Fetal and Early postnatal development of adenylate cyclase and cyclic AMP phosphodiesterase activities in rat brain.
Brain cyclic AMP metabolism was studied in rat offspring at 17, 19 and 21 days of intrauterine life and 0, 1 and 4 postnatal days. Wet weight and protein and DNA and RNA concentrations in brain increased in parallel with body weight until the 4th postnatal day although during the perinatal phase some of these parameters suffered a manifest temporal retardation. In the brain, similar qualitative changes were observed in both adenylate cyclase and high Km cyclic AMP phosphodiesterase activity while the low Km enzyme showed a rise from 17-day fetuses to those of 19 days with no further changes. The increase in cyclic AMP concentration was very mild and the values found in the 21-day fetuses were already similar to those in adults. In the mother's brain a significant reduction in adenylate cyclase activity appeared at 19 and 21 days of gestation. The retardation in the ontogenic development of cyclic AMP metabolism during the perinatal phase in offspring is probably a consequence of their specific metabolic situation while in the mother it may be the result of its endocrine preparation for parturition.


Exploring Vocational Evaluation Practices following Traumatic Brain Injury.
Individuals with traumatic brain injury (TBI) face many challenges when attempting to return to work (RTW). Vocational evaluation (VE) is a systematic process that involves assessment and appraisal of an individual's current work-related characteristics and abilities. The aims of this study are to (1) examine demographic and employment characteristics of vocational rehabilitation providers (VRPs), (2) identify the specific evaluation methods that are used in the VE of individuals with TBI, and (3) examine the differences in assessment method practices based upon evaluator assessment preferences. This exploratory case study used a forty-six-item online survey which was distributed to VRPs. One hundred and nine VRPs accessed the survey. Of these, 74 completed the survey. A majority of respondents were female (79.7%), Caucasian (71.6%), and holding a master's degree (74.3%), and more than half (56.8%) were employed as state vocational rehabilitation counselors (VRCs). In addition, over two-thirds (67.6%) were certified rehabilitation counselors (CRCs). Respondents reported using several specific tools and assessments during the VE process. Study findings reveal differences in use of and rationales for specific assessments amongst VRPs. Understanding VRP assessment practices and use of an evidence-based framework for VE following TBI may inform and improve VE practice.


[Sick sinus syndrome and permanent cardiac pacing].
The authors submit a retrospective analysis of 140 patients with an affection of the sinoatrial node who had a permanent cardiac pacemaker. The analysis comprises an 18-month period; the patients were from the eastern Slovakian region. The authors emphasize different affections of the sinoatrial node and discuss various ways of permanent cardiac pacing and other types of non-pharmacological treatment (e.g. electric ablation). Diseases of the sinoatrial node account for as much as 40% of implantations of a permanent pacemaker on account of bradyarrhythmia. At the clinic this implies a quantitative increase of cardiac pacing on account of diseases of the sinoatrial node by 18%, as compared with a previous period (e.g. the average for 1978-1987). A qualitative change is the introduction of physiological permanent cardiac pacing.


Uptake as a determinant of methotrexate response in mouse leukemias.
Methotrexate-promoted survival of mice bearing different transplantable leukemias was compared with uptake of the drug by leukemia cells in vitro. A high degree of correlation (r(2) = 0.88) showed that uptake may be a major determinant of the antitumor activity of methotrexate against transplantable mouse leukemias.


Self-determined Occupational Performance Model for Children From Economically Disadvantaged Backgrounds.
Background. Children from low-income backgrounds have a higher incidence of handwriting challenges due to the unique social and environmental stressors associated with poverty. Additionally, children from economically disadvantaged households are at risk for motor, cognitive, and social deficits, which further impact their handwriting performance. Purpose. The purpose of this paper is to propose a theoretical model that provides a holistic perspective for addressing the handwriting needs of children from low-socioeconomic backgrounds. Key Issues. The presented conceptual model is derived from the person-environment-occupation model for occupational performance and self-determination theory. These theories reciprocally complement and enhance each other, providing a foundation from which clinicians can guide evaluation and intervention. Implications. Through the use of the proposed model, evaluation and intervention focus on intrinsic motivation while considering the physical, social, and cultural impacts on a child's occupational performance. The provider connects with the child's basic psychological needs, thus improving handwriting outcomes and facilitating improved academic performance.


High-throughput sequencing of microbial community diversity in soil, grapes, leaves, grape juice and wine of grapevine from China.
In this study Illumina MiSeq was performed to investigate microbial diversity in soil, leaves, grape, grape juice and wine. A total of 1,043,102 fungal Internal Transcribed Spacer (ITS) reads and 2,422,188 high quality bacterial 16S rDNA sequences were used for taxonomic classification, revealed five fungal and eight bacterial phyla. At the genus level, the dominant fungi were Ascomycota, Sordariales, Tetracladium and Geomyces in soil, Aureobasidium and Pleosporaceae in grapes leaves, Aureobasidium in grape and grape juice. The dominant bacteria were Kaistobacter, Arthrobacter, Skermanella and Sphingomonas in soil, Pseudomonas, Acinetobacter and Kaistobacter in grape and grapes leaves, and Oenococcus in grape juice and wine. Principal coordinate analysis showed structural separation between the composition of fungi and bacteria in all samples. This is the first study to understand microbiome population in soil, grape, grapes leaves, grape juice and wine in Xinjiang through High-throughput Sequencing and identify microorganisms like Saccharomyces cerevisiae and Oenococcus spp. that may contribute to the quality and flavor of wine.


"It's like losing a part of my family": transition expectations of adolescents living with perinatally acquired HIV and their guardians.
The increased life expectancy of perinatally HIV-infected adolescents necessitates the transition from pediatric to adult infectious disease care. Significant differences exist between pediatric and adult HIV clinic models, and adequate preparation is critical for successful transition. The expectations of youth on the cusp of this transition and their guardians have not previously been explored. Semistructured interviews were conducted with 40 perinatally infected adolescents (mean age, 17.3 years; 90% African American; 57.5% female; 57.5% in high school) currently receiving care in a pediatric infectious disease clinic in the southeast United States and 17 guardians about their expectations related to the pending transition to adult care. Interviews were transcribed and coded for emergent themes. Many adolescents had difficulty articulating expectations of their transition to an adult clinic, reporting they did not know what to expect. Others looked forward to increased responsibility and control, while some expressed concerns over leaving their current providers and having to establish new relationships. Most guardians viewed the transition to adult care as a tool to facilitate maturity. Several indicated they had not discussed transition with their child and were waiting for their child to initiate a conversation about it. Given the importance providers place on preparing youth for transition, it is surprising that many adolescents had no expectations about this impending change. This indicates a need for improved communication between providers and adolescents to enhance preparation and ultimately transition success. Additionally, guardians play an important role in the transition process and may need support to discuss this process with their child.


Development and validation of liquid chromatography combined with tandem mass spectrometry methods for the quantitation of simalikalactone E in extracts of Quassia amara L. and in mouse blood.
Simalikalactone E (SkE) from Quassia amara, has been proved to be a valuable anti-malarial and anti-cancer compound. As SkE is very scarce, methods of quantitation are needed in order to optimise its isolation process and to determine pharmacokinetic data. To validate methods using liquid chromatography coupled to mass spectrometry for the quantitation of SkE in plant extracts and in biological fluids. High- and ultrahigh-performance liquid chromatography (UHPLC) coupled to ion trap mass spectrometry (MS) with single ion monitoring detection and to triple quadrupole-linear ion trap tandem mass spectrometry with multiple reaction monitoring detection methods were developed. Validation procedure was realised according to the International Conference on Harmonisation guideline. Methanol extracts of dried Quassia amara leaves, and mouse-blood samples obtained after various routes of administration, were analysed for SkE. Methods were validated and gave similar results regarding the content of SkE expressed per kilogram of dry leaves in the traditional decoction (160 ± 12 mg/kg) and in the methanol extract (93 ± 2 mg/kg). The recovery of the analyte from mouse blood ranged from 80.7 to 119.8%. Simalikalactone E was only detected using UHPLC-MS/MS (0.2 ± 0.03 mg/L) in mouse blood after intravenous injection: none was detected following intraperitoneal or oral gavage administration of SkE. The LC-MS methods were used for the quantitation of SkE in plant extracts and in mouse blood. These methods open the way for further protocol optimisation of SkE extraction and the determination of its pharmacokinetic data.


Diphencyprone in the treatment of long-standing alopecia areata.
Thirty-six patients with alopecia areata of 1-54 years duration entered a study of treatment with the contact allergen diphencyprone for 8 months. Following sensitization the diphencyprone was applied to one half of the scalp at weekly intervals, the other half acting as a control. Once hair growth was established on one side, the other side was treated. Seven patients did not continue treatment and one patient showed spontaneous regrowth. Of the remaining 28 patients who persisted with treatments, fourteen (50%) regrew hair on the treated side; eight (29%) had a cosmetically acceptable result with the regrowth of terminal hair over the whole scalp. No statistically significant differences were found in age or duration of alopecia between those who regrew and those who did not. We have found diphencyprone to be an effective stimulator of hair growth in patients with severe and long-standing alopecia areata.


Three-dimensional diamagnetic particle deflection in ferrofluid microchannel flows.
Magnetic field-induced particle manipulation is a promising technique for biomicrofluidics applications. It is simple, cheap, and also free of fluid heating issues that accompany other common electric, acoustic, and optical methods. This work presents a fundamental study of diamagnetic particle motion in ferrofluid flows through a rectangular microchannel with a nearby permanent magnet. Due to their negligible magnetization relative to the ferrofluid, diamagnetic particles experience negative magnetophoresis and are repelled away from the magnet. The result is a three-dimensionally focused particle stream flowing near the bottom outer corner of the microchannel that is the farthest to the center of the magnet and hence has the smallest magnetic field. The effects of the particle's relative position to the magnet, particle size, ferrofluid flow rate, and concentration on this three-dimensional diamagnetic particle deflection are systematically studied. The obtained experimental results agree quantitatively with the predictions of a three-dimensional analytical model.


