Update on the role of exercise in cystic fibrosis.
The role of exercise in patients with cystic fibrosis has been recognized for as long as cystic fibrosis has been identified as a clinical syndrome, as exercise intolerance has always been a hallmark of disease progression. Work published in the past year has shed new light on several aspects of this field, including physiologic responses to exercise, responses to exercise programs, and the epidemiologic and prognostic implications of activity and exercise testing. Barker's work is perhaps the most compelling, as it highlights the overwhelming interest and belief in the utility of exercise testing and prescription among cystic fibrosis physicians and the contrasting paucity of programs that test their patients and prescribe exercise for them. More studies are needed to identify the form of exercise programs and tests that are most likely to be effective and to be used by cystic fibrosis centers and patients.


Experiences of discrimination among Black middle school adolescents: A qualitative study.
Discrimination is a common experience among racially and ethnically minoritized (REM) youth and often results in negative health and psychological outcomes. However, few studies provide adolescents with opportunities to directly share their discriminatory experiences, especially within the school context. Using a critical race theory framework and phenomenological approach, the present study explored how Black middle school students experienced and responded to discrimination in school settings. Findings revealed that youth experienced both direct and vicarious discrimination at school from multiple sources. Additionally, their responses indicated developmental and adaptive challenges, as well as a nuanced understanding of discrimination in their daily lives. Implications regarding educators' roles in affirming and supporting Black students' experiences are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


In vitro evidence for impaired cellular immune responsiveness in children with chronic renal failure.
We used mixed lymphocyte culture (MLC) as an assay to evaluate in vitro the cellular immune functions of children with chronic renal insufficiency (CRI) or with chronic renal failure (CRF). The proliferative response of lymphocytes from both groups of patients was significantly reduced as compared to the response of control individuals. In addition, the proliferative response of CRF patients treated with hemodialysis was significantly lower than the response of continuous ambulatorial peritoneal dialysis (CAPD) patients. These data confirm that a marked depression of the cellular immune response is detectable in a pediatric population, as predicted from data from the literature on the adult renal failure population.


Time interval between onset of mitral inflow and onset of early diastolic velocity by tissue Doppler: a novel index of left ventricular relaxation: experimental studies and clinical application.
The goal of this study was to examine the diagnostic utility of the time to onset of early (Ea) diastolic velocity of the mitral annulus by tissue Doppler (TD) in comparison with the time to onset of mitral inflow (T(Ea-E)) for the assessment of left ventricular (LV) relaxation. Tissue Doppler imaging of the mitral annulus provides useful information about myocardial function. So far, studies have focused on the measurement of peak Ea, but have not evaluated the diagnostic utility of the time to onset of Ea. Simultaneous left heart catheterization and Doppler echocardiography (DE) were performed in 10 dogs. Left atrial pressures and LV volumes and pressures were measured before and after constriction of the circumflex (cx) coronary artery. The delay in Ea was next examined in 60 consecutive patients, undergoing simultaneous right heart catheterization and DE. Furthermore, (T(Ea-E)) was used to predict filling pressures in a prospective group of 33 patients. In canine studies, significant prolongation in the time interval (T(Ea-E)) was noted after cx constriction, which had a significant relation with tau (tau) (r = 0.93, p < 0.01). In human studies, Ea was significantly delayed in patients with impaired relaxation and pseudonormal LV filling in comparison with age-matched controls. In the prospective group, pulmonary capillary wedge pressure (PCWP) derived as: PCWP(Doppler) = LV(end-systolic pressure) x e(-IVRT/(T(Ea-E))), where IVRT is isovolumetric relaxation time; PCWP(Doppler) related well to PCWP(catheter) (r = 0.84, p < 0.001). T(Ea-E) is a useful novel index of LV relaxation. It can be used to identify patients with diastolic dysfunction and predict PCWP.


[Identification of transthyretin posttranslational modifications 1n human blood using mass-spectrometric methods].
Transthyretin, one of the major plasma proteins, has a number of posttranslational modifications and mutations, some of which are associated with the development of severe diseases, for instance, familial amyloid neuropathy and Alzheimer's disease. In order to investigate the role of modified forms in the development of these diseases a complex analytical platform, based on two mass-spectrometric approaches (bottom-up and op-down) has been developed. The high efficiency of this method was shown using 10 plasma samples obtained from patients with Alzheimer's disease and healthy individuals.


Dexrazoxane has no impact on sensitivity of childhood leukemic blasts to daunorubicin.
Dexrazoxane (DEX) prevents the formation of free radical, lipid peroxidation and cardiotoxicity caused by anthracyclines. Due to a concern about its possible interference with anthracyclin cytotoxicity, the in vitro effect of DEX on daunorubicin (DNR) cytotoxicity, cell cycle and induction of apoptosis by annexin-V was investigated. The sensitivity to DEX, DNR and their combination was tested by the MTT assay in human promyelocytic leukemia HL-60, the erythroid blast crisis CML K562 cell lines and in 45 children with ALL and AML. Cell cycle analysis and annexin-V expression were performed by flow cytometry. It has been observed that DEX itself weakly, but significantly caused cytotoxicity in both cell lines and in patient samples, especially in initial ALL samples. DEX sensitized K562 and HL60, but not patient samples, to cytotoxicity of DNR. The percentage of necrotic/apoptotic cells, as detected in cell cycle analysis and annexin V staining, was higher after exposure to DEX +/- DNR, when compared to respective samples not treated with DEX, in both cell lines but not in patient samples. Expression of annexin V induced by DEX in both cell lines was enlarged, regardless of the presence of DNR. This difference was not observed in patient samples, however, the number of cells expressing annexin V was higher after exposure to DEX +/- DNR in comparison to respective samples not treated with DEX. In conclusion, it seems that DEX possibly has no impact on the sensitivity of childhood leukemic blasts to DNR, however, has weak cytotoxic properties itself.


circMMD reduction following tumor treating fields inhibits glioblastoma progression through FUBP1/FIR/DVL1 and miR-15b-5p/FZD6 signaling.
Tumor treating fields (TTF) is the latest treatment for GBM. Circular RNA (circRNA) has been demonstrated to play critical roles in tumorigenesis. However, the molecular mechanism of TTF remained largely unknown and the role of circRNA in TTF was not reported. The aim of this study was to elucidate the role and mechanism of circMMD in TTF treatment of GBM. Divergent primer was designed to verify the existence of circMMD in GBM cells. The prognostic role of circMMD was explored in glioma specimens. The knockdown and overexpressed plasmids were used to evaluate the effect of circMMD on GBM cell proliferation and TTF efficacy. RNA pull-down and RNA immunoprecipitation were performed to identify binding proteins of circMMD. Subcutaneous and intracranial tumor models were established to validate findings in vivo. The expression of circMMD was elevated in GBM and its high expression indicated poor prognoses. TTF intervention could reduce circMMD synthesis, which suppressed GBM proliferation and increased TTF-mediated apoptosis. The reduction of circMMD promoted the interaction between FUBP1 and FIR, which decreased DVL1 transcription. Meanwhile, decreased circMMD would promote the activity of miR-15b-5p to degrade FZD6. Finally, the diminished expression of DVL1 and FZD6 expression suppressed the activation of Wnt/β-catenin pathway. Our study revealed a novel mechanism of TTF that TTF-mediated reduction of circMMD could inhibit Wnt/β-catenin pathway to suppress GBM proliferation.


Methionine aminopeptidase 2 is a new target for the metastasis-associated protein, S100A4.
S100A4 is an EF-hand type calcium-binding protein that regulates tumor metastasis and a variety of cellular processes via interaction with different target proteins. Here we report that S100A4 physically interacts with methionine aminopeptidase 2 (MetAP2), the primary target for potent angiogenesis inhibitors, fumagillin and ovalicin. Using a yeast two-hybrid screen, S100A4 was found to interact with the N-terminal half of MetAP2. In vitro pull-down assays showed that S100A4 associates with MetAP2 in a calcium-dependent manner. In addition, the binding site of S100A4 was found located within the region between amino acid residues 170 and 229 of MetAP2. In vivo interaction of S100A4 with MetAP2 was verified by co-immunoprecipitation analysis. Immunofluorescent staining revealed that S100A4 and MetAP2 were co-localized in both quiescent and basic fibroblast growth factor-treated murine endothelial MSS31 cells, in the latter of which a significant change of intracellular distribution of both proteins was observed. Although the binding of S100A4 did not affect the in vitro methionine aminopeptidase activity of MetAP2, the cytochemical observation suggests a possible involvement of S100A4 in the regulation of MetAP2 activity through changing its localization, thereby modulating the N-terminal methionine processing of nascent substrates. These results may offer an essential clue for understanding the functional role of S100A4 in regulating endothelial cell growth and tumor metastasis.


Fabrication of self-assembling D-form peptide nanofiber scaffold d-EAK16 for rapid hemostasis.
We previously reported a class of designer self-assembling peptides that form 3-dimensional nanofiber scaffolds using only l-amino acids. Here we report that using d-amino acids, the chiral self-assembling peptide d-EAK16 also forms 3-dimensional nanofiber scaffold that is indistinguishable from its counterpart l-EAK16. These chiral peptides containing all d-amino acids, d-EAK16, self-assemble into well-ordered nanofibers. However with alternating d- and l-amino acids, EAK16 and EAK16, showed poor self-assembling properties. To fully understand individual molecular building blocks and their structures, assembly properties and dynamic behaviors for rapid hemostasis, we used circular dichroism, atomic force microscopy and scanning electron microscopy to study in detail the peptides. We also used rheological measurement to study the hydrogel gelation property. Furthermore, we used an erythrocyte-agglutination test and a rabbit liver wound healing model, particularly in the transverse rabbit liver experiments, to examine rapid hemostasis. We showed that 1% d-EAK16 for the liver wound hemostasis took ∼20 s, but using 1% of EAK16 and EAK16 that have alternating chiral d- and l-amino acids took ∼70 and ∼80 s, respectively. We here propose a plausible model not only to provide insights in understanding the chiral assembly properties for rapid hemostasis, but also to aid in further design of self-assembling d-form peptide scaffolds for clinical applications.


