EphB receptors influence growth of ephrin-B1-positive statoacoustic nerve fibers.
The Eph family of receptors and ligands has been implicated in a variety of developmental processes, including the provision of inhibitory guidance cues to developing nerve fibers. A unique property of the B class of receptors is that they are able to phosphorylate ephrin-B ligands, allowing for bi-directional, or reverse signalling. While most of the studies to date have focused on central nerve fibers, little is known about the role of Eph molecules in guiding nerve fibers of the peripheral nervous system. In the present study, ephrin-B1 was found to be highly expressed on developing peripheral nerve fibers including auditory and vestibular (statoacoustic) and dorsal root ganglion nerve fibers. In vitro assays revealed that EphB-Fc receptors inhibited further growth of statoacoustic nerve fibers. In contrast, EphA7-Fc and ephrin-B2-Fc did not prevent further growth of SAG. Together, these results suggest a role for EphB receptors in providing guidance signals to ephrin-B1-positive SAG nerve fibers.


A review of the outcome of upper lid lowering for eyelid retraction and complications of spacers at a single unit over five years.
To review the outcome of upper lid lowering for eyelid retraction at a single unit over five years and to report the high complication rate with mersilene mesh as a spacer material. We retrospectively reviewed the case records of 48 patients who underwent upper lid lowering for lid retraction between January 1995 and January 2000. The indication for surgery was eyelid retraction secondary to dysthyroid disease in 41 patients, seventh nerve palsy in 3 cases, overcorrection of ptosis elsewhere in 3 cases and previously treated orbital lymphoma in one patient. A good result was achieved in 80% with a single procedure. Undercorrection occurred in 10% and overcorrection occurred in 8%. Spacer material, either mersilene mesh or more recently vicryl, was used in 42% of lids. Late extrusion of mersilene mesh occurred in 20% of lids that had a spacer inserted an average of 18 months postoperatively. The high extrusion rate with mersilene was unacceptable and the alternative spacer material vicryl is now used. The possibility of revisional surgery because of under- or overcorrection should be explained to patients.


[Effect of fractal dimensions of powdered pharmaceutical aids on their flow rate].
Fractal dimension of the particles of powdered auxiliary substances expresses the raggedness of their surface, which can influence both the bulk density and their flow rate through the opening of the powder funnel. In the size fractions of 0.20-0.25 mm of six powdered auxiliary substances, their linear fractal dimensions within a range of 1.031 to 1.109 and the corresponding flow rates through the circular openings of the powder funnel of diameters of 6; 8; 10, and 12 mm were found. A significant correlation has been demonstrated between the flow rate expressed in volume (cm3/s) and the fractal dimension, which after an increase by one unit characterizes the surface of the particles. With increasing fractal dimension, the porosity of freely poured layer of powdered auxiliary substances is increased and simultaneously also their flow rate expressed in volume. For the usually reported flow rate expressed in weight (g/s), such influence is not significant.


Dynamics of energy condensation in two-dimensional turbulence.
We report a numerical study, supplemented by phenomenological explanations, of "energy condensation" in forced 2D turbulence in a biperiodic box. Condensation is a finite size effect which occurs after the standard inverse cascade reaches the size of the system. It leads to the emergence of a coherent vortex dipole. We show that the time growth of the dipole is self-similar, and it contains most of the injected energy, thus resulting in an energy spectrum which is markedly steeper than the standard k{-5/3} one. Once the coherent component is subtracted, however, the remaining fluctuations have a spectrum close to k{-1}. The fluctuations decay slowly as the coherent part grows.


A novel AFM based method for force measurements between individual hair strands.
Interactions between hairs and other natural fibers are of broad interest for both applications and fundamental understanding of biological interfaces. We present a novel method, that allows force measurements between individual hair strands. Hair fragments can be laser-cut without altering their surface chemistry. Subsequently, they are glued onto Atomic force microscopy (AFM) cantilevers. This allows carrying out measurements between the hair fragment and surface immobilized hair in a well-defined crossed-cylinder geometry. Both force-distance and friction measurements are feasible. Measurements in air with controlled humidity and in aqueous environment show clear differences which can be explained by the dominating role of capillary interactions in air. Friction is found to be anisotropic, reflecting the fine structure of hair cuticula. While the investigations are focused on the particular example of human hair, we expect that the approach can be extended to other animal/plant fibers and thus offers perspectives for broad spectrum systems.


The HIV-1 Antisense Gene ASP: The New Kid on the Block.
Viruses have developed incredibly creative ways of making a virtue out of necessity, including taking full advantage of their small genomes. Indeed, viruses often encode multiple proteins within the same genomic region by using two or more reading frames in both orientations through a process called overprinting. Complex retroviruses provide compelling examples of that. The human immunodeficiency virus type 1 (HIV-1) genome expresses sixteen proteins from nine genes that are encoded in the three positive-sense reading frames. In addition, the genome of some HIV-1 strains contains a tenth gene in one of the negative-sense reading frames. The so-called Antisense Protein (ASP) gene overlaps the HIV-1 Rev Response Element (RRE) and the envelope glycoprotein gene, and encodes a highly hydrophobic protein of ~190 amino acids. Despite being identified over thirty years ago, relatively few studies have investigated the role that ASP may play in the virus lifecycle, and its expression in vivo is still questioned. Here we review the current knowledge about ASP, and we discuss some of the many unanswered questions.


[Pancreatic cancer stem cell].
Prognosis of pancreatic cancer remains dismal due to the resistance against conventional therapies. Metastasis and massive invasion toward surrounding organs hamper radical resection. Small part of entire cancer cells reveal resistance against chemotherapy or radiotherapy, increased tumorigenicity and migratory phenotype. These cells are called as cancer stem cells, as a counter part of normal stem cells. In pancreatic cancer, several cancer stem cell markers have been identified, which enabled detailed characterization of pancreatic cancer stem cells. Recent researches clarified that conventional chemotherapy itself could increase cancer cells with stem cell-phenotype, suggesting the necessity of cancer stem cell-targeting therapy. Based on these observations, pancreatic cancer stem cell-targeting therapies have been tested, which effectively eliminated cancer stem cell fraction and attenuated cancer progression in experimental models. Clinical efficacy of these therapies need to be evaluated, and cancer stem cell-targeting therapy will contribute to improve the prognosis of pancreatic cancer.


Development of a gene therapy strategy for the restoration of survival motor neuron protein expression: implications for spinal muscular atrophy therapy.
Spinal muscular atrophy (SMA) is a motor neuron degeneration disorder, and manifests itself in patients as muscle weakness and paralysis that ultimately leads to death. Currently, there is no effective treatment for this disease. As a first step in developing a treatment for SMA, we are examining whether delivery of the gene encoding survival motor neuron (SMN) protein to primary fibroblast cell lines derived from SMA patients can lead to restoration of nuclear-staining foci, called gems, which are absent in patients with severe SMA. Using adenovirus-mediated gene delivery, we show that SMN can be efficiently expressed in patient fibroblasts, and leads to restoration of nuclear gems, which are thought to be important for the functional rescue of the SMA phenotype. The number of gems per cell is equal to or greater than those found in fibroblasts of normal individuals. Furthermore, ectopic expression of SMN also caused relocalization of Gemin2, an SMN-interacting protein, to gems. Overall, this work is the first demonstration of the feasibility of virus-based delivery of the SMN-coding gene to restore the normal SMN expression pattern in SMA patient-derived cells, and holds promise for gene therapy of SMA, as a potential long-term therapy for this devastating childhood disease.


Immune responses directed at egg proteins during experimental infection with the liver fluke Fasciola hepatica.
Fasciola hepatica is responsible for human disease and economic livestock loss on a global scale. Unlike the well characterized schistosomes, only the adult and juvenile stages of F. hepatica are implicated in disease, whereas the freely voided egg is not thought to contribute to host-parasite interactions. We investigated specific immune responses to soluble F. hepatica egg proteins (SFHEP), during a 14-week experimental infection, demonstrating significant increases in anti-SFHEP IgG1 (P = 0.001), transforming growth factor beta-1 (P = 0.008) and IL-10 (P < 0.001) titres at the onset of egg production. Western blot analysis of soluble SFHEP demonstrates that protein bands migrating at 61.6, 54.8 and 44 kDa become sero-reactive before the appearance of eggs within host faeces. Therefore, expression of some egg-associated proteins indicates progression to chronic disease. Antigenic bands were investigated through mass spectrometry, identifying a protein disulphide isomerase (PDI) (61.6 kDa), an enolase and ferritin-related proteins (54.8 kDa), and a cocktail of dehydrogenases (44 kDa). Biochemical analysis of egg secretions reveals proteolytic activity, which increases over time, indicating that proteases may be continually secreted during the course of egg maturation. The implications of egg-specific immune responses and proteolytic secretions are further discussed.


Use of a biotinylated DNA probe specific for the human Y chromosome in the evaluation of the allograft lung.
A cloned 3.4 kilobase DNA probe derived from the heterochromatin of the Y chromosome was used to investigate the regeneration and reepithelialization of allograft lungs of nine recipients who received sex mismatched donor organs. Patients were monitored for varying periods of time, up to four years, by transbronchial biopsy. In situ hybridization on paraffin-embedded biopsies utilizing the Y probe revealed that bronchial and alveolar epithelium and arterial and venous endothelium of the peripheral lung retained a donor phenotype, irrespective of episodes of acute or chronic rejection (obliterative bronchiolitis) which are known to injure these cellular subsets. In contrast, migratory cells, lymphocytes and macrophages, gradually, at varying rates, infiltrated the allografted lungs, replacing preexisting donor elements. Cases of active OB were manifested by infiltration of bronchioles by sex-mismatched lymphocytes; however, in some instances, quiescent recipient lymphocytes colonized the allograft and were unassociated with histologic rejection. Macrophages of similar sex seemed to cluster together within air spaces. Use of a DNA probe for the Y chromosome and in situ hybridization techniques allow monitoring of cellular alterations over time in recipients with sex mismatched allografts.


