Estimating patient time costs associated with colorectal cancer care.
Nonmedical costs of care, such as patient time associated with travel to, waiting for, and seeking medical care, are rarely measured systematically with population-based data. The purpose of this study was to estimate patient time costs associated with colorectal cancer care. We identified categories of key medical services for colorectal cancer care and then estimated patient time associated with each service category using data from national surveys. To estimate average service frequencies for each service category, we used a nested case control design and SEER-Medicare data. Estimates were calculated by phase of care for cases and controls, using data from 1995 to 1998. Average service frequencies were then combined with estimates of patient time for each category of service, and the value of patient time assigned. Net patient time costs were calculated for each service category, summarized by phase of care, and compared with previously reported net direct costs of colorectal cancer care. Net patient time costs for the 3 phases of colorectal cancer care averaged dollar 4592 (95% confidence interval [CI] dollar 4427-4757) over the 12 months of the initial phase, dollar 2788 (95% CI dollar 2614-2963) over the 12 months of the terminal phase, and dollar 25 (95% CI: dollar 23-26) per month in the continuing phase of care. Hospitalizations accounted for more than two thirds of these estimates. Patient time costs were 19.3% of direct medical costs in the initial phase, 15.8% in the continuing phase, and 36.8% in the terminal phase of care. Patient time costs are an important component of the costs of colorectal cancer care. Application of this method to other tumor sites and inclusion of other components of the costs of medical care will be important in delineating the economic burden of cancer in the United States.


Characterization of the lasing properties of a 5%Yb doped Lu₂SiO₅ crystal along its three principal dielectric axes.
The laser performance of a 5% Yb doped Lu2SiO5 (Yb:LSO) has been investigated in quasi continuous-wave pumping regime along the three principal dielectric axes of the crystal, to obtain a complete characterization of its laser properties. The comparison among the obtained results for differently polarized lasers, in term of relative slope efficiency and absolute efficiency, allows the exploitability of different orientations of the material in order to be determined to obtain efficient laser sources. The laser slope efficiency and the energy conversion efficiency were similar for emission polarized along the three indicatrix axes, with noticeable maximum values of slope efficiency around 90% for polarization along the Y and Z axes. Tunable laser action has been obtained in the range 990 nm - 1084 nm, with sizeable differences in the shape of the tuning curve for polarization along the X, Y and Z axes. In particular, the tuning for polarization along the Z axis is relatively flat and uniform in the range 1023 nm - 1083 nm.


[Scales for evaluation of the overload of caregivers of patients with stroke].
The objective of the study was to evaluate the available productions in literature about scales to measure the overload of caregivers of patients with stroke. It was carried out a bibliographical revision in three databases: LILACS, CINAHL and SCOPUS. In 23 works, 24 different scales were identified, and the most cited were: the Caregiver Strain Index, the Caregiver Burden Scale, the Caregiver Reaction Assessment, the Sense of Competence Questionnaire, the Relatives Stress Scale and the Zarit Burden Interview. The use of scales to measure the overload is an important tool to evaluate the context in which the caregiver is inserted, but is more trustworthy to use more than one measure instrument than use only one. Therefore, the validation of scales becomes important for this population.


Non-contact fluorescence optical tomography with scanning patterned illumination.
This article describes a novel non-contact fluorescence optical tomography scheme which utilizes multiple area illumination patterns, to reduce the ill-posedness of the inverse problem involved in recovering interior fluorescence yield distributions in biological tissue from boundary fluorescence measurements. The image reconstruction is posed as an optimization problem which seeks a tissue optical property distribution minimizing, for all illumination patterns simultaneously, a regularized difference between the observed boundary measurements of light distribution, and the boundary measurements predicted from a physical model. Multiple excitation source illumination patterns are described by line and Gaussian sources scanning the simulated tissue phantom surface and by employing diffractive optics-generated patterns. Multiple measurement data sets generated by scanning excitation sources are processed simultaneously to generate the interior fluorescence distribution in tissue by implementing the fluorescence tomography algorithm in a parallel framework suitable for multiprocessor computers. Image reconstructions for single and multiple fluorescent targets (5mm diameter) embedded in a 512ml simulated tissue phantom are demonstrated, with depths of the fluorescent targets from the illumination plane between 1cm to 2cm. We show both qualitative and quantitative improvements of our algorithm over reconstructions from only a single measurement.


Membrane recruitment of Rac1 triggers phagocytosis.
Rac1 is a &Rgr;-family GTP-binding protein that controls lamellipodia formation and membrane ruffling in fibroblasts. Recently, Rac1 and Cdc42, another member of the &Rgr;-family, have been shown to regulate Fc receptor-mediated phagocytosis in macrophages by controlling different steps of membrane and actin dynamics leading to particle engulfment. Here, we investigated the function of Rac1 using a membrane recruitment system that mimics phagocytosis. Recruitment of an activated Rac1 protein to the cytoplasmic domain of an engineered membrane receptor by using rapamycin as a bridge induces ingestion of latex beads bound to the receptor. Rac1-mediated bead uptake depends on actin polymerisation since actin filaments accumulate at the bead/membrane binding sites and internalisation is inhibited by cytochalasin D. Internalisation is also abolished upon substitution of Phe37 to Leu in the Rac1 effector region. Our results indicate that by promoting actin polymerisation at particle attachment sites, Rac1 by acting through specific downstream effectors induces plasma membrane remodeling that allows particle internalisation in a membrane-enclosed phagosome.


Rotavirus YM gene 4: analysis of its deduced amino acid sequence and prediction of the secondary structure of the VP4 protein.
We have determined the complete nucleotide sequence of the VP4 gene of porcine rotavirus YM. It is 2,362 nucleotides long, with a single open reading frame coding for a protein of 776 amino acids. A phylogenetic tree was derived from the deduced YM VP4 amino acid sequence and 18 other available VP4 sequences of rotavirus strains belonging to different serotypes and isolated from different animal species. In this tree, VP4 proteins were grouped by the hosts that the corresponding viruses infect rather than by the serotypes they belong to, suggesting that this protein is involved in the host specificity of the viruses. In an attempt to predict the secondary structure of the VP4 protein, we selected the more divergent VP4 sequences and made a secondary structure analysis of each protein. In spite of variations within the individual structures predicted, there was a general structural pattern which suggested the existence of at least two different domains. One, comprising the amino-terminal 63% of the protein, is predicted to be a possible globular domain rich in beta-strands alternated with turns and coils. The second domain, represented by the remaining, carboxy-terminal part of VP4, is rich in long stretches of alpha-helix, one of which, 63 amino acids long, has heptad repeats resembling those found in proteins known to form alpha-helical coiled-coils. The predicted secondary structure correlates well with the available data on the protein accessibility delineated by immunological and biochemical findings and with the spike structure of the protein, which has been determined by cryoelectron microscopy.


Platelet-activating factor (PAF) induces corneal neovascularization and upregulates VEGF expression in endothelial cells.
Platelet-activating factor (PAF) is a potent proinflammatory mediator that accumulates in the cornea after injury and induces the expression of genes related to inflammation and wound healing. The current study was conducted to investigate the direct effect of PAF on corneal neovascularization and on the expression of angiogenic growth factors in vascular endothelial cells. Pellets containing carbamyl-PAF (cPAF) were implanted in corneas of wild-type or PAF-receptor (PAF-R)-knockout mice, and the progression of angiogenesis was monitored by microscope. In some experiments, mice were treated with a daily intraperitoneal injection of the PAF-R antagonist LAU8080. Migration assays of human umbilical cord vein endothelial cells (HUVECs) and human dermal microvascular endothelial cells (HMVECs) were performed in a Boyden chamber after addition of various concentrations of cPAF or bovine fibroblast growth factor (FGF-2). Cell proliferation was assessed by fluorescence-binding assay in the presence of cPAF or FGF-2 for 8 days. Vascular endothelial growth factor (VEGF) and FGF-2 expression was studied by RT-PCR and Northern- and Western-blot analyses in cells stimulated with cPAF at different concentrations and for different times. Six days after cPAF pellet implantation, there were new vessels growing from the limbus to the center of the cornea. The PAF-induced neovascularization was significantly reduced in PAF-R-knockout mice and in mice treated with the PAF antagonist. cPAF added to the lower well of the Boyden chamber produced a dose-dependent migration of HUVECs and HMVECs that was inhibited in cells preincubated with LAU8080 or with a VEGF-blocking antibody. In contrast, cPAF did not stimulate proliferation of endothelial cells. cPAF induced VEGF mRNA and protein expression but not FGF-2 expression in HUVECs and HMVECs. PAF stimulates corneal neovascularization by a receptor-mediated mechanism. Induction of VEGF expression and stimulation of vascular endothelial cell migration are initial events in PAF-promoted corneal angiogenesis.


Myosin isoform heterogeneity in single smooth muscle cells.
We review the current understanding of the myosin heavy chain (MHC) isoforms and show that the mRNA levels of smooth muscle (SM)1 and SM2 mimic the expressed levels of SM1 and SM2 protein. The reverse transcriptase-polymerase chain reaction technique has been shown to be sufficiently sensitive to examine SM-MHC expression at the single cell level. Most single smooth muscle cells isolated from adult rabbit carotid express both SM1 and SM2. However, expression of these SM-MHC isoforms at the cellular level is nonuniform and highly variable. This work provides a foundation for future investigations as to the possible unique functional characteristics of the SM-MHC isoforms, SM1 and SM2. This methodology may also prove useful when used with mechanical studies to determine the physiological significance of the alternatively spliced myosin isoforms, including the SM-MHC-head and LC17 isoforms.


