Posterior Circulation Ischemia in the Endovascular Era.
To perform literature review of clinical, radiographic, and anatomical features of posterior circulation ischemia (PCI) and systematic review of the literature on the management of basilar artery occlusion (BAO) and associated outcomes. Review of literature was conducted to identify publications describing the risk factors, etiology, clinical presentation, and imaging for PCI. A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. PubMed and Ovid MEDLINE were searched from 2009 to 2020 for articles relating to management of BAO. A synthesis was compiled summarizing current evidence on management of BAO. PCI accounts for 15%-20% of strokes. Risk factors are similar to anterior circulation strokes. Dizziness (47%), unilateral limb weakness (41%), and dysarthria (31%) are the most common presenting symptoms. A noncontrast head CT will identify PCI in 21% of cases; diffusion-weighted MRI or CT perfusion increase sensitivity to 85%. Recent trials have shown endovascular therapy can achieve >80% recanalization of BAO. In select patients, 30%-60% who receive endovascular treatment can achieve favorable outcome vs without. A total of 13% achieve good outcome and there is an 86% mortality rate. PCI can present with waxing and waning symptoms or clinical findings that overlap with stroke mimics and anterior circulation ischemia, making diagnosis more heavily dependent on imaging. Recanalization is an important predictor of improved functional outcome and survival. In this endovascular era, trials of BAO are fraught with deterrents to enrollment. Despite limitations, endovascular treatment has shown improved outcome in select patients.


One-Pot Synthesis of ABCDE Multiblock Copolymers with Hydrophobic, Hydrophilic, and Semi-Fluorinated Segments.
The scope and accessibility of sequence-controlled multiblock copolymers is demonstrated by direct "in situ" polymerization of hydrophobic, hydrophilic and fluorinated monomers. Key to the success of this strategy is the ability to synthesize ABCDE, EDCBA and EDCBABCDE sequences with high monomer conversions (>98 %) through iterative monomer additions, yielding excellent block purity and low overall molar mass dispersities (Ð<1.16). Small-angle X-ray scattering showed that certain sequences can form well-ordered mesostructures. This synthetic approach constitutes a simple and versatile platform for expanding the availability of tailored polymeric materials from readily available monomers.


Incidentally detected congenital giant left atrial appendage aneurysm in a child: MRI findings.
Left atrial appendage aneurysms are usually congenital and are very infrequent anomalies of the heart. They are very rarely diagnosed during childhood, with most cases symptomatic between the 2nd and 4th decades of life. Diagnosis is vitally important due to potential life-threatening complications. Surgical excision is the treatment of choice. Surgery reduces the risks of cardiac arrest, respiratory distress, arrhythmia, heart failure, thromboembolism, or rupture. We report the case of a 3-year-old boy with incidental diagnosis of a giant aneurysm of the left atrial appendage that was confirmed with magnetic resonance imaging and treated with surgery.


Interaction of convulsive ligands with benzodiazepine receptors.
The gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex, which is composed of distinct proteins embedded in the neuronal plasma membrane, is important for several effects of benzodiazepines, including protection afforded against convulsions. During structural modification of ethyl beta-carboline-3-carboxylate an agent was discovered which has high affinity for brain benzodiazepine receptors but which is a potent convulsant. Also in contrast to benzodiazepines, this type of benzodiazepine receptor ligand favors benzodiazepine receptors in the non-GABA-stimulated conformation, which may explain the convulsive properties.


Blink reflex as a parameter of human operator's functional state.
Eyelid movements (EM)--blinking frequency and duration of closed eyes--may serve as a parameter of fatigue in humans performing as operators. Twenty subjects were told to locate and follow visual signals appearing on a screen at the frequency of 4-5 X h-1 and moving in a background of bright noises. EM was recorded in infra-red rays with tiny sensors attached to glasses' rim. EEG and ECG were recorded simultaneously. It was found that a change in EM is a sensitive parameter of fatigue and better corresponds to decreased quality of performance (time of locating signal and error in following), than changes in R-R interval. In the second experimental series, symptoms of fatigue discovered by EM were accompanied by sound signals, which improved operator's performance by 15-20%. Recording of EM may be used to monitor operator's state in humans and to forecast reliability of performance.


The FZD7-TWIST1 axis is responsible for anoikis resistance and tumorigenesis in ovarian carcinoma.
Frizzled family receptor 7 (FZD7), a Wnt signaling receptor, is associated with the maintenance of stem cell properties and cancer progression. FZD7 has emerged as a potential therapeutic target because it is capable of transducing both canonical and noncanonical Wnt signals. In this study, we investigated the regulatory pathway downstream of FZD7 and its functional roles. We found that FZD7 expression was crucial to the maintenance of the mesenchymal phenotype, anoikis resistance, and spheroid and tumor formation in ovarian cancer (OC). We identified TWIST1 as the crucial downstream effector of the FZD7 pathway. TWIST1, a basic helix loop helix transcription factor, is known to associate with mesenchymal and cancer stem cell phenotypes. Manipulating TWIST1 expression mimicked the functional consequences observed in the FZD7 model, and overexpression of TWIST1 partially rescued the functional phenotypes abolished by FZD7 knockdown. We further proved that FZD7 regulated TWIST1 expression through epigenetic modifications of H3K4me3 and H3K27ac at the TWIST1 proximal promoter. We also identified that the FZD7-TWIST1 axis regulates the expression of BCL2, a gene that controls apoptosis. Identification of this FZD7-TWIST1-BCL2 pathway reaffirms the mechanism of anoikis resistance in OC. We subsequently showed that the FZD7-TWIST1 axis can be targeted by using a small molecule inhibitor of porcupine, an enzyme essential for secretion and functional activation of Wnts. In conclusion, our results identified that the FZD7-TWIST1 axis is important for tumorigenesis and anoikis resistance, and therapeutic inhibition results in cell death in OCs.


Ethnic and mainstream social connectedness, perceived racial discrimination, and posttraumatic stress symptoms.
Carter (2007) proposed the notion of race-based traumatic stress and argued that experiences of racial discrimination can be viewed as a type of trauma. In a sample of 383 Chinese international students at 2 predominantly White midwestern universities, the present results supported this notion and found that perceived racial discrimination predicted posttraumatic stress symptoms over and above perceived general stress. Furthermore, Berry (1997) proposed an acculturation framework and recommended that researchers advance the literature by examining the moderation effects on the association between racial discrimination and outcomes. The present results supported the moderation effect for Ethnic SC (i.e., social connectedness in the ethnic community), but not for Mainstream SC (i.e., social connectedness in mainstream society). A simple effects analysis indicated that a high Ethnic SC weakened the strength of the association between perceived racial discrimination and posttraumatic stress symptoms more than a low Ethnic SC. Moreover, although Mainstream SC failed to be a moderator, Mainstream SC was significantly associated with less perceived general stress, less perceived racial discrimination, and less posttraumatic stress symptoms.


Evaluation of the stability of morphine sulphate in combination with Instillagel.
The Pharmacy Department at the Western General Hospital in Edinburgh prepares a topically applied product in which morphine sulphate is incorporated into Instillagel for use in reducing pain associated with rectal and other cancers. A stability indicating method was required for assessment of the stability of this combination. A gradient high performance liquid chromatography method was developed to assess stability and an LC-MS method was used to characterize the degradants from forced degradation of the components in the formulation. The method was found to have acceptable inter- and intra-day precisions. Under all storage conditions investigated morphine sulphate remained within 98.1% and 103.2% of the initial concentration, lidocaine hydrochloride within 96.07% and 104.9% and chlorhexidine gluconate within 97.3% and 105.5%, except for samples stored at 37 degrees C beyond 240 h. A sample of the admixture was stored up to 7 months at 37 degrees C and was found to be reasonably stable with only the chlorhexidine concentration declining appreciably to 92% of the initial concentration. Some of the degradants of chlorhexidine and morphine were characterized by liquid chromatography mass spectrometry. It could be concluded that the admixture was stable for over 22 days at 4 degrees C protected from light, over 22 days at 25 degrees C exposed to normal light, and for 7 months at 37 degrees C protected from light. The components in the combination were found to have good long-term stability.


Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older.
Elderly subjects have been historically underrepresented in clinical trials involving antiviral hepatitis C therapies. The aim of this analysis was to retrospectively evaluate the safety and efficacy of ledipasvir/sofosbuvir (LDV/SOF) by age groups of <65 years versus ≥65 years among subjects enrolled in phase 3 trials. Four open-label phase 3 clinical trials evaluated the safety and efficacy of LDV/SOF with or without ribavirin (RBV) for the treatment of genotype 1 chronic hepatitis C virus. Sustained virological response at 12 weeks, treatment-emergent adverse events (AEs), and graded laboratory abnormalities were analyzed according to age group. Of the 2293 subjects enrolled in four phase 3 trials, 264 (12%) were ≥65 years of age, of whom 24 were aged ≥75 years. Sustained virological response at 12 weeks was achieved by 97% (1965/2029) of subjects aged <65 years and 98% (258/264) of subjects aged ≥65 years. The most common AEs in both LDV/SOF groups that occurred in ≥10% of subjects were headache and fatigue. The rate of study discontinuation due to AEs was similar in the two age cohorts. The use of RBV in 1042 (45%) subjects increased the number of AEs, treatment-related AEs, and AEs leading to study drug modification/interruption, particularly among elderly subjects. LDV/SOF with or without RBV was highly effective for treatment of genotype 1 chronic hepatitis C virusin subjects aged 65 and older. Addition of RBV did not increase sustained virological response at 12 weeks rates but led to higher rates of AEs, especially in elderly subjects.


Illicit cigarette trade in Metropolitan Santiago de Chile.
To estimate with a rigorous statistical methodology and independent from the tobacco industry the prevalence and consumption of illicit cigarettes in Metropolitan Santiago de Chile, in addition to identifying the variables statistically associated with choosing to smoke illicit cigarettes. Surveys of 851 smokers who reside in the Metropolitan Santiago were collected using a sampling design that combined a randomisation of high-traffic points and a quota sampling to approximate the smoking population. Photographs of packs along with questions on where they were bought were used to define whether cigarettes were licit or illicit. After this identification, the statistical association between the decision to smoke illicit cigarettes and sociodemographic variables and smoking habits was estimated using probit models. The proportion of smokers smoking illicit cigarettes in Metropolitan Santiago was 10.9%. Adjusted by smoking intensity, 16.3% of cigarettes smoked in a month were illicit. Models show that the probability of smoking illicit cigarettes is inversely associated with employment status (ie, employed/inactive/unemployed), and smokers with lower levels of education are more likely to smoke illicit cigarettes. Though smokers' incomes are not directly measured, both employment status and educational levels are indicative that illicit cigarette consumption is more prevalent among low-income groups. The proportion of smokers consuming illicit cigarettes estimated in this research is less than half of the widely publicised claims of the tobacco industry. Furthermore, past and present pricing strategies by the tobacco industry indicate that, contrary to public statements, the tobacco industry is not concerned by illicit trade.


