North-south gradients in plasma concentrations of B-vitamins and other components of one-carbon metabolism in Western Europe: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study.
Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10·4 nmol/l; women, 10·7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north-south gradient. Vitamin B₂ concentrations were highest in Northern Europe (men, 22·2 nmol/l; women, 26·0 nmol/l) and decreased towards Southern Europe (P trend< 0·001). Vitamin B(6) concentrations were highest in Central Europe in men (77·3 nmol/l) and highest in the North among women (70·4 nmol/l), with decreasing concentrations towards Southern Europe in women (P trend< 0·001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.


Rift valley fever outbreak in Sembabule District, Uganda, December 2020.
Rift Valley Fever (RVF) is a viral zoonosis that can cause severe haemorrhagic fevers in humans and high mortality rates and abortions in livestock. On 10 December 2020, the Uganda Ministry of Health was notified of the death of a 25-year-old male who tested RVF-positive by reverse-transcription polymerase chain reaction (RT-PCR) at the Uganda Virus Research Institute. We investigated to determine the scope of the outbreak, identify exposure factors, and institute control measures. A suspected case was acute-onset fever (or axillary temperature > 37.5 °C) and ≥ 2 of: headache, muscle or joint pain, unexpected bleeding, and any gastroenteritis symptom in a resident of Sembabule District from 1 November to 31 December 2020. A confirmed case was the detection of RVF virus nucleic acid by RT-PCR or serum IgM antibodies detected by enzyme-linked immunosorbent assay (ELISA). A suspected animal case was livestock (cattle, sheep, goats) with any history of abortion. A confirmed animal case was the detection of anti-RVF IgM antibodies by ELISA. We took blood samples from herdsmen who worked with the index case for RVF testing and conducted interviews to understand more about exposures and clinical characteristics. We reviewed medical records and conducted an active community search to identify additional suspects. Blood samples from animals on the index case's farm and two neighbouring farms were taken for RVF testing. The index case regularly drank raw cow milk. None of the seven herdsmen who worked with him nor his brother's wife had symptoms; however, a blood sample from one herdsman was positive for anti-RVF-specific IgM and IgG. Neither the index case nor the additional confirmed case-patient slaughtered or butchered any sick/dead animals nor handled abortus; however, some of the other herdsmen did report high-risk exposures to animal body fluids and drinking raw milk. Among 55 animal samples collected (2 males and 53 females), 29 (53%) were positive for anti-RVF-IgG. Two human RVF cases occurred in Sembabule District during December 2020, likely caused by close interaction between infected cattle and humans. A district-wide animal serosurvey, animal vaccination, and community education on infection prevention practices campaign could inform RVF exposures and reduce disease burden.


Differentiating Sitting, Standing, and Walking Through Regional Plantar Pressure Characteristics.
Prolonged static weight bearing (WBR) is thought to aggravate plantar heel pain and is common in the workplace, which may put employees at greater risk of developing plantar heel pain. However, objective measures of physical activity and sedentary behaviors in the workplace are lacking, making it difficult to establish or refute the connection between work exposure and plantar heel pain. Characterizing loading patterns during common workplace postures will enhance the understanding of foot function and inform the development of new measurement tools. Plantar pressure data during periods of sitting, standing, and walking were measured in ten healthy participants using the F-Scan in-shoe measurement system (Tekscan Inc, Boston, MA). Peak and average pressure, peak and average contact area, and average pressure differential were analyzed in ten different regions of the foot. A two-way repeated measures analysis of variance (ANOVA) assessed the posture by foot region interaction for each measurement parameter; significant effects of posture by foot region were identified for all five measurement parameters. Ten foot region by measurement parameter combinations were found to significantly differentiate all three postures simultaneously; seven used pressure measures to differentiate while three used area measures. The heel, lateral midfoot (LM), and medial and central forefoot (CFF) encompassed nine of ten areas capable of differentiating all postures simultaneously. This work demonstrates that plantar pressure is a viable means to characterize and differentiate three common workplace postures. The results of this study can inform the development of measurement tools for quantifying posture duration at work.


A new standard for incapacitated patient decision making: the clinical standard of surrogate empowerment.
Founded upon the primacy of the principle of respect for autonomy, three methods of surrogate decision making traditionally have been promoted to help the family and friends of incapacitated patients. Unfortunately, the standards of advance directives, substituted judgment, and best interests are often inadequate in practice. Studies report that few patients have formal, written advance directives; that patients often change their minds about treatment over time; that many patients are simply not ready or willing to plan ahead--in part, because some patients and families simply don't believe in autonomy; that those patients who do plan ahead often do not communicate their plans; and that while some patients want their directives followed strictly, many prefer that their surrogates use judgment in making decisions. After reviewing articles describing a variety of alternative approaches, a new clinical standard of surrogate empowerment is proposed to reconcile and integrate these observations and concepts. The "procedure" for this clinical standard is presented.


Nonlocal means with dimensionality reduction and SURE-based parameter selection.
Nonlocal means (NLM) is an effective denoising method that applies adaptive averaging based on similarity between neighborhoods in the image. An attractive way to both improve and speed-up NLM is by first performing a linear projection of the neighborhood. One particular example is to use principal components analysis (PCA) to perform dimensionality reduction. Here, we derive Stein's unbiased risk estimate (SURE) for NLM with linear projection of the neighborhoods. The SURE can then be used to optimize the parameters by a search algorithm or we can consider a linear expansion of multiple NLMs, each with a fixed parameter set, for which the optimal weights can be found by solving a linear system of equations. The experimental results demonstrate the accuracy of the SURE and its successful application to tune the parameters for NLM.


Ceramide AD™ Restores Skin Integrity and Function following Exposure to House Dust Mite.
Ceramides are epidermal lipids important for normal skin barrier function. Reduced Ceramide content is associated with atopic dermatitis (AD). House dust mite (HDM) has been localized in AD skin where it plays an exacerbator role. We set to examine the impact of HDM on skin integrity and the effect of three separate Ceramides (AD™, DS, Y30) on HDM-induced cutaneous damage. The effect was tested in vitro on primary human keratinocytes and ex vivo on skin explants. HDM (100 μg/mL) decreased the expression of adhesion protein E-cadherin, supra-basal (K1, K10) and basal (K5, K14) keratins and increased matrix metallopeptidase (MMP)-9 activity. The presence of Ceramide AD™ in topical cream inhibited HDM-induced E-cadherin and keratin destruction and dampened MMP-9 activity ex vivo which was not seen for the control cream or cream containing DS or Y30 Ceramides. The efficacy of Ceramide AD™ was tested in a clinical setting on moderate to very dry skin (as surrogate for environment-induced skin damage). When applied topically for 21 days, Ceramide AD™ significantly reduced transepidermal water loss (TEWL) in patients with very dry skin compared to their TEWL baseline data. Our study demonstrates Ceramide AD™ cream to be effective in restoring skin homeostasis and barrier function in damaged skin and warrants testing in larger clinical trials for possible treatment of AD and xerosis.


A multiobjective hybrid genetic algorithm for the capacitated multipoint network design problem.
The capacitated multipoint network design problem (CMNDP) is NP-complete. In this paper, a hybrid genetic algorithm for CMNDP is proposed. The multiobjective hybrid genetic algorithm (MOHGA) differs from other genetic algorithms (GAs) mainly in its selection procedure. The concept of subpopulation is used in MOHGA. Four subpopulations are generated according to the elitism reservation strategy, the shifting Prufer vector, the stochastic universal sampling, and the complete random method, respectively. Mixing these four subpopulations produces the next generation population. The MOHGA can effectively search the feasible solution space due to population diversity. The MOHGA has been applied to CMNDP. By examining computational and analytical results, we notice that the MOHGA can find most nondominated solutions and is much more effective and efficient than other multiobjective GAs.


Single crystal diamond tips for scanning probe microscopy.
Single crystal diamond tips with perfect pyramidal geometry were obtained by a combination of chemical vapor deposition and selective oxidation of polycrystalline films. The parameters of the deposition process were chosen to provide growth of a textured film consisting of micrometer sized diamond crystallites embedded into nanodiamond ballas-like material. The heating of the film in an air environment was used for selective oxidation of the nanodiamond component. The films obtained contain free standing pyramidal single crystal diamond tips oriented by their apexes to the substrate surface. The tips were used for the fabrication of atomic force microscopy probes and their evaluation in comparison to common silicon probes.


The NOD mouse: a model of immune dysregulation.
Autoimmunity is a complex process that likely results from the summation of multiple defective tolerance mechanisms. The NOD mouse strain is an excellent model of autoimmune disease and an important tool for dissecting tolerance mechanisms. The strength of this mouse strain is that it develops spontaneous autoimmune diabetes, which shares many similarities to autoimmune or type 1a diabetes (T1D) in human subjects, including the presence of pancreas-specific autoantibodies, autoreactive CD4+ and CD8+ T cells, and genetic linkage to disease syntenic to that found in humans. During the past ten years, investigators have used a wide variety of tools to study these mice, including immunological reagents and transgenic and knockout strains; these tools have tremendously enhanced the study of the fundamental disease mechanisms. In addition, investigators have recently developed a number of therapeutic interventions in this animal model that have now been translated into human therapies. In this review, we summarize many of the important features of disease development and progression in the NOD strain, emphasizing the role of central and peripheral tolerance mechanisms that affect diabetes in these mice. The information gained from this highly relevant model of human disease will lead to potential therapies that may alter the development of the disease and its progression in patients with T1D.


