Relationship between Leg Mass, Leg Composition and Foot Velocity on Kicking Accuracy in Australian Football.
Kicking a ball accurately over a desired distance to an intended target is arguably the most important skill to acquire in Australian Football. Therefore, understanding the potential mechanisms which underpin kicking accuracy is warranted. The aim of this study was to examine the relationship between leg mass, leg composition and foot velocity on kicking accuracy in Australian Football. Thirty-one Australian Footballers (n = 31; age: 22.1 ± 2.8 years; height: 1.81 ± 0.07 m; weight: 85.1 ± 13.0 kg; BMI: 25.9 ± 3.2) each performed ten drop punt kicks over twenty metres to a player target. Athletes were separated into accurate (n = 15) and inaccurate (n = 16) kicking groups. Leg mass characteristics were assessed using whole body DXA scans. Foot velocity was determined using a ten-camera optoelectronic, three-dimensional motion capture system. Interactions between leg mass and foot velocity evident within accurate kickers only (r = -0.670 to -0.701). Relative lean mass was positively correlated with kicking accuracy (r = 0.631), while no relationship between foot velocity and kicking accuracy was evident in isolation (r = -0.047 to -0.083). Given the evident importance of lean mass, and its interaction with foot velocity for accurate kickers; future research should explore speed-accuracy, impulse-variability, limb co-ordination and foot-ball interaction constructs in kicking using controlled with-in subject studies to examine the effects of resistance training and skill acquisition programs on the development of kicking accuracy. Key pointsAccurate kickers expressed a very strong inverse relationship between leg mass and foot velocity. Inaccurate kickers were unable to replicate this, with greater volatility in their performance, indicating an ability of accurate kickers to mediate foot velocity to compensate for leg mass in order to deliver the ball over the required distance.Accurate kickers exhibited larger quantities of relative lean mass and lower quantities of relative fat mass in their kicking leg. Higher relative lean mass reduces the relative muscular impulses required to produce a given action, allowing greater limb control with proportionately reduced volitional effort.Kicking accuracy was unable to be explained by either foot velocity or leg mass in isolation; rather, it was the co-contribution and interrelation of these characteristics which were the discriminatory factors between accurate and inaccurate kickers.


Exponential tilting in Bayesian asymptotics.
We use exponential tilting to obtain versions of asymptotic formulae for Bayesian computation that do not involve conditional maxima of the likelihood function, yielding a more stable computational procedure and significantly reducing computational time. In particular we present an alternative version of the Laplace approximation for a marginal posterior density. Implementation of the asymptotic formulae and a modified signed root based importance sampler are illustrated with an example.


Idiopathic CD4 lymphocytopenia manifesting as refractory genital dysplasia.
Idiopathic CD4 lymphocytopenia is an immunodeficiency disorder with low absolute CD4 T-lymphocyte count with no evidence of human immunodeficiency virus or other known cause. A 22-year-old woman presented with a high-grade Pap test result. Work-up demonstrated cervical intraepithelial neoplasia 3 and vaginal intraepithelial neoplasia 3 with extensive condyloma. She presented 6 months after her initial treatment with recurrent disease and was referred to the immunology department, where she was found to have profound lymphopenia. After further evaluation, idiopathic CD4 lymphocytopenia was diagnosed. Idiopathic CD4 lymphocytopenia is a rare acquired immunodeficiency. Although genital dysplasia is common in young women, this case demonstrates the importance of determining other etiologies of recurrent human papillomavirus infections and possible immunodeficiencies that may affect management and outcomes.


T cell receptor gene therapy for autoimmune diseases.
The current quality of autoimmune disease treatments is not satisfactory in regard to efficacy and safety. Antigen-specific immunotherapy is a future therapy that could achieve maximal efficacy with minimal adverse effects. T cells are essential components in antigen-specific immunity. However, we do not have a sufficient strategy for manipulating antigen-specific T cells. We propose that T cell receptor (TCR) gene transfer is a hopeful approach for antigen-specific immunotherapy. We confirmed the efficacy of TCR gene therapy in animal models of systemic autoimmune disease and arthritis. In lupus-prone NZB/W F1 mice, nucleosome-specific TCR and CTLA4Ig transduced cells suppressed autoantibody production and nephritis development. In the therapeutic experiment of collagen-induced arthritis (CIA), arthritis-related TCRs were isolated from single T cells accumulating in the arthritis site. Arthritis-related TCR and TNFRIg transduced cells or TCR and Foxp3 transduced cells suppressed arthritis progression and bone destruction. Therefore, engineered antigen-specific cells manipulated to express appropriate functional genes could be applied to specific immunotherapy.


ROMP- and RAFT-Based Guanidinium-Containing Polymers as Scaffolds for Protein Mimic Synthesis.
Cell-penetrating peptides are an important class of molecules with promising applications in bioactive cargo delivery. A diverse series of guanidinium-containing polymeric cell-penetrating peptide mimics (CPPMs) with varying backbone chemistries was synthesized and assessed for delivery of both GFP and fluorescently tagged siRNA. Specifically, we examined CPPMs based on norbornene, methacrylate, and styrene backbones to determine how backbone structure impacted internalization of these two cargoes. Either charge content or degree of polymerization was held constant at 20, with diguanidinium norbornene molecules being polymerized to both 10 and 20 repeat units. Generally, homopolymer CPPMs delivered low amounts of siRNA into Jurkat T cells, with no apparent backbone dependence; however, by adding a short hydrophobic methyl methacrylate block to the guanidinium-rich methacrylate polymer, siRNA delivery to nearly the entire cell population was achieved. Protein internalization yielded similar results for most of the CPPMs, though the block polymer was unable to deliver proteins. In contrast, the styrene-based CPPM yielded the highest internalization for GFP (≈40 % of cells affected), showing that indeed backbone chemistry impacts protein delivery, specifically through the incorporation of an aromatic group. These results demonstrate that an understanding of how polymer structure affects cargo-dependent internalization is critical to designing new, more effective CPPMs.


The radiological assessment of colonic replacement of the esophagus in children: A review of 43 cases.
To define the characteristic radiological features following colonic replacement of the esophagus in children. The upper gastro-intestinal contrast studies of 43 patients who underwent colonic replacement of the esophagus at our pediatric surgery unit were available for analysis. UGI contrast studies were performed routinely in the post-surgical period in 17 cases (first asymptomatic group), while the rest of contrast studies (26) belonged to a second group of out-patients complaining of dysphagia (18) or dyspepsia (8) following colonic replacement of the esophagus. Based on our observations, we proposed a grading system to describe the degree of colonic redundancy in the thorax. Redundancy of the colonic conduit in the thoracic cavity was a common radiological finding (62.8%). The redundancy was mild (grade 1) in 18 patients, moderate (grade 2) in eight, and severe (grade 3) in only one patient. In 88.9%, the redundancy was in the right hemi-thorax. Patients presenting with postoperative dysphagia had a stricture at the site of the esophago-colic anastomosis in the neck, which should be differentiated from other sites of anatomical narrowing at the inlet and outlet of the thoracic cavity. Gastro-colic reflux was common among patients who underwent colonic replacement of the esophagus without an anti-reflux procedure. Colonic replacement of the esophagus in children results in considerable anatomical alterations. Knowledge about the normal post-surgical changes and imaging features of the commonly encountered complications can increase the diagnostic confidence among radiologists and clinicians when dealing with these cases.


Cephalosporins. III. 7-(O-Aminomethylphenylacetamido)cephalosporanic acids with bicyclic heteroaromatics in the C-3 side chain.
Bicyclic heteroaromatic thiols with a bridge-head nitrogen atom were used for nucleophilic substitution of 7-ACA at the C-3 acetoxy function followed by N-acylation of the 7-amino group with o-aminomethylphenylacetic acid to afford a series of new cephalosporins (24) with potent antibacterial activity against gram-positive and gram-negative organisms. The most active member of this series was 7-(o-aminomethylphenylacetamido)-3-(tetrazolo-[4,5-b]pyridazin-6-ylthiomethyl)-3-cephem-4-carboxylic acid (BB-S 226) (24e) with antibacterial activity superior activity superior to cephalothin and cefazolin.


The role of platelet and endothelial GARP in thrombosis and hemostasis.
Glycoprotein-A Repetitions Predominant protein (GARP or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of GARP in zebrafish. To evaluate the role of GARP in platelet physiology and in thrombus formation using platelet and endothelial conditional GARP knock out mice. Platelet and endothelial specific GARP knockout mice were generated using the Cre-loxP recombination system. The function of platelets without GARP was measured by flow cytometry, spreading analysis and aggregometry using PAR4-activating peptide and collagen related peptide. Additionally, clot retraction and collagen-induced platelet adhesion and aggregation under flow were analyzed. Finally, in vivo tail bleeding time, occlusion time of the mesenteric and carotid artery after FeCl3-induced thrombosis were determined in platelet and endothelial specific GARP knock out mice. Platelet specific GARP knockout mice had normal surface GPIb, GPVI and integrin αIIb glycoprotein expression. Although GARP expression was increased upon platelet activation, platelets without GARP displayed normal agonist induced activation, spreading on fibrinogen and aggregation responses. Furthermore, absence of GARP on platelets did not influence clot retraction and had no impact on thrombus formation on collagen-coated surfaces under flow. In line with this, neither the tail bleeding time nor the occlusion time in the carotid- and mesenteric artery after FeCl3-induced thrombus formation in platelet or endothelial specific GARP knock out mice were affected. Evidence is provided that platelet and endothelial GARP are not important in hemostasis and thrombosis in mice.