Partially supervised speaker clustering.
Content-based multimedia indexing, retrieval, and processing as well as multimedia databases demand the structuring of the media content (image, audio, video, text, etc.), one significant goal being to associate the identity of the content to the individual segments of the signals. In this paper, we specifically address the problem of speaker clustering, the task of assigning every speech utterance in an audio stream to its speaker. We offer a complete treatment to the idea of partially supervised speaker clustering, which refers to the use of our prior knowledge of speakers in general to assist the unsupervised speaker clustering process. By means of an independent training data set, we encode the prior knowledge at the various stages of the speaker clustering pipeline via 1) learning a speaker-discriminative acoustic feature transformation, 2) learning a universal speaker prior model, and 3) learning a discriminative speaker subspace, or equivalently, a speaker-discriminative distance metric. We study the directional scattering property of the Gaussian mixture model (GMM) mean supervector representation of utterances in the high-dimensional space, and advocate exploiting this property by using the cosine distance metric instead of the euclidean distance metric for speaker clustering in the GMM mean supervector space. We propose to perform discriminant analysis based on the cosine distance metric, which leads to a novel distance metric learning algorithm—linear spherical discriminant analysis (LSDA). We show that the proposed LSDA formulation can be systematically solved within the elegant graph embedding general dimensionality reduction framework. Our speaker clustering experiments on the GALE database clearly indicate that 1) our speaker clustering methods based on the GMM mean supervector representation and vector-based distance metrics outperform traditional speaker clustering methods based on the "bag of acoustic features" representation and statistical model-based distance metrics, 2) our advocated use of the cosine distance metric yields consistent increases in the speaker clustering performance as compared to the commonly used euclidean distance metric, 3) our partially supervised speaker clustering concept and strategies significantly improve the speaker clustering performance over the baselines, and 4) our proposed LSDA algorithm further leads to state-of-the-art speaker clustering performance.


Genetic variation in STAT4 is associated with treatment response to pegylated interferon in patients with chronic hepatitis B.
Signaling pathways in the STAT4 gene play an essential role in interferon-mediated antiviral effects. This study was aimed at investigating the role of rs7574865, a single nucleotide polymorphism (SNP) in STAT4, in patients with chronic hepatitis B (CHB) treated with pegylated interferon (PEG-IFN). A total 261 Thai patients (115 HBeAg-positive and 146 HBeAg-negative CHB) treated with 48-week PEG-IFN were recruited. Virological response (VR) at 48 weeks post treatment was defined as HBeAg seroconversion plus HBV DNA < 2,000 IU/mL for HBeAg-positive CHB and HBV DNA < 2,000 IU/mL for HBeAg-negative CHB. The SNP was analyzed by TaqMan PCR assay. The distribution of GG, GT and TT genotypes of rs7574865 was 41.8%, 42.9% and 15.3%, respectively. There was no different in its distribution according to HBeAg status. Overall, patients with TT genotype, compared with non-TT genotype, achieved higher VR (64.3% vs. 30.5%; P < 0.001) and HBsAg clearance (23.8% vs. 5.0%; P < 0.001). There was the same trend in the HBeAg-positive group (VR, 52.4% vs. 30.9%; P = 0.077; HBsAg clearance, 23.8% vs. 6.4%; P = 0.028) and in the HBeAg-negative group (VR, 68.4% vs. 32.3%; P = 0.004; HBsAg clearance, 21.1% vs. 4.7%; P = 0.026). Multiple regression analysis demonstrated that low baseline HBsAg level and TT genotype were factors independently associated with VR and HBsAg clearance. Our data support that SNP rs7574865 is associated with response to PEG-IFN therapy in Thai patients with CHB, regardless of baseline HBeAg status. Thus, the determination of this SNP could maximize cost-effectiveness of PEGIFN in patients with CHB.


Swallowing Impairments Increase Emotional Burden in Spousal Caregivers of Older Adults.
Objective: The aim of this study was to determine the type and extent of caregiver burden uniquely experienced by spousal caregivers of older adults with dysphagia. Method: Using the Round 1 surveys from the National Health and Aging Trends Study and the National Study of Caregiving, we analyzed data on 422 community-dwelling older adults and their spousal caregivers. Results: Approximately 17% of care recipients reported swallowing difficulties. Logistic regression analysis revealed that caregivers of spouses with dysphagia were significantly more likely to experience emotional burden, p = .038; odds ratio (OR) = 2.06; 95% confidence interval (CI): [1.04, 4.09]. Of those spouses caring for partners with dysphagia who reported emotional burden, nearly 70% rated the burden moderate to severe. Discussion: Dysphagia in community-dwelling older adults is associated with increased emotional burden among spousal caregivers. Given the intricate relationship between the health and well-being of both members of the caregiving dyad, these findings support the need for interventions that prioritize dyadic health.


Metastasis to maxillary gingiva from carcinoma of breast. A case report.
A rare case of metastatic infiltrating duct carcinoma involving gingiva in relation to maxillary left canine-premolar of a 40 year old female is presented. The unilateral gingival enlargement in canine-premolar region was quite unusual. Pertinent history and histological examination revealed that the tumor was a metastatic carcinoma, the primary lesion of which was in the breast. The differential diagnosis of gingival enlargements is discussed in this paper. The resemblance of this mass to an inflammatory hyperplastic condition reflects the need for a detailed case history and examination.


[Difficulties in learning mathematics].
To discuss our concern for some aspects of mathematics learning disorders related to the nomenclature employed and their diagnosis; these aspects refer to the term 'dyscalculia' and to its diagnosis (especially syndromatic diagnosis). We also intend to propose a classification that could help to define the terminology. Lastly we are going to consider the different aspects of diagnosis and to determine which of them are indispensable in the diagnosis of primary and secondary disorders. As far as the nomenclature is concerned, we refer to the term 'dyscalculia'. The origins of the term are analysed along with the reasons why it should not be used in children with difficulties in learning mathematics. We propose a classification and denominations for the different types that should undoubtedly be discussed. With respect to the diagnosis, several problems related to the syndromatic diagnosis are considered, since in our country there are no standardised tests with which to study performance in arithmetic and geometry. This means that criterion reference tests are conducted to try to establish current and potential performance. At this stage of the diagnosis pedagogical and psychological studies must be conducted. The important factors with regard to the topographical and aetiological diagnoses are prior knowledge, results from the studies that have been carried out and findings from imaging studies. The importance of a genetic study must be defined in the aetiological diagnosis. We propose a nomenclature to replace the term 'dyscalculia'. Standardised tests are needed for the diagnosis. The need to establish current and potential performance is hierarchized. With regard to the topographical diagnosis, we highlight the need for more information about geometry, and in aetiological studies the analyses must be conducted with greater numbers of children.


Blood Pressure and Later-Life Cognition in Hispanic and White Adults (BP-COG): A Pooled Cohort Analysis of ARIC, CARDIA, CHS, FOS, MESA, and NOMAS.
Ethnic differences in cognitive decline have been reported. Whether they can be explained by differences in systolic blood pressure (SBP) is uncertain. Determine whether cumulative mean SBP levels explain differences in cognitive decline between Hispanic and White individuals. Pooled cohort study of individual participant data from six cohorts (1971-2017). The present study reports results on SBP and cognition among Hispanic and White individuals. Outcomes were changes in global cognition (GC) (primary), executive function (EF) (secondary), and memory standardized as t-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1 SD difference in cognition. Median follow-up was 7.7 (Q1-Q3, 5.2-20.1) years. We included 24,570 participants free of stroke and dementia: 2,475 Hispanic individuals (median age, cumulative mean SBP at first cognitive assessment, 67 years, 132.5 mmHg; 40.8% men) and 22,095 White individuals (60 years,134 mmHg; 47.3% men). Hispanic individuals had slower declines in GC, EF, and memory than White individuals when all six cohorts were examined. Two cohorts recruited Hispanic individuals by design. In a sensitivity analysis, Hispanic individuals in these cohorts had faster decline in GC, similar decline in EF, and slower decline in memory than White individuals. Higher time-varying cumulative mean SBP was associated with faster declines in GC, EF, and memory in all analyses. After adjusting for time-varying cumulative mean SBP, differences in cognitive slopes between Hispanic and White individuals did not change. We found no evidence that cumulative mean SBP differences explained differences in cognitive decline between Hispanic and White individuals.


Mentoring perception and academic performance: an Academic Health Science Centre survey.
To determine the association between professors' self-perception of mentoring skills and their academic performance. Two hundred and fifteen professors from Imperial College London, the first Academic Health Science Centre (AHSC) in the UK, were surveyed. The instrument adopted was the Mentorship Skills Self-Assessment Survey. Statement scores were aggregated to provide a score for each shared core, mentor-specific and mentee-specific skill. Univariate and multivariate regression analyses were used to evaluate their relationship with quantitative measures of academic performance (publications, citations and h-index). There were 104 professors that responded (response rate 48%). There were no statistically significant negative correlations between any mentoring statement and any performance measure. In contrast, several mentoring survey items were positively correlated with academic performance. The total survey score for frequency of application of mentoring skills had a statistically significant positive association with number of publications (B=0.012, SE=0.004, p=0.006), as did the frequency of acquiring mentors with number of citations (B=1.572, SE=0.702, p=0.030). Building trust and managing risks had a statistically significant positive association with h-index (B=0.941, SE=0.460, p=0.047 and B=0.613, SE=0.287, p=0.038, respectively). This study supports the view that mentoring is associated with high academic performance. Importantly, it suggests that frequent use of mentoring skills and quality of mentoring have positive effects on academic performance. Formal mentoring programmes should be considered a fundamental part of all AHSCs' configuration.