A comparison study of linear reconstruction techniques for diffuse optical tomographic imaging of absorption coefficient.
We compare, through simulations, the performance of four linear algorithms for diffuse optical tomographic reconstruction of the three-dimensional distribution of absorption coefficient within a highly scattering medium using the diffuse photon density wave approximation. The simulation geometry consisted of a coplanar array of sources and detectors at the boundary of a half-space medium. The forward solution matrix is both underdetermined, because we estimate many more absorption coefficient voxels than we have measurements, and ill-conditioned, due to the ill-posedness of the inverse problem. We compare two algebraic techniques, ART and SIRT, and two subspace techniques, the truncated SVD and CG algorithms. We compare three-dimensional reconstructions with two-dimensional reconstructions which assume all inhomogeneities are confined to a known horizontal slab, and we consider two 'object-based' error metrics in addition to mean square reconstruction error. We include a comparison using simulated data generated using a different FDFD method with the same inversion algorithms to indicate how our conclusions are affected in a somewhat more realistic scenario. Our results show that the subspace techniques are superior to the algebraic techniques in localization of inhomogeneities and estimation of their amplitude, that two-dimensional reconstructions are sensitive to underestimation of the object depth, and that an error measure based on a location parameter can be a useful complement to mean squared error.


Does playing pay? The fitness-effect of free play during childhood.
Evolutionary developmental psychology claims that the sequences and processes of human development, in fact the mere fact of ontogeny itself, have to be viewed as evolutionary products. However, although the functional benefits of childish behavior (child playing) for cognitive and emotional development have been shown repeatedly, claiming evolutionary adaptiveness of playing in childhood suggests that childish play supports evolutionary success in mature stages of development. This hypothesis is tested in a study with N=134 adults (93 females; age range 20-66 years). Participants were asked to recollect their play experiences during childhood in detail, and to report their current developmental status with respect to several aspects of social success. Results show that the opportunity for and the promotion of free play in childhood significantly predict some indicators of social success. Additional analyses strive to explore mediating processes for this relationship. In particular, the mediating role of individual adaptivity (flexibility of goal adjustment) is investigated. Results suggest that freely playing in childhood promotes developmental resources, in particular individual adaptivity in adulthood, which, in turn, promote developmental success.


Chemopreventive effects of dietary flaxseed on colon tumor development.
Fatty acid composition of dietary fat plays a vital role in colon tumor development in animal models. Fats containing omega-6 fatty acids (e.g., corn oil) enhanced and omega-3 fatty acids (e.g., flaxseed oil) reduced chemically induced colon tumor development in rats. Lignans have also been shown to prevent colon tumor development in experimental animals. The objective of this investigation is to study the effects of dietary flaxseed meal, a source of both omega-3 fatty acid and lignans, on colon tumor development and compare them with the effects of dietary corn meal. Male Fischer rats, two groups of 24 each, were assigned to the AIN-93M diet supplemented with either 15% corn meal or 15% flaxseed meal, respectively. Carcinogenesis was initiated with subcutaneous injections of azoxymethane (15 mg/kg) once a week for 3 consecutive wk. After 35 wk of initiation, rats were anesthetized with ether. Blood was collected by cardiac puncture, and rats were sacrificed. The gastrointestinal tract was isolated. The site, size, and number of tumors were recorded. The fatty acid analysis of the collected serum and colon samples was performed. Expression of cyclooxygenase (COX)-1 and COX-2 was performed by Western blot method. Lignan levels in serum and colon samples were assayed. Colon tumor incidence, multiplicity, and size were found to be 82.6% and 29.4%; 1.3 and 0.3; and 44.4 and 5.3 mm(2) in corn and flaxseed meal groups, respectively. Colon and serum samples of the corn meal group showed higher levels of omega-6 fatty acid levels whereas the flaxseed meal group exhibited higher levels of omega-3 fatty acids. COX-1 and COX-2 expression in the flaxseed group was significantly lower (P < 0.05) as compared to the corn group. Dietary flaxseed meal containing high levels of omega-3 fatty acids and lignans is effective in preventing colon tumor development when compared with dietary corn meal possibly by increasing omega-3 fatty acid levels and decreasing COX-1 and COX-2 levels.


Effect of periodontal treatment on the glomerular filtration rate, reduction of inflammatory markers and mortality in patients with chronic kidney disease: A systematic review.
To assess the effect of periodontal treatment (PT) on glomerular filtration rate (GFR), systemic inflammation, or mortality in patients with chronic kidney disease (CKD). A literature search was performed on PubMed and Web of Science databases on articles published until December 2019. The PRISMA guidelines were used throughout the manuscript. Of the total studies found, only 18 met the inclusion criteria; four retrospective and 14 prospective studies (including 3 randomized controlled trials-RCT). After PT, 3 studies investigated GFR, 2 found significant improvement; 11 (including 2 RCTs) investigated C-reactive protein levels, 9 found a significant improvement (including the 2 RCTs); 5 (including 3 RCTs) investigated Interleukine-6 level, 4 found a significant improvement (including 2 RCTs) and 2 studies evaluated mortality, one (retrospective study) found a significant difference. Within the limitations of the present study, PT seems to improve CKD status, especially by reducing the systemic inflammation. Further RCTs are needed to confirm the results and specifically assess the influence of different types of PT in CKD patients. Taking into consideration the ability of PT to prevent further tooth loss and denutrition, early management of periodontitis is extremely important in patients with impaired renal function.


CorNet: Assigning function to networks of co-evolving residues by automated literature mining.
CorNet is a web-based tool for the analysis of co-evolving residue positions in protein super-family sequence alignments. CorNet projects external information such as mutation data extracted from literature on interactively displayed groups of co-evolving residue positions to shed light on the functions associated with these groups and the residues in them. We used CorNet to analyse six enzyme super-families and found that groups of strongly co-evolving residues tend to consist of residues involved in a same function such as activity, specificity, co-factor binding, or enantioselectivity. This finding allows to assign a function to residues for which no data is available yet in the literature. A mutant library was designed to mutate residues observed in a group of co-evolving residues predicted to be involved in enantioselectivity, but for which no literature data is available yet. The resulting set of mutations indeed showed many instances of increased enantioselectivity.


Diagnosis of community-acquired pneumonia in adults.
Community-acquired pneumonia (CAP) is a common presentation to both primary and secondary care, representing approximately 5% of the acute medical intake in the UK. Treatment is often based on an empirical approach, using broad-spectrum antibiotic regimens, with which the majority of patients will achieve clinical cure. However, in cases of severe CAP, initial treatment failure or severe comorbidity, a more rigorous diagnostic approach is required. This review assesses the evidence base behind the common diagnostic methods for CAP, and presents the case for a rapid and accurate microbiological and radiological diagnosis in improving management and outcomes of this common condition.


A non-transformed oligodendrocyte precursor cell line, OL-1, facilitates studies of insulin-like growth factor-I signaling during oligodendrocyte development.
The process by which oligodendrocyte progenitors differentiate into mature oligodendrocytes is complex and incompletely understood in part because of the paucity of oligodendrocyte precursors cell lines that can be studied in culture. We have developed a non-immortalized rat oligodendrocyte precursor line, called OL-1, which behaves in a fashion consistent with developing oligodendrocytes in vivo. This OL-1 line provides a model for the study of oligodendrocyte development and offers an alternative to the CG-4 cell line. When OL-1 cells are propagated in conditioned growth media, they have morphology consistent with immature oligodendrocytes and exhibit A2B5 antigen positive and myelin basic protein-negative immunoreactivity. Withdrawal of conditioned growth media and culture in serum-free medium results in OL-1 cell maturation, manifested by a shift to myelin basic protein-positive immunoreactivity, A2B5 antigen-negative immunoreactivity, decreased NG2 mRNA expression, increased expression of proteolipid protein mRNA, and increased expression of CNP protein. In addition, the expression of proteolipid protein and its splicing variant DM-20 exhibit a pattern that is similar to brain proteolipid protein expression during development. When OL-1 cells are exposed to Insulin-like growth factor-I, there are significant increases in proteolipid protein mRNA expression (p<0.05), the number of cell processes (p<0.05), and cell number (p<0.05). Treatment with the caspase inhibitors Z-DEVD-FMK and Z-VAD-FMK (inhibitors of caspases 3, 6, 7, 8, 10 and 1, 3, 4, respectively), Insulin-like growth factor-I, or both, results in a similar increase in cell number. Because Insulin-like growth factor-I does not substantially increase the BrdU labeling of OL-1 cells, these data collectively indicate that Insulin-like growth factor-I increases OL-1 cell number predominately by promoting survival, rather than stimulating proliferation. This non-immortalized oligodendrocyte precursor cell line, therefore, exhibits behavior consistent with the in vivo development of oligodendrocytes and provides an excellent model for the study of developing oligodendrocytes.


Functional Context Affects Scene Processing.
Rapid visual perception is often viewed as a bottom-up process. Category-preferred neural regions are often characterized as automatic, default processing mechanisms for visual inputs of their categorical preference. To explore the sensitivity of such regions to top-down information, we examined three scene-preferring brain regions, the occipital place area (OPA), the parahippocampal place area (PPA), and the retrosplenial complex (RSC), and tested whether the processing of outdoor scenes is influenced by the functional contexts in which they are seen. Context was manipulated by presenting real-world landscape images as if being viewed through a window or within a picture frame-manipulations that do not affect scene content but do affect one's functional knowledge regarding the scene. This manipulation influences neural scene processing (as measured by fMRI): The OPA and the PPA exhibited greater neural activity when participants viewed images as if through a window as compared with within a picture frame, whereas the RSC did not show this difference. In a separate behavioral experiment, functional context affected scene memory in predictable directions (boundary extension). Our interpretation is that the window context denotes three-dimensionality, therefore rendering the perceptual experience of viewing landscapes as more realistic. Conversely, the frame context denotes a 2-D image. As such, more spatially biased scene representations in the OPA and the PPA are influenced by differences in top-down, perceptual expectations generated from context. In contrast, more semantically biased scene representations in the RSC are likely to be less affected by top-down signals that carry information about the physical layout of a scene.