The risk of various types of cardiovascular diseases in mutation positive familial hypercholesterolemia; a review.
Familial hypercholesterolemia (FH) is a common, inherited disease characterized by high levels of low-density lipoprotein Cholesterol (LDL-C) from birth. Any diseases associated with increased LDL-C levels including atherosclerotic cardiovascular diseases (ASCVDs) would be expected to be overrepresented among FH patients. There are several clinical scoring systems aiming to diagnose FH, however; most individuals who meet the clinical criteria for a FH diagnosis do not have a mutation causing FH. In this review, we aim to summarize the literature on the risk for the various forms of ASCVD in subjects with a proven FH-mutation (FH+). We searched for studies on FH+ and cardiovascular diseases and also included our and other groups published papers on FH + on a wide range of cardiovascular and other diseases of the heart and vessels. FH + patients are at a markedly increased risk of a broad range of ASCVD. Acute myocardial infarction (AMI) is the most common in absolute numbers, but also aortic valve stenosis is by far associated with the highest excess risk. Per thousand patients, we observed 3.6 incident AMI per year compared to 1.9 incident aortic valve stenosis, however, standardized incidence ratio (SIR) for incident AMI was 2.3 compared to 7.9 for incident aortic valve stenosis. Further, occurrence of ischemic stroke seems not to be associated with increased risk in FH+. Clinicians should be aware of the excess risk of almost all kind of ASCVD in FH+, and the neutral risk of stroke need to be studied further in FH + patients.


Dizziness-related disability following mild-moderate traumatic brain injury.
To investigate the associations between dizziness-related disability after mild- moderate Traumatic Brain Injury (TBI) and personal factors, injury-related factors and post-injury functioning using the International Classification of Functioning, Disability and Health (ICF) as a framework. Baseline assessments for a Randomised Controlled Trial (RCT) were obtained for 65 patients (mean age 39.2 years; SD 12.9 years; 70.8% women) who had dizziness and reduced balance 2-6 months after injury. The severity of the brain injury, physical and psychological self-reported symptoms and results from the performance based tests were used as independent variables. The main outcome measure (dependent variable) was the Dizziness Handicap Inventory (DHI). Multivariate analyses showed that, the dizziness-related disability was predicted by pre-injury comorbidities (p ≤ 0.05) and was associated with self-reported vertigo symptoms (p < 0.001), reduced performance-based balance (p ≤ 0.05) and psychological distress (p ≤ 0.05). These factors accounted for 62% of the variance in DHI. Dizziness and balance problems after mild-moderate TBI appear to be complex biopsychosocial phenomena. Assessments linked to the ICF domains of functioning might contribute to a broader understanding of the needs of these patients. Further, prospective clinical studies with non-dizzy control groups are needed to investigate dizziness-related disability after TBI.


The Perspectives of Advanced Practice Provider Directors on Acute Care Nurse Practitioner Alignment and Hiring.
Demand for acute care is forecasted to grow in the United States. To meet this demand, nurse practitioners (NPs) are increasingly employed in acute care settings. Yet, there is concern about an adequate supply of acute care NPs given demand. Further, professional nursing organizations recommend aligning an NP's role with their education, certification, licensure, and practice. Given workforce constraints and the policy environment, little is known about how hospitals approach hiring NPs for acute care roles. The purpose of this study was to explore advanced practice provider (APP) directors' approaches to hiring NPs within the context of alignment and describe factors that influence hiring decisions. We conducted semi-structured interviews with 17 APP directors in hospitals and health systems. Interviews were recorded, transcribed, and coded using an iterative, hybrid inductive and deductive method. Two themes emerged: (1) local factors that inform aligned hiring and (2) adaptive hiring responses to changing environments. Practices around hiring NPs varied across institutions influenced by organization and state policies and regulations, workforce availability, and institutional culture. Most APP directors recognized trends towards hiring aligned NPs for acute care roles. However, they also identified barriers to fully aligning their NP workforce and described adaptive strategies including hiring physician assistants, building relationships with APP schools, and leveraging hospital resources to develop the APP workforce to meet care delivery demands given the current NP workforce supply. Future research is needed to assess widespread practices around acute care NP alignment and the implications of alignment for patient and organizational outcomes.


Patients and clinicians managing patellofemoral pain should not rely on general web-based information.
To evaluate the credibility and accuracy of PFP-specific web-based content. Cross-sectional evaluation of web-based information. The study protocol was registered with PROSPERO (CRD42018088671). Two search engines (Google and Bing) were used to search for websites offering information about PFP. Two reviewers assessed the websites for credibility-related and PFP-specific content. PFP-specific content was evaluated according to agreement with current international PFP consensus statements. Based on this, content was rated as (i) Accurate/Clearly described; (ii) Partially accurate/Description lacks clarity; (iii) Inaccurate/Misleading description; or (iv) Not mentioned. After exclusion of duplicates, forty online websites were included in our analyses. 43% of websites did not mention their source of information, and 48% did not mention if the source material was peer-reviewed. Misleading/inaccurate information was most commonly found in the definition of PFP (20% websites) and clinical examination (15%). Twenty-two percent of websites recommended surgery as treatment. The item most frequently rated as accurate/clearly described was PFP terminology (87.5%). This study highlights missing, inaccurate or poorly described web-based PFP information. Due to the commonality of PFP and potential for improving self-management, there is an urgent need to develop more accurate and comprehensive web-based patient education resources for PFP.


Effects of mitotane treatment on human steroid metabolism: implications for patient management.
Mitotane (o,p'-DDD), an oral adrenolytic agent for treatment of advanced adrenocortical carcinoma (ACC), is reported to inhibit cortisol biosynthesis in vitro and enhance production from exogenous cortisol of urinary 6β-hydroxycortisol and unidentified polar unconjugated metabolites. We examined urinary steroid profiles by gas chromatography-mass spectrometry of patients with histologically confirmed ACC following surgery, receiving a) hydrocortisone alone (three males and three females) and b) mitotane and hydrocortisone (six males and 11 females). Samples were collected after plasma mitotane had reached the therapeutic range of 14-20 mg/l. Increased excretion of polar unconjugated steroids during mitotane treatment was confirmed, with 6β-hydroxycortisol and 6β-hydroxy-20-dihydrocortisols predominating. The proportion of additionally hydroxylated metabolites was <2% in untreated controls and 52, 35-52% (mean, range) in the mitotane plus hydrocortisone group. Ratios of 5α-/5β- and 20β-/20α-metabolites of administered cortisol were decreased 50-, 15-fold, and 14-, 8-fold respectively (males, females - mean values) but with no change in metabolite ratios that reflect oxidoreduction at C11 or C20. Patterns of decrease in 5α- relative to 5β-reduced metabolites were similar to those of patients with 5α-reductase 2 deficiency or on treatment with the 5α-reductase 2 inhibitor finasteride but different from those of patients on dutasteride, indicating specific inhibition of 5α-reductase 2. We conclude that mitotane causes consistent changes in cortisol catabolism, most of which have not been previously recognised. These need not interfere with early detection of ACC recurrence. Induction of 6β-hydroxylation offers an explanation for a reported decrease in cortisol bioavailability. Mitotane also has potential as a unique steroid metabolic probe for 20β-reduction.


Cosine directional tuning of theta cell burst frequencies: evidence for spatial coding by oscillatory interference.
The rodent septohippocampal system contains "theta cells," which burst rhythmically at 4-12 Hz, but the functional significance of this rhythm remains poorly understood (Buzsáki, 2006). Theta rhythm commonly modulates the spike trains of spatially tuned neurons such as place (O'Keefe and Dostrovsky, 1971), head direction (Tsanov et al., 2011a), grid (Hafting et al., 2005), and border cells (Savelli et al., 2008; Solstad et al., 2008). An "oscillatory interference" theory has hypothesized that some of these spatially tuned neurons may derive their positional firing from phase interference among theta oscillations with frequencies that are modulated by the speed and direction of translational movements (Burgess et al., 2005, 2007). This theory is supported by studies reporting modulation of theta frequency by movement speed (Rivas et al., 1996; Geisler et al., 2007; Jeewajee et al., 2008a), but modulation of theta frequency by movement direction has never been observed. Here we recorded theta cells from hippocampus, medial septum, and anterior thalamus of freely behaving rats. Theta cell burst frequencies varied as the cosine of the rat's movement direction, and this directional tuning was influenced by landmark cues, in agreement with predictions of the oscillatory interference theory. Computer simulations and mathematical analysis demonstrated how a postsynaptic neuron can detect location-dependent synchrony among inputs from such theta cells, and thereby mimic the spatial tuning properties of place, grid, or border cells. These results suggest that theta cells may serve a high-level computational function by encoding a basis set of oscillatory signals that interfere with one another to synthesize spatial memory representations.


Predicted Mercury Soil Concentrations from a Kriging Approach for Improved Human Health Risk Assessment.
Health-risks from contaminated soils are assessed all over the world. An aspect that many risk assessments share is the heterogeneity in the distribution of contaminants. In a preceding study, we assessed potential health-risks for mothers and children living on mercury-contaminated soils in Switzerland using human biomonitoring-values (HBM) and soil samples. We assessed 64 mothers and 107 children who had resided in a defined area for at least 3 months. HBM-concentrations for mercury in urine and hair were measured, a detailed questionnaire was administered for each individual, and more than 4000 individual mercury soil values were obtained in 2015. In this study, we aimed at investigating possible associations of mercury soil- and HBM-values by re-analyzing our data, using predictions of the mercury concentrations at the exact location of the participant's homes with a kriging approach. Although kriging proved to be a useful method to predict mercury soil concentrations, we did not detect an association between mercury soil- and HBM-values, in agreement with earlier findings. Benefits of geostatistical methods seem to be limited in the context of our study. Conclusions made in our preceding study about potential health risks for the residential population are robust and not altered by the current study.


More than just a barrier: using physical models to couple membrane shape to cell function.
The correct execution of many cellular processes, such as division and motility, requires the cell to adopt a specific shape. Physically, these shapes are determined by the interplay of the plasma membrane and internal cellular driving factors. While the plasma membrane defines the boundary of the cell, processes inside the cell can result in the generation of forces that deform the membrane. These processes include protein binding, the assembly of protein superstructures, and the growth and contraction of cytoskeletal networks. Due to the complexity of the cell, relating observed membrane deformations back to internal processes is a challenging problem. Here, we review cell shape changes in endocytosis, cell adhesion, cell migration and cell division and discuss how by modeling membrane deformations we can investigate the inner working principles of the cell.


