Nucleation and growth kinetics of zirconium-oxo-alkoxy nanoparticles.
Nucleation and growth of zirconium-oxo-alkoxy (ZOA) nanoparticles were studied in a sol-gel process in n-propanol solution at a hydrolysis ratio H between 1.0 and 2.7 and zirconium-n-propoxyde precursor concentrations between 0.10 and 0.15 mol l(-1). The chemical transformations were conducted in quasi-perfect micromixing conditions (Damköhler number Da ≤ 1) and the nanoparticle size evolution was monitored in situ with the light scattering method. The size of primary nanoparticles (nuclei) 2R0 = 3.6 nm was found to be almost independent of the preparation conditions. A remarkable similarity with the titanium-oxo-alkoxy (TOA) nanoparticles was observed. In particular, both systems show the induction stage of the sol-gel growth for a hydrolysis ratio H > 2.0 and stable oxometallate units for H≤ 2.0. However in contrast to TOA, no stable hierarchical ZOA units (clusters) with R0≥R≥ 1.0 nm were observed, which makes this system less stable against aggregation, leading to polydispersed nanoparticles.


Exploring the Associations Between Non-Traditional Lipid Parameters and Epicardial Adipose Tissue Volume.
The aim of this retrospective study was to determine the relationship between non-traditional lipid parameters and epicardial adipose tissue (EAT). A total of 770 patients with coronary computed tomography angiography examinations were included. The non-traditional lipid parameters included the atherogenic index of plasma (AIP), the atherogenic coefficient (AC), monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR), and lipoprotein combined index (LCI). To investigate the association between non-conventional lipid markers and the EAT-volume (EAT-v), a univariate and multivariate analyses were conducted. The receiver operating characteristic (ROC) analysis was used to compare the predictive ability among the four non-traditional lipid parameters. In the univariate analysis, we identified factors that might have effects on EAT-v (all P<.05) and adjusted for these in the multivariate analysis. We found that except for MHR, other non-traditional lipid parameters were still associated with high EAT-v after adjustment (all P<.05). In the ROC analysis, the area under the curve (AUC) of AIP was greater than that of other non-traditional lipid parameters and lipid profiles. There was an association between both non-traditional lipid parameters and EAT-v. After adjustment, the AIP remained an independent predictor of EAT-v and it outperformed other non-traditional lipid parameters.


Ultrathin Single-Crystalline CdTe Nanosheets Realized via Van der Waals Epitaxy.
Due to the novel physical properties, high flexibility, and strong compatibility with Si-based electronic techniques, 2D nonlayered structures have become one of the hottest topics. However, the realization of 2D structures from nonlayered crystals is still a critical challenge, which requires breaking the bulk crystal symmetry and guaranteeing the highly anisotropic crystal growth. CdTe owns a typical wurtzite crystal structure, which hinders the 2D anisotropic growth of hexagonal-symmetry CdTe. Here, for the first time, the 2D anisotropic growth of ultrathin nonlayered CdTe as thin as 4.8 nm via an effective van der Waals epitaxy method is demonstrated. The anisotropic ratio exceeds 103 . Highly crystalline nanosheets with uniform thickness and large lateral dimensions are obtained. The in situ fabricated ultrathin 2D CdTe photodetector shows ultralow dark current (≈100 fA), as well as high detectivity, stable photoswitching, and fast photoresponse speed (τrising = 18.4 ms, τdecay = 14.7 ms). Besides, benefitting from its 2D planar geometry, CdTe nanosheet exhibits high compatibility with flexible substrates and traditional microfabrication techniques, indicating its significant potential in the applications of flexible electronic and optoelectronic devices.


[The present status and future of liver transplantation].
Since the introduction of cyclosporine the survival rate of orthotopic liver transplantation (OLT) has been dramatically improved (74% and 64% at one and 5 years reported from Pittsburgh). Additional contributing factors for this improvement are refinement of surgical techniques including using biopump for veno-veno bypass, introduction of OKT3 monoclonal antibody to treat acute allograft rejection, and adoption of new hepatic preservation fluid named as University of Wisconsin solution. There are, however, several continued threats of primary graft dysfunction, hepatic arterial thrombosis, early acute refractory rejection, and so on. Retransplantation is the only hope for these patients, the possibility of which is not negligible. The financial problem is also very large burden to OLT and the cost ranges from $135,000 to $238,000, which is twice of heart transplant and six times of kidney transplant. In our country the biggest barrier to starting OLT is social and medical agreement of brain death which seems hopefully coming close to resolution through persistent public discussion. Much more vigorous efforts should be made for the establishment of more efficient organ procurement system including donor card registration.


Initiator-Loaded Gold Nanocages as a Light-Induced Free-Radical Generator for Cancer Therapy.
Tumor hypoxia greatly suppresses the therapeutic efficacy of photodynamic therapy (PDT), mainly because the generation of toxic reactive oxygen species (ROS) in PDT is highly oxygen-dependent. In contrast to ROS, the generation of oxygen-irrelevant free radicals is oxygen-independent. A new therapeutic strategy based on the light-induced generation of free radicals for cancer therapy is reported. Initiator-loaded gold nanocages (AuNCs) as the free-radical generator were synthesized. Under near-infrared light (NIR) irradiation, the plasmonic heating effect of AuNCs can induce the decomposition of the initiator to generate alkyl radicals (R. ), which can elevate oxidative-stress (OS) and cause DNA damages in cancer cells, and finally lead to apoptotic cell death under different oxygen tensions. As a proof of concept, this research opens up a new field to use various free radicals for cancer therapy.


[Erratum: [Acute Sensory Neuropathies and Acute Autonomic Neuropathies]].
Koike H, "[Acute Sensory Neuropathies and Acute Autonomic Neuropathies]," in Brain Nerve. 2015 Nov; 67(11):1377-87. There was a typo in the abstract. Original: "Guillain-Barr?," Corrected: "Guillain-Barré." The online version of this article has been corrected.


Reference-frame-independent, measurement-device-independent quantum key distribution using fewer quantum states.
Reference-frame-independent quantum key distribution (RFI-QKD) provides a practical way to generate secret keys between two remote parties without sharing common reference frames. On the other hand, measurement-device-independent QKD (MDI-QKD) offers a high level of security, as it is immune to all quantum hacking attempts to measurement devices. The combination of these two QKD protocols, i.e., RFI-MDI-QKD, is one of the most fascinating QKD protocols, since it holds advantages of both practicality and security. For further practicality of RFI-MDI-QKD, it is beneficial to reduce the implementation complexity. Here, we show that RFI-MDI-QKD can be implemented using fewer quantum states than those of its original proposal. We find that, in principle, the number of quantum states for one of the parties can be reduced from six to three without compromising security. Compared to conventional RFI-MDI-QKD where both parties transmit six quantum states, it significantly simplifies the implementation of the QKD protocol. We also verify the feasibility of the scheme with a proof-of-principle experiment.


Navigating the Myriad of von Willebrand Factor Assays.
von Willebrand factor (VWF) represents a large and complex adhesive plasma protein whose main function is to provide a bridge between blood platelets and damaged endothelium, and thus facilitate primary hemostasis. VWF also binds to FVIII, preventing early proteolysis, and delivers this cargo to sites of vascular injury, thereby promoting clot formation and secondary hemostasis. An absence, deficiency, or defect in VWF can lead to a bleeding diathesis called von Willebrand disease (VWD), considered the most common inherited bleeding disorder. Contemporary laboratory assays used in VWD diagnosis/exclusion comprise a myriad of assays that identify the quantity (level) of VWF, as well as the multitude of VWF activities. These may use the following test abbreviations: VWF:Ag, VWF:RCo, VWF:CB, VWF:GPIbR, VWF:GPIbM, VWF:FVIIB, VWF:Ab. The current review explains what these assays are, as well as their place in VWD diagnostics.


Assessing volumetric changes in abdominal aortic aneurysms following endovascular repair.
Volumetric changes in the aneurysm sac were evaluated following endovascular aortic repair (EVAR) in intact abdominal aortic aneurysm (AAA) patients who underwent EVAR. Fifty-two patients, who underwent EVAR from 2015 to 2019, were analysed retrospectively. A total of 158 computed tomography angiography scans was examined by performing reconsctructive volumetric calculations. Total aneurysm volume (TAV), patent lumen volume (PLV) and thrombuscoated aneurysm wall volume (TCAWV) were calculated. The results obtained at six, 12 and 24 months postoperatively were compared with those of the pre-operative period. Mean TAV had regressed 7% by the sixth month (p = 0.1), 27% by the 12th month (p = 0.0003) and 19% by the 24th month (p = 0.0008). Mean TCAWV had increased 2% by the sixth month (p = 0.3), and regressed 26% by the 12th month (p = 0.3) and 14% by the 24th month (p = 0.8). Mean PLV had regressed by 20% by the sixth month (p = 0.008), 29% by the 12th month (p = 0.0002) and 26% by the 24th month (p = 0.0006). For each individual proximal, middle and distal measurement, regression was observed at six and 12 months; however, an increase was observed at 24 months compared to the previous follow ups. The expansion measurements of TAV in the 24th month support the doubts on the medium- to long-term results of EVAR. The largest regression in the aneurysm sac was observed in the distal portion, then in the proximal portion, and the least regression was observed in the middle section.


Association between neighborhood disadvantage and children's oral health outcomes in urban families in the Chicago area.
The prevalence of childhood caries in urban Chicago, compared with national and state data, indicates that neighborhood context influences oral health. Our objective was to delineate the influence of a child's neighborhood on oral health outcomes that are predictive of caries (toothbrushing frequency and plaque levels). Our study population represents urban, Medicaid-enrolled families in the metropolitan Chicago area. Data were obtained from a cohort of participants (child-parent dyads) who participated in the Coordinated Oral Health Promotion (CO-OP) trial at 12 months of study participation (N = 362). Oral health outcomes included toothbrushing frequency and plaque levels. Participants' neighborhood resource levels were measured by the Area Deprivation Index (ADI). Linear and logistic regression models were used to measure the influence of ADI on plaque scores and toothbrushing frequency, respectively. Data from 362 child-parent dyads were analyzed. The mean child age was 33.6 months (SD 6.8). The majority of children were reported to brush at least twice daily (n = 228, 63%), but the mean plaque score was 1.9 (SD 0.7), classified as "poor." In covariate-adjusted analyses, ADI was not associated with brushing frequency (0.94, 95% CI 0.84-1.06). ADI was associated with plaque scores (0.05, 95% CI 0.01-0.09, p value = 0.007). Findings support the hypothesis that neighborhood-level factors influence children's plaque levels. Because excessive plaque places a child at high risk for cavities, we recommend the inclusion of neighborhood context in interventions and policies to reduce children's oral health disparities. Existing programs and clinics that serve disadvantaged communities are well-positioned to support caregivers of young children in maintaining recommended oral health behaviors.