Comparison of overall obesity and body fat distribution in predicting risk of mortality.
Results of studies comparing overall obesity and abdominal adiposity or body fat distribution with risk of mortality have varied considerably. We compared the relative importance and joint association of overall obesity and body fat distribution in predicting risk of mortality. Participants included 5,799 men and 6,429 women aged 30-102 years enrolled in the third National Health and Nutrition Examination Survey who completed a baseline health examination during 1988-1994. During a 12-year follow-up (102,172 person-years), 1,188 men and 925 women died. In multivariable-adjusted analyses, waist-to-thigh ratio (WTR) in both sexes (Ptrend<0.01 for both) and waist-to-hip ratio (WHR) in women (Ptrend 0.001) were positively associated with mortality in middle-aged adults (30-64 years), while BMI and waist circumference (WC) exhibited U- or J-shaped associations. Risk of mortality increased with a higher WHR and WTR among normal weight (BMI 18.5-24.9 kg/m2) and obese (BMI>or=30.0 kg/m2) adults. In older adults (65-102 years), a higher BMI in both sexes (Ptrend<0.05) and WC in men (Ptrend 0.001) were associated with increased survival, while remaining measures of body fat distribution exhibited either no association or an inverse relation with mortality. In conclusion, ratio measures of body fat distribution are strongly and positively associated with mortality and offer additional prognostic information beyond BMI and WC in middle-aged adults. A higher BMI in both sexes and WC in men were associated with increased survival in older adults, while a higher WHR or WTR either decreased or did not influence risk of death.


Techniques for MR imaging of joints in sports medicine.
Technical advances in MR imaging of sports-related bone and joint derangement have improved our ability to evaluate these problems. This article discusses current utilization of MR imaging, advances in local coils, pulse sequences and parameters, and reviews current aspects and indications for MR arthrography.


Is a pregnancy following a second trimester uterine evacuation associated with increased adverse maternal and neonatal outcomes?
To evaluate maternal and neonatal outcomes of pregnancies following a uterine evacuation in the second trimester, in comparison to a first trimester spontaneous pregnancy loss. A retrospective analysis of data of women who conceived ≤6 months following a uterine evacuation due to a spontaneous pregnancy loss and subsequently delivered in a single tertiary medical center between 2016 and 2021. Maternal and neonatal outcomes were compared between women with second trimester (14-23 weeks) and first trimester (<14 weeks) pregnancy loss. The primary outcome of this study was the preterm delivery (<37 weeks) rate. Secondary outcomes were adverse maternal and neonatal outcomes. Univariate analysis was followed by multiple logistic regression models; adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) were calculated. During the study period, 1365 women met the inclusion criteria. Of those, 272 (19.9 %) women gave birth following a second trimester uterine evacuation and 1093 (80.1 %) women following a first trimester uterine evacuation. There were no demographic differences between the two groups. No difference was found in the preterm delivery rate in the subsequent pregnancy (5.1 % vs. 5.3 %, p = 0.91), further confirmed in the multivariate analysis [aOR 1.02 (0.53-1.94), p = 0.96]. No differences were identified with respect to other maternal and neonatal parameters examined, including hypertension disorders of pregnancy, third stage placental complications, mode of delivery and neonatal birth weight. Pregnancy conceived shortly after second trimester uterine evacuation as compared to first trimester, confers no additional risk for preterm delivery or other adverse perinatal outcomes. Further studies to strengthen these findings are needed.


Reporting cancer patients' experiences of care for quality improvement: analysis of 2000 and 2004 survey results for South East England.
National surveys of patients' experiences of English cancer services found improvements between 2000 and 2004, particularly in the areas of information, communication and trust in professionals. We assessed the potential such surveys might have to stimulate service improvements by comparing their inclusion criteria, sampling and timing and by investigating how representative they were of patients registered with cancer in South East England. Where hospital trusts had data from 50 patients with the same cancer, we determined whether national improvements in six key areas held at hospital trust level. Data were extracted from the two national surveys and from the Thames Cancer Registry. The 2000 survey achieved a higher response rate, included a larger number of hospital trusts, and a wider range of cancer sites, but a lower proportion with lung cancer. Each survey sampled patients at different points following diagnosis, with a year elapsing between data collection and reporting. Compared with cancer registry data, breast cancer patients appeared most well-represented. Only three hospital trusts had sufficiently large samples to allow comparison over time. We found no change in experience in three of the key areas, but a significant decline from previously high scores in two. To provide information useful for quality improvement future surveys will need to sample larger numbers of patients from most hospital trusts, including patients with less common cancers or receiving palliative care. Surveys should also sample patients at a consistent time after diagnosis and feedback results more rapidly to services.


Intraocular irrigating solutions. A clinical study of BSS Plus and dextrose bicarbonate fortified BSS as an infusate during pars plana vitrectomy.
To compare the effect of Balanced Salt Solution Plus (BSS Plus, Alcon Laboratories, Fort Worth, Texas, USA) and fortified regular BSS on the cornea and lens, when used for continuous irrigation in pars plana vitrectomy (PPV) surgery. Prospective, investigator masked, randomised study. Forty patients were randomly assigned to undergo PPV using BSS Plus (n=20) or fortified BSS (n=20) [regular BSS, fortified with 10.5 cc. of dextrose in water (D5W) and 13.1 cc. of 8.4% sodium bicarbonate]. Intraoperative features of the corneal epithelium, postoperative changes in the corneal endothelial cell denstiy (ECD) at 3 months, and clarity of the lens during surgery and postoperatively were evaluated. Intraoperative epithelial changes were similar in both groups with 7 (35%) of the cases having the epithelium removed in the BSS Plus group and 8 (40%) in the BSS fortified group (P=0.23). The mean differences in ECD (3 months versus preoperative) in the operated eyes when adjusted for changes in the control eye showed no difference with the type of BSS (P=0.98). Intraoperative lens changes were more significant (P=0.018) in the BSS fortified group. Postoperative lens status at 3 months was similar for both groups. Though there was a trend towards worse postoperative nuclear sclerosis change in the BSS fortified group, it was not significant (P=0.160). Standard BSS fortified with dextrose and bicarbonate is an efficacious infusion fluid during pars plana vitrectomy. Both solutions showed comparable effects on postoperative corneal endothelial cell density and corneal epithelial changes intraoperatively. BSS fortified has more lenticular changes intraoperatively than BSS Plus although no lens had to be removed in either group. The study implications are important since BSS fortified is significantly less expensive than BSS Plus.


[Changes in the effect of Cd2+ on the respiration of isolated rat liver mitochondria after their preincubation with Ca2+, Sr2+, Ba2+, Mn2+ and ruthenium red].
Action of Cd+ on mitochondrial respiration is decreased by some bivalent ions, however the reason of this still remains obscure. Change of Cd2+ action over a wide range of its concentrations on respiration of rat liver mitochondria in states 4, 3 and in the presence of 2, 4-dinitrophenol (DNP) after mitochondrial preincubation with Ca2+, Sr2+, Ba2+, Mn2+ or ruthenium Red (RR) was studied in vitro. In the control (experiments without preincubation), Cd2+ lowers mitochondrial respiration in state 3 as well as that in the presence of DNP, and increases the respiration in state 4. However, the respiration is decreased if Cd2+ concentrations are more than 15 microM; in this case a short-term activation of respiration appears. In comparison with the control, it was demonstrated that the action of Cd2+ on mitochondrial respiration was enhanced in experiments with Ca2+, decreased in experiments with Sr2+ and Mn2+, and did not vary practically in experiments with Ba2+. The activation of respiration in state 4 is increased in experiments with Ca2+ and is absent with Mn2+. Different changes in Cd2+ action on mitochondrial respiration in experiments with Me2+ ions are associated with their influence on mitochondrial membrane permeability, as well as with magnitude of the ion radius. The maximum reduce of Cd2+ action was achieved in experiments with RR, except that respiration in state 3 decreased by Cd2+ to 30 microM more rapidly than with Sr2+ and Mn2+. Under RR experiments the mitochondrial respiration in the presence of DNP as well as that in state 3 is linearly decreased (up to 15 microM Cd2+). A discussion involves issues of Cd2+ transport into the matrix, under uniporter blocking, as well as inorganic phosphate influence on Cd2+ effects, location of regulatory centers of ion permeability and location of active group of respiration enzymes.


[Cilioretinal infarction and retinal vein occlusion].
Twenty cases of central vein occlusion associated with cilio-retinal infarction were studied. The following observations were made: the venous occlusion is mostly secondary to the central venous occlusion of the trunk itself (only one case of main branch occlusion). It is always an occlusion either on papillo-phlebitis or oedematous capillaropathy. In most cases, the evolution is benign, but in very few cases it is forwards is ischemic capillaropathy. Cilio-retinal infarction is secondary to the occlusion of one or several cilioretinal arteries which are not always involved. Injection of the cilioretinal artery is usually delayed in fluorangiography, sometimes there is a typical ebb and flow. Preretinal new vascularization may appear in case of persistent ischemia of a large cilioretinal territory. Functional prognosis depends first of all upon the location of the infarcted territory relative to the foveola. Pathogenesis of this association remains unclear, cilioretinal arterial and venous involvements are concomitant and interdependent, the cilioretinal occlusion seems to be connected with the decrease of the capillary perfusion pressure which is secondary to retinal venous occlusion.


Influence of flavors and stabilizers used on the preferences and properties of aerated tvarog curd cheese.
The Polish market for tvarog (curd cheese)-based products is growing continuously. The as- sortment of these goods include products with different textures, different additives and different flavours. In developing a successful food product one should ensure consumers are sufficiently involved during the development stages. Consumer-led food product development should be a standard procedure. The study aimed to develop a new variants of aerated tvarog spreads. The research was divided into the following steps: evaluation of consumer pref- erences (questionnaire); production of aerated tvarog cheeses (different flavor variants); physico-chemical evaluation of new products (composition, TPA test); evaluation of new products by consumers (questionnaire with a 5-point scale); sensory evaluation of new products by an expert panel (2 types of questionnaire). Sweet tvarog spreads were characterized by a higher degree of aeration than cheeses with a savory flavor. The savory variants had a semi-liquid consistency after aeration. This could result from the addition of salt (6%) to flavor preparation. The products stabilized by gelatine showed a higher degree of aeration than the ones with starch. The savory cheeses showed lower hardness than sweet cheeses (P < 0.05). Both consum- ers and experts gave higher marks to the sweet variants of manufactured tvarog cheeses. The addition of salt to savory flavor preparation probably affected the texture of these products, which was semi-liquid. Texture plays a very important role in the development of new products and affects consumers’ preferences for the product.


