Identification of a poliovirus neutralization epitope through use of neutralizing antiserum raised against a purified viral structural protein.
VP4, one of the poliovirus structural proteins, was purified and used to prepare rabbit anti-VP4 serum. In addition to the anti-VP4 activity, this serum was also found to contain significant anti-VP3 and antivirion activities. The serum also effectively neutralized viral infectivity. The ease with which nonneutralizable variants were obtained indicated that neutralization was due to an antibody population which bound to a single virion epitope. Antigen saturation and immunoprecipitation experiments demonstrated that antibody to this epitope was also responsible for the serum's antivirion and anti-VP3 activities, as well as for a part of the anti-VP4 activity. The identification of a neutralization epitope most probably present on VP3, which cross-reacts with a site on denatured VP4, is the first report of such an epitope on a poliovirus structural protein other than VP1.


Transvaginal bone-anchored sling for the treatment of female stress urinary incontinence: effect of Valsalva leak point pressure and prior pelvic surgery on outcomes.
The effect of lower Valsalva leak point pressure (VLPP) and previous pelvic surgery on outcomes following sling surgery is controversial. We assessed outcomes following bone-anchored sling (BAS) placement in patients with intrinsic sphincteric deficiency (ISD) and previous pelvic surgery. A retrospective review of 149 patients undergoing BAS placement was performed. Patients were stratified by VLPP (> or =60, <60, and <30) and by history of previous anti-incontinence/pelvic floor surgery. Outcomes were assessed using a questionnaire comprising validated urogenital distress inventory (UDI)-6, incontinence impact questionnaire (IIQ)-7 questionnaires and additional items addressing satisfaction. In comparing the three VLPP cohorts, the percentage of patients reporting incontinence episodes of <1/week (64%, 68%, and 63%, respectively) and postoperative UDI/IIQ questionnaire scores were similar (p > 0.2, all comparisons). Lower rates of patients achieving <1 episode of incontinence per week (50%; p = 0.07) and worse UDI/IIQ scores (p = 0.02) were associated with patients with > or =2 prior surgeries. Whereas results are similar following BAS in patients with or without varying degrees of ISD, worse outcomes are associated with prior surgery.


Osteoporosis liaison service in Japan.
A fracture liaison service (FLS) is a secondary fracture prevention program that is led by a coordinator. A program called the osteoporosis liaison service (OLS), which includes FLS, was first implemented in Japan and has become popular for solving problems related to osteoporosis treatment. OLS and FLS have the same purpose, namely preventing fragility fractures, but while FLS focuses mainly on secondary fracture prevention in fracture patients, OLS addresses this issue as well as primary fracture prevention at clinics and in communities.


Management practices associated with Mycobacterium avium subspecies paratuberculosis infection and the effects of the infection on dairy herds.
During 2004, a survey of Mycobacterium avium subspecies paratuberculosis (map) was conducted in 101 randomly selected dairy herds to investigate associations between the infection status of the herds, different management practices, and possible disease indicators, such as indices of mastitis and reproductive performance. Data were collected by means of a questionnaire through personal interviews with the farmers and veterinarians in charge of each farm. At the same time, blood samples were taken from cattle over one year old and analysed with a commercial elisa to detect antibodies to map. Statistical analyses indicated that the following management practices constituted major risk factors: utilisation of colostrum from cows with a previous positive map diagnosis, and housing replacement calves with adult cattle before they were six months old. Seropositivity to map was related to the herds' bulk tank somatic cell counts and incidence of clinical mastitis, but not to their reproductive performance.


Risk Factors of Stenotrophomonas maltophilia Blood Stream Infections: Comparison With Other Gram-Negative Blood Stream Infections in Children.
Stenotrophomonas maltophilia, is a nonfermentative, aerobic, Gram-negative bacilli which is intrinsically resistance to several antibiotics. Treatment options for this bacteria are quite different from the other Gram-negative bacilli, which can represent a therapeutic challenge. To initiate appropriate empiric treatment and to reduce mortality, differentiation of S. maltophilia from other Gram-negative bacteria is critically important. The aim of this study is to distinguish the risk factors of S. maltophilia blood stream infections (BSI) from other Gram-negative BSI. This was a retrospective, case-control study. Patients with S. maltophilia BSI were selected as cases and patients with non-S. maltophilia Gram-negative BSI were selected as controls. Demographic and clinical characteristics of patients were recorded. Forty-eight cases with S. maltophilia BSI and 144 controls were enrolled in the study. Risk factors for S. maltophilia BSI compared with the control group includes prior use of antibiotics, especially carbapenem, pediatric intensive care unit stay, mechanical ventilator use, indwelling catheters and duration of hospitalization. Breakthrough infection by S. maltophilia can occur in severely ill patients being treated with carbapenem. In the presence of risk factors, to reduce morbidity and mortality, S. maltophilia should be kept in mind when starting empiric treatment.


An unusual cause of recurrent spontaneous pneumothorax: the Mounier-Kuhn syndrome.
We present a case of 63-year-old man who was referred to the emergency department with a right-sided pneumothorax. He had a history of spontaneous pneumothorax for 2 times. The chest computed tomographic scan showed tracheobronchomegaly with an increase in the diameter of the trachea and right and left main bronchus. Fiberoptic bronchoscopy revealed enlarged trachea and both main bronchus with diverticulas. These findings are consistent with a diagnosis of Mounier-Kuhn syndrome. Mounier-Kuhn syndrome is a rare clinical and radiologic condition. It is characterized by a tracheal and bronchial dilation. Diagnosis is made by computed tomography and bronchoscopy. Mounier-Kuhn syndrome should be kept in mind in the differential diagnosis of recurrent spontaneous pneumothorax.


Infectious Diseases Institute at Makerere University College of Health Sciences: a case study of a sustainable capacity building model for health care, research and training.
The Infectious Diseases Institute (IDI), established in 2001, was the first autonomous institution of Makerere University set up as an example of what self-governing institutes can do in transforming the academic environment to become a rapidly progressive University addressing the needs of society This paper describes the success factors and lessons learned in development of sustainable centers of excellence to prepare academic institutions to respond appropriately to current and future challenges to global health. Key success factors included a) strong collaboration by local and international experts to combat the HIV pandemic, along with b) seed funding from Pfizer Inc., c) longstanding collaboration with Accordia Global Health Foundation to create and sustain institutional strengthening programs, d) development of a critical mass of multi-disciplinary research leaders and managers of the center, and e) a series of strong directors who built strong governance structures to execute the vision of the institute, with subsequent transition to local leadership. Twenty years of sustained investment in infrastructure, human capital, leadership, and collaborations present Makerere University and the sub-Saharan Africa region with an agile center of excellence with preparedness to meet the current and future challenges to global health.


Early life exposure to famine and risk of dyslipidemia in adults: a systematic review and Meta-analysis.
Dyslipidemia is the major contributor to the global disease burden. Earlier epidemiologic research has linked early-life famine exposure to dyslipidemia and altered lipid profiles in adulthood, but a uniform perspective has yet to be established. In response, this systematic review and meta-analysis is aimed to investigate the association of early life famine exposure and dyslipidemia in adults. Scopus, Medline and Google scholar databases were searched for articles published until October 2020. Studies of famine exposure during prenatal and early postnatal life and their association with dyslipidemia and lipid profiles in adults were included. Random effect model in the Meta-analysis and Mantel- Haenszel model was used to calculate odds ratios and their 95% confidence intervals to evaluate the strength of association between famine exposure and dyslipidemia. The lipid profiles of the exposed and non-exposed groups were compared using the standardized mean difference (SMD). Heterogeneity between studies were assessed using I2 values. We identified 17 studies for assessing the association between early life famine exposure and risk of dyslipidemia in adults. About 11 studies were included for meta-analysis. Prenatal exposure to famine was associated with increased risk of dyslipidemia [OR = 1.74 (95% CI: 1.31, 2.31)], total cholesterol [SMD = 2.07 (95% CI: 1.40, 2.74)], LDL-cholesterol [SMD = 1.16 (95% CI: 0.25, 0.26)] and decreased HDL-cholesterol [SMD = -0.05 (95% CI: -0.10, -0.01)]. Likewise, famine exposure during early postnatal period was associated with increased risk of total cholesterol [SMD = 0.18 (95% CI: 0.11, 0.25), I 2 = 29%] and LDL-cholesterol [SMD = 0.15 (95% CI: 0.07, 0.23), I 2 = 61%]. Famine exposure in early life was found to have an association with increased risk of dyslipidemia and altered lipide profile during adulthood. Our findings highlight the need for promoting better nutrition during pregnancy and infancy to prevent dyslipidemia during adulthood. The online version contains supplementary material available at 10.1007/s40200-022-01062-8.


Cost-effectiveness analysis of enfuvirtide (ENF) added to an optimized therapy compared with an optimized therapy in patients with HIV/AIDS.
Fuzeon (enfuvirtide) (ENF) is the first drug among the HIV fusion inhibitors that has shown high efficacy in HIV-1/AIDS patients resistant to conventional antiretroviral agents. To analyze the cost-effectiveness of ENF plus optimized therapy (OT) in HIV patients. A Markov model was used to calculate the cost-effectiveness of ENF in terms of incremental cost per life-year gained. The model has a 10-year horizon, with monthly cycles, and the perspective is the Spanish National Health System. Efficacy rates and transition probabilities were obtained from clinical and epidemiological trials. Resource use data were retrieved from published literature and a panel of clinicians. Unit costs refer to the year 2003. Incremental cost-effectiveness ratio. Adding ENF to OT increased patient life expectancy by 1.6 years (6.2 years with OT compared with 7.8 years with ENF + OT). Total costs were 160,728 euro for OT and 200,859 euro with ENF + OT, mainly due to increasing life expectancy raising resource use and costs. Incremental cost per life-year gained with ENF was 25,082 euro. ENF plus OT increased life expectancy for HIV-1-treated patients and is an efficient treatment option.


