Cell-surface expression of complement restriction factors and sialyl Lewis antigens in oral carcinoma: relevance to chemo-immunotherapy.
Oral squamous cell carcinomas overexpress tumor-associated antigens, yet these antigens do not induce an immune-mediated anti-tumor response. The absence of an anti-tumor immune response may be due to poor immunogenicity of the tumor antigens or due to presence of factors that restrict immune functions. We have analyzed the expression of the tumor-associated sialyl LewisA (sLeA) and sialyl LewisX (sLeA) antigens, the complement restriction factors (CD59, CD46 and CD55) and the apoptosis associated factors Fas and Fas Ligand. Sialyl Lewis antigens (sLeA and sLeX), are immunogenic in that they elicit complement-fixing IgM antibodies. These antigens are associated with aggressive invasive behavior, tumor progression and poor disease-free survival of patients with human carcinomas. Human oral squamous carcinoma cell lines, SCC12 and SCC71, were analyzed for the density of Sialyl Lewis antigens, CD59, CD46, CD59, Fas and FasL on the cell surface. Expression of these antigens on the cell surface was determined employing a cell-suspension ELISA with monospecific monoclonal antibodies. In both oral carcinoma cell lines, the density of expression of sLeX was higher than that of sLeA and SCC71 had a very low level of sLeA expression. Both cell lines expressed a high density of CD59 and slightly lower levels of CD46 and CD55 on the cell surface, suggesting that even if host antibodies are accessible to the target antigens such as sLeX, they could not mediate complement-dependent cytotoxicity. The SCC lines expressed very low levels of Fas and FasL indicating that there maybe a lack of these signaling molecules for apoptosis. Our data suggests that passive immunotherapy or tumor killing by antibody-complement interaction may require downregulation of complement restriction factors.


Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo.
Effector molecules translocated by the Salmonella pathogenicity island (SPI)1-encoded type 3 secretion system (T3SS) critically contribute to the pathogenesis of human Salmonella infection. They facilitate internalization by non-phagocytic enterocytes rendering the intestinal epithelium an entry site for infection. Their function in vivo has remained ill-defined due to the lack of a suitable animal model that allows visualization of intraepithelial Salmonella. Here, we took advantage of our novel neonatal mouse model and analyzed various bacterial mutants and reporter strains as well as gene deficient mice. Our results demonstrate the critical but redundant role of SopE2 and SipA for enterocyte invasion, prerequisite for transcriptional stimulation and mucosal translocation in vivo. In contrast, the generation of a replicative intraepithelial endosomal compartment required the cooperative action of SipA and SopE2 or SipA and SopB but was independent of SopA or host MyD88 signaling. Intraepithelial growth had no critical influence on systemic spread. Our results define the role of SPI1-T3SS effector molecules during enterocyte invasion and intraepithelial proliferation in vivo providing novel insight in the early course of Salmonella infection.


The detection of CMV pp65 and IE1 in glioblastoma multiforme.
Glioblastoma multiforme (GBM) is a highly lethal brain tumor affecting children and adults, with the majority of affected individuals dying from their disease by 2 years following diagnosis. Other groups have reported the association of cytomegalovirus (CMV) with GBM, and we sought to confirm these findings in a large series of patients with primary GBM from our institution. Immunohistochemical analysis of paraffin embedded tissue sections was performed on 49 newly diagnosed GBM tumors, the largest series reported to date. We confirmed the presence of CMV pp65 on 25/49 (51%) and of IE1 on 8/49 (16%) of these tumors. While pp65 and IE1 are generally found in the nucleus of cells that are permissibly infected by CMV, GBM in this series had mostly cytoplasmic staining, with only 16% having nuclear staining for one or both of these antigens. We infected GBM cell lines with a laboratory strain of CMV, and found that most of the staining was cytoplasmic, with some perinuclear localization of IE1. To test the potential for CMV infected GBM cells to be recognized by CMV pp65 and IE1 specific cytotoxic T lymphocytes (CTL), we used CMV infected GBM cell lines in cytotoxicity assays with human leukocyte antigen partially matched CMV CTL. Lysis of CMV infected GBM tumor cells was accentuated by pre-treating these cell lines with either the demethylating agent decitabine or interferon-γ, both of which were shown to increase MHC Class I and II expression on tumor cells in vitro. These studies confirm the presence of CMV pp65 or IE1 on approximately half of GBM, with the possibility that CMV positive tumor cells can be recognized by CMV pp65/IE1 specific T cells.


Ultrasensitive and Quantitative DNA Methylation Detection Method Based on the MutS Protein.
DNA methylation is closely related to cancer. It is generally accepted that DNA methylation detection is crucial in cancer diagnosis, prognosis, and treatment monitoring. Therefore, there is an urgent demand for developing a simple, rapid, highly sensitive, and highly specific methylation detection method to detect DNA methylation at specific sites quantitatively. In this work, we introduce a DNA methylation detection method based on MutS and methylation-specific PCR, named MutS-based methylation-specific PCR (MB-MSP), which has the advantages of simplicity, speed, high specificity, sensitivity, and broad applicability. Utilizing the MutS's ability to bind mismatched base pairs, we inhibit not only the amplification of unmethylated DNA but also nonspecific primer amplification. We achieved a detection sensitivity of 0.5% for the methylated genes of ACP1, CLEC11A, and SEPT9 by MB-MSP. It has a good linear relationship and a detection time of only 1.5 h. To validate the feasibility of the MB-MSP method in clinical application, we conducted methylation detection on plasma-circulating tumor DNA samples from 10 liver cancer patients and 5 healthy people, achieving a 100% accuracy rate. In conclusion, MB-MSP, as a novel and reliable DNA methylation detection tool, holds significant application value and potential for advancing early cancer diagnosis.


[Systematization of nursing assistance: subsidies for implementation].
This study reviews national literature about the Systematization of Nursing Assistance in order to detect and reflect on the phases of its implementation. An electronic search of the data bases at LILACS, MEDLINE and BDENF revealed 61 published studies on this subject in nursing journals. This present study focuses on negative experiences regarding its implementation and presents a strategy for its successful implementation. The plan was observed to have various phases, but it was observed that the institution's structure, facilities and demands had to be first studied. It was concluded that the process for its implementation would be complex and difficult, but could contribute towards improving the quality of nursing care.


Perioperative care for patients with rheumatic diseases.
The perioperative care of patients with rheumatic diseases is hampered by a lack of evidence-based recommendations. Rheumatologists are called upon to 'clear' their patients for surgery, yet the evidence upon which to base decisions is fractionated and inconsistent. We have systematically reviewed the current literature and developed suggestions for three key areas that require particular deliberations in patients with rheumatic diseases scheduled for surgery: the management of cardiovascular risk, use of immunosuppressive drugs, and states of altered coagulation. For patients with rheumatic diseases associated with increased cardiovascular risk, such as rheumatoid arthritis and systemic lupus erythematosus, we suggest following the American College of Cardiology-American Heart Association guidelines using the underlying disease as a risk modifier. Most evidence suggests a neutral effect of conventional DMARDs in the perioperative period, with no need to discontinue them prior to surgery. Conversely, we suggest minimizing perioperative steroid use and unnecessary 'steroid preps'. The potential benefits of discontinuing biologic drugs in the perioperative setting needs to be carefully balanced with the risks associated with a disease flare. We discuss the American College of Chest Physicians guidelines, which classify individuals with antiphospholipid antibody syndrome as high-risk patients for perioperative thrombosis who are likely to require bridging therapy in most perioperative settings.


[DNA-diagnosis of carriers of the Duchenne muscular dystrophy gene].
Duchenne muscular dystrophy carrier detection has been performed by using probes XJ1.1 (intragenic probe) and probe 754 for a girl. The carrier probability was estimated by means of a computer program GenRisk combining pedigree and DNA-probe data and turned out to be 95%.


[Pediatric cardiac disease: indications for family screening and risk stratification].
In some forms of cardiac disease in childhood, familial occurrence is frequent. This implies the question whether family members should undergo cardiologic screening examinations. For cardiomyopathies the familiarity is so frequent and morbidity so important that examination by echo of all first degree relatives is recommended. As these cardiomyopathies may develop its phenotype all along a lifetime, repetitive examinations usually are indicated. For the primary electrical diseases the so called channelopathies the same is true, as for the high rate of familial occurrence and the high morbidity. Thus ECG screening of first degree relatives is recommended. In a child with congenital heart disease there are no recommendations with regard to familial screening and cardiological examinations usually are indicated only in case of clinical suspicion for heart disease.


PUREAIR protocol: randomized controlled trial of intensive pulmonary rehabilitation versus standard care in patients undergoing surgical resection for lung cancer.
Non-small cell lung cancer is the most common type of lung cancer. Surgery is proven to be the most effective treatment in early stages, despite its potential impact on quality of life. Pulmonary rehabilitation, either before or after surgery, is associated with reduced morbidity related symptoms and improved exercise capacity, lung function and quality of life. We describe the study protocol for the open-label randomized controlled trial we are conducting on patients affected by primary lung cancer (stages I-II) eligible for surgical treatment. The control group receives standard care consisting in one educational session before surgery and early inpatient postoperative physiotherapy. The treatment group receives, in addition to standard care, intensive rehabilitation involving 14 preoperative sessions (6 outpatient and 8 home-based) and 39 postoperative sessions (15 outpatient and 24 home-based) with aerobic, resistance and respiratory training, as well as scar massage and group bodyweight exercise training. Assessments are performed at baseline, the day before surgery and one month and six months after surgery. The main outcome is the long-term exercise capacity measured with the Six-Minute Walk Test; short-term exercise capacity, lung function, postoperative morbidity, length of hospital stay, quality of life (Short Form 12), mood disturbances (Hospital Anxiety and Depression Scale) and pain (Numeric Rating Scale) are also recorded and analysed. Patient compliance and treatment-related side effects are also collected. Statistical analyses will be performed according to the intention-to-treat approach. T-test for independent samples will be used for continuous variables after assessment of normality of distribution. Chi-square test will be used for categorical variables. Expecting a 10% dropout rate, assuming α of 5% and power of 80%, we planned to enrol 140 patients to demonstrate a statistically significant difference of 25 m at Six-Minute Walk Test. Pulmonary Resection and Intensive Rehabilitation study (PuReAIR) will contribute significantly in investigating the effects of perioperative rehabilitation on exercise capacity, symptoms, lung function and long-term outcomes in surgically treated lung cancer patients. This study protocol will facilitate interpretation of future results and wide application of evidence-based practice. ClinicalTrials.gov Registry n. NCT02405273 [31.03.2015].