Flavonoids as anticancer agents: structure-activity relationship study.
The protection against some forms of cancer provided by many common foods has been observed in multiple epidemiological studies. Non-nutritive dietary compounds, such as flavonoids, have been considered as the responsible agents for such observations and since then, much research activity has been done about their potential anticancer effect. As a result, these compounds have been shown to regulate proliferation and cell death pathways leading to cancer. Thus, flavonoids such as the synthetic flavone, flavopiridol; the soy isoflavonoid, genistein; the tea catechin epigallocatechin gallate; or the common dietary flavonol, quercetin, are emerging as prospective anticancer drug candidates and some of them have already entered in clinical trials. In view of the therapeutic potential of flavonoids, many researchers have tried to elucidate possible structure-activity relationships that might lead to new drug discovery. However, and possibly due to the information being very scattered, there is very little understanding about a possible relationship between the flavonoid structure and their anticancer activity. Besides their therapeutic potential, since lots of flavonoids are present in our diet, a greater understanding of their anticancer properties might also modify our dietary habits in order to attack cancer with an effective weapon, prevention. This paper seeks to show, in a brief but comprehensive way, the anticancer properties of flavonoids. Through an understanding of the cancer process and its treatment, flavonoids are studied as possible useful compounds in cancer prevention and cancer therapy. Furthermore, this review attempts to compile and discuss the literature studying structure-activity relationships, in order to show structural requirements implicated in the anticancer activity of flavonoids, which might help to rationalize their development as antitumor agents.


Dysphagia following anterior cervical arthrodesis is associated with continuous, strong retraction of the esophagus.
The prevalence of dysphagia after anterior cervical decompression and arthrodesis is estimated to be 50% within one month and 21% at twelve months. However, its exact etiology is not well understood. The objective of the present study was to explore the relationship between intraoperative intra-esophageal pressure due to surgical retraction, esophageal mucosal blood flow at the level of surgery, and postoperative dysphagia. Our hypothesis was that sustained elevated pressure on the esophagus during anterior cervical arthrodesis is associated with postoperative dysphagia. Seventeen selected patients scheduled for anterior cervical arthrodesis were studied. Throughout the procedure, intraluminal pressure in the upper esophageal sphincter was measured (mm Hg) with a custom-made manometer probe and mucosal perfusion was measured at the level of surgery with a laser Doppler flowmeter. The type of retraction chosen by the surgeon was noted. Postoperatively, the patients were specifically evaluated for dysphagia on the first postoperative day and at six weeks, three months, and six months postoperatively with use of the M.D. Anderson Dysphagia Inventory. Four of the eleven patients who had dynamic retraction and five of the six patients who had static retraction during surgery had postoperative dysphagia. In the group of patients with dysphagia, the average M.D. Anderson Dysphagia Inventory score decreased from 93.8 +/- 12.1 preoperatively to 67.7 +/- 11.4 on the first postoperative day (p < 0.001). The patients with dysphagia had a significantly higher average intraluminal pressure (60.8 +/- 54.3 compared with 54.4 +/- 51.8 mm Hg; p < 0.0001) as well as significantly lower average mucosal perfusion (26.1 +/- 18.1 compared with 40.8 +/- 26.2 tissue perfusion units; p < 0.0001) in comparison with the asymptomatic patients. Patients with dysphagia following anterior cervical arthrodesis were exposed to higher intraoperative esophageal pressure and decreased esophageal mucosal blood flow during surgical retraction as compared with patients without dysphagia. In this small series, dynamic retraction seemed to be associated with a lower prevalence of postoperative dysphagia.


Impact of Endurance Exercise in Hypoxia on Muscle Damage, Inflammatory and Performance Responses.
Sumi, D, Kojima, C, and Goto, K. Impact of endurance exercise in hypoxia on muscle damage, inflammatory and performance responses. J Strength Cond Res 32(4): 1053-1062, 2018-This study evaluated muscle damage and inflammatory and performance responses after high-intensity endurance exercise in moderate hypoxia among endurance athletes. Nine trained endurance athletes completed 2 different trials on different days: exercise under moderate hypoxia (H trial, FiO2 = 14.5%) and normoxia (N trial, FiO2 = 20.9%). They performed interval exercises (10 × 3-minute running at 95% of V[Combining Dot Above]O2max with 60-second of active rest at 60% of V[Combining Dot Above]O2max) followed by 30-minute of continuous running at 85% of V[Combining Dot Above]O2max under either hypoxic or normoxic conditions. Venous blood samples were collected 4 times: before exercise, 0, 60, and 120-minute after exercise. The time to exhaustion (TTE) during running at 90% of V[Combining Dot Above]O2max was also determined to evaluate endurance capacity 120-minute after the training session. The H trial induced a significantly greater exercise-induced elevation in the blood lactate concentration than did the N trial (p = 0.02), whereas the elevation in the exercise-induced myoglobin concentration (muscle damage marker) was significantly greater in the N trial than in the H trial (p = 0.005). There was no significant difference in plasma interleukin-6 (inflammatory marker) concentration between the H and N trials. The TTE was shorter in the N trial (613 ± 65 seconds) than in the H trial (783 ± 107 seconds, p = 0.02). In conclusion, among endurance athletes, endurance exercise under moderate hypoxic conditions did not facilitate an exercise-induced muscle damage response or cause a further reduction in the endurance capacity compared with equivalent exercise under normoxic conditions.


Enhanced Energy Conversion of Z907-Based Solar Cells by Cucurbit[7]uril Macrocycles.
A dye-sensitized solar cell was constructed on the basis of encapsulating the ruthenium polypyridyl photosensitizer Z907 in the macrocycle cucurbit[7]uril (CB7). The work focuses on the photophysical properties of the new host-guest complexes in acetonitrile and water (volume ratio 1:9) and on the top of nanocrystalline titanium dioxide (TiO2) electrode prior to the addition of poly(3-hexylthiophene) polymer and gold electrode. Complexation to CB7 in aqueous solutions has decreased the emission intensity and excited-state lifetime for metal-to-ligand charge transfer (MLCT) state at 650 nm by twofold because of collisional quenching, which opens a non-radiative deactivation channel. Similarly, a twofold decrease in the emission intensity and excited-state lifetime of MLCT at 750 nm on the top of TiO2 electrodes was observed with the addition of CB7. Encapsulation of Z907 dye to CB7 host has, also, led to fourfold enhancement in the short circuit current and power conversion efficiency of the final solar cell. The results support the premise that host-guest complexation of CB7 facilitates faster electron injection from Z907 dye into the conduction band of TiO2 electrodes.


Abrogation of cell surface expression of human class I transplantation antigens by an adenovirus protein in Xenopus laevis oocytes.
Class I transplantation antigens form complexes with a virus protein encoded in the early region E3 of the adenovirus-2 genome. The interaction between this viral glycoprotein, E19, and nascent human class I antigens has been examined by microinjecting purified mRNA into Xenopus laevis oocytes. Both E19 and the two class I antigen subunits, the heavy chain and beta 2-microglobulin (beta 2M), were efficiently translated. The heavy chains did not become terminally glycosylated, as monitored by endoglycosidase H digestion, and were not expressed on the oocyte surface unless they were associated with beta 2M. The E19 protein did not become terminally glycosylated, and we failed to detect this viral protein on the surface of the oocytes. Co-translation of heavy chain and E19 mRNA demonstrated that the two proteins associate intracellularly. However, neither protein appeared to be transported to the trans-Golgi compartment. Similar observations were made in adenovirus-infected HeLa cells. Heavy chains bound to beta 2M became terminally glycosylated in oocytes in the presence of low concentrations of E19. At high concentrations of the viral protein, no carbohydrate modifications and no cell surface expression of class I antigens were apparent. Thus, beta 2M and E19 have opposite effects on the intracellular transport of the heavy chains. These data suggest that adenovirus-2 may impede the cell surface expression of class I antigens to escape immune surveillance.


Dynamics of the sedimentary bacterial communities in a plain river network: similar coalescence patterns with bacterioplankton communities driven by distinct assembly processes.
Microorganisms play important roles in driving the biogeochemical cycles within river ecosystems. It has been suggested that hydrologic conditions could influence microbial communities in rivers, but their specific effects on the behaviours of microbial coalescence have not been thoroughly investigated. In this study, the dynamics of sedimentary bacterial communities within a plain river network were analyzed by amplicon sequencing followed by several ecological models to uncover the underlying assembly processes. Additionally, a comparative analysis between bacterioplankton communities and sedimentary bacterial communities was performed to unveil their coalescence patterns. The results suggested that similar coalescence patterns between sedimentary bacterial and bacterioplankton communities were driven by distinct assembly processes under dynamic hydrological conditions. These findings enhanced our understanding of microbial diversity features within river ecosystems.


The costs and benefits of sexism: resistance to influence during relationship conflict.
This study tested whether men's and women's hostile sexism (HS) and benevolent sexism (BS) were associated with resistance to influence in couples' conflict interactions. Ninety-one heterosexual couples were recorded while trying to produce desired changes in each other. Participants reviewed their discussions and rated how open they were to their partner's perspective. Objective coders also rated the extent to which each partner exhibited hostile communication. We tested key principles arising from ambivalent sexism theory (Glick & Fiske, 1996). First, BS is necessary because mutual interdependence reduces the power of HS to influence women within intimate relationships. We found that the more men endorsed HS, the less open and more hostile both partners were, and the less successful their discussions were in producing desired change. Second, BS reduces the threat of women's dyadic power by revering and respecting women's interpersonal roles while restricting women's influence outside the relationship domain. We found that men who expressed higher agreement with BS were more open to their partners' influence and behaved with less hostility, and their discussions were more successful. These relationship benefits illustrate why BS is effective at disarming women's resistance to wider inequalities. These benefits, however, were contingent on men adopting BS attitudes. When women strongly endorsed BS but their male partner did not, women were less open, behaved with greater hostility, and perceived their discussions as less successful. These results indicate that, because BS increases the stakes within the relationship domain, women who endorse BS will react more negatively when their expectations are not realized.


