% CI, 0.99-2.64; P = .06) and aripiprazole (OR, 1.58; 95% CI, 1.21-2.07; P = .001) but not quetiapine fumarate or olanzapine. The risk for incident type 2 diabetes mellitus was increased among youths initiating SGAs and was highest in those concomitantly using antidepressants. Compared with risperidone, newer antipsychotics were not associated with decreased risk.


On classification with incomplete data.
We address the incomplete-data problem in which feature vectors to be classified are missing data (features). A (supervised) logistic regression algorithm for the classification of incomplete data is developed. Single or multiple imputation for the missing data is avoided by performing analytic integration with an estimated conditional density function (conditioned on the observed data). Conditional density functions are estimated using a Gaussian mixture model (GMM), with parameter estimation performed using both Expectation-Maximization (EM) and Variational Bayesian EM (VB-EM). The proposed supervised algorithm is then extended to the semisupervised case by incorporating graph-based regularization. The semisupervised algorithm utilizes all available data-both incomplete and complete, as well as labeled and unlabeled. Experimental results of the proposed classification algorithms are shown.


Surface lattice solitons.
We study theoretically nonlinear surface waves in optical lattices and show that solitons can exist at the heterointerface between two different semi-infinite 1D waveguide arrays, as well as at the boundaries of a 2D nonlinear lattice. The existence and properties of these surface soliton solutions are investigated in detail.


Systematic benchmarking of imaging spatial transcriptomics platforms in FFPE tissues.
Emerging imaging spatial transcriptomics (iST) platforms and coupled analytical methods can recover cell-to-cell interactions, groups of spatially covarying genes, and gene signatures associated with pathological features, and are thus particularly well-suited for applications in formalin fixed paraffin embedded (FFPE) tissues. Here, we benchmarked the performance of three commercial iST platforms on serial sections from tissue microarrays (TMAs) containing 23 tumor and normal tissue types for both relative technical and biological performance. On matched genes, we found that 10X Xenium shows higher transcript counts per gene without sacrificing specificity, but that all three platforms concord to orthogonal RNA-seq datasets and can perform spatially resolved cell typing, albeit with different false discovery rates, cell segmentation error frequencies, and with varying degrees of sub-clustering for downstream biological analyses. Taken together, our analyses provide a comprehensive benchmark to guide the choice of iST method as researchers design studies with precious samples in this rapidly evolving field.


The role of the Society for Academic Emergency Medicine in the development of guidelines and performance measures.
Measurement of adherence to clinical standards has become increasingly important to the practice of emergency medicine (EM). In recent years, along with a proliferation of evidence-based practice guidelines and performance measures, there has been a movement to incorporate measurement into reimbursement strategies, many of which affect EM practice. On behalf of the Society for Academic Emergency Medicine (SAEM) Guidelines Committee 2009-2010, the purposes of this document are to: 1) differentiate the processes of guideline and performance measure development, 2) describe how performance measures are currently and will be used in pay-for-performance initiatives, and 3) discuss opportunities for SAEM to affect future guideline and performance measurement development for emergency care. Specific recommendations include that SAEM should: 1) develop programs to sponsor guideline and quality measurement research; 2) increase participation in the process of guideline and quality measure development, endorsement, and maintenance; 3) increase collaboration with other EM organizations to review performance measures proposed by organizations outside of EM that affect emergency medical care; and 4) answer calls for participation in the selection and implementation of performance measures through The Joint Commission and the Centers for Medicare and Medicaid Services (CMS).


