Criteria-based expert system for cardiac ischemia evaluation in the emergency department.
To develop and evaluate a cardiac ischemia computer expert system using a criteria-based expert shell for assessment of chest pain patients in a community hospital ED setting. A retrospective, comparison study of the expert system against the clinical judgment of board-certified emergency physicians (EPs) was performed in 1 community hospital ED. All chest pain patients had either a cardiac catheterization, Persantine stress testing, or both within 1 month of ED presentation. A final diagnosis of acute myocardial infarction or unstable angina by a consultant cardiologist represented the criterion standard for cardiac ischemia. Of the 59 patients meeting study criteria, 28 (47%) had cardiac ischemia. The expert system had equal sensitivity (100%) and was more than twice as specific (39% vs 16%) in diagnosing ischemic cardiac disease as were the board-certified EPs (p < 0.001; McNemar's chi-square with Yates' correction). The criteria-based system built around a system of findings ordered by Bayes' rule has potential to augment the ability of the EP to accurately diagnose ischemic heart disease.


Improvement in lung diffusion by endothelin A receptor blockade at high altitude.
Lung diffusing capacity has been reported variably in high-altitude newcomers and may be in relation to different pulmonary vascular resistance (PVR). Twenty-two healthy volunteers were investigated at sea level and at 5,050 m before and after random double-blind intake of the endothelin A receptor blocker sitaxsentan (100 mg/day) vs. a placebo during 1 wk. PVR was estimated by Doppler echocardiography, and exercise capacity by maximal oxygen uptake (Vo(2 max)). The diffusing capacities for nitric oxide (DL(NO)) and carbon monoxide (DL(CO)) were measured using a single-breath method before and 30 min after maximal exercise. The membrane component of DL(CO) (Dm) and capillary volume (Vc) was calculated with corrections for hemoglobin, alveolar volume, and barometric pressure. Altitude exposure was associated with unchanged DL(CO), DL(NO), and Dm but a slight decrease in Vc. Exercise at altitude decreased DL(NO) and Dm. Sitaxsentan intake improved Vo(2 max) together with an increase in resting and postexercise DL(NO) and Dm. Sitaxsentan-induced decrease in PVR was inversely correlated to DL(NO). Both DL(CO) and DL(NO) were correlated to Vo(2 max) at sea level (r = 0.41-0.42, P < 0.1) and more so at altitude (r = 0.56-0.59, P < 0.05). Pharmacological pulmonary vasodilation improves the membrane component of lung diffusion in high-altitude newcomers, which may contribute to exercise capacity.


Does body mass index or weight perception affect contraceptive use?
Overweight and obese women may avoid contraceptive methods they believe are associated with weight gain. The objective of this study was to examine the role of weight and weight perception on contraceptive use. Using cross-sectional data from the MyNewOptions study, we analyzed contraceptive use among 987 privately insured, sexually active women aged 18-40 years. Contraception was categorized into three groups: (1) long-acting reversible contraceptives (LARCs), (2) non-LARC prescription methods and (3) nonprescription methods/no method. Multinomial logistic regression was used to model the effect of body mass index category and weight perception on contraceptive use while controlling for pregnancy intentions, sexual behavior and sociodemographic characteristics. Eighty-three (8.4%) women were using LARCs, 490 (49.6%) women were using non-LARC prescription methods and 414 (42.0%) were using nonprescription methods or no method. In the adjusted multinomial model, overweight [adjusted odds ratio (aOR) 3.84, 95% confidence interval (CI) 1.85-7.98) and obese women (aOR 2.82, 95% CI 1.18-6.72) were significantly more likely to use LARCs compared to normal-weight women. There were greater adjusted odds of overweight and obese women using nonprescription methods/no method compared with non-LARC prescription methods, but this finding did not reach statistical significance. Weight perception was not associated with contraceptive use. In this study sample, overweight and obese women were more likely to use LARCs than normal-weight women. It will be important to further understand how weight influences women and providers' views on contraception in order to better assist women with individualized, patient-centered contraceptive decision making. Overweight and obese women may be reluctant to use contraceptive methods they believe are associated with weight gain (i.e., pills, shot), but how that affects contraceptive use is unclear. Compared with normal-weight women, overweight and obese women in this study were more likely to use LARCs than non-LARC prescription methods.


The older driver--a review.
There are differences between elderly drivers and younger drivers in that the elderly are more likely to have cognitive, motor and sensoriperceptual deficits affecting their driving performance. The elderly driver is more likely to have a chronic illness and to be on medication, that might adversely affect driving. The elderly driver requires more study and help either by retraining or provision of adaptations to vehicles. Fitness to drive is of clinical importance to doctors in most specialities and recent studies would suggest that doctors need to be more aware of the current guidelines on driving and be prepared to offer advice.


Secular decrease in blood pressure and reduction in mortality from cardiovascular disease in Israeli workers.
The reasons for the dramatic reduction in age-adjusted mortality from cardiovascular disease (CVD) since the 1970s in developed countries remain uncertain. In the following study we compare the cardiovascular and all-cause mortality rates over an 11-year period in two well-defined employed male cohorts aged 40-69 years old recruited 24 years apart. Blood pressure and other risk markers for CVD were assessed at the time of inception (1963 for 10 048 male civil servants and 1985-1987 for 2237 male industrial workers). Compared to the 1987 cohort, the 1963 cohort show an increase of 8.7 mmHg in the mean systolic blood pressure (SBP) (95% confidence interval (CI): 7.7, 9.6) and a concomitant hazard ratio for CVD mortality of 1.47 (95% CI: 1.16, 1.87). After adding SBP to the analysis, the hazard ratio for CVD mortality in the 1963 cohort decreased to 1.18 (95% CI: 0.88, 1.43). Adding the other risk modifiers to the analysis did not modify the hazard ratio to the same extent. Similar results were obtained for all-cause mortality. We conclude that declining blood pressure values are a major factor in explaining the secular decrease in CVD mortality over a period of 24 years in Israel.


Suppressor of fused controls perinatal expansion and quiescence of future dentate adult neural stem cells.
Adult hippocampal neurogenesis requires the quiescent neural stem cell (NSC) pool to persist lifelong. However, establishment and maintenance of quiescent NSC pools during development is not understood. Here, we show that Suppressor of Fused (Sufu) controls establishment of the quiescent NSC pool during mouse dentate gyrus (DG) development by regulating Sonic Hedgehog (Shh) signaling activity. Deletion of Sufu in NSCs early in DG development decreases Shh signaling activity leading to reduced proliferation of NSCs, resulting in a small quiescent NSC pool in adult mice. We found that putative adult NSCs proliferate and increase their numbers in the first postnatal week and subsequently enter a quiescent state towards the end of the first postnatal week. In the absence of Sufu, postnatal expansion of NSCs is compromised, and NSCs prematurely become quiescent. Thus, Sufu is required for Shh signaling activity ensuring expansion and proper transition of NSC pools to quiescent states during DG development.


Real-space density kernel method for Kohn-Sham density functional theory calculations at high temperature.
Kohn-Sham density functional theory calculations using conventional diagonalization based methods become increasingly expensive as temperature increases due to the need to compute increasing numbers of partially occupied states. We present a density matrix based method for Kohn-Sham calculations at high temperatures that eliminates the need for diagonalization entirely, thus reducing the cost of such calculations significantly. Specifically, we develop real-space expressions for the electron density, electronic free energy, Hellmann-Feynman forces, and Hellmann-Feynman stress tensor in terms of an orthonormal auxiliary orbital basis and its density kernel transform, the density kernel being the matrix representation of the density operator in the auxiliary basis. Using Chebyshev filtering to generate the auxiliary basis, we next develop an approach akin to Clenshaw-Curtis spectral quadrature to calculate the individual columns of the density kernel based on the Fermi operator expansion in Chebyshev polynomials and employ a similar approach to evaluate band structure and entropic energy components. We implement the proposed formulation in the SPARC electronic structure code, using which we show systematic convergence of the aforementioned quantities to exact diagonalization results, and obtain significant speedups relative to conventional diagonalization based methods. Finally, we employ the new method to compute the self-diffusion coefficient and viscosity of aluminum at 116 045 K from Kohn-Sham quantum molecular dynamics, where we find agreement with previous more approximate orbital-free density functional methods.


Unusual side-effects due to clobazam: a case report with genetic study of CYP2C19.
We describe the case of a 10-year-old girl with two epileptic seizures and subcontinuous spike-waves during sleep, who presented unusual side-effects related to clobazam (CLB) monotherapy. High plasma levels of N-desmethyl-clobazam (N-CLB), the major metabolite of CLB were detected. The patient and her parents underwent molecular analysis of the CYP2C19 gene, which may be implicated in the metabolism of this drug. Our patient presents one copy of the most common mutation (CYP2C19*2) affecting the activity of the isoenzyme and probably another rare or private mutation. CLB and N-CLB plasma level dosages and molecular analysis may be useful when a poor metabolic condition is suspected.


Anatomy of superficial thoracic artery related to subpectoral augmentation mammoplasty.
The aim of this study is to elucidate the anatomic details of superficial thoracic artery related to transaxillary subpectoral augmentation mammoplasty.Thirty-three breasts of Korean cadavers (11 males, 6 females) were dissected. The superficial thoracic artery was found at the lateral part of the pectoralis (P.) major muscle in all cases. It originated mostly from the lateral thoracic artery (42%), thoracoacromial artery (38%), and partly from axillary artery (19%). Most of (82%) the muscle entering point was included in the circle of 2.5-cm radius. The center was located 2.5 cm superior from the intersection of the lateral border of the P. major and inferior border of the fourth rib. It was distant from 12 cm lateral to the midline and 6 cm below the sternal notch. We think that the superficial thoracic artery might be the culprit of bleeding and severe hematoma in transaxillary subpectoral mammoplasty.


How does heat shock affect the life history traits of adults and progeny of the aphid parasitoid Aphidius avenae (Hymenoptera: Aphidiidae)?
Because insects are ectotherms, their physiology, behaviour and fitness are influenced by the ambient temperature. Any changes in environmental temperatures may impact the fitness and life history traits of insects and, thus, affect population dynamics. Here, we experimentally tested the impact of heat shock on the fitness and life history traits of adults of the aphid parasitoid Aphidius avenae and on the later repercussions for their progeny. Our results show that short exposure (1 h) to an elevated temperature (36 degrees C), which is frequently experienced by parasitoids during the summer, resulted in high mortality rates in a parasitoid population and strongly affected the fitness of survivors by drastically reducing reproductive output and triggering a sex-dependent effect on lifespan. Heat stress resulted in greater longevity in surviving females and in shorter longevity in surviving males in comparison with untreated individuals. Viability and the developmental rates of progeny were also affected in a sex-dependent manner. These results underline the ecological importance of the thermal stress response of parasitoid species, not only for survival, but also for maintaining reproductive activities.


