Density-functional theory (DFT) and time-dependent DFT study of the chemical and physical origins of key photoproperties of end-group derivatives of a nonfullerene acceptor molecule for bulk heterojunction organic solar cells.
As emphasized in a recent review article (Chem. Rev. 2022, 122, 14180), organic solar cell (OSC) photoconversion efficiency has been rapidly evolving with results increasingly comparable to those of traditional inorganic solar cells. Historically, OSC performance improvement focused first on the morphology of P3HT: PC 61 BM solar cells then went through different stages to shift lately interest towards nonfullerene acceptors (NFAs) as a replacement of PC 61 BM acceptor (ACC) molecule. Here, we use density-functional theory (DFT) and time-dependent DFT to investigate four novel NFAs of A-D-A (acceptor-donor-acceptor) form derived from the recently synthesized IDIC-4Cl (Dyes Pigm. 2019, 166, 196). Our level of theory is carefully evaluated for IDIC-4Cl and then applied to the four novel NFAs in order to understand how chemical modifications lead to physical changes in cyclic voltammetry (CV) frontier molecular orbital energies and absorption spectra in solution. Finally we design and apply a new type of Scharber plot for NFAs based upon some simple but we think reasonable assumptions. Unlike the original Scharber plots where a larger DON band gap favors a larger PCE, our modified Scharber plot reflects the fact that a smaller ACC band gap may favor PCE by filling in gaps in the DON acceptor spectrum. We predict that only the candidate molecule with the least good acceptor A, with the highest frontier molecular orbital energies, and one of the larger CV lowest unoccupied molecular orbital (LUMO) - highest unoccupied molecular orbital (HOMO) gaps, will yield a PM6:ACC PCE exceeding that of the parent IDIC-4Cl ACC. This candidate also shows the largest oscillator strength for the primary 1 (HOMO, LUMO) charge- transfer transition and the largest degree of delocalization of charge transfer of any of the ACC molecules investigated here.


Lanthanide supramolecular helical diastereoselective breaking induced by point chirality: mixture or P-helix, M-helix.
The self-assembly of lanthanide (europium or lanthanium) bimetallic triple helicates from two closely related chiral ligands resulted in a very different supramolecular phenomenon. One gave rise to significantly diastereoselective formation of a triple helicate, whereas the other led to diastereoselective breaking to generate a mixture of P and M diastereomers in ∼1 : 1.1 ratio. The first X-ray crystal structure of a chiral ligand based lanthanide triple-helicate indicates that successive CH-π interactions were found to maintain the supramolecular helical structure.


Low doses of bovine somatotropin during the transition period and early lactation improves milk yield, efficiency of production, and other physiological responses of Holstein cows.
The objectives of this experiment were to determine whether low doses of bovine somatotropin (bST) during the transition period and early lactation period improved dry matter intake (DMI), body weight (BW), or body condition score (BCS); provoked positive changes in concentrations of somatotropin, insulin, insulin-like growth factor-I (IGF-I), glucose, nonesterified fatty acids, and Ca; or improved milk yield (MY) response without obvious adverse effects on health status. Eighty-four multiparous Holstein cows completed treatments arranged in a 2 x 3 x 2 factorial design that included prepartum and postpartum bST, dry period (30 d dry, 30 d dry + estradiol cypionate, and 60 d dry), and prepartum anionic or cationic diets. Biweekly injections of bST began at 21 +/- 3 d before expected calving date through 42 +/- 2 d postpartum (control = 0 vs. bST = 10.2 mg of bST/d; POSILAC). At 56 +/- 2 d in milk, all cows were injected with a full dose of bST (500 mg of bST/14 d; POSILAC). During the prepartum period and during the first 28 d postpartum, no differences in mean BW, BCS, or DMI were detected between the bST treatment group and the control group. During the first 10 wk of lactation, cows in the bST treatment group had greater mean MY and 3.5% fat-corrected milk yield and lower SCC than did cows in the control group. When cows received a full dose of bST, an increase in milk production through wk 21 was maintained better by cows in the bST group. Mean concentrations of somatotropin, IGF-I, and insulin differed during the overall prepartum period (d -21 to -1). During the postpartum period (d 1 to 28), cows in the bST group had greater mean concentrations of somatotropin and IGF-I in plasma. Concentrations of Ca around calving did not differ because of bST treatment. Results suggest that changes in concentrations of blood measures provoked by injections of bST during the transition period and early lactation period resulted in improved metabolic status and production of the cows without apparent positive or negative effects on calving or health.


Stable Anion-Derived Solid Electrolyte Interphase in Lithium Metal Batteries.
High-energy-density lithium (Li) metal batteries are severely hindered by the dendritic Li deposition dictated by non-uniform solid electrolyte interphase (SEI). Despite its unique advantages in improving the uniformity of Li deposition, the current anion-derived SEI is unsatisfactory under practical conditions. Herein regulating the electrolyte structure of anions by anion receptors was proposed to construct stable anion-derived SEI. Tris(pentafluorophenyl)borane (TPFPB) anion acceptors with electron-deficient boron atoms interact with bis(fluorosulfonyl)imide anions (FSI- ) and decrease the reduction stability of FSI- . Furthermore, the type of aggregate cluster of FSI- in electrolyte changes, FSI- interacting with more Li ions in the presence of TPFPB. Therefore, the decomposition of FSI- to form Li2 S is promoted, improving the stability of anion-derived SEI. In working Li | LiNi0.5 Co0.2 Mn0.3 O2 batteries under practical conditions, the anion-derived SEI with TPFPB undergoes 194 cycles compared with 98 cycles of routine anion-derived SEI. This work inspires a fresh ground to construct stable anion-derived SEI by manipulating the electrolyte structure of anions.


Intervertebral Disc Engineering through Exploiting Mesenchymal Stem Cells: Progress and Perspective.
Intervertebral disc degeneration is a common spinal disorder and may manifest with low back pain or sciatica. The degeneration is characterized by the loss of extracellular matrix integrity and dehydration in the nucleus pulposus. This compromises the viscoelastic property and compressive strength of the disc and therefore the capacity to withstand axial load, eventually causing the disc to collapse or leading to disc bulging or herniation due to abnormal strains on the surrounding annulus. Mesenchymal stem/stromal cells (MSCs) are attractive cell sources for engineering or repair of the disc tissues with respect to their ease of availability and capacity to expand in vitro. Moreover, recent investigations have proposed a potential of MSCs to differentiate into disc-like cells. This review discusses the approaches and concerns for engineering intervertebral disc through manipulating MSCs, with a highlight on the relevance of disc progenitor discovery. Ultimately, stem cell-based engineering of intervertebral disc may facilitate the preservation of motion segment function and address degenerative disc disease in future without spinal fusion.


Validation of Nursing Diagnoses for people with chronic kidney conditions on conservative treatment.
To develop and validate Nursing Diagnoses statements of the International Classification for Nursing Practice (ICNP®) aimed at the care of people with chronic kidney conditions undergoing conservative treatment. This is a methodological research structured in sequenced construction stages, cross-mapping, content validation by the Delphi Technique by specialist nurses, and categorization of Nursing Diagnoses. Forty-two specialist nurses participated in the first round and 34 in the second. A total of 179 Nursing Diagnoses statements were prepared, categorized according to Roy's adaptation model, of which 160 were validated for content, with Content Validity Index ≥ 0.80. The Diagnoses developed and validated show the modes of adaptation to health of people with chronic kidney conditions undergoing conservative treatment, influenced by biological, psychological, social, and cultural needs, with the Physiological Mode being the most prevalent.


The use of mini plates for intermaxillary fixation in a severely comminuted mandibular fracture with bilateral condylar fractures.
Intermaxillary fixation (IMF) is an integral technique utilized by maxillofacial surgeons to appropriately reduce and relate maxillary and mandibular fractures to both one another and the facial skeleton. This case report reviews the management of a comminuted mandibular fracture including inoperable bilateral condylar fractures that precluded the use of convention IMF techniques necessitating an alternative technique. This was achieved in the form of modified bony plates extending intraorally. Postoperative review showed favorable results with occlusion and range of motion comparable to the premorbid function and no unforeseen complications.


Vocal and Tactile Input to Children Who Are Deaf or Hard of Hearing.
Purpose Caregivers may show greater use of nonauditory signals in interactions with children who are deaf or hard of hearing (DHH). This study explored the frequency of maternal touch and the temporal alignment of touch with speech in the input to children who are DHH and age-matched peers with normal hearing. Method We gathered audio and video recordings of mother-child free-play interactions. Maternal speech units were annotated from audio recordings, and touch events were annotated from video recordings. Analyses explored the frequency and duration of touch events and the temporal alignment of touch with speech. Results Greater variance was observed in the frequency of touch and its total duration in the input to children who are DHH. Furthermore, touches produced by mothers of children who are DHH were significantly more likely to be aligned with speech than touches produced by mothers of children with normal hearing. Conclusion Caregivers' modifications in the input to children who are DHH are observed in the combination of speech with touch. The implications for such patterns and how they may impact children's attention and access to the speech signal are discussed.


Onset of incommensurate interfacial instability in a minimal model of dry friction.
We present a minimal model of dry friction between two incommensurate interfaces sliding at high relative velocity. Many of the features of the friction force for the full two-dimensional many-body dynamical system-particularly in the sub-critical velocity regime-are captured by our one-dimensional Einstein model, where the motion of a typical interfacial atom is constrained to be vertical to the sliding plane. Beyond the linear response of force versus sliding velocity, the anharmonic Einstein model predicts a doublet resonance peak, whereupon a catastrophe in the model signals the onset of a plastic deformation mechanism for frictional sliding, namely, the instability of the interface. Higher velocities than this critical value require a much more sophisticated description of the production and coalescence of dislocations into a microstructure.