The Association Between PLAYfun and Physical Activity: A Convergent Validation Study.
Purpose: The purpose of this study was to examine the convergent validity of the PLAYfun tool, a physical literacy-based measure of movement competence, by examining its association with objectively measured physical activity in a sample of children and youth. Method: Participants included 110 children between the ages of seven to 14 years attending a stratified random sample of 27 afterschool programs across the province of Ontario, Canada. The PLAYfun tool was administered to the participants on one occasion at their afterschool program and then they were asked to wear a pedometer for seven consecutive days to measure their physical activity levels. A series of multiple linear regression models were used to examine the association between PLAYfun scores and physical activity, while controlling for age, sex, and time of year (season) in which the data were collected. Results: On its own, the PLAYfun average score accounted for close to 13% of the variance in physical activity, R = .36, R2 = .13, p < .001. The PLAYfun average score was also a significant independent predictor of physical activity, b (SE) = 145.98 (53.46), p < .01, when controlling for age, sex, and season in which the data were collected, R2 = .30, F (4, 105) = 11.04, p < .001. Conclusion: Results from the present study indicate that the PLAYfun tool is a significant predictor of objectively measured physical activity, supporting the convergent validity of the tool.


Tailored therapy for severe asthma.
Patients with severe asthma or COPD have often a suboptimal symptom control due to inadequate treatment. A better understanding of pathogenetic mechanisms, phenotypes, endotypes and the new technologies available in the fields of molecular biology and immunogenetics have made it possible to synthesize specific monoclonal antibodies virtually able to interact with any target antigen, or to open a way for new therapeutic target options. At the moment, the only biologic drug available in clinical practice is omalizumab. To overcome the limits of omalizumab, the research has focused on new monoclonal antibodies presenting higher avidity for IgE (e.g. ligelizumab and lumiximab) and ability to interact also with low affinity IgE receptor (FcϵRII). At present, many new biological drugs with different mechanisms of action and targets are matter of research. It is very important to identify the asthmatic phenotype in order to select the most appropriate drug for the individual patient. The most promising agents are targeted against cytokines of Th2 pattern and related receptors, such as IL-2 (daclizumab) and IL-13 (lebrikizumab) or IL-5 in patients with hypereosinophilia (mepolizumab, reslizumab and benralizumab). Other interesting drugs have as a target TNF-α or its soluble receptor (infliximab, golimumab and etanercept) or IL-1 (canakinumab), a cytokine with an important systemic proinflammatory action. Finally, the discovery of increased levels of C5a in the airways of asthmatic patients has led to the synthesis of a specific monoclonal antibody (eculizumab). Further help should come from the identification of biomarkers that can guide in choosing the best treatment for the individual patient, such as IgE for omalizumab or periostin for lebrikizumab.


Retroperitoneal inflow procedures for iliac occlusive vascular disease.
We reviewed our experience over the past six years with retroperitoneal inflow procedures (aortofemoral and iliofemoral bypass grafts) in high-risk patients with aortoiliac occlusive disease. There were 57 limbs in 40 patients. Twenty percent of the patients were diabetic, 80% were smokers, 40% had heart disease, 54% had hypertension, and 25% had symptomatic chronic obstructive pulmonary disease. The average patient age was 64 years. There was no operative mortality and cumulative patency rate by life-table analysis at four years was 84%. The site of the proximal anastomosis (aorta vs iliac) or the configuration of the graft (unifemoral vs bifemoral) did not influence the patency rate. Retroperitoneal inflow procedures are an excellent alternative in patients who present an unacceptably high risk for standard aortofemoral reconstruction.


Rituximab in the Treatment of Refractory Anti-HMGCR Immune-mediated Necrotizing Myopathy.
A pathogenic role of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies has been proposed. Our objective was to assess efficacy of rituximab (RTX) in anti-HMGCR immune-mediated necrotizing myopathy. All patients who had been treated with RTX were retrospectively reviewed to assess features and outcome. Three of 9 patients demonstrated stable or improved muscle strength ± decline in creatine kinase levels, or T2/short-tau inversion recovery hypersignal decrease on magnetic resonance imaging following RTX treatment. RTX permitted intravenous immunoglobulin discontinuation and corticosteroid reduction to low dose in 2 patients. One-third of patients with refractory anti-HMGCR had improved strength or other evidence of improved disease activity following RTX treatment.


Disruption of differentiated functions during viral infection in vivo. V. Mapping of a locus involved in susceptibility of mice to growth hormone deficiency due to persistent lymphocytic choriomeningitis virus infection.
Lymphocytic choriomeningitis virus (LCMV) Armstrong strain selectively and persistently infects the majority of growth hormone (GH) producing cells in the anterior lobe of pituitary glands of C3H/St mice but negligibly infects GH producing cells of BALB/WEHI mice (Oldstone et al., Virology 142, 175--182, 1985; Oldstone et al., Science 218, 1125--1127, 1982). Although infected GH cells remain free of structural damage, disrupted initiation of GH transcription (Klavinskis and Oldstone, J. Gen. Virol. 68, 1867--1873, 1989; Valsamakis et al., Virology 156, 214--220, 1987) occurs with a resultant decrease in the synthesis of GH, leading to a failure of growth and development (Oldstone et al., Science 218, 1125--1127, 1982). Microsatellite mapping of DNA obtained from 101 individual C3H/St x BALB/WEHI F1 x F1 mice shows that the growth failure correlates with host genes linked (P value 0.0008) on chromosome 17 just outside of the H-2D MHC site between D17 Mit24 and D17 Mit51, a distance of 2.5 cM. The genetic mapping done here excludes alpha-dystroglycan (alpha-DG), a known receptor for LCMV (Cao et al., Science 282, 2079--2081, 1998) in pathogenesis of GH disease, as alpha-DG is encoded in the mouse by a gene residing on chromosome 9 (Yotsumoto et al., Hum. Mol. Genet. 5, 1259--1267, 1996).


Effect of minimal/mild hearing loss on children's speech understanding in a simulated classroom.
While classroom acoustics can affect educational performance for all students, the impact for children with minimal/mild hearing loss (MMHL) may be greater than for children with normal hearing (NH). The purpose of this study was to examine the effect of MMHL on children's speech recognition comprehension and looking behavior in a simulated classroom environment. It was hypothesized that children with MMHL would perform similarly to their peers with NH on the speech recognition task but would perform more poorly on the comprehension task. Children with MMHL also were expected to look toward talkers more often than children with NH. Eighteen children with MMHL and 18 age-matched children with NH participated. In a simulated classroom environment, children listened to lines from an elementary-age-appropriate play read by a teacher and four students reproduced over LCD monitors and loudspeakers located around the listener. A gyroscopic headtracking device was used to monitor looking behavior during the task. At the end of the play, comprehension was assessed by asking a series of 18 factual questions. Children also were asked to repeat 50 meaningful sentences with three key words each presented audio-only by a single talker either from the loudspeaker at 0 degree azimuth or randomly from the five loudspeakers. Both children with NH and those with MMHL performed at or near ceiling on the sentence recognition task. For the comprehension task, children with MMHL performed more poorly than those with NH. Assessment of looking behavior indicated that both groups of children looked at talkers while they were speaking less than 50% of the time. In addition, the pattern of overall looking behaviors suggested that, compared with older children with NH, a larger portion of older children with MMHL may demonstrate looking behaviors similar to younger children with or without MMHL. The results of this study demonstrate that, under realistic acoustic conditions, it is difficult to differentiate performance among children with MMHL and children with NH using a sentence recognition task. The more cognitively demanding comprehension task identified performance differences between these two groups. The comprehension task represented a condition in which the persons talking change rapidly and are not readily visible to the listener. Examination of looking behavior suggested that, in this complex task, attempting to visualize the talker may inefficiently utilize cognitive resources that would otherwise be allocated for comprehension.


The Antidepressant-Like and Analgesic Effects of Kratom Alkaloids are accompanied by Changes in Low Frequency Oscillations but not ΔFosB Accumulation.
Mitragyna speciosa ("kratom"), employed as a traditional medicine to improve mood and relieve pain, has shown increased use in Europe and North America. Here, the dose-dependent effects of a purified alkaloid kratom extract on neuronal oscillatory systems function, analgesia, and antidepressant-like behaviour were evaluated and kratom-induced changes in ΔFosB expression determined. Male rats were administered a low or high dose of kratom (containing 0.5 or 1 mg/kg of mitragynine, respectively) for seven days. Acute or repeated low dose kratom suppressed ventral tegmental area (VTA) theta oscillatory power whereas acute or repeated high dose kratom increased delta power, and reduced theta power, in the nucleus accumbens (NAc), prefrontal cortex (PFC), cingulate cortex (Cg) and VTA. The repeated administration of low dose kratom additionally elevated delta power in PFC, decreased theta power in NAc and PFC, and suppressed beta and low gamma power in Cg. Suppressed high gamma power in NAc and PFC was seen selectively following repeated high dose kratom. Both doses of kratom elevated NAc-PFC, VTA-NAc, and VTA-Cg coherence. Low dose kratom had antidepressant-like properties whereas both doses produced analgesia. No kratom-induced changes in ΔFosB expression were evident. These results support a role for kratom as having both antidepressant and analgesic properties that are accompanied by specific changes in neuronal circuit function. However, the absence of drug-induced changes in ΔFosB expression suggest that the drug may circumvent this cellular signaling pathway, a pathway known for its significant role in addiction.


Simultaneous determination of seven bioactive components in Guizhi Fuling capsule by microwave-assisted extraction combined with ultra performance liquid chromatography tandem mass spectrometry.
A simple, rapid and reliable microwave-assisted extraction (MAE) combined with ultra performance liquid chromatography tandem mass spectrometry method was developed for simultaneous determination of the seven bioactive constituents in Guizhi Fuling capsule (GFC), namely gallic acid, amygdalin, albiflorin, paeoniflorin, paeonol, cinnamic acid and pachymic acid, respectively. The operation of MAE optimised through orthogonal array design experiment was performed at 80°C for 10 min with methanol-water (70:30, v/v) as the extracting solvent. The method was validated including intra- and inter-day precision, repeatability and stability, with relative standard deviation less than 3.9%, 3.3%, 4.4% and 3.1%, respectively. All analytes showed the good linearity (r >0.999), and their average recoveries varied between 98.2% and 101.2%. The results indicated that this method was simple, effective and suitable for the quality control of GFC.