Predictive Power of Tissue and Circulating Biomarkers for the Severity of Biopsy-Validated Chronic Liver Diseases.
Background: Although liver biopsy remains the gold standard for the diagnosis and the monitoring of liver disease, non-invasive biomarkers have been recently suggested to predict liver disease severity, progression, and response to therapy. We investigated multiple tissue and circulating markers of angiogenesis in predicting the severity of biopsy-validated chronic liver diseases in patients with chronic hepatitis C virus (HCV) and in NAFLD/NASH patients. Methods: We studied samples from forty-six patients with HCV and/or NAFLD who underwent liver biopsy, liver ultrasonography, and liver stiffness measurement. Ishak and Brunt scores were calculated. Expression of selective genes and luminex analyses of 17 different circulating pro-angiogenic factors were performed. Results: The phenotype of NAFLD/NASH or HCV subjects was similar, except for insulin, which was expressed at higher levels in NAFLD/NASH patients. A Mann−Whitney test showed significant differences for the circulating levels of HB-EGF and for follistatin between HCV and NAFLD/NASH patients. In HCV patients, we found an inverse correlation between disease stage and BMP-9 and VEGF-A circulating levels, while in NASH/NAFLD direct correlations between stage and BMP-9 and VEGF-A circulating levels were noted. The K-means algorithm divided HCV and NASH/NAFLD patients in two clusters with significant differences between them. Logistic regression models showed a positive relationship with BMP-9 levels for NASH/NAFLD and with HB-EGF circulating concentrations for HCV. ROC analysis showed for BMP-9 > 1188 pg/mL a worse disease in NASH/NAFLD, whereas for HB-EGF < 61 pg/mL a higher severity of disease in HCV. Conclusion: Our data show that circulating biomarker profiles can identify the severity of chronic liver disease of NAFLD/NASH or HCV origin.


T cell immunoglobulin and mucin protein-3 (Tim-3)/Galectin-9 interaction regulates influenza A virus-specific humoral and CD8 T-cell responses.
Reactions to pathogens are usually tuned to effect immunity and limit tissue damage. Several host counterinflammatory mechanisms inhibit tissue damage but these may also act to constrain the effectiveness of immunity to acute infections, as we demonstrate in mice acutely infected with influenza A virus (IAV). We show that compared with wild type (WT), galectin-9 knockout (G9KO) mice mounted a more robust acute phase virus-specific CD8 T-cell response as well as higher and more rapid virus-specific serum IgM, IgG, and IgA responses and also cleared virus more rapidly than did WT mice. Blocking galectin-9 signals to Tim-3-expressing cells using a Tim-3 fusion protein resulted in improved immune responses in WT mice. When IAV immune mice were challenged with a heterologous IAV, the secondary IAV-specific CD8 T-cell responses were four- to fivefold higher in G9KO compared with WT mice. Our results indicate that manipulating galectin signals may represent a convenient approach to improve immune responses to some vaccines.


Consensus for the Early Identification of Secondary Progressive Multiple Sclerosis in Portugal: a Delphi Panel.
Multiple sclerosis is a disease with a heterogeneous evolution. The early identification of secondary progressive multiple sclerosis is a clinical challenge, which would benefit from the definition of biomarkers and diagnostic tools applicable in the transition phase from relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis. We aimed to reach a Portuguese national consensus on the monitoring of patients with multiple sclerosis and on the more relevant clinical variables for the early identification of its progression. A Delphi panel which included eleven Portuguese Neurologists participated in two rounds of questions between July and August of 2021. In the first round, 39 questions which belonged to the functional, cognitive, imaging, biomarkers and additional evaluations were included. Questions for which no consensus was obtained in the first round (less than 80% of agreement), were appraised by the panel during the second round. The response rate was 100% in both rounds and consensus was reached for a total of 33 questions (84.6%). Consensus was reached for monitoring time, evaluation scales and clinical variables such as the degree of brain atrophy and mobility reduction, changes suggestive of secondary progressive multiple sclerosis. Additionally, digital devices were considered tools with potential to identify disease progression. Most questions for which no consensus was obtained referred to the cognitive assessment and the remaining referred to both functional and imaging domains. Consensus was obtained for the determination of the monitorization interval and for most of the clinical variables. Most questions that did not reach consensus were related with the confirmation of progression taking into account only one test/domain, reinforcing the multifactorial nature of multiple sclerosis.


BATEMANATER: a computer program to estimate and bootstrap mating system variables based on Bateman's principles.
Bateman's principles continue to play a major role in the characterization of genetic mating systems in natural populations. The modern manifestations of Bateman's ideas include the opportunity for sexual selection (i.e. I(s) - the variance in relative mating success), the opportunity for selection (i.e. I - the variance in relative reproductive success) and the Bateman gradient (i.e. β(ss) - the slope of the least-squares regression of reproductive success on mating success). These variables serve as the foundation for one convenient approach for the quantification of mating systems. However, their estimation presents at least two challenges, which I address here with a new Windows-based computer software package called BATEMANATER. The first challenge is that confidence intervals for these variables are not easy to calculate. BATEMANATER solves this problem using a bootstrapping approach. The second, more serious, problem is that direct estimates of mating system variables from open populations will typically be biased if some potential progeny or adults are missing from the analysed sample. BATEMANATER addresses this problem using a maximum-likelihood approach to estimate mating system variables from incompletely sampled breeding populations. The current version of BATEMANATER addresses the problem for systems in which progeny can be collected in groups of half- or full-siblings, as would occur when eggs are laid in discrete masses or offspring occur in pregnant females. BATEMANATER has a user-friendly graphical interface and thus represents a new, convenient tool for the characterization and comparison of genetic mating systems.


Social policy in the face of a global pandemic: Policy responses to the COVID-19 crisis.
How have welfare states responded to the coronavirus pandemic? In this introductory article, we provide a synopsis of papers that comprise this special issue on social policy responses to COVID-19, an overview of some of the key questions they raise, and some provisional answers to these questions. Our conclusions are threefold: first, these social policy responses, while entailing new developments in many countries, nonetheless reflect, at least in part, existing national policy legacies. Second, these responses can be understood as a form of "emergency Keynesianism," which is characterized by the massive use of deficit spending during economic crises, with the aim of to supporting rather than challenging core capitalist institutions. Third, there are clear differences in terms of the nature of the reforms enacted during the initial phase of the COVID-19 crisis as compared to reforms enacted as a response to the 2008 financial crisis.


Comparison of the orotidine 5'-monophosphate decarboxylase sequences of eight species.
Predicted amino acid sequences of the enzyme orotidine 5'-phosphate decarboxylase (EC 220.127.116.11) from eight different organisms are compared. The comparisons are made on the basis of primary structural differences, primary amino acid sequence, hydropathy profiles, and secondary structure predictions. The organisms compared are Mus musculus, Aspergillus nidulans, Neurospora crassa, Kluyveromyces lactis, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Escherichia coli, and Salmonella typhimurium.


Response of Different Insect Groups to Various Wavelengths of Light under Field Conditions.
Insects in the same taxonomic group generally have similar responses to light at various wavelengths in the laboratory. However, there is lack of direct evidence of between-group differences in insect responses to various light wavelengths under field conditions. During 2014 and 2015, we evaluated the relative attractiveness of LEDs with 19 single wavelengths to three pest orders and four natural predator orders in cotton fields. The average numbers of Lepidoptera, Hemiptera, Coleoptera, and total pests captured by traps with a 395-nm LED wavelength were higher than those for all others, except 440-nm wavelength captured the largest number of Hemiptera in 2015. For natural enemies, the average numbers of Coleoptera, Neuroptera, and total natural enemies were the largest in traps with a 572-nm LED wavelength, except 538-nm wavelength captured the largest number of Coleoptera in 2014. In general, the ratio of pests to natural enemies captured in the 395-nm wavelength LED trap was significantly more than all others. These results demonstrated that insects in different taxonomic groups have significantly different responses to light at various wavelengths under field conditions; these results will provide insights for in-depth studies on insect phototaxis and guide the long-term monitoring of insects in different groups.


A comprehensive review on the decontamination of lead(ii) from water and wastewater by low-cost biosorbents.
The disadvantages of conventional methods in water and wastewater management including the demand for high energy consumption, the creation of secondary toxic sludge, and operation cost are much too high for developing countries. However, adsorption using low-cost biosorbents is the most efficient non-conventional technique for heavy metals removal. The high adsorption capacities, cost-effectiveness, and the abundance of agricultural waste materials in nature are the important parameters that explain why these biosorbents are economical for heavy metals removal. The present investigation sought to review the biosorption of lead [Pb(ii)] onto low-cost biosorbents to understand their adsorption mechanism. The review shows that biosorption using low-cost biosorbents is eco-friendly, cost-effective, and is a simple technique for water and wastewater treatment containing lead(ii) ions. The batch biosorption tests carried out in most studies show that Pb(ii) biosorption by the low-cost biosorbents is dependent on biosorption variables such as pH of the aqueous solution, contact time, biosorbent dose, Pb(ii) initial concentration, and temperature. Furthermore, batch equilibrium data have been explored in many studies by evaluating the kinetics, isothermal and thermodynamic variables. Most of the studies on the adsorptive removal of Pb(ii) were found to follow the pseudo-second kinetic and Langmuir isotherm models with the thermodynamics variables suggesting the feasibility and spontaneous nature of Pb(ii) sequestration. However, gaps exist to increase biosorption ability, economic feasibility, optimization of the biosorption system, and desorption and regeneration of the used agricultural biosorbents.


Studies on the biodegradation of fosfomycin: growth of Rhizobium huakuii PMY1 on possible intermediates synthesised chemically.
The first step of the mineralisation of fosfomycin by R. huakuii PMY1 is hydrolytic ring opening with the formation of (1R,2R)-1,2-dihydroxypropylphosphonic acid. This phosphonic acid and its three stereoisomers were synthesised by chemical means and tested as their ammonium salts for mineralisation as evidenced by release of P(i). Only the (1R,2R)-isomer was degraded. A number of salts of phosphonic acids such as (+/-)-1,2-epoxybutyl-, (+/-)-1,2-dihydroxyethyl-, 2-oxopropyl-, (S)-2-hydroxypropyl-, (+/-)-1-hydroxypropyl- and (+/-)-1-hydroxy-2-oxopropylphosphonic acid were synthesised chemically, but none supported growth. In vitro C-P bond cleavage activity was however detected with the last phosphonic acid. A mechanism involving phosphite had to be discarded as it could not be used as a phosphorus source. R. huakuii PMY1 grew well on (R)- and (S)-lactic acid and hydroxyacetone, but less well on propionic acid and not on acetone or (R)- and (+/-)-1,2-propanediol. The P(i) released from (1R,2R)-1,2-dihydroxypropylphosphonic acid labelled with one oxygen-18 in the PO3H2 group did not stay long enough in the cells to allow complete exchange of 18O for 16O by enzymic turnover.