Vandetanib-induced inhibition of neuroblastoma cell migration and invasion is associated with downregulation of the SDF-1/CXCR4 axis and matrix metalloproteinase 14.
Rearranged during transfection (RET) is widely expressed in neuroblastoma (NB) and partly contributes to high metastatic potential and survival of NB. The aim of the present study was to investigate whether vandetanib (a RET inhibitor) inhibits proliferation, migration and invasion of NB cells in vitro. The effects of vandetanib on the proliferation, apoptosis and cell cycle and on RET phosphorylation of SK-N-SH and SH-SY5Y cells were evaluated in vitro. The migration and invasion potential of vandetanib-treated NB cells were analyzed using Transwell cell migration and invasion assays, respectively. qPCR, western blotting and immunofluorescence were used to detect mRNA and protein levels in NB cells treated with vandetanib. Our data demonstrated that vandetanib inhibits the proliferation of SK-N-SH and SH-SY5Y cells and that this inhibition is mediated by the induction of G1 phase cell cycle arrest at lower concentrations and by apoptosis at higher concentrations. In the presence of vandetanib, the migration and invasion of two NB cell lines were markedly decreased compared with the control group (p<0.01). In addition, our data showed that the levels of C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinase 14 (MMP14) mRNA expression in NB cell lines treated with vandetanib were significantly lower than those in the cells that were treated with vehicle (p<0.01) and similar results were obtained for protein levels as determined by western blotting and immunofluorescence analysis. Vandetanib may inhibit the proliferation, migration and invasion of NB cells in vitro. The potential mechanisms for the inhibition of NB migration and invasion by vandetanib may partly be attributed to the ability of vandetanib to suppress the expression of CXCR4 and MMP14 in human NB cells.


Sweet's syndrome associated with Salmonella typhimurium infection.
A 41-year-old woman presented with the typical clinical and pathohistological features of acute febrile neutrophilic dermatosis (AFND). The disease had been preceded by diarrhoea and vomiting for 2 weeks. Stool cultures proved positive for Salmonella typhimurium infection. Antibiotic therapy and tapering oral steroids led to a complete remission of skin lesions within 2 weeks. To our knowledge, this is the first report of Sweet's syndrome associated with salmonellosis.


[EVALUATION OF FIBULAR HEAD RESECTION IN PROSTHETIC REPLACEMENT FOR NEOPLASMS OF PROXIMAL TIBIA IN LIMB SALVAGE SURGERY].
To investigate the effects of fibular head resection in prosthetic replacement for neoplasms of the proximal tibia in limb salvage surgery. Between July 1999 and March 2013, 76 patients with neoplasms of the proximal tibia underwent tumor resection, prosthetic replacement, and gastrocnemius medial head flap transfer. Among them, 38 patients underwent fibular head resection (group A) and 38 underwent fibular head preservation (group B). There was no significant difference in gender, age, side, tumor classification and stage, and disease duration between 2 groups (P > 0.05). The complications and the position of the components were observed, and American society for bone tumors scoring system (MSTS93) was used to evaluate the joint function. All patients were followed up 12-150 months (mean, 87 months). Incision infection occurred in 1 patient (2.63%) of group A and 6 patients (15.79%) of group B, showing significant difference (χ2 = 3.934, P = 0.047). Necrosis of gastrocnemius medial head flap was found in 1 patient of group A and 2 patients of group B. Prosthetic loosening and instability of the knee were observed in 4 and 2 cases of group A and in 6 and 4 cases of group B, respectively. In groups A and B, there were 3 and 5 cases of local recurrence, 7 and 6 cases of distant metastasis, and 8 and 7 deaths, respectively. According to MSTS93, the results were excellent in 23 cases, good in 10 cases, fair in 3 cases, and poor in 2 cases, with an excellent and good rate of 86.84% in group A; the results were excellent in 21 cases, good in 11 cases, fair in 3 cases, and poor in 3 cases, with an excellent and good rate of 84.21% in group B; and no significant difference was found in the excellent and good rate between 2 groups (χ2 = 0.106, P = 0.744). Fibular head resection in prosthetic replacement for neoplasms of the proximal tibia in limb salvage surgery is beneficial to intra-operative tissue coverage, and it can reduce trauma by skin transplantation and related complications. Good stability and motion of the joint can be obtained after operation.


Thalidomide as palliative treatment in patients with advanced secondary glioblastoma.
For its numerous abilities including sedation, we have been using thalidomide (TH) as the 'last therapeutic option' in patients with advanced gliomas. We noticed that a small subgroup, i.e. patients with secondary glioblastoma (GBM, whose GBM has evolved over several months or years from a less malignant glioma), survived for prolonged periods. Therefore, we retrospectively evaluated the outcomes of patients with secondary GBM treated with TH at our centre. Starting in the year 2000, we have studied 23 patients (13 females, 10 males, with a median age of 31.5 years) with secondary GBM who have received palliative treatment with TH 100 mg at bedtime. All patients had previously undergone radiotherapy and received at least 1 and up to 5 regimens of chemotherapy. The median duration of TH administration was 4.0 months (range 0.8-32). The median duration of overall survival after the start of TH therapy was 18.3 months (range 0.8-57). Eleven patients with secondary GBM survived longer than 1 year. Symptomatic improvement was most prominent in the restoration of a normal sleep pattern. The palliative effects of TH, especially the normalization of a sleep pattern, were highly valued by patients and families. The prolongation of survival of patients with secondary GBM has not been reported previously.


Methodological issues in health human resource planning: cataloguing assumptions and controlling for variables in needs-based modelling.
Health Human Resource Planning (HHRP) models approximate future nursing requirements based on a variety of factors specific to the model being employed. There is an urgent need to develop a better understanding of the sources of bias in statistical modelling in order to ensure that we are guided by accurate and robust formulae. This paper addresses these issues as they apply in the context of needs-based HHRP research for nursing by presenting a review and discussion of the relevant literature as it relates to: (1) the testing of assumptions, (2) avoiding ecological and atomistic fallacies, (3) how need is directly or indirectly related to health care, and (4) alternatives to aggregate analysis for assessing the relationship between health needs and utilization of nursing services. The paper concludes that multilevel modelling is useful for the simulation analysis of individuals and their ecologies, and that small area variation modelling holds promise for assessing the relationship between health needs and utilization of nursing services.


Impaired nitrazepam metabolism in hypothyroidism.
Delayed metabolism of a number of drugs has been described in hypothyroid patients. We report an elderly hypothyroid female who had prolonged delay in the metabolism of a commonly-used sedative, nitrazepam, and discuss the importance of delayed drug metabolism in hypothyroidism.


Bacteria Endosymbiont, Wolbachia, Promotes Parasitism of Parasitoid Wasp Asobara japonica.
Wolbachia is the most widespread endosymbiotic bacterium that manipulates reproduction of its arthropod hosts to enhance its own spread throughout host populations. Infection with Wolbachia causes complete parthenogenetic reproduction in many Hymenoptera, producing only female offspring. The mechanism of such reproductive manipulation by Wolbachia has been extensively studied. However, the effects of Wolbachia symbiosis on behavioral traits of the hosts are scarcely investigated. The parasitoid wasp Asobara japonica is an ideal insect to investigate this because symbiotic and aposymbiotic strains are available: Wolbachia-infected Tokyo (TK) and noninfected Iriomote (IR) strains originally collected on the main island and southwest islands of Japan, respectively. We compared the oviposition behaviors of the two strains and found that TK strain females parasitized Drosophila melanogaster larvae more actively than the IR strain, especially during the first two days after eclosion. Removing Wolbachia from the TK strain wasps by treatment with tetracycline or rifampicin decreased their parasitism activity to the level of the IR strain. Morphological and behavioral analyses of both strain wasps showed that Wolbachia endosymbionts do not affect development of the host female reproductive tract and eggs, but do enhance host-searching ability of female wasps. These results suggest the possibility that Wolbachia endosymbionts may promote their diffusion and persistence in the host A. japonica population not only at least partly by parthenogenesis but also by enhancement of oviposition frequency of the host females.


CYP2C19- and CYP3A4-dependent omeprazole metabolism in West Mexicans.
Omeprazole has been used as a drug probe for CYP2C19, but no systematic data are available for Mexican populations. The aim of this study was to evaluate the phenotype frequencies of the CYP2C19 polymorphism in West Mexicans. Besides omeprazole, sulfone was measured to evaluate CYP3A4 after administration of the 20-mg dose to 127 healthy volunteers. Logarithms of metabolic indexes of omeprazole/hydroxyomeprazole for CYP2C19 and omeprazole/omeprazole sulfone for CYP3A4 had trimodal distributions. Five subjects (4%) had a log CYP2C19 metabolic index below -0.9, suggesting an ultra-extensive phenotype. Poor metabolizers (log metabolic index > 0.6) were 6%. For CYP3A4, 11 subjects (9%) were below -0.3 of the log metabolic index. The log metabolic index of omeprazole/omeprazole sulfone was above the antimode of 0.6 for 11% of this population. The mean log metabolic index of CYP3A4 extensive metabolizers (80%) was 0.166, which seems to be higher than the data described for Caucasians and lower than that for Asians.


Telescopic Dental Needles versus Conventional Dental Needles: Comparison of Pain and Anxiety in Adult Dental Patients of Kerman University of Medical Sciences-A Randomized Clinical Trial.
Pain felt during dental injections is dependent on dental anxiety. Patients feel increased pain if anxiety in the treatment environment is high, and therefore it is important to reduce anxiety during treatment to reduce pain. The purpose of this study was to compare pain and anxiety levels experienced during injections using a newly invented telescopic-coated dental needle that covers the conventional needle and also has the capability of applying topical anesthesia through its unique design with the conventional dental injection needle. Dental injection anxiety questionnaires were completed by 60 adult patients who were randomly assigned to either the telescopic (a newly invented telescopic-coated dental needle that covers the needles) or the conventional group. Patients also completed visual analog scales to rate their pain perception during injection, their overall experience, and their future anticipated anxiety. Wilcoxon, Mann-Whitney, and Student t tests were used for statistical analysis. Statistical significance was defined as P < .05. A total of 25 men and 35 women with an age range of 19-55 years (mean age of 38.7 ± 2.31 years) participated in this study. Pain levels reported during the injection using the telescopic-coated needle (4.13 ± 1.37) were significantly lower than those using the conventional needle (5.63 ± 1.57), with statistically significant differences between the 2 groups (P < .05). Patients experienced significantly lower overall postinjection anxiety (P < .05) and had more positive overall experience ratings with the telescopic-coated needles. A new telescopic-coated dental needle was superior to a conventional injection system in pain perception and in reducing postinjection dental anxiety.