Evaluation of the Safety and Feasibility of Same-Day Holmium-166 -Radioembolization Simulation and Treatment of Hepatic Metastases.
To evaluate the safety and feasibility of same-day treatment, including the simulation procedure for assessment of intrahepatic and extrahepatic distribution of the microspheres, with holmium-166 (166Ho)-radioembolization. This was a secondary analysis of patients included in the 4 prospective studies (HEPAR I, HEPAR II, HEPAR PLuS, and SIM) on 166Ho-radioembolization. The technical success rate of the same-day treatment protocol, defined as the number of patients who completed the same-day treatment, was measured. Total in-room time, duration of the scout procedure, time to imaging, and duration of the treatment procedure were recorded. Reasons for discontinuation or adjustment of treatment were identified. Adverse events that occurred during the treatment day were recorded. One hundred five of 120 scheduled patients completed the same-day treatment with 166Ho-radioembolization (success rate, 88%). After the simulation procedure, treatment was cancelled in 15 patients because of extrahepatic deposition (n = 8), suboptimal tumor targeting (n = 1), unanticipated vascular anatomy (n = 5), and dissection (n = 1). In another 14 patients, the treatment plan was adjusted. The median total procedure time (ie, simulation, imaging, and treatment) was 6:39 hours:minutes (range, 3:58-9:17 hours:minutes). Back pain was a major same-day treatment-related complaint (n = 28). 166Ho-radioembolization as a same-day treatment procedure is feasible in most selected patients, although treatment was adjusted in 12% of patients and cancelled in 12% of patients. This approach might be beneficial for a select patient population, such as patients needing a radiation segmentectomy.


Ultrastructural Analysis of Chlamydia Pneumoniae in the Alzheimer's Brain.
We recently reported identification of the bacterium Chlamydia pneumoniae in affected brain regions of patients with Alzheimer's disease (AD) (Balin et al., 1998). In this report, we extend those initial observations to demonstrate that, in addition to the frequently described, standard morphological forms of the organism, pleiomorphic forms are also present in the AD brain. All AD and control brain tissues examined were verified to be PCR-positive and negative, respectively, for the organism. DNA sequence determination of PCR products so derived from total DNA of infected AD brains, as well as from total DNA of cell lines infected with the organism following isolation from these same patient samples, confirmed the presence of organism in relevant samples. Various morphologic forms of C. pneumoniae were identified in PCR-positive tissues and these were characterized based on membrane structure, core density, size, and immunolabeling profiles. Structures identified include the typical pear-shaped elementary body, as well as larger, spherical and oblong reticulate bodies. Intact C. pneumoniae were found both intracellularly and extracellularly in the sampled autopsy brains. Intracellular organisms were located principally within microglia, astroglia, and presumptive pericytes. These results suggest that C. pneumoniae found in cells indigenous to the AD brain do not conform universally to the classical morphology observed in other infected cell types. This pleiomorphism may reflect an adaptive response and/or persistent state of infection for these organisms in Alzheimer's Disease.


Comparison of the performance of paired urine and cervical samples for cervical cancer screening in screening population.
The main objective of this work is to determine the performance of urine for human papillomavirus (HPV) detection in cervical cancer screening in screening population. Paired urine and cervical samples were collected from 2038 women (careHPV group: 1002, cobas4800 group: 1036) in 2015. Urine was tested by a new urine-based HPV test and cervical samples by careHPV or cobas4800 HPV test. Women were triaged based on cervical results and then referred to colposcopy with biopsy as clinically indicated. In 2017, women were followed up and screened with cotesting strategy, women with any positive would be referred and biopsied if necessary. In careHPV group, the HPV prevalence of urine was 14.1%, and 16.4% for cervical samples. In cobas4800 group, it was 19.1% and 20.4%, correspondingly. The concordance of urine samples compared with cervical samples was moderate (careHPV group: 86.6%; κ = 0.48; cobas4800 group: 83%; κ = 0.46). The baseline sensitivity and specificity for urine against CIN2+ detection were 85.7%, 86.8% in careHPV group, and 69.2%, 82.3% in cobas4800 group, respectively. Cervical samples were 100% sensitive for both tests (careHPV and cobas4800) and 85.2% specific in careHPV group and 81.9% specific in cobas4800 group, respectively. The corresponding cumulative sensitivity and specificity were 68.8% and 87.1%, 58.8% and 81.9%, 87.5% and 85.5%, and 94.1% and 81.4%. Urine demonstrated certain potential in cervical cancer screening and could be an alternative if no better screening strategies available.


Why it is important to demonstrate linkages between outcomes of care and processes and structures of care.
This first article of the supplement describes the rationale for the Department of Veterans Affairs Cooperative Study, Processes, Structures, and Outcomes in Cardiac Surgery, which was designed to demonstrate statistically and clinically meaningful linkages between processes and structures of care and the outcomes of that care. United States health care is in an era of great enthusiasm for the use of health care outcomes to assess and improve quality of care. An important reason for this enthusiasm is the concern that processes and structures of care, which traditionally have been selected arbitrarily without valid linkages to favorable outcomes, may not result in the desired outcomes of care. Furthermore, health care outcomes are intrinsic to the definition of quality of care and should be relatively free of preconceived biases about how care should be provided. However, the limitations to outcomes-directed quality improvement have been inadequately recognized. These limitations include the following: (1) mortality, the most commonly used outcome, is usually sufficiently rare, resulting in inadequate statistical power; (2) nonfatal outcomes are much more difficult to measure reliably; (3) outcomes may not be measurable for an extended period of time after the care episode, making linkage to quality improvement inefficient; and (4) patients often desire good processes of care as well as favorable outcomes. A review of the literature found relatively few reports linking processes and structures of care to favorable outcomes. Significant relationships between processes of care and outcomes have been reported for several medical conditions (congestive heart failure, acute myocardial infarction, pneumonia, and stroke) when the patient has been considered the unit of analysis. However, there is a paucity of published meaningful process-outcome or structure-outcome linkages for surgical conditions or for any conditions when the hospital has been the focus of analysis. The authors concluded that quality improvement will proceed most efficiently and effectively if all three elements of Donabedian's quality triad (processes, structures, and outcomes) are used and if the processes and structures chosen have been demonstrated to be associated with desired outcomes of care.


Non-steroidal anti-inflammatory drugs may modulate the protease activity of Candida albicans.
The phenotypic pressure exerted by non-steroidal anti-inflammatory drugs (NSAIDs) on autochthonous and pathogenic microbiota remains sparsely known. In this study, we investigated if some NSAIDs increment or diminish the secretion of aspartyl-proteases (Sap) by Candida albicans grown under different phenotypes and oxygen availability using a set of SAP knock-out mutants and other set for genes (EFG1 and CPH1) that codify transcription factors involved in filamentation and protease secretion. Pre-conditioned cells were grown under planktonic and biofilm phenotypes, in normoxia and anoxia, in the presence of plasma concentrations of acetylsalicylic acid, diclofenac, indomethacin, nimesulide, piroxicam, ibuprofen, and acetaminophen. For diclofenac, indomethacin, nimesulide, and piroxicam the secretion rates of Sap by SAP1-6, EFG1, and CPH1 mutants were similar or, even, inferior to parental wild-type strain. This suggests that neither Sap 1-6 isoenzymes nor Efg1/Cph1 pathways may be entirely responsible for protease release when exposed to these NSAIDs. Ibuprofen and acetaminophen enhanced Sap secretion rates in three environmental conditions (normoxic biofilm, normoxic planktonic and anoxic planktonic). In other hand, aspirin seems to reduce the Sap-related pathogenic behavior of candidal biofilms. Modulation of Sap activity may occur according to candidal phenotypic state, oxygen availability, and type of NSAID to which the cells are exposed.


Tumor Marker Kinetics as Prognosticators in Patients with Unresectable Gallbladder Adenocarcinoma Undergoing Palliative Chemotherapy.
To determine the prognostic value of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during palliative chemotherapy. One hundred and twenty-three patients with pathologically confirmed unresectable GBC were included. Differences in serum CEA and CA 19-9 levels before and after chemotherapy were measured. Receiver operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9, and combined changes were performed to assess the optimal cutoff values and survival rates. Patients with decreased tumor markers had significantly better progression-free survival (PFS) and overall survival (OS) than patients with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In the multivariate analysis, increases in serum CA 19-9 during palliative chemotherapy in patients with unresectable GBC was an independent prognosticator of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020), respectively. Patients with increases >10-fold were considered to have progressive disease, whereas individuals with increases >3-fold were likely to benefit from early imaging follow-up. CA 19-9 kinetics was a reliable prognosticator of PFS and OS in patients with unresectable GBC who underwent palliative chemotherapy.


Intraabdominal desmoplastic small round cell tumour: report of two cases in paediatric patients.
Intraabdominal Desmoplastic Small Round Cell Tumour (IDSRCT) is a very rare neoplasia with a unique immunoprofile. Children and young adults are most commonly affected. We report two cases with IDSRCT in children who initially presented with ascites, pain and abdominal mass. Complete surgical excision was possible only in one patient. Although both patients underwent multiagent chemotherapy, they had a relapse of the disease. One patient died two years after diagnosis. The tumour has a very poor prognosis. Survival is correlated to the radical resection of the tumour combined with intense chemotherapy and radiotherapy.


Percutaneous fixation of neonatal humeral physeal fracture: A case report and review of the literature.
Neonatal distal humeral physeal fractures are rare and difficult to diagnose. Thus, missed diagnoses and delayed healing are possible. Few studies have reported surgical treatment, because a callus may develop at the fracture site 5 d after the fracture, resulting in difficult reduction, and reduction of the limb may cause further physeal injury. Other surgical challenges include the provision of adequate anesthesia and complexity of the operation. However, without appropriate reduction and fixation, a varus elbow deformity may develop. Manual reduction and percutaneous pin fixation are ideal treatment options. A 4-day-old neonate with left elbow pain accompanied by limited movement for 4 d was admitted, and diagnosed with delayed physeal fracture of the distal humerus based on physical examination, ultrasonography, and magnetic resonance imaging. The patient was treated by manual reduction combined with percutaneous pin fixation under arthrography. Postoperatively, the reduction was successful. The upper limbs could have been lifted and the fingers could have been moved freely on the second day after the operation. The techniques of manual reduction and percutaneous pin fixation, to treat neonatal distal humeral physeal fractures, are safe and reliable.