A cyclosporine-based immunosuppressive regimen may be better than tacrolimus for long-term liver allograft survival in recipients transplanted for hepatitis C.
Rapid recurrence of severe hepatitis C (HCV) after liver transplantation is a major barrier to survival of the transplanted liver. While cyclosporine (CsA) in vitro has been shown to suppress HCV replication, an effect is not seen with tacrolimus (Tac). Evidence is inconsistent whether or how this translates to clinical practice. To expand the evidence on this issue, we analyzed graft survival and histological outcomes after liver transplantation for HCV hepatitis. Using our longitudinal database (1991 onward) graft outcomes for all liver transplant recipients with HCV were evaluated (105 grafts in 97 patients). Severe activity, severe fibrosis, and graft survival were analyzed. All liver biopsies were scored (blinded) according to the Ludwig scale. Immunosuppression was based on prednisone and a calcineurin inhibitor (Tac n = 89, 85%; CsA n = 15, 14%). Comparisons of outcomes using CsA versus Tac therapy were done using survival analysis via the log-rank test. Graft survival was significantly better in the CsA group. Although there was no apparent difference in severe activity (grade 2), there was a statistically significant difference in graft survival without fibrosing cholestatic hepatitis (P = .01) and a trend toward a difference in fibrosis-free survival (P = 0.1). The rate of sustained response to antiviral therapy was twice as high in the CsA group, 50% versus 22% (P = 0.16; NS). Graft survival in liver transplant recipients with HCV may be greater with CsA-based immunosuppression. There may also be a lower rate of fibrosing cholestatic hepatitis in this group.


Studying the interactome with the yeast two-hybrid system and mass spectrometry.
Protein interactions are crucial to the life of a cell. The analysis of such interactions is allowing biologists to determine the function of uncharacterized proteins and the genes that encode them. The yeast two-hybrid system has become one of the most popular and powerful tools to study protein-protein interactions. With the advent of proteomics, the two-hybrid system has found a niche in interactome mapping. However, it is clear that only by combining two-hybrid data with that from complementary approaches such as mass spectrometry (MS) can the interactome be analyzed in full. This review introduces the yeast two-hybrid system to those unfamiliar with the technique, and discusses how it can be used in combination with MS to unravel the network of protein interactions that occur in a cell.


Degradation and movement in soil of the herbicide isoproturon analyzed by a Photosystem II-based biosensor.
We have examined the persistence and movement of a urea-type herbicide, isoproturon [IPU; 3-(4-isopropylphenyl)-1,1'-dimethylurea], in soil using a novel herbicide-detection device, the prototype of a portable electrochemical biosensor based on Photosystem II particles immobilized on printed electrodes, and evaluated its results against two other methods: (i) chlorophyll-fluorescence bioassay based on polyphasic induction curves, and (ii) standard analysis represented by liquid chromatography. The data of the herbicide's content determined in soil extracts from field experiments correlated in all three methods. The biosensor assay was effective in determining the herbicide's concentration to as low as 10(-7) M. The results of our experiments also showed the kinetics of movement, degradation, and persistence of isoproturon in various depths of soil. After 6 to 9 wk, almost half of the isoproturon was still actively present in the upper soil layers (0-10 and 10-20 cm) and only 5 to 10% of biological activity was inhibited in the deeper soil layer tested (20-30 cm). Thus, inhibition within the limit of detection of both bioassays could be observed up to 9 wk after application in all profiles (0-30 cm), whereas inhibition persisted for up to 11 wk in the upper soil profile (0-10 cm). The use of the biosensor demonstrated its possibility for making rapid and cheap phytotoxicity tests. Our biosensor can give preliminary information about the biological activity of isoproturon in hours--much faster than growth biotests that may take several days or more.


Long-term risk of reproductive cancer among Vietnamese women using the quinacrine hydrochloride pellet system vs. intrauterine devices or tubal ligation for contraception.
To determine the long-term risk of reproductive tract cancer in women using the quinacrine hydrochloride pellet system of permanent contraception (QS) relative to the comparable risk in women using Copper T intrauterine device (IUD) or tubal ligation surgery (TL) for long-term or permanent contraception. This was a retrospective cohort study, conducted in the Northern Vietnamese provinces of Ha Nam, Nam Dinh, Ninh Binh and Thai Binh. Women who had their first QS procedure, last IUD insertion or TL between 1989 and 1996 were interviewed regarding post-procedure health outcomes, particularly reproductive tract cancers. A 95% response rate resulted in 21,040 completed interviews. Reproductive cancer incidence rates were very low (5.77/100,000 women years of follow-up time; 95%CI = 3.72-8.94). No significant excess hazard of reproductive tract cancer was associated with QS. No significant excess long-term risk of reproductive tract cancer was found after an average 16 years of follow-up among a large group of women using QS vs. IUD/TL for contraception.


Ehlers-Danlos syndrome and other heritable connective tissue disorders that impact pregnancies can be detected using next-generation DNA sequencing.
Ehlers-Danlos syndromes (EDS) are a genetically heterogeneous group of inherited connective tissue disorders classified into six major types with a variable collection of findings and different inheritance patterns. Although complications occur in about one-half of pregnancies in women with EDS, the majority can have a good outcome if managed appropriately. Classic EDS is characterized by joint hypermobility, loose skin with poor healing and easy bruising, musculoskeletal problems with chronic pain and at risk for pre-term delivery. In addition, the vascular form of EDS can have cardiac anomalies, aneurysms, gastrointestinal perforation and uterine rupture during pregnancy. Due to overlapping features among the connective tissue disorders, it is difficult to categorize the disorder into specific types without detailed genetic testing which is now available through advanced genomic technology using next-generation DNA sequencing, searching genomic databases and bioinformatics approach. Therefore, obstetrical complications are variable but relate to specific connective tissue disorders requiring an exact diagnosis. There are several dozen genes causing connective tissue disorders that are currently available for testing using next-generation sequencing and bioinformatics to provide pertinent care, treatment and surveillance of the affected pregnant woman but also for her at-risk fetus related to the specific heritable condition.


Legal implications of preparing and dispensing drugs under conditions not in a product's official labeling.
The legal issues surrounding the potential liability of a pharmacist for dispensing or preparing drugs under conditions not contained in the official labeling of a product are examined. Although the specific issue of liability of a pharmacist for preparing a drug in a nonapproved manner or dispensing a drug for a nonapproved use has not been adjudicated, based on evolving legal principles it appears that the pharmacist will be held responsible for the drugs so prepared or dispensed. Preparation of a drug which is adulterated under the federal Food, Drug and Cosmetic Act appears to be negligent, although its precise effect will be dependent upon state law. Liability for dispensing for nonapproved uses may be minimized if the pharmacist, in the exercise of sound professional judgment, concludes that the use is rational, safe and reasonable.


Using NLM exhibits and events to engage library users and reach the community.
In an effort to reach out to library users and make the library a more relevant, welcoming place, the University of Florida's Health Science Center Library hosted exhibits from the National Library of Medicine's (NLM) Traveling Exhibition Program. From 2010 through 2012, the library hosted four NLM exhibits and created event series for each. Through reflection and use of a participant survey, lessons were learned concerning creating relevant programs, marketing events, and forming new partnerships. Each successive exhibit added events and activities to address different audiences. A survey of libraries that have hosted NLM exhibits highlights lessons learned at those institutions.


[Study of the role of sialic acids in the formation of bound form of insulin].
In studying the formation of insulin complexes with transferrin the role played by sialic acids in this process was ascertained. The role of terminal sialic acids, included into the glycoprotein composition, in the formation of complexes of these glycoproteins with a number of components circulating in the blood was noted earlier. To study the role played by sialic acids of transferrin molecule in the formation of complexes with insulin the author used transferrin untreated and treated with neuraminidase, an enzyme splitting the sialic acid molecules from grycoprotein specifically. The influence of these preparations on the biological activity of insulin was studied. Transferrin devoid of sialic acid lost its capacity to form complexes with insulin. Control experiments demonstrated that by itself neuraminidase treatment of preparations of transferrin and insulin failed to influence their biological activity. The results of experiments with the use of neuraminidase demonstrated that sialic acid in donor transferrin molecule could be of great significance in the formation of an insulin-transferrin complex.


The effect of follicle stimulating hormone and epidermal growth factor on the developmental capacity of in-vitro matured mouse oocytes.
This study investigates the effects of follicle stimulating hormone (FSH) or epidermal growth factor (EGF) on the development of mouse oocytes matured in vitro. The data show that addition of FSH or EGF does not significantly increase the proportion of oocytes maturing to metaphase II but does increase the ability of these oocytes to cleave to the 2-cell stage after fertilization. After transfer of 2-cell embryos to pseudopregnant recipients, 64-78% of the embryos implanted, which was significantly reduced compared to embryos from in-vivo matured controls (89%). Fewer fetuses at day 14 of gestation were produced from embryos derived from oocytes matured in basal conditions (26%), or in the presence of EGF (32%), compared to oocytes matured in vivo (64%) or in the presence of FSH (58%). Examination of polar bodies and pronuclei of oocytes matured in vitro suggests that an increase in the rate of triploidy may be partly responsible for the increased fetal loss after maturation in the absence of FSH. This study shows that the fertilization rate after in-vitro maturation can be improved by FSH and EGF and that subsequent embryonic development is improved specifically by FSH.


Hypnotic interviewing: the best way to interview eyewitnesses?
It has been suggested that hypnosis techniques may have the potential to enhance eyewitness memory in forensic investigations. However, laboratory research shows that increases in recall with hypnosis techniques are often associated with decreases in accuracy, false confidence in incorrect information, and increased suggestibility to leading questions and misleading post-event information. These problems limit the usefulness of hypnosis as an interviewing procedure. However, in practical investigations, many factors associated with hypnosis, apart from the hypnotic induction itself, might lead to memory enhancement compared with standard police interviews. For example, hypnotic interviewers, because of their psychological, clinical, and interpersonal skills, may be better interviewers than police officers. They may use effective interviewing strategies such as those associated with the "cognitive interview"; a procedure which has the potential to enhance recall by approximately 35% without the problems of memory distortion associated with hypnosis. It is concluded, therefore, that a cognitive interview procedure should be used in preference to hypnosis.