CD16+ monocytes in breast cancer patients: expanded by monocyte chemoattractant protein-1 and may be useful for early diagnosis.
Human peripheral blood monocytes are a heterogeneous population, including CD14(+) CD16(-) 'classical' monocytes and CD14(+) CD16(+) 'proinflammatory' monocytes. CD16(+) monocytes are expanded in various inflammatory conditions. However, little is known about the CD14(+) CD16(+) monocytes in patients with breast cancer. We detected CD14(+) CD16(+) monocytes in 96 patients with breast cancer and 54 control subjects using flow cytometry. Receiver-operating characteristic (ROC) curve analysis was used to determine the feasibility of CD14(+) CD16(+) monocytes as an indicator for diagnosis of breast cancer. We found that the frequency of CD14(+) CD16(+) monocytes showed a significantly greater increase in breast cancer patients than in controls (16·96% versus 10·84%, P < 0·0001). The area under the ROC curve for CD14(+) CD16(+) monocytes was 0·805 [95% confidence interval (95% CI): 0·714-0·877, P = 0·0001]. Furthermore, the levels of CD16(+) monocytes were significantly negatively associated with the tumour size and pathological staging. In vitro, we showed that CD14(+) CD16(+) monocytes were expanded significantly when the purified CD14(+) monocytes were exposed to Michigan Cancer Foundation (MCF)-7 cells-conditioned medium (MCF-CM) or, separately, to monocyte chemotactic protein 1 (MCP-1). Neutralizing antibodies against MCP-1 inhibited the expansion of CD14(+) CD16(+) monocytes by MCF-CM. Collectively, our findings indicated that MCP-1 can expand CD14(+) CD16(+) monocytes in patients with breast cancer. Furthermore, the CD14(+) CD16(+) monocyte may be a useful indicator in early diagnosis of breast cancer.


Therapeutic Potential of Dupilumab in the Treatment of Chronic Rhinosinusitis with Nasal Polyps: Evidence to Date.
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is one of the most severe forms of chronic rhinosinusitis. CRSwNP is characterized by nasal and facial congestion, loss of sense of smell, rhinorrhea, and post-nasal drip. Treatments have been ineffective at controlling disease recurrence, despite multiple courses of medical and surgical therapies. Oral glucocorticoid therapy is often used to control exacerbations leaving the patient exposed to steroid-induced adverse effects. Thus, there is a clear unmet need for new treatments to achieve better control of the disease. Advances in understanding Type 2 inflammatory processes that occur in about 80% of the Western world patients with CRSwNP have resulted in new avenues for disease control. Biologics in the form of monoclonal antibodies, which target Type 2 inflammation, have helped control the severest forms of atopic dermatitis and asthma. Treatment regimes for CRSwNP now include biologics. In July 2019, dupilumab was the first monoclonal antibody to gain FDA approval for the treatment of CRSwNP. In this review, we summarize the proof of concept clinical trials and Phase 3 trials leading to approval of dupilumab, an anti-IL4 alpha receptor antagonist that blocks the actions of both IL4 and IL13. These studies show that dupilumab is a proven treatment option to control disease. Collective studies demonstrate a high safety profile. Questions arise as to the best use of dupilumab in the context of current treatment paradigms, and for which sub-population of the varied heterogeneous endotypes of CRSwNP patients. Recognizing the high cost of biologics forces the need for cost-effectiveness analysis.


Genome sequencing and population resequencing provide insights into the genetic basis of domestication and diversity of vegetable soybean.
Vegetable soybean is one of the most important vegetables in China, and the demand for this vegetable has markedly increased worldwide over the past two decades. Here, we present a high-quality de novo genome assembly of the vegetable soybean cultivar Zhenong 6 (ZN6), which is one of the most popular cultivars in China. The 20 pseudochromosomes cover 94.57% of the total 1.01 Gb assembly size, with contig N50 of 3.84 Mb and scaffold N50 of 48.41 Mb. A total of 55 517 protein-coding genes were annotated. Approximately 54.85% of the assembled genome was annotated as repetitive sequences, with the most abundant long terminal repeat transposable elements. Comparative genomic and phylogenetic analyses with grain soybean Williams 82, six other Fabaceae species and Arabidopsis thaliana genomes highlight the difference of ZN6 with other species. Furthermore, we resequenced 60 vegetable soybean accessions. Alongside 103 previously resequenced wild soybean and 155 previously resequenced grain soybean accessions, we performed analyses of population structure and selective sweep of vegetable, grain, and wild soybean. They were clearly divided into three clades. We found 1112 and 1047 genes under selection in the vegetable soybean and grain soybean populations compared with the wild soybean population, respectively. Among them, we identified 134 selected genes shared between vegetable soybean and grain soybean populations. Additionally, we report four sucrose synthase genes, one sucrose-phosphate synthase gene, and four sugar transport genes as candidate genes related to important traits such as seed sweetness and seed size in vegetable soybean. This study provides essential genomic resources to promote evolutionary and functional genomics studies and genomically informed breeding for vegetable soybean.


An established cell line from mouse kidney medullary thick ascending limb. I. Cell culture techniques, morphology, and antigenic expression.
The effective use of cultured cells as model systems for investigating the differentiation and regulation of transport processes in renal tubular epithelial cells depends on the availability of functional long-term cell lines derived from specific nephron segments. Conventional culture procedures that treat cells as proliferating microorganisms possess several inherent limitations that could contribute to phenotypic instability and limited proliferative capacity in vitro. In this study, culture techniques were adopted that avoid exposure of cells to proteolytic enzymes, maintain intercellular contacts, and allow cells to remain continually adherent to a collagen gel substratum. This methodology resulted in the development of a continuous epithelial cell line from identified, microdissected segments of the mouse kidney medullary thick ascending limb.


Ministernotomy or minithoracotomy for minimally invasive aortic valve replacement: a Bayesian network meta-analysis.
Establishing the relative merits of ministernotomy (MS) and minithoracotomy (MT) approaches to minimally invasive aortic valve replacement (MIAVR) is difficult given the limited available direct evidence. Network meta-analysis is a Bayesian approach that can combine direct and indirect evidence to better define the benefits and risks of MS and MT. Electronic searches were performed using six databases from their inception to June 2014. Relevant studies utilizing a minimally invasive approach for aortic valve replacement were identified. Data were extracted and analyzed according to predefined clinical endpoints. Both traditional and Bayesian meta-analysis approaches were conducted. Compared to full sternotomy, MT was associated with longer cardiopulmonary bypass (CPB) duration (WMD, 9.99; 95% CI, 3.91, 16.07; I(2)=55%; P=0.001) and cross-clamp duration (WMD, 7.64; 95% CI, 2.86, 12.42; P=0.002; I(2)=74%). When compared to MS using network meta-analysis, no significant difference in duration was detected. Postoperative outcomes including 30-day mortality, stroke, and reoperation for bleeding and wound infection were comparable between MS and MT using both traditional and Bayesian meta-analysis techniques. The current evidence demonstrates that MIAVR via MS or MT is a safe and efficacious alternative to conventional median sternotomy. MT may be associated with longer CPB and cross-clamp durations, but has similar post-operative outcomes compared to MS. An individualized approach tailored to both the patient and surgical team is likely to provide optimal outcomes.


Polaron stability in semiconducting polymer neat films.
We describe a spectroelectrochemical approach to accelerated electrochemical stability studies of conjugated polymers under oxidative stress. The polaron stabilities of alternating copolymers based on (i) thiophene and thiazole, namely PTTz, and (ii) bithiophene and thiazole, namely PTTTz, are compared in neat films with that of P3HT. P3HT is found to be the most stable whilst PTTz is found to be the least stable.


Beta-blockade improves adjacent regional sympathetic innervation during postinfarction remodeling.
The effect of beta-blockade on left ventricular (LV) remodeling, when added to angiotensin-converting enzyme inhibition (ACEI) after anterior myocardial infarction (MI), is incompletely understood. On day 2 after coronary ligation-induced anteroapical infarction, 17 sheep were randomized to ramipril (ACEI, n = 8) or ramipril and metoprolol (ACEI-beta, n = 9). Magnetic resonance imaging was performed before and 8 wk after MI to measure changes in LV end-diastolic, end-systolic, and stroke volume indexes, LV mass index, ejection fraction (EF), and regional percent intramyocardial circumferential shortening. (123)I-labeled m-iodobenzylguanidine (MIBG) and fluorescent microspheres before and after adenosine were infused before death at 8 wk post-MI for quantitation of sympathetic innervation, blood flow, and blood flow reserve in adjacent and remote noninfarcted regions. Infarct size, regional blood flow, blood flow reserve, and the increase in LV mass and LV end-diastolic and end-systolic volume indexes were similar between groups. However, EF fell less over the 8-wk study period in the ACEI-beta group (-13 +/- 11 vs. -22 +/- 4% in ACEI, P < 0.05). The ratio of adjacent to remote region (123)I-MIBG uptake was greater in ACEI-beta animals than in the ACEI group (0.93 +/- 0.06 vs. 0.86 +/- 0.07, P < 0.04). When added to ACE inhibition after transmural anteroapical MI, beta-blockade improves EF and adjacent regional sympathetic innervation but does not alter LV size.


Activation of lordotic responding in female rats by suppression of serotonergic activity.
After systemic administration of several serotonergic antagonists, female rats that had been ovariectomized, adrenalectomized, and estrogen-primed showed lordotic responding. Lordosis could also be elicited after direct placement of serotonergic receptor blockers into hypothalamic sites known to contain serotonergic terminals. None of the treatments activated the soliciting component of the estrous behavior pattern of the female rat. It is postulated that the hypothalamus contains serotonergic terminals which suppress lordotic responding.


