[Biological value of various types of dietary soy bean proteins].
Chemistry and experiments on animals (male Wistar rats) were made to determine the biological value of 4 samples of soybean proteins: 2 protein isolates (Ardex SP-6 and Ardex-M, ADM USA); soybean protein concentrate (UNICO, UNIMILS, Holland), and textured soybean concentrate (manufactured by the All-Union Research Institute of Fat). The content of essential amino acids and amino acid score of the protein samples were measured relative to three standard aminograms. The "growing" (the protein efficacy ratio and net protein ratio) and balance (net protein utilization) characteristics of the biological value were determined in experiments on rats fed diets containing soybean proteins as the only source of proteins (10% of caloric value). The Dtr of the proteins under study was defined. All the evaluable proteins were found to be almost similar as regards the biological value. The Dtr of protein isolates was discovered to be higher as compared to that of soybean protein concentrates.


Is Routine Axillary Imaging Necessary in Clinically Node-Negative Patients Undergoing Neoadjuvant Chemotherapy?
The National Comprehensive Cancer Network guidelines recommend axillary imaging prior to neoadjuvant chemotherapy (NAC) in breast cancer patients who are clinically node negative (cN0) by physical examination. However, the benefit of this approach remains uncertain. The purpose of this study was to determine whether abnormal axillary imaging pre-NAC predicts nodal metastases post-NAC (ypN+) in cN0 patients. cN0 patients undergoing NAC followed by axillary surgery were identified. Rates of ypN+ were compared among patients with abnormal pre-treatment axillary imaging vs. normal or no pre-treatment imaging using Fisher's exact test. From May 2008 to March 2016, 402 eligible cN0 patients were identified. The median age of the patients was 49.5 years, and the median tumor size was 4 cm. Of these patients, 38% were estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-), 30% were HER2+ , and 32% were triple negative. All had pre-NAC mammograms, 40% axillary ultrasound, 83% MRI, and 51% PET. Abnormal nodes on imaging were seen in 208 patients (52%); 128 had pre-NAC node biopsy, and 75 were positive. Overall, 28% of the patients (n = 111) were ypN+ post-NAC. Although the incidence of ypN+ was significantly higher in patients with abnormal nodes on pre-NAC imaging (p = 0.001), 54% did not require axillary lymph node dissection (ALND) post-NAC. Among the patients with normal nodes on pre-NAC imaging, 20% were ypN+ post-NAC. Half of patients with abnormal nodes on pre-NAC imaging did not require ALND post-NAC, while 20% of those with normal pre-NAC nodes had disease post-NAC, indicating that in cN0 patients already selected for NAC, axillary imaging pre-NAC does not predict the need for axillary surgery post-NAC with sufficient accuracy to be clinically useful.


Professional behavior in the orthopedic resident. A method for evaluation and development.
The affective behavior of orthopedic residents may be the most important indicator of their ability to function as orthopedic surgeons. Seven years of personal observations were combined with the experience of more than 300 participants in the Basic Course for Orthopaedic Educators, and recorded from the results of a recent questionnaire answered by members of the Association of Orthopaedic Chairmen. The affective domain was found to supply the answers to most of the problems of orthopedic residents. An evaluation of affective behavior early in the residency program may help to determine residents' suitability for a career in orthopedic surgery.


Distinct calcium signaling pathways regulate calmodulin gene expression in tobacco.
Cold shock and wind stimuli initiate Ca(2+) transients in transgenic tobacco (Nicotiana plumbaginifolia) seedlings (named MAQ 2.4) containing cytoplasmic aequorin. To investigate whether these stimuli initiate Ca(2+) pathways that are spatially distinct, stress-induced nuclear and cytoplasmic Ca(2+) transients and the expression of a stress-induced calmodulin gene were compared. Tobacco seedlings were transformed with a construct that encodes a fusion protein between nucleoplasmin (a major oocyte nuclear protein) and aequorin. Immunocytochemical evidence indicated targeting of the fusion protein to the nucleus in these plants, which were named MAQ 7.11. Comparison between MAQ 7.11 and MAQ 2.4 seedlings confirmed that wind stimuli and cold shock invoke separate Ca(2+) signaling pathways. Partial cDNAs encoding two tobacco calmodulin genes, NpCaM-1 and NpCaM-2, were identified and shown to have distinct nucleotide sequences that encode identical polypeptides. Expression of NpCaM-1, but not NpCaM-2, responded to wind and cold shock stimulation. Comparison of the Ca(2+) dynamics with NpCaM-1 expression after stimulation suggested that wind-induced NpCaM-1 expression is regulated by a Ca(2+) signaling pathway operational predominantly in the nucleus. In contrast, expression of NpCaM-1 in response to cold shock is regulated by a pathway operational predominantly in the cytoplasm.


Bilateral Inflammatory Aural Polyps: A Manifestation of Samter's Triad.
We report an unusual case of bilateral inflammatory aural polyps in a patient with Samter's triad. This 52-year-old patient had a history of chronic rhinosinusitis with sinonasal polyps, asthma, and aspirin sensitivity, with progressive right-sided hearing loss, otorrhea, and aural fullness. She was found to have bilateral aural polyps, with the larger obstructing lesion on the right. A computed tomography supported these findings and revealed bilateral opacification of the middle ear cleft and mastoid air cells. An initial right tympanomastoidectomy was performed with the specimen histologically resembling a typical sinonasal polyp. We speculate that this patient's middle ear polyposis is secondary to the inflammatory changes of Samter's triad. This has not been described previously in the literature.


Reading comprehension interventions for middle school students with learning disabilities: a synthesis of 30 years of research.
The authors conducted a synthesis of studies of reading comprehension interventions for middle school students (Grades 6-8) identified with a learning disability. They identified 12 studies between 1979 and 2009 with treatment and comparison designs and 2 single-participant studies. Findings from the studies indicate large effect sizes for researcher-developed comprehension measures. Few studies (n = 4) reported standardized measures of reading comprehension, which indicated medium effect sizes. The majority of study treatments (n = 13) utilized strategy instruction related to main idea or summarization.


Comparison of cellular immunity in patients with chronic hepatitis B, inactive hepatitis B surface antigen carriers and spontaneously recovered individuals.
Different clinical outcomes of acute HBV infection have been partially explained by individual differences in immune response. In this study we investigated interferon gamma (IFN-γ) secretion of peripheral blood mononuclear cells (PBMC) in vitro against specific (Hepatitis B core antigen; recombinant HB-cAg) and non-specific (CMV, EBV, Influenza peptide pool; CTL CEF peptide pool "plus") antigens using enzyme linked immunospot (ELISPOT) assay in 7 patients with chronic hepatitis B (CHB group), 8 inactive carriers Of HBV (carrier group) and 8 subjects who spontaneously recovered from acute HBV infection as detected by anti-HBs positivity (immune group). Phytohemaglutinin served as the positive test control. Response against recombinant HBcAg was 88±135, 50±110, 105±150 spot forming cell (SFC)/10(5) PBMC, in CHB, carrier and immune groups, respectively. HBcAg-specific T-cell response was slightly higher in the immune group; however, statistically there was no significant difference between the groups. Assessment of cellular immunity by IFN-γ ELISPOT was not sufficient to explain the various outcomes of HBV infection such as resolution, chronicity and carriership.


A neural net representation of experienced and nonexperienced users during manual wheelchair propulsion.
A neural net approach was used to classify and analyze combinations of the physiological and kinematic responses (the factor patterns) of experienced and novice individuals during wheelchair propulsion, and to determine the key characteristics (individual factors) used in making this determination. A sequence of artificial neural networks (ANN) was developed and used to classify differences between eight nonimpaired controls and seven individuals using wheelchairs, who ranged in age from 24 to 36 years. The subjects propelled a wheelchair on a specially constructed dynamometer at three different velocity levels during which stroke pattern, force, energy, and efficiency data were collected. The data from 10 subjects (5 from each group) were used to train a net, with the data from the remaining 5 subjects used to test the resulting net. The nets correctly classified the training subjects in all 10 cases and correctly classified all 5 test subjects, indicating that the developed networks were able to generalize to new data sets. It was concluded that a minimal net consisting of only three variables, peak VO2 at the high velocity, hand force on the rim at the low velocity, and push angle at the high velocity, could accurately represent the differences between these groups.


Guanine alkylation by the potent carcinogen aflatoxin B1: quantum chemical calculations.
We report a series of ab initio and density functional theory simulations of guanine alkylation by aflatoxin B 1 exo-8,9-epoxide. This reaction represents an initial step of carcinogenesis associated with aflatoxin B 1, a potent genotoxic fungal metabolite. Effects of hydration were considered in the framework of the Langevin dipoles solvation model and the solvent reaction field method of Tomasi and co-workers. In silico-calculated activation free energies are in good agreement with the experimental value of 15.1 kcal/mol. This agreement presents strong evidence in favor of the validity of the proposed S(N)2 reaction mechanism and points to the applicability of quantum chemical methods in studies of reactions associated with carcinogenesis. In addition, we predict that the preference of aflatoxin B 1 exo-8,9-epoxide over the endo stereoisomer for the reaction with guanine exists in the aqueous solution and is only further amplified in the DNA duplex. Finally, through comparison with an analogous reaction between 3a,6a-dihydrofuro[2,3- b]furan exo-4,5-epoxide and guanine, we show that the large planar body of aflatoxin B 1 does not enhance its reactivity and related carcinogenicity. This explains why the planar region of related mycotoxins sterigmatocystin and aflatoxin G 1 could have been evolutionarily optimized in a different way.


Non-Invasive Strategies for Nose-to-Brain Drug Delivery.
Intranasal drug administration is a promising method for delivering drugs directly to the brain. Animal studies have described pathways and potential brain targets, but nose-to-brain delivery and treatment efficacy in humans remains debated. We describe the proposed pathways and barriers for nose-to-brain drug delivery in humans, drug properties that influence central nervous system delivery, clinically tested methods to enhance absorption, and the devices used in clinical trials. This review compiles the available evidence for nose-to-brain drug delivery in humans and summarizes the factors involved in nose-to-brain drug delivery.