Chemical composition, functional, powder, and sensory properties of tarhana enriched with wheat germ.
In this study, the effect of supplementing wheat germ in the formulation of tarhana, a fermented Turkish soup, was investigated to determine the physicochemical, functional, powder, and sensory properties. For this purpose, wheat germ was added to the tarhana formulation using five different replacement ratios (100 + 0, 90 + 10, 80 + 20, 70 + 30, and 50 + 50% weight wheat flour + weight wheat germ). The replacement of wheat flour with wheat germ resulted in the following: a higher moisture content, a*, browning (BI) and yellowness (YI) indexes, total color change (ΔE*), pH, ash, protein, cellulose, fat, and total phenolic contents, and foaming capacity values and lower Hue angle, chroma, L*, starch content, water hydration and oil holding capacities, wettability time, hygroscopicity, and the Carr index and Hausner ratio values (p < 0.05). The changes in the BI, YI, ΔE*, protein, cellulose, and starch contents, water hydration, and oil holding capacities, and foaming capacity values were found to be linear depending on the replacement percentage. Results of the chemical analysis of the tarhana samples revealed that the ash, protein, and cellulose contents of tarhana can be significantly increased depending on the replacement percentage (p < 0.05). A highly acceptable tarhana sample, selected by the panelists, that closely resembled the control was produced from a 90% wheat flour + 10% wheat germ mixture.


Temporal morphological and functional impact of complete urinary diversion on the bladder: a model of bladder disuse in rats.
Urinary diversion has been used as a surgical option for some bladder diseases. We developed a urinary diversion model in the rat and examined the effects of urinary diversion on the bladder. We distributed female Sprague-Dawley® rats into age matched control, sham urinary diversion and urinary diversion groups. Each group was subsequently evaluated 1 or 8 weeks after urinary diversion or sham operation. Diversion was done by surgical disconnection of the ureters from the bladder and implantation to the uterine cervix. Conscious cystometry was examined. Bladders were harvested for histological examination and quantification of smooth muscle, urothelium and collagen. Vaginal histology was assessed. Bladder muscarinic and purinergic receptor expression was examined. All rats survived the urinary diversion procedure. Bladder weight decreased in the diversion group. Cystometry showed decreased intercontractile interval and voided volume in the urinary diversion group compared to those in the control and sham operated groups. Compliance was decreased in diverted rats. Smooth muscle and urothelium were decreased as a percent of total bladder cross-sectional area. Collagen increased in 1 and 8-week diverted rats vs controls. Histological examination of the vaginal wall revealed mild swelling in 2 rats. Urinary diversion caused decreased muscarinic 3 and ligand gated purinergic 1 receptor expression but no change in muscarinic 2 or ligand gated purinergic 2 receptors. Creating a urinary diversion model by ureterovaginostomy in the rat is feasible. Urinary diversion causes distinct functional and morphometric bladder alterations.


Treatment of children and adolescents with idiopathic short stature.
Idiopathic short stature (ISS) is defined as shortness in childhood without a specific cause. ISS may be familial or nonfamilial and may be associated with or without delay of pubertal development. Treatment can be considered in an attempt to reduce the psychological burden caused by short stature in childhood and adult life. If counselling alone is not sufficient, medical modifications of the growth process can be attempted. In cases with pubertal delay, sex steroids, such as testosterone and oxandrolone, can favourably influence height velocity and growth tempo, although adult height is not affected. Medications that prolong the process of growth--for example, gonadotropin-releasing hormone agonists or aromatase inhibitors--might increase adult height, but findings to date are still experimental. Growth hormone therapy is approved for the treatment of very short children with reduced adult height expectation, as evidence has accumulated that this therapy can increase height in childhood and in adult life. Sensitivity to growth hormone is impaired in patients with ISS; therefore, doses higher than a replacement dose have to be applied. This treatment still needs to be optimized in terms of efficacy, cost-effectiveness and long-term safety. A debate is ongoing concerning the psychological benefit of height increase, with clinicians warning against the medicalization of a deviation in height.


Validation of a custom spine biomechanics simulator: A case for standardization.
Mechanical testing machines used in cadaveric spine biomechanics research vary between labs. It is a necessary first step to understand the capabilities and limitations in any testing machine prior to publishing experimental data. In this study, a reproducible protocol that uses a synthetic spine was developed and used to quantify the inherent rotation error and the ability to apply loads in a single physiologic plane (pure-moment) of a custom spine biomechanics simulator. Rotation error was evaluated by comparing data collected by the test machine and the data collected by an optical motion capture system. Pure-moment loading was assessed by comparing the out-of-plane loads to the primary plane load. Using synthetic functional spine units previously shown to have mechanics similar to the cadaveric human spine, the simulator was evaluated using a dynamic test protocol reflective of its future use in the study of cadaveric spine specimens. Rotation errors inherent in the test machine were <0.25° compared to motion capture. Out of plane loads were <4.0% of the primary plane load, which confirmed pure-moment loading. The authors suggest that a standard validation protocol for biomechanical spine testing machines is needed for transparency and accurate field-wide data interpretation and comparison. We offer recommendations based on the reproducible use of a synthetic spinal specimen for consideration.


Attention in Drosophila.
As bluntly summarized by a psychologist over a century ago, everyone knows what attention is [James (1890). The Principles of Psychology]. Attention describes our capacity to focus perception on one or a group of related stimuli while filtering out irrelevant stimuli. The ease we have in recognizing this astounding capacity in ourselves is matched by a surprising difficulty in identifying it in others, and this is especially the case for measuring attention in other animals. Identifying and measuring attention-like processes in simple animals such as flies requires, to some extent, even more rigor than asking the same question for our closer animal relatives, such as apes and monkeys. This is because flies have completely different brains than humans do, so to study attention in these creatures one must rely purely on operational or behavioral measures rather than comparative neuroanatomy. There is a long history of using sophisticated behavioral paradigms to study visual responses in Drosophila melanogaster, and these studies have often provided early evidence of attention-like processes in flies. More recently, these fly paradigms have been applied to measuring visual attention directly, and the combination of electrophysiology with these preparations has provided insight into how a fly might pay attention. Together with more efficient methods for measuring some aspects of attention, such as stimulus suppression, these approaches should begin to uncover how visual attention might work in a small brain.


Neurofibroma with rhabdomyomatous differentiation: benign 'Triton' tumour of the vagina.
The benign 'Triton' tumour is a neural tumour with benign rhabdomyomatous differentiation: it must be distinguished from the better known malignant counterpart. We describe the first case outside the peripheral soft tissues and the first to be studied ultrastructurally. It also represents the second lesion identified in an adult patient.


Age-related changes in the knee meniscus.
Aging is the most prominent risk factor for the development of osteoarthritis (OA), which affects knees and causes major health burdens. Meniscal dysfunction mostly based on degeneration contributes to the development and progression of knee OA. Meniscal degeneration is caused by various extrinsic factors, such as repetitive trauma or leg malalignment, while meniscal aging is considered as internal changes, such as molecular or cellular changes. Little is known about age-related changes in the meniscus. Therefore, this review aimed to summarize and clarify the understanding of the aged meniscus. There are few articles about natural aging in the meniscus, because most reports only demonstrate the effects of OA on the meniscus. We searched PubMed (1948 to November 2016) to identify and summarize all English-language articles evaluating natural aging in the meniscus. There is evidence of compositional change in the meniscus with aging, involving cells, collagens, and proteoglycans. In addition, as recent reports on the natural aging of cartilage have indicated, senescence of the meniscal cells may also lead to disruption of meniscal cells and tissue homeostasis. Due to the low turnover rate of collagen, accumulation of advanced glycation end-products largely contributes to tissue stiffness and vulnerability, and finally results in degenerative changes or tears. Furthermore, environmental factors such as joint fluid secreted by inflamed synovium could also contribute to meniscal tissue deterioration. Age-related changes induce meniscal tissue vulnerability and finally lead to meniscal dysfunction.


The effect of Mg2+ and chelating agents on intermediary steps of the reaction ofNa+,K+-activated ATPase.
(1) It has been investigated how varying concentrations of free magnesium with and without EDTA influence the properties of the phospho-enzyme formed in the presence of sodium by the (Na+ plus K+)-activated enzyme system. (2) The phospho-enzyme formed in the presence of sodium and a high concentration of free magnesium has the same rate of (a) spontaneous dephosphorylation, (b) dephosphorylation after addition of potassium, and (c) dephosphorylation after addition of ADP, as a phospho-enzyme formed in the presence of sodium and a low concentration of magnesium. (3) With sodium and a given concentration of free magnesium, high or low, EDTA present during formation of the phospho-enzyme leads to a decrease in the rate of (a) spontaneous dephosphorylation, and (b) dephosphorylation after addition of potassium to the phospho-enzyme. (4) The rate of dephosphorylation after addition of ADP to phospho-enzyme formed without and with EDTA is the same. But as the rate of spontaneous dephosphorylation is lower with EDTA than without, ADP gives a higher increase in the rate of dephosphorylation of phospho-enzyme formed with EDTA than without. (5) The experiments thus show that the reported different sensitivity towards potassium and ADP of phospho-enzyme formed in the presence of a low and high concentration of free magnesium, respectively, is due to the EDTA used to decrease the free magnesium concentration and not to the decrease in the free magnesium as such.


Modification of the relationship between the Quetelet index and mortality by weight-loss history among older women.
The effect of weight on mortality was examined using data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study for white women aged 65 to 74 years at baseline. There was a U-shaped curve relating the Quetelet index categories to total mortality, with increased risk for both lean and heavy women. However, the increased risk to lean subjects occurred only among those who had lost more than 8.55% from their reported lifetime maximum weight. Controlling for baseline medical conditions, excluding early years of follow-up, and limiting the analysis to never-smokers did not greatly change the results. Lean women with stable weight have the lowest risk of mortality, while those who have lost weight have a high risk. Heavy women have a high risk of mortality regardless of weight-loss history. Thus, the effect of weight on mortality is modified by history of weight loss in older women, even when accounting for factors associated with weight loss and increased mortality risk.


Melanoma cells resistant towards MAPK inhibitors exhibit reduced TAp73 expression mediating enhanced sensitivity to platinum-based drugs.
The efficacy of targeted MAPK signalling pathway inhibitors (MAPKi) in metastatic melanoma therapy is limited by the development of resistance mechanisms that results in disease relapse. This situation still requires treatment alternatives for melanoma patients with acquired resistance to targeted therapy. We found that melanoma cells, which developed resistance towards MAPKi show an enhanced susceptibility to platinum-based drugs, such as cisplatin and carboplatin. We found that this enhanced susceptibility inversely correlates with the expression level of the p53 family member TAp73. We show that the lower expression of the TAp73 isoform in MAPKi-resistant melanoma cells enhances accumulation of DNA double-strand breaks upon cisplatin and carboplatin treatment by reducing the efficiency of nucleotide excision repair. These data suggest that a subgroup of melanoma patients with acquired resistance to MAPKi treatment and low TAp73 expression can benefit from chemotherapy with platinum-based drugs as a second-line therapy.


