Sequence Homology between Chloroplast DNAs from Several Higher Plants.
An estimate has been made of the amount of sequence homology present in the chloroplast DNA (ctDNA) of several higher plants by the technique of DNA-DNA hybridization. Approximately 85% of tomato, 60% of spinach, 45% of kale, and 15% of barley ctDNA sequences were found to hybridize with tobacco ctDNA under conditions in which maximum hybridization in homologous reactions reached 85%. All heteroduplexes contained significant amounts of sequence mismatch as indicated by a 3 to 9 C decrease in melting temperature as compared to homoduplex.The data suggest that considerable sequence homology exists between the ctDNAs of these plants and that some sequences are held in common among all of the species tested.


Role of CYP27A in cholesterol and bile acid metabolism.
The CYP27A gene encodes a mitochondrial cytochrome P450 enzyme, sterol 27-hydroxylase, that is expressed in many different tissues and plays an important role in cholesterol and bile acid metabolism. In humans, CYP27A deficiency leads to cerebrotendinous xanthomatosis. To gain insight into the roles of CYP27A in the regulation of cholesterol and bile acid metabolism, cyp27A gene knockout heterozygous, homozygous, and wild-type littermate mice were studied. In contrast to homozygotes, heterozygotes had increased body weight and were mildly hypercholesterolemic, with increased numbers of lipoprotein particles in the low density lipoprotein size range. Cyp7A expression was not increased in heterozygotes but was in homozygotes, suggesting that parts of the homozygous phenotype are secondary to increased cyp7A expression and activity. Homozygotes exhibited pronounced hepatomegaly and dysregulation in hepatic cholesterol, bile acid, and fatty acid metabolism. Hepatic cholesterol synthesis and synthesis of bile acid intermediates were increased; however, side chain cleavage was impaired, leading to decreased bile salt concentrations in gallbladder bile. Expression of Na-taurocholate cotransporting polypeptide, the major sinusoidal bile salt transporter, was increased, and that of bile salt export pump, the major canalicular bile salt transporter, was decreased. Gender played a modifying role in the homozygous response to cyp27A deficiency, with females being generally more severely affected. Thus, both cyp27A genotype and gender affected the regulation of hepatic bile acid, cholesterol, and fatty acid metabolism.


Physician associates: an asset for physician training and a 21st-century NHS?
The introduction of physician associates in the UK reflects a need within our healthcare system to continue providing high-quality care amid a backdrop of ever-increasing demand, while acknowledging a medical workforce demanding flexibility and choice in their training alongside a well-resourced working environment. This article looks at the fundamental benefits that could be drawn from the physician associate workforce, while highlighting the historical progress of the profession and emphasising ongoing issues and limitations that will provide insight for the future development of the profession.


A Domain Enriched Deep Learning Approach to Classify Atherosclerosis using Intravascular Ultrasound Imaging.
Intravascular ultrasound (IVUS) imaging is widely used for diagnostic imaging in interventional cardiology. The detection and quantification of atherosclerosis from acquired images is typically performed manually by medical experts or by virtual histology IVUS (VH-IVUS) software. VH-IVUS analyzes backscattered radio frequency (RF) signals to provide a color-coded tissue map, and is the method of choice for assessing atherosclerotic plaque in situ. However, a significant amount of tissue cannot be analyzed in reasonable time because the method can be applied just once per cardiac cycle. Furthermore, only hardware and software compatible with RF signal acquisition and processing may be used. We present an image-based tissue characterization method that can be applied to entire acquisition sequences post hoc for the assessment of diseased vessels. The pixel-based method utilizes domain knowledge of arterial pathology and physiology, and leverages technological advances of convolutional neural networks to segment diseased vessel walls into the same tissue classes as virtual histology using only grayscale IVUS images. The method was trained and tested on patches extracted from VH-IVUS images acquired from several patients, and achieved overall accuracy of 93.5% for all segmented tissue. Imposing physically-relevant spatial constraints driven by domain knowledge was key to achieving such strong performance. This enriched approach offers capabilities akin to VH-IVUS without the constraints of RF signals or limited once-per-cycle analysis, offering superior potential information acquisition speed, reduced hardware and software requirements, and more widespread applicability. Such an approach may well yield promise for future clinical and research applications.


Tibial plateau levelling osteotomy implant removal: a retrospective analysis of 129 cases.
To evaluate a cohort of dogs undergoing tibial plateau levelling osteotomy (TPLO) implant removal to determine key clinical features, prevalence, and indications for implant removal. Medical records of dogs undergoing TPLO implant removal at a private referral practice (Dallas Veterinary Surgical Center) between 2004-2008 were reviewed. Patient signalment, implant type, presence of concurrent medical disease, surgeon, antibiotic use, aerobic bacterial culture result, and operative findings were recorded. Data were analyzed using paired t-test, Fisher's exact test, and Wilcoxon-rank sum test. Statistical significance was set at p <0.05. The TPLO implants were removed from 126 dogs (n = 129, 4.8% of TPLO procedures) during the study period. Average time interval from TPLO to implant removal was 16.0 ± 17.8 months. The most common clinical signs were the presence of an open wound (n = 80), draining tract (n = 64), and lameness (n = 59). Culture of tissue or fluid from the implant bed or implants was positive for bacterial growth in 95/115 cases. A significantly greater proportion of the implants removed were Slocum TPLO plates (n = 109; 6.1%) when compared to other TPLO plate types (n = 20; 2.3%) (p <0.0001). No association was identified between a positive bacterial culture and measured variables. Local bacterial infection and clinical signs of inflammation were the most common reasons for TPLO implant removal. There may be an increased implant-associated complication rate for Slocum TPLO plates in the study population.


Evidence Based Burn Depth Assessment Using Laser-Based Technologies: Where Do We Stand?
Early clinical assessment of burn depth and associated healing potential (HP) remains extremely challenging, even for experienced surgeons. Inaccurate diagnosis often leads to prolonged healing times and unnecessary surgical procedures, resulting in incremental costs, and unfavorable outcomes. Laser Doppler imaging (LDI) is currently the most objective and accurate diagnostic tool to measure blood flow and its associated HP, the main predictor for a patient's long-term functional and aesthetic outcome. A systematic review was performed on non-invasive, laser-based methods for burn depth assessment using skin microcirculation measurements to determine time to healing: Laser Doppler flowmetry (LDF), LDI and laser speckle contrast imaging (LSCI). Important drawbacks of single point LDF measurements are direct contact with numerous small points on the wound bed and the need to carry out serial measurements over several days. LDI is a fast, "non-contact," single measurement tool allowing to scan large burned areas with a 96% accuracy. LDI reduces the number of surgeries, improves the functional and aesthetic outcome and is cost-effective. There is only limited evidence for the use of LSCI in burn depth assessment. LSCI still needs technical improvements and scientific validation, before it can be approved for reliable burn assessment. LDI has proven to be invaluable in determining the optimal treatment of a burn patient. For unclear reasons, LDI is still not routinely used in burn centers worldwide. Additional research is required to identify potential "barriers" for universal implementation of this evidence-based burn depth assessment tool.


Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains.
Using an aerobic oxidative coupling, different new imidazo[1,2-a]-N-heterocycles with gem-difluroroalkyl side chains have been prepared in fair yields by the reaction of gem-difluoroenones with aminopyridines, -pyrimidines and -pyridazines. Condensed heterocycles of this type play an important role as key core structures of various bioactive compounds. Further, starting with a chloroimidazopyridazine derivative, Pd-catalyzed coupling reactions as well as nucleophilic substitutions have been performed successfully in order to increase the molecular diversity.


Tumor Microvessel Density as a Potential Predictive Marker for Bevacizumab Benefit: GOG-0218 Biomarker Analyses.
Combining bevacizumab with frontline chemotherapy statistically significantly improved progression-free survival (PFS) but not overall survival (OS) in the phase III GOG-0218 trial. Evaluation of candidate biomarkers was an exploratory objective. Patients with stage III (incompletely resected) or IV ovarian cancer were randomly assigned to receive six chemotherapy cycles with placebo or bevacizumab followed by single-agent placebo or bevacizumab. Five candidate tumor biomarkers were assessed by immunohistochemistry. The biomarker-evaluable population was categorized into high or low biomarker-expressing subgroups using median and quartile cutoffs. Associations between biomarker expression and efficacy were analyzed. All statistical tests were two-sided. The biomarker-evaluable population (n = 980) comprising 78.5% of the intent-to-treat population had representative baseline characteristics and efficacy outcomes. Neither prognostic nor predictive associations were seen for vascular endothelial growth factor (VEGF) receptor-2, neuropilin-1, or MET. Higher microvessel density (MVD; measured by CD31) showed predictive value for PFS (hazard ratio [HR] for bevacizumab vs placebo = 0.40, 95% confidence interval [CI] = 0.29 to 0.54, vs 0.80, 95% CI = 0.59 to 1.07, for high vs low MVD, respectively, P interaction = .003) and OS (HR = 0.67, 95% CI = 0.51 to 0.88, vs 1.10, 95% CI = 0.84 to 1.44, P interaction = .02). Tumor VEGF-A was not predictive for PFS but showed potential predictive value for OS using a third-quartile cutoff for high VEGF-A expression. These retrospective tumor biomarker analyses suggest a positive association between density of vascular endothelial cells (the predominant cell type expressing VEGF receptors) and tumor VEGF-A levels and magnitude of bevacizumab effect in ovarian cancer. The potential predictive value of MVD (CD31) and tumor VEGF-A is consistent with a mechanism of action driven by VEGF-A signaling blockade.


2-(penta-1,3-diynyl)-5-(3,4-dihydroxybut-1-ynyl)thiophene, a novel NQO1 inducing agent from Echinops grijsii Hance.
A natural alkynol group-substituted thiophene, 2-(penta-1,3-diynyl)-5-(3,4-dihydroxybut-1-ynyl)-thiophene (PDDYT), was isolated from the roots of Echinops grijsii Hance. It possessed potent NAD(P)H: quinone oxidoreductase1 (NQO1) inducing activity and could activate Keap1-Nrf2 pathway effectively in murine hepatoma Hepa 1c1c7 cells. Further investigations indicated that the activation of Keap1-Nrf2 pathway by PDDYT might be attributed to the activation of Akt and depleting the cellular glutathione (GSH).