Issues of conceptualization and measurement of social support in the construction of nursing theory.
Social support has emerged in the last decade as a significant health behavior and, therefore, a promising focus of theory development in nursing. Nursing's concern with health, environment, and person provides an ideal perspective from which to take the lead in research, instrument development, and theory construction in social support. The focus of this article is the present development of the construct to assist nurse scholars toward an adequate conception of social support. Theoretical frameworks underlying definitions are examined, and issues of measurement and clinical assessment are discussed.


Successful Treatment of Hereditary Hemorrhagic Telangiectasia With Octreotide.
Hereditary hemorrhagic telangiectasia (HHT) is a disorder characterized by telangiectasias and arteriovenous malformations. We present a case report of a 74-year-old man diagnosed with HHT having a favorable response to a somatostatin analogue for treatment. This patient had been suffering from chronic anemia from recurrent gastrointestinal bleeding, requiring oral/intravenous iron replacement, frequent endoscopic ablations, and blood transfusions. Due to insufficient treatment, he was started on subcutaneous octreotide, with significant improvement as evidenced by a steady increase in the hemoglobin level, decreased endoscopic interventions, and decreased blood transfusions, making this the first case of HHT successfully treated with octreotide.


Fine mapping of an epilepsy modifier gene on mouse Chromosome 19.
Mutations in voltage-gated sodium channels are associated with several types of human epilepsy. Variable expressivity and penetrance are common features of inherited epilepsy caused by sodium channel mutations, suggesting that genetic modifiers may influence clinical severity. The mouse model Scn2a(Q54) has an epilepsy phenotype due to a mutation in Scn2a that results in elevated persistent sodium current. Phenotype severity in Scn2a(Q54) mice is dependent on the genetic background. Congenic C57BL/6J.Q54 mice have delayed onset and low seizure frequency compared to (C57BL/6J x SJL/J)F1.Q54 mice. Previously, we identified two modifier loci that influence the Scn2a(Q54) epilepsy phenotype: Moe1 (modifier of epilepsy 1) on Chromosome 11 and Moe2 on Chromosome 19. We have constructed interval-specific congenic strains to further refine the position of Moe2 on Chromosome 19 to a 5-Mb region. Sequencing and expression analyses of genes in the critical interval suggested two potential modifier candidates: (1) voltage-gated potassium channel subunit subfamily V, member 2 (Kcnv2), and (2) SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 2 (Smarca2). Based on its biological role in regulating membrane excitability and the association between ion channel variants and seizures, Kcnv2 is a strong functional candidate for Moe2. Modifier genes affecting the epilepsy phenotype of Scn2a(Q54) mice may contribute to variable expressivity and penetrance in human epilepsy patients with sodium channel mutations.


Sunitinib plus paclitaxel in patients with advanced esophageal cancer: a phase II study from the Hoosier Oncology Group.
The combination of sunitinb (37.5 mg orally daily) + paclitaxel (90 mg/m intravenously on days 1, 8, 15 every 4 weeks) was examined in patients with advanced esophageal or gastroesophageal junction cancer, and progression-free survival (PFS) was compared to that of historical controls. The end points included response rate, overall survival, and toxicities. Twenty-eight patients were enrolled at six centers. Median age was 59.5 years. The 24-week PFS rate was 25% (90% confidence interval [CI], 12-42%). Three (11%) of 23 evaluable patients had a response (1 complete response and 2 partial response) (90% CI, 3-25%). Median overall survival was 228 days (90% CI, 140-283 days). Grade 3/4 toxicities included leukopenia/neutropenia (25%), anemia (18%), fatigue (11%), and hemorrhage (11%). There were four grade 5 toxicities including upper gastrointestinal hemorrhage (n = 2), gastrointestinal/esophageal fistula (n = 1), and unexplained death (n = 1). In our study, we found that sunitinib + paclitaxel in patients with advanced esophageal or gastroesophageal junction cancer had a 24-week PFS no better than the PFS of historical controls. The combination also had a high rate of serious toxicities and will not be pursued.


The effect of uneven surfaces on inter-joint coordination during walking in children with cerebral palsy.
Clinical gait analysis on uneven surfaces contributes to the ecological assessment of gait deviations of children with spastic cerebral palsy (CP). Walking on uneven surfaces requires specific motor strategies, which can be assessed by lower-limb kinematic and inter-joint coordination analyses. This study aimed to assess and compare kinematics and inter-joint coordination between children with CP and their typically developing (TD) peers when walking on even and two levels of uneven surfaces (medium and high). A total of 17 children with CP and 17 TD children (11.5 ± 3.5 and 10.4 ± 4.5 years old, respectively) were asked to complete 6-8 gait trials on a 4-m walkway of each surface (n = 3) in randomized blocks while fit with retro-reflective markers on their lower-limbs. Children with CP showed proximal gait adaptations (i.e., hip and knee) on uneven surfaces. Compared with the TD group, the CP group showed decreased hip extension during late stance (49-63%, d = 0.549, p < 0.001), and a more in-phase knee-hip coordination strategy during swing phase (75-84% of gait cycle, d = 1.035, p = 0.029 and 92-100%, d = 1.091, p = 0.030) when walking on an uneven (high), compared to even surface. This study provides a better understanding of kinematic strategies employed by children with spastic CP when facing typical daily life gait challenges. Further studies are needed to evaluate the benefits of integrating uneven surfaces in rehabilitation care.


Use of non-steroidal anti-inflammatory drugs in pregnancy and oligohydramnios: a review.
The aim of this review is to evaluate the relationship between the use of non-steroidal anti-inflammatory drugs (NSAIDs) during last trimesters of the pregnancy and the reduction of amniotic fluid. Electronic databases were searched (PubMed, Medline, and Scopus). Selection criteria included studies reporting the relationship between oligohydramnios and use of NSAID during pregnancy. We analyzed the median age of women, weeks of pregnancy at the beginning of the drug administration, kind of medication, period of exposure and dosage, deepest vertical pocket (DVP), and amniotic fluid index (AFI). Of the 68 records identified, we analyzed 29 studies investigating the administration of NSAIDs, including 11 studies examined the administration of the Indomethacin, four articles have focused on the use of Nimesulide, and only two manuscripts considered the use of Diclofenac. We found a strict correlation between the development of oligohydramnios and the use of NSAIDs. The oligohydramnios is reversible, and the normal amount of amniotic fluid is restored after the interruption of the treatment. The use of NSAIDs should be considered when maternal benefits outweigh the potential fetal risk, at the lowest effective dose for shortest duration. Beyond 48 h of NSAIDs treatment, we consider ultrasound monitoring of amniotic fluid, and we suggest stopping therapy if a decline AFI is present.


Dark excited States of carotenoid regulated by bacteriochlorophyll in photosynthetic light harvesting.
In photosynthesis, carotenoids play important roles in light harvesting (LH) and photoprotective functions, which have been described mainly in terms of two singlet excited states of carotenoids: S(1) and S(2). In addition to the "dark" S(1) state, another dark state, S*, was recently identified and its involvement in photosynthetic functions was determined. However, there is no consistent picture concerning its nature or the mechanism of its formation. One particularly anomalous behavior obtained from femtosecond transient absorption (TA) spectroscopy is that the S*/S(1) population ratio depends on the excitation intensity. Here, we focus on the effect of nearby bacteriochlorophyll (BChl) on the relaxation dynamics of carotenoid in the LH complex. We performed femtosecond TA spectroscopy combined with pre-excitation of BChl in the reconstituted LH1 complex from Rhodospirillum rubrum S1. We observed that the energy flow from S(1), including its vibrationally excited hot states, to S* occurs only when nearby BChl is excited into Q(y), resulting in an increase in S*/S(1). We also examined the excitation-intensity dependence of S*/S(1) by conventional TA spectroscopy. A comparison between the pre-excitation effect and excitation-intensity dependence shows a strong correlation of S*/S(1) with the number of BChls excited into Q(y). In addition, we observed an increase in triplet formation as the S* population increased, indicating that S* is an electronic excited state that is the precursor to triplet formation. Our findings provide an explanation for observed spectroscopic features, including the excitation-intensity dependences debated so far, and offer new insights into energy deactivation mechanisms inherent in the LH antenna.


TRAUMA INDUCES INTRAVASCULAR HEMOLYSIS, EXACERBATED BY RED BLOOD CELL TRANSFUSION AND ASSOCIATED WITH DISRUPTED ARGININE-NITRIC OXIDE METABOLISM.
Background: Severe injury can provoke systemic processes that lead to organ dysfunction, and hemolysis of both native and transfused red blood cells (RBCs) may contribute. Hemolysis can release erythrocyte proteins, such as hemoglobin and arginase-1, the latter with the potential to disrupt arginine metabolism and limit physiologic NO production. We aimed to quantify hemolysis and arginine metabolism in trauma patients and measure association with injury severity, transfusions, and outcomes. Methods: Blood was collected from injured patients at a level I trauma center enrolled in the COMBAT (Control of Major Bleeding After Trauma) trial. Proteomics and metabolomics were performed on plasma fractions through liquid chromatography coupled with mass spectrometry. Abundances of erythrocyte proteins comprising a hemolytic profile as well as haptoglobin, l -arginine, ornithine, and l -citrulline (NO surrogate marker) were analyzed at different timepoints and correlated with transfusions and adverse outcomes. Results: More critically injured patients, nonsurvivors, and those with longer ventilator requirement had higher levels of hemolysis markers with reduced l -arginine and l -citrulline. In logistic regression, elevated hemolysis markers, reduced l -arginine, and reduced l -citrulline were significantly associated with these adverse outcomes. An increased number of blood transfusions were significantly associated with elevated hemolysis markers and reduced l -arginine and l -citrulline independently of New Injury Severity Score and arterial base excess. Conclusions: Severe injury induces intravascular hemolysis, which may mediate postinjury organ dysfunction. In addition to native RBCs, transfused RBCs can lyse and may exacerbate trauma-induced hemolysis. Arginase-1 released from RBCs may contribute to the depletion of l -arginine and the subsequent reduction in the NO necessary to maintain organ perfusion.