Altered distribution of digoxin in renal failure--a cause of digoxin toxicity?
Three cases are described in which renal failure was accompanied by a lowered apparent volume of distribution of digoxin. In two cases this resulted in frank digoxin toxicity and in one equivocal toxicity. In all three cases digoxin plasma levels were greater than 2 ng/ml. The possible causes of the abnormal distribution of digoxin in renal failure are discussed. Recommendations are outlined for the use of digoxin in patients with renal failure aimed at circumventing the problem raised by a lowered apparent volume of distribution of the drug.


Myocardial inflammation in autoimmune diseases: investigation by cardiovascular magnetic resonance and endomyocardial biopsy.
Myocardial inflammation often coexists with different types of autoimmune diseases. Our aim was to investigate the presence of myocarditis in these patients by Cardiovascular Magnetic Resonance (CMR) and endomyocardial biopsy. Twenty patients, aged 20-55 yrs with autoimmune diseases and cardiac symptoms (3 with Takayasu's arteritis, 3 with systemic lupus erythematosus, 5 with rheumatoid arthritis, 7 with autoimmune thyroid disease and 2 with systemic sclerosis) and 20 patients with the same autoimmune diseases but without cardiac symptoms (controls) were studied. The presence of myocarditis and LV function were evaluated by CMR. Myocarditis was documented using T2-weighted (T2-W), T1-weighted (T1-W) before and after contrast media injection and late enhanced images. In 10 patients (positive for myocarditis by CMR with either low LVEF or recent increase in troponin), endomyocardial biopsy was also performed. Myocardial specimens were evaluated by histology and polymerase chain reaction techniques (PCR). Myocarditis was identified in 18/20 patients by CMR. In the T2-W images the signal ratio of myocardium to skeletal muscle was 1.89+/-0.25 (control values 1.57+/-0.13, p<0.05). From the T1-W images the relative myocardial enhancement was 11.31+/-11.18 (control values 3.09+/-0.05, p<0.05). Epicardial late gadolinium enhanced areas were identified in 18/20. In myocardial specimens, histology revealed inflammation in 5/10 (50%) and PCR documented viral or microbial genomes in 8/10 (80%). Positive histology and PCR were in agreement with 50% and 80% of positive CMR examinations, respectively. Herpes virus was identified in 3/10, Adeno in 1/10, Coxsackie B6 in 1/10, echo in 1/10, Parvo-B19 in 3/10, CMV in 1/10 and Chlamydia trachomatis in 8/10. Myocardial inflammation is a common finding in patients with autoimmune diseases and cardiac symptoms. The diagnosis can be confirmed by CMR, which is a noninvasive and reliable tool for the investigation of these patients.


The impact of virtual learning on Multimedia University student performance: a cross-sectional study.
Background: The Covid-19 pandemic has imposed adaption to virtual learning for students and educators across all levels of education in the world. The effectiveness of virtual learning varies amongst age groups. It has been suggested that the adoption of virtual learning will continue to be implemented even after pandemic, particularly in higher education. Therefore, it is crucial to validate the effectiveness of a virtual learning approach among university students to ensure a smooth transition from a conventional education model to a hybrid education model. Thus, this study aims to evaluate the impact of virtual learning on students' performance in a virtual classroom. Methods: We analysed survey data collected from undergraduate students at Multimedia University, Malaysia. Convenience sampling and self-administered online surveys were used to understand the impact of virtual learning. Multiple regression analysis was performed using SPSS software Results: A total of 210 first and second year degree and diploma students responded to the online surveys. Factors affecting virtual learning were segregated into three categories: virtual teaching techniques, technology issues, and environment distraction. Respondents stated that the critical factor that affect the effectiveness of virtual learning and impacts on students' performance was the virtual teaching techniques employed by educators. Conclusions: This study concluded that virtual teaching techniques have significant impact on students' performance whereas technology issues and environment distraction do not significantly influence students' performance during virtual learning. Although this study is limited to students from Multimedia University, it lays the groundwork for future research to involve students from other universities or other countries. A future study can address more factors that affect virtual learning and students' performance, such as students' attitude and motivation.


Nutrient additions in pristine Patagonian Sphagnum bog vegetation: can phosphorus addition alleviate (the effects of) increased nitrogen loads.
Sphagnum-bog ecosystems have a limited capability to retain carbon and nutrients when subjected to increased nitrogen (N) deposition. Although it has been proposed that phosphorus (P) can dilute negative effects of nitrogen by increasing biomass production of Sphagnum mosses, it is still unclear whether P-addition can alleviate physiological N-stress in Sphagnum plants. A 3-year fertilisation experiment was conducted in lawns of a pristine Sphagnum magellanicum bog in Patagonia, where competing vascular plants were practically absent. Background wet deposition of nitrogen was low (≈ 0.1-0.2 g · N · m(-2) · year(-1)). Nitrogen (4 g · N · m(-2) · year(-1)) and phosphorus (1 g · P · m(-2) · year(-1)) were applied, separately and in combination, six times during the growing season. P-addition substantially increased biomass production of Sphagnum. Nitrogen and phosphorus changed the morphology of Sphagnum mosses by enhancing height increment, but lowering moss stem density. In contrast to expectations, phosphorus failed to alleviate physiological stress imposed by excess nitrogen (e.g. amino acid accumulation, N-saturation and decline in photosynthetic rates). We conclude that despite improving growth conditions by P-addition, Sphagnum-bog ecosystems remain highly susceptible to nitrogen additions. Increased susceptibility to desiccation by nutrients may even worsen the negative effects of excess nitrogen especially in windy climates like in Patagonia.


A scoping review of the integration of ethics education in undergraduate nursing high-fidelity human simulation-based learning.
To systematically assemble, examine and map the extant literature pertaining to the integration of ethics education in high-fidelity simulation-based learning experiences in nursing undergraduate programmes. The value of ethics education for undergraduate nursing students is well established in the literature. Whether high-fidelity human simulation (HFHS) supports the development of ethical reasoning or positively impacts the acquisition of ethical knowledge and reasoning skills in undergraduate nursing students is inconsistently addressed. A scoping review was conducted using the Arksey and O'Malley framework. CINAHL, ProQuest Nursing & Allied Health Source, ProQuest Dissertations & Theses A&I, MEDLINE, Web of Science, ERIC, Scopus, PsycINFO, and the Joanna Briggs Institute EBP databases were searched for English-language manuscripts published between 2012 and 2020. The PRISMA-ScR was used. Eight papers that met the inclusion criteria were extracted for this review. Three broad categories were identified: the 'what' in ethics education, the 'how' of ethics education and the 'when' of ethics education in high-fidelity human simulation. The integration of ethics education into simulation-based learning has the potential to positively promote nursing students' ability to develop knowledge of and skills in ethical practice. However, the inclusion of ethics education scenarios in HFHS is a relative new teaching innovation in undergraduate nursing education. As such, there continues to be no consensus on the 'what', 'how' or 'when' of ethics education for best practice in ethics education for undergraduate nursing programmes. Quality improvement processes and research studies are needed to determine: the types of ethical dilemmas and debriefing sessions and optimal timing of HFHS ethics simulation in undergraduate nursing education, student support needed for running HFHS, and the learning needs of nurse educators seeking to incorporate ethics within HFHS.


Three-body nonadditive potential for argon with estimated uncertainties and third virial coefficient.
The three-body nonadditive interaction energy between argon atoms was calculated at 300 geometries using coupled cluster methods up to single, double, triple, and noniterative quadruple excitations [CCSDT(Q)], and including the core correlation and relativistic effects. The uncertainty of the calculated energy was estimated at each geometry. The analytic function fitted to the energies is currently the most accurate three-body argon potential. Values of the third virial coefficient C(T) with full account of quantum effects were computed from 80 to 10000 K by a path-integral Monte Carlo method. The calculation made use of an existing high-quality pair potential [Patkowski, K.; Szalewicz, K. J. Chem. Phys. 2010, 133, 094304] and of the three-body potential derived in the present work. Uncertainties in the potential were propagated to estimate uncertainties in C(T). The results were compared with available experimental data, including some values of C(T) newly derived in this work from previously published high-accuracy density measurements. Our results are generally consistent with the available experimental data in the limited range of temperatures where data exist, but at many conditions, especially at higher temperatures, the uncertainties of our calculated values are smaller than the uncertainties of the experimental values.


Hepatic morphology in cardiac dysfunction: a clinicopathologic study of 1000 subjects at autopsy.
Chronic passive congestion (CPC) and centrilobular necrosis (CLN) are well recognized pathologic changes, but their exact relationship to different forms of cardiac dysfunction is uncertain. We reviewed clinical data and hepatic, renal, and adrenal morphology related to cardiac dysfunction in 1000 autopsy subjects at The Johns Hopkins Hospital whose hearts had been studied after postmortem arteriography and fixation in distention. Fourteen pathologic variables, including body and organ size, and microscopic changes graded on a semiquantitative scale, and 18 clinical variables including congestive heart failure, shock, and cardiovascular disease, were analyzed statistically. Distinct patterns of cardiac dysfunction emerged for the two spectra of hepatic morphologic change. Among patients with variable CPC, but slight or absent CLN, the amount of CPC was predicted in a multivariate analysis by severity of right-sided congestive heart failure. CPC severity correlated with cardiac weight and chamber enlargement (P less than 0.001). Among patients with variable CLN, but slight or absent CPC, CLN was predicted by profound hypotension and by renal failure. In addition, CLN, but not CPC, was significantly correlated with renal acute tubular necrosis (P less than 0.001) and adrenal cortical medullary junction necrosis (P less than 0.05), two lesions associated with shock. Among all 1000 patients CPC and CLN were highly significantly correlated (P less than 0.001). The results show that hepatic CPC arises from conditions producing elevated systemic venous pressure but that CLN arises from reduced systemic arterial pressure; and the presence of one potentiates the development of the other.


Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a Wistar rat model.
Oxaliplatin (4 mg/kg), cisplatin (2 mg/kg with 20 mg/kg mannitol) and ormaplatin (2 mg/kg) were administered i.p. twice weekly for 4.5 weeks. Lactose injections (0.9%) were used as a control for oxaliplatin and 0.9% saline injections were used as a control for cisplatin and ormaplatin. Morphometric changes to dorsal root ganglia L4-L6 were quantitated as a measure of neurotoxicity. Drug treatment resulted in a decrease in cell and nuclear area and an increase in the percentage of cells with eccentric nucleoli for neuronal cell bodies in the DRG. Immediately following treatment the order of morphometric changes was ormaplatin > cisplatin > or = oxaliplatin. The accumulation of platinum in the DRG was measured by inductively coupled plasma mass spectrometry. The order of accumulation was cisplatin > oxaliplatin > ormaplatin. Following an 8-week recovery period the order of morphometric changes to the DRG was ormaplatin approximately equal to oxaliplatin > cisplatin. This correlated with a greater retention of platinum by the DRG for ormaplatin and oxaliplatin than for cisplatin. The results suggest that ormaplatin is uniquely neurotoxic immediately following treatment in the Wistar rat model. However, following an 8-week recovery period both ormaplatin and oxaliplatin are more neurotoxic than cisplatin and this neurotoxicity correlates with a greater retention of platinum by the DRG.


The summit of a moral pilgrimage: Confucianism on healthy ageing and social eldercare.
To effectively address ageing and develop adequate eldercare needs, among others, new ethical visions are much needed. One of the ways to formulate sound ethical visions for contemporary issues is to reclaim, reinterpret and revive old moral ideas and ideals rooted in different indigenous cultural traditions. Drawing thought, wisdom and inspirations from classical Confucianism, the article offers a Confucian ethical outlook on healthy ageing and social eldercare. The popular perception of ageing in the West as well as China regards old age as a period of inevitable decline. However, Kong Zi (Confucius) treats human life as an ongoing moral pilgrimage, with old age the summit of the lifelong journey. This Confucian ethical view on ageing as the culmination of a lifelong moral cultivation has various important themes. They include the primary feature of learning in healthy ageing, the essential role of social eldercare embedded in the popular Confucian norm 'filial piety' (xiao), intergenerational flourishing and the necessity to respect the rights and dignity of each old person. Such a Confucian socio-ethical vision can not only help identify contemporary failings in the area of eldercare but also generate novel ideas and frameworks to help China and the world to face population ageing and elderly care in a more positive way.


A designed peptide targeting CXCR4 displays anti-acute myelocytic leukemia activity in vitro and in vivo.
Leukemia cells highly expressing chemokine receptor CXCR4 can actively response to stroma derived factor 1α (CXCL12), trafficking and homing to the marrow microenvironment, which causes poor prognosis and relapse. Here we demonstrate that a novel designed peptide (E5) targeting CXCR4 inhibits CXCL12- and stroma-induced activation in multiple acute myelocytic leukemia (AML) cell lines and displays anti-AML activity. We show that E5 has high affinity to multiple AML cells with high CXCR4 level in a concentration dependent manner. E5 significantly inhibits CXCL12- or murine stromal cell (MS-5)-induced migration of leukemia cells and prevents the cells from adhering to stromal cells. Mechanistic studies demonstrate that E5 down-regulates CXCL12-induced phosphorylation of Akt, Erk, and p38, which affects the cytoskeleton F-actin organization and ultimately results in the inhibition of CXCL12- and stroma-mediated leukemia cell responses. E5 can induce concentration-dependent apoptosis in the four AML cell lines tested while did not affect the viability of MS-5 or human umbilical vein cell (ea.hy926) even at 80 µM, both of which have a low level of CXCR4. In vivo experimental results show that immunocompromised mice transplanted with HL-60 cells survived longer when treated with E5 twice a week in comparison to those treated with cyclophosphamide.


An examination of the acquired preparedness model among college student marijuana users.
ObjectiveTo examine the Acquired Preparedness Model using a behavioral impulsivity facet and positive marijuana expectancies to examine direct and indirect effects on marijuana use and related problems. Participants: 250 college students (61.7% female, 54% white) recruited from a southeastern university. Methods: Participants completed an online survey of delay reward discounting, marijuana expectancies, consideration of future consequences, and marijuana-related outcomes. Results: Delay reward discounting and consideration of future consequences related to marijuana-related problems, but not marijuana use. However, positive marijuana expectancies did not mediate the relation between impulsivity and marijuana outcomes. Conclusions: These results emphasize delay reward discounting and consideration of future consequences as important factors associated with marijuana-related problems. Interventions aimed at decreasing delay reward discounting and augmenting future orientation may be effective in college students who report light to moderate marijuana use. Future studies would benefit from longitudinal study designs using multiple impulsivity measures among light and heavy users.


Liquid chromatographic enantioseparation of aryl alpha-amino ketones on a crown ether-based chiral stationary phase.
A liquid chromatographic chiral stationary phase based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 covalently bonded to silica gel was applied in the resolution of aryl alpha-amino ketones including cathinone, the main psychoactive alkaloid found in the leaves of the khat plant. The resolution was excellent, the separation factors ranging between 1.72 and 8.58 and the resolution factors (R(S)) ranging between 2.60 and 11.10. The chromatographic resolution behaviour was dependent on the type and the content of organic and acidic modifiers and the ammonium acetate concentration in aqueous mobile phase and the column temperature.


Adaptation to community relocation: the interactive influence of psychological resources and contextual factors.
This longitudinal study examined the interactive influences of psychological resources and contextual factors on short-term adaptation to community relocation in a sample of older women (N = 102, mean age = 71.6). The effects of three psychological resources (environmental mastery, autonomy, and personal growth) and three contextual factors (pressure to move, difficulty of the move, and unexpected gains experienced) on emotional reactions to relocation were examined. The pattern of findings suggests that women with greater psychological resources were more resilient in the face of negative circumstances but that the emotional "boost" of unexpected gains was greatest for women with lower premove resources. These results underscore the importance of considering event-relevant psychological resources and contextual factors and including both negative and positive aspects of the adaptational process.


[The evolution of knowledge about the inflammatory bowel diseases].
Crohns disease and ulcerative colitis has affected people for many centuries however its incidence most likely used to be very low. The knowledge of the idiopathic intestinal inflammation at that time was also very limited - an interest about the disease has emerged since the second half of 19th century. Despite all the progress in medicine its etiology still remains unclear.Diagnosis had for a long been based only on clinical investigation and later radiography, endoscopy came in to use in the 1970s. First significant advances in therapy came during the 1940s and 1950s with the invention of aminosalicylates, antibiotics and corticoids. The most advanced conservative therapy today is biological treatment although the importance of gastrointestinal surgery should not be overlooked.The aim of this article is to briefly review the development of knowledge of the idiopathic intestinal inflammation with an emphasis on the 20th century.


Hard metal interstitial lung disease: high-resolution computed tomography appearance.
Hard metal interstitial lung disease (HM-ILD) is a rare form of interstitial lung disease caused by aerosolized particulates containing cobalt inhaled during the manufacture or grinding of hard metal. The high-resolution computed tomography (HRCT) appearance of HM-ILD includes reticulation, traction bronchiectasis, and large peripheral cystic spaces in a mid and upper lung distribution. This appearance, along with a consistent occupational exposure, should specifically suggest the diagnosis of HM-ILD.


siRNA binding proteins of microglial cells: PKR is an unanticipated ligand.
Small interfering RNA (siRNA), double-stranded RNA (dsRNA) 21-23 nucleotides (nt) long with two nt 3' overhangs, has been shown to mediate powerful sequence-specific gene silence in mammalian cells through RNA interference (RNAi). Due to its high efficiency and high specificity siRNA has been used as a powerful post genomic tool and a potent therapeutic candidate. However, there is still a lot to learn about the mobility of siRNA inside cells and the cellular factors that might interfere with the specificity and activity of siRNA. Microglia are the brain's effector cells of the innate immune system and suitable targets in the development of novel therapeutic strategies. Here, we show the cellular uptake and intracellular distribution of siRNA in murine microglial N9 cells. siRNA was internalized by microglial N9 cells without transfection reagent and mainly localized to the endosomes However, no significant gene silencing effects were observed. Its cellular uptake and cellular distribution pattern were similar with that of a same length single stranded DNA (ssDNA). Further, cellular binding proteins of siRNA were purified and identified by mass spectrometry. Negative control siRNA and siRNA targeted to beta-actin were used in this part of experiment. Most of the siRNA binding proteins for negative control siRNA and siRNA targeted to beta-actin were dsRNA-binding proteins, such as dsRNA-dependent protein kinase R (PKR). Furthermore, both control siRNA and siRNA targeted to beta-actin activated PKR in N9 cells, which suggest that siRNA might cause off-target effects through activation of PKR.


[Virtual reality in video-assisted thoracoscopic lung segmentectomy].
The branching patterns of pulmonary arteries and veins vary greatly in the pulmonary hilar region and are very complicated. We attempted to reconstruct anatomically correct images using a freeware program. After uploading the images to a personal computer, bronchi, pulmonary arteries and veins were traced by moving up and down in the images and the location and thickness of the bronchi and pulmonary vasculture were indicated as different-sized cylinders. Next, based on the resulting numerical data, a 3D image was reconstructed using Metasequoia shareware. The reconstructed images can be manipulated by virtual surgical procedures such as reshaping, cutting and moving. These system would be very helpful in complicated video-assisted thoracic surgery such as lung segmentectomy.


Retrieval of Displaced Implant Attributable to an Ill-Fitting Denture From the Maxillary Sinus Six Months After Transcrestal Sinus Floor Augmentation and Implant Placement.
Asymptomatic displacement of dental implants into the maxillary sinus after a transcrestal sinus augmentation is a rare complication that can occur when there is poor bone quality and minimal residual bone height. Patient compliance with postoperative appointments and failure to comply with denture-wearing instructions are critical contributing factors. To the best of the authors' knowledge, no cases of implant dislodgement attributable to a removable prosthesis have been reported in the literature, although some studies have suggested that improper occlusal forces can cause a long-standing implant to develop peri-implantitis and subsequent displacement of an implant into the sinus cavity. A 71-year-old female presented 6 months after undergoing transcrestal sinus lift and implant surgery that involved a modified Summers technique using mineralized solvent-dehydrated cancellous bone allograft and placement of six maxillary implants. A displaced dental implant was retrieved from the right maxillary sinus, which had an intact Schneiderian membrane. The patient was asymptomatic and infection free. The displaced implant was accessed and retrieved via a lateral window sinus technique. No clinical signs of sinus infection were evident, and there were no additional complications during the 2-year follow-up period. This case report demonstrates a technique for the retrieval of implants that have been dislodged and migrated into the maxillary sinus cavity caused by an ill-fitting denture and improper masticatory forces.