Anionic Lipid Clustering Model.
Many molecular features contribute to the antimicrobial activity of peptides. One aspect that contributes to the antimicrobial activity of a peptide, in many cases, results from the fact that many antimicrobial peptides are polycationic and the lipids on the surface of bacteria are often anionic. In certain cases this can result in the clustering of anionic lipids as a result of the binding of the cationic peptide to the surface of the bacterial membrane. This lipid clustering can be detrimental to the viability of the bacteria to which the peptide binds. Several factors, including the charge, size, and conformational flexibility of the peptide, will determine the efficiency of lipid clustering. In addition, the lipid composition of the bacterial membrane is very variable, and it plays a critical role in this mechanism. As a result, one can test the importance of this factor by determining the species specificity of the antimicrobial activity of the peptide. The molecular mechanism by which lipid clustering affects bacterial viability is uncertain in many cases. This phenomenon can be used to increase the antimicrobial potency of peptides in some case and can also predict the bacterial species specificity of some agents.


Internalized Functional DNA Aptamers as Alternative Cancer Therapies.
Despite major advances, cancer remains one of the largest burdens of disease worldwide. One reason behind this is that killing tumor cells without affecting healthy surrounding tissue remains a largely elusive prospect, despite the widespread availability of cytotoxic chemotherapeutic agents. To meet these modern healthcare requirements, it is essential to develop precision therapeutics that minimise off-target side-effects for various cancer types. To this end, highly specific molecular targeting agents against cancer are of great interest. These agents may work by targeting intracellular signalling pathways following receptor binding, or via internalization and targeting to specific subcellular compartments. DNA aptamers represent a promising molecular tool in this arena that can be used for both specific cell surface targeting and subsequent internalization and can also elicit a functional effect upon internalization. This review examines various cancer targeting cell-internalizing aptamers, with a particular focus towards functional aptamers that do not require additional conjugation to nanoparticles or small molecules to elicit a biological response. With a deeper understanding and precise exploitation of cancer specific molecular pathways, functional intracellular DNA aptamers may be a powerful step towards more widespread development of precision therapeutics.


The relationship between disorders of K+ and Mg+ homeostasis.
Potassium and magnesium balance are frequently altered by common pathological conditions. Isolated disturbances of potassium balance do not produce secondary abnormalities in magnesium homeostasis. In contrast, primary disturbances in magnesium balance, particularly magnesium depletion, produce secondary potassium depletion. This appears to result from an inability of the cell to maintain the normally high intracellular concentration of potassium, perhaps as a result of an increase in membrane permeability to potassium and/or inhibition of Na+-K-ATPase. As a result, the cells lose potassium, which is excreted in the urine. Repletion of cell potassium requires correction of the magnesium deficit. Are such magnesium dependent alterations in potassium balance of any clinical significance? Within the context of electrolyte disturbances, magnesium replacement is often necessary before hypokalemia and potassium depletion can be satisfactorily corrected with potassium supplements. The hyponatremia often seen with chronic diuretic usage may also be related to depleted intracellular potassium stores. In a small group of patients with chronic congestive heart failure, magnesium replacement alone was sufficient to correct this hyponatremia. Finally, magnesium and potassium depletion may play an important role in the development of cardiac arrhythmias in certain select groups of patients, such as those with overt ischemic heart disease. The frequency of magnesium depletion in some clinical disease states warrants renewed interest in the relationship between magnesium and potassium homeostasis.


Predictors of immune response and reactogenicity to AS03B-adjuvanted split virion and non-adjuvanted whole virion H1N1 (2009) pandemic influenza vaccines.
In 2009, 943 children aged 6 months to 10 years were randomised to receive two doses of an oil-in water AS03B-adjuvanted split virion or a non-adjuvanted whole virion H1N1 (2009) vaccine. The large numbers allowed investigation of possible predictors of immune response and reactogenicity. We used regression analysis to examine the effect of variables including past receipt of seasonal vaccine, antipyretics post-vaccination, interval between doses and pre-existing antibodies to H1N1 (2009) on immunogenicity. We also examined the relationship between immunogenicity and reactogenicity and whether prior infection or underlying conditions affected reactogenicity. For both vaccines, haemagglutination-inhibition titres were 60% higher in children with fever ≥38 °C after vaccination and 29% lower in those previously given seasonal vaccine. Early use of antipyretics did not affect immunogenicity. Post-vaccination titres were higher with longer intervals between doses and in those with evidence of prior infection, but reactogenicity in the latter was unaffected. In the adjuvanted vaccine group, reactions were more common in children with atopy. Both vaccines were safe and immunogenic in those with prior infection. Reduction in the interval between doses for earlier protection would be at the cost of reduced immunogenicity. The effect of seasonal vaccine on immunogenicity merits further investigation.


[Endometriosis of the large intestine. A report of 2 clinical cases].
Intestinal involvement of endometriosis requiring treatment is 5%, but only 0.7% needs intestinal resection. The authors report two cases of colic endometriosis and illustrate problems in diagnosis and management of this disease. Usually intestinal endometriosis takes the form of asymptomatic superficial serosal implants, encountered incidentally at laparotomy for other diseases, but it can also result in obstruction and occasionally bleeding. Any premenopausal woman with episodic bowel symptoms associated with gynecologic complaints should be suspected of endometriosis of the colon. Diagnosis can be suspected by double-contrast enema examination and colonoscopy with biopsy, although neither is likely to establish the diagnosis with certainty. In fact there are no radiologic or diagnostic imaging findings that are specific for endometriosis and unequivocal diagnosis requires microscopic examination. Differential diagnosis includes primary carcinoma of the colon and other benign diseases (pelvic inflammatory disease, diverticulitis, inflammatory bowel disease, pelvic abscess, polyps, etc.). The treatment of patients with uncomplicated, but symptomatic gastrointestinal endometriosis depends on the age of the patient and her childbearing attitude. Resection of the affected bowel should be done in patient with pain, bleeding, changes in bowel habits and intestinal obstruction and it is necessary to avoid neglecting a malignant tumor. Total abdominal hysterectomy and bilateral oophorectomy is the treatment of choice in the perimenopausal and menopausal women. In symptomatic women desiring children the only resection of involved colon may be appropriate treatment. In these subjects hormonal therapy can be useful.


Job choice and personality: a profile of Michigan occupational and physical therapists.
The aim of this descriptive study was to compare the personality profiles of occupational therapists (OTs) and physical therapists (PTs) and examine the relationship between personality and job choice. The Kiersey-Bates Personality Inventory (70-item questionnaire) and a brief demographic survey were mailed to a random sample of 400 Ts and 400 PTs in Michigan. A total of 294 completed surveys were returned for analysis, for a combined response rate of 37%. Results showed that while the demographic profiles of OTs and PTs were similar, there were very significant differences between OTs and PTs with respect to personality. The implications of these findings for professional health education are discussed.


Chemicophysical surface treatment and the experimental demonstration of Schottky-Mott rules for metal/semiconductor heterostructure interfaces.
Metal/semiconductor (MS) heterostructure is of wide interest in a number of areas including physics, chemistry, materials science, materials engineering, chemical engineering, and electrical engineering. It is an important element of modern technology. The present investigation describes a novel experimental technique to address the influence of interfacial chemical passivation on the Schottky-Mott [Naturwiss. 26, 843 (1938); Cambridge Philos. Soc. 34, 568 (1938)] rules for MS heterostructure, and to try to establish these rules. The success of the experiment derives from three remarkable findings: First, a semiconductor (Al(x)Ga(1-x)N), which is robust and relatively less susceptible to an easy reaction with foreign chemicals, is needed for the demonstration. Second, reactive ion etching together with wet chemical etching by certain selected chemical (such as KOH), but not by others (for example, H(3)PO(4) or aqua regia), can clean the semiconductor surface well, and remove/passivate the dangling chemical bonds from this surface. Third, a judicious selection of deposition parameters for the deposition of metal(s) preferably on a certain selected semiconductor can lead to metal deposition on the semiconductor surface by van der Waals type of epitaxy. Transmission electron microscopy and x-ray diffraction indicate that MS heterostructures, thus prepared, are very different from others; they appear to provide convincing experimental verification of the Schottky-Mott rules, and to establish these rules without any ambiguity. Others fail to do it.


Economic Impact of Low Adherence to COPD Management Guidelines in Spain.
The objective of this study was to assess the non-adherence level of Spanish clinical practice to guideline recommendations for the treatment of chronic obstructive pulmonary disease (COPD) and to estimate the potential impact on pharmaceutical expenditure resulting from transitioning current treatment patterns according to guidelines. A model was developed to compare current prescribing patterns with two alternative scenarios: the first aligned with the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2020) recommendations, and the second with the Spanish Guidelines for COPD (GesEPOC 2017). Current treatment practice was obtained from publications that describe treatment patterns by pulmonology departments in Spain. The economic impact between patterns was calculated from the perspective of the Spanish National Health System (NHS), considering the annual pharmacological costs of COPD inhaled maintenance therapy. Two additional analyses were performed: one that included current prescribing patterns of patients managed by pulmonology and primary care centers in Spain (published aggregated data); and another that only considered the appropriate use of inhaled corticosteroids (ICS) treatment according to guidelines. It was estimated that 54% and 38% of patients were not treated in line with GOLD and GesEPOC recommendations, respectively, mainly due to a broader use of ICS-based therapies. Adapting treatment to recommendations could provide a potential annual cost-saving of €17,792,022 (according to GOLD) and €5,881,785 (according to GesEPOC). In scenario analysis 1, a 26% of non-adherence to GesEPOC guideline was observed with a potential annual pharmacological cost-saving of €2,707,554. In scenario analysis 2, considering only inappropriate use of ICS treatment, an annual cost-saving of €17,863,750 (according to GOLD) and €9,904,409 (according to GesEPOC) was calculated. More than a third of treatments for COPD patients in Spain are not prescribed in accordance with guideline recommendations. The adaptation of clinical practice to guideline recommendations could provide important cost-savings for the Spanish NHS.