Academic Peer Detailing-The Preparation and Experience of Detailers Involved in a Project to Disseminate a Comparative Effectiveness Module.
Academic detailing uses communication skills, relationship building, and feedback to facilitate behavior change. This report, part of a larger initiative to disseminate evidence summaries of systematic reviews, demonstrates the feasibility of disseminating a comparative effectiveness module to physicians using peer detailers and examines the development of faculty for this process. We describe planning and implementation of a train-the-detailer session, detailer reactions to the process, and results of the dissemination project. We recruited 10 experienced primary care clinical faculties in Family and Social Medicine at the Albert Einstein College of Medicine. Detailers attended a 90-minute train-the-detailer session and detailed 150 practitioners at community practices. We evaluated the experiences of the learners and detailers with questionnaires, a focus group, and individual interviews of the detailers. The experiences of detailing in different contexts were uniformly positive. Learners felt the materials were valuable, and that they would implement them or already had implemented them. In the postsurvey completed by 65 of the 150 detailed learners, 97% percent stated that they changed their practice or had already incorporated the practice change before the detailing. All detailers reported a change in their own practice. Detailers found the teaching materials and detailers' guide helpful. Some initially expressed a concern about not knowing enough, which lessened with detailing experience. Peer detailing seems doable and well received, especially with the availability of high quality, previously prepared, and tested evidence-based content and materials. Detailers were easily recruited and trained to apply their teaching skills in this new format. The amount of time spent in training sessions on detailing training as opposed to content mastery can be adjusted depending on faculty needs.


Glacier foreland insect uptake synthetic compounds: an emerging environmental concern.
Pesticides, synthetic fragrances and polycyclic aromatic hydrocarbons contaminated two glacier-fed streams (Amola, Mandrone) and one spring (Grostè) in the Italian Alps. Ten compounds (chlorpyrifos (CPY), chlorpyrifos-methyl (CPY-m), galaxolide (HHCB), tonalide (AHTN), fluorene (Flu), phenanthrene (Phen), anthracene (Ant), fluoranthene (Fl), pyrene (Pyr), benzo[a]anthracene (BaA)) accumulated in aquatic larvae of chironomids (Diamesa steinboecki, D. latitarsis, D. bertrami, D. tonsa, D. zernyi, Pseudokiefferiella parva, Orthocladiinae) and tipulids. Their tissue concentrations (detected by gas chromatography coupled with mass spectrometry) ranged from 1.1 ± 0.1 ng/g d.w. (= dry weight) (CPY-m in D. tonsa from Amola) to 68.0 ± 9.1 ng/g d.w. (Pyr in D. steinboecki from Mandrone). HHCB, AHTN, and CPY, with one exception, were accumulated by all aquatic insects. Six compounds (CPY, CPY-m, HHCB, AHTN, Fl, Pyr) also contaminated carabids (Nebria germarii, N. castanea, N. jockischii) predating adults of merolimnic insects. Their tissue concentrations ranged from 1.1 ± 0.3 ng/g d.w. (CPY-m in N. germarii from Mandrone) to 84.6 ± 0.3 ng/g d.w. (HHCB in N. castanea from Grostè). HHCB and AHTN were accumulated by all Nebria species. Intersite and interspecies differences were observed, which might be attributed to different environmental contamination levels. There was a stronger similarity between species from the same site than among the same species from different sites, suggesting that uptake is not species specific. At all sites, the concentration of xenobiotics was higher in larvae than in water and comparable or higher in carabids than in larvae from the same site, suggesting trophic transfer by emerging aquatic insects to their riparian predators.


[Bacteriologic and serologic diagnosis of enteral infections].
Infections of the gastrointestinal tract still are numerous, ranging on the second place after infections of the respiratory tract. Some of them show quite severe or prolonged course. In contrast to other infections, especially those of the urinary tract, laboratory diagnostic of enteritis is only scarcely ordered. During the last ten years new methods and knowledge of etiologic germs like Campylobacter, Yersinia, various types of E. coli, Clostridium difficile, Rotavirus, Adenovirus, Giardia, Blastomyces and Cryptosporidia have been accumulated. A better etiologic diagnosis of these infections should enable the clinician to start a more precise and therefore more effective therapy.


Luminescent (N^C^C) Gold(III) Complexes: Stabilized Gold(III) Fluorides.
We report the design, synthesis, and application of a (N^C^C)-ligand framework able to stabilize highly electron-deprived gold(III) species. This novel platform enabled the preparation of C(sp(2))-gold(III) fluorides for the first time in monomeric, easy-to-handle, bench-stable form by a Cl/F ligand-exchange reaction. Devoid of oxidative conditions or stoichiometric use of toxic Hg salts, this method was applied to the preparation of multiple [C(sp(2))-Au(III)-F] complexes, which were used as mechanistic probes for the study of the unique properties and intrinsic reactivity of Au-F bonds. The improved photophysical properties of [(N^C^C)Au(III)] complexes compared to classical pincer (C^N^C)-Au systems paves the way for the design of new late-transition-metal-based OLEDs.


Biofilm structures (EPS and bacterial communities) in drinking water distribution systems are conditioned by hydraulics and influence discolouration.
High-quality drinking water from treatment works is degraded during transport to customer taps through the Drinking Water Distribution System (DWDS). Interactions occurring at the pipe wall-water interface are central to this degradation and are often dominated by complex microbial biofilms that are not well understood. This study uses novel application of confocal microscopy techniques to quantify the composition of extracellular polymeric substances (EPS) and cells of DWDS biofilms together with concurrent evaluation of the bacterial community. An internationally unique, full-scale, experimental DWDS facility was used to investigate the impact of three different hydraulic patterns upon biofilms and subsequently assess their response to increases in shear stress, linking biofilms to water quality impacts such as discolouration. Greater flow variation during growth was associated with increased cell quantity but was inversely related to EPS-to-cell volume ratios and bacterial diversity. Discolouration was caused and EPS was mobilised during flushing of all conditions. Ultimately, biofilms developed under low-varied flow conditions had lowest amounts of biomass, the greatest EPS volumes per cell and the lowest discolouration response. This research shows that the interactions between hydraulics and biofilm physical and community structures are complex but critical to managing biofilms within ageing DWDS infrastructure to limit water quality degradation and protect public health.


micro-Acetato-O:O'-bis{[bis(salicylidene)ethylenediaminato]manganese(III)} perchlorate.
In the title complex, [Mn(2)(C(16)H(14)N(2)O(2))(2)(C(2)H(3)O(2))]ClO(4), two [Mn(salen)] moieties [salen is bis(salicylidene)ethylenediamine] are connected through a micro-acetate bridge in a syn-anti fashion. The Mn.Mn distance is 5.365 (1) A.


Prediction of cross-recognition of peptide-HLA A2 by Melan-A-specific cytotoxic T lymphocytes using three-dimensional quantitative structure-activity relationships.
The cross-recognition of peptides by cytotoxic T lymphocytes is a key element in immunology and in particular in peptide based immunotherapy. Here we develop three-dimensional (3D) quantitative structure-activity relationships (QSARs) to predict cross-recognition by Melan-A-specific cytotoxic T lymphocytes of peptides bound to HLA A*0201 (hereafter referred to as HLA A2). First, we predict the structure of a set of self- and pathogen-derived peptides bound to HLA A2 using a previously developed ab initio structure prediction approach [Fagerberg et al., J. Mol. Biol., 521-46 (2006)]. Second, shape and electrostatic energy calculations are performed on a 3D grid to produce similarity matrices which are combined with a genetic neural network method [So et al., J. Med. Chem., 4347-59 (1997)] to generate 3D-QSAR models. The models are extensively validated using several different approaches. During the model generation, the leave-one-out cross-validated correlation coefficient (q (2)) is used as the fitness criterion and all obtained models are evaluated based on their q (2) values. Moreover, the best model obtained for a partitioned data set is evaluated by its correlation coefficient (r = 0.92 for the external test set). The physical relevance of all models is tested using a functional dependence analysis and the robustness of the models obtained for the entire data set is confirmed using y-randomization. Finally, the validated models are tested for their utility in the setting of rational peptide design: their ability to discriminate between peptides that only contain side chain substitutions in a single secondary anchor position is evaluated. In addition, the predicted cross-recognition of the mono-substituted peptides is confirmed experimentally in chromium-release assays. These results underline the utility of 3D-QSARs in peptide mimetic design and suggest that the properties of the unbound epitope are sufficient to capture most of the information to determine the cross-recognition.


A natural meliorate: revolutionary tissue engineering in endodontics.
Platelet-Rich Fibrin (PRF) was first described by Choukroun et al., (2001). It has been referred to as a second-generation platelet concentrate, which has been shown to have several advantages over traditionally prepared platelet-rich plasma. PRF has a physiologic architecture that is very favourable to the healing process, obtained due to the slow polymerization process. The development of platelet concentrate as bioactive surgical additives that are applied locally to promote wound healing stems from the use of fibrin adhesive. Developments in the field of tissue engineering have made the generation of artificial substitutes in several areas of medicine. Various clinical applications in endodontics include Periapical surgeries, Revascularisationprocedures, Regenerative pulpotomy, Perforation repair. This article aims to discuss the various applications of PRF in the field of Endodontics with few case reports.


