[Lower urinary tract infections in men. Urethritis, cystitis and prostatitis].
Recommendations for the treatment of lower non-catheter-related urinary tract infection (UTI) in men are rarely evidence-based. Their management requires the localization of the site of infection, whether it be the urethra, bladder or prostate, and includes antibiotic therapy and in most cases urological assessment. They are often associated with urinary tract procedures or anatomical or functional abnormalities. Nearly 80 % of male UTIs are caused by Enterobacteriaceae. The prevalence of broad-spectrum beta-lactamase-producing strains (ESBL) and quinolone-resistant strains is increasing. The aim of this article is to define three types of lower, non-catheter-related UTI in men - urethritis, cystitis and prostatitis - their microbiology and management in Switzerland.


Influence of dietary nutrient density, feed form, and lighting on growth and meat yield of broiler chickens.
The objective of this study was to examine main and interactive effects of nutrient density (ND), feed form (FF; mash, pellet), and lighting program (12L:12D, 20L:4D) on production characteristics and meat yield of broilers raised to 35 d of age. Diets (starter, grower, and finisher) were formulated so that amino acid levels were in proportion to the dietary energy level. Lighting programs were initiated at 4 d of age. Body weight was not affected by ND when diets were fed in a pellet form but decreased in a linear manner with lower ND when fed as a mash. Final BW of birds fed mash were less than those of birds fed pellet diets. Feed to gain ratio decreased with increasing ND but was not affected by FF. Feed intake decreased with increasing ND and was lower for birds fed mash. The effect of ND on feed intake was less when birds were fed mash in contrast to pellet diets (P(ND x F) < 0.0001). Dietary ND had no effect on mortality, but feeding mash decreased mortality (3.8%) compared with feeding pelleted feed (5.6%). Lighting programs affected production characteristics independently of ND and FF. Use of 12L:12D reduced BW, feed to gain ratio, feed intake, and mortality compared with 20L:4D. Similarly, carcass components were not affected by ND when fed in pellet form but decreased with lower ND when fed as a mash. Overall, carcass yields were reduced when broilers were fed mash or provided with 12L:12D. Female birds had higher carcass yields and increased proportional breast meat deposition compared with males.


Integration of hypoxic HIF-α signaling in blood cancers.
Hypoxia (low O2) is a fundamental microenvironmental determinant of bone marrow (BM) pathophysiology. Recent data from molecular and clinical studies indicate that hematopoiesis and leukemogenesis are dependent upon hypoxia-inducible factors (HIFs), a family of essential transcriptional activators mediating the metazoan hypoxic response. In blood cancers, the synergism between HIF overexpression and stabilization within the hypoxic BM microenvironment promotes disease progression, therapy resistance and relapse. In this review, we will summarize current advances in the understanding of HIF signaling in blood cancers and its translational implications for hypoxic-targeted therapy.


Macrophages in prostatic fluid.
Non-specific esterase staining has been found useful in the detection of macrophages in prostatic fluid (PF). In the early stage of acute prostatitis most of the leucocytes in a smear of PF took up the stain, suggesting the dominant participation of macrophages in the inflammatory area in this stage of the disease. In chronic prostatitis, only a few leucocytes took up the stain. In female acute cystitis, none of the large numbers of leucocytes exhibited staining at any stage of the disease. The reason for this is still to be determined. Frozen sections of prostatic tissue from patients with chronic prostatitis revealed similar cells around the acini and these appeared to be the source of the macrophages which appeared in the PF.


Immunohistochemical detection of hypoxia-inducible factor-1alpha in human renal allograft biopsies.
Although it generally is accepted that renal hypoxia may occur in various situations after renal transplantation, direct evidence for such hypoxia is lacking, and possible implications on graft pathophysiology remain obscure. Hypoxia-inducible factors (HIF) are regulated at the protein level by oxygen-dependent enzymes and, hence, allow for tissue hypoxia detection. With the use of high-amplification HIF-1alpha immunohistochemistry in renal biopsies, hypoxia is shown at specific time points after transplantation with clinicohistologic correlations. Immediately after engraftment, in primarily functioning grafts, abundant HIF-1alpha is present and correlates with cold ischemic time >15 h and/or graft age >50 yr (P < 0.04). In contrast, a low HIF-1alpha score correlates with primary nonfunction, likely reflecting loss of oxygen consumption for tubular transport. Protocol biopsies at 2 wk show widespread HIF-1alpha induction, irrespective of histology. Beyond 3 mo, both protocol biopsies and indicated biopsies are virtually void of HIF-1alpha, with the only exception being clinical/subclinical rejection. HIF-derived transcriptional adaptation to hypoxia may counterbalance, at least partly, the negative impact of cold preservation and warm reflow injury. Transient hypoxia at 2 wk may be induced by hyperfiltration, hypertrophy, calcineurin inhibitor-induced toxicity, or a combination of these. Lack of detectable HIF-1alpha at 3 mo and beyond suggests that at this time point, graft oxygen homeostasis occurs. The strong correlation between hypoxia and clinical/subclinical rejection in long-term grafts suggests that hypoxia is involved in such graft dysfunction, and HIF-1alpha immunohistochemistry could enhance the specific diagnosis of acute rejection.


Toward understanding, managing, and protecting microbial ecosystems.
Microbial communities are at the very basis of life on earth, catalyzing biogeochemical reactions driving global nutrient cycles. However, unlike for plants and animals, microbial diversity is not on the biodiversity-conservation agenda. The latter, however, would imply that microbial diversity is not under any threat by anthropogenic disturbance or climate change. This maybe a misconception caused by the rudimentary knowledge we have concerning microbial diversity and its role in ecosystem functioning. This perspective paper identifies major areas with knowledge gaps within the field of environmental microbiology that preclude a comprehension of microbial ecosystems on the level we have for plants and animals. Opportunities and challenges are pointed out to open the microbial black box and to go from descriptive to predictive microbial ecology.


Lipid-based submicron capsules as a strategy to include high concentrations of a hydrophobic lightening agent in a hydrogel.
This study aimed at increasing the concentration of a hydrophobic lightening agent, Omegalight® , in a hydrophilic cosmetic product by means of encapsulation in lipid-based submicron capsules. The core of these capsules is entirely made of the commercial lightening agent. Lipid-based encapsulation systems (LNC) were prepared by the PIT method. Their physicochemical properties were followed over 6 months by dynamic light scattering and zeta potential measurements, and in parallel, the potential degradation of the active ingredient was monitored by HPLC. The stability of the capsules in a cosmetic gel was studied by spectrofluorimetry and rheology measurements. Sensory analysis was used to determine the influence of the presence of capsules in the gel on the consumer's experience. LNC encapsulating Omegalight® were prepared on a laboratory scale and then on a semi-pilot scale. Their hydrodynamic diameters are around 230 nm. The concentration of Omegalight® in the capsules reaches about 84% w/w, which corresponds to 42% of active ingredient. LNC can be dispersed without degradation at concentrations of up to 20% w/w in a hydrogel without modification of the physicochemical or sensory properties of the gel. Lipid-based capsules (LNC), an encapsulation system useful for the epidermal delivery of hydrophobic compounds, were adapted to the encapsulation of a commercial lightening agent. The encapsulation permits the dispersion in a stable manner of a very high concentration of a hydrophobic active molecule in a hydrogel while maintaining the physicochemical and sensory properties of the gel.


[Epidemiology of suicide].
Epidemiology for suicide cannot give precise numbers: between 440,000 (WHO) and 818,000 persons in the world commit suicide each year. For Europe, suicides increased regularly to a maximum in 1982-84 (median = 17/100,000). Suicide victims tend to be younger. The author doubts that psychiatric causes can explain suicide and be the only factor of importance for prevention. Suicide of adolescents is only the visible tip of a general behavior learned since childhood. The suicidal "solution" (ideas, parasuicides, attempted suicides, and suicides) is probably a social phenomenon. Efficacious prevention requires a global societal approach. Programs of research and prevention in the Netherlands are presented.


Tunable type-II lateral MoSi2N4/WSi2N4 heterostructures for photocatalytic applications.
Combining various two-dimensional crystals has emerged as an exciting way to tailor the properties of lateral heterostructures for new-generation optoelectronic devices. Herein, a seamless lateral heterostructure based on MoSi2N4 and MoSi2N4 monolayers along armchair interfaces is predicted, and its electronic and optical properties are investigated by using first principles calculations. Our calculations indicate that the MoSi2N4/WSi2N4 lateral heterostructures (HSs) possess excellent stability due to the very small lattice mismatch. In contrast to their parent monolayers with wide indirect band gaps, all (MoSi2N4)m(WSi2N4)n lateral HSs are direct gap semiconductors, and their direct gap nature is independent of compositions and strains. The band alignment of (MoSi2N4)m(WSi2N4)16-m lateral HSs undergoes a quasi-type-I to type-II to quasi-type-II to quasi-type-I band transition with an increase in m. (MoSi2N4)8(WSi2N4)8 is a type-II semiconductor, and the band arrangement changes from type-II to quasi-type-I upon applying tensile strain. Compared with pristine materials, the band edges of MoSi2N4/WSi2N4 lateral HSs are more favorable for photocatalytic water splitting. Furthermore, MoSi2N4/WSi2N4 lateral HSs exhibit higher visible light absorption. These results greatly expand the optoelectronic applications of Mxenes in the 2D realm.


Transcriptional adaptation of Shigella flexneri during adherence to epithelial cells.
Shigella adhesion to host cells is a transitional stage from an extracellular to an intracellular environment. However, the dynamic adaptations of Shigella during adhesion are poorly understood. To address this, we performed the first transcriptome analysis of Shigella flexneri 2457T during adhesion. A total of 1,757 genes were differentially regulated (>twofold). The majority of plasmid-borne ipa-mxi-spa locus genes were downregulated, indicating these virulence genes were strictly regulated after successful adhesion. Altered expression of genes involved in stress response indicates that adherent S. flexneri encountered envelope stress and oxidative stress. Shigella flexneri also experienced reduced energy production during adherence. Transcript profiling and cell culture assays using glpD and glpK mutants showed that enhancement of glycerol catabolism were related with adhesion ability of S. flexneri. In addition, regulation of expression of some ionic transport system may be required for S. flexneri adhesion. Expression levels of 26 genes were further examined using qRT-PCR, which were congruent with transcriptome data. A comparison with expression profile during intracellular growth revealed major differences in genes involved in translation, surface modification, and utilization of carbon and iron. These results contribute to the knowledge of the adaptation mechanisms of S. flexneri during adhesion.