Yersinia enterocolitica: A Follow-up of the Outbreak in the Norwegian Armed Forces in 2014.
In the spring of 2014, there was an outbreak of Yersinia enterocolitica (YE) gastroenteritis in four Norwegian military camps-the largest outbreak ever reported in Norway. YE is usually transmitted via food, and the gastrointestinal disease caused by the bacterium is considered a public health problem in several countries. Common symptoms of YE gastroenteritis are abdominal pain, diarrhea, fever, nausea, and vomiting. Post-infectious complications can occur after YE gastroenteritis, the most common of which are erythema nodosum and reactive arthritis. Based on self-reported data, we describe the duration of illness, the duration of any absence from service, and the incidence of symptoms of post-infectious complications in two groups of servicepeople: one diagnosed with YE gastroenteritis and the other with an unspecified acute infectious gastroenteritis. The Norwegian Armed Forces Health Register (NAFHR) is a central health register that contains data from conscripts and from military and civilian personnel in the Norwegian Armed Forces. In this study, we identified all individuals with a diagnosis of YE gastroenteritis in the NAFHR in the period from January 1 to June 30, 2014 (n = 128) as well as all those with a diagnosis of an unspecified acute infectious gastroenteritis in the same period (n = 323) to participate as controls. In October 2018, a link to an internet-based questionnaire was distributed by e-mail to all identified individuals. The questionnaires collected data on the duration of illness, the duration of absence from service, and the incidence of symptoms of post-infectious complications. Of all those who received the questionnaire, 72 (59%) were included in the YE group and 117 people (36%) were included in the control group. Half of those in the YE group were ill for more than 13 days, while almost all (90%) of those in the control group recovered after 1 week. There were no differences between the groups in the incidence of symptoms of post-infectious complications during the 6 weeks after recovery. There was a significantly larger proportion of officers than conscripts in the YE group who reported symptoms of post-infectious complications. None of the respondents reported symptoms of post-infectious complications in the 6 months after the termination of military service. One strength of this study is that we were able to investigate a large outbreak of YE gastroenteritis in a group of individuals with good underlying health. Weaknesses are the low response rate, especially in the control group, and the fact that we sent out the questionnaire >4 years after the acute gastroenteritis occurred. YE gastroenteritis among personnel in the Norwegian Armed Forces was associated with a significantly longer duration of illness and a longer duration of absence from service than that resulting from an unspecified acute infectious gastroenteritis. However, YE gastroenteritis was not associated with more symptoms of post-infectious complications.


Evaluating Community Factors Associated With Individually Held Intimate Partner Violence Beliefs Across 51 Countries.
Globally, one in three women will experience intimate partner violence (IPV) within her lifetime. IPV attitudes are highly predictive of IPV. While a wealth of literature on risk factors related to IPV exist, an overarching critique in the field is the lack of studies examining risk factors across the socioecological framework. Using data from multiple administrative and individual surveys, this study fills a gap in the literature by evaluating the effect of meso-influences on physical IPV attitudes (i.e., permissibility of a man beating his wife) while accounting for known micro- and macro-risk factors in 64,466 individuals across 51 low-, middle- and high-income countries. Mixed-effects modeling was used to evaluate factors and identify comparative contributions of each factor representing the socio-ecological levels. We tested five multivariate logistic models. The final model indicated that greater perceived neighborhood disorder and less perceived neighborhood security were associated with physical IPV attitudes, while individual endorsement of interpersonal violence, belief in corporal punishment of children, holding greater patriarchal beliefs, being male, being separated from a significant partner, reporting greater household hunger and nationally lower levels of female literacy were associated with beliefs that IPV is acceptable. Overall, the findings of this study support that IPV is a complex behavior, influenced by factors across socio-ecological domains. However, data on neighborhood structural factors (i.e., exosystem) would help unpack the mechanisms between macro-, meso- and micro-level factors and may be important for protecting women from violence.


A role for human immunodeficiency virus type 1 Vpr during infection of peripheral blood mononuclear cells.
Studies analysing human immunodeficiency virus type 1 replication in primary cells have demonstrated that Vpr, although dispensable, plays a role along with the matrix (MA) protein in allowing nuclear localization of viral preintegration complexes in non-dividing monocyte-derived macrophages (MDMs). In the current study, experimental infection conditions to analyse the role of Vpr, independently of MA, during infection of PHA/IL-2-stimulated peripheral blood mononuclear cells (PBMC) were designed. It was shown that the absence of Vpr results in a subtle effect on virus production in long-term infection. PCR analysis of the steps of virus retrotranscription during a single cycle of replication in stimulated PBMC revealed that the absence of Vpr alone correlates with an impairment in the nuclear localization of viral DNA. Our data indicate that Vpr is involved in the virus life-cycle during infection of dividing PBMC, presumably as it is during infection of MDMs.


Menin controls growth of pancreatic beta-cells in pregnant mice and promotes gestational diabetes mellitus.
During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet beta-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal beta-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated beta-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.


The expression of social dominance following neonatal lesions of the amygdala or hippocampus in rhesus monkeys (Macaca mulatta).
As part of ongoing studies on the neurobiology of socioemotional behavior in the nonhuman primate, the authors examined the social dominance hierarchy of juvenile macaque monkeys (Macaca mulatta) that received bilateral ibotenic acid lesions of the amygdala or the hippocampus or a sham surgical procedure at 2 weeks of age. The subjects were reared by their mothers with daily access to large social groups. Behavioral observations were conducted while monkeys were given access to a limited preferred food. This testing situation reliably elicited numerous species-typical dominance behaviors. All subjects were motivated to retrieve the food when tested individually. However, when a group of 6 monkeys was given access to only 1 container of the preferred food, the amygdala-lesioned monkeys had less frequent initial access to the food, had longer latencies to obtain the food, and demonstrated fewer species-typical aggressive behaviors. They were thus lower ranking on all indices of social dominance. The authors discuss these findings in relation to the role of the amygdala in the establishment of social rank and the regulation of aggression and fear.


Clinical comparison of the midvastus and medial parapatellar surgical approaches.
The medial parapatellar approach and the midvastus approach are the two most commonly used surgical approaches in total knee replacement. This study compared surgical and clinical parameters associated with both surgical approaches in primary total knee replacement. One hundred nine patients who underwent bilateral primary total knee replacements had a medial parapatellar approach to one knee and a midvastus approach to the opposite knee. The prosthetic design and physical therapy were identical in all 109 patients. The patients and physical therapists were blinded to the type of approach used on each knee. The comparison included the surgical parameters of difficulty of exposure, surgical time, incidence of lateral retinacular release, and total blood loss. The clinical parameters of pain, range of motion, ability to perform a straight leg raise, and complications were compared at 8 days, 6 weeks and 6 months. The comparison between the two surgical approaches showed a statistically significant difference in four parameters, all of which favored the midvastus approach. The patients who had the midvastus approach required fewer lateral retinacular releases, had less pain at 8 days, had less pain at 6 weeks, and had a higher incidence of ability to straight leg raise at 8 days. There was no statistical difference between the two surgical approaches in all other surgical and clinical parameters. There was no increased difficulty of exposure using the midvastus approach when compared with the medial parapatellar approach even in patients with severe varus or valgus deformities. Notably, all clinical parameters were equal at 6 months. From a clinical standpoint, the midvastus approach had an advantage over the medial parapatellar approach because the patients had significantly less pain and had the ability to straight leg raise at 8 days. Because the managed care environment dictates a shorter hospital stay, patients who have the midvastus surgical approach have less pain and earlier control of the operative leg, and may be discharged from the hospital earlier. However, the clinical results at 6 months based on the patient's pain relief, range of motion, and ability to straight legraise were identical between the two surgical approaches.


Constitutional abnormalities of IDH1 combined with secondary mutations predispose a patient with Maffucci syndrome to acute lymphoblastic leukemia.
Maffucci syndrome is a nonhereditary disorder caused by somatic mosaic isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2) mutations and is characterized by multiple enchondromas along with hemangiomas. Malignant transformation of enchondromas to chondrosarcomas and secondary neoplasms, such as brain tumors or acute myeloid leukemia, are serious complications. A 15-year-old female with Maffucci syndrome developed B-cell precursor acute lymphoblastic leukemia (BCP-ALL). A somatic mutation in IDH1 was detected in hemangioma and leukemic cells. KRAS mutation and deletion of IKZF1 were detected in leukemic cells. Patients with Maffucci syndrome may, therefore, be at risk of BCP-ALL associated with secondary genetic events that affect lymphocyte differentiation.


Mutagen sensitivity and risk of gliomas: a case-control analysis.
Although the risk factors contributing to the etiology of brain tumors remain largely unknown, this pilot study suggests that genetically determined sensitivity to environmental carcinogens may play a role in the pathogenesis of these tumors. In this study, we examined short-term lymphocyte cultures from 45 adult malignant glioma patients and 117 age-, sex-, and ethnicity-matched healthy controls for mutagen-induced chromatid breaks and evaluated their family history of cancer, smoking, and demographic variables to ascertain the association between mutagen sensitivity and risk of brain tumors. The mutagen selected was gamma-radiation. The mean number of induced breaks/cell was 0.72 (SD=0.45) for the cases and 0.45 (SD = 0.35) for the controls (P < 0.0001). Using the median number of induced breaks/cell in the controls as the breakpoint for defining mutagen sensitivity, we observed an unadjusted odds ratio of 5.36 (95% confidence interval = 2.12-13.69) for mutagen sensitivity and brain tumor risk and an adjusted odds ratio of 5.79 (2.26-14.83), when we controlled for epidemiological risk factors including smoking, race, income, and education. Although a larger study is needed to confirm this intriguing result, these preliminary findings suggest that increased sensitivity to radiation is an independent risk factor for gliomas.