Indoor dampness and molds and development of adult-onset asthma: a population-based incident case-control study.
Previous cross-sectional and prevalent case-control studies have suggested increased risk of asthma in adults related to dampness problems and molds in homes. We conducted a population-based incident case-control study to assess the effects of indoor dampness problems and molds at work and at home on development of asthma in adults. We recruited systematically all new cases of asthma during a 2.5-year study period (1997-2000) and randomly selected controls from a source population consisting of adults 21-63 years old living in the Pirkanmaa Hospital district, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls, after we excluded 76 (7.5%) controls with a history of asthma. In logistic regression analysis adjusting for confounders, the risk of asthma was related to the presence of visible mold and/or mold odor in the workplace (odds ratio, 1.54; 95% confidence interval, 1.01-2.32) but not to water damage or damp stains alone. We estimated the fraction of asthma attributable to workplace mold exposure to be 35.1% (95% confidence interval, 1.0-56.9%) among the exposed. Present results provide new evidence of the relation between workplace exposure to indoor molds and adult-onset asthma.


Photochemical pump and NMR probe to monitor the formation and kinetics of hyperpolarized metal dihydrides.
On reaction of IrI(CO)(PPh3)21 with para-hydrogen (p-H2), Ir(H)2I(CO)(PPh3)22 is formed which exhibits strongly enhanced 1H NMR signals for its hydride resonances. Complex 2 also shows similar enhancement of its NMR spectra when it is irradiated under p-H2. We report the use of this photochemical reactivity to measure the kinetics of H2 addition by laser-synchronized reactions in conjunction with NMR. The single laser pulse promotes the reductive elimination of H2 from Ir(H)2I(CO)(PPh3)22 in C6D6 solution to form the 16-electron precursor 1, back reaction with p-H2 then reforms 2 in a well-defined nuclear spin-state. The build up of this product can be followed by incrementing a precisely controlled delay (τ), in millisecond steps, between the laser and the NMR pulse. The resulting signal vs. time profile shows a dependence on p-H2 pressure. The plot of kobs against p-H2 pressure is linear and yields the second order rate constant, k2, for H2 addition to 1 of (3.26 ± 0.42) × 102 M-1 s-1. Validation was achieved by transient-UV-vis absorption spectroscopy which gives k2 of (3.06 ± 0.40) × 102 M-1 s-1. Furthermore, irradiation of a C6D6 solution of 2 with multiple laser shots, in conjunction with p-H2 derived hyperpolarization, allows the detection and characterisation of two minor reaction products, 2a and 3, which are produced in such low yields that they are not detected without hyperpolarization. Complex 2a is a configurational isomer of 2, while 3 is formed by substitution of CO by PPh3.


Evaluation of two-stage weaning and trace mineral injection on receiving cattle growth performance and behavior.
The objective was to evaluate the effects of two-stage weaning and injectable trace mineral (ITM) on receiving cattle growth performance and behavior. Angus and Simmental × Angus steers (n = 136; body weight [BW] = 200 ± 26 kg) were utilized in a 2 × 2 factorial design. Calves were blocked by source, and assigned to one of four treatments: 1) two-stage weaning and ITM (2MM), 2) two-stage weaning and saline injection (2SAL), 3) abrupt weaning and ITM (AbtMM), or 4) abrupt weaning and saline injection (AbtSAL). On d-6, calves were weighed, plastic calf weaner devices (used to prevent calf from nursing) were inserted in two-stage weaned calves, and ITM or saline injections (1 mL/45.4 kg BW) were administered. On day 0, plastic calf weaner devices were removed, and calves were weighed and shipped 272 km to Urbana, IL. Steer behavior was observed the 2 d following separation from dam. Receiving period was day 0 to 42 and growing period was day 42 to 124. Data were analyzed using the MIXED procedure of SAS and pen (six per treatment) was the experimental unit. Abruptly weaned calves had greater (P < 0.01) preweaning average daily gain (ADG) than two-stage weaned calves. Treatment did not affect (P ≥ 0.16) ADG during the receiving or growing period; however, calves that received ITM tended (P 0.06) to have greater ADG from day 0 to 124. During the receiving period, abruptly weaned calves tended (P = 0.08) to eat more than two-stage calves and ITM calves ate more (P = 0.03) than calves that received saline. There was a weaning strategy × ITM interaction (P < 0.01) for dry matter intake (DMI) from day 0 to 124; 2MM calves ate more (P < 0.01) than 2SAL, but DMI was not different (P = 0.58) between AbtMM and AbtSAL calves. There was a weaning strategy × ITM interaction (P < 0.01) for gain-to-feed ratio (G:F) from day 0 to 124; 2SAL calves had greater (P = 0.05) G:F than AbtSAL, with 2MM and AbtMM calves being intermediate and not different (P = 0.38) than each other. Two-stage weaning decreased (P ≤ 0.02) the percentage of calves walking, standing, and vocalizing, and increased (P ≤ 0.02) the percentage of calves lying and eating following separation from dam. Two-stage weaning decreased preweaning ADG and behavioral signs of stress at feedlot arrival, but had no effect on overall growth. In addition, ITM had no effect on calf BW or behavior, but increased overall DMI in two-stage weaned calves compared to abruptly weaned calves and tended to increase overall ADG regardless of weaning strategy.


Tissue distribution of YM758, a novel If channel inhibitor, in pregnant and lactating rats.
In this study the tissue distribution of radioactivity in pregnant and lactating rats was investigated by quantitatively determining radioactivity concentrations and by whole-body autoradioluminograms after a single oral administration of 14C-YM758. In addition, the transfer of radioactivity into the reproductive tissues, foetus, and milk is discussed in terms of the localization of transporters in syncytiotrophoblast and mammary gland. The radioactivity concentrations in the liver were the highest of all the tissues and organs tested at all the sampling times. The radioactivity in main tissues (liver and kidney), including reproductive tissues (amniotic fluid, placenta, ovary, and uterus), was not retained for a long time, as in the plasma. The tissue/plasma (T/P) ratio of radioactivity in the foetus was below 1.0, which might be due to Mdr1-mediated export of YM758 into blood via the blood-placenta barrier since YM758 is a substrate for hMDR1, not for hBCRP/rBcrp. The T/P ratio of radioactivity in the maternal milk 1 and 4 h after oral administration of 14C-YM758 was 7.2 and 11.0, respectively. To understand better the distribution of new drugs into the reproductive tissues/milk, and to interpret further the results of reproductive safety studies for drug development, the contribution of transporters expressed in the blood-placenta barrier and mammary gland to the drug-transfer into placenta and milk should be considered.


Interactive effects of subjective memory complaints and hypertension on learning and memory performance in the elderly.
This study evaluated whether the relation between subjective memory complaints and cognitive performance is influenced by the presence of hypertension in the elderly. One hundred and five healthy older adults, 70-89 years of age, with and without hypertension treatment or diagnosis, completed a scale of subjective memory complaints. Participants were divided into those with mild memory concerns and those with minimal or no complaints. All participants completed a battery of neuropsychological tests including measures of verbal and nonverbal memory. After controlling for differences in age, gender, education, and overall intellectual ability, there were significant main effects for memory concerns and significant interactions for memory complaints and hypertension on several measures of memory performance. There were no main effects for hypertension on memory performance. Simple effects analyses of the interactions showed that the hypertensive complainers demonstrated poorer performance on measures of long-term memory and greater reliance on short-term recall than the hypertensive non-complainers. There were no differences in memory performance for the non-hypertensive groups. Among healthy elderly community-dwelling adults, those with mild subjective memory complaints in the context of hypertension demonstrated greater objective cognitive difficulties than those without hypertension as well as a greater reliance on a less efficient learning strategy. These findings suggest that memory concerns in the presence of hypertension may be important when evaluating treatment efficacy in these individuals and for identifying differences in cognitive aging.


Carcinoembryonic antigen in monitoring of response to cetuximab plus FOLFIRI or FOLFOX-4 in patients with metastatic colorectal cancer.
First-line treatment of metastatic colorectal cancer with combinations of cetuximab and irinotecan-based or oxaliplatin-based chemotherapy has shown promising efficacy. The clinical response to such treatment is generally assessed by tumor measurement through imaging. This study was performed to evaluate the correlation between serial changes in imaging results and carcinoembryonic antigen (CEA) levels. In 64 patients with metastatic colorectal cancer receiving cetuximab plus FOLFIRI or FOLFOX-4 chemotherapy we retrospectively analyzed the relationship between changes in serum CEA and changes in imaging results throughout the treatment course. Response in terms of serum CEA change was defined as a >/=50% drop in CEA level for more than 4 weeks. The sensitivity and specificity of serum CEA changes after targeted chemotherapy in relation to imaging results were 80.5% (33/41) and 73.9% (17/23), respectively, with a diagnostic accuracy of 78.1% (50/64). The progression-free survival time of responders assessed by serum CEA change was significantly longer than that of nonresponders (p=0.0091). Our results highlight the importance of serum CEA monitoring in assessing the response to targeted chemotherapy and in predicting the prognosis of patients with metastatic colorectal cancer.


Alcohol neurolysis of the sciatic and femoral nerves to improve pressure ulcer healing.
Successful pressure ulcer treatment is challenging and is often plagued with prolonged hospitalizations, multiple surgeries, and high recurrence rates. Pressure ulcer secondary to spinal cord injury is further complicated by spasticity, which contributes to both ulcer continuance and healing. This report illustrates the use of neurolytic regional techniques for spasticity control and pressure ulcer healing. We present our experience with a paraplegic man who suffered from chronic right trochanteric and ischial pressure ulcers that failed to heal despite surgical and conservative treatment. We report the successful treatment of knee and hip flexor spasticity with a femoral and sciatic alcohol neuroablation technique. It was not until the successful control of his lower extremity spasticity that the pressure ulcers showed signs of healing. Neuroablation nay be considered for spasticity control when more conservative approaches fail or are not feasible.


Liquid Chromatography-Tandem Mass Spectrometry-Based Metabolomics Analysis of Indigo Naturalis Treatment of Ulcerative Colitis in Mice.
Ulcerative colitis (UC), often known as UC, is an inflammatory disease of the intestines that has frequent and long-lasting flare-ups. It is unknown precisely how the traditional Chinese drug Indigo Naturalis (IN) heals inflammatory bowel disease, despite its long-standing use in China and Japan. Finding new metabolite biomarkers linked to UC could improve our understanding of the disease, speed up the diagnostic process, and provide insight into how certain drugs work to treat the condition. Our work is designed to use a metabolomic method to analyze potential alterations in endogenous substances and their impact on metabolic pathways in a mouse model of UC. To determine which biomarkers and metabolisms are more frequently connected with IN's effects on UC, liquid chromatography-tandem mass spectrometry analysis of the serum metabolomics of UC mice and normal mice was performed. The outcomes demonstrated that IN boosted the health of UC mice and reduced the severity of their metabolic dysfunction. In the UC model, it was also found that IN changed the way 17 biomarkers and 3 metabolisms functioned.