The feasibility and safety of endoscopic resection for benign hypopharyngeal tumors.
For hypopharyngeal tumors, surgical therapy under general anesthesia is the mainstay of treatment; however, the endoscopic treatment of benign hypopharyngeal tumors has not been fully evaluated for its feasibility and safety. We determined the technical feasibility and safety of endoscopic treatment for benign hypopharyngeal tumors. A total of 22 patients (15 men, 7 women) with benign hypopharyngeal tumors underwent endoscopic resection. All tumors were treated using one of two endoscopic mucosal resection (EMR) techniques: the injection and cut method for the polypoid lesions (6 cases) or EMR using a cap (EMR-C) for the flat or protruding lesions with wide bases (16 cases). In all 22 patients, the most common findings detected during routine GI endoscopy were lymphoepithelial cysts (11 cases) followed by papillomas (5 cases). All benign hypopharyngeal tumors were successfully removed by endoscopic resection without sedation. There were no major procedure-induced complications. Minor complications occurred in 3 patients and included minimal bleeding (n=1), pain (n=1) and low-grade fever (n=1). As a treatment modality for benign hypopharyngeal tumors, endoscopic resection is a simple, less invasive, safe, and likely cost-effective method. Endoscopic resection should be considered an alternative to surgical therapy in appropriately selected patients.


Effect of visual biofeedback of posterior tongue movement on articulation rehabilitation in dysarthria patients.
Articulation is driven by various combinations of movements of the lip, tongue, soft palate, pharynx and larynx, where the tongue plays an especially important role. In patients with cerebrovascular disorder, lingual motor function is often affected, causing dysarthria. We aimed to evaluate the effect of visual biofeedback of posterior tongue movement on articulation rehabilitation in dysarthria patients with cerebrovascular disorder. Fifteen dysarthria patients (10 men and 5 women; mean age, 70.7 ± 10.3 years) agreed to participate in this study. A device for measuring the movement of the posterior part of the tongue was used for the visual biofeedback. Subjects were instructed to produce repetitive articulation of [ka] as fast and steadily as possible between a lungful with/without visual biofeedback. For both the unaffected and affected sides, the range of ascending and descending movement of the posterior tongue with visual biofeedback was significantly larger than that without visual biofeedback. The coefficient of variation for these movements with visual biofeedback was significantly smaller than that without visual biofeedback. With visual biofeedback, the range of ascent exhibited a significant and strong correlation with that of descent for both the unaffected and affected sides. The results of this study revealed that the use of visual biofeedback leads to prompt and preferable change in the movement of the posterior part of the tongue. From the standpoint of pursuing necessary rehabilitation for patients with attention and memory disorders, visualization of tongue movement would be of marked clinical benefit.


Clinical Characteristics and Metabolic Predictors of Rapid Responders to Dipeptidyl Peptidase-4 Inhibitor as an Add-on Therapy to Sulfonylurea and Metformin.
Dipeptidyl peptidase-4 (DPP-4) inhibitor add-on therapy is a new option for patients with inadequately controlled type 2 diabetes who are taking combined metformin and sulfonylurea (SU). We evaluated the efficacy and safety of this triple therapy and the characteristics of rapid responders and hypoglycemia-prone patients. We included 807 patients with type 2 diabetes who were prescribed a newly added DPP-4 inhibitor to ongoing metformin and SU in 2009 to 2011. Glycemia and other metabolic parameters at baseline, 12, 24, and 52 weeks, as well as episodes of hypoglycemia were analyzed. Rapid responders were defined as patients with ≥25% reduction in glycosylated hemoglobin (HbA1c) within 12 weeks. At baseline, while on the submaximal metformin and SU combination, the mean HbA1c level was 8.4%. Twelve weeks after initiation of DPP-4 inhibitor add-on, 269 patients (34.4%) achieved an HbA1c level ≤7%. Sixty-six patients (8.2%, 47 men) were rapid responders. The duration of diabetes was shorter in rapid responders, and their baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and homeostasis model assessment of insulin resistance were significantly higher. Patients who experienced hypoglycemia after taking DPP-4 inhibitor add-on were more likely to be female, to have a lower body weight and lower triglyceride and FPG levels, and to have higher homeostasis model assessment of β-cells. An oral hypoglycemic triple agent combination including a DPP-4 inhibitor was effective in patients with uncontrolled diabetes. Proactive dose reduction of SU should be considered when a DPP-4 inhibitor is added for rapid responders and hypoglycemia-prone patients.