Genetic association of crown rust resistance gene Pc68, storage protein loci, and resistance gene analogues in oats.
Segregating F(3) families, derived from a cross between oat cultivar Swan and the putative single gene line PC68, were used to determine the association of seed storage protein loci and resistance gene analogues (RGAs) with the crown rust resistance gene Pc68. SDS-PAGE analysis detected three avenin loci, AveX, AveY, and AveZ, closely linked to Pc68. Their diagnostic alleles are linked in coupling to Pc68 and were also detected in three additional lines carrying Pc68. Another protein locus was linked in repulsion to Pc68. In complementary studies, three wheat RGA clones (W2, W4, and W10) detected restriction fragment length polymorphisms (RFLPs) between homozygous resistant and homozygous susceptible F(3) DNA bulks. Four oat homologues of W2 were cloned and sequenced. RFLPs detected with two of them were mapped using F(3) and F(4) populations. Clone 18 detected a locus, Orga2, linked in repulsion to Pc68. Clone 22 detected several RFLPs including Orga1 (the closest locus to Pc68) and three RGA loci (Orga22-2, Orga22-3, and Orga22-4) loosely linked to Pc68. The diagnostic RFLPs linked in coupling to Pc68 were detected by clone 22 in three additional oat lines carrying Pc68 and have potential utility in investigating and improving crown rust resistance of oat.


Bower decorations attract females but provoke other male spotted bowerbirds: bower owners resolve this trade-off.
Elaborate secondary sexual traits offset the costs that they impose on their bearer by facilitating reproductive benefits, through increased success in intrasexual contests or increased attractiveness to choosy mates. Some traits enhance both strategies. Conversely, I show that spotted bowerbirds Chlamydera maculata may face a trade-off. The trait that best predicts their mating success, numbers of Solanum berries exhibited on a bower, also provokes increased intrasexual aggression in the form of bower destructions by neighbouring bower owners, which reduce the quality of the male's bower. At natural berry numbers, levels of mating success in the population are skewed, but levels of destruction do not vary with berry number. When berry numbers are artificially exaggerated, increased levels of destructions occur, but mating success does not increase. When offered excess berries, either to add to the bower or artificially placed on the bower, bower owners preferred to use numbers of berries related to the number that they displayed naturally. This decision is made without direct experience of the attendant changes in destruction or mating success. This indicates that bower owners may assess their own social standing in relation to their neighbours and modulate their display accordingly.


Effect of Small Change in Oil Phase Composition on Rheological and Textural Properties of w/o Emulsion.
In this work, we have modified oil phase composition in one component (mineral oil, isocetyl palmitate, special Olive butter and dimethicone 200/350) and the aim of our work was to establish the influence of that alteration on emulsion rheological and textural properties. Additionally, continuous and oscillatory rheological measurements along with texture analysis were assessed in order to predict emulsion application behavior. Based on the obtained results, the change of oil phase has induced a change in the observed rheological and textural parameters and investigated samples can be divided into two distinct groups: the first group - samples with special Olive butter and dimethicone 200/350 and the second group - samples with isocetyl palmitate and mineral oil. Results confirmed that instrumental measurements, as sensitive tools, can be used in order to differentiate emulsions regarding textural properties and especially regarding their actual usage and sensory properties. PRACTICAL APPLICATIONS: It is a known fact that the structure of semisolid systems can be characterized by various rheological and textural parameters that are also apt to define certain sensory attributes. Sensory attributes dependent on structure characteristics and flow properties, used for the description of the product in pickup and rub-out phase, could be predicted by instrumental, i.e., rheological and textural measurements. Expensive and time-consuming studies performed with human panelists could be, at least to some extent, replaced with simple rheological and textural measurements. These findings could also contribute to the faster and easier introduction of new raw materials, regarding their characterization and prediction of their influence on the final product characteristics. A combined approach like this could be helpful as both time and money-saving tool for full characterization of a novel consumer-acceptable emulsion product.


A pH-sensitive silica nanoparticles for colon-specific delivery and controlled release of catechin: Optimization of loading efficiency and in vitro release kinetics.
Catechin is a naturally occurring flavonoid of the flavan-3-ol subclass with numerous biological functions; however, these benefits are diminished due to several factors, including low water solubility and degradation in the stomach's harsh environment. So, this study aimed to develop an intelligent catechin colon-targeting delivery system with a high loading capacity. This was done by coating surface-decorated mesoporous silica nanoparticles with a pH-responsive enteric polymer called Eudragit®-S100. The pristine wormlike mesoporous silica nanoparticles (< 100 nm) with high surface area and large total pore volume were effectively synthesized and modified with the NH2 group using the post-grafting strategy. Various parameters, including solvent polarity, catechin-carrier mass ratio, and adsorption time, were studied to improve the loading of catechin into the aminated silica nanoparticles. Next, the negatively charged Eudragit®-S100 was electrostatically coated onto the positively charged aminated nanocarriers to shield the loaded catechin from the acidic environment of the stomach (pH 1.9) and to facilitate site-specific delivery in the acidic environment of the colon (pH 7.4). The prepared nanomaterials were evaluated using several methods, including The Brauner-Emmett-Teller, surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope, Powder X-Ray Diffraction, Fourier Transform Infrared Spectroscopy, Energy-Dispersive X-ray Spectroscopy, and Differential Scanning Calorimetry. In vitro dissolution studies revealed that Eudragit®-S100-coated aminated nanomaterials prevented the burst release of the loaded catechin in the acidic environment, with approximately 90% of the catechin only being released at colonic pH (pH > 7) with a supercase II transport mechanism. As a result, silica nanoparticles coated with Eudragit®-S100 would provide an innovative and promising approach in targeted nanomedicine for the oral delivery of catechin and related medicines for treating diseases related to the colon, such as colorectal cancer and irritable bowel syndrome.


Mechanisms of Toxicity and Modulation of Hemoglobin-based Oxygen Carriers.
Several adverse events have been associated with the infusion of hemoglobin-based oxygen carriers (HBOCs), including transient hypertension, gastrointestinal, pancreatic/liver enzyme elevation, and cardiac/renal injury in humans. Although several mechanisms have been suggested, the basis of HBOC toxicity is still poorly understood. Scavenging of vascular endothelial nitric oxide (NO) and heme-mediated oxidative side reactions are thought to be the major causes of toxicity. However, based on more recent preclinical studies, oxidative pathways (driven by the heme prosthetic group) seem to play a more prominent role in the overall toxicity of free Hb or HBOCs. HBOCs display a diversity of physicochemical properties, including molecular size/cross-linking characteristics leading to differences in oxygen affinity, allosteric, redox properties, and even oxidative inactivation by protein/heme clearing mechanisms. These diverse characteristics can therefore be manipulated independently, leaving open the possibility of engineering a safe and effective HBOC. To date, several antioxidative strategies have been proposed to counteract the redox side reactions of current generation HBOCs.


Development of a trigger tool to identify adverse events and no-harm incidents that affect patients admitted to home healthcare.
Adverse events (AEs) and no-harm incidents are common and of great concern in healthcare. A common method for identification of AEs is retrospective record review (RRR) using predefined triggers. This method has been used frequently in inpatient care, but AEs in home healthcare have not been explored to the same extent. The aim of this study was to develop a trigger tool (TT) for the identification of both AEs and no-harm incidents affecting adult patients admitted to home healthcare in Sweden, and to describe the methodology used for this development. The TT was developed and validated in a stepwise manner, in collaboration with experts with different skills, using (1) literature review and interviews, (2) a five-round modified Delphi process, and (3) two-stage RRRs. Ten trained teams from different sites in Sweden reviewed 600 randomly selected records. In all, triggers were found 4031 times in 518 (86.3%) records, with a mean of 6.7 (median 4, range 1-54) triggers per record with triggers. The positive predictive values (PPVs) for AEs and no-harm incidents were 25.4% and 16.3%, respectively, resulting in a PPV of 41.7% (range 0.0%-96.1% per trigger) for the total TT when using 38 triggers. The most common triggers were unplanned contact with physician and/or registered nurse, moderate/severe pain, moderate/severe worry, anxiety, suffering, existential pain and/or psychological pain. AEs were identified in 37.7% of the patients and no-harm incidents in 29.5%. This study shows that adapted triggers with definitions and decision support, developed to identify AEs and no-harm incidents that affect patients admitted to home healthcare, may be a valid method for safety and quality improvement work in home healthcare.


Preoperative autologous blood donation: clinical, economic, and ethical issues.
Many patients are donating their own blood before surgery to avoid blood-borne infections, often on the advice of their physicians. But autologous blood transfusion, while safer than allogeneic transfusion, is not completely risk-free. It is also expensive, its benefits are difficult to assess, and its increasing popularity raises many difficult ethical issues, such as whether the benefit of allogeneic transfusion supports its additional expense. Record-keeping, collection, and transfusion errors are occasional risks of autologous transfusions. In addition, risks associated with blood donation, from mild dizziness to precipitation of angina, should be considered when high-risk patients are referred for autologous collection. Only approximately half of autologous units collected are actually used, and the cost per quality-adjusted year of life saved may be as high as $1 million, depending on the type of surgical procedure. Although recombinant human erythropoietin can stimulate red blood cell production before autologous donation and decrease the need for transfusion, it is not clear whether this strategy, which can cost thousands of dollars per patient, will be cost-effective. Perioperative hemodilution may become an important component in efforts to reduce patient exposure to allogeneic blood, but its use remains controversial.


Computer-based image analysis for plus disease diagnosis in retinopathy of prematurity.
Presence of plus disease in retinopathy of prematurity (ROP) is an important criterion for identifying ROP requiring treatment. Plus disease is defined by a standard published photograph selected more than 20 years ago by expert consensus. However, diagnosis of plus disease has been shown to be subjective and qualitative. Computer-based image analysis using quantitative methods has potential to improve the objectivity of plus disease diagnosis. The objective was to review the published literature involving computer-based image analysis for ROP diagnosis. The PubMed and Cochrane library databases were searched for the keywords "retinopathy of prematurity" AND "image analysis" AND/OR "plus disease." Reference lists of retrieved articles were searched to identify additional relevant studies. All relevant English-language studies were reviewed. There are four main computer-based systems-ROPtool (area under the receiver operating characteristic curve [AUROC], plus tortuosity 0.95, plus dilation 0.87), RISA (AUROC, arteriolar TI 0.71, venular diameter 0.82), Vessel Map (AUROC, arteriolar dilation 0.75, venular dilation 0.96), and CAIAR (AUROC, arteriole tortuosity 0.92, venular dilation 0.91)-attempting to objectively analyze vessel tortuosity and dilation in plus disease in ROP. Some show promise for identification of plus disease using quantitative methods. This has potential to improve the diagnosis of plus disease and may contribute to the management of ROP using both traditional binocular indirect ophthalmoscopy and image-based telemedicine approaches.