Phosphorylation of Ataxin-10 by polo-like kinase 1 is required for cytokinesis.
Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurologic disorder, whose symptoms include cerebellar ataxia and epilepsy. The disease is caused by ATTCT expansion in the ATXN10 gene, which encodes the Ataxin-10 protein. Here we identified polo-like kinase 1 (Plk1) as one of Ataxin-10's binding partners. We show that epitope-tagged Ataxin-10 and Plk1 coimmunoprecipitate, and Plk1 phosphorylates Ataxin-10 at S77 and T82 in vitro. Knockdown of ATXN10 with siRNA in HeLa cells results in cytokinesis defects-multinucleation, which are rescued by wild-type Ataxin-10, but not the phosphor-deficient 2A mutant. Phosphorylation-specific antibodies towards pS77 detect specific signals at the midbody. Like the knockdown, overexpression of the 2A mutant generates multinucleated cells and the 2A mutant shows decreased interaction with the Plk1 polo-box domain. In addition, we found that Ataxin-10 is ubiquitinated, and is subject to proteasome-dependent degradation, which is delayed in the 2A mutant. We propose a model in which Plk1 phosphorylation of Ataxin-10 influences its degradation and cytokinesis, which may provide mechanistic insight to SCA10's pathogenesis.


The impact of managed care on pharmacy practice.
As prescription drug costs continue their rapid rise, managed care organizations (MCOs) are giving greater attention to containing drug costs. This article examines the impact of managed care on pharmacy practice and reviews types of reimbursement for managed care prescriptions. The author outlines cost-containment measures for MCOs and pharmacy benefit management companies, including the use of mail order pharmacies, electronic claims payment, establishment of formularies, therapeutic interchange and generic incentives, and other measures. Cost-containment steps for pharmacies focus on identifying dispensing costs, decreasing overhead, and reducing ingredient costs. The author recommends that pharmacists begin to demonstrate and establish the value of their cognitive services, especially in patient counseling, in order to obtain reimbursement for these services.


Declining Utilization Patterns of Percutaneous Adhesiolysis Procedures in the Fee-For-Service (FFS) Medicare Population.
Percutaneous epidural adhesiolysis is a minimally invasive therapeutic modality used in the treatment of patients with chronic low back and lower extremity pain, often recalcitrant to other modalities including epidural injections and surgical interventions. While the initial utilization since its introduction and development of appropriate Current Procedural Terminology (CPT) codes increased up until 2008, but since 2009, there has been a significant decline in utilization of these procedures in the Medicare population. These procedures declined by 53.2% at an annual rate of 10.3% from 2009 to 2016. A recent update analysis on the reversal and decline of growth of utilization of interventional techniques in managing chronic pain in the Medicare population from 2009 to 2018 revealed an even further decline of adhesiolysis procedures. An analysis of the utilization patterns of percutaneous adhesiolysis procedures in managing chronic low back and lower extremity pain in the Medicare population from 2000 to 2018, with comparative analysis from 2000 to 2009 and 2009 to 2018. To assess the utilization patterns of percutaneous adhesiolysis in managing chronic low back pain in the Medicare population. The Centers for Medicare and Medicaid Services (CMS) Physician Supplier Procedure Summary Master of Fee-For-Service (FFS) Data from 2000 to 2018 was used.In this analysis, various variables were assessed in reference to usage patterns of percutaneous adhesiolysis procedures with analysis of growth or declining utilization patterns. We also assessed specialty-based utilization, as well as statewide utilization. The decline of percutaneous adhesiolysis procedures began in 2009 and has continued since then. From 2009 to 2018, the overall decline was 69.2%, with an annual decline of 12.3% compared to an overall 62.6% increase from 2000 to 2009, with an annual increase of 5.6%. Compared to multiple other interventions, including epidural injections and facet joint interventions, percutaneous adhesiolysis has declined at a rapid rate. This assessment in the FFS Medicare population in the United States shows an irreversible decline of utilization of percutaneous adhesiolysis procedures, which has been gradually deteriorating with a 69.2% decline from 2009 to 2018 with an annual decline of 12.3% during that same time period.


Association between plasma 25-hydroxyvitamin D and colorectal adenoma according to dietary calcium intake and vitamin D receptor polymorphism.
The anticarcinogenic potential of vitamin D might be mediated by not only calcium metabolism but also other mechanisms initiated by vitamin D receptor (VDR). The authors measured plasma 25-hydroxyvitamin D in healthy volunteer examinees who underwent total colonoscopy in Tokyo, Japan, 2004-2005, and evaluated its influence on colorectal adenoma, both alone and in interaction with VDR polymorphisms, which correspond to the FokI and TaqI restriction sites. The main analysis of plasma 25-hydroxyvitamin D included 737 cases and 703 controls. Compared with the lowest quintile of plasma 25-hydroxyvitamin D, only the highest was related to a significantly decreased odds ratio of colorectal adenoma (odds ratio = 0.64, 95% confidence interval: 0.45, 0.92). In contrast, all but the lowest quintile of dietary calcium intake presented similarly reduced odds ratios (odds ratio for the highest = 0.67, 95% confidence interval: 0.47, 0.95). Of note, the association between plasma 25-hydroxyvitamin D levels and colorectal adenoma was modified by the TaqI polymorphism of the VDR gene (P(interaction) = 0.03) but not by dietary calcium intake (P(interaction) = 0.93). These observations highlight the importance of vitamin D in colorectal tumorigenesis. Vitamin D might protect against colorectal neoplasia, mainly through mechanisms other than the indirect mechanism via calcium metabolism.


Preparation of a novel magnetic cellulose nanocrystal and its efficient use for enzyme immobilization.
A novel biocompatible magnetic cellulose nanocrystal (MCNC) composite was in situ prepared via a simple co-precipitation-electrostatic-self-assembly technique and was structurally characterized. The results showed that the anionic cellulose nanocrystals (CNCs) were successfully composited with cationic chitosan-coated Fe3O4 by self-assembly technology. The electrostatic interaction between CNCs and chitosan, and that between chitosan and Fe3O4, were the key driving forces for the formation of the composite. Papain, a widely used protease, could be successfully immobilized on the activated MCNCs with formaldehyde. The immobilized papain exhibited higher thermal stability than the free enzyme, with the relative activity being higher than 80% after incubation at 40 °C for 7 h while that of free papain was less than 30%. Also, the pH stability of immobilized papain was superior to that of free papain. Moreover, the immobilized papain showed significantly better tolerance to the three solvents tested compared with its free counterpart. The optimum range of pH for immobilized papain (pH 5-10) was remarkably wider than that of free enzyme (pH 5-7). The relative activities of immobilized papain at 50-70 °C were more than 90%, which significantly surpassed those of free papain. The immobilized papain also manifested excellent storage stability, with relative activity being as high as 93.6% after 16 days of storage at 4 °C. Furthermore, the obtained kinetic constant values showed that papain immobilized on the MCNCs had relatively high catalytic efficiency. Additionally, the immobilized papain could be easily separated and recycled from the reaction system through magnetic forces. Obviously, the prepared MCNCs as novel supports are promising and competitive for enzyme immobilization.


Health-related quality of life predicts long-term survival in patients with peripheral artery disease.
We examined whether health-related quality of life (HRQoL) predicts long-term survival in patients with peripheral artery disease (PAD) independent of established prognostic risk factors. In 2004, data on 711 consecutive patients with PAD undergoing vascular surgery were collected from 11 hospitals in The Netherlands. After 1 year, patients were contacted to complete the EuroQol Questionnaire (EQ-5D), of which 503 complied. HRQoL assessed by the EQ-5D was divided into tertiles (i.e. poor, intermediate and good HRQoL). Mortality was subsequently assessed 3 years after surgery. Of the 503 patients, 55 (11%) patients died during follow-up. Mortality was 21% in patients with poor HRQoL, 8% in patients with intermediate HRQoL, and 5% in patients with good HRQoL. Patients with poor HRQoL (HR = 5.4; 95% CI 2.3-12.5) had a worse survival compared to patients with a good HRQoL, after adjusting for established prognostic factors. In conclusion, the study indicates that poor HRQoL predicts long-term survival in patients with PAD, and provides prognostic value above established risk factors.


A Newly Developed Exergame-Based Telerehabilitation System for Older Adults: Usability and Technology Acceptance Study.
Telerehabilitation has gained significance as a tool to deliver and supervise therapy and training as effective as traditional rehabilitation methods yet more accessible and affordable. An exergame-based telerehabilitation system has recently been developed within the scope of the international Continuum-of-Care (COCARE) project. The system comprises training devices for use in clinics (Dividat Senso) and at home (Dividat Senso Flex), an assessment system, and a rehabilitation cockpit, and its focus lies on home-based motor-cognitive training, which is remotely managed by health care professionals (HPs). This study aims to analyze the usability, acceptance, and enjoyment of the COCARE system from the perspective of primary (older adults [OAs]) and secondary (HPs) end users. At 3 trial sites (located in Switzerland, Italy, and Cyprus), participants engaged in a single-session trial of the COCARE system, including testing of exergames and assessments. Mixed methods encompassing qualitative approaches (eg, think aloud) and quantitative measures (eg, Exergame Enjoyment Questionnaire [EEQ], System Usability Scale [SUS], and Unified Theory of Acceptance and Use of Technology [UTAUT] questionnaire) were used to analyze participants' perceptions of the system and identify potential barriers to its implementation in a home setting. In addition, the associations of performance during gameplay and assessments, demographics, and training motivation (Behavioral Regulation in Exercise Questionnaire-3 [BREQ-3]) with usability, acceptance, and enjoyment were explored. A total of 45 OAs and 15 HPs participated in this study. The COCARE system achieved good acceptance ratings (OAs: 83%, range 36%-100% and HPs: 81%, range 63.8%-93.3% of the maximum score), and OAs indicated high enjoyment (mean 73.3, SD 12.7 out of 100 points in the EEQ) during the exergame session. The system's usability, assessed with the SUS, received scores of 68.1 (SD 18.8; OAs) and 70.7 (SD 12.3; HPs) out of 100 points, with substantial differences observed between the trial sites. Several requirements for improvement were identified. Commonly mentioned barriers to adoption included the movement-recognition sensitivity of the Senso Flex, its limited markings, and difficulties in understanding certain instructions for assessments and games. Performance in games and assessments showed the highest significant correlations with the SUS (Spearman ρ=0.35, P=.02 to ρ=0.52, P<.001). The BREQ-3 had significant correlations with all usability measures, thereby even large significant correlations with enjoyment (Spearman ρ=0.58; P<.001). Age had moderately significant correlations with the SUS (Spearman ρ=-0.35; P=.02) and the UTAUT total score (ρ=-0.35; P=.02) but no significant correlation with the EEQ. Concerning sex and years of education, no significant correlations were found. The study's findings will inform the further development of the COCARE system toward a user-friendly and widely accepted version, enhancing cognitive and physical functions in OAs. Future randomized controlled trials should evaluate the system's feasibility and effectiveness.