An allosteric circuit in caspase-1.
Structural studies of caspase-1 reveal that the dimeric thiol protease can exist in two states: in an on-state, when the active site is occupied, or in an off-state, when the active site is empty or when the enzyme is bound by a synthetic allosteric ligand at the dimer interface approximately 15 A from the active site. A network of 21 hydrogen bonds from nine side chains connecting the active and allosteric sites change partners when going between the on-state and the off-state. Alanine-scanning mutagenesis of these nine side chains shows that only two of them-Arg286 and Glu390, which form a salt bridge-have major effects, causing 100- to 200-fold reductions in catalytic efficiency (k(cat)/K(m)). Two neighbors, Ser332 and Ser339, have minor effects, causing 4- to 7-fold reductions. A more detailed mutational analysis reveals that the enzyme is especially sensitive to substitutions of the salt bridge: even a homologous R286K substitution causes a 150-fold reduction in k(cat)/K(m). X-ray crystal structures of these variants suggest the importance of both the salt bridge interaction and the coordination of solvent water molecules near the allosteric binding pocket. Thus, only a small subset of side chains from the larger hydrogen bonding network is critical for activity. These form a contiguous set of interactions that run from one active site through the allosteric site at the dimer interface and onto the second active site. This subset constitutes a functional allosteric circuit or "hot wire" that promotes site-to-site coupling.


Avulsed Nasoenteric Bridle System Magnet as an Intranasal Foreign Body.
Nasoenteric tubes provide short-term nutrition support to patients unable to take an adequate oral diet. Bridling systems may be used to secure tubes to guard against displacement. We present the first case of an avulsed magnet from a bridling system to raise awareness of this potential complication. The primary methods of securing a nasogastric tube are reviewed, and comparative assessment of the 3 main systems is presented. Diagnosis and management of nasal foreign bodies relevant to this case are reviewed and prevention/safety considerations discussed.


Mitochondrial-derived vesicles in skeletal muscle remodeling and adaptation.
Mitochondrial remodeling is crucial to meet the bioenergetic demand to support muscle contractile activity during daily tasks and muscle regeneration following injury. A set of mitochondrial quality control (MQC) processes, including mitochondrial biogenesis, dynamics, and mitophagy, are in place to maintain a well-functioning mitochondrial network and support muscle regeneration. Alterations in any of these pathways compromises mitochondrial quality and may potentially lead to impaired myogenesis, defective muscle regeneration, and ultimately loss of muscle function. Among MQC processes, mitophagy has gained special attention for its implication in the clearance of dysfunctional mitochondria via crosstalk with the endo-lysosomal system, a major cell degradative route. Along this pathway, additional opportunities for mitochondrial disposal have been identified that may also signal at the systemic level. This communication occurs via inclusion of mitochondrial components within membranous shuttles named mitochondrial-derived vesicles (MDVs). Here, we discuss MDV generation and release as a mitophagy-complementing route for the maintenance of mitochondrial homeostasis in skeletal myocytes. We also illustrate the possible role of muscle-derived MDVs in immune signaling during muscle remodeling and adaptation.


Endotoxin-induced suppression of pulmonary antibacterial defenses against Staphylococcus aureus.
In order to evaluate the effect of endotoxin on lung host defenses, Sprague-Dawley rats were intravenously injected with either placebo or 5 mg/kg of Escherichia coli lipopolysaccharide B. Two hours after treatment, animals were challenged with Staphylococcus aureus by either low dose aerosol inhalation or high dose intratracheal instillation of the bacteria into the lungs. Quantitative lung bacteriologic examination and bronchoalveolar lavage (BAL) for total and differential cell counts were performed immediately (zero hour) and at 4 h after bacterial challenge. Lung phagocytic defenses against aerosolized S. aureus challenges are provided solely by the alveolar macrophage (AM) in the absence of inflammation. In aerosol-challenged control rats, 20.6 +/- 2.0% of the initial deposited bacterial challenge remained viable in the lung at 4 h. Animals pretreated with endotoxin, however, showed a significant decrease in pulmonary bactericidal activity (31.3 +/- 3.4% bacteria remaining at 4 h), indicating a defect in alveolar macrophage (AM) function. Further assessment of the bactericidal oxidative metabolism of endotoxin-treated AM by luminol-enhanced chemiluminescence indicated an increased production of free radical oxygen species when compared with control nontreated cells in both the unstimulated (66 +/- 4 versus 38 +/- 7 x 10(3) cpm in control) and stimulated (250.5 +/- 17.1 versus 147.1 +/- 6.2 x 10(3) cpm in control) states. Total and differential cell counts in both control and endotoxin-treated aerosol-challenged rats were similar.(ABSTRACT TRUNCATED AT 250 WORDS)


A ten years experience on diagnosis of rickettsial diseases using the indirect immunoperoxidase methods.
An accurate diagnosis of Tsutsugamushi disease (TD) can be made within a few hours after receiving serum specimens by detecting the specific IgG and IgM antibodies in the patient's serum. Using the indirect immunoperoxidase test we found a total of 730 cases of TD in 32 out of 47 prefectures when serum samples from 2,224 cases of suspected disease or fever of unknown origin or from patients with febrile exanthema of unknown cause were examined during a 10 years period (from May 1980 till December 1989). In addition, 27 cases of spotted fever group rickettsial infection were confirmed and one case of African spotted fever group infection was also detected in 1988. Furthermore, possibly the first case of TD was found in People's Republic of Congo (Africa) in 1989.


Consensus Control of Mixed-Order Nonlinear Multiagent Systems: Framework and Case Study.
This article investigates the consensus problem of mixed-order nonlinear multiagent systems (MASs). First, a new research framework of consensus control for MASs with hybrid-order dynamics is established. In this framework, the order of low-order dynamic subsystems is increased to higher-order dynamic subsystems by means of increasing order technology, so that the mixed-order MASs can be changed into the same-order MASs. Thus, the distributed controller of hybrid-order MASs can be designed by using the consensus control method of the same-order MASs. Second, through a case study of a stochastic mixed first- and second-order nonlinear MASs, this article further expounds the design idea of the framework structure and gives the concrete design form of the distributed controller and the stability analysis of the closed-loop system. Finally, simulations are given to verify the effectiveness of the distributed control protocol in this case.


The Next Step in Understanding Impaired Reactive Balance Control in People With Stroke: The Role of Defective Early Automatic Postural Responses.
Postural muscle responses are often impaired after stroke. We aimed to identify the contribution of deficits in very early postural responses to poorer reactive balance capacity, with a particular focus on reactive stepping as a key strategy for avoiding falls. A total of 34 chronic stroke survivors and 17 controls were subjected to translational balance perturbations in 4 directions. We identified the highest perturbation intensity that could be recovered without stepping (single stepping threshold [SST]) and with maximally 1 step (multiple stepping threshold [MST]). We determined onset latencies and response amplitudes of 7 leg muscles bilaterally and identified associations with balance capacity. People with stroke had a lower MST than controls in all directions. Side steps resulted in a higher lateral MST than crossover steps but were less common toward the paretic side. Postural responses were delayed and smaller in amplitude on the paretic side only. We observed the strongest associations between gluteus medius (GLUT) onset and amplitude and MST toward the paretic side ( R2 = 0.33). Electromyographic variables were rather weakly associated with forward and backward MSTs ( R2 = 0.10-0.22) and with SSTs ( R2 = 0.08-0.15). Delayed and reduced paretic postural responses are associated with impaired reactive stepping after stroke. Particularly, fast and vigorous activity of the GLUT is imperative for overcoming large sideways perturbations, presumably because it facilitates the effective use of side steps. Because people with stroke often fall toward the paretic side, this finding indicates an important target for training.


Recent progress in understanding the genetic susceptibility to osteoporosis.
Family and twin studies have established a genetic contribution to the etiology of osteoporosis. The genes and allelic variants conferring osteoporotic risk are largely undefined, but the number of candidates has increased steadily in recent years (Table I). Osteoporosis is a complex disease, and allelic variation in many other candidate-genes including those that encode growth factors, cytokines, calciotropic hormones, and bone matrix proteins are likely to also play a role and warrant systematic investigation. Most family and association studies to date have focused on the genetic contributions to bone density, a major determinant of bone strength and fracture risk. Bone density is not the only determinant of skeletal fragility, however, and genetic influences on fracture risk are independent of bone density [Cummings et al., 1995]. The microarchitectural properties and overall size and geometry of bone also influence skeletal strength [Bouxsein et al., 1996], and the genetic influences on these phenotypes should be investigated more rigorously. Even fewer studies have assessed the association between candidate-gene variation and the risk of fracture, the most important clinical outcome of osteoporosis. Large-scale molecular epidemiologic studies will be increasingly necessary in the future to quantify the relative, absolute and attributable risks of fracture associated with specific genetic variants. Osteoporosis is a complex, multifactorial disease, and most candidate-gene association studies have had limited statistical power to assess gene-gene and gene-environment interaction. Although gender plays an important role in the development of osteoporosis, genetic studies have almost exclusively focused on women, and have not tested whether gender modifies the association between genetic variation and osteoporotic risk. Therefore, future genetic studies will need to recruit larger samples of individuals including men. Rapid additional progress in our understanding of the molecular basis of osteoporosis can be expected in the near future as ongoing genome-wide linkage [Spotila et al., 1996] and candidate-gene association analyses are completed. Linkage analyses in families at high-risk for rare metabolic bone diseases should also yield important clues to the pathogenesis of osteoporosis. Recent examples are the mapping of loci for both high [Johnson et al., 1997] and low [Gong et al., 1996] bone mass to chromosome 11q and osteopetrosis to chromosome 1p [Van Hul et al., 1997]. Similar ongoing studies in baboons [Rogers and Hixson, 1997] and mice [Beamer et al., 1997] may reveal additional loci whose human homologs contribute to osteoporotic risk. The improved understanding of osteoporosis that will emerge from these genetic studies should lead to better diagnosis of this disease and new treatment and prevention strategies.