Continuing warfarin therapy is superior to interrupting warfarin with or without bridging anticoagulation therapy in patients undergoing pacemaker and defibrillator implantation.
Current guidelines recommend stopping oral anticoagulation and starting bridging anticoagulation with intravenous heparin or subcutaneous enoxaparin when implanting a pacemaker or defibrillator in patients at moderate or high risk for thromboembolic events. A limited body of literature suggests that device surgery without cessation of oral anticoagulation may be feasible. The purpose of this study was to evaluate the safety of device surgery in orally anticoagulated patients without interrupting warfarin therapy. We performed a retrospective study of 459 consecutive patients on chronic warfarin therapy who underwent device surgery from April 2004 to September 2008. Warfarin was continued in 222 patients during the perioperative period. Warfarin was temporarily held and bridging therapy administered in 123 patients. Warfarin was temporarily held without bridging therapy in 114 patients. There were no significant differences with regard to age, sex, or risk factors for thromboembolism in the three groups. Patients who continued taking warfarin had a lower incidence of pocket hematoma (P = .004) and a shorter hospital stay (P <.0001) than did patients in the bridging group. Holding warfarin without bridging is associated with a higher incidence of transient ischemic attacks (P = .01). Temporarily interrupting anticoagulation is associated with increased thromboembolic events, whereas cessation of warfarin with bridging anticoagulation is associated with a higher rate of pocket hematoma and a longer hospital stay. Continuing warfarin with a therapeutic international normalized ratio appears to be a safe and cost-effective approach when implanting a pacemaker or defibrillator in patients with moderate to high thromboembolic risk.


Weighing outcomes by time or against time? Evaluation rules in intertemporal choice.
Models of intertemporal choice draw on three evaluation rules, which we compare in the restricted domain of choices between smaller sooner and larger later monetary outcomes. The hyperbolic discounting model proposes an alternative-based rule, in which options are evaluated separately. The interval discounting model proposes a hybrid rule, in which the outcomes are evaluated separately, but the delays to those outcomes are evaluated in comparison with one another. The tradeoff model proposes an attribute-based rule, in which both outcomes and delays are evaluated in comparison with one another: People consider both the intervals between the outcomes and the compensations received or paid over those intervals. We compare highly general parametric functional forms of these models by means of a Bayesian analysis, a method of analysis not previously used in intertemporal choice. We find that the hyperbolic discounting model is outperformed by the interval discounting model, which, in turn, is outperformed by the tradeoff model. Our cognitive modeling is among the first to offer quantitative evidence against the conventional view that people make intertemporal choices by discounting the value of future outcomes, and in favor of the view that they directly compare options along the time and outcome attributes.


Neuronal ensemble control of prosthetic devices by a human with tetraplegia.
Neuromotor prostheses (NMPs) aim to replace or restore lost motor functions in paralysed humans by routeing movement-related signals from the brain, around damaged parts of the nervous system, to external effectors. To translate preclinical results from intact animals to a clinically useful NMP, movement signals must persist in cortex after spinal cord injury and be engaged by movement intent when sensory inputs and limb movement are long absent. Furthermore, NMPs would require that intention-driven neuronal activity be converted into a control signal that enables useful tasks. Here we show initial results for a tetraplegic human (MN) using a pilot NMP. Neuronal ensemble activity recorded through a 96-microelectrode array implanted in primary motor cortex demonstrated that intended hand motion modulates cortical spiking patterns three years after spinal cord injury. Decoders were created, providing a 'neural cursor' with which MN opened simulated e-mail and operated devices such as a television, even while conversing. Furthermore, MN used neural control to open and close a prosthetic hand, and perform rudimentary actions with a multi-jointed robotic arm. These early results suggest that NMPs based upon intracortical neuronal ensemble spiking activity could provide a valuable new neurotechnology to restore independence for humans with paralysis.


Soft contact lens identification.
Measuring procedures used for hydrogel contact lenses are sufficiently difficult to make identification of a given soft lens annoyingly time-consuming and sometimes impossible. Etching a number or letter on the lens when it is received from the laboratory allows the practitioner to tell whether the proper lens is being worn, even while the lens is still on the patient's eye. A sharp pointed tool on a dry hydrogel lens produces this identifying number.


Imaging the cellular uptake of tiopronin-modified gold nanoparticles.
Well-dispersed gold nanoparticles (NP) coated with tiopronin were synthesized by X-ray irradiation without reducing agents. High-resolution transmission electron microscopy shows that the average core diameters of the NPs can be systematically controlled by adjusting the tiopronin to Au mole ratio in the reaction. Three methods were used to study the NP uptake by cells: quantitative measurements by inductively coupled plasma mass spectrometry, direct imaging with high lateral resolution transmission electron microscopy and transmission X-ray microscopy. The results confirmed that the NP internalization mostly occurred via endocytosis and concerned the cytoplasm. The particles, in spite of their small sizes, were not found to arrive inside the cell nuclei. The synthesis without reducing agents and solvents increased the biocompatibility as required for potential applications in analysis and biomedicine in general.


Effects of training time and feedback on ventilation skills in lay rescuers.
Lay rescuers have difficulties acquiring ventilation skills during training. Non-feedback manikins are still widely employed, although skill acquisition is suboptimal. We analysed if a longer training time and verbal feedback, given by an instructor, improved ventilation skill acquisition with non-feedback manikins. Forty-three high school students without prior medical training participated in this prospective randomised trial. Under one-to-one instructor guidance, 25 volunteers were trained on a manikin with a mouth-to-mask device for 10 min, and 18 volunteers for 20 min. After training, volunteers were assessed and verbal feedback was given: ventilate more if the mean tidal volume <0.5 L, ventilate less if >0.7 L or ventilate the same for 0.5-0.7 L. The volunteers were then reassessed. At the assessment, tidal volume, minute volume, peak airway pressure, ventilation rate and stomach inflation rate were comparable between the 10 and 20 min groups. After verbal feedback, at reassessment both groups increased tidal volume (assessment 0.75+/-0.24 vs reassessment 0.80+/-0.16 l/min; p=0.007), minute volume (9.1+/-3.0 vs 10.0+/-2.4 l/min; p=0.001), peak airway pressure (17.0+/-5.2 vs 18.3+/-3.4 cmH(2)O; p=0.003) and stomach inflation rate (67 vs 88%; p=0.02), while ventilation rate (12.3+/-2.1 vs 12.6+/-2.3 ventilations/min; p=NS) remained comparable. Both 10 and 20 min ventilation training times resulted in comparable skills. Volunteers hyperventilated the manikin and produced excessive stomach inflation in this model. This increased even further after verbal feedback.


Inhibition of ribonucleotide reductase by gallium in murine leukemic L1210 cells.
Our previous studies of the mechanism of cell growth inhibition by gallium have suggested that the block in cellular iron uptake induced by transferrin-gallium results in an inhibition of the iron-dependent M2 subunit of ribonucleotide reductase. However, it is not known whether the inhibitory effect of gallium on ribonucleotide reductase is solely the result of limiting iron availability for enzyme activity or whether a direct effect of intracellular gallium on the enzyme is also involved. In the present study, utilizing a cell-free assay, we show that gallium nitrate directly inhibits CDP and ADP reductase activity. Inhibition of DNA synthesis by gallium nitrate thus appears to be due to a combination of a block in iron availability to ribonucleotide reductase and a direct inhibition of the enzyme by gallium.


Skeletal muscle metabolism in sea-acclimatized king penguins. I. Thermogenic mechanisms.
At fledging, king penguin juveniles undergo a major energetic challenge to overcome the intense and prolonged energy demands for thermoregulation and locomotion imposed by life in cold seas. Among other responses, sea acclimatization triggers fuel selection in skeletal muscle metabolism towards lipid oxidation in vitro, which is reflected by a drastic increase in lipid-induced thermogenesis in vivo However, the exact nature of skeletal muscle thermogenic mechanisms (shivering and/or non-shivering thermogenesis) remains undefined. The aim of the present study was to determine in vivo whether the capacity for non-shivering thermogenesis was enhanced by sea acclimatization. We measured body temperature, metabolic rate, heart rate and shivering activity in fully immersed king penguins (Aptenodytes patagonicus) exposed to water temperatures ranging from 12 to 29°C. Results from terrestrial pre-fledging juveniles were compared with those from sea-acclimatized immature penguins (hereafter 'immatures'). The capacity for thermogenesis in water was as effective in juveniles as in immatures, while the capacity for non-shivering thermogenesis was not reinforced by sea acclimatization. This result suggests that king penguins mainly rely on skeletal muscle contraction (shivering or locomotor activity) to maintain endothermy at sea. Sea-acclimatized immature penguins also exhibited higher shivering efficiency and oxygen pulse (amount of oxygen consumed or energy expended per heartbeat) than pre-fledging juvenile birds. Such increase in shivering and cardiovascular efficiency may favor a more efficient activity-thermoregulatory heat substitution providing penguins with the aptitude to survive the tremendous energetic challenge imposed by marine life in cold circumpolar oceans.


The Ly-49D receptor activates murine natural killer cells.
Proteins encoded by members of the Ly-49 gene family are predominantly expressed on murine natural killer (NK) cells. Several members of this gene family have been demonstrated to inhibit NK cell lysis upon recognizing their class I ligands on target cells. In this report, we present data supporting that not all Ly-49 proteins inhibit NK cell function. Our laboratory has generated and characterized a monoclonal antibody (mAb) (12A8) that can be used to recognize the Ly-49D subset of murine NK cells. Transfection of Cos-7 cells with known members of the Ly-49 gene family revealed that 12A8 recognizes Ly-49D, but also cross-reacts with the Ly-49A protein on B6 NK cells. In addition, 12A8 demonstrates reactivity by both immuno-precipitation and two-color flow cytometry analysis with an NK cell subset that is distinct from those expressing Ly-49A, C, or G2. An Ly-49D+ subset of NK cells that did not express Ly-49A, C, and G2 was isolated and examined for their functional capabilities. Tumor targets and concanovalin A (ConA) lymphoblasts from a variety of H2 haplotypes were examined for their susceptibility to lysis by Ly-49D+ NK cells. None of the major histocompatibility complex class I-bearing targets inhibited lysis of Ly-49D+ NK cells. More importantly, we demonstrate that the addition of mAb 12A8 to Ly-49D+ NK cells can augment lysis of Fc gamma R+ target cells in a reverse antibody-dependent cellular cytotoxicity-type assay and induces apoptosis in Ly-49D+ NK cells. Furthermore, the cytoplasmic domain of Ly-49D does not contain the V/Ix-YxxL immunoreceptor tyrosine-based inhibitory motif found in Ly-49A, C, or G2 that has been characterized in the human p58 killer inhibitory receptors. Therefore, Ly-49D is the first member of the Ly-49 family characterized as transmitting positive signals to NK cells, rather than inhibiting NK cell function.


Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive disease and hospital-treated pneumonia among people aged ≥65 years: a retrospective case-control study.
Streptococcus pneumoniae contributes considerably to the burden of pneumonia and invasive pneumococcal disease (IPD), with the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for preventing all-cause pneumonia still undetermined. The aim of this study was to control for common biases and confounders associated with previous observational studies and to assess PPSV23 vaccine effectiveness in preventing IPD and the most resource-intensive type of community-acquired pneumonia, hospital-treated pneumonia (HTP). This was a retrospective case-control study nested in a population-based cohort, with age-, sex-, and risk-matched controls as the base case. Demographic information, laboratory data, and diagnoses were extracted from the chronic disease registry and from inpatient and outpatient records in the Clalit Health Services database. Vaccine effectiveness for PPSV23 was assessed using multivariable conditional logistic regression. Subgroup, sensitivity, and secondary analyses were conducted to validate findings. A total of 470 070 individuals aged ≥65 years were members of Clalit Health Services during the study period (1 January 2007 through 31 December 2010). The case cohort consisted of 212 participants with IPD and 23 441 with HTP. The adjusted association between vaccination and IPD was protective (odds ratio [OR], 0.58; 95% confidence interval [CI], .41-.81), whereas there was no demonstrated protective effect between vaccination and HTP (OR, 1.01; 95% CI, .97-1.04). The sensitivity analysis and all but 1 subgroup analysis provided consistent results to the base case. The PPSV23 vaccine is effective against the most severe invasive forms of pneumococcal disease, but the lack of effectiveness of PPSV23 in protecting against all-cause HTP should be considered for future vaccine policies.


What Plant Genetic Resources for Food and Agriculture Are Available under the Plant Treaty and Where Is This Information?
Plant genetic resources for food and agriculture (PGRFA) are the building blocks upon which global food and nutrition security depend and are key to plant breeding for more resistant crops, but how available are they? To understand what PGRFA are available under the mechanisms created by the International Plant Treaty's access and benefit-sharing, we conducted a comparative analysis of the five largest sources of pooled global data concerning PGRFA, including data conserved by and available to users under the Plant Treaty's access and benefit-sharing (ABS) mechanism. These data sources were the registry of notification letters maintained by the Plant Treaty Secretariat and four international PGRFA databases: Genesys, European Search Catalogue for Plant Genetic Resources (EURISCO), World Information and Early Warning System on Plant Genetic Resources for Food and Agriculture (WIEWS) and Global Information System on PGRFA (GLIS). Our analysis revealed that a comprehensive and consistent overview of the PGRFA available under the Plant Treaty's ABS conditions is not available. The GLIS is the most logical longer-term candidate to promote the provision of up-to-date and comprehensive snapshots of what PGRFA the Plant Treaty framework make available, primarily because it provides a mechanism (digital objective identifiers) to link together information from a range of information sources, including Genesys, WIEWS and EUEISCO and other online publications, and data sets concerning PGRFA in the multilateral system. Successful adoption of the GLIS could be promoted by creating novel incentives endorsed by the Governing Body to encourage Contracting Parties, Article 15 organizations, and individuals to share information about the materials they are making available under the Plant Treaty, in addition to the capacity-building for some GLIS users that is also necessary. These incentives could be included among the package of measures currently being considered by the Plant Treaty's Working Group to Enhance the Functioning of the Multilateral System of Access and Benefit-Sharing.


First report on prevalence of SARS-CoV-2 infection among health-care workers in Nicaragua.
The Nicaraguan COVID-19 situation is exceptional for Central America. The government restricts testing and testing supplies, and the true extent of the coronavirus crisis remains unknown. Dozens of deaths have been reported among health-care workers. However, statistics on the crisis' effect on health-care workers and their risk of being infected with SARS-CoV-2 are lacking. We aimed to estimate the prevalence of SARS-CoV-2 infection in health-care workers and to examine correlations with risk factors such as age, sex and comorbidities. Study participants (N = 402, median age 38.48 years) included physicians, nurses and medical assistants, from public and private hospitals, independent of symptom presentation. SARS-CoV-2 was detected on saliva samples using the loop-mediated isothermal amplification assay. A questionnaire was employed to determine subjects' COVID-19-associated symptoms and their vulnerability to complications from risk factors such as age, sex, professional role and comorbidities. The study was performed five weeks into the exponential growth period in Nicaragua. We discovered that 30.35% of health-care workers participating in our study had been infected with SARS-CoV-2. A large percentage (54.92%) of those who tested positive were asymptomatic and were still treating patients. Nearly 50% of health-care workers who tested positive were under 40, an astonishing 30.33% reported having at least one comorbidity. In our study, sex and age are important risk factors for the probability of testing positive for SARS-CoV-2 with significance being greatest among those between 30 and 40 years of age. In general, being male resulted in higher risk. Our data are the first non-governmental data obtained in Nicaragua. They shed light on several important aspects of COVID-19 in an underdeveloped nation whose government has implemented a herd-immunity strategy, while lacking an adequate healthcare system and sufficient PPE for health-care workers. These data are important for creating policies for containing the spread of SARS-CoV-2.


Self-assembled aggregates of rod-coil block copolymers and their solubilization and encapsulation of fullerenes
Amphiphilic poly(phenylquinoline)-block-polystyrene rod-coil diblock copolymers were observed to self-organize into robust, micrometer-scale, spherical, vesicular, cylindrical, and lamellar aggregates from solution. These diverse aggregate morphologies were seen at each composition, but their size scale decreased with a decreasing fraction of the rigid-rod block. Compared to coil-coil block copolymer micelles, the present aggregates are larger by about two orders of magnitude and have aggregation numbers of over 10(8). The spherical and cylindrical aggregates have large hollow cavities. Only spherical aggregates with aggregation numbers in excess of 10(9) were formed in the presence of fullerenes (C60, C70) in solution, resulting in the solubilization and encapsulation of over 10(10) fullerene molecules per aggregate.


Asiatic acid, a triterpene, inhibits cell proliferation through regulating the expression of focal adhesion kinase in multiple myeloma cells.
The aim of the present study was to investigate whether asiatic acid (AA), a pentacyclic triterpene derived from Centella asiatica, exerts anti-proliferative effects on multiple myeloma RPMI 8226 cells and to determine the molecular mechanism underlying the anticancer action of AA. The study sought to analyze the potential role of AA on the proliferation of the RPMI 8226 cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium assay. Cell cycle arrest was detected by flow cytometry, and the expression levels of focal adhesion kinase (FAK) in the myeloma cells induced by AA were analyzed using the western blotting and immunoprecipitation methods. The results indicated that AA significantly inhibited cell proliferation in a time- and dose-dependent manner and led to G2/M phase arrest at concentrations of 35 and 40 μmol/l in the RPMI 8226 cells. The expression levels of FAK and p-FAK were distinctly decreased following AA treatment (at the concentration of 40 μmol/l) for 24 h compared with that of the control groups. Taken together, these results demonstrated that AA was able to regulate cell cycle progression in RPMI 8226 cells, thereby significantly inhibiting cell growth. Furthermore, AA decreased the expression levels of FAK, indicating that the antitumor mechanism of AA may be associated with the inhibition of signal transduction mediated by FAK.


Exploring the Bacterial Community in Aged Fecal Sources from Dairy Cows: Impacts on Fecal Source Tracking.
(1) Background: This paper discusses the impact of agricultural activities on stream health, particularly in relation to dairy cow fecal pollution. The study explores the fecal microbiome of cattle and the potential ecological implications of aging fecal pollution on waterways. (2) Methods: The study examines changes in the bacterial community available for mobilization from in-situ decomposing cowpats and the effects of simulated rainfall. The microbiome of individual cowpats was monitored over 5.5 months. We used 16S rRNA metagenomics and machine learning software, FEAST (Fast Expectation-mAximization for microbial Source Tracking), for bacterial and fecal source assignments. (3) Results: The phyla Bacillota and Bacteroidota are dominant in the fecal microbiota of fresh cow feces but shift to Pseudomonodota, Actinomycetota, and environmental Bacteroidota in aged cowpats. Potential impacts of these bacterial community shifts on inputs to local agricultural streams are discussed in relation to water quality monitoring and aging sources of fecal contamination. We identified taxon orders that are potential indicators of fresh cattle sources (Oscillospirales and Bacteroidales) and aged sources (Peptostreptococcales-Tissierellales) in water bodies. (4) The paper highlights that bacterial metagenomic profiling can inform our understanding of the ecology of microbial communities in aquatic environments and the potential impacts of agricultural activities on ecosystem health.


Contributions of force field interaction forms to Green-Kubo viscosity integral in n-alkane case.
Decades of molecular simulation history proved that the Green-Kubo method for shear viscosity converges without any problems in atomic and simple molecular liquids, unlike liquids with high values of viscosity. In the case of highly viscous liquids, the time decomposition method was developed in 2015 by Maginn and co-authors [Y. Zhang, A. Otani, and E. J. Maginn, J. Chem. Theory Comput. 11, 3537-3546 (2015)] which allows us to improve the convergence of the Green-Kubo integral. In this paper, the contributions of intramolecular and intermolecular force field parts to the viscosity integral are discovered to gain the understanding of the Green-Kubo method. The n-alkanes from n-ethane to n-pentane at 330 K in the optimized potentials for liquid simulations-all atom force field are used as reference models. The dependencies of these contributions and decay times of the corresponding correlation functions on the chain length are observed. The nonequilibrium simulations are carried out to verify the Green-Kubo results. The obtained values of viscosity are compared with experimental data.