Performance of substance abusers with memory deficits on measures of malingering.
The effects of memory impairment on various malingering indices were assessed in a substance abusing population. Groups were formed by using scores from the Delayed Memory Index of the Wechsler Memory Scale-Revised and selecting individuals from an addictions recovery unit in the top and bottom quintiles. Quintile group differences were found for number correct on free and forced-choice recall on the 21-Item Wordlist; total time for grouped and ungrouped dots on the Rey Dot Counting procedure; and addition errors on the Memorization of 16 Items test. All differences found were in the direction of better performance by subjects with better Delayed Memory Index scores; however, all of the differences were small. With the exception of the free recall index from the 21-Item Wordlist, all subjects had scores on the malingering measures beyond the cutoffs typically used to detect malingering in clinical populations. These findings suggest that, even in memory-impaired populations, memory measures of malingering are valid.


Design of metabolic and enzymic machinery to fit lifestyle and environment.
Biochemical theory, spectacular as its growth has been in the last half-century, finds its experimental basis in a remarkably few organisms. The rat, the ox, the pig, the hen plus a few micro-organisms consitute the primary source of biochemistry's experimental material, while, by contrast, modern systematics estimates a bewildering and often overlooked diversity of over 10(6) animal species. As a result of this highly limited 'sampling' of nature, classical biochemistry has supplied an equally limited insight into how far biochemical mechanisms can be extended or adapted for (1) allowing an organism's exploitation of its environment and (2) accommodating environmental change. The situation has improved in more recent years, so that it is now possible to decipher at least the broad strategic outlines of biochemical adaptation to the environment. This essay focuses particular attention on the influence of O2 availability on muscle metabolic organization and control. By drawing examples of muscle metabolism spanning a range from obligate-anaerobic to obligate-aerobic organization, it is possible to demonstrate that certain kinds of metabolic features are highly conserved, whereas others are changed time and time again, in different combinations and permutations. The latter properties constitute the 'raw material' for adapting metabolism to specific O2 regimes, and include (1) the kinds and amounts of enzymes present in muscle, (2) the fine regulatory circuitry allowing for controlled transition from low to high work loads and (3) compensation mechanisms for the adjustment of enzyme reactions with respect to such external parameters as temperature, pressure, salinity and so forth. Within the inescapable limitations of phylogenetic origins and the time available for responding to specific environmental conditions, adequate adaptations of the fundamental design of muscle metabolism have evolved to exploit environments differing greatly in O2 availability and to accommodate a wide range of muscle functions.


Neural substrates of framing effects in social contexts: A meta-analytical approach.
We hypothesize that framing effects (risk-averse in the positive frame and risk-seeking in the negative frame) are likely to occur when ambiguous social contexts result in ambiguous or ambivalent risk preferences, leading the decision-maker to search for more subtle cues, such as verbal framing. In a functional magnetic resonance imaging (fMRI) study, we examined framing effects in both unambiguous homogeneous group and more ambiguous heterogeneous group contexts. We began by conducting a meta-analysis and identified three regions of interest: the right inferior frontal gyrus, the left anterior cingulate (ACC)/ventromedial prefrontal cortex (vmPFC), and the left amygdala. Our own fMRI data were collected while the participants made choices between a sure option and a gamble framed in terms of the number of lives to either save or die. The framing effect was evident in a heterogeneous context with a mixture of kin and strangers, but disappeared in a homogeneous group of either all kin-members or all strangers. The fMRI results revealed a greater activation in the right middle/inferior frontal gyrus under the negative than the positive framing, and less ACC/vmPFC deactivation under positive framing in the heterogamous/ambiguous context. The activation of the amygdala was correlated with greater risk-seeking preference in homogeneous kinship contexts.


Blood transfusion practices in a tertiary care center in Northern India.
Blood transfusion plays vital roles in the medical and surgical practice. To achieve optimum use of blood, transfusion has to be appropriate and judicious consuming minimal resources and manpower. To evaluate the pattern of blood transfusion requests and utilization with the aim of determining transfusion practice. Blood request forms and cross-match worksheets at the blood bank were analyzed over a 6-month period. Numbers of requisitions, blood units cross-matched, issued out, transfused, and nontransfused were calculated. Nonusage probability (NUP) and the cross-match to transfusion ratio (CTR) for each clinical unit were computed. Two thousand two hundred and sixty-eight units of blood were cross-matched for 1487 patient's transfusion requests, out of which only 1455 (64.2%) were transfused giving a total CTR of 1.6 for the hospital. The CTR for the various clinical units were: Obstetrics and gynecology (O and G) 2.7, surgery 2.1, orthopedics 1.9, medicine 1.1, pediatrics 1, and oncology 1. The overall CTR (1.6) of the hospital was within the optimal range except for the O and G and surgery department which were having very high NUP and CTR indicating their suboptimal transfusion practices. Introducing revised transfusion guidelines, maximum surgical blood ordering schedule and type, screen, save, and abbreviated cross-match method can help toward adequate requisition and utilization of blood thereby reducing wastage of resources, time, and manpower.


Management of tibial non-union with tricalcium phosphate and BMP 7.
We present the case of a 30-year-old woman who was referred with an established tibial non-union with a bone defect following a spiral fracture of the tibia. Initial attempts at union with intramedullary fixation and then autograft were unsuccessful. We achieved union by debriding the fibrous tissue and packing the defect with Bone Morphogenetic Protein 7 (Osigraft, Stryker, UK) and a tricalcium phosphate bone void filler (Calstrux, Stryker, UK). We did not use any additional surgical fixation and the patient was supported in an aircast boot.


Imaging and clinical correlates with regorafenib in metastatic colorectal cancer.
In colorectal cancer (CRC), imaging is important in determining tumor stage, selecting treatment strategies, and in assessing response to therapy. However, some challenges remain with established imaging techniques, such as computed tomography, and with some commonly used response criteria, such as Response Evaluation Criteria in Solid Tumors, which measures change in size of several target lesions instead of change in tumor morphology or metabolic function. In addition, these assessments are not typically conducted until after 8 weeks of treatment, meaning that potential non-responders are often not identified in a timely manner. Regorafenib, an oral tyrosine kinase inhibitor indicated for the treatment of metastatic CRC, blocks the activity of several protein kinases involved in angiogenesis, oncogenesis, metastasis, and tumor immunity. Timely differentiation of regorafenib responders from non-responders using appropriate imaging techniques that recognize not only changes in tumor size but also changes in tumor density or vasculature, may reduce unnecessary drug-related toxicity in patients who are unlikely to respond to treatment. This review discusses the latest developments in computed tomography, magnetic resonance imaging, and positron emission tomography tumor imaging modalities, and how these aid in identifying patients with metastatic CRC who are responders or non-responders to regorafenib treatment.


Age and Genetic Background Modify Hybrid Male Sterility in House Mice.
Hybrid male sterility (HMS) contributes to reproductive isolation commonly observed among house mouse (Mus musculus) subspecies, both in the wild and in laboratory crosses. Incompatibilities involving specific Prdm9 alleles and certain Chromosome (Chr) X genotypes are known determinants of fertility and HMS, and previous work in the field has demonstrated that genetic background modifies these two major loci. We constructed hybrids that have identical genotypes at Prdm9 and identical X chromosomes, but differ widely across the rest of the genome. In each case, we crossed female PWK/PhJ mice representative of the M. m. musculus subspecies to males from a classical inbred strain representative of M. m. domesticus: 129S1/SvImJ, A/J, C57BL/6J, or DBA/2J. We detected three distinct trajectories of fertility among the hybrids using breeding experiments. The PWK129S1 males were always infertile. PWKDBA2 males were fertile, despite their genotypes at the major HMS loci. We also observed age-dependent changes in fertility parameters across multiple genetic backgrounds. The PWKB6 and PWKAJ males were always infertile before 12 weeks and after 35 weeks. However, some PWKB6 and PWKAJ males were transiently fertile between 12 and 35 weeks. This observation could resolve previous contradictory reports about the fertility of PWKB6. Taken together, these results point to multiple segregating HMS modifier alleles, some of which have age-related modes of action. The ultimate identification of these alleles and their age-related mechanisms will advance understanding both of the genetic architecture of HMS and of how reproductive barriers are maintained between house mouse subspecies.


Apical cargo traverses endosomal compartments on the passage to the cell surface.
Epithelial polarity is based on intracellular sorting machinery that maintains the asymmetric distribution of lipids and proteins to the cell surface. Dependent on their lipid raft affinity, newly synthesized apical polypeptides are segregated into distinct vesicle populations subsequent to the passage through the Golgi apparatus. Using a combined fluorescence microscopic and biochemical approach, we found that lipid raft-associated sucrase-isomaltase (SI) as well as non-raft-associated lactase-phlorizin hydrolase (LPH) traverse endosomal compartments before entering the apical membrane. Fluorescent fusion proteins of both hydrolases were co-stained with Rab4-, Rab8- and Rab11-positive endosomes in polarized Madin-Darby canine kidney and non-polarized COS-1 cells. Immunoisolation of post-Golgi vesicles subsequent to different times of TGN release revealed that LPH and SI navigate in chronological order through Rab4-, Rab8- and Rab11-positive endosomes. Thereafter, the two hydrolases are segregated into distinct vesicle populations. In addition, apical membrane traffic could be significantly inhibited by RNA interference-mediated depletion of these guanosine triphosphatases. These results suggest that in epithelial cells, lipid raft-dependent and -independent apical cargo follow a transendosomal route.