Pirellulosomes: a new type of membrane-bounded cell compartment in planctomycete bacteria of the genus Pirellula.
A distinct type of cellular organization was found in two species of the planctomycete genus Pirellula, Pirellula marina and Pirellula staleyi. Both species possess two distinct regions within the cell which are separated by a single membrane. The major region of the cell, the pirellulosome, contains the fibrillar condensed nucleoid. The other area, the polar cap region, forms a continuous layer surrounding the entire pirellulosome and displays a cap of asymmetrically distributed material at one cell pole. Immuno- and cytochemical-labelling of P. marina demonstrated that DNA is located exclusively within the pirellulosome; cell RNA is concentrated in the pirellulosome, with some RNA also located in the polar cap region.


Evidence of lethal and sublethal injury in food-borne bacterial pathogens exposed to high-intensity pulsed-plasma gas discharges.
To apply scanning electron microscopy, image analysis and a fluorescent viability stain to assess lethal and sublethal injury in food-borne bacteria exposed to pulsed-plasma gas discharges (PPGD). The fluorescent redox probe 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) was used for enumerating actively respiring cells of Campylobacter jejuni, Escherichia coli, Listeria monocytogenes, Staphylococcus aureus and Salmonella enterica serovar Typhimurium that were suspended in sterile water at 4 degrees C and exposed to separate PPGD and heat treatments. While there was good agreement between use of respiratory staining (RS) and direct-selective agar plate counting (PC) for enumerating untreated bacteria, there were c. 1 and 3 log-unit differences in surviving cell numbers per millilitre for test organisms subjected to PPGD and heat treatments respectively, when enumerated by these different viability indicators. PPGD-treated bacteria were markedly altered at the cellular level when examined by scanning electron microscopy. Use of this RS method revealed that substantial subpopulations of test bacteria rendered incapable of forming colonies by separate PPGD and heat treatments may remain metabolically active. Use of this RS method offers interesting perspectives on assessing established and novel microbial inactivation methods, and may also provide a better understanding of mechanisms involved in microbial inactivation induced by high-intensity PPGD treatments.


Sheep elastin genes. Isolation and preliminary characterization of a 9.9-kilobase genomic clone.
A sheep genomic library containing sheep DNA in the bacteriophage vector Charon 4A was screened for elastin-gene sequences with partially purified, 32P-labelled elastin mRNA (mRNAE). A recombinant containing a 9.9-kb (kilobase) insert was selected from several positive clones by secondary and tertiary screening for further characterization. Positive identification of this elastin clone, designated SE1, was made with radiolabelled mRNAE by hydridization-selected translation and Southern blotting of restriction-enzyme fragments of SE1 DNA. Hybridization of either mRNAE or elastin complementary DNA to restriction fragments of SE1 showed that most of these fragments of SE1 contained elastin-coding sequences. Orientation of the insert was established by preferential hybridization of a short complementary elastin DNA to restriction fragments adjacent to the right arm of Charon 4A. Reciprocal hybridizations of nick-translated SE1 and sheep genomic DNA on Southern blots showed that two restriction fragments of SE1 contained sequence elements which were repeated at high frequency in a restriction-endonuclease-EcoR1 digest of total sheep genomic DNA. In the accompanying paper [Davidson, Shibahara, Boyd, Mason, Tolstoshev & Crystal (1984) Biochem. J. 220, 653-663], it is shown that a subcloned fragment of this elastin gene quantitatively and specifically hybridized to mRNAE sequences in sheep tissue RNA. Electron microscopy of SE1-mRNAE hybrids indicated the presence of at least seven large R-loops. Measurements of these structures indicated that SE1 is likely to contain less than 2 kb of coding sequence and more than 8 kb of intervening sequence, with an average exon size of 120 base-pairs. Thus the elastin gene is distributed over an extended region of the sheep genome and contains numerous intervening and coding sequences.


Off-label prescribing during pregnancy.
Obstetricians frequently prescribe drugs for indications other than those on the product label. Reasons for such off-label use during pregnancy include prevention of repetitive abortion, inhibition of premature labor, reduction of fetal or neonatal infection, reduction in development of preeclampsia and its complications, and ripening of the cervix or induction of labor. A physician has a legal right to prescribe for off-label indications despite regulatory, manufacturer, and cost constraints. Such prescribing habits would not be considered experimental if based on sound scientific evidence. Adequate and well-controlled studies are difficult, however, to perform during pregnancy. Evidence of widespread use and support from another qualified clinician are methods of justifying off-label prescribing. Each patient is entitled to know why she and her fetus would benefit from the treatment and whether any unnecessary risk is anticipated. Legible documentation of these discussions in the medical records is important.


A case study of the diet-microbiota-parasite interplay in bumble bees.
Diets and parasites influence the gut bacterial symbionts of bumble bees, but potential interactive effects remain overlooked. The main objective of this study was to assess the isolated and interactive effects of sunflower pollen, its phenolamides and the widespread trypanosomatid Crithidia sp. on the gut bacterial symbionts of Bombus terrestris males. Bumble bee males emerged in microcolonies fed on either (i) willow pollen (control), (ii) sunflower pollen or (iii) willow pollen spiked with phenolamide extracts from sunflower pollen. These microcolonies were infected by Crithidia sp. or were pathogen-free. Using 16S rRNA amplicon sequencing (V3-V4 region), we observed a significant alteration of the beta diversity, but not of the alpha diversity, in the gut microbial communities of males fed on sunflower pollen compared to males fed on control pollen. Similarly, infection by the gut parasite Crithidia sp. altered the beta diversity, but not the alpha diversity, in the gut microbial communities of males irrespective of the diet. By contrast, we did not observe any significant alteration of the beta or alpha diversity in the gut microbial communities of males fed on phenolamide-enriched pollen compared to males fed on control pollen. Changes in the beta diversity indicate significant dissimilarities of the bacterial taxa between the treatment groups, while the lack of difference in alpha diversity demonstrates no significant changes within each treatment group. Bumble bees harbour consistent gut microbiota worldwide, but our results suggest that the gut bacterial communities of bumble bees are somewhat shaped by their diets and gut parasites as well as by the interaction of these two factors. This study confirms that bumble bees are suitable biological surrogates to assess the effect of diet and parasite infections on gut microbial communities.


Reactant stationary approximation in enzyme kinetics.
In the application of the quasi-steady-state approximation, it is generally assumed that there is an initial transient during which the substrate concentration remains approximately constant while the complex concentration builds up. In this paper, we address the assumption that the substrate concentration does not change significantly during this initial transient and name it the reactant stationary approximation. For the single enzyme, single substrate reaction, the reactant stationary approximation is generally considered a sufficient condition to apply the quasi-steady-state approximation. Studying the dynamic behavior of this reaction with endogenous substrate, we show that the quasi-steady-state approximation and reactant stationary approximation are two separate approximations. We discuss the consequence of this result for the determination of reaction parameters in enzyme catalyzed reactions.


Early diabetes-induced biochemical changes in the retina: comparison of rat and mouse models.
Recently, various transgenic and knock-out mouse models have become available for studying the pathogenesis of diabetic retinopathy. At the same time, diabetes-induced retinal changes in the wild-type mice remain poorly characterised. The present study compared retinal biochemical changes in rats and mice with similar (6-week) durations of streptozotocin-induced diabetes. The experiments were performed on Wistar rats and C57Bl6/J mice. Retinal glucose, sorbitol, fructose, lactate, pyruvate, glutamate, alpha-ketoglutarate and ammonia were measured spectrofluorometrically by enzymatic methods. Vascular endothelial growth factor (VEGF) protein was assessed by ELISA, and poly(ADP-ribosyl)ation by immunohistochemistry and western blot analysis. Free mitochondrial and cytosolic NAD(+)/NADH ratios were calculated from the glutamate and lactate dehydrogenase systems. Retinal glucose concentrations were similarly increased in diabetic rats and mice, vs controls. Diabetic rats manifested approximately 26- and 5-fold accumulation of retinal sorbitol and fructose, respectively, whereas elevation of both metabolites in diabetic mice was quite modest. Correspondingly, diabetic rats had (1) increased retinal malondialdehyde plus 4-hydroxyalkenal concentrations, (2) reduced superoxide dismutase (SOD), glutathione peroxidase, glutathione reductase and glutathione transferase activities, (3) slightly increased poly(ADP-ribose) immunoreactivity and poly(ADP-ribosyl)ated protein abundance, and (4) VEGF protein overexpression. Diabetic mice lacked these changes. SOD activity was 21-fold higher in murine than in rat retinas (the difference increased to 54-fold under diabetic conditions), whereas other antioxidative enzyme activities were 3- to 10-fold lower. With the exception of catalase, the key antioxidant defence enzyme activities were increased, rather than reduced, in diabetic mice. Diabetic rats had decreased free mitochondrial and cytosolic NAD(+)/NADH ratios, consistent with retinal hypoxia, whereas both ratios remained in the normal range in diabetic mice. Mice with short-term streptozotocin-induced diabetes lack many biochemical changes that are clearly manifest in the retina of streptozotocin-diabetic rats. This should be considered when selecting animal models for studying early retinal pathology associated with diabetes.


Resting energy expenditure in asymptomatic HIV-infected females.
The purpose of this study was to investigate whether resting energy expenditure (REE) is elevated in early, asymptomatic human immunodeficiency virus (HIV)-infected females and to study the contribution of a cytokine, tumor necrosis factor-alpha (TNF-alpha), to hypermetabolism. Cross-sectional comparison of REE in asymptomatic HIV+ females and a control group matched for age, body mass index (BMI), and fat-free mass (FFM). Twenty-six females aged 35 +/- 7 years (10 HIV+ [mean CD4+ T cell count 636/mm3] and 16 healthy controls) participated in this study. REE was measured by indirect calorimeter using a Deltatrac ventilated hood with a continuous rate of 40 L/min for 30 minutes after a 40-minute equilibrium period. All tests were performed after a 12-hour overnight fast. Twenty-four-hour urinary nitrogen was calculated to correct for respiratory quotient. Body composition was measured by bioelectrical impedance (BioAnalogics, Beaverton, OR). TNF-alpha was measured by ELISA (R & D Systems, Minneapolis, MN). Absolute REE was 17% higher (1755 kcal/kg +/- 410 versus 1497 kcal/kg +/- 197) in the HIV+ group compared with the control group (p < 0.05). REE remained significantly higher in the HIV+ group when REE was adjusted for body composition differences (p = 0.04). Results revealed a 23% higher level of TNF-alpha in the HIV+ subjects (p < 0.01); however, only a weak correlation existed between TNF-alpha and REE (r = .352). This study documented that hypermetabolism and elevated TNF-alpha exist in HIV+ females in the early stages of disease.