Characteristics associated with ability to prevent adverse drug reactions in hospitalized patients.
We conducted a retrospective analysis to identify characteristics of preventable adverse drug reactions (ADRs). We reviewed reports on 612 ADRs occurring in hospitalized patients over 4 years, identified by the hospital's spontaneous ADR reporting program, and classified the events as potentially preventable or not preventable. Characteristics related to ADR preventability in the univariate analysis were the patient's clinical service, organ system involved in the ADR, class of drug causing the ADR, relationship to dosage, type of ADR, and probability that the reaction was due to the drug. Among these, relationship to dosage (p<0.001) and type of ADR (p<0.001) appeared to be most strongly related to preventability. In a multivariate analysis, preventable ADRs were associated with dosing (OR 3.82, 95% CI 2.42-6.03) and previous allergy to the drug (OR 3.46, 95% CI 1.01-11.88). An ADR that was classified as an allergic (OR 0.50, 95% CI 0.27-0.94) or idiosyncratic reaction (OR 0.44, 95% CI 0.28-0.71) was unlikely to be considered preventable. Preventable ADRs in hospitalized patients are likely to be dosage related or to occur among patients allergic to the specific agent.


Serologic and biochemical analysis of HLA B15 and B5 complexes.
Charge heterogeneity of HLA-B15 and HLA-B5 complexes was analyzed by one-dimensional isoelectric focusing (1D-IEF). Frozen peripheral blood lymphocytes were metabolically labeled with 35S methionine. The class I antigens were immunoprecipitated with monoclonal antibody 4E, which detects a determinant shared by HLA-B locus and Aw19-complex antigens. The desialated 1D-IEF banding patterns were correlated to microcytotoxicity data of a panel of donors from a variety of racial groups. Serologic analysis indicated the presence of specific variants: Te76, Te78, and Te79. 1D-IEF analysis clearly showed polymorphism in the B15 and B5 complexes. The Bw62 associated variant Te79 exhibited bands distinct from Bw62. One Bw62 typed donor produced a band that was different from other Bw62 typed cells. A migration pattern difference was discovered between blacks and Caucasians that were typed Bw57. Investigated antigens included HLA-B35, w46, 51, w52, w53, w57, w58, w62, w63, w70, Te76, Te78, and Te79.


Subacute two stage metatarsal lengthening with gradual distraction for brachymetatarsia: A consecutive case series and literature review.
This study examined the functional and clinical outcomes of subacute two stage metatarsal lengthening with gradual distraction for brachymetatarsia. This technique was developed to overcome the disadvantages of one-stage metatarsal lengthening and gradual distraction. Four feet of three patients with congenital brachymetatarsia underwent subacute two stage metatarsal lengthening with gradual distraction. Pain, function, and alignment were assessed preoperatively and at follow-ups using the American Orthopaedic Foot and Ankle Society (AOFAS) lesser metatarsophalangeal-interphalangeal scale, and any complications were recorded. The patients were followed up for a mean of 18.1 ± 6.9 (range, 12.6-28.1) months. The mean metatarsal length gain was 15.2 ± 3.2 (range, 12.1-18.5) mm, and the corresponding percent increase was 32.5 % ± 7.0 % (range, 25.7-41.1 %). The mean AOFAS score (0-100) was 97.5 ± 5.0 at the final follow-up. The external fixator index was 10.2 ± 1.5 (range, 8.1-11.6) days/cm. None of the patients experienced metatarsophalangeal stiffness, subluxation or dislocation of the metatarsophalangeal joint, loss of correction, pin tract infection, delayed union, nonunion, or angular deformities. Subacute two stage metatarsal lengthening with gradual distraction is a reliable alternative treatment for brachymetatarsia.


Study of Nonlinear Models of Oscillatory Systems by Applying an Intelligent Computational Technique.
In this paper, we have analyzed the mathematical model of various nonlinear oscillators arising in different fields of engineering. Further, approximate solutions for different variations in oscillators are studied by using feedforward neural networks (NNs) based on the backpropagated Levenberg-Marquardt algorithm (BLMA). A data set for different problem scenarios for the supervised learning of BLMA has been generated by the Runge-Kutta method of order 4 (RK-4) with the "NDSolve" package in Mathematica. The worth of the approximate solution by NN-BLMA is attained by employing the processing of testing, training, and validation of the reference data set. For each model, convergence analysis, error histograms, regression analysis, and curve fitting are considered to study the robustness and accuracy of the design scheme.


Exploration of the valproic acid binding site on histone deacetylase 8 using docking and molecular dynamic simulations.
Epigenetic therapy is an important focus of research for drug development in the treatment of cancer. Valproic acid (VPA) is an HDAC inhibitor that has been evaluated in clinical studies. Despite its success in treating cancer, the mechanism of inhibition of VPA in HDAC is unknown. To this end, we have used docking and molecular dynamic simulations to investigate VPA binding to HDAC, employing both native and rebuilt 3-D structures. The results showed that VPA, via its carboxyl group, coordinates the Zn atom and other local residues (H141-142 and Y360) located at the catalytic site (CS) of HDAC. This causes electrostatic and hydrogen bonding interactions while having little interaction with the hydrophobic side chains, resulting in a low affinity. However, after several docking studies on different native HDAC 3-D structures and after using several snapshots from MD simulations, it became apparent that VPA bound with highest affinity at a site located at the acetyl-releasing channel, termed the hydrophobic active site channel (HASC). The affinity of VPA for HASC was due to its highly hydrophobic properties that allow VPA to take part in van der Waals interactions with Y18, I19, Y20, V25, R37, A38, V41, H42, I135 and W137, while VPA's carboxylate group has several hydrogen bonding interactions with the backbones of S138, I19, N136 and W137. MD simulations showed that the HASC door continuously opened and closed, which affected the affinity of VPA to the HASC, but the affinity toward the HASC was consistently higher than that obtained for the CS, suggesting that the HASC could be involved in the mechanism of inhibition.


Advancing Treatment of Bone Metastases through Novel Translational Approaches Targeting the Bone Microenvironment.
Bone metastases represent a lethal condition that frequently occurs in solid tumors such as prostate, breast, lung, and renal cell carcinomas, and increase the risk of skeletal-related events (SREs) including pain, pathologic fractures, and spinal cord compression. This unique metastatic niche consists of a multicellular complex that cancer cells co-opt to engender bone remodeling, immune suppression, and stromal-mediated therapeutic resistance. This review comprehensively discusses clinical challenges of bone metastases, novel preclinical models of the bone and bone marrow microenviroment, and crucial signaling pathways active in bone homeostasis and metastatic niche. These studies establish the context to summarize the current state of investigational agents targeting BM, and approaches to improve BM-targeting therapies. Finally, we discuss opportunities to advance research in bone and bone marrow microenvironments by increasing complexity of humanized preclinical models and fostering interdisciplinary collaborations to translational research in this challenging metastatic niche.


A theoretical review on the interplay among EFL teachers' professional identity, agency, and positioning.
Language teaching is by nature a complex and social practice with numerous personal and contextual aspects. It hinges upon how teachers perceive themselves, the way they are perceived by others, and their roles and positioning in the classroom and its occurring interactions. Despite the proliferation of research on English as a foreign language (EFL) teachers' professional identity, its association to agency and positioning has been widely ignored in academia. Urged by this backdrop, the current study was a bid to theoretically explore the relationship among teachers' professional identity, agency, and positioning in language education. To do so, the theoretical and empirical underpinnings of this line of research are reviewed referring to different definitions, dimensions, approaches, and conceptualizations of each construct. Additionally, to approve their strong linkage, scientific findings from previous studies are built upon. Furthermore, the implications of this line of inquiry for different stakeholders in EFL contexts, especially teachers are presented in detail. Finally, the study enumerates a number of research gaps in this domain and suggests some future directions for enthusiastic scholars.


Exploring the Relationship Between Intolerance of Uncertainty and Trust in Physicians from Spousal and Parent-Child Perspectives.
The present study aimed to probe the intergenerational transmission of intolerance of uncertainty (IU) and trust in physicians. Besides, through the actor-partner interdependence model (APIM), the predictive effect of parents' IU on their own and their spouses' trust in physicians was examined. A mediation model was further constructed to probe the mechanisms by which parents' IU affects children's trust in physicians. The Intolerance of Uncertainty Scale-12 (IUS-12) and the Wake Forest Physician Trust Scale (WFPTS) were employed to conduct the questionnaire survey among 384 families (each family with a father, mother, and one child). IU and trust in physicians were found to be intergenerationally transmitted. The results of the APIM analyses showed that fathers' total IUS-12 scores negatively predicted their own (β = -0.419, p < 0.01) and mothers' (β = -0.235, p < 0.01) total WFPTS scores. Mothers' total IUS-12 scores negatively predicted their own (β = -0.353, p < 0.01) and fathers' (β = -0.138, p = 0.017) total WFPTS scores. The results of mediation analyses indicated that parents' total WFPTS scores and children's total IUS-12 scores mediated the effect of parents' total IUS-12 scores on children's total WFPTS scores. The public's IU is a crucial influencing factor of their trust in physicians. Besides, the IU between couples and between parents and children could be mutually affected. On the one hand, husbands' IU could affect their own and their wives' trust in physicians, and vice versa. On the other hand, parents' IU and trust in physicians could affect their children's IU and trust in physicians, respectively.


Influence of insecticidal derivative (cartap hydrochloride) from the marine polycheate on certain enzyme systems of the fresh water fish Oreochromis mossambicus.
The activities of phosphatases and transaminases were studied in muscle and liver of the fresh water fish, Oreochromis mossambicus on exposure to different sublethal concentrations (0.25, 0.5, 0.75 and 1 mgl(-1)) of cartap hydrochloride (insecticidal derivative from marine polycheate) for 96 h. There was an overall decrease in phosphatases and transaminases activity in muscle and liver of the fish subjected to cartap hydrochloride.