Deep learning based classification of solid lipid-poor contrast enhancing renal masses using contrast enhanced CT.
Establish a workflow that utilizes convolutional neural nets (CNN) to classify solid, lipid-poor, contrast enhancing renal masses using multiphase contrast enhanced CT (CECT) images and to assess the performance of the resulting network. In this institutional review board approved study of 143 patients with predominantly solid, lipid-poor, contrast enhancing renal lesions (46 benign and 97 malignant), patients with a pre-operative multiphase CECT of the abdomen and pelvis obtained between June 2009 and June 2015 were retrospectively queried. Benign renal masses included oncocytoma and lipid-poor angiomyolipoma and the malignant group included clear cell, papillary, and chromophobe carcinomas.Region of interests of whole tumor volumes were manually segmented, and CT phase images with the largest cross-section of the segmented tumor in the axial plane were used for assessment. Post-surgical pathological evaluation was used to establish diagnosis.The segmented images of renal masses were used as input to a CNN. The data were augmented and split into training (83.9%) and validation sets (16.1%) to determine the hyperparameters of the CNN. Thereafter. the performance of the resulting CNN was quantified using eightfold cross-validation. The CNN-based classifier demonstrated an overall accuracy of 78% (95% confidence interval: 76-80%), sensitivity of 70% (95% confidence interval: 66-74%), specificity of 81% (79-83%) and an area under the curve of 0.82. A CNN-based classifier to diagnose solid enhancing malignant renal masses based on multiphase CECT images was developed. It was established that a CNN-based classifier could be trained to accurately distinguish malignant renal lesions.


Synthetic Biology-Driven Microbial Production of Resveratrol: Advances and Perspectives.
Resveratrol, a bioactive natural product found in many plants, is a secondary metabolite and has attracted much attention in the medicine and health care products fields due to its remarkable biological activities including anti-cancer, anti-oxidation, anti-aging, anti-inflammation, neuroprotection and anti-glycation. However, traditional chemical synthesis and plant extraction methods are impractical for industrial resveratrol production because of low yield, toxic chemical solvents and environmental pollution during the production process. Recently, the biosynthesis of resveratrol by constructing microbial cell factories has attracted much attention, because it provides a safe and efficient route for the resveratrol production. This review discusses the physiological functions and market applications of resveratrol. In addition, recent significant biotechnology advances in resveratrol biosynthesis are systematically summarized. Furthermore, we discuss the current challenges and future prospects for strain development for large-scale resveratrol production at an industrial level.


Sjögren's syndrome in patients with interstitial cystitis.
Patients with interstitial cystitis, a chronic nonbacterial inflammation of the bladder, were investigated for the presence of systemic autoimmune diseases, in particular for Sjögren's syndrome (SS). Ten patients were included in the study on the basis of a diagnosis of interstitial cystitis according to usual criteria. They underwent clinical and laboratory investigations including those for keratoconjunctivitis (KCS) and focal lymphocytic sialoadenitis (FLS). In 2 patients both KCS and FLS were present allowing the diagnosis of primary SS according to classification criteria. Additionally, in 6 patients one of the 2 hallmarks of primary SS was present, KCS in 3 and FLS in 3. Interstitial cystitis is a new example of a disease that occurs in association with SS, supporting the concept that interstitial cystitis is an autoimmune cystitis. The clinical relevance of the finding is that a high index of suspicion for SS is indicated in patients with interstitial cystitis.


The effect of nursing-implemented sedation on the duration of mechanical ventilation in the ICU.
We aimed to compare the effects of nursing-implemented sedation protocol and daily interruption of sedative infusion on the duration of mechanical ventilation. Fifty patients receiving mechanical ventilation and requiring sedation in the intensive care unit (ICU) were randomly selected to receive either daily interruption of sedative infusion (Group P, n=25) or nursing-implemented sedation protocol (Group N, n=25). In Group P, daily interruption of sedative infusions without any sedation protocol was performed by physicians. In Group N, nursing-implemented sedation protocol prepared by physicians was applied. In this group, if the ideal level of sedation was not achieved, information was given by nurses to physicians. Patients in each group were compared according to demographic variables, duration of mechanical ventilation and sedation, length of stay in the ICU, and mortality. Demographic variables, length of stay in the ICU and mortality were similar between the two groups. In Group P, duration of sedation and mechanical ventilation were significantly shorter than in Group N. Light sedation was seen more frequently in Group P and deep sedation in Group N. Daily interruption of sedative infusions provided shorter duration of sedation and mechanical ventilation than nursing-implemented sedation with protocol. Although nurse-implemented sedation protocol has been found acceptable, if the number of nurses is lacking, we believe the nurse-implemented sedation protocol should not be applied.


Risk Factors of Reperfusion Failure following Primary Angioplasty for ST-Segment Elevation Myocardial Infarction (STEMI).
Although percutaneous coronary intervention (PCI) improves outcomes compared to thrombolysis, a substantial number of ST-elevation myocardial infarction (STEMI) patients do not achieve optimal myocardial reperfusion. This study was designed to evaluate factors related to suboptimal myocardial reperfusion after primary PCI in patients with STEMI. Totally, 155 patients (124 men; mean age = 56.6 ± 11.03 years, range = 31- 85 years) with STEMI undergoing primary PCI were retrospectively studied. Additionally, the relationships between the occurrence of reperfusion failure and variables such as age, sex, cardiac risk factors, family history, Body Mass Index, time of symptom onset, ejection fraction, previous PCI, coronary artery bypass graft surgery or previous myocardial infarction, and angiographic data were analyzed. Procedural success was 97.1% and complete ST resolution occurred in 43.2%. Age; cardiac risk factors; family history; body mass index; previous MI, coronary artery bypass graft surgery, or PCI; and use of thrombectomy device and GPIIb/IIIa inhibitor were not the determining factors (p value > 0.05). According to our multivariate analysis, time of symptom onset (OR [95% CI]: 045 [0.2 to 0.98]; p value = 0.044) and ejection fraction (OR [95% CI]:0.37 [0.26 to .091]; p value = 0.050) had reverse and male gender had direct significant associations with failed reperfusion (OR [95% CI]: 0.34 [0.11 to 1.08]; p value = 0.068). More degrees of ST resolution occurred when the right coronary artery was the culprit vessel (p value = 0.001). The presence of more than three cardiac risk factors was associated with failed reperfusion (p value = 0.050). Considering the initial risk profile of patients with acute STEMI, including time of symptom onset and ejection fraction, as well as the accumulation of cardiac risk factors in a given patient, we could predict failed myocardial reperfusion to design a more aggressive therapeutic strategy.


Management of depression in medical patients.
The management of depression in the medically ill is a complex task that requires considerable clinical skills. The aim of this review is to outline evaluation strategies which may lead to a more effective use of current psychiatric diagnostic criteria and to suggest clinical guidelines for the use of antidepressant medications and psychotherapeutic techniques. The multifactorial determinants and modes of expression of depression in the medical patient require further research. Treatment outcome studies involving drug treatment or short-term psychotherapeutic approaches or both are needed. Antidepressant drugs remain the most specific and readily available treatment of major depressive disorders in the setting of medical disease. In case of organic affective syndromes, treatment should be primarily directed to the physical condition.


Isolation and on-line identification of antioxidant compounds from three Baccharis species by HPLC-UV-MS/MS with post-column derivatisation.
The aqueous extracts of aerial parts of Baccharis trimera (Less.) DC., B. crispa Spreng. and B. usterii Heering (Asteraceae) displayed significant radical scavenging activity in a diphenylpicrylhydrazole (DPPH)/TLC assay. In order to rapidly identify the active principles, the crude extracts were analysed by HPLC-UV, and an HPLC-micro-fractionation of the extract of B. usterii was performed. Six quinic acids derivatives (1-6) were isolated from B. usterii by MPLC. The fractions were monitored by DPPH/TLC assay and a series of radical-scavenging quinic acid derivatives could be identified. The comparison of the HPLC profiles of the extracts of B. usterii, B. trimera and B. crispa was performed. In order to obtain complementary on-line structural information for all peaks of interest, HPLC-MS/MS together with HPLC-UV involving post-column addition of UV shift reagents was undertaken on the crude extract. The interpretation of these data permitted the on-line identification of known compounds, some of which are reported for the first time in this plant.


Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for the detection of hemoglobins as the protein biomarkers for fecal occult blood.
In this study, we discover that hemoglobins (Hb), highly water-soluble globular proteins that are the most predominant proteins detected by matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) mass spectrometry in blood, can be used as protein biomarkers for fecal occult blood (FOB). Hemoglobins were extracted from the feces with pure water and separated from the solids in feces through centrifugation. Singly charged molecular ions of Hb-related alpha chains (theoretical MW: 15 126) and beta chains (theoretical MW: 15 867) were detected by MALDI-TOF operated in linear mode using 4-hydroxy-alpha-cyanocinnamic acid (alpha-CHC) as the matrix (with a volumetric ratio of 1:1). The detection limit of FOB using this method is estimated to be lower than 0.1 microg blood per mg of feces, which is approximately 10 to 100 times lower than that of the conventional chemical approaches. The foods and dietary supplements that commonly interfere with the conventional chemical assays of FOB - such as animal blood food products and tablets containing iron and vitamin C - do not interfere with the detection of Hb biomarkers during MALDI-TOF analysis.


Comparison of human and Hotelling observer performance for a fan-beam CT signal detection task.
A human observer study was performed for a signal detection task for the case of fan-beam x-ray computed tomography. Hotelling observer (HO) performance was calculated for the same detection task without the use of efficient channels. By considering the full image covariance produced by the filtered backprojection (FBP) algorithm and avoiding the use of channels in the computation of HO performance, the authors establish an absolute upper bound on signal detectability. Therefore, this study serves as a baseline for relating human and ideal observer performance in the case of fan-beam CT. Eight human observers participated in a two-alternative forced choice experiment where the signal of interest was a small simulated ellipsoid in the presence of independent, identically distributed Gaussian detector noise. Theoretical performance of the HO, which is equivalent to the ideal observer in this case (see Sec. 13.2.12 in Barrett and Myers [Foundations of Image Science (Wiley, Hoboken, NJ, 2004)], was also computed and compared to the performance of the human observers. In addition to a reference FBP implementation, two FBP implementations with inherent loss of HO signal detectability (e.g., by apodizing the ramp filter) were also investigated. Each of these latter two implementations takes the form of a discrete-to-discrete linear operator (i.e., a matrix), which has a nontrivial null-space resulting in the loss of detectability. Estimated observer detectability index (d(A)) values for the human observers and SNR values for the HO were obtained. While Hanning filtering in the FBP implementation with a cutoff frequency of 1/4 of the Nyquist frequency reduces HO SNR (due to the reconstruction matrix's nontrivial null-space), this filtering was shown to consistently improve human observer performance. By contrast, increasing the image pixel size was seen to have a comparable effect on both the HO and the human observers, degrading performance. These results, which characterize HO and human observer performance for a signal detection task in fan-beam FBP noise, form a basis for applying model observer metrics to fan-beam CT when knowledge of the full image-domain noise statistics is important. Further, by calculating HO performance without relying on channels, these results are particularly relevant when an information theoretic approach is considered, e.g., in optimization of the image reconstruction algorithm with respect to preservation of signal detectability. Finally, the HO (which is here equivalent to the ideal observer) provides an absolute upper bound on detection performance, and our results therefore provide insight into the performance of human observers relative to the optimum for two different cases wherein ideal observer performance is compromised through degradation of the data quality. In one case (regularization), human performance is improved to practically ideal performance, and in the other (larger pixel size), ideal and human observer performance are approximately degraded equivalently.