Eukaryotic translation initiation factor 3B accelerates the progression of esophageal squamous cell carcinoma by activating β-catenin signaling pathway.
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors. Eukaryotic translation initiation factors 3B (EIF3B) is considered to influence tumor proliferation, invasion, apoptosis and cell cycle, which act together to promote the progression of tumors. However, the role of EIF3B in ESCC is unknown. This study aims to explore the clinical and biological role of EIF3B in ESCC. EIF3B expressions were up-regulated in both ESCC tissues and cell lines. Overexpression of EIF3B was associated with tumor depth, lymph node metastasis and advanced TNM stage. Importantly, patients with high EIF3B expression suffered shorter overall and disease-free survival. Knockdown of EIF3B could inhibit cell proliferation and invasion, promote cell apoptosis, and interfere the cell cycle in vitro. EIF3B-knockdown cells could form smaller subcutaneous tumors in vivo. Finally, we demonstrated EIF3B could activate β-catenin signaling pathway. Immunohistochemical staining and Western blot were performed to detect the EIF3B expression in ESCC patient tissues and cell lines. The association between EIF3B expression and patients' prognosis was analyzed by Kaplan-Meier and Cox regression. Then, CCK-8, colony-formation, Transwell and wound-healing assay were performed to compare the bio-functional change after knockdown of EIF3B. Flow cytometry was applied to analyze the change of cell apoptosis and cycle induced by EIF3B knockdown. Tumor xenograft assay was done to verify the in-vitro results. EIF3B might serve as a novel marker for predicting prognosis of ESCC patients and as a potential therapeutic target, individually or together with other subunits of EIF3 complex.


Effect of temperature on concentrated electrolytes for advanced lithium ion batteries.
Salt-concentrated electrolytes are emerging as promising electrolytes for advanced lithium ion batteries (LIBs) that can offer high energy density and improved cycle life. To further improve these electrolytes, it is essential to understand their inherent behavior at various operating conditions of LIBs. Molecular dynamics (MD) simulations are extensively used to study various properties of electrolytes and explain the associated molecular-level phenomena. In this study, we use classical MD simulations to probe the properties of the concentrated electrolyte solution of 3 mol/kg lithium hexafluorophosphate (LiPF6) salt in the propylene carbonate solvent at various temperatures ranging from 298 to 378 K. Our results reveal that the properties such as ionic diffusivity and molar conductivity of a concentrated electrolyte are more sensitive to temperature compared to that of dilute electrolytes. The residence time analysis shows that temperature affects the Li+ ion solvation shell dynamics significantly. The effect of temperature on the transport and dynamic properties needs to be accounted carefully while designing better thermal management systems for batteries made with concentrated electrolytes to garner the advantages of these electrolytes.


[Successful treatment of Erdheim-Chester disease by 2-chlorodeoxyadenosine-based chemotherapy. Two case studies and a literature review].
Erdheim-Chester disease is an extremely rarely occuring condition and thus an optimal treatment is not known. Two new cases have been diagnosed in our centre in 2008 and 2009. Both patients had diabetes insipidus, B symptoms (subfebrile to febrile states) and pain in long bones of lower limbs. Imaging showed high accumulation of fluorodeoxyglucose as well as Tc-pyrophosphate in long bones of lower as well as upper limbs, aortic wall thickening with periaortic fibrosis and perirenal fibrosis. In addition, one of the patients had multiple lesions in the brain. 2-chlorodeoxyadenosine 5 mg/m2 s.c. and cyclophosphamide 150 mg/m2 administered on days 1 to 5 in 28-day cycles were selected for the treatment of both patients. Dexamethasone 24 mg/day for 5 days was added to this treatment in the second patient. Six cycles of the treatment were planned. Both patients were prescribed bisphosphonates--zoledronate and clodronate, respectively. Treatment effect was assessed with PET-CT and MR. Following treatment completion, brain infiltrates were reduced to a small residuum in the first patient who did not anymore complain of leg pain. However, there was no reduction in fluorodeoxyglucose accumulation in bone lesions and thus treatment response was assessed as partial remission. This patient is currently receiving a second line treatment and treatment follow-up is 26 months from the diagnosis. Repeated PET-CTs in the second patient showed a significant reduction in accumulation of fluorodeoxyglucose in all pathological lesions. Febrile states and pain in long bones as well as pathological fatigue ceased after the treatment. Increased CPR and fibrinogen gradually returned to their normal levels. This response is assessed as complete remission. This patient's follow-up is 16 months from the diagnosis. Administration of 2-chlorodeoxyadenosine (5 mg/m2 s.c.) + cyclophosphamide (150 mg/m2 intravenously) and dexamethasone (24 mg/day) led to partial remission in one patient; nearly complete remission of CNS infiltrates but persistent elevation of fluorodeoxyglucose accumulation in bone lesions. Complete remission with a significant reduction in accumulation of fluorodeoxyglucose in all disease lesions with normalization of originally increased inflammatory markers and disappearance of all symptoms of the disease was achieved in the second patient.


A MOLECULAR REEXAMINATION OF INTROGRESSION BETWEEN HELIANTHUS ANNUUS AND H. BOLANDERI (COMPOSITAE).
Heiser (1949) hypothesized that a weedy race of Helianthus bolanderi had originated by the introgression of genes from H. annum into a serpentine race of H. bolanderi. Although Heiser's investigation of these species is frequently cited as one of the best examples of introgression in plants, definitive evidence of gene exchange is lacking (Heiser, 1973). To determine whether the weedy race of H. bolanderi actually originated via introgression, we analyzed allozyme, chloroplast-DNA (cpDNA), and nuclear-ribosomal-DNA (rDNA) variation. Evidence from enzyme electrophoresis did not support the proposed introgressive origin of weedy H. bolanderi. We detected a total of 37 low-frequency alleles distinguishing the serpentine race of H. bolanderi from H. annuus. Weedy H. bolanderi possessed only four of the 37 marker alleles. Further analysis demonstrated that serpentine H. bolanderi combined seven of the 35 alleles distinguishing H. annuus from weedy H. bolanderi, indicating that serpentine H. bolanderi shares three more marker alleles with H. annuus than does weedy H. bolanderi. These results are similar to expectations for race divergence from a single common ancestor and suggest that, if introgression occurred, the majority of marker alleles were rapidly lost following the initial hybridization event. Even more compelling evidence opposing Heiser's (1949) hypothesis, however, was from restriction-fragment analysis of cpDNA and nuclear rDNA. We detected a total of 17 cpDNA and five rDNA restriction-site mutations among the 19 populations examined. No parallel or back mutations were observed in phylogenetic trees constructed using either cpDNA or rDNA mutations, and both phylogenies were completely congruent regarding the alignment of all three taxa. In addition, the weedy race of H. bolanderi possessed a unique cpDNA, which was outside the range of variation observed among populations of either of the presumed parental species. Mean sequence divergences between the cpDNAs of weedy H. bolanderi and those of serpentine H. bolanderi and H. annuus were 0.30% and 0.35%, respectively. These estimates are comparable to sequence-divergence values observed between closely related species in other plant groups. Given the lack of parallel or convergent mutations in the cpDNA and rDNA phylogenetic trees, the complete congruence of these trees with flavonoid- and allozyme-variation patterns, and the presence of a unique and divergent chloroplast genome in the weedy race of H. bolanderi, we suggest that the weedy race of H. bolanderi was not derived recently through introgression, as hypothesized, but is relatively ancient in origin.


Phosphomannose isomerase, a novel plant selection system: potential allergenicity assessment.
Phosphomannose isomerase (PMI), an enzyme not present in many plants, catalyzes the reversible interconversion of mannose 6-phosphate and fructose 6-phosphate. Plant cells lacking this enzyme are incapable of surviving on synthetic medium containing mannose. Thus PMI/mannose selection has utility in the identification of transformed plant cells. As part of the safety assessment transgenic plants undergo before commercialization, PMI has been evaluated for its potential allergenicity. Purified PMI protein was readily digestible in a simulated gastric environment. PMI has no sequence homology to known allergens, does not contain multiple disulfide bonds, and has no N-glycosylation consensus sequences. No detectable changes in glycoprotein profiles were detected in PMI-transformed plants as compared to nontransgenic controls. These results indicate that PMI lacks many of the attributes associated with known oral allergens.


An Improved Approach of Mesh Segmentation to Extract Feature Regions.
The objective of this paper is to extract concave and convex feature regions via segmenting surface mesh of a mechanical part whose surface geometry exhibits drastic variations and concave-convex features are equally important when modeling. Referring to the original approach based on the minima rule (MR) in cognitive science, we have created a revised minima rule (RMR) and presented an improved approach based on RMR in the paper. Using the logarithmic function in terms of the minimum curvatures that are normalized by the expectation and the standard deviation on the vertices of the mesh, we determined the solution formulas for the feature vertices according to RMR. Because only a small range of the threshold parameters was selected from in the determined formulas, an iterative process was implemented to realize the automatic selection of thresholds. Finally according to the obtained feature vertices, the feature edges and facets were obtained by growing neighbors. The improved approach overcomes the inherent inadequacies of the original approach for our objective in the paper, realizes full automation without setting parameters, and obtains better results compared with the latest conventional approaches. We demonstrated the feasibility and superiority of our approach by performing certain experimental comparisons.