Prevalence and Pattern of Internet Addiction Among Adolescents in Ibadan, Nigeria: A Cross-Sectional Study.
Background and objective Despite the potential benefits the Internet offers, it is prone to excessive and uncontrolled use, thus resulting in a condition called Internet addiction (IA). This study aimed to describe the prevalence of Internet addiction (IA) among in-school adolescents in Ibadan, Southwest Nigeria. Materials and methods A descriptive cross-sectional study was conducted among 632 adolescents using a two-stage sampling technique. IA was assessed using the 20-question Internet addiction test (IAT). Responses to each question ranged from "0" (i.e., "never") to "5" (i.e., "always"). Cumulative IAT scores > 50% suggested the presence of IA. Chi-square tests were conducted to determine the association between adolescents' characteristics and IA. Statistically significant variables were pooled into the binary logistic regression model. P-values < 0.05 were statistically significant. Results The mean age of the adolescents was 16.03 ± 1.26 years, and 347 (54.9%) were males. A total of 284 (44.9%) adolescents had IA: 174 (42%) accessed the Internet in both home and school settings (ᵡ2 = 4.103, p = 0.043), and 174 (42%) accessed the Internet at home only (ᵡ2 = 5.003, p = 0.025). Adolescents who accessed the Internet from both home and school settings had higher odds of developing IA (adjusted odds ratio (AOR) = 1.408, 95% confidence interval (CI) = 0.986-2.012, p = 0.060), as well as those who accessed the Internet from home settings only (AOR = 1.404, 95%CI = 1.010-1.953, p = 0.043). Adolescents who gained four to six hours of Internet connection weekly had two times odds of developing IA (AOR = 1.404, 95%CI = 1.010-1.953, p = 0.043), and those who gained more than six hours of Internet connection had more than three times odds of developing IA (AOR = 3.424, 95%CI = 1.937-6.053, p = 0.043). Conclusion To prevent IA, adolescents should develop self-control skills and self-regulation of Internet use. Likewise, Internet access should be restricted from both home and school settings, and adolescents' Internet access should be monitored and regulated from both home and school settings.


Delay in the diagnosis and treatment of pulmonary tuberculosis in Uzbekistan: a cross-sectional study.
Early diagnosis and prompt effective therapy are crucial for the prevention of tuberculosis (TB) transmission, particularly in regions with high levels of multi-drug resistant TB. This study aimed to evaluate the extent of delay in diagnosis and treatment of TB in Uzbekistan and identify associated risk factors. A cross-sectional study was performed on hospital patients with newly diagnosed TB. The time between the onset of respiratory symptoms and initiation of anti-TB treatment was assessed and delays were divided into patient, health system and total delays. Univariable and multivariable logistic regression analysis was used to evaluate determinants of diagnostic and treatment delay. Among 538 patients enrolled, the median delay from onset of symptoms until treatment with anti-TB drugs was 50 days. Analysis of the factors affecting health-seeking behaviour and timely treatment showed the presence of the patient factor. Self-medication was the first health-seeking action for 231 (43%) patients and proved to be a significant predictor of delay (p = 0.005), as well as coughing (p = 0.009), loss of weight (p = 0.001), and visiting private and primary healthcare facilities (p = 0.03 and p = 0.02, respectively). TB diagnostic and treatment delay was mainly contributed to by patient delay and should be reduced through increasing public awareness of TB symptoms and improving public health-seeking behaviour for timely initiation of anti-TB treatment. Efforts should be made to minimise irrational use of antibiotics and support interventions to restrict over-the-counter availability of antibiotics.


Mechanisms influencing the factors of urban built environments and coronavirus disease 2019 at macroscopic and microscopic scales: The role of cities.
In late 2019, the coronavirus disease 2019 (COVID-19) pandemic soundlessly slinked in and swept the world, exerting a tremendous impact on lifestyles. This study investigated changes in the infection rates of COVID-19 and the urban built environment in 45 areas in Manhattan, New York, and the relationship between the factors of the urban built environment and COVID-19. COVID-19 was used as the outcome variable, which represents the situation under normal conditions vs. non-pharmacological intervention (NPI), to analyze the macroscopic (macro) and microscopic (micro) factors of the urban built environment. Computer vision was introduced to quantify the material space of urban places from street-level panoramic images of the urban streetscape. The study then extracted the microscopic factors of the urban built environment. The micro factors were composed of two parts. The first was the urban level, which was composed of urban buildings, Panoramic View Green View Index, roads, the sky, and buildings (walls). The second was the streets' green structure, which consisted of macrophanerophyte, bush, and grass. The macro factors comprised population density, traffic, and points of interest. This study analyzed correlations from multiple levels using linear regression models. It also effectively explored the relationship between the urban built environment and COVID-19 transmission and the mechanism of its influence from multiple perspectives.


Use of sodium zirconium cyclosilicate for up-titration of renin-angiotensin-aldosterone system inhibitor therapy in patients with heart failure: a case series.
Patients often receive suboptimal dosing of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy over concerns of hyperkalaemia. However, studies have shown associations between suboptimal dosing or interruptions to therapy and adverse clinical events. Therefore, effective treatments for hyperkalaemia that can enable optimal RAASi therapy are needed. This case series examines eight patients whose commencement on the novel potassium binder sodium zirconium cyclosilicate (SZC) allowed for the initiation and/or up-titration of RAASi therapy. Eight patients aged 64-87 years with heart failure (HF) with reduced ejection fraction all developed hyperkalaemia (serum potassium (sK+) >5.0 mmol/L) while receiving RAASi therapy. Following initiation of SZC, all patients experienced eventual stabilization of sK+ levels. All patients were able to initiate, restart, or up-titrate RAASi therapy with five patients achieving optimal medical therapy. Left ventricular ejection fraction improved in four patients, two patients are now re-classified as New York Heart Association Class I, and an additional patient had improved exercise tolerance. Follow-up for Patient 8 is still ongoing. These real-world cases demonstrate that use of SZC to manage hyperkalaemia in patients with HF is feasible and allows optimization of RAASi therapy.


The Umgeni bridge, a resin bonded pontic using a preformed fibre post an aesthetic procedure of low biological and fiscal cost.
A missing anterior tooth or open embrasures destroys the aesthetics of a smile. The replacement of a missing anterior tooth is one of the most rewarding and challenging aspects of restorative dentistry. There are a number of techniques to do this, however, most involve the use of a technician, which means additional cost to the patient and multiple visits. In today's financial climate with practice expenses climbing and medical aid remuneration dwindling, one must seek methods to reduce costs and provide patients with more affordable dentistry. In addition, in crisis situations such as the traumatic loss of a tooth an immediate replacement technique albeit temporary is necessary. To replace a missing anterior tooth directly and immediately presents a rewarding challenge to the clinician. The Umgeni bridge named after the river that flows on the north side of Durban, is particularly useful in replacing congenitally missing laterals after completion of orthodontic treatment in the case of congenitally missing laterals and cleft palates.


Inflammasome Contribution to the Activation of Th1, Th2, and Th17 Immune Responses.
Inflammasomes are cytosolic polyprotein complexes formed in response to various external and internal stimuli, including viral and bacterial antigens. The main product of the inflammasome is active caspase 1 which proteolytically cleaves, releasing functional interleukin-1 beta (IL-1β) and interleukin-18 (IL-18). These cytokines play a central role in shaping immune response to pathogens. In this review, we will focus on the mechanisms of inflammasome activation, as well as their role in development of Th1, Th2, and Th17 lymphocytes. The contribution of cytokines IL-1β, IL-18, and IL-33, products of activated inflammasomes, are summarized. Additionally, the role of cytokines released from tissue cells in promoting differentiation of lymphocyte populations is discussed.


Sugarbeet (Beta vulgaris L.): shoot regeneration from callus and callus protoplasts.
The successful application of recombinant DNA technology for crop plants requires efficient regeneration systems. A detailed study on the regeneration potential of callus and callus-derived protoplasts of a recalcitrant species, sugarbeet, was performed. A reproducible and highly efficient method for induction of regenerable friable callus was established from etiolated hypocotyl explants. A reduced sucrose concentration proved beneficial. Successful shoot regeneration could be demonstrated in 10 out of 12 tested lines. Seed germination, followed by callus induction and shoot regeneration required only a single culture medium. Additionally, the regeneration capacity of roots and root-derived callus was demonstrated. Highly efficient plant regeneration was also achieved when using protoplasts isolated from regenerable friable callus induced on etiolated hypocotyls explants. To our knowledge this represents the first report on callus protoplast to plant regeneration in sugarbeet.


New synthetic route of alkyl-terminated silicon nanoparticles and their optical characteristics.
New synthetic route and characterization of alkyl-capped nanocrystalline silicon (R-n-Si) were achieved from the reaction of silicon tetrachloride with sodium/benzophenone ketal, followed by n-butyllithium. Optical characteristics of silicon nanoparticles were characterized by Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-vis), and photoluminescence (PL) spectroscopy. Butyl-capped silicon nanoparticles exhibited an emission band at 410 nm with excitation wavelength of 360 nm. Average size of n-butyl-capped silicon nanoparticles was obtained by particle size analyzer (PSA) and transmission electron microscopy (TEM). Average size of n-butyl-capped Si nanoparticles was about 6.5 nm.


Comparison of beclomethasone dipropionate and prednisolone 21-phosphate enemas in the treatment of ulcerative proctitis.
In a double-blind randomized clinical trial 18 patients with exacerbations of distal ulcerative colitis were treated for 4 weeks with enemas containing either prednisolone 21-phosphate 30 mg (PP) or beclomethasone dipropionate 1 mg (BDP) a surface-active corticosteroid. All 8 patients treated with PP showed clinical and endoscopic improvement in contrast with only 4 of 10 patients treated with BDP. Endocrinologic evaluation showed a significant decrease in morning plasma cortisol, in cortisol increase after synacthen, and in urinary free cortisol excretion after PP therapy, but no changes in these variables after BDP therapy. We conclude that PP enemas are more active in the treatment of ulcerative proctitis, but they cause a suppression of the adrenal cortex, in contrast to BDP.


