Synergism between IFN-gamma and IL-1 alpha/beta in growth inhibition of an allografted tumor.
Soluble effector molecules involved in the rejection of allografted mouse Meth A (3-methylcholanthrene-induced ascites type tumor) cells were examined. A potent antiproliferative activity against the tumor cells was detected in the culture supernatant of leukocytes that had infiltrated into the peritoneal cavity of C57BL/6 mice on days 6-8 after transplantation, when the i.p. transplanted Meth A cells were undergoing rejection. Studies with neutralizing antibodies indicated that both IFN-gamma and IL-1 alpha/beta were required for the activity but that TNF-alpha was not. Actually, mouse rIFN-gamma and rIL-1 alpha/beta used, at the concentrations found in the culture supernatant determined by ELISA, were able to reconstitute the potent antiproliferative activity, although each cytokine alone had a weak growth inhibitory activity against Meth A cells. The half-maximal inhibition was observed with 0.02-0.03 U/ml of rIL-1 alpha/beta at 1-100 U/ml of rIFN-gamma. The synergistic growth inhibitory effect of these cytokines also was observed with four of 15 mouse transformed cell lines tested, indicating that the effect was not specific to Meth A cells. These findings suggest that IFN-gamma and IL-1 alpha/beta participate as soluble effector molecules in the rejection of some allografted tumor cells including Meth A cells.


Running a domiciliary nebuliser service.
A nebuliser service should be provided locally, according to local needs. It should be centralised and administered by a designated consultant or consultants and written guidelines should be provided for medical and para-medical staff. The service should: (1) provide compressor/nebuliser units suitable for the prescribed treatment, (2) provide a system for equipment replacement, repair and maintenance, and (3) show patients how to use the equipment and give them comprehensive written instructions.


End-of-life care for ethnic minority groups.
Death and dying are profound events that bring into focus important ethical and medical questions for all patients, whatever their cultural background. For ethnic minority groups and their families, specific issues or barriers may arise related to culturally appropriate health care practices, cultural or religious differences, diverse health beliefs, and access to services for care and support during end-of-life conditions. National policy and local initiatives in both the United States and the United Kingdom support the development of services that address the care of ethnic minorities. This article examines end-of-life care for ethnic minority groups.


The amygdala regulates the antianxiety sensitization effect of flumazenil during repeated chronic ethanol or repeated stress.
The benzodiazepine receptor antagonist flumazenil reduces anxiety-like behavior and sensitization of anxiety-like behavior in various models of ethanol withdrawal in rodents. The mechanism and brain region(s) that account for this action of flumazenil remain unknown. This investigation explored the potential role of several brain regions (amygdala, raphe, inferior colliculus, nucleus accumbens, and paraventricular hypothalamus) for these actions of flumazenil. Rats were surgically implanted with guide cannulae directed over the brain region of interest and then treated with an ethanol diet for three 7-day dietary cycles (5 days on ethanol diet followed by 2 days on control diet). At approximately 4 hours, flumazenil was administered intracranially into each of the first 2 withdrawals. Examinations of anxiety-like behavior followed 1 week later during a third withdrawal. In other animals, restraint stress sessions or intra-amygdala DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) injections, preceded by intraperitoneal flumazenil injections, were substituted for the first 2 ethanol treatment cycles to assess the potential anxiety-sensitizing action of stress or a benzodiazepine receptor inverse agonist, respectively. Flumazenil treatment of the amygdala during the first 2 withdrawals blocked the development of sensitized anxiety seen during a third withdrawal. Similar actions of flumazenil were found when stress sessions substituted for the first 2 cycles of ethanol exposure and withdrawal. Amygdala treatment with DMCM magnified the anxiety response to the single subthreshold chronic ethanol treatment, and prophylactic flumazenil blocked this effect. Intra-amygdala flumazenil inhibits the development of anxiety sensitized by repeated ethanol withdrawal, stress/ethanol withdrawal, or DMCM/ethanol withdrawal. These actions suggest that site-specific and persistent effects of flumazenil on gamma-aminobutyric acid-modulatory processes in this brain region are relevant to sensitized behavioral effects seen in alcoholism.


Should pre-hospital resuscitative thoracotomy be reserved only for penetrating chest trauma?
The indications for pre-hospital resuscitative thoracotomy (PHRT) remain undefined. The aim of this paper is to explore the variation in practice for PHRT in the UK, and review the published literature. MEDLINE and PUBMED search engines were used to identify all relevant articles and 22 UK Air Ambulance Services were sent an electronic questionnaire to assess their PHRT practice. Four European publications report PHRT survival rates of 9.7, 18.3, 10.3 and 3.0% in 31, 71, 39 and 33 patients, respectively. All patients sustained penetrating chest injury. Six case reports also detail survivors of PHRT, again all had sustained penetrating thoracic injury. One Japanese paper presents 34 cases of PHRT following blunt trauma, of which 26.4% survived to the intensive therapy unit but none survived to discharge. A UK population reports a single survivor of PHRT following blunt trauma but the case details remain unpublished. Ten (45%) air ambulance services responded, each service reported different indications for PHRT. All perform PHRT for penetrating chest trauma, however, length of allowed pre-procedure down time varied, ranging from 10 to 20 min. Seventy percent perform PHRT for blunt traumatic cardiac arrest, a procedure which is likely to require aggressive concurrent circulatory support, despite this only 5/10 services carry pre-hospital blood products. Current indications for PHRT vary amongst different geographical locations, across the UK, and worldwide. Survivors are likely to have sustained penetrating chest injury with short down time. There is only one published survivor of PHRT following blunt trauma, despite this, PHRT is still being performed in the UK for this indication.


Modeling strategies to improve parameter estimates in prognostic factors analyses with patient-reported outcomes in oncology.
The inclusion of patient-reported outcome (PRO) questionnaires in prognostic factor analyses in oncology has substantially increased in recent years. We performed a simulation study to compare the performances of four different modeling strategies in estimating the prognostic impact of multiple collinear scales from PRO questionnaires. We generated multiple scenarios describing survival data with different sample sizes, event rates and degrees of multicollinearity among five PRO scales. We used the Cox proportional hazards (PH) model to estimate the hazard ratios (HR) using automatic selection procedures, which were based on either the likelihood ratio-test (Cox-PV) or the Akaike Information Criterion (Cox-AIC). We also used Cox PH models which included all variables and were either penalized using the Ridge regression (Cox-R) or were estimated as usual (Cox-Full). For each scenario, we simulated 1000 independent datasets and compared the average outcomes of all methods. The Cox-R showed similar or better performances with respect to the other methods, particularly in scenarios with medium-high multicollinearity (ρ = 0.4 to ρ = 0.8) and small sample sizes (n = 100). Overall, the Cox-PV and Cox-AIC performed worse, for example they did not select one or more prognostic collinear PRO scales in some scenarios. Compared with the Cox-Full, the Cox-R provided HR estimates with similar bias patterns but smaller root-mean-squared errors, particularly in higher multicollinearity scenarios. Our findings suggest that the Cox-R is the best approach when performing prognostic factor analyses with multiple and collinear PRO scales, particularly in situations of high multicollinearity, small sample sizes and low event rates.


Primary care in two cultures.
Differences were found between primary care as practised by the same doctor in Saudi Arabia and England within a twelve-month period. Many of these differences reflect demographic and cultural divergence between the two communities. Other factors suggested to explain areas of divergence were the administrative differences, systems of audit, language and empathy problems.


The emerging role of microRNAs in drug responses.
In recent years, pharmacogenomic research has begun to integrate genetics, gene expression and pharmacological phenotypes. MicroRNAs (miRNAs), 21- to 25-nucleotide, non-coding RNAs that are present in almost all metazoan genomes, are a class of gene regulators that downregulate gene expression at the post-transcriptional level. Experimental evidence for the role of miRNAs in regulating pharmacology-related genes and drug responses is increasing. Given the universal roles of miRNAs in various diseases, including cancer, miRNAs (eg, chemotherapy) are anticipated to have potential therapeutic effects in various diseases. The incorporation of miRNAs into pharmacogenomic research could provide improved insight into drug responses. However, more studies are necessary to evaluate the effects of these molecules in patients.


Efficacy of management strategies for aromatase inhibitor-induced arthralgia in breast cancer patients: a systematic review.
Aromatase inhibitors are the gold standard in the treatment of hormone receptor-positive breast cancer, but lead to an arthralgia syndrome which is implicated in 13-22% of noncompliance. This is the first systematic review of the efficacy of existing management strategies for this side effect. Eligible studies were retrieved from computer searches of Medline, Cochrane and Embase and the significant intervention groups were identified. The risk of bias of selected studies was evaluated and the relevant data items were extracted, summarized and analyzed. A total of 21 studies were discussed in this review representing 12 different interventions. While several trials had positive findings, the major methodological limitations of the studies meant that no definitive evidence could be found supporting any of the interventions. Future trials are needed which address the methodological problems identified in this review. Exercise holds promise for future research based on its proven benefit in breast cancer.


Autoimmune dacryoadenitis of NOD/LtJ mice and its subsequent effects on tear protein composition.
Sjögren's syndrome (SjS) is a human autoimmune disease characterized by exocrine dysfunction resulting from chronic autoimmune attack primarily against the lacrimal and/or salivary glands. Although, we previously established a good correlation between SjS in humans and autoimmune exocrinopathy in NOD/LtJ mice an in-depth evaluation of lacrimal gland disease in the NOD/LtJ mouse has remained limited. This leaves a major gap in our understanding of the dacryoadenitis/keratoconjunctivitis sicca in this model. Here we characterize the development of the autoimmune dacryoadenitis in NOD/LtJ and NOD.B10-H2(b) mice in comparison with age- and sex-matched nonautoimmune CD1 mice. We observed a decline in tear production beginning at 8 weeks of age in both NOD/LtJ and NOD.B10-H2(b) mice, continuing throughout the 40 to 46 weeks studied. This correlated with a quantifiable increase in mixed T- and B-lymphocyte infiltrations in the extraorbital lacrimal glands. In addition, temporal differences in tear protein expression between NOD/LtJ and CD1 mice were identified using two-dimensional gel electrophoresis and tandem mass spectrometry. Thus, using this model we can identify potentially important pathophysiological mechanisms of the autoimmune attack and possible diagnostic markers for development of SjS-associated dacryoadenitis.