In situ sensor technology for simultaneous spectrophotometric measurements of seawater total dissolved inorganic carbon and pH.
A new, in situ sensing system, Channelized Optical System (CHANOS), was recently developed to make high-resolution, simultaneous measurements of total dissolved inorganic carbon (DIC) and pH in seawater. Measurements made by this single, compact sensor can fully characterize the marine carbonate system. The system has a modular design to accommodate two independent, but similar measurement channels for DIC and pH. Both are based on spectrophotometric detection of hydrogen ion concentrations. The pH channel uses a flow-through, sample-indicator mixing design to achieve near instantaneous measurements. The DIC channel adapts a recently developed spectrophotometric method to achieve flow-through CO2 equilibration between an acidified sample and an indicator solution with a response time of only ∼ 90 s. During laboratory and in situ testing, CHANOS achieved a precision of ±0.0010 and ± 2.5 μmol kg(-1) for pH and DIC, respectively. In situ comparison tests indicated that the accuracies of the pH and DIC channels over a three-week time-series deployment were ± 0.0024 and ± 4.1 μmol kg(-1), respectively. This study demonstrates that CHANOS can make in situ, climatology-quality measurements by measuring two desirable CO2 parameters, and is capable of resolving the CO2 system in dynamic marine environments.


Moving upstream in the war on WNTs.
Cholangiocarcinoma is a relatively rare cancer of the biliary ducts that is highly refractory to treatment. The factors that drive cholangiocarcinoma are poorly understood, though chronic liver fluke infection is a risk factor for disease. In this issue of the JCI, Boulter and colleagues demonstrate that the WNT/β-catenin signaling pathway is upregulated in patients with sporadic cholangiocarcinoma. The authors determined that macrophages generate WNT ligands in cholangiocarcinomas and depletion or inhibition of this cell population in animal models of cholangiocarcinoma reduced tumor burden and proliferation. Moreover, pharmacological inhibition of WNT secretion or β-catenin activity was efficacious in animal models. Together the results of this study suggest that targeting WNT has potential as a therapeutic strategy for cholangiocarcinoma.


Early loss of Fhit in the respiratory tract of rodents exposed to environmental cigarette smoke.
The Fhit gene, encompassing the most active common human chromosomal fragile region, FRA3B, has been shown to act as a tumor suppressor. Several studies have shown significant Fhit alterations or Fhit protein loss in lung cancers from smokers compared with lung cancers from nonsmokers. To evaluate the role of Fhit under controlled experimental conditions, we exposed rodents to environmental cigarette smoke (ECS) and evaluated Fhit expression or Fhit protein in the respiratory tract. After 14 days of exposure to ECS, loss of Fhit protein in the bronchial/bronchiolar epithelium affected half of the tested B6-129(F(1)) mice, either wild type or Fhit(+/-). After 28 days, it affected the vast majority of the tested SKH-1 hairless mice and of A/J mice and all (UL53-3 x A/J)F(1) mice, either wild type or P53(+/-). In Sprague-Dawley rats, exposure to ECS for up to 30 days caused a time-dependent loss of Fhit in pulmonary alveolar macrophages. Moreover, ECS down-regulated Fhit expression and significantly decreased Fhit protein in the rat bronchial epithelium. The oral administration of N-acetylcysteine attenuated the ECS-related loss of Fhit, whereas oltipraz, 5,6-benzoflavone, phenethyl isothiocyanate, and indole 3-carbinol, and their combinations had no significant effect. Parallel studies evaluated a variety of molecular, biochemical, and cytogenetic alterations in the respiratory tract of the same animals. In conclusion, there is unequivocal evidence that Fhit is an early, critical target in smoke-related lung carcinogenesis in rodents, and that certain chemopreventive agents can attenuate the occurrence of this gene alteration.


High-cell density culture of poly(lactate-co-3-hydroxybutyrate)-producing Escherichia coli by using glucose/xylose-switching fed-batch jar fermentation.
Poly(lactate-co-3-hydroxybutyrate) [P(LA-co-3HB)] is produced in engineered Escherichia coli harboring the genes encoding an LA-polymerizing enzyme (LPE) and monomer-supplying enzymes. In this study, high cell-density fed-batch jar fermentation was developed using xylose and/or glucose as the carbon source. Fed-batch fermentation was initially performed with 20 g/L sugar during the batch phase for 24 h, and subsequent sugar feeding from 24 to 86 h. The feeding rate was increased in a stepwise manner. When xylose alone was used for cultivation, the cells produced the polymer at 11.6 g/L, which was higher than the 4.3 g/L obtained using glucose as the sole carbon source. However, in the first 24 h the growth in the glucose culture was greater than in the xylose culture. Based on these results, glucose was used for cell growth (at the initial stage) and xylose was used for polymer production (at the feeding stage). As expected, in the glucose/xylose switching fermentation method, polymer production was significantly enhanced, eventually reaching 26.7 g/L. The enhanced polymer production obtained by using xylose was presumably due to overflow metabolism. In fact, during xylose feeding, acetic acid excretion was greater than that in case of the glucose grown culture, suggesting the channeling of the metabolic flux from acetyl-CoA towards polymer production over into the tricarboxylic acid cycle in the xylose-fed cultures. Therefore, this sequential glucose/xylose feed strategy is potentially useful for production of acetyl-CoA derived compounds in E. coli.


Influence of Five Drying Methods on Active Compound Contents and Bioactivities of Fresh Flowers from Syringa pubescens Turcz.
The flower of Syringa pubescens Turcz. is used in Chinese folk medicine and also as a flower tea for healthcare. The effects of five drying methods on the active compound contents, the antioxidant abilities, anti-inflammatory properties and enzyme inhibitory activities were evaluated. The plant materials were treated using shade-drying, microwave-drying, sun-drying, infrared-drying and oven-drying. The seven active compounds were simultaneously determined using an HPLC method. Furthermore, the chemical profile was assessed using scanning electron microscopy, ultraviolet spectroscopy and infrared spectroscopy. The antioxidant capacities and protective effects on L02 cells induced with hydrogen peroxide were measured. The anti-inflammatory effects on lipopolysaccharide-induced RAW264.7 cells were investigated. The enzyme inhibitory activities were determined against α-amylase, α-glucosidase cholinesterases and tyrosinase. The results indicated that drying methods had significant influences on the active compound contents and biological properties. Compared with other samples, the OD samples possessed low IC50 values with 0.118 ± 0.004 mg/mL for DPPH radical, 1.538 ± 0.0972 for hydroxyl radical and 0.886 ± 0.199 mg/mL for superoxide radical, while the SHD samples had stronger reducing power compared with other samples. The SHD samples could be effective against H2O2-induced injury on L02 cells by the promoting of T-AOC, GSH-PX, SOD and CAT activities and the reducing of MDA content compared with other samples. Furthermore, SPF samples, especially the SHD sample, could evidently ameliorate inflammation through the inhibition of IL-6, IL-1β and TNF-α expression. All the studied SPF samples exhibited evidently inhibitory effects on the four enzymes. The IC50 values of inhibitory activity on α-glucosidase and α-amylase from SHD sample were 2.516 ± 0.024 and 0.734 ± 0.034 mg/mL, respectively. SD samples had potential inhibitory effects on cholinesterases and tyrosinase with IC50 values of 3.443 ± 0.060 and 1.732 ± 0.058 mg/mL. In consideration of active compound contents and biological activities, it was recommended that SHD and SD be applied for drying SPF at an industrial scale.


A brainstem circuit for phonation and volume control in mice.
Mammalian vocalizations are critical for communication and are produced through the process of phonation, in which expiratory muscles force air through the tensed vocal folds of the larynx, which vibrate to produce sound. Despite the importance of phonation, the motor circuits in the brain that control it remain poorly understood. In this study, we identified a subpopulation of ~160 neuropeptide precursor Nts (neurotensin)-expressing neurons in the mouse brainstem nucleus retroambiguus (RAm) that are robustly activated during both neonatal isolation cries and adult social vocalizations. The activity of these neurons is necessary and sufficient for vocalization and bidirectionally controls sound volume. RAm Nts neurons project to all brainstem and spinal cord motor centers involved in phonation and activate laryngeal and expiratory muscles essential for phonation and volume control. Thus, RAm Nts neurons form the core of a brain circuit for making sound and controlling its volume, which are two foundations of vocal communication.


GABA receptors induced in Xenopus oocytes by chick brain mRNA: evaluation of TBPS as a use-dependent channel-blocker.
Sensitivity to GABA was induced in Xenopus laevis oocytes by injection of poly(A)+ mRNA extracted from 19-day chick embryo brain. The effect of the convulsant drug t-butylbicyclophosphorothionate (TBPS) was studied on the responses to bath-applied GABA using voltage-clamp techniques. TBPS reversibly inhibited the GABA-evoked current (IGABA) in a dose-dependent manner; however, the chloride currents evoked by carbachol or serotonin, or the spontaneous chloride fluctuations, were unaffected. The onset of the block by TBPS was faster in the presence of GABA. The recovery from the block after TBPS wash-out was also agonist-stimulated. At the steady state block, TBPS showed a mixed type of inhibition: increasing the GABA concentration decreased but failed to abolish completely the inhibition by TBPS. The TBPS block was independent of the direction of the chloride flow: both inward and outward IGABA were blocked. The time course of the decay of IGABA was markedly changed in the presence of TBPS: above 40 microM GABA, this time course showed essentially two exponentials and TBPS abolished only the fast component, whereas at a low concentration (less than or equal to 4 microM), IGABA was relatively constant and uniformly reduced by TBPS. It is suggested that TBPS may stabilize a closed form of the liganded receptor-channel complex.