Primary thyroid lymphoma: The two ends of the spectrum.
We describe two different cases of prinary thyroid lymphoma (PTL). PTL is a rare malignancy. Nevertheless, it frequently presents diagnostic and therapeutic challenges. The first patient, a 79-year-old female, presented with a large, painless thyroid mass accompanied by severe obstructive symptoms of the upper respiratory and gastrointestinal track. The second patient (67-year-old female) presented with nodular goiter. Thyroidectomy - performed on the first patient for alleviation of obstructive symptoms - revealed the presence of a diffuse large B-cell lymphoma. Although she was administered standard chemotherapy she deceased four months later. In the second patient, primary thyroid lymphoma was an incidental finding following thyroidectomy performed for nodular goiter. These two cases illustrate the variable course of PTL, the possibility of which should be kept into consideration in clinical practice.


Novel glycine transporter type-2 reuptake inhibitors. Part 2: beta- and gamma-amino acid derivatives.
Several beta- and gamma-amino acid derivatives were prepared as glycine transport inhibitors and their ability to block the uptake of [(14)C]-glycine in COS7 cells transfected with human glycine transporter-2 (hGlyT-2) were evaluated. A range of lipophilic side chains were tolerated in the beta-amino acid series (i.e., Ph, CH(2)Ph, CH(CH(3))(2), and CH(2)CH(CH(3))(2)). In the gamma-amino acid series, minimal differences in potency were observed between the alpha,beta-unsaturated analogs and the corresponding saturated derivatives. In both series, a 4-biphenyl or 4-phenoxyphenyl substituent appended to the urea or cyanogunaidine moiety was necessary for in vitro activity.


Dispersion of coupled mode-gap cavities.
The dispersion of a coupled resonator optical waveguide made of photonic crystal mode-gap cavities is pronouncedly asymmetric. This asymmetry cannot be explained by the standard tight binding model. We show that the fundamental cause of the asymmetric dispersion is the inherent dispersive cavity mode profile; i.e., the mode wave function depends on the driving frequency, not the eigenfrequency. This occurs because the photonic crystal cavity resonances do not form a complete set. We formulate a dispersive mode coupling model that accurately describes the asymmetric dispersion without introducing any new free parameters.


Circ_0006174 promotes colorectal cancer progression by sponging microRNA-142-3p and regulating X-linked inhibitor of apoptosis expression.
Circular RNAs (circRNAs) are crucial in the regulation of gene expression and biological processes. However, in colorectal cancer, the expression characteristics and biological function of circRNA_0006174 (circ_0006174) is not fully understood. This work is aimed to investigate the biological function of circ_0006174 in colorectal cancer and its molecular mechanism. Circ_0006174, microRNA-142-3p and X-linked inhibitor of apoptosis expression levels were detected in colorectal cancer tissues and cells using quantitative real-time polymerase chain reaction analysis or Western blot. The effects of circ_0006174 on colorectal cancer cell proliferation, apoptosis, migration and invasion were detected using the cell counting kit-8 method, bromodeoxyuridine experiments, flow cytometry analysis and Transwell experiments. The targeting relationship among circ_0006174, microRNA-142-3p and X-linked inhibitor of apoptosis was analysed by bioinformatics prediction, dual-luciferase reporter experiment and RNA immunoprecipitation experiment. Circ_0006174 was up-regulated in colorectal cancer tissues as well as in cell lines, and its high expression was remarkably associated with enlarged tumour volume and advanced tumour, node, metastasis stage of the patients. Circ_0006174 overexpression enhanced colorectal cancer cell proliferation, migration and invasion, and inhibited colorectal cancer cell apoptosis; while knocking down circ_0006174 caused the opposite effects. Circ_0006174 directly targeted and negatively regulated microRNA-142-3p expression, and X-linked inhibitor of apoptosis, a target gene of microRNA-142-3p, could be indirectly and positively modulated by circ_0006174. Circ_0006174 facilitates colorectal cancer cell proliferation, migration and invasion, and represses colorectal cancer cell apoptosis by regulating microRNA-142-3p/X-linked inhibitor of apoptosis axis.


Silver dressings: their role in wound management.
Dressings have a part to play in the management of wounds; whether they are sutured or open, usually chronic wounds of many aetiologies which are healing by secondary intention. They traditionally provide a moist wound environment, but this property has been extended through simple to complex, active dressings which can handle excessive exudate, aid in debridement, and promote disorganised, stalled healing. The control of infection remains a major challenge. Inappropriate antibiotic use risks allergy, toxicity and most importantly resistance, which is much reduced by the use of topical antiseptics (such as povidone iodine and chlorhexidine). The definition of what is an antimicrobial and the recognition of infection has proven difficult. Although silver has been recognised for centuries to inhibit infection its use in wound care is relatively recent. Evidence of the efficacy of the growing number of silver dressings in clinical trials, judged by the criteria of the Cochrane Collaboration, is lacking, but there are good indications for the use of silver dressings, to remove or reduce an increasing bioburden in burns and open wounds healing by secondary intention, or to act as a barrier against cross contamination of resistant organisms such as MRSA. More laboratory, and clinical data in particular, are needed to prove the value of the many silver dressings which are now available. Some confusion persists over the measurement of toxicity and antibacterial activity but all dressings provide an antibacterial action, involving several methods of delivery. Nanocrystalline technology appears to give the highest, sustained release of silver to a wound without clear risk of toxicity.


Effect of hypoxia on ventilatory and arousal responses to CO2 during NREM sleep with and without flurazepam in young adults.
We examined the ventilatory response to CO2 at two levels of oxygenation during wakefulness and sleep in healthy young adults before and after the ingestion of a single dose of 30 mg flurazepam. Progressive hypercapnia was produced at two levels of arterial O2 saturation (greater than 99 and 87%) by having subjects re-breathe from a tight-fitting face mask and a reservoir bag containing gas mixtures with two different O2 concentrations. Ventilation was measured with an inductive plethysmograph. O2 saturation was measured with an ear oximeter. Sleep was monitored using standard techniques by recording the electroencephalogram, eye movements, and chin electromyogram. During wakefulness, hypoxia increased the slope of the ventilatory response to CO2 and shifted the response slightly to the left. NREM sleep lowered the slope of the CO2 response under both hyperoxic and hypoxic conditions. The slope of the hyperoxic CO2 response curve was not affected by flurazepam during wakefulness or sleep. After administration of flurazepam to the subjects, the shift of the CO2 response curve to the left produced by hypoxia (additive effect) during NREM sleep was slightly less as compared to control, but hypoxia still increased the slope of the CO2 ventilatory response. During hypoxic hypercapnia, the PCO2 at arousal from sleep was significantly lower than during hyperoxic hypercapnia, but the level of ventilation at arousal during hypercapnia was similar in the control condition and after flurazepam. We conclude that (a) both natural and flurazepam-induced sleep depress ventilatory responses to hyperoxic and hypoxic hypercapnia and alter, in a complex fashion, the effects of hypoxia and hypercapnia on ventilation; and (b) hypoxia and hypercapnia interact as arousal stimuli in both natural and flurazepam-induced sleep.


Lack of detectable radiation hypersensitivity in lymphoblastoid cells from multiple pedigrees of familial Alzheimer disease.
Recent reports suggest that cultivated nonneuronal cells from individuals with Alzheimer disease (AD) and other specific hereditary neurodegenerative disorders show hypersensitivity to DNA-damaging agents such as x-rays and radiomimetic chemicals. The hypothesis proposed is that a number of chronic neurologic degenerations, including AD, may be the result of accumulation of damaged DNA, resulting from a defect in DNA repair. We investigated this hypothesis by evaluating cells from individuals from pedigrees of familial Alzheimer disease (FAD) for hypersensitivity to x-irradiation. Sensitivity was assayed by viability measured by trypan blue dye exclusion and micronucleus formation. We tested B-lymphoblastoid cell lines from nine patients and nine unaffected family members from pedigrees with FAD, three unrelated controls, three ataxia telangiectasia (AT) patients, and three Down syndrome individuals. The AT cell lines showed the expected reduced viability and increased micronucleus formation after x-ray treatment. The FAD and control lines showed marked heterogeneity with both assays. There was no significant differences between the FAD patients and controls. The wide variability in the response of cell lines from controls and patients indicates the need for more sensitive assays for detection of radiation sensitivity in cells from various neurologic disorders.


Disease burden attributed to alcohol: How methodological advances in the Global Burden of Disease 2013 study have changed the estimates in Sweden.
The Global Burden of Disease (GBD) study continuously refines its estimates as new data and methods become available. In the latest iteration of the study, GBD 2013, changes were made related to the disease burden attributed to alcohol. The aim of this study was to briefly present these changes and to compare the disease burden attributed to alcohol in Swedish men and women in 2010 using previous and updated methods. In the GBD study, the contribution of alcohol to the burden of disease is estimated by theoretically assessing how much of the disease burden can be avoided by reducing the consumption of alcohol to zero. The updated methods mainly consider improved measurements of alcohol consumption, including less severe alcohol dependence, assigning the most severe injuries and removing the protective effect of drinking on cardiovascular diseases if combined with binge drinking. The overall disease burden attributed to alcohol in 2010 increased by 14% when using the updated methods. Women accounted for this overall increase, mainly because the updated methods led to an overall higher alcohol consumption in women. By contrast, the overall burden decreased in men, one reason being the lower overall alcohol consumption with the new methods. In men, the inclusion of less severe alcohol dependence resulted in a large decrease in the alcohol attributed disease burden. This was, however, evened out to a great extent by the increase in cardiovascular disease and injuries. CONCLUSIONS WHEN USING THE UPDATED GBD METHODS, THE OVERALL DISEASE BURDEN ATTRIBUTED TO ALCOHOL INCREASED IN WOMEN, BUT NOT IN MEN.