Memory systems, processes, and tasks: taxonomic clarification via factor analysis.
The nature of various memory systems was examined using factor analysis. We reanalyzed data from 11 memory tasks previously reported in Mitchell and Bruss (2003). Four well-defined factors emerged, closely resembling episodic and semantic memory and conceptual and perceptual implicit memory, in line with both memory systems and transfer-appropriate processing accounts. To explore taxonomic issues, we ran separate analyses on the implicit tasks. Using a cross-format manipulation (pictures vs. words), we identified 3 prototypical tasks. Word fragment completion and picture fragment identification tasks were "factor pure," tapping perceptual processes uniquely. Category exemplar generation revealed its conceptual nature, yielding both cross-format priming and a picture superiority effect. In contrast, word stem completion and picture naming were more complex, revealing attributes of both processes.


Disability, anxiety and depression associated with medication-overuse headache can be considerably reduced by detoxification and prophylactic treatment. Results from a multicentre, multinational study (COMOESTAS project).
The objective of this article is to investigate whether headache-related disability, depression and anxiety can be reduced by detoxification and prophylactic treatment in patients with medication-overuse headache (MOH). Patients with MOH were included from six centres in Europe and Latin America in a seven-month cohort study. Before and six months after treatment, the degree of disability was measured by the Migraine Disability Assessment (MIDAS) questionnaire, while anxiety and depression were measured by the Hospital Anxiety and Depression Scale (HADS). A total of 694 patients with MOH were included, of whom 492 completed the study. Headache days were reduced by 58.4% from 23.6 to 9.8 days per month at six months ( P < 0.001). The MIDAS score was reduced by 57.1% from baseline 59.9 to 25.7 ( P < 0.001). Number of patients with depression was reduced by 50.7% from 195 to 96 and number of those with anxiety was reduced by 27.1% from 284 to 207 (both P < 0.001). Disability, depression and anxiety were considerably reduced in patients with MOH by detoxification and prophylactic treatment. This emphasises the urgent need for increased awareness about avoiding overuse of headache medications and demonstrates that not only headache frequency but also disability are remarkably improved by adequate intervention.


Reducing Ovarian Cancer Mortality Through Early Detection: Approaches Using Circulating Biomarkers.
More than two-thirds of all women diagnosed with epithelial ovarian cancer (EOC) will die from the disease (>14,000 deaths annually), a fact that has not changed considerably in the last three decades. Although the 5-year survival rates for most other solid tumors have improved steadily, ovarian cancer remains an exception, making it the deadliest of all gynecologic cancers and five times deadlier than breast cancer. When diagnosed early, treatment is more effective, with a 5-year survival rate of up to 90%. Unfortunately, most cases are not detected until after the cancer has spread, resulting in a dismal 5-year survival rate of less than 30%. Current screening methods for ovarian cancer typically use a combination of a pelvic examination, transvaginal ultrasonography, and serum cancer antigen 125 (CA125), but these have made minimal impact on improving mortality. Thus, there is a compelling unmet need to develop new molecular tools that can be used to diagnose early-stage EOC and/or assist in the clinical management of the disease after a diagnosis, given that more than 220,000 women are living with ovarian cancer in the United States and are at risk of recurrence. Here, we discuss the state of advancing liquid-based approaches for improving the early detection of ovarian cancer.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.


Smart doxorubicin nanoparticles with high drug payload for enhanced chemotherapy against drug resistance and cancer diagnosis.
Considering the obvious advantages in efficacy and price, doxorubicin (DOX) has been widely used for a range of cancers, which is usually encapsulated in various nanocarriers for drug delivery. Although effective, in most nanocarrier-based delivery systems, the drug loading capacity of DOX is rather low; this can lead to undesired systemic toxicity and excretion concern. Herein, we report for the first time the usage of pure doxorubicin nanoparticles (DOX NPs) without addition of any carriers for enhanced chemotherapy against drug-resistance. The drug payload reaches as high as 90.47%, which largely surpassed those in previous reports. These PEG stabilized DOX NPs exhibit good biocompatibility and stability, long blood circulation time, fast release in an acidic environment and high accumulation in tumors. Compared with free DOX, DOX NPs display a dramatically enhanced anticancer therapeutic efficacy in the inhibition of cell and tumor growth. Moreover, they can also be readily incorporated with other anticancer drugs for synergistic chemotherapy to overcome the drug resistance of cancers. The fluorescence properties of DOX also endow these NPs with imaging capabilities, thus making it a multifunctional system for diagnosis and treatment. This work demonstrates great potential of DOX NPs for cancer diagnosis, therapy and overcoming drug tolerance.


[Detection of specific markers: our research on the marker in patients with Kawasaki disease].
Anti-endothelial cell antibodies (AECA) were antibodies targeting the antigens expressed on the endothelial cell surface. It has been reported that AECA were detected frequently in patients with vasculitis and were associated with disease activity and vasculitis symptoms. Consequently, AECA are thought to be involved in pathophysiology of vasculitis, including Kawasaki disease (KD); however, the role of AECA is not clear yet. One of the causes is that target proteins of AECA have been poorly identified. Therefore, we try to detect new target proteins of AECA in patients with vasculitis using proteomics. We have identified 63 proteins out of about 150 endothelial cell-specific candidate target proteins of AECA in patients with vasculitis so far. One of the identified proteins was peroxiredoxin2 (Prx2), an antioxidant enzyme. Our research suggests that the anti-Prx2 antibodies are detected frequently in patients with vasculitis and may have pathogenic roles in vasculitis via inflammatory cytokines/chemokines production and inhibition of anti-oxidative activity of Prx2. In this paper, we overview our study of the autoantigens detected by AECA in patients with vasculitis, and will provide some data on clinical significance of autoantibodies to Prx2, a target protein of AECA, in patients with KD.


H19 and IGF2 gene expression in human normal, hyperplastic, and malignant endometrium.
We examined H19 and insulin-like growth factor 2 (IGF2) gene expression in normal endometrium (12 cases), hyperplasia (27 cases), and cancer (27 cases) by non-radioactive in situ hybridization. H19 was not expressed in the epithelium of normal endometrium, but its frequency of expression was 15% in hyperplastic and 60% in neoplastic epithelium. In stroma cells, H19 frequency of expression was 75% in normal endometrium, 55% in hyperplasia, and 37% in carcinoma. According to the grade of endometrial cancer cell differentiation, H19 showed increased frequency and level of expression in the epithelium from well to moderately and poorly differentiated tissues. Our results indicate that H19 expression in epithelial cells of endometrial hyperplasia and cancer merits further investigation and could be useful as a complementary histopathologic and prognostic marker among other modalities in endometrial cancer. IGF2 expression did not appear useful for diagnostic or prognostic purposes.


Cystic echinococcosis of the thyroid gland in children and adults.
In humans, cystic echinococcosis is one of the most serious helminthic diseases worldwide. The larval stages (cysts) of Echinococcus granulosus are mainly located in the liver and the lung. Other locations of infection are rare, which may occasionally hinder its diagnosis. A 14-year-old girl from Kosovo presented with a cystic lesion in the left thyroid lobe of 4 years duration. Although two percutaneous punctures had been performed, she developed a recurrence and therefore had to undergo thyroid surgery. The results of the histopathologic examination revealed a hydatid cyst, and consequently, the patient received a long-term course of medication, namely, albendazole. Imaging of the cranium and chest were normal. A computed tomography of the abdomen detected a further cyst in the liver which did not show the typical signs of cystic echinococcosis. An echinococcus cyst in the thyroid gland is rare, especially in children. In a review of the literature published since 1965, only 12 children have been reported. Although by definition percutaneous drainage is contraindicated to avoid the spread of protoscolices, it is documented in eleven patients without complications. Surgical extirpation is mandatory. Chemotherapy with benzomidazole derivatives is necessary to avoid recurrence.


In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum in Yaounde, Cameroon.
The in vitro activities of dihydroartemisinin (the biologically active metabolite of artemisinin derivatives), chloroquine, monodesethylamodiaquine (the biologically active metabolite of amodiaquine), quinine, mefloquine, halofantrine, and pyrimethamine were assessed in 65 African isolates of Plasmodium falciparum from Yaounde, Cameroon using an isotopic microtest. The 50% inhibitory concentration (IC50) values for dihydroartemisinin were within a narrow range from 0.25 to 4.56 nM, with a geometric mean of 1.11 nM (95% confidence interval = 0.96-1.28 nM). Dihydroartemisinin was equally active (P > 0.05) against the chloroquine-sensitive isolates (geometric mean IC50 = 1.25 nM, 95% confidence interval = 0.99-1.57 nM) and the chloroquine-resistant isolates (geometric mean IC50 = 0.979 nM, 95% confidence interval = 0.816-1.18 nM). A significant positive correlation was observed between the responses to dihydroartemisinin and mefloquine (r = 0.662) or halofantrine (r = 0.284), suggesting in vitro cross-resistance. There was no correlation between the responses to dihydroartemisinin and other antimalarial drugs.


Neuroticism associated with cocaine-induced psychosis in cocaine-dependent patients: a cross-sectional observational study.
Cocaine consumption can induce transient psychotic symptoms, which has been correlated with more severe addiction and aggressive behavior. However, little is known about the nature of the relationship between personality traits and psychotic symptoms in cocaine-dependent patients. This study examined the relationship between neuroticism and cocaine-induced psychosis. A total of 231 cocaine-dependent patients seeking treatment were recruited to the study. Personality was evaluated by the Zuckerman-Kuhlman Personality Questionnaire. Cocaine-induced psychosis questionnaire, SCID-I, and SCID-II were used to evaluate comorbidity and clinical characteristics. Data analysis was performed in three steps: descriptive, bivariate, and multivariate analyses. Cocaine-induced psychosis was reported in 65.4% of the patients and some personality disorder in 46.8%. Two personality dimensions (Neuroticism-Anxiety and Aggression-Hostility) presented a significant effect on the risk of experiencing psychotic symptoms (t(229) = 2.69, p = 0.008; t(229) = 2.06, p = 0.004), and patients with psychotic symptoms showed higher scores in both variables. On the multivariate analysis, only Neuroticism remained as a significant personality factor independently associated with psychotic symptoms (Wald = 7.44, p<0.05, OR = 1.08, CI 95% 1.02-1.16) after controlling for age, gender and number of consumption substances. An association between high neuroticism scores and presence of psychotic symptoms induced by cocaine has been found, independently of other consumption variables. Personality dimensions should be evaluated in cocaine-dependent patients in order to detect high scores of neuroticism and warn patients about the risk of developing cocaine-induced psychotic symptoms.