A Wish List for Drug Development in Pediatrics.
This commentary illustrates and summarizes some of the many issues with dosage forms and drug delivery that arise in everyday practice for clinicians caring for pediatric patients. While advances in drug development for children and expansion of labeling information in this age group have made great strides in improving care, there is much to be desired in the area of dosage forms. From liquids that are unpalatable to the need for extemporaneous compounding of parenteral doses in syringes that are meant for immediate use but used to store medications for hours to weeks, the list of challenges is long. Many of these problems exist for drugs which have long been generic, but some problems have arisen from new drugs as well. Pediatric clinicians and dosage form developers should work together to create solutions.


Simultaneous determination of a novel thrombin inhibitor and its two metabolites in human plasma by liquid chromatography/tandem mass spectrometry.
I, 3-(2-phenethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylene-c arboxamidomethylpyridinyl)-pyrazinone dihydrochloride monohydrate, is a potent, orally active thrombin inhibitor. The compound also has two metabolites which have been shown to have thrombin inhibitory activity: benzylic alcohol M3 metabolite (II) and hydroxymethylpyrazinone M7 metabolite (III). A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous determination of I and its two metabolites in human plasma has successfully been developed. The method consists of treating 0.5 ml plasma with 2 N NaOH and extracting I, II, III and internal standard (IV) with ethyl acetate:methyl-t-butyl ether (1:3, v/v). The analytes were then back-extracted into 2% formic acid. The analytes were chromatographed by high performance liquid chromatography (HPLC) and detected by MS/MS. Positive ionization was used on a heated nebulizer probe monitoring precursor --> product ion combinations in multiple reaction monitoring mode. The linear range is 0.5-1000 nM for I and III and 0.75-1000 nM for II. Recoveries were 88, 74, 78 and 102.1% for I, II and III and the internal standard, respectively in human plasma. Intraday variation using this method was < or = 7.9% for I, < or = 9.0%, for II and < or = 9.5% for III across the standard curve range. This method exhibits good linearity and reproducibility for the three analytes.


Mycobacterial STAND adenylyl cyclases: The HTH domain binds DNA to form biocrystallized nucleoids.
Mycobacteria harbor a unique class of adenylyl cyclases with a complex domain organization consisting of an N-terminal putative adenylyl cyclase domain fused to a nucleotide-binding adaptor shared by apoptotic protease-activating factor-1, plant resistance proteins, and CED-4 (NB-ARC) domain, a tetratricopeptide repeat (TPR) domain, and a C-terminal helix-turn-helix (HTH) domain. The products of the rv0891c-rv0890c genes represent a split gene pair, where Rv0891c has sequence similarity to adenylyl cyclases, and Rv0890c harbors the NB-ARC-TPR-HTH domains. Rv0891c had very low adenylyl cyclase activity so it could represent a pseudoenzyme. By analyzing the genomic locus, we could express and purify Rv0890c and find that the NB-ARC domain binds ATP and ADP, but does not hydrolyze these nucleotides. Using systematic evolution of ligands by exponential enrichment (SELEX), we identified DNA sequences that bound to the HTH domain of Rv0890c. Uniquely, the HTH domain could also bind RNA. Atomic force microscopy revealed that binding of Rv0890c to DNA was sequence independent, and binding of adenine nucleotides to the protein induced the formation of higher order structures that may represent biocrystalline nucleoids. This represents the first characterization of this group of proteins and their unusual biochemical properties warrant further studies into their physiological roles in future.


Notifying contacts of HIV-infected patients. Strategies to use until health agencies assume responsibility.
Although physicians have a moral and professional duty to prevent the spread of human immunodeficiency virus (HIV) by seeing that the infected patient's contacts are informed of the risks, they have no legal guidelines on how to approach the problem. Medical organizations recommend that physicians notify an endangered third party if the infected patient refuses to cease high-risk activity and the authorities do not take action. However, many questions remain about practical application of these recommendations. Some federal recommendations place the burden of notifying the third party on the infected patient, then on the public health authority, and finally on the physician. However, these suggestions are not law. Legal precedent has placed responsibility on the physician for warning persons exposed to an infected patient that a risk exists. However, warning someone who is not clearly at risk can also invite a lawsuit. At present, there is no clear public policy to give guidance either. By considering the infectivity of the virus, injury potential of the infection, and the exposed person's relationship with the patient, the physician can better weigh the risk of breaching patient confidentiality versus ignoring the health dangers to the third party. Thorough counseling of the patient about infectivity, careful documentation of all conversations and efforts, and use of good judgment are the best tools that physicians have at present for handling this legal void.


The Association Between Perceived Electronic Health Record Usability and Professional Burnout Among US Physicians.
To describe and benchmark physician-perceived electronic health record (EHR) usability as defined by a standardized metric of technology usability and evaluate the association with professional burnout among physicians. This cross-sectional survey of US physicians from all specialty disciplines was conducted between October 12, 2017, and March 15, 2018, using the American Medical Association Physician Masterfile. Among the 30,456 invited physicians, 5197 (17.1%) completed surveys. A random 25% (n=1250) of respondents in the primary survey received a subsurvey evaluating EHR usability, and 870 (69.6%) completed it. EHR usability was assessed using the System Usability Scale (SUS; range 0-100). SUS scores were normalized to percentile rankings across more than 1300 previous studies from other industries. Burnout was measured using the Maslach Burnout Inventory. Mean ± SD SUS score was 45.9±21.9. A score of 45.9 is in the bottom 9% of scores across previous studies and categorized in the "not acceptable" range or with a grade of F. On multivariate analysis adjusting for age, sex, medical specialty, practice setting, hours worked, and number of nights on call weekly, physician-rated EHR usability was independently associated with the odds of burnout with each 1 point more favorable SUS score associated with a 3% lower odds of burnout (odds ratio, 0.97; 95% CI, 0.97-0.98; P<.001). The usability of current EHR systems received a grade of F by physician users when evaluated using a standardized metric of technology usability. A strong dose-response relationship between EHR usability and the odds of burnout was observed.


Interaction of substance P, compound 48/80 and mastoparan with the alpha-subunit C-terminus of G protein.
Pretreatment of purified calf brain G proteins with activated pertussis toxin or antibodies raised against the C-terminus of their alpha subunits prevented the increase in GTPase activity induced by substance P, compound 48/80 and mastoparan. These results suggest that these mast cell secretagogues activate G proteins directly via an interaction with the C-terminus of alpha subunits of G proteins by mimicking the agonist-liganded receptors.


2,2'-{(1E,1'E)-[Ethane-1,2-diylbis(aza-nylyl-idene)]bis-(methanylyl-idene)}bis-(4-iodo-phenol).
The title compound, C20H14I2N2O2, a di-iodo-Schiff base, crystallizes in space group Pbca with one mol-ecule per asymmetric unit. The mol-ecular structure reveals two intra-molecular O-H⋯N hydrogen bonds that give the mol-ecule a twisted structure with non-coplanar rings. In the crystal structure, the mol-ecular packing is stabilized by π-π stacking, hydrogen- and halogen-bonding (C-H⋯I; O⋯I) inter-actions.


Bacteriophage MS-2 removal by submerged membrane bioreactor.
A membrane bioreactor (MBR) may serve as a pre-disinfection or disinfection unit, in addition to its solid/liquid separation and biological conversion functions, to produce sewage effluent of high quality. This bench-scale pilot study focuses on investigating the performance of a submerged MBR in pathogen removal and the factors affecting the removal, using a 0.4-microm hollow-fiber membrane module submerged in an aeration tank and bacteriophage MS-2 as the indicator organism. Removal of the MS-2 phage was found to be contributed by physical filtration by the membrane itself, biomass activity in the aeration tank and bio-filtration achieved by the biofilm developed on the membrane surface. The membrane alone gave poor virus removal (0.4+/-0.1 log) but the overall removal increased substantially with the presence of biomass and the membrane-surface-attached biofilm. The contributions of the suspended biomass and attached biofilm to the phage removal are dependent on the inter-related parameters including the concentration of mixed liquor suspended solids (MLSS), the sludge retention time (SRT) and the food to mass (F/M) ratio. The correlations between effluent flux/trans-membrane pressure and virus removal give evidence that phage removal in the MBR is most likely susceptible to both biological and physical factors including the quantity and property of the biomass and the biofilm and the membrane pore size reduction.


Intrahepatic arterioportal fistula and its treatment with detachable balloon and transcatheter embolization with coils and microspheres.
Although intrahepatic arterioportal fistula (APF) due to acquired or congenital causes are infrequent, they are listed among the causes of portal hypertension. The aim of this study was to present the results of intrahepatic APF treatment with embolotherapy in six cases. Transarterial detachable balloon and coil embolization was used on six consecutive cases with traumatic intrahepatic APF from 1989 to 2003. Six-month follow-up angiography was obtained in every case. Successful disconnection of hepatic arterial and portal system was achieved in five cases. At least symptomatic improvement was achieved in one. Transcatheter embolization may be the first line of treatment for intrahepatic APF.


Long-term thalidomide use in refractory cutaneous lesions of systemic lupus erythematosus.
To evaluate the efficacy of long-term thalidomide treatment in cutaneous lesions of systemic lupus erythematosus (SLE), not responsive to conventional therapy. Were selected 18 SLE patients (ACR criteria) with active cutaneous lesions not responsive to chloroquine, photoprotectors and low doses prednisone and who presented good response to thalidomide but relapsed after withdrawal of the drug. All female patients had no risk of pregnancy. Thalidomide was reintroduced and maintained at low dose (25-100 mg/day) for a minimum of 6 months. Eighteen patients (16 females) with mean age of 34.2 yo (16-57 y.o.) received thalidomide for 6-21 months (mean 8.5 m). The mean dose of prednisone at beginning of study was 38.3 mg/d and at the end was 9.7 mg/d (p < 0.05). Complete remission of cutaneous lesions was observed in thirteen patients (72%) and partial remission in five (28%). Side effects observed were: drowsiness in eight patients, intestinal constipation in 5, transient oliguria in 1, paresthesia of hand with normal electromyography in another one. All side effects disappeared with reduction of thalidomide dose and no patient needed to stop treatment owing to side effect. Thalidomide is a good alternative therapy to SLE patients with refractory cutaneous lesions and without any risk of pregnancy.