Impact of High-Dose Caffeine on the Preterm Ovine Cerebrum and Cerebellum.
Caffeine is one of the few treatments available for infants with apnea of prematurity. As the recommended dosing regimen is not always sufficient to prevent apnea, higher doses may be prescribed. However, little is currently known about the impact of high-dose caffeine on the developing brain; thus, our aim was to investigate the consequences of a high-dose regimen on the immature ovine brain. High-dose caffeine (25 mg/kg caffeine base loading dose; 20 mg/kg daily maintenance dose; n = 9) or saline (n = 8) was administered to pregnant sheep from 105 to 118 days of gestation (DG; term = 147 days); this is broadly equivalent to 28-33 weeks of human gestation. At 119DG, the cerebral cortex, striatum, and cerebellum were assessed histologically and by immunohistochemistry. Compared with controls, caffeine-exposed fetuses showed (i) an increase in the density of Ctip2-positive layers V-VI projection neurons (p = 0.02), Tbr1-positive layers V-VI projection neurons (p < 0.0001), astrocytes (p = 0.03), and oligodendrocytes (p = 0.02) in the cerebral cortex, (ii) a decrease in the density of Cux1-positive layers II-IV projection neurons (p = 0.01) in the cerebral cortex, and (iii) a reduction in the area of Purkinje cell bodies in the cerebellum (p = 0.03). Comparing high-dose caffeine-exposed fetuses with controls, there was no difference (p > 0.05) in: (i) the volume of the cerebral cortex or striatum, (ii) the density of neurons (total and output projection neurons) in the striatum, (iii) dendritic spine density of layer V pyramidal cells, (iv) the density of cortical GABAergic interneurons, microglia, mature oligodendrocytes or proliferating cells, (v) total cerebellar area or dimensions of cerebellar layers, or (vi) the density of cerebellar white matter microglia, astrocytes, oligodendrocytes, or myelin. Daily exposure of the developing brain to high-dose caffeine affects some aspects of neuronal and glial development in the cerebral cortex and cerebellum in the short-term; the long-term structural and functional consequences of these alterations need to be investigated.


Knowing self and caring through service learning.
Professional caring is the essence of nursing practice. Reflection on personal assumptions and beliefs challenge stereotypic views that influence professional caring and nursing care. An innovative educational pedagogy known as service learning creates an opportunity for students to reflect on self in the context of service to others; it is through this pedagogy that personal assumptions and beliefs are challenged as students become registered nurses. A qualitative descriptive study engaged undergraduate first and second year nursing students through interviews and reflections. The purposes of this study were to describe students' perception of self and caring in service learning, any changes in the perceptions of self over time, and the connection of self to others. Results identified three major themes: understanding self, becoming a nurse and learning to care with increasing depth over the two years. Implications for nursing curriculum and further research are discussed.


MR enhancement of the internal auditory canal induced by tissue implant after resection of acoustic neurinoma.
We studied intrameatal changes in MR enhancement induced by free-tissue implant over time after surgery for acoustic neurinoma. Twenty-one patients were examined by MR imaging after suboccipital resection of an acoustic neurinoma. Precontrast and postcontrast MR images were obtained within 3 days after surgery (early MR images), then 6 weeks (intermediate MR images) and 6 months (late MR images) after surgery. A muscle graft as a free-tissue implant was used within the internal auditory canal in 18 of the 21 patients to seal pneumatic cells of the petrosal bone inadvertently opened and to prevent leakage of cerebrospinal fluid. On the early MR images, only minimal leptomeningeal or perineural enhancement was seen in 16 patients. There was no sign of residual tumor; however, enhancement increased and changed from linear to nodular on the intermediate MR images in 16 of the 18 cases in which a muscle graft had been used during surgery, mimicking a small intrameatal tumor. This nodular enhancement was still visible on the late MR images in 13 of the 16 cases. Nodular MR enhancement within the internal auditory canal a few weeks to months after surgery for acoustic neurinoma may be induced by packing material and should be considered when interpreting postoperative MR images.


Attitudes toward obstetrics training. Residents surveyed at McGill University and University of Montreal.
To determine family medicine residents' attitudes toward family practice training in obstetrics and neonatology before and after implementation of a modified obstetrics curriculum at McGill University (MG). Two-group pretest and posttest. Fifty-seven respondents, 31 at MG, 26 at University of Montreal (UM), were case matched as first-year and second-year residents. Departments of Family Medicine at MG and UM. Family medicine residents at MG and UM. A modified obstetrics curriculum was introduced at MG (study group); no modifications were introduced at UM (control group). First- and second-year residents' attitudes toward the adequacy of training were assessed through responses to a questionnaire administered in July 1992 and July 1994. Changes in response scores before and after implementation of the modified curriculum. Repeated multivariate analysis of variance (MANOVA) showed respondents believed family practice obstetrics training was adequate in general, but that family practitioners were inadequately trained in emergency obstetric skills. Scores for items assessing neonatology skills increased significantly in the MG group after the intervention. Residents' overall confidence in their obstetrics training did not appear to improve, but this might be due to a time lag between curriculum modification and attitudinal change. McGill residents' confidence in neonatology skills improved significantly after curriculum modification.


Addiction stigma and the biopolitics of liberal modernity: A qualitative analysis.
Definitions of addiction have never been more hotly contested. The advance of neuroscientific accounts has not only placed into public awareness a highly controversial explanatory approach, it has also shed new light on the absence of agreement among the many experts who contest it. Proponents argue that calling addiction a 'brain disease' is important because it is destigmatising. Many critics of the neuroscientific approach also agree on this point. Considered from the point of view of the sociology of health and illness, the idea that labelling something a disease will alleviate stigma is a surprising one. Disease, as demonstrated in that field of research, is routinely stigmatised. In this article we take up the issue of stigma as it plays out in relation to addiction, seeking to clarify and challenge the claims made about the progress associated with disease models. To do so, we draw on Erving Goffman's classic work on stigma, reconsidering it in light of more recent, process oriented, theoretical resources, and posing stigmatisation as a performative biopolitical process. Analysing recently collected interviews conducted with 60 people in Australia who consider themselves to have an alcohol or other drug addiction, dependence or habit, we explore their accounts of stigma, finding experiences of stigma to be common, multiple and strikingly diverse. We argue that by treating stigma as politically productive - as a contingent biopolitically performative process rather than as a stable marker of some kind of anterior difference - we can better understand what it achieves. This allows us to consider not simply how the 'disease' of addiction can be destigmatised, or even whether the 'diseasing' of addiction is itself stigmatising (although this would seem a key question), but whether the very problematisation of 'addiction' in the first place constitutes a stigma process.


[Interpretation of the European Federation of Periodontology S3 level clinical practice guideline for prevention and treatment of peri-implant diseases].
The S3 level clinical practice guideline for the prevention and treatment of peri-implant diseases, developed by the European Federation of Periodontology, was published in June, 2023 (DOI: 10.1111/jcpe.13823), which culminated in the recommendations for implementation of various different interventions before, during and after implant placement/loading. Aim of the present article is to summarize and interpret the key points of this guideline and help clinicians understand this guideline better, in order to standardize the prevention and treatment of peri-implant diseases.


Breast surface estimation for radar-based breast imaging systems.
Radar-based microwave breast-imaging techniques typically require the antennas to be placed at a certain distance from or on the breast surface. This requires prior knowledge of the breast location, shape, and size. The method proposed in this paper for obtaining this information is based on a modified tissue sensing adaptive radar algorithm. First, a breast surface detection scan is performed. Data from this scan are used to localize the breast by creating an estimate of the breast surface. If required, the antennas may then be placed at specified distances from the breast surface for a second tumor-sensing scan. This paper introduces the breast surface estimation and antenna placement algorithms. Surface estimation and antenna placement results are demonstrated on three-dimensional breast models derived from magnetic resonance images.


The effect of baricity of intrathecal morphine in children receiving tetracaine spinal anaesthesia for cardiac surgery: a preliminary report.
This prospective, randomized study examined the effect of baricity of intrathecal preservative-free morphine on the duration of postoperative analgesia and incidence of side-effects in infants and children receiving high spinal anaesthesia with hyperbaric tetracaine in combination with a light general anaesthetic. Fourteen infants and children, aged 7-91 months, undergoing repair of either uncomplicated atrial or ventricular septal defects, were randomized to receive either 10 microg x kg(-1) of intrathecal morphine in combination with 0.5% tetracaine D10 (hyperbaric morphine group) or intrathecal morphine mixed with saline and injected sequentially after the administration of 0.5% tetracaine D10 (hypobaric morphine group). After spinal injection, patients were positioned in 30 degrees of Trendelenburg for a minimum of 10 min. Postoperatively, patients were monitored for a minimum of 12 h. Pain scores and the incidence and severity of side-effects were recorded every 1 h. All patients were extubated at the conclusion of surgery without any incidence of respiratory depression. There was a decreased incidence of vomiting in the hypobaric morphine group and no significant difference in the duration of analgesia. When intrathecal morphine is administered in conjunction with a hyperbaric tetracaine spinal to paediatric cardiac patients in the head down position, sequential administration of the hypobaric solution may mitigate side-effects.


Clostridium difficile infection in the absence of a colon.
Clostridium difficile (CD) infection is almost always confined to the colon causing a spectrum of illness ranging from diarrhoea to fulminant colitis. CD infection of the small intestine has been described but the identification of CD toxin in the stoma effluent of a patient with an end ileostomy is rare. We describe a 91-year-old woman, with a history of proctocolectomy for ulcerative colitis, presenting with profuse ileostomy diarrhoea after a course of antibiotics. Ileostomy effluent was positive for CD toxin but the patient died despite appropriate treatment. This suggests that the small intestine is susceptible to CD infection in antibiotic-treated patients many years after a colectomy. CD enteritis should be considered in all patients with increased ileostomy diarrhoea despite the absence of a colon.


Stock portfolio structure of individual investors infers future trading behavior.
Although the understanding of and motivation behind individual trading behavior is an important puzzle in finance, little is known about the connection between an investor's portfolio structure and her trading behavior in practice. In this paper, we investigate the relation between what stocks investors hold, and what stocks they buy, and show that investors with similar portfolio structures to a great extent trade in a similar way. With data from the central register of shareholdings in Sweden, we model the market in a similarity network, by considering investors as nodes, connected with links representing portfolio similarity. From the network, we find investor groups that not only identify different investment strategies, but also represent individual investors trading in a similar way. These findings suggest that the stock portfolios of investors hold meaningful information, which could be used to earn a better understanding of stock market dynamics.


Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with 90Y: a phase I study.
A Phase I radioimmunotherapy trial was conducted in which radioconjugated monoclonal antibody (MAb) was directly infused into the tumor or postoperative tumoral bed in patients with high-grade malignant glioma. BC-4, a murine MAb that recognizes tenascin, was used in these studies. The MAb was labeled with 90Y, a pure beta emitter with maximum energy of 2.284 MeV, which can penetrate into tissue up to 0.5-0.7 cm. Stable 90Y-labeled MAb conjugates were prepared using the chelator p-isothiocyanatobenzyl derivative of diethylenetriaminepentaacetic acid (ITC-Bz-DTPA), obtaining >95% labeling efficiency and conserving the antibodies' immunoreactivity (>85%). Twenty patients, 2 with anaplastic astrocytoma and 18 with glioblastoma, were included in the study. All of the patients had been treated previously with conventional therapies (surgery, external radiotherapy, and chemotherapy) and presented with progressive disease not amenable to further treatment. A dose-escalation study was performed using doses ranging from 5-30 mCi (185-1110 MBq) of 90Y-labeled MAb BC-4. The protein dose of MAb was always 1 mg. Three patients were treated at the 5, 10, 15, and 20 mCi levels, and the 25- and 30-mCi doses were each administered to 4 patients. Systemic toxicity was completely absent in all of the patients. The maximum tolerated dose to the brain was 25 mCi (925 MBq). The average dose to the tumor was 3200 cGy/mCi. Doses to the liver, bone marrow, and kidneys were below 10 cGy/mCi in all of the cases. Biodistribution studies demonstrated that the 90Y-labeled MAb accreted exclusively in the neoplastic area without any diffusion into the normal brain or other normal organs. No clinical responses were recorded because of the very advanced stage of disease at the time of radioimmunotherapy.


Active-site mutations in the Xrn1p exoribonuclease of Saccharomyces cerevisiae reveal a specific role in meiosis.
Xrn1p of Saccharomyces cerevisiae is a major cytoplasmic RNA turnover exonuclease which is evolutionarily conserved from yeasts to mammals. Deletion of the XRN1 gene causes pleiotropic phenotypes, which have been interpreted as indirect consequences of the RNA turnover defect. By sequence comparisons, we have identified three loosely defined, common 5'-3' exonuclease motifs. The significance of motif II has been confirmed by mutant analysis with Xrn1p. The amino acid changes D206A and D208A abolish singly or in combination the exonuclease activity in vivo. These mutations show separation of function. They cause identical phenotypes to that of xrn1Delta in vegetative cells but do not exhibit the severe meiotic arrest and the spore lethality phenotype typical for the deletion. In addition, xrn1-D208A does not cause the severe reduction in meiotic popout recombination in a double mutant with dmc1 as does xrn1Delta. Biochemical analysis of the DNA binding, exonuclease, and homologous pairing activity of purified mutant enzyme demonstrated the specific loss of exonuclease activity. However, the mutant enzyme is competent to promote in vitro assembly of tubulin into microtubules. These results define a separable and specific function of Xrn1p in meiosis which appears unrelated to its RNA turnover function in vegetative cells.


Comparative feasibility of implementing rapid diagnostic test and microscopy for parasitological diagnosis of malaria in Uganda.
In Uganda, parasite-based diagnosis is recommended for every patient suspected to have malaria before prescribing anti-malarials. However, the majority of patients are still treated presumptively especially in low-level health units. The feasibility of implementing parasite-based diagnosis for uncomplicated malaria in rural health centres (HCs) was investigated with a view to recommending measures for scaling up the policy. Thirty HCs were randomized to implement parasite-based diagnosis based on rapid diagnostic tests [RDTs] (n = 10), blood microscopy (n = 10) and presumptive diagnosis (control arm) (n = 10). Feasibility was assessed by comparing the proportion of patients who received parasite-based diagnosis; with a positive malaria parasite-based diagnosis who received artemether-lumefantrine (AL); with a negative malaria parasite-based diagnosis who received AL; and patient waiting time. Clinicaltrials.gov: NCT00565071. 102, 087 outpatients were enrolled. Patients were more likely to be tested in the RDT 44, 565 (96.6%) than in microscopy arm 19, 545 (60.9%) [RR: 1.59]. RDTs reduced patient waiting time compared to microscopy and were more convenient to health workers and patients. Majority 23, 804 (99.7%) in presumptive arm were prescribed AL. All (100%) of patients who tested positive for malaria in RDT and microscopy arms were prescribed anti-malarials. Parasitological-based diagnosis significantly reduced AL prescription in RDT arm [RR: 0.62] and microscopy arm [RR: 0.72] compared to presumptive treatment. Among patients not tested in the two intervention arms, 12, 044 (96.1%) in microscopy and 965 (61.6%) in RDT arm were treated with AL [RR: 1.56]. Overall 10, 558 (29.4%) with negative results [5, 110 (23.4%) in RDT and 5, 448 (39.0%) in microscopy arms] were prescribed AL. It was more feasible to implement parasite-based diagnosis for malaria using RDT than with microscopy. A high proportion of patients with negative malaria results are still prescribed anti-malarials. There is need to increase access to parasite-based diagnosis where microscopy is used. In order to fully harness the benefits of parasitological confirmation of malaria, it is necessary to reduce the prescription of anti-malarials in negative patients.


Clusters of Severe Eosinophilic Asthma in a Korean Asthma Cohort.
Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups. We aimed to describe the characteristics of SEA and identify its patient subgroups. Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts. Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (n = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/μL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (n = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/μL). Lastly, cluster 3 (n = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/μL), and good treatment response in terms of improved lung function and control status. Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted.


Nutritional improvement of food proteins by enzymatic modification, especially by plastein synthesis reaction.
The present paper reviews our recents studies on the plastein reaction applied to improve nutritional quality of conventional and unconventional proteins, with special emphasis on the papaincatalyzed incorporation of essential amino acids (used in ethyl ester form) into the proteins : L-methionine into soybean protein, L-lysine into wheat gluten and L-tyrosine into fish protein (after removal of phenylalanine). The paper deals also with an attempt to improve proteins extracted from the photosynthetic microorganisms, Spirulina maxima (a blue-green alga), Rhodopseudomonas capsulatus (a non-sulfur purple bacterium) and Trifolium repens L. (a type of white clover) by way of incorporating simultaneously the three amino acids, L-methionine, L-lysine and L-tryptophan. This process, when properly carried out, can produce plasteins whose essential amino acid patterns have approximated the FAO/WHO suggested pattern (1973). Besides the plastein reaction, its novel modification has been developed, which will be more conveniently applied to a larger-scale process for the amino acid incorporation. A brief discussion is added in this regard.


Evaluation of fracture resistance of reattached vertical fragments bonded with fiber-reinforced composites: an in vitro study.
Aim of this in vitro study was to evaluate the resistance to fracture of vertically fractured and reattached fragments bonded with fiber-reinforced composites. Root canals of 45 teeth were prepared, and the teeth were intentionally fractured into two separate fragments. Control groups (n = 15 each) consisted unfractured teeth with instrumented and obturated. Fractured teeth were divided into three groups (n = 15) and were attached using (1) dual-cure resin cement (RelyX U100), (2) dual-cure resin cement and polyethylene fiber (Ribbond), (3) dual-cure resin cement and glass fibers (stick-net). Force was applied at a speed of 0.5 mm/min to the root until fracture. RESULTS AND STATISTICAL ANALYSIS: Group 1 (RelyX U100 group) demonstrated lowest fracture resistance. Group 4 (control group) showed highest fracture resistance followed by group 2 (Ribbond group) and group 3 (Stick-Net groups). Statistically no significant difference was there between groups 2, 3 and 4. Vertically fractured teeth can be treated by filling the root canal space with dual-cure adhesive resin cement or by adding polyethylene fiber or glass fiber to increase the fracture resistance of the reattached tooth fragments, an alternative to extraction.


Informal workers and access to healthcare: a qualitative study of facilitators and barriers to accessing healthcare for beer promoters in the Lao People's Democratic Republic.
Informal workers often face considerable risks and vulnerabilities as a consequence of their work and employment conditions. The purpose of this study was to examine the interplay between the experience of informal work and access to health, using as an example, female beer promoters employed in the informal economy, in the Lao People's Democratic Republic. In-depth interviews were undertaken with 24 female beer promoters working in beer shops, restaurants and entertainment venues in Vientiane City. The recruitment strategy of snowball sampling was used. Interviews explored the beer promoter's experience of the organization of work, perceived healthcare needs, access to healthcare and insurance, and health seeking practices. The data was analysed thematically and subsequently using Bourdieu's concepts of habitus, capital and field. Most of the beer promoters included in the study were 18 years of age, single, had worked as beer promoters for more than one year and just over half were working to support their higher education. The beer promoters demonstrated a holistic view of health, also viewing good health as contributing to being beautiful - an important attribute in their work. Many reported that their work conditions, including the noisy environment, exposure to second-hand tobacco smoke, long hours on their feet and sexual harassment negatively affected their physical and mental health. Only four participants had any form of health insurance with access to healthcare constrained by individual characteristics, health system factors and the conditions of their informal employment. Drawing on the work of Bourdieu, the study shows how both employment and illness are linked to habitus embodied in everyday practices, access to capital and the position the female beer promoters hold in the social hierarchy in the field of employment.