Pediatric blunt abdominal trauma: current management.
Nonoperative management of pediatric blunt abdominal injury has changed significantly in the last few years. Improved resource utilization in the diagnosis of pediatric abdominal injury has been described. Hemodynamic status, rather than grade of injury, now guides care. Stable patients spend less time in the hospital, return to school upon discharge, and are allowed lower hemoglobin levels prior to transfusion. ICUs are reserved for those with recent or ongoing bleeding, previously unstable patients, or children with concomitant injuries necessitating ICU. Risk factors for failure and evidence for adjuncts to nonoperative management are emerging. Operative management of certain pancreatic injuries may have more favorable outcomes than nonoperative management. Sufficient evidence has become available to radically change the management of pediatric abdominal injury, which is being incorporated into new evidence-based management algorithms.


Islet adaptive changes to fructose-induced insulin resistance: beta-cell mass, glucokinase, glucose metabolism, and insulin secretion.
Beta-cell mass, hexokinase/glucokinase (HK/GK) activity, glucose metabolism and insulin secretion were studied in the islets of rats with fructose-induced insulin resistance (IR). Normal male Wistar rats were fed a standard commercial diet and water without (control, C) or with 10% fructose-rich diet (FRD) for 3 weeks. Blood glucose (strips), triglyceride (commercial kit), and insulin (RIA) levels were measured at the time of death. Glucose-induced insulin release, glucose metabolism ((14)CO(2) and (3)H(2)O production from D-[U-(14)C]- and D-[5-(3)H]-glucose) and HK/GK activity (G-6-P production), transcription (RT-PCR), protein expression (Western blot), and cellular compartmentalization were measured in isolated islets (collagenase digestion). FRD rats presented normoglycemia but impaired glucose tolerance, hypertriglyceridemia, hyperinsulinemia, and increased HOMA-IR index. In these rats, beta-cell mass decreased significantly by 33%, with a 44% increase in the percentage of apoptotic cells. Glucose-induced insulin release and islet glucose metabolism were higher in FRD rats. While GK activity (total and cytosolic fraction) and protein expression were significantly higher in FRD islets, HK showed no change in any of these parameters. Our results demonstrate that the changes induced by dietary-induced IR upon beta-cell function and mass are strongly conditional on the nutrient model used. In our model (intact animals with impaired glucose tolerance), GK activity increases through mechanisms previously shown only in vitro or under highly hyperglycemic conditions. Such an increase plays a pivotal role in the adaptive increased release of insulin in response to IR, even in the presence of marked beta-cell mass reduction.


Microvesicles derived from Alde-Low EPCs support the wound healing capacity of AT-MSCs.
Mesenchymal stem cells (MSCs) are defined as multipotent cells that can give rise to various kinds of differentiated mesenchymal cells, and are thus considered to be useful for clinical therapy. However, the big hurdles of MSC therapy are the inability of MSCs to reach the appropriate tissues or sites with high efficiency and engraftment after transplantation. In this study, we investigated how adipose tissue-derived MSCs (AT-MSCs) improve their homing ability after intravenous injection. We previously found that human endothelial progenitor cells with low aldehyde dehydrogenase activity (Alde-Low EPCs) are suitable for the treatment of ischemic tissues. In addition, we demonstrated that microvesicles (MVs) derived from Alde-Low EPCs possessed the ability to improve the homing ability of non-functional Alde-High EPCs, resulting in wound healing. We initially transfected MVs derived from Alde-Low EPCs (EMVs) to human AT-MSCs, which were originally unable to cure ischemic tissues by intravenous transplantation. Remarkably, AT-MSC transfected EMVs dramatically repaired the ischemic skin flap compared with AT-MSC derived-MV (MMVs) transfected AT-MSCs or control AT-MSCs. We then found that the expression of CXCR4, an important chemokine receptor for cell migration, was highly elevated in EMV-transfected AT-MSCs. Moreover, AT-MSCs transfected with EMVs, but not control AT-MSCs, migrated to wound sites after intravenous injection. Consequently, CD45(+) inflammatory cells were successfully recruited at the wound sites after the injection of EMV-transfected AT-MSCs. These results demonstrate that EMVs are a useful source to improve the homing ability and wound healing ability of MSCs at the wound sites.


A bootstrap approach to evaluating person and item fit to the Rasch model.
Historically, rule-of-thumb critical values have been employed for interpreting fit statistics that depict anomalous person and item response patterns in applications of the Rasch model. Unfortunately, prior research has shown that these values are not appropriate in many contexts. This article introduces a bootstrap procedure for identifying reasonable critical values for Rasch fit statistics and compares the results of that procedure to applications of rule-of-thumb critical values for three example datasets. The results indicate that rule-of-thumb values may over- or under-identify the number of misfitting items or persons.


Family partnership in care: integrating families into the coronary intensive care unit.
Since the introduction of Family Partnership in Care in the CICU and other pilot units, many changes have been made. Education sessions are now unit specific rather than in groups with multiple units. This facilitates the discussion of unit-specific educational and implementation needs. In addition, unit-specific sessions allow for some case scenario/role playing activities to facilitate learning and application of the FPCP elements to the unique culture of the unit. Finally, less emphasis is placed on the documentation, while greater emphasis is placed on the philosophy behind the program and the nurses values and attitudes towards families. Overall, the implementation of the FPCP in CICU has had a positive impact on staff and patients. Staff awareness regarding the importance of involving family in the patient's care and the benefits of this has been heightened. Staff who were initially very skeptical have become strong advocates for the program. The successful shift with families in "doing for" to "working with" has enhanced the professional practice of many nursing staff and contributed to the overall unit functioning. Finally, the feedback from patients and their care partners and the independence and informed decision-making fostered by designing a plan of care with staff validates the importance of this program in a critical care area.


Methodological problems in the study of contagious yawning.
The recent interest in contagious yawning has raised several challenges as the varied methods of testing have left some unresolved issues. We do not know how differences in key variables affect the observed rates of yawning, and we highlight these as being in need of direct testing. Different researchers analyze their results differently, and we make some recommendations for more rigorous, thorough and informative analyses. Ultimately, problems arise when authors compare studies that used different methods and different analyses without acknowledging how these differences may have affected the results. In these cases, authors make inappropriate comparisons, which lead to conclusions that add confusion to the literature. Our goal in raising awareness of these issues is to generate new experiments and improve the discussion of existing research. With its link to empathy, a more standardized study of contagious yawning may be a useful tool for a variety of disciplines.


Clinical trials and primary breast cancer. The therapeutic implications.
The therapeutic cure of breast cancer involves local and metastatic control. In the past they have been conceptually separated with local control being considered the focus for primary therapy and metastatic control an issue only at the time of relapse. With new understanding of tumor cell biology and the natural history of breast cancer, it has been recognized that the two issues cannot be easily separated. The emotionalism that has accompanied breast cancer research, and its results, both within the oncologic community, and in the public mind, have made the design, interpretation, and analysis of breast cancer trials a difficult area. The author reviews the existing clinical trial literature base in primary therapy and attempts to develop its therapeutic implications.


The frequency of human papillomavirus infection in polish patients with vulvar squamous cell carcinoma.
Vulvar cancer is a rare condition representing about 4% of all female genital tract tumors. In contrast to the established relationship of virtually all cervical cancer cases with the human papillomavirus (HPV) infection, the reported HPV positivity in vulvar carcinoma ranges widely. Using the Linear Array HPV Genotyping Test, we investigated the HPV incidence in a group of 46 Polish patients with vulvar squamous cell carcinoma (age range, 37-93 years; median age, 70.2 years) in clinical stages T1-2, N0-2, and M0. The presence of HPV DNA was confirmed in 7 of 46 (15%) primary tumor samples. HPV 16 was found in 5 tumors (71%). HPVs 6 and 58 were detected in the remaining 2 cases of virus-associated tumors. We conclude that a fraction of cancers of vulva associated with HPV is insignificant, given the HPV prevalence of 8.6% in the Polish population aged 55 to 59 years (the oldest cohort of Polish women studied to date).


Depression Induced by CUMS Leads to Bladder Cancer Development and Local Tumor Immunosuppression in Mice.
Depression is a common mental disease in bladder cancer patients, leading to a loss of happiness, an increase in the suicide rate, and higher mortality. However, the influence of depression on bladder tumor tissue remains unknown. In this current study, a subcutaneous bladder cancer xenograft model was established on male C57 mice with mouse bladder cell line MB49. Chronic unpredictable mild stress (CUMS) was established to simulate depression in bladder cancer patients. The depression caused by CUMS was confirmed by testing sucrose preference and plasma cortisol and adrenocorticotropic hormone (ACTH) levels. Then, we measured and weighed tumors to demonstrate the promotion of tumor growth by CUMS. Immune-related cells and molecules were examined to reveal the mechanism. There is a significant decrease of CD8+/CD4+T cells ratio, NK cells, IL-2, and IFN-γ and a significant increase of T regs, IL-6, IL-1β, TNF-α, IL-10, and PGE2 in CUMS group, indicating the inhibition of immunity in the tumor microenvironment. Our results supported the perspective that depression exacerbated bladder cancer and revealed a possible mechanism. We suggest attaching importance to the psychological health of bladder cancer patients to prevent a worse prognosis induced by depression.


Organization of the cytoskeleton and the focal contacts of bovine aortic endothelial cells cultured on type I and III collagen.
We investigated the organization of the cytoskeleton and the focal contacts of bovine aortic endothelial cells cultured on type I and III collagen. The influence of these collagens on cell morphology and the distribution pattern of actin, vimentin, talin, and vinculin was analyzed by light microscopy, conventional electron microscopy, immunofluorescence, and immunogold labeling after lysis-squirting. Whereas the morphology of the endothelial cells is not markedly influenced, the structure of the cytoskeleton and the focal contacts of the cells are altered by the different collagen types. Stress fibers are more distinct in cells grown on type I collagen; cells on type III collagen show a more diffuse distribution of actin molecules. Intermediate filaments seem not to be affected by the collagens. The areas of focal contacts are larger in cells on type I collagen. Additionally, the labeling pattern of talin and vinculin is denser in focal contacts of cells grown on type I collagen. These results suggest an important role of the type of collagen in mediation of the organization of the microfilament system and the adhesion structures of bovine aortic endothelial cells in culture.


Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts.
The multifaceted interactions between gastrointestinal (GI) helminth parasites, host gut microbiota and immune system are emerging as a key area of research within the field of host-parasite relationships. In spite of the plethora of data available on the impact that GI helminths exert on the composition of the gut microflora, whether alterations of microbial profiles are caused by direct parasite-bacteria interactions or, indirectly, by alterations of the GI environment (e.g. mucosal immunity) remains to be determined. Furthermore, no data is thus far available on the downstream roles that qualitative and quantitative changes in gut microbial composition play in the overall pathophysiology of parasite infection and disease. In this study, we investigated the fluctuations in microbiota composition and local immune microenvironment of sheep vaccinated against, and experimentally infected with, the 'brown stomach worm' Teladorsagia circumcincta, a parasite of worldwide socio-economic significance. We compared the faecal microbial profiles of vaccinated and subsequently infected sheep with those obtained from groups of unvaccinated/infected and unvaccinated/uninfected animals. We show that alterations of gut microbial composition are associated mainly with parasite infection, and that this involves the expansion of populations of bacteria with known pro-inflammatory properties that may contribute to the immunopathology of helminth disease. Using novel quantitative approaches for the analysis of confocal microscopy-derived images, we also show that gastric tissue infiltration of T cells is driven by parasitic infection rather than anti-helminth vaccination. Teladorsagia circumcincta infection leads to an expansion of potentially pro-inflammatory gut microbial species and abomasal T cells. This data paves the way for future experiments aimed to determine the contribution of the gut flora to the pathophysiology of parasitic disease, with the ultimate aim to design and develop novel treatment/control strategies focused on preventing and/or restricting bacterial-mediated inflammation upon infection by GI helminths. Video Abstract.


One-year follow-up of a multifocal intraocular lens with optimized elevated phase shift.
To evaluate the standard outcomes of a multifocal intraocular lens (mIOL) with optimized elevated phase shift (EPS). Qvision, Ophthalmology Department, VITHAS Almería, Spain. Retrospective observational. 41 patients, consecutively operated on cataracts or refractive lens exchange with the implantation of the Liberty 640PM (EPS 2.0) and followed during 12 months, were included in the analysis. Retrieved variables were visual acuities at far, intermediate, and near distances; defocus curves (VADC); and prediction error of 4 formulas optimized for IOLMaster 500 and Pentacam AXL Wave. Patient-reported outcomes were also obtained for assessing spectacle independence, satisfaction, bothersome to dysphotopsia, difficulties in daily life tasks, and decision to be operated with the same mIOL. The median monocular efficacy with best distance correction was 0, 0.1, and 0.1 logMAR at far, intermediate, and near distances, respectively, with patients achieving binocularly a median of 0 logMAR at the 3 distances. VADC showed a depth of field of 3 diopters (D) above 0.2 logMAR with a median increase of 0.07 logMAR from -1.5 to -2.5 D. Complete spectacle independence was achieved at far distance, whereas 97.6% and 85.4% was achieved at intermediate and near distances, respectively. 7.3% of patients were bothered by dysphotopsia, and 92.6% of patients were likely to be operated again. EPS 2.0 restored patients' vision in the full range of the depth of field with a nearly monotone decrease of visual performance from far to near, achieving high rates of spectacle independence at all distances and with low positive dysphotopsia rates ( ClinicalTrials.gov Identifier: NCT05735990).


Antihypertensive efficacy of nicardipine-based treatment in patients of different age and in patients with isolated systolic hypertension.
The relationship between age and the antihypertensive efficacy of calcium antagonists has been investigated by different authors with conflicting results. In order to evaluate this relationship an Italian multicentre study investigated 2184 patients with mild to moderate hypertension with an age range of 24-90 years. Initial treatment consisted of nicardipine monotherapy (daily dose 40-80 mg/day in two or three oral administrations); after 4 weeks other antihypertensive agents could be added in non-responders (seated blood pressure greater than 160/95 mmHg). The patients were divided into four groups according to age (less than or equal to 55 years, 56-65 years, 66-75 years and greater than 75 years). Nicardipine-based treatment reduced systolic and diastolic blood pressures to similar levels independently of the age of the patients. The correlation between systolic blood pressure reduction and age was only 0.141 (NS). The percentage of patients treated with nicardipine monotherapy was similar in all age groups, but the incidence of side effects, mostly transient and mild, was lower in older than in younger patients. In patients older than 65 years with isolated systolic hypertension (systolic pressure greater than 160 and diastolic pressure less than 90 mmHg), nicardipine-based therapy significantly lowered systolic blood pressure only from 180 +/- 11/87 +/- 6 to 148 +/- 14/84 +/- 8 mmHg.


A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type.
Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group ( http://www.emsa-sg.org ), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson's disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.


Prognosis for recovery of function in acute renal failure. Value of the renal image obtained using iodohippurate sodium I 131.
Twenty-four survivors of acute, nonobstructive, nonnephritic renal failure had a renal scan using iodohippurate sodium I 131 performed early in the acute illness. Scans were judged according to whether the renal images were prominent, faint, or absent during the first 30 minutes after intravenous injection of 100 to 250 microcuries of iodohippurate sodium I 131. All ten patients with prominent renal images attained life-sustaining renal function with an average postrecovery creatinine clearance of 80 ml/min. Of the seven patients with faint renal images, six recovered life-sustaining renal function (average creatinine clearance of 39 ml/min), and one required chronic hemodialysis. Seven patients had no renal image initially; four recovered life-sustaining renal function with an average creatinine clearance of 25 ml/min; three required chronic hemodialysis. We conclude that, for patients with acute renal failure, the appearance of the renal image obtained using this substance is an important indicator of renal viability and of the likelihood for functional recovery.


Repeated local ellipsoid protrusion supplements HLA surface characterization.
Allorecognition of donor HLA is a major risk factor for long-term kidney graft survival. Although several molecular matching algorithms have been proposed that compare physiochemical and structural features of the donors' and recipients' HLA proteins in order to predict their compatibility, the exact underlying mechanisms are still not fully understood. We hypothesized that the ElliPro approach of single ellipsoid fitting and protrusion ranking lacks sensitivity for the characteristic shape of HLA molecules and developed a prediction pipeline named Snowball that is fitting smaller ellipsoids iteratively to substructures. Aggregated protrusion ranks of locally fitted ellipsoids were calculated for 712 publicly available HLA structures and 78 predicted structures using AlphaFold 2. Amino-acid sequence and protrusion ranks were used to train deep neural network predictors to infer protrusion ranks for all known HLA sequences. Snowball protrusion ranks appear to be more sensitive than ElliPro scores in fine parts of the HLA such as the helix structures forming the HLA binding groove in particular when the ellipsoids are fitted to substructures considering atoms within a 15 Å radius. A cloud-based web service was implemented based on amino-acid matching considering both protein- and position-specific surface area and protrusion ranks extending the previously presented Snowflake prediction pipeline.


A Biologically-Based Computational Approach to Drug Repurposing for Anthrax Infection.
Developing drugs to treat the toxic effects of lethal toxin (LT) and edema toxin (ET) produced by B. anthracis is of global interest. We utilized a computational approach to score 474 drugs/compounds for their ability to reverse the toxic effects of anthrax toxins. For each toxin or drug/compound, we constructed an activity network by using its differentially expressed genes, molecular targets, and protein interactions. Gene expression profiles of drugs were obtained from the Connectivity Map and those of anthrax toxins in human alveolar macrophages were obtained from the Gene Expression Omnibus. Drug rankings were based on the ability of a drug/compound's mode of action in the form of a signaling network to reverse the effects of anthrax toxins; literature reports were used to verify the top 10 and bottom 10 drugs/compounds identified. Simvastatin and bepridil with reported in vitro potency for protecting cells from LT and ET toxicities were computationally ranked fourth and eighth. The other top 10 drugs were fenofibrate, dihydroergotamine, cotinine, amantadine, mephenytoin, sotalol, ifosfamide, and mefloquine; literature mining revealed their potential protective effects from LT and ET toxicities. These drugs are worthy of investigation for their therapeutic benefits and might be used in combination with antibiotics for treating B. anthracis infection.


Measurements of tissue polypeptide-specific antigen and prostate-specific antigen in prostate cancer patients under intermittent androgen suppression therapy.
The present study evaluated serial serum measurements of tissue polypeptide-specific antigen (TPS) in comparison with prostate-specific antigen (PSA) for assessment of tumour progression in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Twenty-three men were recruited into an IAS trial consisting of an initial 8 months of androgen suppression, followed by cycles of treatment cessation and resumption of therapy upon increases of PSA > 20 ng ml(-1) to prolong the hormone responsiveness of the tumour cells. Periods of androgen suppression resulted in reversible reduction in serum testosterone (< 1.8 nmol I(-1)) and PSA (< 4 ng ml(-1)) and decreases in tumour volume (mean reduction for first cycle 24 +/- 10%), indicating partial growth arrest and apoptotic regression of the tumours. In contrast to PSA values, non-specifically elevated TPS values were found in 8 of 23 patients. In 15 of 23 patients, TPS fell during periods of apoptotic tumour regression and increased simultaneously with testosterone and preceded the increases in PSA by 2 months during the period of treatment cessation. Although TPS represents a highly sensitive marker of tumour proliferation in this IAS clinical model of controlled tumour regression and regrowth, its low specificity compared with PSA limits its usefulness to monitoring of prostate cancer patients with proven absence of non-specific elevations of this marker.


Oncolytic peptide nanomachine circumvents chemo resistance of renal cell carcinoma.
Due to intrinsic and acquired chemo/radiotherapy-resistance, renal cell carcinoma shows limited therapeutic response to clinically utilized targeting drugs. Here a tumor-activated oncolytic peptide nanomachine is devised to selectively lysing tumor cell membrane without causing drug resistance. Specifically, in the acidic tumor microenvironment, the oncolytic peptide nanomachine automatically activated through morphologically transformation from nanoparticles to nanofibrils with restoring α-helical conformation, which physically bind to tumor cell membrane with multiple (spatially correlated and time-resolved) interactions and subsequently lyse local cell membrane. The IC50 of the oncolytic peptide nanomachine is as low as 2.44 μM and it inhibit up to 90% of tumor cells within 2 h with unique bystander killing effect. In vivo, the tumor inhibition rate of the oncolytic peptide nanomachine is 71% without off-target activity and hemolytic activity. These results support that tumor-selective oncolytic peptide nanomachine represent a promising alternative approach for multidrug-resistant tumor treatments by inducing cell membrane lysis.