Does action planning moderate the intention-habit interaction in the exercise domain? A three-way interaction analysis investigation.
Both habit strength and action planning have been found to moderate the intention-exercise behaviour relationship, but no research exists that has investigated how habit strength and action planning simultaneously influence this relationship. The present study was designed to explore this issue in a prospective sample of undergraduate students (N = 415): action planning, habit strength, intention, attitudes, subjective norms and perceived behavioural control were assessed at baseline and exercise behaviour was assessed 2 weeks later. Both habit strength and action planning moderated the intention-exercise relationship, with stronger relationship at higher levels of planning or habit strength. Decomposing a significant action planning × habit strength × intention interaction showed that the strength of the intention-exercise relationship progressed linearly through levels of action planning and habit strength. These novel results show that action planning strengthens the intention-habit strength interaction in the exercise domain: exercise interventions should therefore focus on simultaneously bolstering action planning and habit strength.


3D Interconnected and Multiwalled Carbon@MoS2 @Carbon Hollow Nanocables as Outstanding Anodes for Na-Ion Batteries.
Currently, the specific capacity and cycling performance of various MoS2 /carbon-based anode materials for Na-ion storage are far from satisfactory due to the insufficient structural stability of the electrode, incomplete protection of MoS2 by carbon, difficult access of electrolyte to the electrode interior, as well as inactivity of the adopted carbon matrix. To address these issues, this work presents the rational design and synthesis of 3D interconnected and hollow nanocables composed of multiwalled carbon@MoS2 @carbon. In this architecture, (i) the 3D nanoweb-like structure brings about excellent mechanical property of the electrode, (ii) the ultrathin MoS2 nanosheets are sandwiched between and doubly protected by two layers of porous carbon, (iii) the hollow structure of the primary nanofibers facilitates the access of electrolyte to the electrode interior, (iv) the porous and nitrogen-doping properties of the two carbon materials lead to synergistic Na-storage of carbon and MoS2 . As a result, this hybrid material as the anode material of Na-ion battery exhibits fast charge-transfer reaction, high utilization efficiency, and ultrastability. Outstanding reversible capacity (1045 mAh g-1 ), excellent rate behavior (817 mAh g-1 at 7000 mA g-1 ), and good cycling performance (747 mAh g-1 after 200 cycles at 700 mA g-1 ) are obtained.


Preoperative flow analysis of arteriovenous malformations and obliteration response after stereotactic radiosurgery.
Morphological and angioarchitectural features of cerebral arteriovenous malformations (AVMs) have been widely described and associated with outcomes; however, few studies have conducted a quantitative analysis of AVM flow. The authors examined brain AVM flow and transit time on angiograms using direct visual analysis and a computer-based method and correlated these factors with the obliteration response after Gamma Knife radiosurgery. A retrospective analysis was conducted at a single institution using a prospective registry of patients managed from January 2013 to December 2019: 71 patients were analyzed using a visual method of flow determination and 38 were analyzed using a computer-based method. After comparison and validation of the two methods, obliteration response was correlated to flow analysis, demographic, angioarchitectural, and dosimetric data. The mean AVM volume was 3.84 cm3 (range 0.64-19.8 cm3), 32 AVMs (45%) were in critical functional locations, and the mean margin radiosurgical dose was 18.8 Gy (range 16-22 Gy). Twenty-seven AVMs (38%) were classified as high flow, 37 (52%) as moderate flow, and 7 (10%) as low flow. Complete obliteration was achieved in 44 patients (62%) at the time of the study; the mean time to obliteration was 28 months for low-flow, 34 months for moderate-flow, and 47 months for high-flow AVMs. Univariate and multivariate analyses of factors predicting obliteration included AVM nidus volume, age, and flow. Adverse radiation effects were identified in 5 patients (7%), and 67 patients (94%) remained free of any functional deterioration during follow-up. AVM flow analysis and categorization in terms of transit time are useful predictors of the probability of and the time to obliteration. The authors believe that a more quantitative understanding of flow can help to guide stereotactic radiosurgery treatment and set accurate outcome expectations.


Open reduction for intra-articular calcaneal fractures: evaluation using computed tomography.
Radiographic and computed tomography features of unilateral intra-articular calcaneal fractures after open reduction and internal fixation were compared with late functional outcomes to identify prognostic factors. Sixty-one of 67 patients treated between 1997 and 2002 could walk painlessly postoperatively (average, 19.7 months). Functional results (Laasonen's criteria) were excellent or good in 92.5%. Factors associated with better functional results were lower age (p = .0227), greater Böhler angle at the time of injury (p < .0001), lower Sanders' grade (p = .0497), increased height of fractured regions (p = .0249), better reduction of the posterior facet (p = .0126), and better reduction of the calcaneocuboid joint (p = .0023). Only the latter two were found to be surgical prognostic factors.


A Partial E3 Deletion in Replication-Defective Adenoviral Vectors Allows for Stable Expression of Potentially Toxic Transgene Products.
Adenovirus (Ad) is used extensively for construction of viral vectors, most commonly with deletion in its E1 and/or E3 genomic regions. Previously, our attempts to insert envelope proteins (Env) of HIV-1 into such vectors based on chimpanzee-derived Ad (AdC) viruses were thwarted. Here, we describe that genetic instability of an E1- and E3-deleted AdC vector of serotype C6 expressing Env of HIV-1 can be overcome by reinsertion of E3 sequences with anti-apoptotic activities. This partial E3 deletion presumably delays premature death of HEK-293 packaging cell lines due to Env-induced cell apoptosis. The same partial E3 deletion also allows for the generation of stable glycoprotein 140 (gp140)- and gp160-expressing Ad vectors based on AdC7, a distinct AdC serotype. Env-expressing AdC vectors containing the partial E3 deletion are genetically stable upon serial cell culture passaging, produce yields comparable to those of other AdC vectors, and induce transgene product-specific antibody responses in mice. A partial E3 deletion thereby allows expansion of the repertoire of transgenes that can be expressed by Ad vectors.


Shiga toxins even when different are encoded at identical positions in the genomes of related temperate bacteriophages.
The nucleotide sequence of an 11,142-bp region including the stx2 operon in the genome of the temperate bacteriophage 933W in the EDL933 strain of Escherichia coli O157 was determined and compared to the respective regions derived from other lambdoid bacteriophages. In phage 933W, a region of ORFs interlinked by overlapping start-stop codons (ATGA) was detected preceding the toxin gene. These ORFs show a high degree of sequence identity to genes of the nin region of phage lambda. Immediately downstream of these nin genes we identified an ORF that may code for an anti-terminator similar to the lambda Q protein. It is concluded that toxin expression is directly associated with the initiation of cell lysis. Downstream of the stx2 operon we identified an ORF that is homologous to the holin gene S of bacteriophage PA-2. PCR primers were designed, which, based on a comparison of the phage sequences, appeared to be common to both stx1- and stx2-harbouring phages. However, only seven of the 22 STEC strains investigated from serogroups O157, O26, O103 and O111 yielded the expected PCR amplification product. The data reported here may be useful in developing new strategies for inhibiting the expression of Stx and for developing universal diagnostic primers for use in tracking the origin and evolution of Shiga toxins and the phages that carry them.


The effect of beta-endorphin on natural cytotoxicity and antibody dependent cellular cytotoxicity.
The ability of the central nervous system to modulate immune responsiveness has received increasing attention. A potential mechanism that would allow the central nervous system to alter the immune system is the release of neuroendocrine and neurotransmitter polypeptides into the peripheral circulation with subsequent modulation of immunocyte function. In this report, we demonstrate that the neuropeptide, beta-[D-ALA2]-endorphin augments natural cytotoxicity but does not effect antibody-dependent cellular cytotoxicity. The observations are discussed in relation to the mechanisms for natural cytotoxicity and antibody dependent cellular cytotoxicity.


Oat seed globulin: subunit characterization and demonstration of its synthesis as a precursor.
The predominant storage protein of oat (Avena sativa L.) seeds is a saline-soluble globulin with a mol wt of 320,000 which is composed of six large (M(r) = 35,000 to 40,000) and six small (M(r) = 20,000 to 25,000) subunits. Experiments were conducted to further describe the subunit polypeptides and to identify the initial translation products of globulin mRNAs. Approximately 20 large subunits and 10 small subunits were resolved by two-dimensional gel analysis. The large and small subunits had acidic and basic isoelectric points, respectively. Disulfide-linked complexes of one large and one small subunit were isolated by extraction in buffer lacking a reducing agent. The NH(2)-terminal sequence of the small subunits was homologous to a small subunit of soybean glycinin. Immunoprecipitation of in vitro translation products of poly(A)(+) RNA with anti-oat globulin sera yielded M(r) = 60,000 to 68,000 polypeptides. In vivo labeling of spikelets with radioactive amino acids resulted in high amounts of incorporation into polypeptides with M(r) = 65,000 to 68,000 which were immunoprecipitated with anti-globulin sera. These two results suggest oat globulin is synthesized as a higher mol wt precursor which is subsequently processed to yield the large and small subunit polypeptides.


Influence of hot pressing on the microstructure and fracture toughness of two pressable dental glass-ceramics.
Empress 1 and Empress 2 are well-known pressable all-ceramic dental materials that have generated substantial interest for many clinicians and patients. These two materials are reputed to benefit from heat pressing during the laboratory fabrication procedures, leading to better crystal distribution within a glass matrix, and hence an improved strength. The present study aimed to evaluate the effect of heat pressing on fracture toughness, microstructural features, and porosity. Results showed that Empress 1 had similar fracture toughness values before the pressing procedure, after it, and after the repressing procedure. The microstructural features were also similar among these specimens, but a more uniform distribution of leucite crystals was observed following the pressing and repressing procedures. Empress 2 demonstrated two different fracture toughness values. This was associated with the alignment of lithium disilicate crystals that occurred after the pressing and repressing procedures, which led to different indentation induced crack lengths, depending upon whether cracks propagated parallel to or perpendicular to the aligned crystals, the former having lower toughness than those that propagated in the perpendicular direction. Porosity, in terms of both the size and number of pores, was found to decrease after the pressing and repressing procedures for both materials. Repressing resulted in significant growth of the lithium disilicate crystals in Empress 2, but there was no change for the leucite crystals in Empress 1. The change in the lithium disilicate crystals' size did not have a noticeable effect on the fracture toughness of Empress 2. It was concluded that heat pressing did not significantly affect the fracture toughness of Empress 1, but resulted in two different values for Empress 2. It also decreased the size and number of pores for both materials, which could contribute to the strength improvement found after heat pressing, which has been reported in previous studies.