Leptin levels in nonalcoholic steatohepatitis and chronic hepatitis C.
Leptin is a peptide which regulates food intake and energy expenditure. Moreover, it is involved in the homeostasis of body composition and is linked to the regulation of insulin signaling, thus playing an important role in liver fat storage. Steatosis is a common finding in chronic hepatitis C, and both viral and metabolic factors have been suggested to explain the presence of this histological characteristic. In order to study leptin in chronic liver disease characterized by the presence of steatosis, we evaluated its serum levels in patients with nonalcoholic steatohepatitis (NASH), in chronic hepatitis C (CHC) patients with no histological findings of steatosis, and CHC patients with steatosis but no risk factors for its development. We studied 6 male patients with NASH whose diagnosis was made on the basis of histological findings and clinical criteria. From among a cohort of 170 CHC patients we put together 2 groups of 6 male patients each (with or without steatosis at liver biopsy examination), who had no risk factors for NASH. Male patients were chosen in order to avoid gender influence on leptin levels. Further criteria for admission were similar impairment of liver metabolic function as assessed by the monoethylglycinexylidide (MEGX) test and, in patients with CHC, similar body mass index (BMI) and histological staging. Moreover, we evaluated leptin/BMI ratio, in order to rule out BMI influence on leptin levels. Leptin levels were assessed by means of radioimmunoassay. We found that BMI was higher in NASH compared to CHC (27.2 +/- 2.9 vs. 23.9 +/- 1.8; p = 0.01). Analysis of serum leptin levels showed an increasing trend starting from patients with CHC without steatosis (3.2 +/- 0.4 ng/ml), through CHC patients with steatosis (4.2 +/- 0.7 ng/ml) up to patients with NASH (5.7 +/- 2 ng/ml), although the differences observed were not statistically significant. Moreover, the ratio of leptin to BMI also followed the same trend showing increasing values (CHC without steatosis = 0.04 +/- 0.02; CHC patients with steatosis = 0.17 +/- 0.03; NASH = 0.203 +/- 0.07). Leptin levels and BMI showed a significant relationship (n = 18; r = 0.60; p < 0.01). The increasing trend observed in leptin serum levels among the different groups of patients showed that in chronic liver disease characterized by the presence of steatosis, leptin signaling is preserved. Moreover, CHC factors different from the metabolic ones should be investigated in order to explain the presence of steatosis. Further studies on broader groups of patients are needed to verify these preliminary results.


Mitochondrial genome variations, mitochondrial-nuclear compatibility, and their association with metabolic diseases.
Two genomes regulate the energy metabolism of eukaryotic cells: the nuclear genome, which codes for most cellular proteins, and the mitochondrial genome, which, together with the nuclear genome, coregulates cellular bioenergetics. Therefore, mitochondrial genome variations can affect, directly or indirectly, all energy-dependent cellular processes and shape the metabolic state of the organism. This review provides a current and up-to-date overview on how codependent these two genomes are, how they appear to have coevolved, and how variations within the mitochondrial genome might be associated with the manifestation of metabolic diseases. This review summarizes and structures results obtained from epidemiological studies that identified links between mitochondrial haplogroups and individual risks for developing obesity and diabetes. This is complemented by findings on the compatibility of mitochondrial and nuclear genomes and cellular bioenergetic fitness, which have been acquired from well-controlled studies in conplastic animal models. These elucidate, more mechanistically, how single-nucleotide variants can influence cellular metabolism and physiology. Overall, it seems that certain mitochondrial genome variations negatively affect mitochondrial-nuclear compatibility and are statistically linked with the onset of metabolic diseases, whereas, for others, greater uncertainty exists, and additional research into this exciting field is required.


Pledgeted mattress sutures reduce recurrent reflux after laparoscopic Nissen fundoplication.
In response to a perceived increase in the incidence of recurrent reflux after adopting the laparoscopic Nissen fundoplication, we adjusted our technique to include the use of pledgeted, horizontal mattress sutures for crural closure and wrap construction. We assessed the impact of this technical modification in children who underwent laparoscopic fundoplication between 1997 and 2007 at a large children's hospital. The medical history, indications, technical details, and outcomes were reviewed. Differences between groups were assessed with chi(2), logistic regression, and Kaplan-Meier analysis. A total of 384 subjects were identified. Neurologic deficits were present in 77%. The crural closure and wrap were constructed with simple sutures in 226 and with pledgeted, horizontal mattress sutures in 158. The cumulative incidences of recurrent reflux, gagging/retching, wrap failure on imaging studies, and reoperation were significantly greater with the use of simple sutures (P < .01, .03, < .01, and < .01, respectively). Kaplan-Meier analysis confirmed a significant difference in the probability of recurrent reflux with simple sutures despite a significant difference in postoperative follow-up. Operative time was the same with both methods. The use of pledgeted, horizontal mattress sutures for crural closure and wrap construction in laparoscopic Nissen fundoplication may reduce the incidence of recurrent reflux.


Selective Induction of Homeostatic Th17 Cells in the Murine Intestine by Cholera Toxin Interacting with the Microbiota.
Th17 cells play a role as an inflammation mediator in a variety of autoimmune disorders, including inflammatory bowel disease, and thus are widely considered to be pathogenic. However, Th17 cells are present in the normal intestine and show a homeostatic phenotype; that is, they participate in the maintenance of intestinal homeostasis rather than inducing inflammation. We observed an enlarged Th17 population in the small intestine of C57BL/6.IgA-/- mice compared with wild-type mice, which was further amplified with cholera toxin (CT) immunization without causing intestinal inflammation. The increased Th17 induction and the correspondingly 10-fold higher CT B subunit-specific serum IgG response in IgA-/- mice after CT immunization was microbiota dependent and was associated with increased segmented filamentous bacteria in the small intestine of IgA-/- mice. Oral administration of vancomycin greatly dampened both CT immunogenicity and adjuvanticity, and the differential CT responses in IgA-/- and wild-type mice disappeared after intestinal microbiota equalization. Using gnotobiotic mouse models, we found that CT induction of homeostatic intestinal Th17 responses was supported not only by segmented filamentous bacteria, but also by other commensal bacteria. Furthermore, transcriptome analysis using IL-17AhCD2 reporter mice revealed a similar gene expression profile in CT-induced intestinal Th17 cells and endogenous intestinal Th17 cells at homeostasis, with upregulated expression of a panel of immune-regulatory genes, which was distinctly different from the gene expression profile of pathogenic Th17 cells. Taken together, we identified a nonpathogenic signature of intestinal homeostatic Th17 cells, which are actively regulated by the commensal microbiota and can be selectively stimulated by CT.


Sweet potato (Ipomoea batatas L.) leaf polyphenols ameliorate hyperglycemia in type 2 diabetes mellitus mice.
The hypoglycemic effects and potential mechanism of sweet potato leaf polyphenols (SPLP) on type 2 diabetes mellitus (T2DM) were investigated. Results showed that oral administration of SPLP to mice could alleviate body weight loss, decrease fasting blood glucose levels (by 64.78%) and improve oral glucose tolerance compared with those of untreated diabetic mice. Furthermore, increased fasting serum insulin levels (by 100.11%), ameliorated insulin resistance and improved hepatic glycogen (by 126.78%) and muscle glycogen (increased by 135.85%) were observed in the SPLP treatment group. SPLP also could reverse dyslipidemia, as indicated by decreased total cholesterol, triglycerides, low density lipoprotein-cholesterol and promoted high density lipoprotein-cholesterol. Histopathological analysis revealed that SPLP could relieve liver inflammation and maintain the islet structure to inhibit β-cell apoptosis. A quantitative real-time polymerase chain reaction confirmed that SPLP could up-regulate the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3β signaling pathway to improve glucose metabolism and up-regulate the phosphatidylinositol 3-kinase/protein kinase B/glucose transporter 4 signaling pathway in the skeletal muscle to enhance glucose transport. This study provides useful information to support the application of SPLP as a natural product for the treatment of T2DM.


Grassland harvesting alters ant community trophic structure: An isotopic study in tallgrass prairies.
Disturbances have long been recognized as important forces for structuring natural communities but their effects on trophic structure are not well understood, particularly in terrestrial systems. This is in part because quantifying trophic linkages is a challenge, especially for small organisms with cryptic feeding behaviors such as insects, and often relies on conducting labor-intensive feeding trials or extensive observations in the field. In this study, we used stable isotopes of carbon and nitrogen to examine how disturbance (annual biomass harvesting) in tallgrass prairies affected the trophic position, trophic range, and niche space of ants, a widespread grassland consumer. We hypothesized that biomass harvest would remove important food and nesting resources of insects thus affecting ant feeding relationships and trophic structure. We found shifts in the feeding relationships inferred by isotopic signatures with harvest. In particular, these shifts suggest that ants within harvest sites utilized resources at lower trophic levels (possibly plant-based resources or herbivores), expanded trophic breadth, and occupied different niche spaces. Shifts in resource use following harvest could be due to harvest-mediated changes in both the plant and arthropod communities that might affect the strength of competition or alter plant nitrogen availability. Because shifts in resource use alter the flow of nutrients across the food web, disturbance effects on ants could have ecosystem-level consequences through nutrient cycling.


The number of ribosomal RNA genes in Thermus thermophilus HB8.
We have examined the number of rRNA genes in Thermus thermophilus HB8 by hybridization of Bam HI -, Hind III - and Pst I - digests of DNA to 3'- (3 2p) 23S, 16S and 5S rRNAs according to the Southern procedure. The restriction gels gave two radioactive bands with 23S and 5S rRNA. Furthermore, band positions were indistinguishable from one another when 23S and 5S rRNAs were used as probes to Bam HI and Hind III digests, indicating that each band contains sequences corresponding to the 3'-end of 23S and 5S rRNAs. The Pst I digest also gave two radioactive bands with 23S and 5S rRNAs as probes, where one band position was identical, but the other different. The 16S rRNA did hybridize with two fragments, using a Bam HI, as well as a Bam HI - Hind III double digest. The Hind III digest gave one band using 16S rRNA as a probe. It is concluded that the Thermus thermophilus HB8 chromosome carries at least two sets of genes for 23S, 16S and 5S rRNAs.