Predicting miRNA-mediated gene silencing mode based on miRNA-target duplex features.
There are two main mechanisms of miRNA-mediated gene silencing: either mRNA degradation or translational repression. However, the precise mechanism of target mRNAs regulated by miRNA remains unclear. As a complementary approach to experiment, a computational method was proposed to recognize the mechanism of miRNA-mediated gene silencing in human. We have analyzed extensive features correlated with miRNA-mediated silencing mechanism of mRNA. It is found that, the duplex structure, the number of binding sites and the structural accessibility of target site region are effective factors in determining whether a target mRNA is cleaved or only translationally inhibited. An SVM-based classifier was constructed to predict the regulation mode of miRNA based on these informative features. The results indicated that the approach proposed is effective in distinguishing whether a target mRNA is cleaved or translationally inhibited in human. Furthermore, the web server microDoR (http://reprod.njmu.edu.cn/microdor) has been developed and is freely available for users.


Histochemical characteristics of masseter and temporalis muscles after 5 weeks of maxillomandibular fixation--an investigation in Macaca mulatta.
This study describes the histochemical characteristics and cross-sectional areas of the superficial masseter and temporalis muscles in juvenile rhesus monkeys after 5 weeks of maxillomandibular fixation. Four juvenile male Macaca mulatta underwent mandibular surgery and 5 weeks of maxillomandibular fixation as part of a study of temporomandibular joint (TMJ) adaptations after condylar replacement. Immediately before the time the animals were killed (5 weeks postsurgically), biopsies of the masseter and temporalis muscles were obtained and submitted to histochemical analysis and calculation of muscle-fiber areas. The data were compared to histochemistry from 12 juvenile control Macaca mulatta. Significant decreases in mean cross-sectional area were exhibited in both type I (p less than 0.05) and type II (p less than 0.01) fibers in all muscles when compared to controls (n = 12). The ratio of type I to type II fibers, however, remained constant during maxillomandibular fixation in masseter and temporalis muscle samples, indicating no change in relative types of fibers. We conclude from this experimental investigation that (1) significant atrophy occurs in the temporalis and masseter muscles after 5 weeks of maxillomandibular fixation, and (2) this atrophy occurs in both type I and type II fibers, indicating that overall recruitment of the muscle (and not just of one fiber type of motor unit) was affected during fixation.


Endocarditis and giant mitral valve aneurysms.
In a 65-year-old man with infective endocarditis, multiple mitral valve aneurysms were detected by echocardiography. Surgical treatment was successful. Aneurysms of the valve are a relatively rare complication of infective endocarditis. Prompt diagnosis and treatment can prevent complications such as embolisation and rupture of the aneurysms. For a patient with a history of unknown fever, this point should be kept in mind.


Molecular structure of the complex formed between the anticancer drug cisplatin and d(pGpG): C222(1) crystal form.
The three dimensional molecular structure of the adduct formed between the anticancer drug cisplatin and a DNA dinucleotide d(pGpG) has been determined by x-ray diffraction analysis at 1.37 A resolution and refined to a final R-factor of 0.11. This structure, solved by using data from a previously reported crystal form in the space group C222(1), resembles that found in the space group P2(1)2(1)2 (Sherman, et al., Science, 230, 412-417, 1985; ibid, J. Amer. Chem. Soc. 110, 7368-7381, 1988). In both structures, four crystallographically independent cis-[Pt(NH3)2(d(pGpG]] molecules aggregate into a tetrameric cluster that is stabilized by a large number of intermolecular hydrogen bonds and base-base stacking interactions. In each molecule, the platinum atom is coordinated to the N7 atoms of two guanine bases arranged in a head-to-head orientation, resulting in a large dihedral angle between the guanines. Intermolecular guanine-guanine base pairings between different intrastrand crosslinked molecules are used extensively in the crystal lattice.


[Influences of hypertension and diabetes on arterial compliances and endothelial microparticle level].
To study the influences of hypertension and diabetes on arterial compliances and endothelial microparticle level. Fifty patients with hypertension and diabetes, 46 with hypertension, and 48 with diabetes were enrolled in this study, with 50 healthy volunteers group serving as the normal control. Large arterial compliance (C1) and small arterial compliance (C2) were measured using CVProfilor DO2020 cardiovascular profiling system, and the levels of CD31+/CD42- endothelial microparticles (EMPs) were determined by flow cytometry in these subjects. Compared with the hypertensive patients, diabetic patients and healthy volunteers, the patients with both hypertension and diabetes showed significantly decreased C1 and C2. C1 and C2 were significantly decreased in the hypertensive patients in comparison with those in the diabetic patients and the healthy volunteers. Compared with the healthy volunteers group, the diabetic patients showed markedly decreased C2 but normal C1. The levels of CD31+/CD42- EMPs were significantly increased in patients with both hypertension and diabetes compared with the other groups, and the diabetic patients had higher EMPs levels than the hypertensive patients. Pearson regression analysis indicated that C1 and C2 were inversely, while the levels of EMPs positively, correlated to the pulse pressure and 2 h plasma glucose; the levels of EMPs were not related with fasting glycemia. Hypertension appears to have greater impact on arterial compliance, especially C1, while diabetes is the major factor responsible for increased release of EMPs.


Hastening Progress in Cyclospora Requires Studying Eimeria Surrogates.
Cyclospora cayetanensis is an enigmatic human parasite that sickens thousands of people worldwide. The scarcity of research material and lack of any animal model or cell culture system slows research, denying the produce industry, epidemiologists, and regulatory agencies of tools that might aid diagnosis, risk assessment, and risk abatement. Fortunately, related species offer a strong foundation when used as surrogates to study parasites of this type. Species of Eimeria lend themselves especially well as surrogates for C. cayetanensis. Those Eimeria that infect poultry can be produced in abundance, share many biological features with Cyclospora, pose no risk to the health of researchers, and can be studied in their natural hosts. Here, we overview the actual and potential uses of such surrogates to advance understanding of C. cayetanensis biology, diagnostics, control, and genomics, focusing on opportunities to improve prevention, surveillance, risk assessment, and risk reduction. Studying Eimeria surrogates accelerates progress, closing important research gaps and refining promising tools for producers and food safety regulators to monitor and ameliorate the food safety risks imposed by this emerging, enigmatic parasite.


Medical student evaluation using augmented standardized patients: new development and results.
Standardized patients (SPs), individuals who realistically portray patients, are widely used in medical education to teach and assess communication skills, eliciting a history, performing a physical exam, and other important clinical skills. They are typically healthy individuals with few or no abnormal physical findings. One limitation is that each SP can only portray a limited set of physical symptoms. We have developed a functioning prototype that uses sound-based augmented reality (AR) to expand the capabilities of an SP to exhibit physically-manifested abnormalities. The previous research and evaluation of this prototype have been published in medicine meets virtual reality conference in January 2006. Current research has combined a virtual crackle sound with a healthy SP's real breath sound at end of inspiration in real time. The technology used is intended to correlate the inspiration timing of SP's. A learner will hear this simulated sound through an electronic-stethoscope wirelessly.


Health professionals' views of medical teleconsultation uptake in the Brazilian Unified Health System: A description using the NASSS framework.
The COVID-19 pandemic accelerated efforts to deploy and regulate medical teleconsultation in Brazil. Studying the Brazilian Unified Public Health System (SUS) experiences in implementing teleconsultations can help to inform their sustainability. This study identifies the changes required to integrate specialized teleconsultation in local workflows in SUS. A case study of teleconsultation performed by a University Hospital and a Municipal Specialty Outpatient Clinic in the south of Brazil collected information from two focus groups with specialised doctors, two key informant interviews and associated documents. The Non-adoption, Abandonment, Scale-up, Spread, and Sustainability (NASSS) framework domains of condition, technology, proposal value, users and organization informed a qualitative thematic analysis of this data. Several forms of teleconsultation were used to manage paediatrics and endocrine conditions including instant messaging, WhatsApp, telephone calls and video consultations which were also used for dermatology. In Brazil, telephone interactions are not considered teleconsultation. In contrast, video consultations were longer than face-to-face appointments, facilitate the understanding and evaluation of conditions, and offered continuity of care, comfort, and safety, without the need for patients to travel, reducing the risk of infection. Patients accepted video consultations to varying degrees but some found it difficult to use the technology. The willingness of doctors to provide any form of teleconsultation was important. Management support was key to defining workflows, coordinating care pathways, and providing technical support. This study highlights particularities of teleconsultation uptake for the included specialities. The NASSS framework provides a useful means of identifying the changes to enable teleconsultation continuity for specialised care in SUS.


Seasonal and environmental effects on upper thermal limits of eastern sand darter (Ammocrypta pellucida).
Anthropogenic stressors are predicted to increase water temperature, which can influence physiological, individual, and population processes in fishes. We assessed the critical thermal maximum (CTmax) of eastern sand darter (Ammocrypta pellucida), a small benthic fish listed as threatened under the Species at Risk Act in Canada. Field trials were conducted stream side June-November 2019 in the Grand River, Ontario, to encompass a range of ambient water temperatures (7-25°C) for which agitation temperature (Tag) and CTmax were determined. Additional measures were taken in the comparatively more turbid Thames River to test the effect of turbidity on both measures. In the Grand, Tag and CTmax ranged from 23°C to 33°C and 27°C to 37°C, respectively, and both significantly increased with ambient water temperature, with a high acclimation response ratio (0.49). The thermal safety margin (difference between ambient temperatures and CTmax) was smallest in July and August (~11°C) indicating that eastern sand darter lives closer to its physiological limit in summer. The between-river comparison indicated that turbidity had no significant influence on Tag and CTmax. Comparison of CTmax with in-river temperatures suggested that mean stream temperature 24 hours before the trial was most important for determining CTmax. Fish mass, temperature variance and maximum temperature in the 24-hour period prior to the CTmax trial were also shown to have some effect on determining CTmax. Overall, study results better define the sensitivity of eastern sand darter to temperature changes across the growing season and provide information to assess the availability of suitable thermal habitat for conservation purposes.


