Preparation and evaluation of polymeric microparticulates for improving cellular uptake of gemcitabine.
Gemcitabine must be administered at high doses to elicit the required therapeutic response because of its very short plasma half-life due to rapid metabolism. These high doses can have severe adverse effects. In this study, polymeric microparticulate systems of gemcitabine were prepared using chitosan as a mucoadhesive polymer and Eudragit L100-55 as an enteric copolymer. The physicochemical and biopharmaceutical properties of the resulting systems were then evaluated. There was no endothermic peak for gemcitabine in any of the polymeric gemcitabine microparticulate systems, suggesting that gemcitabine was bound to chitosan and Eudragit L100-55 and its crystallinity was changed into an amorphous form. The polymeric gemcitabine microparticulate system showed more than 80% release of gemcitabine in 30 minutes in simulated intestinal fluid. When mucin particles were incubated with gemcitabine polymeric microparticulates, the zeta potential of the mucin particles was increased to 1.57 mV, indicating that the polymeric gemcitabine microparticulates were attached to the mucin particles. Furthermore, the F53 polymeric gemcitabine microparticulates having 150 mg of chitosan showed a 3.8-fold increased uptake of gemcitabine into Caco-2 cells over 72 hours compared with gemcitabine solution alone. Overall, these results suggest that polymeric gemcitabine microparticulate systems could be used as carriers to help oral absorption of gemcitabine.


Rauvomines A and B, Two Monoterpenoid Indole Alkaloids from Rauvolfia vomitoria.
Two unusual normonoterpenoid indole alkaloids rauvomine A (1) and rauvomine B (2), together with two known compounds peraksine (3) and alstoyunine A (4), were isolated from the aerial parts of Rauvolfia vomitoria. The structures with absolute configurations of 1 and 2 were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound 2 is a novel C18 normonoterpenoid indole alkaloid with a substituted cyclopropane ring that forms an unusual 6/5/6/6/3/5 hexcyclic rearranged ring system. The plausible biogenetic pathways of 1 and 2 were proposed. Compound 2 exhibited significant anti-inflammatory activity.


Mitophagy-related genes could facilitate the development of septic shock during immune infiltration.
Septic shock often occurs following critically low blood pressure in patients with sepsis, and is accompanied by a high death rate. Although mitophagy is associated with infection and immune responses, its role in septic shock remains unknown. This study screened effective mitophagy-related genes (MRGs) for medical practice and depicted immune infiltration situations in patients with septic shock. Gene expression profiles of GSE131761 from the Gene Expression Omnibus database were compiled for differential analysis, weighted gene co-expression network analysis, and immune infiltration analysis, while other GSE series were used as validation datasets. A series of validation methods were used to verify the robustness of hub genes, while a nomogram and prognosis model were established for medical practice. Six genes were screened via combinations of differentially expressed genes, weighted gene co-expression network analysis, and MRGs. From this, 3 hub genes (MAP1LC3B, ULK1, and CDC37) were chosen for subsequent analysis based on different validation methods. Gene set enrichment analysis showed that leukocyte trans-endothelial migration and the p53 signaling pathway were abnormally activated during septic shock. Immune infiltration analysis indicated that the imbalance of neutrophils and CD4 naive T cells was significantly correlated with septic shock progression. A nomogram was generated based on MAP1LC3B, ULK1, and CDC37, as well as age. The stability of our model was confirmed using a calibration plot. Importantly, patients with septic shock with the 3 highly expressed hub genes displayed worse prognosis than did patients without septic shock. MAP1LC3B, ULK1, and CDC37 are considered hub MRGs in the development of septic shock and could represent promising diagnostic and prognostic biomarkers in blood tissue. The validated hub genes and immune infiltration pattern expand our knowledge on MRG functional mechanisms, which provides guidance and direction for the development of septic shock diagnostic and therapeutic markers.


Injury inequalities among U.S. construction workers.
This study explores racial/ethnic inequalities in work-related injuries among U.S. construction workers. Data from the 2004-2017 National Health Interview Survey were used to estimate work-related injuries by race/ethnicity in construction. Disparities in demographic, socioeconomic, and injury status among construction workers were examined by race/ethnicity. Injury differences were also evaluated in multiple logistic regression analyses controlling for potential confounders. Compared to white, non-Hispanic workers, minority workers were more likely to have lower socioeconomic statuses (e.g., lower educational attainment, lack of health insurance coverage, and family income below the poverty level), which considerably increased the likelihood of work-related injuries. The odds of work-related injuries were 70% higher among racial/ethnic minorities than white, non-Hispanics in construction. Injuries were also more severe among minorities than white, non-Hispanic workers. Among workers with a work-related injury, nearly 85% of Hispanics reported missing at least one workday due to injury, 45.6% higher than the proportion of 57.9% for their white, non-Hispanic counterparts. After adjusting for major demographic and socioeconomic factors, the work-related injury difference between race/ethnicity was no longer statistically significant. However, the odds of work-related injury remained significantly higher among workers who were younger (35-54 years vs. ≥ 55 years: aOR = 2.2, 95% CI: 1.3-3.6); male (aOR = 5.3, 95% CI: 2.9-9.8); not college-educated (aOR = 1.5, 95% CI: 1.0-2.2); had a family income below the poverty threshold (aOR = 1.8, 95% CI: 1.2-2.8); or held a blue-collar occupation (aOR = 2.0, 95% CI: 1.2-3.4). These findings suggest that the injury differences between race/ethnicity were strongly associated with demographics and socioeconomic inequalities in these worker groups. The identified injury disparities should be reduced or eliminated, following the hierarchy of controls paradigm.


