[New insights towards catheter-based identification of vulnerable plaque].
Sudden cardiac death or unheralded acute coronary syndromes are common initial manifestations of coronary atherosclerosis and most such events occur at sites of non-flow limiting coronary atherosclerosis. Autopsy data suggests that plaque composition is a key determinant of the propensity of atherosclerotic lesions to provoke clinical events. Most of these events are related to plaque rupture and subsequent thrombotic occlusion at the site of non-flow limiting atherosclerotic lesions in epicardial coronary arteries. Detection of these non-obstructive, lipid rich, high-risk plaques may have an important impact on the prevention of acute myocardial infarction and sudden death. Currently, there are several intravascular tools capable of locally evaluating determinants of plaque vulnerability such as the size of the lipid core, thickness of the fibrous cap, inflammation within the cap and positive remodeling. These new modalities have the potential to provide insights into the pathophysiology of the natural history of coronary plaque by means of prospective studies.


Proinflammatory effect in whole blood by free soluble bacterial components released from planktonic and biofilm cells.
Aggregatibacter actinomycetemcomitans is an oral bacterium associated with aggressive forms of periodontitis. Increasing evidence points to a link between periodontitis and cardiovascular diseases, however, the underlying mechanisms are poorly understood. This study investigated the pathogenic potential of free-soluble surface material, released from live planktonic and biofilm A. actinomycetemcomitans cells. By employing an ex vivo insert model (filter pore size 20 nm) we demonstrated that the A. actinomycetemcomitans strain D7S and its derivatives, in both planktonic and in biofilm life-form, released free-soluble surface material independent of outer membrane vesicles. This material clearly enhanced the production of several proinflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IL-8, MIP-1 beta) in human whole blood, as evidenced by using a cytokine antibody array and dissociation-enhanced-lanthanide-fluorescent-immunoassay. In agreement with this, quantitative real-time PCR indicated a concomitant increase in transcription of each of these cytokine genes. Experiments in which the LPS activity was blocked with polymyxin B showed that the stimulatory effect was only partly LPS-dependent, suggesting the involvement of additional free-soluble factors. Consistent with this, MALDI-TOF-MS and immunoblotting revealed release of GroEL-like protein in free-soluble form. Conversely, the immunomodulatory toxins, cytolethal distending toxin and leukotoxin, and peptidoglycan-associated lipoprotein, appeared to be less important, as evidenced by studying strain D7S cdt/ltx double, and pal single mutants. In addition to A. actinomycetemcomitans a non-oral species, Escherichia coli strain IHE3034, tested in the same ex vivo model also released free-soluble surface material with proinflammatory activity. A. actinomycetemcomitans, grown in biofilm and planktonic form, releases free-soluble surface material independent of outer membrane vesicles, which induces proinflammatory responses in human whole blood. Our findings therefore suggest that release of surface components from live bacterial cells could constitute a mechanism for systemic stimulation and be of particular importance in chronic localized infections, such as periodontitis.


Silicon Photoanodes Partially Covered by Ni@Ni(OH)2 Core-Shell Particles for Photoelectrochemical Water Oxidation.
Two obstacles hindering solar energy conversion by photoelectrochemical (PEC) water-splitting devices are the charge separation and the transport efficiency at the photoanode-electrolyte interface region. Herein, core-shell-structured Ni@Ni(OH)2 nanoparticles were electrodeposited on the surface of an n-type Si photoanode. The Schottky barrier between Ni and Si is sensitive to the thickness of the Ni(OH)2 shell. The photovoltage output of the photoanode increases with increasing thickness of the Ni(OH)2 shell, and is influenced by interactions between Ni and Ni(OH)2 , the electrolyte screening effect, and the p-type nature of the Ni(OH)2 layer. Ni@Ni(OH)2 core-shell nanoparticles with appropriate shell thicknesses coupled to n-type Si photoanodes promote the separation of photogenerated carriers and improve the charge-injection efficiency to nearly 100 %. An onset potential of 1.03 V versus reversible hydrogen electrode (RHE) and a saturated current density of 36.4 mA cm-2 was obtained for the assembly.


GeneMill: A 21st century platform for innovation.
GeneMill officially launched on 4th February 2016 and is an open access academic facility located at The University of Liverpool that has been established for the high-throughput construction and testing of synthetic DNA constructs. GeneMill provides end-to-end design, construction and phenotypic characterization of small to large gene constructs or genetic circuits/pathways for academic and industrial applications. Thus, GeneMill is equipping the scientific community with easy access to the validated tools required to explore the possibilities of Synthetic Biology.


Self-adaptive amorphous CoOxCly electrocatalyst for sustainable chlorine evolution in acidic brine.
Electrochemical chlorine evolution reaction is of central importance in the chlor-alkali industry, but the chlorine evolution anode is largely limited by water oxidation side reaction and corrosion-induced performance decay in strong acids. Here we present an amorphous CoOxCly catalyst that has been deposited in situ in an acidic saline electrolyte containing Co2+ and Cl- ions to adapt to the given electrochemical condition and exhibits ~100% chlorine evolution selectivity with an overpotential of ~0.1 V at 10 mA cm-2 and high stability over 500 h. In situ spectroscopic studies and theoretical calculations reveal that the electrochemical introduction of Cl- prevents the Co sites from charging to a higher oxidation state thus suppressing the O-O bond formation for oxygen evolution. Consequently, the chlorine evolution selectivity has been enhanced on the Cl-constrained Co-O* sites via the Volmer-Heyrovsky pathway. This study provides fundamental insights into how the reactant Cl- itself can work as a promoter toward enhancing chlorine evolution in acidic brine.


The landscape of CAR T-cell therapy in the United States and China: A comparative analysis.
The clinical trials of CAR T-cell therapy are growing fast in recent years, and most of the trials are initiated by sponsors from the United States and China. Exhibiting the distinctions between the clinical trials in the two countries is of great value for understanding the panorama of CAR T-cell clinical trials and forecasting the future of this promising therapy. We analyzed the critical elements of 289 clinical trials posted on the clinicaltrials.gov website by sponsors from the two countries and evaluated the efficacy data in available 50 published CAR T-cell studies. Our analysis shows that China has become the country with the largest number of CAR-T cell clinical trials by the end of 2017, while overall subject sample size and study center numbers are still larger, and the design of the clinical trials is more cautious in the United States. There are obvious differences between the two countries in CAR-targeted antigens in solid tumors and genetic modifications besides CARs for enhancing the potency of CAR T-cells. Although the currently available response rates are promising in both countries, it is inexpedient to conclude that the clinical efficacy is comparable between the two countries considering the smaller patient sample sizes and discrete distribution of median cell doses in China. And finally, the flexible regulatory regime of cell therapy in China, which expedites the bursting of CAR T-cell therapy, is also firstly introduced in our study.


Medically assisted dying in Canada and unjust social conditions: a response to Wiebe and Mullin.
In the paper, titled 'Choosing death in unjust conditions: hope, autonomy and harm reduction,' Wiebe and Mullin argue that people living in unjust social conditions are sufficiently autonomous to request medical assistance in dying (MAiD). The ethical issue is that some people may request MAiD primarily because of unjust social conditions, not their illness, disease, disability or decline in capability. It is easily agreed that people living in unjust social conditions can be autonomous. Nevertheless, Wiebe and Mullin fail to appreciate that autonomy is only a necessary condition for MAiD. In addition to autonomy, one must decide that providing assisted dying to a patient because they are living in unjust social conditions is ethical. Central to making this ethical decision is the principle of non-maleficence, famously articulated as 'do no harm.' The authors admit that performing MAiD in response to unjust social circumstances is harmful, but they justify this harmful action by appealing to the principle of harm reduction. A fundamental flaw of their approach is that it relies on the legislative definition of intolerable suffering, which is based on circular reasoning and given that 99.2% of patients that have applied for MAiD satisfied this criterion, it is essentially equivalent to no standard/criterion. Canadian society is struggling with the ethical implications of its permissive MAiD programme, and, fundamental to this debate, will be determining the proper balance between autonomy and non-maleficence for people living in unjust social conditions.


Animal models of ethanol dependence and liver injury in rats and baboons.
A model has been developed for the administration to rats and baboons of ethanol as part of a nutritionally adequate liquid diet. With this regimen, ethanol intake was much higher than with conventional procedures. All animals gained or maintained their body weight, and liver morphology was normal in the controls. Isocaloric substitution of carbohydrate by ethanol (36% of total calories in rats and 50% in baboons) resulted in the production of fatty liver in all animals, while the baboons also developed alcoholic hepatitis and cirrhosis with increased activities of serum glutamic oxaloacetic transaminase. Inebriation and manifestation of dependence on withdrawal of the diet were observed in baboons and quantitated in the rat. Chemical alterations produced by ethanol at the fatty liver stage were characterized by hyperlipemia, striking triglyceride accumulation in the liver, and enhanced activities of microsomal drug metabolizing enzymes, including the microsomal ethanol oxidizing system (MEOS). In showing that all aspects of liver injury observed in alcoholics can be reproduced in animals by the feeding of pure ethanol with an adequate diet, this study incriminates ethanol itself as a cause for the hepatic complications. This new experimental model is proposed as a tool for the study of the pathogenesis and treatment of alcoholic liver injury and dependence.


Spontaneous Superficial Femoral Artery Mycotic Aneurysm.
Peripheral artery mycotic aneurysms are rare occurrences. In this case, we review a 52-year-old lady with poorly controlled diabetes who developed a spontaneous left superficial artery mycotic aneurysm. She underwent excision and subsequent extra-anatomic bypass with a great saphenous vein graft. She had full functional recovery after a short period of rehabilitation.


Ferret hepatitis E virus infection in Japan.
We examined 85 fecal samples from pet ferrets in 10 animal hospitals in Japan for the detection of ferret hepatitis E virus (HEV) RNA. We found that 6 (7.1%) of the samples were positive for ferret HEV RNA. Phylogenetic analysis based on the partial ORF1 indicated that these ferret HEV strains were clearly separated from the Netherlands strains and were divided into 2 distinct clusters. These results suggest that ferret HEV is genetically diverse, and since ferrets are not indigenous to Japan, ferret HEV has been introduced into Japan through importation.