Demographic transition of the Swedish cystic fibrosis community--results of modern care.
Assessing the results of modern cystic fibrosis (CF)-care and estimating the future population and its demography is important to evaluate the treatment regimens and to calculate the future needs of health-care resources. This paper updates previous incidence calculations. It assesses the results of modern CF-care in terms of survival and changing demography in Sweden. The incidence of CF in Sweden was calculated as 1/5600 live-births. Of the CF-population alive in 1999, 45% were > or = 18 years old. The mean annual mortality rate since 1991 was 0.9% (+/-0.4) and the median age at death 26 years (range 0-72). Of those born > or = 1991, 95% were estimated to survive their 25th birthday. The incidence of CF in Sweden is low. Modern CF-care in Sweden shows good results. The CF-population is growing rapidly and the adult part of the population will soon be larger than the paediatric. Continuously adapted resources are required to assure the future treatment quality especially for the growing adult CF-population.


Expression of matrix metalloprotease-2 (MMP-2) and the activator membrane type 1 (MT1-MMP) in canine mammary carcinomas.
An immunohistochemical approach was used to examine the expression of MMP-2 and the activator MT1-MMP in a series of 50 canine mammary carcinomas of different histotype and stage. MMP-2 and MT1-MMP were mainly expressed in the cytoplasm of carcinoma cells and in fibroblasts. Immunolabelling for both MMP-2 and MT1-MMP was also seen on the tumour cell membranes. This labelling pattern showed no significant association with either the histological sub-type or stage of the carcinomas. Therefore, although distinct patterns of expression of MMP-2 and MT-MMP1 were shown by these carcinomas, functional studies by means of zymography would be required to provide useful information on tumour behaviour.


The RecA proteins of Deinococcus radiodurans and Escherichia coli promote DNA strand exchange via inverse pathways.
The RecA protein of Escherichia coli, and all filament-forming homologues identified to date, promote DNA strand exchange by a common, ordered pathway. A filament is first formed on single-stranded DNA, followed by uptake of the duplex substrate. These proteins are thereby targeted to single-strand gaps and tails where recombinational DNA repair is required. The observed course of DNA strand exchange promoted by the RecA protein from the extremely radioresistant bacterium Deinococcus radiodurans is the exact inverse of this established pathway. This reaction lies at the heart of a remarkably efficient system for the repair of DNA damage.


Head and neck sarcomas: a review.
Sarcomas of the head and neck are rare. They present a challenge to the head and neck oncologist that is frequently quite different from that found in epithelial, salivary, and endocrine malignancies of the head and neck. The focus of this article is on diagnostic criteria, prognostic indicators, and therapy, and due to the large number of lesions, an in-depth review of the commonest: osteosarcoma (OS), chondrosarcoma (CS), rhabdomyosarcoma (RMS), fibrosarcoma (FS), malignant fibrous histiocytoma (MFH), and synovial sarcoma (SS). Less common variants will also be mentioned. Twelve cases are presented, consisting of OS(2), RMS(1), CS(3), MFH(2), SS(2), FS(1), and miscellaneous(1). Conclusions consist of an enunciation of the general principles of management of sarcoma of the head and neck.


Using one's talents in honor of God: Lambert ten Kate (1674-1731) and Isaac Newton's natural philosophy.
Lambert ten Kate (1674-1731), the scholar of language, religious writer, art theoretician and collector, and natural philosophy enthusiast, was part of an informal network of Amsterdam-based mathematics and natural philosophy enthusiasts who played a pivotal role in the early diffusion of Newton's natural philosophical ideas in the Dutch Republic. Because Ten Kate contributed to several areas of research, it is worth asking whether connections can be found between his different scholarly activities and, more specifically, whether his oeuvre as a whole was shaped by his religious views, as has been suggested. In this essay, I shall argue that his oeuvre was indeed shaped by his religious beliefs, which reflect elements typical of Dutch doperdom, but also reflect a more general Christian orientation that transcends confessional divides. More particularly, I aim to show that, if we want to understand why Ten Kate was drawn to the natural philosophy of his day, and especially to Isaac Newton's (1642-1727), and why he sought to promote it, we also need to pay attention to this broader Christian orientation in his thought. Along the way, I shall add nuance to earlier characterizations of how ten Kate mobilized Isaac Newton's natural philosophy according to his own agenda.


The value of a kurtosis metric in estimating the hazard to hearing of complex industrial noise exposures.
A series of Gaussian and non-Gaussian equal energy noise exposures were designed with the objective of establishing the extent to which the kurtosis statistic could be used to grade the severity of noise trauma produced by the exposures. Here, 225 chinchillas distributed in 29 groups, with 6 to 8 animals per group, were exposed at 97 dB SPL. The equal energy exposures were presented either continuously for 5 d or on an interrupted schedule for 19 d. The non-Gaussian noises all differed in the level of the kurtosis statistic or in the temporal structure of the noise, where the latter was defined by different peak, interval, and duration histograms of the impact noise transients embedded in the noise signal. Noise-induced trauma was estimated from auditory evoked potential hearing thresholds and surface preparation histology that quantified sensory cell loss. Results indicated that the equal energy hypothesis is a valid unifying principle for estimating the consequences of an exposure if and only if the equivalent energy exposures had the same kurtosis. Furthermore, for the same level of kurtosis the detailed temporal structure of an exposure does not have a strong effect on trauma.


In vitro and in vivo candicidal activities of 2-(p-n-hexylphenylamino)-1,3-thiazoline.
The 2-amino-1,3-thiazoline, 2-(p-n-hexylphenylamino)-1,3-thiazoline (MDL 20,245) killed 10(5) logarithmic or stationary phase Candida albicans/ml in less than 1 h. Miconazole killed logarithmic phase cells at that rate, but miconazole, clotrimazole or econazole killed stationary phase cells at a slower rate of 10(2)-10(4) cells/ml in 24 h. MDL 20,245 induced efflux of K+ and L[U-14C] lysine from C. albicans, indicating that the candicidal mechanism is to exert direct damage upon the cytoplasmic membrane. The activity of MDL 20,245 in vitro was antagonized by fatty acids, triglycerides and phospholipids. Topical application of MDL 20,245 ointment (10% w/v) twice per day for 4 days to rats suppressed C. albicans-induced vaginitis 100%. Single-dose regimens of MDL 20,245, miconazole or clotrimazole correlated with 97, 90 and 73% suppression, respectively. These data suggest that MDL 20,245 may be effective in the treatment of C. albicans-induced vaginitis in humans.


The Mechanism of High-Output Cardiac Hypertrophy Arising From Potassium Channel Gain-of-Function in Cantú Syndrome.
Dramatic cardiomegaly arising from gain-of-function (GoF) mutations in the ATP-sensitive potassium (KATP) channels genes, ABCC9 and KCNJ8, is a characteristic feature of Cantú syndrome (CS). How potassium channel over-activity results in cardiac hypertrophy, as well as the long-term consequences of cardiovascular remodeling in CS, is unknown. Using genome-edited mouse models of CS, we therefore sought to dissect the pathophysiological mechanisms linking KATP channel GoF to cardiac remodeling. We demonstrate that chronic reduction of systemic vascular resistance in CS is accompanied by elevated renin-angiotensin signaling, which drives cardiac enlargement and blood volume expansion. Cardiac enlargement in CS results in elevation of basal cardiac output, which is preserved in aging. However, the cardiac remodeling includes altered gene expression patterns that are associated with pathological hypertrophy and are accompanied by decreased exercise tolerance, suggestive of reduced cardiac reserve. Our results identify a high-output cardiac hypertrophy phenotype in CS which is etiologically and mechanistically distinct from other myocardial hypertrophies, and which exhibits key features of high-output heart failure (HOHF). We propose that CS is a genetically-defined HOHF disorder and that decreased vascular smooth muscle excitability is a novel mechanism for HOHF pathogenesis.


Effect of molecular architecture on ring polymer dynamics in semidilute linear polymer solutions.
Understanding the dynamics of ring polymers is a particularly challenging yet interesting problem in soft materials. Despite recent progress, a complete understanding of the nonequilibrium behavior of ring polymers has not yet been achieved. In this work, we directly observe the flow dynamics of DNA-based rings in semidilute linear polymer solutions using single molecule techniques. Our results reveal strikingly large conformational fluctuations of rings in extensional flow long after the initial transient stretching process has terminated, which is observed even at extremely low concentrations (0.025 c*) of linear polymers in the background solution. The magnitudes and characteristic timescales of ring conformational fluctuations are determined as functions of flow strength and polymer concentration. Our results suggest that ring conformational fluctuations arise due to transient threading of linear polymers through open ring chains stretching in flow.


gamma-Glutamylcysteine and thiosulfate are the major low-molecular-weight thiols in halobacteria.
Six representative species of extremely halophilic bacteria were found to contain approximately millimolar concentrations of gamma-glutamylcysteine in the absence of significant glutathione. Thiosulfate also accumulated in the halobacteria, apparently as a major product of cysteine oxidation.


Inhibition of the IFN-β Response in Hepatocellular Carcinoma by Alternative Spliced Isoform of IFN Regulatory Factor-3.
The intrinsic oncolytic specificity of vesicular stomatitis virus (VSV) is currently being exploited to develop alternative therapeutic strategies for hepatocellular carcinoma (HCC). We have observed earlier that, in contrast to cultured human HCC cells, primary human hepatocytes (PHHs) are refractory to VSV infection. Impairment of the type I interferon (IFN) pathway in HCC cells has been suggested to be the mechanism by which these cells become susceptible to VSV infection. The goal of this study was to elucidate the nature of the IFN defect in human HCC. We demonstrate here that the defect in IFN-β signaling in HCC cells results from a deregulated IFN regulatory factor-3 (IRF3) pathway. Expression of IRF3-spliced variant (IRF3-nirs3) was constitutively observed in HCC cells and, importantly, also in primary HCC samples. In contrast, IRF3 was readily activated in PHHs after stimulation with dsRNA or infection with VSV. In addition, overexpression of IRF3-nirs3 significantly abrogated the IFN-β response to VSV infection and improved viral growth. Our data provide evidence that aberrant splicing of IRF3 in HCC contributes to the defect in IFN-mediated antiviral defenses. This work may provide a potential molecular basis for selecting HCC patients for oncolytic VSV therapy in future clinical trials.