Utilization of crystalline or protein-bound lysine for growth and carcass traits of barrows and gilts fed individually or in groups.
An experiment consisting of two 4-wk trials was conducted to determine Lys use for growth and carcass traits in barrows and gilts fed individually or in groups. One hundred twelve growing pigs (56 barrows and 56 gilts; average initial BW of 18.6 kg) were used in each trial. Pigs were fed individually or in groups of 3. There were 28 pigs individually penned, and 84 pigs in 28 pens (3 pigs/pen). There were 2 replications per treatment in each trial for a total of 4 replications. Dietary treatments consisted of a corn-soybean meal (SBM) basal diet (0.48% Lys) and diets containing 0.56%, 0.65%, and 0.74% standardized ileal digestible (SID) Lys that were achieved by adding Lys to the basal diet from either SBM or crystalline source as L-Lys HCL (CLys). At the end of each trial, all pigs were scanned using real-time ultrasound to determine 10th-rib back fat depth and LM area, and fat-free lean gain (FFLG) was calculated. Blood samples were taken from all pigs weekly to determine plasma urea N (PUN). Pigs fed CLys and Lys from SBM were not different in final BW, ADG, ADFI, or G:F. The ADG and G:F increased linearly (P < 0.01) as dietary Lys concentration increased. The SID Lys intake increased linearly (P < 0.01) as dietary Lys concentration increased and was not different when comparing pigs fed diets with CLys or SBM. The amount of SID Lys required per unit of growth or BW gain increased linearly (about 13 to 15.50 g/kg) in pigs fed either CLys or SBM Lys. Pigs fed individually had a greater (P < 0.05) ADG (0.59 vs. 0.57 kg) and ADFI (1.36 vs. 1.29 kg) than pigs fed in groups. The SID Lys intake was greater (P < 0.05) in pigs fed individually in comparison with pigs fed in a group (8.51 vs. 8.06 g/d). Fat-free lean gain and LM area increased (P < 0.01) as dietary Lys concentration increased regardless of Lys source. Pigs fed CLys diets had a greater (P < 0.05) LM area than pigs fed SBM at 0.74% SID Lys. Gilts had a greater (P < 0.01) LM area (14.28 vs. 13.58 cm(2)) and FFLG (264 vs. 245 g/d) than barrows. Pigs fed individually with CLys had less (P < 0.01) PUN than pigs fed Lys from SBM. Barrows fed individually had less (sex × feeding method, P < 0.01) PUN than gilts (26.75 vs. 29.32 g/100 mL). The results indicate that Lys from SBM-bound and CLys source were utilized similarly for growth and carcass traits regardless of sex or feeding method.


[Prescription of drugs not appropriate for children in a Pediatric Intensive Care Unit].
To assess the extent of use of drugs not appropriate for children in prescriptions issued in a tertiary pediatric intensive care unit (PICU), according to FDA standards. Observational cross-sectional study. The prescriptions issued to all patients admitted to the PICU at Hospital de Clínicas de Porto Alegre, Brazil, over a six-week period were assessed. Patients' age, sex, weight, prior disease, reason for admission to the PICU and pediatric index of mortality (PIM) were recorded, as were all drugs prescribed, their indications, presentations, doses, frequencies and means of administration. Adequacy for prescription of drugs in three pediatric age ranges was defined according to USA Food and Drug Administration (FDA) approval classification, based on the USP DI 2001 drug reference database. Data were obtained in the months of July and August 2002, on different days, for six consecutive weeks, based on prescriptions issued to 51 patients in 54 admissions to the PICU. Median patient age was 10.5 months; 61% of patients were male. Two thirds of patients (65%) presented prior disease. 87% of admissions were due to clinical reasons, of which 57% were respiratory complaints. A total of 747 prescription items were registered, with prevalence of 10.5% for non-approved uses and 49.5% for off-label uses. No statistically significant difference was found in the distribution of prevalence of irregular prescription either by the three age ranges or by level of severity of disease at admission (according to PIM risk categories). The high prevalence of prescription of drugs not appropriate for children confirms, in the Brazilian context, the inadequate and inadvertent use of drugs either not approved or off-label for PICU use. This demonstrates the need to encourage further studies on the quality, efficacy and safety of drugs for pediatric use.


Percutaneous treatment of high-output chylothorax with embolization or needle disruption technique.
Surgical ligation of the thoracic duct is associated with a high degree of morbidity; therefore, a minimally invasive approach is desirable. Herein, eight percutaneously treated patients are described. In four patients, the thoracic duct was embolized with use of coils and glue. In the other four patients, lymphatic ducts were disrupted by multiple needle punctures. The median chest tube drainage substantially decreased in both patient groups from more than 1,300 mL the day before the procedure to less than 300 mL 2 days after the procedure. The median times to chest tube removal were 7 days in the embolization group and 3.5 days in the needle disruption group.


Capacitive energy storage in nanostructured carbon-electrolyte systems.
Securing our energy future is the most important problem that humanity faces in this century. Burning fossil fuels is not sustainable, and wide use of renewable energy sources will require a drastically increased ability to store electrical energy. In the move toward an electrical economy, chemical (batteries) and capacitive energy storage (electrochemical capacitors or supercapacitors) devices are expected to play an important role. This Account summarizes research in the field of electrochemical capacitors conducted over the past decade. Overall, the combination of the right electrode materials with a proper electrolyte can successfully increase both the energy stored by the device and its power, but no perfect active material exists and no electrolyte suits every material and every performance goal. However, today, many materials are available, including porous activated, carbide-derived, and templated carbons with high surface areas and porosities that range from subnanometer to just a few nanometers. If the pore size is matched with the electrolyte ion size, those materials can provide high energy density. Exohedral nanoparticles, such as carbon nanotubes and onion-like carbon, can provide high power due to fast ion sorption/desorption on their outer surfaces. Because of its higher charge-discharge rates compared with activated carbons, graphene has attracted increasing attention, but graphene had not yet shown a higher volumetric capacitance than porous carbons. Although aqueous electrolytes, such as sodium sulfate, are the safest and least expensive, they have a limited voltage window. Organic electrolytes, such as solutions of [N(C2H5)4]BF4 in acetonitrile or propylene carbonate, are the most common in commercial devices. Researchers are increasingly interested in nonflammable ionic liquids. These liquids have low vapor pressures, which allow them to be used safely over a temperature range from -50 °C to at least 100 °C and over a larger voltage window, which results in a higher energy density than other electrolytes. In situ characterization techniques, such as nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), and electrochemical quartz crystal microbalance (EQCM) have improved our understanding of the electrical double layer in confinement and desolvation of ions in narrow pores. Atomisitic and continuum modeling have verified and guided these experimental studies. The further development of materials and better understanding of charged solid-electrolyte interfaces should lead to wider use of capacitive energy storage at scales ranging from microelectronics to transportation and the electrical grid. Even with the many exciting results obtained using newer materials, such as graphene and nanotubes, the promising properties reported for new electrode materials do not directly extrapolate to improved device performance. Although thin films of nanoparticles may show a very high gravimetric power density and discharge rate, those characteristics will not scale up linearly with the thickness of the electrode.


Oral cavity morphology among children at risk of sleep disordered breathing.
The aim of this study was to evaluate oral cavity morphology in children at risk of sleep disordered breathing (SDB). The study included children 3-17 years of age. The risk of SDB was evaluated using the paediatric sleep questionnaire (PSQ); afterwards, children at risk of SDB were enrolled in the study group. A control group was randomly established from patients with negative PSQ results. The oral cavity morphology evaluation included assessment of the oropharynx using Mallampati classification (MC), palatine tonsil size using the Pirquet scale, occlusion and the presence of a high-arched palate and lingual frenulum. A total of 131 children were evaluated, 65 in the study and 66 in the control group. The mean ages were 9.5 ± 3.0 and 9.4 ± 3.1 years, respectively. The presence of higher scores on the MC, higher scores in the Pirquet scale, a crossbite, a high-arched palate and a short frenulum were significantly more frequent in the study group than the control group. The evaluation of oral morphology is an important part of paediatric examination. Enlarged palatine tonsils; higher scores on the MC; and the presence of a crossbite, short lingual frenulum and high-arched palate may suggest abnormal breathing during sleep in children.


False-positive mammography and mammography screening intentions among black women: the influence of emotions and coping strategies.
Introduction: Abnormal mammograms confirmed as benign are known as false-positive mammography (FPM) results. Research indicates that a history of FPM results may be linked to diagnostic delays in Black women, yet much of the research on FPM has focused on White women.Objectives: The purpose of this study was to examine: 1) The influence of FPM on breast cancer (BrCa) screening beliefs and intentions among Black women and 2) Whether emotional states, personality traits or coping behaviors altered the previously described relationships.Design: BrCa-free, Black women, aged 40 and older who completed screening mammograms in 2016 were recruited for a case-control study from 2016 to 2017. Women with FPM results were cases, and women with normal results served as matched controls. Print surveys assessing demographics, personality traits, emotions, BrCa screening history, BrCa beliefs, and africentric coping behaviors were mailed to participants. The final sample consisted of 118 respondents (55 cases, 63 controls). Ordinary least squares (OLS) models were constructed. Personality traits and emotions were tested as mediators and coping behaviors as moderators of the relationship between FPM results and BrCa beliefs.Results: FPM status was associated with a higher perception of barriers to mammography, and an elevated perception of barriers was associated with lower intentions to complete mammography. Collective coping behaviors functioned as a moderator and were associated with a decreased perception of mammography barriers in women with FPM results.Conclusions: FPM status had a detrimental impact on mammography intention indirectly through the perception of mammography barriers, but the use of africentric coping behaviors moderated the relationship between FPM status and perceived barriers to mammography. Culturally specific research focused on Black women is needed to explore influences on BrCa screening beliefs and mammography completion in this population.


Lasso estimation of hierarchical interactions for analyzing heterogeneity of treatment effect.
Individuals differ in how they respond to a given treatment. In an effort to predict the treatment response and analyze the heterogeneity of treatment effect, we propose a general modeling framework by identifying treatment-covariate interactions honoring a hierarchical condition. We construct a single-step l1 norm penalty procedure that maintains the hierarchical structure of interactions in the sense that a treatment-covariate interaction term is included in the model only when either the covariate or both the covariate and treatment have nonzero main effects. We developed a constrained Lasso approach with two parameterization schemes that enforce the hierarchical interaction restriction differently. We solved the resulting constrained optimization problem using a spectral projected gradient method. We compared our methods to the unstructured Lasso using simulation studies including a scenario that violates the hierarchical condition (misspecified model). The simulations showed that our methods yielded more parsimonious models and outperformed the unstructured Lasso for correctly identifying nonzero treatment-covariate interactions. The superior performance of our methods are also corroborated by an application to a large randomized clinical trial data investigating a drug for treating congestive heart failure (N = 2569). Our methods provide a well-suited approach for doing secondary analysis in clinical trials to analyze heterogeneous treatment effects and to identify predictive biomarkers.