Pyran copolymer as an effective adjuvant to chemotherapy against a murine leukemia and solid tumor.
Pyran (divinyl ether-maleic anhydride) copolymer (NSC 46015) is a polyanion with interferon-inducing and macrophage-stimulating properties, and therefore it has been studied as a possible antitumor agent. Extensive studies using pyran as an adjuvant to chemotherapy against the LSTRA murine leukemia and the Lewis lung carcinoma were performed. Pyran was effective over a dose range of 0.1 to 100 mg/kg/day. Single and multiple dose schedules were both capable of producing significant numbers of cures or increasing life-span, but pyran was ineffective if used without remission inducing chemotherapy. Various molecular weights of pyran copolymer were compared against NSC 46015 for adjuvant activity as well. In general, NSC 46015 tended to be the most efficacious, but all the pyran sizes that were tested possessed significant activity.


An alternative formula to the Cockcroft-Gault and the modification of diet in renal diseases formulas in predicting GFR in individuals with type 1 diabetes.
Chronic kidney disease is currently on the rise and not only leads to ESRD necessitating dialysis or transplantation but also increases cardiovascular disease risk. Measurement of the GFR, the gold standard for assessing kidney function, is expensive and cumbersome. Several prediction formulas that are based on serum creatinine are currently used to estimate the GFR, but none has been validated in a large cohort of individuals with diabetes. The performance of two commonly used formulas, the abbreviated Modification of Diet in Renal Disease (MDRD) study formula for the GFR and the Cockcroft-Gault estimate of creatinine clearance, were examined against GFR measured by the renal clearance of iothalamate in 1286 individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT). The performance of these formulas was assessed by computing bias, precision, and accuracy. The DCCT participants had normal serum creatinine, unlike the MDRD patients, and somewhat lower creatinine excretion than subjects in the original cohort Cockcroft Gault, which led to biased and highly variable estimates of GFR when these formulas were applied to the DCCT subjects. The MDRD substantially underestimated iothalamate GFR, whereas the Cockcroft Gault formula underestimated it when it was <120 ml/min per 1.73 m(2) and overestimated it when iothalamate GFR was >130 ml/min per 1.73 m(2). Overall, only one third of the formula's estimates were within +/-10% of iothalamate GFR. By underestimating GFR, these formulas were likely to flag early declines in kidney function. Refitting the MDRD formula to the DCCT data gave a more accurate and unbiased prediction of GFR from serum creatinine; percentage of estimate within 10% of measured GFR increased to 56%. A substantial variability in the estimates, however, remained.


The UK Resilience Programme: a school-based universal nonrandomized pragmatic controlled trial.
The study aimed to assess the effectiveness of an 18-hr cognitive behavioral group intervention in reducing depressive symptoms (and associated outcomes) in a universal sample of students in mainstream schools in England. The intervention, the UK Resilience Programme (UKRP), was based on the Penn Resiliency Program for Children and Adolescents. Students (N = 2,844; 49% female; 67% White) were ages 11-12 at 16 schools. Classes of students were assigned arbitrarily into intervention (UKRP) or control (usual school provision) conditions based on class timetables. Outcome measures were the Children's Depression Inventory (Kovacs, 1992) (depressive symptoms, primary outcome); Revised Children's Manifest Anxiety Scale (C. R. Reynolds & Richmond, 1985) (anxiety); and child-reported Goodman (1997) Strengths and Difficulties Questionnaire (behavior). Students were surveyed at baseline, postintervention, 1-year follow-up, and 2-year follow-up. At postintervention, UKRP students reported lower levels of depressive symptoms than control group students, but the effect was small (d = 0.093, 95% CI [-0.178, -0.007], p = .034) and did not persist to 1-year or 2-year follow-ups. There was no significant impact on symptoms of anxiety or behavior at any point. UKRP produced small, short-term impacts on depression symptoms and did not reduce anxiety or behavioral problems. These findings suggest that interventions may produce reduced impacts when rolled out and taught by regular school staff. We discuss the implications of these findings for policy and for future dissemination efforts.