Organization of extracellular matrix in epiphyseal growth plate.
Three cations of varying size and charge density, egg-white lysozyme, protamine and ruthenium red, were used to stain the extracellular matrix of epiphyseal cartilage growth plate. With these stains, it was possible to distinguish three types of proteoglycans or materials associated with them, which may well have as their major differences the type of cross linking to the tissue. One type was stained by ruthenium red and protamine but not by lysozyme, was extractable with 3 M guanidinium chloride and was relatively uniformly dispersed throughout the matrix of the growth plate. The other two types were stained by all three cations, were not extractable with 3 M guanidinium chloride and were intimately associated with fibrils. One of these was found on the collagen fibrils, was relatively scanty in the resting zone near the articular surface, relatively restricted to the extralacunar area in the columnar zones and appeared to diminish in amount in the hypertrophic zone. This material often had a 640-A periodic array on the surface of collagen fibrils. The third type also was stained by all three cations and was not extractable with 3 M guanidinium chloride. It was distinguished from the other class of lysozyme-reactive matrix components by the larger volume of distribution occupied by the stained material. It also had a different distribution in that it was widely dispersed in the resting zone, was restricted to the lacuna in the columnar zone and was absent in the hypertrophic zone. Thus, cartilage matrix as well as the chondrocytes undergo differentiation in the epiphyseal growth plate.


Meta-analysis of the efficacy of psychological and educational interventions to improve academic performance of students with learning disabilities in Iran.
with due attention to the importance of learning disabilities and necessity of presenting interventions for improvement of these disorders in order to prevent future problems, this study used meta-analysis of the research model on the impact of psychological and educational interventions to improve academic performance of students with learning disabilities. with the use of meta-analysis method by integrating the results of various researches, this study specifies the effect of psychological and educational interventions. In this order, 57 studies, which their methodology was accepted, were selected and meta-analysis was performed on them. The research instrument was a meta-analysis checklist. The effect size for the effectiveness of psychological-educational interventions on improving the academic performance of students with mathematics disorder (0.57), impaired writing (0.50) and dyslexia (0.55) were reported. The result of meta-analysis showed that according to Cohen's table, the effect size is above average, and it can be said that educational and psychological interventions improve the academic performance of students with learning disabilities.


A look at the pediatrician as parent: experiences with the introduction of varicella vaccine.
Many physicians voiced reservations about routine use of the varicella vaccine for healthy children after its licensing in 1995. Anecdotal evidence suggested that some pediatricians who were parents themselves were electing not to vaccinate their own children against chickenpox. Little has been written about pediatrician-parents' behaviors in caring for their own children, and how these practices may differ from the behavior that these same pediatricians apply in practice. Pediatricians' tacit attitudes toward medical interventions might be better understood from their behaviors as parents than from their clinical practices, which may be influenced by a sense of responsibility to follow guidelines of professional organizations. Varicella vaccination practices were examined to determine whether pediatricians' behaviors in parenting their own children differed from their recommendations for their patients. A mail survey was sent to 1,762 New York State pediatricians selected randomly from the membership directory of the American Academy of Pediatrics. The response rate was 43% (764/1,762); 63% of responding pediatricians were parents. Eighty-five percent of pediatricians recommended varicella vaccine routinely in practice. Of the pediatricians' own eligible children, 88% (256/291) had been vaccinated against chickenpox. We found a high overall rate of compliance with recommendations for routine use of varicella vaccine. Pediatricians who were parents were just as likely as nonparent pediatricians to recommend the vaccine routinely for their patients. Importantly, pediatrician-parents demonstrated no "double standard"; at the time of the study, 88% of pediatricians' own eligible children had been vaccinated against varicella.


T1, T2, and relative proton density at 0.35 T for spleen, liver, adipose tissue, and vertebral body: normal values.
An MRI installation (Magnetom, Siemens, software version B1 of NUMARIS) working at 0.35 T was used to estimate T1, T2, and relative proton density in the spleen, liver, adipose tissue, and vertebral body in 14 healthy volunteers. Two double-echo sequences were applied for all subjects: TR = 500 ms, TE1 = 35 and TE2 = 70 ms; and TR = 1600 ms, TE1 = 35 and TE2 = 70 ms. The images were sampled in regions of interest and appropriate relaxation expressions fitted to the ROI data yielding relaxation parameters and relative proton densities. Relaxation expressions, included in standard software (Siemens), were compared to more elaborate functions, developed in parallel to this study. The latter were found more appropriate, especially for high T1 values, and gave the following mean values for the four tissues (estimated uncertainty of mean in parentheses) T1 (ms) 915(36), 428(5), 261(7), and 501(11); T2 (ms) 79.7(8.8), 51.0(0.2), 59.8(1.0), and 64.7(0.8); and corresponding relative proton density (rho, arbitrary units) 2088(136), 2182(10), 2915(49), and 2136(21). The uncertainty in the values was estimated in the fitting procedure and does not include systematic errors. The relative noise in the ROIs was about 9% and the reproducibility of the ROI mean values about 8%.