Relationship between Duration of Untreated Psychosis and Intrinsic Corticostriatal Connectivity in Patients with Early Phase Schizophrenia.
Patients with first-episode psychosis experience psychotic symptoms for a mean of up to 2 years prior to initiation of treatment, and long duration of untreated psychosis (DUP) is associated with poor clinical outcomes. Meanwhile, evidence compiled from numerous studies suggests that longer DUP is not associated with structural brain abnormalities. To date, few studies have examined the relationship between DUP and functional neuroimaging measures. In the present study, we used seed-based resting-state functional connectivity to examine the impact of DUP on corticostriatal circuitry. We included 83 patients with early phase schizophrenia and minimal exposure to antipsychotic drugs (<2 years), who underwent resting state scanning while entering 12 weeks of prospective treatment with second-generation antipsychotic drugs. Functional connectivity maps of the striatum were generated and examined in relation to DUP as a covariate. Mediation analyses were performed on a composite measure of corticostriatal connectivity derived from the significant results of our DUP analysis. We found that longer DUP correlated with worse response to treatment as well as overall decreased functional connectivity between striatal nodes and specific regions within frontal and parietal cortices. Moreover, the relationship between DUP and treatment response was significantly mediated by corticostriatal connectivity. Our results indicate that variation in corticostriatal circuitry may play a role in the relationship between longer DUP and worsened response to treatment. Future prospective studies are necessary to further characterize potential causal links between DUP, striatal circuitry and clinical outcomes.


Utility of the ultrasound elastographic systolic thyroid stiffness index in reducing fine-needle aspirations.
The purpose of this study was to evaluate whether ultrasound elastography performed by using carotid pulsation as a compression source and generating the systolic thyroid stiffness index (STSI) can be used as a pre-fine-needle aspiration (FNA) screening tool. Ultrasound data previously acquired from 62 thyroid nodules in 59 patients who underwent a thyroid FNA were used. Pulsation from the carotid artery was used as the compression source, and the strain was calculated offline. A metric called the STSI was computed for each nodule during systole. On the basis of the derived STSI value, thyroid nodules were retrospectively classified into 2 types: I, no FNA (observation only); and II, FNA. The STSI value of malignant nodules (n = 12) was significantly higher than that of benign nodules (n = 39; P < .00002). Using an STSI cutoff value of 10, 31 nodules were classified as type I, all of which were benign, whereas 20 nodules were classified as type II, 12 malignant and 8 benign, with sensitivity of 100% and specificity of 79.4%. This suggests that ultrasound elastography could have screened out 31 type I nodules, reducing the number of FNAs by 60.8%. Thyroid ultrasound elastography has the potential to substantially reduce the number of FNA biopsies by detecting type I benign nodules. Patients with suspicious type II nodules would be referred for an FNA. Future prospective studies are needed to confirm the efficacy of thyroid ultrasound elastography as a triage tool to FNA.


Effect of Feeding High Gamma-Aminobutyric Acid-Containing Giant Embryo Black Sticky Rice (Oryza sativa L.) on Anxiety-Related Behavior of C57BL/6 Mice.
The aim of this study was to determine the effect of feeding high gamma-aminobutyric acid (GABA)-containing black sticky rice giant embryo (BSRGE, Oryza sativa L.) on anxiety-related behavior of C57BL/6 mice. Experimental feedstuff (BSRGE with high GABA+AIN-76A) and control (AIN-76A) were provided to C57BL/6 mouse for 10 days. Antianxiety effects of BSRGE with high GABA were measured using an elevated plus maze. On day 8, the number of open arm entries by GABA and control groups were 1.10 ± 1.60 (mean ± SD) and 0.00 ± 0.00 (P = .030). On day 10, the number of open arm entries by the GABA group was 2.00 ± 1.89, which was significantly (P = .025) higher than that in the control group (0.40 ± 0.84). On day 8, the time the mice spent in open arm in the GABA group and control group was 3.60 ± 7.06 and 0.00 ± 0.00 sec (P = .068), respectively. On day 10, the time the mice in the GABA and control groups spent in open arm was 6.20 ± 5.35 sec and 1.80 ± 3.82 sec (P = .042), respectively. In repeated analysis of variance for the number of entries into open arm and time spent in open arm, significant differences were found between the two groups. Therefore, BSRGE with high GABA content might have an antianxiety effect. This study can serve as a preliminary study so that further antianxiety effects of BSRGE can be determined in more extended animal or clinical research studies in the future.


Abnormal callosal morphology in male adult dyslexics: relationships to handedness and phonological abilities.
The classical notion that developmental dyslexia may somehow relate to impaired communication between hemispheres has not yet received convincing support. Sixteen dyslexic adults and 12 controls received a high resolution brain MRI scan for morphometric study of the corpus callosum. Automatized measurements of callosal area and calculation of indices defining the general morphology of the callosal mid-surface were performed. Each participant received global intelligence and reading achievement evaluation; dyslexics were further proposed specific neuropsychological tests specially designed to explore the mechanisms of reading impairment. It just appears from the group comparisons (1) that the dyslexics' corpus callosum displays a more circular and evenly thicker general shape, and (2) that the midsagittal surface is on the average larger than in controls, in particular in the isthmus. Moreover, the different morphometric characteristics of the dyslexic brain correlated with the degree of impairment on various tests exploring phonological abilities. In vivo morphometry of the corpus callosum may provide valuable hints for understanding developmental learning disorders and their consequences in adults.


Alternative treatments for resin-based composite and amalgam restorations with marginal defects: a 12-month clinical trial.
This clinical trial sought to evaluate the effectiveness of alternative treatment for replacing amalgam and resin-based composite restorations with marginal defects. The study recruited 66 patients with 271 restorations. Each restoration was assigned randomly to one of five groups: Sealant, Refurbishing, Repair, Replacement, and Untreated. Two clinicians evaluated the restorations according to USPHS/Ryge criteria at baseline (Kappa 0.74) and one year after the treatment (Kappa 0.81). The scoring of the margins improved (from bravo to alfa) after the experimental treatments. None of the treatments showed significant degradation of the margins during the 12-month observation period.


[Significance of human papillomavirus infections].
Human papillomavirus is one of the most frequent sexually transmitted diseases; more than three quarters of sexually active population are infected during their lifetime. Most of papillomavirus infections clear spontaneously, however persistent high-risk human papillomavirus 16 and 18 are responsible for over 70% of all cases of cervical cancer and related to a major part of cancers in the vulva, vagina, penis, anal region, and oropharynx. It is estimated that approximately 5.2% of all cancers are associated with oncogenic human papillomavirus infection.


Constitutional mutations in RTEL1 cause severe dyskeratosis congenita.
Dyskeratosis congenita (DC) and its phenotypically severe variant, Hoyeraal-Hreidarsson syndrome (HHS), are multisystem bone-marrow-failure syndromes in which the principal pathology is defective telomere maintenance. The genetic basis of many cases of DC and HHS remains unknown. Using whole-exome sequencing, we identified biallelic mutations in RTEL1, encoding a helicase essential for telomere maintenance and regulation of homologous recombination, in an individual with familial HHS. Additional screening of RTEL1 identified biallelic mutations in 6/23 index cases with HHS but none in 102 DC or DC-like cases. All 11 mutations in ten HHS individuals from seven families segregated in an autosomal-recessive manner, and telomere lengths were significantly shorter in cases than in controls (p = 0.0003). This group had significantly higher levels of telomeric circles, produced as a consequence of incorrect processing of telomere ends, than did controls (p = 0.0148). These biallelic RTEL1 mutations are responsible for a major subgroup (∼29%) of HHS. Our studies show that cells harboring these mutations have significant defects in telomere maintenance, but not in homologous recombination, and that incorrect resolution of T-loops is a mechanism for telomere shortening and disease causation in humans. They also demonstrate the severe multisystem consequences of its dysfunction.


Growth and characterisation of NiAl and N-doped NiAl films deposited by closed field unbalanced magnetron sputtering ion plating using elemental ni and Al targets.
Closed Field Unbalanced Magnetron Sputtering Ion Plating (CFUBMSIP) has been used to deposit undoped and nitrogen doped NiAI thin films onto glass and stainless steel 316 substrates. These films have potential applications in tribological, electronic media and thermal barrier coatings. The surface characteristics, composition, mechanical and structural properties have been investigated using stylus profilometry, X-ray diffraction (XRD), Energy dispersive spectroscopy (EDAX), Atomic force microscopy (AFM) and nanoindentation. The average thickness of the films was approximately 1 microm. The X-ray diffraction spectra revealed the presence of the beta NiAl phase. The EDAX results revealed that all of the undoped and nitrogen doped NiAl thin films exhibited the near equiatomic NiAl composition with the best results being achieved using 300 Watts DC power for Ni and 400 Watts DC power for Al targets respectively. AFM results of both types of films deposited on glass samples exhibited a surface roughness of less than 100 nm. The nanoindenter results for coatings on glass substrates displayed hardness and elastic modulus of 7.7 GPa and 100 GPa respectively. The hardest coatings obtained were obtained at 10% of nitrogen.


Public policy and child lead poisoning: implementation of Title X.
Nurses who care for pediatric patients in all settings must be aware of the critical effects of lead poisoning in children. Lead causes toxic effects in the human body, especially in children. These hazards have led to government involvement related to the issues of lead poisoning. Currently, governmental programs are set up under Title X: The Residential Lead Based Paint Hazard Reduction Act of 1992. However, the political changes and potential cuts in government spending may affect programs such as Title X. Because of this and their important role in child health, pediatric nurses should understand the political process, the implementation of such programs, and effects of potential funding cuts.


3-Hydroxy-3-methylglutaryl coenzyme A reductase: regulation of enzymatic activity by phosphorylation and dephosphorylation.
The activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) [mevalonate:NADP+ oxidoreductase (CoA-acylating); EC 126.96.36.199] was inhibited by ATP+Mg2+. Inactivation of HMG-CoA reductase by ATP+Mg2+ was dependent on time, temperature, and ATP concentration. Incubation of microsomal HMG-CoA reductase with [gamma-32P]ATP+Mg2+ was associated with a reciprocal increase in [32P]protein-bound radioactivity and a decrease in enzymatic activity. Incubation of 32P-labeled microsomal HMG-CoA reductase with a partially purified cytosolic phosphatase resulted in a time-dependent reciprocal release of [32P]protein-bound radioactivity and reactivation of enzyme activity. Phosphorylation of HMG-CoA reductase was confirmed by immunoprecipitation of partially purified [gamma-32P]-ATP+Mg2+-inactivated microsomal HMG-CoA reductase with a reductase-specific antiserum. Sodium dodecyl sulfate electrophoresis of the [gamma-32P]immunoprecipitate revealed that the 32P radioactivity was located in the electrophoretic position of HMG-CoA reductase. These results established that the reversible inactivation of HMG-CoA reductase by ATP+Mg2+ was due to covalent modification of the enzyme by a phosphorylation-dephosphorylation reaction sequence. The existence of HMG-CoA reductase in interconvertible active and inactive forms provides a mechanism for the rapid short-term regulation of the pathway for cholesterol biosynthesis.