Individual and contextual influences on adolescent smoking.
Cigarette smoking among adolescents remains one of the most important public health challenges. Despite much attention to research on the etiology of smoking, notably the examination of factors that differentiate adolescent smokers from never smokers, much less is known about factors that predict the development of dependence once an adolescent tries smoking. This paper reviews individual and contextual influences on the progression of smoking among adolescents. Highlights include a consideration of multiple levels of influence, from intra-individual factors, such as genetics, demographics, temperament and comorbidities, to social influences, such as families and peers, to the more macro, societal/cultural levels of influence, including advertising and tobacco-related policies. More recent work examining microcontextual influences through the use of Ecological Momentary Assessments is also discussed. Finally, the need to consider both developmental and transdisciplinary approaches to understanding the development of nicotine dependence in adolescents is emphasized.


Collaborative care model for depression in rural Nepal: a mixed-methods implementation research study.
Despite carrying a disproportionately high burden of depression, patients in low-income countries lack access to effective care. The collaborative care model (CoCM) has robust evidence for clinical effectiveness in improving mental health outcomes. However, evidence from real-world implementation of CoCM is necessary to inform its expansion in low-resource settings. We conducted a 2-year mixed-methods study to assess the implementation and clinical impact of CoCM using the WHO Mental Health Gap Action Programme protocols in a primary care clinic in rural Nepal. We used the Capability Opportunity Motivation-Behaviour (COM-B) implementation research framework to adapt and study the intervention. To assess implementation factors, we qualitatively studied the impact on providers' behaviour to screen, diagnose and treat mental illness. To assess clinical impact, we followed a cohort of 201 patients with moderate to severe depression and determined the proportion of patients who had a substantial clinical response (defined as ≥50% decrease from baseline scores of Patient Health Questionnaire (PHQ) to measure depression) by the end of the study period. Providers experienced improved capability (enhanced self-efficacy and knowledge), greater opportunity (via access to counsellors, psychiatrist, medications and diagnostic tests) and increased motivation (developing positive attitudes towards people with mental illness and seeing patients improve) to provide mental healthcare. We observed substantial clinical response in 99 (49%; 95% CI: 42% to 56%) of the 201 cohort patients, with a median seven point (Q1:-9, Q3:-2) decrease in PHQ-9 scores (p<0.0001). Using the COM-B framework, we successfully adapted and implemented CoCM in rural Nepal, and found that it enhanced providers' positive perceptions of and engagement in delivering mental healthcare. We observed clinical improvement of depression comparable to controlled trials in high-resource settings. We recommend using implementation research to adapt and evaluate CoCM in other resource-constrained settings to help expand access to high-quality mental healthcare.


Segmented Pt/Ru, Pt/Ni, and Pt/RuNi nanorods as model bifunctional catalysts for methanol oxidation.
Five-segment (Pt-Ru-Pt-Ru-Pt, Pt-Ni-Pt-Ni-Pt, and Pt-RuNi-Pt-RuNi-Pt) nanorods with the same overall rod length and the same total Pt segment length were prepared by sequential electrodeposition of the metals into the pores of commercially available anodic aluminum oxide (AAO) membranes. Field-emission scanning electron microscopy (FESEM) showed that the nanorods were about 210 nm in diameter and about 1.5 microm in length. The alternating Pt and oxophilic metal(s) segments could be easily differentiated in backscattered-electron images. X-ray diffraction (XRD) analysis of the nanorods indicated that Pt and Ni were polycrystalline with fcc structures, Ru was hcp, and the co-deposited RuNi adopted the nickel fcc structure with some negative shifts in the Bragg angles. The chemical states of Pt, Ru, and Ni on the nanorod surface were assayed by X-ray photoelectron spectroscopy (XPS), and the presence of Pt(0), Pt(II), Pt(IV), Ru(0), Ru(VI), Ni(0), and Ni(II) was observed. The nanorods were catalytically active for the room-temperature electrooxidation of methanol in acidic solutions. The relative rates of reaction showed the Pt-RuNi pair sites as having the lowest overpotential to dissociate water, the highest catalytic activity in methanol oxidation, and the strongest CO-tolerance in the potential window employed. The use of segmented nanorods with identifiable Pt-oxophilic metal(s) interfaces removes many of the ambiguities in the interpretation of experimental data from conventional alloy catalysts, thereby enabling a direct comparison of the activities of various types of pair sites in methanol oxidation.


Nasopharyngeal symptoms in patients with obstructive sleep apnea syndrome. Effect of nasal CPAP treatment.
Nasal side effects are often reported during nasal continuous positive airway pressure (CPAP) treatment of obstructive sleep apnea syndrome (OSAS) and may make the use of nasal CPAP difficult. The aim of this study was to evaluate the effect of nasal CPAP on nasopharyngeal symptoms in OSAS patients. The frequency and severity of nasopharyngeal symptoms and signs were prospectively evaluated in 49 consecutive OSAS patients (37 men, 12 women, mean (SD) age 54 (7) years, body mass index 35 (6) kg/m2) immediately before and after 6 months' treatment with nasal CPAP. Nasopharyngeal symptoms were common already before starting nasal CPAP: 74% of patients reported dryness, 53% sneezing, 51% mucus in the throat, 45% blocked nose, and 37% rhinorrhea. During nasal CPAP treatment, severity and frequency of sneezing (75%) and rhinorrhea (57%) increased. This increase was related to the season when nasal CPAP was applied, and was more profound in winter than in summer. Mild abnormalities on rhinoscopy and paranasal sinus X-rays were common both at baseline and at follow-up with no significant change during treatment. Nasopharyngeal problems were found to be frequent in patients with OSAS before nasal CPAP treatment, and tended to increase during the treatment.


Dual-Stimuli-Activatable Hybrid Prodrug for the Self-Immolative Delivery of an Anticancer Agent and Hydrogen Sulfide with Turn-On Fluorescence.
Stimuli-responsive fluorogenic prodrugs are advantageous for the targeted drug delivery enabling real-time non-invasive monitoring with turn-on fluorescence. We report herein the dual-stimuli (ROS and CA)-responsive thiocarbamate-based prodrug (AM-TCB) for the turn-on fluorogenic delivery of the naphthalimide-based anticancer agent amonafide along with the gasotransmitter hydrogen sulfide (H2 S). A carbamate-based prodrug AM-CB was also designed, capable of releasing the anticancer agent amonafide without any H2 S. The prodrugs were synthesized using multi-step organic synthesis. UV-Vis and fluorescence spectroscopic studies revealed selective reactivity of the boronate ester group of prodrugs towards ROS (primarily H2 O2 ) with the release of amonafide and COS/CO2 via self-immolative processes. Hydrolysis of the generated COS by carbonic anhydrase (CA) produces H2 S. While the prodrug AM-TCB retained the anticancer activity of free amonafide in cancer cells (MDA-MB-231 and HeLa), unlike amonafide, it enhanced the cellular viability of the non-malignant cells (HEK-293). Fluorescence imaging in HeLa cells revealed the simultaneous delivery of the anticancer agent and H2 S from AM-TCB with turn-on fluorescence. Western blot studies further revealed the cytoprotective effects of the released H2 S from AM-TCB. The present adjuvant strategy therefore would be helpful in future for ameliorating the anticancer drug-induced side-effects.


Enhancement of GABA-activated currents by arginine vasopressin in rat dorsal root ganglion neurons.
A growing number of studies have shown that arginine vasopressin (AVP) plays an analgesia role in the modulation of nociception. Previous studies have focused on the central mechanisms of AVP analgesia. The aim of the present study was to find out whether peripheral mechanisms are also involved. The effect of AVP on GABA-activated currents (IGABA) and GABAA receptor function in freshly isolated dorsal root ganglion (DRG) neurons of rats were studied using whole cell patch clamp technique. The result showed that, IGABA were potentiated by pre-treatment with AVP (1 × 10⁻¹⁰-1 × 10⁻⁵ mol/L) in a concentration-dependent manner. Meanwhile, the GABA concentration-response curve was shifted upwards, with an increase of (49.1 ± 4.0)% in the maximal current response but with no significant change in the EC50 values. These results indicate that the enhancing effect is non-competitive. In addition, the effects of AVP on IGABA might be voltage-independent. This potentiation of IGABA induced by AVP was almost completely blocked by the V1a receptor antagonist SR49059 (3 × 10⁻⁶ mol/L). Also it could be removed by intracellular dialysis of either GDP-β-S (5 × 10⁻⁴mol/L), a non-hydrolyzable GDP analog, or GF109203X (2 × 10⁻⁶ mol/L), a selective protein kinase C (PKC) inhibitor, with the re-patch clamp. These results suggest that AVP up-regulates the function of the GABAA receptor via G protein-coupled receptors and PKC-dependent signal pathways in rat DRG neurons, and this potentiation may underlie the analgesia induced by AVP.


LPS induces altered phosphate labeling of proteins in murine peritoneal macrophages.
Covalent modification of proteins via phosphorylation is a well-documented mechanism whereby intracellular events are controlled by external stimuli. Treatment of thioglycollate-elicited, C57Bl/6 murine peritoneal macrophages with nanogram quantities of bacterial lipopolysaccharide (LPS) consistently results in altered 32Pi labeling of a specific set of proteins (e.g., proteins of 67, 37, 33, and 28 kD), as measured by autoradiography after SDS-polyacrylamide gel electrophoresis. Induction of this pattern of phosphorylation is duplicated by the lipid A moiety of LPS. The LPS-stimulated changes in phosphate labeling are both dose- and time-dependent. Of various pharmacologic agents tested, the phosphorylation pattern induced in macrophages by the tumor promoter phorbol myristic acetate shows similarity to the pattern induced by LPS. Analysis of pp 28 and pp 37 from both LPS- and PMA-treated macrophages by limited proteolysis demonstrates that these phosphoproteins are structurally related and that the sites of phosphorylation are similar for both treatment conditions. Macrophages from the genetically LPS-unresponsive C3H/HeJ strain show no alteration in their pattern of phosphorylation after treatment with LPS. Control macrophages, from C3H/HeN mice, respond to LPS in a fashion identical to that seen in C57Bl/6 macrophages. Pretreatment of macrophages with IFN-gamma potentiates the effect of LPS (i.e., yields a level of altered phosphate labeling greater than that observed with LPS or PMA alone). Together, the data indicate that LPS causes altered phosphate labeling of a defined set of proteins, and that the circumstances of this response are consistent with a possible role in coupling LPS-initiated signals to the induction of functional competence in macrophages.