Reoperation in the management of post-operative disc space infection.
Post-operative intervertebral disc space infection had been recognised as a clinical entity with its own characteristics. Various treatments have been described. During the last six years 3127 open lumbar intervertebral disc operations were performed of which 15 (0.5%) showed a post-operative discitis. We treated our patients by reoperation of the infected intervertebral disc space. The reason of reoperation consists of acquiring material for bacteriological culture and removing loose fragments. It appears to us that reoperation is facilitating early mobilisation of patients. Also attention is paid to new diagnostic possibilities.


Monitoring bacterially induced calcite precipitation in porous media using magnetic resonance imaging and flow measurements.
A range of nuclear magnetic resonance (NMR) techniques are employed to provide novel, non-invasive measurements of both the structure and transport properties of porous media following a biologically mediated calcite precipitation reaction. Both a model glass bead pack and a sandstone rock core were considered. Structure was probed using magnetic resonance imaging (MRI) via a combination of quantitative one-dimensional profiles and three-dimensional images, applied before and after the formation of calcite in order to characterise the spatial distribution of the precipitate. It was shown through modification and variations of the calcite precipitation treatment that differences in the calcite fill would occur but all methods were successful in partially blocking the different porous media. Precipitation was seen to occur predominantly at the inlet of the bead pack, whereas precipitation occurred almost uniformly along the sandstone core. Transport properties are quantified using pulse field gradient (PFG) NMR measurements which provide probability distributions of molecular displacement over a set observation time (propagators), supplementing conventional permeability measurements. Propagators quantify the local effect of calcite formation on system hydrodynamics and the extent of stagnant region formation. Collectively, the combination of NMR measurements utilised here provides a toolkit for determining the efficacy of a biological-precipitation reaction for partially blocking porous materials.


Direct measurements of the spin and the cyclotron gaps in a 2D electron system in silicon.
Using magnetocapacitance data in tilted magnetic fields, we directly determine the chemical potential jump in a strongly correlated two-dimensional electron system in silicon when the filling factor traverses the spin and the cyclotron gaps. The data yield an effective g factor that is close to its value in bulk silicon and does not depend on the filling factor. The cyclotron splitting corresponds to the effective mass that is strongly enhanced at low electron densities.


Estimation of the hamaker coefficient for a fuel-cell-supported catalyst system.
Hamaker coefficients are estimated for various nanoparticle-support systems commonly used in polymer electrolyte membrane fuel cells. The interaction energies, cohesion between nanoparticles, and adhesion of nanoparticles on the support are also estimated from the experimental data. Comparison between the bulk properties of platinum metal, calculated from the optical spectra available in the literature, and the nanoparticles are provided. Measurements to obtain the optical properties of the systems of interest are also reported. Implications of the van der Waals forces on the supported catalyst structure properties are discussed. The algorithm used in calculation of the Hamaker coefficient using Lifshitz theory was evaluated with known materials, using the spectral parameters available in the literature, and the results are presented.


Metallic hair pin aspiration into the left tertiary bronchus.
Foreign body aspiration is commonly described in infants and children. However, recently, a new high-risk group was identified among young women, especially those from the Muslim population who wear the traditional hair scarf. This is due to the habit of holding the scarf pin in between the lips to free hands to adjust the scarf more easily. Talking, laughing, or coughing while fixing the scarf may result in inadvertent inhalation of the pin into the tracheobronchial tree. We present a case of scarf pin inhalation and the challenges encountered in managing this patient during the successful removal of the pin via flexible bronchoscopy under fluoroscopy guidance. This particular case was technically challenging for us as the sharp tip of the needle was pointing upward and piercing the bronchial mucosa.


Improving medical resident perceptions of health plan decision making.
To determine the effect on medical residents' perceptions resulting from attending a medical policy meeting. Pre- and postsurveys administered to residents attending BlueCross BlueShield of Tennessee's (BCBST) Medical Policy Subcommittee meeting. This group is a subcommittee of the Medical Policy Review Committee (MPRC), which is responsible for the final approval of medical policies at BCBST. Residents were invited to attend BCBST's Medical Policy Subcommittee meeting to determine what impact observing this process would have on their attitudes toward health insurers' use of scientific evidence. This subcommittee, which consists of both BCBST medical directors and network physicians, plays a key role in determining whether new medical technologies or new uses of established technologies are medically necessary, cosmetic, not medically necessary, or investigational. Residents were given a pre- and postsurvey to assess their attitudes regarding the methods insurance companies use to make coverage decisions. Medical residents rated BCBST's use of scientific evidence higher after attending the subcommittee meeting. Only 4 of the 10 residents surveyed prior to the subcommittee meeting agreed with the statement, "Insurance companies base their coverage decisions for medical treatment on scientific evidence." In the postsurvey, all 10 residents indicated that they agreed with the statement. Other questions showed similar positive changes in residents' opinions of the health plans' decision making. Many medical residents likely have negative perceptions of health insurers and may be prone to believe that medical policy decisions are based predominantly on financial impact. Such attitudes can easily persist as they move into private practice. Although drawing firm conclusions from this small study is difficult, exposing residents to actual decision-making processes within insurance companies may be one means of improving their opinions of how such decisions are made.