Influence of microwave radiation on free Candida antarctica lipase B activity and stability.
The influence of microwave heating on free Candida antarctica lipase B activity and stability was studied over the temperature range from 40 to 110 degrees C. Concerning the lipase activity, identical initial rate and conversion yield were obtained under microwave radiation and classical thermal heating for the alcoholysis between ethyl butyrate and butanol in a solvent-free system. On the other hand, the kinetics of the free lipase inactivation in butanol appears to be influenced by the heating mode. The Arrhenius plot obtained under classical heating was linear over all the temperature range studied whereas a biphasic Arrhenius plot was obtained under microwaves. The non-classical effect of the microwave heating on the initial rate of the enzymatic inactivation was thus dependent on the temperature of incubation.


Insertion/deletion polymorphism of the ACE gene is associated with type 2 diabetes.
In an attempt to examine the role of an ACE gene insertion/deletion (I/D) polymorphism in type 2 diabetes, we conducted a case-control association study among 132 couple-pairs from northern China. The genotype frequencies for II, ID, and DD were 39.8, 39.8, and 20.3%, respectively, in the case group and 44.8, 44.8, and 10.4% in the control group. The DD frequency was significantly higher in the case group than in the control group (chi(2)(1) = 4.77, P = 0.03), suggesting that the DD genotype is associated with an increased susceptibility to type 2 diabetes in our study population.


[Expression of programmed cell death 4 and its correlation with proliferation and apoptosis in laryngeal squamous cell carcinoma].
To study the expression of PDCD4 and its relationship with cell proliferation and apoptosis in laryngeal squamous cell carcinomas and to evaluate its clinical significance. The immunohistochemical staining method was applied to investigate the expression of PDCD4 and Ki-67 in 60 laryngeal squamous cell carcinomas tissues and 21 their surrounding laryngeal normal mucosa tissues. TUNEL method was applied to detect the apoptosis. The proliferation index (PI) and apoptosis index (AI) were defined. The positive rate of PDCD4 protein was significantly lower in laryngeal squamous cell carcinomas than that in the laryngeal normal mucosa tissues (P < 0.01). The expression of PDCD4 had relation with the differentiation grading and lymph node metastasis (P < 0.05), but not related to tumor sites and TNM stage. The PI of laryngeal squamous cell carcinomas tissues was higher than that of the normal laryngeal mucosa tissues (P < 0.01). No relation was found among PI and tumor sites, differentiation grading and lymph node metastasis. PI had correlation with TNM stage (P < 0.05). The AI of the cancer was higher than that of normal laryngeal mucosa tissues (P < 0.01). There was no relationship between AI and tumor sites, TNM stage and lymph node metastasis. AI correlated with differentiation grading (P < 0.01). The PI in PDCD4 positive group was significantly lower than in PDCD4 negative group (P < 0.05). The AI in PDCD4 positive group was significantly higher than in PDCD4 negative group (P < 0.05). The expression of PDCD4 is low in laryngeal squamous cell carcinomas and it may play important roles in occurrence and development of laryngeal squamous cell carcinomas through the inducing apoptosis and inhibiting proliferation.


Decreased expression of LKB1 predicts poor prognosis in pancreatic neuroendocrine tumor patients undergoing curative resection.
Liver kinase B1 (LKB1) is a key regulatory protein of cellular metabolism, proliferation, and polarity. The present study aimed to characterize the expression pattern of LKB1 in pancreatic neuroendocrine tumors (pNETs) and evaluate the relationship between LKB1 expression and prognosis in pNETs. We retrospectively analyzed the pathologic and clinical data of 71 pNET patients who underwent curative surgical resection in Guangdong General Hospital. LKB1 mRNA and protein levels in tumor tissues and paired nontumor tissues were evaluated in 24 patients by quantitative real-time reverse-transcription polymerase chain reaction and Western blot, respectively. Immunohistochemical expression of LKB1 in tumor tissues was detected in all of the 71 patients, and the immunohistochemical expression level was re-coded in two classes (high versus low/negative) and correlated with clinicopathological parameters and survival outcomes. The association between LKB1 expression and clinicopathological characters was evaluated by chi-square test and Student's t-test. Kaplan-Meier curves and log-rank test were used to analyze the survival outcomes, including overall survival (OS) and disease-free survival (DFS). Compared to adjacent normal tissues, LKB1 mRNA level and protein expression level in tumor tissues were both increased. The immunostaining of LKB1 was mainly found within the cytoplasm. Overall, 52 of 71 (73.2%) cases were positive for LKB1 protein, which showed either a diffuse staining pattern or a partial staining pattern. Decreased LKB1 expression was correlated with older age (P=0.042), increased Ki-67 index (P=0.004), increased mitotic count (P=0.001), and advanced histologic grade (P=0.001). Moreover, patients with low/negative LKB1 expression had shorter OS and DFS than those with high expression. Our results suggested that LKB1 expression could be a useful prognostic marker for recurrence and survival in pNET patients who had received curative resection.


[The effect of allopurinol on the synthesis of adenine nucleotides and ribonucleic acid from inosine via a salvage pathway in the brain of rats].
The authors investigated in experiments on rats the action of allopurinol and isoproterenol on the metabolism of adenine nucleotides and the total fraction of ribonucleic acids in the brain, liver heart and kidneys. It was revealed that allopurinol enhances the synthesis of adenine nucleotides from administered inosine in the brain and liver of rats. In the heart and kidneys allopurinol did not affect the synthesis of these compounds. Isoproterenol has a more marked effect on the metabolism of adenine nucleotides in the heart only: it reduced the amount of adenine nucleotides and enhanced their synthesis from inosine. It is assumed that the protective effect of allopurinol on the restoration of the reduced amount of these substances in brain and liver after their ischaemization could take place also by their increased resynthetization from accumulated inosine.


Socioeconomic status, psychological resources, and inflammatory markers: Results from the MIDUS study.
Our objective was to investigate interactions of psychological resources and socioeconomic status (SES)-as well as potential gender differences and the explanatory role of childhood and adult stress exposures, health behaviors, and negative and positive affect-in predicting markers of systemic inflammation. We utilized a sample of adults from the Midlife Development in the U.S. (MIDUS) study who provided biomarker data (N = 1,152). SES was operationalized as a composite of education, income, and occupational prestige, and the psychological resources construct was operationalized as a latent factor measured with optimism, perceived control, and self-esteem. Linear regression models examined these 2 factors and their interaction in predicting interleukin-6 (IL-6) and C-reactive protein (CRP) measured on average 2 years later, as well as 3-way interactions involving gender and the impact of covariate adjustment. Psychological resources interacted with SES in men (for IL-6: p < .001; for CRP: p = .04) but not in women. In men, greater psychological resources was associated with lower concentrations of IL-6 at lower levels of SES but higher concentrations of both markers at higher levels of SES. The inverse association between resources and IL-6 at low SES was moderately attenuated upon adjustment for negative affect. Socioeconomic status might modulate the linkage between psychological resources and systemic inflammation in men. At lower levels of SES, resources may be related to lower inflammation in part through lower negative affect. Associations with higher inflammation at higher SES add to growing evidence suggesting that adaptive psychological characteristics may be associated with markers of poorer physiological function under certain conditions. (PsycINFO Database Record


Natural 30 base pair and 69 base pair deletion variants of the LMP1 oncogene do stimulate NF-kappaB-mediated transcription.
An increasing number of reports shows a link between the Epstein-Barr virus (EBV) and lymphoid neoplasia. The latent membrane protein 1 (LMP1) is likely to play a determinant role in this process since this EBV encoded protein has oncogenic properties and is usually expressed in EBV-associated lymphoproliferative diseases (LPD), except Burkitt's lymphoma. We previously identified in LPD patients mutational hot spots and a 30 bp or 69 bp deletion in the LMP1 gene region coding for the C-terminal domain. These deletions are located in an area shown to be important for the activation of the transcription factor NF-kappaB. These findings lead us to test whether these natural deletion variants may have a functional effect. We measured the stimulation of their activity using a luciferase reporter plasmid containing NF-kappaB responsive elements. We tested the NF-kappaB inducing activity of four naturally occurring LMP1 deletion variants. Our results show that these deletion variants activate NF-kappaB to the same level as the wild-type form, indicating that the crucial residues for NF-kappaB activation are conserved among the variants isolated and lie within the last 32 amino acids of the C-terminal domain of the LMP1 oncogene.


A systemic small RNA signaling system in plants.
Systemic translocation of RNA exerts non-cell-autonomous control over plant development and defense. Long-distance delivery of mRNA has been proven, but transport of small interfering RNA and microRNA remains to be demonstrated. Analyses performed on phloem sap collected from a range of plants identified populations of small RNA species. The dynamic nature of this population was reflected in its response to growth conditions and viral infection. The authenticity of these phloem small RNA molecules was confirmed by bioinformatic analysis; potential targets for a set of phloem small RNA species were identified. Heterografting studies, using spontaneously silencing coat protein (CP) plant lines, also established that transgene-derived siRNA move in the long-distance phloem and initiate CP gene silencing in the scion. Biochemical analysis of pumpkin (Cucurbita maxima) phloem sap led to the characterization of C. maxima Phloem SMALL RNA BINDING PROTEIN1 (CmPSRP1), a unique component of the protein machinery probably involved in small RNA trafficking. Equivalently sized small RNA binding proteins were detected in phloem sap from cucumber (Cucumis sativus) and lupin (Lupinus albus). PSRP1 binds selectively to 25-nucleotide single-stranded RNA species. Microinjection studies provided direct evidence that PSRP1 could mediate the cell-to-cell trafficking of 25-nucleotide single-stranded, but not double-stranded, RNA molecules. The potential role played by PSRP1 in long-distance transmission of silencing signals is discussed with respect to the pathways and mechanisms used by plants to exert systemic control over developmental and physiological processes.