Homozygous Gly530Ser substitution in COL5A1 causes mild classical Ehlers-Danlos syndrome.
Skin hyperelasticity, tissue fragility with atrophic scars, and joint hypermobility are characteristic for the classical type of Ehlers-Danlos syndrome (EDS). The disease is usually inherited as an autosomal dominant trait; however, recessive mode of inheritance has been documented in tenascin-X-deficient EDS patients. Mutations in the genes coding for collagen alpha1(V) chain (COL5A1), collagen alpha2(V) chain (COL5A2), tenascin-X (TNX), and collagen alpha1(I) chain (COL1A1) have been characterized in patients with classical EDS, thus confirming the suspected genetic heterogeneity. Recently, we described a patient with severe classical EDS due to a Gly1489Glu substitution in the alpha1(V) triple-helical domain who was, in addition, heterozygous for a disease-modifying Gly530Ser substitution in the alpha1(V) NH(2)-terminal domain [Giunta and Steinmann, 2000: Am. J. Med. Genet. 90:72-79; Steinmann and Giunta, 2000: Am. J. Med. Genet. 93:342]. Here, we report on a 4-year-old boy with mild classical EDS, born to healthy consanguineous Turkish parents; the mother presented a soft skin, while the father had a normal thick skin. Ultrastructural analysis of the dermis revealed in the patient the typical "cauliflower" collagen fibrils, while in both parents variable moderate aberrations were seen. Mutation revealed the presence of a homozygous Gly530Ser substitution in the alpha1(V) collagen chains in the patient, while both parents were heterozygous for the same substitution. An additional mutation in either the COL5A1 and COL5A2 genes was excluded. Furthermore, haplotype analysis with polymorphic microsatellite markers excluded linkage to the genes coding for alpha3(V) collagen (COL5A3), tenascin-X (TNX), thrombospondin-2 (THBS2), and decorin (DCN). These new findings support further our previous hypothesis that the heterozygous Gly530Ser substitution is disease modifying and now suggest that in the homozygous state it is disease causing.


Myxoid Plexiform Fibrohistiocytic Tumor Masquerading as Ganglion Cyst: A Case Report and Literature Review.
Background. Plexiform fibrohistiocytic tumor is a distinctive mesenchymal neoplasm of low-grade malignancy, with the capacity for biphasic differentiation toward a fibroblastic or histiocyte-like morphology. Clinically, these lesions affect different areas of the body and appear as painless, slowly growing, dermal or subcutaneous masses. To date, only three cases of myxoid variant have been reported in the English literature. Case Presentation. A 45-year-old female patient presented with a subcutaneous nodule in the right popliteal fossa. The initial impression was a benign ganglion cyst. The soft tissue tumor has been treated by local excision. The histopathological and the immunohistochemical findings supported the diagnosis of myxoid plexiform fibrohistiocytic tumor. The postoperative course was uneventful, and the patient received regular follow-up examination. She is alive without any recurrence. Conclusions. This case demonstrates how to distinguish this distinctive plexiform fibrohistiocytic tumor from other problematic soft tissue tumors. It is also remarkable for its rarely reported extensive myxoid change. Currently, there is no clear-cut correlation between the clinicopathologic findings and the behavior of this unusual variant.


Toward digitally screening and profiling AD: A GAMLSS approach of MemTrax in China.
To establish a normative range of MemTrax (MTx) metrics in the Chinese population. The correct response percentage (MTx-%C) and mean response time (MTx-RT) were obtained and the composite scores (MTx-Cp) calculated. Generalized additive models for location, shape and scale (GAMLSS) were applied to create percentile curves and evaluate goodness of fit, and the speed-accuracy trade-off was investigated. 26,633 subjects, including 13,771 (51.71%) men participated in this study. Age- and education-specific percentiles of the metrics were generated. Q tests and worm plots indicated adequate fit for models of MTx-RT and MTx-Cp. Models of MTx-%C for the low and intermediate education fit acceptably, but not well enough for a high level of education. A significant speed-accuracy trade-off was observed for MTx-%C from 72 to 94. GAMLSS is a reliable method to generate smoothed age- and education-specific percentile curves of MTx metrics, which may be adopted for mass screening and follow-ups addressing Alzheimer's disease or other cognitive diseases. GAMLSS was applied to establish nonlinear percentile curves of cognitive decline. Subjects with a high level of education demonstrate a later onset and slower decline of cognition. Speed-accuracy trade-off effects were observed in a subgroup with moderate accuracy. MemTrax can be used as a mass-screen instrument for active cognition health management advice.


Specific inhibition of HLA class I and II antibodies by soluble antigens--a method for the identification of antibody specificity in sera from alloimmunized individuals.
HLA class I and II antigens were purified to be used for the determination of the specificity of lymphocyte reactive antibodies in renal transplant patients. Purification of HLA antigens was achieved by affinity chromatography using rabbit antibodies directed to human beta 2 microglobulin, W6/32 antibodies that recognize a nonpolymorphic determinant on HLA class I molecules, and BU25 monoclonal antibodies directed to a monomorphic determinant on HLA class II molecules. Pooled platelets and spleen lymphocytes from a large number of donors were used as a source of class I and II antigens. HLA antigen preparations, highly enriched as shown in Western blot experiments, were obtained that caused a dose-dependent inhibition of the binding as well as of the cytotoxicity of W6/32 and BU25 antibodies. The HLA class I preparation did not inhibit the binding of monoclonal antibodies to T or B cell-specific surface markers or to HLA class II antigens. Similar kinds of results were obtained with the HLA class II antigen preparation, which only specifically blocked the class II antibody binding. The antigen preparations were tested for their ability to block binding of antibodies in sera from alloimmunized patients. In order to avoid complications by soluble HLA antigens, all sera were absorbed in ELISA plates coated with anti-class I and anti-class II monoclonal antibodies. The HLA class I and class II antigen preparations were found to be HLA-specific. All data were compared with the conventional method to determine HLA specificity--i.e., specific blocking of class I and class II reactivity using monoclonal antibodies and unabsorbed sera. Soluble HLA antigens, added directly to mixtures of patient sera and lymphocytes used in the cytotoxicity or binding tests, can therefore be used for determination of the presence of HLA antibodies in sera of alloimmunized patients.


Molecular characterization of T-cell immunoglobulin mucin domain-3 and Galectin-9 genes of swamp- and riverine-type water buffaloes.
Molecular characterization of T-cell immunoglobulin mucin domain-3 (TIM-3) and Galectin-9 (GAL-9) genes of swamp- and riverine-type water buffaloes was conducted to compare these genes with other species; determine the unique characteristic specific in water buffalo; and provide baseline information for the assessment of disease progression in buffalo species. TIM-3 and GAL-9 genes were amplified, purified, sequenced and characterized. The sequence result of TIM-3 in both types of water buffaloes contained 843 nucleotides encoding to 280 amino acids while GAL-9 of swamp-type and riverine-type water buffaloes contained 1023 and 972 nucleotides encoding to 340 and 323 amino acids, respectively. Meanwhile, the nucleotide and amino sequence of TIM-3 in water buffalo were 83-98% and 94-97% identical with other artiodactyl species, respectively. On the other hand, GAL-9 nucleotide and amino acid sequence in water buffalo were 85-98% and 76-96% identical with other artiodactyl species. The tyrosine-kinase phosphorylation motif and potential glycosylation sites were conserved within the tribe Bovinae. It is imperative to have further studies in the assessment of the role of these genes in disease progression in water buffalo during chronic infection. The study is the first report that describes the genetic characteristic of TIM-3 and GAL-9 genes in water buffalo.


Quality of life post radical prostatectomy: a male perspective.
The purpose of this qualitative study was to explore the meaning and effect of urinary incontinence and impotence on the quality of life for men with prostate cancer. The Cancer Recovery Model guided the study. This model is based on the assumption that the chronicity of cancer is a function of recovery as well as illness and focuses on the strength of an individual to regain his powers of survival until death. The study identified indicators for quality of life for men who have had a radical prostatectomy for cancer that should be included in developing discharge teaching plans and reinforced in community followup.


Cortical Versus Cancellous Solvent-Dehydrated Bone Allograft for Alveolar Ridge Preservation: A Histologic Study.
Allografts have been routinely used for immediate grafting of extraction sites as modalities of alveolar ridge preservation (ARP). Solvent-dehydrated bone allograft (SDBA), which is commonly utilized for socket grafting, exists in the form of cortical and cancellous particles. This study aims to provide a histologic comparison of cortical and cancellous SDBA for ARP. A total of 35 extraction sockets were allocated to receive either a cortical (17 sites) or cancellous (18 sites) SDBA, followed by application of a resorbable collagen wound dressing in both groups. At approximately 4 months, a bone core biopsy sample was obtained during implant placement. Histomorphometric assessment was then conducted to compare the differences between both forms of SDBA. Within its limitations, a higher percentage of vital bone was observed in the cortical bone group compared to the cancellous bone group (28.6% vs 20.1%, respectively, P = .042), while there was a lack of statistically significant differences among other fractions of the bone biopsy sample (residual graft particles and nonmineralized tissues such as connective tissue or other components).