Activatable molecular probes for cancer imaging.
The development of highly sensitive and specific molecular probes for cancer imaging still remains a daunting challenge. Recently, interdisciplinary research at the interface of imaging sciences and bionanoconjugation chemistry has generated novel activatable imaging probes that can provide high-resolution imaging with ultra-low background signals. Activatable imaging probes are designed to amplify output imaging signals in response to specific biomolecular recognition or environmental changes in real time. This review introduces and highlights the unique design strategies and applications of various activatable imaging probes in cancer imaging.


A Mixed-Method Social Network Analysis of Low-Income Diverse Older Volunteers.
Although volunteering has been associated with numerous social benefits for diverse older adults, there is little information on how they establish relationships within a multicultural volunteering program outside of their co-ethnic communities. This convergent mixed-method social network study adopts the bonding and bridging social capital theory to explore the structures and dynamics of social interactions within a multicultural volunteer program. Low-income Russian, Khmer, Somali, Nepali, and English-speaking older volunteers in the Senior Companions Program (SCP) in a Midwest metropolitan (N = 83) participated in the surveys and focus groups. Homophily coefficients (r) show that the SCP volunteers mostly interacted with people who identified with the same nationality (r = .86), race (r = .87), and gender (r = .50). Qualitative results suggested that volunteers strengthened their social networks through within-cultural social bonding while appreciating opportunities for cross-cultural social bridging. Compared with within-cultural social bonding, cross-cultural social bridging in multicultural volunteer programs require intentional facilitation, resources, and organizational commitment.


Molecular genetic transfection of the coccidian parasite Sarcocystis neurona.
Sarcocystis neurona is an apicomplexan parasite that is the major cause of equine protozoal myeloencephalitis (EPM). The biology of this pathogen remains poorly understood in part due to unavailability of molecular genetic tools. Hence, with an objective to develop DNA transfection capabilities for S. neurona, the 5' flanking region of the SnSAG1 gene was isolated from a genomic library and used to construct expression plasmids. In transient assays, the reporter molecules beta-galactosidase (beta-gal) and yellow fluorescent protein (YFP) could be detected in electroporated S. neurona, thereby confirming the feasibility of transgene expression in this organism. Stable transformation of S. neurona was achieved using a mutant dihydrofolate reductase thymidylate synthase (DHFR-TS) gene of Toxoplasma gondii that confers resistance to pyrimethamine. This selection system was used to create transgenic S. neurona that stably express beta-gal and YFP. As shown in this study, these transgenic clones can be useful for analyzing growth rate of parasites in vitro and for assessing drug sensitivities. More importantly, the DNA transfection methods described herein should greatly facilitate studies examining intracellular parasitism by this important coccidian pathogen.


Modulation of TLR2 protein expression by miR-105 in human oral keratinocytes.
Mammalian biological processes such as inflammation, involve regulation of hundreds of genes controlling onset and termination. MicroRNAs (miRNAs) can translationally repress target mRNAs and regulate innate immune responses. Our model system comprised primary human keratinocytes, which exhibited robust differences in inflammatory cytokine production (interleukin-6 and tumor necrosis factor-alpha) following specific Toll-like receptor 2 and 4 (TLR-2/TLR-4) agonist challenge. We challenged these primary cells with Porphyromonas gingivalis (a Gram-negative bacterium that triggers TLR-2 and TLR-4) and performed miRNA expression profiling. We identified miRNA (miR)-105 as a modulator of TLR-2 protein translation in human gingival keratinocytes. There was a strong inverse correlation between cells that had high cytokine responses following TLR-2 agonist challenge and miR-105 levels. Knock-in and knock-down of miR-105 confirmed this inverse relationship. In silico analysis predicted that miR-105 had complementarity for TLR-2 mRNA, and the luciferase reporter assay verified this. Further understanding of the role of miRNA in host responses may elucidate disease susceptibility and suggest new anti-inflammatory therapeutics.


Effect of whole-body vibration on neuromuscular performance and body composition for females 65 years and older: a randomized-controlled trial.
We examined whether the effect of multipurpose exercise can be enhanced by whole-body vibration (WBV). One hundred and fifty-one post-menopausal women (68.5 ± 3.1 years) were randomly assigned to three groups: (1) a training group (TG); (2) training including vibration (VTG); and (3) a wellness control group (CG). TG and VTG performed the same training program twice weekly (60 min), consisting of aerobic and strength exercises, with the only difference that leg strength exercises (15 min) were performed with (VTG) or without (TG) vibration. CG performed a low-intensity "wellness" program. At baseline and after 18 months, body composition was determined using dual-X-ray-absorptiometry. Maximum isometric strength was determined for the legs and the trunk region. Leg power was measured by countermovement jumps using a force-measuring plate. In the TG lean body mass, total body fat, and abdominal fat were favorably affected, but no additive effects were generated by the vibration stimulus. However, concerning muscle strength and power, there was a tendency in favor of the VTG. Only vibration training resulted in a significant increase of leg and trunk flexion strength compared with CG. In summary, WBV embedded in a multipurpose exercise program showed minor additive effects on body composition and neuromuscular performance.


Comparison of chi-squared automatic interaction detection classification trees vs TNM classification for patients with head and neck squamous cell carcinoma.
To compare chi-squared automatic interaction detection (CHAID) classification trees vs the seventh edition of the TNM classification for patients with head and neck squamous cell carcinoma and to assess whether CHAID classification trees might improve results obtained with the TNM classification. Patient disease was classified according to CHAID classification trees and the TNM classification, and the results were compared. Academic research. A total of 3373 patients with carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. The 2 classification methods were evaluated objectively, measuring intrastage homogeneity (hazard consistency), interstage heterogeneity (hazard discrimination), and disease stage distribution among patients (balance). In addition, to assess agreement between CHAID classification trees and the TNM classification, we calculated the κ statistic, weighted linearly and quadratically. Objective evaluation of the quality of the classification methods indicated that CHAID classification trees performed better than the TNM classification in terms of hazard consistency (2.51 for CHAID and 3.01 for TNM) and hazard discrimination (70.9% for CHAID and 52.7% for TNM) but not balance (-31.7% for CHAID and -15.5% for TNM). Analysis of concordance between the classification methods showed that the quadratic κ statistic was 0.77 (95% CI, 0.76-0.78) and the linear κ statistic was 0.59 (95% CI, 0.57-0.60) (P < .001 for both). CHAID classification trees performed better than the TNM classification and offer potential inclusion of new prognostic factors.


Functional expression and affinity selection of single-chain cro by phage display: isolation of novel DNA-binding proteins.
A robust selection system affording phage display of the DNA-binding helix-turn-helix protein Cro is presented. The aim of the work was to construct an experimental system allowing for the construction and isolation of Cro-derived protein with new DNA-binding properties. A derivative of the phage lambda Cro repressor, scCro8, in which the protein subunits had been covalently connected via a peptide linker was expressed in fusion with the gene 3 protein of Escherichia coli filamentous phage. The phage-displayed single-chain Cro was shown to retain the DNA binding properties of its wild-type Cro counterpart regarding DNA sequence specificity and binding affinity. A kinetic analysis revealed the rate constant of dissociation of the single-chain Cro-phage/DNA complex to be indistinguishable from that of the free single-chain Cro. Affinity selection using a biotinylated DNA with a target consensus operator sequence allowed for a 3000-fold enrichment of phages displaying single-chain Cro over control phages. The selection was based on entrapment of phage/DNA complexes formed in solution on streptavidin-coated paramagnetic beads. The expression system was subsequently used to isolate variant scCro8 proteins, mutated in their DNA-binding residues, that specifically recognized new, unnatural target DNA ligands.


[Anti-scarring effect of rapamycin following filtering surgery in rabbit eyes].
To study the effect of rapamycin on scar formation in rabbit eyes following filtering operation and explore the possible mechanism. Ninety-six healthy adult rabbits were subjected to trabeculectomy of the left eye and subsequently randomly divided into 4 groups (n=24) for treatment with castor oil (control) or rapamycin (1%, 3%, or 5%) eye drops of the operated eyes 4 times a day. The morphology and function of the filtering blebs of the rabbits were compared at 7, 14, 21 and 28 days after the operation; at each of the time points, 6 rabbits from each group were euthanized for detection of expressions of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) in the tissues in the surgical area using immunohistochemistry. Cultured rabbit subconjunctival fibroblasts (RTFSs) were treated with different concentrations of rapamycin (0.06, 0.25, 1, and 4 mg/L) and the cell apoptosis was detected using flow cytometry. In the first, second and third weeks after the operation, the rate of functional follicle formation was significantly higher in the 3 rapamycin groups than in the control group (P < 0.05), and the number of α- SMA-positive fibroblasts decreased over time in the 3 rapamycin groups. In cultured RTFSs, treatment with rapamycin at different concentrations resulted in increased apoptosis of the cells, and rapamycin above 0.25 mg/L significantly increased the cell apoptosis in a dose-dependent manner. Rapamycin can inhibit hyperplasia of the filtering passage tissue, helps to preserve the functional filtering blebs and prolong their life span, and induces apoptosis of RTFS.