Kinetic modelling of the photocatalytic inactivation of bacteria.
This work analyzes the kinetic modelling of the photocatalytic inactivation of E. coli in water using different types of kinetic models; from an empirical equation to an intrinsic kinetic model including explicit radiation absorption effects. Simple empirical equations lead to lower fitting errors, but require a total of 12 parameters to reproduce the results of four inactivation curves when the catalyst concentration was increased. Moreover, these parameters have no physical meaning and cannot be extrapolated to different experimental conditions. The use of a pseudo-mechanistic model based on a simplified reaction mechanism reduces the number of required kinetic parameters to 6, being the kinetic constant the only parameter that depends on the catalyst concentration. Finally, a simple modification of a kinetic model based on the intrinsic mechanism of photocatalytic reactions including explicit radiation absorption effects achieved the fitting of all the experiments with only three parameters. The main advantage of this approach is that the kinetic parameters estimated for the model become independent of the irradiation form, as well as the reactor size and its geometrical configuration, providing the necessary information for scaling-up and design of commercial-scale photoreactors for water disinfection.


Evaluation of salivary surface tension in a cohort of young healthy adults.
To determine salivary pH, flow rate (FR) and surface tension (γs) in a cohort of 30 healthy young adults. To acquire cohort biological independent variables (age, gender, weight, height, medications, smoking, pathologies, and allergies) and to correlate them with pH, FR and γs obtained values. Evaluate the possible variation of the γs values during the time after the withdrawal and the influence of the operational abilities of the experimenting operators. Evaluate the relationship between γs, pH and FR and the dependence between pH and FR. Non-stimulated saliva samples were taken in four different time span, for three days, with a drooling method for 15 minutes. The saliva sample was analyzed, in terms of γs, by two different operators (OP1 and OP2), twice consecutive (γs-1 and γs-2) for a total of 360 measurements. The γs was calculated using the du Noüy method. The FR was evaluated by weighing technique and pH by pH indicator papers. The measurements of γs performed by two different operators (OP1, OP2) showed respectively average values of 46.46 mN/m and 43.45 mN/m, while the mean FR was 0.29 ± 0.13 mL/min and the average pH was 7.1 ± 0.43. There were no significant correlations between γs and the biological variables analyzed. We can consider as reference values, in a sample of young adults, γs 45.56 ± 6.51 mN/m.


[Differences in expression and functional organization of the rat tyrosine aminotransferase gene in two lines of Morris hepatoma, 8994 and 7777].
Expression and structural organization of tyrosine aminotransferase (TAT) gene in Morris hepatoma cell line 7777 with active and glucocorticoid-inducible TAT gene and in hepatoma 8994, where TAT gene does not function were analysed. No differences in the number of receptor macromolecules, translocation and nuclear binding of hormone-receptor complexes in hormone sensitive (7777) and resistant (8994) cell lines were demonstrated. Dexamethasone increases TAT gene transcription in 7777 cell line but not 8994. Restriction analysis of TAT gene does not reveal any differences either in structural or in regulatory regions. Gel retardation assay with cloned TAT fragment (-400 b.p.) from normal hepatocytes showed identical shift of mobility in 7777 and 8994 cell lines. Moreover, 5'-flanking sequence (-890 b.p.) of TAT gene linked to the bacterial CAT gene is transiently expressed in both cell lines. We have shown that HpaII site (-105 b.p.) of TAT gene is methylated in those cells where TAT gene does not function (thymus, spleen, Zajdela ascites hepatoma) and is demethylated in TAT gene expressing hepatoma 7777 and normal rat hepatocytes. In hepatoma 8994 there are no DNAse I hypersensitive regions, typical to functioning TAT gene from hepatoma 7777 and normal hepatocytes.


Poly(vinyl alcohol)/hydroxyapatite Monolithic In-Needle Extraction (MINE) device: Preparation and examination of drug affinity.
Polymer-ceramic materials based on poly(vinyl alcohol) (PVA) and hydroxyapatite were applied as sorption material in Monolithic In-Needle Extraction (MINE) device. The presented device provides new possibilities for the examination of bisphosphonates affinity for bone and will be a helpful tool in evaluation of potential antiresorptive drugs suitability. A ceramic part of monoliths was prepared by incorporation of hydroxyapatite (HA) into the reaction mixture or by using a soaking method (mineralization of HA on the PVA). The parameters of synthesis conditions were optimized to achieve a monolithic material having the appropriate dimensions after the soaking process enabling placing of the monolithic material inside the needle. Furthermore, the material must have had optimal dimensions after the re-soaking process to fit perfectly to the needle. Among the sixteen monolithic materials, eight of them were selected for further study, and then four of them were selected as a sorbent material for the MINE device. The material properties were examined on the basis of several parameters: swelling ratio, initial mass reversion and initial diameter reversion, mass growth due to the HA formation, and antiresorptive drug sorption. The MINE device might be then used as a tool for examination of interactions between bisphosphonate and bone. The simulated body fluid containing sodium risedronate (RSD) as a standard compound was passed through the MINE device. The obtained device allowed for sorption about 0.38mg of RSD. The desorption process was carried out in five steps allowing insightful analysis. The MINE device turned out to be a helpful tool for determination of the bisphosphonates affinity to the ceramic part of sorbent (hydroxyapatite) and to assess the usefulness of them as antiresorptive drugs in the future.


Designing and Fabricating Ordered Mesoporous Metal Oxides for CO₂ Catalytic Conversion: A Review and Prospect.
In the past two decades, great progress has been made in the aspects of fabrication and application of ordered mesoporous metal oxides. Ordered mesoporous metal oxides have attracted more and more attention due to their large surface areas and pore volumes, unblocked pore structure, and good thermal stabilities. Compared with non-porous metal oxides, the most prominent feature is their ability to interact with molecules not only on their outer surface but also on the large internal surfaces of the material, providing more accessible active sites for the reactants. This review carefully describes the characteristics, classification and synthesis of ordered mesoporous metal oxides in detail. Besides, it also summarizes the catalytic application of ordered mesoporous metal oxides in the field of carbon dioxide conversion and resource utilization, which provides prospective viewpoints to reduce the emission of greenhouse gas and the inhibition of global warming. Although the scope of current review is mainly limited to the ordered mesoporous metal oxides and their application in the field of CO₂ catalytic conversion via heterogeneous catalysis processes, we believe that it will provide new insights and viewpoints to the further development of heterogeneous catalytic materials.


Broadband ultrasonic attenuation of children and young adults in Japan.
The purpose of this study was to establish broadband ultrasonic attenuation (BUA: dB/MHz) as bone mineral density (BMD) norms for healthy young Japanese and to evaluate the standard values for an ultrasonic bone analyzer (Cuba Clinical, McCue Ultrasonics Ltd., Winchester, England), which facilitates BMD measurement without exposure to radiation. The subjects were 472 healthy young individuals with no endocrine or skeletal disorders, 197 males (mean age 16 y 5 m) and 275 females (mean age 15 y 7 m) aged from 5 to 29 years. BUA was measured at the left calcaneus. The subjects were divided into five age-stratified different age groups of five years intervals. The mean BUA values (dB/MHz) obtained were 40.6, 60.9, 78.0, 90.4 and 86.0 for males, and 41.9, 61.0, 73.4, 68.4 and 70.8 for females in the 5-9, 10-14, 15-19, 20-24 and 25-29 age groups, respectively. A significant positive correlation was observed between BUA and age in both males and females except in the male 25-29 age group and the female 20-24 and 25-29 age groups. A significantly different BUA between males and females was found in the 20-24 and 25-29 age groups (p < 0.001). The BUA values obtained in this study may serve as BMD norms for children and young adults. It might be thought that measuring BUA from childhood through early adulthood made it possible to determine peak values and peak periods of BMD, providing useful information for assessment of growth and development.


Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.
Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein Gs. Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we report the cryo-electron microscopy structure of the peptide-activated GLP-1R-Gs complex at near atomic resolution. The peptide is clasped between the N-terminal domain and the transmembrane core of the receptor, and further stabilized by extracellular loops. Conformational changes in the transmembrane domain result in a sharp kink in the middle of transmembrane helix 6, which pivots its intracellular half outward to accommodate the α5-helix of the Ras-like domain of Gs. These results provide a structural framework for understanding class B GPCR activation through hormone binding.


Spectral shifts of matrix isolated species as criteria for acid-base interactions with solid Xe.
The vibrational spectra of H(2)SO(4)/H(2)O vapors trapped in solid Xe are reported and the spectral shifts are compared to the analogous spectra in argon matrices. In the same matrix layer the nu(OH) stretches of highly acidic species (H(2)SO(4) and H(2)SO(4)*H(2)O) show distinctly larger red shifts as opposed to species of lower acidity or to modes which do not involve directly the O-H bond. A correlation is obtained of the spectral shifts with energies empirically estimated from acidic properties attributed to a variety of molecular species. The hydrogen bonding observed between acidic species and Xe atoms is considered relevant to the formation of xenon hydrides in irradiated matrices. The spectral interpretation is complemented by B3LYP and MP2 calculations of the interaction energies and fundamental modes of vibration.