The significant health threat from sunbed use as a self treatment in patients with acne.
Patients with acne are increasingly using sunbeds as a self treatment despite the harmful effects. Little is known about sunbed use in adult patients with acne under dermatology care. This questionnaire study explored prevalence and behaviours surrounding sunbed use in patients with acne at a UK dermatology centre. Over a quarter (26%) of respondents used sunbeds and of these, 72% used them at least weekly. Respondents using sunbeds were more likely to be older, to be female, to have a longer duration of acne diagnosis and to have previously been offered blue-light therapy by their doctor (P < 0.05 for all) Reasons for use included recommendations from external sources (including the Internet), the perceived greater efficacy compared with physician-prescribed treatments and that light therapy was not offered by their doctor. Nearly half (49%) of respondents were taking isotretinoin at the time of sunbed use, which carries an increased risk for photosensitivity and sunburn in this cohort. Dermatologists have a responsibility to address this gap in public awareness by directly counselling patients at risk of sunbed use, particularly for those concomitantly prescribed oral retinoid therapy.


[In vitro manipulation of bone marrow cells for bone marrow transplantation].
Recently, in vitro manipulations of bone marrow cells have been developed for the prevention of relapse in autologous bone marrow transplantation (BMT) and for the prevention of graft versus host disease in allogeneic BMT. Two methods were mainly employed clinically for the depletion of cells from transplanted bone marrow cells. Firstly, bone marrow cells were treated in vitro with monoclonal antibodies reactive to leukemia cells or T cells using complement, immunotoxin or magnetic bead. Secondly, bone marrow cells were incubated with cancer drugs such as 4-HC or mafosfamide. Our results and other reports using in vitro purging of leukemia or lymphoma cells suggest that these autologous BMTs are effective modes of cancer therapy in patients with hematological malignancies.


Dynamics of an infectious diseases with media/psychology induced non-smooth incidence.
This paper proposes and analyzes a mathematical model on an infectious disease system with a piecewise smooth incidence rate concerning media/psychological effect. The proposed models extend the classic models with media coverage by including a piecewise smooth incidence rate to represent that the reduction factor because of media coverage depends on both the number of cases and the rate of changes in case number. On the basis of properties of Lambert W function the implicitly defined model has been converted into a piecewise smooth system with explicit definition, and the global dynamic behavior is theoretically examined. The disease-free is globally asymptotically stable when a certain threshold is less than unity, while the endemic equilibrium is globally asymptotically stable for otherwise. The media/psychological impact although does not affect the epidemic threshold, delays the epidemic peak and results in a lower size of outbreak (or equilibrium level of infected individuals).


Influence of ligand rigidity and ring substitution on the structural and electronic behavior of trivalent iron and gallium complexes with asymmetric tridentate ligands.
Species 1-6 are [M(III)(L)2]ClO4 complexes formed with the PhO--CH=N-CH2-Py imines, (L(I))- and (L(tBuI))-, and PhO--CH2-NH-CH2-Py amines, (L(A))- and (L(tBuA))-, in which PhO- is a phenolate ring and Py is a pyridine ring and the prefix tBu indicates the presence of tertiary butyl groups occupying the positions 4 and 6 of the phenol ring. Monometallic species with d5 high-spin iron (1, 2, 3, 4) and d10 gallium (5, 6) were synthesized and characterized to assess the influence of the ligand rigidity and the presence of tertiary butyl-substituted phenol rings on their steric, electronic, and redox behavior. Characterization by elemental analysis, mass spectrometry, IR, UV-visible, and EPR spectroscopies, and electrochemistry has been performed, and complexes [FeIII(L(tBuI))2]ClO4 (2), [FeIII(L(tBuA))2]ClO4 (4), and [Ga(III)(L(tBuI))2]ClO4 (5) have been characterized by X-ray crystallography. The crystal structures show the imine ligands meridionally coordinated to the metal centers, whereas the amine ligands are coordinate in a facial mode. Cyclic voltammetry shows that the complexes with the ligands (L(tBuI))- and (L(tBuA))- were able to generate ligand-based phenoxyl radicals, whereas unsubstituted ligands displayed ill-defined redox processes. EPR spectroscopy supports high-spin configurations for the iron complexes. UV-visible spectra are dominated by charge-transfer phenomena, and imine compounds exhibit dramatic hyperchromism when compared to equivalent amines. The tertiary butyl groups on the phenolate ring enhance this trend. Detailed B3LYP/6-31G(d)-level calculations have been used to account for the results observed.


Superoperator representation of nonlinear response: unifying quantum field and mode coupling theories.
Computing response functions by following the time evolution of superoperators in Liouville space (whose vectors are ordinary Hilbert space operators) offers an attractive alternative to the diagrammatic perturbative expansion of many-body equilibrium and nonequilibrium Green's functions. The bookkeeping of time ordering is naturally maintained in real (physical) time, allowing the formulation of Wick's theorem for superoperators, giving a factorization of higher order response functions in terms of two fundamental Green's functions. Backward propagations and analytic continuations using artificial times (Keldysh loops and Matsubara contours) are avoided. A generating functional for nonlinear response functions unifies quantum field theory and the classical mode coupling formalism of nonlinear hydrodynamics and may be used for semiclassical expansions. Classical response functions are obtained without the explicit computation of stability matrices.


Psychiatric sequelae of disasters.
In addition to physical injuries, survivors of disasters also suffer psychological trauma. Resulting mental anguish and illness can be profoundly debilitating and complicate the recovery and rehabilitation process. Front-line trauma teams caring for survivors of disasters must know the risks, assessment, and appropriate response to psychological injury. This article reviews the development of understanding mental disturbance after disasters and current approaches to evaluation and treatment.


Weaving a transcultural thread.
This article describes the development and implementation of an educational strategy to enhance knowledge about transcultural nursing in a College of Nursing undergraduate program. Concepts of diversity and transcultural nursing were integrated into the entire undergraduate curriculum. This content was presented over six quarters in seminar courses throughout the undergraduate program. A team of faculty members developed this series of courses called "Nurse and Society" that included cultural diversity, ethics, professionalism, and policy as strands or threads woven through the courses. Based on faculty evaluations at the end of each course, most graduating students were aware of the need to provide culturally congruent care. However, there is a need to develop a sound programmatic evaluation that includes empirical outcomes of cultural competence among graduates.


Diabetic Muscle Infarction Masquerading as Necrotizing Fasciitis.
A 43-year-old male patient with past medical history of diabetes mellitus (DM), end stage renal disease (ESRD) on hemodialysis (HD), congestive heart failure (CHF), obstructive sleep apnea (OSA), and chronic anemia presented with complaints of left thigh pain. A computerized tomogram (CT) of the thigh revealed evidence of edema with no evidence of a focal collection or gas formation noted. The patient's clinical symptoms persisted and he underwent magnetic resonance imaging (MRI) of his thigh which was reported to show small areas of muscle necrosis with fluid collection. These findings in the acute setting concerned necrotizing fasciitis. After careful discussion following a multidisciplinary approach, a decision was made to perform a fasciotomy with tissue debridement. The patient was treated with IV antibiotics and discharged with a vacuum assisted wound drain. The surgical pathology revealed evidence of muscle edema with necrosis. Seven weeks later the patient presented with similar complaints on the other thigh (right thigh). MRI of the thighs revealed worsening edema with features suggestive of myositis and possible muscle infarction. A CT guided biopsy of the right quadriceps muscle revealed fibrotic interstitial connective tissue and no evidence of necrosis. This favored a diagnosis of diabetic muscle infarction. The disease was managed with pain control, strict diabetes management, and aggressive dialysis.


Exact calculation of the tortuosity in disordered linear pores in the Knudsen regime.
The squared reciprocal tortuosity kappa-2=D/D0 for linear diffusion on lattices and in pores in the Knudsen regime is calculated analytically for a large variety of disordered systems. Here, D0 and D are the self-diffusion coefficients of the smooth and the corresponding disordered system, respectively. To this end, a building-block principle is developed that composes the systems into substructures without cross correlations between them. It is shown how the solutions of the different building blocks can be combined to gain D/D0 for pores of high complexity from the geometrical properties of the systems, i.e., from the volumes of the different substructures. As a test, numerical simulations are performed that agree perfectly with the theory.


Prevalence, incidence, intensity and associated morbidity of intestinal helminths in south Thailand.
Intensive surveys for Ascaris lumbricoides, Trichuris trichiura and hookworm were carried out in two villages in Phang Nga Province, southern Thailand, in order to measure prevalence, estimate incidence and determine the relation between intensity of infection and morbidity before and after chemotherapy. The study populations were a small upland village community (Nai Tone) and a grade school in a small coastal village (Boh Saen). About half of the Nai Tone villagers were given a broad spectrum antihelminthic (albendazole), and the Boh Saen students were all treated successively with three drugs: piperazine citrate to treat for Ascaris, pyrantel pamoate to treat for hookworm, and mebendazole to treat for Trichuris. Stool examinations were made using the quick Kato smear technique, questionnaires were administered concerning a variety of possible symptoms, and anthropometric and blood biochemical parameters were measured both before and after treatment. The prevalence of Ascaris was 31.0 and 22.6%, hookworm was 89.1 and 88.0% and Trichuris was 59.7 and 77.8% in the Nai Tone and Boh Saen study populations, respectively. Average intensity of Ascaris was highest in the 0-9 year age class (greater than 32,000 epg) in Nai Tone Village. Hookworm intensity of infection was higher in males than in females in all age classes, and in Nai Tone Village at least 25% of males and 20% of females had 8000 or more epg of faeces. Trichuris intensity of infection was highest between 5 and 10 years of age in both populations. The only signs or symptoms showing a significant (P less than 0.05) difference between high and low classes of intensity of infection and a significant improvement (P less than 0.01) after drug treatment, were headache and flatulance in the case of hookworm infection in Boh Saen School. The presence of multiple infections made testing of hypotheses concerning particular parasite species difficult.