Brain tumor chemotherapy using a rat glioma model.
The antitumor agent chloroethylcyclohexyl-nitrosourea (CCNU) was examined using a rat glioma model. A i.p. administration of three times 40 mg/kg CCNU was highly effective and increased the life-span of tumor-bearing rats from 53 to 86%. A total quantity of CCNU amounting to less than 30 mg/kg was not effective. On the other hand, large dosages exceeding LD10 proved to be toxic. The depression of platelets and white blood cells was mild after a single dosage of 40 mg/kg CCNU which recovered on about the 6th day. In the CCNU-treated animals there was an increase of the extent of necrobiosis. Ballooning of tumor cells with nuclear pyknoses and a lack of mitotic features occurred. Microcystic changes appeared sometimes to be more frequent than in control groups.


Cytoplasmic suppression of malignancy.
Using both normal and transformed rat liver epithelial cells to prepare cytoplasmic hybrids (cybrids) we have found evidence to support the theory that the cytoplasm from a normal cell can suppress tumorigenicity. A unique aspect of this study is that all of the cells utilized, both normal and malignantly transformed, were derived from an original cloned cell. We found that fusing cytoplasts from normal cells to malignantly transformed whole cells resulted in cybrid clones which, when injected into newborn rat pups, isogenic with those from which the cell culture was initiated, yielded tumors in 51% of the animals injected compared to 92% of the animals injected with the tumorigenic parent. Those animals that did develop tumors from the cybrid cells survived longer than those injected with cells from the tumorigenic parent. Thus, the cybrid, formed of cytoplasm from both parents, was less tumorigenic than the malignantly transformed parent cell. When reconstituted cells were prepared by fusing cytoplasts from normal cells with karyoplasts from malignantly transformed cells, a situation in which essentially all of the cytoplasm of the reconstituted cell is derived from normal cells, the tumorigenic phenotype was extinguished.


How wide a urethra should we produce?
To determine the correct size for an individually tailored neourethra. The urethra to be reconstructed should be a continuation of the native, proximal urethra in both size and structure. Similarly to anorectal malformations, the normal urethra terminates where the normal healthy structure disappears, that is at the division of the corpus spongiosum, and the width at this point should be regarded as a reference feature for reconstruction. Eighty-two patients aged 10 months to 16 years admitted for primary hypospadias repair were examined. Two measurements were performed: one with the meatus intact and one after incision of the hypoplastic ventral wall to the bifurcation of the corpus spongiosum. Hegar dilators of 1-7.5 mm were used. The size of the external meatus before and after incision was compared with normal values from the literature. After incision of the external meatus, its width had increased considerably in most patients from a mean value of 2.97+/-1.107 (SD) mm to 4.17+/-0.742 mm. The mean size of the external meatus in healthy boys was 3.69+/-0.43 mm. Upon incision, the external meatus was shifted proximally from distal 50%, middle 39% and proximal 11% to 24.4%, 59.7% and 15.9%, respectively. The width of the external meatus at the division of the corpus spongiosum should be regarded as the reference size in reconstruction of a neourethra. Incision of the hypoplastic urethral wall results in a proximal shift of the external meatus and consequently in hypospadias classification.


Nurses' Experiences of Psychiatric Care in Acute Care Units with an Open Door Policy.
Social distancing and the recent lock down due to COVID-19 has increased the feeling of disconnection, isolation, and suffering in vulnerable individuals and has brought forward questions regarding open acute care psychiatric units that cannot be answered by the literature. In Greece, there is no available research on how open ward environments are perceived and experienced by mental health professionals. The aim of the present study was to illuminate nurses' experiences of working in a public psychiatric hospital which traditionally operates with open doors. Eleven nursing care providers were interviewed, and thematic analysis was employed to explore their experiences of working in locked psychiatric acute care units. Participants described nursing care in units with an open door policy as "acceptance," "availability of staff," "real respect for the person," "ensuring patients' rights," "listening to the person," and "negotiation and not imposition." Trust in therapeutic relationships was perceived as greatly dependent on the trust being given to patients indirectly by the open door policy. Being trusted enhanced patients' self-determination and self-confidence leading to their empowerment. Containment of an acute mental health crisis took place through medication and meaningful discussions with patients and significant others rather than locking the door of the unit. Overall, meaningful care led to professional emancipation, but compassion fatigue narratives emphasized the need for continuous education, support and clinical supervision as necessary support for mental health nurses in a system of mental health provision often reduced to the point of crisis.


Clinical and financial outcomes of pulmonary resection for lung cancer in safety-net hospitals.
Safety-net hospitals (SNHs) have previously been associated with inferior outcomes and greater resource use. However, this relationship has not been explored in the contemporary setting of pulmonary lobectomy. In the present national study we characterized the association between SNHs and mortality, complications, and resource use. All adults (18 years of age or older) who underwent elective lobectomy for lung cancer were identified within the 2010 to 2019 Nationwide Readmissions Database. Hospitals in the highest quartile of safety-net burden were categorized as SNHs, and others non-SNHs. Multivariable regressions were developed to assess the independent association between safety-net status and outcomes of interest. Of an estimated 282,011 patients who met inclusion criteria, 41,015 (14.5%) were treated at SNHs. Patients at SNHs were younger but as commonly female, compared with non-SNHs. After multivariable adjustment, there was no association between SNHs and mortality. However, treatment at SNHs was linked to higher odds of pneumonia (adjusted odds ratio [AOR], 1.11; 95% CI, 1.02-1.21) and prolonged ventilation (AOR, 1.36; 95% CI, 1.11-1.66), as well as infectious (AOR, 1.24; 95% CI, 1.08-1.43), intraoperative (AOR, 1.22; 95% CI, 1.07-1.39), and overall complications (AOR, 1.07; 95% CI, 1.01-1.14). Patients at SNHs also showed a greater need for a blood transfusion (AOR, 1.37; 95% CI, 1.23-1.53). In addition, SNHs were associated with increased length of stay (+0.33 days; 95% CI, 0.17-0.48) and greater costs (+$4130; 95% CI, 3.34-4.92), relative to non-SNHs. Hospital safety-net status was associated with greater odds of perioperative complications and greater health care expenditure. Further investigation is necessary uncover the mechanisms contributing to these complications and eradicate persistent disparities in lobectomy.


Postmortem revelation of sickle cell disease following fatal episode of acute bronchial asthma.
A 19-year-old black male with previous history of mild bronchial asthma presented sudden dyspnea and died in a state of respiratory distress in spite of resuscitation attempts. Autopsy showed typical lesions of acute bronchial asthma in a context of long-standing asthma associated with a massive and disseminated intravascular sickling. Hemoglobin electrophoresis diagnosed heterozygous sickle cell disease. This rare case raises the problem of the accuracy of death certificate, especially the difficulties to distinguish postmortem lesions as the underlying cause of death or the contributory cause of death.


An update on high-yield hepatocyte isolation methods and on the potential clinical use of isolated liver cells.
Isolated hepatocytes are a suitable system for the study of hepatic physiology and metabolism. They are also used for pharmacological and toxicological studies related to hepatic uptake, metabolism, excretion and toxicity of xenobiotics, as well as morphological and metabolic effects induced in the liver as a result of drug or toxic substance exposure. In this paper, the enzymatic methods for hepatocyte isolation in some mammalian species are reviewed, and methods for evaluating cell purification and assessment of cellular morphology and function are also examined. More recently, interest in hepatocyte transplantation has increased, and the clinical experimentation of hepatocyte-based liver support systems has attracted the attention of scientists and hepatologists. From a clinical perspective, using isolated hepatocytes could be useful both for supporting an acutely devastated liver, a chronically diseased liver, and for correcting genetic disorders resulting in metabolically deficient states. Reports of clinical usage of isolated allogenic hepatocytes in hepatocellular transplantation and of xenogenic liver cells in constructing bio-artificial liver support systems are promising, and are renewing interest in the development of methods for isolation and purification of hepatocytes.


[Modern therapy of diverticular disease].
New concepts are developed in the therapy of diverticular disease. 5-aminosalicylates can be administered in patients with slight forms of diverticulitis. In moderate diverticulitis antibiotics should be applied alternatively or additionally. In cases of severe diverticulitis patients should be kept fasting with parenteral nutrition and intravenous broad spectrum antibiotics. Small abscesses can be treated conservatively while abscesses larger than 4 cm should be drained in a first step and than treated surgically. A free perforation is still an absolute indication for emergency operation. In recurring diverticulitis indication for resection of the affected segment of the bowel should be considered depending on the extent of former attacks.


Physiological differences between neurons in layer 2 and layer 3 of primary visual cortex (V1) of alert macaque monkeys.
The physiological literature does not distinguish between the superficial layers 2 and 3 of the primary visual cortex even though these two layers differ in their cytoarchitecture and anatomical connections. To distinguish layer 2 from layer 3, we have analysed the response characteristics of neurons recorded during microelectrode penetrations perpendicular to the cortical surface. Extracellular responses of single neurons to sweeping bars were recorded while macaque monkeys performed a fixation task. Data were analysed from penetrations where cells could be localized to specific depths in the cortex. Although the most superficial cells (depth, 145-371 microm; presumably layer 2) responded preferentially to particular stimulus orientations, they were less selective than cells encountered immediately beneath them (depth, 386-696 microm; presumably layer 3). Layer 2 cells had smaller spikes, higher levels of ongoing activity, larger receptive field activating regions, and less finely tuned selectivity for stimulus orientation and length than layer 3 cells. Direction selectivity was found only in layer 3. These data suggest that layer 3 is involved in generating and transmitting precise, localized information about image features, while the lesser selectivity of layer 2 cells may participate in top-down influences from higher cortical areas, as well as modulatory influences from subcortical brain regions.


Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia.
The overall survival (OS) rate of adult patients suffering from acute myeloid leukaemia (AML) remains unsatisfactory at less than 40%. Current risk stratification systems fail to provide accurate guidelines for precise treatment. Novel biomarkers for predicting prognosis are urgently needed. Plexin B2 (PLXNB2), a functional receptor of angiogenin (ANG), has been found to be aberrantly expressed in multitudinous tumours. We detected overexpression of PLXNB2 mRNA in AML via transcriptome microarray analysis. This study aims to explore the potential role of PLXNB2 as a biomarker of prognosis and a prospective target of AML. qRT‒PCR was conducted to verify the expression of PLXNB2 mRNA in bone marrow mononuclear cells from AML patients. Immunohistochemical and immunofluorescence staining were performed and confirmed increased expression of PLXNB2 protein in AML bone marrow tissues. Data on PLXNB2 expression, prognosis and clinical features were accessed from multiple bioinformatic databases, including The Cancer Genome Atlas (TCGA). Genes coexpressed and correlated with PLXNB2 were identified and analysed in the TCGA AML cohort. Metascape was applied for functional and pathway enrichment analysis of genes related to PLXNB2. Small molecular agents and traditional Chinese medicines potentially targeting genes related to PLXNB2 were screened via the Connectivity Map, TCMSP and HIT databases. PLXNB2 mRNA and protein levels are higher in AML samples than in normal controls. Overexpression of PLXNB2 is associated with worse OS in AML. Patients with high PLXNB2 expression might benefit more from haematopoietic stem cell transplantation (HSCT) (indicated by prolonged OS) than those with only chemotherapy treatment. Differentially expressed genes between the high and low PLXNB2 expression groups were overlapped with PLXNB2-coexpressed genes, and genes that overlapped were enriched in immune functions, endothelial cell regulation and cell interaction gene sets, indicating the potential function of PLXNB2 in AML. A total of 36 hub genes were identified from the differentially expressed genes, and MRC1, IL10, CD163 and CCL22 had significant prognostic value for AML. Analysis of the connectivity map and traditional agents revealed that honokiol, morphines, triptolide and paeoniflorin could be potential treatment regimens. The overexpression of PLXNB2 is an adverse prognostic factor in adult AML patients and could be used as a potential biomarker. PLXNB2 might exert an oncogenic role by modulating immune functions, endothelial cell functions and cell interactions. AML patients with high PLXNB2 expression could benefit more from HSCT.


Transport of degradable/nondegradable and aged microplastics in porous media: Effects of physicochemical factors.
The degradable properties of degradable plastics allow them to form microplastics (MPs) faster. Therefore, degradable MPs may easily be transported in the underground environment. Research on degradable MPs transport in porous media is necessary and urgent. In this study, polylactic acid (PLA) and polyvinyl chloride (PVC) were selected to compare the transport differences between degradable and nondegradable MPs under different factors (flow rates, ionic strengths (ISs), pH, and coexisting cations) through column experiments, and UV irradiation was used to further simulate the effect of aging on different types of MPs. Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) were used to characterize functional groups and to determine the surface elements of MPs, respectively. The results showed that MPs were more mobile at higher flow rate, lower IS, higher pH, and monovalent cations. The order of transport capacity of MPs was PVC < aged PVC < PLA < aged PLA. This result was mainly attributed to the more negative Zeta potential and higher dispersion stability of aged PLA and PLA, which were caused by abundant O-functional groups. Compared with PVC, the O/C ratio of PLA increased significantly after aging, indicating that PLA was more prone to aging. The advection-dispersion-equation (ADE) fitted the transport data of MPs well. The interaction energy of MPs and quartz sand was accurately predicted by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. This work contributes to a comprehensive understanding of the transport of degradable MPs in the environment.


Spectroscopic and structural elucidation of 4-dimethylaminopyridine and its hydrogensquarate.
A distortion of the aromatic character and stabilization of the imino-form as a result of the protonation of 4-dimethylaminopyridine was established by IR-, UV- and 1H NMR-spectral analysis of 4-diaminopyridinium hydrogensquarate. Quantum chemical calculations were carried out at MP2 and B3LYP levels of theory and a 6-311++G** basis set with a view to determining the changes in geometrical parameters and IR-spectroscopic characteristics resulting from Npy protonation. Linear-dichroic IR-spectroscopy coupled with the orientation techniques of solid samples as liquid crystal suspensions and melted solid polycrystalline films was applied for the identification of the IR-bands, characteristic for the structural fragments of the neutral and imino-form of the pyridine derivative. The spectral results were compared with the structure, obtained by a single crystal X-ray analysis. The salt contains dimmers of hydrogensquarate anions and Npy protonated cations of which the former are stabilized by strong intermolecular OH...O interactions (2.552 angstroms and 143.1(2) degrees). The 4-diaminopyridinium cation interacts with the anion through moderate NH...O bonds (2.729 angstroms and 165.0(0) degrees ). Individual cations are pi-pi stacked with their neighbors at a distance of 3.406 angstroms.


Mechanism of interferon action. Kinetics of decay of the antiviral state and protein phosphorylation in mouse fibroblasts treated with natural and cloned interferons.
The kinetics of decay of the antiviral state and protein phosphorylation induced with natural mouse interferon (IFN) and with cloned human IFN were examined in monolayer cultures of mouse Ll929 fibroblast cells. The antiviral state measured by single cycle virus yield reduction with either vesicular stomatitis virus or reovirus decayed significantly within 2 to 3 days following removal of IFN and by 5 to 8 days virus yields had returned to the level of untreated control cells. Trypsinization of IFN-treated cells did not detectably alter the rate of decay of the antiviral state; however, the decay occurred slightly more rapidly in actively growing as compared to stationary cell cultures. The decay of the IFN-induced protein kinase which catalyzes the phosphorylation of endogenous protein P1 and purified initiation factor eIF-2 alpha correlated with the decay of the antiviral state. The decay rates of the antiviral state and protein kinase observed in mouse L929 cells that had been treated with natural mouse IFN synthesized in Newcastle disease virus-induced L929 cells were comparable to the decay rates observed in L929 cells that had been treated with recombinant human IFN-alpha A/D synthesized in Escherichia coli. The induction and decay of the antiviral state and protein kinase following treatment with a single dose of IFN did not significantly affect the sensitivity of the cell population to a subsequent treatment with a single dose of IFN. However, continuous treatment of L929 cells with natural mouse IFN or recombinant human IFN prevented the decay of both the antiviral state and protein kinase but also ultimately lead to cell death. The results suggest that protein phosphorylation may play an important role in the mechanism of IFN action in mouse L929 fibroblasts.


Rhodococcus equi and Nocardia brasiliensis infection of the brain and liver in a patient with acute nonlymphoblastic leukemia.
Resolution of neutropenia is usually followed by resolution of fever in patients with febrile neutropenia. However, in some cases fever continues even when the patient is no longer neutropenic. Described here is a case of acute myeloblastic leukemia complicated by brain abscess, pulmonary nodules, and hepatic lesions. The patient's fever had continued after the neutropenia resolved; brain and hepatic cultures grew Rhodococcus equi and Nocardia brasiliensis. Although Rhodococcus infections occur frequently in patients with HIV infection, they are uncommon in patients with acute leukemia.


Response of total belowground soil biota in Alhagi sparsifolia monoculture at different soil vertical profiles in desert ecosystem.
The soil organisms are extremely important for the land-based ecosystem. There is a growing interest in studying the variety and composition of the entire underground soil organism community at a large ecological scale. Soil organisms show different patterns in relation to soil physiochemical properties (SPPs) in various ecosystems. However, there is limited knowledge regarding their response to soil vertical profiles (SVPs) in monoculture of Alhagi sparsifolia, which is the primary shrub in the deserts of China, and is well-known for its contributions to sand dune stabilization, traditional Chinese medicine, and forage. Here, we investigated the population dynamics of soil bacteria, fungi, archaea, protists and metazoa across six different SVPs ranging from 0 to 100 cm in monoculture of A. sparsifolia, in its natural desert ecosystem. Our findings indicate that the soil biota communities displayed a declining pattern in the alpha diversity of bacteria, protists, and metazoa with an increase in soil depth. However, the opposite trend was observed for fungi and archaea. The beta diversity of soil biota was significantly affected by SVPs, particularly for metazoa, fungi and protists as revealed by Non-Metric Dimensional Scaling. The most prevalent soil bacterial, fungal, archaeal, protist, and metazoa classes were Actinobacteria, Sordariomycetes, Nitrososphaeria, Filosa-Sarcomonadea, and Nematoda, respectively. The correlation among vertical distribution of the most abundant biotic communities and variations in SPPs exhibited that the variations in total carbon (TC) and total nitrogen (TN) had the most significant influence on bacterial changes, while available potassium (AK) had an impact on fungi. Archaea were affected by TC and pH, protists by the C/N-Ratio and TP, and metazoa by TN, AK, and soil water capacity (SWC). Collectively, our findings provide a new perspective on the vertical distribution and distinct response patterns of soil biota in A. sparsifolia monoculture under natural desert ecosystem of China.


Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer.
Urothelial Cancer - Genomic Analysis to Improve Patient Outcomes and Research (NCT02643043), UC-GENOME, is a genomic analysis and biospecimen repository study in 218 patients with metastatic urothelial carcinoma. Here we report on the primary outcome of the UC-GENOME-the proportion of subjects who received next generation sequencing (NGS) with treatment options-and present the initial genomic analyses and clinical correlates. 69.3% of subjects had potential treatment options, however only 5.0% received therapy based on NGS. We found an increased frequency of TP53E285K mutations as compared to non-metastatic cohorts and identified features associated with benefit to chemotherapy and immune checkpoint inhibition, including: Ba/Sq and Stroma-rich subtypes, APOBEC mutational signature (SBS13), and inflamed tumor immune phenotype. Finally, we derive a computational model incorporating both genomic and clinical features predictive of immune checkpoint inhibitor response. Future work will utilize the biospecimens alongside these foundational analyses toward a better understanding of urothelial carcinoma biology.


Implantation of Intracranial Electrodes Predicts Worse Outcome in Mesial Temporal Lobe Epilepsy.
Anteromesial resection is an effective method for treating seizures arising from the medial temporal lobe, as these cases are often the most straightforward and have the best outcomes. Nevertheless, some patients who go on to have a mesial resection are recommended to have an implantation of electrodes before surgery. Whether the need for such an implant alters the rate of seizure freedom is not well-studied in this particular subgroup of epilepsy patients. We performed a retrospective review of consecutive anteromesial surgeries for medial temporal lobe epilepsy performed between 2005 and 2020. Of a total of 39 patients, 19 required electrode implantation (electrode group) and 20 did not (no-electrode group). The primary outcomes assessed were reduction in seizure frequency and Engel score. Complication rates were also compared. Postresection seizure frequency reduction was nonsignificantly higher in the no-electrode group (97.0 ± 10.3%) than in the electrode group (88.5 ± 23.7%, P = 0.15). The rate of Engel I outcome was nonsignificantly higher in the no-electrode group (84.2%) than in the electrode group (65.0%, P = 0.17). Major complication rates were nonsignificantly higher in the no-electrode group (15.8 ± 1.9%) than in the electrode group (5.0 ± 1.1%, P = 0.26). Power analysis revealed that 74 patients would need to be included in each group to reach statistical significance. Although not statistically significant, our study showed a trend for improved seizure control if a decision was made not to implant electrodes prior to potentially curative anteromesial resection. Engel I outcome in this group reached approximately 85%. A larger multi-instiutional study may be required to reach statistical significance.