Shape of fair weather clouds.
We introduce a model which accounts for the shape of cumulus clouds exclusively in terms of thermal plumes or thermals. The plumes are explicitly represented by a simple potential flow generated by singularities (sources and sinks) and are thus laminar, but with their motion create a field which supports the cloud. We compare this model with actual clouds by means of various shape descriptors including the fractal dimension, and find agreement.


A hydrothermal anvil made of graphene nanobubbles on diamond.
The hardness and virtual incompressibility of diamond allow it to be used in high-pressure anvil cell. Here we report a new way to generate static pressure by encapsulating single-crystal diamond with graphene membrane, the latter is well known for its superior nano-indentation strength and in-plane rigidity. Heating the diamond-graphene interface to the reconstruction temperature of diamond (~1,275 K) produces a high density of graphene nanobubbles that can trap water. At high temperature, chemical bonding between graphene and diamond is robust enough to allow the hybrid interface to act as a hydrothermal anvil cell due to the impermeability of graphene. Superheated water trapped within the pressurized graphene nanobubbles is observed to etch the diamond surface to produce a high density of square-shaped voids. The molecular structure of superheated water trapped in the bubble is probed using vibrational spectroscopy and dynamic changes in the hydrogen-bonding environment are observed.


The effect of oxysterols, individually and as a representative mixture from food, on in vitro cultured bovine ovarian granulosa cells.
The cytotoxicity of five oxysterols identified in cooked fish, 7-ketocholesterol, 7beta-hydroxycholesterol, cholesterol 5alpha,6alpha-epoxide, cholestanetriol and 4-cholesten-3-one, was investigated in primary cultures of bovine ovarian granulosa cells. Cells were exposed to the oxysterols individually and to a mixture of the same oxysterols for 24 h. Cell viability as determined by trypan blue exclusion and mitochondrial integrity (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) reduction) was reduced by 0.5 and 2.5 microM 7beta-hydroxycholesterol, cholesterol 5alpha,6alpha-epoxide, cholestanetriol and 4-cholesten-3-one, but not by 0.5 or 2.5 microM 7-ketocholesterol under the same culture conditions. A mixture of 7-ketocholesterol, 7beta-hydroxycholesterol, cholesterol 5alpha,6alpha-epoxide, cholestanetriol and 4-cholesten-3-one 0.5 microM each; 2.5 microM oxysterol in total) did not change cell viability relative to controls. Lipid peroxidation, as determined by thiobarbituric acid reactive substances assay, was unaffected by a 24-hour exposure of granulosa cells to individual oxysterols but was increased slightly by the oxysterol mixture. The specific activities of antioxidant enzymes superoxide dismutase and catalase were increased to different extents (1.17- to 6.43-fold), relative to controls, by the administration of individual oxysterols and the oxysterol mixture. These results indicate that while some individual oxysterols can induce cytotoxic effects and defensive responses in bovine ovarian granulosa cells, administration of the same oxysterols as a mixture does not elicit the same responses. In addition, the oxysterols tested exerted a pro-apoptotic effect on granulosa cells when administered individually at concentrations of 0.5 and 2.5 microM, but not when administered as a 2.5 microM oxysterol mixture. The results suggest that major oxysterols are not universally cytotoxic, they may complete with other oxysterols for receptor sites, and that the simultaneous presence of several different oxysterol species may reduce the adverse effects of individual oxysterols.


Preoperative magnetic resonance imaging diagnosis of the floating anterior inferior glenohumeral ligament.
Approximately a century ago, labral avulsion from the glenoid was described as a source of recurrent anterior shoulder dislocation. Since then, the significance of other origins of shoulder instability has been a controversial issue. Cadaveric dissection, biomechanical evaluation, and surgical observation have led to the discovery of additional pathologic conditions associated with glenohumeral instability that must be properly identified and addressed for operative success. Recently, several authors have emphasized the importance of lesions of the glenohumeral ligament as a cause of post-traumatic shoulder instability. One such condition is bipolar avulsion of the anterior inferior glenohumeral ligament (AIGHL), or floating AIGHL. In previous reports, this finding has only been identified during surgery. We present a case of traumatic anterior shoulder dislocation in which a preoperative diagnosis of floating AIGHL was made by magnetic resonance imaging. Recognition of this rare lesion before surgical intervention is advantageous for appropriate preoperative planning and management of patients with posttraumatic anterior glenohumeral instability.


Stimuli-Responsive "Cluster Bomb" for Programmed Tumor Therapy.
In this paper, mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX) and capped with tumor-homing/-penetrating peptide tLyP-1-modified tungsten disulfide quantum dots (WS2-HP) was designed and applied as a stimuli-responsive "Cluster Bomb" for high-performance tumor suppression. The peptide tLyP-1 on the surface can both facilitate the homing of DOX@MSN-WS2-HP to 4T1 tumor and greatly enhance the penetration of WS2-HP in tumor. The benzoic-imine bonds as the linkers between "bomblets" and "dispenser" are stable under normal physical conditions and quite labile at pH 6.8. After arriving at the mild acidic tumor microenvironment, the nanoplatform can rapidly break into two parts: (1) electropositive DOX@MSN-NH2 for efficient chemotherapy on surface tumor cells and (2) small-sized WS2-HP with improved tumor penetrating ability for near-infrared (NIR)-light-triggered photothermal therapy (PTT) among deep-seated tumor cells. Having killed the tumor cells in different depths, DOX@MSN-WS2-HP exhibited significant antitumor effect, which will find great potential in clinical trials.