A Novel Sensor System for In Vivo Perception Reconstruction Based on Long Short-Term Memory Networks.
Monitoring bodily pressure could provide valuable medical information for both doctors and patients. Long-term implantation of in vivo sensors is highly desirable in situations where perception reconstruction is needed. In particular, for fecal incontinence, artificial anal sphincters without perceptions could not remind patients when to defecate and even cause ischemic tissue necrosis due to uncontrolled clamping pressure. To address these issues, a novel self-packaging strain gauge sensor system is designed for in vivo perception reconstruction. In addition, long short-term memory (LSTM) networks, which show excellent performance in processing time series-related features and fitting properties, are used in this article to improve the prediction accuracy of the perception model. The proposed system has been tested and compared with the traditional linear regression (LR) approach using data from in vitro experiments. The results show that the Root-Mean-Square Error (RMSE) is reduced by more than 69%, which demonstrates that the prediction accuracy of the proposed LSTM model is higher than that of the LR model to reach a more accurate prediction of the amount of intestinal content. Furthermore, outcomes of in vivo experiments show that the robustness of the novel sensor system based on long short-term memory networks is verified through experiments with limited data.


Micropropagation by tissue culture triggers differential expression of infectious endogenous Banana streak virus sequences (eBSV) present in the B genome of natural and synthetic interspecific banana plantains.
The genome of Musa balbisiana spp. contains several infectious endogenous sequences of Banana streak virus (eBSV). We have shown previously that in vitro micropropagation triggers the activation of infectious eBSOLV (endogenous sequences of Banana streak Obino l'Ewai virus) in the synthetic tetraploid interspecific hybrid FHIA21 (AAAB). In this work, we show that another synthetic tetraploid (AAAB) hybrid and two natural triploid (AAB) plantains are equally prone to the activation of infectious eBSOLV during tissue culture. These results are a strong indication that such activation is a general phenomenon in interspecific Musa cultivars, whether synthetic or natural. We also report the first in-depth study of the correlation between the duration of tissue culture and the level of activation of infectious eBSOLV, and show that specific and common activation patterns exist in these banana plants. We hypothesize that these patterns result from the concomitant activation of infectious eBSOLV and a decrease in the virus titre in neoformed plantlets, resulting from cell multiplication outcompeting virus replication. We provide experimental data supporting this hypothesis. No activation of infectious eBSGFV (endogenous sequences of Banana streak Goldfinger virus) by tissue culture was observed in the two natural AAB plantain cultivars studied here, whereas such activation occurred in the AAAB synthetic hybrid studied. We demonstrate that this differential activation does not result from differences in the structure of eBSGFV, as all banana genomes harbour eaBSGFV-7.


The Hippo Pathway and Viral Infections.
The Hippo signaling pathway is a novel tumor suppressor pathway, initially found in Drosophila. Recent studies have discovered that the Hippo signaling pathway plays a critical role in a wide range of biological processes, including organ size control, cell proliferation, cancer development, and virus-induced diseases. In this review, we summarize the current understanding of the biological feature and pathological role of the Hippo pathway, focusing particularly on current findings in the function of the Hippo pathway in virus infection and pathogenesis.


Impaired Neurite Contact Guidance in Ubiquitin Ligase E3a (Ube3a)-Deficient Hippocampal Neurons on Nanostructured Substrates.
Recent discoveries indicate that during neuronal development the signaling processes that regulate extracellular sensing (e.g., adhesion, cytoskeletal dynamics) are important targets for ubiquitination-dependent regulation, in particular through E3 ubiquitin ligases. Among these, Ubiquitin E3a ligase (UBE3A) has a key role in brain functioning, but its function and how its deficiency results in the neurodevelopmental disorder Angelman syndrome is still unclear. Here, the role of UBE3A is investigated in neurite contact guidance during neuronal development, in vitro. The microtopography sensing of wild-type and Ube3a-deficient hippocampal neurons is studied by exploiting gratings with different topographical characteristics, with the aim to compare their capabilities to read and follow physical directional stimuli. It is shown that neuronal contact guidance is defective in Ube3a-deficient neurons, and this behavior is linked to an impaired activation of the focal adhesion signaling pathway. Taken together, the results suggest that the neuronal contact sensing machinery might be affected in Angelman syndrome.


Circulating extracellular vesicles are associated with lipid and insulin metabolism.
We have reported that hypertrophic adipocytes release extracellular vesicles (EVs) and the number of circulating adipocyte-derived EVs correlated with insulin and homeostasis model assessment-insulin resistance (HOMA-IR) in a pilot study using obese patients. Here, we explored the association between circulating EV level and various metabolic parameters, including obesity and lipid and glucose metabolisms, among 203 subjects (76 men and 127 women; median age, 54 yr) with or without risk factor for metabolic diseases, who received a 75-g oral glucose tolerance test (OGTT). Circulating EV number was significantly higher in men than in women ( P < 0.001). Circulating EV number in individuals with impaired OGTT pattern was significantly higher compared with those with normal OGTT patterns ( P < 0.05). Multiple regression analysis revealed that circulating EV number correlated most strongly and significantly with elevated triglyceride (TG; t = 8.55, P < 0.001). Additionally, circulating EV number correlated significantly with homeostasis model assessment-β-cell function (HOMA-β; t = 2.38, P < 0.05). Receiver operating characteristic curve revealed that the cutoff value of EV numbers in individuals with elevated serum TG levels (≧150 mg/dl) was identified (136,738 EVs/μl of plasma, P < 0.001, sensitivity 0.842, false-positive rate of 0.257). Perilipin and asialoglycoprotein receptor 1 were detected on a part of isolated circulating EVs, indicating EV release from adipocytes and hepatocytes, which were related to lipid and glucose metabolism. Circulating EVs represent a promising metabolic biomarker for lipid and glucose metabolism and have potential for monitoring metabolic status in humans, including individuals without metabolic risk factors.


Synthesis, structure, and complexation of a large 28-mer macrocycle containing two binding sites for either anions or metal ions.
The "one-pot" synthesis and characterization of a large 28-mer macrocycle (H(4)L(2)) with oxamido units capable of complexing guest ions through oxygen or nitrogen donor atoms is reported. Single-crystal structure determination of H(8)L(2)(NO(3))(4) and (Cu(2)[H(2)L(2)](H(2)O)(2))(NO(3))(2) demonstrated that the macrocycle contains two sites capable of complexing two nitrate anions or two copper(II) ions, involving a large structural reorganization in the conformation of the macrocyclic framework on coordination of the copper(II) ions when compared to the nitrate. Electrochemical and magnetic susceptibility measurements on the dinuclear Cu(II) complex and the related mononuclear and trinuclear Cu(II) complexes derived from the related 14-mer macrocycle were carried out and illustrate the role of the oxamido groups in mediating metal-metal interaction and delocalization.


Betel-quid use is associated with the risk of the metabolic syndrome in adults.
Betel-quid use has been associated with obesity and hyperglycemia in previous studies. The aim was to test whether betel-quid use contributes to the metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel III. Associations between betel-quid use and the metabolic syndrome, obesity, hypertriacylglycerolemia, low HDL cholesterol, hyperglycemia, and high blood pressure after adjustment for sex, age, smoking, alcohol drinking, physical activity, and dietary intakes were studied in nonpregnant adults aged 20-64 y (n = 1986) from the Nutrition and Health Survey in Taiwan (1993-1996). The prevalence of the metabolic syndrome was not significantly different between the men and women (10.1% compared with 9.7%), whereas the prevalence of betel-quid use was higher in the men than in the women (31% compared with 2.3%; P < 0.001). The daily rate of betel-quid use was associated with the metabolic syndrome [odds ratio (OR) associated with a betel-quid consumption rate of 10 times/d: 1.31; 95% CI: 1.12, 1.55; P = 0.003], abdominal obesity (OR: 1.42; 95% CI: 1.2, 1.7; P = 0.001), hypertriacylglycerolemia (OR: 1.33; 95% CI: 1.02, 1.73; P = 0.037), and high blood pressure (OR: 1.2; 95% CI: 1.01, 1.4; P = 0.04). However, the daily rate of betel-quid use was not associated with low HDL cholesterol or hyperglycemia. The daily rate of betel-quid use is independently and positively associated with the metabolic syndrome in adults.


Location of Keratin-associated Proteins in Developing Fiber Cuticle Cells using Immunoelectron Microscopy.
To investigate the location of keratin-associated proteins (KAPs) in developing hair fiber cuticle cells using transmission electron microscopy with immunogold techniques and specific antibodies. Other studies were aimed at detecting the presence of cornified envelope proteins including involucrin and loricrin. MATEIALS AND METHODS: Polyclonal antibodies were produced in rabbits against peptides from KAPS 5.1, KAPS 10.1 ultra high-sulfur proteins. The KAP proteins were found to form part of the developing exocuticle and a- layer. Cornified envelope proteins (involucrin and loricrin) were absent consistent with recent findings. The results have been discussed in terms of a revised model for fiber cuticle surface barriers including their role in fiber cuticle surface function.


[Unusual suicide caused by a stab wound in the neck].
A case is reported of a man with a deep nape stabwound completely severing the medulla of the spine. A strangely formed bottle neck fragment is the assumed weapon. Further investigations allow a scene reconstruktion, police inquiries throw light on a previous acute psychotic disorder of the suicide.


Oral lesions as clinical markers of highly active antiretroviral therapy failure: a nested case-control study in Mexico City.
Clinical markers that may predict virological failure during highly active antiretroviral therapy (HAART) have not been evaluated adequately. The aim of the present study was to evaluate the usefulness of human immunodeficiency virus (HIV)-related oral lesions as clinical predictors of virological failure in HIV-infected patients receiving HAART. A nested case-control study was conducted within a cohort of 1134 HIV-infected patients receiving HAART who attended the AIDS Clinic of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City during the period 1997-2005. Case patients were patients who, after achieving an undetectable viral load, had at least 1 viral load determination > or = 2000 copies/mL while receiving treatment. Control subjects were patients who, after achieving an undetectable viral load, continued to have undetectable viral loads during the follow-up period. There were 2-3 control subjects for each case patient, matched according to duration of follow-up. Oral examinations were blinded to viral loads and CD4+ lymphocyte counts. Analyses were performed with multivariate conditional logistic regression models, and associations were shown as odds ratios (ORs) with 95% confidence intervals (CI). Positive predictive values were calculated. The target cohort consisted of 431 HIV-infected individuals; 47 case patients and 132 control subjects underwent complete oral examinations and formed the basis of the analysis. At the visit at which an undetectable viral load was determined, case patients and control subjects showed a similar frequency of HIV-related oral lesions (21.3% vs. 17.4%) (OR, 1.39; 95% CI, 0.57-3.38; P=.47). At the visit at which virological failure was determined, case patients showed a higher risk for HIV-related oral lesions (OR, 14.5; 95% CI, 4.21-49.94; P<.001) and oral candidosis (OR, 26.2; 95% CI, 3.34-205.9; P<.001) than did control subjects. The positive predictive value of HIV-related oral lesions and oral candidosis to identify patients who experienced virological failure while receiving HAART was 80% and 83%, respectively. HIV-related oral lesions and, specifically, oral candidosis may be considered to be clinical markers of virological failure in HIV-infected patients receiving HAART.