Provider motivations and barriers to cancer clinical trial screening, referral, and operations: Findings from a survey.
Provider and institutional practices have been shown to have a large impact on cancer clinical trial enrollment. Understanding provider perspectives on screening for trial eligibility is necessary to improve enrollment. A questionnaire about incentives, barriers, process tools, and infrastructure related to opening trials and referring patients to onsite and offsite trials was administered to diverse stakeholders, including professional societies, advocacy organizations, and industry networks. Descriptive statistics were used to summarize findings. Overall, 693 responses were received, primarily from physicians (42.7%) and nurses (35.6%) employed at hospital health systems (43.7%) and academic centers (36.5%). Approximately half (49.2%) screened all patients for onsite clinical trials with screening typically done by manual chart review (81.9%). The greatest incentive reported for offering trials was providing the best treatment options for patients (67.7%). Contracting and paperwork (48.5%) were the greatest barriers to opening more onsite trials. Offsite referrals were rare. Screening for trial eligibility is a largely manual and ad hoc process, with screening and referral to offsite trials occurring infrequently. Administrative and infrastructure barriers commonly prevent sites from opening more onsite trials. These findings suggest that automated trial screening tools built into workflows that screen in a site-agnostic manner could result in more frequent trial eligibility screening, especially for offsite trials. With recent momentum, in part in response to the COVID-19 pandemic, to improve clinical trial efficiencies and broaden access and participant diversity, implementing tools to improve screening and referral processes is timely and essential. There are many factors that contribute to low adult enrollment in cancer clinical trials, but previous research has indicated that provider and institutional barriers are the largest contributors to low cancer clinical trial enrollment. In this survey, we sought to gain insight into cancer clinical trial enrollment practices from the perspective of health care providers such as physicians and nurses. We found that only approximately half of respondents indicated their institution systematically screens their patients for clinical trials and this process is manual and time consuming. Furthermore, we found that providers infrequently search for and refer patients to clinical trials at other sites. Creating better screening methods could improve enrollment in clinical trials.


Meliacine, an antiviral compound from Melia azedarach L., inhibits interferon production.
A glycopeptide isolated from the high plant Melia azedarach L. (meliacine) inhibits the in vitro replication of several RNA and DNA animal viruses. Interferon (IFN) production was depressed greatly in meliacine treated L929 cells and primary mouse embryo fibroblast cultures (MEF) induced with Newcastle disease virus (NDV) or poly(rI).poly(rC). This action was observed when meliacine was added before, simultaneously or early after induction with poly(rI).poly(rC) or NDV. In addition, accumulation of acid-resistant IFN was strongly diminished in adult mice treated intraperitoneally with meliacine. Though meliacine causes a strong inhibition of IFN both in vitro and in vivo, we do not know how selectively it affects the IFN system.


Exogenous glucagon-like peptide-1 acts in sites supplied by the cranial mesenteric artery to reduce meal size and prolong the intermeal interval in rats.
Three experiments were done to better assess the gastrointestinal (GI) site(s) of action of GLP-1 on food intake in rats. First, near-spontaneous nocturnal chow meal size (MS), intermeal intervals (IMI) length and satiety ratios (SR = MS/IMI) were measured after infusion of saline, 0.025 or 0.5 nmol/kg GLP-1 into the celiac artery (CA, supplying the stomach and upper duodenum), cranial mesenteric artery (CMA, supplying small and all of the large intestine except the rectum), femoral artery (FA, control) or portal vein (PV, control). Second, infusion of 0.5 nmol/kg GLP-1 was tested after pretreatment with the GLP-1 receptor (GLP-1R) antagonist exendin-4(3-39) via the same routes. Third, the regional distribution of GLP-1R in the rat GI tract was determined using rtPCR. CA, CMA and FA GLP-1 reduced first MS relative to saline, with the CMA route more effective than the others. Only CMA GLP-1 prolonged the IMI. None of the infusions affected second MS or later eating. CA and CMA GLP-1 increased the SR, with the CMA route more effective than the CA route. CMA exendin-4 (3-39) infusion reduced the effect of CMA GLP-1. Finally GLP-1R expression was found throughout the GI tract. The results suggest that exogenous GLP-1 acts in multiple GI sites to reduce feeding under our conditions and that GLP-1R in the area supplied by the CMA, i.e., the small and part of the large intestine, plays the leading role.


Efficient asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one by Candida parapsilosis cells in an ionic liquid-containing system.
Hydrophilic ionic liquids (ILs) were employed as green solvents to construct an IL-containing co-solvent system for improving the asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one by immobilized Candida parapsilosis cells. Among 14 hydrophilic ILs examined, 1-(2'-hydroxyl)ethyl-3-methylimidazolium nitrate (C(2)OHMIM·NO(3)) was considered as the most suitable IL for the bioreduction with the fastest initial reaction rate, the highest yield and the highest product e.e., which may be due to the good biocompatibility with the cells. For a better understanding of the bioreduction performed in the C(2)OHMIM·NO(3)-containing co-solvent system, the effects of several crucial variables were systematically investigated. The optimal C(2)OHMIM·NO(3) content, substrate concentration, buffer pH, co-substrate concentration and temperature were 10% (v/v), 3.0 mmol/L, 5.0, 98.1 mmol/L and 30°C, respectively. Under the optimal conditions, the initial reaction rate, the maximum yield and the product e.e. were 17.3 µmol/h g(cell), 95.2% and >99.9%, respectively, which are much better than the corresponding results previously reported. Moreover, the immobilized cells remained more than 83% of their initial activity even after being used repeatedly for 10 batches in the C(2)OHMIM·NO(3)-containing system, exhibiting excellent operational stability.


Tumors of the autonomic nervous system.
Tumors of the adrenal medulla, extra-adrenal paraganglia of the sympathetic neuroendocrine system, and paraganglia of the head and neck are derivedfrom neural crest cells. These tumors manifest as growing masses and can cause endocrine dysfunction due to unregulated secretion of hormones. Tumors arising in the adrenal medulla (pheochromocytomas) and extraadrenal paraganglia (paragangliomas) usually present in adulthood. Their diagnosis is based on histologic features, immunohistochemical stains, and electron microscopy. These features are reviewed, as are familial syndromes and their associated gene mutations.


Maternal and placental ANRIL polymorphisms and preeclampsia susceptibility.
Aim: The possible effects of maternal and placental ANRIL polymorphisms on preeclampsia were examined. Methods: The maternal blood of 315 preeclamptic and 317 control women and the placentas of 103 preeclamptic and 133 control women were enrolled in the study. ANRIL polymorphisms were genotyped using a PCR-RFLP method. Results: The maternal ANRIL rs1333048C variant showed a relationship with a lower risk of preeclampsia in codominant and dominant models. The maternal ANRIL rs4977574G variant had a relationship with a lower risk of preeclampsia in codominant and recessive models. There was an association between the placental rs1333048C variant and a lower risk of preeclampsia in codominant and dominant models. Conclusion: Maternal ANRIL rs1333048C and rs4977574G variants and placental rs1333048 variant showed a relationship with a lower risk of preeclampsia.


[Therapeutic drainage of abdominal cavity cyst performed under USG control -- the relations of its results and effectiveness].
278 patients with the cyst of pancreas, liver and kidneys diagnosed ultrasonographically have undergone the scintigraphic examination of their changes. In case of patients where transit of contents beyond the cyst limits has not been found, the results of volume obtained by 3 methods (the volume measured ultrasonographically volume drained and volume estimated by the method of radiomarker dilution) have been compared. The authors have proven that the best results have achieved in those patients where the drainage has been performed in the most accurate way. It means that the drained volume has been the closest to the actual volume which corresponds to that one achieved by the method of radiomarker dilution.


Reversal of β-Amyloid-Induced Microglial Toxicity In Vitro by Activation of Fpr2/3.
Microglial inflammatory activity is thought to be a major contributor to the pathology of neurodegenerative conditions such as Alzheimer's disease (AD), and strategies to restrain their behaviour are under active investigation. Classically, anti-inflammatory approaches are aimed at suppressing proinflammatory mediator production, but exploitation of inflammatory resolution, the endogenous process whereby an inflammatory reaction is terminated, has not been fully investigated as a therapeutic approach in AD. In this study, we sought to provide proof-of-principle that the major proresolving actor, formyl peptide receptor 2, Fpr2, could be targeted to reverse microglial activation induced by the AD-associated proinflammatory stimulus, oligomeric β-amyloid (oAβ). The immortalised murine microglial cell line BV2 was employed as a model system to investigate the proresolving effects of the Fpr2 ligand QC1 upon oAβ-induced inflammatory, oxidative, and metabolic behaviour. Cytotoxic behaviour of BV2 cells was assessed through the use of cocultures with retinoic acid-differentiated human SH-SY5Y cells. Stimulation of BV2 cells with oAβ at 100 nM did not induce classical inflammatory marker production but did stimulate production of reactive oxygen species (ROS), an effect that could be reversed by subsequent treatment with the Fpr2 ligand QC1. Further investigation revealed that oAβ-induced ROS production was associated with NADPH oxidase activation and a shift in BV2 cell metabolic phenotype, activating the pentose phosphate pathway and NADPH production, changes that were again reversed by QC1 treatment. Microglial oAβ-stimulated ROS production was sufficient to induce apoptosis of bystander SH-SY5Y cells, an effect that could be prevented by QC1 treatment. In this study, we provide proof-of-concept data that indicate exploitation of the proresolving receptor Fpr2 can reverse damaging oAβ-induced microglial activation. Future strategies that are aimed at restraining neuroinflammation in conditions such as AD should examine proresolving actors as a mechanism to harness the brain's endogenous healing pathways and limit neuroinflammatory damage.


The effects of GABAergic drugs on grooming behaviour in the open field.
In a previous study it was demonstrated that sodium valproate, a drug that increases GABA cerebral concentrations, decreases grooming in the open field. This effect was not modified by morphine or naloxone. To provide evidence for the participation of the GABA system in the expression of grooming, other GABAergic drugs were acutely administered to rats before the test in the open field. The drugs, in the doses tested, did not modify locomotion, rearing, freezing or defaecation. Aminooxiacetic acid 10 mg/kg, barbital 60 mg/kg, baclofen 1.5 mg/kg, clonazepam 0.1 mg/kg, sodium valproate 150 mg/kg and 4,5,6,7-tetrahydroxi-azolo-5,4c-pyridine-3-ol (THIP) 0.75 mg/kg were the lowest doses to decrease the frequencies of grooming. The estimated ED50 to suppress grooming behaviour in the open field were 1.75 mg/kg baclofen, 52 mg/kg barbital, 0.86 mg/kg clonazepam and 1.0 mg/kg THIP. The decrease in grooming produced by the lowest effective doses of aminooxiacetic acid, clonazepam, sodium valproate and THIP was antagonized by concomitant administration of picrotoxin 1 mg/kg or bicuculline 1 mg/kg. The effects of baclofen and barbital on grooming were not modified by the antagonists. It is concluded that the GABA system, through GABA A and GABA B receptors may play a role in the expression of novelty-induced grooming behaviour.