Integrative Biology and Big-Data-Centrism: Mapping out a Bioscience Ethics Perspective with a S.W.O.T. Matrix.
In current biomedicine, omics technologies drive systems-oriented modes of research to achieve a more holistic and personalized view of health and disease. This shift in scientific approach co-occurs with an era of biocapitalism characterized by markets for biomaterial (e.g., DNA, cells, and tissues) as exploitable resources, high-throughput technologies as tools, and "Big Data" as currency. Prediagnostics and genomics-based analyses successfully entered the public domain more or less unfiltered, offering numerous business opportunities envisioning individuals to contribute to the health sector by providing biomaterial and data as well as by using technology, thus becoming participants and informed coproducers of health. Exploring strengths and weaknesses, as well as opportunities and threats by S.W.O.T. analysis, we highlight some chances, pitfalls, and biases of this sector from a bioscience ethics stance. We conclude that the shift from diagnostic to predictive interpretation of data that comes along with integrative biology seems to escape the general and sometimes the experts' awareness. Moreover, rapid translation into products for the global health market is based on marketable views on health and disease that in turn affect basic research through, for example, funding policies and the research questions being asked. Along with this, biological reductionism is revived fuelling simplified understandings of the genotype phenotype relationship in terms of biology and the human dimension in a broader sense, as well as visions of achieving human perfection through novel biotechnologies.


The cumulative damage index method: a new method for evaluating the effectiveness of control measures for Plutella xylostella (Lepidoptera: Plutellidae).
All previously and currently used methods for effectiveness evaluation of control measures for the diamondback moth (DBM) do not simultaneously take the actual damage and population size into consideration. Here, we propose a new method, the cumulative damage index method, in which the number of larvae and their amount of food consumption are simultaneously included in the calculation of the theoretical cumulative damage index (T) and actual cumulative damage index (A). Evaluation was based on the reduced degree of damage calculated according to indexes T and A. Based on the new method, the corrected effectiveness of the combined use of biological measures, chemical insecticides, Bacillus thuringiensis (Bt) and P. xylostella granulosis virus (PxGV) on DBM was 35.85, 2.37, 12.50 and 11.77% respectively. Under the action of natural factors, the Population Developmental Index (I) of DBM was 5.1 ± 1.4; under the integrated actions of natural factors and these four types of measure, index I of DBM was 0.34 ± 0.1, 6.1 ± 1.5, 2.1 ± 0.5 and 1.1 ± 0.3 respectively. The sole effectiveness of Trichogramma spp. when integrated with other natural factors, integrated biological measures and chemical insecticides was 21.43 ± 1.69%, 45.27 ± 4.09% and 20.68 ± 2.60% respectively. There was some difference between the effectiveness evaluated by the new method and index I, and the actual damage caused by DBM could be reflected well by index A. The new method is more scientifically appropriate and practical for effectiveness evaluation than existing methods. © 2014 Society of Chemical Industry.


Down but not out in posterior cingulate cortex: Deactivation yet functional coupling with prefrontal cortex during demanding semantic cognition.
The posterior cingulate cortex (pCC) often deactivates during complex tasks, and at rest is often only weakly correlated with regions that play a general role in the control of cognition. These observations led to the hypothesis that pCC contributes to automatic aspects of memory retrieval and cognition. Recent work, however, has suggested that the pCC may support both automatic and controlled forms of memory processing and may do so by changing its communication with regions that are important in the control of cognition across multiple domains. The current study examined these alternative views by characterising the functional coupling of the pCC in easy semantic decisions (based on strong global associations) and in harder semantic tasks (matching words on the basis of specific non-dominant features). Increasingly difficult semantic decisions led to the expected pattern of deactivation in the pCC; however, psychophysiological interaction analysis revealed that, under these conditions, the pCC exhibited greater connectivity with dorsolateral prefrontal cortex (PFC), relative to both easier semantic decisions and to a period of rest. In a second experiment using different participants, we found that functional coupling at rest between the pCC and the same region of dorsolateral PFC was stronger for participants who were more efficient at semantic tasks when assessed in a subsequent laboratory session. Thus, although overall levels of activity in the pCC are reduced during external tasks, this region may show greater coupling with executive control regions when information is retrieved from memory in a goal-directed manner.


A COVID-19 forecasting system for hospital needs using ANFIS and LSTM models: A graphical user interface unit.
Centers for Disease Control and Prevention data showed that about 40% of coronavirus disease 2019 (COVID-19) patients had been suffering from at least one underlying medical condition were hospitalized; in which nearly 33% of them needed to be admitted to the intensive care unit (ICU) to receive specialized medical services. Our study aimed to find a proper machine learning algorithm that can predict confirmed COVID-19 hospital admissions with high accuracy. We obtained data on daily COVID-19 cases in regular medical inpatient units, emergency department, and ICU in the time window between 21 July 2020 and 21 November 2021. Data for the first 183 days (training data set) were used for long short-term memory (LSTM) network, adaptive neuro-fuzzy inference system (ANFIS), support vector regression (SVR) and decision tree model training, whilst the remaining data for the last 60 days (test data set) were used for model validation. To predict the number of ICU and non-ICU patients, we used these models. Finally, a user-friendly graphical user interface unit was designed to load any time series data (here the trend of population of COVID-19 patients) and train LSTM, ANFIS, SVR or tree models for the prediction of COVID-19 cases for one week ahead. All models predicted the dynamics of COVID-19 cases in ICU and non- wards. The values of root-mean-square error and R 2 as model assessment metrics showed that ANFIS model had better predictive power among all models. Artificial intelligence-based forecasting models such as ANFIS system or deep learning approach based on LSTM or regression models including SVR or tree regression play a key role in forecasting the required number of beds or other types of medical facilities during the coronavirus pandemic. Thus, the designed graphical user interface of the present study can be used for optimum management of resources by health care systems amid COVID-19 pandemic.


GC-MS profiling of fatty acids in green coffee (Coffea arabica L.) beans and chemometric modeling for tracing geographical origins from Ethiopia.
This study was aimed at the development of objective analytical method capable of verifying the production region of the coffee beans. One hundred samples of green coffee (Coffea arabica L.) beans from the major producing regions, comprising various sub-regional types, were studied for variations in their fatty acid compositions by using gas chromatography coupled with mass spectrometry. Principal component analysis (PCA) was used to visualize data trends. Linear discriminant analysis (LDA) was used to construct classification models. Twenty-one different fatty acids were detected in all of the samples. The total fatty acid content varied from 83 to 204 g kg-1 across the regions. Oleic, linoleic, palmitic, stearic and arachidic acids were identified as the most discriminating compounds among the production regions. The recognition and prediction abilities of the LDA model for classification at regional level were 95% and 92%, respectively, and 92% and 85%, respectively, at sub-regional level. Fatty acids contain adequate information for use as descriptors of the cultivation region of coffee beans. Chemometric methods based on fatty acid composition can be used to detect fraudulently labeled coffees, with regard to the production region. These can benefit the coffee production market by providing consumers with products of the expected quality. © 2019 Society of Chemical Industry.


DNA damage checkpoint execution and the rules of its disengagement.
Chromosomes are susceptible to damage during their duplication and segregation or when exposed to genotoxic stresses. Left uncorrected, these lesions can result in genomic instability, leading to cells' diminished fitness, unbridled proliferation or death. To prevent such fates, checkpoint controls transiently halt cell cycle progression to allow time for the implementation of corrective measures. Prominent among these is the DNA damage checkpoint which operates at G2/M transition to ensure that cells with damaged chromosomes do not enter the mitotic phase. The execution and maintenance of cell cycle arrest are essential aspects of G2/M checkpoint and have been studied in detail. Equally critical is cells' ability to switch-off the checkpoint controls after a successful completion of corrective actions and to recommence cell cycle progression. Interestingly, when corrective measures fail, cells can mount an unusual cellular response, termed adaptation, where they escape checkpoint arrest and resume cell cycle progression with damaged chromosomes at the cost of genome instability or even death. Here, we discuss the DNA damage checkpoint, the mitotic networks it inhibits to prevent segregation of damaged chromosomes and the strategies cells employ to quench the checkpoint controls to override the G2/M arrest.


Late-Stage Functionalization of Platensimycin Leading to Multiple Analogues with Improved Antibacterial Activity in Vitro and in Vivo.
Bacterial fatty acid synthases are promising antibacterial targets against multidrug-resistant pathogens. Platensimycin (PTM) is a potent FabB/FabF inhibitor, while its poor pharmacokinetics hampers the clinical development. In this study, a focused library of PTM derivatives was prepared through thiolysis of PTM oxirane (1), followed by various C-C cross-coupling reactions in high yields. Antibacterial screening of these compounds in vitro yielded multiple hits with improved anti-Staphylococcus activities over PTM. Among them, compounds A1, A3, A17, and A28 exhibited improved antibacterial activities over PTM against methicillin-resistant Staphylococcus aureus (MRSA) in a mouse peritonitis model. Compound A28 was further shown to be effective against MRSA infection in a mouse wound model, in comparison to mupirocin. Therefore, the facile preparation and screening of these PTM derivatives, together with their potent antibacterial activities in vivo, suggest a promising strategy to improve the antibacterial activity and pharmacokinetic properties of PTM.


The effect of prior exercise on ex vivo induction of heme oxygenase-1 in human lymphocytes.
It was postulated that prior demanding exercise would suppress the induction of the oxidant-responsive protein Heme Oxygenase-1 (HO-1) in mononuclear cells following subsequent ex vivo H(2)O(2) treatment. Eight male subjects completed two trials in a randomized order (one rest and one exercise) and ex vivo HO-1 protein induction was determined following H(2)O(2) treatment in lymphocytes and monocytes before and after each trial using a newly developed and reproducible assay. Lymphocytes obtained 2 h post-exercise showed a modest reduction in HO-1 protein expression in response to ex vivo treatment with H(2)O(2) (p<0.05). The plasma concentration of the HO-1 suppressor alpha1-antitrypsin increased immediately post-exercise (p<0.05) and it is tentatively suggested that this may explain the modest transient reduction in ex vivo HO-1 protein induction in lymphocytes in response to an independent oxidant challenge following a prior bout of demanding exercise.


Hints for Leptonic CP Violation or New Physics?
One of the major open questions in the neutrino sector is the issue of leptonic CP violation. Current global oscillation data show a mild preference for a large, potentially maximal value for the Dirac CP phase in the neutrino mixing matrix. In this Letter, we point out that new physics in the form of neutral-current-like nonstandard interactions with real couplings would likely yield a similar conclusion even if CP in the neutrino sector were conserved. Therefore, the claim for a discovery of leptonic CP violation will require a robust ability to test new physics scenarios.