Imaging of the post-operative shoulder: does injection of iodinated contrast in addition to MR contrast during arthrography improve diagnostic accuracy and patient throughput?
Post-operative shoulder patients are often difficult to image due to scar tissue, metallic artifact, and residual irregularity of anatomic structures. The purpose of this study was to assess MR versus MR arthrography versus CT arthrography in the post-operative shoulder. Also, we assessed whether injecting CT contrast in addition to MR contrast during arthrography improved patient care. One hundred consecutive post-operative conventional shoulder MR and MR arthrography exams performed on the same patients were reviewed retrospectively by two musculoskeletal radiologists. A combination of gadolinium and CT contrast was injected at arthrography so CT imaging could be performed post arthrography if metallic artifact precluded MR imaging. Twenty-two of these patients also had CT exams performed post-arthrography due to metallic artifact on MR exam. Exams were assessed for labral tears and supraspinatus tendon tears. All patients went on to arthroscopy. Of these 100 patients, 35 had SLAP (superior labral anterior to posterior) tears, 22 had posterior labral tears, 24 had anterior labral tears, and 46 had full-thickness supraspinatus tendon tears on conventional MR exam. On MR arthrography, 48 patients had SLAP tears, 26 had posterior labral tears, 27 had anterior labral tears, and 54 had full-thickness supraspinatus tendon tears. MR arthrogram detected 12 SLAP tears, three posterior labral tears, three anterior labral tears, and nine supraspinatus tendon tears not detected on conventional MR exam. Twenty-two patients had additional imaging performed with CT arthrography due to metallic artifacts precluding MR assessment of shoulder pathology. There were four SLAP tears, six posterior labral tears, five anterior labral tears, and five supraspinatus tendon tear seen on CT arthrography not seen on MR exam. MR arthrography is more accurate than conventional MR in assessment of post-operative shoulder pathology. CT arthrography can detect additional pathology when there is metallic artifact in post-operative patients. It is beneficial to inject a combination of gadolinium and CT contrast at arthrography so CT imaging can be performed post-arthrography if metallic artifact precludes imaging shoulder pathology by MR.


Non-invasive vibrometry-based diagnostic detection of acetabular cup loosening in total hip replacement (THR).
Total hip replacement is aimed at relieving pain and restoring function. Currently, imaging techniques are primarily used as a clinical diagnosis and follow-up method. However, these are unreliable for detecting early loosening, and this has led to the proposal of novel techniques such as vibrometry. The present study had two aims, namely, the validation of the outcomes of a previous work related to loosening detection, and the provision of a more realistic anatomical representation of the clinical scenario. The acetabular cup loosening conditions (secure, and 1 and 2 mm spherical loosening) considered were simulated using Sawbones composite bones. The excitation signal was introduced in the femoral lateral condyle region using a frequency range of 100-1500 Hz. Both the 1 and 2 mm spherical loosening conditions were successfully distinguished from the secure condition, with a favourable frequency range of 500-1500 Hz. The results of this study represent a key advance on previous research into vibrometric detection of acetabular loosening using geometrically realistic model, and demonstrate the clinical potential of this technique.


Probing the electronic effect of carbon nanotubes in catalysis: NH(3) synthesis with Ru nanoparticles.
Carbon nanotubes (CNTs) have been shown to modify some properties of nanomaterials and to modify chemical reactions confined inside their channels, which are formed by curved graphene layers. Here we studied ammonia synthesis over Ru as a probe reaction to understand the effect of the electron structure of CNTs on the confined metal particles and their catalytic activity. The catalyst with Ru nanoparticles dispersed almost exclusively on the exterior nanotube surface exhibits a higher activity than the CNT-confined Ru, although both have a similar metal particle size. Characterization with TEM, N(2) physisorption, H(2) chemisorption, temperature-programmed reduction, CO adsorption microcalorimetry, and first-principles calculations suggests that the outside Ru exhibits a higher electron density than the inside Ru. As a result, the dissociative adsorption of N(2), which is an electrophilic process and the rate-determining step of ammonia synthesis, is more facile over the outside Ru than that over the inside one.


Herpes zoster - typical and atypical presentations.
Varicella- zoster virus infection is an intriguing medical entity that involves many medical specialties including infectious diseases, immunology, dermatology, and neurology. It can affect patients from early childhood to old age. Its treatment requires expertise in pain management and psychological support. While varicella is caused by acute viremia, herpes zoster occurs after the dormant viral infection, involving the cranial nerve or sensory root ganglia, is re-activated and spreads orthodromically from the ganglion, via the sensory nerve root, to the innervated target tissue (skin, cornea, auditory canal, etc.). Typically, a single dermatome is involved, although two or three adjacent dermatomes may be affected. The lesions usually do not cross the midline. Herpes zoster can also present with unique or atypical clinical manifestations, such as glioma, zoster sine herpete and bilateral herpes zoster, which can be a challenging diagnosis even for experienced physicians. We discuss the epidemiology, pathophysiology, diagnosis and management of Herpes Zoster, typical and atypical presentations.


For new Escherichia coli o antigens, o158, o159, o160 and o161, and two new h antigens, h53 and h54.
Four Escherichia coli strains were established as antigenic test strains for four new o groups, o158, o159, o160 and o161. The strains of o158 and o159 were isolated from cases of infantile diarrhoea in Great Britain, while the o160 and o161 strains were isolated from faecal specimens in Arabia. The o161 strain was at the same time designated as test strain of a new H antigen, H54, while a strain belonging to o group 148 was established as antigenic test strain for H53; this strain was also isolated from human faeces in Arabia.


[Retroperitoneal tumor diagnosed as metastatic lymph node from gastric adenocarcinoma following laparoscopic resection].
A 55-year-old woman who presented with a retroperitoneal tumor was referred to our department. At the age of 51, she underwent a total gastrectomy for gastric cancer. Postoperatively, TS-1 administration was given for Virchow lymph node metastasis, which disappeared within 2 years and TS-1 was stopped. However, computed tomography revealed a retroperitoneal tumor adjacent to the inferior vena cava, which gradually increased and began to compress the inferior vena cava. Under a diagnosis of retroperitoneal tumor, laparoscopic resection was performed. Pathological findings led to a diagnosis of lymph node metastasis from an adenocarcinoma of the stomach.


Quinotrierixin inhibits proliferation of human retinal pigment epithelial cells.
To investigate the effect of quinotrierixin, a previously reported inhibitor of X-box binding protein 1 (XBP1), on cell proliferation and viability in human retinal pigment epithelium (RPE) cells. Subconfluent human RPE cells (ARPE-19) were exposed to quinotrierixin for 16-24 h. Cell proliferation was determined with 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay, hemocytometer counts, and CyQUANT NF Cell Proliferation Assay. Apoptosis was detected with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling assay. XBP1 mRNA splicing and expression of endoplasmic reticulum stress response genes were determined in cells exposed to thapsigargin in the presence or absence of quinotrierixin. Overexpression of spliced XBP1 was achieved with adenovirus. Quinotrierixin reduced RPE cell proliferation in a dose-dependent manner without inducing apoptosis. In cells exposed to thapsigargin, quinotrierixin inhibited XBP1 mRNA splicing and PKR-like endoplasmic reticulum kinase activation, and reduced cellular and nuclear levels of spliced XBP1 and C/EBP homologous protein. Paradoxically, quinotrierixin exacerbated endoplasmic reticulum stress-induced phosphorylation of eIF2α, which in turn led to decreased protein translation. Overexpressing spliced XBP1 partially reversed the inhibition of cell proliferation by quinotrierixin. These results suggest that inhibiting XBP1 splicing contributes to quinotrierixin's negative effect on RPE cell proliferation, but other mechanisms such as reduction of protein translation are also involved. Quinotrierixin inhibits RPE cell proliferation and may be used as a novel antiproliferative drug for treating proliferative vitreoretinopathy. Future studies are needed to investigate the in vivo effect of quinotrierixin on RPE proliferation in animal models of proliferative vitreoretinopathy.


[Antidepressant effects of dopamine agonists. Experimental and clinical findings].
Results of preclinical and clinical studies implicate that, in addition to serotonin and norepinephrin, dopaminergic mechanisms play a role in the pathogenesis and treatment of depression. Newer antidepressants such as bupropion, sertraline, and venlafaxine act as partial inhibitors of presynaptic dopamine reuptake. Experimental studies show that dopaminergic effects contribute to the development of anxiety, depression, and anhedonia. These studies revealed, among the new nonergot dopamine agonists, anxiolytic properties for ropinirole and anxiolytic, antidepressive, and antianhedonic effects of pramipexole which seem to relate to its specific action on D(2) and D(3) receptors in the mesolimbic system and prefrontal cortex. In addition, affective disorders may be associated with impairments of neuronal plasticity, and pramipexole seems to exert neurotrophic properties. Controlled and open studies in depressed patients with Parkinson's disease show therapeutic effects of dopamine agonists on motor deficits, anhedonia, and depression. Various dopamine agonists have been tested in open studies in patients with depression and may add to the spectrum of treatment options in mood disorders. Recently published placebo-controlled trials in small patient groups implicate that pramipexole is effective as additional treatment to mood stabilizers in I and II bipolar depression.


Fetal forms of oligoaminopeptidase, dipeptidylaminopeptidase IV, and sucrase in human intestine and meconium.
Particles of meconium sedimenting at 105,000 g contain sucrase and various brush border peptidase activities. Oligoaminopeptidase, dipeptidylaminopeptidase, and sucrase solubilized by papain from meconium particles of preterm newborns or from brush border of human fetuses during the 4th month of gestation were compared with the same enzymes prepared from adult jejunal and ileal brush border. The following are characteristics of fetal intestinal brush border enzymes: (a) a faster anodal electrophoretic mobility in polyacrylamide and in agar gel; (b) the same specific activity, as measured by quantitative crossed immunoelectrophoresis utilizing an antiserum against adult brush border membranes; (c) complete fusion of the immunoprecipitation lines with the adult enzymes by using the same antiserum; and (d) a different binding pattern to Helix pomatia lectin and lentil lectin. The results suggest that the charge difference between adult and fetal human brush border enzymes, which causes the difference in the gel electrophoretic mobility, is most probably due, at least in part, to differences in carbohydrate composition of these glycoproteins. Extensive neuraminidase digestion causes no or only minor changes of the electrophoretic mobility of the meconial enzymes. The difference between adult and meconial enzymes is therefore apparently not, or not only, due to different sialic acid content. These results suggest that many intestinal brush border enzymes in fetal life and at birth are in forms structurally different from those in adult life.