Current Trends for ST-segment Elevation Myocardial Infarction during the Past 5 Years in Rural Areas of China's Liaoning Province: A Multicenter Study.
Since 2010, two versions of National Guidelines aimed at promoting the management of ST-segment elevation myocardial infarction (STEMI) have been formulated by the Chinese Society of Cardiology. However, little is known about the changes in clinical characteristics, management, and in-hospital outcomes in rural areas. In the present multicenter, cross-sectional study, participants were enrolled from rural hospitals located in Liaoning province in Northeast China, during two different periods (from June 2009 to June 2010 and from January 2015 to December 2015). Data collection was conducted using a standardized questionnaire. In total, 607 and 637 STEMI patients were recruited in the 2010 and 2015 cohorts, respectively. STEMI patients in rural hospitals were older in the second group (63 years vs. 65 years, P = 0.039). We found increases in the prevalence of hypertension, prior percutaneous coronary intervention (PCI), and prior stroke. Over the past 5 years, the cost during hospitalization almost doubled. The proportion of STEMI patients who underwent emergency reperfusion had significantly increased from 42.34% to 54.47% (P < 0.0001). Concurrently, the proportion of primary PCI increased from 3.62% to 10.52% (P < 0.0001). The past 5 years have also seen marked increases in the use of guideline-recommended drugs and clinical examinations. However, in-hospital mortality and major adverse cardiac events did not significantly change over time (13.01% vs. 10.20%, P = 0.121; 13.34% vs. 13.66%, P = 0.872). Despite the great progress that has been made in guideline-recommended therapies, in-hospital outcomes among rural STEMI patients have not significantly improved. Therefore, there is still substantial room for improvement in the quality of care.


Characterization of a Tn551-mutant of Staphylococcus aureus defective in the production of several exoproteins.
A Tn551 insertional pleiotropic mutant defective in the production of several exoproteins was isolated from Staphylococcus aureus 196E and characterized. The pleiotropism of the mutant was due to a single insertion of the transposon as evidenced by Southern blot hybridization and by the transfer of its phenotype by transduction to S. aureus ISP479. The mutants showed diminished or null levels of alpha- and beta-hemolysis, DNase, coagulase, and protein A in the supernatants of broth cultures. Production of proteases, lipase, staphylokinase, or enterotoxin A was not modified. The mutants did synthesize the cell-bound form of protein A and also the extracellular form of this protein coded by pRIT11, which lacks the COOH-terminal segment of the molecule. These observations suggest that the sae locus does not involve a positive regulatory gene acting at the transcriptional level. The phenotype of the mutant was different from that of other insertional mutants affecting exoprotein synthesis, such as agr, xpr, or sar. This new mutation has been designated sae (for S. aureus exoprotein expression).


Risk-to-Benefit Relationship of Contralateral Prophylactic Mastectomy: The Argument for Bilateral Mastectomies with Immediate Reconstruction.
The increasing trend of women with unilateral breast cancer to electively undergo contralateral prophylactic mastectomy in addition to treatment of the index breast has been controversial. The authors set out to better frame the risks and benefits of contralateral prophylactic mastectomy in the treatment of unilateral breast cancer by evaluating outcomes of a large, consecutive cohort of patients. An institutional review board-approved review of a single-surgeon (N.T.) experience (2013 to 2018) was conducted of all consecutive patients with unilateral breast cancer treated with mastectomy and immediate reconstruction. Patient characteristics, surgical pathologic results, and 30-day complications were assessed. Outcomes of patients with unilateral cancer who underwent unilateral mastectomy versus bilateral mastectomy (with one breast being contralateral prophylactic mastectomy) were compared. Logistic regression models evaluated various risk factors for potential associations with positive pathologic findings in the contralateral prophylactic mastectomy specimen and/or postoperative complications. Of 244 patients, 68 (27.9 percent) underwent unilateral mastectomy and 176 (72.1 percent) underwent contralateral prophylactic mastectomy. Surgical pathologic results of the prophylactic breast revealed occult ductal carcinoma in situ or invasive cancer in 13 patients (7.3 percent) and lobular carcinoma in situ in eight patients (4.6 percent). Incidence of complications was similar between groups [unilateral mastectomy, 19.12 percent (n = 13); contralateral prophylactic mastectomy, 13.07 percent (n = 23); p = 0.234]. Immediate reconstruction for unilateral mastectomy and contralateral prophylactic mastectomy have similar complication risk profiles, among patients as a whole and between individual breasts. These findings contribute to our understanding of the clinical impact prophylactic mastectomy and reconstruction may have on optimizing the counseling among extirpative surgeons, reconstructive surgeons, and patients. Therapeutic, III.


Hematin treatment of acute porphyria. Early remission of an almost fatal relapse.
Intravenous infusions of hematin in a young woman with acute porphyria in profound relapse was followed within 48 hours by remission of symptoms and rapid recovery. From a state of severe central and peripheral nervous-system involvement, the patient recovered so completely that she was able to leave the hospital in less than a month, with only a residual weakness of her arms. Serial studies of serum and urinary levles of porphyrin precursors and serum level of hematin provided highly important information about the effect of hematin on acute porphyria.


Proliferation‑inhibiting pathways in liver regeneration (Review).
Liver regeneration, an orchestrated process, is the primary compensatory mechanism following liver injury caused by various factors. The process of liver regeneration consists of three stages: Initiation, proliferation and termination. Proliferation‑promoting factors, which stimulate the recovery of mitosis in quiescent hepatocytes, are essential in the initiation and proliferation steps of liver regeneration. Proliferation‑promoting factors act as the 'motor' of liver regeneration, whereas proliferation inhibitors arrest cell proliferation when the remnant liver reaches a suitable size. Certain proliferation inhibitors are also expressed and activated in the first two steps of liver regeneration. Anti‑proliferation factors, acting as a 'brake', control the speed of proliferation and determine the terminal point of liver regeneration. Furthermore, anti‑proliferation factors function as a 'steering‑wheel', ensuring that the regeneration process proceeds in the right direction by preventing proliferation in the wrong direction, as occurs in oncogenesis. Therefore, proliferation inhibitors to ensure safe and stable liver regeneration are as important as proliferation‑promoting factors. Cytokines, including transforming growth factor‑β and interleukin‑1, and tumor suppressor genes, including p53 and p21, are important members of the proliferation inhibitor family in liver regeneration. Certain anti‑proliferation factors are involved in the process of gene expression and protein modification. The suppression of liver regeneration led by metabolism, hormone activity and pathological performance have been reviewed previously. However, less is known regarding the proliferation inhibitors of liver regeneration and further investigations are required. Detailed information regarding the majority of known anti‑proliferation signaling pathways also remains fragmented. The present review aimed to understand the signalling pathways that inhbit proliferation in the process of liver regeneration.


Quality of Public Open Spaces and Recreational Walking.
We examined associations between specific public open space (POS) attributes and recreational walking to local POS. Between October 2004 and December 2006, 1465 adults of the RESIDential Environments Project, conducted in Perth, Australia, reported whether they walk to a POS for recreation. For each participant, we identified all open spaces larger than 0.8 hectares within 1.6 kilometers from home. On the basis of field audit data, we created 3 scores (presence, count, size-weighted presence) for 19 specific open space attributes. With logistic regression analyses, we found that walking to a POS was associated with the presence of gardens, grassed areas, walking paths, water features, wildlife, amenities, dog-related facilities, and off-leash areas for dogs. It was also associated with the highest number of these attributes in a single open space, but not with the total number of attributes in all POSs within 1.6 kilometers of home. Building 1 high-quality local park may be more effective in promoting recreational walking than is providing many average-quality parks.


Mid-Term Results of the First Dorsal Metacarpal Artery Flap for Thumb Defects.
Background: The thumb plays an important role in the function of the hand. Sensate reconstruction of the pulp is important in restoring function to the thumb. The aim of this study is to present outcomes of a sensate islanded first dorsal metacarpal artery (FDMA) flap used for the reconstruction of skin defects of the thumb. Methods: Patients who had a FDMA flap reconstruction of thumb pulp defects in the orthopaedics and traumatology clinic of affiliated hospital were included in the study. This included eight thumbs of eight patients. The range of motion, sensation and cosmetic satisfaction in the donor and recipient areas were evaluated at a minimum of 2-year follow-up. Results: There were no partial or complete flap failures. The mean static 2-point discrimination was 15 mm and the mean Semmes-Weinstein monofilament test score was 3.93. Cortical re-orientation was observed in 65% of patients. Near normal range of motion and Kapandji scores were regained in all patients. Conclusions: Excellent motion and sensory outcomes were obtained following the FDMA flap reconstruction of thumb pulp defects. The donor morbidity of the flap is minimal, and this flap can be considered as one of the primary options for reconstruction of thumb pulp defects. Level of Evidence: Level V (Therapeutic).


Josephson Field-Effect Transistors Based on All-Metallic Al/Cu/Al Proximity Nanojunctions.
We demonstrate proximity-based all-metallic mesoscopic superconductor-normal metal-superconductor (SNS) field-effect controlled Josephson transistors (SNS-FETs) and show their full characterization from the critical temperature Tc down to 50 mK in the presence of both electric and magnetic fields. The ability of a static electric field-applied by means of a lateral gate electrode-to suppress the critical current Is in a proximity-induced superconductor is proven for both positive and negative gate voltage values. Is reached typically about one-third of its initial value, saturating at high gate voltages. The transconductance of our SNS-FETs obtains values as high as 100 nA/V at 100 mK. On the fundamental physics side, our results suggest that the mechanism at the basis of the observed phenomenon is quite general and does not rely on the existence of a true pairing potential, but rather the presence of superconducting correlations is enough for the effect to occur. On the technological side, our findings widen the family of materials available for the implementation of all-metallic field-effect transistors to synthetic proximity-induced superconductors.