Timing of hypertonic saline inhalation for cystic fibrosis.
Inhalation of hypertonic saline improves sputum rheology, accelerates mucociliary clearance and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane Review. To determine whether the timing of hypertonic saline inhalation (in relation to airway clearance techniques or in relation to time of day) has an impact on its clinical efficacy in people with cystic fibrosis. We identified relevant randomised and quasi-randomised controlled trials from the Cochrane Cystic Fibrosis Trials Register, the Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings. Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register: 28 February 2019. Any trial of hypertonic saline in people with cystic fibrosis where timing of inhalation was the randomised element in the study protocol with either: inhalation up to six hours before airway clearance techniques compared to inhalation during airway clearance techniques compared to inhalation up to six hours after airway clearance techniques; or morning compared to evening inhalation with any definition provided by the author. Both authors independently assessed the trials identified by the search for potential inclusion in the review. The certainty of the evidence was assessed using GRADE. The searches identified 104 trial reports which represented 51 trials, of which three cross-over trials (providing data on 77 participants) met our inclusion criteria. We present three comparisons: inhalation before versus during airway clearance techniques; inhalation before versus after airway clearance techniques; and inhalation during versus after airway clearance techniques. One trial (50 participants), given its three-arm design, was eligible for all three comparisons. No trials compared morning versus evening inhalation of hypertonic saline. The evidence from the three trials was judged to be of low quality downgraded for limitations (high risk of bias due to blinding) and indirectness (all participants are adults, and therefore not applicable to children). Intervention periods ranged from one treatment to three treatments in one day. There were no clinically important differences between the timing regimens of inhaling hypertonic saline before, during or after airway clearance techniques in the mean amount of improvement in lung function or symptom scores (77 participants), with the between-group comparisons being non-significant (low-certainty evidence). While there may be little or no difference in the rating of satisfaction when hypertonic saline was inhaled before versus during the airway clearance techniques (64 participants) (with the 95% confidence interval including the possibility of both a higher and lower rating of satisfaction), satisfaction may be lower on a 100-mm scale when inhaled after the airway clearance techniques compared to before: mean difference (MD) 20.38 mm (95% confidence interval (CI) 12.10 to 28.66) and when compared to during the techniques, MD 14.80 mm (95% CI 5.70 to 23.90). Perceived effectiveness showed similar results: little or no difference for inhalation before versus during airway clearance techniques (64 participants); may be lower when inhaled after the airway clearance techniques compared to before, MD 10.62 (95% CI 2.54 to 18.70); and also when compared to during the techniques, MD 15.60 (95% CI 7.55 to 23.65). There were no quality of life or adverse events reported in any of the trials. Timing of hypertonic saline inhalation makes little or no difference to lung function (low-certainty evidence). However, inhaling hypertonic saline before or during airway clearance techniques may maximise perceived efficacy and satisfaction. The long-term efficacy of hypertonic saline has only been established for twice-daily inhalations; however, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until evidence comparing these regimens is available. The identified trials were all of very short intervention periods, so longer-term research could be conducted to establish the effects arising from regular use, which would incorporate the influence of changes in adherence with long-term use, as well as generating data on any adverse effects that occur with long-term use.


Association between dietary patterns and chronic kidney disease combined with hyperuricemia.
Background and aims: Chronic kidney disease (CKD) combined with hyperuricemia is a concerning health issue, but the association between this condition and dietary patterns remains poorly understood. The aim of this study was to assess the associations between dietary patterns and CKD combined with hyperuricemia. Methods: This cross-sectional study was conducted involving 12 318 participants aged 18-79 years during 2018-2020. Dietary intake information was collected using a validated 110-item food frequency questionnaire. Factor analysis was used to identify major dietary patterns. CKD was defined as the presence of albuminuria or an estimated glomerular filtration rate <60 mL min-1 1.73 m-2. Hyperuricemia was defined as serum uric acid levels >420 μmol L-1 both in men and women. Logistic regression models were applied to assess the association between dietary patterns and the risk of CKD combined with hyperuricemia. Results: Five major dietary patterns were identified: 'healthy pattern', 'traditional pattern', 'animal foods pattern', 'sweet foods pattern', and 'tea-alcohol pattern', which together explained 38.93% of the variance in the diet. After adjusting for potential confounders, participants in the highest quartile of the traditional pattern had a lower risk of CKD combined with hyperuricemia (OR = 0.49, 95% CI: 0.32-0.74, Pfor trend < 0.01). Conversely, participants in the highest quartile of the sweet foods pattern had a higher risk compared to those in the lowest quartile (OR = 1.69, 95% CI: 1.18-2.42, Pfor trend < 0.01). However, no significant association was observed between the healthy pattern, animal foods pattern and tea-alcohol pattern and the risk of CKD combined with hyperuricemia. Conclusions: Our results suggest that the traditional pattern is associated with a reduced risk of CKD combined with hyperuricemia, whereas the sweet foods pattern is associated with an increased risk.


Cell lineages and tissue boundaries in cardiac arterial and venous poles: developmental patterns, animal models, and implications for congenital vascular diseases.
Multiple cell populations with different embryological histories are involved in the morphogenesis of the cardiac arterial and venous poles as well as in the correct alignment and connection of the developing vessels with the cardiac chambers. Formation of the aorta and the pulmonary trunk is a complicated process orchestrated via a specific sequence of highly integrated spatiotemporal events of cell proliferation, migration, differentiation, and apoptosis. The peculiar susceptibility of this intricate cell network to be altered explains the frequency of congenital cardiovascular diseases of the arterial and venous poles. We review this topic from the "vascular point of view," putting major emphasis on (1) the existence of different cell lineages from which smooth muscle cells of the aorticopulmonary trunk can be derived, (2) the establishment of cell/tissue boundaries in the cardiovascular connecting regions, and (3) the animal models that can mimic human congenital defects of the arterial and venous poles of the heart.


Interactions between Thaumarchaea, Nitrospira and methanotrophs modulate autotrophic nitrification in volcanic grassland soil.
Ammonium/ammonia is the sole energy substrate of ammonia oxidizers, and is also an essential nitrogen source for other microorganisms. Ammonia oxidizers therefore must compete with other soil microorganisms such as methane-oxidizing bacteria (MOB) in terrestrial ecosystems when ammonium concentrations are limiting. Here we report on the interactions between nitrifying communities dominated by ammonia-oxidizing archaea (AOA) and Nitrospira-like nitrite-oxidizing bacteria (NOB), and communities of MOB in controlled microcosm experiments with two levels of ammonium and methane availability. We observed strong stimulatory effects of elevated ammonium concentration on the processes of nitrification and methane oxidation as well as on the abundances of autotrophically growing nitrifiers. However, the key players in nitrification and methane oxidation, identified by stable-isotope labeling using (13)CO2 and (13)CH4, were the same under both ammonium levels, namely type 1.1a AOA, sublineage I and II Nitrospira-like NOB and Methylomicrobium-/Methylosarcina-like MOB, respectively. Ammonia-oxidizing bacteria were nearly absent, and ammonia oxidation could almost exclusively be attributed to AOA. Interestingly, although AOA functional gene abundance increased 10-fold during incubation, there was very limited evidence of autotrophic growth, suggesting a partly mixotrophic lifestyle. Furthermore, autotrophic growth of AOA and NOB was inhibited by active MOB at both ammonium levels. Our results suggest the existence of a previously overlooked competition for nitrogen between nitrifiers and methane oxidizers in soil, thus linking two of the most important biogeochemical cycles in nature.


Gender differences in the development of heart failure after acute coronary syndrome: Insight from the CORALYS registry.
Impact of gender on heart remodeling after acute coronary syndrome (ACS) and consequently on development of heart failure (HF) remains to be elucidated. CORALYS is a multicenter, retrospective, observational registry enrolling consecutive patients admitted for ACS and treated with percutaneous coronary intervention. HF hospitalization was the primary endpoint while all-cause mortality and the composite endpoint of incidence of first HF hospitalization and cardiovascular mortality were the secondary ones. Among 14,699 patients enrolled in CORALYS registry, 4578 (31%) were women and 10,121 (69%) males. Women were older, had more frequently hypertension and diabetes and less frequently smoking habit. History of myocardial infarction (MI), STEMI at admission and multivessel disease were less common in women. After median follow up of 2.9 ± 1.8 years, women had higher incidence of primary and secondary endpoints and female sex was an independent predictor of HF hospitalization (HR 1.26;1.05-1.50; p = 0.011) and cardiovascular death/HF hospitalization (HR 1.18;1.02-1.37; p = 0.022). At multivariable analysis women and men share as predictors of HF diabetes, history of cancer, chronic kidney disease, atrial fibrillation, complete revascularization and left ventricular ejection fraction. Chronic obstructive pulmonary disease (HR 2.34;1.70-3.22, p < 0.001) and diuretics treatment (HR 1.61;1.27-2.04, p < 0.001) were predictor of HF in men, while history of previous MI (HR 1.46;1.08-1.97, p = 0.015) and treatment with inhibitors of renin-angiotensin system (HR 0.69;0,49-0.96 all 95% CI, p = 0.030) in women. Women are at increased risk of HF after ACS and gender seems to be an outcome-modifier of the relationship between a variable and primary outcome.


Stemness enhancement of human neural stem cells following bone marrow MSC coculture.
Rapid loss of stemness capacity in purified prototype neural stem cells (NSCs) remains a serious challenge to basic and clinical studies aiming to repair the central nervous system. Based on the essential role of mesodermal guidance in the process of neurulation, we hypothesized that coculture of human NSCs (hNSCs) with human bone marrow-derived mesenchymal stromal stem cells (hMSCs) could enhance the stemness of hNSCs through Notch-1 signaling. We have now tested the hypothesis by assessing behaviors of hNSCs and hMSCs under systematically designed coculture conditions relative to monocultures, with or without Notch-1 manipulation in vitro. Our data demonstrate that expression levels of Notch-1 and Hes-1 as determined by immunocytochemistry are significantly higher in hNSCs cocultured with hMSCs than those of controls. Furthermore, coculturing significantly increases immunoreactivity of CD15, a neural stemness marker, but decreases CD24, a marker of neural/neuronal commitment in hNSCs. The effect is independent from the physical status of cell growth since coculture and notch signaling actually promotes hNSC adhesion. Importantly, coculture with hMSCs markedly augments hNSC proliferation rate (e.g., higher yield in G2/M phase subpopulation in a notch-dependent manner detected by flow cytometry) without diminishing their lineage differentiation capabilities. The results suggest that coculture of hNSCs with hMSCs enhances stemness biology of hNSCs partially via activation of Notch-1 signal transduction. Our finding sheds new light on mesoderm-ectoderm cell fate determination via contact-based hMSC-hNSC interactions and provides mechanistic leads for devising effective regimens to sustain and augment stemness of in vitro established hNSC and hMSC lines for basic science, translational and clinical applications.