[Immunochemical markers of embryonic lens differentiation in Rana temporaria. I. Composition and properties of water-soluble lens antigens].
Antisera were obtained to the total extract and individual electrophoretic fractions of lens proteins: alpha-, beta-, gamma1- and gamma2-crystallins. The crystallins under study are immunochemically heterogenous: each class of lens proteins contains 2--4 antigens. Using the indirect method of fluorescent antibodies, it was established that the appearance of crystallins during development coincided with the onset of formation of the presumptive lens fibers. No crystallins were found in the lens placode and early lens vesicle. gamma-Crystallins appear later than the other lens proteins and are characteristic, mainly, for the lens fibers; at the advanced stages of organogenesis gamma-crystallins are regularly found in the epithelial cells of the developing lens as well.


[Expression and Clinical Significance of Exosome Component 4 in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma].
To explore the expression of Exosome Component 4(EXOSC4) in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance. The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance. The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05). High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.


Responding to the needs of children in crisis.
This paper explores the issues confronting service providers setting up child and family mental health programmes in conflict, post conflict and disaster areas. Drawing on clinical experience and research in humanitarian settings, it calls for greater attention to the child's perspective, their individuality and the cultural, social and political context in which they live. It argues that those concerned with the psychopathology of children in crises should widen their frame of reference beyond narrowly defined traumatic reactions to include other mental health and psychosocial issues, including the current problems of daily life and the needs of children with pre-existing psychiatric disorders. It recommends culturally valid means of assessment, the creation of age-appropriate services and training for primary healthcare workers. Children's mental health needs in crises are varied, complex and intimately connected with their needs for security, food, shelter, education and family connection. This requires holistic, rights-based approaches that can access resources to address basic needs, advocate for security and protection, and recognize and address the needs of the more vulnerable children. This is the approach recommended by the Inter Agency Standing Committee Guidelines for Mental health and Psychosocial Support in Emergency Settings.


X-ray diffraction tomography employing an annular beam.
We demonstrate depth-resolved materials characterization by scanning a sample through an annular beam of X-rays. We measure Bragg X-ray diffraction from a sample with a planar detector positioned centrally in a circular dark field defined by the annular beam. The diffraction maxima are optically encoded with the position of crystalline phases along this beam. Depth-resolved material phase images are recovered via tomosynthesis. We demonstrate our technique using a heterogeneous three-dimensional object comprising three different phases; cyclotetramethylene - tetranitramine, copper and nickel, distributed in a low density medium. Our technique has wide applicability in analytical imaging and is scalable with respect to both scan size and X-ray energy.


Prosody in autism spectrum disorders: a critical review.
Many individuals with autism spectrum disorders present with unusual or odd-sounding prosody. Despite this widely noted observation, prosodic ability in autism spectrum disorders is often perceived as an under-researched area. This review seeks to establish whether there is a prosodic disorder in autism, what generalizations can be made about its various manifestations and whether these manifestations vary according to the diagnosis. A literature review was carried out to establish what areas of prosody in autism spectrum disorders have been researched to date, what the findings have been and to determine what areas are yet to be researched. It is shown that prosody in autism spectrum disorders is an under-researched area and that where research has been undertaken, findings often conflict. The findings of these conflicting studies are compared and recommendations are made for areas of future research. Research in this area has covered mostly prosodic expression, although some more recent studies cover comprehension, processing and the relationship of receptive prosodic ability to theory of mind. Findings conflict and methodology varies greatly.


[The experimental pharmacotherapy of the liver lesion induced by indomethacin].
In experiments on albino rats it was established that three administrations of indomethacin in a dose of 0.01 g/kg body weight induced a severe damage of the liver characterized by disturbances of hepatocytic membranes, bile-producing and protein-producing functions of the liver, an enhancement of lipid peroxidation, a decrease of reduced glutathione pool. Antioxidants (tocopherol acetate, essentiale, legalon, flacumin) limit manifestations of indomethacin, hepatotoxicity, as a result of which tha functional-biochemical disorders in the liver show up to a lesser degree. During the combined use of antioxidants in indomethacin-induced lesions of the liver their hepatoprotective activity increases.


Mandibular body fracture repair with wire-reinforced interdental composite splint in small dogs.
To report the outcome of mandibular body fractures treated with a wire-reinforced interdental composite splint (WRICS) in small breed dogs. Retrospective case series. Client-owned small breed dogs (n = 24). Medical records (1998-2012) of small breed dogs (<10 kg) with mandibular body fractures treated by WRICS were reviewed for signalment, history, type of fracture, treatment, and clinical and radiological follow-up. The angle of the fracture line (ANG) was measured on dental radiographs. A mandibular injury severity score (MISS) and a dental injury score (DIS) were evaluated as potential prognostic factors. Fractures most commonly involved P4-M1 (56%), and healed in a mean time of 2.37 ± 0.7 months. Healing was slower (P = .012) if teeth were present in the fracture line and required extraction, hemisection, or root canal therapy prior to WRICS placement (2.39 ± 0.7 months) than if no dental treatment was required (1.46 ± 0.8 months). Contrary to the MISS, the DIS was associated with longer time to bone healing (P = .001; r = .63) and risk of complications (P = .004). Bone healing time was decreased (P = .003; r = .61) with increasing fracture angles. WRICS can be considered to treat mandibular body fractures in small breed dogs if the fracture is not severely comminuted, and if at least the canine and first molar tooth can be used for anchorage. More severe lesions, such as those with teeth in the fracture line and a shorter fracture surface, are associated with prolonged bone healing.


Simulated annealing algorithm for binary phase only filters in pattern classification.
A binary phase only filter is encoded with a simulated annealing algorithm to classify two similar characters in a variety of fonts. Characters that cannot be distinguished with conventional filter encoding methods are clearly distinguished with the optimized binary phase only filter using a simulated annealing algorithm. This method gives zero error classification rate for tested characters. Correlation performance of the optimized binary phase only filter is compared with the binary phase only filters encoded with conventional methods. The computational requirements for optimizing the filter are not excessive.


Prevalence and Prognostic Impact of Diabetes in Takotsubo Syndrome: Insights From the International, Multicenter GEIST Registry.
In view of low prevalence rates, diabetes is discussed as a protective factor for the occurrence of Takotsubo syndrome (TTS). Furthermore, it was associated with improved outcome in a small single-center analysis. Therefore, this study assessed the prevalence and prognostic relevance of concomitant diabetes in TTS. A total of 826 patients with TTS were enrolled in an international, multicenter, registry-based study (eight centers in Italy and Germany). All-cause mortality was compared between patients with diabetes and patients without diabetes, and the independent predictive value of diabetes was evaluated in multivariate regression analysis. The prevalence of diabetes was 21.1% (n = 174). TTS patients with diabetes were older (P < 0.001), were more frequently male (P = 0.003), had a higher prevalence of hypertension (P < 0.001), physical triggers (P = 0.041), and typical apical ballooning (P = 0.010), had a lower left ventricular ejection fraction (P = 0.008), had a higher rate of pulmonary edema (P = 0.032), and had a longer hospital stay (P = 0.009). However, 28-day all-cause mortality did not differ between patients with diabetes and patients without diabetes (6.4% vs. 5.7%; hazard ratio [HR] 1.11 [95% CI 0.55-2.25]; P = 0.772). Longer-term follow-up after a median of 2.5 years revealed a significantly higher mortality among TTS patients with diabetes (31.4% vs. 16.5%; P < 0.001), and multivariate regression analysis identified diabetes as an independent predictor of adverse outcome (HR 1.66 [95% CI 1.16-2.39]; P = 0.006). Diabetes is not uncommon in patients with TTS, is associated with increased longer-term mortality rates, and is an independent predictor of adverse outcome irrespective of additional risk factors.


Building Career Paths for Ph.D., Basic and Translational Scientists in Clinical Departments in the United States: An Official American Thoracic Society Workshop Report.
Rationale: To identify barriers and opportunities for Ph.D., basic and translational scientists to be fully integrated into clinical units. Objectives: In 2022, an ad hoc committee of the American Thoracic Society developed a project proposal and workshop to identify opportunities and barriers for scientists who do not practice medicine to develop successful careers and achieve tenure-track faculty positions in clinical departments and divisions within academic medical centers (AMCs) in the United States. Methods: This document focuses on results from a survey of adult and pediatric pulmonary, critical care, and sleep medicine division chiefs as well as a survey of workshop participants, including faculty in departmental and school leadership roles in both basic science and clinical units within U.S. AMCs. Results: We conclude that full integration of non-clinically practicing basic and translational scientists into the clinical units, in addition to their traditional placements in basic science units, best serves the tripartite mission of AMCs to provide care, perform research, and educate the next generation. Evidence suggests clinical units do employ Ph.D. scientists in large numbers, but these faculty are often hired into non-tenure track positions, which do not provide the salary support, start-up funds, research independence, or space often associated with hiring in basic science units within the same institution. These barriers to success of Ph.D. faculty in clinical units are largely financial. Conclusions: Our recommendation is for AMCs to consider and explore some of our proposed strategies to accomplish the goal of integrating basic and translational scientists into clinical units in a meaningful way.


Experiences about HIV-AIDS preventive-control activities. Discourses from non-governmental organizations professionals and users.
The main aim of this study was to identify the experiences of professionals in nongovernmental organizations (NGO) in Catalonia (Spain) working in HIV/AIDS prevention and control activities and potential areas of improvement of these activities and their evaluation. A further aim was to characterize the experiences, knowledge and practices of users of these organizations with regard to HIV infection and its prevention. A phenomenological qualitative study was conducted with the participation of both professionals and users of Catalan nongovernmental organizations (NGO) working in HIV/AIDS. Theoretical sampling (professional) and opportunistic sampling (users) were performed. To collect information, the following techniques were used: four focus groups and one triangular group (professionals), 22 semi-structured interviews, and two observations (users). A thematic interpretive content analysis was conducted by three analysts. The professionals of nongovernmental organizations working in HIV/AIDS adopted a holistic approach in their activities, maintained confidentiality, had cultural and professional competence and followed the principles of equality and empathy. The users of these organizations had knowledge of HIV/AIDS and understood the risk of infection. However, a gap was found between knowledge, attitudes and behavior. NGO offer distinct activities adapted to users' needs. Professionals emphasize the need for support and improvement of planning and implementation of current assessment. The preventive activities of these HIV/AIDS organizations are based on a participatory health education model adjusted to people's needs and focused on empowerment.