Structural Description of the Nipah Virus Phosphoprotein and Its Interaction with STAT1.
The structural characterization of modular proteins containing long intrinsically disordered regions intercalated with folded domains is complicated by their conformational diversity and flexibility and requires the integration of multiple experimental approaches. Nipah virus (NiV) phosphoprotein, an essential component of the viral RNA transcription/replication machine and a component of the viral arsenal that hijacks cellular components and counteracts host immune responses, is a prototypical model for such modular proteins. Curiously, the phosphoprotein of NiV is significantly longer than the corresponding protein of other paramyxoviruses. Here, we combine multiple biophysical methods, including x-ray crystallography, NMR spectroscopy, and small angle x-ray scattering, to characterize the structure of this protein and provide an atomistic representation of the full-length protein in the form of a conformational ensemble. We show that full-length NiV phosphoprotein is tetrameric, and we solve the crystal structure of its tetramerization domain. Using NMR spectroscopy and small angle x-ray scattering, we show that the long N-terminal intrinsically disordered region and the linker connecting the tetramerization domain to the C-terminal X domain exchange between multiple conformations while containing short regions of residual secondary structure. Some of these transient helices are known to interact with partners, whereas others represent putative binding sites for yet unidentified proteins. Finally, using NMR spectroscopy and isothermal titration calorimetry, we map a region of the phosphoprotein, comprising residues between 110 and 140 and common to the V and W proteins, that binds with weak affinity to STAT1 and confirm the involvement of key amino acids of the viral protein in this interaction. This provides new, to our knowledge, insights into how the phosphoprotein and the nonstructural V and W proteins of NiV perform their multiple functions.


Comorbid posttraumatic stress disorder: impact on treatment outcome for obsessive-compulsive disorder.
The study tested the effect of comorbid posttraumatic stress disorder (PTSD) on behavior therapy outcome for obsessive-compulsive disorder (OCD). Subjects were 15 patients with treatment-refractory OCD who were admitted consecutively to a short-term residential facility. Eight met DSM-IV criteria for comorbid PTSD. Patients participated in coached and self-directed behavior treatments of exposure and response prevention as well as in group treatments targeting specific OCD symptoms and related difficulties. Severity of OCD and depression were assessed at admission and exit. Patients with comorbid PTSD showed no significant improvements in OCD and depression symptoms. OCD and depression symptoms improved significantly more in patients without comorbid PTSD than in patients with comorbid PTSD. Behavioral treatment (with or without medication) of OCD may be adversely affected by the presence of comorbid PTSD.


Collocated observations of cloud condensation nuclei, particle size distributions, and chemical composition.
Cloud condensation nuclei (CCN) number concentrations alongside with submicrometer particle number size distributions and particle chemical composition have been measured at atmospheric observatories of the Aerosols, Clouds, and Trace gases Research InfraStructure (ACTRIS) as well as other international sites over multiple years. Here, harmonized data records from 11 observatories are summarized, spanning 98,677 instrument hours for CCN data, 157,880 for particle number size distributions, and 70,817 for chemical composition data. The observatories represent nine different environments, e.g., Arctic, Atlantic, Pacific and Mediterranean maritime, boreal forest, or high alpine atmospheric conditions. This is a unique collection of aerosol particle properties most relevant for studying aerosol-cloud interactions which constitute the largest uncertainty in anthropogenic radiative forcing of the climate. The dataset is appropriate for comprehensive aerosol characterization (e.g., closure studies of CCN), model-measurement intercomparison and satellite retrieval method evaluation, among others. Data have been acquired and processed following international recommendations for quality assurance and have undergone multiple stages of quality assessment.


New metal-free one-pot synthesis of substituted allenes from enones.
A new metal-free, one-pot synthesis of substituted allenes from enones was discovered for the first time, in which a tertiary amine as a base was found to be an effective promoter in such novel transformations. The present synthetic protocol proceeded readily with high compatibility of sensitive functional groups, and it provides a new efficient way to access a series of synthetically important allenes without the use of metallic reagents or catalysts.


Highly Transparent, Flexible and Conductive CNF/AgNW Paper for Paper Electronics.
Conductive paper has the advantages of being low-cost, lightweight, disposable, flexible, and foldable, giving it promising potential in future electronics. However, mainstream conductive papers are opaque and rigid, which seriously affect the wide application of conductive paper. In this paper, we demonstrate a highly transparent, flexible, and conductive paper, fabricated by mixing cellulose nanofibers (CNFs) with silver nanowires (AgNWs) and then plasticizing with choline chloride/urea solvent. The as-prepared CNF/AgNW paper showed high transparency (~90% transmittance) and flexibility (~27% strain), and low sheet resistance (56 Ω/sq). Moreover, the resistance change of CNF/AgNW paper increased only ~1.1% after 3000 bending-unbending cycles under a 150° large angle, implying a long working life and stability. In view of this, our methodology has the potential to open a new powerful route for fabrication of paper-based green electronics.


Remote ischemic conditioning for stroke: A critical systematic review.
Remote ischemic conditioning (RIC) is the application of brief periods of ischemia to an organ or tissue with the aim of inducing protection from ischemia in a distant organ. It was first developed as a cardioprotective strategy but has been increasingly investigated as a neuroprotective intervention. The mechanisms by which RIC achieves neuroprotection are incompletely understood. Preclinical studies focus on the hypothesis that RIC can protect the brain from ischemia reperfusion (IR) injury following the restoration of blood flow after occlusion of a large cerebral artery. However, increasingly, a role of chronic RIC (CRIC) is being investigated as a means of promoting recovery following an ischemic insult to the brain. The recent publication of two large, randomized control trials has provided promise that RIC could improve functional outcomes after acute ischemic stroke, and that there may be a role for CRIC in the prevention of recurrent stroke. Although less developed, there is also proof-of-concept to suggest that RIC may be used to reduce vasospasm after subarachnoid hemorrhage or improve cognitive outcomes in vascular dementia. As a cheap, well-tolerated and almost universally applicable intervention, the motivation for investigating possible benefit of RIC in patients with cerebrovascular disease is great. In this review, we shall review the current evidence for RIC as applied to cerebrovascular disease.


Planned external fixation to locked intramedullary nailing conversion for open fractures of shaft of femur and tibia.
To determine the outcome of initial external fixation and then conversion to intramedullary nailing in patients having open fracture of shaft of femur or tibia. Descriptive study. Combined Military Hospital (CMH), Quetta, from July 2002 to July 2004. Out of 59 patients with fractures of shaft of tibia and femur, 16 were selected for the study who had open fractures in Gustilio type I, II and III. They were initially managed with external fixators and later on converted to planned locked intramedullary nailing. Interlocking nailing was done on routine operation list in the third week after Ex Fix (external fixator) was removed. Record of patients was kept, and was statistically analyzed on SPSS. Out of the 16 patients, 12 had fractures of femur and 4 had fractures of tibia. Male to female ratio was 7:1. Mean duration of external fixation was 6.22 weeks. Six patients underwent closed interlocking nailing and 10 patients with open method. Fifteen fractures (94%) united within 6 months, and one fracture had delayed union. Two patients had superficial wound infection and one patient had deep infection. Immediate external fixation followed by early closed interlocking nailing is a safe and effective treatment for open fractures of shaft of femur and tibia.


Bronchoscopy for foreign body aspiration and effects of nebulized albuterol and budesonide combination.
A foreign body aspiration in the tracheobronchial tree is a dangerous medical condition in the childhood period. Although rigid bronchoscopy is a safe procedure, it may cause complications. The aim of this study was to present our bronchoscopy experience and to evaluate the efficacy of pre-operative administration of nebulized albuterol and budesonide combination for reducing intra-operative complications in foreign body aspirated cases. In this retrospective study our pediatric cases in which a foreign body was removed from tracheobronchial tree in last 8 years were analyzed. After excluding the patients who needed emergent and negative bronchoscopies, the remaining clinically stable 84 patients were compared for the effects of preoperative administration of nebulized albuterol and budesonide combination on bronchoscopy complications. There were 51 boys (60.3%) and 33 girls (39.7%). There were 38 children in the non-nebulized group and 46 children in the nebulized group. We found that the combined albuterol and budesonide nebulization decrease complications such as arterial oxygen desaturation (p<0.05), and bronchospasm (p<0.05) during the bronchoscopic intervention. Preoperative nebulization of albuterol and budesonide combination may decrease perioperative complications of bronchoscopy.


Functional and Biochemical Characterization of the MazEF6 Toxin-Antitoxin System of Mycobacterium tuberculosis.
The Mycobacterium tuberculosis genome harbors nine toxin-antitoxin (TA) systems that are members of the mazEF family, unlike other prokaryotes, which have only one or two. Although the overall tertiary folds of MazF toxins are predicted to be similar, it is unclear how they recognize structurally different RNAs and antitoxins with divergent sequence specificity. Here, we have expressed and purified the individual components and complex of the MazEF6 TA system from M. tuberculosis. Size exclusion chromatography-multiangle light scattering (SEC-MALS) was performed to determine the oligomerization status of the toxin, antitoxin, and the complex in different stoichiometric ratios. The relative stabilities of the proteins were determined by nano-differential scanning fluorimetry (nano-DSF). Microscale thermophoresis (MST) and yeast surface display (YSD) were performed to measure the relative affinities between the cognate toxin-antitoxin partners. The interaction between MazEF6 complexes and cognate promoter DNA was also studied using MST. Analysis of paired-end RNA sequencing data revealed that the overexpression of MazF6 resulted in differential expression of 323 transcripts in M. tuberculosis. Network analysis was performed to identify the nodes from the top-response network. The analysis of mRNA protection ratios resulted in identification of putative MazF6 cleavage site in its native host, M. tuberculosis. IMPORTANCE M. tuberculosis harbors a large number of type II toxin-antitoxin (TA) systems, the exact roles for most of which are unclear. Prior studies have reported that overexpression of several of these type II toxins inhibits bacterial growth and contributes to the formation of drug-tolerant populations in vitro. To obtain insights into M. tuberculosis MazEF6 type II TA system function, we determined stability, oligomeric states, and binding affinities of cognate partners with each other and with their promoter operator DNA. Using RNA-seq data obtained from M. tuberculosis overexpression strains, we have identified putative MazF6 cleavage sites and targets in its native, cellular context.