Levodopa delivery systems: advancements in delivery of the gold standard.
Despite the fact that Parkinson's disease (PD) was discovered almost 200 years ago, its treatment and management remain immense challenges because progressive loss of dopaminergic nigral neurons, motor complications experienced by the patients as the disease progresses and drawbacks of pharmacotherapeutic management still persist. Various therapeutic agents have been used in the management of PD, including levodopa (l-DOPA), selegiline, amantadine, bromocriptine, entacapone, pramipexole dihydrochloride and more recently istradefylline and rasagiline. Of all agents, l-DOPA although the oldest, remains the most effective. l-DOPA is easier to administer, better tolerated, less expensive and is required by almost all PD patients. However, l-DOPA's efficacy in advanced PD is significantly reduced due to metabolism, subsequent low bioavailability and irregular fluctuations in its plasma levels. Significant strides have been made to improve the delivery of l-DOPA in order to enhance its bioavailability and reduce plasma fluctuations as well as motor complications experienced by patients purportedly resulting from pulsatile stimulation of the striatal dopamine receptors. Drug delivery systems that have been instituted for the delivery of l-DOPA include immediate release formulations, liquid formulations, dispersible tablets, controlled release formulations, dual-release formulations, microspheres, infusion and transdermal delivery, among others. In this review, the l-DOPA-loaded drug delivery systems developed over the past three decades are elaborated. The ultimate aim was to assess critically the attempts made thus far directed at improving l-DOPA absorption, bioavailability and maintenance of constant plasma concentrations, including the drug delivery technologies implicated. This review highlights the fact that neuropharmaceutics is at a precipice, which is expected to spur investigators to take that leap to enable the generation of innovative delivery systems for the effective management of PD.


Small-angle light scattering from an anisotropic sphere in the Rayleigh-Gans-Debye approximation: the Mueller matrix formalism.
An explicit form of the Mueller matrix is given for an anisotropic sphere fulfilling the requirements of the Rayleigh-Gans-Debye (RGD) approximation. The angular dependences of single matrix elements are compared with Lorenz-Mie predictions for an isotropic sphere. Good agreement between the Lorenz-Mie model and that of RGD is observed where the latter is applicable. The magnitude and sign of the matrix elements depend on the size parameter kR (k = 2pi/lambda;R is the radius of the sphere) as well as on the magnitude and sign of the (ñ - 1)/Deltan parameter, where ñ is the relative refractive index and Deltan is the relative anisotropy of the sphere.


Participatory scenario planning to facilitate human-wildlife coexistence.
Fostering human-wildlife coexistence requires transdisciplinary approaches that integrate multiple sectors, account for complexity and uncertainty, and ensure stakeholder participation. One such approach is participatory scenario planning, but to date, this approach has not been used in human-wildlife contexts. We devised a template for how participatory scenario planning can be applied to identify potential avenues for improving human-wildlife coexistence. We drew on 3 conceptual building blocks, namely the SEEDS framework, the notion of critical uncertainties, and the three-horizons technique. To illustrate the application of the proposed template, we conducted a case study in the Zambezi region of Namibia. We held 5 multistakeholder workshops that involved local people as well as numerous nongovernment and government stakeholders. We identified 14 important wildlife species that generated multiple services and disservices. The subsequent benefits and burdens, in turn, were inequitably distributed among stakeholders. Government actors played particularly influential roles in shaping social-ecological outcomes. We identified 2 critical uncertainties for the future: the nature of governance (fragmented vs. collaborative) and the type of wildlife economy (hunting vs. photography based). Considering these uncertainties resulted in 4 plausible scenarios describing future human-wildlife coexistence. Stakeholders did not agree on a single preferred scenario, but nevertheless agreed on several high-priority strategies. Bridging the remaining gaps among actors will require ongoing deliberation among stakeholders. Navigating the complex challenges posed by living with wildlife requires moving beyond disciplinary approaches. To that end, our template could prove useful in many landscapes around the world.


[Maternal representations during pregnancy and early mother-infant interactions].
In this paper we aim to explore how maternal representations during pregnancy influence the early mother-infant interactions and the style of attachment of the baby. Two different cases are presented in order to focus on how maternal representations of herself as a mother and of the future baby influence the early interactions and the style of attachment of the children. It is stressed in one case the particular fixity of the maternal phantasmatic world and in the other the modifiability which can be influenced, in the latter case, by the conscious fantasies and the relationship with her own family and her own child.


Adherence to Antidiabetic Medications Among Sudanese Individuals With Type 2 Diabetes Mellitus: A Cross-Sectional Survey.
Adherence to antidiabetic medications is crucial for optimum glycemic control and decreasing complications. This study aimed to assess adherence to antidiabetic medications and the associated factors among individuals with type 2 diabetes attending Jabir Abu Eliz Diabetes Centre in Khartoum state, Sudan. This was a descriptive cross-sectional study, recruited 213 individuals with type 2 diabetes, and used a pretested questionnaire. Data were analyzed using the Statistical Package of Social Sciences version 21. Logistic regression analysis was used to check for factors that linked to poor adherence to diabetes medication. The median duration of antidiabetic medications use was 8 years; 15.0% were highly adherent to diabetes medications, 44.6% were medium adherent, and 40.4% showed low adherence. Main factors and barriers were medication side effects (18.3%), use of herbal medicine (12.3%), and unavailability of medication (7%). Predictors to nonadherence were gender, and housing status (0.043 and 0.042, respectively). Level of adherence to diabetes medication was unsatisfactory as only 15% showed high adherence. Predictors of nonadherence were gender, and housing status. Effective interventions should be implemented to improve medication adherence, like appropriate patient education and involvement in the treatment plan.


Gramicidins A, B, and C form structurally equivalent ion channels.
The membrane structure of the naturally occurring gramicidins A, B, and C was investigated using circular dichroism (CD) spectroscopy and single-channel recording techniques. All three gramicidins form channels with fairly similar properties (Bamberg, E., K. Noda, E. Gross, and P. Läuger. 1976. Biochim. Biophys. Acta. 419:223-228.). When incorporated into lysophosphatidylcholine micelles, however, the CD spectrum of gramicidin B is different from that of gramicidin A or C (cf. Prasad, K. U., T. L. Trapane, D. Busath, G. Szabo, and D. W. Urry. 1983. Int. J. Pept. Protein Res. 22:341-347.). The structural identity of the channels formed by gramicidin B has, therefore, been uncertain. We find that when gramicidins A and B are incorporated into dipalmitoylphosphatidylcholine vesicles, their CD spectra are fairly similar, suggesting that the two channel structures could be similar. In planar bilayers, gramicidins A, B, and C all form hybrid channels with each other. The properties of the hybrid channels are intermediate to those of the symmetric channels, and the appearance rates of the hybrid channels (relative to the symmetric channels) corresponds to what would be predicted if all three gramicidin molecules were to form structurally equivalent channels. These results allow us to interpret the different behavior of channels formed by the three gramicidins solely on the basis of the amino acid substitution at position 11.


A new species of Halipegus Looss, 1899 (Trematoda: Derogenidae) parasitic in Rana psilonota Webb, 2001 of Atenquique, Jalisco, Mexico.
During an inventory of parasites of anurans in Occidental Mexico, an apparently undescribed species of Halipegus was found under the tongue of Rana psilonota Webb, 2001. The objective of this study is to describe this new species. Halipegus psilonotae differs from all other congeners by the combination of the following characters: parasite under the tongue of frogs, body size small, ventral sucker representing 0.19-0.2 of body length, ovary smaller than testes, egg filament short (27.5-40).


Fluorescent Probes for Super-Resolution Microscopy of Lysosomes.
Lysosomes are membrane-enclosed small spherical cytoplasmic organelles. Malfunctioning and abnormalities in lysosomes can cause a plethora of neurodegenerative diseases. Consequently, understanding the structural information on lysosomes down to a subnanometer level is essential. Recently, super-resolution imaging techniques enable us to visualize dynamical processes occurring in suborganelle structures inside living cells down to subnanometer accuracy by breaking the diffraction limit. A brighter and highly photostable fluorescent probe is essential for super-resolution microscopy. In this regard, this mini-review deals with the various types of super-resolution techniques and the probes that are used to specifically stain and resolve the structure of the lysosomes.


The iron-catalyzed oxidation of dithiothreitol is a biphasic process: hydrogen peroxide is involved in the initiation of a free radical chain of reactions.
Dithiothreitol (DTT) is the most common agent used to reduce disulfide bonds in proteins. In the presence of transition metals and O2, however, DTT can induce oxidative damage in biomolecules. By means of polarographic measurements, it was established that the DTT oxidation catalyzed by Fe3+ is a biphasic process, characterized by a lag phase of several minutes during which O2 is consumed at a slow rate, by a mechanism involving the DTT-dependent reduction of Fe3+ to Fe2+ and the conversion of O2 to H2O2. Some lines of evidence indicate that the reduction of Fe3+ is the rate-limiting step: (i) The replacement of Fe3+ with Fe2+ leads to a decrease in the length of the lag phase. (ii) The rate of Fe2+ formation by DTT is the same as the initial rate of O2 uptake, (iii) The rate of sulfhydryl oxidation under anaerobic conditions is very slow. EDTA stimulates the iron-catalyzed oxidation of DTT probably by accelerating Fe3+ reduction. The lag phase is followed by a rapid uptake of O2 involving both O2.(-)-dependent and O2.(-)-independent free radical reactions, which can proceed, albeit more slowly, in the absence of H2O2 (i.e., in the presence of catalase). Glutamine synthetase is inactivated faster when added during the phase of rapid O2 uptake than when added before the beginning of the reaction. In both cases, catalase protects the enzyme, suggesting that only reactive species generated by H2O2 decomposition are able to induce the inactivation.