Correlation of medial/lateral rotation of the humerus with glenohumeral translation.
To correlate glenohumeral translation in the anterior/posterior direction with medial and lateral rotation of the humerus. In addition, the length of the anterior and posterior component of the glenohumeral capsuloligamentous complex was varied in order to gain insight into the contribution of each component to limiting translation. All measurements were made with the humerus positioned at 90 degrees of abduction and 0 degrees of flexion/ extension. Six fresh cadaveric shoulders were used. Each scapula was mounted in a cement pot to rest it in its correct anatomical position. Seven tests were carried out on each shoulder. A series of measurements of translation of the humerus in the anterior direction and posterior direction were taken at 20 degrees intervals of lateral rotation and then at 20 degrees intervals of medial rotation until the limit of lateral or medial rotation had clearly been reached (test 1). The capsuloligamentous complex was then incised and a beaded chain and catches were sutured across the joint to mimic the capsuloligamentous complex at different lengths (tests 2 to 7). (a) When the glenohumeral capsuloligamentous complex is intact, the humerus translates maximally in the glenoid (between 20 and 30 mm) when the humerus is between 40 degrees and 100 degrees of lateral rotation. (b) As the glenohumeral capsuloligamentous complex increases in length, so does the extent of translation. (c) In medial rotation, the length of the posterior capsule, rather than the length of the anterior capsule, has the greater effect on anterior/posterior translation. (d) In lateral rotation the length of the anterior capsule, rather than the length of the posterior capsule, has the greater effect on anterior/posterior translation. (e) The glenohumeral ligamentous complex acts more as a cuff, enclosing the joint, rather than as a sling, as is commonly thought.


Metabolism and excretion of an oral taxane analog, [14C]3'-tert-butyl-3'-N-tert-butyloxycarbonyl-4-deacetyl-3'-dephenyl-3'-N-debenzoyl-4-O-methoxy-paclitaxel (BMS-275183), in rats and dogs.
3'-tert-Butyl-3'-N-tert-butyloxycarbonyl-4-deacetyl-3'-dephenyl-3'-N-debenzoyl-4-O-methoxy-paclitaxel (BMS-275183) is a taxane analog that has the potential for oral use in the treatment of various types of cancer. In this study, the metabolism and excretion of [(14)C]BMS-275183 were evaluated after a single oral administration of [(14)C]BMS-275183 to rats and dogs (15 and 1 mg/kg, respectively). To aid metabolite identification by mass spectrometry (MS), a stable labeled (phenyl-(13)C(6)) BMS-275183 was included in 1:1 ratio of (13)C(6)/(12)C in the dose administration. Fecal excretion was the major route of elimination for [(14)C]BMS-275183 in both species (85-86 and <9% of the dose in feces and urine, respectively). The highest radioactivity in plasma was observed at 1 h postdose, suggesting rapid absorption of the drug in both species. The total radioactivity in plasma was measurable up to 24 h postdose. Metabolites were identified by liquid chromatography-MS and/or NMR spectroscopy. [(14)C]BMS-275183 was the prominent component in rat and dog plasma and was detected up to 24 h along with various oxidative and hydrolytic metabolites. [(14)C]BMS-275183 was extensively metabolized in both species, forming mainly oxidative metabolites, and unchanged parent drug accounted for <3.5% of the administered dose in urine and feces. The prominent metabolites resulted from oxidation of the tert-butyl groups on the side chain and further oxidation and cyclization of the tert-butylhydroxylated metabolites. A total of 30 oxidative metabolites including M13, a prominent ester cleavage metabolite, were identified in rat and dog samples.


Half-metallic behavior in ruthenium-cyclopentadienyl organometallic sandwich molecules.
We have theoretically investigated spin transport properties of one-dimensional ruthenium-cyclopentadienyl sandwich molecules, Run(Cp)n+1, between two gold electrodes. Calculations were performed based on the non-equilibrium Green's function formalism and density functional theory. The results clearly reveal that for n = 1, no spin-polarized behavior is observed due to the fully occupied valence shell of ruthenocene molecule, while for the higher n values, the total magnetic moments increase with increasing size of the cluster and a half metallic behavior has been achieved. This can be attributed to the altered ligand field of π-conjugate systems generated by metal centers. Interestingly, for n values higher than 1, not only do the current-voltage curves exhibit an efficient spin-current generation but also a pronounced negative differential resistance behavior can be detected in the bias region. Our results will be strongly informative for the design and control of high-performance organometallic sandwich molecules based on spin-electronic devices.


miR-146a-5p Alleviates Radiation-Induced Liver Fibrosis by Regulating PTPRA-SRC Signaling in Mice.
Patients with hepatobiliary tumors who accept radiotherapy are at risk for radiation-induced liver fibrosis. MicroRNAs (miRNAs) have been implicated in the pathogenesis of radiation-induced liver damage and possess potential as novel biomarkers and therapeutic targets. However, the role of miR-146a-5p in radiation-induced liver fibrosis is less well understood. The current study was designed to evaluate the role of miR-146a-5p in radiation-induced liver fibrosis in mice and to investigate the possible mechanisms involved in miR-146a-5p-mediated effects. The experiments were performed on Institute of Cancer Research (ICR) mice which received fractionated radiation (30 Gy in 5 fractions) to the liver. The results show radiation could induce histopathological changes, liver dysfunction and fibrosis accompanied with decreased miR-146a-5p expression. miR-146a-5p agomir treatment resulted in recovery of liver function and reduced the amount of alpha-smooth muscle actin (α-SMA), collagen 1, protein tyrosine phosphatase receptor type A (PTPRA) and phosphorylated SRC in the livers of irradiated mice. Therefore, our study reveals that miR-146a-5p inhibits the progression of hepatic fibrosis after radiation treatment. And the beneficial role of miR-146a-5p may be relevant to PTPRA-SRC signaling pathway.


Fluid ionic composition influences hydraulic conductance of xylem conduits.
The direct effect of fluid composition on xylem hydraulic conductance is investigated in excised stem segments of chrysanthemum (Dendranthema x grandiflorum Tzvelev cv. Cassa) plants. Dynamic changes in hydraulic conductance are accurately measured at 30 s intervals before and after modifications of the composition of the standard fluid (deionized water). It is investigated whether osmotic properties of the flowing solution influence overall hydraulic conductance by affecting the hydraulic conductance of vessel-to-vessel pit membranes, as has previously been suggested. Various iso-osmotic salt solutions (20 mOsm kg-1) of different composition raised the hydraulic conductance of 20 cm long stem segments approximately 5-8% compared to deionized water. In contrast, carbohydrate solutions with similar osmotic strength and pH did not cause any change in hydraulic conductance. KCl solutions that greatly differed in osmotic strength all increased hydraulic conductance, but the response was not correlated with the osmotic strength of the solution. Increasing the number of vessels that were open from one cut end to the other by shortening the stem segments greatly increased the hydraulic conductance response. Changing from deionized water to a salt solution caused an immediate increase in hydraulic conductance, while a shift back to deionized water resulted in a slow decline. This decline lasted longer when the salt solution contained divalent cations compared to monovalent cations. It is concluded that the presence of cations and not the osmotic strength in the flowing solution influenced the hydraulic conductance. The phenomenon is not caused by the vessel-to-vessel pit membranes, which in fact suppressed the effect, due to their large contribution to the overall resistance to water flow.


Primary malignant neurilemmona (schwannoma) of the liver in a case of neurofibromatosis.
A case of primary malignant neurilemmal tumour of the liver, associated with neurofibromatosis, is presented. The terminology of such tumours is reviewed. It is concluded that this particular tumour was a malignant neurilemmoma (schwannoma), and the case represents a previously unrecorded association.


To err is human; to structurally prime from errors is also human.
Natural language contains disfluencies and errors. Do listeners simply discard information that was clearly produced in error, or can erroneous material persist to affect subsequent processing? Two experiments explored this question using a structural priming paradigm. Speakers described dative-eliciting pictures after hearing prime sentences that either were disfluent but with a consistent dative structure or were sentences that began as datives but were corrected to transitives (e.g., The mechanic is giving the new part… uh… is recognizing the new part). If an erroneous and corrected sentence fragment is discarded, then the original form of an ultimately transitive utterance should not influence future production. However, if the syntactic parse of an error is not discarded, then it should influence speakers' subsequent choice of syntactic structure. In both experiments, structural priming was significantly reduced when primes were corrected to a non-dative structure (relative to disfluent but ultimately dative primes). However, target descriptions did show an influence from corrected errors when the prime and target shared the same verb. Thus, a parse mapping a verb to a specific argument structure can persist despite being explicitly marked as an error, reflecting the incremental and predictive nature of comprehension.


Functional performance and social relations among the elderly in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil: a population-based epidemiological study.
This study was conducted in a probabilistic sam- ple of 2,055 elderly in Greater Metropolitan Belo Horizonte, Minas Gerais State, Brazil, to examine components of social network (conjugal status and visits by the children, other relatives, and friends) and social support (satisfaction with personal relations and having persons on whom to rely) associated with limitations in performing basic activities of daily living (ADL). Multivariate analysis used the Hurdle model. Performance of ADL showed independent and statistically significant associations with social network (fewer meetings with friends and not having children) and personal support (dissatisfaction/indifference towards personal relations). These associations remained after adjusting for social and demographic characteristics, health status, and other indicators of social relations. Our results emphasize the need for greater attention to social network and social support for elderly with functional limitations and those with weak social networks and social support.


[STudies on the likelihood of growth of Streptococcus faecium following thermal treatment in meat suspensions (author's transl)].
A number of strains of enterococci was isolated from pasteurized meat products. Two variants of Streptococcus faecium (E1 and E20) took part in the present study. Using these organisms, heating tests in suspensions of pork (sealed plastic pouches) were performed. Mixtures of ingredients ('preparation of cooked ham') were added in the majority of experiments. Dextrose was replaced by sorbitol in one experiment, by glycyrrhizin in another. Following thermal treatment at 68.9 degrees C (various heating times), duplicate pouches were incubated at 8 and 37 degrees C. When the mixture of ingredients were added to the meat suspension, thermoresistance of the test strains was found to increase markedly. For E20, D 68.9 degrees C values of 63 and 2.5 min were measured respectively in the systems with or without ingredients (pH 6.3 in both cases). When dextrose was replaced by one or by the two other sweeteners, the levels of thermoresistance did not show any changes. During incubation at 37 degrees C, the surviving cells almost invariably grew to high counts; however similar results were not observed at 8 degrees C. At this temperature a decrease in viable counts during five months' storage was recorded; this was particularly the case with longer periods of heating. On growth of Streptococcus faecium in the presence of dextrose, the pH of the meat suspension decreased from 6.3 to 4.7-4.9. As a result, the residual nitrite fell to very low levels. These phenomena were not observed in the experiments in which dextrose was replaced by the other sweeteners.