An ensemble learning approach for prediction of phosphorylation sites.
Protein phosphorylation plays a fundamental role in most of the cellular regulatory pathways. Experimental identification of phosphorylation sites is labour-intensive and often limited by the availability and optimisation of enzymatic reaction. An ensemble learning approach that combines different encodings using a meta-learner was developed which was catalyzed by four protein kinase families and three residues. A predictor is constructed to predict the true and false phosphorylation sites based on Support Vector Machines (SVM), and knowledge based encoding method is used for amino sequences. Different encoding methods catch different aspects of amino sequences feature. The stacking SVM approach was applied to combine these aspects and improved both sensitivity and specificity.


k-Oligocarrageenan Promoting Growth of Hybrid Maize: Influence of Molecular Weight.
k-Oligocarrageenan (OC) is an effective biostimulator and a protector against disease infections for plants. However, the effect of OC molecular weight (MW) on plant growth is not fully understood. In this work, OCs with three different MWs (42, 17 and 4 kDa) was prepared by varying the degradation reaction time using ascorbic acid as a reagent. The product structure was confirmed by Fourier-transform infrared spectroscopy (FTIR) data. The growth promotion for maize (Zea mays L.) plants was investigated by foliar spray application of the prepared OCs. Field trials were carried out in two years, 2018 and 2019. The results showed that among treatments, OC with 4 kDa exhibited the best performance in both crop growth and grain yield parameters which indicated increases compared to the control in plant height (6.9-19.9%), length of ears (12.2%), diameter of ears (9.1%), fresh grain weight (17.8%), dry grain weight (20.0%) and grain yield (21.3%). Moreover, low MW OC augmented NP uptake in the plant growth while no effect on K uptake was observed. Therefore, OC with low MWs is potentially promising to apply as a promoter to enhance yield of crops.


Effect of facemask use on respiratory patterns of women in speech and singing.
Research into respiratory behavior during singing and speech makes extensive use of standard respiratory and vented pneumotachograph facemasks. This study investigated whether the use of such facemasks would affect respiratory behavior in terms of lung volume (excursion, at initiation and at termination) or duration (of inspiration and of expiration) during speech or singing. The respiratory patterns of 6 females were recorded using uniaxial surface magnetometry during 4 tasks: quiet breathing, a /pa/ syllabic train, reading ("The Rainbow Passage"), and singing a Christmas carol ("Silent night"). Each task was performed in 4 facemask conditions: wearing no facemask, wearing a facemask rim only, wearing a standard respiratory facemask, and wearing a vented pneumotachograph facemask. No significant effect was found for any of the facemask conditions on lung volume or duration measures during any tasks. The results confirm earlier studies that the vented pneumotachograph facemask does not affect breathing behavior in speech research studies and extends the finding to the study of breathing behavior in singing and to the use of a standard respiratory facemask.


Perinatal factors associated with neonatal mortality in very low birth weight infants: a multicenter study.
Objectives. To assess risk factors associated withneonatal mortality in very low birth weight (VLBW) infants (< 1500 g) and the impact of the administration of antenatal corticosteroids. Retrospective analysis of a VLBW infant cohort from 26 tertiary care and teaching sites member of the South American Neonatal Network (NEOCOSUR), which includes Argentina, Brazil, Chile, Paraguay, Peru, and Uruguay, conducted between 2000 and 2011 on 11 455 records. Maternal and neonatal characteristics and morbidity were compared between deceased VLBW infants and those who survived to discharge. Outcome measures associated with neonatal mortality were established by logistic regression. The effect of antenatal corticosteroids on neonatal morbidity and mortality was estimated using the matching method. The neonatal mortality rate was 22.3%, and variability among sites was elevated. Factors that were independently associated with a lower mortality of VLBW infants included the administration of antenatal corticosteroids (OR: 0.49, 95% CI: 0.43-0.54), a better birth weight Z-score (OR: 0.63, 0.61-0.65), arterial hypertension (OR: 0.67, 0.58-0.77), and C-section (OR: 0.75, 0.65-0.85). The matching method allowed reducing the risk of death by 38% in association with antenatal corticosteroids. Major perinatal factors were identified in association with neonatal mortality in VLBW infants, and the impact of antenatal corticosteroid use in the NEOCOSUR Network was demonstrated.


Continuous administration of EGFR-TKIs following radiotherapy after disease progression in bone lesions for non-small cell lung cancer.
There have been reports suggesting that continuous administration of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is advantageous for patients in which disease progression was observed after the establishment of clinical benefit from EGFR-TKIs. We retrospectively evaluated the clinical course of patients who received continuous administration of EGFR-TKIs after disease progression was detected solely in bone lesions. The medical records of patients administered gefitinib or erlotinib between 2002 and 2010 were reviewed. We evaluated the progression-free survival (PFS) and overall survival (OS) in patients who had bone metastases after the establishment of clinical benefit from EGFR-TKI and who received radiation therapy for the bone lesion and continuous treatment with EGFR-TKI. Ten patients were enrolled in this study. The median PFS and OS were 88 days and 330 days, respectively. Furthermore, a longer duration from the start of first EGFR-TKI to detection of bone metastases (p=0.0049) was identified as being significantly associated with a longer PFS. Our data suggest that continuous administration of EGFR-TKI is a treatment option for patients with bone metastases who previously benefited from therapy with EGFR-TKI.


A case of perazine-induced enteritis--allergy or pseudoallergy?
Almost all adverse reactions to neuroleptic drugs in the gastro-intestinal system can be explained by their peripheral cholinergic blocking action with subsequent inhibition of intestinal tone and peristalsis. As a rare condition, severe diarrhoea due to enteritis may occur. A case with this complication is presented, the etiology and pathogenetic factors are discussed.


The contribution of computational studies to organometallic catalysis: descriptors, mechanisms and models.
With the growing availability of cheap and fast computing resources, increasingly detailed and sophisticated computational studies of homogeneous organometallic catalysis have become feasible. In addition, databases of calculated descriptors can be used to analyse and interpret the key factors contributing to a wide range of experimental observations, facilitating the development of novel catalysts. Such descriptors, most frequently used to capture ligand properties, can also be used to quantify catalyst similarities and derive maps of ligand space which guide experimental screening. Recent publications have shown that descriptor databases can be combined with calculated mechanistic information to gain more detailed insight into catalytic cycles, useful for the design of catalysts. This perspective seeks to describe the contribution of computational studies to the field of homogeneous organometallic catalysis, and to summarise the challenges and opportunities for the future of computational prediction and evaluation of catalytically active transition metal complexes.


Mechanism for the Activation of Plasma Membrane H-ATPase from Rice (Oryza sativa L.) Culture Cells by Molecular Species of a Phospholipid.
The activation of H(+)-ATPase solubilized from plasma membrane of rice (Oryza sativa L. var Nipponbare) culture cells was examined by the exogenous addition of various phospholipids, free fatty acids, glycerides, polar head groups of phospholipids and molecular species of phosphatidylcholine (PC). H(+)-ATPase activity appeared to be stimulated by phospholipids in the following order: asolectin > phosphatidylserine > PC > lysophosphatidylcholine > phosphatidylglycerol, and maximal ATPase activation was noted at around 0.05 to 0.03% (w/v) of asolectin or molecular species of PC. Polar head groups such as glycerol, inositol, and serine only slightly activated ATPase activity or not at all, while ethanolamine and choline had no effect. Activation was dependent on the degree of saturation or unsaturation of the fatty acyl chain and its length. The activity decreased with increase in the length of fatty acyl chain from dimyristoryl(14:0)-PC to distearoyl(18:0)-PC and the degree of unsaturation from dioleoyl(18:1)-PC to dilinolenoyl(18:3)-PC. Maximum activation was observed when PC possessing 1-myristoyl(14:0)-2-oleoyl(18:1) or 1-oleoyl-2-myristoyl was added to the reaction mixture. These data show that the activation of plasma membrane H(+)-ATPase by PC depends on a combination of saturated (myristic acid 14:0, palmitic acid 16:0, and stearic acid 18:0) and unsaturated (oleic acid 18:1, linoleic acid 18:2, and arachidonic acid 20:4) fatty acids at the sn-1 and sn-2 positions of the triglycerides.


Using image-based machine learning and numerical simulation to predict pesticide inline mixing uniformity.
Accurate pesticide inline mixing uniformity (PIMU) evaluation for direct nozzle injection systems (DNIS) helps evaluate system performance and develop efficient inline mixers. Based on supervised machine learning (ML), inline mixing images and computational fluid dynamics (CFD) simulations are directly associated for realizing intelligent PIMU predictions. Image sets can be reduced to less than 3% of the data size at the same time as retaining 98% of information using principal component analysis (PCA). The CFD results, as referenced values for ML, were justified by mixture sampling experiments. Enhanced images for the long-mixing tube effectively trained models including generalized linear model (GLM), support vector regression (SVR), BP-neural network (NNW), and classification and regression trees (CART). By testing the re-collected images, the verification accuracy of GLM was less than 95% and it failed to recognize uniformity differences under varying working conditions, whereas NNW, CART and SVR realized it with an accuracy for NNW and CART higher than 97% and for SVR slightly lower than 97%. By testing images of the jet mixer, the prediction accuracy compared with the CFD results of NNW and CART was also higher than 97%, although that for SVR was relatively lower, and insignificant declines in accuracy were observed on comparing the results with mixture sampling experiments. PCA facilitates evaluations of CFD-referenced PIMU using image-based ML. Models trained by enhanced image sets of the long-mixing tube have satisfactory performance. NNW and CART performed slightly better than SVR, and they can be used as tools to improve the rationality when evaluating PIMU in DNIS. © 2022 Society of Chemical Industry.