Modulating transcallosal and intra-hemispheric brain connectivity with tDCS: Implications for interventions in Aphasia.
Transcranial direct current stimulation (tDCS) can enhance or diminish cortical excitability levels depending on the polarity of the stimulation. One application of non-invasive brain-stimulation has been to modulate a possible inter-hemispheric disinhibition after a stroke. This disinhibition model has been developed mainly for the upper extremity motor system, but it is not known whether the language/speech-motor system shows a similar inter-hemispheric interaction. We aimed to examine physiological evidence of inter- and intra-hemispheric connectivity changes induced by tDCS of the right inferior frontal gyrus (IFG) using arterial-spin labeling (ASL) MRI. Using an MR-compatible DC-Stimulator, we applied anodal stimulation to the right IFG region of nine healthy adults while undergoing non-invasive cerebral blood flow imaging with arterial-spin labeling (ASL) before, during, and after the stimulation. All ASL images were then normalized and timecourses were extracted in regions of interest (ROIs), which were the left and right IFG regions, and the right supramarginal gyrus (SMG) in the inferior parietal lobule. Two additional ROIs (the right occipital lobe and the left fronto-orbital region) were taken as control regions. Using regional correlation coefficients as a surrogate marker of connectivity, we could show that inter-hemispheric connectivity (right IFG with left IFG) decreased significantly (p < 0.05; r-scores from 0.67 to 0.53) between baseline and post-stimulation, while the intra-hemispheric connectivity (right IFG with right SMG) increased significantly (p < 0.05;r-scores from 0.74 to 0.81). A 2 × 2 ANOVA found a significant main effect of HEMISPHERE (F(8) = 6.83, p < 0.01) and a significant HEMISPHERE-by-TIME interaction (F(8) = 4.24, p < 0.05) in connectivity changes. The correlation scores did not change significantly in the control region pairs (right IFG with right occipital and right IFG with left fronto-orbital) over time. Using an MR-compatible DC stimulator we showed that ASL-MRI can detect tDCS-induced modulation of brain connectivity within and between hemispheres. These findings might affect trial designs focusing on modulating the non-dominant hemisphere to enhance language/speech-motor functions.


Nitric Oxide Deficiency in Mitochondrial Disorders: The Utility of Arginine and Citrulline.
Mitochondrial diseases represent a growing list of clinically heterogeneous disorders that are associated with dysfunctional mitochondria and multisystemic manifestations. In spite of a better understanding of the underlying pathophysiological basis of mitochondrial disorders, treatment options remain limited. Over the past two decades, there is growing evidence that patients with mitochondrial disorders have nitric oxide (NO) deficiency due to the limited availability of NO substrates, arginine and citrulline; decreased activity of nitric oxide synthase (NOS); and NO sequestration. Studies evaluating the use of arginine in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) presenting with stroke-like episodes showed symptomatic improvement after acute administration as well as a reduction in the frequency and severity of stroke-like episodes following chronic use. Citrulline, another NO precursor, was shown through stable isotope studies to result in a greater increase in NO synthesis. Recent studies showed a positive response of arginine and citrulline in other mitochondrial disorders besides MELAS. Randomized-controlled studies with a larger number of patients are warranted to better understand the role of NO deficiency in mitochondrial disorders and the efficacy of NO precursors as treatment modalities in these disorders.


Mining for Micropeptides.
Advances in computational biology and large-scale transcriptome analyses have revealed that a much larger portion of the genome is transcribed than was previously recognized, resulting in the production of a diverse population of RNA molecules with both protein-coding and noncoding potential. Emerging evidence indicates that several RNA molecules have been mis-annotated as noncoding and in fact harbor short open reading frames (sORFs) that encode functional peptides and that have evaded detection until now due to their small size. sORF-encoded peptides (SEPs), or micropeptides, have been shown to have important roles in fundamental biological processes and in the maintenance of cellular homeostasis. These small proteins can act independently, for example as ligands or signaling molecules, or they can exert their biological functions by engaging with and modulating larger regulatory proteins. Given their small size, micropeptides may be uniquely suited to fine-tune complex biological systems.


Idiopathic Splenic Artery Pseudoaneurysm Rupture as an Uncommon Cause of Hemorrhagic Shock.
Splenic artery pseudoaneurysms are infrequently encountered but critical to recognize. Limited literature to date describes associations with pancreatitis, trauma, and rarely peptic ulcer disease. Hemorrhage and abdominal pain are the most common manifestations. There is typically overt gastrointestinal blood loss but bleeding can also extend into the peritoneum, retroperitoneum, adjacent organs, or even a pseudocyst. Most patients with ruptured splenic artery pseudoaneurysms present with hemodynamic instability. Here, we describe a patient recovering from acute illness in the intensive care unit but with otherwise no obvious risk factors or precipitants for visceral pseudoaneurysm. He presented with acute onset altered mental status, nausea, and worsening back and abdominal pain and was found to be in hypovolemic shock. The patient was urgently stabilized until more detailed imaging could be performed, which ultimately revealed the source of blood loss and explained his rapid decompensation. He was successfully treated with arterial coiling and embolization. Thus, we herein emphasize the importance of prompt recognition of hemorrhagic shock and of aggressive hemodynamic stabilization, as well as a focused diagnostic approach to this problem with specific treatment for splenic artery pseudoaneurysm. Finally, we recommend that multidisciplinary management should be the standard approach in all patients with splenic artery pseudoaneurysm.


Numerical Estimation of Limiting Current Density by Focusing on Mass Transfer within Porous Spacers in an Electro-Dialysis.
Estimating and increasing limiting current density (LCD) levels is of fundamental importance for the development of electrodialysis (ED) systems, and it is becoming clear that the use of porous spacers can significantly increase such LCD levels. In this study, a three-dimensional numerical simulation was proposed for evaluating the mass transfer within a porous spacer unit cell and for estimating LCD levels. It was found that our proposed method is effective for estimating the minimum value of an LCD, which is a significant factor related to the safe operation of ED systems. Furthermore, it was found that increasing the minimum effective Sherwood number provides a key to increasing LCD levels. Porous spacer design guidelines were proposed based on the numerical simulation results, after which a new spacer was introduced, designed according to those guidelines. It was found that flow disturbances on the membrane caused by porous spacer structures can lead to increases in effective Sherwood numbers and that LCD levels could be increased by eliminating the flow stagnation behind the structures on the membrane. The LCD of our new spacer was found to be higher than that of the spacers with the highest LCD levels in use at present. Therefore, we can conclude that the proposed design guidelines are effective for increasing LCD levels.


Factors controlling packaging of peptide hormones into secretory granules.
Endocrine, exocrine, and neuronal cells package only a subset of their secretory products into the electron-dense secretory granules. To investigate the factors controlling selective packaging of proteins into these granules, we utilized the mouse pituitary tumor cell line, AtT-20, which retained the capability to sort adrenocorticotropic hormone (ACTH) into secretory granules in vitro. Packaging of ACTH was blocked by treatment with weak bases, but was unaffected when N-linked glycosylation or sulfation was inhibited. To test whether the targeting information is specified by sorting domains present on peptide hormone sequences, we determined if a protein could be diverted to the dense secretory granules by attachment to a peptide hormone sequence. A plasmid DNA was constructed that encoded a hybrid protein in which a fragment of a viral membrane protein was fused to the carboxy terminus of human growth hormone. AtT-20 cells transfected with the hybrid were found to target it to dense secretory vesicles efficiently. These results support the hypothesis that sorting domains on peptide hormones direct their packaging into dense secretory vesicles.


Electrocatalysts Derived from Copper Complexes Transform CO into C2+ Products Effectively in a Flow Cell.
Electrochemical reactors that electrolytically convert CO2 into higher-value chemicals and fuels often pass a concentrated hydroxide electrolyte across the cathode. This strongly alkaline medium converts the majority of CO2 into unreactive HCO3 - and CO3 2- byproducts rather than into CO2 reduction reaction (CO2RR) products. The electrolysis of CO (instead of CO2 ) does not suffer from this undesirable reaction chemistry because CO does not react with OH- . Moreover, CO can be more readily reduced into products containing two or more carbon atoms (i. e., C2+ products) compared to CO2 . We demonstrate here that an electrocatalyst layer derived from copper phthalocyanine (CuPc) mediates this conversion effectively in a flow cell. This catalyst achieved a 25 % higher selectivity for acetate formation at 200 mA/cm2 than a known state-of-art oxide-derived Cu catalyst tested in the same flow cell. A gas diffusion electrode coated with CuPc electrolyzed CO into C2+ products at high rates of product formation (i. e., current densities ≥200 mA/cm2 ), and at high faradaic efficiencies for C2+ production (FEC2+ ; >70 % at 200 mA/cm2 ). While operando Raman spectroscopy did not reveal evidence of structural changes to the copper molecular complex, X-ray photoelectron spectroscopy suggests that the catalyst undergoes conversion to a metallic copper species during catalysis. Notwithstanding, the ligand environment about the metal still impacts catalysis, which we demonstrated through the study of a homologous CuPc bearing ethoxy substituents. These findings reveal new strategies for using metal complexes for the formation of carbon-neutral chemicals and fuels at industrially relevant conditions.


The ambiguous base-pairing and high substrate efficiency of T-705 (Favipiravir) Ribofuranosyl 5'-triphosphate towards influenza A virus polymerase.
T-705 (Favipiravir) is a broad-spectrum antiviral molecule currently in late stage clinical development for the treatment of influenza virus infection. Although it is believed that T-705 potency is mediated by its ribofuranosyl triphosphate (T-705 RTP) metabolite that could be mutagenic, the exact molecular interaction with the polymerase of influenza A virus (IAVpol) has not been elucidated. Here, we developed a biochemical assay to measure the kinetics of nucleotide incorporation by IAVpol in the elongation mode. In this assay, T-705 RTP was recognized by IAVpol as an efficient substrate for incorporation to the RNA both as a guanosine and an adenosine analog. Compared to natural GTP and ATP, the discrimination of T-705 RTP was about 19- and 30-fold, respectively. Although the single incorporation of the ribonucleotide monophosphate form of T-705 did not efficiently block RNA synthesis, two consecutive incorporation events prevented further primer extension. In comparison, 3'-deoxy GTP caused immediate chain termination but was incorporated less efficiently by the enzyme, with a discrimination of 4,900-fold relative to natural GTP. Collectively, these results provide the first detailed biochemical characterization to evaluate the substrate efficiency and the inhibition potency of nucleotide analogs against influenza virus polymerase. The combination of ambiguous base-pairing with low discrimination of T-705 RTP provides a mechanistic basis for the in vitro mutagenic effect of T-705 towards influenza virus.