Evaluation of the alpha and beta adrenoceptor-mediated activities of the novel, orally active inotropic agent, ibopamine, in the cardiovascular system of the pithed rat: comparison with epinine and dopamine.
The alpha and beta adrenoceptor-mediated effects of the novel, orally active inotropic prodrug, ibopamine, have been studied in the pithed rat and compared with those effects mediated by dopamine and the active form of ibopamine, epinine. All three agents produced alpha adrenoceptor-mediated pressor responses in pithed rats, and the vasopressor effects of ibopamine and epinine, but not dopamine, were potentiated by beta adrenoceptor blockade with propranolol (3 mg/kg i.v.). Catecholamine depletion with reserpine (5 mg/kg i.p.) did not affect the vasoconstrictor response elicited by any of these agents, indicating a direct effect in the vasculature. Epinine was 10 times more potent than ibopamine or dopamine. The pressor response to all three agents was antagonized by the alpha-1 adrenoceptor antagonist, prazosin (0.1 mg/kg i.v.) and the alpha-2 adrenoceptor antagonist, rauwolscine (0.5 mg/kg i.v.), suggesting the involvement of both alpha adrenoceptor subtypes in the vasopressor responses elicited by these compounds. After complete blockade of alpha adrenoceptors using a combination of phenoxybenzamine (3 mg/kg i.v.), prazosin (0.1 mg/kg i.v.) and rauwolscine (1 mg/kg i.v.), higher doses of ibopamine, epinine and dopamine produced a propranolol-sensitive, beta-1 adrenoceptor-mediated positive chronotropic response that was significantly reduced in reserpine-pretreated rats, indicating a significant indirect component in the activity of these compounds at the level of the myocardium. Epinine and dopamine were equipotent and were 10 times more potent than ibopamine as directly acting beta-1 adrenoceptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)


An assessment of a pilot asthma education program for childcare workers in a high-prevalence county.
To assess changes in knowledge, attitudes, and intentions among childcare workers before and after an asthma-management-education session. Between May and August 2004 five asthma-education sessions were provided for childcare workers from Sonoma County, California. A total of 71 childcare workers came to the sessions. Before and after each session we assessed the participants' knowledge, attitudes, and intentions about asthma. Participant knowledge of asthma causes (eg, air quality, common cold) and interventions (eg, bronchodilators), asthma trigger control plans, ability to identify a child who needs medical attention for asthma, and comfort level with caring for a child with asthma increased significantly. Their knowledge about asthma triggers, early warning signs, and asthma control plans was high before and after the asthma education intervention. Their stated intentions to utilize their asthma knowledge were high before and after the training, which may indicate willingness to implement knowledge and attitude change. Asthma education can improve childcare workers' knowledge about asthma-control strategies and attitudes toward asthma interventions.


Magnetism in metal-organic capsules.
Nickel and cobalt seamed metal-organic capsules have been isolated and studied using structural, magnetic and computational approaches. Antiferromagnetic exchange in the Ni capsule results from coordination environments enforced by the capsule framework.


Genetic and environmental influences on longitudinal changes in leisure-time physical activity from adolescence to young adulthood.
The aim of this study was to estimate genetic and environmental influences on the longitudinal evolution of leisure-time physical activity habits from adolescence to young adulthood. Data were gathered at four time points, at mean ages 16.2, 17.1, 18.6, and 24.5 years. At baseline, the sample comprised 5,216 monozygotic and dizygotic twins, born 1975-1979, and, at the last follow-up point, of 4,531 monozygotic and dizygotic twins. Physical activity volume was assessed as frequency of leisure-time physical activity and participants were categorized into three groups: inactive, moderately active, and active. Genetic and environmental influences were estimated using a multivariate, longitudinal Cholesky decomposition with a 'multifactorial liability threshold' approach. The results suggest that, in both sexes the heritability of leisure-time physical activity remained moderate (~43-52%) during adolescence, declining to ~30% in young adulthood. Shared environmental influences increased from adolescence (~18-26%) to young adulthood (43% in men and 49% in women). Specific environmental influences remained relatively stable during the total follow-up (~20-30%). New genetic, shared, and specific environmental influences at every follow-up point were suggested by the low correlations across occasions. In conclusion, the study demonstrated gender differences in genetic influences in the evolution of leisure-time physical activity habits from adolescence to young adulthood. However, shared environmental influences, especially in women, were crucial in explaining longitudinal changes in leisure-time physical activity. These outcomes emphasize the need of gender-specific measures to promote physical activity habits during young adulthood.


The Vav binding site (Y315) in ZAP-70 is critical for antigen receptor-mediated signal transduction.
Stimulation of antigen receptors in T and B cells leads to the activation of the Src and Syk families of protein tyrosine kinases (PTK). These PTKs subsequently phosphorylate numerous intracellular substrates, including the 95-kD protooncogene product Vav. Vav is essential for both T and B cell development and T and B cell antigen receptor-mediated signal transduction. After receptor ligation, Vav associates with phosphorylated Syk and ZAP-70 PTKs, an interaction that depends upon its SH2 domain. Here we demonstrate that a point mutation of tyrosine 315 (Y315F) in ZAP-70, a putative Vav SH2 domain binding site, eliminated the Vav- ZAP-70 interaction. Moreover, the Y315 mutation impaired the function of ZAP-70 in antigen receptor signaling. Surprisingly, this mutation also resulted in marked reduction in the tyrosine phosphorylation of ZAP-70, Vav, SLP-76, and Shc. These data demonstrate that the Vav binding site in ZAP-70 plays a critical role in antigen receptor-mediated signal transduction.


Cost analysis of a project to digitize classic articles in neurosurgery.
In summer 2000, the Cushing/Whitney Medical Library at Yale University began a demonstration project to digitize classic articles in neurosurgery from the late 1800s and early 1900s. The objective of the first phase of the project was to measure the time and costs involved in digitization, and those results are reported here. In the second phase, metadata will be added to the digitized articles, and the project will be publicized. Thirteen articles were scanned using optical character recognition (OCR) software, and the resulting text files were carefully proofread. Time for photocopying, scanning, and proofreading were recorded. This project achieved an average cost per item (total pages plus images) of $4.12, a figure at the high end of average costs found in other studies. This project experienced high costs for two reasons. First, the articles contained many images, which required extra processing. Second, the older fonts and the poor condition of many of these articles complicated the OCR process. The average article cost $84.46 to digitize. Although costs were high, the selection of historically important articles maximized the benefit gained from the investment in digitization.


Determination of the ortho to para ratio of H2Cl+ and H2O+ from submillimeter observations.
The opening of the submillimeter sky with the Herschel Space Observatory has led to the detection of new interstellar molecular ions, H2O(+), H2Cl(+), and HCl(+), which are important intermediates in the synthesis of water vapor and hydrogen chloride. In this paper, we report new observations of H2O(+) and H2Cl(+) performed with both Herschel and ground-based telescopes, to determine the abundances of their ortho and para forms separately and derive the ortho-to-para ratio. At the achieved signal-to-noise ratio, the observations are consistent with an ortho-to-para ratios of 3 for both H2O(+) and H2Cl(+), in all velocity components detected along the lines-of-sight to the massive star-forming regions W31C and W49N. We discuss the mechanisms that contribute to establishing the observed ortho-to-para ratio and point to the need for a better understanding of chemical reactions, which are important for establishing the H2O(+) and H2Cl(+) ortho-to-para ratios.


Application of Lung Ultrasound During the COVID-19 Pandemic: A Narrative Review.
This review highlights the ultrasound findings reported from a number of studies and case reports and discusses the unifying findings from coronavirus disease (COVID-19) patients and from the avian (H7N9) and H1N1 influenza epidemics. We discuss the potential role for portable point-of-care ultrasound (PPOCUS) as a safe and effective bedside option in the initial evaluation, management, and monitoring of disease progression in patients with confirmed or suspected COVID-19 infection.


Microwave-induced enzyme-catalyzed chemoselective reduction of organic azides.
A lipase enzyme, suspended in organic media along with organic azides and irradiated under microwaves, enhances the reaction rate over thermal heating and affords the corresponding amines in high yields. The present biocatalytic method employing lipase is a significant development with remarkable regio- and chemoselectivity under microwave irradiation in organic media with excellent yields for the reduction of azide functionality.


RB1 aberrations predict outcomes of immune checkpoint inhibitor combination therapy in NSCLC.
Immune checkpoint inhibitors (ICI) have changed the treatment of non-small cell lung cancer (NSCLC). Furthermore, compared with monotherapy, ICI combination therapy had better efficacy and partly different mechanism. Therefore, we aim to investigate and improve biomarkers specialized for ICI combination therapy. We enrolled 53 NSCLC patients treated with ICI combination therapy and collected their tissue and plasma samples to perform next-generation sequencing (NGS) with a 425-gene panel. The line of treatment was the only clinical factor significantly affecting objective response rate (ORR) and progression-free survival (PFS). Surprisingly, classical markers PD-L1 and TMB only had limited predictive values in the ICI combination therapy. Instead, we found RB1 mutation was significantly associated with prognosis. Patients with mutated RB1 had shorter PFS than those with wild RB1 (134d vs 219d, p=0.018). Subsequent analysis showed the RB1 related mutated cell cycle and chromosomal instability were also deleterious to prognosis (103d vs 411d, p<0.001; 138d vs 505d, p=0.018). Additionally, patients with more circulating tumor DNA (ctDNA) had significantly shorter PFS (41d vs 194d, p=0.0043). This study identified that NSCLC patients with mutated RB1 were less sensitive to ICI combination therapy. RB1 mutations and following cell cycle abnormalities and chromosomal instability can potentially guide clinical management.


Carcinoma of the recto-vaginal septum. Comprehensive literature review.
Carcinoma of the recto-vaginal septum is an extremely rare entity. We performed a MEDLINE-based search on recto-vaginal septum carcinoma, focussing on its management, in order to clarify which are the best treatment options for this disease. In addition an unpublished case report has been added to the review. 34 case reports were included in our review. Surgery and adjuvant chemoradiation therapy seem to be the most common treatment option. However, since primary surgical treatment leads to mutilation by removing a large portion of the vagina and the anal sphincter with a permanent terminal colostomy, primary platinum-based chemoradiation therapy could be considered. In case of extragastrointestinal stromal tumours primary surgical treatment seems to be the best option. Due to the rarity of this entity only limited data is available. Therefore further investigation is necessary.


Flemish equine veterinarians' perceptions on the use of and client communication about complementary and alternative veterinary medicine.
Complementary and alternative veterinary medicine (CAVM) is increasingly popular in horses. As CAVM usage could have risks, client-veterinarian communication about CAVM is crucial. Evaluating equine veterinarians' attitude towards CAVM, their CAVM usage and veterinarian-client communication about CAVM. Cross-sectional study. A telephone survey was conducted among equine veterinarians providing ambulatory care on a daily or weekly basis. The first section of the survey included questions about the veterinarians' attitude towards CAVM and their CAVM usage. The second section focused on veterinary-client communication about CAVM. When herbs are included as CAVM modality, 83% of the participants applied CAVM. Nighty-eight percent had already communicated with horse owners about CAVM and 81% agreed to be open to talk about CAVM. However, 95% agreed that sometimes CAVM usage takes place without disclosure to the veterinarian. The majority of participants communicated about CAVM on a weekly (40%) or daily (22%) basis, most often in person during consultations (99%) or via phone (32%). The median percentage of conversations about CAVM initiated by the owner was 50% (range 50%-80%). When the veterinarian initiated the conversation, this was usually by mentioning it as a treatment option, mostly in addition to conventional treatments. Some participants directly asked about CAVM use in the information-gathering phase. A convenience sample was used due to lack of data on the number of equine veterinarians in Flanders. Potential favourability bias with higher participation of veterinarians interested in CAVM. Equine veterinarians generally had a positive attitude towards CAVM use, although this depended on the specific modality. Veterinarian-client communication about CAVM occurs frequently in ambulatory care. An open dialogue with horse owners about CAVM is important to provide information about CAVM and thus enable them to make informed decisions concerning CAVM usage, together with their veterinarian.