Multi locus sequence typing of Chlamydia reveals an association between Chlamydia psittaci genotypes and host species.
Chlamydia comprises a group of obligate intracellular bacterial parasites responsible for a variety of diseases in humans and animals, including several zoonoses. Chlamydia trachomatis causes diseases such as trachoma, urogenital infection and lymphogranuloma venereum with severe morbidity. Chlamydia pneumoniae is a common cause of community-acquired respiratory tract infections. Chlamydia psittaci, causing zoonotic pneumonia in humans, is usually hosted by birds, while Chlamydia abortus, causing abortion and fetal death in mammals, including humans, is mainly hosted by goats and sheep. We used multi-locus sequence typing to asses the population structure of Chlamydia. In total, 132 Chlamydia isolates were analyzed, including 60 C. trachomatis, 18 C. pneumoniae, 16 C. abortus, 34 C. psittaci and one of each of C. pecorum, C. caviae, C. muridarum and C. felis. Cluster analyses utilizing the Neighbour-Joining algorithm with the maximum composite likelihood model of concatenated sequences of 7 housekeeping fragments showed that C. psittaci 84/2334 isolated from a parrot grouped together with the C. abortus isolates from goats and sheep. Cluster analyses of the individual alleles showed that in all instances C. psittaci 84/2334 formed one group with C. abortus. Moving 84/2334 from the C. psittaci group to the C. abortus group resulted in a significant increase in the number of fixed differences and elimination of the number of shared mutations between C. psittaci and C. abortus. C. psittaci M56 from a muskrat branched separately from the main group of C. psittaci isolates. C. psittaci genotypes appeared to be associated with host species. The phylogenetic tree of C. psittaci did not follow that of its host bird species, suggesting host species jumps. In conclusion, we report for the first time an association between C. psittaci genotypes with host species.


Thermo- and pH-responsive fibrillization of squid suckerin A1H1 peptide.
Stimuli-responsive smart materials have attracted considerable attention with numerous applications in nanotechnology, sensing, and biomedicine. Suckerin family proteins found in squid ring teeth represent such a class of peptide-based smart materials with their self-assemblies featuring excellent thermo-plasticity and pH-dependence. Similar to block copolymers, suckerin proteins are comprised of two repeating sequence motifs, where M1 motifs are abundant in alanine and histidine residues and M2 are rich in glycine. Experimental studies of suckerin assemblies suggested that M1 regions mainly formed nano-confined β-sheets within an amorphous matrix made of M2 modules stabilizing these β-rich nano-assemblies. The histidine-containing M1 modules are believed to govern the pH- and temperature-sensitive properties of suckerin assemblies. To better understand the stimuli-responsive properties of suckerin assemblies at the molecular level, we systematically studied the self-assembly dynamics of A1H1 peptides - a representative M1 sequence - at different temperatures and pH conditions with atomistic discrete molecular dynamic simulations. Our simulations with twenty A1H1 peptides demonstrated that below the transition temperature Tagg, they could readily self-assemble from isolated monomers into well-defined β-sheet nanostructures by both primary and secondary nucleation of β-sheets and subsequent aggregation growth via elongation and coagulation. Interestingly, the dissociation of pre-formed A1H1 β-sheet nanostructures featured a melting temperature Tm higher than Tagg, exhibiting the thermal hysteresis that is characteristic of first-order phase transitions with high energy barriers. In acidic environments where all histidine residues were protonated, the stability of the A1H1 β-sheet nano-assemblies was reduced and the β-rich assemblies easily dissociated into unstructured monomers at significantly lower temperatures than in the neutral solution. The computationally derived molecular mechanisms for pH- and temperature-dependent A1H1 self-assembly will help to understand the supramolecular assembly structures and functions of the large suckerin family and aid in the future design of peptide-based stimuli-responsive smart materials.


Selective Nrf2 Gene Deletion in the Rostral Ventrolateral Medulla Evokes Hypertension and Sympathoexcitation in Mice.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master transcriptional regulator of redox homeostasis that impacts antioxidant gene expression. Central oxidative stress and reduced antioxidant enzyme expression in the rostral ventrolateral medulla (RVLM) contributed to sympathoexcitation in chronic heart failure. In the current study, we hypothesized that deletion of Nrf2 in the RVLM would increase sympathetic drive and blood pressure. Experiments were performed in Nrf2-floxed mice treated with microinjection of lentiviral-Cre-GFP or lentiviral-GFP into the RVLM. Two weeks after viral administration, Nrf2 message, protein, oxidative stress, cardiovascular function, and sympathetic outflow were evaluated. We found that (1) Nrf2 mRNA and protein in the RVLM were significantly lower in Cre mice compared with control GFP mice. Nrf2-targeted antioxidant enzymes were downregulated, whereas reactive oxygen species were elevated. (2) Blood pressure measurements indicated that Cre mice displayed a significant increase in blood pressure (mean arterial pressure, 123.7±3.8 versus 100.2±2.2 mm Hg; P<0.05, n=6), elevated urinary norepinephrine (NE) concentration (456.4±16.9 versus 356.5±19.9 ng/mL; P<0.05, n=6), and decreased spontaneous baroreflex gain (up sequences, 1.66±0.17 versus 3.61±0.22 ms/mm Hg; P<0.05, n=6; down sequences, 1.89±0.12 versus 2.98±0.19 ms/mm Hg; P<0.05, n=6). (3) Cre mice displayed elevated baseline renal sympathetic nerve activity and impaired inducible baroreflex function. These data suggest that Nrf2 gene deletion in the RVLM elevates blood pressure, increases sympathetic outflow, and impairs baroreflex function potentially by impaired antioxidant enzyme expression.


Abortion in sheep caused by a nonclassified, anaerobic, flagellated bacterium.
Twenty-eight pregnant ewes were inoculated IV with approximately 6 X 10(8) nonclassified, anaerobic, flagellated bacteria (NAFB) that had been isolated from an aborted lamb. Abortion occurred in 3 of the ewes and 1 ewe gave birth to a weak lamb. The remaining 24 ewes and 3 other ewes inoculated orally with NAFB did not develop clinical signs of illness. Suppuration and vasculitis were seen in the placentas of the 3 aborted lambs, 1 of which had necropurulent hepatitis indistinguishable from that usually attributed to Campylobacter fetus infection. The NAFB was isolated from fetal placenta, abomasal content, or internal organs of 2 aborted lambs and the weak lamb. A morphologically similar organism was seen in the abomasal content of the other aborted lamb, but the organism did not grow on bacteriologic culture medium. Therefore, in susceptible pregnant ewes, NAFB can cause fetal placentitis and hepatitis and subsequent birth of weak lambs or abortion.


Pechini synthesis of lanthanide (Eu3+/Tb3+or Dy3+) ions activated BaGd2O4 nanostructured phosphors: an approach for tunable emissions.
Trivalent lanthanide (Eu(3+), Tb(3+) and Dy(3+)) ions activated tunable color emitting BaGd2O4 (BG) phosphors were synthesized by a facile Pechini-type sol-gel process. The X-ray diffraction pattern confirmed the orthorhombic phase after annealing at 1300 °C for 5 h. Morphological studies were performed based on the analysis of transmission electron microscopy images, which showed needle type nanorods. The BG phosphor exhibited good photoluminescence (PL) properties in the respective regions when doped with Eu(3+), Tb(3+) and Dy(3+) ions. The Eu(3+) co-activated BG:Tb(3+) phosphor yielded tunable emissions including tri-band established white light emission based on the co-activator concentration and excitation wavelength. The energy transfer from Tb(3+) to Eu(3+) ions was controlled by selecting a suitable excitation wavelength and the decay measurements were carried out for analyzing the energy transfer efficiency. The cathodoluminescence properties of these phosphors were almost similar to PL properties when doped with individual Eu(3+), Tb(3+), and Dy(3+) ions, but were different when co-doped with Eu(3+)/Tb(3+) or Eu(3+)/Dy(3+) ions. In the case of Eu(3+)/Tb(3+) doped samples, the energy transfer process occurred unlike the PL channel. The calculated Commission International de l'Eclairage chromaticity coordinates of individual ion doped BG phosphors confirmed red, green, and white emissions and for co-doped samples they showed tunable emission.


Pediatric Multiple Sclerosis in the United Arab Emirates: Characteristics From a Multicenter Study and Global Comparison.
We delineate the clinical characteristics, incidence, and prevalence of pediatric-onset multiple sclerosis in Abu Dhabi, United Arab Emirates, from 2010 to 2014. Eighty-two patients (65% female) were identified. Fifty-three (64.6%) were Emiratis (45 from Abu Dhabi and 8 from 5 other emirates) and 29 were expatriates. Mean age of onset was 15.9 years overall, 15.3 years in males and 16.3 years in females. Patients with onset before age 12 years presented with visual symptoms while those with onset after age 12 years presented with a mixture of visual, motor and sensory symptoms. Interferon beta-1a was the most frequently used disease-modifying therapy (48%). In Abu Dhabi Emirati nationals, the age- and sex-adjusted prevalences were 26/100 000 for males and 36/100 000 for females. The total incidence in Emirati nationals from 2010 to 2014 was 2.3/100 000 for ages 10 to 14 years and 7.2/100 000 for ages 15 to 19 years. By comparison with international cohorts, the incidence of pediatric-onset multiple sclerosis in Abu Dhabi is higher whereas gender distribution is similar.


Inside the lifestyle of the virophage.
We sought to better characterize Sputnik, the first isolated virophage, and to analyze its parasitic lifestyle during co-infection with Marseillevirus (a new giant virus) in Acanthamoeba castellanii. A combination of electron microscopy, immunofluorescence microscopy, and real-time PCR was used to characterize the kinetics of the viral replication cycle. RT-PCR was performed to detect RNAs inside the Sputnik virions. Sputnik is a new viral entity carrying an almost complete ready-to-use set of viral RNAs (20 out of 21). Sputnik does not replicate with Marseillevirus but delays its replication cycle. While Marseillevirus is successfully internalized by A. castellanii following co-infections with Mamavirus and Sputnik, it does not initiate a replication cycle. In contrast, both Marseillevirus and Mamavirus can replicate in the amoeba in case of co-infection, but the development of one is exclusive from the other inside a single amoeba cell. This work provides new insight into the Sputnik replication cycle with another giant virus and confirms that Sputnik is a virophage. It shows new dimensions of the interactions existing among giant viruses.