MYC amplification and polysomy 8 in chondrosarcoma: array comparative genomic hybridization, fluorescent in situ hybridization, and association with outcome.
To identify recurrent regions of genomic gain or loss in chondrosarcoma in a clinically relevant and statistically valid fashion. Array comparative genomic hybridization (CGH) results of 15 frozen tumor samples of high-grade chondrosarcoma for chromosome 8 are presented. A separate subset of 116 cartilaginous tumors with outcome data was used for validation. Array CGH identified gain at 8q24.12-q24.13, the region of the MYC (c-Myc) oncogene, as a frequent change in high-grade chondrosarcoma. In the validation arm of 116 cartilaginous tumors, MYC was frequently amplified in G2 (15%), G3 (20%), and dedifferentiated (21%) chondrosarcomas. No amplification was identified in samples of enchondroma and grade 1 chondrosarcoma. In samples without MYC amplification, polysomy 8 was a frequent finding in grade 1 (18%), grade 2 (31%), grade 3 (80%), and dedifferentiated (29%) chondrosarcomas, but was not found in any samples of enchondroma. MYC protein expression was identified in all samples with amplification, but was also frequent in the remaining samples without amplification or polysomy 8. Kaplan-Meier survival curves for overall survival showed a statistically significant difference for patients with MYC amplification or polysomy 8 (P = .034). Univariate analysis involving Cox proportional hazards models showed that grade (P = .003), polysomy 8 (P = .045), and MYC amplification (P = .053) correlated with shorter overall survival. By multivariate analysis, grade of chondrosarcoma (P = .026) was the only factor to reach statistical significance. MYC amplification and polysomy 8 can be used as markers of prognostic importance in chondrosarcoma. Molecular targeting of MYC expression may have therapeutic potential in the future for subsets of chondrosarcoma.


Survival study of leukoplakia malignant transformation in a region of northern Spain.
Oral leukoplakia is the most common potentially malignant disorder (PMD) of the oral cavity. The objectives of this study are to determine the clinicopathologic features in a group of patients with oral leukoplakia of Northern Spain (Galicia), determining the factors associated to clinical risk and analyzing the malignant transformation of these patients. We included 85 patients. We recorded sex and age, habits like alcohol and tobacco, size, clinical appearance, site, number of lesions, and presence or absence of dysplasia. We assess the association between risk factors and transformation and developed a logistic regression analysis. Finally we used the Kaplan-Meier and log-rank test for the survival analysis. 7 patients (8.2%) had malignant transformation. The mean follow-up of the patients was 4.13 years versus 5.58 years of those who developed carcinoma. Only location and initial dysplasia have a statistically significant relationship with malignant transformation, but when applied the long rank test only the presence of dysplasia remains statistically significant(P<0,026). Oral Cancer Free Survival was 81.9% (0.150) at 11 years for the group without dysplasia. We found that the presence of dysplasia is the only risk factor that is statistically related to the development of a carcinoma.


In Vitro and In Vivo Evaluation of ABCG2 (BCRP) Inhibitors Derived from Ko143.
Breast cancer resistance protein (BCRP, ABCG2) is an efflux transporter that plays a crucial role in multidrug resistance to antineoplastic drugs. Ko143, an analogue of the natural product fumitremorgin C, is a potent inhibitor of ABCG2 but is rapidly hydrolyzed to an inactive metabolite in vivo. To identify ABCG2 inhibitors with improved metabolic stability, we have assessed a series of Ko143 analogues for their ability to inhibit ABCG2-mediated transport in ABCG2-transduced MDCK II cells and determined the stability of the most potent compounds in liver microsomes. The most promising analogues were evaluated in vivo by positron emission tomography. In vitro, three of the tested analogues were potent ABCG2 inhibitors and stable in microsomes. In vivo, they increased the distribution of the ABCG2/ABCB1 substrate [11C]tariquidar to the brain both in wild-type (with Abcb1a/b transport blocked by tariquidar) and Abcb1a/b(-/-) mice. One analogue was more potent than Ko143 in both animal models.


The impact of the open-access status on journal indices: a review of medical journals.
Background: Over the past few decades, there has been an increase in the number of open access (OA) journals in almost all disciplines. This increase in OA journals was accompanied an increase in funding to support such movements. Medical fields are among the highest funded fields, which further promoted its journals to move toward OA publishing. Here, we aim to compare OA and non-OA journals in terms of citation metrics and other indices. Methods: We collected data on the included journals from Scopus Source List on 1 st November 2018. We filtered the list for medical journals only. For each journal, we extracted data regarding citation metrics, scholarly output, and wither the journal is OA or non-OA. Results: On the 2017 Scopus list of journals, there was 5835 medical journals. Upon analyzing the difference between medical OA and non-OA journals, we found that OA journals had a significantly higher CiteScore (p< 0.001), percent cited (p< 0.001), and source normalized impact per paper (SNIP) (p< 0.001), whereas non-OA journals had higher scholarly output (p< 0.001). Among the five largest journal publishers, Springer Nature published the highest frequency of OA articles (31.5%), while Wiley-Blackwell had the lowest frequency among its medical journals (4.4%). Conclusion: Among medical journals, although non-OA journals still have higher output in terms of articles per year, OA journals have higher citation metrics.


Targeted Mutagenesis of the Multicopy Myrosinase Gene Family in Allotetraploid Brassica juncea Reduces Pungency in Fresh Leaves across Environments.
Recent breeding efforts in Brassica have focused on the development of new oilseed feedstock crop for biofuels (e.g., ethanol, biodiesel, bio-jet fuel), bio-industrial uses (e.g., bio-plastics, lubricants), specialty fatty acids (e.g., erucic acid), and producing low glucosinolates levels for oilseed and feed meal production for animal consumption. We identified a novel opportunity to enhance the availability of nutritious, fresh leafy greens for human consumption. Here, we demonstrated the efficacy of disarming the 'mustard bomb' reaction in reducing pungency upon the mastication of fresh tissue-a major source of unpleasant flavor and/or odor in leafy Brassica. Using gene-specific mutagenesis via CRISPR-Cas12a, we created knockouts of all functional copies of the type-I myrosinase multigene family in tetraploid Brassica juncea. Our greenhouse and field trials demonstrate, via sensory and biochemical analyses, a stable reduction in pungency in edited plants across multiple environments. Collectively, these efforts provide a compelling path toward boosting the human consumption of nutrient-dense, fresh, leafy green vegetables.


A Systematic Approach to HIV-1 Vaccine Immunogen Selection.
A tremendous loss of financial and human resources from seven large-scale HIV vaccine efficacy trials suggest a need for a systematic approach to vaccine selection. We conducted a systematic analysis of three important envelope glycoprotein (Env) vaccine candidates: BG505 SOSIP.664, 1086.C gp140, and 1086.C gp120 to determine the most promising by comparing their structure and antigenicity. We found that the BG505 SOSIP trimer and 1086.C gp140 clearly outperformed the 1086.C gp120 monomer. BG505 SOSIP.664 bound the strongest to the most potent and broadest broadly neutralizing antibodies (bnAbs) PG9, PGT145, VRC01, and PGT121. Of interest, although BG505 SOSIP.664 did not bind to the CH58 mAb, 1086.C gp140 bound strongly to this mAb, which belongs to a class of non-neutralizing antibodies that may be protective based on correlates of protection studies of the RV144 HIV vaccine trial. The 1086.C gp120 monomer was the least antigenic of the three vaccine immunogens, binding the weakest to bnAbs and CH58 mAb. Taken together, the evidence provided here combined with previous preclinical immunogenicity and efficacy data strongly argue that the BG505 SOSIP.664 trimer and 1086.C gp140 are likely to be better vaccine immunogens than the monomeric 1086.C gp120, which was just recently tested and shown to be nonefficacious in a phase IIb/III trial. Thus, to best utilize our financial and valuable human resources, we propose a systematic approach by not only comparing structure and antigenicity, but also immunogenicity and efficacy of Env vaccine candidates in the preclinical phase to the selection of only the most promising vaccine candidates for clinical testing.


Left atrial fibroelastoma.
We describe a 67-year-old man with a history of stroke who was found to have a mass at the left atrial ridge, at the free wall of the left atrium between the left atrial appendage and the pulmonary vein. The mass was removed surgically and pathological analysis showed fibroelastoma. A literature search showed that fibroelastoma in the left atrial ridge frequently causes embolic stroke.