The involvement of polyamines in the proliferation of cultured retinal pigment epithelial cells.
To investigate the involvement of polyamines (putrescine, spermidine, and spermine) in the proliferation of retinal pigment epithelium (RPE) using cultured bovine RPE cells. The polyamine content and the activities of rate-limiting enzymes in polyamine biosynthesis (ornithine decarboxylase [ODC] and S-adenosylmethionine decarboxylase [SAMDC]) and in polyamine biodegradation (spermidine spermine N1-acetyltransferase [SAT]) were measured after proliferative stimulation by 10% fetal calf serum (FCS). DNA synthesis was determined by [3H]thymidine incorporation into the acid-insoluble fraction after the addition of an inhibitor of ODC (alpha-difluoromethylornithine [DFMO]) or SAMDC (methylglyoxal bis[guanylhydrazone] [MGBG]). The effects of exogenous polyamines on DNA synthesis after the additions of inhibitors also were determined. ODC and SAMDC activities were elevated after stimulation by FCS and reached their peaks 16 hours and 4 hours, respectively, after the addition of FCS. SAT activity was not increased. Polyamine content was increased significantly after stimulation by FCS. DFMO did not inhibit DNA synthesis induced by FCS, and only putrescine content was decreased significantly among polyamines. However, MGBG inhibited DNA synthesis in a dose-dependent manner, and the amounts of spermidine and spermine were decreased significantly. Exogenous polyamines, especially spermine, restored MGBG-induced inhibition of DNA synthesis. Polyamines are essential for the proliferation of cultured bovine RPE cells. These data suggest that, of the polyamines, spermine has the greatest effect on DNA synthesis although other polyamines can substitute for spermine at higher concentrations with similar results. As for polyamine metabolism in RPE proliferation, it is possible that SAMDC is the key enzyme rather than ODC.


Chronic Kidney Disease and Heart Failure-Everyday Diagnostic Challenges.
Is advanced chronic kidney disease (CKD) a cardiac "no man's land"? Chronic heart failure (HF) is widely believed to be one of the most serious medical challenges of the 21st century. Moreover, the number of patients with CKD is increasing. To date, patients with estimated glomerular filtration rates <30 mL/min/1.73 m2 have frequently been excluded from large, randomized clinical trials. Although this situation is slowly changing, in everyday practice we continue to struggle with problems that are not clearly addressed in the guidelines. This literature review was conducted by an interdisciplinary group, which comprised a nephrologist, internal medicine specialists, and cardiologist. In this review, we discuss the difficulties in ruling out HF for patients with advanced CKD and issues regarding the cardiotoxicity of dialysis fistulas and the occurrence of pulmonary hypertension in patients with CKD. Due to the recent publication of the new HF guidelines by the European Society of Cardiology, this is a good time to address these difficult issues. Contrary to appearances, these are not niche issues, but problems that affect many patients.


Alternatively folded states of an immunoglobulin.
Well-defined, non-native protein structures of low stability have been increasingly observed as intermediates in protein folding or as equilibrium structures populated under specific solvent conditions. These intermediate structures, frequently referred to as molten globule states, are characterized by the presence of secondary structure, a lack of significant tertiary contacts, increased hydrophobicity and partial specific volume as compared to native structures, and low cooperativity in thermal unfolding. The present study demonstrates that under acidic conditions (pH less than 3) the antibody MAK33 can assume a folded stable conformation. This A-state is characterized by a high degree of secondary structure, increased hydrophobicity, a native-like maximum wavelength of fluorescence emission, and a tendency toward slow aggregation. A prominent feature of this low-pH conformation is the stability against denaturant and thermal unfolding that is manifested in highly cooperative reversible phase transitions indicative of the existence of well-defined tertiary contacts. These thermodynamic results are corroborated by the kinetics of folding from the completely unfolded chain to the alternatively folded state at pH 2. The given data suggest that MAK33 at pH 2 adopts a cooperative structure that differs from the native immunoglobulin fold at pH 7. This alternatively folded state exhibits certain characteristics of the molten globule but differs distinctly from it by its extraordinary structural stability that is characteristic for native protein structures.


Differences in self-reported oral health behavior between dental students and dental technology/dental hygiene students in Jordan.
The aim of this study was to compare differences in oral health behavior between dental students and dental technology/dental hygiene students in Jordan. One hundred and five dental students and seventy-eight dental technology/dental hygiene students were recruited into this study. All subjects were recruited from the students who were receiving training at the clinics and laboratories that belong to the Faculty of Dentistry, Jordan University of Science and Technology. The Hiroshima University-Dental Behavioral Inventory (HU-DBI) was used to assess the oral heath behavior of the subjects. Significant differences were found between students from different disciplines. Dental students were found to worry more about visiting their dentist, to be less aware of bleeding gums when brushing and were less bothered by the color of their gums compared with dental technology and dental hygiene (DT/DH) students (P < 0.05, P < 0.001 and P < 0.05, respectively). Dental students tended to be more professionally educated about brushing and to have a belief that they cannot clean their teeth well without using toothpaste (P < 0.01 and P < 0.001, respectively). Most of them did not feel they have brushed well unless they brush with strong strokes (P < 0.05). A logistic regression model showed that it might be possible to distinguish dental students from DT/DH students by using three items of the HU-DBI and the level of dental education. The difference in the HU-DBI scores was not a major feature. There were significant differences in oral health attitudes/behavior between dental students and DT/DH students. The findings might reflect differences in students' training experience and education between different specialties.


Dynamic feature extraction of coronary artery motion using DSA image sequences.
This paper aims to define and describe features of the motion of coronary arteries in two and three dimensions, presented as geometrical parameters that identify motion patterns. The main left coronary artery centerlines, obtained from digital subtraction angiography (DSA) image sequences, are first reconstructed. Thereafter, global and local motion features are evaluated along the sequence. The global attributes are centerline and point trajectory lengths, displacement amplitude, and virtual reference point, while local attributes are displacement direction, perpendicular/radial components, rotation direction, and curvature and torsion. These kinetic features allow us to obtain a detailed quantitative description of the displacements of arteries' centerlines, as well as associated epicardium deformations. Our modeling of local attributes as quasi-homogeneous on a segment analysis, enables us to propose a novel numeric to symbolic image transformation, which provides the required facts for knowledge-based motion interpretation. Experimental results using real data are consistent with cardiac dynamic behavior.


Metabolism of benz[alpha]anthracene by human bone marrow in vitro.
The metabolism of polycyclic aromatic hydrocarbons by bone marrow, mononuclear cells from normal donors and leukaemia patients in remission has been investigated. When benz[alpha]anthracene (BA) was included with marrow under cell culture conditions, it was converted to materials which were resolved into three peaks by normal phase HPLC, and which had the chromatographic characteristics of BA-dihydrodiols. Formation of hydroxymethyl-or dihydrodiol-derivatives of 7, 12-dimethylbenz[alpha]anthracene were not detected under the same conditions. The BA-metabolites were identified as BA-5,6-dihydrodiol, BA-10,11-dihydrodiol and BA-8,9-dihydrodiol. The identification was based upon chromatographic properties of the metabolites during normal and reverse phase chromatography and on UV spectral and fluorometric characterization. It was not possible to detect the formation of BA-3,4-dihydrodiol since this dihydrodiol co-elutes with BA-8,9-dihydrodiol and BA-10,11-dihydrodiol during normal phase and reverse phase chromatography, respectively. the UV spectra of BA-3,4-dihydrodiol does not have features which enable it to be readily identified in the presence of these other compounds. Formation of the dihydrodiol-metabolites was dependent on cell number and temperature. Two general cytochrome P450 inhibitors, carbon monoxide and piperonyl butoxide, blocked the formation of metabolites but the cyclooxygenase inhibitor, indomethacin had no effect. Large variations were observed in the capacity of marrow from different individuals to form benz[alpha]anthracene-dihydrodiols but, in each sample where dihydrodiols were formed, the relative amount of each metabolite was BA-8,9-dihydrodiol >> BA-5,6-dihydrodiol > BA-10,11-dihydrodiol. Factors which may contribute to this variation, including disease status, genetic and environmental agents, are considered.


Interdisciplinary Skills Review Program to Improve Team Responses During Postpartum Hemorrhage.
To develop an interdisciplinary, interactive, skills review program to improve team responses during a postpartum hemorrhage (PPH). Online didactic modules in combination with an interdisciplinary skills program consisting of seven hemorrhage-related stations. The project was conducted in the Women's Health Department in a quaternary-care Magnet- and Baby Friendly-designated academic medical center in Philadelphia, Pennsylvania. Women cared for at this center have comorbidities that place them at greater risk for PPH. A need was identified to implement a multidisciplinary and comprehensive program to assess hemorrhage risk and appropriately recognize and intervene with all PPHs in this setting. The 276 participants, including registered nurses, obstetric and family medicine attending physicians and residents, advanced practice nurses, and ancillary staff in the hospital's Women's Health Department, completed the initial obstetric hemorrhage program. The program included online didactic modules, seven interdisciplinary skills stations led by trained nurses and providers, and an in situ simulation. Successful completion of the online modules was a prerequisite for participation in the skills stations. All participants completed a written program evaluation at the conclusion of the program. Results of the postassessment survey indicated that participants rated the program 3.94 of 4.00 for overall effectiveness to improve interdisciplinary team responses to PPH. Comments were overwhelmingly positive, and participants expressed increased confidence and knowledge related to PPH after completion of the program. An interdisciplinary program that included online didactic modules, interactive skills stations, and simulation improved team confidence and responses to PPH.


Further investigation on ATP metabolism and red cell membrane integrity.
Among 15 enzymes PFK decreased most during preservation at 4 degrees C for 6-8 weeks, and this was prevented by the addition of adenine and inosine, but not by adenine or inosine only. PFK inactivation in hemolysate was also prevented by ATP. In order to maintain low fragility, isotonic sucrose solution was newly devised. Maltose and lactose followed and mannitol was also effective. The decrease in fragility accompanied the decrease in the cell volume and the increase of Na+, K+, H+ and Cl- in the medium. However, the filtrability of red cells was sometimes decreased in case of extremely lowered fragility. Therefore, appropriate ratios of isoosmotic sucrose (hardly permeable) and NaCl (relatively rapidly permeable) solutions must be selected for preservation of blood. Various properties in vitro of rabbit cells were well maintained and their posttransfusion viability was also prolonged when using this medium. Elimination of hypoxanthine could be achieved by hydron coated charcoal prior to transfusion.


The avian inferior olive derives from the alar neuroepithelium of the rhombomeres 7 and 8: an analysis by using chick-quail chimeric embryos.
Homotopic and isochronic transplantation of the alar plate of the rhombomeres 7 and 8 was performed between chick and quail embryos at the stage of 10-14 somites. Analysis of the graft derivatives in 12-day-old chimeric embryos by means of the quail nucleolar marker showed that the ipsilateral inferior olive is formed from the transplanted neuroepithelium. In all embryos some cells originating from the graft were also found scattered throughout the contralateral inferior olive. The present results demonstrate that the inferior olive derives from the alar plate of the rhombomeres 7 and 8 and support the notion that a small contingent of inferior olivary neurones crosses the interolivary commissure during development.