The nutrient factor queuine: biosynthesis, occurrence in transfer RNA and function.
Queuine, 7-(( (4,5-cis-dihydroxy-2-cyclopenten-1-yl)-amino]-methyl)-7-deazagu ani ne is synthesized de novo only in eubacteria and is preseent in place of guanine 34 in specific tRNAs containing anticodones GUN where N is one of the four canonical nucleotides. The biosynthetic pathway starting with GTP shares common steps with that of pteridines and riboflavin, and involves iron ions and a 'vitamin B12' coenzyme. Lower and higher eukaryotes are supplied with queuine by nutrition or the intestinal flora. The modification of tRNA with queuine is tissue specific and depends on the metabolic state of cells and tissues. Starvation for queuine and/or Q-deficiency in tRNA causes a few specific changes in the pattern of protein synthesis involving lactate dehydrogenases and cytochromes.


[Desire for a child: a mad passion?].
Could the desire for having a baby be considered as a pathological state? Indeed this desire is the most legitimate expression of a human being and must not be questioned. Nevertheless, as professionals, we are in a position to ask if any kind of solicitation concerning Assisted Reproductive Techniques (ART) would be well-grounded. As a matter of fact, we stand quite often on the front line when facing the growing demands of a population, which rightly embodies the great strides in the medical field after having integrated every restraint of a once mortal chronic disease. What methods linked to psychodynamic clinic can we use in order to take care of an unsatisfied infantile wish dressed up in a mask of a passionate wish of having a baby?


Does video recording alter the behavior of police during interrogation? A mock crime-and-investigation study.
A field study conducted in a midsized city police department examined whether video recording alters the process of interrogation. Sixty-one investigators inspected a staged crime scene and interrogated a male mock suspect in sessions that were surreptitiously recorded. By random assignment, half the suspects had committed the mock crime; the other half were innocent. Half the police participants were informed that the sessions were being recorded; half were not. Coding of the interrogations revealed the use of several common tactics designed to get suspects to confess. Importantly, police in the camera-informed condition were less likely than those in the -uninformed condition to use minimization tactics and marginally less likely to use maximization tactics. They were also perceived by suspects-who were all uninformed of the camera manipulation-as trying less hard to elicit a confession. Unanticipated results indicated that camera-informed police were better able to discriminate between guilty and innocent suspects in their judgments and behavior. The results as a whole indicate that video recording can affect the process of interrogation-notably, by inhibiting the use of certain tactics. It remains to be seen whether these findings generalize to longer and more consequential sessions and whether the camera-induced differences found are to be judged as favorable or unfavorable.


Thoracoscopic lung biopsy is a safe procedure in diagnosing usual interstitial pneumonia.
To evaluate the effect of lung biopsy on the survival of patients when histopathologic confirmation of usual interstitial pneumonia (UIP) is needed. Idiopathic pulmonary fibrosis is a distinct clinical entity with histopathologic features of UIP. Surgical biopsy is needed when clinical and radiologic findings are not typical. The safety of lung biopsy is a matter of debate, and the results of short-term mortality (< 30 days) after biopsy are variable. Seventy-six patients with UIP, including 34 patients who underwent video-assisted thoracoscopic surgery (VATS) biopsy and 42 patients who underwent open-lung biopsy, were included in this retrospective study. All biopsies were reevaluated for UIP histopathology. Clinical data such as age at the time of biopsy, type of biopsy, preoperative pulmonary function, major postoperative complications, date and cause of death, and survival time after the biopsy were gathered. Median survival was used to compare the survival between different groups, and cumulative survival was estimated using Kaplan-Meyer method. Thoracoscopic biopsy was safe for diagnosing UIP, with no short-term mortality. In contrast, open-lung biopsy was followed by four deaths (5.3%) within 1 month after the procedure. All fatal cases were accompanied by a histopathologic pattern of diffuse alveolar damage. Age of the patient at the time of biopsy was a significant predicting factor for survival. Patients < 50 years old lived 181 months (range, 119 to 242 months), and patients > 50 years old lived 75 months (range, 55 to 95 months). VATS biopsy is a safe procedure in diagnosing UIP.


Retinal Penetration of Intravitreally Injected Tissue Plasminogen Activator: A Rat Model Study.
To determine whether intravitreal unconjugated tissue plasminogen activator (tPA) (alteplase) can penetrate the intact neural retina and reach the subretinal space in an experimental model. This study was performed in 24 Sprague-Dawley rats aged 12 weeks. Under general anesthesia, the right eye was injected with either 0.75 μg of 3 μL tPA (14 rats; study group) or saline (10 rats, control group) into the vitreous. Animals were euthanized at 3, 24, and 48 h. The eyes were enucleated, and cryosections were prepared for immunofluorescence staining. Goat anti-tPA antibody was used to detect tPA. In the study group, staining for tPA was detected in the deep retinal layers in all eyes. The staining was deeper and more intense at 3 and 24 h than at 48 h. There was no tPA staining in the retina of eyes injected with saline. This experimental study shows that unconjugated tPA administered into the vitreous is capable of penetrating the deep retinal layers and the subretinal space. These findings suggest that further clinical research is warranted on the benefits of intravitreal tPA in the treatment of submacular hemorrhage.


Infant vocal-motor coordination: precursor to the gesture-speech system?
This study was designed to provide a general picture of infant vocal-motor coordination and test predictions generated by Iverson and Thelen's (1999) model of the development of the gesture-speech system. Forty-seven 6- to 9-month-old infants were videotaped with a primary caregiver during rattle and toy play. Results indicated an age-related increase in frequency of vocal-motor coordination, greater coordination with arm (specifically right arm) than leg or torso movements, and a temporal pattern similar to that in adult gesture-speech coproductions. Rhythmic vocalizations (consonant-vowel repetitions) were more likely to occur with than without rhythmic movement, and with rhythmic manual than with nonmanual activity, and the rate of vocal-manual coordination was higher in babblers than in prebabblers.


[Plasticity of bone marrow mesenchymal stem cells differentiating into cardiomyocytes and the potential of cardiac therapeutics].
Current treatments for ischemic cardiomyopathy aim at minimizing the deteriorated consequences of damaged myocardium. Recent stem cell researches have provided major impetus for the possibility of treating heart failure by generating new myocardium and vascular structures. Bone marrow mesenchymal stem cells (MSCs) , also referred to as marrow stromal cells, differentiate readily into chondrocytes, adipocytes, and osteocytes. Recent provocative data suggest that they can also express phenotypic characteristics of endothelial, neural, smooth muscle, skeletal myoblasts, and cardiac myocytes. The multilineage potential, no immune reaction if self-transplantation, and the relative easiness of expansion in culture make MSCs a promising source of cells for medical therapies. Recent researches demonstrate that implantation of intramyocardial MSCs can prevent deteriorated remodeling and improve cardiac function, although the underlying mechanisms need to be further clarified. This review summarized recent studies in the recognition of MSCs, particularly the MSC plasticity into cardiomyocytes, factors and signal pathways that mediate MSC differentiation, and animal studies as well as clinic trials of the implantation of MSCs in postinfarct myocardium.


External control of fluoridation in the public water supplies of Brazilian cities as a strategy against caries: a systematic review and meta-analysis.
Among the methods currently available to provide fluoride in population levels, fluoridated water is the most successful for presenting high efficacy, safety and good cost-benefit. However, recent studies on external control have shown great variability of fluoride concentrations in the water from treatment stations in Brazilian cities, which must present concentration between 0.6 and 0.8 mg/L to be considered acceptable in most cities. Thus, this study aimed to perform a systematic review of the literature to assess the adequacy of fluoride concentration in the water in Brazilian cities using external control. The protocol was registered in PROSPERO. Six databases were used as primary search sources and three databases were used to partially capture the "gray literature". Only observational studies that assessed the fluoride concentration of artificially fluoridated water from the public supply network were included. The JBI Critical Appraisal Tools for Systematic Reviews was used to assess the risk of bias of the studies. A proportion meta-analyses using random-effect models were performed. The heterogeneity between studies was determined by I2 statistic. Meta-regressions were conducted to identify relevant moderators to be used in stratified meta-analyses. Publication bias was investigated by Egger's tests. The search provided 2038 results, from which 14 met the eligibility criteria and were included in the data extraction of the review. Overall, the water samples were collected from 449 different sources in three Brazilian regions. Thirteen studies presented a low risk of bias. The mean concentration of fluoride ranged from 0.17 to 0.89 ppmF. The meta-analyis demonstrated that more than half of the water samples analyzed had fluoride concentration levels outside the acceptable range (56.6%; 95% CI 45.5; 67.3), with high heterogeneity. More than half of the public water supply analyzed in the studies selected had fluoride concentration levels outside the acceptable range, which may affect the risk of developing oral diseases in the Brazilian population, having an important impact on public health.


Nonflammable Polyfluorides-Anchored Quasi-Solid Electrolytes for Ultra-Safe Anode-Free Lithium Pouch Cells without Thermal Runaway.
The safe operation of rechargeable batteries is crucial because of numerous instances of fire and explosion mishaps. However, battery chemistry involving metallic lithium (Li) as the anode is prone to thermal runaway in flammable organic electrolytes under abusive conditions. Herein, an in situ encapsulation strategy is proposed to construct nonflammable quasi-solid electrolytes through the radical polymerization of a hexafluorobutyl acrylate (HFBA) monomer and a pentaerythritol tetraacrylate (PETEA) crosslinker. The quasi-solid system eliminates the inherent flammability of ether electrolytes with zero self-extinguishing time owing to the gas-phase radical capturing ability of HFBA. Additionally, the graphitized carbon layer generated during the decomposition of PETEA at high temperatures obstructs the heat and oxygen required for combustion. When coupled with Au-modified reduced graphene oxide anodic current collectors and lithium sulfide cathodes, the assembled anode-free Li-metal cell based on the quasi-solid electrolyte exhibits no signs of cell expansion or gas generation during cycling, and thermal runaway is eliminated under multiple mechanical, electrical, and thermal abuse scenarios and even rigorous strikes. This nonflammable quasi-solid configuration with gas- and condensed-phase flame-retardant mechanisms can drive a technological leap in anode-free Li-metal pouch cells and secure the practical applications necessary to power this society in a safe manner.


Survival of breast cancer patients in Connecticut in relation to socioeconomic and health care access indicators.
The purpose of this study of 16,931 black and white Connecticut women diagnosed with invasive breast cancer in 1988-1995 was to examine survival in relation to surrogate or proxy indicators of both socioeconomic status (SES) and access to primary care. Patients were followed through 1998, and the risk of death was elevated for the lowest (vs. highest) SES category independent of stage at diagnosis and other characteristics, especially among patients diagnosed before age 65 years. The health care access indicator was not associated with risk of death when other patient characteristics (including the SES variable and stage at diagnosis) were taken into account. Unexplained elevations, relative to the rest of the state, in risk of death were found for patients diagnosed while living in two of the state's four largest cities.