Self-Driven Jamming in Growing Microbial Populations.
In natural settings, microbes tend to grow in dense populations [1-4] where they need to push against their surroundings to accommodate space for new cells. The associated contact forces play a critical role in a variety of population-level processes, including biofilm formation [5-7], the colonization of porous media [8, 9], and the invasion of biological tissues [10-12]. Although mechanical forces have been characterized at the single cell level [13-16], it remains elusive how collective pushing forces result from the combination of single cell forces. Here, we reveal a collective mechanism of confinement, which we call self-driven jamming, that promotes the build-up of large mechanical pressures in microbial populations. Microfluidic experiments on budding yeast populations in space-limited environments show that self-driven jamming arises from the gradual formation and sudden collapse of force chains driven by microbial proliferation, extending the framework of driven granular matter [17-20]. The resulting contact pressures can become large enough to slow down cell growth, to delay the cell cycle in the G1 phase, and to strain or even destroy the microenvironment through crack propagation. Our results suggest that self-driven jamming and build-up of large mechanical pressures is a natural tendency of microbes growing in confined spaces, contributing to microbial pathogenesis and biofouling [21-26].


Functionalised polysiloxanes as injectable, in situ curable accommodating intraocular lenses.
The aged eye's ability to change focus (accommodation) may be restored by replacing the hardened natural lens with a soft gel. Functionalised polysiloxane macromonomers, designed for application as an injectable, in situ curable accommodating intraocular lens (A-IOL), were prepared via a two-step synthesis. Prepolymers were synthesised via ring opening polymerisation (ROP) of octamethylcyclotetrasiloxane (D(4)) and 2,4,6,8-tetramethylcyclotetrasiloxane (D(4)(H)) in toluene using trifluoromethanesulfonic acid (TfOH) as catalyst. Hexaethyldisiloxane (HEDS) was used as the end group to control the molecular weight of the prepolymers, which were then converted to macromonomers by hydrosilylation of the SiH groups with allyl methacrylate (AM) to introduce polymerisable groups. The resulting macromonomers had an injectable consistency and thus, were able to be injected into and refill the empty lens capsular bag. The macromonomers also contained a low ratio of polymerisable groups so that they may be cured on demand, in situ, under irradiation of blue light, in the presence of a photo-initiator, to form a soft polysiloxane gel (an intraocular lens) in the eye. The pre-cure viscosity and post-cure modulus of the polysiloxanes, which are crucial factors for an injectable, in situ curable A-IOL application, were controlled by adjusting the end group and D(4)(H) concentrations, respectively, in the ROP. The macromonomers were fully cured within 5 min under light irradiation, as shown by the rapid change in modulus monitored by photo-rheology. Ex vivo primate lens stretching experiments on an Ex Vivo Accommodation Simulator (EVAS) showed that the polysiloxane gel refilled lenses achieved over 60% of the accommodation amplitude of the natural lens. An in vivo biocompatibility study in rabbits using the lens refilling (Phaco-Ersatz) procedure demonstrated that the soft gels had good biocompatibility with the ocular tissue. The polysiloxane macromonomers meet the targeted optical and mechanical properties of a young natural crystalline lens and show promise as candidate materials for use as injectable, in situ curable A-IOLs for lens refilling procedures.


Fitness and physical activity in youth with type 1 diabetes mellitus in good or poor glycemic control.
Patients with type 1 diabetes mellitus (T1DM) may experience poor muscle health as a result of chronic hyperglycemia. Despite this, muscle function in children with T1DM with good or poor glycemic control has yet to be examined in detail. To assess differences in muscle-related fitness variables in children with T1DM with good glycemic control (T1DM-G), as well as those with poor glycemic control (T1DM-P), and non-diabetic, healthy controls. Eight children with T1DM-G [glycosylated hemoglobin (HbA1c) ≤ 7.5% for 9 months], eight children with T1DM-P (HbA1c ≥ 9.0% for 9 months), and eight healthy controls completed one exercise session. Anaerobic and aerobic muscle functions were assessed with a maximal isometric grip strength test, a Wingate test, and an incremental continuous cycling test until exhaustion. Blood samples were collected at rest to determine HbA1c at the time of testing. Physical activity was monitored over 7 d using accelerometry. Children with T1DM-P displayed lower peak oxygen consumption (VO2peak ) values (mL/kg/min) compared to healthy controls (T1DM-P: 33.2 ± 5.6, controls: 43.5 ± 6.3, p < 0.01), while T1DM-G (43.5 ± 6.3) had values similar to controls and T1DM-P. There was a negative relationship between VO2peak and HbA1c% (r = -0.54, p < 0.01). All groups were similar in all other fitness variables. There were no group differences in physical activity variables. Children with T1DM-G did not display signs of impaired muscle function, while children with T1DM-P have signs of altered aerobic muscle capacity.


Lunx is a superior molecular marker for detection of non-small cell lung cancer in peripheral blood [corrected].
The clinical management of non-small cell lung cancer (NSCLC) would benefit greatly by a test that was able to detect small amounts of NSCLC in the peripheral blood. In this report, we used a novel strategy to enrich tumor cells from the peripheral blood of 24 stage I to IV NSCLC patients and determined expression levels for six cancer-associated genes (lunx, muc1, KS1/4, CEA, CK19, and PSE). Using thresholds established at three standard deviations above the mean observed in 15 normal controls, we observed that lunx (10 of 24, 42%), muc1 (5 of 24, 21%), and CK19 (5 of 24, 21%) were overexpressed in 14 of 24 (58%) peripheral blood samples obtained from NSCLC patients. Patients who overexpressed either KS1/4 (n = 2) or PSE (n = 1) also overexpressed either lunx or muc1. Of patients with presumed curable and resectable stage I to II disease (n = 7), at least one marker was overexpressed in three (43%) patients. In advanced stage III to IV patients (n = 17), at least one marker was overexpressed in 11 patients (65%). These results provide evidence that circulating tumor cells can be detected in NSCLC patients by a high throughput molecular technique. Further studies are needed to determine the clinical relevance of gene overexpression.


Meaningful work in supportive environments: experiences with the recovery process.
This ethnographic study examined what makes work meaningful for persons with persistent mental illness and how this meaningfulness relates to their recovery. Twelve persons between 32 and 58 years of age who had been involved an average of 19 years with a formal mental health system participated in in-depth interviews and a focus group. Thematic analysis and case studies were understood in the context of the investigator's 15 months of participant observation of 35 persons with psychiatric disabilities working at an affirmative business. The meaning of work varied with participants perception of their illness and their self-concept. Changes in their self-efficacy and self-concept were driven by their participation in work activities to operate the affirmative business. Findings suggest that therapists could potentially facilitate these changes in clients' sense of self-efficacy and self-concept by helping them make connections with meaningful occupations and contributions to organizations in the community and to experience challenges and successes in the context of meaningful work.


Antibody response to Covid-19 vaccine (AstraZeneca) amongst Healthcare Workers in a Tertiary Hospital in Nigeria.
With no known cure, accelerated development of vaccines became pertinent to contain the COVID-19 pandemic. To assess the IgG antibody response to the viral spike protein and determinants of developing IgG antibodies after vaccination with two doses of the AstraZeneca vaccine. This was a prospective cohort study amongst healthcare workers. Serum samples were obtained before vaccination and at 4 and 12 weeks after the first and second doses of the vaccine respectively. Qualitatively testing for the presence of IgG antibodies to the viral spike protein was conducted using the Vidas SARS-CoV-2 IgG and IgM analyser while IgG antibodies were quantitatively assessed by antibody titre estimation using a stepwise two-fold serial dilution method. A total of 155 subjects between the ages of 25 to 64 years were studied. 85 (54.8%) had positive anti-spike IgG antibodies before vaccination. Out of the remaining 70 subjects, 87.3% and subsequently 96.2% developed IgG antibodies to the viral spike protein 4 and 8 weeks after the first and second doses of the vaccine respectively. The AstraZeneca vaccine was found to stimulate antibody response more than natural infection. Prior positive IgG antibodies from natural infection was found to boost antibody response to vaccination. The antibody titre levels rose with vaccination but waned overtime after the second dose of the vaccine. The AstraZeneca COVID-19 vaccine elicits an immunogenic IgG antibody response that is augmented by prior infection but however declines a few weeks after the second dose of the vaccine. En l'absence de remède connu, le développement accéléré de vaccins est devenu pertinent pour contenir la pandémie de COVID-19. Évaluer la réponse des anticorps IgG à la protéine de pointe virale après vaccination avec deux doses du vaccin AstraZeneca. Il s'agissait d'une étude de cohorte prospective parmi les travailleurs de la santé. Des échantillons de sérum ont été obtenus avant la vaccination et à 4 et 12 semaines après la premier et la deuxième doses du vaccin respectivement. Des tests qualitatifs pour la présence d'anticorps IgG dirigés contre la protéine de pointe virale ont été effectués à l'aide de l'analyseur Vidas SARS-CoV-2 IgG et IgM, tandis que les anticorps IgG ont été évalués quantitativement par estimation du titre d'anticorps à l'aide d'une méthode de dilution en série en deux étapes. Au total, 155 sujets âgés de 25 à 64 ans ont été étudiés. 85 (54,8 %) avaient des anticorps IgG anti-pic positifs avant la vaccination. Sur les 70 sujets restants, 87,3 % puis 96,2 % ont développé des anticorps IgG contre la protéine de pointe virale 4 et 8 semaines après la première et la deuxième doses du vaccin respectivement. Le vaccin AstraZeneca s'est avéré stimuler la réponse anticorps plus que l'infection naturelle. Des anticorps IgG antérieurement positifs d'une infection naturelle ont été trouvés pour stimuler la réponse des anticorps à la vaccination. Les niveaux de titre d'anticorps ont augmenté avec la vaccination mais ont cependant diminué avec le temps après la deuxième dose du vaccin. Le vaccinAstraZeneca COVID-19 suscite une réponse immunogène en anticorps IgG qui est augmentée par une infection antérieure mais qui décline cependant quelques semaines après la deuxième dose du vaccin. COVID-19, Travailleurs de la santé, Vaccination, vaccin AstraZeneca, Immunogène, Anticorps, réponse d'anticorps, Titre d'anticorps.