Relationship between ease of swallowing and deglutition-related muscle activity in various postures.
The purpose of this study was to investigate the relationship between the ease of swallowing and the deglutition-related muscle activity in various body and head postures by surface electromyography (EMG). Bipolar surface electrodes were placed on the right suprahyoid and infrahyoid muscles of nine healthy adults (19-28 years) while swallowing jelly. Ten postures per subject were examined: five body angulations (0 degrees [supine], 30 degrees, 60 degrees, 90 degrees [upright] and 120 degrees from the horizontal) and two head positions (chin-up and chin-down). The duration and amplitude of suprahyoid and infrahyoid muscle activity were measured by an electromyograph, and the ease of swallowing was subjectively determined by using a rating scale (0 = difficult to swallow, 10 = easy to swallow). The group-average duration and amplitude of muscle activity and the group-average rating scales mostly showed insignificant changes with the body angulations independent of the head positions. Interestingly, the duration and amplitude of muscle activity during swallowing were negatively correlated with the rating scales, indicating that a shorter duration and smaller activity of muscle activity corresponds to easier swallowing. Consequently, the duration and amplitude of suprahyoid and infrahyoid muscle activity measured by surface EMG would be a useful indicator of the easy-to-swallow performance.


Development of a Medium Density Combined-Species SNP Array for Pacific and European Oysters (Crassostrea gigas and Ostrea edulis).
SNP arrays are enabling tools for high-resolution studies of the genetic basis of complex traits in farmed and wild animals. Oysters are of critical importance in many regions from both an ecological and economic perspective, and oyster aquaculture forms a key component of global food security. The aim of our study was to design a combined-species, medium density SNP array for Pacific oyster (Crassostrea gigas) and European flat oyster (Ostrea edulis), and to test the performance of this array on farmed and wild populations from multiple locations, with a focus on European populations. SNP discovery was carried out by whole-genome sequencing (WGS) of pooled genomic DNA samples from eight C. gigas populations, and restriction site-associated DNA sequencing (RAD-Seq) of 11 geographically diverse O. edulis populations. Nearly 12 million candidate SNPs were discovered and filtered based on several criteria, including preference for SNPs segregating in multiple populations and SNPs with monomorphic flanking regions. An Affymetrix Axiom Custom Array was created and tested on a diverse set of samples (n = 219) showing ∼27 K high quality SNPs for C. gigas and ∼11 K high quality SNPs for O. edulis segregating in these populations. A high proportion of SNPs were segregating in each of the populations, and the array was used to detect population structure and levels of linkage disequilibrium (LD). Further testing of the array on three C. gigas nuclear families (n = 165) revealed that the array can be used to clearly distinguish between both families based on identity-by-state (IBS) clustering parental assignment software. This medium density, combined-species array will be publicly available through Affymetrix, and will be applied for genome-wide association and evolutionary genetic studies, and for genomic selection in oyster breeding programs.


No surge in illicit cigarettes after implementation of menthol ban in Nova Scotia.
In May 2015, the Canadian province of Nova Scotia became the first jurisdiction in the world to ban menthol cigarettes specifically. The tobacco industry warned that 'the primary effect of this law will be to increase the illegal tobacco market in Nova Scotia'. This is the first attempt to examine the impact of the menthol ban on trends in illicit cigarettes. Data on the number of illicit cigarettes seized in Nova Scotia covering the period from 2007/2008 to 2017/2018 was obtained from the Provincial Tax Commission. Data from before and after the ban are compared. According to the local authorities, while the enforcement efforts in Nova Scotia have not declined, the number of seized illicit cigarettes declined significantly, from >60 000 cartons in 2007/2008 to <10 000 cartons in 2017/2018. Since the menthol ban, the seizure volume remained stable, with no statistically significant difference in the number of cigarettes seized before and after the menthol ban (t=-0.71, p=0.55). There were only a few small seizures of menthol cigarettes in the year following the ban, after which there have been no further seizures of menthol cigarettes. Contrary to the tobacco industry's assertions, there was no surge in illicit cigarettes after the 2015 ban on menthol cigarette sales in Nova Scotia. Credible, industry-independent evidence on illicit cigarette trade is desperately needed to support the implementation of tobacco control policies.


miRNA Stability in Frozen Plasma Samples.
MicroRNAs (miRNAs) represent a family of small non-coding ribonucleic acids that post-transcriptionally inhibits the expression of their target messenger RNAs (mRNAs), thereby acting as general gene repressors. In this study we examined the relative quantity and stability of miRNA subjected to a long period of freezing; we compared the stability of eight miRNAs in the plasma of five human healthy controls before freezing and after six and 12 months of storage at -80 °C. In addition, we examined the plasma frozen for 14 years and the amount of miRNA still available. Using a Life Technologies protocol to amplify and quantify plasma miRNAs from EDTA (Ethylene Diamine Tetraacetic Acid)-treated blood, we analyzed the stability of eight miRNAs, (miR-125b-5p, miR-425-5p, miR-200b-5p, miR-200c-3p, miR-579-3p, miR-212-3p, miR-126-3p, and miR-21-5p). The miRNAs analyzed showed a high stability and long frozen half-life.


Working with practitioners to develop training in peri-natal loss and bereavement: Evaluating three workshops.
Peri-natal loss is as profound as any other bereavement [Chambers, H.M., Chan, F.J., 2000. Support for women/families after peri-natal death. (Cochrane Review). Issue 1. The Cochrane Library, Oxford, Update Software], is commonplace, and its traumatic potential has long been overlooked by clinicians and researchers [Spechard, 1997. Traumatic death in pregnancy: the significance of meaning and attachment. In: Figley, C.R., Bride, B., Mazza, N., (Eds.), Death and Trauma: The Traumatology of Grieving. Taylor and Francis, London, 1997, pp. 67-98]. Previous miscarriage, stillbirth or neonatal death is implicated in post-natal depression and behaviour management difficulties after the birth of subsequent children. The involvement of the health visitor in supporting grieving parents may be crucial to medium and long-term family health [Hill, C., 1997. Evaluating the quality of after death care. Nursing Standard 12(8), 38-39]. However, service provision for such families appears to be inconsistent and depends on the skills, confidence and time constraints of individual practitioners, with little in the way of guidance and support in this sensitive area of care [Dent, A., Condon, L., Blair, P., Flemming, P., 1996. A study of bereavement care after a sudden and unexpected death. Archives of disease in childhood, 74, 552-526]. This paper outlines the development and evaluation of a series of workshops around peri-natal loss initially offered to health visitors in North Staffordshire (UK), and then expanded to incorporate midwives. The authors formally evaluated the three workshops (and their impact) retrospectively, and implemented the findings to further develop the workshops, thus ensuring relevance to professional practice. The rationale behind the introduction of the workshops and the contents are introduced; approaches to the evaluation process described; presentation of the findings offered; followed by a discussion of the key issues.


Neck muscle fatigue affects postural control in man.
We hypothesised that, since anomalous neck proprioceptive input can produce perturbing effects on posture, neck muscle fatigue could alter body balance control through a mechanism connected to fatigue-induced afferent inflow. Eighteen normal subjects underwent fatiguing contractions of head extensor muscles. Sway during quiet stance was recorded by a dynamometric platform, both prior to and after fatigue and recovery, with eyes open and eyes closed. After each trial, subjects were asked to rate their postural control. Fatigue was induced by having subjects stand upright and exert a force corresponding to about 35% of maximal voluntary effort against a device exerting a head-flexor torque. The first fatiguing period lasted 5 min (F1). After a 5-min recovery period (R1), a second period of fatiguing contraction (F2) and a second period of recovery (R2) followed. Surface EMG activity from dorsal neck muscles was recorded during the contractions and quiet stance trials. EMG median frequency progressively decreased and EMG amplitude progressively increased during fatiguing contractions, demonstrating that muscle fatigue occurred. After F1, subjects swayed to a larger extent compared with control conditions, recovering after R1. Similar findings were obtained after F2 and after R2. Although such behaviour was detectable under both visual conditions, the effects of fatigue reached significance only without vision. Subjective scores of postural control diminished when sway increased, but diminished more, for equal body sway, after fatigue and recovery. Contractions of the same duration, but not inducing EMG signs of fatigue, had much less influence on body sway or subjective scoring. We argue that neck muscle fatigue affects mechanisms of postural control by producing abnormal sensory input to the CNS and a lasting sense of instability. Vision is able to overcome the disturbing effects connected with neck muscle fatigue.


Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a case-control study.
Findings from longitudinal follow-up studies in patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) have shown that most patients will eventually develop the synucleinopathies Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Neuroinflammation in the form of microglial activation is present in synucleinopathies and is a potential therapeutic target to halt or delay the neurodegenerative process. We aimed to investigate whether neuroinflammation is present in patients with IRBD and its possible relation to nigrostriatal dopamine function. In this prospective, case-control, PET study, patients with IRBD and no clinical evidence of parkinsonism and cognitive impairment were recruited from tertiary sleep centres in Spain (Barcelona) and Denmark (Aarhus). We included patients with polysomnography-confirmed IRBD according to established criteria. Healthy controls were recruited through newspaper advertisements. Controls had no motor or cognitive complaints, a normal neurological examination, and a mean group age similar to the IRBD group. In patients with IRBD, we assessed microglial activation in the substantia nigra, putamen, and caudate with 11C-PK11195 PET, and dopaminergic axon terminal function in the putamen and caudate with 18F-DOPA PET. Controls underwent either 11C-PK11195 PET or 18F-DOPA PET. We compared 18F-DOPA uptake and 11C-PK11195 binding potential between groups with an unpaired, two-tailed Student's t test. Between March 23, 2015, and Oct 19, 2016, we recruited 20 consecutive patients with IRBD and 19 healthy controls. 11C-PK11195 binding was increased on the left side of the substantia nigra in patients with IRBD compared with controls (Student's t test, mean difference 0·153 [95% CI 0·055 to 0·250], p=0·003), but not on the right side (0·121 [-0·007 to 0·250], p=0·064). 11C-PK11195 binding was not significantly increased in the putamen and caudate of patients with IRBD. 18F-DOPA uptake was reduced in IRBD in the left putamen (-0·0032 [-0·0044 to -0·0021], p<0·0001) and right putamen (-0·0032 [-0·0044 to -0·0020], p<0·0001), but not in the caudate. In patients with IRBD, increased microglial activation was detected by PET in the substantia nigra along with reduced dopaminergic function in the putamen. Further studies, including more participants than were in this study and longitudinal follow-up, are needed to support our findings and evaluate whether the presence of activated microglia in patients with IRBD represents a marker of short-term conversion to a clinically defined synucleinopathy in the near future. Danish Council for Independent Research, Instituto de Salud Carlos III (Spain).