Enzyme regulation in c(4) photosynthesis : identification and localization of activities catalyzing the synthesis and hydrolysis of fructose-2,6-bisphosphate in corn leaves.
Activities catalyzing the synthesis of fructose-2,6-bisphosphate (fructose-6-phosphate,2-kinase or Fru-6-P,2K) and its breakdown (fructose-2,6-bisphosphatase or Fru-2,6-P(2)ase) were identified in leaves of corn (Zea mays), a C(4) plant. Fru-6-P,2K and Fru-2,6-P(2)ase were both localized mainly, if not entirely, in the leaf mesophyll cells. A partially purified preparation containing the two activities revealed that the kinase and phosphatase were regulated by metabolite effectors in a manner generally similar to their counterparts in C(3) species. Thus, corn Fru-6-P,2K was activated by inorganic phosphate (Pi) and fructose-6-phosphate, and was inhibited by 3-phosphoglycerate and dihydroxyacetone phosphate. Fru-2,6-P(2)ase was inhibited by its products, fructose-6-phosphate and Pi. However, unlike its spinach equivalent, corn Fru-2,6-P(2)ase was also inhibited by 3-phosphoglycerate and, less effectively, by dihydroxyacetone phosphate. The C(4) Fru-6-P,2K and Fru-2,6-P(2)ase were also quite sensitive to inhibition by phosphoenolpyruvate, and each enzyme was also selectively inhibited by certain other metabolites.


Fertility preferences and contraceptive use in Pakistan.
"The objective of this paper is...to analyse the levels and trends of fertility preferences in Pakistan during the 1975-1980 period and to see if any changes in the preferences have occurred over time even in the absence of the information, education and communication (IE&C) component of the family planning programme. Our hypothesis is that there exists a conscious choice of reproductive goals among married couples and there is no likelihood of any significant change in these expressed choices over time for the last twenty years." The data are from the 1979-1980 Population, Labour Force and Migration (PLM) Survey and the 1975 Pakistan Fertility Survey. "The analysis of data obtained for the two national surveys indicates that the surveys in question are highly consistent with regard to fertility preferences. They also indicate that the magnitude of family size preferences did not change appreciably between the two surveys. Moreover, the period and cumulative fertility behaviour in both the surveys did not record any significant variation.... When contraceptive behaviour was analysed with the reported fertility preferences, it appeared that the women were quite consistent in their stated fertility attitudes." Comments by Khalil A. Siddiqui are included (pp. 617-8).


Stable lines and clones of long-term proliferating normal, genetically unmodified murine common lymphoid progenitors.
Common lymphoid progenitors (CLPs) differentiate to T and B lymphocytes, dendritic cells, natural killer cells, and innate lymphoid cells. Here, we describe culture conditions that, for the first time, allow the establishment of lymphoid-restricted, but uncommitted, long-term proliferating CLP cell lines and clones from a small pool of these cells from normal mouse bone marrow, without any genetic manipulation. Cells from more than half of the cultured CLP clones could be induced to differentiate to T, B, natural killer, dendritic, and myeloid cells in vitro. Cultured, transplanted CLPs transiently populate the host and differentiate to all lymphoid subsets, and to myeloid cells in vivo. This simple method to obtain robust numbers of cultured noncommitted CLPs will allow studies of cell-intrinsic and environmentally controlled lymphoid differentiation programs. If this method can be applied to human CLPs, it will provide new opportunities for cell therapy of patients in need of myeloid-lymphoid reconstitution.


[Undergraduate education of medical technologists to promote scientific and technological literacy].
It is becoming increasingly important for today's medical technologists to receive proper training on the safety of medical treatment and healthcare in order to accommodate the rapid changes and advancement in medical technology. In particular, because of the increase of hospital-acquired infections, the role of medical technologists involved in infection control has become much more important. In addition, particularly in Japan, the career options available to students graduating with a degree in medical technology have become much more diverse, ranging from research laboratories to clinical services; however, undergraduate education for medical technologists is limited. It is therefore deemed necessary for undergraduate students to be provided with adequate training from their universities by offering a wider selection of classes in this subject area. In this paper, we summarize our preliminary findings on the trial lessons that are offered to medical technology students in their microbiology class. These lessons are designed to enhance students' academic potential and to engage their interest.


The separation of different cell classes from lymphoid organs. 3. Te purfication of erythroid cells by pH-induced density changes.
1. Mammalian erythrocytes swell as the pH of the isotonic suspending medium is lowered, as a direct consequence of the specialized permeability properties of the erythrocyte membrane. Lymphocytes and granulocytes from a variety of sources did not exhibit this property. 2. The behaviour of mouse bone marrow erythroid cells at various stages of differentiation was studied by using a change in buoyant density with pH as an index of swelling. The ability to swell with a pH drop was acquired while the cell was still nucleated. All non-nucleated cells showed swelling. Most small erythroblasts shared this property, whereas most large erythroblasts did not. 3. The density shift with pH was used to provide a purification scheme specific for erythroid cells. The bone marrow cells were first centrifuged to equilibrium in an isotonic albumin density gradient at neutral pH. Regions of the gradient containing the erythroid cells were collected, and the cells were recovered and redistributed in an albumin gradient at acid pH. The erythroid cells showed a specific density shift which removed them from contaminants. Preparations containing 90-97% erythroblasts were obtained by this technique. 4. Differentiation within the erythroid series was accompanied by a general increase in cell buoyant density at neutral pH. This density increase may have been a discontinuous process, since erythroid cells appeared to form a number of density peaks. 5. The pH shift technique, in association with established density distribution and sedimentation velocity procedures, provides a range of cell separation techniques for biological or biochemical studies of erythroid cell differentiation in the complex cell mixtures in bone marrow or spleen.


Down's syndrome. I. Cytogenetics.
A number of 107 children with clinical diagnosis of Down's syndrome have been studied. In 80% of the cases the parents have been cytogenetically investigated, too. Of these, 82.2% (88 cases) had free trisomy, 9.4% (10) had 46/47 + 21,4.7% (5 cases) had 14/21 translocation, 1 case (0.3%) had 21/21 translocation, one case translocation in inverse tandem, one case had iosochromosome 21, one case had 48.XXY + 21. These observations may be of help in establishing the prophylaxis of the syndrome, i.e.; 1. Cytogenetic investigation of all children suspect of having Down's syndrome, and in the case of translocation, of their parents as well. In the case of hereditary translocations it is recommended that the whole kinship be studied; 2. Monitoring of pregnancies of mothers over the age of 35 seems necessary.


The effect of a third BNT162b2 vaccine on breakthrough infections in health care workers: a cohort analysis.
In August 2021, 6 months after mass vaccination of the Israeli population with the two-dose BNT162b2 mRNA vaccine, a surge of coronavirus disease 2019 infections, mostly from the delta variant, appeared also among the vaccinated. In response, the Israeli Ministry of Health initiated a booster (third dose) vaccination program. We assessed the protective effect of the third dose among health care workers (HCWs). Infections with severe acute respiratory syndrome coronavirus 2 are monitored systematically among HCWs at the Hadassah tertiary care medical centre in Jerusalem, Israel. In this cohort, we included breakthrough infections, defined as those occurring >180 days since the second vaccine dose. The follow-up period lasted 120 days. We compared infection rates between HCWs who received the booster dose and those who received only the two-dose regimen. The rate of breakthrough infections among HCWs who received only the two-dose regimen was 21.4% (85 of 398). The rate in the boosted group was 0.7% (35/4973; relative risk 30, 95% CI 20-50). Those results were seen in all age groups. The significantly lower rate of breakthrough infections in boosted HCWs indicates substantial protection by a third vaccine dose.


Reduction in susceptibility to natural killer cell-mediated lysis of human FO-1 melanoma cells after induction of HLA class I antigen expression by transfection with B2m gene.
Induction of HLA class I antigens on cultured melanoma cells FO-1 after transfection with a human or a mouse B2m gene was associated with a statistically significant reduction in their susceptibility to natural killer (NK) cell-mediated lysis. These results indicate that the structural differences between human and mouse beta 2-mu do not abolish the ability of the HLA class I molecular complex to modulate NK cell-mediated lysis of melanoma cells FO-1. The role of HLA class I antigens in the phenomenon is corroborated by the ability of anti-HLA class I MAb to enhance, although to a different extent, the susceptibility of transfected FO-1 cells to NK cell-mediated lysis. Gamma interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) significantly reduced the susceptibility to NK cell-mediated lysis of transfected FO-1 cells. Surprisingly, TNF-alpha reduced the extent of lysis more than IFN-gamma, although the latter cytokine enhanced HLA class I antigen expression more than the former one. This finding, in conjunction with a reduction in the susceptibility to NK cell-mediated lysis of untransfected FO-1 cells incubated with IFN-gamma or TNF-alpha, suggests that the two cytokines reduce NK cell-mediated lysis of transfected cells by modulating not only the expression of HLA class I antigens, but also that of other structures. Induction of HLA class I antigens and their modulation with IFN-gamma did not affect the susceptibility to lymphokine-activated killer (LAK) cell-mediated lysis of transfected FO-1 cells. Characterization of the molecular mechanism(s) underlying abnormalities in HLA class I antigen expression by melanoma cells and of the role of these molecules in the interactions of melanoma cells with various types of effector cells may suggest novel immunotherapeutic approaches to melanoma.


Antimicrobial resistance of nasopharyngeal pneumococci from children from day-care centres and orphanages in Russia: results of a unique prospective multicentre study.
This study assessed the antimicrobial resistance of nasopharyngeal pneumococci isolated from children aged < 5 years in day-care centres and orphanages throughout Russia during 2001-2002. Swabs were collected from 2484 children in 43 day-care centres and eight orphanages in 11 cities of European Russia, and from 1669 children in 37 day-care centres and three orphanages in eight cities of Asian Russia, with a total of 1144 and 912 Streptococcus pneumoniae isolates being recovered in European and Asian Russia, respectively. All macrolide-non-susceptible (MICs 0.5-128 mg/L) and fluoroquinolone-non-susceptible (ciprofloxacin MICs > or = 4 mg/L) isolates were tested for resistance mechanisms and clonal relatedness. Non-susceptibility rates, by CLSI criteria, were 19.3%, 0.9% and 0.4% for penicillin G, cefotaxime and amoxycillin-clavulanate, respectively. Resistance to macrolides and lincosamides was also relatively low, i.e., < 7% for clindamycin and 14- and 15-membered macrolides. The highest rates of non-susceptibility were for tetracycline and co-trimoxazole (52.0% and 64.5%, respectively). No clones resistant to ciprofloxacin (MICs > or = 8 mg/L) were found, but 1.7% of isolates were non-susceptible (MIC 4 mg/L). No resistance was found to levofloxacin, gemifloxacin, telithromycin or vancomycin. Pulsed-field gel electrophoresis analysis showed no relationship between ciprofloxacin- and macrolide-non-susceptible isolates in European and Asian Russia. Resistance among macrolide-resistant isolates resulted mostly from the presence of erm(B) and mef(A), and from changes in L4; additionally, L22 mutations were common in isolates from Asian Russia. Non-susceptibility to quinolones was associated with mutations in parC and parE among European isolates. Asian Russian isolates had mutations in parC and gyrA, and alterations in parE were more common. There were substantial differences in non-susceptibility and mechanisms of resistance between pneumococci from Asian and European Russia, with orphanages appearing to be 'hot-spots' of resistance.