Interactive Effects of Immunoglobulin Gamma and Human Leucocyte Antigen Genotypes on Response to Interferon Based Therapy of Hepatitis C Virus.
We examined the role that immunoglobulin GM 23 and KM allotypes-genetic markers of γ and κ chains, respectively-play in response to treatment of hepatitis C virus (HCV) infection in Egyptian patients. A total of 120 persons who had responded to HCV treatment and 125 with persistent HCV infection were genotyped for the presence of GM23 and KM determinants. HLA -C genotyping was also done. Association of GM 23+ and KM3 was significantly associated with non response to treatment (P < 0.0001). Individuals who lacked this GM genotype (but were positive for KM1,2 and 3) were likely to respond to treatment (P=0.045). Association of heterozygous GM23 (+/-) with KM 1,2 and 3 or KM3 alone was significantly associated with SVR (P = 0.001) and (P = 0.0001) respectively. Particular combinations of HLA and GM genotypes were associated significantly with the response to HCV treatment. The combination of HLAC2C2 and GM23+ was associated with persistence of infection (P = 0.027) while the association of HLAC2C2 and heterozygous GM23+/- was associated with SVR (P = 0.001). The association of HLAC1C1 and heterozygous GM23+/- was significantly associated with SVR (P = 0.001) and also subjects with HLA C1/C2 and heterozygous GM23+/- were likely to respond to treatment (P = 0.003) while subjects with HLA C1/C2 and GM23+ show tendency to resist to treatment (P = 0.0001). Our results didn't support a role for KM allotypes, GM23 allotype plays a role in the persistence of HCV infection in the presence or absence of KM1,3. Interaction between certain GM and HLA-C genotypes may favor adequate response to interferon based therapies.


Mycobacterium scrofulaceum disease: experience from a tertiary medical centre and review of the literature.
Introduction:Mycobacterium scrofulaceum infection has been identified in cases of paediatric cervical lymphadenitis but is less well defined in adults. To further characterize manifestations of M. scrofulaceum disease and treatment approaches, we reviewed our medical centre's experience and other published reports. Methods: We performed a retrospective chart review of patients at our medical centre with a positive M. scrofulaceum culture over a 15-year period. We compare our findings with those published in the literature to identify commonalities in disease presentations and treatment outcomes. Results: We identified 17 patients in our centre with positive M. scrofulaceum cultures, 10 of whom were diagnosed with clinical infection. The types of disease encountered included pulmonary and pleural infection (4), bone and joint infections with a foreign body (2), skin and soft tissue infection (2), brain abscess (1) and paediatric cervical adenitis (1). Structural lung disease was a common finding in cases of pulmonary infection. All adult patients except those with bone and joint infections had some type of immunomodulatory condition and/or structural lung disease. In seven patients, M. scrofulaceum was isolated in urinary or respiratory cultures without signs of clinical disease. Conclusion:M. scrofulaceum is a rare cause of non-tuberculosis mycobacterial infection in humans but can infect any tissue. Adults with pulmonary disease often have underlying structural lung disease, and those with extrapulmonary disease commonly have immunosuppressive conditions or foreign body-associated infections. Treatment outcomes are generally favourable; however, in patients with pulmonary M. scrofulaceum disease prognosis is more guarded.


Aggregatibacter actinomycetemcomitans serotypes associate with periodontal and coronary artery disease status.
We investigated the association between the Aggregatibacter actinomycetemcomitans serotypes, periodontal status and coronary artery disease (CAD). The study population included 497 patients who underwent coronary angiography, and clinical oral examination. Quantitative polymerase chain reaction assays were designed to identify the serotypes from saliva samples. Aggregatibacter actinomycetemcomitans serotype frequencies were as follows: serotype "c" 35.7%, "b" 28.6%, "a" 26.2%, "e" 7.1%, "d" 2.4% and "f" 0%. The subjects with a detectable serotype had less teeth and higher bleeding on probing than those with no serotype. Serotypes "b" and "c" associated with periodontal probing depths and periodontal inflammatory burden. The saliva and subgingival bacterium quantities and serum antibody levels against A. actinomycetemcomitans were highest in patients harbouring serotype "c." Serotypes "b" and "c" were most frequent (59.3%) in patients with CAD (p = .040), and they associated with the risk of stable CAD with an odds ratio of 2.67 (95% confidence interval 1.06-7.44). Also, the severity of CAD (p = .018) associated with serotypes "b" and "c." Aggregatibacter actinomycetemcomitans serotypes "b" and "c" associate with both periodontal and CAD status. Detectable serotypes associate with the quantity and the serology of the bacterium emphasizing both local and systemic effect of the A. actinomycetemcomitans serotypes.


A method for determining surface tension, viscosity, and elasticity of gels via ultrasonic levitation of gel drops.
A method for obtaining the elasticity, surface tension, and viscosity of ultrasonically levitated gel drops is presented. The drops examined were made of agarose, a hydrogel. In contrast to previous studies where fluid properties are obtained using ultrasonic levitation of a liquid drop, herein the material studied was a gel which has a significant elasticity. The work presented herein is significant in that gels are of growing importance in biomedical applications and exhibit behaviors partially determined by their elasticities and surface tensions. Obtaining surface tension for these substances is important but challenging since measuring this quantity using the standard Wilhelmy plate or DuNuoy ring methods is not possible due to breakage of the gel. The experiments were conducted on agarose gels having elasticities ranging from 12.2 to 200.3 Pa. A method is described for obtaining elasticity, surface tension, and viscosity, and the method is experimentally demonstrated for surface tension and viscosity. For the range of elasticities explored, the measured surface tension ranged from 0.1 to 0.3 N/m, and the viscosity ranged from 0.0084 to 0.0204 Pa s. The measurements of surface tension are, to the authors' knowledge, the first obtained of a gel using ultrasonic levitation.