Incidence trends of cannabis and cocaine use from periodic Spanish general population surveys: effect of standardizing results by age structure.
This study estimates life-time incidence trends of cannabis and cocaine use over 38 years from general population surveys of drug use (GPSDU) in Spain, taking into account changes of population age structure. Periodic cross-sectional studies. Eight biennial GPSDU from 1995 to 2009 in Spain. Interviewees aged 15-64 years who reported age of first ever cannabis and/or cocaine use between 10 and 64 years between 1971 and 2008. Estimates of raw and standardized incidences were calculated as a weighted mean of the incidences from all surveys. Standardization was conducted to take into account changes of population age structure. Incidence trends were extracted applying weighted cubic smoothing splines to incidence estimates. For both substances, estimated raw incidence trends increased up until 2000 (rates of 11.5 ± 0.7 and 3.6 ± 0.5 per 1000, respectively, for cannabis and cocaine), and then decreased significantly (in 2008, 9.6 ± 1.2 and 2.7 ± 0.6, respectively). In contrast, standardized rates exhibit a steadily increasing trend up to 2000 (9.0 ± 0.6 and 2.8 ± 0.4), followed by a statistically non-significant increasing trend afterwards (in 2008, 9.5 ± 1.2 and 2.8 ± 0.6). The largest increases of incidence were observed in both male and female subjects aged 15-19 years. Using data from Spanish general population surveys of drug use, an apparently decreasing trend of raw incidence rates in both cannabis and cocaine use from 2000 became non-decreasing trends when these rates were standardized. First experiences of cannabis and cocaine use in Spain occur mainly in younger ages (15-19 years).


Interactions of Histone Acetyltransferase p300 with the Nuclear Proteins Histone and HMGB1, As Revealed by Single Molecule Atomic Force Spectroscopy.
One of the important properties of the transcriptional coactivator p300 is histone acetyltransferase (HAT) activity that enables p300 to influence chromatin action via histone modulation. p300 can exert its HAT action upon the other nuclear proteins too--one notable example being the transcription-factor-like protein HMGB1, which functions also as a cytokine, and whose accumulation in the cytoplasm, as a response to tissue damage, is triggered by its acetylation. Hitherto, no information on the structure and stability of the complexes between full-length p300 (p300FL) (300 kDa) and the histone/HMGB1 proteins are available, probably due to the presence of unstructured regions within p300FL that makes it difficult to be crystallized. Herein, we have adopted the high-resolution atomic force microscopy (AFM) approach, which allows molecularly resolved three-dimensional contour mapping of a protein molecule of any size and structure. From the off-rate and activation barrier values, obtained using single molecule dynamic force spectroscopy, the biochemical proposition of preferential binding of p300FL to histone H3, compared to the octameric histone, can be validated. Importantly, from the energy landscape of the dissociation events, a model for the p300-histone and the p300-HMGB1 dynamic complexes that HAT forms, can be proposed. The lower unbinding forces of the complexes observed in acetylating conditions, compared to those observed in non-acetylating conditions, indicate that upon acetylation, p300 tends to weakly associate, probably as an outcome of charge alterations on the histone/HMGB1 surface and/or acetylation-induced conformational changes. To our knowledge, for the first time, a single molecule level treatment of the interactions of HAT, where the full-length protein is considered, is being reported.


Steam catalytic cracking and lump kinetics of naphtha to light olefins over nanocrystalline ZSM-5 zeolite.
This study investigates the reaction pathways and kinetics to comprehend the catalytic cracking of dodecane, a heavy naphtha model compound, over the nanocrystalline ZSM-5 catalyst in the presence and absence of steam with the aim of increasing olefin production. The nanocrystalline zeolite was characterized using XRD and BET, and the surface acidity was measured by NH3-TPD and Py-FTIR. The steam treated ZSM-5 contributed to an increase in pore volume with extra-framework alumina, resulting in highly catalytic active sites and hence higher olefin selectivity. The high conversion of dodecane (>90%) was achieved during catalytic cracking in the presence and absence of steam. In the presence of steam, the short pores of nano ZSM-5 led to an increase in the naphtha-to-olefin conversion with lesser dry gas and coke formation. The activation energies of primary cracking in the presence and absence of steam were slightly different. Lower activation energies through secondary cracking routes and higher reaction rate constants were obtained via assisted-steam catalytic cracking, promoted the selectivity towards light olefin products. Meanwhile the hydrogenation and alkylation reactions toward LPG and C5+ were favored in the absence of steam. Moreover, the ZSM-5 nano zeolite pores promoted more β-scission reactions, resulting in higher selectivity towards ethylene and dry gas.


Observations on the mechanisms of glucosuria during glucose loads in normal and nondiabetic subjects.
The study of 14 normal young men by glucose titration procedures has defined the magnitude of splay in this population, differing from previously reported data in its unexpected deviation from the line of theoretic unity high on the titration curve. Compared to these normal subjects, a group of glucosuric men could be divided into two subclasses, those with normal maximal rate of glucose reabsorption (Tm(G)) and those with subnormal Tm(G), both with comparably abnormal splay. Most consistent glucosurics fall into the latter group. Nephritic patients studied were not such a homogeneous group in terms of age and sex, but did manifest an abnormal splay during their titration curves in most cases. They also demonstrated a greater than normal reabsorptive rate of glucose per unit measured glomerular filtration rate. It is concluded that renal glucosuria must be defined not only in terms of the concept of Tm(G) but also by deviation of the glucose titration curve expressing an unusual degree of splay. The latter is presumed, as has been suggested by others, to be a characteristic of nonhomogeneity of glucose handling units in the kidney. This seems subject to exaggeration in the adaptations which accompany chronic renal disease.


Studies on the effectiveness of liver and bacterial beta-glucuronidase enzymes in the hydrolysis of urinary beta-glucosiduronides of some tryptophan metabolites.
The effectiveness of Escherichia coli and bovine liver beta-glucuronidases in the hydrolysis of the urinary beta-glucosiduronides of tryptophan metabolites was studied. Moreover, the effect of the prolonged contact of these conjugates to the urinary enzyme was investigated in the first and second voiding urine samples. It is found that both enzymes have no important role in releasing the free carcinogens from their glucosiduronides. The presence of free carcinogens could be attributed to the spontaneous hydrolysis of some labile conjugates. However, the prolonged contact of the freely active substances during the sleeping hours with the epithelium of the bladder may enhance the process of bladder carcinogenicity. The increased accumulation of these metabolites in the first voiding urine could be interpreted in terms of their rate of excretion rather than by the enzymatic hydrolysis of their conjugates.


Clinical implications of the Hippo-YAP pathway in multiple cancer contexts.
The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy. The analysis of YAP expressions can facilitate the identification of patients who respond better to an anti-cancer drug treatment comprising RAF-, MEK-, and EGFR-targeted inhibitors. The prominence of YAP for those aspects of cancer biology denotes that these factors are ideal targets for the development of anti-cancer medications. Therefore, our report strongly indicates that the YAP is of potential prognostic utility and druggability in various human cancers. [BMB Reports 2018; 51(3): 119-125].


[Study of the introduction of the European Credit Transfer System (ECTS) in pediatrics and modification of the teaching methodology].
Spanish medical faculties have initiated the new curriculum reform process within the framework of the European Higher Education Area and are required to incorporate the European Credit Transfer System (ECTS) to new syllabi before 2010. To test the introduction of the ECTS in pediatrics and modify the teaching methodology. The theoretical and practical programs were adapted; academic objectives and a student evaluation system were established. Students were surveyed on starting the second term of the 2004-05 academic year before the theory examination and again on terminating the academic year: a 5-point Likert-type scale was used for responses. Priorities for generic and specific competencies selected by students were compared with those selected by the National Deans Conference (NDC). The results were analyzed using non-parametric tests. Fifteen credits became 11 ECTS, with 297 student working hours. The theory program was reduced from 80 to 52 lessons. The students prepared 14 tutor-supervised case presentations. The teaching staff considered that learning of theory was similar to previous years (66 %) and that practical learning improved (73.3 %). The students thought the program should continue (73.2 %) but 98.8 % considered the workload excessive. The students believed that their practical training and their ability to prepare and make case presentations significantly improved during the semester. Academic performance was significantly higher than that in students of the previous year. Students agreed with NDC priorities for 9/9 general and 4/17 specific competencies. Estimation of workload by students was significantly higher than that by staff, and 73.3 % of the students believed that workload should be reduced and the examination system improved. Introducing the ECTS improved academic performance, practical training, and self-directed learning. The project was satisfactory for staff and students. Student workload was underestimated.


Combining molecular dynamics and an electrodiffusion model to calculate ion channel conductance.
Establishing the relation between the structures and functions of protein ion channels, which are protein assemblies that facilitate transmembrane ion transport through water-filled pores, is at the forefront of biological and medical sciences. A reliable way to determine whether our understanding of this relation is satisfactory is to reproduce the measured ionic conductance over a broad range of applied voltages. This can be done in molecular dynamics simulations by way of applying an external electric field to the system and counting the number of ions that traverse the channel per unit time. Since this approach is computationally very expensive we develop a markedly more efficient alternative in which molecular dynamics is combined with an electrodiffusion equation. This alternative approach applies if steady-state ion transport through channels can be described with sufficient accuracy by the one-dimensional diffusion equation in the potential given by the free energy profile and applied voltage. The theory refers only to line densities of ions in the channel and, therefore, avoids ambiguities related to determining the surface area of the channel near its endpoints or other procedures connecting the line and bulk ion densities. We apply the theory to a simple, model system based on the trichotoxin channel. We test the assumptions of the electrodiffusion equation, and determine the precision and consistency of the calculated conductance. We demonstrate that it is possible to calculate current/voltage dependence and accurately reconstruct the underlying (equilibrium) free energy profile, all from molecular dynamics simulations at a single voltage. The approach developed here applies to other channels that satisfy the conditions of the electrodiffusion equation.