Bridging functional nanocomposites to robust macroscale devices.
At the intersection of the outwardly disparate fields of nanoparticle science and three-dimensional printing lies the promise of revolutionary new "nanocomposite" materials. Emergent phenomena deriving from the nanoscale constituents pave the way for a new class of transformative materials with encoded functionality amplified by new couplings between electrical, optical, transport, and mechanical properties. We provide an overview of key scientific advances that empower the development of such materials: nanoparticle synthesis and assembly, multiscale assembly and patterning, and mechanical characterization to assess stability. The focus is on recent illustrations of approaches that bridge these fields, facilitate the design of ordered nanocomposites, and offer clear pathways to device integration. We conclude by highlighting the remaining scientific challenges, including the critical need for assembly-compatible particle-fluid systems that ultimately yield mechanically robust materials. The role of domain boundaries and/or defects emerges as an important open question to address, with recent advances in fabrication setting the stage for future work in this area.


The identification and development of specific monoclonal antibodies to squamous cell carcinoma.
We have developed specific monoclonal antibodies to immunogenic glycoproteins expressed selectively on the cell membrane of squamous cell malignancies. These proteins serve to act as tumor markers that characterize this malignancy; there has be no evidence of cross reactivity to normal epithelial cells. Analysis of patterns of expression reveals that those membrane proteins identified by monoclonals AD7 and 5C6 appear early in cellular transformation to malignancy. At such a time, immunohistochemical recognition is seen in the presence of genotypic alterations, yet phenotypic changes may not be apparent. Of additional interest is that these monoclonal antibodies exhibit strong ADCC allowing the tumor proteins to not only serve as a marker of malignancy but as a target for therapeutic destruction.


Explanatory model for the interaction of factors in the caries process.
The interaction of factors in the caries process has recently been discussed in a number of articles. Based on this, a new explanatory model has been constructed, consisting of an equilateral triangle with one of the apices on a horizontal line, along which dietary and oral hygiene habits are scaled. The triangle represents the total area of interaction. A horizontal line of resistance cuts off a lower part corresponding to the area within which caries does not occur. Through planogeometric calculations the remaining part of the triangle can be divided into areas, approximately corresponding to the relative caries values of various combinations of dietary and oral hygiene habits. The model has proved to be a useful instrument for demonstrating and creating an understanding of interactive processes among various groups of dental health personnel. The example presented is based on a pilot study of 55 4-year-old children in Malmö.


YouTube as a Source of Patient Information on Oral Manifestations of COVID-19: A Cross-Sectional Evaluation of Its Utility, Dependability, and Content.
Objectives This study aims to assess the quality of the most viewed videos on the YouTube website describing the oral manifestations of COVID-19 and appraise the medical information in the content. Materials and methods The top 200 most-viewed videos on YouTube using the keywords "COVID-19 oral manifestation," "oral symptoms of COVID-19," "oral lesions of COVID-19," "coronavirus and oral findings," and "dental manifestation of COVID-19" were analyzed. Two independent reviewers classified the English-language videos as useful, misleading, or personal views and identified the source of the videos. Reliability was calculated on a 5-point scale adapted from the DISCERN tool. The global quality scale (GQS) was used to determine the quality of the videos. In addition, the completeness of the information regarding the clinical presentation, pathogenesis, diagnostic tests, and treatment of COVID-19 oral manifestations was evaluated. Results After excluding non-English and irrelevant videos, 55 videos were analyzed. Thirty-two videos were classified as useful. Independent users uploaded the most videos (19, 51%). The mean reliability and GQS scores for useful videos were (3.24+1.4) and (2+0.75), respectively. The GQS score was significantly related to the reliability score (p<0.01). Videos scoring high in GQS also show high-reliability scores. In addition, videos with high GQS scores showed more comprehensive content, scoring >9 in the content aspect. The COVID tongue was the most discussed topic, followed by oral ulcers and oral mucormycosis. Conclusions Most of the YouTube videos were useful and had moderate quality. However, they show low reliability and lack comprehensive medical information on the topic. Healthcare providers should play a more active role in the educational information given on social media (SM) during global disease outbreaks.


Whirly1 enhances tolerance to chilling stress in tomato via protection of photosystem II and regulation of starch degradation.
In plants, the chilling response involves decreased photosynthetic capacity and increased starch accumulation in chloroplasts. However, the mechanisms that modulate these processes remain unclear. We found that the SlWHY1 gene is significantly induced by chilling stress (4°C) in tomato. Three SlWHY1 overexpression (OE) lines grew better than the wild type (WT) under chilling stress; the OE plants retained intact photosynthetic grana lamellae and showed enhanced hydrolysis of starch. By contrast, RNAi lines that inhibited SlWHY1 were more affected than the corresponding WT cultivar. Their grana lamellae were damaged and starch content increased. The psbA gene encodes the key photosystem II (PSII) protein D1. We show that SlWHY1 binds to the upstream region (A/GTTACCCT/A) of SlpsbA and enhances the de novo synthesis of D1 in chloroplasts. Additionally, SlWHY1 regulates the expression of the starch-degrading enzyme α-amylase (SlAMY3-L) and the starch synthesis-related enzyme isoamylase gene (SlISA2) in the nucleus, thus modulating the starch content in chloroplasts. We demonstrate that SlWHY1 enhances the resistance of tomato to chilling stress by maintaining the function of PSII and degrading starch. Thus, overexpression of WHY1 may be an effective strategy for enhancing resistance to chilling stress of chilling-sensitive crops in agricultural production.


[The role of coronary intervention to coronary artery stenosis in Kawasaki disease].
One characteristic of coronary artery lesions seen in the acute phase of children with Kawasaki disease is the formation of giant coronary aneurysms, with high-grade stenosis lesion causing calcification both proximal and distal to the coronary aneurysm as patients reach school age. In balloon angioplasty the usual treatment for stenosis lesions, the presence of calcification makes expansion difficult, and bypass surgery is less than ideal in terms of long-term patency. As a result, these patients are usually given drug therapy and told to limit physical activity. The use of rotational atherectomy enables safe catheterization in these Kawasaki patients in lesions where balloon expansion cannot be obtained by balloon angioplasty. Efficacy is maintained over the long term, as well as during development as patients reach school age. It is now known that the presence of Kawasaki disease-like coronary aneurysms is a predictor of in-hospital outcomes in early-onset(patients under 40 years of age) acute coronary syndrome, which suggests the importance of monitoring children with Kawasaki disease coronary aneurysms into adulthood.


Comprehensive Analyses of Glucose Metabolism in Glioma Reveal the Glioma-Promoting Effect of GALM.
Glioma is the most common tumor with the worst prognosis in the central nervous system. Current studies showed that glucose metabolism could affect the malignant progression of tumors. However, the study on the dysregulation of glucose metabolism in glioma is still limited. Herein, we firstly screened 48 differentially expressed glucose metabolism-related genes (DE-GMGs) by comparing glioblastomas to low-grade gliomas. Then a glucose metabolism-related gene (GMG)-based model (PC, lactate dehydrogenase A (LDHA), glucuronidase beta (GUSB), galactosidase beta 1 (GLB1), galactose mutarotase (GALM), or fructose-bisphosphatase 1 (FBP1)) was constructed by a protein-protein interaction (PPI) network and Lasso regression. Thereinto, the high-risk group encountered a worse prognosis than the low-risk group, and the M2 macrophage was positively relevant to the risk score. Various classical tumor-related functions were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Since protein GALM was rarely studied in glioma, we detected high expression of GALM by western blot and immunohistochemistry in glioma tissues. And experiments in vitro showed that GALM could promote the epithelial-to-mesenchymal transition (EMT) process of glioma cells and could be regulated by TNFAIP3 in glioma cells. Overall, our study revealed the critical role of glucose metabolism in the prognosis of patients with glioma. Furthermore, we demonstrated that GALM was significantly related to the malignancy of glioma and could promote glioma cells' EMT process.


MUDD mapping: an interactive teaching-learning strategy.
MUDD, an acronym for my understanding through dialogue and debate, is a teaching-learning strategy that assists learners in understanding a particular topic. MUDD mapping can be used as an independent activity carried out by learners in a study group or by a faculty member to conduct an assessment of how well learners are grasping the subject. The authors describe how MUDD mapping was used and illustrates how faculty can facilitate its application in a teaching-learning activity.


Direct Hydroxylation of Benzene to Phenol by Cytochrome P450BM3 Triggered by Amino Acid Derivatives.
The selective hydroxylation of benzene to phenol, without the formation of side products resulting from overoxidation, is catalyzed by cytochrome P450BM3 with the assistance of amino acid derivatives as decoy molecules. The catalytic turnover rate and the total turnover number reached 259 min-1 P450BM3-1 and 40 200 P450BM3-1 when N-heptyl-l-proline modified with l-phenylalanine (C7-l-Pro-l-Phe) was used as the decoy molecule. This work shows that amino acid derivatives with a totally different structure from fatty acids can be used as decoy molecules for aromatic hydroxylation by wild-type P450BM3. This method for non-native substrate hydroxylation by wild-type P450BM3 has the potential to expand the utility of P450BM3 for biotransformations.


Increased endothelin-1 production in fibroblasts derived from patients with systemic sclerosis.
To determine whether fibroblasts from patients with systemic sclerosis (SSc) produce excessive amounts of endothelin-1 (ET-1), which is recognised as having vasoconstrictive properties and as having a potent mitogenic effect on fibroblasts. Dermal fibroblasts were removed from 11 patients with SSc and from five normal controls (NC). The assay of ET-1 protein was measured by an ELISA that used two anti-ET-1 antibodies. The gene expression of prepro ET-1 mRNA was evaluated by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. Levels of ET-1 protein were significantly higher in SSc fibroblast cultures than in those of normal fibroblasts (p < 0.01). The expression of prepro ET-1 mRNA was also higher in SSc fibroblasts than in normal fibroblasts. The addition of interleukin-1 beta (IL-1 beta) increased the production of ET-1 by fibroblasts. The findings indicate that the overproduction of ET-1 is a novel abnormal function in SSc fibroblasts, and that ET-1 induced by fibroblasts may play a role in the fibrosis and Raynaud's phenomenon of SSc.