Photochemical nucleophile-olefin combination, aromatic substitution reaction. Its synthetic development and mechanistic exploration.
The photochemical nucleophile-olefin combination, aromatic substitution (photo-NOCAS) reaction has been a cornerstone of research in our laboratory for several years. In this Account we present an overview of the mechanistic exploration and rationalization of this photoinduced electron transfer reaction. We have investigated the mechanism and defined the synthetic scope and limitations by variations in reaction conditions and structural modification of the substrates. During our studies, we have come across several other pathways in competition with the photo-NOCAS reaction that dominate once specific conditions are altered. These alternative reactions are also discussed briefly.


The relationship between light, dopamine release and horizontal cell coupling in the mudpuppy retina.
1. The effect of different experimental conditions on electrical coupling between horizontal cells in the mudpuppy retina was studied by comparing the changes in responses to illumination of the central and peripheral portions of the receptive field, using centred spot and annulus stimuli. An increase in the amplitude of the response to a centred spot stimulus and a decrease in the amplitude of the response to a concentric annulus indicated a decrease in coupling, and vice versa. 2. Dopamine (10-250 microM) caused a decrease in coupling between horizontal cells. The uncoupling effect of dopamine was much greater in dark-adapted than in light-adapted retinas. The effect of the D1-receptor agonist SKF38393 was similar to that of dopamine. The effect of the D2-receptor agonist LY171555 on coupling was opposite to that of dopamine; this was attributed to a reduction in endogenous dopamine release. 3. The D1 antagonist SCH23390 (15 microM) caused an increase in coupling between horizontal cells. This effect was much greater in light-adapted than in dark-adapted retinas. 4. The glutamate analogue 2-amino-4-phosphonobutyrate (APB), which hyperpolarizes on-centre bipolar cells and blocks their responses to light, caused an increase in coupling between horizontal cells. This effect of APB was greater in light-adapted retinas than in dark-adapted retinas. The effect of APB on coupling could be reversed by the addition of dopamine, but the effect of dopamine on coupling could not be reversed by the addition of APB. These results suggest that APB increases horizontal cell coupling by causing a decrease in dopamine release. 5. In dark-adapted retinas, 2.5 min exposure to an adapting light caused a decrease in coupling between horizontal cells; the uncoupling effect of the adapting light was blocked in the presence of either SCH23390 or APB. 6. The results suggest that coupling between horizontal cells in the mudpuppy retina is decreased by dopamine acting at D1 receptors, that the release of dopamine affecting horizontal cells is greater under light-adapted conditions, and that the pathway by which exposure to light increases this dopamine release is mainly via on-centre bipolar cells.


Absence of mutations in the coding region of the alpha-synuclein gene in pathologically proven Parkinson's disease.
A missense mutation of the alpha-synuclein gene has been associated with parkinsonism in a large Italian kindred. Recently, alpha-synuclein was also identified in Lewy bodies. Using reverse transcribed-polymerase chain reaction (RT-PCR) technique, we sequenced the entire coding region of the alpha-synuclein gene using brain tissue from 24 pathologically proven Parkinson's disease cases. No mutations were found in any of the patients, suggesting that a mutation at the coding region of the alpha-synuclein gene is unlikely to be responsible for nigrostriatal degeneration in typical sporadic Parkinson's disease.


[Infectious endocarditis in injection drug users. Part 1. Etiology, pathogenesis, and clinical features].
Clinical features of infectious endocarditis (IE) in injection drug users are described with reference to its etiology, pathogenesis, and treatment. The prevalence of IE among different age groups of drug addicts and frequency of its most common etiological variants depending on microflora composition are analysed. Clinical manifestations of IE are considered. A major concern being diagnosis of IE, the most widely used diagnostic criteria and laboratory/instrumental diagnostic tools are discussed. The priority of antibacterial therapy of IE is emphasized and its rational schemes are proposed.


The application of terminomics for the identification of protein start sites and proteoforms in bacteria.
Protein terminomics, or the study of amino acids sequences at the protein amino or carboxyl terminus has rapidly evolved as a proteomic discipline due to significant methodological improvements in the labelling and recovery of terminal peptides as well as the increased speed and sensitivity of current mass spectrometry instrumentation. The most significant beneficiaries of these developments include an increased awareness and understanding of complex proteolytic cascades that regulate key biological processes and in genome annotation. Most terminomics research to date has focused on gaining insight into important biological processes such as inflammation, wound healing and cancer. The application of terminomics to the study of important biological questions in prokaryotes is gaining traction. Here we review current applications and progress of terminomics in prokaryotes, discuss the significance of protease research in bacterial pathogenesis and protein maturation, and suggest novel applications of terminomics in the study of infectious disease.