The dynamics of questing ticks collected for 164 consecutive months off the vegetation of two landscape zones in the Kruger National Park (1988-2002). Part I. Total ticks, Amblyomma hebraeum and Rhipicephalus decoloratus.
Despite a large number of studies on tick biology, there is limited information on long- term changes in tick populations. This study thus aimed to assess the long-term population dynamics of questing ixodid ticks in two landscape zones of the Kruger National Park (KNP). Questing ixodid ticks were collected in the KNP from August 1988 to March 2002 by monthly dragging of the vegetation in three habitats (grassland, woodland and gully) at two sites (Nhlowa Road and Skukuza). Findings pertaining to total tick numbers and Amblyomma hebraeum and Rhipicephalus decoloratus specifically are presented here. Fourteen tick species were collected, as well as four others that could be identified only to generic level. More ticks (211 569 vs 125 810) were collected at Nhlowa Road than at Skukuza. Larvae were the most commonly collected stage of all the major tick species. A. hebraeum was the most commonly collected tick (63.6%) at Nhlowa Road, whereas R. decoloratus accounted for 15.3% of the ticks collected there. At Skukuza, 31.6% and 27.1% of the collected ticks were R. decoloratus and A. hebraeum respectively. Most A. hebraeum larvae were collected in summer and the fewest in winter and early spring, mostly in woodland and least often in grassland habitats. Most R. decoloratus larvae were collected in spring and the fewest in autumn and winter, and were more frequently collected in woodland and grassland than in gullies. The largest collections of most tick species were made during the early 1990 s, while numbers were lowest in the mid-1990 s after a drought during 1991 and 1992 and then increased towards the late 1990 s, followed by a final decrease. The changes in tick numbers over time probably reflect differences in their host communities at the two sites and the effect of climatic conditions on both hosts and free-living ticks. The population dynamics of questing ticks reflect a complex interaction between ticks, their hosts and the environment.


Machine Learning and Cloud-Based Knowledge Graphs to Recognize Suicidal Mental Tendencies.
To improve the quality of knowledge service selection in a cloud manufacturing environment, this paper proposes a cloud manufacturing knowledge service optimization decision method based on users' psychological behavior. Based on the characteristic analysis of cloud manufacturing knowledge service, establish the optimal evaluation index system of cloud manufacturing knowledge service, use the rough set theory to assign initial weights to each evaluation index, and adjust the initial weights according to the user's multiattribute preference to ensure that the consequences are allocated correctly. The system can help counselors acquire psychological knowledge in time and identify counselors with suicidal tendencies to prevent danger. This paper collected some psychological information data and built a knowledge graph by creating a dictionary and generating entities and relationships. The Han language processing word segmentation tool generates keywords, and CHI (Chi-square) feature selection is used to classify the problem. This feature selection is a statistical premise test that is acceptable when the chi-square test results are distributed with the null hypothesis. It includes the Pearson chi-square test and its variations. The Chi-square test has several benefits, including its distributed processing resilience, ease of computation, broad information gained from the test, usage in research when statistical assumptions are not satisfied, and adaptability in organizing information from multiple or many more group investigations. For improving question and answer efficiency, compared with other models, the BiLSTM (bidirectional long short-term memory) model is preferred to build suicidal tendencies. The Han language processing is a method that is used for word segmentation, and the advantage of this method is that it plays a key role in the word segmentation tool and generates keywords, and CHI (Chi-square) feature selection is used to classify the problem. Text classifier detects dangerous user utterances, question template matching, and answer generation by computing similarity scores. Finally, the system accuracy test is carried out, proving that the system can effectively answer the questions related to psychological counseling. The extensive experiments reveal that the method in this paper's accuracy rate, recall rate, and F1 value is much superior to other standard models in detecting psychological issues.


Calcineurin governs thermotolerance and virulence of Cryptococcus gattii.
The pathogenic yeast Cryptococcus gattii, which is causing an outbreak in the Pacific Northwest region of North America, causes life-threatening pulmonary infections and meningoencephalitis in healthy individuals, unlike Cryptococcus neoformans, which commonly infects immunocompromised patients. In addition to a greater predilection for C. gattii to infect healthy hosts, the C. gattii genome sequence project revealed extensive chromosomal rearrangements compared with C. neoformans, showing genomic differences between the two Cryptococcus species. We investigated the roles of C. gattii calcineurin in three molecular types: VGIIa (R265), VGIIb (R272), and VGI (WM276). We found that calcineurin exhibits a differential requirement for growth on solid medium at 37°, as calcineurin mutants generated from R265 were more thermotolerant than mutants from R272 and WM276. We demonstrated that tolerance to calcineurin inhibitors (FK506, CsA) at 37° is linked with the VGIIa molecular type. The calcineurin mutants from the R272 background showed the most extensive growth and morphological defects (multivesicle and larger ring-like cells), as well as increased fluconazole susceptibility. Our cellular architecture examination showed that C. gattii and C. neoformans calcineurin mutants exhibit plasma membrane disruptions. Calcineurin in the C. gattii VGII molecular type plays a greater role in controlling cation homeostasis compared with that in C. gattii VGI and C. neoformans H99. Importantly, we demonstrate that C. gattii calcineurin is essential for virulence in a murine inhalation model, supporting C. gattii calcineurin as an attractive antifungal drug target.


Human recombinant interleukin 2-activated sheep lymphocytes lyse sheep pulmonary microvascular endothelial cells.
Administration of lymphokine-activated killer (LAK) cells in combination with interleukin 2 (IL-2) has been effective in reducing tumor mass in humans, but has been accompanied by significant toxicity. We used a chronic awake sheep model to investigate the cause of the vascular leak syndrome associated with IL-2 administration. Sheep repeatedly infused with human recombinant IL-2 (hrIL-2) developed mild pulmonary hypertension, systemic hypotension, acidemia, hypoxemia, and increased flow of protein rich lung lymph. We hypothesized that LAK cells may damage lung endothelium in vivo and cause increased lung vascular permeability. Sheep peripheral blood and lung lymph lymphocytes incubated in vitro with hrIL-2 generated cytotoxic activity for human K-562 cells and sheep pulmonary microvascular endothelial cells. In addition, cytotoxic effector cells were isolated from the peripheral blood of a sheep which had received hrIL-2. These observations suggest that LAK cells possess the ability to damage endothelial cells and may contribute to an increased pulmonary vascular permeability observed following hrIL-2 infusion in sheep.


Additive Effect of Risk Factors for Trabeculectomy Failure in Glaucoma Patients: A Risk-group From a Cohort Study.
The purpose of the study was to assess the role of significant risk factors and develop a risk-group category related to the trabeculectomy (Trab) failure. A retrospective cohort study was developed between January 2009 and June 2014. In total, 120 eyes included in this study had a glaucoma diagnosis and undergone to Trab with mitomycin. The main outcome measures were surgical success and failure rate. Multivariate (Cox proportional hazards regression model) analyses were used to examine the predictive value of significant factors. A risk-group category was build based on the number of significant risk factors for patients. The risk group category was tested using the Kaplan-Meier method and log-rank test. With a median follow-up of 33 months (3 to 72 mo), the complete surgical success in 1, 2, 3, and 4 years was 82%, 63.5%, 52%, and 27.6%, respectively. The probability of freedom from a complete surgical failure was 88%, 84.5%, 78%, and 70% in 1, 2, 3, and 4 years, respectively. Glaucoma type (P=0.008), previous ophthalmic surgery (P=0.04), glaucoma medication use ≥3 years (P=0.010) and 4 glaucoma medication use pre-Trab (P=0.038) were identified as risk factors for surgical failure. The probability of freedom of surgical failure in 3 years was 93%, 83%, and 37.6% (P=0.003), for low (no factors), intermediate (1 to 2 factors), and high-risk group (3 to 4 factors). Trab with mitomycin produces satisfactory intraocular pressure control over time. However, several risk factors influence the efficacy of the surgical procedure. Our data show that there seems to exist an additive effect among risk factors with similar pathophysiology.


The Effects of Oscillatory Biofield Therapy on Pain and Functional Limitations Associated with Carpal Tunnel Syndrome: Randomized, Placebo-Controlled, Double-Blind Study.
Biofield treatments have been used for pain control in patients with cancer and chronic pain. However, research on the effect of biofield treatment on specific somatic disorders is lacking. This study intends to investigate the effect of oscillating biofield therapy (OBFT) on symptoms of carpal tunnel syndrome. Randomized, placebo-controlled, double-blind study. Thirty patients with chronic carpal tunnel syndrome participated in the study. Patients were randomly assigned to active or placebo treatment groups. Those in the treatment group received six sessions of OBFT with intention to treat during a period of 2 weeks. Patients in the placebo group had the same number of treatment sessions with mock OBFT treatment. The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; Symptom Severity Scale (SSS); and Functional Status Scale (FSS) were used for outcome assessment. Both clinically and statistically significant changes in intensity of pain with activity (95% confidence interval [CI], 2.5-4.2; p = 0.000), night pain (p = 0.000, 95% CI, 3.2-5.7), DASH questionnaire (95% CI, 12.0-21.9; p = 0.000), SSS (95% CI, 0.64-1.15; p = 0.003), and FSS (95% CI, 0.41-0.97; p = 0.029) were found between the treatment and placebo groups. Statistically significant reduction in number of patients with positive results on the Phalen test (87%; p = 0.000), Tinel sign (73%; p = 0.000), and hand paresthesia (80%; p = 0.000) was noted in the treatment group. During 6-month follow-up, 86% of patients in the treatment group remained pain free and had no functional limitations. OBFT can be a viable and effective treatment for improving symptoms and functional limitations associated with chronic carpal tunnel syndrome.