Retinoblastoma--a histologic and immunohistologic study.
Histopathology and various immunohistochemical markers were studied in 40 cases of human retinoblastoma. In histopathology, tumour type, extent and invasion were studied. In immunohistochemistry, both glial and neural markers were used to know the histogenesis of this tumour. The glial markers, glial fibrillary acidic protein and vimentin, were detected in retinal astrocytes and Muller's cells in normal retina and perivascular glia in retinoblastoma. The neural marker, neurone-specific enolase stained neurones in outer and inner nuclear layers in normal retina, Flexner-Wintersteiner rosettes in retinoblastoma and tumour cells is differentiated retinoblastoma. Another neural marker, neurofilament triplet polypeptide stained neurones in inner nuclear layer of normal retina and Flexner-Wintersteiner rosettes in well-differentiated retinoblastoma. These results support the view that retinoblastoma has predominantly neuronal origin.


Milk production, methane emissions, nitrogen, and energy balance of cows fed diets based on different forage systems.
Eight lactating Italian Friesian cows were housed in individual respiration chambers in a repeated Latin square design to determine their dry matter intake (DMI) and their milk and methane production, as well as to collect the total feces and urine to determine the N and energy balances. Four diets, based on the following forages (% of dry matter, DM), were tested: corn silage (CS, 49.3), alfalfa silage (AS, 26.8), wheat silage (WS, 20.0), and a typical hay-based Parmigiano Reggiano cheese production diet (PR, 25.3 of both alfalfa and Italian ryegrass hay). The greatest DMI was observed for cows fed PR (23.4 vs. 20.7 kg/d, the average of the other 3 diets). The DM digestibility was lower for PR (64.5 vs. 71.7%, the average of the other diets). The highest ash-free neutral detergent fiber digestibility values were obtained for CS (50.7%) and AS (47.4%). In the present study, no differences in milk production were observed between diets, although PR showed a higher milk yield trend. The highest milk urea N concentration (mg/dL) was found for the cows fed the WS diet (13.8), and the lowest was observed for the cows fed AS (9.24). The highest milk urea N concentration for the cows fed WS was also correlated with the highest urinary N excretion (g/d), which was found for the cows fed that same diet (189 vs. 147 on average for the other diets). The protein digestibility was higher for the cows fed the CS and WS diets (on average 68.5%) than for the cows fed AS and PR (on average 57.0%); dietary soybean inclusion was higher for CS and WS than for AS and PR. The rumen fermentation pattern was affected by the diet; the cows fed the PR diet showed a higher rumen pH and decreased propionate production than those fed CS, due to the lower nonfiber carbohydrate content and higher ash-free neutral detergent fiber content of the PR diet than the CS diet. Feeding cows with PR diet increased the acetate:propionate ratio in comparison with the CS diet (3.30 vs. 2.44 for PR and CS, respectively). Cows fed the PR diet produced a greater daily amount of methane and had a greater methane energy loss (% of digestible energy intake) than those fed the CS diet (413 vs. 378 g/d and 8.67 vs. 7.70%), but no differences were observed when methane was expressed as grams per kilogram of DMI or grams per kilogram of milk. The PR diet resulted in a smaller net energy for lactation content than the CS diet (1.36 vs. 1.70 Mcal/kg of DM for the PR and CS diets, respectively). Overall, our research suggests that a satisfactory milk production can be attained by including different high-quality forages in balanced diets without any negative effect on milk production or on the methane emissions per kilogram of milk.


Intrinsic Molecular Processes: Impact on Mutagenesis.
Mutations provide resources for genome evolution by generating genetic variability. In addition, mutations act as a driving force leading to disease pathogenesis, and thus have important implications for disease diagnosis, prognosis, and treatment. Understanding the mechanisms underlying how mutations occur is therefore of prime importance for elucidating evolutionary and pathogenic processes. Recent genomics studies have revealed that mutations occur non-randomly across the human genome. In particular, the distribution of mutations is highly associated with intrinsic molecular processes including transcription, chromatin organization, DNA replication timing, and DNA repair. Interplay between intrinsic processes and extrinsic mutagenic exposure may thus imprint a characteristic mutational landscape on tumors. We discuss the impact of intrinsic molecular processes on mutation acquisition in cancer.


Spatial integration of visual motion with separate speed and direction information.
We present evidence to support the possibility that motion information is divided into two scalars: direction and speed, to integrate local motions over a wide spatial range. With various motion stimuli composed of numerous red and green dots, observers perceived that peripheral dots moved similar to central dots on the basis of the same direction or speed, even when speed or direction was different. The results indicate that the direction and speed of local motion can be processed separately and that the distributions are analyzed independently to integrate the local motions. This process, based on two motion scalars, may be useful for the perception of complex motions that would be difficult to perceive with a process based on motion vectors.


[Cutaneous grafts].
Skin grafting is one of the most widely used techniques for healing wounds with soft tissue damage. Autologous grafts of various thicknesses are usually used and the properties of the graft depend on its thickness. These include thin, split-thickness and full-thickness skin grafts. Two complementary technical innovations have optimized the use of harvesting sites: mesh expanded autografts for thin and split-thickness grafts and skin expander implants for full-thickness skin grafts. Thorough knowledge of the different types of graft will permit fast, good quality healing if the receiving beds are well vascularized.


SWADESH: a multimodal multi-disease brain imaging and neuropsychological database and data analytics platform.
Multimodal neuroimaging data of various brain disorders provides valuable information to understand brain function in health and disease. Various neuroimaging-based databases have been developed that mainly consist of volumetric magnetic resonance imaging (MRI) data. We present the comprehensive web-based neuroimaging platform "SWADESH" for hosting multi-disease, multimodal neuroimaging, and neuropsychological data along with analytical pipelines. This novel initiative includes neurochemical and magnetic susceptibility data for healthy and diseased conditions, acquired using MR spectroscopy (MRS) and quantitative susceptibility mapping (QSM) respectively. The SWADESH architecture also provides a neuroimaging database which includes MRI, MRS, functional MRI (fMRI), diffusion weighted imaging (DWI), QSM, neuropsychological data and associated data analysis pipelines. Our final objective is to provide a master database of major brain disease states (neurodegenerative, neuropsychiatric, neurodevelopmental, and others) and to identify characteristic features and biomarkers associated with such disorders.


Expression of microRNA and microRNA processing machinery genes during early quail (Coturnix japonica) embryo development.
MicroRNA (miRNA) are small regulatory RNA molecules that are implicated in regulating and controlling a wide range of physiological processes including cell division, differentiation, migration, apoptosis, morphogenesis, and organogenesis. The aim of this study was to determine the expression pattern of 32 miRNA and 18 miRNA processing machinery genes during somite formation in quail embryos. The embryos were collected at stages HH (Hamburger and Hamilton) 4, 6, and 9 of embryo development (19, 24, and 30 h of incubation, respectively). Total RNA including miRNA was isolated from 4 groups of embryos (each group consisting of 6 to 8 embryos) were collected at each of the 3 stages (19, 24, and 30 h). The expression pattern of candidate miRNA and miRNA processing machinery genes was performed using quantitative real-time PCR. The results demonstrated that 7 miRNA (let-7a, mir-122, mir-125b, mir-10b, P < 0.01; let-7b, mir-26a, and mir-126, P < 0.05) were differentially expressed during early quail embryo development. In addition, the expression profile of 18 miRNA processing machinery genes was not significantly increased at 30 h of incubation compared with both 19 and 24 h. Our results suggest that machinery genes for miRNA biogenetic pathways are functional, and hence, miRNA may be involved in the regulation of early quail development. These 7 differentially expressed miRNA are suggested to play critical roles in quail embryo somite formation.


Strains of Escherichia coli associated with urogenital disease in dogs and cats.
Selected strains of Escherichia coli associated with urogenital disease in dogs and cats were evaluated for 3 virulence factors associated with human uropathogenic strains. Urogenital strains of E coli from dogs and cats had high prevalence of alpha hemolysin and were clustered in 5 to 10 somatic serogroups, attributes also shared by human uropathogenic strains. However, the canine and feline urogenital strains failed to have increased prevalence of mannose-resistant hemagglutination, as has been reported for human uropathogenic strains.


Potential role of rituximab in metastatic castrate-resistant prostate cancer.
Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma. The findings in this report suggest that further investigation is warranted for utilizing B-cell targeted therapy in delaying progression of castrate-resistant prostate cancer.


Effect of fermentation parameters on bio-alcohols production from glycerol using immobilized Clostridium pasteurianum: an optimization study.
This article addresses the issue of effect of fermentation parameters for conversion of glycerol (in both pure and crude form) into three value-added products, namely, ethanol, butanol, and 1,3-propanediol (1,3-PDO), by immobilized Clostridium pasteurianum and thereby addresses the statistical optimization of this process. The analysis of effect of different process parameters such as agitation rate, fermentation temperature, medium pH, and initial glycerol concentration indicated that medium pH was the most critical factor for total alcohols production in case of pure glycerol as fermentation substrate. On the other hand, initial glycerol concentration was the most significant factor for fermentation with crude glycerol. An interesting observation was that the optimized set of fermentation parameters was found to be independent of the type of glycerol (either pure or crude) used. At optimum conditions of agitation rate (200 rpm), initial glycerol concentration (25 g/L), fermentation temperature (30°C), and medium pH (7.0), the total alcohols production was almost equal in anaerobic shake flasks and 2-L bioreactor. This essentially means that at optimum process parameters, the scale of operation does not affect the output of the process. The immobilized cells could be reused for multiple cycles for both pure and crude glycerol fermentation.