Synthesis of a Near-Infrared BODIPY Dye for Bioimaging and Photothermal Therapy.
The development of robust photothermal agents for near-infrared (NIR) imaging is a great challenge. Herein, we report the design and synthesis of a new photothermal agent, based on the aza-boron-dipyrromethene framework (azaBDP). This compound possessed excellent photostability and high photothermal-conversion efficiency (50 %) under NIR laser irradiation. When the photothermal properties of this compound were utilized for tumor inhibition, stable long-term fluorescence was observed in living animals. Photothermal treatment efficiently suppressed tumor growth, as evidenced by in vitro and in vivo experiments. Furthermore, NIR emission could be detected by using an imaging system and therapeutic self-monitoring was achieved by using NIR imaging.


Evaluation of (Wet) and (Dry) Mediastinal Chest Drainage in Minimally Invasive and Conventional Cardiac Surgery.
Drainage of fluid and evacuation of air from the pericardial and pleural spaces after cardiothoracic surgery is necessary to prevent effusion, tamponade, and pneumothorax, and also to detect hemorrhage. For this purpose, negative-pressure drains are placed in the mediastinum and pleural cavities. We compared the efficacy and safety of two systems wet and dry drainage for the management and monitoring of negative pressure and anti-reflux valve safety systems, to promote healing of the pleural and pericardial cavities. Two devices for mediastinal chest drainage [Venice PAS (Wet) and Rome PAS (Dry); both Eurosets SRL, Medolla, Italy] were evaluated in terms of safety, efficacy and clinical outcomes in a cohort of 60 patients who underwent elective cardiac surgery procedures. The patients were divided into a minimally invasive cardiac surgery (MICS) group [n=30; mitral valve surgery (MVS) by right anterolateral mini-thoracotomy] and a conventional cardiac surgery (CCS) group [n=30; coronary arterial bypass grafting (CABG) in full sternotomy] at a single institution (Anthea Hospital GVM Care & Research, Bari, Italy). Negative pressure was managed with a target value of -20 cmH2O measured in the chest tube and was related to the device: deviation of ± 1 cmH2O for the Venice PAS (Wet) and 0 cmH2O for the Rome PAS (Dry) in the MICS group; deviation of 1 ± 0.8 cmH2O for the Venice PAS (Wet) and 0.8±0.2 cmH2O for the Rome PAS (Dry) in the CCS group. A constant volumetric air leak meter (VALM) value and the absence of air-leak bubbling were correlated with the absence of air in the pleural cavity and complete pulmonary re-expansion to restore normal respiratory dynamics in the MICS group for both models of chest drainage. The maximum total pericardial blood drained was 1104 ± 302 ml with Venice PAS (Wet) and 1530 ± 230 with Rome PAS (Dry) in the CCS group. There were no reports of cardiac tamponade in either group. The two mediastinal chest drainage devices [Venice PAS (Wet) and Rome PAS (Dry)] in this study were effective, accurate for measuring the applied negative pressure, and safe in their application after cardiac surgery procedures via minimally invasive and conventional approaches for blood and liquid drainage, prevention of cardiac tamponade, and restoration of normal respiratory dynamics after surgical pneumothorax. Both systems are equipped with anti-reflux valves to prevent air and blood from entering the drainage, and no adverse events were reported.


Giant renal calculus in a solitary functioning kidney.
We report a case of giant renal calculus 230 x 140 mm in size and weighing 1,350 g in a solitary functioning kidney treated by nephrolithotomy. A 47-year-old man presented with right lumbar pain, abdominal mass and microscopic hematuria. Physical examination revealed a stony hard mass on the right side of the abdomen, extending from the subcostal region to the iliac crest. A giant renal calculus in his right kidney and atrophic nonfunctioning left kidney was diagnosed by ultrasonography, IVP and CT scan. Right nephrolithotomy was performed. Analysis revealed a calcium phosphate stone. This case is the largest and the heaviest stone reported in the literature in a solitary functioning kidney.


A unique case of well differentiated papillary mesothelioma involving an inguinal hernia.
Well Differentiated Papillary Mesothelioma (WDPM) is an uncommon tumor occurring predominantly in the peritoneum of young women with no history of asbestos exposure. In this report, we present a case of 48 year old male patient presenting with indirect inguinal hernia and incidental finding of a WDPM in the hernial sac during surgery. The unusual site of presentation and the relative rarity of this neoplasm in males evoke much clinico-pathological interest.


Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea.
As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer's perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy.


[Structural study of the basal bodies of the flagella of Bacillus brevis var. G.-B. P+].
The structural organisation of the flagellum basal body was studied in Bacillus brevis var. G.-B. P+ by electron microscopy. It was compared with that of Escherichia coli MS 1350. The basal body of a B. brevis flagellum contains, in addition to two pairs of rings on a rod, another ring-like structure (d = 13.6 nm, h = 4.3 nm) which we referred to as a "collar". The collar makes the basal body of B. brevis different from that of B. subtilis, another Gram-positive bacterium. The collar seems to fasten the flagellum of B. brevis to the cell wall. We have concluded that the basal body can differ not merely among bacterial systematic groups, but also among bacteria belonging to one and the same genus. The role of individual elements in the structure of the basal body of bacterial flagella is discussed.


Characteristics of candidate genes associated with embryonic development in the cow: Evidence for a role for WBP1 in development to the blastocyst stage.
The goal was to gain understanding of how 12 genes containing SNP previously related to embryo competence to become a blastocyst (BRINP3, C1QB, HSPA1L, IRF9, MON1B, PARM1, PCCB, PMM2, SLC18A2, TBC1D24, TTLL3 and WBP1) participate in embryonic development. Gene expression was evaluated in matured oocytes and embryos. BRINP3 and C1QB were not detected at any stage. For most other genes, transcript abundance declined as the embryo developed to the blastocyst stage. Exceptions were for PARM1 and WBP1, where steady-state mRNA increased at the 9-16 cell stage. The SNP in WBP1 caused large differences in the predicted three-dimensional structure of the protein while the SNP in PARM1 caused smaller changes. The mutation in WBP1 causes an amino acid substitution located close to a P-P-X-Y motif involved in protein-protein interactions. Moreover, the observation that the reference allele varies between mammalian species indicates that the locus has not been conserved during mammalian evolution. Knockdown of mRNA for WBP1 decreased the percent of putative zygotes becoming blastocysts and reduced the number of trophectoderm cells and immunoreactive CDX2 in the resulting blastocysts. WBP1 is an important gene for embryonic development in the cow. Further research to identify how the SNP in WBP1 affects processes leading to differentiation of the embryo into TE and ICM lineages is warranted.


Emotional labor strategies and job burnout in preschool teachers: Psychological capital as a mediator and moderator.
Preschool teachers can easily become exhausted and worn out, otherwise known as job burnout. Studies have explored the effects of emotional labor strategies and psychological capital on job burnout; however, few have examined their trilateral relationship, especially the role of psychological capital with respect to emotional labor strategies and job burnout. This study explored the mediating and moderating effects of psychological capital in the relationship between three kinds of emotional labor strategies and job burnout in preschool teachers. A cross-sectional study was conducted among preschool teachers in China. A total of 355 preschool teachers completed a self-report questionnaire, including three scales that measured emotional labor strategies, psychological capital, and job burnout. Resultant data were analyzed based on correlations, multiple regressions, and structural equation modeling. Results showed that for preschool teachers, two emotional labor strategies (deep acting and expression of natural emotion) were found to be negatively correlated with psychological capital and positively correlated with job burnout. However, surface acting was positively correlated with psychological capital and negatively correlated with job burnout. Psychological capital partially mediated the effects of the three emotional labor strategies on job burnout. Additionally, psychological capital significantly moderated the effects of surface acting and deep acting on job burnout. Psychological capital can significantly mediate and moderate the effects of emotional labor strategies on job burnout.


Unplanned postoperative catheterization during admission for coronary artery bypass grafting is neither cheap nor benign, but may rescue patients.
Literature describing outcomes of myocardial ischemia after coronary artery bypass grafting is sparse. We hypothesized these patients had more complications and incurred higher costs of care. Using adult cardiac surgery data and cardiac catheterization (CathPCI) data from the Virginia Cardiac Services Quality Initiative, we identified patients who underwent unplanned cardiac catheterization after coronary artery bypass grafting from 2018 to 2021. Adult cardiac surgery data were matched to CathPCI data examining earliest in-hospital catheterization. Patients not requiring catheterization served as the control group. We identified 10,597 patients who underwent isolated coronary artery bypass grafting, of whom 41 of 10,597 underwent unplanned cardiac catheterization. A total of 21 of 41 patients (51%) received percutaneous coronary intervention, most commonly for non-ST-elevation myocardial infarction (n = 7, 33%) and ST-elevation myocardial infarction (n = 6, 29%). Postoperative cardiac arrest occurred in 14 patients (40%). In patients who underwent percutaneous coronary intervention, 14 (67%) had a single lesion, 4 (19%) had 2 lesions, and 3 (14%) had 3 lesions. The left anterior descending artery (38%) was the most frequently intervened upon vessel. Patients who underwent catheterization were more likely to require balloon pump support (26% vs 11%), to have prolonged ventilation (57% vs 20%), to have renal failure (17% vs 7.1%), and to undergo reintubation (37% vs 3.8%, all P < .04). There was no statistical difference in operative mortality (4.9% vs 2.3%, P = .2) or failure to rescue (4.9% vs 1.6%, P = .14). Total costs were higher in patients who underwent unplanned catheterization ($81,293 vs $37,011, P < .001). Unplanned catheterization after coronary artery bypass grafting is infrequent but associated with more complications and a higher cost of care. Therefore, determination of an association with operative mortality in patients with suspected ischemia after coronary artery bypass grafting requires additional study.