Delayed HIV diagnosis common in Sweden, 2003-2010.
Early diagnosis of HIV is important for the prognosis of individual patients, because antiretroviral treatment can be started at the appropriate time, and for public health, because transmission can be prevented. Data were collected from 767 HIV patients who were diagnosed in Sweden during 2003-2010 and were infected in Sweden or born in Sweden and infected abroad. A recent infection testing algorithm (RITA) was applied to BED-EIA test results (OD-n < 0.8), CD4 counts (≥ 200 cells/μl), and clinical information. A recent infection classification was used as indicator for early diagnosis. Time trends in early diagnosis were investigated to detect population changes in HIV testing behavior. Patients with early diagnosis were compared to patients with delayed diagnosis with respect to age, gender, transmission route, and country of infection (Sweden or abroad). Early diagnosis was observed in 271 patients (35%). There was no statistically significant time trend in the yearly percentage of patients with early diagnosis in the entire study group (p = 0.836) or in subgroups. Early diagnosis was significantly more common in men who have sex men (MSM) (45%) than in heterosexuals (21%) and injecting drug users (27%) (p < 0.001 and p = 0.001, respectively) in both univariate and multivariable analyses. The only other factor that remained associated with early diagnosis in multivariable analysis was young age group. Approximately one-third of the study patients were diagnosed early with no significant change over time. Delayed HIV diagnosis is a considerable problem in Sweden, which does not appear to diminish.


Voluntary suppression of thoughts is influenced by anxious and ruminative tendencies in healthy volunteers.
Replicating thought suppression effects with the Think/No-Think paradigm (TNT) has failed in some studies investigating the phenomenon of below-baseline recall of suppressed stimuli. Attempts have been made to isolate factors that might explain inter-individual differences in suppression performance. Certain personality traits, whether associated with a pathological state or investigated in a community sample, have been shown to interfere with successful thought suppression and might be responsible for some of the negative results obtained in TNT studies. In the present study we investigate the influence of psychometric measures of depression and anxiety in a fairly large sample of healthy volunteers. We show that high brooding and anxious tendencies predict worse suppression performance. While no suppression was shown when investigating the TNT not taking the psychometric measures into account, including these two traits in the analysis resulted in a pattern of below-baseline recall only for low brooders and low anxious participants. We argue that inclusion of variables measuring personality traits is warranted using the TNT and that these variables already exert their influence at minimal levels of variance, significantly improving the interpretability of the results. Future research should therefore cautiously investigate potential confounding personality characteristics before analysing their data.


Effect of C1 inhibitor on inflammatory and physiologic response patterns in primates suffering from lethal septic shock.
We evaluated the effect of C1 inhibitor (C1-inh), an inhibitor of the classical pathway of complement and the contact system, on the physiologic and inflammatory response in baboons suffering from lethal Escherichia coli sepsis. Five animals pretreated with 500 U/kg C1-inh (treatment group; n = 5), followed by a 9-h continuous infusion of 200 U/kg C1-inh subsequent to bacterial challenge, were compared with five controls receiving E. coli alone. Of the treatment group, one animal survived and another lived beyond 48 h, whereas all control animals died within 27 h. In four of five treated animals, less severe pathology was observed in various target organs. C1-inh administration did not prevent the hemodynamic or hematologic changes observed upon E. coli infusion. The activation of fibrinolysis and the development of disseminated intravascular coagulation were essentially unaffected by C1-inh. However, C1-inh supplementation significantly reduced decreases in plasma levels of factor XII and prekallikrein and abrogated the systemic appearance of C4b/c, indicating substantial inhibition of activation of the contact system and the classical complement pathway, respectively. Furthermore, treated animals displayed a reduced elaboration of various cytokines including TNF, IL-10, IL-6, and IL-8. Thus, the administration of C1-inh may have a beneficial but modest effect on the clinical course and outcome of severe sepsis in nonhuman primates. We suggest that activated complement and/or contact system proteases may, at least in part, contribute to the attendant manifestations of septic shock through an augmentation of the cytokine response.


Clinical governance: vision or mirage?
Clinical governance was intended to ensure clinical quality in the National Health Service. Its first full description, in the British Medical Journal in 1998, seemed to some to be more rhetoric than substance. Now, 3 years on, its proponents believe it is starting to achieve its purpose. The British Medical Journal has again published a paper, this time subtitled 'turning vision into reality'. Expectations might have been that this paper would present evidence of how clinical governance is changing practice to ensure quality, but analysis of the paper shows that it does little more than repeat the rhetoric of the earlier description. It describes how clinical governance might be organized and what it might do, but not what it has done. Its authors repeat the idea that everyone can be 'the best' and achieve 'exellence', which is not reality at all. Anyone introducing a new method of managing the National Health System has the same obligation as those who introduce new treatments to provide evidence that the method works, and that the financial and non-financial costs are not too high. The new paper fails to provide that evidence.