Aspirin and omeprazole for secondary prevention of cardiovascular disease in patients at risk for aspirin-associated gastric ulcers.
Cardiovascular disease is the most important cause of morbidity and mortality in the world and low-dose aspirin is considered the cornerstone of the cardiovascular disease prevention. However, low-dose aspirin use is associated with gastrointestinal adverse effects in the whole gastrointestinal tract. In this setting, co-therapy with a proton pump inhibitor is the most accepted strategy to reduce aspirin related upper gastrointestinal damage. In addition, some adverse effects have been described with proton pump inhibitors long term use. Areas covered: Low-dose aspirin related beneficial and adverse effects in cardiovascular system and gastrointestinal tract are reviewed. In addition, this manuscript summarizes current data on upper gastrointestinal damage prevention and adverse events with proton pump inhibition. Finally, we discuss the benefit/risk ratio of proton pump inhibitor use in patients at risk of gastrointestinal damage taking low-dose aspirin. Expert commentary: Nowadays, with the current available evidence, the combination of low-dose aspirin with proton pump inhibitor is the most effective therapy for cardiovascular prevention in patients at high gastrointestinal risk. However, further studies are needed to discover new effective strategies with less related adverse events.


Interface chemistry of an amide electrolyte for highly reversible lithium metal batteries.
Metallic lithium is a promising anode to increase the energy density of rechargeable lithium batteries. Despite extensive efforts, detrimental reactivity of lithium metal with electrolytes and uncontrolled dendrite growth remain challenging interconnected issues hindering highly reversible Li-metal batteries. Herein, we report a rationally designed amide-based electrolyte based on the desired interface products. This amide electrolyte achieves a high average Coulombic efficiency during cycling, resulting in an outstanding capacity retention with a 3.5 mAh cm-2 high-mass-loaded LiNi0.8Co0.1Mn0.1O2 cathode. The interface reactions with the amide electrolyte lead to the predicted solid electrolyte interface species, having favorable properties such as high ionic conductivity and high stability. Operando monitoring the lithium spatial distribution reveals that the highly reversible behavior is related to denser deposition as well as top-down stripping, which decreases the formation of porous deposits and inactive lithium, providing new insights for the development of interface chemistries for metal batteries.


Update on trauma care in Canada. 5. Trauma and hypothermia.
Trauma may be accompanied by hypothermia in all climates. Because of the associated increased death rate due to hypothermia (core body temperature less than 35 degrees C), traumatized patients must be protected from it. The body maintains heat balance by hypothalamic regulation of endogenous heat generation and heat loss. Decreased core temperature causes generalized physiologic deceleration and homeostatic disturbances in all organ systems. To prevent hypothermia in polytraumatized patients a number of methods may be used: warming crystalloid, increasing ambient temperature, the use of warming devices, irrigation of body cavities with warmed fluids, heating of inspired gases and, in severe cases when there is circulatory instability, the use of extracorporeal membrane oxygenation.


Evaluation of Mesial Root Canals of Mandibular Molars Obturated with Gutta-Percha and Resilon Techniques.
The aim of this study was to evaluate the obturation of mesial root canals of mandibular first molars performed with different filling techniques and materials (gutta-percha and resilon). Seventy-eight mesial root canals of human mandibular first molars were prepared using the K3 rotary system, and the apical preparation was set up to size 35.04. The root canals were obturated with single cone, System B, Thermafil and Real Seal 1 techniques using either gutta-percha/ThermaSeal Plus (n=13) or Resilon/Real Seal SE (n=13). Rhodamine B dye was incorporated into the sealers. Each specimen was horizontally sectioned at 2 milimeters (mm), 4 mm and 6 mm from the apex, and the samples were examined under a stereomicroscope to evaluate the presence and type of isthmuses and the percentage areas of gutta-percha/Resilon, sealer and voids. Confocal laser scanning microscopy (CLSM) was used to evaluate the sealer penetration into dentinal tubules. The Kruskal-Wallis and Dunn's tests were used to analyse the stereomicroscope data, while the ANOVA and Tukey tests were used to analyse the CLSM data (P<0.05). Thermafil and Real Seal 1 fillings showed more gutta-percha/Resilon and less sealer (P<0.05) at the 2 mm level, but the percentage of voids was similar in all groups (P>0.05). At the 4 mm level, more sealer (P<0.05) was found in the single cone groups using both materials. The System B groups exhibited better performance at the 6 mm level. The percentage of sealer penetration showed no statistically significant differences among the obturation techniques for all evaluated levels. Similar results (P>0.05) were found for both material/sealers. None of the materials or techniques completely filled the mesial root canals of mandibular molars, but the plasticised techniques were more efficient. The obturations using both materials and sealers were similar.


Enhanced HIV infectivity and changes in GP120 conformation associated with viral incorporation of human leucocyte antigen class I molecules.
Assembly of human immunodeficiency virus type 1 (HIV-1) occurs at the level of the plasma membrane of the host cell. During this process HIV incorporates significant quantities of cell surface-derived molecules into its lipid bilayer including human leucocyte antigen (HLA) class I and II, intercellular adhesion molecule-1 and lymphocyte function antigen-1. Several studies indicate that virion-bound host-cell-derived molecules are functional and affect the biological properties of HIV-1. Virion-associated HLA class II and intercellular adhesion molecule-1 enhance the infectivity of T-cell line-adapted (TCLA) viruses. No role for virion-associated HLA class I molecules has yet been identified. To investigate the role of HLA class I molecules in HIV replication and infectivity. HLA class I negative human cells lines transfected with the HLA Cw4 gene were infected with different TCLA viruses as well as primary X4 isolates. The infectivity of HLA Cw4 positive and negative viruses was determined on indicator cell lines and on phytohaemagglutinin-activated peripheral blood mononuclear cells. An entry polymerase chain reaction assay was used to determine differences in entry-competence of Cw4 positive and negative viruses. The expression of selected gp120 epitopes on native Env molecules derived from Cw4 positive and negative viruses was determined by a monoclonal antibody-based enzyme-linked immunosorbent assay. Immunoprecipitation experiments were performed to investigate the presence of gp120/HLA Cw4 complexes. Neutralization assays determined the differences in susceptibility to neutralization between HLA Cw4 negative and positive viruses. The infectivity of primary HIV-1 X4 isolates and of TCLA viruses is increased upon viral incorporation of HLA Cw4 molecules. This effect is associated with changes in viral envelope proteins conformation including an enhanced expression of the V3 loop of gp120, and of epitopes that are exposed upon CD4 binding. The gp120 conformational changes are consistent with the formation of a multimolecular complex between HLA class I and gp120/160. HLA Cw4 incorporation is also associated to a lower susceptibility to antibody neutralization. These findings have important implications for understanding the immune response to cryptic and conformational epitopes of the viral envelope.


Targeting PKM2 improves the gemcitabine sensitivity of intrahepatic cholangiocarcinoma cells via inhibiting β-catenin signaling pathway.
Gemcitabine is considered the standard first-line chemotherapeutic agent for patients with intrahepatic cholangiocarcinoma (ICC). However, its therapeutic efficacy is hampered by the development of chemoresistance. Pyruvate kinase M2 (PKM2), a crucial mediator of the final step in glycolysis, has been implicated in the origination and advancement of diverse malignancies. Its expression is increased in many tumor types and this may correlate with increased drug sensitivity. However, the specific effect of PKM2 on the gemcitabine sensitivity in ICC remains to be elucidated. In this research, we aimed to elucidate the role and functional significance of PKM2 in ICC, as well as the heightened susceptibility of ICC cells to gemcitabine by targeting PKM2 and the underlying molecular mechanisms. Immunohistochemical and immunofluorescence analyses revealed elevated expression of PKM2 in both tumor cells and macrophages in human ICC tissues. Reducing PKM2 levels significantly restrained the proliferation of tumor cells, impeded cell cycle advance, induced programmed cell death, and suppressed metastasis. In addition, knockdown or pharmacological inhibition of PKM2 could enhance the response of ICC cells to gemcitabine in vitro. Interestingly, conditioned medium co-culture system suggested that conditioned medium from M2 macrophages increased gemcitabine sensitivity of ICC cells. However, silencing PKM2 or pharmacological inhibition of PKM2 in M2 macrophages did not ameliorate the gemcitabine resistance mediated by M2 macrophages derived conditioned medium. Mechanistically, downregulation of PKM2 repressed the expression of β-catenin and its downstream transcriptional targets, thereby hindering the propagation of β-catenin signaling cascade. Finally, the results of the subcutaneous xenograft experiment in nude mice provided compelling evidence of a synergistic interaction between PKM2-IN-1 and gemcitabine in vivo. In summary, we reported that PKM2 may function as an advantageous target for increasing the sensitivity of ICC to gemcitabine treatment. Targeting PKM2 improves the gemcitabine sensitivity of ICC cells via inhibiting β-catenin signaling pathway.


Ultra-broad and sharp-transition bandpass terahertz filters by hybridizing multiple resonances mode in monolithic metamaterials.
We present three monolithic metamaterial-based THz bandpass filters, the skewed circular slot rings, meandered slots and Jerusalem cross slots, to fit in the THz gap. These THz bandpass filters are comprised of a metal-dielectric-metal (MDM) structure that supports multiple resonances of electric dipole, magnetic dipole, and standing-wave-like modes. By exciting and further hybridizing these individual resonance modes, we demonstrate excellent performance of broad bandwidth and sharp band-edge transition beyond conventional bandpass filters. By further employing our ad hoc Genetic Algorithm (GA) and Periodic Method of Moments (PMM) to optimize our designs, we achieve an ultra-broad 3dB fractional bandwidth and sharp band-edge transition up to 82.2% and 58.3 dB/octave, respectively, benefiting the practical applications such as material recognition in security systems, imaging, and absorbers.