Spelt (Triticum spelta L.) and winter wheat (Triticum aestivum L.) wholemeals have similar sterol profiles, as determined by quantitative liquid chromatography and mass spectrometry analysis.
From a nutritional point of view, cereal lipids include valuable molecules, such as essential fatty acids, phytosterols, and fat-soluble vitamins. Spelt (Triticum spelta L.) is an alternative hulled bread cereal mostly grown in Belgium, where it is mainly intended for animal feed but should increasingly be used for human consumption. The present research focused on phytosterol quantification by LC/APCI-MS2 in saponified wholemeal extracts of 16 dehulled spelt and 5 winter wheat (Triticum aestivum L.) varieties grown in Belgium during 2001-2002 at the same location. Glycosylated sterols and free and formerly esterified sterols could be determined in saponified extracts. Results show that the mean phytosterol content is comparable in both cereals (whereas other lipids, such as oleic and linoleic acids, are increased in spelt wholemeal): spelt extract has, on average, 527.7 microg of free and esterified sterols g(-1) of wholemeal and 123.8 microg of glycosylated sterols g(-1) of wholemeal versus 528.5 and 112.6 microg x g(-1) in winter wheat (values not corrected for recoveries). This is the first report on the application and validation of an LC/MS2 method for the quantification of phytosterols in spelt and winter wheat.


Harmony Search Algorithm for Word Sense Disambiguation.
Word Sense Disambiguation (WSD) is the task of determining which sense of an ambiguous word (word with multiple meanings) is chosen in a particular use of that word, by considering its context. A sentence is considered ambiguous if it contains ambiguous word(s). Practically, any sentence that has been classified as ambiguous usually has multiple interpretations, but just one of them presents the correct interpretation. We propose an unsupervised method that exploits knowledge based approaches for word sense disambiguation using Harmony Search Algorithm (HSA) based on a Stanford dependencies generator (HSDG). The role of the dependency generator is to parse sentences to obtain their dependency relations. Whereas, the goal of using the HSA is to maximize the overall semantic similarity of the set of parsed words. HSA invokes a combination of semantic similarity and relatedness measurements, i.e., Jiang and Conrath (jcn) and an adapted Lesk algorithm, to perform the HSA fitness function. Our proposed method was experimented on benchmark datasets, which yielded results comparable to the state-of-the-art WSD methods. In order to evaluate the effectiveness of the dependency generator, we perform the same methodology without the parser, but with a window of words. The empirical results demonstrate that the proposed method is able to produce effective solutions for most instances of the datasets used.


Tongue squamous cell carcinoma metastasis to percutaneous endoscopic gastrostomy site: A case report of an unusual cause of gastrointestinal bleeding.
Percutaneous endoscopic gastrostomy tubes are often placed in patients with head and neck malignancy for long-term nutritional support. Though rare, head and neck squamous cell carcinoma can metastasize to the percutaneous endoscopic gastrostomy tube site and may initially present as a developing mass or as bleeding at the percutaneous endoscopic gastrostomy site. Patients with head and neck squamous cell carcinoma should be evaluated diligently before and after percutaneous endoscopic gastrostomy placement in order to avoid this rare but life-threatening complication. We present a case of tongue squamous cell carcinoma that metastasized to the percutaneous endoscopic gastrostomy tube site causing gastrointestinal bleeding.


The influence of sequential chemotherapy and radiotherapy on mitogen-induced lymphocyte transformation in patients with acute lymphoblastic leukemia.
Although these studies do not allow a definitive differentiation between the relative influence of chemotherapy and radiotherapy on mitogen-induced lymphocyte transformation, the data suggested both radiotherapy and chemotherapy can cause depression; however, radiotherapy may have a more pronounced effect. The relationship between the absolute peripheral blood lymphocyte count and phytohemagglutin and pokeweed mitogen-induced lymphocyte transformation was also analyzed. These data revealed that patients who are receiving or who have received intensive therapy may have normal peripheral absolute lymphocyte counts with impaired lymphocyte transformation. Serial studies of lymphocyte transformation were evaluated in 10 children with acute lymphoblastic leukemia who received both chemotherapy and radiotherapy.


Retinoic acid is a major regulator of chondrocyte maturation and matrix mineralization.
During the process of endochondral bone formation, chondrocytes undergo a series of complex maturational changes. Our recent studies indicate that this maturational process is influenced by the vitamin A derivative retinoic acid (RA). To learn how this agent regulates chondrocyte development, we characterized matrix gene expression during maturation of cartilage cells in chick sternum. RNAs were isolated from the cephalic portion of day 13, 14, 16, 18, and 20 chick embryo sternum and analyzed via northern blots. Type II collagen RNA levels remained fairly constant during this developmental period. In contrast, expression of type X collagen and alkaline phosphatase (APase) genes was first detected at day 16, followed by that of osteonectin (ON) and osteopontin (OP). To explore the mechanisms triggering these changes, chondrocytes were isolated from the cephalic portion of day 17-18 sternum (US cells) and grown in monolayer in standard serum-containing medium. After 3 weeks in culture, most of the cells enlarged and became type X collagen-positive, but they exhibited low APase activity and contained only trace amounts of ON and OP mRNAs. Treatment of parallel 3-week-old cultures with RA (10-100 nM) rapidly increased expression of the APase, ON, and OP genes severalfold. In concert with a significant increase in APase activity, there was abundant calcium accumulation in the RA-treated cultures. Electron microscopy confirmed the formation of large matrix-associated mineral crystals and the presence of numerous matrix vesicles. The effects of RA were also studied in cultures of immature chondrocytes isolated from the caudal portion of sternum (LS cells).(ABSTRACT TRUNCATED AT 250 WORDS)


Double high-dose chemotherapy and stem cell transplantation in adult Wilms' tumor.
High-dose chemotherapy intensification and hematopoietic stem cell support remains a valuable treatment option for the rare patient with relapsed Wilms' tumor. We report a 22-year-old adult male with an initially diagnosed stage II Wilms' tumor, treated by nephrectomy followed by adjuvant chemotherapy. After 1 year, an intra-abdominal relapse was treated with salvage ifosfamide carboplatin etoposide chemotherapy followed by autologous hematopoietic stem cell mobilization. It was intended that he would receive two tandem cycles of high-dose chemotherapy; the first consisting of melphalan etoposide carboplatin; however, the patient did not return to receive the second cycle while in remission, but did return later with grossly relapsed disease. He was then treated with a novel preparative regimen incorporating high-dose topotecan (topotecan, melphalan and cyclophosphamide). This case confirms the feasibility of double high-dose chemotherapy with hematopoietic stem cell support in relapsed Wilms' tumor. A detailed discussion with an extensive review of the literature, regarding studies evaluating the role and indications of high-dose chemotherapy in Wilms' tumor is provided.


Evaluation of the Translucency Properties for CAD/CAM Full Ceramic Crowns Fabricated From Glass Ceramics (E.max) or High Translucency Zirconia (Lava Plus): A Clinical Study.
Introduction Nowadays, cosmetic demands are the first reason to visit dental clinic. However, most ceramic prostheses need an excessive removal of the dental structure, whether for full crowns or veneer preparation. With the innovation in ceramic materials, high translucent zirconia that demands minimal preparation with high aesthetic results was used for computer-aided design/computer-aided manufacturing (CAD/CAM) Full ceramic crown fabrication. The objective of this study was to compare the translucency properties of CAD/CAM full ceramic crowns fabricated from glass ceramics (E.max) and high translucency zirconia (Lava plus, 3M EPSE). Material and methods The sample consisted of 60 full ceramic crowns divided into two groups; the first group consisted of 30 IPS E.max CAD/CAM full ceramic crowns, while the second one consisted of 30 high translucent zirconia CAD/CAM full ceramic crowns. Translucency for both groups was evaluated directly after cementation by observing the blue light passing through the prostheses. Pearson Chi-Square test was used to study the difference in translucency between the two study groups. Results IPS E.max CAD showed a higher translucency compared to lava plus high translucency zirconia; in addition, this difference was statistically significant (p=0.028). Conclusion Within the limitation of this study, we found that the translucency of dental ceramic was affected by the ceramic material. As IPS E.max CAD was significantly higher in terms of translucency compared to High Translucent Zirconia.


[Restriction fragment length polymorphism of Bam HI and Rsa I loci in the retinoblastoma gene].
The retinoblastoma (Rb) gene probe p123 M1.8 and p68 Rs2.0 were used to study the frequencies of the Bam HI and Rsa I restriction fragment length polymorphisms (RFLPs) in the RB gene among the population of Han nationality in Guangdong province. The result showed that the heterozygote rate of the Rsa I locus was only 55.0%, remarkably different from reports in the literature. Linkage study of the Bam HI and the Rsa I RFLPs demonstrated that 10.5% of the Rsa I polymorphic loci were heterozygous for the Bam HI RFLP. Thus the combined use of the two RFLPs can give information for about 65.5% of the population.


Age-dependent effects of a high-fat diet combined with dietary advanced glycation end products on cognitive function and protection with voluntary exercise.
To determine whether a high fat diet (HFD) combined with an advanced glycation end products (AGEs) diet will induce worse cognitive impairment than a HFD alone and to investigate whether voluntary exercise is capable of improving cognitive function after the combined diet, young and middle-aged male C57BL/6J mice were randomly assigned to four groups, i.e., control, HFD, combined diet, and combined diet treated with voluntary exercise. Compared to HFD, combined diet induced worse memory abilities only in middle-aged mice, as exhibited by the reduced number of crossings and reduced distance in the target zone during a probe trial. Exercise reversed combined-diet-induced cognitive impairment for both ages of mice. For young mice, the neuro-protective effects of exercise were mainly associated with inhibition of NLRP3, Dnmt3a, Dnmt3b, and H3K9me2 and elevation of OST48; it also elevated Bacilli and reduced Epsilonproteobacteria, Campylobacterales, and Helicobacter. For middle-aged mice, exercise elevated Tet2, inhibited NF-κB and NLRP3, and rebalanced circadian clock proteins and the RAGE-OST48 axis; also, exercise elevated Coriobacteriia/Coriobacteriaceae, Erysipelotrichaceae, and Allobaculum and restored intestinal permeability.