[Effect of glutamine on apoptosis of the small intestine in young rats with endotoxemia and its mechanism].
To study the effect of glutamine on intestinal epithelial apoptosis by examining changes regarding Bcl-2 and Bax mRNA expressions in the small intestine of young rats with endotoxemia and to explore the protective mechanism that glutamine may have. A total of 120 18-day-old rats were randomly assigned into Endotoxemia, Glutamine-treated and Control groups (n = 40 each). The endotoxemia model was established by intraperitoneal injection of endotoxin (4 mg/kg of O55B5 Escherichia coli lipopolysaccharide). Rats in the Glutamine-treated group were intraperitoneally injected with N (2)-L-alanyl-L-glutamine (2 g/kg) along with endotoxin. Rats in the Control group were intraperitoneally injected with an equal volume of normal saline. The entire ileum was collected at 2, 4, 6, 24, and 72 hrs after injection. Bcl-2 and Bax mRNA expressions were detected by semi-quantities reverse transcriptase chain reaction. Bcl-2 mRNA was not expressed in the Control and the Endotoxemia groups but increased in the Glutamine-treated group at each time point. Bax mRNA expression was weak in the Control group, and significantly increased in the Endotoxemia group at each time point. The Glutamine-treated group showed noticeably reduced Bax mRNA expression at 2 hrs post-injection while other time points were similar to the Control group. The ratio of Bax and Bcl-2 mRNA expression at each time point in the Endotoxemia group was significantly higher than that in the Control group while the Glutamine-treated group demonstrated significantly lower ratio of Bax and Bcl-2 mRNA expression than both. Glutamine treatment increased Bcl-2 mRNA expression and decreased Bax mRNA expression, as a result, the ratio of Bax and Bcl-2 mRNA expression decreased. The effects of glutamine resulted in a suppression of intestinal epithelial apoptosis and maintained the integrity of the gut barrier structure.


Network models in drug discovery and regenerative medicine.
Network motifs and modelling paradigms are attracting increasing attention as modelling tools in drug design and development, and in regenerative medicine. There is a gradual but inexorable convergence between these hitherto disparate disciplines. This review summarizes some very recent work in these areas, leading to an understanding of the complementary roles networks play and factors driving this convergence: network paradigms can be excellent ways of modelling and understanding drug molecules and their action, an understanding of the robustness and vulnerabilities of biological targets may improve the efficacy of drug design and discovery, drug design has an increasingly large role to play in directing stem cell properties, stem cell regulatory networks can be modelled in useful ways using network models at a reasonable level of scale, and the network tools of drug design are also very useful for the design of biomaterials used in regenerative medicine.


Light-guided intrabodies for on-demand in situ target recognition in human cells.
Due to their high stability and specificity in living cells, fluorescently labeled nanobodies are perfect probes for visualizing intracellular targets at an endogenous level. However, intrabodies bind unrestrainedly and hence may interfere with the target protein function. Here, we report a strategy to prevent premature binding through the development of photo-conditional intrabodies. Using genetic code expansion, we introduce photocaged amino acids within the nanobody-binding interface, which, after photo-activation, show instantaneous binding of target proteins with high spatiotemporal precision inside living cells. Due to the highly stable binding, light-guided intrabodies offer a versatile platform for downstream imaging and regulation of target proteins.


Testing thermogenesis as the basis for the evolution of cetacean sleep phenomenology.
Cetacean sleep phenomenology consists of a combination of unihemispheric slow wave sleep and a massive reduction in the amount of rapid eye movement sleep. Despite various proposals, the selection pressure driving the evolution of this combined sleep phenomenology is unknown. It was recently suggested that the need to produce heat in the thermally challenging aquatic environment might have been the selection pressure. Mechanisms of heat loss and heat production can be measured directly or indirectly. The present study was designed to test the thermogenetic proposal by recording indirect measurements of heat loss (surface area to volume ratio) and heat production (tail-beats per minute). A strong correlation was found between these two parameters, such that increases in potential heat loss were matched by increases in potential heat production. This result suggests that the need to compensate for heat loss can provide an evolutionary rationale for the appearance of extant cetacean sleep physiology.


Nitrosylated iron-thiolate-sulfinate complexes with {Fe(NO)}6/7 electronic cores: relevance to the transformation between the active and inactive NO-bound forms of iron-containing nitrile hydratases.
The five-coordinated iron-thiolate nitrosyl complexes [(NO)Fe(S,S-C6H3R)2]- (R = H (1), m-CH3 (2)), [(NO)Fe(S,S-C6H2-3,6-Cl2)2]- (3), [(NO)Fe(S,S-C6H3R)2]2- (R = H (10), m-CH3 (11)), and [(NO)Fe(S,S-C6H2-3,6-Cl2)2]2- (12) have been isolated and structurally characterized. Sulfur oxygenation of iron-thiolate nitrosyl complexes 1-3 containing the {Fe(NO)}6 core was triggered by O2 to yield the S-bonded monosulfinate iron species [(NO)Fe(S,SO2-C6H3R)(S,S-C6H3R)]- (R = H (4), m-CH3 (5)) and [(NO)Fe(S,SO2-C6H2-3,6-Cl2)(S,S-C6H2-3,6-Cl2)]2(2-) (6), respectively. In contrast, attack of O2 on the {Fe(NO)}7 complex 10 led to the formation of complex 1 accompanied by the minor products, [Fe(S,S-C6H4)2]2(2-) and [NO3]- (yield 9%). Reduction of complexes 4-6 by [EtS]- in CH3CN-THF yielded [(NO)Fe(S,SO2-C6H3R)(S,S-C6H3R)]2- (R = H (7), m-CH3 (8)) and [(NO)Fe(S,SO2-C6H2-3,6-Cl2)(S,S-C6H2-3,6-Cl2)]2- (9) along with (EtS)2 identified by 1H NMR. Compared to complex 10, complexes 7-9 with the less electron-donating sulfinate ligand coordinated to the {Fe(NO)}7 core were oxidized by O2 to yield complexes 4-6. Obviously, the electronic perturbation of the {Fe(NO)}7 core caused by the coordinated sulfinate in complexes 7-9 may serve to regulate the reactivity of complexes 7-9 toward O2. The iron-sulfinate nitrosyl species with the {Fe(NO)}6/7 core exhibit the photolabilization of sulfur-bound [O] moiety. Complexes 1-4-7-10 (or 2-5-8-11 and 3-6-9-12) are interconvertible under sulfur oxygenation, redox processes, and photolysis, respectively.


Structural and Morphological Transformations of Covalent Organic Nanotubes.
Covalent organic nanotubes (CONTs) are porous one-dimensional frameworks connected through imine bonds via Schiff base condensation between aldehydes and amines. The presence of two amine groups at the ortho position in the structurally demanding tetraaminotriptycene (TAT) building block leads to multiple reaction pathways between the ditopic aldehyde and the tetratopic amine. We have synthesized five different monomers of CONT-1 by the Schiff base condensation reaction between TAT and o-anisaldehyde. The conversion of imine to imidazole bonding in a monomer is probed using NMR, mass spectrometry, and X-ray diffraction techniques. Solid-state NMR provide insights into the CONTs' structural connectivity. A theoretical investigation suggests that the π-π stacking could be the driving force for rapid imine to imidazole conversion within the CONT-1. Microscopic imaging sheds further light on the self-assembly process of the CONTs, indicating both head-to-head and side-by-side assembly.


Supramolecular-templated thick mesoporous titania films for dye-sensitized solar cells: effect of morphology on performance.
Highly crystallized mesoporous titania films of varying thicknesses and different morphologies, namely ordered body-centered orthorhombic and disordered wormlike mesostructure, have been successfully synthesized via a supramolecular-templated route and subsequent layer-by-layer deposition. The performance of these mesoporous films in dye-sensitized solar cells was investigated, achieving a maximum efficiency of 6-7% at the film thickness of 5-6 mum. The ordered mesoporous titania films outperformed the disordered counterpart of the same thickness in both short circuit current and efficiency. This behavior is elaborated with the dye-loading, optical, and charge-transport behavior as affected by the variation in mesoporous film morphology. The improved cell performance of the ordered mesoporous film is ascribed to the enhanced electron transport in the regularly packed titania network because of the enhanced crystalline grain connectivity. Nevertheless, the dependence of cell performance on the film morphology is weakened when the film thickness was above approximately 3.5 mum, because of the serious film cracks.


Time factor and treatment strategies in subclinical disease.
Rational biological development of treatment strategies for subclinical metastases has lagged behind such efforts with primary cancers: most adjuvant therapies for subclinical disease have been developed empirically, based on clinical observation. This paper reviews recent studies that point to rapid growth of subclinical disease. The effect of rapid growth of occult metastases and undetectable extensions of primary cancer is to increase the radiation dose necessary for their elimination if treatment duration is extended. This increase may be evident even when changes are made to short courses of treatment, consistent with no lag time between the start of treatment and rapid growth or regrowth of subclinical tumour deposits. This provides a strong rationale for avoiding gaps or delays in adjuvant treatments and suggest that accelerated regimens of radiation or chemoradiation may be advantageous in the treatment of subclinical disease provided that the total dose can be maintained or not greatly reduced from those used conventionally. Conversely, an escalation of total dose with a concomitant increase in overall treatment duration may not result in improved control rates because the rapid growth of small clonogen deposits might counterbalance the effect of the higher dose.


The importance of having a flexible scope ISO 15189 accreditation and quality specifications based on biological variation--the case of validation of the biochemistry analyzer Dimension Vista.
Technological innovation requires the laboratories to ensure that modifications or incorporations of new techniques do not alter the quality of their results. In an ISO 15189 accredited laboratory, flexible scope accreditation facilitates the inclusion of these changes prior to accreditation body evaluation. A strategy to perform the validation of a biochemistry analyzer in an accredited laboratory having a flexible scope is shown. A validation procedure including the evaluation of imprecision and bias of two Dimension Vista analysers 1500 was conducted. Comparability of patient results between one of them and the lately replaced Dimension RxL Max was evaluated. All studies followed the respective Clinical and Laboratory Standards Institute (CLSI) protocols. 30 chemistry assays were studied. Coefficients of variation, percent bias and total error were calculated for all tests and biological variation was considered as acceptance criteria. Quality control material and patient samples were used as test materials. Interchangeability of the results was established by processing forty patients' samples in both devices. 27 of the 30 studied parameters met allowable performance criteria. Sodium, chloride and magnesium did not fulfil acceptance criteria. Evidence of interchangeability of patient results was obtained for all parameters except magnesium, NT-proBNP, cTroponin I and C-reactive protein. A laboratory having a well structured and documented validation procedure can opt to get a flexible scope of accreditation. In addition, performing these activities prior to use on patient samples may evidence technical issues which must be corrected to minimize their impact on patient results.