Alternative splicing of DNA damage response genes and gastrointestinal cancers.
Alternative splicing, which is a common phenomenon in mammalian genomes, is a fundamental process of gene regulation and contributes to great protein diversity. Alternative splicing events not only occur in the normal gene regulation process but are also closely related to certain diseases including cancer. In this review, we briefly demonstrate the concept of alternative splicing and DNA damage and describe the association of alternative splicing and cancer pathogenesis, focusing on the potential relationship of alternative splicing, DNA damage, and gastrointestinal cancers. We will also discuss whether alternative splicing leads to genetic instability, which is considered to be a driving force for tumorigenesis. Better understanding of the role and mechanism of alternative splicing in tumorigenesis may provide new directions for future cancer studies.


[Visually-guided discrimination and preference of sexuality in female macaque monkeys].
Visual information about face and body including facial expression and bodily behavioral patterns has been known to play an important role in social and emotional communication in monkeys. Its involvement in sexual activity has also been demonstrated in male monkeys but it is poorly understood in female monkeys. In the present study, visually-guided discrimination and preference of sexuality were investigated in female macaque monkeys performing operant bar-press tasks in an experimental cage which had a transparent panel facing a display. In the sex discrimination task, two rhesus monkeys (Macaca mulatta) were trained to discriminate sex of a monkey shown in a picture which was randomly selected from six photographs (three males and three females) and was presented on the display. The monkey pressed a right or left bar for male or female monkey, respectively, to get water as a reward. Under this discrimination task, the monkeys could discriminate the sexes of monkeys shown in newly presented pictures. When choice bars were reversed, correct responses significantly decreased below chance level. In the sex preference task, three rhesus monkeys and three Japanese monkeys (M. juscata) were used. The monkeys voluntarily pressed the bar to watch the video movie showing either male or female rhesus monkeys. The movies were presented as long as the subject kept pressing the bar. The same movie was continued when the monkey pressed the bar again within 10s after the previous release of the bar, while it was changed to the other when 10s passed after the subject released the bar. The total duration of the responses in daily sessions was measured. In this visual preference task, four out of six monkeys showed sex preference. Three adult Japanese monkeys (6-8 y) pressed the bar to watch the video movie of male monkeys which was taken in breeding season with longer duration than that of female monkeys taken in the same season. The other two adult rhesus monkeys (7 8 y) did not show the sexual preference. The one remaining youngest rhesus monkey (5 y) preferred to watch the female movie which was taken in non-breeding season. The visual preference was observed not only in winter but also in summer when tested. The present results suggest that visual information alone is sufficient to discriminate sex and produce sex preference in some female monkeys. The seasonal changes in visual appearance of objects seem to be more determinant factors for the preference than the endogenous factors of subjects.


Characteristics of oligodeoxyribonucleotides that induce interferon (IFN)-alpha in the pig and the phenotype of the IFN-alpha producing cells.
The immunostimulatory effects of oligodeoxyribonucleotides (ODN) containing unmethylated CpG dinucleotides (CpG-ODN) in certain base contexts have been extensively studied in man and mice. One major action is their ability to trigger production of massive amounts of interferon-alpha (IFN-alpha) by plasmacytoid dendritic cells (PDC), also referred to as natural IFN-alpha/beta producing cells (NIPC). The present study using porcine PBMC activated by CpG-ODN or plasmid DNA revealed a considerable variation in the IFN-alpha production in response to various CpG-ODN constructs. Several phosphodiester ODNs, such as 5' TTTTCAATTCGAAGATGAAT 3' (ODN H), and the plasmid pcDNA3 all required pre-incubation with lipofectin in order to induce IFN-alpha. Intact unmethylated CpGs were also important, because methylation or substitution of the cytosines and CpG-inversion strongly reduced the IFN-alpha induction by single- or double-stranded forms of ODN H. Certain CpG-ODNs that contained flanking phosphorothioate or phosphodiester poly-G sequences were potent inducers of IFN-alpha without pre-incubation with lipofectin, for instance the ODN 2216 (5' GGGGGACGATCGTCGGGGGG 3'). While poly-G sequences have been suggested to increase uptake of ODNs by cells, they did not obviate the need for lipofectin when added to the ODN H. However, they resulted in up to five-fold increases of the IFN-alpha levels caused by ODN H upon lipofection, indicating other enhancing effects of poly-G sequences on the induction of IFN-alpha. The identity of the IFN-alpha producing cells (IPC) stimulated by CpG-ODN or plasmid DNA was studied by means of flow cytometry using combined staining for intracellular IFN-alpha and surface markers. Approximately 1-3 IPC/10(3) PBMC were detected, compared to only 3 IPC/10(4) PBMC stimulated by Aujeszky's disease virus. The IPC frequencies were confirmed by detection of IFN-alpha mRNA positive cells by in situ hybridisation. The IPC induced by CpG-ODN or plasmid DNA had a similar phenotype, expressing CD2 and CD4 and intermediate levels of MHC class II and the myeloid marker SWC3, but not the markers of T and B cells or monocytes (CD3, CD21 and CD14). Consequently, porcine IPC that respond to CpG-DNA seem to correspond to the PDC/NIPC.


Smoke yields of tobacco-specific nitrosamines in relation to FTC tar level and cigarette manufacturer: analysis of the Massachusetts Benchmark Study.
This research assessed the relationship between the deliveries of carcinogenic tobacco-specific nitrosamines (TSNAs) and the Federal Trade Commission (FTC) "tar" ratings of US commercial cigarettes. Analysis of covariance (ANCOVA) was used to assess the explanatory power of FTC tar, the particular manufacturer, and other cigarette characteristics to predict the yields of four TSNAs (N'-nitrosonornicotine [NNN], 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone [NNK], N'-nitrosoanatabine [NAT], and N'-nitrosoanabasine [NAB]) in 26 US commercial brands tested in the 1999 Massachusetts Benchmark Study. When FTC tar alone was used to predict TSNA yield, the squared correlation coefficient (R(2)) was only 38% for NNN, 76% for NNK, 46% for NAT, and 49% for NAB. Inclusion of manufacturer-specific variables significantly (p < 0.001) increased the estimated R(2) for three of the four species of nitrosamine to: 78% for NNN, 88% for NNK, and 81% for NAT. Inclusion of other cigarette characteristics (filter type, paper permeability, tobacco weight, tip dilution) did not reduce the significance of the manufacturer-specific effects. Federal Trade Commission nicotine and carbon monoxide (CO) yields were no better at predicting TSNA levels. FTC ratings for tar, nicotine, and carbon monoxide do not tell the entire story about the comparative yields of toxic agents in marketed cigarette brands. The significant manufacturer-specific effects suggest that proprietary blending and processing of tobacco matter as well. Public, brand-by-brand disclosure of the yields of TSNA and possibly other smoke constituents appears to be warranted.


Electrical generation and detection of spin waves in a quantum Hall ferromagnet.
Spin waves are collective excitations of magnetic systems. An attractive setting for studying long-lived spin-wave physics is the quantum Hall (QH) ferromagnet, which forms spontaneously in clean two-dimensional electron systems at low temperature and in a perpendicular magnetic field. We used out-of-equilibrium occupation of QH edge channels in graphene to excite and detect spin waves in magnetically ordered QH states. Our experiments provide direct evidence for long-distance spin-wave propagation through different ferromagnetic phases in the N = 0 Landau level, as well as across the insulating canted antiferromagnetic phase. Our results will enable experimental investigation of the fundamental magnetic properties of these exotic two-dimensional electron systems.


Determination of retinol, alpha-tocopherol, alpha- and beta-carotene by direct extraction of human serum using high performance liquid chromatography.
In this report we describe a modified reverse phase HPLC method that avoids the solvent evaporation step and allows simple and rapid determination of retinol, alpha-tocopherol, alpha-carotene and beta-carotene and achieves complete separation of alpha- and beta-carotene. Retinyl acetate, alpha-tocopheryl acetate and retinyl palmitate in ethanol were added to serum as internal standards. Serum was then deproteinized with an equal volume of ethanol, and the lipid was extracted with ethyl acetate-butanol (1:1 v/v). A portion of this solution was injected into a C18 reverse phase chromatographic column and absorbencies of the vitamins and internal standards were measured at 292 nm for tocopherols, 325 nm for retinoids and 450 nm for carotenoids; peak-height ratios were used to quantify each vitamin. The analytical recoveries for retinol, alpha-tocopherol alpha- and beta-carotene at various concentrations tested were 95-103, 90-98, 92-99 and 94-96%, respectively. The intra- and interassay variations for low and high concentrations of retinol, alpha-tocopherol, alpha- and beta-carotene ranged from 2.4 to 6.7 for intraassay and from 4.3 to 8.5 for interassay replication. The detection limits were 1.25 (0.04), 19 (0.44), 0.35 (0.006) and 0.94 (0.017) micrograms/dL (delta mol/L) for retinol, alpha-tocopherol, alpha- and beta-carotene, respectively.


[Liver damage caused by chronic cadmium poisoning].
A case report is given of a 46 year old person concerned professionally with melting gold, who exhibited bioptically and histologically verified lesions of the liver after chronic intoxication with cadmium. This patient was exposed throughout 8 years during his job activities to cadmium vapors. He exhibited during the time of investigation decreased renal function with tubular proteinuria as well as a polyneuropathy. In addition, hepatic lesions could be found, as small focal necrosis, fatty degeneration and fibrosis. Cadmium content of the liver was increased 13 times above normal.