Design and Application of Sensors for Chemical Cytometry.
The bulk cell population response to a stimulus, be it a growth factor or a cytotoxic agent, neglects the cell-to-cell variability that can serve as a friend or as a foe in human biology. Biochemical variations among closely related cells furnish the basis for the adaptability of the immune system but also act as the root cause of resistance to chemotherapy by tumors. Consequently, the ability to probe for the presence of key biochemical variables at the single-cell level is now recognized to be of significant biological and biomedical impact. Chemical cytometry has emerged as an ultrasensitive single-cell platform with the flexibility to measure an array of cellular components, ranging from metabolite concentrations to enzyme activities. We briefly review the various chemical cytometry strategies, including recent advances in reporter design, probe and metabolite separation, and detection instrumentation. We also describe strategies for improving intracellular delivery, biochemical specificity, metabolic stability, and detection sensitivity of probes. Recent applications of these strategies to small molecules, lipids, proteins, and other analytes are discussed. Finally, we assess the current scope and limitations of chemical cytometry and discuss areas for future development to meet the needs of single-cell research.


Contrast-enhanced MR angiography: theory and optimization.
It is now possible to perform contrast arteriography safely and rapidly by taking advantage of gadolinium contrast agents and three-dimensional MR imaging. Although the development of this approach to arteriography is in its infancy, the image quality already rivals conventional arteriography. As we continue to develop this technique by taking advantage of more pulse sequence tricks, improving hardware, and improving contrast agents, the field of vascular imaging will undoubtedly be transformed. This article discusses the fundamental concepts underlying this approach to angiography.


[Acute noninflammatory renal failure. New pathogenetic aspects in light of findings obtained in autopsy and biopsy of kidneys].
Thorough studies of kidney specimens obtained at autopsy or by renal biopsy revealed, that in noninflammatory acute renal failure oliguria/anuria is caused by increased activation o the renal renin-angiotensin system and increased generation of adenosine. At the polyuric phase moderately increased adenosine in kidney tissue seems to be the main factor responsible for decreased glomerular filtration.


Can .OH scavengers protect against direct UV-C damage in vivo?
It has previously been shown that ethanol and tert-butanol protect poly(U) against strand breaks from pulsed laser ultraviolet (UV) photons (lambda = 248 nm). This protection is believed to be based on a modification of direct DNA damage, not on scavenging hydroxyl radicals. In this paper, several .OH scavengers were tested in vivo with Escherichia coli DNA repair-deficient mutants to see if protection could also be demonstrated with non-laser UV photons (lambda approximately 254 nm). No protection was observed.


Short-term bioelectric stimulation of collective cell migration in tissues reprograms long-term supracellular dynamics.
The ability to program collective cell migration can allow us to control critical multicellular processes in development, regenerative medicine, and invasive disease. However, while various technologies exist to make individual cells migrate, translating these tools to control myriad, collectively interacting cells within a single tissue poses many challenges. For instance, do cells within the same tissue interpret a global migration 'command' differently based on where they are in the tissue? Similarly, since no stimulus is permanent, what are the long-term effects of transient commands on collective cell dynamics? We investigate these questions by bioelectrically programming large epithelial tissues to globally migrate 'rightward' via electrotaxis. Tissues clearly developed distinct rear, middle, side, and front responses to a single global migration stimulus. Furthermore, at no point poststimulation did tissues return to their prestimulation behavior, instead equilibrating to a 3rd, new migratory state. These unique dynamics suggested that programmed migration resets tissue mechanical state, which was confirmed by transient chemical disruption of cell-cell junctions, analysis of strain wave propagation patterns, and quantification of cellular crowd dynamics. Overall, this work demonstrates how externally driving the collective migration of a tissue can reprogram baseline cell-cell interactions and collective dynamics, even well beyond the end of the global migratory cue, and emphasizes the importance of considering the supracellular context of tissues and other collectives when attempting to program crowd behaviors.


Association Between Domain-Specific Physical Activity and Chronic Low Back Pain in Community-Dwelling Older Adults: A Cross-Sectional Study.
To investigate the association between physical activity (PA) domains and chronic low back pain (LBP) in older adults. A cross-sectional study where sociodemographic, behavioral, and health variables; PA; and presence of chronic LBP were collected. Higher scores of PA defined the "more active" participants. Binary logistic regression was used to test the association between PA domains and chronic LBP. A total of 516 participants were included. The mean age was 71.8 (95% confidence interval, CI, [71.1, 72.5]) years, and 29%, 27%, 25%, and 31% were identified as "more active" in the household, sports, leisure-time, and total PA domains, respectively. "More active" participants in sports (odds ratio = 0.62, 95% CI [0.40, 0.97]), leisure-time (odds ratio = 0.54, 95% CI [0.35, 0.85]) and total (odds ratio = 0.60, 95% CI [0.39, 0.92]) PA domains were less likely to report chronic LBP. High levels of sports, leisure-time, and total PA were inversely associated with chronic LBP.


Trigger of a migraine headache among Thai adolescents smartphone users: a time series study.
The study aims to investigate the effect of modern technology in the trigger of migraine headaches in high school students by using generalized estimating equation analysis. The prospective time series study was conducted in one hundred and forty-five smartphones using high school students in Chiang Mai Province who each completed a headache diary giving a total of 12,969 data entries. The smartphone output power was measured and recorded by a smartphone application. Smartphone use, sleep quality, anxiety, and depression also were assessed. Results revealed that the prevalence of repeated headache be 13.4% and migraine 16.9%. The migraine had the strongest association with handfree device use and internet use, followed by age and anxiety. Furthermore, the strongest effect of smartphone output power in triggering a migraine was found at ≤ 1.79×10-5 and 1.80-1.99×10-5 mW ranges. Meanwhile, Lag_6 of daily smartphone output power exposure produced the migraine effect in a reverse dose-response manner. The smartphone electromagnetic radiation was a primary migraine trigger. The study results led to the recommendation to avoid triggers by use of smartphone talking with hand-free devices to prevent a recurrent migraine.


Adult 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and effects on male reproductive organs in three differentially TCDD-susceptible rat lines.
The contribution of genetic factors to adult male reproductive system toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was analyzed in three rat lines differentially resistant to TCDD acute lethality: line A, B, and C rats (selectively bred from TCDD-resistant Han/Wistar [Kuopio; H/W] and TCDD-sensitive Long-Evans [Turku/AB; L-E] rats). The resistance is linked to a mutated H/W-type aryl hydrocarbon receptor allele in line A and to an H/W-type unknown "B" allele in line B. Line C rats do not have resistance alleles. Mature male line A, B and C rats were given single oral doses up to 1000, 300, and 30 micrograms/kg TCDD, respectively. The dose-responses of TCDD effects on male reproductive organ weights, sperm numbers, and serum testosterone concentrations were analyzed 17 days after exposure. Serum testosterone concentrations were decreased by the highest doses of TCDD, and there were no major sensitivity differences among the rat lines. Correspondingly, the decrease in relative weight of ventral prostate and seminal vesicles was seen only after a dose of >/=100 micrograms/kg TCDD. Thus the effect was observed only in resistant lines A and B. The relative weights of testes and epididymides were not affected. Significant decrease in spermatogenesis was observed in each rat line, but the amount of decrease was reduced by resistance alleles. The highest TCDD dose decreased the daily sperm production by 37, 38, and 60% in line A, B, and C rats, respectively. Therefore, the resistance alleles appear to selectively modify the TCDD effects on the adult male reproductive system. The fact that the influence of resistance alleles on spermatogenesis is different from that on androgenic status indicates that the effect of TCDD on sperm numbers is not fully related to decreased serum testosterone.


Responsiveness to montelukast is associated with bronchial hyperresponsiveness and total immunoglobulin E but not polymorphisms in the leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes in Korean children with exercise-induced asthma (EIA).
As previous studies have shown that cysteinyl leukotrienes are important mediators in exercise-induced bronchoconstriction (EIB), and leukotriene receptor antagonists (LTRAs) such as montelukast have been shown to improve post-exercise bronchoconstrictor responses, we herein investigated whether clinical responsiveness to montelukast was associated with polymorphisms in the genes encoding leukotriene C4 synthase (LTC4S) and cysteinyl leukotriene receptor 1 (CysLTR1) and/or clinical parameters in Korean asthmatic children with EIB. The study population consisted of 100 asthmatic children with EIB. The individuals studied were given exercise challenge tests before and after receiving montelukast (5 mg/day) for 8 weeks. Responders were defined as children showing>10% post-treatment improvement in forced expiratory volume in 1 s (FEV1). The LTC4S A(-444)C and CysLTR1 T(+927)C polymorphisms were genotyped by PCR-restriction fragment length polymorphism analysis. Of 100 enrolled children, 68 were classified as responders and 32 were classified as non-responders. No significant association was observed between montelukast responsiveness and LTC4S or CysLTR1 genotype, either alone or in combination. In contrast, montelukast-induced improvement in FEV(1) after exercise was correlated with higher pre-treatment PC20 (methacholine) values (r=0.210, P=0.036) and lower total IgE levels (r=-0.216, P=0.031). The LTC4S A(-444)C and CysLTR1 T(+927)C genotypes do not appear to be useful for predicting clinical responsiveness to montelukast, whereas bronchial hyperresponsiveness and total IgE appear to predict the degree of montelukast responsiveness in Korean asthmatic children with EIB.


Association of viable Mycobacterium leprae with Type 1 reaction in leprosy.
The working hypothesis is that, viable Mycobacterium leprae (M. leprae) play a crucial role in the precipitation of Type 1 reaction (T1R) in leprosy. A total of 165 new multibacillary patients were studied. To demonstrate presence of viable M. leprae in reactional lesion (T1R+), three tests were used concurrently viz. growth in the mouse foot pad (MFP), immunohistochemical detection of M. leprae secretory protein Ag85, and 16s rRNA--using in situ RT-PCR. Mirror biopsies and non reactional lesions served as controls (T1R-). A significantly higher proportion of lesion biopsy homogenates obtained at onset, from T1R(+) cases have shown unequivocal growth in MFP, proving the presence of viable bacteria, as compared to T1R(-) (P < 0.005). In contrast, few Mirror biopsies were positive in both T1R(+) and T1R(-). With respect to Ag85, while the overall positivity was higher in T1R(+) (74%), however the intensity of staining (Grade 2+) was disproportionately higher in T1R(+) BT-BB lesions 11/20 (55%). In the rebiopsies obtained during a repeat episode of T1R, Ag 85 as well as 16s rRNA, positivity (62% & 100%) was higher in T1R(+). It is inferred therefore 'viable' bacteria are an essential component in T1R and difference in the quality of bacilli, not the quantity or the ratio of dead to viable play a role in the precipitation of T1R. In conclusion, the findings show that 'metabolically active' M. leprae is a component/prerequisite and the secretory protein Ag 85, might be the trigger for precipitation of T1R.