A Staphylococcus capitis strain with unusual bacteriocin production.
Staphylococcus capitis is a member of the human and mammal skin microbiomes and is considered less harmful than Staphylococcus aureus. S. capitis subsp. urealyticus BN2 was isolated from a cat and expressed strong antibacterial activity against a range of Gram-positive species, most notably including S. aureus strains with resistance to methicillin (MRSA) and strains with intermediate resistance to vancomycin (VISA). These latter strains are normally relatively resistant to bacteriocins, due to cell wall and cell membrane modifications. Genomic sequencing showed that the strain harboured at least two complete gene clusters for biosynthesis of antagonistic substances. The complete biosynthetic gene cluster of the well-known lantibiotic gallidermin was encoded on a large plasmid and the mature peptide was present in isopropanol cell extracts. In addition, a chromosomal island contained a novel non-ribosomal peptide synthetase (NRPS) gene cluster. Accidental deletion of two NRPS modules and partial purification of the anti-VISA activity showed that this novel bacteriocin represents a complex of differently decorated, non-ribosomal peptides. Additionally, a number of phenol-soluble modulins (PSMs) was detected by mass spectrometry of whole cells. Producing these compounds, the strain was able to outcompete several S. aureus strains, including MRSA and VISA, in tube cultures.


Frequency of B-lymphocyte transformation by Epstein-Barr virus decreases with entry into the cell cycle.
The relationship between in vitro B-cell activation and transformation by Epstein-Barr virus (EBV) was studied. B cells were fractionated using discontinuous Percoll gradients to purify cells with resting morphology. Activation of resting cells for 24 hr with anti-Ig (mu chain specific) or Staphylococcus aureus Cowan I (SAC) resulted in transition of susceptible cells into the G1 phase of the cell cycle as shown by an increase in cell size, an increase in uridine incorporation and an increase in sensitivity to B-cell growth factor (BCGF). Entry into S phase was achieved by extending the period of activation to 48-96 hr with high concentrations of SAC or anti-mu or using BCGF. SAC-activated cells entered S phase on Day 2 and anti-mu treated cells on Day 3. Control (G0) cells and cell activated for varying lengths of time (G0/G1, G1/S) were exposed to EBV and plated in a limiting dilution assay to determine the frequency of EBV-transformable cells. Control cells and cells activated for 24 hr had a transformation frequency of 1-2%. With continued activation with SAC or anti-mu, however, transformation frequency decreased at a rate paralleling the entry of the population into S phase. Treating cells with low concentrations of anti-mu or SAC in combination with BCGF decreased the transformation frequency to levels lower than anti-mu or SAC alone, further suggesting that entry into S phase is accompanied by a reduction in transformability. These results indicate that resting B cells are highly susceptible to transformation, and that with in vitro activation into the cell cycle B cells become resistant to EBV transformation.


Multivariate Analysis to Predict the Horizontal Anterior Chamber Diameter from Other Anterior Chamber Parameters Using Scheimpflug Imaging: Is There a Better Method Than Adding a Fixed Constant?
To evaluate the predictive association between the horizontal anterior chamber diameter (HACD) and other measurements using Scheimpflug imaging, and to assess whether a method superior to using fixed constants can be proposed. This hospital-based study was performed in the Cornea and Refractive Surgery Services, New Medical Center (NMC) specialty hospital, Abu Dhabi. Initially, 100 candidates were included serially in the model building group (group1). All candidates underwent detailed evaluation and Scheimpflug imaging (CSO, Sirus, Italy). Subsequently, another 100 candidates were included serially in the validation group (group 2). Candidates in both groups underwent the same tests. In group 1, the mean HACD was 12.25 ± 0.48 mm. This measurement correlated significantly with the horizontal visible iris diameter (HVID), anterior chamber depth, angle (ACA), and volume (ACV) (r = 0.2-0.7). The overall regression equation was HACD = 5.62 + 0.01 × ACV + 0.45 × HVID - 0.013 × ACA (adjusted R2 = 0.66, p < 0.001). Situation-based equations derived from the outcomes of group 1 were tested in group 2. Equation A included all factors found significant during model-building, Equation B included only non-volumetric significant factors, and situation C only included the HVID. Equations D through F used direct substitution by HVID plus a constant to predict HACD (the constant was 0.0, 0.5, and 1.0 for Equations D, E, and F, respectively). The predicted HACD (pHACD) was within ±0.5 mm of the actual HACD (aHACD) in 93%, 88%, 87%, 83%, 69%, and 16% case for Equations A, B, C, D, E, and F, respectively. The mean prediction error was -0.14 ± 0.27 mm (p = 0.08), -0.15 ± 0.28 mm (p = 0.03), -0.18 ± 0.30 mm (p = 0.001), -0.18 ± 0.32 mm (p < 0.001), 0.33 ± 0.35 mm (p < 0.001), and 0.83 ± 0.35 mm (p < 0.001) for Equations A, B, C, D, E, and F, respectively. Regression equations using Scheimpflug-derived anterior chamber parameters may predict HACD to varying degrees, depending on the input parameters. Adding 0.5 or 1.0 mm to the corneal diameter (CD) to estimate the HACD is not recommended.


Efficacy of Apigenin and Miltefosine Combination Therapy against Experimental Cutaneous Leishmaniasis.
Leishmaniasis is a neglected tropical disease caused by several different species of Leishmania. Treatment of leishmaniasis involves a limited drug arsenal that is associated with severe side effects, high costs, and drug resistance. Therefore, combination therapy has emerged as a strategy to improve leishmaniasis treatment. Here, we report the interaction of miltefosine and apigenin in vitro and in vivo. Combination therapy using low doses of these two drugs results in good clinical and parasitological responses.


Organocatalysis "on water". Regioselective [3 + 2]-cycloaddition of nitrones and allenolates.
The first example of a regioselective and organocatalyzed 1,3-dipolar cycloaddition reaction between conjugated alkynoates and nitrones "on water" is described.


Molecular detection of Paracoccidioides brasiliensis in road-killed wild animals.
Paracoccidioides brasiliensis infections have been little studied in wild and/or domestic animals, which may represent an important indicator of the presence of the pathogen in nature. Road-killed wild animals have been used for surveillance of vectors of zoonotic pathogens and may offer new opportunities for eco-epidemiological studies of paracoccidiodomycosis (PCM). The presence of P. brasiliensis infection was evaluated by Nested-PCR in tissue samples collected from 19 road-killed animals; 3 Cavia aperea (guinea pig), 5 Cerdocyon thous (crab-eating-fox), 1 Dasypus novemcinctus (nine-banded armadillo), 1 Dasypus septemcinctus (seven-banded armadillo), 2 Didelphis albiventris (white-eared opossum), 1 Eira barbara (tayra), 2 Gallictis vittata (grison), 2 Procyon cancrivorus (raccoon) and 2 Sphiggurus spinosus (porcupine). Specific P. brasiliensis amplicons were detected in (a) several organs of the two armadillos and one guinea pig, (b) the lung and liver of the porcupine, and (c) the lungs of raccoons and grisons. P. brasiliensis infection in wild animals from endemic areas might be more common than initially postulated. Molecular techniques can be used for detecting new hosts and mapping 'hot spot' areas of PCM.


A new species of Cyrtodactylus Gray, 1827 (Squamata, Gekkonidae) from Yunnan, China.
A new species of Cyrtodactylus is described on the basis of five specimens collected from the karst formations of Zhenkang County, Yunnan Province, China. Cyrtodactylus zhenkangensis sp. nov. is recognized by having a unique combination of morphological characters, the most diagnostic being: 12-15 enlarged femoral scales on each thigh; 2-5 femoral pores on each thigh in males, 0-3 pitted scales on each thigh in females; eight or nine precloacal pores in a continuous row or separated by one poreless scale in males, 7-9 pitted scales in females; subcaudals enlarged, arranged alternately as single and double on anterior and mostly single at middle and posterior; dorsal surface of head with obvious reticulations. Phylogenetic analyses show that the new species is a member of the C. wayakonei species group and a sister taxon to a clade consisting of C. wayakonei and C. martini based on Maximum Likelihood analyses and Bayesian Inference and differs from its congeners by at least 12.0% genetic divergence in a fragment of the COI gene.


Does problem complexity matter for environmental policy delivery? How public authorities address problems of water governance.
Problem complexity is often assumed to hamper effective environmental policy delivery. However, this claim is hardly substantiated, given the dominance of qualitative small-n designs in environmental governance research. We studied 37 types of contemporary problems defined by German water governance to assess the impact of problem complexity on policy delivery through public authorities. The analysis is based on a unique data set related to these problems, encompassing both in-depth interview-based data on complexities and independent official data on policy delivery. Our findings show that complexity in fact tends to delay implementation at the stage of planning. However, different dimensions of complexity (goals, variables, dynamics, interconnections, and uncertainty) impact on the different stages of policy delivery (goal formulation, stages and degrees of implementation) in various ways.


Live attenuated Varicella-Zoster vaccine.
Varicella-zoster (VZ) virus causes two diseases, varicella and zoster. Because it was recognized that, after varicella, latent VZ virus persisted in the host and because varicella was thought to be a milde disease, there was little impetus in North America to develop a live VZ vaccine. More recently, it has become apparent that currently available methods of prevention and treatment of severe varicella are not always efficacious. With the development of a live attenuated VZ vaccine by Takahashi and the successful use of the vaccine in immunocompromised children in Japan, there has been an increased interest in North America in immunization against varicella. In this article the natural history of VZ infections and the immunologic reactions to VZ virus are described, and the development and use of VZ vaccine in Japan are reviewed. Plans for trials of VZ vaccine in immunocompromised North American children are outlined. The major questions concerning the large-scale use of VZ vaccine are presented.