Effects of postnatal omega-3 fatty acid supplementation on offspring pro-resolving mediators of inflammation at 6 months and 5 years of age: A double blind, randomized controlled clinical trial.
Resolution of inflammation is an active process involving specialised pro-resolving mediators (SPMs) generated from the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid supplementation during infancy may provide an intervention strategy to modify SPMs and reduce oxidative stress. This study evaluates the effect of omega-3 fatty acid supplementation in infancy on SPMs and F2-isoprostanes from 6 months to 5 years of age. In a double-blind, placebo-controlled, parallel-group study design, 420 infants were randomized to a daily supplement of omega-3 fatty acids (280mg DHA and 110mg EPA) or olive oil (control), from birth to age 6 months. Blood was collected at birth (cord blood), 6 months, 12 months and 5 years. Plasma SPMs included 18-HEPE, E-series resolvins, 17-HDHA, D-series resolvins, 14-HDHA, 10S,17S-DiHDoHE, MaR1 and PD1. F2-isoprostanes were measured in plasma and urine, as markers of oxidative stress in vivo. The change in the concentration of 18-HEPE from birth to 6 months was greater in the omega-3 fatty acid group (Ptimepoint*group=0.04) with levels at 6 months significantly higher than controls (P=0.02). Other SPMs were not different between the groups at any time point. Plasma 18-HEPE concentration were associated with erythrocyte EPA concentrations after age and group adjustments (P<0.001), but not with allergic outcomes at 12 months. There were no between-group differences in plasma and urinary F2-isoprostanes at any time point. Omega-3 fatty acid supplementation from birth to 6 months of age increased SPM at 6 months but the effects were not sustained after supplementation ceased. Given that 18-HEPE is a biologically active metabolite, future studies should examine how the increase in 18-HEPE relates to potential health benefits of omega-3 fatty acid supplementation in infancy.


Heterogeneous synthetic phenotype of cloned scleroderma fibroblasts may be due to aberrant regulation in the synthesis of connective tissues.
Clones of dermal fibroblasts from the skin of 4 normal subjects and 5 patients with progressive systemic sclerosis (PSS; scleroderma) were established, and their synthetic and proliferative characteristics were compared. A limiting-dilution assay was used to determine frequencies of cloning in the microcultures of dermal fibroblasts plated. The clones derived from single cells were expanded in vitro and examined (in passages C-H) for growth and synthesis of glycosaminoglycan (GAG) and collagenase-sensitive protein (CSP). The clonogenicity of PSS fibroblasts was not significantly different from that of normal fibroblasts. Normal fibroblast clones were characterized by low levels of GAG and CSP synthesis, and there was a correlation between the GAG and CSP phenotypes. In contrast, clones of PSS fibroblasts were often, but not always, high producers of GAG and CSP, but there was no correlation between the levels of GAG and CSP synthesis. It appears that scleroderma skin is composed of fibroblast clones that are unable to regulate the synthesis of connective tissue components and often synthesize large amounts of connective tissue macromolecules.


Inward current oscillation underlying tonic contraction caused via ETA receptors in pig detrusor smooth muscle.
Endothelin-1 (ET-1) is a powerful vasoconstricting peptide. Recent studies showed synthesis of ET-1 and the presence of ET receptors in urinary bladder smooth muscle cells. In the present study, we investigated the possible role of ET-1 in detrusor contraction and its underlying mechanisms in terms of electrical activity. ET-1 caused dose-dependent tonic contraction of bladder smooth muscle strips. Whole cell patch-clamp experiments revealed that ET-1 induced a single transient inward current in the majority of detrusor cells and that additional inward current oscillations were induced in one-third of the cells. The inward current oscillation and tonic contraction shared several characteristic features: 1) both activities lasted for a considerable time after ET-1 washout and 2) only prior application of ETA receptor antagonists, not ETB receptor antagonists, significantly suppressed ET-1-induced contractions and the oscillating inward currents. It was concluded that the inward current oscillation underlies ET-1-induced tonic contraction. Experiments with ion substitution and channel blockers suggested that periodic activation of Ca2+-activated Cl- channels caused the oscillating inward currents.


Extension of the Universal Force Field for Metal-Organic Frameworks.
We have extended the Universal Force Field for Metal-Organic Frameworks (UFF4MOF) to cover all moieties present in the most extensive framework library to date, i.e., the Computation-Ready Experimental (CoRE) database (Chem. Mater. 2014, 26, 6185). Thus, we have extended the parameters to include the fourth and fifth row transition metals, lanthanides, and an additional atom type for sulfur, while the parameters of original UFF and of UFF4MOF are not modified. Employing the new parameters significantly enlarges the number of structures that may be subjected to a UFF calculation, i.e., more than doubling accessible MOFs of the CoRE structures and thus reaching over 99% of CoRE structure coverage. In turn, 95% of optimized cell parameters are within 10% of their experimental values. We contend these parameters will be most useful for the generation and rapid prototyping of hypothetical MOF structures from SBU databases.


Crystal structures reveal catalytic and regulatory mechanisms of the dual-specificity ubiquitin/FAT10 E1 enzyme Uba6.
The E1 enzyme Uba6 initiates signal transduction by activating ubiquitin and the ubiquitin-like protein FAT10 in a two-step process involving sequential catalysis of adenylation and thioester bond formation. To gain mechanistic insights into these processes, we determined the crystal structure of a human Uba6/ubiquitin complex. Two distinct architectures of the complex are observed: one in which Uba6 adopts an open conformation with the active site configured for catalysis of adenylation, and a second drastically different closed conformation in which the adenylation active site is disassembled and reconfigured for catalysis of thioester bond formation. Surprisingly, an inositol hexakisphosphate (InsP6) molecule binds to a previously unidentified allosteric site on Uba6. Our structural, biochemical, and biophysical data indicate that InsP6 allosterically inhibits Uba6 activity by altering interconversion of the open and closed conformations of Uba6 while also enhancing its stability. In addition to revealing the molecular mechanisms of catalysis by Uba6 and allosteric regulation of its activities, our structures provide a framework for developing Uba6-specific inhibitors and raise the possibility of allosteric regulation of other E1s by naturally occurring cellular metabolites.


The Characterization of Sex Differences in Hypoglycemia-Induced Activation of HPA Axis on the Transcriptomic Level.
Activation of the hypothalamic-pituitary-adrenal (HPA) axis using an insulin tolerance test (ITT) is a medical diagnostic procedure that is frequently used in humans to assess the HPA and growth-hormone (GH) axes. Whether sex differences exist in the response to ITT stress is unknown. Thus, investigations into the analysis of transcripts during activation of the HPA axis in response to hypoglycemia have revealed the underlying influences of sex in signaling pathways that stimulate the HPA axis. We assessed four time points of ITT application in Balb/c mice. After insulin injection, expression levels of 192 microRNAs and 41 mRNAs associated with the HPA, GH and hypothalamic-pituitary-gonadal (HPG) axes were determined by real-time RT-PCR in the hypothalamus, pituitary and adrenal tissues, as well as blood samples (Raw data accession: https://drive.google.com/drive/folders/10qI00NAtjxOepcNKxSJnQbJeBFa6zgHK?usp=sharing ). Although the ITT is commonly used as a gold standard for evaluating the HPA axis, we found completely different responses between males and females with respect to activation of the HPA axis. While activation of several transcripts in the hypothalamus and pituitary was observed after performing the ITT in males within 10 min, females responded via the pituitary and adrenal immediately and durably over 40 min. Additionally, we found that microRNA alterations precede mRNA responses in the HPA axis. Furthermore, robust changes in the levels of several transcripts including Avpr1b and Avpr2 observed at all time points strongly suggest that transcriptional control of these genes occurs mostly via differential signaling in pituitary and blood between males and females. Male and female HPA axis responses to ITT involve a number of sophisticated regulatory signaling pathways of miRNAs and mRNAs. Our results highlight the first robust markers in several layers of HPA, HPG and GH axis involved in ITT/hypoglycemia stress-induced dynamics.


Efficacy and safety of recombinant human activated protein C for severe sepsis.
Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers of coagulation and inflammation in patients with severe sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis. We conducted a randomized, double-blind, placebo-controlled, multicenter trial. Patients with systemic inflammation and organ failure due to acute infection were enrolled and assigned to receive an intravenous infusion of either placebo or drotrecogin alfa activated (24 microg per kilogram of body weight per hour) for a total duration of 96 hours. The prospectively defined primary end point was death from any cause and was assessed 28 days after the start of the infusion. Patients were monitored for adverse events; changes in vital signs, laboratory variables, and the results of microbiologic cultures; and the development of neutralizing antibodies against activated protein C. A total of 1690 randomized patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group). The mortality rate was 30.8 percent in the placebo group and 24.7 percent in the drotrecogin alfa activated group. On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4 percent (95 percent confidence interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1 percent (P=0.005). The incidence of serious bleeding was higher in the drotrecogin alfa activated group than in the placebo group (3.5 percent vs. 2.0 percent, P=0.06). Treatment with drotrecogin alfa activated significantly reduces mortality in patients with severe sepsis and may be associated with an increased risk of bleeding.


Hallucinations in neurodegenerative diseases.
Patients with neurodegenerative disease frequently experience hallucinations and illusionary perceptions. As early symptoms, hallucinations may even have diagnostic relevance (i.e., for the diagnosis of Lewy Body Dementia). In the later course of the disease, hallucinations may appear as characteristic symptoms and often constitute a particular challenge for therapeutic endeavors. Here, the distinction of disease-inherent hallucinations from medication-associated perceptual disturbances is particularly relevant. Synucleinopathies and tauopathies have different risk profiles for hallucinations. In synucleinopathies hallucinations are much more frequent and phenomenology is characterized by visual, short-lived hallucinations, with insight preserved for a long time. A "double hit" theory proposes that dysfunctionality of both associative visual areas and changes of limbic areas or the ventral striatum are required. In contrast, in tauopathies the hallucinations are more rare and mostly embedded in confusional states with agitation and with poorly defined or rapidly changing paranoia. The occurrence of hallucinations has even been proposed as an exclusion criterion for tauopathies with Parkinsonian features such as progressive supranuclear palsy. To date, treatment remains largely empirical, except the use of clozapine and cholinesterase inhibitors in synucleinopathies, which is evidence-based. The risk of increased neuroleptic sensitivity further restricts the treatment options in patients with Lewy Body Dementia. Coping Strategies and improvement of visual acuity and sleep quality may be useful therapeutic complements.