Pediatric dental emergencies.
Odontogenic infections and orofacial trauma are the most common types of pediatric dental emergencies. The avulsion of a child's permanent tooth or spread of an odontogenic infection through facial planes present serious medical problems requiring expedited care to achieve a favorable prognosis.


Cigarette smoke extract induces DNA damage but not apoptosis in human bronchial epithelial cells.
Whether DNA damage caused by cigarette smoke leads to repair or apoptosis has not been fully elucidated. The current study demonstrates that cigarette smoke induces single-strand DNA damage in human bronchial epithelial cells. Cigarette smoke also stimulated caspase 3 precursors as well as intact poly (ADP-ribose) polymerase (PARP) production, but did not activate caspase 3 or cleave PARP, while the alkaloid camptothecin did so. Neither apoptosis nor necrosis was induced by cigarette smoke when the insult was removed within a designated time period. In contrast, DNA damage following cigarette smoke exposure was repaired as evidenced by decreasing terminal dUTP-biotin nick-end labeling positivity. The PARP inhibitor, 3-aminobenzamide blocked this repair. Furthermore, cells subjected to DNA damage were able to survive and proliferate clonogenically when changed to smoke-free conditions. These results suggest that cigarette smoke-induced DNA damage in bronchial epithelial cells is not necessarily lethal, and that PARP functions in the repair process. Our data also suggest that the potency of cigarettes as a carcinogen may result from their ability to induce DNA damage while failing to trigger the apoptotic progression permitting survival of cells harboring potentially oncogenic mutations.


Comparative study of peripheral blood smear and quantitative buffy coat in malaria diagnosis.
A rapid test for diagnosis of malaria based on acridine orange staining of centrifuged blood samples in a microhaematocrit tube (QBC) was compared with Leishman stained thin peripheral blood smear in 287 samples. Malaria was diagnosed in 44 patients by Leishman staining technique and in 65 patients by QBC method. The QBC method allowed detection of an additional 21 cases. Thus the prevalence rate of malaria during the study was 22.65%. In 222 Patients who were negative by the QBC technique, the Leishman stained smears were also negative for malarial parasite. Although QBC method was superior to the smear for malarial parasite detection, species identification was difficult by this technique. The QBC method provides a reliable, quick, easily mastered, accurate method for diagnosis of malaria. The QBC system can also be used in the diagnosis of other parasitic diseases from blood (Filariasis). However, Leishman stained thin blood film still appear superior for species identification.


Early oral hydration in patients with high enterocutaneous fistula.
Enterocutaneous fistula is defined as an abnormal connection between the gastrointestinal tract and the skin. In addition to the early recognition and treatment of sepsis, nutritional support, wound management, the adequate replacement of lost fluids with a properly set and timely rehydration treatment, together with the control of fistula production represent the first steps in treatment management. The authors present an overview of oral rehydration therapy, describing the properties and effects of individual solutions on fistula. The absorption of fluids and electrolytes into the gastrointestinal tract is performed by the group of sodium-dependent glucose cotransporters (sodium-glucose linked transporter, SGLT1). The water and electrolyte absorption mechanisms described in the article can be used in the treatment of a patient with a high fistula. The amount of administered hypotonic fluids (water, tea) should not exceed 500 ml/day. The remaining volume, depending on fistula loss, must be supplemented with isoosmolar fluids. With a good tolerance of oral rehydration solutions and compliance with the other steps of treatment, it is possible to remain on oral intake during the entire duration of treatment without the need to prohibit it completely, thus improving the patient's overall comfort. Reducing the intake of hypotonic fluids (tap water, tea) and administering an isotonic solution help to reduce the production of the fistula, thereby contributing to its spontaneous closure.


Delivery of steroids into the eye for the treatment of macular edema.
Steroids have been in extensive use in ophthalmology since their discovery in 1948. Steroids are effective for the treatment of macular edema and may be delivered into the eye either topically, systemically, subconjunctivally, sub-Tenon, intravitreally and through injectable sustained release devices. Various steroid formulations and devices are commercially available. Each carries advantages and disadvantages, which requires the ophthalmologist to exercise careful medical judgment upon treatment selection. This article focuses in steroid delivery into the eye for the treatment of macular edema, and reviews the current and future treatment options, summarizing their clinical efficacy and possible adverse effects. Steroids have an important role in the treatment of macular edema, regardless of its cause. Steroids are efficacious, low-cost, and much clinical experience has been accumulated regarding their use over the years. Prolonged systemic steroid use may be associated with severe systemic and local side effects, directly proportional to dosage and time. Intravitreal delivery of steroids has gained popularity as the medication is administered close to the target tissue, significantly reducing the possibility of systemic adverse effects. The biggest problem associated with intravitreal steroids still remains unacceptably high risk of glaucoma and cataract formation. Various controlled-release intravitreal delivery devices are currently commercially available, and more are in the pipeline. While they still carry the risk of local side effects, they are efficacious and can control macular edema for months and years after a single administration.


Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice.
We previously reported that intraperitoneal (i.p.) injection (20 mg/kg) of (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, decreased beta-amyloid (Abeta) levels and plaques via promotion of the non-amyloidogenic alpha-secretase proteolytic pathway in "Swedish" mutant amyloid precursor protein overexpressing (APPsw, Tg) mice. Here, we find that EGCG administered orally in drinking water (50 mg/kg) similarly reduces Abeta deposition in these mice. Following a six month treatment of an 8 month old cohort, immunohistochemical analysis of coronal sections reveals that plaque burdens were reduced in the cingulate cortex, hippocampus, and entorhinal cortex by 54%, 43%, and 51%, respectively. Congo red plaque burdens were decreased in the cingulate cortex, hippocampus, and entorhinal cortex by 53%, 53%, and 58%, respectively as well. ELISA of brain homogenates of the treatment Tg mice revealed consistent reductions in both Abeta1-40 and 1-42 soluble and insoluble forms. In the present study we also investigated the effect EGCG administration had on tau pathology and cognition in Tg mice. Both i.p. and orally-treated Tg animals were found to have modulated tau profiles, with markedly suppressed sarkosyl-soluble phosphorylated tau isoforms. Radial arm water maze (RAWM) testing for working memory indicated that EGCG provided cognitive benefit to Tg mice with both i.p. and oral administration, although i.p.-treated animals showed a more pronounced benefit because of the greater impairment of their Tg controls at the time of testing. Taken together, these data further the notion of EGCG dietary supplementation as a potentially safe and effective prophylaxis for Alzheimer's disease.


Upregulation of TET activity with ascorbic acid induces epigenetic modulation of lymphoma cells.
The Ten Eleven Translocation (TET) enzymes have been found to be mutated in both diffuse large B-cell (DLBCL) and peripheral T-cell (PTCL) lymphomas resulting in DNA hypermethylation. Recent studies in embryonal stem cells showed that ascorbic acid (AA) is a cofactor for TET with a binding site at the catalytic domain, and enhances TET activity. We hypothesized that AA could potentially enhance TET activity in lymphoma cells to cause DNA demethylation, reactivate expression of tumor suppressor genes and enhance chemosensitivity. We demonstrate in vitro that AA treatment of DLBCL and PTCL cells using AA concentrations achievable intravenously increased TET activity leading to DNA demethylation. This epigenetic effect is independent of hydrogen peroxide. AA treatment increased the expression of SMAD1, a tumor suppressor gene known to be suppressed by methylation, and increased chemosensitivity of lymphoma cells. Twenty-nine percent (10/34) of unselected lymphoma patients had plasma AA levels that were deficient suggesting an additional clinical mechanism of TET hypofunction. These data indicate that AA has the potential to modify TET function in lymphoma and enhance chemosensitivity. In addition, the AA deficiency seen in some patients may further impair TET function and contribute to resistance. Clinical trials testing intravenous AA with chemotherapy are warranted.


Factors Associated With Visual Field Progression in Cirrus Optical Coherence Tomography-guided Progression Analysis: A Topographic Approach.
To identify factors associated with visual field (VF) progression in optical coherence tomography (OCT)-guided progression analysis (GPA) using a topographic approach. Topographic components of OCT-GPA maps (Cirrus HD-OCT; Carl Zeiss Meditec) were classified according to location (temporal, superotemporal, superonasal, nasal, inferornasal, and inferotemporal), size (small, medium, and large), shape (wedge and irregular types), and pattern of retinal nerve fiber layer (RNFL) progression (widening, deepening, and new development). All positive findings in OCT-GPA (RNFL thickness maps, profiles, and average RNFL thickness) were defined as strong RNFL progression. VF progression was determined by linear regression analysis of VF mean deviation over time. Univariate and multivariate logistic regression analyses were performed to evaluate the association of VF progression with OCT-GPA parameters. In total, 276 primary open-angle glaucoma patients were followed up for 5.1 years. According to OCT-GPA, 89 eyes were found to have RNFL progression. Of these, VF progression was detected in 27 (30.3%) eyes. Eyes with progressed VF group showed topographically different characteristics, which were wedge-shaped (80.6%), large-sized (40.0%), and widening (69.5%) or deepening (11.1%) pattern of RNFL progression in the inferotemporal (44.4%) and superotemporal (30.6%) regions, compared with eyes with non-progressed VF group. In multivariate analysis, strong RNFL progression and widening or deepening pattern of RNFL progression were significantly associated with VF progression (P=0.012 and 0.016, respectively). Topographic analysis in OCT-GPA maps showed different characteristics between progressed VF and nonprogressed VF groups. Glaucoma patients with widening or deepening pattern of RNFL progression should be carefully monitored for greater risk of VF progression.


Dissecting protein-protein interactions in proteasome assembly: Implication to its self-assembly.
The 26S proteasome is a multi-catalytic ATP-dependent protease complex that recognizes and cleaves damaged or misfolded proteins to maintain cellular homeostasis. The 26S subunit consists of 20S core and 19S regulatory particles. 20S core particle consists of a stack of heptameric alpha and beta subunits. To elucidate the structure-function relationship, we have dissected protein-protein interfaces of 20S core particle and analyzed structural and physiochemical properties of intra-alpha, intra-beta, inter-beta, and alpha-beta interfaces. Furthermore, we have studied the evolutionary conservation of 20S core particle. We find the size of intra-alpha interfaces is significantly larger and is more hydrophobic compared with other interfaces. Inter-beta interfaces are well packed, more polar, and have higher salt-bridge density than other interfaces. In proteasome assembly, residues in beta subunits are better conserved than alpha subunits, while multi-interface residues are the most conserved. Among all the residues at the interfaces of both alpha and beta subunits, Gly is highly conserved. The largest size of intra-alpha interfaces complies with the hypothesis that large interfaces form first during the 20S assembly. The tight packing of inter-beta interfaces makes the core particle impenetrable from outer wall of the cylinder. Comparing the three domains, eukaryotes have large and well-packed interfaces followed by archaea and bacteria. Our findings provide a structural basis of assembly of 20S core particle in all the three domains of life.