Homemade Kefir Consumption Improves Skin Condition-A Study Conducted in Healthy and Atopic Volunteers.
Diet has a fundamental role in the homeostasis of bodily functions, including the skin, which, as an essential protective barrier, plays a crucial role in this balance. The skin and intestine appear to share a series of indirect metabolic pathways, in a dual relationship known as the "gut-skin axis". Hence, the gut-skin axis might be receptive to modulation via dietary modification, where probiotics can be included, thus representing a potential therapeutic target in inflammatory skin diseases, such as atopic dermatitis (AD), in order to control and/or ameliorate symptoms. Kefir is one of the most ancient fermented foods, with probiotic characteristics that have been associated with a wide variety of health-promoting benefits, and it presents a microbiological diversity that makes its application as a probiotic in the gut-skin relationship of the utmost interest. However, the impact of a diet containing kefir on skin health has yet to be reported in scientific literature. This study aimed to assess the impact of the intake of homemade kefir in the skin of healthy and atopic volunteers. The intervention resulted in a boost on barrier function in both skin types verified only in the respective kefir intake groups. An improvement in the degree of severity of AD was also confirmed for the kefir intake group. Atopic individuals may benefit from kefir intake, especially in regard to their skin hydration. Finally, the effects observed on skin barrier function in this study probably culminate from the effects of all the ingredients in kefir, including the complex microbiota, its metabolites and macro- and micronutrients resulting from the fermentation. This work opens the way for more advanced research on the impact of the probiotic kefir on cutaneous health, further clarifying its mechanism of action namely via gut-skin axis.


Lipid peroxidation in preeclamptic and eclamptic pregnancies.
Preeclampsia and eclampsia remain one of the most serious complications of pregnancy, and the pathophysiology of the diseases is not fully understood. To investigate lipid peroxidation status in preeclamptic and eclamptic pregnancies, we measured the serum malondialdehyde (MDA) level, a product of lipid peroxide, in pregnant women with or without preeclampsia or eclampsia. Serum MDA levels were raised in women with preeclamptic (4.5 +/- 0.6 mumol/L) (P < 0.005) or eclamptic (4.9 +/- 0.8 mumol/L) (P < 0.005) pregnancies compared with uncomplicated pregnancy (3.3 +/- 0.7 mumol/L). An increased MDA level was also present in uncomplicated pregnancy compared to non-pregnant women (2.6 +/- 0.4 mumol/L) (P < 0.05). Serum MDA levels were significantly decreased at the third day post-delivery in either uncomplicated pregnancy (P < 0.05), preeclamptic pregnancy (P < 0.005) or eclamptic pregnancy (P < 0.005). A positive correlation was seen between MDA level and both systolic and diastolic blood pressure in preeclamptic and eclamptic pregnancies. These results provide further evidence that excessive lipid peroxidation may contribute to the pathophysiology and pathogenesis of preeclamptic and eclamptic pregnancies.


Source reconstruction via the spatiotemporal Kalman filter and LORETA from EEG time series with 32 or fewer electrodes.
The clinical routine of non-invasive electroencephalography (EEG) is usually performed with 8-40 electrodes, especially in long-term monitoring, infants or emergency care. There is a need in clinical and scientific brain imaging to develop inverse solution methods that can reconstruct brain sources from these low-density EEG recordings. In this proof-of-principle paper we investigate the performance of the spatiotemporal Kalman filter (STKF) in EEG source reconstruction with 9-, 19- and 32- electrodes. We used simulated EEG data of epileptic spikes generated from lateral frontal and lateral temporal brain sources using state-of-the-art neuronal population models. For validation of source reconstruction, we compared STKF results to the location of the simulated source and to the results of low-resolution brain electromagnetic tomography (LORETA) standard inverse solution. STKF consistently showed less localization bias compared to LORETA, especially when the number of electrodes was decreased. The results encourage further research into the application of the STKF in source reconstruction of brain activity from low-density EEG recordings.


Directed nanoparticle motion on an interfacial free energy gradient.
Using total internal reflection fluorescence microscopy (TIRFM), we have observed the directed motion of 20 nm probe particles on specific regions of surfaces that exhibited strong gradients of hydrophobicity. Patterned surfaces were prepared by selective photodegradation (using a contact photomask) of a hydrophobically modified fused silica surface. The lateral distribution of hydrophobicity was characterized in situ using the selective affinity of amphiphilic probes (i.e., hydrophobic interaction microscopy). Probe particles were observed to move unidirectionally from regions of lower to higher to hydrophobicity over distances of approximately 1 microm when the hydrophobicity gradient was greater than d(cos theta)/dx = 0.05 +/- 0.02 microm(-1), where theta is the water contact angle on the bare surface. Only adsorption events were observed on energetically homogeneous surface regions.


Research Progress of PI3K/PTEN/AKT Signaling Pathway Associated with Renal Cell Carcinoma.
Renal cell carcinoma is a common renal malignancy of the urinary system and the most malignant type of kidney cancer. Phosphatidylinositol 3-kinase (PI3K) is an intracellular phosphatidylinositol kinase associated with oncogene products such as v-src and with serine/threonine kinase activity, and its increased activity correlates with the development of several cancers. Protein kinase B (AKT) is a cyclic guanosine phosphate-dependent protein kinase that plays an important role in cell survival and apoptosis. Phosphatase and tensin homolog (PTEN), a newly discovered oncogene in recent years, participates in tumorigenesis and development by competing with tyrosine kinases for common substrates. The product encoded by PTEN was found to negatively regulate the PI3K/Akt signaling pathway, thereby inhibiting cell proliferation and promoting apoptosis. The PI3K/PTEN/AKT signaling pathway has also been identified in several studies as being involved in the development of several malignancies, including renal cell carcinoma. Radiotherapy is currently one of the most effective means of treatment for renal cell carcinoma, whereas it is predisposed to significant tolerance during the course of radiotherapy, thereby leading to treatment failure. Therefore, new treatment options may potentiate the efficiency of renal cell carcinoma treatment. With the development of tumor molecular biology, targeted biological therapy for malignant tumors has gradually become a research hotspot. Given the above research background, this study reviews the application of the PI3K/PTEN/AKT signaling pathway in renal cell carcinoma, aiming to provide more references for the treatment of clinical renal cell carcinoma.


Does endotoxin play a major role in inducing the depression of macrophage function during polymicrobial sepsis?
Endotoxin (ETX) is thought to be the primary inducer of proinflammatory mediator release associated with bacterial sepsis. Furthermore, a number of studies indicate that preexposure of animals to high doses of ETX produces macrophages (M luminal diameters) that are refractory to ex vivo stimulation with ETX. However, it is unknown if levels of ETX comparable to those typically encountered in sepsis induce a similar refractory state in M luminal diameters. To assess this, peritoneal M luminal diameters (PM luminal diameters) were harvested from C3H/HeN mice (ETX sensitive) at 1 hour (early) or 24 hours (late) following cecal ligation and puncture (CLP) to induce polymicrobial sepsis, sham CLP, or laparotomy followed by peritoneal implantation of a minipump delivering either saline or ETX (0.025 microgram/g of body weight, every 24 hours). Peritoneal M luminal diameter cultures were incubated with ETX, either 0 or 10 micrograms/mL, for 24 hours, and their ability to release interleukin-1, interleukin-6, and tumor necrosis factor was assessed by bioassay. Chronic low-dose ETX with 0 microgram of ETX media added produced early (at 1 hour) in vivo activation of PM luminal diameter interleukin-1 release, which was comparable to that seen in mice subjected to CLP. However, unlike PM luminal diameter taken from CLP mice, PM luminal diameters from mice implanted with the ETX minipump at 1 or 24 hours showed no marked decline in their ability to respond to ETX (10 micrograms). Comparable changes were seen for interleukin-6 and tumor necrosis factor release. Bacterial component(s) other than ETX per se induces the sustained dysfunction in PM luminal diameter capacity to produce proinflammatory cytokines during sepsis and/or peritonitis. Thus, agents directed against ETX alone may not be adequate in the treatment of polymicrobial sepsis.


Clinical and molecular findings in a cohort of 152 Brazilian severe early onset inherited retinal dystrophy patients.
Leber congenital amaurosis (LCA) and early-onset retinal dystrophy (EORD) are severe inherited retinal dystrophy that can cause deep blindness childhood. They represent 5% of all retinal dystrophies in the world population and about 10% in Brazil. Clinical findings and molecular basis of syndromic and nonsyndromic LCA/EORD in a Brazilian sample (152 patients/137 families) were studied. In this population, 15 genes were found to be related to the phenotype, 38 new variants were detected and four new complex alleles were discovered. Among 123 variants found, the most common were CEP290: c.2991+1655A>G, CRB1: p.Cys948Tyr, and RPGRIP1: exon10-18 deletion.