CYP27A1 and CYP24 expression as a function of malignant transformation in the colon.
Vitamin D deficiency is strongly associated with the risk of developing colorectal cancer (CRC). Because of the propensity of bioactive 1,25-dihydroxyvitamin D3 to cause toxic hypercalcemia, considerable effort has been directed to identifying safer drugs while retaining the efficacy of the parent compound. However, vitamin D precursors do not present toxicity concerns and may be sufficient for CRC chemoprevention or chemotherapy, providing the appropriate enzymes are present in colonic epithelia. We previously showed that CYP27B1 is present at equally high levels in the colon and CRC irrespective of differentiation but was not present in metastases. In this study we used quantitative immunohistochemistry to show that CYP27A1, converting D3 to 25-hydroxycholecalciferol, is present in increasing concentrations in the nuclei of normal colonic epithelia, aberrant crypt foci (ACF), and adenomatous polyps. Whereas total cellular CYP27A1 remains high in CRC and lymph node metastases, the amount of enzyme present in the nuclei decreases with tumor cell dedifferentiation while rising in the cytoplasm. Similarly, increasing amounts of the deactivating enzyme CYP24 are present in the nuclei of normal colonic epithelia, ACFs, and adenomatous polyps. Although the amount of total CYP24 decreases slightly in CRC as a function of tumor cell dedifferentiation and metastasis, location of this enzyme shifts almost entirely from the nuclear compartment to the cytoplasmic compartment. These data indicate that non-toxic vitamin D precursors should be sufficient for CRC chemoprevention, but that neither vitamin D nor its precursors may be sufficient for CRC chemotherapy.


Low-Complexity Repetitive Epitopes of Plasmodium falciparum Are Decoys for Humoural Immune Responses.
Induction of humoural immunity is critical for clinical protection against malaria. More than 100 malaria vaccine candidates have been investigated at different developmental stages, but with limited protection. One of the roadblocks constrains the development of malaria vaccines is the poor immunogenicity of the antigens. The objective of this study was to map the linear B-cell epitopes of the Plasmodium falciparum erythrocyte invasion-associated antigens with a purpose of understanding humoural responses and protection. We conducted a large-scale screen using overlapping peptide microarrays of 37 proteins from the P. falciparum parasite, most of which are invasion-associated antigens which have been tested in clinical settings as vaccine candidates, with sera from individuals with various infection episodes. Analysis of the epitome of the antigens revealed that the most immunogenic epitopes were predominantly located in the low-complexity regions of the proteins containing repetitive and/or glutamate-rich motifs in different sequence contexts. However, in vitro assay showed the antibodies specific for these epitopes did not show invasion inhibitory effect. These discoveries indicated that the low-complexity regions of the parasite proteins might drive immune responses away from functional domains, which may be an instructive finding for the rational design of vaccine candidates.


Tracheostomy Update: When and How.
Tracheostomy remains one of the most commonly performed surgical procedures in the setting of acute respiratory failure. Tracheostomy literature focuses on 2 aspects of this procedure: when (timing) and how (technique). Recent trials have failed to demonstrate an effect of tracheostomy timing on most clinically important endpoints. Nonetheless, relative to continued translaryngeal intubation, studies suggest that tracheostomy use is associated with less need for sedation and enhanced patient comfort. Evidence likewise suggests that percutaneous dilational tracheostomy is advantageous with respect to cost and complication profile and should be considered the preferred approach in appropriately selected patients.


Efficacy and Safety of Endoscopic Stenting for Crohn's Disease Related Strictures: A Systematic Review and Meta-analysis.
Endoscopic stenting is an evolving treatment for symptomatic Crohn's strictures. Several case series and small studies have reported its efficacy. Future studies can be designed based on a systematic review of the evaluation of efficacy. Hence, this meta-analysis was conducted to assess the critical role of stents in the management of intestinal strictures associated with Crohn's disease (CD). A literature search of various databases from 2000 to February 2022 was conducted for studies evaluating the outcome of stents in patients with CD-related stricture. The outcomes assessed included technical and clinical success, adverse events, symptom recurrence, and the need for a surgical resection. Pooled event rates across studies were expressed with summative statistics. Ten studies with 170 patients were included in the present analysis. The pooled event rates for technical success, clinical success, stent migration, and post-procedural pain were 98.2% (95% CI, 95.8-100), 71.3% (95% CI, 57.4-85.1), 32% (95% CI, 0.0-65.3) and 20.2% (95% CI, 4.1-36.2), respectively. The cumulative recurrence rate and need for surgery were 40.1% (95% CI, 20.3-59.9) and 8.6% (95% CI, 1.7-15.5), respectively. Subgroup analysis showed that partially-covered (PC) self-expanding metallic stent (SEMS) was significantly better than fully-covered SEMS with a lower stent migration rate and symptom recurrence rate. Overall efficacy of stents in the management of CD-related stricture remains moderate with a low complication rate. Among the stents, PC-SEMS may be associated with a more favorable outcome. Future studies will be needed to determine the long-term benefits of endoscopic stenting.


Mode shapes of a damaged and repaired tympanic membrane as analysed by the finite element method.
This work makes use of recent finite element discretization of the human tympanic membrane where the known anisotropy of the tympanic membrane is implemented by a series of thin beam elements superimposed on thin shell membrane elements. These thin beam elements were introduced in order to simulate the fibre structure of the tympanic membrane. The onset of tympanosclerosis has been modelled as a gradual increase in tympanic membrane density and modulus in the affected area. This increased density results in a fall of 55% of the first natural frequency for only a 16% area of drum sclerosis. Additionally the amplitude response is significantly reduced. Repair of the membrane was simulated by removal of the fibre system from the affected area. Under these circumstances the natural frequencies virtually return to the healthy state but the mode shapes of vibration do not. The repair to the membrane, although not significantly altering frequency values, has resulted in a disruption to the normal mode shape patterns with consequences in the movements conveyed to the stapes and cochlear fluids.


Full-Endoscopic Lumbar Decompression with Minimal Nerve Root Retraction for Impending Neurologic Deficit in Degenerative Lumbar Spine Diseases.
The aim of this retrospective case study was to analyze the outcomes of minimal nerve root retraction in patients with impending neurologic deficit in degenerative lumbar spine disease using the full-endoscopic spine surgery. Thirty-seven consecutive patients with impending neurologic deficit underwent endoscopic spine surgery through either the transforaminal or the interlaminar approach. Their clinical outcomes were evaluated with visual analog scale (VAS) leg pain score, Oswestry Disability Index (ODI), and MacNab's criteria. The outcome of motor deficitis was evaluated with the Medical Research Council (MRC) grade. Completeness of decompression was documented with a postoperative magnetic resonance imaging (MRI) and computed tomography (CT) scan. A total of 40 lumbar levels of 37 patients were operated, VAS score of the leg improved from 7.7 ± 1 to 1.9 ± 0.6 (p < 0.0001). ODI score improved from 74.7 ± 6.5 to 25.4 ± 3.49 (p < 0.0001). Motor weakness improved significantly immediately after surgery. The mean MRC grade increased to 1.97, 3.65, 4.41, and 4.76 preoperatively, at 1 week, at 3 months, and at the final follow-up, respectively, and all the patients with foot drop and cauda equina syndrome symptom recovered completely. One patient with great toe drop recovered partially to MRC grade 3. Mean follow-up of the study was 13.3 ± 6.1 months. According to MacNab's criteria, 30 patients (80.1%) had good and 7 patients (18.9%) had excellent results. Three patients required revision surgery. Minimal nerve root retraction during full-endoscopic spine surgery is safe and effective for treatment of the impending neurologic deficit. We could achieve a thorough decompression of the affected nerve root with acceptable clinical outcome and minimal postoperative morbidity.


A Simple Method for 2-D In Vivo Dosimetry by Portal Imaging.
To improve patient safety and treatment quality, verification of dose delivery in radiotherapy is desirable. We present a simple, easy-to-implement, open-source method for in vivo planar dosimetry of conformal radiotherapy by electronic portal imaging device (EPID). Correlation ratios, which relate dose in the mid-depth of slab phantoms to transit EPID signal, were determined for multiple phantom thicknesses and field sizes. Off-axis dose is corrected for by means of model-based convolution. We tested efficacy of dose reconstruction through measurements with off-reference values of attenuator thickness, field size, and monitor units. We quantified the dose calculation error in the presence of thickness changes to simulate anatomical or setup variations. An example of dose calculation on patient data is provided. With varying phantom thickness, field size, and monitor units, dose reconstruction was almost always within 3% of planned dose. In the presence of thickness changes from planning CT, the dose discrepancy is exaggerated by up to approximately 1.5% for 1 cm changes upstream of the isocenter plane and 4% for 1 cm changes downstream. Our novel electronic portal imaging device in vivo dosimetry allows clinically accurate 2-dimensional reconstruction of dose inside a phantom/patient at isocenter depth. Due to its simplicity, commissioning can be performed in a few hours per energy and may be modified to the user's needs. It may provide useful dose delivery information to detect harmful errors, guide adaptive radiotherapy, and assure quality of treatment.


Gamification in Biomedical Science Education: The Successful Implementation of Resimion, a Scenario-Based Learning Tool.
Introduction: Scenario-based learning and gamification have many advantages in comparison to traditional didactic teaching methods, including development of many higher-level skills such as analysis and evaluation. It is hoped that these simulations provide a real-world experience in a format accessible to students. Integration of these tools into teaching excelled during the COVID-19 pandemic, an event that completely changed education and initiated the greatest advancement in digital learning to date. We discuss our experiences using Resimion, a novel scenario-based learning tool that was adapted to biomedical science, both for teaching and assessment. Methods: Our cohort included 769 students studying BSc(Hons) Biomedical Science at the University of the West of England from 2020 to 2023. Data was obtained from assessments within four different modules, two at FHEQ level 5 and two at level 6. Students were grouped based on reasonable adjustment (RA) status, including physical issues, specific learning differences and neurodiversity, with differences between student groups and assessment types analysed by ANOVA. Results: Data clearly demonstrate good engagement from students utilising Resimion software, representing 18,436 student interactions in total, across both assessed and non-assessed activities. RAs of any type did not alter submission rates (p = 0.53) or student outcome in any of the assessment types analysed. However, submission rates for Resimion assessments were notably higher than for other assessment types (p = 0.002). Whist outcomes were not significantly different, students with RAs did take significantly longer to complete the Haematology and Transfusion assessments (p = 0.0012). Specifically, neurodiverse students and those with specific learning differences used on average 81% of their allocated time, students with other RAs used 76%, whereas students without RAs used just 56% (p ≤ 0.0001), highlighting the appropriate adjustment of extra time provided for these students. It was further observed that 1.3% of Resimion activities undertaken by students utilised the in-built inclusivity features in the software. Both students with known RAs, and those without, utilised these features, therefore also aiding students without a formal diagnosis. Conclusion: The scenario-based learning tool Resimion was successfully integrated into the teaching of biomedical science and provided an engaging platform for students, with comparable results to other traditional assessment types.