Solid-State Lithium Metal Battery of Low Capacity Fade Enabled by a Composite Electrolyte with Sulfur-Containing Oligomers.
A solid-state lithium metal battery of low capacity fade is acquired using the electrolyte membrane of a polyurethane-acrylate-thiocarbonate (PUAT) oligomer, macromolecules, lithium salt, and an oxide additive. Two types of composite electrolytes have been prepared: the free-standing electrolyte (PUAT-FS) and the electrode-coated electrolyte (PUAT-EC). Featuring a less PUAT content and a finer granular size, PUAT-FS is less ion-conductive than PUAT-EC; 0.44 mS cm-1 in contrast to 0.51 mS cm-1 at room temperature. Nonetheless, the lithium iron phosphate battery of PUAT-FS is far superior to that of PUAT-EC in terms of cycling stability. When cycled at 0.1C and room temperature, the PUAT-FS battery reaches a maximum discharge capacity of 169.7 mAh g-1 at its 20th cycle and decreases to 141.0 mAh g-1 at the 500th cycle, 83.1% retention. The capacity fading rate of the PUAT-FS battery is 0.034% per cycle at 0.1C, significantly less than that of the PUAT-EC battery, 0.138% per cycle. Other maximum capacities and fading rates of the PUAT-FS battery are 152.5 mAh g-1 and 0.050% per cycle at 0.2C in 800 cycles and 126.1 mAh g-1 and 0.051% per cycle at 0.5C in 1000 cycles. These features of a low fading rate and high capacity are attributed to a balanced ratio of oligomer to macromolecule (1:1 w/w) in the free-standing electrolyte and the sulfur-containing oligomer.


Effect of dietary linoleic acid on the progression of chronic renal failure in rats.
The role of linoleic acid in chronic renal failure (CRF) is controversial. In the present study 21 male Wistar rats submitted to 5/6 renal mass reduction (R) and 16 normal controls (C) were fed a supplement (S) or normal (N) linoleic acid diet for 60 days starting 10 days after CRF. As expected, serum creatinine, cholesterol and triglycerides (mean +/- SEM) were higher in the CRF groups compared to the C groups (P<0.05). The RS group presented lower cholesterol (84 +/- 4 vs 126 +/- 13 mg%) and triglyceride (88 +/- 9 vs 132 +/- 19 mg%) levels compared to the RN group. Proteinuria and kidney weight did not differ between CRF groups. Glomerular area increased 78% in RS and 100% in RN compared to control rats. Glomerular sclerosis index tended to be lower in RS (27%) compared to RN (38%), tubulointerstitial damage was similar between CRF groups (RS = 1.91 +/- 0.2 and RN = 2.14 +/- 0.3), and mesangial fractional volume increased to the same extent in both CRF groups. The data suggest that a linoleic acid-enriched diet did not protect against the progression of CRF after 60 days.


Perceived roughness of 1/f(beta) noise surfaces.
We report results from a new methodology for investigating the visually perceived properties of surface textures. Densely sampled two-dimensional 1/f(beta) noise processes are used to model natural looking surfaces, which are rendered using combined point-source and ambient lighting. Surfaces are shown in motion to provide rich cues to their relief. They are generated in real time to enable observers to dynamically manipulate surface parameters. A method of adjustment is employed to investigate the effects that the two surface parameters, magnitude roll-off factor and RMS height, have on perceived roughness. The results are used to develop an estimation method for perceived roughness.


Ischemic and non-ischemic myocyte damage and antimyosin monoclonal imaging.
Antimyosin monoclonal antibody is a specific marker of impaired sarcolemmal integrity resulting not only from ischemia but also from non-ischemic myocardial injury, such as infection, inflammatory, or immunologic reactions, and alcohol or drug intoxication. In addition, antimyosin accumulation has been demonstrated in some forms of cardiomyopathy with unknown as well as known etiologies. Antimyosin positivity appears to indicate precisely the extent of myocardial necrosis and to reflect cardiac dysfunction in an acute stage of active myocardial damage caused by ischemia and inflammation. However, the correlation is not necessarily good in the chronic stages of the disease or in idiopathic cardiomyopathic hearts; in other words, cardiac antimyosin uptake can be detected even in myocardial tissue with a normal histologic appearance independent of the presence of inflammatory responses, myocyte necrosis, or functional or morphologic deterioration. Thus, antimyosin is useful not only for detecting and quantifying acute myocardial necrosis but also for specifically identifying ongoing or latently progressing myocardial degeneration and sarcolemmal disruption, which will certainly lead to myocardial necrosis. These characteristics may contribute to the early detection of myocardial damage and lead to the investigation of pathophysiologic mechanisms. Further progress in immunologic and radiolabeling techniques is necessary for better specificity and less antigenicity against humans in antimyosin monoclonal antibody imaging.


NK/T cell lymphoma associated with peripheral eosinophilia.
NK/T cell lymphoma, nasal type is an aggressive and uncommon malignancy. Disease that occurs outside of the aerodigestive tract exhibits an even more aggressive clinical behaviour and does not respond as well to conventional therapy compared to its nasal counterpart. We report such a case of NK/T cell lymphoma, nasal type, that presented as an anterior chest wall mass, arising from the left pectoralis muscle. An interesting feature we wish to highlight is the associated eosinophilia that corresponded to disease activity, exhibiting fluctuations with surgical resection and chemotherapy. To the best of our knowledge this is the third reported case of NK/T cell lymphoma that is associated with peripheral eosinophilia. Our case highlights the role of certain NK cell subsets that play a major role in eosinophilic activation in NK/T lymphomas and calls for more research into further classification of this disease by virtue of its NK cell subsets.


[Exogenous H₂O₂ regulated secondary metabolism of Scutellaria baicalensis and enhanced drug quality].
The increasing demand of Chinese materia medica could not be supplied by wild resource, and the cultivated medicinal materials become popular, which led to decreased quality of many medicinal materials due to the difference of the circumstance between the wild and the cultivated. How to improve quality becomes key points of Chinese medicine resource. The leaves of Scutellaria baicalensis were sprayed with H₂O₂, the activities of superoxide dismutase (SOD) and catalase (CAT) changed little, but there had been a marked decrease of peroxidase (POD) and ascorbic oxidase (APX), which showed that the antioxidase system declined. Meanwhile, H₂O₂, as enhanced the expression of phenylalnine ammonialyase (PAL) and β-glucuronidase (GUS) as well as activity of PAL, promoted the biosynthesis and biotransformation of flavonoids. At the day 2 after treated, H₂O₂ of 0.004 μmol·L⁻¹ the contents of the baicalin and the wogonoside decreased slightly, but the contents of the baicalein and the wogonin increased significantly, the baicalein from 0.094% to 0.324%, the wogonin from 0.060% to 0.110%, i. e. increased 246% and 83.3%, respectively.


Alternative stable conformation capable of protein misinteraction links tRNA synthetase to peripheral neuropathy.
While having multiple aminoacyl-tRNA synthetases implicated in Charcot-Marie-Tooth (CMT) disease suggests a common mechanism, a defect in enzymatic activity is not shared among the CMT-causing mutants. Protein misfolding is a common hypothesis underlying the development of many neurological diseases. Its process usually involves an initial reduction in protein stability and then the subsequent oligomerization and aggregation. Here, we study the structural effect of three CMT-causing mutations in tyrosyl-tRNA synthetase (TyrRS or YARS). Through various approaches, we found that the mutations do not induce changes in protein secondary structures, or shared effects on oligomerization state and stability. However, all mutations provide access to a surface masked in the wild-type enzyme, and that access correlates with protein misinteraction. With recent data on another CMT-linked tRNA synthetase, we suggest that an inherent plasticity, engendering the formation of alternative stable conformations capable of aberrant interactions, links the tRNA synthetase family to CMT.


Graduates' development of interprofessional practice capability during their early socialisation into professional roles.
Graduates entering the healthcare workforce can expect to undertake interprofessional practices, requiring them to work at the intersection of knowledge and practice boundaries that have been built over years of socialisation in their respective professions. Yet, in complex health environments, where health challenges go beyond the knowledge and skills of any single profession, there is a growing concern that healthcare practitioners lack capability to collaborate with each other. This article presents the findings from a year-long hermeneutic phenomenological study of graduates' temporal experiences of practice roles in their respective fields of healthcare and in collaboration with other professions. Research findings emerged through an inductive analytic process using thematic analysis techniques and provides an insight into graduates' early professional practice in contemporary healthcare contexts and the development of their professional practice at the interface of professional boundaries. The 18 graduates from six health professions developed their professional practice in working contexts where intersecting professional boundaries resulted in strengthening professional identity in their chosen professions, through articulating distinct knowledge and skills to other professions during collaborative work. Concurrently they established flexible working relationships with members of other professions, resulting in expanding health perspectives and extending practice knowledge and skills beyond their distinct professions. The study provides new understanding of the relationship between areas of professionalism, identity, and collaborative practice in an evolving health workforce, through the experiences of graduates in their early work as registered health practitioners.


[Efficacy of physiotherapy and hygienic procedures in treatment of adults and children with chronic blepharitis and dry eye syndrome].
110 patients aged from 3 to 42 years old were examined to estimate the efficacy of chronic blepharitis treatment: 50 patients with chronic blepharitis and dry eye syndrome (DES), 28 with DES due to computer vision syndrome and 32 with isolated chronic blepharitis. All patients received eyelid massage. If the secretion was too thick and difficult to evacuate from meibomian glands then duct probing was performed. In addition a complex of hygienic procedures was performed using phytoproducts ("Geltec-Medika", Russia): blepharoshampoo, blepharolotion, blepharogel 1 and 2. Moist warm pads (with blepharolotion and calendula extraction) were applied on the eyelids in 25 patients. Massage and probing of meibomian gland ducts and hygienic procedures were showed to be effective in management of clinical signs of chronic blepharitis including coexisting DES. Moist warm pads improve efficacy of background therapy in patients with meibomian gland hypofunction and have no effect in blepharitis with excessive meibomian gland secretion. Eyelid hygiene was showed to be effective in adults and children as well including infants.


Chronic sino-naso-orbital fungal infection due to Pseudallescheria boydii in a nonimmunocompromised host--a case report.
A case of recurrent sino-naso-orbital fungal infection due to Pseudallescheria boydii described in a 28 yrs. old man, who appeared immunocompetent, and was found negative for HIV I and II by ELISA tested on two occasions. The fungal culture was negative. It is very essential to identify P boydii as Miconazole is the only antifungal drug of choice for this fungus. The pathologist plays an important role in identifying this fungus when fungal culture fails to yield the growth. The pathologist has to look for clinching clues such as "intercalary conidia" and "chlamydoconidia" to distinguish P boydii from Aspergillus.


Pulmonary infarction complicating thoracoscopic removal of congenital foregut cyst.
A 42-year old woman presented with rheumatoid arthritis, dyspnoea and a congenital foregut cyst referred by a rheumatologist for thoracic surgery. The cyst was removed by video-assisted thoracoscopic surgery. The patient developed acute haemoptysis in the immediate postoperative period, which necessitated pulmonary resection due to infracted right lower lobe. This case report highlights the complication related to an unusual anatomy of a congenital foregut cyst.