The epidemiology of hyperferritinaemia.
To discover the causes of markedly raised ferritin levels in patients seen at a teaching hospital in Newcastle Upon Tyne, United Kingdom. Demographic and medical data were collected for all patients over 18 years who had a serum ferritin levels recorded as >=1500 microg/L during the period January to September 2002. The cause or causes for their hyperferritinaemia were identified from their medical notes. Patients from a defined local population were identified. A total of 19583 measurements were provided of which 406 from 199 patients were >=1500 microg/L. An annual incidence for the local population was determined to be 0.44/1000. 150/199 medical notes were scrutinised and 81 patients were identified as having a single cause for their raised ferritin level. The most common single cause was alcoholic liver disease in the local population and renal failure was the most common single cause in the overall population. Confirmed hereditary haemochromatosis was the 10th most common cause. Liver disease contributed to hyperferritinaemia in 44% of the patients. Weight loss may have contributed to hyperferritinaemia in up to 11%. Alcohol related liver disease, haemat-ological disease, renal failure and neoplasia are much more common causes of marked hyperferritinaemia than haemochromatosis. The role of weight loss in hyperferritinaemia may warrant further investigation.


Clinical use of optical coherence tomography during percutaneous coronary intervention and coronary procedures in Southeast Asia: a survey-based expert consensus summary.
Optical coherence tomography (OCT), an established intravascular imaging technique, enables rapid acquisition of high-resolution images during invasive coronary procedures to assist physician decision-making. OCT has utility in identifying plaque/lesion morphology (e.g., thrombus, degree of calcification, and presence of lipid) and vessel geometry (lesion length and vessel diameter) and in guiding stent optimisation through identification of malapposition and underexpansion. The use of OCT guidance during percutaneous coronary interventions (PCI) has demonstrated improved procedural and clinical outcomes in longitudinal registries, although randomised controlled trial data remain pending. Despite growing data and guideline endorsement to support OCT guidance during PCI, its use in different countries is not well established. This article is based on an advisory panel meeting that included experts from Southeast Asia (SEA) and is aimed at understanding the current clinical utility of intracoronary imaging and OCT, assessing the barriers and enablers of imaging and OCT adoption, and mapping a path for the future of intravascular imaging in SEA. This is the first Southeast Asian consensus that provides insights into the use of OCT from a clinician's point of view.


Prognostic significance of the p185 protein in colorectal cancer.
The amplification and/or overexpression of the c-erbB-2/neu oncogene may play a role in tumor development and progression. The aim of this prospective study was to evaluate the prognostic value of p185 protein in colorectal cancer using immunohistochemical techniques. We analyzed 106 colorectal tumor tissue specimens from patients who had been operated on by the same surgeon and subjected to a median follow-up of 3 years. Thirty-three per cent of patients showed p185 overexpression related to an advanced stage of the disease. In patients with adenocarcinoma tumors of the colon without distant metastases, p185 detection was found to be of clinical prognostic relevance (p = 0.06).


Major hurdles of immune-checkpoint inhibitors in pancreatic ductal adenocarcinoma.
In 2030, pancreatic ductal adenocarcinoma (PDAC) will become the second leading cause of cancer-related mortality in the world. Unfortunately, neither conventional chemotherapy nor novel immunotherapeutic strategies can provide durable responses and the survival prognosis remains very low. PDAC is notorious for its immune-resistant features and unique genomic landscape facilitating tumor escape from immunosurveillance. Novel immune-checkpoint inhibitors (ICI) failed to show promising efficacy and other multi-modal approaches are currently being validated in multiple clinical trials. In this paper, we provide our opinion on the major mechanisms responsible for PDAC resistance to ICI therapy and provide our view on future strategies which may overcome those barriers.


Factors Influencing Sustained Engagement with ECG Self-Monitoring: Perspectives from Patients and Health Care Providers.
Patient-generated health data (PGHD) collected digitally with mobile health (mHealth) technology has garnered recent excitement for its potential to improve precision management of chronic conditions such as atrial fibrillation (AF), a common cardiac arrhythmia. However, sustained engagement is a major barrier to collection of PGHD. Little is known about barriers to sustained engagement or strategies to intervene upon engagement through application design. This article investigates individual patient differences in sustained engagement among individuals with a history of AF who are self-monitoring using mHealth technology. This qualitative study involved patients, health care providers, and research coordinators previously involved in a randomized, controlled trial involving electrocardiogram (ECG) self-monitoring of AF. Patients were adults with a history of AF randomized to the intervention arm of this trial who self-monitored using ECG mHealth technology for 6 months. Semistructured interviews and focus groups were conducted separately with health care providers and research coordinators, engaged patients, and unengaged patients. A validated model of sustained engagement, an adapted unified theory of acceptance and use of technology (UTAUT), guided data collection, and analysis through directed content analysis. We interviewed 13 patients (7 engaged, 6 unengaged), 6 providers, and 2 research coordinators. In addition to finding differences between engaged and unengaged patients within each predictor in the adapted UTAUT model (perceived ease of use, perceived usefulness, facilitating conditions), four additional factors were identified as being related to sustained engagement in this population. These are: (1) internal motivation to manage health, (2) relationship with health care provider, (3) supportive environments, and (4) feedback and guidance. Although it required some modification, the adapted UTAUT model was useful in understanding of the parameters of sustained engagement. The findings of this study provide initial requirement specifications for the design of applications that engage patients in this unique population of adults with AF.


Ethical Issues Regarding Neurosurgical Management of Penetrating Brain Injury in the French Armed Forces.
Combat penetrating brain injury (PBI) differs significantly from PBI in civilian environments. Differences include technical factors such as the weapons involved, strained resource environments, and limited medical materials and human resources available. Ethical issues regarding the management of PBI in military settings may occur. This case study examines the case of a 20-year-old member of the French Armed Forces that suffered a penetrating brain injury in a combat situation. The four-quadrant method along with the four principles of medical ethics (respect for autonomy, beneficence, nonmaleficence, and justice) was used to analyze this case and to apply ethics to the practice of military medicine. Nowadays, we possess the medical and surgical resources as well as the aeromedical evacuation capability to save the life of a soldier with a penetrating craniocerebral wound. Nonetheless, the functional outcome of this type of wound places military doctors in an ethical dilemma. The line of conduct and clinical protocol established by the French Medical Health Service is to manage all PBIs when the patient's life can be saved and to provide all available financial and social support for the rehabilitation of patients and their family.


Dislocation of the mandible during the course of cataract surgery.
Spontaneous dislocation of the mandible is a well-described clinical entity with which the ophthalmologist may not be familiar. However, the widespread use of intravenous sedation places susceptible individuals at risk for the development of dislocation of the mandible. The authors describe a patient who underwent routine cataract surgery and suffered a dislocation of the mandible that initially went unrecognized. Ophthalmic surgeons who use intravenous sedation need to be aware of this complication and need to recognize the symptoms so that patients may receive timely attention.


[New considerations about the so-called Hippocratic oath].
The history of the different interpretations of the so-called Hippocratic oath are examined in the frame of recent studies, putting in light the actual state of researches in the development of medical ethics.


Performance of neural networks for localizing moving objects with an artificial lateral line.
Fish are able to sense water flow velocities relative to their body with their mechanoreceptive lateral line organ. This organ consists of an array of flow detectors distributed along the fish body. Using the excitation of these individual detectors, fish can determine the location of nearby moving objects. Inspired by this sensory modality, it is shown here how neural networks can be used to extract an object's location from simulated excitation patterns, as can be measured along arrays of stationary artificial flow velocity sensors. The applicability, performance and robustness with respect to input noise of different neural network architectures are compared. When trained and tested under high signal to noise conditions (46 dB), the Extreme Learning Machine architecture performs best with a mean Euclidean error of 0.4% of the maximum depth of the field D, which is taken half the length of the sensor array. Under lower signal to noise conditions Echo State Networks, having recurrent connections, enhance the performance while the Multilayer Perceptron is shown to be the most noise robust architecture. Neural network performance decreased when the source moves close to the sensor array or to the sides of the array. For all considered architectures, increasing the number of detectors per array increased localization performance and robustness.


Performance analysis for wireless networks: an analytical approach by multifarious Sym Teredo.
IPv4-IPv6 transition rolls out numerous challenges to the world of Internet as the Internet is drifting from IPv4 to IPv6. IETF recommends few transition techniques which includes dual stack and translation and tunneling. By means of tunneling the IPv6 packets over IPv4 UDP, Teredo maintains IPv4/IPv6 dual stack node in isolated IPv4 networks behindhand network address translation (NAT). However, the proposed tunneling protocol works with the symmetric and asymmetric NATs. In order to make a Teredo support several symmetric NATs along with several asymmetric NATs, we propose multifarious Sym Teredo (MTS), which is an extension of Teredo with a capability of navigating through several symmetric NATs. The work preserves the Teredo architecture and also offers a backward compatibility with the original Teredo protocol.


Concerning mistreatment of older people: clinical and ethical thoughts based on a study of known cases.
Following a report by the Health Ministry recommending a greater implication of general practitioners (GP) in the diagnosis and care of mistreated older people, we wanted to evaluate what was actually their role in this matter. A study was made of files of mistreated older persons referred to the social services in a Parisian suburb. For each file, we noted who raised the first suspicions of mistreatment, who diagnosed it, what happened next, and what precisely the GP's role was. Out of 600 files, we found 12 cases, concerning 14 persons (two couples). Although all the patients had health problems requiring frequent consultations with their GP, none of these situations were diagnosed by the GP. In all cases, the GP played only a secondary role, if at all. The following points are discussed: The link between family problems and history cannot be ignored in the follow up of such situations. The GP's role is discussed regarding clinical knowledge of mistreatment and the legal rules they have to deal with. Our results bring to light how the balance between the person's autonomy and the necessary direct action is especially delicate in this field.


Current situation of COVID-19 in northern Cyprus.
The public health burden of the novel coronavirus disease 2019 (COVID-19) is expected to increase and urgent strict measures by decision-makers is critical for the containment of the novel coronavirus (SARS-CoV-2) outbreak worldwide. This study aimed to give a real-time analysis of COVID-19 presence in northern Cyprus. All official SARS-CoV-2 positive cases were tracked and reported in terms of the origin, nationality, and transmission routes. Preventive measures taken after the first reported case were analyzed for their effectiveness as control strategies. The index case of SARS-CoV-2 in northern Cyprus was identified as a female German tourist. First local case had travel history from the United Kingdom after which local transmission occurred. Rapid and strict containment measures have currently delayed a peak in observed cases. Rapid implementation of social-distancing measures, good hygiene measures and travel/gathering bans in northern Cyprus has been effective in controlling the outbreak.