Right Ventricular Myocardial Ischemia with Arrhythmia in an Asphyxiated Newborn.
Background Infant and neonatal myocardial infarction (MI) has been described in association with congenital heart disease, coronary artery abnormalities, myocarditis, and tumors. MI in the perinatal period in a structurally normal heart and with ventricular arrhythmia as a presenting feature has not been thoroughly described. Published case reports describe treatment methods extrapolated from adult MI. However, due to the rare occurrence, the most appropriate acute treatment for both MI and ventricular arrhythmia in newborn infants remains unknown. Case A male term infant with perinatal asphyxia and need for extensive cardiopulmonary resuscitation at birth had ventricular tachyarrhythmia and ST-elevations on electrocardiogram. Four hours after birth, he died from cardiogenic failure. A thrombus at the right coronary artery was found on autopsy. Conclusion MI in the perinatal period in a structurally normal heart is very rare and mortality is high. Although acute treatments extrapolated from adult MI has been described to result in favorable outcomes in newborn infants, guidelines are lacking on how to manage acute MI and associated ventricular arrhythmia.


Shoulder pain after stroke: a review of the evidence base to inform the development of an integrated care pathway.
Shoulder pain is a common complication of stroke. It can impede rehabilitation and has been associated with poorer outcomes and prolonged hospital stay. This systematic review was undertaken to inform the development of an evidence-based integrated care pathway (ICP) for the management of hemiplegic shoulder pain (HSP). 1) To provide a background understanding of the functional anatomy of the shoulder and its changes following stroke. 2) To review the literature describing incidence and causation of HSP and the evidence for factors contributing to its development. 3) To appraise the evidence for effectiveness of different interventions for HSP. Data sources comprised a computer-aided search of published studies on shoulder pain in stroke or hemiplegia and references to literature used in reviews (total references = 121). Although a complex variety of physical changes are associated with HSP, these broadly divide into 'flaccid' and 'spastic' presentations. Management should vary accordingly; each presentation requiring different approaches to handling, support and intervention. (1) In the flaccid stage, the shoulder is prone to inferior subluxation and vulnerable to soft-tissue damage. The arm should be supported at all times and functional electrical stimulation may reduce subluxation and enhance return of muscle activity. (2) In the spastic stage, movement is often severely limited. Relieving spasticity and maintaining range requires expert handling; overhead exercise pulleys should never be used. Local steroid injections should be avoided unless there is clear evidence of an inflammatory lesion. HSP requires co-ordinated multidisciplinary management to minimize interference with rehabilitation and optimize outcome. Further research is needed to determine effective prophylaxis and document the therapeutic effect of different modalities in the various presentations. Development of an integrated care pathway provides a reasoned approach to management of this complex condition, thus providing a sound basis for prospective evaluation of different interventions in the future.


Predicting bleaching results with computer imaging.
Vital bleaching can be a relatively unpredictable treatment. Photographs of previous cases and cosmetic imaging, although useful, may lead to unrealistic expectations on the part of the patient. The high-tech mystique of computer imaging and viewing one's own teeth has a significant impact on the dental patient. Whether imaged by the dentist or an auxiliary, patients must be aware of alternatives that may exist both before and during treatment. Cosmetic imaging should be used as an adjunct to, not as the prime motivator for, treatment planning in bleaching cases. Excellent communication between the practitioner and patient is the most important factor in assuring positive bleaching results and patient satisfaction.


Carbohydrate-based cancer vaccines: target cancer with sugar bullets.
With the booming development of glycobiology and glycochemistry, more and more structures of tumor-associated carbohydrate antigens (TACAs) are identified. Their broad expression and high specificity in cancer make them important targets to develop cancer vaccines or immunotherapies. However, most of the TACAs are T cell-independent antigens, they cannot elicit a powerful enough immune response to prevent or treat cancer. Immunotolerance and immunosuppression are more easily induced due to their endogenous properties and the declining immunity of the patients. This review summarizes the recent efforts to overcome these obstacles: coupling the carbohydrate antigens to proper carriers such as proteins or some small molecule carriers, and chemically modifying the structures of the TACAs to enhance the immunogenicity of TACAs and break the immunotolerance.


Antiretroviral therapy in drug-naive patients infected with human immunodeficiency virus.
A vast amount of knowledge has accumulated since the discovery of the immunodeficiency diseases caused by human immunodeficiency virus-1 (HIV-1) in the early 1980s. An expert panel of HIV researchers and clinicians produced the first set of treatment guidelines in 1997. Since then, these guidelines have been updated based on available clinical information and supplemented by expert opinion when scientific data were incomplete. The latest version of the HIV treatment guidelines are summarized here, with attention focused on the rationale for treatment of asymptomatic as well as symptomatic individuals, including when and what to start as a first regimen of highly active antiretroviral therapy (HAART). Components of initial and follow-up evaluations are detailed, with attention given to available HIV viral load tests and their use. Because adherence to HAART is critical to immune recovery and stabilization, data on predictors of both good and poor medication compliance, as well as strategies to maximize medication adherence are presented. Lastly, recommendations for the use of HIV genotypic and phenotypic resistance testing in antiretroviral naive patients are presented.


Tension-free vaginal tape (TVT) for treatment of stress urinary incontinence in women with low-pressure urethra.
To assess the results of TVT in patients with urinary stress incontinence, urethral hypermobility, and low-pressure urethra. We retrospectively analysed 265 consecutive women who underwent a TVT procedure for urodynamic stress urinary incontinence over a 31-month period. Women were divided into two groups depending on their preoperative maximum urethral closure pressure (MUCP). Group 1 (61 women with MUCP<or=20 cm H2O) were compared with 204 women (group 2) with a MUCP>20 cm H2O. Subjective and objective outcome data were assessed from routine postoperative visits. Office and hospital records were reviewed to check patients' characteristics, intraoperative findings, and surgical outcomes. Women with low-pressure urethra were older than those with MUCP>20 cm H2O; they were more likely to have had a hysterectomy or anti-incontinence surgery. The mean duration of follow-up was 31 (+/-11) months. Cure rates among patients with low- or normal-pressure urethra were similar (77% and 86%, P=0.70). Nevertheless, the former were more likely to complain of voiding dysfunction. TVT is a highly effective treatment even in women with intrinsic sphincter deficiency.


Exploiting evolutionarily conserved pathways to promote plasticity of human spinal circuits.
Humans evolved from species that walked on all 4 limbs, which means that experiments in quadrupeds can guide and support experiments in humans. This is particularly helpful for neural rehabilitation because the central nervous system is plastic in nature, meaning that activities promoting central nervous system activity can alter subsequent output properties. This is known as neuroplasticity and can be measured as changes in spinal cord excitability through reflexes as a proxy. By targeting evolutionarily conserved pathways that act on similar interneurons within the spinal cord to either increase or decrease excitability, it may be possible to preferentially modulate spinal cord excitability based on a desirable outcome. For example, rhythmic movement reduces spinal cord excitability whereas brief sensory input to cutaneous afferents increases spinal cord excitability. Alterations in spinal cord excitability have been shown to outlast the activity duration, suggesting that neuroplasticity is not transient. This evidence suggests that both rhythmic movement and sensory input can induce acute neuroplasticity of spinal cord excitability. The overall purpose of this dissertation was 2-fold: (i) to provide reviews of how evolutionarily conserved pathways are studied in humans and how they contribute to human rhythmic movement; and (ii) experimentally examine how these conserved pathways, which converge onto similar interneuron circuitry, can be exploited to cause bidirectional changes in spinal cord excitability. Reviews indicate that humans have retained characteristics of quadrupedal locomotion and, in particular, activity of the arms affects the excitability of the legs, and vice versa. Cutaneous input is integrated throughout the body during locomotion, such that cutaneous sensations elicit neuromechanical responses that are nerve-specific and modulated according to the phase of movement. In experiment 1, there was increased spinal cord excitability following patterned stimulation of cutaneous afferents innervating the bottom of the foot. In experiment 2, stimulation to cutaneous afferents innervating both the top and bottom of the foot amplified voluntary plantar- and dorsiflexion. In experiment 3, cervicolumbar connections were exploited to amplify plasticity in spinal cord excitability induced by rhythmic movement. Finally, in experiment 4, there were interactions of rhythmic movement and fatigue, which both reduce spinal cord excitability, with cutaneous stimulation, which increases spinal cord excitability, such that reductions in spinal cord excitability associated with fatigue were mitigated by cutaneous stimulation. Taken together, these experiments suggest that cutaneous stimulation can increase spinal cord excitability, whereas quadrupedal locomotor activity can decrease spinal cord excitability. These conserved pathways can be exploited to intentionally modify spinal cord excitability in a bidirectional fashion, which provides fruitful information for the exploration of rehabilitation and sport performance practices.


Factor V Leiden and prothrombin G20210A mutations and the risk of atherothrombotic events in systemic lupus erythematosus.
Because genetic predisposition to atherothrombosis in systemic lupus erythematosus (SLE) remains to be determined, the most common genetic prothrombotic factors, prothrombin G20210A and factor V Leiden mutations, were studied. Seventy-four SLE patients with vascular ischemia (SLE cases) were studied and stratified into myocardial infarction and/or cerebrovascular accident subgroup (MI/CVA), and coronary heart disease subgroup without overt arterial thrombotic events (CHD). Seventy-one SLE patients without atherothrombosis were investigated as SLE controls. Factor V Leiden was detected in six cases (five in MI/CVA, one in CHD group) and three controls (OR 2.00, 95%CI 0.48-8.32). Two cases (both CHD patients) had prothrombin G20210A mutation vs. three controls (OR 0.63, 95%CI 0.1-3.88). Anticardiolipin antibodies (aCL) were increased in cases vs. controls (39/74 vs. 27/71); however, this was not statistically significant (OR 1.82, 95%CI 0.94-3.52). Neither univariate nor multivariate analysis indicated that investigated mutations are risk factors for atherothrombosis in SLE cases, MI/CVA, or CHD subgroups. Overall, disease activity was the strongest risk factor for atherothrombosis (p=0.0014) in SLE cases. Combination of disease activity+gender was the best predictor of atherothrombotic process (p=0.00045) in this cohort. In MI/CVA subgroup, disease activity was the only predictor (p=0.0058). In CHD patients, the best predictive value was conferred by combination of hypertension+gender+disease activity (p=0.00077). No other investigated risk factor (including aCL) conferred an increased risk individually or potentiated the other risk factors. The results deny the role of investigated mutations in atherothrombosis in SLE, but they underscore the importance of disease activity (i.e., ongoing inflammation) in pathogenesis of atherosclerosis and arterial thrombosis.