Competence to give informed consent for medical procedures.
This study shows that referrals to psychiatry for evaluation for competence to give informed consent generally were made on patients who refused medical treatment. In this sample of referred patients, the only patients found to be incompetent to give informed consent were those with organic brain syndromes. No one with either schizophrenia or depression was found to be incompetent. It is possible that schizophrenic and depressed patients may generally be competent to give informed consent to medical treatment. This finding might be true notwithstanding the fact that many such patients have been found in other studies to be incompetent to consent to voluntary psychiatric treatment. For example, a patient may have delusions that others can read his mind and thoughts, but he still can understand that he needs dialysis for renal failure. Alternatively, it may be relatively rare that an emergency procedure is necessary before a patient's psychosis can be brought under control and consequently internists and surgeons themselves may prefer to wait. The significance of the results is unclear. Because of active interest in the doctrine of informed consent for psychiatric and medical patients by both physicians and attorneys and the few studies within this population, there is a strong need for more study regarding competence to give informed consent. Further study is especially important for psychotic patients for whom psychiatric consultation is not requested.(ABSTRACT TRUNCATED AT 250 WORDS)


Parietal cell vagotomy without drainage for the treatment of duodenal ulcer.
PVC without drainage for the treatment of duodenal ulcer is a safe procedure. There are fewer gastrointestinal complaints of the type frequently observed after more orthodox gastric surgery. Diarrhea and dumping may be noted after PCV but the incidence of both is less, and when they do occur they are milder and more easily controlled than after other types of operations. The ultimate recurrent ulcer rate remains unresolved because insufficient time for observation and follow-up has elapsed. Since most recurrent ulcers that occur after other gastric procedures present within the first two years after operation, the documentation by several authors of a recurrent ulcer rate of 2-4% in patients followed two to four years after operation suggests that PCV is a highly effective procedure. Yet the high recurrence rates of 22% reported by one group indicates that the operation is not highly effective for everyone. The factors responsible for the discrepancy between the high and low recurrence rates reported by different authors are not evident at this time.


Superior mechanical recovery in male and female MRL/MpJ tendons is associated with a unique genetic profile.
Tendon ruptures heal by forming a mechanically inferior scar. We have shown that male Murphy Roths large (MRL/MpJ) mice exhibit improved tendon healing, suggesting that they can inform biological mechanisms that lead to effective tendon healing. As sex impacts healing, we assessed the effect of sex on tendon healing in MRL/MpJ and normal healer C57BL/6 (B6) mice and compared the associated biological environment with identify genes that may be integral to the improved healing outcome. We hypothesized that (a) male MRL/MpJ mice will heal with improved mechanical properties compared to females; and (b) that regenerative tendon healing will be associated with decreased fibrotic pathways, decreased inflammation, and increased activity of matrix metalloproteinases (MMPs). A midsubstance punch was introduced, and tendons were harvested after (a) 1 or 7 days for profiling of 84 genes; (b) 7 or 14 days for the assessment of MMP-2 and MMP-9 activity; and (c) 6 weeks for mechanical assessment. MRL/MpJ tendons healed with the better restoration of mechanical properties than B6 tendons. Sex did not affect the mechanical properties of healing B6 or MRL/MpJ tendons. Comparison of the gene expression profiles in the context of the mechanical outcome revealed several differences between MRL/MpJ and B6 tendon healing, including, lower inflammation, an earlier higher expression of TGF-β-related genes that diminish by 7 days, and genes associated with enhanced cell migration in MRL/MpJ in comparison to B6 tendons. We expect that the timecourse and expression levels of these genes in scarless MRL/MpJ tendon healing represent the balanced environment that leads to improved tendon healing.


Role of ClpP in the Biogenesis and Degradation of RuBisCO and ATP Synthase in Chlamydomonas reinhardtii.
Ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) associates a chloroplast- and a nucleus-encoded subunit (LSU and SSU). It constitutes the major entry point of inorganic carbon into the biosphere as it catalyzes photosynthetic CO2 fixation. Its abundance and richness in sulfur-containing amino acids make it a prime source of N and S during nutrient starvation, when photosynthesis is downregulated and a high RuBisCO level is no longer needed. Here we show that translational attenuation of ClpP1 in the green alga Chlamydomonas reinhardtii results in retarded degradation of RuBisCO during S- and N-starvation, suggesting that the Clp protease is a major effector of RubisCO degradation in these conditions. Furthermore, we show that ClpP cannot be attenuated in the context of rbcL point mutations that prevent LSU folding. The mutant LSU remains in interaction with the chloroplast chaperonin complex. We propose that degradation of the mutant LSU by the Clp protease is necessary to prevent poisoning of the chaperonin. In the total absence of LSU, attenuation of ClpP leads to a dramatic stabilization of unassembled SSU, indicating that Clp is responsible for its degradation. In contrast, attenuation of ClpP in the absence of SSU does not lead to overaccumulation of LSU, whose translation is controlled by assembly. Altogether, these results point to RuBisCO degradation as one of the major house-keeping functions of the essential Clp protease. In addition, we show that non-assembled subunits of the ATP synthase are also stabilized when ClpP is attenuated. In the case of the atpA-FUD16 mutation, this can even allow the assembly of a small amount of CF1, which partially restores phototrophy.


Lectin-based affinity tag for one-step protein purification.
The production of pure protein is indispensable for many applications in life sciences, however protein purification protocols are difficult to establish, and the experimental procedures are usually tedious and time-consuming. Therefore, a number of tags were developed to which proteins of interest can be fused and subsequently purified by affinity chromatography. We report here on a novel lectin-based affinity tag using the D-mannose-specific lectin LecB from Pseudomonas aeruginosa. A fusion protein was constructed consisting of yellow fluorescent protein and LecB separated by an enterokinase cleavage site. This protein was overexpressed in Escherichia coli Tuner (DE3), and the cell extract was loaded onto a column containing a mannose agarose matrix. Electrophoretically pure fusion protein at a yield of 24 mg/L culture was eluted with a D-mannose containing buffer The determination of equilibrium adsorption isotherms revealed an association constant of the lectin to the mannose agarose matrix of Ka = 3.26 x 10(5)/M. Enterokinase treatment of the purified fusion protein resulted in the complete removal of the LecB-tag. In conclusion, our results indicate that the lectin LecB of P. aeruginosa can be used as a tag for the high-yield one-step purification of recombinant proteins.


Post treatment imaging in head and neck tumours.
Cancer is a leading cause of death in most parts of the world. Most patients will undergo multiple imaging studies following treatment. The regular follow up of these patients often leads to the early detection of tumour recurrence or the onset of treatment complications. Early diagnosis may result in the timely institution of appropriate therapy thereby improving the survival and morbidity rates. This review addresses difficulties related to demonstrating early tumour recurrence and nodal metastasis and focuses on the complications seen in the central nervous system, cranial nerves and brachial plexus following radiotherapy.


The human S100 protein MRP-14 is a novel activator of the beta 2 integrin Mac-1 on neutrophils.
The 14-kDa myeloid-related protein (MRP-14) and its heterodimeric partner, MRP-8, are members of the S100 family of calcium-binding proteins (S100A9 and S100A8, respectively). Their importance in neutrophil function is implied by their unusual abundance in neutrophil cytosol (approximately 40% of cytosolic protein). Previous work from our laboratory has demonstrated the extracellular association of these proteins with vascular endothelium adjacent to transmigrating leukocytes. We report here a function for MRP-14 as a stimulator of neutrophil adhesion mediated by the beta 2 integrin, Mac-1. MRP-14 is an affinity regulator of Mac-1 because it promotes binding of soluble ligand and expression of an "activation reporter" epitope of high affinity beta 2 integrins recognized by mAb24. The activity of MRP-14 is confined to regulating integrin function because, unlike other inflammatory agonists, there was no release of L-selectin, up-regulation of cytosolic Mac-1, or induction of neutrophil respiratory burst or calcium flux. Furthermore, MRP-14 does not act as a chemoattractant or cause alterations in cell shape or cytoskeleton. MRP-8 has a regulatory role in MRP-14 activity, inhibiting the adhesion induced by MRP-14 through the formation of the heterodimer. In terms of mechanism of action, MRP-14 does not increase Mac-1 function by direct binding to this integrin but recognizes a distinct receptor on neutrophils. This receptor interaction is pertussis toxin sensitive, indicating that MRP-14-generated signals leading to a Mac-1 affinity increase are heterotrimeric G protein dependent. We postulate that MRP-14 and MRP-8 are important in vivo candidates for the regulated adhesion of neutrophils through control of Mac-1 activity.


Identification of Some New Triply Periodic Mesophases from Molten Block Copolymers.
Using field-theoretic simulations based on a self-consistent field theory (SCFT) with or without finite compressibility, nanoscale mesophase formation in molten linear AB and ABC block copolymers is investigated in search of candidates for new and useful nanomaterials. At selected compositions and segregation strengths, the copolymers are shown to evolve into some new nanostructures with either unusual crystal symmetry or a peculiar morphology. There exists a holey layered morphology with Im3 symmetry, which lacks one mirror reflection compared with Im3m symmetry. Also, a peculiar cubic bicontinuous morphology, whose channels are connected with tetrapod units, is found to have Pn3m symmetry. It is shown that there is another network morphology with tripod connections, which reveals P432 symmetry. The optimized free energies of these new mesophases and their relative stability are discussed in comparison with those of double gyroids and double diamonds.


Scanning electron microscopy study of the tongue and lingual papillae of the California sea lion (Zalophus californianus californianus).
We observed the three-dimensional structures on the external surface and the connective tissue cores (CTCs) of the California sea lion (Zalophus californianus californianus), after exfoliation of the epithelium of the lingual papillae (filiform, fungiform, and vallate papillae), using scanning electron microscopy (SEM) and conventional light microscopy. Macroscopically, the tongue was V-shaped and its apex was rounded. At the posterior area of the tongue, five vallate papillae were arranged in a V shape. In the epithelium, numerous taste buds were distributed on the top of the vallate papillae. On the dorsal surface from the apex to the boundary between the anterior and posterior tongue, filiform papillae were densely distributed. The CTCs of the filiform papillae consisted of a main protrusion (primary core) and many small cores (secondary cores). From the apex to the anterior one-third of the tongue, dome-like fungiform papillae were densely distributed, whereas fewer were located at the posterior two-thirds of the tongue. Several taste buds were found in the epithelium on the fungiform papillae. The size of the filiform papillae gradually increased from the apex to the boundary between the anterior and posterior tongue. At the lingual radix, the conical papillae, which were bigger than any filiform papillae, were densely distributed. The morphological characteristics of the tongue of the California sea lion appear to have been transformed to adapt to an aquatic environment; however, they possess some structures similar to those of land mammals.