CRYPTOCOCCOSIS: A bibliographic narrative review on antifungal resistance.
Cryptococcosis is an infectious fungal disease widely studied for its epidemiological importance in the context of public health, given the high morbidity and mortality associated with this invasive fungal infection. Many cases of the disease present clinical resistance and progress to death, even in the presence of antifungal therapy. The prolonged use of triazole drugs to maintain the treatment of cryptococcosis in AIDS patients, can lead to selective pressure from mutant strains, among other resistance mechanisms, justifying the poor clinical evolution of some cases. In this study, a narrative review of the literature on the occurrence of antifungal resistance in cryptococcosis agents was performed. Publications from 2010 to 2022 that address this topic were selected using Google Scholars and Scopus website. Data from the studies were analyzed for the values of minimum inhibitory concentration (MIC) of drugs used in the management of cryptococcosis. The review showed that the highest MIC values occurred for voriconazole, especially against C. neoformans. It is concluded that there is a lack of studies with statistical analysis of the data obtained, in order to provide a better dimensioning of the resistance rates of cryptococcosis agents to different antifungal agents, both in geographical and temporal context.


Lipopolysaccharide-Induced lncRNA TMC3-AS1 is Highly Expressed in Osteoporosis and Promotes Osteoblast Apoptosis by Suppressing the Formation of Mature miR-708.
LncRNA TMC3-AS1 expression is affected by lipopolysaccharide (LPS), a contributor to osteoporosis (OS). Therefore, we hypothesized that TMC3-AS1 could inhibit osteoblast apoptosis and interact with miR-708, a regulator of osteoblast apoptosis in OS. Differential expression of TMC3-AS1 and miR-708 (mature and premature) in OS patients and controls was analyzed using RT-qPCR. Subcellular location of TMC3-AS1 in osteoblasts was analyzed using subcellular fractionation assay. The direct interaction between TMC3-AS1 and premature miR-708 was analyzed using RNA pulldown assay. The role of TMC3-AS1 and miR-708 in the expression of each other was explored with overexpression assays. Cell apoptosis induced by LPS was analyzed using cell apoptosis assay. TMC3-AS1 and premature miR-708 were highly expressed in OS and were upregulated by LPS in osteoblasts. In contrast, mature miR-708 was under-expressed in OS and downregulated by LPS. TMC3-AS1 directly interacted with premature miR-708 and was detected in both the nuclear and cytoplasm fractions. TMC3-AS1 decreased premature miR-708 level and increased mature miR-708 level. Moreover, TMC3-AS1 increased LPS-induced cell apoptosis and suppressed the role of miR-708 in cell apoptosis. TMC3-AS1 is highly expressed in OS and promotes LPS-induced osteoblast apoptosis by reducing miR-708 maturation.


[Potentiation by promethazine of hypotensive effects of adrenergic drugs on intraocular pressure].
Experiments including previous installations of promethazine (pipolphen) into the conjunctival sac followed by the topical administration of beta-adrenergic blocker timolol or a sympathomimetic drug isoptoepinal (adrenaline) have been performed on 24 rabbits (48 eyes). The substantial changes in the action mode of the mentioned drugs as the enhancement of their hypotensive effect on the intraocular pressure (IOP) have been demonstrated under the performance of the above mentioned procedure. When applied after promethazine instillations, timolol induced significantly increased outflow facility of the aqueous humor that was not usually noted in the cases of timolol topical instillations without a pretreatment of the eye with promethazine. The similar increased hypotensive effect on the IOP was noted for adrenaline when it has been used after promethazine treatment. The possible mechanisms underlying the changes in pharmacological activities of the investigated adrenergic drugs are discussed.


Mixed malignant germ cell tumor of the fallopian tube.
Immature teratomas of the fallopian tube are exceedingly rare with only three reported cases in the English literature. Reported here is a case of primary mixed malignant germ cell tumor of the fallopian tube composed of immature teratoma and yolk sac tumor.


[Overcontinence in females after orthotopic replacement of the urinary bladder].
Treatment results were analysed for 27 patients (mean age 53 +/- 7 years) after orthotopic urinary diversion (by the method of Studer, Hautmann) following radical cystectomy. Radical cystectomy was performed without nerve preservation in all the patients. Overcontinence was detected in 4 (26.6%) of 15 patients who had undergone urinary diversion by a conventional method. At the average, residual urine was 220 ml. The modified operation for prevention of urine retention was made in 12 subsequent cystectomies. Neobladder topography was studied with MR imaging (MRI) of the pelvic organs and videoroentgenoreservoiroscopy, urodynamic examination was combined with electromyography of the pelvic base muscles. MRI has found that in patients without retention the reservoir was above linea pubbo-coccigeus both at rest and voiding. In patients with overcontinence at rest topographic details by MRI did not differ from those in patients without retention but in stress reservoir changed position. The modification proposed allows one to avoid change in reservoir position and to prevent formation of acute urethra-reservoir angle. Thus, the cause of retention (overcontinence) of the continent orthotopic intestinal neobladder is eliminated.


Analysis of the Fc receptor-like-3 (FCRL3) locus in Caucasians with autoimmune disorders suggests a complex pattern of disease association.
A four-marker haplotype in the 5' region of the Fc receptor-like 3 gene (markers FCRL3_3 to FCRL3_6) has been identified recently as contributing to rheumatoid arthritis (RA) susceptibility in the Japanese population. The promoter FCRL3_3*C allele also showed significant association with autoimmune thyroid disease and systemic lupus erythematosus. These findings raise the possibility that this locus may influence autoimmune disease susceptibility across many populations. We analyzed the same four 5' FCRL3 single nucleotide polymorphism markers, together with three additional exonic single nucleotide polymorphisms in the FCRL3 gene, in cohorts of white Caucasians with Graves' disease (n = 625), type 1 diabetes (n = 279), autoimmune Addison's disease (AAD; n = 200), and RA (n = 769). Healthy controls from the United Kingdom (n = 490) and New Zealand (n = 593) were used. Six of the seven FCRL3 markers showed association with AAD (P = 0.005-0.0001), with maximum evidence at the FCRL3_3*T allele [P([corrected]) = 0.0008; odds ratio (OR), 1.61; 5-95% confidence intervals (CIs), 1.26-2.05]. The most common seven-marker FCRL3 haplotype (TGGGAAA) was also found to be significantly associated with AAD (P([corrected]) = 1.1 x 10(-4); OR, 1.71; 5-95% CIs, 1.33-2.18). There was nominal evidence for allelic association at the marker FCRL3_8 in Graves' disease (OR, 1.50; 5-95% CIs, 1.06-2.13) and at FCRL3_9 with RA (OR, 1.25; 5-95% CIs, 1.01-1.54). The FCRL3 haplotype that is associated with AAD in Caucasians appears to be protective for autoimmune diseases in the Japanese population, demonstrating that this haplotype is unlikely to contain a single primary etiological allele for autoimmunity. Our observations suggest that the susceptibility to autoimmunity at the FCRL3 locus is more complex than initially thought and may extend either side of the currently associated region to include the adjacent FCRL2 gene.


Prehospital and Emergency Care in Adult Patients with Acute Traumatic Brain Injury.
Traumatic brain injury (TBI) is a major healthcare problem and a major burden to society. The identification of a TBI can be challenging in the prehospital setting, particularly in elderly patients with unobserved falls. Errors in triage on scene cannot be ruled out based on limited clinical diagnostics. Potential new mobile diagnostics may decrease these errors. Prehospital care includes decision-making in clinical pathways, means of transport, and the degree of prehospital treatment. Emergency care at hospital admission includes the definitive diagnosis of TBI with, or without extracranial lesions, and triage to the appropriate receiving structure for definitive care. Early risk factors for an unfavorable outcome includes the severity of TBI, pupil reaction and age. These three variables are core variables, included in most predictive models for TBI, to predict short-term mortality. Additional early risk factors of mortality after severe TBI are hypotension and hypothermia. The extent and duration of these two risk factors may be decreased with optimal prehospital and emergency care. Potential new avenues of treatment are the early use of drugs with the capacity to decrease bleeding, and brain edema after TBI. There are still many uncertainties in prehospital and emergency care for TBI patients related to the complexity of TBI patterns.


The influence of democratic racism in nursing inquiry.
Neoliberal ideology and exclusionary policies based on racialized identities characterize the current contexts in North America and Western Europe. Nursing knowledge cannot be abstracted from social, political and historical contexts; the task of examining the influence of race and racial ideologies on disciplinary knowledge and inquiry therefore remains an important task. Contemporary analyses of the role and responsibility of the discipline in addressing race-based health and social inequities as a focus of nursing inquiry remain underdeveloped. In this article, we examine nursing's engagement with ideas about race and racism and explore the ways in which nursing knowledge and inquiry have been influenced by race-based ideological discourses. Drawing on Henry and Tator's framework of democratic racism, we consider how strategic discursive responses-the discourses of individualism, multiculturalism, colour-blindness, political correctness and denial-have been deployed within nursing knowledge and inquiry to reinforce the belief in an essentially fair and just society while avoiding the need to acknowledge the persistence of racist discourses and ideologies. Greater theoretical, conceptual and methodological clarity regarding race, racialization and related concepts in nursing inquiry is needed to address health and social inequities.


Fitness versus longevity in age-structured population dynamics.
We examine the dynamics of an age-structured population model in which the life expectancy of an offspring may be mutated with respect to that of the parent. While the total population of the system always reaches a steady state, the fitness and age characteristics exhibit counter-intuitive behavior as a function of the mutational bias. By analytical and numerical study of the underlying rate equations, we show that if deleterious mutations are favored, the average fitness of the population reaches a steady state, while the average population age is a decreasing function of the average fitness. When advantageous mutations are favored, the average population fitness grows linearly with time t, while the average age is independent of the average fitness. For no mutational bias, the average fitness grows as t2/3.