Wind streaks on venus: clues to atmospheric circulation.
Magellan images reveal surface features on Venus attributed to wind processes. Sand dunes, wind-sculpted hills, and more than 5830 wind streaks have been identified. The streaks serve as local "wind vanes," representing wind direction at the time of streak formation and allowing the first global mapping of near-surface wind patterns on Venus. Wind streaks are oriented both toward the equator and toward the west. When streaks associated with local transient events, such as impact cratering, are deleted, the westward component is mostly lost but the equatorward component remains. This pattern is consistent with a Hadley circulation of the lower atmosphere.


Low-valent ruthenium and iridium hydride complexes as alternatives to Lewis acid and base catalysts.
The discovery of a new chemical reaction often leads to new applications and new chemical principles. Low-valent ruthenium and iridium hydride complexes are highly useful redox Lewis acid and base catalysts. Nitriles are activated by these catalysts and undergo reactions with either nucleophiles or electrophiles under neutral conditions. Hydration of nitriles, esterification of nitriles with alcohols, and amidation of nitriles with amines can be performed catalytically together with formation of ammonia. The catalytic reactions of pronucleophiles such as nitriles and carbonyl compounds with electrophiles such as alkenes, alkynes, carbonyl compounds, imines, and nitriles take place generally.


Solvent-dependent cation exchange in metal-organic frameworks.
We investigated which factors govern the critical steps of cation exchange in metal-organic frameworks by studying the effect of various solvents on the insertion of Ni(2+) into MOF-5 and Co(2+) into MFU-4l. After plotting the extent of cation insertion versus different solvent parameters, trends emerge that offer insight into the exchange processes for both systems. This approach establishes a method for understanding critical aspects of cation exchange in different MOFs and other materials.


[Multiple malignant neoplasms in patients with prostate tumours in the health district of Leon].
We analyze the characteristics of the patients with prostate tumours who developed a multiple malignant primary neoplasms (MMPN) in the health district of León, the impact on survival and the prognostic variables. We have used the data from the Tumour Registry of the Hospital of León and we have selected all those patients who were diagnosed of a prostate tumor between 1993 and 2002. Later we made two groups: the first with 67 patients with MMPN and a second group with 145 patients with single prostate tumours diagnosed during 1996 and 1997. Prevalence of MMPM was of 5.57 percent. Patients with MMPN were 3 years younger than those with single tumours, with a high frequency (41 percent) of familial oncologic antecedents on first degree parents. The more frequent association was the synchronous urologic neoplasm. During the next two years from diagnosed of prostate tumour, 86 percent of patients with MMPN were diagnosed of their second neoplasm. Survival of metachronous MMPN patients was lower than synchronous MMPN patients, being the variables with prognosis significance the age, metachronous MMPN, stage of second neoplasms and if the second neoplasms was or not urologic. MMPN in patients with prostatic tumours are frequent in our medium. A genetic base may be associated in these patients. Prognosis of metachronous MMPN patients is worse. No differences were observed about prognosis with single tumour patients.


L-cysteine supplementation as an adjuvant therapy for type-2 diabetes.
Diabetes remains a major public health issue. According to the American Diabetes Association, 23.5 million, or 10.7% of people in the USA aged 20 years and older, have diabetes. Type-2 diabetes is treated both by controlling the diet and with oral hypoglycemic drugs. However, for many patients, achieving a tight control of glucose is difficult with current regimens. This chapter discusses a relatively low-cost dietary supplement that could be used as an adjuvant therapy for type-2 diabetes. A review of the literature indicates that cysteine-rich whey protein improves glucose metabolism in diabetic animals and type-2 diabetic patients. Similarly, in animal studies, improvement in glucose metabolism is observed after supplementation with L-cysteine, or molecules containing a cysteine moiety. This chapter discusses the biochemical mechanisms by which L-cysteine can upregulate the insulin-dependent signaling cascades of glucose metabolism. Further studies are needed to examine whether clinical interventions using L-cysteine as an adjuvant therapy indeed help to control glycemia and vascular inflammation in the diabetic patient population.


A robust and simple-to-design multiplex DNA methylation assay based on MS-MLPA-CE-SSCP.
Aberrant DNA methylation is a potential diagnostic marker for complex diseases, such as cancer. With the increase in the number of genes known to exhibit disease-associated aberrant methylation, the need for accurate multiplex assays for quantifying DNA methylation has increased. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is one method that has been highlighted in this context. However, two limitations make the custom design of MS-MLPA assays impractical: the need for long probes containing stuffer sequences and a reliance on only one restriction enzyme. Here, we developed a variation of MS-MLPA that employs a simpler probe-design process. To overcome the above-mentioned limitations, we used stuffer-free MS-MLPA probes that are subsequently analyzed using high-resolution capillary electrophoresis-based single-strand conformational polymorphism (CE-SSCP) instead of conventional length-dependent CE. Moreover, multiple methylation-sensitive restriction enzymes (HhaI, HpaII, and AciI) were used simultaneously; thus, probes satisfying desired criteria were available for all targets. Using this assay concept, we analyzed 17 genes associated with hepatocellular carcinoma. Our results showed that the custom-designed assay based on MS-MLPA-CE-SSCP provided robust multiplex quantification of DNA methylation levels.


A retrospective study of patients with systemic lupus erythematosus combined with Pneumocystis jiroveci pneumonia treated with caspofungin and trimethoprim/sulfamethoxazole.
Systemic lupus erythematosus (SLE) complicated with Pneumocystis jiroveci pneumonia (PCP) is a clinical complex with unsatisfying treatment efficacy and poor prognosis which is difficult to be diagnosed at early stage. The present study aimed to investigate the clinical features of SLE with PCP, recognize the early onset indicating factors, and evaluate the treatment efficacy of combined caspofungin and trimethoprim/sulfamethoxazole (coSMZ).We reviewed data of 9 patients admitted with SLE-PCP and treated with caspofungin combined with coSMZ at Tangshan Gongren Hospital from January 2013 to December 2017. Patients' clinical manifestation and laboratory data [leucocyte, lymphocyte, cluster of differentiation 4 (CD4)T cell, lactate dehydrogenase (LDH), blood gas, etc] were compared before and after treatments. And the early onset factors of SLE-PCP, treatment efficacy of combined caspofungin and CoSMZ were analyzed.Among these 9 patients, 8 patients suffered renal impairment, and all of them had been taking prednisone in the past 3 months at an average dose of 29.4 ± 13.6 mg/day. In addition, they had taken at least one kind of immunosuppressants. Laboratory data (leucocyte, lymphocyte, CD4T cell, PaO2, LDH) were remarkably abnormal at hospital admission, but they were improved significantly after 2 weeks of treatment, which is also statistically significant (P < .05), except that leukocyte had no significance change to the value at admission (P = .973). In addition, none of the studied patients died.The results of the study indicated that long-term use of glucocorticoids and immunosuppressants, low CD4T cell count, and renal impairment are the early-onset factors for SLE-PCP, caspofungin, when combined with CoSMZ, it could be a promising and effective strategy to treat SLE with PCP.


Comparing Natural Gas Leakage Detection Technologies Using an Open-Source "Virtual Gas Field" Simulator.
We present a tool for modeling the performance of methane leak detection and repair programs that can be used to evaluate the effectiveness of detection technologies and proposed mitigation policies. The tool uses a two-state Markov model to simulate the evolution of methane leakage from an artificial natural gas field. Leaks are created stochastically, drawing from the current understanding of the frequency and size distributions at production facilities. Various leak detection and repair programs can be simulated to determine the rate at which each would identify and repair leaks. Integrating the methane leakage over time enables a meaningful comparison between technologies, using both economic and environmental metrics. We simulate four existing or proposed detection technologies: flame ionization detection, manual infrared camera, automated infrared drone, and distributed detectors. Comparing these four technologies, we found that over 80% of simulated leakage could be mitigated with a positive net present value, although the maximum benefit is realized by selectively targeting larger leaks. Our results show that low-cost leak detection programs can rely on high-cost technology, as long as it is applied in a way that allows for rapid detection of large leaks. Any strategy to reduce leakage should require a careful consideration of the differences between low-cost technologies and low-cost programs.


The incidence of endometrial hyperplasia and cancer in 1031 patients with a granulosa cell tumor of the ovary: long-term follow-up in a population-based cohort study.
Concurrent presence of endometrial hyperplasia or cancer in patients with granulosa cell tumors (GCTs) is common, with reported incidences of 25.6% to 65.5%. Consequently, bilateral salpingo-oophorectomy and hysterectomy is usually recommended in patients with a GCT, but this remains debatable. Our aim was to evaluate the need for hysterectomy in patients with GCTs by studying the incidence of pathologically confirmed endometrial abnormalities at the time of diagnosis of GCT and during follow-up. All cases of GCT between 1991 and 2012 were evaluated for endometrial pathology using the Dutch nationwide network and registry of histopathology and cytopathology (PALGA). A total of 1031 cases of GCT were identified at a mean ± SD age of 55 ± 17 years. The incidence of GCTs in the period 1991-2012 was 0.61 per 100,000 women per year. Concurrent endometrial cancer at the time of diagnosis of GCT was found in 58 patients (5.9%) and endometrial hyperplasia in 251 patients (25.5%), including complex hyperplasia in 89 patients (9.1%) and simple hyperplasia in 162 patients (16.5%). Long-term follow-up of 490 patients (47.5%) without a hysterectomy showed that endometrial abnormalities were found in 10 patients (2.0%) of which 2 had endometrial cancer. Interestingly, 8 (80%) of the 10 patients with endometrial abnormalities had recurrent GCT at the time of diagnosis of endometrial hyperplasia or cancer. Our data suggest that after surgical removal of GCT, development of an endometrial abnormality, especially cancer, is very rare. Therefore, hysterectomy is not recommended in patients with a GCT without endometrial abnormalities at the time of diagnosis.