The relationship between calcium uptake and hormone release in the isolated neurohypophysis. A reassessment.
The release of peptide hormones and uptake of radiolabelled calcium were measured in isolated rat neurohypophyses incubated in vitro. Neuropeptide release was provoked either by depolarising the tissue with raised extracellular potassium, or by application of biphasic electrical stimulus pulses. Potassium stimulation increased uptake of radiolabelled calcium, but electrical stimulation caused no measurable change, suggesting that non-neuronal elements unresponsive to electrical stimulation were responsible for the uptake. This possibility is supported by the results of 2 further series of experiments, in which the neurohypophyses were manipulated in vivo before incubation in vitro. First, the experimental animals were given a 2% solution of sodium chloride in place of drinking water for 3 days, to deplete the neuropeptide content of the incubated tissue. After such treatment, potassium-stimulated neuropeptide release was greatly reduced, but calcium uptake was increased relative to that of normal tissue. Secondly, the pituitary stalk was lesioned electrolytically 14 days before the incubation, thus completely eliminating the neural elements of the neurohypophysis. Potassium stimulation then released no neuropeptide, but calcium uptake increased as in normal tissue. It thus appears that calcium uptake does not always closely parallel neuropeptide release, in contrast with previous results, and that depolarisation of the non-neuronal elements is responsible for the measurable uptake of calcium. The results do not contradict existing concepts of the central role of calcium influx in stimulus-secretion coupling in neurohypophyseal terminals, but serve to emphasise the need for care in the interpretation of calcium uptake data in tissues which are not homogeneous. The neurohypophyseal glial cells (pituicytes) are a likely site for the calcium uptake caused by potassium depolarisation.


A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys.
Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples.


Circulating microparticle signature in coronary and peripheral blood of ST elevation myocardial infarction patients in relation to pain-to-PCI elapsed time.
Circulating microparticle (cMP) levels are increased in the acute phase of ST-elevation myocardial infarction (STEMI) and associate with microvascular obstruction; however, the precise cMP-parental cell signature and activation level are not elucidated. Here, we aimed to study the cMP signature in STEMI-patients and whether cMP phenotype changes in relation to onset of pain-to-PCI [ischemic time (IT)]-elapsed time. Blood was taken at PCI from the culprit coronary and the peripheral circulation in STEMI-patients (N=40). Two control groups were included: peripheral blood of age-matched patients recovering from STEMI [after 72 h] and of control individuals (N=20/group). cMP-parental origin and activation level were characterized by triple-labeling flow cytometry. Procoagulant annexin V-positive cMPs bearing parental cell markers as well as markers of activated cells displayed a significantly different profile in STEMI-patients, in control individuals and in patients recovering from STEMI. cMPs derived from monocytes, endothelium, and activated vascular cells were higher in the culprit coronary artery than in peripheral blood in STEMI-patients, especially in patients intervened at short IT. Indeed, cMP levels in coronary blood were inversely related to IT duration (more abundant in thrombi with pain-to-PCI time<180 min). A characteristic [CD66b+/CD62E+/CD142+] cMP signature in the systemic circulation reflects the formation of coronary thrombotic occlusions in STEMI-patients. Changes in the cMP signature in the culprit coronary artery blood reveal the sensitivity of MPs to detect the ischemia-elapsed time. Interestingly, cMPs in peripheral blood may be sensitive markers of the thrombo-occlusive vascular process developing in the coronary arteries of STEMI-patients.


[Intramedullary holocord tumor. Report of an autopsy case and review of literature].
This report describes a case of cystic astrocytoma that extended from C4 to the conus, and reviews intramedullary holocord tumors. A two-year-old body was admitted because of gait disturbance. He had suffered from rigidity of his left upper and lower limbs and thoracic scoliosis for six months prior to admission. On admission, neurologic examination revealed spastic paraparesis with muscle atrophy of the left lower extremity, sphincter disturbances and neck rigidity. All deep tendon reflexes were bilaterally hyperactive. Spine roentgenography demonstrated widening of the interpedicular distance from the midthoracic to the upper lumbar segments. A lumbar myelography disclosed a block at the L2 level, and a suboccipital myelography revealed a block with tapering of contrast medium at the level of the C2 vertebra. A laminectomy was performed from C1 to L3, and a myelotomy was performed from C4 to L2. Grossly total removal of solid tumor which extended from Th3 to Th8 was carried out. There were large intramedullary cysts extending from C4 to Th3, and from Th9 to L2. Eight hours after surgery, high fever, tachycardia and anuria developed, and he died next day. Cross section of the spinal cord revealed the tumor cells infiltrated diffusely in the midthoracic region, and histologically the tumor was diagnosed to be astrocytoma. The cystic portion was separate from the central canal, and the lining of the cyst was a band of fibroglial tissue without infiltration of tumor cells. A tumor of this kind extending throughout the almost whole spinal cord is extremely rate. For such a holocord tumor complete removal is the ideal treatment, but the possibilities for removal must be evaluated in terms of the tumor's relationship to the spinal cord, the histological nature and the general condition of the patient.


Evaluation of Multiple Liver Cancer Scoring Systems.
Liver cancer is one of the most common malignant tumors in the world, and its incidence and mortality are increasing year by year. The prognosis of liver cancer depends on the stage of liver cancer, the treatment method, the liver function, and individual differences. The prognosis of liver cancer mainly worsens with the progression of the stage. The prediction and staging system of liver cancer prognosis plays a very important role in the outcome of liver cancer prognosis, providing some guidance for clinical practice and bringing benefits for patients. This article reports on the prediction models and staging systems that have been applied in the field of liver cancer in the past 5 years, objectively analyzes the advantages and disadvantages, applicable population of each model and staging system, and searches for other patient and clinical characteristics that need to be considered for successfully establishing a prediction model, aiming to improve the specificity, sensitivity, and accuracy of liver cancer prediction and increase the overall survival rate of liver cancer.


Case-control study of ovarian cancer in Japan.
A case-control study of 80 women with ovarian epithelial carcinoma and 160 individually age-matched controls were conducted to assess various factors associated with the incidence of ovarian cancer in Hokkaido, Japan. Among the characteristics studied, the following factors were significantly greater in the cases than in the controls: (1) blood group A; (2) never married or married late in life; (3) more frequent surgery for retroflexion of the uterus; (4) less use of contraceptive appliances; and (5) less daily use of cosmetics. It was inferred from these observations that ovarian cancer patients had a genetic predisposition and dysfunctional ovaries. Gonadal dysfunction among ovarian cancer patients presumably explained not only altered personality and behavior patterns, but also facilitated the pituitary gonadotropin activity which has been suggested as increasing the incidence of the disease experimentally.


Photochemotherapy in treatment of psoriatic variants.
Our procedure for treating psoriatic variants--psoriasis pustulosa generalisata (PPG) and psoriasis erythrodermica (PE)--was based on the following points: (a) to quickly obtain a good tolerance level to photochemotherapy (PUVA) by applying corticosteroids and/or methotrexate (MX); (b) to discontinue the application of systemic drugs with the help of photochemotherapy, and (c) to maintain the improved condition by applying radiation in gradually prolonged intervals, thus enabling the biologic forces of the organism to participate, undisturbed by drugs, in the healing process. In some PE cases, sole PUVA therapy was sufficient, while in others small doses of MX were added to maintain the improved condition. In PPG, skin manifestations completely disappeared and general symptoms were calmed in the first application of this combined therapeutic procedure. However, in the later relapses PUVA had little share in such a combined treatment.


Single-cell RNA sequencing for the study of lupus nephritis.
Single-cell RNA sequencing (scRNA-seq) has recently undergone rapid advances in the development of this technology, leading to high throughput and accelerating discovery in many biological systems and diseases. The single-cell resolution of the technique allows for the investigation of heterogeneity in cell populations, and the pinpointing of pathological populations contributing to disease. Here we review the development of scRNA-seq technology and the analysis that has evolved with the ever-increasing throughput. Finally, we highlight recent applications of scRNA-seq to understand the molecular pathogenesis of lupus and lupus nephritis.


Influence of increased environmental temperature on oxidation processes in rat liver mitochondria.
Exposure of rats to elevated temperature of 28 degrees C or 35 degrees C for 3 days six hours daily resulted in a decreased rate of oxidation with succinate or glutamate + malate as substrates, by the mitochondria of liver. The higher decrease was observed in environment temperature of 35 degrees C. There was no change in ADP/O ratio. The activities of NADH: cytochrome c reductase and cytochrome oxidase were stimulated but activities of succinate dehydrogenase and succinate cytochrome reductase were decreased.


Biosynthesis of pullulan using immobilized Aureobasidium pullulans cells.
Immobilization of Aureobasidium pullulans by adsorption on solid supports and entrapment in open pore polyurethane foam were attempted. By adsorption, the highest cell loading of 0.012-0.018 g dry wt/cm(2) support was obtained in pH 2.0 medium. Under this acidic condition, the net surface charges (zeta potentials) of both the cells and supports were close to zero and no pullulan was synthesized. Cationic coatings of Cytodex and polyethylenimine were not efficient in enhancing the binding strength between the cells and the supports. Surface immobilized cells and polyurethane foam entrapped cells exhibited a similar fermentation characteristics resulting in ca. 18 g/L pullulan and ca. 5 g/L leaked cells. However, cells entrapped in the polyurethane foam were more shear resistant. The immobilized cells thus could be repeatedly used for pullulan biosynthesis.