Modeling locomotion of a soft-bodied arthropod using inverse dynamics.
Most bio-inspired robots have been based on animals with jointed, stiff skeletons. There is now an increasing interest in mimicking the robust performance of animals in natural environments by incorporating compliant materials into the locomotory system. However, the mechanics of moving, highly conformable structures are particularly difficult to predict. This paper proposes a planar, extensible-link model for the soft-bodied tobacco hornworm caterpillar, Manduca sexta, to provide insight for biologists and engineers studying locomotion by highly deformable animals and caterpillar-like robots. Using inverse dynamics to process experimentally acquired point-tracking data, ground reaction forces and internal forces were determined for a crawling caterpillar. Computed ground reaction forces were compared to experimental data to validate the model. The results show that a system of linked extendable joints can faithfully describe the general form and magnitude of the contact forces produced by a crawling caterpillar. Furthermore, the model can be used to compute internal forces that cannot be measured experimentally. It is predicted that between different body segments in stance phase the body is mostly kept in tension and that compression only occurs during the swing phase when the prolegs release their grip. This finding supports a recently proposed mechanism for locomotion by soft animals in which the substrate transfers compressive forces from one part of the body to another (the environmental skeleton) thereby minimizing the need for hydrostatic stiffening. The model also provides a new means to characterize and test control strategies used in caterpillar crawling and soft robot locomotion.


[Compartment syndrome after femoral contusion. Case report and review of the literature].
Compartment syndromes of the lower arm and lower leg are quite well known by now and have been often described in the literature. Those of the upper arm and thigh are rarer and those after pure closed lesion of the soft parts of the thigh are the subject of only sporadic reports in the literature. A recently observed case of this kind prompted the present case report and review of the literature.


[Psychological issues related to multiple sclerosis].
This study sought to investigate some psychological issues related to multiple sclerosis (MS), in particular, the relations existing between illness representations, personality factors and coping strategies and, consequently, the specific coping strategies employed in adjusting emotionally to MS. Sixty-nine MS patients attending the University Polyclinic of Modena were administered the following battery: a questionnaire regarding demographic and illness features, the Illness Perception Questionnaire-Revised (IPQ-R), the Coping Orientations to Problems Experienced Questionnaire (COPE) and Cognitive Behavioural Assessment Hospital Form (CBA-H). Patients' physical disability level was also evaluated using the Expanded Disability Status Scale (EDSS). Results suggest that personality factors and patients' perception of their illness play an important role in activating one or other type of coping strategy. Regarding problem-focused coping strategies, the most significant predictors that emerged from stepwise linear multiple regression analysis were perception of the disease as cyclical (timeline cyclical dimension) and a low score in neuroticism, indicating good emotional stability of the subject. For emotion-centered coping strategies, the regression model identified as best predictors: the belief that chance or bad luck are the most important causes of the illness, perception of the disease as cyclical, extroversion and a cooperative mode of interacting with others, and the presence of interpersonal difficulties. Finally, with regard to disadaptive coping strategies, the best predictors resulting from the analysis were, once again, perception of the disease as cyclical, and interpersonal difficulties.


p53 protein expression in tumours from head and neck subsites, larynx and hypopharynx, and differences in relationship to survival.
The present study involves an immunohistochemical analysis of p53 protein expression in head and neck tumours located at two separate subsites, the larynx and hypopharynx. It attempts to relate differences in expression to differences in the behaviour of these tumours. Detection of the p53 protein was performed using immunohistochemistry on 32 specimens of hypopharyngeal squamous cell carcinoma and 35 specimens of laryngeal squamous cell carcinoma. p53 overexpression was found in 66% of the hypopharyngeal tumours and in 51% of the laryngeal specimens analysed. Some differences between the two tumour types were noted in the pattern staining. p53 staining in those with hypopharyngeal tumours was associated with a statistically significant increased survival. For laryngeal carcinoma the converse was true but did not reach statistical significance. Differences in the behaviour of different head and neck tumour types may be reflected in differences in expression of the p53 protein. While p53 protein expression does not appear to be a useful prognostic indicator in laryngeal carcinoma it might be a useful prognostic indicator in tumours of the hypopharynx. Moreover, it may help predict those tumours which are radioresistant, thus suggesting other modes of treatment for these tumours. Of particular importance is the molecular basis for the observed differences in survival associated with p53 expression in the two tumour sites. This is under further investigation.


Reported eating behavior and attitudes improvement after a nutrition intervention program in a group of young female dancers.
The aim of the study was to evaluate the effectiveness of an intervention program that combined nutrition education and prevention of disordered eating in a group of female professional dance students. Thirty-two dancers, aged 19-25 years, took part in the program. Evaluation was done by a series of questionnaires that participants were asked to complete on 3 occasions. Assessments of body composition and dietary intake were also performed. Significant improvements in nutrition knowledge as well as a decrease in abnormal eating behavior and dietary restraint were observed at post intervention. At 6-month follow-up, the positive effects were maintained and further benefits were recorded; only nutrition knowledge showed a minor decline. Participants who were at higher risk for adopting abnormal eating behavior benefited the most from the program. These findings encourage the implementation of intervention programs in groups of young women that experience particular pressures for controlling body weight.


Is nitric oxide in exhaled air produced at airway or alveolar level?
The aim of this study was to determine whether the nitric oxide (NO) measured in exhaled air is produced at airway or alveolar level. Exhaled NO was measured using a chemiluminescence analyser, and carbon dioxide (CO2 concentration using a Morgan capnograph in single exhalations in 12 healthy subjects (mean age 32 yrs; 6 males and 6 females). For each subject, five exhalations were made directly into the NO analyser and five were made through a T-piece system, which allowed measurement of expiratory flow rate. The peak NO levels measured via the T-piece system were 41.2 (SEM 10.8) parts per billion (ppb), significantly lower than direct levels 84.8 (14.0) ppb (p<0.001). The levels of NO tended to rise to an early peak and plateau, while the CO2 levels continued to rise to peak late in the exhalation. The mean times to reach peak NO levels were 32.2 s (direct) and 23.1 s (T-piece), which were significantly different from that of peak CO2 levels 50.5 s (direct) and 51.4 s (T-piece) (p<0.001). At peak NO level, the simultaneous CO2 level mean 4.9% (SEM 0.14)%, was significantly lower than the peak CO2 reached, 5.8 (0.21)% (p<0.001). We conclude that peak nitric oxide levels are dependent on measurement conditions. There are significant differences between the time to peak of carbon dioxide and nitric oxide. Therefore, most nitric oxide, unlike carbon dioxide, is produced in airways and not at alveolar level.


Reflex myoclonus in cortical-basal ganglionic degeneration involves a transcortical pathway.
The short-latency reflex myoclonus that appears to be characteristic of cortical-basal ganglionic degeneration (CBGD) was investigated in two patients. Stimulating the digital nerves of the middle finger caused exaggerated reflex activity in the first dorsal interosseus (FDI) muscle of that hand with a latency of 46-51 ms. Magnetic stimulation over the contralateral cortex, delivered 25 ms after the digital nerve stimulus, resulted in greater than expected facilitation of FDI, implying spatial summation. Poststimulus time histograms (PSTH) of individual FDI motor units indicated that this spatial summation was occurring "upstream" from the motoneurons. It is argued that this occurs at the motor cortex. Magnetic stimulation over the cortex in normal subjects results in short-latency facilitation of the contralateral motoneurons followed by inhibition. This inhibition was less in the patients with CBGD. It is argued that this results from the loss of an intrinsic cortical and corticothalamic inhibitory mechanism.


"Deep Extrinsic Muscle Involvement" Is a Fallacy in the American Joint Committee on Cancer's Seventh Edition of Tumor Staging of Oral Cavity Cancers.
The seventh edition of tumor staging by the American Joint Committee on Cancer (AJCC) includes extrinsic muscle involvement to define stage T4a tongue carcinomas. The anatomic location of extrinsic muscles predisposes them to early involvement even in superficial tumors. The purpose of this study was to expose a fallacy in this staging system for extrinsic muscle involvement. This was a prospective cohort study of 87 patients with oral tongue squamous cell carcinoma. Magnetic resonance imaging (MRI) parameters were 1) the distance of the extrinsic muscles from the surface measured on the normal side in millimeters (range, mean, and standard deviation); 2) maximum transverse, craniocaudal, and anteroposterior tumor dimensions (range, mean, and standard deviation); and 3) tumor involvement of the muscles recorded on the involved side for the number and percentage of each muscle involved. Histopathologic depth of invasion also was recorded. Sixty-seven patients were men and 20 were women (age range, 18 to 74 yr; mean age, 51 yr). The mean distances of the most superficial part of the muscle to the normal surface at MRI for the genioglossus (anteroventral), hyoglossus, and styloglossus were 3.98, 2.13 and 0.66 mm, respectively. The patterns of extrinsic muscle involvement showed hyoglossus, styloglossus, and genioglossus involvement in 79 (90.8%), 58 (66.76%), and 31 (35.6%), respectively. In patients with a pathologic depth of invasion shallower than 10 mm, involvement of the hyoglossus, styloglossus, and genioglossus was seen in 80, 35, and 15%, respectively. The extrinsic muscles of the tongue are not deep. Even superficial thin tumors can involve these muscles. The eighth edition of tumor staging by the AJCC, which includes tumor thickness in the staging system, is in the process of being implemented. The present study justifies the removal of extrinsic muscle involvement in defining stage T4 of the oral cavity.


Cytotoxic activity of selected trifluoromethyl ketones against oral tumor cells.
Several trifluoromethyl ketones (TF1-4) and related non-fluorinated ketones (TF5 and 6) were tested for their relative cytotoxicity on four human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, HSC-4 and promyelocytic leukemia HL-60) and three normal human cells [gingival fibroblasts (HGF), pulp cells (HPC) and periodontal ligament fibroblasts (HPLF)]. Trifluoromethylated a-diketone (TF1, CF3COCOPh) and alpha-hydroxy ketones (TF2, CF3CH(OH)COPh; TF3, CF3CH(OH)COCH2Ph) showed higher tumor-specific cytotoxic activity than the corresponding non-fluorinated analogs (TF5, CH3COCOPh; TF6, CH3CH(OH)COPh), while the anti-tumor potency of trifluoromethyl ketone (TF4, CF3COCH2Ph) was lower. Among four tumor cell lines, HL-60 cells were the most sensitive to TF1-4, followed by HSC-2 and HSC-3 cells. HSC-4 cells were the most resistant in most cases. Agarose gel electrophoresis showed that TF1-3 did not induce intemucleosomal DNA fragmentation nor activated caspase-3. The cytotoxic activities of TF1-3 were not significantly affected by FeCl3. Electron microscopy of TF2- or 3-treated HL-60 cells showed the development of autophagosomes in HL-60 cells, without the production of an apoptotic body, or affecting the mitochondria and cell surface microvilli. The autophagy inhibitor, 3-methyladenine (3-MA), partially inhibited the TF2- or 3-induced cytotoxicity. These data suggest the induction of non-apoptotic cell death by TF2 or 3.