[A comparative analysis of clinical and pathologic diagnoses in 79 pediatric autopsy cases].
This study is a comparative analysis between pathologic and clinical diagnoses of 79 pediatric autopsy cases. We found that 14 cases were misdiagnosed. The rate of misdiagnosis is 17.72%. The 79 cases were divided into four groups of children aged approximately 28 days, approximately 5 years, approximately 10 years and approximately 14 years, the rate of misdiagnosis of the first group is 29.63%. This rate is apparently higher than other age groups(P < 0.05). The younger the age group is, the higher the chances of misdiagnosis. Respiratory disease was the main misdiagnosis rating 42.86%, while the two misdiagnosed cases were found to be tuberculosis. We suggest that doctors be aware of the perinatal factor when they diagnose newborns and try to find out the primary cause of illness, the threat of tuberculosis to children. Pediatricians should heed.


Effect of sire on mu- and m-calpain activity and rate of tenderization as indicated by myofibril fragmentation indices of steaks from Brahman cattle.
The objectives of this study were to assess the influence of sire on mu- and m-calpain activities, to evaluate the relationships of activities of these enzymes to other traits related to beef palatability, and to assess the influence of sire on the rate of tenderization (as measured by myofibril fragmentation index [MFI]) in Brahman longissimus muscle. Brahman calves (n = 87), sired by nine bulls, were born, weaned, fed, and slaughtered in central Florida. Traits evaluated were mu- and m-calpain activities and MFI after 1, 7, 14, and 21 d of aging. Other traits were analyzed to determine their associations with mu- and m-calpain activity and MFI, including calpastatin activity, percentage of raw and cooked lipids, Warner-Bratzler shear force (WBSF) values after 7, 14, and 21 d of aging, and sensory panel rating of tenderness, juiciness, and connective tissue amount after 14 d of aging. Data were analyzed using a model with sire, sex, year, and slaughter group (calves of the same sex slaughtered on the same date) as fixed effects, and adjusted to a constant adjusted 12th-rib fat thickness. Sire affected mu-calpain activity (P < 0.04), calpastatin activity (P < 0.01), d-14 MFI (P < 0.02), d-7 WBSF (P < 0.05), d-14 WBSF (P < 0.04), and sensory panel juiciness score (P < 0.01), but not (P < 0.75) m-calpain activity. Measures of tenderness and palatability were generally moderately to strongly correlated (both simple and residual correlations) with calpastatin and m-calpain activity. Myofibril fragmentation index residuals (adjusted for all model components except sire) after all aging periods were fitted using nonlinear regression to the exponential curve (MFI(i) = kappa0 + kappa1 exp[kappa2 t(i)] + epsilon(i), where t(i) represents aging in days, k0 is ultimate MFI after aging, kappa1 is the difference between initial and ultimate MFI, kappa2 is the rate of increase in MFI, and epsilon(i) is the error term associated with the ith observation, assumed to be independent and identically distributed normally). Sires had different estimates and combinations of estimates, which were used to plot MFI change with time. These curves visually differed for sires and suggested that postmortem tenderization extent and rate differ as well. Use of a combination of these estimated parameters in a selection/carcass sorting program represents an alternative consideration for tenderization improvement programs.


Reduced E-cadherin expression is associated with increased lymph node metastasis and unfavorable prognosis in non-small cell lung cancer.
E-cadherin is a calcium-dependent, epithelial cell adhesion molecule whose reduced expression has been associated with tumor dedifferentiation and increased lymph node metastasis in clinical studies involving several carcinomas. In this study, 111 patients who had previously undergone complete resection and systematic mediastinal lymph node dissection for non-small cell lung cancer (NSCLC) were studied retrospectively. In the primary tumor, as well as in the lymph node metastases, E-cadherin expression was detected by immunohistochemistry using a monoclonal antibody (HECD-1; Takara, Otsu, Japan). There was a significant inverse correlation between E-cadherin expression and lymph node stage (Pearson correlation coefficient -0.52, p = 0.0001) as well as tumor differentiation (Pearson correlation coefficient -0.27, p = 0.005). Moreover, Kaplan and Meier survival estimates showed a significant correlation between E-cadherin expression and patient survival in log rank testing (p = 0.006). In the patient group with the highest proportion of E-cadherin positive tumor cells, 60% of the patients were still estimated to be alive at 36 mo, versus 32% of the patients in the group classified as showing negative E-cadherin expression. Our findings provide clinical evidence that reduced E-cadherin expression is associated with tumor dedifferentiation, increased lymphogenous metastasis and poor survival. It seems therefore that E-cadherin expression might be an important prognostic factor in NSCLC.


Long-term antiretroviral therapy initiated during primary HIV-1 infection is key to achieving both low HIV reservoirs and normal T cell counts.
To characterize viro-immunological outcomes following long-term combined antiretroviral therapy (cART) initiated during primary HIV infection (PHI) or chronic HIV infection (CHI) and to identify factors predictive of optimal viro-immunological responder (OVIR) status. This was a prospective, single-centre cohort study of HIV-1-infected patients on effective cART. Total cell-associated HIV DNA levels and T cell counts before and during treatment were used to identify factors predictive of OVIR status {i.e. low HIV DNA level [<2.3 log10 copies/10(6) peripheral blood mononuclear cells (PBMCs)], together with normalization of the absolute/relative CD4+ T cell counts and CD4+/CD8+ ratio}. A total of 307 patients were enrolled, of whom 35 started cART during PHI (<4 months post-infection) and 272 during CHI. HIV DNA decay was modelled with a non-linear mixed-effects model that showed two phases of HIV DNA decay, both of which were significantly more pronounced in the PHI group. At the end of follow-up, after a median of 4 years of viral suppression (<50 copies/mL), HIV DNA levels were lower in the PHI group than in the CHI group (median = 2.15 versus 2.84 log10 copies/10(6) PBMCs; P< 0.0001). Immune reconstitution was more rapid and sustained in the PHI group (median = 883 versus 619 CD4+ cells/mm(3); 41% versus 31% CD4+; CD4+/CD8+ 1.31 versus 0.77; all P< 0.0001). Finally, OVIR status was obtained in 19/35 (54%) and 7/272 (3%) patients in the PHI and CHI groups (P< 0.0001), respectively. In a logistic regression analysis, cART initiation during PHI (OR = 16, 95% CI = 3.5-72.3) and HIV DNA level <3.3 log10 before treatment (OR = 4.8, 95% CI = 1.2-19.3) were independently predictive of OVIR status. Initiating cART during PHI represents a major opportunity to reduce HIV reservoirs and achieve optimal immune reconstitution.


Accurate and efficient quantum chemistry calculations for noncovalent interactions in many-body systems: the XSAPT family of methods.
We present an overview of "XSAPT", a family of quantum chemistry methods for noncovalent interactions. These methods combine an efficient, iterative, monomer-based approach to computing many-body polarization interactions with a two-body version of symmetry-adapted perturbation theory (SAPT). The result is an efficient method for computing accurate intermolecular interaction energies in large noncovalent assemblies such as molecular and ionic clusters, molecular crystals, clathrates, or protein-ligand complexes. As in traditional SAPT, the XSAPT energy is decomposable into physically meaningful components. Dispersion interactions are problematic in traditional low-order SAPT, and two new approaches are introduced here in an attempt to improve this situation: (1) third-generation empirical atom-atom dispersion potentials, and (2) an empirically scaled version of second-order SAPT dispersion. Comparison to high-level ab initio benchmarks for dimers, water clusters, halide-water clusters, a methane clathrate hydrate, and a DNA intercalation complex illustrate both the accuracy of XSAPT-based methods as well as their limitations. The computational cost of XSAPT scales as O(N(3))-O(N(5)) with respect to monomer size, N, depending upon the particular version that is employed, but the accuracy is typically superior to alternative ab initio methods with similar scaling. Moreover, the monomer-based nature of XSAPT calculations makes them trivially parallelizable, such that wall times scale linearly with respect to the number of monomer units. XSAPT-based methods thus open the door to both qualitative and quantitative studies of noncovalent interactions in clusters, biomolecules, and condensed-phase systems.


Vaginal flatus and the associated risk factors in Iranian women: a main research article.
Objective. The aim of the study was to determine the prevalence of vaginal flatus and some related risk factors in Iranian women. Methods. After conducting a pilot study, a sample size of 1000 subjects of 18 to 80 years was determined; of those 58 were unable to cooperate for various reasons. Age, parity, marital status, birth history, body mass index, and the weight of the largest newborn were collected. After a full gynecologic examination looking for pelvic organ prolapse, patients were asked about vaginal flatus and the frequency and time of occurrence. The results were studied using the chi-square test and independent t-test considering an alpha error of less than 0.05. Results. The prevalence of vaginal flatus was mainly 20% in this study, but embarrassment was observed in 5.7% of these women. 4% in the group were with no history of sexual contact (virgin). Vaginal flatus mostly started after vaginal delivery (45%) or spontaneously (34%); however, it was also reported after cesarean section and other pelvic operations. The most common activity leading to vaginal flatus was intercourse (54%); however, the time which had resulted in more inconvenience for the patients was during physical activities (92%). BMI and age were significantly lower in the patients (P < 0.0001). The grade of prolapse was lower in the patients (P < 0.0001). Conclusion. Low age, low body mass index, and vaginal delivery can affect the incidence of a noisy vagina.


Comparative double-blind trial of intra-articular injections of two long-acting forms of betamethasone.
Two injectable betamethasone preparations, betamethasone dipropionate/betamethasone phosphate and betamethasone acetate/betamethasone phosphate were compared in a controlled trial on 22 "matched patient pairs" with rheumatic diseases. The two preparations were injected intra-articularly in knee joints affected by active synovitis. The time until onset of action and the duration of clinically adequate anti-inflammatory effect were recorded. All injections produced clinically significant effects. The interval before recurrence of symptoms varied from 2 days to more than 3 months. The dipropionate form showed statistically significantly longer duration of action. No difference was noted in the time until onset of action. Local side effects were not observed. The double-blind method of clinical evaluation proved useful in comparing duration of action between long-acting corticosteroids.