Overcoming clinical inertia in the management of postoperative patients with diabetes.
To assess the impact of an intervention designed to increase basal-bolus insulin therapy administration in postoperative patients with diabetes mellitus. Educational sessions and direct support for surgical services were provided by a nurse practitioner (NP). Outcome data from the intervention were compared to data from a historical (control) period. Changes in basal-bolus insulin use were assessed according to hyperglycemia severity as defined by the percentage of glucose measurements >180 mg/dL. Patient characteristics were comparable for the control and intervention periods (all P≥.15). Overall, administration of basal-bolus insulin occurred in 9% (8/93) of control and in 32% (94/293) of intervention cases (P<.01). During the control period, administration of basal-bolus insulin did not increase with more frequent hyperglycemia (P = .22). During the intervention period, administration increased from 8% (8/96) in patients with the fewest number of hyperglycemic measurements to 60% (57/95) in those with the highest frequency of hyperglycemia (P<.01). The mean glucose level was lower during the intervention period compared to the control period (149 mg/dL vs. 163 mg/dL, P<.01). The proportion of glucose values >180 mg/dL was lower during the intervention period than in the control period (21% vs. 31% of measurements, respectively, P<.01), whereas the hypoglycemia (glucose >70 mg/dL) frequencies were comparable (P = .21). An intervention to overcome clinical inertia in the management of postoperative patients with diabetes led to greater utilization of basal-bolus insulin therapy and improved glucose control without increasing hypoglycemia. These efforts are ongoing to ensure the delivery of effective inpatient diabetes care by all surgical services.


Management of Closed Incisions Using Negative-Pressure Wound Therapy in Orthopedic Surgery.
Negative-pressure wound therapy (NPWT) has been a major advance in the management of open wounds, especially in orthopedic trauma surgery. Due to the success of NPWT, surgeons began using NPWT on closed incisions as a way to help prevent surgical wound dehiscence, especially in at-risk patients for wound problems. It has been well established that obesity, diabetes mellitus, and smoking in addition to other comorbidities increase the risk of wound dehiscence and surgical site infections in orthopedic patients. This article reviews the current literature and provides an overview on the use of NPWT on closed incisions in orthopedic trauma procedures and joint arthroplasty.


A framework for assessing local transmission risk of imported malaria cases.
A key issue in achieving and sustaining malaria elimination is the need to prevent local transmission arising from imported cases of malaria. The likelihood of this occurring depends on a range of local factors, and these can be used to allocate resources to contain transmission. Therefore, a risk assessment and management strategy is required to identify risk indexes for malaria transmission when imported cases occur. These risks also need to be quantified and combined to give a weighted risk index score. This can then be used to allocate the resources to each administrative region to prevent transmission according to the degree of risk. A list of potential risk indexes were generated from a literature review, expert consultation and panel discussion. These were initially classified into 4 first-level indexes including infection source, transmitting conditions, population vulnerability and control capacity. Each of these was then expanded into more detailed second-level indexes. The Delphi method was then used to obtain expert opinion to review and revise these risk indexes over two consecutive rounds to quantify agreement among experts as to their level of importance. Risk indexes were included in the final Transmission Risk Framework if they achieved a weighted importance score ≥ 4. The Analytic Hierarchy Process was then used to calculate the weight allocated to each of the final risk indexes. This was then used to create an assessment framework that can be used to evaluate local transmission risk in different areas. Two rounds of Delphi consultation were conducted. Twenty-three experts were used at each round with 100% recovery rate of participant questionnaires. The coordination coefficients (W) for the two rounds of Delphi consultation were 0.341 and 0.423, respectively (P < 0.05). Three first-level indexes and 13 second-level indexes were identified. The Analytic Hierarchy Process was performed to calculate the weight of the indexes. For the first-level indexes, infection source, transmitting conditions, and control capacity, the index weight was 0.5396, 0.2970 and 0.1634 respectively. For the three top second-level indexes, number of imported malaria cases, Anopheles species, and awareness of timely medical visit of patient, the index weight was 0.3382, 0.2475, and 0.1509 respectively. An indexed system of transmission risk assessment for imported malaria was established using the Delphi method and the Analytic Hierarchy Process. This was assessed to be an objective and practical tool for assessing transmission risk from imported cases of malaria into China.


Fluidics.
The primary function of the fluidics of a flow cytometer is to deliver cells to the sensing area in a single file well aligned with the detectors. In a sorting instrument, the fluidics must also be capable of physically isolating those cells selected on the basis of measurements made by the instrument. The unit discusses primary and secondary fluidic functions, types of sensing area, types of sample delivery, potential problems affecting sample flow, and sorting.


Blockade of BLyS inhibits B cell responses and antibody production for the prevention of chronic transplant rejection.
Chronic rejection, closely related to the activation of B cells and donor-specific antibody (DSA) production, has unsatisfactory therapeutic outcomes. B lymphocyte stimulator (BLyS) is a major regulatory factor that controls the activation and differentiation of B cells. However, it remains unclear whether BLyS blockade can regulate B and plasma cells in the transplantation setting and affect chronic rejection. Here, we investigated the efficacy of the BLyS inhibitors belimumab and telitacicept in controlling B-cell response and preventing chronic rejection. The effects of belimumab and telitacicept on B-cell activation, differentiation and antibody production in vitro were determined. A chronic rejection model in mouse was established by allogeneic cardiac transplantation with CTLA4-Ig treatment. Allograft survival, histology, DSA levels, and B-cell responses were analyzed to evaluate the chronic rejection-preventive effects of belimumab and telitacicept. In vitro experiments confirmed that belimumab and telitacicept inhibited B-cell activation and differentiation and reduced antibody production. In vivo experiments indicated that they significantly prolonged allograft survival, attenuated chronic rejection through significant suppression of myocardial ischemic necrosis and interstitial fibrosis, and reduced DSA-IgG levels, C4d deposition, and inflammatory cell infiltration. Furthermore, the frequencies of B cells, plasma cells and IgG producing cells in the recipients' spleen, lymph nodes, bone marrow, and blood were decreased after BLyS inhibitors treatment. This study demonstrated that belimumab and telitacicept inhibit B-cell responses and antibody production and alleviate chronic transplant rejection. Therefore, BLyS inhibitors are expected to be used for the prevention of chronic rejection in clinical practice.


Molecular characterization of genetically-modified crops: Challenges and strategies.
Molecular characterization lays a foundation for safety assessment and subsequent monitoring of genetically modified (GM) crops. Due to the target-specific nature, conventional polymerase chain reaction (PCR)-based methods cannot comprehensively detect unintended gene insertions, let alone unknown GM events. As more and more new developed GM crops including new plant breeding technology (NPBT) generated crops are in the pipeline for commercialization, alternative -omics approaches, particularly next generation sequencing, have been developed for molecular characterization of authorized or unauthorized GM (UGM) crops. This review summarizes first those methods, addresses their challenges, and discusses possible strategies for molecular characterization of engineered crops generated by NPBT, highlighting needs for a global information-sharing database and cost-effective, accurate and comprehensive molecular characterization approaches.


Multi-Response Optimization of Process Parameters for Imidacloprid Removal by Reverse Osmosis Using Taguchi Design.
In this study, a multi-response optimization method using Taguchi's robust design approach is proposed for imidacloprid removal by reverse osmosis. Tests were conducted with different membrane type (BW30, LFC-3, CPA-3), transmembrane pressure (TMP = 20, 25, 30 bar), volume reduction factor (VRF = 2, 3, 4), and pH (3, 7, 11). Quality and quantity of permeate are optimized with the multi-response characteristics of the total dissolved solid (TDS), conductivity, imidacloprid, and total organic carbon (TOC) rejection ratios and flux of permeate. The optimized conditions were determined as membrane type of BW30, TMP 30 bar, VRF 3, and pH 11. Under these conditions, TDS, conductivity, imidacloprid, and TOC rejections and permeate flux were 97.50 97.41, 97.80, 98.00% and 30.60 L/m2·h, respectively. Membrane type was obtained as the most effective factor; its contribution is 64%. The difference between the predicted and observed value of multi-response signal/noise (MRSN) is within the confidence interval.


β-Thalassemia heterozygote state detrimentally affects health expectation.
Thalassemia minor (Tm) individuals, are generally considered healthy. However, the prognosis of Tm individuals has not been extensively studied. The aim of this study was to evaluate the prognosis of Tm versus controls without β-thalassemia carrier state. A total of 26,006 individuals seeking thalassemia screening at the AOOR Villa Sofia-V. Cervello, Palermo (Italy) were retrospectively studied. Logistic penalised regression model was used to estimate risk of potential complications and survival techniques were used to study mortality. We identified a total of 4943 Tm and 21,063 controls. Tm was associated with significantly higher risks of hospitalisation for cirrhosis (OR 1·94, 95% CI 1·30 to 2·90, p = 0·001), kidney disorders (OR 2·11, 95% CI 1·27 to 3·51, p = 0·004), cholelithiatis (OR 1·39, 95% CI 1·08 to 1·79, p = 0·010), and mood disorders (OR 2·08, 95% CI 1·15 to 3·75, p = 0·015). No statistically difference in life expectancy between thalassemia minor and control group was found (HR 1·090, 95% CI 0·777 to 1·555, p < 0·590; log-rank test p = .426). This study shows that Tm affects the prognosis of Tm carriers regarding health expectation. Probably, iron overload and anaemia for several years may be at the basis of these effects.


Biased cognition in East Asian and Western cultures.
The majority of cognitive bias research has been conducted in Western cultures. We examined cross-cultural differences in cognitive biases, comparing Westerners' and East Asians' performance and acculturation following migration to the opposite culture. Two local (UK, Hong Kong) and four migrant (short-term and long-term migrants to each culture) samples completed culturally validated tasks measuring attentional and interpretation bias. Hong Kong residents were more positively biased than people living in the UK on several measures, consistent with the lower prevalence of psychological disorders in East Asia. Migrants to the UK had reduced positive biases on some tasks, while migrants to Hong Kong were more positive, compared to their respective home counterparts, consistent with acculturation in attention and interpretation biases. These data illustrate the importance of cultural validation of findings and, if replicated, would have implications for the mental health and well-being of migrants.