Rough sets and social ski-driver optimization for drug toxicity analysis.
Toxicity testing is an important step for developing new drugs, and animals are widely used in this step by exposing them to the toxicants. Zebrafishes are widely used for measuring and detecting the toxicity. However, measuring and testing toxicity manually is not feasible due to the large number of embryos. This work presents an automated model to investigate the toxicity of two toxicants (3, 4-Dichloroaniline (34DCA) and p-Tert-Butylphenol (PTBP)). The proposed model consists of two steps. In the first step, a set of features is extracted from microscopic images of zebrafish embryos using the Segmentation-Based Fractal Texture Analysis (SFTA) technique. Secondly, a novel rough set-based model using Social ski-driver (SSD) is used to find a global minimal subset of features that preserves important information of the original features. In the third step, the AdaBoost classifier is used to classify an unknown sample to alive or coagulant after exposing the embryo to a toxic compound. For detecting the toxicity, the proposed model is compared with (i) three deterministic rough set reduction algorithms and (ii) the PSO-based algorithm. The classification performance rate of our model was ranged from 97.1% to 99.5% and it outperformed the other algorithms. The results of our experiments proved that the proposed drug toxicity model is efficient for rough set-based feature selection and it obtains a high classification performance.


Instrumentation: endoscopes and equipment.
The technology and instrumentation for neuroendoscopy are described: endoscopes (principles, designs, applications), light sources, instruments, accessories, holders, and navigation. Procedures for cleaning, sterilizing, and storing are included. The description is based on the author's own technical development and neuroendoscopic experience, published technology and devices, and publications on endoscopic surgery. The main work horses in neuroendoscopy are rigid glass rod endoscopes (Hopkins optics) due to the optical quality, which allows full high-definition video imaging, different angles of view, and autoclavability, which is especially important in neuroendoscopy due to the risk of Creutzfeldt-Jakob disease infection. Applications are endoscopy assistance to microsurgery, stand-alone endoscopy controlled approaches such as transnasal skull base, ventriculoscopy, and cystoscopy in the cranium. Rigid glass rod optics are also applicable in spinal endoscopy and peripheral nerve decompression using special tubes and cannulas. Rigid minifiberoptics with less resolution may be used in less complex procedures (ventriculoscopy, cystoscopy, endoscopy assistance with pen-designs) and have the advantages of smaller diameters and disposable designs. Flexible fiberoptics are usually used in combination with rigid scopes and can be steered, e.g. through the ventricles, in spinal procedures for indications including syringomyelia and multicystic hydrocephalus. Upcoming flexible chip endoscopes ("chip-in-the-tip") may replace flexible fiberoptics in the future, offering higher resolution and cold LED-illumination, and may provide for stereoscopic neuroendoscopy. Various instruments (mechanical, coagulation, laser guides, ultrasonic aspirators) and holders are available. Certified methods for cleaning and sterilization, with special requirements in neuroapplications, are important. Neuroendoscopic instrumentation is now an established technique in neurosurgical practice and is experiencing rapid development (stereoscopy, integrated operating room).


A real-life comparison of hypoglycaemia symptomatology between insulin-treated type 2 diabetes participants with and without impaired awareness of hypoglycaemia.
We aim to compare and correlate Gold and Clarke questionnaire scores with hypoglycaemic symptomatic responses between insulin-treated type 2 diabetes participants with and without IAH in a real-life study. Insulin-treated type 2 diabetes participants attending an outpatient diabetes clinic in Singapore were asked to complete the Gold and Clarke questionnaires, record capillary blood glucose (CBG) and hypoglycaemic symptoms for 4 weeks. Data were collected from 153 participants (M:F = 98:55) with mean age 61.0 ± 9.4 years, duration of diabetes 19.5 ± 8.8 years and HbA1c 68 ± 17 mmol/mol (8.4 ± 1.5%). Gold and Clarke methods classified 19.6% and 26.8% of participants with IAH, respectively. Using CBG threshold of <3 mmol/L, significantly greater proportion of participants with intact awareness were experiencing autonomic symptoms than those with IAH with either method (Gold: 69% vs. 18%, p = 0.006; Clarke: 85% vs. 46%, p = 0.010). Significantly greater proportion of participants with IAH experienced no hypoglycaemia symptoms than those with intact awareness (Gold: 3.4% vs. 36%, p = 0.015; Clarke: 3.7% vs. 31%, p = 0.031). Participants with IAH had significantly higher rates of severe hypoglycaemia in the preceding year compared to those without (Gold: 17% vs. 3.3%; Clarke: 15% vs. 2.7%, p = 0.012). Gold and Clarke questionnaires are appropriate tools in ascertaining IAH status in insulin-treated type 2 diabetes participants. This is the first time whereby the hypoglycaemia symptomology has robustly validated the Gold and Clarke questionnaire in insulin-treated type 2 diabetes participants.


Pattern of glycosaminoglycans and glycoproteins associated with nuclei of regenerating liver of rat.
1. Hyaluronic acid was detected as the largest glycosaminoglycan component in the glycosaminoglycan fraction from purified nuclei of regenerating livers as in the case of normal livers (Furukawa, K. and Tarayama, H. (1977) Biochim. Biophys. Acta 499, 278--289). However, the nuclear content of glycosaminoglycans tended to decrease after partial hepatectomy, reaching one-third of the normal liver level at 24--30 h after partial hepatectomy. On the other hand, two new polyanionic components were detected in the glycosaminoglycan fraction from regenerating liver nuclei. 2. One of these new components seems to be a sulfated glycopeptide. The 35SO4 incorporation into this component was stimulated biphasically after partial hepatectomy; the first stimulation occurring immediately after partial hepatectomy and the second stimulation occurring almost in parallel to the DNA synthesis. 3. Another polyacnionic component which also increases in the nuclear content after partial hepatectomy lacks hexuronic acid, sialic acid and 35SO4 and yet it is intensely stained by Alcian Blue. Preliminary investigations revealed the presence of hexose, ribose and phosphate as the major components. 4. In contrast to the primary localization of hyaluronic acid in the chromatin fraction and also in the nonhistone chromosomal protein fraction from it, these new polyanionic components were detected mainly in the karyosol fraction.


Determination of enantiomeric and stable isotope ratio fingerprints of active secondary metabolites in neroli (Citrus aurantium L.) essential oils for authentication by multidimensional gas chromatography and GC-C/P-IRMS.
Neroli essential oil (EO), extracted from bitter orange blossoms, is one of the most expensive natural products on the market due to its poor yield and its use in fragrance compositions, such as cologne. Multiple adulterations of neroli EO are found on the market, and several authentication strategies, such as enantioselective gas chromatography (GC) and isotope ratio mass spectrometry (IRMS), have been developed in the last few years. However, neroli EO adulteration is becoming increasingly sophisticated, and analytical improvements are needed to increase precision. Enantiomeric and compound-specific isotopic profiling of numerous metabolites using multidimensional GC and GC-C/P-IRMS was carried out. These analyses proved to be efficient for geographical tracing, especially to distinguish neroli EO of Egyptian origin. In addition, δ2H values and enantioselective ratios can identify an addition of 10% of petitgrain EO. These results demonstrate that enantioselective and stable isotopic metabolite fingerprint determination is currently a necessity to control EOs.


Predictors of functional outcomes and recurrent shoulder instability after arthroscopic anterior stabilization.
To investigate what factors might predict the results of arthroscopic stabilization for anterior shoulder instability. One hundred and forty-three patients averaging 25 (15-58) years with traumatic anterior shoulder instability who underwent arthroscopic stabilization were reviewed at a median follow-up of 81 (24-172) months. Sixty-two (56.4 %) individuals were involved in contact sport activities, and there were 40 (30 %) patients who had only one dislocation prior to having surgery. Rowe score was measured preoperatively and at follow-up. Thirty-three (23.1 %) patients experienced recurrent instability 12 (1-120) months after surgery, and 15 of those underwent further surgery. There was a statistically significant lower risk of failure (p = 0.027) for patients who had a surgical procedure after only one episode of shoulder dislocation. Patients treated after the second or further episode of shoulder dislocation exhibited a mean odds ratio for failure of 3.8 (95 % confidence interval 1.2-11.6, p = 0.044) with regard to first-time dislocators. The Rowe score significantly improved from a preoperative value of 25 (5-55) to a postoperative value of 100 (40-100) (p < 0.001). A significantly higher postoperative Rowe score was found in patients older than 24 years of age at the operation (p = 0.011) and in patients with less than eight dislocations prior to surgery (p = 0.05). These results suggest that better functional results following arthroscopic stabilization can be expected in patients over 24 years of age and in those with a fewer number of dislocations preoperatively. A lower rate of recurrence can be expected if the patient undergoes surgery after the first episode of dislocation. Prognostic study, Level II.


Aluminum of acid soils in the food chain and senility.
Aluminum is liberated from aluminosilicates of soil clays and protracted Al intake by humans in food and medications has been shown to be a potential hazard to human health. Encephalopathology, senility, and lower statistical longevity were found to be geographically and geochemically linked to acid soil conditions. We examined the interrelation of soil environmental supply of Al3+(6H2O) to the food-plant-animal-human chain (e.g., in tea leaves, approximately 1000 mg L-1) and to identified health hazards. Because F forms a strong ligand with Al, we also analyzed the extent that F accumulation is associated with Al accumulation in plants such as tea. Food and medicinal intake of Al needs to be considered in relation to kidney weakness and Al accumulation in humans. Acid soil and plant management could be modified to reduce the hazard of Al in senile dementia (2 to 4 percent of persons age greater than 65 years) and in diseases of the central nervous system endemic in certain acid soil areas.