Pregnane X receptor polymorphism affects CYP3A4 induction via a ligand-dependent interaction with steroid receptor coactivator-1.
The human pregnane X receptor is a ligand-dependent transcription factor that plays critical roles in regulating detoxification genes such as CYP3A4 by recruiting transcriptional coactivators such as steroid receptor coactivator-1 in a ligand-dependent manner. In a previous study (Pharmacogenetics and Genomics 2005, 15: 337-341), we reported a novel pregnane X receptor single nucleotide polymorphism, Q158K, which impaired transactivation of CYP3A4. By using DNA affinity precipitation assay and electrophoretic mobility shift assay, we have now shown that Q158K does not alter the binding affinity of pregnane X receptor for the CYP3A4 promoter. Instead, as shown using a mammalian two-hybrid assay, it decreased the interaction of pregnane X receptor with steroid receptor coactivator-1 in the presence of rifampin, clotrimazole, paclitaxel, or nifedipine but not in their absence. Rifampin treatment markedly increased pregnane X receptor protein in the wild-type pregnane X receptor-transfected cells as shown by coimmunoprecipitation but not in Q158K pregnane X receptor-transfected cells. The impaired transactivation of the CYP3A4 promoter was reversed by transfecting steroid receptor coactivator-1 expression plasmids. An additional nine pregnane X receptor variants were isolated and selected by random mutagenesis. Mutations Q158, W223, F257, I346, and L424 also reduced CYP3A4 transactivation and interaction in mammalian two-hybrid assays only in the presence of ligands. Although Q158K did not greatly affect the interaction of pregnane X receptor to silencing mediator of retinoid and thyroid hormone receptor, pregnane X receptor-silencing mediator of retinoid and thyroid hormone receptor interaction was impaired in the F257L and I346T variants with or without the presence of pregnane X receptor ligands. Our data indicate that the impaired induction by the Q158K variant is probably due to defective steroid receptor coactivator-1 interaction in the presence of a pregnane X receptor ligand. As the whole ligand binding domain of pregnane X receptor is required for the interaction with steroid receptor coactivator-1, we propose that, not only the Q158K variant found in Chinese, but also in native pregnane X receptor variants in other ethnic groups (D163G, A370T, R381W, and I403V) affect CYP3A4 induction by altering steroid receptor coactivator-1 recruitment.


Positron Emission Tomography (PET) Imaging Tracers for Serotonin Receptors.
Serotonin (5-hydroxytryptamine, 5-HT) and 5-HT receptors (5-HTRs) have crucial roles in various neuropsychiatric disorders and neurodegenerative diseases, making them attractive diagnostic and therapeutic targets. Positron emission tomography (PET) is a noninvasive nuclear molecular imaging technique and is an essential tool in clinical diagnosis and drug discovery. In this context, numerous PET ligands have been developed for "visualizing" 5-HTRs in the brain and translated into human use to study disease mechanisms and/or support drug development. Herein, we present a comprehensive repertoire of 5-HTR PET ligands by focusing on their chemotypes and performance in PET imaging studies. Furthermore, this Perspective summarizes recent 5-HTR-focused drug discovery, including biased agonists and allosteric modulators, which would stimulate the development of more potent and subtype-selective 5-HTR PET ligands and thus further our understanding of 5-HTR biology.


Attenuation of herpes simplex virus neurovirulence with picornavirus cis-acting genetic elements.
Viral pathogenesis depends on a suitable milieu in target host cells permitting viral gene expression, propagation, and spread. In many instances, viral genomes can be manipulated to select for propagation in certain tissues or cell types. This has been achieved for the neurotropic poliovirus (PV) by exchange of the internal ribosomal entry site (IRES), which is responsible for translation of the uncapped plus-strand RNA genome. The IRES of human rhinovirus type 2 (HRV2) confers neuron-specific replication deficits to PV but has no effect on viral propagation in malignant glioma cells. We report here that placing the critical gamma(1)34.5 virulence genes of herpes simplex virus type 1 (HSV) under translation control of the HRV2 IRES results in neuroattenuation in mice. In contrast, IRES insertion permits HSV propagation in malignant glioma cell lines that do not support replication of HSV recombinants carrying gamma(1)34.5 deletions. Our observations indicate that the conditions for alternative translation initiation at the HRV2 IRES in malignant glioma cells differ from those in normal central nervous system (CNS) cells. Picornavirus regulatory sequences mediating cell type-specific gene expression in the CNS can be utilized to target cancerous cells at the level of translation regulation outside their natural context.


Designing a research agenda to improve the quality of emergency care.
A systematic approach to develop a research agenda for improving the quality of emergency care is presented. This approach is based on the six domains of quality outlined by the Institute of Medicine (effective, timely, efficient, safe, patient-centered, and equitable care) and a sequence of four research steps (evidence, synthesis, assessment, and intervention). Examples related to the care of patients with acute myocardial infarction are used to illustrate the proposed approach. Examples of other emergency medicine research topics relevant to the Institute of Medicine quality domains are also presented. Research to improve the quality of emergency care can benefit from a more systematic consideration of the domains of quality and the research steps necessary to generate evidence and inform quality improvement efforts in practice.


Negative studies published in Indian medical journals are underpowered.
51 inconclusive studies published in 14 Indian medical journals were analyzed for adequacy of power by post hoc power calculation. No study was found to be adequately powered (%80%) at small effect size, only 8 studies were adequately powered for medium effect size and 30 studies were adequately powered at large effect size.


The Use of a High-Pressure Water-Ice Jet for Removing Worn Paint Coating in Renovation Process.
The paper presents the results of investigations into the possibility of using ahigh-pressure water-ice jet as a new method for removing a worn-out paint coating from the surface of metal parts (including those found in means of transportation) and for preparing the base surface for the application of renovation paint coating. Experimental investigations were carried out in four stages, on flat specimens, sized S × H = 75 × 115 mm, cut from sheet metal made of various materials such as steel X5CrNi18-10, PA2 aluminium alloy and PMMA polymethyl methacrylate (plastic). In the first stage, the surfaces of the samples were subjected to observation of surface morphology under a scanning electron microscope, and surface topography (ST) measurements were made on a profilographometer. Two ST parameters were analysed in detail: the maximum height of surface roughness Sz and the arithmetic mean surface roughness Sa. Next, paint coatings were applied to the specimens as a base. In the third stage, the paint coating applied was removed by means of a high-pressure water-ice jet (HPWIJ) by changing the values of the technological parameters, i.e., water jet pressure pw, dry ice mass flow rate m˙L, distance between the sprinkler head outlet and the surface being treated (the so-called working jet length) l2 and spray angle κ for the following constants: the number of TS = 4 holes, water hole diameter φ = 1.2 mm and sprinkler head length Lk = 200 mm. Afterwards, the surface morphology was observed again and the surface topography of the specimen was investigated by measuring selected 3D parameters of the ST structure, Sz and Sa. The results of investigations into the influence of selected HPWIJ treatment parameters on the surface QF removal efficiency obtained are also presented. Univariate regression functions were developed for the mean stripping efficiency based on the following: dry ice mass flow rate m˙L, working jet length l2 and spray angle κ. Based on these functions, the values of optimal parameters were determined that allow the maximum efficiency of the process to be obtained. A 95% confidence region for the regression function was also developed. The results demonstrated that HPWIJ treatment does not interfere with the geometric structure of the base material, and they confirmed the possibility of using this treatment as an efficient method of removing a worn paint layer from bases made of various metal and plastic materials, and preparing it for applying a new layer during renovation.


A Screening Method for the Isolation of Escherichia coli O157:H7 from Ground Beef.
A screening method was developed for the isolation of Escherichia coli O157:H7 from raw ground beef. Suspensions at a 1:10 dilution of beef were made in a modified EC broth with novobiocin (mEC+n; EC broth with 1.12 g/L instead of 1.5 g/L Bile salts #3 and novobiocin at 20 mg/L). The samples were macerated in a Stomacher for 2 min and either shaken at 37°C (100 RPM) for 6 h, or incubated static at 35°C for 24 h. Appropriate dilutions of the cultures were then spread plated on 150×15 mm plates of MacConkey sorbitol agar (MSA). The MSA plates were incubated at 42°C overnight. A set of two plates consisting of a deep (40 ml/plate) phenol red sorbitol agar plate with 4-methylumbelliferyl ß-D-glucuronide (PRS-MUG), and a Levine EMB agar plate with added agar for a final concentration of 3%, were gridded into 12 numbered sections. Sorbitol negative colonies were picked from the MSA plates, spread on the appropriate section of the EMB, and stabbed into the corresponding section on the PRS-MUG plate. Those cultures that were sorbitol negative and MUG negative on PRS-MUG and were typically E. coli on EMB were confirmed biochemically and serologically. By this procedure O157:H7 was isolated from 5 of 10 meat samples inoculated at 0.6 organisms/g, and 10 of 10 samples at the 5/g level using the 6 h shaken method. With the 24 h static incubation method, O157:H7 was isolated from 8 of 10 samples at the 0.6/g level and 10 of 10 at the 5/g level. Thirteen strains of O157:H7 inoculated at levels between 0.4 and 0.6/g were tested and 9 of the 13 were isolated with the 6 h method, and 13 of the 13 with the 24 h method. The method is reliable and simple enough to be used in large screening programs.


Fuzzy Logic, Artificial Neural Network, and Adaptive Neuro-Fuzzy Inference Methodology for Soft Computation and Modeling of Ion Sensing Data of a Terpyridyl-Imidazole Based Bifunctional Receptor.
Anion and cation sensing aspects of a terpyridyl-imidazole based receptor have been utilized in this work for the fabrication of multiply configurable Boolean and fuzzy logic systems. The terpyridine moiety of the receptor is used for cation sensing through coordination, whereas the imidazole motif is utilized for anion sensing via hydrogen bonding interaction and/or anion-induced deprotonation, and the recognition event was monitored through absorption and emission spectroscopy. The receptor functions as a selective sensor for F- and Fe2+ among the studied anions and cations, respectively. Interestingly, the complexation of the receptor by Fe2+ and its decomplexation by F- and deprotonation of the receptor by F- and restoration to its initial form by acid are reversible and can be recycled. The receptor can mimic various logic operations such as combinatorial logic gate and keypad lock using its spectral responses through the sequential use of ionic inputs. Conducting very detailed sensing studies by varying the concentration of the analytes within a wide domain is often very time-consuming, laborious, and expensive. To decrease the time and expenses of the investigations, soft computing approaches such as artificial neural networks (ANNs), fuzzy logic, or adaptive neuro-fuzzy inference system (ANFIS) can be recommended to predict the experimental spectral data. Soft computing approaches to artificial intelligence (AI) include neural networks, fuzzy systems, evolutionary computation, and other tools based on statistical and mathematical optimizations. This study compares fuzzy, ANN, and ANFIS outputs to model the protonation-deprotonation and complexation-decomplexation behaviors of the receptor. Triangular membership functions (trimf) are used to model the ANFIS methodology. A good correlation is observed between experimental and model output data. The testing root mean square error (RMSE) for the ANFIS model is 0.0023 for protonation-deprotonation and 0.0036 for complexation-decomplexation data.