Does Physical Loading Affect The Speed and Accuracy of Tactical Decision-Making in Elite Junior Soccer Players?
A soccer player's capability to control and manage his behaviour in a game situation is a prerequisite, reflecting not only swift and accurate tactical decision-making, but also prompt implementation of a motor task during intermittent exercise conditions. The purpose of this study was to analyse the relationship between varying exercise intensity and the visual-motor response time and the accuracy of motor response in an offensive game situation in soccer. The participants (n = 42) were male, semi-professional, soccer players (M age 18.0 ± 0.9 years) and trained five times a week. Each player performed four different modes of exercise intensity on the treadmill (motor inactivity, aerobic, intermittent and anaerobic activity). After the end of each exercise, visual-motor response time and accuracy of motor response were assessed. Players' motion was captured by digital video camera. ANOVA indicated no significant difference (p = 0.090) in the accuracy of motor response between the four exercise intensity modes. Practical significance (Z-test = 0.31) was found in visual-motor response time between exercise with dominant involvement of aerobic metabolism, and intense intermittent exercise. A medium size effect (Z-test = 0.34) was also found in visual-motor response time between exercise with dominant involvement of aerobic metabolism and exercise with dominant involvement of anaerobic metabolism, which was confirmed by ANOVA (897.02 ± 57.46 vs. 940.95 ± 71.14; p = 0.002). The results showed that different modes of exercise intensity do not adversely affect the accuracy of motor responses; however, high-intensity exercise has a negative effect on visual-motor response time in comparison to moderate intensity exercise. Key pointsDifferent exercise intensity modes did not affect the accuracy of motor response.Anaerobic, highly intensive short-term exercise significantly decreased the visual-motor response time in comparison with aerobic exercise.Further research should focus on the assessment of VMRT from a player's real - field position view rather than a perspective view.


Glucagon and insulin release from the allografted canine pancreas.
Six previously pancreatectomized dogs were transplanted with duct-ligated, pancreatic allografts. Glucagon and insulin levels in the venous outflow from the graft and in the systemic circulation were determined during the first 60 minutes after transplantation. Two of the dogs were subjected to L-arginine stimulation 5 days after transplantation and the glucagon levels in the venous outflow from the graft were determined. The glucagon and insulin concentrations increased rapidly after transplantation, describing a biphasic curve. In response to L-arginine stimulation, an increased glucagon release was observed.


Construct validity of Ryff's Scale of Psychological Well-being in Spanish older adults.
The purpose of this study was to investigate factorial and content validity of the 9-item per dimension Ryff's Scale of Psychological Well-being in a sample of older Spanish adults. The scale is made up of six subscales: Self-acceptance, Environmental mastery, Positive relations with others, Autonomy, Personal growth, and Purpose in life. After translating the scale, it was administered to 422 retired people ages 65 and older. The internal consistency coefficients of the subscales were modest to low, but similar to the ones reported in previous studies. Although correlation profiles of the subscales replicated previous findings and are consistent with a distinction between two types of well-being (eudaimonic and hedonic), results from a second-order principal factor analysis including alternative well-being measures are rather ambiguous. As for the proposed 6-factor structure of the scale, neither exploratory principal component analysis nor confirmatory factor analysis supported clearly this factor structure, with or without second-order latent constructs.


Characteristics of the similarity index in a Korean medical journal.
Journal editors have exercised their control over submitted papers having a high similarity index. Despite widespread suspicion of possible plagiarism on a high similarity index, our study focused on the real effect of the similarity index on the value of a scientific paper. This research examined the percent values of the similarity index from 978 submitted (420 published) papers in the Korean Journal of Anesthesiology since 2012. Thus, this study aimed to identify the correlation between the similarity index and the value of a paper. The value of a paper was evaluated in two distinct phases (during a peer-review process vs. after publication), and the value of a published paper was evaluated in two aspects (academic citation vs. social media appearance). Yearly mean values of the similarity index ranged from 16% to 19%. There were 254 papers cited at least once and 179 papers appearing at least once in social media. The similarity index affected the acceptance/rejection of a paper in various ways; although the influence was not linear and the cutoff measures were distinctive among the types of papers, both extremes were related to a high rate of rejection. After publication, the similarity index had no effect on academic citation or social media appearance according to the paper. The finding suggested that the similarity index no longer had an influence on academic citation or social media appearance according to the paper after publication, while the similarity index affected the acceptance/rejection of a submitted paper. Proofreading and intervention for finalizing the draft by the editors might play a role in achieving uniform quality of the publication.


Case report: Cowper's syringocele treated with Holmium:YAG laser.
A syringocele is a cystic dilation of Cowper's duct. We report on a 15-year-old boy with persistent dysuria attributable to a syringocele, which was treated by endoscopic unroofing with the holmium:YAG laser. The classification, pathophysiology, and management options of Cowper's syringocele are briefly reviewed.


Myxoid liposarcoma: MRI features with histological correlation.
Myxoid liposarcoma is classified in the group of sarcomas with adipose differentiation, which is the second most common group of sarcomas. However, myxoid liposarcoma is not a homogeneous entity, because the behavior and clinical course of these tumours can vary widely. This study aimed to describe the magnetic resonance imaging (MRI) features of myxoid liposarcomas and to determine whether the MRI features are associated with the histologic grade and can differentiate between low-grade and high-grade tumours and thus help in clinical decision making. We studied 36 patients with myxoid liposarcomas treated at our centre between 2010 and 2018. We analysed clinical variables (age, sex, and tumour site) and MRI features (size, depth, borders, fatty component, myxoid component, non-fatty/non-myxoid component, apparent diffusion coefficient (ADC), and type of enhancement after the administration of intravenous contrast material). We correlated the MRI features with the histologic grade and the percentage of round cells. In our series, patients with myxoid liposarcomas were mainly young adults (median age, 43 years). There were no differences between sexes; 97.2% were located in the lower limbs, 86.1% were deep, and 77.8% had well-defined borders. Of the 23 myxoid liposarcomas that contained no fat, 16 (69.6%) were high grade (p = 0.01). All the tumors with a myxoid component of less than 25% were high grade (p = 0.01); 83.3% of those with a non-fatty/non-myxoid component greater than 50% were high grade (p = 0.03) and 61.5% had more than 5% round cells (p = 0.01). Diffusion sequences were obtained in 14 of the 36 patients; ADC values were high (median, 2 × 10-3 mm2/s), although there were no significant associations between low-grade and high-grade tumours. Contrast-enhanced images were available for 30 (83.3%) patients; 83.3% of the tumours with heterogeneous enhancement were high grade (p = 0.01). MRI can be useful for differentiating between high- and low-grade myxoid liposarcomas and can help in clinical decision making.


The road to consensus: considerations for the safe use and prescribing of COX-2-specific inhibitors.
We describe a process which aimed to achieve consensus on evidence-based considerations for the safe prescribing and use of the COX-2-specific inhibitors available in Australia among a group of 31 clinicians and other health professionals, drawn from practice, academia and industry. Difficulties were encountered at several points: the composition of the working group was contentious; the evidence, drawn from large clinical studies, was criticised by some for problems of study design, data analysis and reporting; interpretation of study results was influenced by the interpreter's knowledge, skills and biases; and the formulation of the "Considerations" became more controversial as summary statements were contracted and simplified. Agreement on the final draft was achieved among 23 of 31 participants. Evidence-based practice guidelines are a welcome development in modern medicine, but the consensus required to produce them can mask important diversity of opinion.


Delivering clinical studies of exercise in the COVID-19 pandemic: challenges and adaptations using a feasibility trial of isometric exercise to treat hypertension as an exemplar.
The COVID-19 pandemic has significantly impacted on the delivery of clinical trials in the UK, posing complicated organisational challenges and requiring adaptations, especially to exercise intervention studies based in the community. We aim to identify the challenges of public involvement, recruitment, consent, follow-up, intervention and the healthcare professional delivery aspects of a feasibility study of exercise in hypertensive primary care patients during the COVID-19 pandemic. While these challenges elicited many reactive changes which were specific to, and only relevant in the context of 'lockdown' requirements, some of the protocol developments that came about during this unprecedented period have great potential to inform more permanent practices for carrying out this type of research. To this end, we detail the necessary adaptations to many elements of the feasibility study and critically reflect on our approach to redesigning and amending this ongoing project in order to maintain its viability to date. Some of the more major protocol adaptations, such as moving the study to remote means wherever possible, had further unforeseen and undesirable outcomes (eg, additional appointments) with regards to extra resources required to deliver the study. However, other changes improved the efficiency of the study, such as the remote informed consent and the direct advertising with prescreening survey. The adaptations to the study have clear links to the UK Plan for the future of research delivery. It is intended that this specific documentation and critical evaluation will help those planning or delivering similar studies to do so in a more resource efficient and effective way. In conclusion, it is essential to reflect and respond with protocol changes in the current climate in order to deliver clinical research successfully, as in the case of this particular study.


Radiation-induced autophagy is associated with LC3 and its inhibition sensitizes malignant glioma cells.
Autophagy is a novel response of cancer cells to ionizing radiation (IR) or chemotherapy, but its significance or mechanism remains largely elusive. Autophagy is characterized with the prominent formation of autophagic vacuoles in the cytoplasm. It is a protein degradation system that involves autophagic/lysosomal compartment. The process begins with sequestering a portion of the cytoplasm, forming the autophagosome. The autophagosome then fuses with the lysosome and lyses its contents. To study radiation-induced autophagy with specific molecules, we assessed changes in the expression of microtubule-associated protein light chain 3 (LC3) and its intracellular distribution after IR in comparison with starvation-induced autophagy. First, we showed that IR induced cell cycle arrest and autophagy, but not apoptosis, in human malignant glioma U373-MG cells. Type II LC3, that is specifically associated with the membrane of the autophagosome, increased after IR and amino acid starvation. Exogenous LC3 distributed on punctate structures, indicative of the formation of autophagosomes. Autophagy inhibitors, 3-methyladenine and bafilomycin A1, radiosensitized U373-MG cells. Furthermore, gammaH2AX foci, that show the extent of DNA double-strand breaks, were more pronounced and prolonged in the cells treated with IR and autophagy inhibitors than in those cells treated with IR only. Our results suggest that autophagy inhibitors may represent a new application of radiosensitization for malignant glioma cells.