Uterine leiomyoma and menstrual cycle characteristics in a population-based cohort study.
We examined the association of uterine leiomyoma with menstrual cycle characteristics in a population of non-care-seeking women. This cross-sectional study uses data from the Seveso Women's Health Study (SWHS), a population-based cohort in Italy. Participants included 341 premenopausal women, 30-60 years old, who had an intact uterus and were not pregnant, lactating, or using oral contraception or intra-uterine devices. We examined the presence of any ultrasound-detected uterine leiomyoma in relation to self-reported menstrual cycle length, flow length and heaviness of flow. The association of leiomyoma number, volume, tissue layer location and axial position with menstrual cycle characteristics was also examined. Uterine leiomyomata were detected in 73 women (21.4%). After adjustment for covariates, the presence of a leiomyoma was not significantly related to menstrual cycle length, flow length or heaviness of flow [odds ratio (OR) for scanty flow =1.9, 95% confidence interval (CI) 0.8-4.3; OR for heavy flow =1.3, 95% CI 0.7-2.5; relative to moderate flow]. Number, volume, tissue layer location (subserosal or intramural) and axial position (anterior or posterior) of the leiomyoma were also not related to menstrual cycle characteristics. In this Italian population of women not seeking gynaecological care, menstrual characteristics are not related to leiomyoma.


Multiband localized spoof plasmons in closed textured cavities.
In this work, we explore the existence of multiband localized spoof plasmons (LSPs) in closed textured cavities with multiple groove depths. It is interesting to note that the spoof LSPs in each band resemble those generated by the textured 2D cavities of the same periodicity with the corresponding single groove depth, and the field distributions and confinement characteristics of the plasmon-like modes in such a corrugated cavity are different from the conventional cavity. Hence, these multiple resonance band structures can find potential applications in the microwave and terahertz frequencies.


Kinetics of Light-Responsive CNT / PNIPAM Hydrogel Microactuators.
Light-responsive microactuators composed of vertically aligned carbon nanotube (CNT) forests mixed with poly(N-isopropylacrylamide) (PNIPAM) hydrogel composites are studied. The benefit of this composite is that CNTs act as a black absorber to efficiently capture radiative heating and trigger PNIPAM contraction. In addition, CNT forests can be patterned accurately using lithography to span structures ranging from a few micrometers to several millimeters in size, and these CNT-PNIPAM composites can achieve response times as fast as 15 ms. The kinetics of these microactuators are investigated through detailed analysis of high-speed videos. These are compared to a theoretical model for the deswelling dynamics, which combines thermal convection and polymer diffusion, and shows that polymer diffusion is the rate-limiting factor in this system. Applications of such CNT/hydrogel actuators as microswimmers are discussed, with light-actuating micro-jellyfish designs exemplified, and >1500 cycles demonstrated.


Linking energy-sanitation-agriculture: Intersectional resource management in smallholder households in Tanzania.
In order to create sustainable systems for resource management, residues from cooking and ecological sanitation (EcoSan) can be employed in recycling-driven soil fertility management. However, the link between energy, sanitation, and agricultural productivity is often neglected. Hence, the potential self-sufficient nature of many smallholdings in sub-Saharan Africa is underexploited. To compare those cooking and sanitation technologies most commonly used in north-western Tanzania with locally developed alternatives, with respect to (i) resource consumption, (ii) potential to recover resources, and (iii) environmental emissions. This study examines technologies at the household level, and was carried out using material flow analysis (MFA). The specific bioenergy technologies analysed include: three-stone fires; charcoal burners; improved cooking stoves (ICS), such as rocket and microgasifier stoves; and biogas systems. The specific sanitation alternatives studied comprise: pit latrines; two approaches to EcoSan; and septic systems. The use of ICS reduces total resource consumption; using charcoal or biogas does not. The residues from microgasifiers were analysed as having a substantial recovery potential for carbon (C) and phosphorus (P). The fact that input substrates for biogas digesters are post-agricultural in nature means that biogas slurry is not considered an 'untapped resource' despite its ample nutrient content. Exchanging pit latrines for water-based sanitation systems places heavy pressure on already scarce water resources for local smallholders. In contrast, the implementation of waterless EcoSan facilities significantly promotes nutrient recovery and reduces environmental emissions, particularly through greenhouse gas emission and nutrient leaching. Recycled outputs from the triple energy-sanitation-agriculture nexus display complementary benefits: residues from cooking can be used to restore organic matter in soils, while sanitation residues contribute to fertilisation. The combination of microgasifiers and EcoSan-facilities is the most appropriate in order to simultaneously optimise resource consumption, reduce environmental impacts, and maximise recycling-based soil management in smallholder farming systems.


Regulatory effect of lithium on thyroxine metabolism in murine neural and anterior pituitary tissue.
The conversion of T4 to T3 in the brain and anterior pituitary gland contributes significantly to the T3 content of these tissues and appears to be an important modulator of thyroid hormone action. In the present study, the antimanic agent lithium was demonstrated in cultured neural and pituitary tissue to have a significant inhibitory effect on the activity of low Km (type II) iodothyronine 5'-deiodinase (I5'D), the enzyme mediating T3 formation. At medium lithium concentrations of 3.3-5 mM, 15'D activity was decreased 44 +/- 3% (P less than 0.001) in the NB41A3 mouse neuroblastoma cell line and 48 +/- 2% (P less than 0.001) in the GH3 rat pituitary tumor cell line. This inhibitory effect was only observed in intact cells. Significant inhibition of this enzymatic process was also noted in the anterior pituitary gland of thyroidectomized rats injected 3-24 h earlier with either 4 or 10 mmol/kg BW LiCl. This decrease in low Km I5'D activity was accompanied by significant decreases in the serum T3 concentration and the pituitary nuclear T3 content. Renal high Km (type I) I5'D activity was unaffected by lithium administration. These studies demonstrate that lithium, an agent of proven therapeutic benefit in patients with manic-depressive illness, can affect changes in T4 metabolism and cellular T3 content in neural and anterior pituitary tissue. Given the prominent mood changes that occur in patients with disordered thyroid function, this finding suggests that the therapeutic benefits of lithium in affective illness may be derived in part from alterations in thyroid hormone economy in the brain.


Inventing diagnosis: Theophilus' De urinis in the classroom.
This paper shows how the two earliest Latin expositions of Theophilus' De urinis understood diagnosis in different ways. The "Chartres" commentator sees urine as a sign of physiological process and something which is derived from a disease state. By contrast, the Digby commentator is more concerned with how uroscopy functions at the bedside as a tool that enables us to infer disease states from urine. Though they understand the role of diagnosis differently, both commentaries reflect the new intellectual context of twelfth century medicine, where physical signs cease to be mere prognostic omens, and become tools for attaining knowledge of processes otherwise inaccessible to the senses.


Structural and functional comparison of anchorin CII (cartilage annexin V) and muscle annexin V.
Annexin V has been isolated from chicken muscle and cartilage either by EDTA extraction or by plasma membrane purification and solubilization with detergent to obtain the hydrophilic and hydrophobic variants. The hydrophobic variant of the cartilage annexin V associated with phosphatidylserine-containing liposomes in a Ca(2+)-independent manner, whereas the EDTA-extracted molecule required Ca2+ for association with the liposomes. The collagen-binding assay used is based on the principle of a cell attachment assay using mildly pepsinized collagen type II or intact collagen type I as the solid-phase substrate. Soluble intact collagen type I or II was added as competitive inhibitor. The lipophilic and the EDTA-extracted anchorins CII from cartilage were inhibited to the same extent by collagen type II on pepsinized collagen type II as the solid-phase substrate. The EDTA-extracted muscle annexin V exhibited a fivefold lower affinity to collagen type II than its counterpart from cartilage. Peptide mapping studies and amino acid sequencing of selected peptides from the hydrophobic cartilage annexin V and the hydrophilic cartilage and muscle annexin V revealed 100% identity to the established chicken annexin V protein sequence in the corresponding amino acids 7-29 and 118-126. These results indicate that annexin V may occur in multiple pools within one cell type and/or tissue and that its biological function may depend on the subcellular distribution as well as the microenvironment in the tissue.


Developmental toxicity of levo-alpha-acetylmethadol (LAAM) in tolerant rats.
Mated Crl:CD VAF/Plus female rats, in a range-finding study (n = 5-6 per dose) and a subsequent definitive study (n = 30 per dose) were used to determine the developmental toxicity, including the teratogenic potential of levo-alpha-acetylmethadol (LAAM) hydrochloride, in tolerant rats. Tolerance was induced by initially administering the drug by gavage (10 ml/kg) at 2 mg/kg/day and increasing the dose every 2 weeks for 12 weeks until the doses of 2, 6, 9, 12, and 15, or 2, 6, and 12 mg/kg/day were achieved in the range-finding or definitive study, respectively. Females were then mated to stock males and treated throughout mating and gestation. Controls received distilled water on a similar regimen. The range-finding experiment was used for initial clinical evaluations and to determine tissue concentrations of LAAM and metabolites. In plasma, liver, and brain collected from dams and fetuses pooled by litter on gestation day 20, LAAM and its two N-demethylated metabolites, norLAAM and dinorLAAM, showed dose-dependent increases in concentration and in tissue to plasma ratios. Tissue to dam plasma ratios were highest in dam liver (17-60), intermediate in fetal liver (3-16), and fetal brain (3-14), and lowest in dam brain (0.8-5.6) and fetal plasma (0.3-2.1). In the definitive study, caesarean section examinations were performed following euthanization on gestation day 20 on all surviving females followed by teratologic examination of the fetuses. Drug-related outcomes, including increased activity, secondary hair loss, scabbing, focal swelling, and material around the nose, were exhibited by all groups receiving LAAM. Maternal toxicity was evident as decreased body weights, with maximum reduction at the 6-mg/kg/day dose, and reduction in feed consumption. There was also evidence of developmental toxicity in the form of postimplantation losses at all doses of LAAM. There were no deaths attributable to LAAM. No grossly observable visceral or skeletal anomalies related to LAAM were observed in the fetuses. In conclusion, the no-observable-effect level when administered to tolerant rats was less than 2 mg/kg/day with regard to clinical signs, body weight, body weight gain, and feed consumption, and with regard to developmental toxicity as reflected by postimplantation losses. Despite maternal and developmental toxicity, there was no evidence of selective fetal toxicity or teratogenic activity attributable to LAAM.