Efficacy and Safety of High-Density Lipoprotein/Apolipoprotein A1 Replacement Therapy in Humans and Mice With Atherosclerosis: A Systematic Review and Meta-Analysis.
Background: Although elevation of HDL-C levels by pharmaceutical drugs have no benefit of cardiovascular endpoint, the effect of high-density lipoprotein/apolipoprotein A1 (HDL/apoA-1) replacement therapy on atherosclerosis is controversial. The current meta-analysis analyzed the effects of HDL/apoA-1 replacement therapies on atherosclerotic lesions both in humans and mice. Methods: The PubMed, Cochrane Library, Web of Science, and EMBASE databases were searched through June 6, 2020. The methodological quality of the human studies was assessed using Review Manager (RevMan, version 5.3.). The methodological quality of the mouse studies was assessed using a stair list. STATA (version 14.0) was used to perform all statistical analyses. Results: Fifteen randomized controlled human trials and 17 animal studies were included. The pooled results showed that HDL/apoA-1 replacement therapy use did not significantly decrease the percent atheroma volume (p = 0.766) or total atheroma volume (p = 0.510) in acute coronary syndrome (ACS) patients (N = 754). However, HDL/apoA-1 replacement therapies were significantly associated with the final percent lesion area, final lesion area, and changes in lesion area (SMD, -1.75; 95% CI: -2.21~-1.29, p = 0.000; SMD, -0.78; 95% CI: -1.18~-0.38, p = 0.000; SMD: -2.06; 95% CI, -3.92~-0.2, p = 0.03, respectively) in mice. Conclusions: HDL/apoA-1 replacement therapies are safe but do not significantly improve arterial atheroma volume in humans. The results in animals suggest that HDL/apoA-1 replacement therapies decrease the lesion area. Additional studies are needed to investigate and explain the differences in HDL/apoA-1 replacement therapy efficacies between humans and animals. Trial registration number: Human pooled analysis: PROSPERO, CRD42020210772. prospectively registered.


Design and Characterization of Pressure Monitoring and Insertion system for Intraparenchymal Convection Enhanced Delivery.
Neurological disorders are a significant societal and economic burden. Common pharmacological therapies often can only manage symptoms and have limited efficacy. Intraparenchymal convection enhanced delivery (IP CED) is a neurosurgical technique for direct brain delivery of therapeutics. Currently, the main applications of IP CED are targeted chemotherapy for glioblastoma and gene therapy. While IP CED has advantages over systemic approaches, its benefits can be drastically reduced by inadequate coverage as low as 21% of target anatomy, excessive infusion durations greater than 2 hours, and off-target effects. Addressing the limitations of IP CED requires thorough investigation and optimization of the relevant fluid dynamic and operational parameters. In this work, we present the design, fabrication, and characterization of low-cost, open-source, and fully automated CED cannula insertion control and pressure-monitoring systems. Using these automated CED control systems, we investigate the effects of pressure, insertion velocity, and flow rates on several outcome variables, including reflux, volume distribution, and infusion cloud morphology during CED infusions in brain phantoms.Clinical Relevance- CED pressure properties may be able to implicate reflux incidents and could provide clinicians with valuable, real-time information regarding ongoing infusions without the need for costly medical imaging modalities.


pH-dependent deformations of the energy landscape of avidin-like proteins investigated by single molecule force spectroscopy.
Avidin and avidin-like proteins are widely used in numerous techniques since the avidin-biotin interaction is known to be very robust and reliable. Within this study, we investigated this bond at the molecular level under harsh conditions ranging from very low to very high pH values. We compared avidin with streptavidin and a recently developed avidin-based mutant, chimeric avidin. To gain insights of the energy landscape of these interactions we used a single molecule approach and performed the Single Molecule Force Spectroscopy atomic force microscopy technique. There, the ligand (biotin) is covalently coupled to a sharp AFM tip via a distensible hetero-bi-functional crosslinker, whereas the receptor of interest is immobilized on the probe surface. Receptor-ligand complexes are formed and ruptured by repeatedly approaching and withdrawing the tip from the surface. Varying both pulling velocity and pH value, we could determine changes of the energy landscape of the complexes. Our results clearly demonstrate that avidin, streptavidin and chimeric avidin are stable over a wide pH range although we could identify differences at the outer pH range. Taking this into account, they can be used in a broad range of applications, like surface sensors at extreme pH values.


Diversification under sexual selection: the relative roles of mate preference strength and the degree of divergence in mate preferences.
The contribution of sexual selection to diversification remains poorly understood after decades of research. This may be in part because studies have focused predominantly on the strength of sexual selection, which offers an incomplete view of selection regimes. By contrast, students of natural selection focus on environmental differences that help compare selection regimes across populations. To ask how this disparity in focus may affect the conclusions of evolutionary research, we relate the amount of diversification in mating displays to quantitative descriptions of the strength and the amount of divergence in mate preferences across a diverse set of case studies of mate choice. We find that display diversification is better explained by preference divergence rather than preference strength; the effect of the latter is more subtle, and is best revealed as an interaction with the former. Our findings cast the action of sexual selection (and selection in general) in a novel light: the strength of selection influences the rate of evolution, and how divergent selection is determines how much diversification can occur. Adopting this view will enhance tests of the relative role of natural and sexual selection in processes such as speciation.


Neuroendoscopic management of symptomatic septum pellucidum cysts.
Ten rare cases of symptomatic septum pellucidum cysts in patients who underwent endoscopic fenestration are described. The approaches and techniques used in the management of these cysts and the endoscopic surgical indications are discussed. In the past 5 years, 10 patients (age range, 3-60 yr) with symptomatic septum pellucidum cysts underwent neuroendoscopic fenestration. The most common symptom was intermittent headache (seven patients) accompanied by dizziness, vomiting, and epileptic seizures. Two patients presented with epileptic seizures. One patient presented with abnormally increased head circumference. Magnetic resonance imaging scans of 10 patients showed septum pellucidum cysts, two with hydrocephalus, and two with pituitary microadenoma. All 10 patients underwent endoscopic fenestration with a rigid endoscope via a frontal approach. Eight cases were performed freehand. Two cases were assisted by a frameless neuronavigation system. Postoperatively, the mass effect of the cysts and the symptoms resolved immediately, and computed tomographic or magnetic resonance imaging scans showed significant decrease in the cyst size and no recurrence during follow-up. Ventricular sizes in the two patients with hydrocephalus were normal. Neuroendoscopic pellucidotomy could be an effective, safe, and convenient therapeutic method for symptomatic septum pellucidum cysts. This approach might provide communication between the cyst and the ventricular system, thus avoiding shunting or craniotomy. We consider that it is appropriate to use the rigid endoscope via the frontal approach. It is helpful to fill the ventricles with lactated Ringer's solution and leave an external drain after surgery.


Investment in seed physical defence is associated with species' light requirement for regeneration and seed persistence: evidence from Macaranga species in Borneo.
The seed stage is often critical in determining the regeneration success of plants. Seeds must survive an array of seed predators and pathogens and germinate under conditions favourable for seedling establishment. To maximise recruitment success plants protect seeds using a diverse set of chemical and physical defences. However, the relationship between these defence classes, and their association with other life history traits, is not well understood. Data on seed coat thickness and fracture resistance, and the abundance and diversity of potential defensive compounds were collected for 10 tree species of Macaranga from Borneo. The data were used to test whether there is a trade-off in physical versus chemical defence investment, and to determine how investment varies with seed mass, and light requirement for regeneration. Across species there was no correlation between seed coat thickness and abundance of potential defensive compounds, indicating the absence of a direct trade-off between defence classes. While chemical defences were not correlated to other traits, physical defences were positively correlated with light requirement for regeneration. For a subset of five Macaranga species we evaluated the relative investment in chemical and physical defence to seed persistence in the soil, measured as the time to half initial seed viability (seed half-life). Half-life was negatively related to the ratio of potential defensive compound abundance to seed coat thickness, suggesting that species with long persistence invested in physical defence more than stored chemical defences. These results indicate that investment in seed defences are associated with species' light requirements for regeneration, rather than scaling positively with seed mass. Furthermore, chemical defences, although highly variable among species, do not appear to be critical to long term persistence of Macaranga seeds, and may be important in defending seeds from natural enemies distinct from those found in the soil.


Studies on surface properties of asbestos. III. Interactions between asbestos and polynuclear aromatic hydrocarbons.
The purpose of this study is to reveal the nature of the physicochemical interactions between asbestos and polynuclear aromatic hydrocarbons (PAH) in an organic liquid medium, and to assist in the understanding of synergistic effects between asbestos and PAH in bronchopulmonary cancers. The adsorption curves of three PAH (phenanthrene, fluorene, dimethyl-7,12-benzanthracene) on chrysotile and crocidolite are multistep isotherms and show the formation of bidimensional condensed layers (2D) of PAH. This phenomenon is observed with solids having a dominant basic character (asbestos, magnesia) but is not detected with acidic solids (alumina, silica-alumina). The elimination of water and dissolved gases (O2, CO2) in the liquid medium increased the affinity of asbestos for PAH. The coadsorption CO2-phenanthrene on the substrate decreased the adsorbed quantities of solute but did not inhibit the formation of layers (2D). The adsorption is weaker on leached chrysotile, than on original chrysotile; the amorphous silica coating the fibers has no affinity for PAH; the adsorption is only due to some active sites present on the surface of residual chrysotile which is accessible to phenanthrene. The formation of layers (2D) is due to strong interactions between PAH having an induced or permanent dipole moment and the active electron donor sites present on the mineral surface. The equilibrium equation between the adsorbed layer and the PAH in solution is established by reference to theoretical studies, and the results allowed us to classify the charge density of the mineral surface. The interactions between PAH and asbestos allowed us to explain the differences introduced in the kinetics of PAH uptake toward the cells when PAH is preadsorbed on asbestos. This fact could, in part, explain the synergistic effects observed in carcinogenesis.


Automated trajectory planning for laser interstitial thermal therapy in mesial temporal lobe epilepsy.
Surgical resection of the mesial temporal structures brings seizure remission in 65% of individuals with drug-resistant mesial temporal lobe epilepsy (MTLE). Laser interstitial thermal therapy (LiTT) is a novel therapy that may provide a minimally invasive means of ablating the mesial temporal structures with similar outcomes, while minimizing damage to the neocortex. Systematic trajectory planning helps ensure safety and optimal seizure freedom through adequate ablation of the amygdalohippocampal complex (AHC). Previous studies have highlighted the relationship between the residual unablated mesial hippocampal head and failure to achieve seizure freedom. We aim to implement computer-assisted planning (CAP) to improve the ablation volume and safety of LiTT trajectories. Twenty-five patients who had previously undergone LiTT for MTLE were studied retrospectively. The EpiNav platform was used to automatically generate an optimal ablation trajectory, which was compared with the previous manually planned and implemented trajectory. Expected ablation volumes and safety profiles of each trajectory were modeled. The implemented laser trajectory and achieved ablation of mesial temporal lobe structures were quantified and correlated with seizure outcome. CAP automatically generated feasible trajectories with reduced overall risk metrics (P < .001) and intracerebral length (P = .007). There was a significant correlation between the actual and retrospective CAP-anticipated ablation volumes, supporting a 15 mm diameter ablation zone model (P < .001). CAP trajectories would have provided significantly greater ablation of the amygdala (P = .0004) and AHC (P = .008), resulting in less residual unablated mesial hippocampal head (P = .001), and reduced ablation of the parahippocampal gyrus (P = .02). Compared to manually planned trajectories CAP provides a better safety profile, with potentially improved seizure-free outcome and reduced neuropsychological deficits, following LiTT for MTLE.