A network approach to understand co-occurrence and relative importance of different reasons for suicide: a territory-wide study using 2002-2019 Hong Kong Coroner's Court reports.
Suicide is a complex and multifaceted issue, and suicidal behaviors are often driven by multiple, interacting factors. It has been challenging to identify reasons for suicide using existing scientific methodologies. This study aims to identify critical reasons for suicide and suicidal behaviors through the application of novel network science methods. Based on cases investigated by the Hong Kong Coroner's Court from 2002 to 2019, we modelled identified reasons for 13,001 suicide cases as a co-occurrence network, and calculated each reason's eigencentrality to determine their respective relative importance. We then analyzed the temporal and demographic changes in the structure and eigencentrality of the network. We further conducted simulation studies based on the United Nations population projection to assess potential burden of different reasons for suicide on the population in the coming years. School-related issues had the highest eigencentrality (eigencentrality = 0.49) for individuals younger than 20 years of age. Financial issues were crucial for adults aged 20-59 years, but their importance differed between males (eigencentrality = 0.51) and females (eigencentrality = 0.14). Physical illness (eigencentrality = 0.80) was the core concern for adults over 60 years. Across the Hong Kong population, the reasons for suicide appear to have shifted from financial issues in the early 2000s (eigencentrality = 0.46) to issues related to physical illnesses since 2011 (eigencentrality = 0.58). Simulation findings indicate that, by 2050, most suicides in Hong Kong will be due to physical illness-related issues (eigencentrality = 0.69) due to the rapidly aging population. There have been important sex and age differences over time, in reasons for suicide. Given the projected increasing age of the Hong Kong population over the next decades, older adults with physical illnesses appear to be the highest contributors to suicide cases in the overall population. This novel network analysis approach provides important data-driven information upon which to base effective proactive public health suicide prevention strategies and interventions. Hong Kong Jockey Club Charities Trust, Collaborative Research Fund (C7151-20G), and General Research Fund (17606521).


The SCAR/WAVE complex is necessary for proper regulation of traction stresses during amoeboid motility.
Cell migration requires a tightly regulated, spatiotemporal coordination of underlying biochemical pathways. Crucial to cell migration is SCAR/WAVE-mediated dendritic F-actin polymerization at the cell's leading edge. Our goal is to understand the role the SCAR/WAVE complex plays in the mechanics of amoeboid migration. To this aim, we measured and compared the traction stresses exerted by Dictyostelium cells lacking the SCAR/WAVE complex proteins PIR121 (pirA(-)) and SCAR (scrA(-)) with those of wild-type cells while they were migrating on flat, elastic substrates. We found that, compared to wild type, both mutant strains exert traction stresses of different strengths that correlate with their F-actin levels. In agreement with previous studies, we found that wild-type cells migrate by repeating a motility cycle in which the cell length and strain energy exerted by the cells on their substrate vary periodically. Our analysis also revealed that scrA(-) cells display an altered motility cycle with a longer period and a lower migration velocity, whereas pirA(-) cells migrate in a random manner without implementing a periodic cycle. We present detailed characterization of the traction-stress phenotypes of the various cell lines, providing new insights into the role of F-actin polymerization in regulating cell-substratum interactions and stresses required for motility.


Expression of c-myc RNA in bursal lymphoma cell lines: identification of c-myc-encoded proteins by hybrid-selected translation.
We examined expression of the c-myc locus in four cell lines established from bursal lymphomas induced by avian leukosis virus. In all four lines the level of myc-related RNA was elevated. In three lines a majority of the myc-containing RNAs lacked viral-LTR-related sequences, in contrast to results obtained with primary tumors. This suggests that LTR sequences are not required for maintenance of high level c-myc expression. One line, RP9, has a complex pattern of myc RNAs containing LTR sequences, and one of these RNAs is packaged into virions. Using hybrid selection of RNAs with myc DNA, followed by in vitro translation, we detected translation of myc-related proteins from RNA of all four cell lines. The sizes of these proteins differ among the cell lines. The major polypeptides detected were 64, 57, and 54 kilodaltons. Events leading to elevation of c-myc transcription may be accompanied by alterations in mRNA initiation or processing that generate different protein products.


Hippocampus and amygdala: An insight-related network involved in metaphorical solution to mental distress problem.
This study was designed to determine whether metaphorical solutions to mental distress problems result in an insightful mental experience and activate the hippocampus and amygdala: areas associated with insight. We recruited 22 healthy university students. Trials presented 75 micro-counseling scenarios while event-related functional magnetic resonance imaging (fMRI) was applied to detect neural responses. Each scenario included a mental distress problem and one of the following solution types: metaphorical, literal, or problem-restatement. The results revealed that, compared with literal solutions or problem-restatement solutions, metaphorical solutions activated two neural networks: one associated with basic metaphorical language processing (i.e., the left inferior frontal gyrus and middle and superior temporal gyri), and a specific network associated with insightful problem solving (i.e., the bilateral hippocampus, amygdala, and fusiform gyrus). Our findings indicate that the use of metaphorical solutions to mental distress problems reliably produces salient neural activities for insight.


Enhanced modified moving average analysis of T-wave alternans using a curve matching method: a simulation study.
T-wave alternans (TWA) are beat-to-beat amplitude oscillations in the T-waves of electrocardiograms (ECGs). Numerous clinical studies have demonstrated the link between these oscillations and ventricular arrhythmias. Several methods have been developed in recent years to detect and quantify this important feature. Most methods estimate the amplitude differences between pairs of consecutive T-waves. One such method is known as modified moving average (MMA) analysis. The TWA magnitude is obtained by means of the maximum absolute difference of even and odd heartbeat series averages computed at T-waves or ST-T complexes. This method performs well for different levels of TWA, noise, and phase shifts, but it is sensitive to the alignment of the T-waves. In this paper we propose a preprocessing stage for the MMA method to ensure an optimal alignment of such averages. The alignment is performed by means of a continuous time warping technique. Our assessment study demonstrates the improved performance of the proposed algorithm.


Clinical application of a solid three-dimensional model for orbital wall fractures.
Orbital wall fractures have been diagnosed conventionally by plain X-rays, CT imaging, and more recently by three-dimensional CT imaging. However, it is not easy to know the three-dimensional appearances of orbital wall fractures. Anatomically precise reconstruction of the orbital wall is essential for the appearance and function of the eyes. Life-size solid models of fractured orbital walls and also solid models of bone grafts for the reconstruction were produced by milling polyurethane foam on the basis of CT data. These models are very valuable because they provide not only satisfactory understanding of the three-dimensional morphology, but the models at hand are the ideal guides during the operation, and the prefabricated bone grafts, based on the models make a complete surgical simulation.


Synthesis of 3-dialkylaminopropyl-2-thiohydant derivatives as potential antiarrhythmic agents.
A series of 3-dialkylaminopropyl-5-monosubstituted-2-thiohydantoins were synthesized as potential antiarrhythmic agents; their pharmacological activity is comparable to that of quinidine, but weaker than that of phenytoin.


Stability and characterization of mixture of three particle system containing ZnO-CuO nanoparticles and clay.
The aim of this study was to understand heteroaggregation of mixture of ZnO and CuO nanoparticles (NPs) with clay, for the first time as per the authors' knowledge. Aggregation studies of mixture of ZnO and CuO nanoparticles with clay was done (ionic strength =5 mM; pH 7; nanoparticles concentration = 0.1 mg/L, 1 mg/L, 10 mg/L; Clay concentration = 1, 10, and 100 mg/L and HA concentration = 0.1,1, and 10 mg/L as total organic carbon). Critical coagulation concentration (CCC) and attachment efficiency values of suspensions with ZnO: CuO ratio = 0.1, 1, 10 were also determined. Aggregation and liquid portions of mixture suspension at equal mass ratio were characterized for size, zeta potential (ZP), metal and ion contents, pH and conductivity. Results indicated that CCC was found to be 120.7 mM for ZnO: CuO ratio 10 and 1144 mM for ZnO: CuO ratio 1. Values of attachment efficiency were obtained to be 0.9 and 0.8 for these two ZnO:CuO ratio. At natural water ionic strength (IS) condition, aggregate rate constant of mixture of particles ranged from 0.281 to 8.63 nm/min for 10 mg/L NP concentration. Aggregation in suspension containing mixture of particles was found to be affected by NP concentration, clay concentration, and humic acid (p < 0.05). During a 1-h aggregation study, 2.67 mg Cu metal/g aggregate and 0.38 mg Zn/g aggregate were found in aggregates of 5 mM suspension. Overall, this study provided information on aggregation characterization of mixture of metal oxide nanoparticles (ZnO and CuO) in HA and clay presence, which is useful in understanding aggregation formation and in characterizing exposure dose for environmental risk assessment. More detailed information on a three -particle system with natural colloids is required for predicting their fate in aquatic system and defining risk.


A mixed method study to compare use and experience of hospital care and a nurse-led acute respiratory assessment service offering home care to people with an acute exacerbation of chronic obstructive pulmonary disease.
Over the past 10 years hospital at home schemes for the treatment of an acute exacerbation of Chronic Obstructive Pulmonary Disease have proliferated throughout developed countries. For selected patients treatment at home is no less advantageous in terms of readmission rates and length of stay than treatment in hospital. Although care at home might seem to be a more desirable option than admission to hospital, little is known about care preferences and how people exercise service choice. 1. to determine patients' recent use of and satisfaction with health care services during exacerbations of Chronic Obstructive Pulmonary Disease. 2. To determine and compare patients' and families' perceived future care preferences. 3. To complete an in-depth exploration of care experiences and preferences with a subset of respondents and their families. A mixed method design was used consisting of a postal survey and in-depth qualitative interviews with a subset of questionnaire respondents. An outreach service provided by a large university hospital within Scotland, UK. One hundred and four out-patients registered with the Acute Respiratory Assessment Service and who had experienced hospital inpatient care during the past year, and their families. A subset of respondents was invited to take part in qualitative interviews. The majority of respondents indicated a preference for the home care service, and this was positively associated with high coping skills. There was a strong relationship between personal and family preferences. There was no linear relationship between a clinical measure of severity of lung disease and service use or care preferences. Results from the qualitative interviews endorsed and explained these findings. A range of factors combined to influence service use at a particular point in time, implying a need for increased self-management support from nurses and increased service provision.


Collagen vascular diseases.
Collagen vascular diseases are multisystem disorders that frequently affect the skin. At times, cutaneous disease is the initial manifestation. This article focuses on lupus erythematosus, dermatomyositis, and sclerodermoid syndromes.