Lacrimal sac tumors.
This is a clinicopathologic study of 115 lacrimal sac neoplasms in adults (mean 52 years). The most common presenting signs and symptoms were epiphora (53%), recurrent dacryocystitis (38%), and/or lacrimal sac mass (36%). The tumors were divided into epithelial (82 cases) and nonepithelial (33 cases) neoplasms. Benign epithelial tumors included squamous and transitional cell papillomas (32), oncocytomas (4), and benign mixed tumors (2). The malignant epithelial neoplasms included squamous cell carcinoma (22), transitional cell carcinoma (5), adenocarcinoma (4), mucoepidermoid (3), adenoid cystic (3), and poorly differentiated carcinoma (1). The nonepithelial tumors consisted of fibrous histiocytoma (13), lymphoid lesions (10), malignant melanoma (6), hemangiopericytoma (1), lipoma (1), granulocytic sarcoma (1), and neurofibroma (1). Review of the literature, including our own series, discloses a 55% malignancy rate for tumors originating in the lacrimal sac. Malignant epithelial neoplasms, especially invasive transitional cell carcinoma, often recur locally and can metastasize and be fatal. Epithelial malignancies tend to grow along the epithelium of the lacrimal drainage system, and thus cure is dependent on a wide surgical excision of the tumor and of the entire lacrimal drainage system (canaliculi, sac, and nasolacrimal duct) combined with a lateral rhinostomy and radiation therapy.


A novel airlift photobioreactor with baffles for improved light utilization through the flashing light effect.
A newly developed flat panel airlift photobioreactor with a defined circulation path was tested for microalgal culture. The bioreactor exposed the cells to intermittent light to improve the efficiency of light utilization through the flashing-light effect. During batch cultures in the new photobioreactor, the biomass productivity of Chlorella vulgaris was 1.7 times greater than in a randomly mixed bubble column of identical dimension. A reduction in light path from 30 to 15 mm increased the biomass productivity by 2.5-fold. A maximum dry biomass productivity of 0.11 g l(-1) h(-1) was obtained at an artificial illumination of 980 mu E m(-2) s(-1).


Internal nanocavity based high-resolution and stable structural colours fabricated by laser printing.
Bioinspired structural colors are attracting increasing attention in photonics, display, labeling and so forth. High-resolution and stable coloration is significant but is challenging to be fabricated in a facile and low-cost way. Herein, multilayer architecture containing an internal nanocavity as the structural color unit is obtained conveniently by direct nanosecond laser printing in atmosphere condition. Arbitrary colorful patterns with submicron accuracy can be realized only by a single step. And such structural colors induced by inner structures in the interlayer are antipollutive, antioxidative and easy to clean.


Adaptive correction of depth-induced aberrations in multiphoton scanning microscopy using a deformable mirror.
We demonstrate adaptive aberration correction for depth-induced spherical aberration in a multiphoton scanning microscope with a micromachined deformable mirror. Correction was made using a genetic learning algorithm with two-photon fluorescence intensity feedback to determine the desired shape for an adaptive mirror. For a 40x/0.6 NA long working distance objective, the axial scanning range was increased from 150 mm to 600 mm.


Micellization and Solvation Properties of Newly Synthesized Imidazolium- and Aminium-Based Surfactants.
This work aimed to study the solvation properties of newly synthesized cationic surfactants: 1-hexyl-1-methyl-1H-imidazol-1-ium bromide (R6Im), 1-dodecyl-1-methyl-1H-imidazol-1-ium bromide (R12Im), N,N,N-tributylhexan-1-aminium bromide (R6N4), and N,N,N-tributyldodecan-1-aminium bromide (R12N4) in water and ethanol-water solvents with a 0.237 mole fraction of ethanol at 298.15 K using conductivity, refractive index, surface tension, and density measurements. Critical micelle concentration (CMC) for the synthesized surfactants was determined and discussed. Thermodynamic parameters including association constant, molal volume, and polarizability were calculated and discussed. Some surface properties of surfactants including excess surface concentration and minimum area per molecule were also calculated and discussed. A good agreement was found between the CMC values obtained from different techniques, such as conductivity, refractive index, and surface tension. Imidazolium surfactants had been proved to decrease the CMC and increase the association constant with the increase of ethanol mole fraction, while tributylamine had been proved to increase the CMC and decrease the association constant with the increase of ethanol mole fraction. Also, imidazolium surfactants had been proved to have higher CMC than tributylamine, which may be related to higher solvation of imidazolium surfactants than that of tributylamine. Both surfactants (R12Im) and (R12N4) were proved to have lesser CMC.


[Reconstruction of visceral arteries with homografts in excision of the pancreas].
At present, surgical treatment with R(0) resection offers the only chance of cure for patients suffering from pancreatic cancer. Carcinomas of the pancreas are frequently diagnosed at an inoperable stage because of local tumor progression by vessel wall infiltration. In a small series of patients, efforts have been made to increase curative resection rates for advanced pancreatic cancer by excision and reconstruction of the involved visceral arteries. Whether this provides clinical benefit remains uncertain. Since 2001 we have been employing "en bloc" tumor resection for advanced pancreatic carcinomas with extended infiltration of visceral vessels. Technical experience was gained previously by performing portal vein resection as well as arterial excision and reconstruction by direct anastomosis in the presence of malignant wall infiltration. A total of ten patients underwent vascular reconstruction by arterial homograft interposition. In six of ten cases, combined extended reconstructions of the hepatic and superior mesenteric arteries were performed. One patient died during the perioperative course due to fulminant bleeding. One patient developed severe diarrhea. During a 3- to 18-month follow-up, one case of liver metastasis and one case of local tumor recurrence were documented. In selective cases, operability and R(0) resection can be achieved in advanced pancreatic cancer by performing extended resection procedures with vascular reconstruction using arterial homografts. Vascular substitution of visceral arteries can be conducted without ischemic disturbances of the small bowel and liver. Only a few perioperative complications were observed.


Effects of seasonal climatic variability on several toxic contaminants in urban lakes: Implications for the impacts of climate change.
Climate change is supposed to have influences on water quality and ecosystem. However, only few studies have assessed the effect of climate change on environmental toxic contaminants in urban lakes. In this research, response of several toxic contaminants in twelve urban lakes in Beijing, China, to the seasonal variations in climatic factors was studied. Fluorides, volatile phenols, arsenic, selenium, and other water quality parameters were analyzed monthly from 2009 to 2012. Multivariate statistical methods including principle component analysis, cluster analysis, and multiple regression analysis were performed to study the relationship between contaminants and climatic factors including temperature, precipitation, wind speed, and sunshine duration. Fluoride and arsenic concentrations in most urban lakes exhibited a significant positive correlation with temperature/precipitation, which is mainly caused by rainfall induced diffuse pollution. A negative correlation was observed between volatile phenols and temperature/precipitation, and this could be explained by their enhanced volatilization and biodegradation rates caused by higher temperature. Selenium did not show a significant response to climatic factor variations, which was attributed to low selenium contents in the lakes and soils. Moreover, the response degrees of contaminants to climatic variations differ among lakes with different contamination levels. On average, temperature/precipitation contributed to 8%, 15%, and 12% of the variations in volatile phenols, arsenic, and fluorides, respectively. Beijing is undergoing increased temperature and heavy rainfall frequency during the past five decades. This study suggests that water quality related to fluoride and arsenic concentrations of most urban lakes in Beijing is becoming worse under this climate change trend.


Effective Treatment for Recurrent Ovarian Cancer Guided by Drug Sensitivity from Ascites-Derived Organoid: A Case Report.
So far, ovarian cancer has still been the most lethal gynecological malignancy. The chemotherapy and targeted medication are the mainstay for the recurrent ovarian cancer treatment. About 70% of the advanced-stage cases will relapse. Ascites-derived organoid is a pre-clinical model for the precise prediction of the therapeutic effectiveness for the ovarian cancer: it can be used to assess the drug sensitivity, to guide individualized precise treatment, and to improve advanced stage as well as recurrent ovarian cancer patient' survival and prognosis. Until now, there has been no report concerning the establishment of the organoid out of the patient's ascites and the concurrent usage of drug sensitivity test to guide the individualized precise treatment for the ovarian cancer. Here, we report a case of recurrent ovarian cancer of a 59-year-old female patient whose CA125 at its peak increased to 4523.4 U/mL. Then, patient's own ovarian cancer organoid was constructed from the ascites by the abdominocentesis; concurrently, medication sensitivity test was performed on the organoid to guide individualized precise treatment. After the treatment, CA125 decreased to 33.7 U/mL, and the patient's condition relieved effectively. This is the first published case report using ascites-derived organoid and the drug sensitivity test thereof to guide the precise treatment of recurrent ovarian cancer.


Antioxidant and Antihypertensive Effects of a Chemically Defined Fraction of Syrah Red Wine on Spontaneously Hypertensive Rats.
A particularly phenolic-rich fraction extracted from red wine from the São Francisco valley (Northeastern Brazil) was chemically characterized and its hypotensive and antioxidant effects on spontaneously hypertensive rats were studied both in vitro and in vivo. The liquid-liquid pH dependent fractionation scheme afforded a fraction with high content of bioactive phenolics such as flavonols, flavonol glycosides, phenolic acids and anthocyanins, whose identities were confirmed by liquid chromatography coupled to mass spectrometry analysis. Pretreatment of spontaneously hypertensive rats with this wine fraction at doses of 50 and 100 mg/kg by gavage. for 15 days was able to decrease mean arterial pressure and heart rate as well as decrease serum lipid peroxidation. The fraction at concentrations of 0.01-1000 µg/mL induced concentration-dependent relaxation of isolated rat superior mesenteric artery rings pre-contracted with phenylephrine and this effect was not attenuated by endothelium removal. Our results demonstrate it is possible for phenolic constituents of red wine that are orally bioavailable to exert in vivo hypotensive and antioxidant effects on intact endothelial function.


Axonal transport in transplanted frog sciatic nerve.
Axonal transport was studied in transplanted frog sciatic nerves-dorsal ganglia for periods up to three months. The ganglia were either labeled prior to, or after varying periods of transplantation and the distribution of labeled proteins compared. The survival of the preparations was assessed by studying their ability to transmit compound action potentials, to maintain axonal transport and by their ultrastructural appearance. The sensory neurons retained their fast axonal transport and excitability during the transplantation periods. Morphologically about 30% of the axons appeared normal after one month of transplantation. The amount and distribution of protein incorporated radioactivity in the ganglia and the nerve changed with time but the decrease in the ganglia was not accompanied by a corresponding increase in the nerve. There was no evidence for a distinct slow phase of transport in spite of a functional fast transport system. The results indicate that either slow transport stops when the normal balance between release, degradation and recirculation is distributed by the presence of a ligature or that there is a continuous change in the composition of transported material with the time after labeling which is not reflected in altered transport characteristics.