Transcriptional and post-transcriptional processes regulate gene expression in oxygen-deprived roots of maize.
To investigate the regulation of gene expression in maize ( Zea mays L.) in response to oxygen deprivation (flooding), we quantitated run-on transcription in isolated nuclei, steady-state mRNA accumulation and mRNA loading with ribosomes for seven genes that encode proteins synthesized predominantly in oxygen-deprived roots (anaerobic polypeptides) and seven genes that encode proteins synthesized in aerobic roots (aerobic polypeptides). Run-on transcription of anaerobic polypeptide genes was induced in response to oxygen deprivation and run-on transcription of the aerobic polypeptide genes continued during the stress treatment. The increased accumulation of mRNAs that encode anaerobic polypeptides occurred concomitant with the induction of gene transcription and efficient association of these mRNAs with large polysomes. The steady-state accumulation of aerobic polypeptide mRNAs was within twofold of aerobic levels and in a number of cases fewer ribosomes were loaded per transcript. These results demonstrate that selected synthesis of anaerobic polypeptides involves transcriptional as well as significant post-transcriptional regulation of gene expression. The repression of synthesis of many aerobic polypeptides occurs without interruption of gene transcription and is due to translational regulation and possibly the sequestration of mRNAs on mRNPs. Ribosome loading patterns indicated that this translational control occurs at both initiation and post-initiation phases in a message-specific manner.


COLOR PATTERN EVOLUTION, ASSORTATIVE MATING, AND GENETIC DIFFERENTIATION IN BRIGHTLY COLORED BUTTERFLYFISHES (CHAETODONTIDAE).
In butterflyfishes (Chaetodontidae), color pattern evolves rapidly and is often the only morphological trait separating closely related species. Vivid coloration is frequently assumed to provide critical signals for mate recognition and mate choice, but few direct experimental tests are available. Here we analyze the relationship between color pattern change, mate choice, and genetic differentiation in a group of three very closely related allopatric butterflyfishes. We found that in only one member of this group, Chaetodon multicinctus, is color pattern evolution associated with mate preference and genetic divergence. For its two sister species, C. punctatofasciatus and C. pelewensis, color pattern change has not resulted in assortative mating (based on laboratory pairing experiments and field observations) or in significant mtDNA or allozyme differentiation. In a contact zone on reefs in the Solomon Islands and Papua New Guinea, hybridization between the two forms has nearly homogenized color pattern differences. Outside these areas, however, color pattern remains distinct. Genetic variation is homogeneous over a much larger geographic scale. Sequence variation in the tRNA-proline end of the mitochondrial control region and allozyme variation was distributed widely within C. punctatofasciatus and C. pelewensis, which suggests few constraints to mitochondrial or nuclear gene flow across the color pattern boundary. These contrasting patterns strongly suggest that selection is maintaining color pattern differences in allopatry in the face of potentially homogenizing levels of gene flow. The mating pattern data show that this selection is not operating on mate recognition in the strictest sense, but probably on some other aspect of the social system of these territorial fish. In this case, divergence in mating preference can follow color pattern evolution, but is not contemporaneous with it.


Posttraumatic stress symptoms and cognitive-based smoking processes among trauma-exposed, treatment-seeking smokers: the role of dysphoria.
Despite the co-occurrence and clinically significant relationship between trauma exposure and smoking, there is little understanding of the mechanisms underlying the posttraumatic stress symptoms-smoking relationship. This study examined whether dysphoria (ie, a psychopathologic symptom dimension that reflects depression's core affective, cognitive, and psychomotor features) accounted for the covariance between posttraumatic stress symptom severity and an array of smoking processes among trauma-exposed daily smokers. Participants (n = 189; 47.6% female; Mage = 41.15; SD = 12.47) were trauma-exposed, treatment-seeking daily cigarette smokers who completed measures of posttraumatic stress symptom severity, dysphoria, and 4 cognitive-based smoking processes that interfere with smoking cessation-avoidance/inflexibility to smoking, perceived barriers to smoking cessation, negative affect reduction motivation for smoking, and negative affect reduction/negative reinforcement expectancies from smoking. Dysphoria indirectly and significantly accounted for the relationship between posttraumatic stress symptom severity and smoking outcomes. The present results provide initial empirical support that dysphoria accounts for the covariance between posttraumatic symptom severity and various clinically relevant smoking variables in trauma-exposed, treatment-seeking smokers. The findings suggest the potential importance of targeting dysphoria during smoking cessation among trauma-exposed individuals.


Analysis of the spatial-frequency-dependent DQE of optically coupled digital mammography detectors.
The effect of optical coupling efficiency on the spatial-frequency-dependent propagation of signal and noise is considered for x-ray image detectors for digital mammography in which a phosphor screen is optically coupled to a charge-coupled device (CCD) image array. For experimental purposes, optical coupling between a Gd2O2S:Tb phosphor screen and a CCD image array was provided by relay lenses. Neutral density filters were inserted between the lenses to vary the optical coupling efficiency without altering the inherent spatial resolution. The total coupling efficiency, defined as the number of electrons (e-) recorded in the CCD per x-ray interaction in the phosphor, was calculated in each case. The modulation transfer function, and the contributions to the total noise power spectrum (NPS) of x-ray quantum noise, secondary quantum noise, and inherent detector noise were measured as a function of coupling efficiency. These data were used to calculate the spatial-frequency-dependent detective quantum efficiency [DQE(f)]. The NPS due to x-ray quantum noise had a significant spatial-frequency dependence for coupling efficiencies of more than 9 e- per x-ray interaction, but little spatial-frequency dependence for coupling efficiencies of less than 2 e- per x-ray interaction. These results indicate that to preserve high spatial-frequency values of DQE(f), and to ensure that images are x-ray quantum-noise limited at high spatial frequencies, a coupling efficiency on the order of 10 e- per x-ray interaction is required.(ABSTRACT TRUNCATED AT 250 WORDS)


Phylogenetic analyses of Septoria species based on the ITS and LSU-D2 regions of nuclear ribosomal DNA.
The phylogenetic relationships of 17 selected Septoria spp. (eight with a known Mycosphaerella teleomorph), Phloeospora ulmi (teleomorph M. ulmi) and 18 additional taxa (10 with a Mycosphaerella teleomorph) were inferred from ITS and D2-LSU nrDNA sequences. In total, 10 anamorph genera associated with Mycosphaerella were represented. Intraspecific variation in ITS was limited in Septoria, with the exception of three strains that all were identified as S. rubi but originated from different Rubus spp. and probably belong to different species of Septoria. The results of D2 region sequencing confirmed Mycosphaerella sense lato (including Davidiella and Eruptio) as monophyletic. The cereal pathogen Septoria tritici, which is closely related to S. passerinii as found in ITS analysis, clusters with Ramularia spp. in the D2 analyses, distant from the other Septoria spp. The pathogens S. apiicola, S. linicola and S. populicola cluster in a major clade containing Phl. ulmi, and other Septoria spp. and Cercospora spp. Short branch lengths in this clade suggest a very recent evolution. Septoria castaneicola and S. pyricola also might represent relatively distant lineages. Both analyses of the regions indicated that Septoria is not monophyletic within Mycosphaerella and that conidiomatal structure (acervulus, pycnidium) has little value for predicting phylogenetic relatedness. As a consequence, the separation between the acervular Phloeospora and pycnidial Septoria is untenable. The loss of the teleomorph most likely has occurred several times in the evolutionary history of Mycosphaerella.


Virtual Remediation Versus Methylphenidate to Improve Distractibility in Children With ADHD: A Controlled Randomized Clinical Trial Study.
Objective: Virtual environments have been used to assess children with ADHD but have never been tested as therapeutic tools. We tested a new virtual classroom cognitive remediation program to improve symptoms in children with ADHD. Method: In this randomized clinical trial, 51 children with ADHD (7-11 years) were assigned to a virtual cognitive remediation group, a methylphenidate group, or a psychotherapy group. All children were evaluated before and after therapy with an ADHD Rating Scale, a Continuous Performance Test (CPT), and a virtual classroom task. Results: After therapy by virtual remediation, children exhibited significantly higher numbers of correct hits on the virtual classroom and CPT. These improvements were equivalent to those observed with methylphenidate treatment. Conclusion: Our study demonstrates for the first time that a cognitive remediation program delivered in a virtual classroom reduces distractibility in children with ADHD and could replace methylphenidate treatment in specific cases.


The tubulin code in neuronal polarity.
Cells depend on the asymmetric distribution of their components for homeostasis, differentiation and movement. In no other cell type is this requirement more critical than in the neuron where complex structures are generated during process growth and elaboration and cargo is transported over distances several thousand times the cell body diameter. Microtubules act both as dynamic structural elements and as tracks for intracellular transport. Microtubules are mosaic polymers containing multiple tubulin isoforms functionalized with abundant posttranslational modifications that are asymmetrically distributed in neurons. An increasing body of evidence supports the hypothesis that the combinatorial information expressed through tubulin genetic and chemical diversity controls microtubule dynamics, mechanics and interactions with microtubule effectors and thus constitutes a 'tubulin code'. Here we give a brief overview of tubulin isoform usage and posttranslational modifications in the neuron, and highlight recent progress in understanding the molecular mechanisms of the tubulin code.


Carotid artery stenting update.
Stroke is the third leading cause of death and the most common cause of long-term disability in the USA. Approximately 25% of strokes are due to carotid artery disease. The mechanisms of stroke include thrombotic occlusion, thrombus embolism, atheroembolism and dissection or subintimal hematoma. Today, endarterectomy is the standard of care for management of significant carotid artery disease. The SAPPHIRE trial has proved the noninferiority of carotid artery stenting versus carotid endarterectomy in 'high-risk' patients, which led to the US FDA approval of carotid stent for high-risk patients. The CREST trial is the largest randomized trial comparing stenting versus endarterectomy and showed no significant difference in death, stroke or myocardial infarction. Over the last 15 years, the accumulation of experience, the improvement of stent platforms and embolic protection devices, and the strong demand from patients for a less invasive alternative to carotid endarterectomy has made carotid artery stenting an equally efficient and safe procedure for the prevention of stroke.