Factors associated with local recurrence after skin-sparing mastectomy and immediate breast reconstruction for invasive breast cancer.
To examine the incidence of local recurrence (LR) and factors associated with it in a population of patients who underwent skin-sparing mastectomy (SSM) and immediate reconstruction for invasive carcinoma. The efficacy of SSM has been challenged by concerns about increased risks of LR. A consecutive series of 173 patients (176 cancers) with invasive carcinoma underwent SSM and immediate breast reconstruction (June 1986 to December 1997). Data were analyzed by the Kaplan-Meier method, the log-rank statistic test, and the Cox proportional hazards model. Mean patient age was 47 +/- 9 years (27% were 40 or younger). The AJCC stages were 1 = 43%, 2 = 52%, and 3 = 5%. Thirty percent of tumors were poorly differentiated. With a median follow-up of 73 months, the LR rate was 4.5%. The mean local relapse-free interval was 26 months. Seventy-five percent of patients who presented with LR developed distant metastases and died of disease within a mean of 21 months. On univariate analysis, factors associated with higher LR rate were tumor stage 2 or 3, tumor size larger than 2 cm, node-positive disease, and poor tumor differentiation. Actuarial 1-, 3-, and 5-year overall survival rates were 98%, 94%, and 88%, respectively. On multivariate analysis, factors associated with decreased survival were advanced stage, presence of LR, and absence of hormone therapy. LR was a highly significant predictor of tumor-related death. There is a low incidence of LR after SSM, and it is associated with advanced disease at presentation. LR is an independent risk factor for tumor-related death.


Social support facilitates physical activity by reducing pain.
Objectives The link between social support and physical activity has primarily been examined cross-sectionally, with a focus on the direct association between the two variables. In a distinct body of work, there has been growing interest in the role of social support in reducing pain (emotional and physical). We examined the relationship between social support and physical activity over time. We further examined whether reduced pain mediates the relationship between social support and physical activity. Design Data were drawn from Waves 15, 16, and 17 of the Household Income and Labour Dynamics in Australia survey. Methods Mediation models were used to test our hypotheses in (a) a representative sample of 12,517 people residing in Australia, and (b) a subsample of 927 people with a condition that causes chronic or recurring pain. Results Social support was a weak predictor of subsequent physical activity in both the full sample and the subsample of people with a condition that causes chronic or recurring pain. However, in both samples, mediation analyses demonstrated a significant indirect effect of social support on physical activity through reduced pain. Conclusions One pathway through which social support impacts physical activity is by reducing peoples' pain. Increasing and strengthening peoples' social support networks may confer benefits for their physical activity levels, including among those whose physical activity is limited by pain. Statement of contribution What is already known on this subject? Social support can have a positive effect on health behaviours, including physical activity. There is somewhat inconsistent evidence for a positive direct relationship between social support and physical activity. Pain can be a barrier to physical activity, but may be attenuated by social support. What does this study add? Social support affected physical activity indirectly by reducing peoples' pain. This was true for both the general population and a subsample with a chronic pain condition. Improving peoples' social support networks may confer benefits for their physical activity.


Dynamic contour tonometry: presentation of a new tonometer.
With tonometers currently in use intraocular pressure is indirectly determined by measuring a physical quantity related to a specified deformation of the cornea. We present a new principle of direct, continuous, and transcorneal intraocular pressure measurement, describe its theoretical foundation, and evaluate its application on the basis of an in vitro model. On a living human eye an optimized pressure-sensitive contact surface was determined by performing pressure measurements with differently shaped tonometer heads. Based on these results and on the theoretical model, a Dynamic Contour Tonometer was constructed and validated on eye bank bulbi against a manometric reference pressure. A concave contact surface with a radius of curvature of 10.5 mm creates a distribution of forces between the central contour matching area of the tip and the cornea that equals the forces generated by the internal pressure of the eye. A sensor integrated into the surface having the same contour measures the intraocular pressure closely to the manometric reference pressure in human cadaver eyes. The accuracy of the tonometer appears to be unaffected by variations in corneal properties. Dynamic Contour Tonometry eliminates most of the systematic errors arising from individual changes of corneal properties that adversely influence all types of applanation tonometers. The advantage of measuring the true pressure in combination with the capability of registering dynamic pressure fluctuations discloses new tonometric opportunities to diagnose and classify different types of glaucoma.


Charge carrier dynamics in conducting polymer PEDOT using ab initio molecular dynamics simulations.
As conducting polymers become increasingly important in electronic devices, understanding their charge transport is essential for material and device development. Various semi-empirical approaches have been used to describe temporal charge carrier dynamics in these materials, but there have yet to be any theoretical approaches utilizing ab initio molecular dynamics. In this work, we develop a computational technique based on ab initio Car-Parrinello molecular dynamics to trace charge carrier temporal motion in archetypical conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT). Particularly, we analyze charge dynamics in a single PEDOT chain and in two coupled chains with different degrees of coupling and study the effect of temperature. In our model we first initiate a positively charged polaron (compensated by a negative counterion) at one end of the chain, and subsequently displace the counterion to the other end of the chain and trace polaron dynamics in the system by monitoring bond length alternation in the PEDOT backbone and charge density distribution. We find that at low temperature (T = 1 K) the polaron distortion gradually disappears from its initial location and reappears near the new position of the counterion. At the room temperature (T = 300 K), we find that the distortions induced by polaron, and atomic vibrations are of the same magnitude, which makes tracking the polaron distortion challenging because it is hidden behind the temperature-induced vibrations. The novel approach developed in this work can be used to study polaron mobility along and between the chains, investigate charge transport in highly doped polymers, and explore other flexible polymers, including n-doped ones.


Data-driven network alignment.
In this study, we deal with the problem of biological network alignment (NA), which aims to find a node mapping between species' molecular networks that uncovers similar network regions, thus allowing for the transfer of functional knowledge between the aligned nodes. We provide evidence that current NA methods, which assume that topologically similar nodes (i.e., nodes whose network neighborhoods are isomorphic-like) have high functional relatedness, do not actually end up aligning functionally related nodes. That is, we show that the current topological similarity assumption does not hold well. Consequently, we argue that a paradigm shift is needed with how the NA problem is approached. So, we redefine NA as a data-driven framework, called TARA (data-driven NA), which attempts to learn the relationship between topological relatedness and functional relatedness without assuming that topological relatedness corresponds to topological similarity. TARA makes no assumptions about what nodes should be aligned, distinguishing it from existing NA methods. Specifically, TARA trains a classifier to predict whether two nodes from different networks are functionally related based on their network topological patterns (features). We find that TARA is able to make accurate predictions. TARA then takes each pair of nodes that are predicted as related to be part of an alignment. Like traditional NA methods, TARA uses this alignment for the across-species transfer of functional knowledge. TARA as currently implemented uses topological but not protein sequence information for functional knowledge transfer. In this context, we find that TARA outperforms existing state-of-the-art NA methods that also use topological information, WAVE and SANA, and even outperforms or complements a state-of-the-art NA method that uses both topological and sequence information, PrimAlign. Hence, adding sequence information to TARA, which is our future work, is likely to further improve its performance. The software and data are available at http://www.nd.edu/~cone/TARA/.


Small-molecule HIV-1 entry inhibitors targeting the epitopes of broadly neutralizing antibodies.
Highly active antiretroviral therapy currently used for HIV/AIDS has significantly increased the life expectancy of HIV-infected individuals. It has also improved the quality of life, reduced mortality, and decreased the incidence of AIDS and HIV-related conditions. Currently, however, affected individuals are typically on a lifetime course of several therapeutic drugs, all with the potential for associated toxicity and emergence of resistance. This calls for development of novel, potent, and broad anti-HIV agents able to stop the spread of HIV/AIDS. Significant progress has been made toward identification of anti-HIV-1 broadly neutralizing antibodies (bNAbs). However, antibody-based drugs are costly to produce and store. Administration (by injection only) and other obstacles limit clinical use. In recent years, several highly promising small-molecule HIV-1 entry inhibitors targeting the epitopes of bNAbs have been developed. These newly developed compounds are the focus of the present article.


Control of the LexA regulon by pH: evidence for a reversible inactivation of the LexA repressor during the growth cycle of Escherichia coli.
The LexA repressor controls the expression of several genes, including lexA, recA, and sfiA, which are induced when exponentially growing bacteria are exposed to DNA-damaging agents. Induction of this so-called SOS response takes place while LexA is cleaved in a reaction that requires the RecA protein and damaged DNA. We have shown that large fluctuations in the cellular concentration of the LexA repressor and in the rate of transcription of the sfiA gene also occur spontaneously during bacterial growth in complex medium such as LB. The possibility that changes in external or internal pH may explain these fluctuations has been explored. A consistent pattern was established whereby conditions leading to either increased or decreased pH were associated with altered expression of the lexA and sfiA genes. These data can be explained by a model in which the LexA repressor exists in either of two forms in equilibrium: a form favoured at homeostatic internal pH, which has a low affinity for the operators of LexA-controlled genes; and a form accumulated in response to a transient decrease in internal pH, which has a high affinity for operators.


[Rebuilding of binocular vision after strabismus surgeries for thyroid-associated ophthalmopathy].
To evaluate the rule of the rebuilding of binocular vision after surgery in strabismus for thyroid-associated ophthalmopathy. The binocular vision was examined and compared in 30 patients before and after strabismus surgeries. The strabismus degrees were 20-80(delta) before surgeries and 2-12(delta) after surgeries. As shown by synoptophores examinations, 19 patients (63.3%) had degree one before strabismus surgeries and the number increased to 28 (93.3%) after the surgeries. Synoptophore fusion area was 0-12(0) [mean (6.1 +/- 4.7)0] before strabismus surgeries and was 0-30(0) [mean (14.4 +/- 5.1)0] after the surgeries (P < 0.001). Nine patients (30%) had stereovision before strabismus surgeries, and the number increased to 22 (73.3%) after the surgeries. Pre-surgery stereoacuity was as follows: none < or = 60", 2 patients 80-200", and 4 patients 300-800"; while the post-surgery stereoacuity was as follows: 4 patients < or = 60", 6 patients 80-200", and 10 patients 300-800" (P < 0.05). Strabismus surgeries for thyroid-associated ophthalmopathy can effectively improve ocular movement and rebuilt binocular vision.