Holobiont nutrition: considering the role of the gastrointestinal microbiota in the health benefits of whole grains.
Intake of whole grains and other food products high in dietary fiber have long been linked to the prevention of chronic diseases associated with inflammation. A contribution of the gastrointestinal microbiota to these effects has been suggested, but little is known on how whole grains interact with gut bacteria. We have recently published the first human trial that made use of next-generation sequencing to determine the effect of whole grains (whole grain barley, brown rice or a mixture of the two) on fecal microbiota structure and tested for associations between the gut microbiota and blood markers of inflammation, glucose and lipid metabolism. Our study revealed that whole grains impacted gut microbial ecology by increasing microbial diversity and inducing compositional alterations, some of which are considered to have beneficial effects on the host. Interestingly, whole grains, and in particular the combination of whole grain barley and brown rice, caused a reduction in plasma interleukin-6 (IL-6), which was linked to compositional features of the gut microbiota. Therefore, the study provided evidence that a short-term increased intake of whole grains led to compositional alterations of the gut microbiota that coincided with improvements in systemic inflammation. In this addendum, we summarize the findings of the study and provide a perspective on the importance of regarding humans as holobionts when considering the health effects of dietary strategies.


Factors for increased morbidity and mortality in uremia: hyperphosphatemia.
Hyperphosphatemia is a metabolic abnormality present in the majority of patients treated by dialysis. Inorganic phosphorus (iP) can be categorized as a true uremic toxin given its known in vivo and in vitro effects and the ability to reduce these effects by normalizing iP levels. However, despite regular and adequate dialysis treatment, the goal of normalization of phosphorus levels rarely is achieved. This article briefly evaluates the significance of hyperphosphatemia in hemodialysis patients, current therapeutic approaches, and describes a new model for evaluating the dialysis prescription for iP balance.


Phosphorus-enriched hemodialysates: formulations and clinical use.
Although hyperphosphatemia is a cardinal feature of renal failure, the occasional patient suffering from end-stage renal disease (ESRD) may present with hypophosphatemia. For example, hypophosphatemia can develop in ESRD patients if they suffer from malnutrition or if they are aggressively dialyzed. Hypophosphatemia is commonly prevented or treated with the oral or the intravenous administration of soluble phosphate salts; however, determination of the required oral or intravenous dose is difficult. Under appropriate circumstances, phosphorus-enriched dialysates can also be employed for the purpose of phosphorus administration. Various preparations of soluble phosphate salts can be used to enrich hemodialysates.


Fungal strains and the development of tolerance against natamycin.
Antimicrobial resistance is a relevant theme with respect to both antibacterial and antifungal compounds. In this study we address the possible development of tolerance against the antifungal food preservative natamycin. A selection of 20 fungal species, originating from a medical as well as a food product context, was subjected to increasing concentrations of natamycin for prolonged time, a procedure designated as "training". The range of Minimum Inhibitory Concentrations (M.I.C.) before (1.8-19.2μM) and after (1.8-19.8μM) training did not change significantly, but natamycin-exposure caused an increase of M.I.C. in 13 out of 20 tested strains. The average M.I.C. increased from 6.1 to 8.6μM and 4 strains showed a >2-fold increase of tolerance after training. One strain (of Aspergillus ochraceus) also showed increased tolerance to amphotericin B and nystatin. However, two Fusarium strains showed similar or even decreased tolerance for these other polyene antifungals. The work reported here shows that a continuous and prolonged increasing selection pressure induced natamycin tolerance in individual strains. This implies that such a selection pressure should be avoided in the technical application of natamycin to ensure its continued safe use as a food preservative.


Irreversible electroporation: just another form of thermal therapy?
Irreversible electroporation (IRE) is (virtually) always called non-thermal despite many reports showing that significant Joule heating occurs. Our first aim is to validate with mathematical simulations that IRE as currently practiced has a non-negligible thermal response. Our second aim is to present a method that allows simple temperature estimation to aid IRE treatment planning. We derived an approximate analytical solution of the bio-heat equation for multiple 2-needle IRE pulses in an electrically conducting medium, with and without a blood vessel, and incorporated published observations that an electric pulse increases the medium's electric conductance. IRE simulation in prostate-resembling tissue shows thermal lesions with 67-92°C temperatures, which match the positions of the coagulative necrotic lesions seen in an experimental study. Simulation of IRE around a blood vessel when blood flow removes the heated blood between pulses confirms clinical observations that the perivascular tissue is thermally injured without affecting vascular patency. The demonstration that significant Joule heating surrounds current multiple-pulsed IRE practice may contribute to future in-depth discussions on this thermal issue. This is an important subject because it has long been under-exposed in literature. Its awareness pleads for preventing IRE from calling "non-thermal" in future publications, in order to provide IRE-users with the most accurate information possible. The prospect of thermal treatment planning as outlined in this paper likely aids to the important further successful dissemination of IRE in interventional medicine. Prostate 75:332-335, 2015. © 2014 The Authors. The Prostate Published by Wiley Periodicals, Inc.


Body mass index and outcomes in patients receiving chemotherapy for intermediate-grade B-cell non-Hodgkin lymphoma.
We conducted a retrospective cohort study examining the influence of obesity on treatment outcome and survival among 712 patients with intermediate-grade B-cell NHL receiving frontline therapy between 1988 and 2001. Baseline adiposity was approximated by body mass index categorized according to the World Health Organization schema. Logistic and Cox proportional hazards regression modeling was used to adjust for baseline patient demographic, disease, and treatment variables. Approximately 37% of cohort patients were overweight (BMI 25 to <30 kg/m(2)) and more than 23% were obese (BMI >or= 30 kg/m(2)). Risk factors were similar across groups and treatment intensity did not vary by BMI. Median follow-up was 45.7 and 62.8 months for PFS and OS, respectively. After adjustment for other significant prognostic factors, BMI in the overweight range was associated with significantly reduced hazard for both PFS (OR 0.72, p = 0.011) and OS (OR 0.74, p = 0.030). Increased BMI is associated with significantly improved survival among patients with treatment-naive, intermediate-grade B-cell NHL. Prospective confirmation of these results is warranted given the increasing prevalence of both NHL and obesity.


The in vivo isometric point of the lateral ligament of the elbow.
Many reports have discussed reconstruction of the lateral ulnar collateral ligament for the treatment of posterolateral rotatory instability of the elbow, but information regarding the isometric point of the lateral ligament of the elbow is limited. The purposes of the present study were to investigate the in vivo and three-dimensional length changes of the lateral ulnar collateral ligament and the radial collateral ligament during elbow flexion in order to clarify the role of these ligaments as well as to identify the isometric point for the reconstructed lateral ulnar collateral ligament on the humerus where the grafted tendon should be anchored. We studied in vivo and three-dimensional kinematics of the normal elbow joint with use of a markerless bone-registration technique. Magnetic resonance images of the right elbows of seven healthy volunteers were acquired in six positions between 0 degrees and 135 degrees of flexion. We created three-dimensional models of the elbow bones, the lateral ulnar collateral ligament, and the radial collateral ligament. The ligament models were based on the shortest calculated paths between each origin and insertion in three-dimensional space with the bone as obstacles. We calculated two types of three-dimensional distances for the ligament paths with each flexion position: (1) between the center of the capitellum and the distal insertions of the ligaments (to investigate the physiological change in ligament length) and (2) between eight different humeral origins and the one typical insertion of the lateral ulnar collateral ligament (to identify the isometric point of the reconstructed lateral ulnar collateral ligament). The three-dimensional distance for the lateral ulnar collateral ligament was found to increase during elbow flexion, whereas that for the radial collateral ligament changed little. The path of the lateral ulnar collateral ligament gradually developed a detour because of the osseous protrusion of the lateral condyle with flexion. The most isometric point for the reconstructed lateral ulnar collateral ligament was calculated to be at a point 2 mm proximal to the center of the capitellum. The radial collateral ligament is essentially isometric, but the lateral ulnar collateral ligament is not. The lateral ulnar collateral ligament is loose in elbow extension and becomes tight with elbow flexion.


[Risk factors for 4-year mortality in older adults. Toledo Study].
multiple factors contribute to mortality in older adults. Measures of physical and cognitive function are strong predictors of mortality, but the extent to which function, health-related quality of life and other factors contribute independently to mortality risk is not known. we performed a prospective study of a representative sample of people aged 65 years and older (n=3,214) followed-up for 4 years. Individuals from the sample were interviewed to obtain information about sociodemographic characteristics, comorbidity, functional status, health-related quality of life, and healthcare utilization. The main outcome measure was 4-year mortality. To assess the independent impact of each risk factor on mortality, several multivariate survival models were built using the Cox proportional hazard model. in the 4 years of monitoring, 478 people died (14.9%). The variables independently associated with mortality risk were age 75 years or older (HR = 1.93), male gender (HR = 1.73), heart disease (HR = 1.32), chronic respiratory disease (HR = 1.78), activities of daily living disability (HR = 1.55), instrumental activities of daily living disability (HR = 2.19), cognitive impairment (HR = 1.39), poor health-related quality of life (HR = 1.85) and hospital admission in the year prior to the interview (HR = 1.51). objective measures of physical and cognitive function are independent predictors of 4-year mortality in the elderly. Poor health-related quality of life is associated with mortality. The magnitude of this association is comparable to that of other well-know predictors of mortality. Instruments to measure health-related quality of life can be useful to evaluate health requirements in the elderly.