First aid with color atlas for the use of intestinal ultrasound for inflammatory bowel disease in daily clinical practice.
Intestinal ultrasound (IUS) is a promising modality for the management of inflammatory bowel disease (IBD) and has the potential to particularly contribute in monitoring disease activity, an advantage crucial for optimizing the therapeutic strategy. While many IBD physicians appreciate and are interested in the use of IUS for IBD, currently only a limited number of facilities can employ this examination in daily clinical practice. A lack of guidance is one of the major barriers to introducing this procedure. Standardized protocols and assessment criteria are needed such that IUS for IBD can be considered a feasible, reliable examination in clinical practice, and multicenter clinical studies can be conducted for further clinical evidence of the application of IUS in IBD for best patient care. In this article, we provide an overview of how to start IUS for IBD and introduce basic procedures. Furthermore, IUS images from our practice are provided as a color atlas for understanding sonographic findings and scoring systems. We anticipate this "first aid" article will be helpful to promote IUS for IBD in daily practice.


How parents express their worry in calls to a medical helpline: a mixed methods study.
Telephone triage is used globally in out-of-hours primary care, to prioritize who needs urgent assessment. Even though children rarely are severely ill, calls about sick children are among the most prevalent, mainly due to parental worry. Pediatric calls are considered challenging, as the call-handler must rely on parents' second-hand information. We aimed to investigate if parents' worry can be used as a predictor of severe illness, and if the content of the calls varies between different grades of worry. In a convergent mixed methods study design we asked patients to rate their degree-of-worry before talking to a call-handler. We used quantitative data of degree-of-worry, triage- and patient outcome in pediatric calls (n = 2857), and the qualitative content from 54 calls with subsequent hospitalization ≥24 h. High degree-of-worry was associated with hospitalization ≥24 h (OR 3.33, 95% CI 1.53-7.21). Qualitative findings both confirmed and expanded knowledge of degree-of-worry. Worry was the predominant cause for contact overall, and was mainly triggered by loss-of-control. In calls with high degree-of-worry, the prevalence of loss-of-control was especially high, and the parents had additionally often contacted healthcare services recently. Parents with a foreign accent often rated their worry as high, and these callers were often ignored or interrupted. Calls with low degree-of-worry seemed to occur early during the disease. High degree of parental worry was associated with severe illness. At the end of calls, call-handlers should ensure that the parent has regained control of the situation to reach increased reassurance and to prevent renewed unnecessary contact. Safety-netting is crucial, as many parents made contact early during the illness and deterioration may develop later. The scoring of parental degree-of-worry may be used as an indicator of potentially severe illness and can easily be implemented at out-of-hours call-centers globally. Original study registered at clinicaltrials.gov ( NCT02979457 ).


Intra-articular soft-tissue masses of the ankle. Meniscoid lesions and transarticular fibrous bands.
Meniscoid lesions and fibrous bands are unique lesions, most likely of differing origin. Although they are similar in clinical presentation, their appearance at arthroscopy is clearly different. The meniscoid lesion is attached only at its origin at the inferolateral gutter on the anterior talofibular ligament. Fibrous bands are attached at two ends and may be found anywhere in the joint but are most common extending dramatically over the anterior joint line. Unexpected encountering of a fibrous band should alert the surgeon to carefully inspect the joint for other associated (occult) pathology. Because of the frequent association of bands with antecedent fracture, the observation of this lesion should lead the clinician to consider antecedent intra-articular fracture (transchondral fracture, malleolar fracture, and tibial pilon fracture) as a likely co-pathology. Careful examination of the ankle and review of the radiographs and other available images may be helpful in assessing the joint for these injuries when fibrous bands are encountered. The association of meniscoid lesion with prior soft tissue injury (sprain) is also important to understanding this lesion. Excision of both these abnormal lesions in concert with repair of coexistent pathology is associated with improvement of symptoms. Finally, both fibrous bands and meniscoid lesions are associated with symptoms that warrant closer inspection and observation. Whether the operative intervention is open or closed, the reader can benefit from the information presented.


Electronic Structure-Dependent Surface Plasmon Resonance in Single Au-Fe Nanoalloys.
The relationship between composition and plasmonic properties in noble metal nanoalloys is still largely unexplored. Yet, nanoalloys of noble metals, such as gold, with transition elements, such as iron, have unique properties and a number of potential applications, ranging from nanomedicine to magneto-plasmonics and plasmon-enhanced catalysis. Here, we investigate the localized surface plasmon resonance at the level of the single Au-Fe nanoparticle by applying a strategy that combines experimental measurements using near field electron energy loss spectroscopy with theoretical studies via a full wave numerical analysis and density functional theory calculations of electronic structure. We show that, as the iron fraction increases, the plasmon resonance is blue-shifted and significantly damped, as a consequence of the changes in the electronic band structure of the alloy. This allows the identification of three relevant phenomena to be considered in the design and realization of any plasmonic nanoalloy, specifically: the appearance of new states around the Fermi level; the change in the free electron density of the metal; and the blue shift of interband transitions. Overall, this study provides new opportunities for the control of the optical response in Au-Fe and other plasmonic nanoalloys, which are useful for the realization of magneto-plasmonic devices for molecular sensing, thermo-plasmonics, bioimaging, photocatalysis, and the amplification of spectroscopic signals by local field enhancement.


Potential Regulation for Surface-Enhanced Raman Scattering Detection and Identification of Carotenoids.
Surface-enhanced Raman scattering (SERS) is often impaired by the limited affinity of molecules to plasmonic substrates. Here, we use carbon fiber microelectrodes modified with silver nanoparticles as a plasmonic microsubstrate with tunable affinity for enrichment and molecular identification by SERS. The silver nanoparticles self-assemble by electrostatic interaction with diamine molecules that are electrochemically grafted onto the surface of the microelectrodes. β-carotene and trans-β-Apo-8'-carotenal, producing similar resonant SERS spectra, are employed as model molecules to study the effect of electroenrichment and SERS screening for different electrode potentials. The data show that at a characteristic electrode potential, the low affinity of polyene chains without hydrophilic groups to the substrate can be overcome. Different potentials were applied to recognize the two types of carotenoids by their typical SERS signal, and the applicability of this strategy was further confirmed in the environment of a real cell culture. The results indicate that by regulating the potential, carotenoid molecules with a similar molecular structure can be selectively quantified and identified by SERS. The developed SERS-active microelectrode is expected to help the development of portable, miniaturized point-of-care diagnostic SERS sensors.


A comparison of conventional and new rubber dam systems in dental practice.
Rubber dam is an important tool in dentistry-in the past as well as today. As a result of a lack of acceptance of the conventional system, introduced by Barnum in 1869, new systems were developed (eg, OptraDam® by Ivoclar Vivadent AG, Schaan, Liechtenstein). This system was advertised as being very comfortable and easy to use, without distracting clamps. The aim of this study was to investigate if a new rubber dam system would be better accepted by patients and dentists than the conventional one. Two hundred patients from the Department of Conservative Dentistry and Periodontology received at least one treatment with the conventional rubber dam (Dental Dam, Coltène Whaledent, Langenau, Germany) and one with the new rubber dam (OptraDam®, Ivoclar Vivadent). Staff/students and patients were asked to complete questionnaires with regard to the advantages and disadvantages of the particular system after every treatment. Among patients, students, and dentists in the dental school environment there is a high degree of acceptance of rubber dam in general. During the study there were only very few situations in which neither of the systems could be used. The conventional rubber dam was preferred by all patients, students, and dentists (p<0.0001). Our study confirms that there is a high degree of acceptance of the rubber dam when it is compulsory to use. The reasons for the refusal during the daily workload of a practice remain unclear, but appear to be independent of the material or design available. A new design does not necessarily imply better acceptance.


Influence of iron-bearing phyllosilicates on the dechlorination kinetics of 1,1,1-trichloroethane in Fe(II)/cement slurries.
This study examines the effect of iron-bearing phyllosilicates on dechlorination rates of chlorinated aliphatic hydrocarbons (CAHs) in iron-based degradative solidification/stabilization (DS/S-Fe(II)). Laboratory batch experiments were conducted to evaluate dechlorination rates of 1,1,1-trichloroethane (1,1,1-TCA) in a mixture solution of Fe(II), cement and three different iron-bearing phyllosilicates (biotite, vermiculite, and montmorillonite). A first-order rate model was generally used to describe the dechlorination kinetics and the rate constants were dependent on soil mineral type (biotite, vermiculite, and montmorillonite), Fe(II) dose, and the mass ratio of cement to soil mineral. The pseudo-first-order rate constant for montmorillonite was lower than that for biotite and vermiculite by factors of 11-27 when the mass ratio of cement to phyllosilicates was fixed at one. The presence of biotite and vermiculite increase and the presence of montmorillonite decrease the degradation rate that would be observed in their absence. The effect of cement/mineral ratio on rate constants with three different soil minerals indicates that biotite was more reactive than the other two phyllosilicates. This may be due to high accessible natural Fe(II) content in biotite. Montmorillonite appears to inhibit dechlorination by either inactivating Fe(II) by ion exchange or by physically blocking active sites on cement hydration products.


Delineation of the clinical and radiological features of Stuve-Wiedemann syndrome childhood survivors, four new cases and review of the literature.
Stuve-Wiedemann syndrome (SWS; MIM 601559) is a rare autosomal recessive disease caused by mutations in the leukemia inhibitor factor receptor gene (LIFR). Common clinical and radiological findings are often observed, and high neonatal mortality occurs due to respiratory distress and hyperthermic episodes. Despite initially considered as a lethal disorder during the newborn period, in recent years, several SWS childhood survivors have been reported. We report a detailed clinical and radiological characterization of four unrelated childhood SWS molecularly confirmed patients and review 22 previously reported childhood surviving cases. We contribute to the definition of the childhood survival phenotype of SWS, emphasizing the evolving phenotype, characterized by skeletal abnormalities with typical radiological findings, distinctive dysmorphic features, and dysautonomia. Based on the typical features and clinical course, early diagnosis is possible and crucial to plan appropriate management and prevent potential complications. Genetic confirmation is advisable in order to improve genetic counseling to the patients and their families.