Rationale and methods of the Substance Use and Psychological Injury Combat Study (SUPIC): a longitudinal study of Army service members returning from deployment in FY2008-2011.
The Substance Use and Psychological Injury Combat Study (SUPIC) will examine whether early detection and intervention for post-deployment problems among Army Active Duty and National Guard/Reservists returning from Iraq or Afghanistan are associated with improved long-term substance use and psychological outcomes. This paper describes the rationale and significance of SUPIC, and presents demographic and deployment characteristics of the study sample (N = 643,205), and self-reported alcohol use and health problems from the subsample with matched post-deployment health assessments (N = 487,600). This longitudinal study aims to provide new insight into the long-term post-deployment outcomes of Army members by combining service member data from the Military Health System and Veterans Health Administration.


Lost in time: Relocating the perception of duration outside the brain.
It is well-accepted in neuroscience that animals process time internally to estimate the duration of intervals lasting between one and several seconds. More than 100 years ago, Henri Bergson nevertheless remarked that, because animals have memory, their inner experience of time is ever-changing, making duration impossible to measure internally and time a source of change. Bergson proposed that quantifying the inner experience of time requires its externalization in movements (observed or self-generated), as their unfolding leaves measurable traces in space. Here, studies across species are reviewed and collectively suggest that, in line with Bergson's ideas, animals spontaneously solve time estimation tasks through a movement-based spatialization of time. Moreover, the well-known scalable anticipatory responses of animals to regularly spaced rewards can be explained by the variable pressure of time on reward-oriented actions. Finally, the brain regions linked with time perception overlap with those implicated in motor control, spatial navigation and motivation. Thus, instead of considering time as static information processed by the brain, it might be fruitful to conceptualize it as a kind of force to which animals are more or less sensitive depending on their internal state and environment.


Expression of cyclo-oxygenases-1 and -2, and microsomal prostaglandin E synthase-1 in penile and preputial papillomas and squamous cell carcinomas in the horse.
Penile and preputial papilloma and squamous cell carcinoma (SCC) are commonly diagnosed in horses. Papillomas have the potential to progress to potentially lethal SCC. Knowledge of pathogenetic mechanisms may help in prevention and definition of treatment targets. Retrospective study using archived material. To determine the expression of cyclo-oxygenase 1 (COX-1), cyclo-oxygenase 2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) in penile and preputial normal tissue, papilloma and SCC in horses, and whether expression of these enzymes is influenced by degree of inflammation and differentiation grade. Tumour differentiation grade, degree of inflammation and COX-1, COX-2 and mPGES-1 expression in 75 formalin-fixed paraffin embedded samples of penile and preputial papilloma and SCC of 68 horses were investigated by histopathology and immunohistochemistry. Inflammation was more prominent in SCC compared with papilloma. No correlation between expression of COX-1 or COX-2 and inflammation was found. Expression of mPGES-1 was weakly correlated with inflammation. Expression of COX-1, COX-2 and mPGES-1 was found in 42.6%, 50.7% and 96.0% of lesions respectively, but less than 1% of cells were immunopositive for COX-1 and COX-2 in 59.4% and 84.2% of cases respectively. Expression of COX-1 was moderately negatively correlated with differentiation grade, COX-2 was not correlated and mPGES-1 was poorly negatively correlated. Expression of COX-1 and COX-2 in penile and preputial SCC in the horse is poor and COX inhibitors may thus be of little value for prevention or treatment. Microsomal PGES-1 is more prominently expressed in well-differentiated tissue compared with poorly differentiated tissue. Further research on the role of mPGES-1 in carcinogenesis is needed to assess its potential use as a treatment target. Knowledge of arachidonic pathway enzyme expression and their role in equine penile and preputial carcinogenesis may help in developing preventive and therapeutic strategies.


Integrated geophysical surveys on waste dumps: evaluation of physical parameters to characterize an urban waste dump (four case studies in Italy).
Geophysical surveys were carried out on different waste dumps to evaluate key geometric and physical parameters. Depending on the dump dimensions and physical characteristics different geophysical techniques were used. Vertical electrical sounding, electrical resistivity tomography, induced polarization and seismic refraction techniques were integrated to eliminate the non-uniqueness of solutions and for a better understanding of the results. Physical parameters inside and outside the dumps were compared. The change of physical parameters such as resistivity, chargeability, and P-wave velocity allowed evaluation of waste dump geometry, leachate saturation levels, and thickness of waste. Furthermore, in illegal dumps, the size and waste type disposed could be evaluated. Calculated results were compared with plans and book-keeping from the dumps investigated.


SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1α complex.
SirT1 is a class III histone deacetylase that has been implicated in metabolic and reactive oxygen species control. In the vasculature it has been shown to decrease endothelial superoxide production, prevent endothelial dysfunction and atherosclerosis. However, the mechanisms that mediate SirT1 antioxidant functions remain to be characterized. The transcription factor FoxO3a and the transcriptional coactivator peroxisome proliferator activated receptor γ-coactivator 1α (PGC-1α) have been shown to induce the expression of antioxidant genes and to be deacetylated by SirT1. Here we investigated SirT1 regulation of antioxidant genes and the roles played by FoxO3a and PGC-1α in this regulation. We found that SirT1 regulates the expression of several antioxidant genes in bovine aortic endothelial cells, including Mn superoxide dismutase (MnSOD), catalase, peroxiredoxins 3 and 5 (Prx3, Prx5), thioredoxin 2 (Trx2), thioredoxin reductase 2 (TR2), and uncoupling protein 2 (UCP-2) and can be localized in the regulatory regions of these genes. We also found that knockdown of either FoxO3a or PGC-1α prevented the induction of antioxidant genes by SirT1 over-expression. Furthermore, SirT1 increased the formation of a FoxO3a/PGC-1α complex as determined by co-immunoprecipitation (IP) assays, concomitantly reducing H2O2-dependent FoxO3a and PGC-1α acetylation. Data showing that FoxO3a knockdown increases PGC-1α acetylation levels and vice versa, suggest that SirT1 activity on FoxO3a and PGC-1α may be dependent of the formation of a FoxO3a/PGC-1α complex. A unifying mechanism for SirT1 activities is suggested. We show that SirT1 regulation of antioxidant genes in vascular endothelial cells depends on the formation of a FoxO3a/PGC-1α complex.


Overproduction of penicillin-binding protein 7 suppresses thermosensitive growth defect at low osmolarity due to an spr mutation of Escherichia coli.
Escherichia coli delta prc mutants lacking periplasmic protease Prc, which was originally found involved in the C-terminal processing of penicillin-binding protein (PBP) 3, show thermosensitive growth at low osmolarity. We isolated thermoresistant revertants containing extragenic suppressor (spr) mutations. In the prc+ background the mutations also caused thermosensitivity at low osmolarity. They were all mapped at about 48 min on the chromosome and most probably allelic to one another. From this chromosomal region we cloned a gene that could correct the thermosensitive defect of an spr mutant, which turned out to be a multicopy suppressor of spr. Analysis of the nucleotide sequence predicted that the gene would code for a low-molecular-weight PBP, and penicillin-binding experiments revealed the product to be PBP 7. Disruption of the gene on the chromosome caused no apparent growth defect. PBP 7 seemed to be degraded by protease Prc. Overproduction of mutant PBP 7 that had the active site serine residue replaced with alanine did not correct the spr thermosensitivity, suggesting importance of the DD-endopeptidase activity in the multicopy suppression.


TASTRAK spectroscopy of polonium-210 alpha-particle activity at bone surfaces: evidence for a concentrated surface deposit less than 3 microns deep.
The technique of alpha-particle spectroscopy by CR-39 type TASTRAK plastic has been used to study the depth distribution of natural alpha-particle emitters at the surface of human bone. The predominant component of this alpha-particle activity was 210Po supported by 210Pb, although a smaller activity of 226Ra was also detected. Autopsy samples of human femur and cranium were obtained from subjects age 63 to 86. Both cortical and trabecular surfaces were analyzed. The results indicate that 210Pb-supported 210Po is concentrated at the surfaces of human bone from elderly subjects, in a narrow band 3 microns deep or less, by a factor of about four. As a result, the alpha-particle dose to the nuclei of cells lining bone surfaces is around 1.8 times greater than that calculated for a uniform volume distribution. Polonium-210 activity indicates the distribution of 210Pb, and of stable lead, received by continuous intake throughout life at a very low level. A persistent bone surface concentration of lead and other osteotropic metals may be associated with the hypermineralized layer about 1 micron thick which occurs at the surface of resting bone mineral.


E-waste recycling intention paradigm of small and medium electronics store managers in Bangladesh: An S-O-R perspective.
Each year Bangladesh produces around 400,000 metric tonnes of e-waste. E-waste accumulation is expected to increase by 20% annually. In order to facilitate e-waste recycling, it is crucial to identify the factors. In this study, building on the stimulus-organism-response framework, we develop a research model to explore the effect of information publicity, ascription of responsibility and convenience of recycling on the recycling attitude, subjective norm, personal norm and perceived behaviour control which lead to recycling intention. Data were gathered from 127 small and medium electronics store managers. The structural equation modelling technique was used to test the paths. The result suggests a significant influence of the element of stimulus (S) on the element of organism (O). The relationship between the element of organism (O) and the element of response (R) is partial. This paper contributes to the body of work dedicated to helping us better understand the recycling behaviour from the stimulus-organism-response perspective. From the viewpoint of practice, this research sheds light on some of the challenges that the implementer might face when making strategy and policy for e-waste management in Bangladesh.


The relationship between physical exercise and mobile phone addiction among Chinese college students: Testing mediation and moderation effects.
During the COVID-19 pandemic, suspensions of activities and long periods of self-isolation led to a sharp increase in excessive use of mobile phones, which sparked public concern about mobile phone addiction (MPA). In recent years, more and more attention has been paid to physical exercise as a protective effect of MPA. However, more studies are needed to reveal this relationship and the exact mechanisms, based on which this study tested the mediating and moderating roles of self-control, rumination, psychological distress, and loneliness between physical exercise and MPA. In this cross-sectional study, primary data was collected by questionnaire from 1,843 college students (19.75 ± 1.3) from five universities in Sichuan Province in Mainland China. Mobile Phone Addiction Tendency Scale (MPATS), Physical Activity Rating Scale-3 (PARS-3), Self-Control Scale (SCS), Ruminative Response Scale (RRS), Depression Anxiety Stress Scale-21 (DASS-21), and UCLA Loneliness Scale (UCLA-20) were investigated. The mediating models were examined using SPSS PROCESS macro 3.3 software, in which the mediation variables were self-control, rumination, and psychological distress, and the moderation was loneliness. Gender, major, and grade were included as control variables. Self-control, rumination, and psychological distress played a simple mediating role between physical exercise and MPA. Moreover, not only self-control and rumination but also self-control and psychological distress played the chain mediating roles between physical exercise and MPA. The chain pathways were moderated by loneliness. Specifically, the effect was more substantial among college students with higher loneliness. The conclusions corroborate and clarify that self-control, rumination, and psychological distress mediated the association between physical exercise and MPA, and the mediation effects were moderated via loneliness. This present study advanced our understanding of how and when college students' physical exercise was related to MPA. It also illustrates that educators and parents should pay more attention to college students' physical exercise.