Reversal of Osteoporotic Activity by Endothelial Cell-Secreted Bone Targeting and Biocompatible Exosomes.
Exosomes, also known as extracellular vesicles, are naturally occurring, biocompatible, and bioacive nanoparticles ranging from 40 to 150 nm in diameter. Bone-secreted exosomes play important roles in bone homeostasis, the interruption of which can lead to diseases such as osteoporosis, rheumatoid arthritis, and osteopetrosis. Though the relationship between vascular and bone homeostasis has been recognized recently, the role of vascular endothelial cell (EC)-secreted exosomes (EC-Exos) in bone homeostasis is not well understood. Herein, we found that EC-Exos show more efficient bone targeting than osteoblast-derived exosomes or bone marrow mesenchymal stem cell-derived exosomes. We also found that EC-Exos can be internalized by bone marrow-derived macrophages (BMMs) to alter their morphology. EC-Exos can inhibit osteoclast activity in vitro and inhibit osteoporosis in an ovariectomized mouse model. Sequencing of exosome miRNA revealed that miR-155 was highly expressed in EC-Exos-treated BMMs. The miR-155 level in EC-Exos was much higher than that in BMMs and ECs, indicating that miR-155 was endogenous cargo of EC-derived vesicles. Blockage of BMMs miR-155 levels reversed the suppression by EC-Exos of osteoclast induction, confirming that exosomal miR-155 may have therapeutic potential against osteoporosis. Taken together, our findings suggest that EC-Exos may be utilized as a bone targeting and nontoxic nanomedicine for the treatment of bone resorption disorders.


Auditory rehabilitation: needs and realities on long-stay wards for elderly people.
A survey was made of the problem of age-related hearing impairment within a sample of National Health Service long-stay wards for elderly people. Detailed assessment of hearing was completed for 188 residents derived from 15 long-stay wards, located within nine Scottish hospitals. The sample residents were more than four times as likely to need a hearing aid as their contemporaries in the general population. Of the 131 people considered to be potential hearing aid candidates, 103 (78%) demonstrated a positive attitude towards hearing aids ownership. Medical policies on the study wards were not considered sensitive to the needs of the hearing-impaired; screening was haphazard and specialist referral problematic.


The value of youth: equalizing age differentials in marriages.
"The objective of this paper is to present a model of constrained utility-maximizing behaviour which is able to explain several features of marriage. The model predicts that individuals meet in the marriage market and trade characteristics, in which they are relatively well endowed, to obtain characteristics in which they are less well endowed. The model implies a positive age differential in favour of the husband due to biological differences. This differential is shown to be attentuated by differences in earnings capacity and human capital investments. The model also has implications for dynamic aspects of marriage and provides an explanation for the secular increase in females' age of first marriage and difficulty experienced by females in the post thirty-year age group in finding suitable partners. An examination of unit record data on residents of metropolitan California from the 1980 United States Census reveals systematic patterns in the data are consistent with the theory."


Cancer stem cells and microglia in the processes of glioblastoma multiforme invasive growth.
The development of antitumor medication based on autologous stem cells is one of the most advanced methods in glioblastoma multiforme (GBM) treatment. However, there are no objective criteria for evaluating the effectiveness of this medication on cancer stem cells (CSCs). One possible criterion could be a change in the number of microglial cells and their specific location in the tumor. The present study aimed to understand the interaction between microglial cells and CSCs in an experimental glioblastoma model. C6 glioma cells were used to create a glioblastoma model, as they have the immunophenotypic characteristics of CSCs. The glioma cells (0.2×106) were stereotactically implanted into the brains of 60 rats. On the 10th, 20th and 30th days after implantation, the animals were 15 of the animals were sacrificed, and the obtained materials were analyzed by morphological and immunohistochemical analysis. Implantation of glioma cells into the rat brains caused rapid development of tumors characterized by invasive growth, angiogenesis and a high rate of proliferation. The maximum concentration of microglia was observed in the tumor nodule between days 10 and 20; a high proliferation rate of cancer cells was also observed in this area. By day 30, necrosis advancement was observed and the maximum number of microglial cells was concentrated in the invasive area; the invasive area also exhibited positive staining for CSC marker antibodies. Microglial cells have a key role in the invasive growth processes of glioblastoma, as demonstrated by the location of CSCs in the areas of microglia maximum concentration. Therefore, the present study indicates that changes in microglia position and corresponding suppression of tumor growth may be objective criteria for evaluating the effectiveness of biomedical treatment against CSCs.


Improving Emergency Department Patient-Physician Conversation Through an Artificial Intelligence Symptom-Taking Tool: Mixed Methods Pilot Observational Study.
Establishing rapport and empathy between patients and their health care provider is important but challenging in the context of a busy and crowded emergency department (ED). We explore the hypotheses that rapport building, documentation, and time efficiency might be improved in the ED by providing patients a digital tool that uses Bayesian reasoning-based techniques to gather relevant symptoms and history for handover to clinicians. A 2-phase pilot evaluation was carried out in the ED of a German tertiary referral and major trauma hospital that treats an average of 120 patients daily. Phase 1 observations guided iterative improvement of the digital tool, which was then further evaluated in phase 2. All patients who were willing and able to provide consent were invited to participate, excluding those with severe injury or illness requiring immediate treatment, with traumatic injury, incapable of completing a health assessment, and aged <18 years. Over an 18-day period with 1699 patients presenting to the ED, 815 (47.96%) were eligible based on triage level. With available recruitment staff, 135 were approached, of whom 81 (60%) were included in the study. In a mixed methods evaluation, patients entered information into the tool, accessed by clinicians through a dashboard. All users completed evaluation Likert-scale questionnaires rating the tool's performance. The feasibility of a larger trial was evaluated through rates of recruitment and questionnaire completion. Respondents strongly endorsed the tool for facilitating conversation (61/81, 75% of patients, 57/78, 73% of physician ratings, and 10/10, 100% of nurse ratings). Most nurses judged the tool as potentially time saving, whereas most physicians only agreed for a subset of medical specialties (eg, surgery). Patients reported high usability and understood the tool's questions. The tool was recommended by most patients (63/81, 78%), in 53% (41/77) of physician ratings, and in 76% (61/80) of nurse ratings. Questionnaire completion rates were 100% (81/81) by patients and 96% (78/81 enrolled patients) by physicians. This pilot confirmed that a larger study in the setting would be feasible. The tool has clear potential to improve patient-health care provider interaction and could also contribute to ED efficiency savings. Future research and development will extend the range of patients for whom the history-taking tool has clinical utility. German Clinical Trials Register DRKS00024115; https://drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024115.


[Dislocated hips in cerebral palsy (author's transl)].
The authors have observed 119 excentrated hips in 81 spastic children. Most of the cases were noted in non walking children under the age of ten. However some excentrated hips were seen in older patients eventually able to walk. The importance of a three dimensional approach of the problem is pointed out. The results of the surgical procedures are analysed. It appeared that it was important to restore a muscle balance before any pelvic or femoral osteotomy. Triple pelvic osteotomy was indicated of obtaining a better orientation of the acetabulum in younger children. Its complications were infrequent. Chiari's osteotomy was indicated in older children. The authors point out the importance of an early diagnosis in cases of lack of muscles balance which can be corrected by minor surgical procedures on soft tissues.


Hospital-based epilepsy care in Uganda: A prospective study of three major public referral hospitals.
This study sets out to describe the current demographics of people with epilepsy (PWE) attending hospital-based care in Uganda and the epilepsy treatment practices within three of the largest Ugandan public referral hospitals. In a six-month prospective cohort study, 626 children and adults attending epilepsy clinics at Mulago National Referral Hospital, Butabika National Referral Mental Hospital and Mbarara Regional Referral Hospital were enrolled. Using a study questionnaire, data were collected at baseline and at 3 weeks, 3 months, and 6 months following enrollment. Specific data surrounding individual patient demographics, clinical characteristics and severity of epilepsy, and treatment of epilepsy with antiepileptic drugs (AEDs) were collected. Female patients totaled to 50.8%, with a nearly equal gender distribution at each hospital. There was no statistical difference in gender or age between sites. The majority of PWE had completed primary school, with less than 15% of patients completing more than a secondary education. Seizure severity was high, with most patients having multiple seizures per week at the initial onset of epilepsy, and greater than 90% of patients reporting a loss of consciousness with seizures. The majority of patients (54.95%) also reported a developmental or learning delay. Most patients were on 1 AED (46.01%) or 2 AEDs (36.90%), with carbamazepine being the most frequently prescribed AED. There was a trend towards improved seizure severity over the follow-up period, as assessed by the corresponding Personal Impact of Epilepsy Scale (PIES) subscale. People with epilepsy attending hospital-based care in Uganda tend to have severe forms of epilepsy requiring management with AEDs. Current hospital-based practices show a positive trend for seizure burden and quality of life of PWE in Uganda. Further interventions to improve overall access to biomedical care are required to continue to advance the management of PWE across all communities. This article is part of the Special Issue "The Intersection of Culture, Resources, and Disease: Epilepsy Care in Uganda".


High magneto-optical activity and low optical losses in metal-dielectric Au/Co/Au-SiO(2) magnetoplasmonic nanodisks.
Metal-dielectric Au-Co-SiO(2) magnetoplasmonic nanodisks are found to exhibit large magneto-optical activity and low optical losses. The internal architecture of the nanodisks is such that, in resonant conditions, the electromagnetic field undertakes a particular spatial distribution. This makes it possible to maximize the electromagnetic field at the magneto-optically active layers and minimize it in the other, optically lossy ones.


Assessment of fibrinolytic markers in patients with deep vein thrombosis.
The association of the fibrinolytic markers with deep vein thrombosis (DVT) is still a matter of debate. The present study aimed to investigate the association between fibrinolytic markers and DVT. This observational study recruited 52 adult cases with lower limb DVT and 52 healthy adult volunteers as controls. The quantitative determination of plasminogen activator inhibitor-1 (PAI-1), plasminogen, thrombin activable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA) and α2-antiplasmin (α2-AP) was performed by ELISA. TAFI, plasminogen and t-PA were significantly higher in cases than controls and PAI-1 was significantly lower in cases than controls. In addition, TAFI, plasminogen and t-PA levels were significantly increased in unprovoked and idiopathic DVT cases than controls. The present study suggests that the fibrinolytic markers tested in patients with a remote history of DVT are different than in individuals with no history of DVT and, with further study, may prove useful as screening assays for DVT risk.


Calendar methods of fertility regulation: a rule of thumb.
"[Many] illiterate women, particularly in the third world, find [it] difficult to apply usual calendar methods for the regulation of fertility. Some of them are even unable to make simple subtractions. In this paper we are therefore trying to evaluate the applicability and the efficiency of an extremely simple rule which entails only [the ability to count] a number of days, and always the same way." (SUMMARY IN ITA)