Autoimmune pancreatitis--recent advances.
Autoimmune pancreatitis (AIP) is recognized as a distinct clinical entity, identified as a chronic inflammatory process of the pancreas in which the autoimmune mechanism is involved. Clinically and histologically, AIP has two subsets: type 1--lymphoplasmatic sclerosing pancreatitis with abundant infiltration of the pancreas and other affected organs with immunoglobulin G4-positive plasma cells, and type 2--duct centric fibrosis, characterized by granulocyte epithelial lesions in the pancreas without systemic involvement. In the diagnosis of AIP, two diagnostic criterions are used--the HISORt criteria and Asian Diagnostic Criteria. In the differential diagnosis, the pancreatic cancer must be excluded by endosonographically guided pancreatic biopsy. Typical signs of AIP are concomitant disorders in other organs (kidney, liver, biliary tract, salivary glands, colon, retroperitoneum, prostate). Novel clinicopathological entity was proposed as an 'IgG4-related sclerosing disease' (IgG4-RSC). Extensive IgG4-positive plasma cells and T lymphocyte infiltration is a common characteristics of this disease. Recently, IgG4-RSC syndrome was extended to a new entity, characterized by IgG4 hypergammaglobulinemia and IgG4-positive plasma cell infiltration, this being considered an expression of a lymphoproliferative disease, 'IgG4-positive multiorgan lymphoproliferative syndrome'. This syndrome includes Mikulicz's disease, mediastinal fibrosis, autoimmune hypophysitis, and inflammatory pseudotumor--lung, liver, breast. In the therapy of AIP, steroids constitute first-choice treatment. High response to the corticosteroid therapy is an important diagnostic criterion. In the literature, there are no case-control studies that determine if AIP predisposes to pancreatic cancer. Undoubtedly, AIP is currently a hot topic in pancreatology.


A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site-mediated translation.
Death-associated protein 5 (DAP5) (also named p97 and NAT1) is a member of the translation initiation factor 4G (eIF4G) family that lacks the eIF4E binding site. It was previously implicated in apoptosis, based on the finding that a dominant negative fragment of the protein protected against cell death. Here we address its function and two distinct levels of regulation during apoptosis that affect the protein both at translational and posttranslational levels. DAP5 protein was found to be cleaved at a single caspase cleavage site at position 790, in response to activated Fas or p53, yielding a C-terminal truncated protein of 86 kDa that is capable of generating complexes with eIF4A and eIF3. Interestingly, while the overall translation rate in apoptotic cells was reduced by 60 to 70%, in accordance with the simultaneous degradation of the two major mediators of cap-dependent translation, eIF4GI and eIF4GII, the translation rate of DAP5 protein was selectively maintained. An internal ribosome entry site (IRES) element capable of directing the translation of a reporter gene when subcloned into a bicistronic vector was identified in the 5' untranslated region of DAP5 mRNA. While cap-dependent translation from this transfected vector was reduced during Fas-induced apoptosis, the translation via the DAP5 IRES was selectively maintained. Addition of recombinant DAP5/p97 or DAP5/p86 to cell-free systems enhanced preferentially the translation through the DAP5 IRES, whereas neutralization of the endogenous DAP5 in reticulocyte lysates by adding a dominant negative DAP5 fragment interfered with this translation. The DAP5/p86 apoptotic form was more potent than DAP5/p97 in these functional assays. Altogether, the data suggest that DAP5 is a caspase-activated translation factor which mediates cap-independent translation at least from its own IRES, thus generating a positive feedback loop responsible for the continuous translation of DAP5 during apoptosis.


Application of latent semantic analysis for open-ended responses in a large, epidemiologic study.
The Millennium Cohort Study is a longitudinal cohort study designed in the late 1990s to evaluate how military service may affect long-term health. The purpose of this investigation was to examine characteristics of Millennium Cohort Study participants who responded to the open-ended question, and to identify and investigate the most commonly reported areas of concern. Participants who responded during the 2001-2003 and 2004-2006 questionnaire cycles were included in this study (n = 108,129). To perform these analyses, Latent Semantic Analysis (LSA) was applied to a broad open-ended question asking the participant if there were any additional health concerns. Multivariable logistic regression was performed to examine the adjusted odds of responding to the open-text field, and cluster analysis was executed to understand the major areas of concern for participants providing open-ended responses. Participants who provided information in the open-ended text field (n = 27,916), had significantly lower self-reported general health compared with those who did not provide information in the open-ended text field. The bulk of responses concerned a finite number of topics, most notably illness/injury, exposure, and exercise. These findings suggest generalized topic areas, as well as identify subgroups who are more likely to provide additional information in their response that may add insight into future epidemiologic and military research.


[Supraglottitis in adults at a single center experience 1989-2009].
Acute epiglottitis in children has almost vanished since the start of Hib vaccinations. Supraglottitis often develops in adults more slowly than in children. We reviewed all patients at Tampere University Hospital over the age of 18, who had been recorded with a diagnosis of epiglottitis or supraglottitis upon discharge from the hospital between 1989 and 2009. The most common symptoms were sore throat and pain on swallowing. Streptococcus was the most common causative agent. Most of the 308 patients had received conservative treatment. Supraglottitis should be remembered as possible diagnosis when an adult person complains of a sore throat.


Circularly Polarized Light Detection by Chiral Photonic Cellulose Nanocrystal with ZnO Photoconductive Layer in Ultraviolet Region.
Circularly polarized light (CPL) detection and polarization state recognition are required for a wide range of applications. Conventional polarization detection with optical components causes difficulties for miniaturization and integration. An effective design strategy is proposed for direct CPL detection with chiral material. Here, we realized direct CPL detection based on the combination of chiral photonic cellulose nanocrystal (CNC) and ultraviolet-sensitive ZnO photoconductive material. The CNC layer deposited by evaporation-induced self-assembly established the left-handed chiral nematic structure with a photonic bandgap (PBG) to recognize left-handed CPL (LCPL) and right-handed CPL (RCPL) at specific wavelengths. The PBG of CNC layer has been modulated by the adjustment of chiral nematic pitch to match the semiconductor bandgap of ZnO film in ultraviolet region. The photocurrents under RCPL and LCPL are 2.23 × 10-6 A and 1.77 × 10-6 A respectively and the anisotropy factor Δgpc of 0.23 is acquired for the CPL detection based on the chiral photonic CNC. This design provides a new approach to the detection of CPL polarization state with competitive performance.


L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently.
The type 3 secretion system (T3SS) was obtained in many Gram-negative bacterial pathogens, and it is crucial for their pathogenesis. Environmental signals were found to be involved in the expression regulation of T3SS, which was vital for successful bacterial infection in the host. Here, we discovered that L-glutamine (Gln), the most abundant amino acid in the human body, could repress enterohemorrhagic Escherichia coli (EHEC) T3SS expression via nitrogen metabolism and therefore had potential as an antivirulence agent. Our in vitro and in vivo evidence demonstrated that Gln could decline EHEC infection by attenuating bacterial virulence and enhancing host defense simultaneously. We repurpose Gln as a potential treatment for EHEC infection accordingly.


120 W Greenlight HPS Laser Photoselective Vaporization of the Prostate for Treatment of Benign Prostatic Hyperplasia in Men with Detrusor Underactivity.
Most men with benign prostatic hyperplasia (BPH) have bothersome lower urinary tract symptoms (LUTS). This study aimed to investigate the safety and efficacy of high-performance system (HPS) laser photoselective vaporization of the prostate (PVP) for the treatment of BPH in men with detrusor underactivity (DU). From March 2009, 371 patients with BPH were divided into 2 groups according to the findings of preoperative urodynamic study: 239 (64.4%) patients with bladder outlet obstruction (BOO) and 132 (35.6%) patients with bladder outlet obstruction with detrusor underactivity (BOO+DU). 120 W HPS laser PVP was performed to resolve the BOO. The perioperative data and postoperative results at 1 month and 12 months, including the International Prostate Symptom Score (IPSS), maximum urinary flow (Qmax), and postvoid residual urine (PVR) values, were evaluated. Compared with the preoperative parameters, significant improvements in IPSS, Qmax, and PVR were observed in each group at 1 and 12 months after the operation. In addition, IPSS, Qmax, and PVR were not significantly different between the BOO and BOO+DU groups at 1 and 12 months after the operation. Surgery to relieve BOO in the patients with BPH seems to be an appropriate treatment modality regardless of the existence of DU.


Calpain translocation during muscle fiber necrosis and regeneration in dystrophin-deficient mice.
Previous studies have shown that calpains are autolytically cleaved during the disease process of mdx dystrophy, a mouse model for Duchenne muscular dystrophy, indicating that calpains may be activated and play a role in proteolysis that occurs in muscular dystrophy (J. Biol. Chem. 270(18), 10909-10914, 1995). In the present study, we investigated the location of calpain in dystrophic muscle fibers over the course of mdx dystrophy, to relate the protease distribution to its state of activation, and to determine whether calpain translocation was an early event in mdx dystrophy. Immunolabeling of health, fully differentiated muscle fibers showed calpain present throughout the cytosol, but more concentrated near the plasma membrane. However, degenerating mdx fibers did not contain higher concentrations of calpain at the plasma membrane and showed only a homogeneous, cytosolic distribution. Calpain distribution was similarly diffuse in young myotubes and regenerating fibers with increased cytosolic concentration in early myotubes. Calpain distribution in adult mdx tissue was similar to that occurring in healthy, fully differentiated fibers, although adult mdx fibers displayed higher concentrations of membrane-associated calpain than those observed in C57 controls. The association of calpain with the plasma membrane was verified by immunoblots of isolated sarcolemmal membrane from adult mdx and control muscle which showed calpain present predominantly in the cytosol along with some membrane association. Thus, changes in calpain distribution coincide with changes in enzymatic cleavage over the course of mdx dystrophy shown previously. Furthermore, the stages of pathology at which calpain cleavage is least coincides with those stages when calpain is most concentrated at the cell membrane, suggesting that calpain is retained in an inactive form at the plasma membrane.


Longitudinal analysis of body weight and average daily feed intake during the feedlot test period in Angus cattle.
The objectives of this study were to compare different models for analysing body weight (BW) and average daily feed intake (ADFI) data collected during a 70-day feedlot test period and to explore whether genetic parameters change over time to evaluate the implications of selection response. (Co)variance components were estimated using repeatability and random regression models in 2,071 Angus steers. Models included fixed effects of contemporary group, defined as herd-year-observation_date-age, with additive genetic and permanent environmental components as random effects. Models were assessed based on the log likelihood, Akaike's information criterion and the Bayesian information criterion. For both traits, random regression models (RRMs) presented a better fit, indicating that genetic parameters change over the test period. Using a two-trait RRM, the heritability from day 1 up to day 70 for BW increased from 0.40 to 0.50, while for ADFI, it decreased from 0.44 to 0.33. The genetic correlation increased from 0.53 at day 1 up to 0.79 at day 70. Selection based on an index assuming no change in genetic parameters would yield a 2.78%-3.13% lower selection response compared to an index using parameters estimated with RRMs and assuming these genetic parameters are correct. Results imply that it may be beneficial to implement RRMs to account for the change of parameters across the feedlot period in feed efficiency traits.