Comparison of single neuron models in terms of synchronization propensity.
A plausible model for coherent perception is the synchronization of chaotically distributed neural spike trains over wide cortical areas. A recently introduced propensity criterion provides a tool for a quantitative comparison of different neuron models in terms of their ability to synchronize to an applied perturbation. We explore the propensity of several systems and indicate the requirements to be satisfied by a plausible candidate for modeling neuronal activity. Our results show that the conflicting requirements of stability and sensitivity leading to high propensity to synchronization can be satisfied by a strongly nonuniform attractor made of two distinct regions: a saddle focus plus a sufficiently separated saddle node.


Elevated serum leptin levels: a risk factor for non-small-cell lung cancer?
Leptin is intimately intertwined in the molecular pathophysiology of several cancer types; with regard to lung cancer, however, limited research has been conducted, with overall conflicting results. The present case-control study comprises 66 non-small-cell lung cancer (NSCLC) cases and 132 healthy controls matched for gender and age. Lifestyle, sociodemographic and medical history information has been obtained in addition to body mass index (BMI) measurements and weight change during the last 2 months. Serum leptin and adiponectin levels were determined following a standard protocol. In multiple logistic regression analyses, elevated serum leptin emerged as a risk factor for NSCLC independent of central obesity, more pronounced after controlling for BMI and recent weight loss (odds ratio = 4.58, 95% confidence interval: 1.94-10.82). Additionally, smoking and animal foods consumption were strongly associated with the disease, whereas plant foods consumption showed a protective association. The observed higher serum leptin levels in NSCLC cases might be attributed to direct or indirect effects mediated by cancer- or cachexia-related cytokines. In line with the growth-promoting properties of leptin in the lung tissue documented elsewhere, increased serum leptin concentration may represent a tumor-promoting event during non-small-cell lung carcinogenesis.


Kuru-plaques in creutzfeldt-jakob disease.
A case of Creutzfeldt-Jakob disease of cerebellar type is reported. In this case the cerebellar cortex exhibited classical Kuru-plaques. From a comparison of this finding with 50 cerebella from senile patients and patients with cerebellar atrophies it is concluded that the Kuru-plaque is specific for Creutzfeldt-Jakob disease, possible even for its cerebellar variant.


New drugs and new toxicities: pembrolizumab-induced myocarditis.
Pembrolizumab is an immune checkpoint inhibitor that significantly improves clinical outcomes in numerous solid organ malignancies. Despite successful therapeutic responses, this new drug comes with a constellation of adverse reactions. Herein, we chronicle the case of a patient with metastatic non-small-cell lung cancer treated with pembrolizumab. After two cycles, he developed new-onset dyspnoea on exertion. Electrocardiogram showed idioventricular rhythm with diffuse ST-segment elevations. Echocardiography revealed severe biventricular cardiac dysfunction. Based on diagnostic workup and exclusion of probable aetiologies, the patient was diagnosed with pembrolizumab-induced myocarditis. The treatment was initiated with corticosteroids and guideline-conform heart failure therapy. He demonstrated a marked clinical response with resolution of congestive heart failure symptoms. This article summarises the clinical evidence regarding the epidemiology, pathophysiology, clinical features, diagnostic modalities and management of patients with pembrolizumab-associated myocarditis. In addition, it highlights that programmed death receptor-1 inhibition can cause a spectrum of autoimmune adverse events requiring clinical monitoring and periodic screenings.


Latin American and Caribbean Health Resources: The VHL Regional Portal.
This column provides an overview of the Virtual Health Library (VHL) Regional Portal, a resource provided by Pan American Health Organization and others with the purpose of communicating and exchanging health experiences and information for Latin American and Caribbean countries. The content is organized in four sub-portals: the VHL Model, which describes health information and knowledge management to structures and guides; LILACS, the Latin American and Caribbean Index Health Science Literature; DeCS, Descriptors Health Sciences, a controlled vocabulary; and Training, which gathers and organizes information for librarians, developers, and users who are interested in construction and use of VHL methodologies. An overview of the resource and sample search is discussed.


On the role of glucocorticoid in glucose-induced insulin secretion.
To explore the role of endogenous glucocorticoid in insulin secretion, the plasma concentrations of insulin in the fasting state and in response to intravenous administration of glucose were determined in adrenalectomized and sham-adrenalectomized rats. Adrenalectomy produced a decrease in the fasting plasma insulin two days after the operation when there was found no change in the blood glucose levels. Likewise, plasma insulin response to glucose was clearly reduced in adrenalectomized rats, although there was no difference among the two groups in increment of the blood glucose after the glucose load. At this moment, a stimulatory action of insulin on glucose metabolism was rather decreased in the adipose tissue from the adrenalectomized rats when compared with that from the control rats. The pancreatic tissue from the adrenalectomized rats secreted much less amount of insulin in response to perifused glucose not only in the early phase but also in the second phase of release pattern. The pancreas from the adrenalectomized rats treated with dexamethasone showed the opposite changes. These findings support the hypothesis that the endogenous glucocorticoid may play a role in maintaining sensitivity of the B cell to insulinogenic stimuli.


Characterization of the Pseudomonas aeruginosa recA analog and its protein product: rec-102 is a mutant allele of the P. aeruginosa PAO recA gene.
We cloned a 2.3-kilobase-pair fragment of the Pseudomonas aeruginosa PAO chromosome which is capable of complementing recA mutations of Escherichia coli. The recA-complementing activity was further localized to a 1.5-kilobase-pair PvuII-HindIII fragment. Southern blot analysis under conditions of high stringency indicated that DNA sequence homology is shared by the E. coli recA gene and the P. aeruginosa recA analog. The cloned recA analog was shown to restore resistance to methyl methanesulfonate, nitrofurantoin, and UV irradiation to E. coli recA mutants. Upon introduction of the cloned P. aeruginosa gene, these mutants regained recombination proficiency in HfrH-mediated conjugation and the ability to induce lambda prophages and SOS functions (din gene transcription) after exposure to DNA-damaging agents. Lambda prophage carrying a cI ind mutation was not inducible, suggesting that the mechanism of induction of these SOS functions by the P. aeruginosa RecA analog is similar to that by the activated E. coli RecA protein. The product of the recA analog was identified in minicells as a protein of approximately 47,000 daltons. Western blot analysis using anti-E. coli RecA antibody demonstrated that this protein is antigenically cross-reactive with the E. coli recA protein. The recA-containing fragment was cloned into the broad-host-range vector pCP13 and introduced into Rec- strains of P. aeruginosa containing the rec-102 allele. The plasmid was shown to restore recombination proficiency in FP5-mediated conjugations and to restore resistance to UV irradiation and methyl methanesulfonate to these Rec- mutants. It was shown that a wild-type allele of rec-102 is necessary for UV-mediated induction of D3 and F116 prophages. The cloned recA analog restored the UV inducibility of these prophages in rec-102 mutants. These data indicate that rec-102 is a mutant allele of the P. aeruginosa recA gene and suggest that there has been considerable conservation of the recA gene in the evolution of the gram-negative bacteria.


[Example of a phase IV trial involving several physicians and aiming at answering a scientific question: EOL].
The aim of this trial was to test the hypothesis that a reduced number of doses improves compliance in current medical practice. Compliance with twice a day dosage was compared with compliance with three doses a day. Two bioequivalent presentations of nicardipine were used, the regular presentation (t.i.d.) and the slow-release (b.i.d.). The trial was controlled, randomized, open, in two parallel groups: (1)'t.i.d.' group: one tablet of regular nicardipine, 20 mg, three times a day, three months; (2) 'b.i.d.' group: one capsule of slow-release nicardipine, twice a day, three months. 2651 general practitioners randomized 7274 hypertensive patients. The primary criterion was documented in 93.7 per cent of the cases at the end of the trial. The remaining 6.3 per cent comprised treatment withdrawal (2.8 per cent) and patients lost to follow-up (3.5 per cent). The primary criterion study was compliance, assessed by a self-questionnaire filled in by the patient and a standardised interview by the physician. Compliance was slightly better in the b.i.d. group than in the t.i.d. group (p < 0.001). Remaining pill count was also used but it was a failure. A random sample of investigators made on-site visits. Discordant data were infrequent and were limited to dates of visits. Difficulties with on-site visits were mostly due to a rather frequent lack of source records.


Asymmetric distribution of cytokinins determines root hydrotropism in Arabidopsis thaliana.
The phenomenon of plant root tips sensing moisture gradient in soil and growing towards higher water potential is designated as root hydrotropism, which is critical for plants to survive when water is a limited factor. Molecular mechanisms regulating such a fundamental process, however, are largely unknown. Here we report our identification that cytokinins are key signaling molecules directing root growth orientation in a hydrostimulation (moisture gradient) condition. Lower water potential side of the root tip shows more cytokinin response relative to the higher water potential side. Consequently, two cytokinin downstream type-A response regulators, ARR16 and ARR17, were found to be up-regulated at the lower water potential side, causing increased cell division in the meristem zone, which allows the root to bend towards higher water potential side. Genetic analyses indicated that various cytokinin biosynthesis and signaling mutants, including the arr16 arr17 double mutant, are significantly less responsive to hydrostimulation. Consistently, treatments with chemical inhibitors interfering with either cytokinin biosynthesis or cell division completely abolished root hydrotropic response. Asymmetrically induced expression of ARR16 or ARR17 effectively led to root bending in both wild-type and miz1, a previously known hydrotropism-defective mutant. These data demonstrate that asymmetric cytokinin distribution is a primary determinant governing root hydrotropism.