Diabetes Self-Management and the Associated Factors Among Adult Omanis with Type 1 Diabetes.
This study aimed to assess and explore factors affecting diabetes self-management (DSM) among Omani adults with type one diabetes mellitus (T1DM). This cross-sectional study was conducted from May to November 2018. Convenience sampling was used to recruit participants from three referral hospitals in Oman. Data were collected using the Diabetes Self-Management Questionnaire, Empowerment Scale (short form), Medical Outcome Study Social Support Scale, Diabetes Knowledge Test and glycosylated haemoglobin test results. Linear multiple regression analysis was used to explore possible predictors of DSM. A total of 210 people participated in the study (response rate: 87.5%). The majority of participants were female (70.5%) with a mean age of 26.82 ± 8.25 years. The mean score for DSM was 6.8 ± 1.4, which represents 68% of the total maximum score. More than one-third (36.2%) of the participants had poor glycaemic control. The predictors of high levels of DSM were being employed (P = 0.049), earning a low monthly income of less than 300 Omani rials (P = 0.014), having other chronic diseases (P = 0.029), a high diabetes self-efficacy (DSE; P = 0.003) and high social support (SS; P = 0.006). According to the findings of this study, Omanis with T1DM have suboptimal DSM levels. Factors such as diabetes knowledge, DSE and SS are modifiable factors that can be targeted by interventions from different healthcare professionals to enhance DSM.


Antibodies to hepatitis C virus in autologous blood donors.
Hepatitis C virus (HCV) is the major cause of posttransfusion hepatitis. Two anti-HCV enzyme immunoassay (EIA) kits and one recombinant immunoblot assay (RIBA) were used to test serum samples of 1476 donations from 692 autologous blood donors to assess the prevalence of anti-HCV and its relationship to transfusion history. Of all autologous blood donations, 23 (1.6%) reacted when tested with one EIA kit and 29 (2.0%) reacted when tested by the other EIA kit. Of the autologous donors, 12 (1.78%) reacted by the first EIA kit and 14 (2.02%) by the second. Discrepancies in the EIA results from different donations by the same donor were seen in seven donors. The RIBA was positive or indeterminate in 33 percent of the EIA-reactive donations and in 41 percent of EIA-reactive donors. All RIBA-positive and -indeterminate samples reacted with both EIA kits. There was no significant difference in the EIA-reactive rates of autologous and first-time homologous blood donors. Previously transfused autologous blood donors had a higher anti-HCV EIA-reactive rate than nontransfused autologous donors, but the difference was not significant. In regard to hepatitis C, the use of autologous blood for homologous transfusion appears to be as safe as the use of blood from first-time homologous donors. Universal testing of previously transfused patients for hepatitis C appears premature at this time. Discrepant anti-HCV EIA results from different donations from the same individual have implications regarding donor deferral.


Genetic variation in the oxytocin receptor (OXTR) gene is associated with Asperger Syndrome.
Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction, alongside unusually repetitive behaviors and narrow interests. ASC are highly heritable and have complex patterns of inheritance where multiple genes are involved, alongside environmental and epigenetic factors. Asperger Syndrome (AS) is a subgroup of these conditions, where there is no history of language or cognitive delay. Animal models suggest a role for oxytocin (OXT) and oxytocin receptor (OXTR) genes in social-emotional behaviors, and several studies indicate that the oxytocin/oxytocin receptor system is altered in individuals with ASC. Previous studies have reported associations between genetic variations in the OXTR gene and ASC. The present study tested for an association between nine single nucleotide polymorphisms (SNPs) in the OXTR gene and AS in 530 individuals of Caucasian origin, using SNP association test and haplotype analysis. There was a significant association between rs2268493 in OXTR and AS. Multiple haplotypes that include this SNP (rs2268493-rs2254298, rs2268490-rs2268493-rs2254298, rs2268493-rs2254298-rs53576, rs237885-rs2268490-rs2268493-rs2254298, rs2268490-rs2268493-rs2254298-rs53576) were also associated with AS. rs2268493 has been previously associated with ASC and putatively alters several transcription factor-binding sites and regulates chromatin states, either directly or through other variants in linkage disequilibrium (LD). This study reports a significant association of the sequence variant rs2268493 in the OXTR gene and associated haplotypes with AS.


Transactivation of the epidermal growth factor receptor by angiotensin II in glomerular podocytes.
Activation of angiotensin II (ANG2) receptors stimulates extracellular signal-regulated kinases (ERKs) that, in some cell systems, are mediated by transactivating the epidermal growth factor (EGF) receptor (EGFR) through mechanisms involving matrix metalloprotease (MMP)-stimulated processing of heparin-binding EGF (HB-EGF) from its precursor. The signaling pathways linked to ANG2-dependent ERK activation were determined in an immortalized mouse podocyte cell line by monitoring ANG2-stimulated phosphorylation of ERK1/2. ANG2 induced transient ERK phosphorylation that was maximal at 5 min and then rapidly dissipated. ANG2-dependent ERK activation was inhibited by: (1) the type-1 ANG2-selective antagonist losartan; (2) the type-2 ANG2-selective antagonist PD123319; (3) an inhibitor of MMP2/9; (4) the EGFR kinase inhibitor AG1478, and (5) the HB-EGF antagonists CRM197 and heparin. ANG2-dependent ERK activation was mediated by both protein kinase C (PKC)- and calcium-dependent mechanisms and was associated with tyrosine phosphorylation of EGFR. To determine if ANG2-dependent HB-EGF release could act in a paracrine fashion on adjacent cells, HEK293 cells were stably transfected with green fluorescent protein-tagged ERK2 (GFP-ERK2). In stably transfected HEK293 cells, EGF stimulated phosphorylation of endogenous ERK1/2 as well as GFP-ERK2. In contrast, ANG2 had no effect on ERK phosphorylation in stably transfected HEK293 cells. When podocytes were co-cultured with stably transfected HEK293 cells, however, treatment with ANG2 rapidly stimulated GFP-ERK2 phosphorylation. Both the MMP2/9 inhibitor and AG1478 attenuated ANG2-dependent phosphorylation of GFP-ERK2 in the co-culture system. These data indicate that ERK activation is induced by ANG2 in podocytes by mechanisms involving ANG2-dependent release of HB-EGF which, in turn, may act in an autocrine and paracrine fashion to stimulate ERK activity.


Drying time of tray adhesive for adequate tensile bond strength between polyvinylsiloxane impression and tray resin material.
Use of custom tray and tray adhesive is clinically recommended for elastomeric impression material. However there is not clear mention of drying time of tray adhesive in achieving appropriate bonding strength of tray material and impression material. This study is to investigate an appropriate drying time of tray adhesives by evaluating tensile bonding strength between two types of polyvinylsiloxane impression materials and resin tray, according to various drying time intervals of tray adhesives, and with different manufacturing company combination of impression material and tray adhesive. Adhesives used in this study were Silfix (Dentsply Caulk, Milford, Del, USA) and VPS Tray Adhesive (3M ESPE, Seefeld, Germany) and impression materials were Aquasil Ultra (monophase regular set, Dentsply Caulk, Milford, Del, USA) and Imprint II Garant (regular body, 3M ESPE, Seefeld, Germany). They were used combinations from the same manufacture and exchanged combinations of the two. The drying time was designed to air dry, 5 minutes, 10 minutes, 15 minutes, 20 minutes, and 25 minutes. Total 240 of test specimens were prepared by auto-polymerizing tray material (Instant Tray Mix, Lang, Wheeling, Il, USA) with 10 specimens in each group. The specimens were placed in the Universal Testing machine (Instron, model 3366, Instron Corp, University avenue, Nowood, MA, USA) to perform the tensile test (cross head speed 5 mm/min). The statistically efficient drying time was evaluated through ANOVA and Scheffe test. All the tests were performed at 95% confidence level. The results revealed that at least 10 minutes is needed for Silfix-Aquasil, and 15 minutes for VPS Tray Adhesive-Imprint II, to attain an appropriate tensile bonding strength. VPS Tray Adhesive-Imprint II had a superior tensile bonding strength when compared to Silfix-Aquasil over 15 minutes. Silfix-Aquasil had a superior bonding strength to VPS Tray Adhesive-Aquasil, and VPS Tray Adhesive-Imprint II had a superior tensile bonding strength to Silfix-Imprint II at all drying periods. Significant increase in tensile bonding strength with Silfix-Aquasil and VPS Tray adhesive-Imprint II combination until 10 and 15 minutes respectively. Tray adhesive-impression material combination from the same company presented higher tensile bonding strength at all drying time intervals than when using tray adhesive-impression material of different manufactures.


Unique substrate specificity of anaplastic lymphoma kinase (ALK): development of phosphoacceptor peptides for the assay of ALK activity.
The anaplastic lymphoma kinase (ALK), whose constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin's lymphomas, shares with the other members of the insulin receptor kinase (IRK) subfamily an activation loop (A-loop) with the triple tyrosine motif Y-x-x-x-Y-Y. However, the amino acid sequence of the ALK A-loop differs significantly from the sequences of both the IRK A-loop and the consensus A-loop for this kinase subfamily. A major difference is the presence of a unique "RAS" triplet between the first and second tyrosines of the ALK A-loop, which in IRK is replaced by "ETD". Here we show that a peptide reproducing the A-loop of ALK is readily phosphorylated by ALK, while a homologous IRK A-loop peptide is not unless its "ETD" triplet is substituted by "RAS". Phosphorylation occurs almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif, as judged by Edman analysis of the phosphoradiolabeled product. Consequently, a peptide in which the first tyrosine had been replaced by phenylalanine (FYY) was almost unaffected by ALK. In contrast, a peptide in which the second and third tyrosines had been replaced by phenylalanine (YFF) was phosphorylated more rapidly than the parent peptide (YYY). A number of substitutions in the YFF peptide outlined the importance of Ile and Arg at positions n - 1 and n + 6 in addition to the central triplet, to ensure efficient phosphorylation by ALK. Such a peculiar substrate specificity allows the specific monitoring of ALK activity in crude extracts of NPM-ALK positive cells, using the YFF peptide, which is only marginally phosphorylated by a number of other tyrosine kinases.