Pathogenesis of hepatitis B virus-associated hepatocellular carcinoma.
Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) remains the most common form of HCC in large areas of Asia and Africa. It remains common even in some countries where hepatitis C virus (HCV)-associated HCC has become the predominant form, such as Japan. Integration of HBV in HCC DNA is found at random sites in the host genome in nearly all patients with HBV-associated HCC. It is not clear how often this integration results in insertional mutagenesis, but previously unknown growth regulating genes and cancer-associated genes have been found frequently near HBV integration sites in HCC in recent studies. In addition, HBV encodes a transactivating protein, the X protein, which could enable the randomly integrated HBV to alter the function of host genes that are not near the integration site. Mutations at two adjacent codons in HBV (1762(T)/1764(A) mutations) within the X gene are frequently found in HCC patients, and may play a role in the mutagenic or transactivational role of HBV in HCC. The presence of cirrhosis in most patients with HBV-associated HCC, and the presence of mutations in tumor suppressor genes in many, suggests that these are also factors in hepatocarcinogenesis. Few studies have examined the mutations of more than one gene in the same HCC patients. Fewstudies have evaluated the interactions between HBV mutations, host gene mutations, cirrhosis, and other potentially mutagenic stresses at the cellular level, with progression to HCC, and few studies have been conducted to determine whether these changes must accumulate in succession to lead to HCC. The recent availability of rapid sequencing methods and DNA microarray technologies has permitted expression profiling and permutation analysis of an array of genes to explore the pattern and succession of molecular changes leading to HBV-associated HCC. To date, these methods have been used to show patterns of molecular changes that differ in HBV-associated HCC (compared to HCV-associated HCC or to HCC in patients lacking either virus) and patterns that can predict survival (and hence may directly indicate different mechanisms of disease), and may soon make possible a universally accepted clinical classification scheme for HCC.


The effect of povidone-iodine paint on fungal infection.
Povidone-Iodine (Betadine) Paint was used in thirteen patients with a proven fungal infection. Ten patients had pityriasis versicolor, two had trichophyton rubrum and one M. canis. In the pityriasis versicolor group, seven out of the ten patients were either improved or cleared up completely within 7 days. There were no adverse reactions in this group of patients and the material proved quite acceptable to them. Scanning electron micrographs were carried out on three of the patients and demonstrated the decrease in fungal elements after treatment and clinical improvement.


Influence of bursectomy on operative morbidity and mortality after radical gastrectomy for gastric cancer: results of a randomized controlled trial.
Bursectomy, a procedure dissecting the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon, has been commonly performed with radical gastrectomy for gastric cancer patients. Although possibly improving the prognosis of gastric cancers, adverse events related to bursectomy should be evaluated in prospective studies. This prospective randomized controlled trial was conducted by experienced surgeons in 11 Japanese institutions. Patients with T2 or T3 gastric adenocarcinoma were intraoperatively randomized to radical gastrectomy plus D2 lymphadenectomy either with or without bursectomy. Postoperative morbidity and mortality were compared between the two groups. A total of 210 patients were assigned to the bursectomy group (104 patients) and the nonbursectomy group (106 patients) between July 2002 and January 2007. Background characteristics were well balanced. Intraoperative blood loss was greater in the bursectomy group than in the nonbursectomy group (median 475 vs. 350 ml, p = 0.047), whereas other surgical factors did not vary significantly. The overall morbidity rate was 14.3% (30 patients), the same for the two groups. Likewise, the incidence of major postoperative complications, including pancreatic fistula, anastomotic leakage, abdominal abscess, bowel obstruction, hemorrhage, and pneumonia, were not significantly different between the two groups. The medians of the amylase level of the drainage fluid on postoperative day 1 were similar for the two groups (median 282 vs. 314 IU/L, p = 0.543). The hospital mortality rate was 0.95%: one patient per group. Experienced surgeons could safely perform a D2 gastrectomy with an additional bursectomy without increased major surgical complications.


The relationships among birth season, sunlight exposure during infancy, and allergic disease.
The recent increase in the prevalence of allergic diseases is hypothetically attributed to immune dysregulation in turn caused by a reduction in exposure to sunlight. We explored relationships between birth season, sunlight exposure, exercise duration, and an allergic disease. We performed a questionnaire-based survey on allergic diseases among elementary school students. Birth time was categorized according to the season (summer and winter). The prevalence of atopic dermatitis (AD) "symptoms ever" was higher in the children born in winter than in those born in summer (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.03-1.49; P=0.024). Birth in winter was associated with an increase in the "symptoms in the past 12 months" prevalence of food allergy (FA) (aOR, 1.56; 95% CI, 1.09-2.24; P=0.015). The lifetime prevalence of allergic diseases except FA was higher in the children whose parents considered their sunlight exposure prior to 24 months of ageas inadequate than those who considered their exposure as adequate ("diagnosis ever" asthma: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; allergic rhinitis [AR]: aOR, 1.4; 95% CI, 1.17-1.67; P<0.001; AD: aOR, 1.26; 95% CI, 1.06-1.51; P=0.01). Neither recent sunlight exposure nor exercise duration was associated with the prevalence of an allergic disease. Birth in winter may be associated with development of AD and FA. Inadequate sunlight exposure before the age of 24 months might possibly increase the risks of development of asthma, AR, and AD.


CP5 system, for simple and highly efficient protein purification with a C-terminal designed mini tag.
There are many strategies to purify recombinant proteins of interest, and affinity purification utilizing monoclonal antibody that targets a linear epitope sequence is one of the essential techniques used in current biochemistry and structural biology. Here we introduce a new protein purification system using a very short CP5 tag. First, we selected anti-dopamine receptor D1 (DRD1) rabbit monoclonal antibody clone Ra62 (Ra62 antibody) as capture antibody, and identified its minimal epitope sequence as a 5-amino-acid sequence at C-terminal of DRD1 (GQHPT-COOH, D1CE sequence). We found that single amino acid substitution in D1CE sequence (GQHVT-COOH) increased dissociation rate up to 10-fold, and named the designed epitope sequence CP5 tag. Using Ra62 antibody and 2 peptides with different affinity, we developed a new affinity protein purification method, CP5 system. Ra62 antibody quickly captures CP5-tagged target protein, and captured CP5-tagged protein was eluted by competing with higher affinity D1CE peptide. By taking the difference of the affinity between D1CE and CP5, sharp elution under mild condition was achieved. Using CP5 system, we successfully purified deubiquitinase CYLD and E3 ubiquitin ligase MARCH3, and detected their catalytic activity. As to G protein-coupled receptors (GPCRs), 9 out of 12 cell-free synthesized ones were purified, demonstrating its purification capability of integral membrane proteins. CP5 tagged CHRM2 expressed by baculovirus-insect cell was also successfully purified by CP5 system. CP5 system offers several distinct advantages in addition to its specificity and elution performance. CP5 tag is easy to construct and handle because of its short length, which has less effect on protein characters. Mild elution of CP5 system is particulaly suitable for preparing delicate proteins such as enzymes and membrane proteins. Our data demonstrate that CP5 system provides a new promising option in protein sample preparation with high yield, purity and activity for downstream applications in functional and structural analysis.


Coming out to talk about suicide: gay men and suicidality.
International studies report increased rates of mental health problems and subsequent suicidality among homosexual populations. While international health-care policy is concerned with reducing suicide among young people, important research findings relating to gay people and suicidality remain unacknowledged in the Suicide Prevention Strategy for England. This qualitative study, utilizing single case studies, was used to gain an in-depth understanding of the life experiences contributing to the suicidality of four gay men. The methodology was psychoanalytically informed, using free association narrative interviewing. The initial data analysis involved interpretation of each of the case studies and a subsequent analysis exploring the shared experiences found in each of the individual narratives. Thematically, these are described as 'knowing and not knowing', 'the centrality of the father-son relationship', 'the loneliness of outsiderness', 'leading a double life', and 'crime and punishment'. The significance of the life experiences these themes illustrate reveal why some gay men might not only experience long-term mental health problems, but also engage in suicidality. Individually and collectively, the analyses provide important insights for mental health nurses becoming more attuned to provide sensitive mental health care to those who have a gay sexual orientation.


Amino Acid Imprinted UiO-66s for Highly Recognized Adsorption of Small Angiotensin-Converting-Enzyme-Inhibitory Peptides.
Introduction of targeted defects into microporous UiO-66s for manipulating their three-dimensional size and surface properties can endow them with adsorption and separation areas involving angiotensin-converting-enzyme-inhibitory (ACE-inhibitory) peptides. Three hydrophobic amino acids (AAs) (i.e., proline (Pro), phenylalanine (Phe), and tryptophan (Trp)) having different physical/chemical properties were applied to in situ tailor defects in UiO-66 through targeted incoordination of missing linkers or missing nodes. Characterization results revealed a uniform oval shape of the developed defects with lengths ranging from 1.8 to 3.1 nm, which was also highly consistent with our molecular simulation. Among these three defective UiO-66s, Phe and Trp imprinted UiO-66s significantly promoted the adsorption affinity of small ACE-inhibitory peptides (uptake: 1.25 mmol g-1 for DDFF and 1.37 mmol g-1 for DDWW) and ultrahigh selectivity for DDFF (249) or DDWW (279) from inactive KKKK solution based on a lock-and-key mechanism. As a result, the imprinted UiO-66 showed an enrichment capacity for ACE-inhibitory peptides about eight times higher than that of pristine UiO-66. Therefore, the amino acid imprinting strategy endorsed by its facile and discerning ability can be envisioned to be of great value for small functional peptide separation and oriented enrichment in biomedicines.


The chromosomal location of mouse interferon alpha genes.
The chromosomal location of mouse leukocyte-interferon (IFN-alpha) genes was determined by Southern blot analysis of DNA from a panel of Chinese hamster x mouse somatic cell hybrids using a mouse IFN-alpha cDNA as a hybridization probe. All resolvable mouse genes are located on mouse chromosome 4. In addition, two common restriction site polymorphisms within these genes were identified in several mouse strains.