On the current status of the evolutionary theory of behavior dynamics.
The evolutionary theory of behavior dynamics is a complexity theory that instantiates the Darwinian principles of selection, reproduction, and mutation in a genetic algorithm. The algorithm is used to animate artificial organisms that behave continuously in time and can be placed in any experimental environment. The present paper is an update on the status of the theory. It includes a summary of the evidence supporting the theory, a list of the theory's untested predictions, and a discussion of how the algorithmic operations of the theory may correspond to material reality. Based on the evidence reviewed here, the evolutionary theory appears to be a strong candidate for a comprehensive theory of adaptive behavior.


Modelling the impacts of pests and diseases on agricultural systems.
The improvement and application of pest and disease models to analyse and predict yield losses including those due to climate change is still a challenge for the scientific community. Applied modelling of crop diseases and pests has mostly targeted the development of support capabilities to schedule scouting or pesticide applications. There is a need for research to both broaden the scope and evaluate the capabilities of pest and disease models. Key research questions not only involve the assessment of the potential effects of climate change on known pathosystems, but also on new pathogens which could alter the (still incompletely documented) impacts of pests and diseases on agricultural systems. Yield loss data collected in various current environments may no longer represent a adequate reference to develop tactical, decision-oriented, models for plant diseases and pests and their impacts, because of the ongoing changes in climate patterns. Process-based agricultural simulation modelling, on the other hand, appears to represent a viable methodology to estimate the impacts of these potential effects. A new generation of tools based on state-of-the-art knowledge and technologies is needed to allow systems analysis including key processes and their dynamics over appropriate suitable range of environmental variables. This paper offers a brief overview of the current state of development in coupling pest and disease models to crop models, and discusses technical and scientific challenges. We propose a five-stage roadmap to improve the simulation of the impacts caused by plant diseases and pests; i) improve the quality and availability of data for model inputs; ii) improve the quality and availability of data for model evaluation; iii) improve the integration with crop models; iv) improve the processes for model evaluation; and v) develop a community of plant pest and disease modelers.


Correlation between Early Tumor Marker Response and Imaging Response in Patients with Advanced Hepatocellular Carcinoma Treated with Lenvatinib.
This study investigated early tumor marker response and treatment response in patients with advanced hepatocellular carcinoma (HCC) treated with lenvatinib. Twenty patients with advanced HCC who received lenvatinib were enrolled in this retrospective study. α-Fetoprotein (AFP) and des-γ-carboxyprothrombin (DCP) levels were measured before treatment as well as 2 and 4 weeks after treatment. The objective response rate was evaluated by mRECIST at 6 weeks. The response rate was 30% (complete response/partial response/stable disease/progressive disease: n = 0/6/6/8 cases) by mRECIST. At 4 weeks, the AFP levels of 12 patients (80%) were lower than at baseline. The AFP levels of 9 patients (60%) continued decreasing from 2 weeks to 4 weeks (sustained-reduction group). In this group, the response rate was 67%. The median AFP change rate was -39% at 4 weeks. In imaging responders, the AFP change rate significantly decreased (p = 0.02). The DCP change rate had no significant correlation with imaging response. The AFP-sustained-reduction group had significantly higher adherence to lenvatinib than the non-sustained-reduction group (p = 0.02). With lenvatinib therapy for HCC, the AFP levels of most patients had declined at 2 weeks, and at 4 weeks the AFP-sustained-reduction group demonstrated a higher objective response.


Reproducibility of nasal potential difference measurements in cystic fibrosis.
Nasal potential difference (NPD) measurement has been advocated as a diagnostic tool for cystic fibrosis (CF) patients and as a method for assessing the response to new therapies. The purpose of this study was to examine the reproducibility of NPD measurements performed in a single center. A total of 68 CF patients with a mean (+/- SD) age of 16 +/- 8 years (age range, 6 to 52 years) underwent NPD measurements on at least two occasions. A total of 25 patients with classic CF (mean age, 21 +/- 8 years) and 43 patients with nonclassic CF (mean age, 14 +/- 8 years) underwent sweat tests and NPD measurements. The mean sweat chloride values were 102 +/- 18 and 54 +/- 14 mEq/L, respectively, for classic CF and nonclassic CF groups. All patients underwent repeat NPD measurements. The basal NPD and the response to amiloride (DeltaAmil) and response to Cl(-) free and isoproterenol (DeltaCl(-) free + iso) were very similar in both measurements. In the classic CF group, the basal potential difference values were -40 +/- 12 vs -39 +/- 11 mV (p = 0.57), respectively, for the first and second measurements; 27 +/- 9 vs 26 +/- 10 mV (p = 0.55), respectively, for DeltaAmil; and 2.1 +/- 3.8 vs 0.4 +/- 2.9 mV (p = 0.07), respectively, for DeltaCl(-) free + iso. In the nonclassic CF group, the values were -32 +/- 13 vs -28 +/- 10 mV (p = 0.008), respectively; 19 +/- 10 vs 17 +/- 8 mV (p = 0.388), respectively; and -3.2 +/- 4.6 vs -3.3 +/- 4.4 mV (p = 0.876), respectively. When performed in a single center, NPD is a reproducible test for CF patients and thus may be a useful outcome measurement for assessment of the efficacy of new treatments.


Optical Mapping of Brain Activity Underlying Directionality and Its Modulation by Expertise in Mandarin/English Interpreting.
Recent neuroimaging research has suggested that unequal cognitive efforts exist between interpreting from language 1 (L1) to language 2 (L2) compared with interpreting from L2 to L1. However, the neural substrates that underlie this directionality effect are not yet well understood. Whether directionality is modulated by interpreting expertise also remains unknown. In this study, we recruited two groups of Mandarin (L1)/English (L2) bilingual speakers with varying levels of interpreting expertise and asked them to perform interpreting and reading tasks. Functional near-infrared spectroscopy (fNIRS) was used to collect cortical brain data for participants during each task, using 68 channels that covered the prefrontal cortex and the bilateral perisylvian regions. The interpreting-related neuroimaging data was normalized by using both L1 and L2 reading tasks, to control the function of reading and vocalization respectively. Our findings revealed the directionality effect in both groups, with forward interpreting (from L1 to L2) produced more pronounced brain activity, when normalized for reading. We also found that directionality was modulated by interpreting expertise in both normalizations. For the group with relatively high expertise, the activated brain regions included the right Broca's area and the left premotor and supplementary motor cortex; whereas for the group with relatively low expertise, the activated brain areas covered the superior temporal gyrus, the dorsolateral prefrontal cortex (DLPFC), the Broca's area, and visual area 3 in the right hemisphere. These findings indicated that interpreting expertise modulated brain activation, possibly because of more developed cognitive skills associated with executive functions in experienced interpreters.


Tricho-hepato-enteric syndrome: Retrospective multicenter experience in Saudi Arabia.
Trichohepatoenteric syndrome (THES) is a very rare disorder that is characterized by intractable congenital diarrhea, woolly hair, intrauterine growth restriction, facial dysmorphism, and short stature. Our knowledge of THES is limited due to the small number of reported cases. Thirty patients diagnosed with THES, all molecularly confirmed by whole exome sequencing (WES) to have biallelic variants in TTC37 or SKIV2L, were included in the study. Clinical, biochemical, and nutritional phenotypes and outcome data were collected from all participants. The median age of THES patients was 3.7 years (0.9-23 years). Diarrhea and malnutrition were the most common clinical features (100%). Other common features included hair abnormalities (96%), skin hyperpigmentation (87%), facial dysmorphic abnormalities (73%), psychomotor retardation (57%), and hepatic abnormalities (30%). Twenty-five patients required parenteral nutrition (83%) with a mean duration of 13.34 months, and nearly half were eventually weaned off. Parenteral nutrition was associated with a poor prognosis. The vast majority of cases (89.6%) had biallelic variants in SKIV2L, with biallelic variants in TTC37 accounting for the remaining cases. A total of seven variants were identified in TTC37 (n = 3) and SKIV2L (n = 4). The underlying genotype influenced some phenotypic aspects, especially liver involvement, which was more common in TTC37-related THES. Our data helps define the natural history of THES and provide clinical management guidelines.


Characterization of an established human, malignant, glioblastoma cell line (GBM) and its response to conventional drugs.
A cell line, GBM, was established from a human malignant glioblastoma and was characterized with particular reference to its response to conventional drugs. The GBM cell line exhibited a 73 +/- 7 h doubling time in monolayer cultures. Expression of glial fibrillary acidic and S-100 proteins was observed. Karyotype analysis of GBM cells at early passages revealed the presence of two near-triploid clones (A and B) with multiple chromosome rearrangements; a 100% frequency for clone B was observed in the established cell line. GBM cells had tumorigenic properties, since the s.c. injection of cultured cells into nude mice gave rise to slowly growing tumors. The morphology of GBM cells was retained during in vitro and in vivo passages, as judged by light microscopy. GBM cells were relatively resistant to most conventional drugs; among the tested drugs, only taxol exhibited a marked cytotoxic effect comparable to that found in cells of a different tumor type. GBM cells were found positive for the epidermal growth factor receptor, HER2-neu and P-glycoprotein by flow cytometry of cells labelled with monoclonal antibodies. In spite of the expression of relatively high gamma-glutamyltransferase activity, the intracellular glutathione level was comparable to that of other chemosensitive tumor cells. This glioblastoma cell line is a suitable model for the identification and preclinical studies of new agents and provides an additional system to explore the molecular basis of the intrinsic drug resistance of glioblastoma.


The optical research progress of nanophosphors composed of transition elements in the fourth period of near-infrared windows I and II for deep-tissue theranostics.
Research in the field of nano-optics is advancing by leaps and bounds, among which near-infrared (NIR) light optics have attracted much attention. NIR light has a longer wavelength than visible light, such that it can avoid shielding caused by biological tissues. This advantage has driven its importance and practicality in human treatment applications and has attracted significant attention from researchers in academia and industry. In the broad spectrum of infrared light wavelengths, the most noticeable ones are the NIR biological window I of 700-900 nm and window II of 1000-1700 nm. Luminescent materials can effectively cover the NIR biological window with different doping strategies. These doped elements are mostly transition elements with multielectron orbitals. Several nanomaterials based on narrow-spectrum lanthanides have been developed to correspond to biological applications of different wavelengths. However, this review explicitly introduces the absorption and reflection/luminescence interactions between NIR light and biological tissues independently. Unlike the adjustment of the wavelength of the lanthanide series, this review analyzes the NIR optical properties of the fourth-period element ions in transition elements (such as Cr3+ and Ni2+). These elements have a broadband wavelength of NIR light emission and higher quantum efficiency, corresponding to the absorption and emission spectrum and photobiological absorption of different NIR windows for therapeutic diagnosis. Finally, this review lists and explores other broadband NIR phosphors and has tried to discover the possibility of non-invasive precision medicine in the future.