Combination of balanced ultrafiltration with modified ultrafiltration attenuates pulmonary injury in patients undergoing open heart surgery.
To explore the effects of ultrafiltration technique in preventing and relieving pulmonary injury in children undergoing open heart surgery and cardiopulmonary bypass (CPB). Thirty cases with congenital heart defects were divided into a control group and an experimental group. In the control group, conventional cardiopulmonary bypass was used without ultrafiltration; while in the experimental group, cardiopulmonary bypass with balanced ultrafiltration and modified ultrafiltration were used. Pulmonary static compliance (Cstat), airway resistance (Raw), alveolar-arterial oxygen difference (A-a DO2), hematocrit (HCT), serum albumin (Alb), interleukin-6 (IL-6), endothelia-1 (ET-1) and thromboxane (TXB2) were measured. The pulmonary function was improved, HCT and serum albumin concentrations were increased, and some harmful medium-size solutes were decreased in the experimental groups compared with the control group. Combination of balanced ultrafiltration with modified ultrafiltration can effectively concentrate blood, exclude harmful inflammatory mediators, and attenuate lung edema and inflammatory responsive pulmonary injury.


Economic evaluation of sacral nerve stimulation for faecal incontinence.
Sacral nerve stimulation (SNS) is an established treatment for faecal incontinence in patients who have failed conservative management. This study established the cost-effectiveness of treating patients with SNS compared with non-surgical treatment. A decision analysis model was performed. Data from 70 patients were obtained from medical records, bowel habit diaries and Short Form 36 quality of life questionnaires. Direct medical and non-medical costs were ascertained using the 2005/2006 national tariff, national statistics, and medication, pad and device costs. Indirect non-medical costs were also estimated. Incontinence episodes were reduced from a median of 12 per fortnight at baseline to one per fortnight with SNS. Based on direct medical and non-medical costs, the incremental cost-effectiveness ratio (ICER) for SNS was pound25 070 per QALY gained. It cost pound1038 more per year to treat patients with SNS for a median reduction of 286 incontinence episodes, equating to pound3.63 per episode reduced. When indirect non-medical costs were included the ICER was reduced to pound12 959 per QALY gained. The ICER of pound25 070 is within the pound30 000 per QALY threshold recommended by the National Institute for Health and Clinical Excellence as an effective use of National Health Service resources with proper justification.


Antioxidant enzyme and element status in heroin addiction or heroin withdrawal in rats: effect of melatonin and vitamin E plus Se.
Heroin use, withdrawal syndrome, and heroin-related deaths are still the most serious public health problems. Antioxidants and bio-elements are essential for metabolism in living organisms. To our knowledge, there are no data about the effect of antioxidant therapy on the levels of bio-elements and antioxidant enzymes in the naloxone (NX)-induced heroin withdrawal syndrome. Therefore, in the present study for the first time, we have investigated the role of antioxidant therapy, melatonin, and vitamin E plus Se, on the trace and major elements and antioxidant enzymes in the heroin addiction or heroin withdrawal in rats. Glutathione peroxidase levels were increased and catalase levels were decreased in the all study groups when compared to the sham group. The level of superoxide dismutase (SOD) in the fixed dose of heroin (FDH) given group was lower; however, in the variable doses of heroin (VDH) given group SOD level was higher. Furthermore, in withdrawal syndrome, Fe, Mg, Mn, and Ti levels were diminished and Al, Ca, and Cu levels were increased in the FDH+NX group. Moreover, Mg, Mn, and Se levels were also diminished and Al level was increased in the VDH+NX group. In conclusion, our results obviously indicated that heroin effected both bio-element status and antioxidant enzyme activities and, exogenous melatonin or vE+Se therapy might relieve on the element and antioxidant enzyme the destructive activity caused by heroin.


Digital dermatoglyphics of Bulgarians from northeast Bulgaria.
Digital dermatoglyphics were collected from 1,065 male and 1,065 female Bulgarians from northeast Bulgaria. None of the subjects had a diagnosed or suspected genetic or chronic disease of any kind. The fingerprints were classified by the 18-type system of Monique de Lestrange, modified to provide rapid and easy comparison with simpler classification systems. All the standard finger pattern indices were calculated. Certain modifications were introduced into the delta indices, it being borne in mind that each tented arch possesses a triradius and each complex (three-centered, accidental) whorl contains three triradii. A deltadiagram was constructed and its configuration was compared with those of some other populations. In addition, a new radioulnar index was proposed, representing a ratio between all the radial and all the ulnar patterns. The total, absolute, ulnar and radial finger ridge counts were calculated and their sample distributions were investigated. The dermatoglyphic features were evaluated and presented for each sex and each hand separately in order to investigate both the sex and bilateral differences. The set of data presented in this paper is a component of the physical anthropology of the general Bulgarian population. At the same time these data can be used as controls when analyzing the dermatoglyphic findings in Bulgarian patients with genetic diseases or congenital malformations.


Complete mitochondrial genome sequences of the northern spotted owl (Strix occidentalis caurina) and the barred owl (Strix varia; Aves: Strigiformes: Strigidae) confirm the presence of a duplicated control region.
We report here the successful assembly of the complete mitochondrial genomes of the northern spotted owl (Strix occidentalis caurina) and the barred owl (S. varia). We utilized sequence data from two sequencing methodologies, Illumina paired-end sequence data with insert lengths ranging from approximately 250 nucleotides (nt) to 9,600 nt and read lengths from 100-375 nt and Sanger-derived sequences. We employed multiple assemblers and alignment methods to generate the final assemblies. The circular genomes of S. o. caurina and S. varia are comprised of 19,948 nt and 18,975 nt, respectively. Both code for two rRNAs, twenty-two tRNAs, and thirteen polypeptides. They both have duplicated control region sequences with complex repeat structures. We were not able to assemble the control regions solely using Illumina paired-end sequence data. By fully spanning the control regions, Sanger-derived sequences enabled accurate and complete assembly of these mitochondrial genomes. These are the first complete mitochondrial genome sequences of owls (Aves: Strigiformes) possessing duplicated control regions. We searched the nuclear genome of S. o. caurina for copies of mitochondrial genes and found at least nine separate stretches of nuclear copies of gene sequences originating in the mitochondrial genome (Numts). The Numts ranged from 226-19,522 nt in length and included copies of all mitochondrial genes except tRNAPro , ND6, and tRNAGlu . Strix occidentalis caurina and S. varia exhibited an average of 10.74% (8.68% uncorrected p-distance) divergence across the non-tRNA mitochondrial genes.


T1 colorectal cancer with synchronous liver metastasis.
The patient was a 68-year-old man who was admitted to our hospital with a liver tumor. Abdominal ultrasonography and computed tomography revealed a liver tumor 30 mm in diameter. On colonoscopy, a pedunculated tumor with a central depression (20 mm in diameter) was observed in the ascending colon, and this tumor was considered to be invading deeply into the submucosal layer. Right hemicolectomy with D3 lymphadenectomy and partial hepatectomy were performed simultaneously. On histopathological examination of the resected specimen, the tumor was a well-differentiated tubular adenocarcinoma with 3,000 μm invasion of the submucosal layer. The liver tumor showed histological findings similar to those of the primary colorectal carcinoma. The pathological stage according to the 7th edition of the TNM classification was stage IV (T1N0M1). Nine months after the operation, computed tomography revealed hepatic hilar lymph node metastases and a great deal of ascites. The patient ultimately died 14 months after the operation.


Mosquito survey in Mauritania: Detection of Rift Valley fever virus and dengue virus and the determination of feeding patterns.
In Mauritania, several mosquito-borne viruses have been reported that can cause devastating diseases in animals and humans. However, monitoring data on their occurrence and local distribution are limited. Rift Valley fever virus (RVFV) is an arthropod-borne virus that causes major outbreaks throughout the African continent and the Arabian Peninsula. The first Rift Valley fever (RVF) epidemic in Mauritania occurred in 1987 and since then the country has been affected by recurrent outbreaks of the disease. To gain information on the occurrence of RVFV as well as other mosquito-borne viruses and their vectors in Mauritania, we collected and examined 4,950 mosquitoes, belonging to four genera and 14 species. The mosquitoes were captured during 2018 in the capital Nouakchott and in southern parts of Mauritania. Evidence of RVFV was found in a mosquito pool of female Anopheles pharoensis mosquitoes collected in December on a farm near the Senegal River. At that time, 37.5% of 16 tested Montbéliarde cattle on the farm showed RVFV-specific IgM antibodies. Additionally, we detected IgM antibodies in 10.7% of 28 indigenous cattle that had been sampled on the same farm one month earlier. To obtain information on potential RVFV reservoir hosts, blood meals of captured engorged mosquitoes were analyzed. The mosquitoes mainly fed on humans (urban areas) and cattle (rural areas), but also on small ruminants, donkeys, cats, dogs and straw-colored fruit bats. Results of this study demonstrate the circulation of RVFV in Mauritania and thus the need for further research to investigate the distribution of the virus and its vectors. Furthermore, factors that may contribute to its maintenance should be analyzed more closely. In addition, two mosquito pools containing Aedes aegypti and Culex quinquefasciatus mosquitoes showed evidence of dengue virus (DENV) 2 circulation in the city of Rosso. Further studies are therefore needed to also examine DENV circulation in Mauritania.


Learning walks in an Australian desert ant, Melophorus bagoti.
The central Australian ant Melophorus bagoti is the most thermophilic ant in Australia and forages solitarily in the summer months during the hottest period of the day. For successful navigation, desert ants of many species are known to integrate a path and learn landmark cues around the nest. Ants perform a series of exploratory walks around the nest before their first foraging trip, during which they are presumed to learn about their landmark panorama. Here, we studied 15 naive M. bagoti ants transitioning from indoor work to foraging outside the nest. In 3-4 consecutive days, they performed 3-7 exploratory walks before heading off to forage. Naive ants increased the area of exploration around the nest and the duration of trips over successive learning walks. In their first foraging walk, the majority of the ants followed a direction explored on their last learning walk. During learning walks, the ants stopped and performed stereotypical orientation behaviours called pirouettes. They performed complete body rotations with stopping phases as well as small circular walks without stops known as voltes. After just one learning walk, these desert ants could head in the home direction from locations 2 m from the nest, although not from locations 4 m from the nest. These results suggest gradual learning of the visual landmark panorama around the foragers' nest. Our observations show that M. bagoti exhibit similar characteristics in their learning walks to other desert ants of the genera Ocymyrmex and Cataglyphis.