Where am I in virtual reality?
It is currently not well understood whether people experience themselves to be located in one or more specific part(s) of their body. Virtual reality (VR) is increasingly used as a tool to study aspects of bodily perception and self-consciousness, due to its strong experimental control and ease in manipulating multi-sensory aspects of bodily experience. To investigate where people self-locate in their body within virtual reality, we asked participants to point directly at themselves with a virtual pointer, in a VR headset. In previous work employing a physical pointer, participants mainly located themselves in the upper face and upper torso. In this study, using a VR headset, participants mainly located themselves in the upper face. In an additional body template task where participants pointed at themselves on a picture of a simple body outline, participants pointed most often to the upper torso, followed by the (upper) face. These results raise the question as to whether head-mounted virtual reality might alter where people locate themselves making them more "head-centred".


DAF-fluorescence without NO: elicitor treated tobacco cells produce fluorescing DAF-derivatives not related to DAF-2 triazol.
Diaminofluorescein-dyes (DAFs) are widely used for visualizing NO· production in biological systems. Here it was examined whether DAF-fluorescence could be evoked by other means than nitrosation. Tobacco (Nicotiana tabacum) suspension cells treated with the fungal elicitor cryptogein released compound(s) which gave a fluorescence increase in the cell-free filtrate after addition of DAF-2 or DAF-FM or DAR-4M. DAF-reactive compounds were relatively stable and identified as reaction products of H(2)O(2) plus apoplastic peroxidase (PO). CPTIO prevented formation of these products. Horseradish-peroxidase (HR-PO) plus H(2)O(2) also generated DAF-fluorescence in vitro. Using RP-HPLC with fluorescence detection, DAF derivatives were further analyzed. In filtrates from cryptogein-treated cells, fluorescence originated from two novel DAF-derivatives also obtained in vitro with DAF-2+HR-PO+H(2)O(2). DAF-2T was only detected when an NO donor (DEA-NO) was present. Using high resolution mass spectrometry, the two above-described novel DAF-reaction products were tentatively identified as dimers. In cells preloaded with DAF-2 DA and incubated with or without cryptogein, DAF-fluorescence originated from a complex pattern of multiple products different from those obtained in vitro. One specific peak was responsive to exogenous H(2)O(2), and another, minor peak eluted at or close to DAF-2T. Thus, in contrast to the prevailing opinion, DAF-2 can be enzymatically converted into a variety of highly fluorescing derivatives, both inside and outside cells, of which none (outside) or only a minor part (inside) appeared NO· dependent. Accordingly, DAF-fluorescence and its prevention by cPTIO do not necessarily indicate NO· production.


Hershey Foods Corporation: a case study in managed dental care.
Throughout the development and implementation of Health Smile. Hershey Foods has been committed to quality-based health plan options for its employees that serve as the route to cost-effective care. It is known that the company will need to make a short-term investment, rather than have unrealistic expectations of immediate cost savings. However, much of the long-term potential for Hershey Foods rests on the primary dentist's ability to use resources conservatively for the most effective patient outcomes. Health Smile represents Hershey Foods' best effort at forming a partnership relationship between a purchaser, provider, and a patient.


Metabolic engineering of mannitol production in Lactococcus lactis: influence of overexpression of mannitol 1-phosphate dehydrogenase in different genetic backgrounds.
To obtain a mannitol-producing Lactococcus lactis strain, the mannitol 1-phosphate dehydrogenase gene (mtlD) from Lactobacillus plantarum was overexpressed in a wild-type strain, a lactate dehydrogenase(LDH)-deficient strain, and a strain with reduced phosphofructokinase activity. High-performance liquid chromatography and (13)C nuclear magnetic resonance analysis revealed that small amounts (<1%) of mannitol were formed by growing cells of mtlD-overexpressing LDH-deficient and phosphofructokinase-reduced strains, whereas resting cells of the LDH-deficient transformant converted 25% of glucose into mannitol. Moreover, the formed mannitol was not reutilized upon glucose depletion. Of the metabolic-engineering strategies investigated in this work, mtlD-overexpressing LDH-deficient L. lactis seemed to be the most promising strain for mannitol production.


Single-Cell Transcriptome Data Clustering via Multinomial Modeling and Adaptive Fuzzy K-Means Algorithm.
Single-cell RNA sequencing technologies have enabled us to study tissue heterogeneity at cellular resolution. Fast-developing sequencing platforms like droplet-based sequencing make it feasible to parallel process thousands of single cells effectively. Although a unique molecular identifier (UMI) can remove bias from amplification noise to a certain extent, clustering for such sparse and high-dimensional large-scale discrete data remains intractable and challenging. Most existing deep learning-based clustering methods utilize the mean square error or negative binomial distribution with or without zero inflation to denoise single-cell UMI count data, which may underfit or overfit the gene expression profiles. In addition, neglecting the molecule sampling mechanism and extracting representation by simple linear dimension reduction with a hard clustering algorithm may distort data structure and lead to spurious analytical results. In this paper, we combined the deep autoencoder technique with statistical modeling and developed a novel and effective clustering method, scDMFK, for single-cell transcriptome UMI count data. ScDMFK utilizes multinomial distribution to characterize data structure and draw support from neural network to facilitate model parameter estimation. In the learned low-dimensional latent space, we proposed an adaptive fuzzy k-means algorithm with entropy regularization to perform soft clustering. Various simulation scenarios and the analysis of 10 real datasets have shown that scDMFK outperforms other state-of-the-art methods with respect to data modeling and clustering algorithms. Besides, scDMFK has excellent scalability for large-scale single-cell datasets.


High-level expression of β-N-Acetylglucosaminidase BsNagZ in Pichia pastoris to obtain GlcNAc.
β-N-Acetylglucosaminidases (NAGase) can remove N-acetylglucosamine (GlcNAc) from the non-reducing end of chitin or chitosan. GlcNAc has many important physiological functions in organism, which can be used for the treatment of rheumatoid arthritis clinically and be used as food antioxidant, infant food additive and diabetic sweetener. Thus, it is very important to develop genetic-engineering strains with high-yield NAGase to hydrolyze chitin into GlcNAc. Here, the NAGase gene of Bacillus subtilis 168 (BsnagZ) was synthesized according to the codon bias of Pichia pastoris and expressed in P. pastoris. The expression level of BsNagZ in P. pastoris increased over the induced time and the highest activity reached 0.76 U/mL at the 7th day. The recombinant BsNagZ was purified for characterization. The optimal temperature and pH are 60 °C and 6.0, respectively. It can both keep over 80% activities after pre-incubation at 55 °C for one hour and at 4 °C for 12 h from pH 4.5 to 10.0. To further improve the expression level of BsNagZ, a recombinant strain with four copy BsnagZs was screened using a high concentration of zeocin. The highest BsNagZ activity reached 3.2 U/mL at the 12th day, which was fourfold higher than that of single-copy strain. Combined with commercial chitinase CtnSg, GlcNAc can be produced by recombinant BsNagZ when used colloidal chitin as the substrate. Our study highlights that the NAGase was first successfully expressed in P. pastoris and GlcNAc can be produced via NAGase hydrolyzing the colloidal chitin.


Carotid artery stenting without using any embolic protective device A single Centre experience.
Despite the use of embolic protective devices in the majority of cases applied with carotid stenting to prevent embolic neurological complications related to the carotid stenting procedure, this procedure is applied to some cases without protection. The aim of this study was to present the clinical outcomes of carotid artery stent application without a cerebral embolism protective device. A retrospective examination was made of a total of 171 patients applied with a stent between 2014 and 2017. The patients included in the study were applied with a stent because they were symptomatic and determined with >50% narrowing in the carotid artery on angiography or asymptomatic with >60% narrowing. The degree of carotid artery narrowing was determined with Doppler ultrasonography before angiographic examination and with the North American symptomatic carotid endarterectomy trial measurement criteria during angiography. After stenting the carotid artery, patients were observed at the hospital for 24 hours RESULTS: In 10 (5.8%) patients, there was a mid cerebral artery branch infarct ipsilateral to the stent. No reperfusion bleeding was observed in any patient. In 5 (2.9%) patients, encephalopathy and agitation not exceeding 24 hours was observed. Hypotension was determined in 8 (4.6%) patients and headache lasting <24 hours in 53 (31%) patients. 1 (0.5%) patient, rectus abdominis bleeding developed one week after the procedure and within 24 hours, the patient was exitus. Revascularisation interventions to be able to prevent the development of stroke are evaluated as important treatment options in patients with symptomatic or severe carotid stenosis. With careful patient selection in experienced centres and a multi-disciplinary approach both before and after the procedure, pleasing results can be obtained without the use of embolic protective devices. Carotid artery stenting, Embolic protective device, Stroke.


Site Covalent Modification of Methionyl Peptides for the Production of FRET Complexes.
Flax cyclic peptides (orbitides, linusorbs (LOs)) [1-8-NαC],[1-MetO2]-linusorb B1 ([MetO2]-LO1) and [1-9-NαC],[1-MetO2]-linusorb B2 ([MetO2]-LO2) are biologically active. These LOs lack active nuclei commonly used in peptide modification. We have developed reactions to activate methionine methyl sulphide to produce stable derivatives. In these reactions, LOs are converted to sulfonium intermediates and subsequently to derivatives containing active nuclei while preserving their fundamental structures. The reaction conditions preserved cyclic peptide fundamental structure and organic solvent solubility. [Met]-LO1 and [Met]-LO2 analogues containing activated groups (-CN, -COOEt, and -NH2 ) in the form of methionine, methionine (S)-oxide, and methionine (S,S)-dioxide amino acids were synthesized and characterized by LCMS and 1D and 2D NMR spectroscopy. Coumarin orbitide complexes produced in this manner bind Eu(3+) yielding FRET compounds that absorb energy through coumarin antennae and emit photons at lanthanide wavelengths.