Melodic contour identification and sentence recognition using sung speech.
For bimodal cochlear implant users, acoustic and electric hearing has been shown to contribute differently to speech and music perception. However, differences in test paradigms and stimuli in speech and music testing can make it difficult to assess the relative contributions of each device. To address these concerns, the Sung Speech Corpus (SSC) was created. The SSC contains 50 monosyllable words sung over an octave range and can be used to test both speech and music perception using the same stimuli. Here SSC data are presented with normal hearing listeners and any advantage of musicianship is examined.


Dopamine, through the extracellular signal-regulated kinase pathway, downregulates CD4+CD25+ regulatory T-cell activity: implications for neurodegeneration.
Fighting off neuronal degeneration requires a well controlled T-cell response against self-antigens residing in sites of the CNS damage. The ability to evoke this response is normally suppressed by naturally occurring CD4+CD25+ regulatory T-cells (Treg). No physiological compound that controls Treg activity has yet been identified. Here, we show that dopamine, acting via type 1 dopamine receptors (found here to be preferentially expressed by Treg), reduces the suppressive activity and the adhesive and migratory abilities of Treg. Treg activity was correlated with activation of the ERK1/2 (extracellular signal-regulated kinase 1/2) signaling pathway. Systemic injection of dopamine or an agonist of its type 1 receptors significantly enhanced, via a T-cell-dependent mechanism, protection against neuronal death after CNS mechanical and biochemical injury. These findings shed light on the physiological mechanisms controlling Treg and might open the way to novel therapeutic strategies for downregulating Treg activity (e.g., in neuronal degeneration) or for strengthening it (in autoimmune diseases).


Construct validity comparisons of three methods for measuring patient compliance.
A multitrait - multimethod design was employed to assess the construct validity of three commonly used methods for assessing patient compliance: physiological assessments (e.g., blood chemistries), ratings by health professionals, and patient self-reports. Subjects were patients receiving ambulatory hemodialysis treatments for end-stage renal disease, whose regimen required them to take medications, to follow dietary restrictions, and to limit fluid intake. Study findings indicated that of the three methods examined, the nurse rating approach was the most valid (although it contained only about 50 percent valid variance). Measures derived from physiological assessments contained a substantial proportion of residual error (over 70 percent), and the patient self-report method contained only about 12 percent valid variance (with about 18 percent method-effects variance, and 68 percent residual-error variance). These results make clear the need for additional research directed at developing valid methods for evaluating patient compliance behaviors.


The Cyclopropyl Group as a Neglected Donor in Donor-Acceptor Cyclopropane Chemistry.
D-A cyclopropanes bearing a simple cyclopropyl group as donor are shown to undergo a variety of [3+ n]-cycloaddition reactions ( n = 2-4). This behavior contrasts sharply with that of common D-A cyclopropanes with aliphatic donors. Kinetic experiments demonstrate that, in terms of donor ability, the cyclopropyl substituent lies between electron-rich and electron-neutral aryl donors.


The ontogeny of antipredator behavior in paradise fish larvae (Macropodus opercularis) IV. The effect of exposure to siblings.
Twenty-five-day-old larval paradise fish show less avoidance behavior toward a model predator than 20-day-old fish larvae. Laboratory experiments tested two possible hypotheses: The decrease of avoidance behavior is the result of (a) change in the size ratio of larvae/model, or (b) experience with larval siblings. Larval paradise fish did not show greater avoidance of larger models or models with larger eyespots. However, if isolated for 3 days, the antipredator behavior of 25-day-old larvae became similar to younger ones. In further experiments, we raised the larvae in a larger holding tank in order to decrease the rate of encounters among conspecifics. In line with our assumptions, these larvae also showed enhanced avoidance toward a model predator. In sum, our experiments revealed that the continuous exposure to conspecific larvae was the main cause for the reduced antipredator behavior toward models. To account for our results, we suggest that larvae of nonschooling paradise fish habituate to the continuous presence of larval conspecifics and, as a result, they show decreased avoidance to the model predator. We hypothesize that this habituation process might not work in other fish species that show early schooling behavior in their development. In other words, they would not generalize the experience of conspecifics to potential predators.


HTLV infection in blood donors from Mato Grosso do Sul state: a closer look at HTLV screening in Brazilian blood banks.
Human T-lymphotropic virus (HTLV) infection has a worldwide distribution and currently, more than 2.5 million individuals have been infected in Brazil. The study aimed to investigate HTLV infection prevalence among blood donors in Mato Grosso do Sul, characterizing seroepidemiological profiles of HTLV-1/2 positive individuals and evaluating the blood bank's HTLV screening system. A cross-sectional survey was conducted among blood donors from Mato Grosso do Sul state (MS)-Central Brazil, between January to December 2021. The information was obtained from databases, samples from the collection of HEMOSUL, and active searching, with the completion of laboratory analyses. 35,278 blood donors were screened for anti-HTLV-1/2 by chemiluminescence immunoassay (CMIA). Among them, 78 were initially reactive for anti-HTLV-1/2 (2.21/1000). Out of 78, 67 returned to the blood center to collect a second sample for retesting with a second screening with CMIA. After confirmation, 8 samples were indeterminate, and 8 were confirmed as positive for HTLV antibodies. New tests were performed for the 8 positive samples, and 6 were confirmed as HTLV-1 infection (0.17/1,000), one as negative, and one as indeterminate. The present study describes the low prevalence of HTLV infection in blood donors from MS and contributes to the definition of the regional infection profile. The prevalence found in this study (0.017%-0.17/1000) shows to be a much lower value than the rates reported in other states in Brazil. We highlight the need for confirmatory testing for those seropositive donors in screening assays and the need for adequate counseling and patient management for those confirmed HTLV individuals.


Functional interdependence of the actin regulators CAP1 and cofilin1 in control of dendritic spine morphology.
The vast majority of excitatory synapses are formed on small dendritic protrusions termed dendritic spines. Dendritic spines vary in size and density that are crucial determinants of excitatory synaptic transmission. Aberrations in spine morphogenesis can compromise brain function and have been associated with neuropsychiatric disorders. Actin filaments (F-actin) are the major structural component of dendritic spines, and therefore, actin-binding proteins (ABP) that control F-actin dis-/assembly moved into the focus as critical regulators of brain function. Studies of the past decade identified the ABP cofilin1 as a key regulator of spine morphology, synaptic transmission, and behavior, and they emphasized the necessity for a tight control of cofilin1 to ensure proper brain function. Here, we report spine enrichment of cyclase-associated protein 1 (CAP1), a conserved multidomain protein with largely unknown physiological functions. Super-resolution microscopy and live cell imaging of CAP1-deficient hippocampal neurons revealed impaired synaptic F-actin organization and dynamics associated with alterations in spine morphology. Mechanistically, we found that CAP1 cooperates with cofilin1 in spines and that its helical folded domain is relevant for this interaction. Moreover, our data proved functional interdependence of CAP1 and cofilin1 in control of spine morphology. In summary, we identified CAP1 as a novel regulator of the postsynaptic actin cytoskeleton that is essential for synaptic cofilin1 activity.


Tf2NH-Catalyzed Formal [3 + 2] Cycloaddition of Ynamides with Dioxazoles: A Metal-Free Approach to Polysubstituted 4-Aminooxazoles.
An unprecedented Tf2NH-catalyzed formal [3 + 2] cycloaddition of ynamides with dioxazoles was developed to construct various polysubstituted 4-aminooxazoles. This approach features a metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost catalyst, exceptionally mild reaction conditions, a very short reaction time, a broad substrate scope, and high efficiency. This metal-free protocol may find applications in pharmaceutical-oriented synthesis.


[The nurse as endoscopist].
A new diagnostic strategy for evaluation of patients with symptoms suggestive of colorectal cancer involves an increased use of flexible sigmoidoscopy. The number of endoscopists is declining, and therefore we found it interesting to describe a endoscopy training programme for the first two Danish nurses. Two nurses were enrolled in a five-module practical training programme including a multiple-choice test and simulator training. After their completion of at least 100 sigmoidoscopies, a questionnaire on patient satisfaction was administered together with recording of technical details of the sigmoidoscopies during a three-month period. During the three-month period, the nurses performed 69 sigmoidocopies. Of these, 88% reached a triangular lumen, the median examination time was 25 minutes, intubation of the sigmoid was successful in all cases and video review of the sigmoidoscopies revealed that no significant pathology had been misdiagnosed. Patient satisfaction among those examined by nurses showed that fewer patients experienced pain during the endoscopy than those examined by doctors. The training programme was completed as planned, and the nurses obtained endoscopic skills comparable to that of doctors concerning patient satisfaction. Sigmodoscopy can be performed at an acceptably high standard by nurses. Training nurses to perform endoscopy requires a significant number of teaching hours and close supervision.


Strand bias in targeted gene repair is influenced by transcriptional activity.
Modified single-stranded DNA oligonucleotides can direct nucleotide exchange in Saccharomyces cerevisiae. Point and frameshift mutations are corrected in a reaction catalyzed by cellular enzymes involved in various DNA repair processes. The present model centers on the annealing of the vector to one strand of the helix, followed by the correction of the designated base. The choice of which strand to target is a reaction parameter that can be controlled, so here we investigate the properties of strand bias in targeted gene repair. An in vivo system has been established in which a plasmid containing an actively transcribed, but mutated, hygromycin-enhanced green fluorescent protein fusion gene is targeted for repair and upon conversion will confer hygromycin resistance on the cell. Overall transcriptional activity has a positive influence on the reaction, elevating the frequency. If the targeting vector is synthesized so that it directs nucleotide repair on the nontranscribed strand, the level of gene repair is higher than if the template strand is targeted. We provide data showing that the targeting vector can be displaced from the template strand by an active T7 phage RNA polymerase. The strand bias is not influenced by which strand serves as the leading or lagging strand during DNA synthesis. These results may provide an explanation for the enhancement of gene repair observed when the non-template strand is targeted.