GPI-anchored glutathione S-transferase as marker allows affinity sorting of transfection-positive cells.
Cell transfection efficiency is still a limiting factor in gene function research. A method that allows isolation and enrichment of the transfection-positive cells is an effective solution. Here, we report a transfection-positive cell sorting system that utilizes GPI-anchored GST (Glutathione S-transferase) as a plasmid marker. The Glutathione S-transferase fusion protein will be expressed and displayed on the cell surface through GPI anchor, and hence permits the positive cells to be isolated using Glutathione (GSH) Magnetic Beads. We prove that the system works efficiently in both the adherent Lenti-X 293T cells and the suspension K-562 cells. The affinity cell sorting procedure efficiently enriched positive cells from 20% to 98% in K-562 cells. The applications in gene knockdown and overexpression experiments in K-562 cells dramatically enhanced the extent of gene alteration, with the gene knockdown efficiency increasing from 7% to 60% and the gene overexpression level rising from 47 to 253 times. This Glutathione S-transferase affinity transfection-positive cell sorting method is simple and fast to operate, large-instrument free, low cost, and hence possesses great potential in gene function study in vitro.


A novel ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM) regimen for pulmonary Mycobacterium avium disease.
To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units. The tedizolid and moxifloxacin doses used were non-optimized; the tedizolid dose was that associated with bacteriostasis. Drugs were administered daily for 28 days. Each HFS-MAC was sampled in the central and peripheral compartment to ascertain that the intended drug exposures had been achieved. The peripheral compartments were sampled at regular intervals over the 28 days to quantify the burden of MAC. MAC-infected macrophages in the HFS-MAC achieved multi-fold higher intracellular versus extracellular concentrations of rifabutin, moxifloxacin, ceftazidime/avibactam. The non-optimized ceftazidime/avibactam plus tedizolid dual therapy held the bacterial burden at the same level as day 0 (stasis) throughout the 28 days. The standard therapy reduced the bacterial load 2 log10 cfu/mL below stasis on day 14 but started failing after that. The CARTM regimen achieved 3.2 log10 cfu/mL kill below stasis on day 21, but had started to fail by day 28. The CARTM regimen promises to have kill rates better than standard therapy. Experiments to identify exposures of each of the four drugs associated with optimal effect in the CARTM combination are needed in order to design a short-course chemotherapy regimen.


The chemoreceptor dimer is the unit of conformational coupling and transmembrane signaling.
Transmembrane chemoreceptors are central components in bacterial chemotaxis. Receptors couple ligand binding and adaptational modification to receptor conformation in processes that create transmembrane signaling. Homodimers, the fundamental receptor structural units, associate in trimers and localize in patches of thousands. To what degree do conformational coupling and transmembrane signaling require higher-order interactions among dimers? To what degree are they altered by such interactions? To what degree are they inherent features of homodimers? We addressed these questions using nanodiscs to create membrane environments in which receptor dimers had few or no potential interaction partners. Receptors with many, few, or no interaction partners were tested for conformational changes and transmembrane signaling in response to ligand occupancy and adaptational modification. Conformation was assayed by measuring initial rates of receptor methylation, a parameter independent of receptor-receptor interactions. Coupling of ligand occupancy and adaptational modification to receptor conformation and thus to transmembrane signaling occurred with essentially the same sensitivity and magnitude in isolated dimers as for dimers with many neighbors. Thus, we conclude that the chemoreceptor dimer is the fundamental unit of conformational coupling and transmembrane signaling. This implies that in signaling complexes, coupling and transmembrane signaling occur through individual dimers and that changes between dimers in a receptor trimer or among trimer-based signaling complexes are subsequent steps in signaling.


Safety and efficacy of a new parenteral lipid emulsion (SMOFlipid) in surgical patients: a randomized, double-blind, multicenter study.
A new lipid emulsion based on soybean oil, medium chain triglycerides, olive oil and fish oil (SMOFlipid) was tested for safety, tolerance, metabolic and clinical efficacy in surgical patients. In a prospective, double-blind European multicenter study, postoperative patients (elective abdominal or thoracic surgery) were randomized to receive isonitrogenous, isoenergetic (30-35 kcal/kg) total parenteral nutrition over 5 postoperative days including either SMOFlipid 20% or standard soybean oil emulsion (Lipovenoes 20%) as lipid source (1.5 g kg(-1) day(-1)). Metabolic efficacy measurements included serum levels of triglycerides (AUC), phospholipids, and total cholesterol. Safety/tolerance parameters were: hematology; clinical chemistry; coagulation profile; clinical course (arterial blood pressure, heart rate, body temperature), and documentation of adverse events. Clinical efficacy was monitored by length of hospital stay and mortality. The 2 groups (per-protocol population: SMOFlipid n = 99, and Lipovenoes n = 100) were similar with respect to demographic characteristics and types of surgical intervention. Concentrations of serum triglycerides, phospholipids, and total cholesterol were comparable in both groups and within the expected ranges. Laboratory and clinical parameters were not different. A trend towards a reduced length of hospital stay was observed with SMOFlipid (15.7 +/- 6.3 vs. 17.8 +/- 13.2 days). SMOFlipid is clinically safe and well tolerated in postoperative patients. There are indications that SMOFlipid may be associated with a better liver tolerance and a shorter length of hospitalization.


FORTRAN source listing for simulating three-dimensional convergent beam patterns with absorption by the Bloch wave method.
The FORTRAN source code is given for a computer program that calculates the two-dimensional intensity distribution in convergent-beam transmission electron microdiffraction (CBED) patterns from perfect crystals. The program uses the eigenvalue or Bloch-wave method. It allows three-dimensional dynamical diffraction, and so includes all higher-order Laue zone effects without approximation. No symmetry reduction is included. The program accepts noncentrosymmetric or centrosymmetric crystal structures and allows absorption corrections to be included. It uses the "EISPACK" subroutines for the diagonalisation of a general complex matrix. Up to 100 CBED disks may be included. The code is also available via "Bitnet."


Cardiac Rehabilitation and Complementary Physical Training in Elderly Patients after Acute Coronary Syndrome: A Pilot Study.
Background and Objectives: Nearly 23% of elderly patients hospitalized due to acute coronary syndrome have reduced muscle strength. It is assumed that these patients would better benefit from a complex training-a combination of endurance, strength, balance, coordination, and flexibility-in order to reduce the loss of muscle strength and mass and improve functional capacity. The aim of this study was to assess the effectiveness and safety of two different complementary resistance and balance training programs during short-term cardiac rehabilitation (CR) in elderly patients after a percutaneous or surgical intervention due to acute coronary syndrome. Materials and Methods: This randomized controlled trial was conducted from January 2020 to February 2021 in one Lithuanian rehabilitation hospital. A total of 63 participants who met the inclusion criteria were randomly assigned to three groups (at the ratio of 1:1:1): control (CG, n = 19), intervention 1 (IG-1, n = 26), and intervention 2 (IG-2, n = 18). All the patients attended a usual inpatient CR program of a mean duration of 18.7 ± 1.7 days, while the patients assigned to the intervention groups (IG-1 and IG-2) additionally received different resistance and balance training programs three days a week. Functional capacity, with 6-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET), as well as physical performance, with the short physical performance battery (SPPB) test and one repetition maximum test (1RM) for leg press, were assessed at baseline and after CR. Results: The mean age of the participants was 72.9 ± 5.5 years; 73% were men. All parameters of functional capacity and physical performance improved significantly after CR (p < 0.05), except for peak VO2 that improved only in the IG-1. Comparison of CR effectiveness among the groups revealed no significant differences. Conclusions: All three rehabilitation programs were safe and well tolerated by elderly patients aged ≥65 years as well as improved functional capacity (6-minute walk distance and peak workload) and physical performance (SPPB and 1RM). Complementary resistance and balance training with traditional physical therapy means and exercises with mechanical devices did not show greater benefits for the results of physical performance compared with the usual CR program.


Incidental detection of apical hypertrophic cardiomyopathy by myocardial perfusion imaging.
Echocardiography plays a central role in the diagnosis of hypertrophic cardiomyopathy (HCM). However, apical involvement of HCM may be missed because of foreshortening and inadequate clinical suspicion. These patients may be referred for single-photon emission computed tomography imaging. We present three cases of HCM predominantly involving the cardiac apex, whose diagnosis was first suspected on myocardial perfusion imaging. These patients were referred for chest pain syndromes to exclude significant coronary artery disease. All were undiagnosed on initial routine transthoracic echocardiography, and none were specifically suspected by the referring clinicians. All cases underwent an adenosine stress rest technetium-99m tetrofosmin myocardial perfusion protocol, and were subsequently referred for transpulmonary contrast echocardiography. Single-photon emission computed tomography imaging revealed increased tracer uptake in all cases, most marked in the apical myocardium. Inferior wall ischaemia was detected in one case, consistent with a coronary stenosis seen at angiography. Apical hypokinesia was noted in two patients on gated studies. Contrast echocardiography confirmed the diagnosis of HCM with apical involvement in all cases. Echocardiography is the first-line imaging technique for the diagnosis of HCM, but apical involvement may be missed unless a contrast study is performed. The presence of increased apical tracer uptake on perfusion imaging should alert the referring physician to the possibility of apical HCM, irrespective of earlier echocardiographic findings.


Brain radiation-related black dots on susceptibility-weighted imaging.
Small blood vessel injury is a feature of post irradiation brain. Susceptibility weighted imaging (SWI) is a technique that exploits the magnetic properties of tissues, such as blood and iron content and is thus sensitive to hemorrhage as a marker of small vessel injury. Our purpose was to assess post irradiation brain findings using SWI. We evaluated 12 patients with follow-up MRI studies who underwent cranial irradiation for primary or metastatic tumors. From their clinical records, the latency interval, type of radiation, and total dose were established. The number and the distribution of "black dots" on SWI were analyzed. We also compared the findings on SWI with those seen on other MRI sequences. In all patients, black dots were clearly identified on SWI, while on conventional MRI (T2 and FLAIR) none were visible. Two patients with glial tumors received radiation with fields conforming to tumor beds, while all other patients received whole brain irradiation or craniospinal radiation. The total radiation doses ranged from 45-54 Gy. Latency interval between the time of irradiation and time of detection of the black dots was four to 60 months (mean, 31 months). In ten patients diffuse black dots were observed and in two patients these were located in the irradiated field. Black dots occurred in the cerebrum, cerebellum, and choroid plexuses. None of these dots showed enhancement. Follow-up in four patients showed that the numbers of these black dots had increased. Black dots were not present before radiation in any patient. Radiation-related black dots are an effect of cranial irradiation and may be related to small vessel damage. SWI is a sensitive technique for evaluation of these black dots.