Surveillance for early detection of aggressive parathyroid disease: carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation.
Familial hyperparathyroid syndromes involving mutations of HRPT2 (also CDC73), a tumor suppressor, are important to identify because the relatively high incidence of parathyroid malignancy associated with such mutations warrants a specific surveillance strategy. However, there is a dearth of reports describing experience with surveillance and early detection informed by genetic insight into this disorder. Familial isolated hyperparathyroidism (FIHP) is a rare cause of parathyroid (PT) tumors without other neoplasms or endocrinopathies. Germline mutations in CASR, MEN1, and rarely, HRPT2 have been identified in kindreds with FIHP. HRPT2 mutations may be enriched in FIHP families with PT carcinoma, underscoring the importance of identifying causative mutations. A 13-year-old boy, whose father had died of PT carcinoma, developed primary hyperparathyroidism. A left superior PT mass was identified by ultrasonography and removed surgically. Aggressive histological features of the boy's tumor included fibrous trabeculae, mitoses, and microscopic capsular infiltration. Two years later, under close biochemical surveillance, primary hyperparathyroidism recurred 5 months after documentation of normocalcemia and normal parathyroid status. Ultrasound and MRI identified a newly enlarged right superior PT gland but indicated no recurrent disease in the left neck. Histologic features typical of a benign adenoma were evident after surgical extirpation of the gland. Leukocyte DNA analysis revealed a frameshift mutation in exon 2 of HRPT2. The initial tumor manifested the expected germline HRPT2 mutation, plus a distinct somatic frameshift mutation, consistent with the Knudson "two hit" concept of biallelic inactivation of a classic tumor suppressor gene. Genetic screening of the patient's 7 asymptomatic and previously normocalcemic siblings revealed three with the same germline HRPT2 mutation. One of the siblings newly identified as mutation-positive was noted to be hypercalcemic at the time of the genetic screening. He was found to have a PT adenoma with aggressive features. Two of the five children of another mutation-positive sibling also carry the same HRPT2 mutation. Despite the reported rarity of HRPT2 mutations in FIHP, a personal or family history of PT carcinoma in FIHP mandates serious consideration of germline HRPT2 mutation status. This information can be used in diagnostic and management considerations, leading to early detection and removal of potentially malignant parathyroid tumors.


Variation in embolism occurrence and repair along the stem in drought-stressed and re-watered seedlings of a poplar clone.
Root pressure and plasma membrane intrinsic protein (PIP) availability in the xylem have been recognized to participate in the refilling of embolized conduits, yet integration of the two mechanisms has not been reported in the same plant. In this study, 4-month-old seedlings of a hybrid poplar (Populus alba × Populus glandulosa) clone 84K were subjected to two contrasting soil-water treatments, with the drought treatment involving withholding of water for 17 days to reduce the soil-water content to 10% of the saturated field capacity, followed by a re-watering cycle. The percentage loss of stem hydraulic conductance (PLC) sharply increased, and stomatal conductance and photosynthesis declined in response to drought stress; these processes were gradually restored following the subsequent re-watering. Embolism was most severe in the middle portions of the stem, followed by the basal and top portions of the stems of seedlings subjected to drought stress and subsequent re-watering. Although drought stress eliminated root pressure, re-watering partially restored it in a short period of time. The expression of PIP genes in the xylem was activated by drought stress, and some PIP genes were further stimulated in the top portion after re-watering. The dynamics of root pressure and differential expression of PIP genes along the stem coincided with changes in PLC, suggesting that root pressure and PIPs work together to refill the embolized vessels. On the basis of the recovery dynamics in PLC and g(smax) (maximum stomatal conductance) after re-watering, the stomatal closure and xylem cavitation exhibited fatigue due to drought stress.


Robotic versus laparoscopic rectal resection for sphincter-saving surgery: pathological and short-term outcomes in a single-center analysis of 130 consecutive patients.
Minimally invasive sphincter-saving rectal resection represents a challenging procedure. Robotic surgery for rectal cancer has several advantages over conventional surgery in performing precise dissection and was proved to be safe and effective in previous studies. However, comparison between laparoscopic and robotic rectal resection has drawn contradictory results. The aim of the present study was to compare robotic and laparoscopic sphincter-saving rectal resections for short-term and pathological outcomes. Between January 2013 and May 2016, we performed a total of 258 robotic surgeries, including 146 colorectal resections (56%). For this study, we included the first 65 sphincter-saving robotic resections and compared them to the last 65 consecutive laparoscopic resections. The laparoscopic group was constituted by the last 65 consecutively operated patients who matched the inclusion criteria. Patients' baseline characteristics were similar in both the groups. Conversion rate was greater in the laparoscopic group (17 vs. 5%, p=0.044). Reoperation rate, overall and severe morbidity, and median hospital stay were similar in both the groups. Quality of mesorectal excision specimen was considered complete or near complete in 97 and 96% in the laparoscopic and robotic groups, respectively. There was no difference in the rates of negative circumferential radial margin, distal margin, and surgical success measured by composite criteria. The main finding of this study was that robotic proctectomy for sphincter-saving procedures offers similar quality of TME with a statistically significant lower rate of conversion when compared to laparoscopic proctectomy.


Ingestion of white spirit resulting in perineal skin burns: a case report and review of the literature.
In the literature, possible systemic effects on health of inhalation or ingestion of white spirit are well described. Only a few case reports discuss the toxic skin effects that can occur following massive ingestion. Ingestion of large amounts of white spirit produces a watery diarrhoea with a high concentration of white spirit, resulting in perineal skin burns when there is prolonged contact. We describe a patient who developed partial thickness perineal skin burns after ingestion of white spirit and review the literature. The present data indicate that conservative therapy of the skin burns is recommended.


Combined action of extracellular signal-regulated kinase and p38 kinase rescues Molt4 T cells from nitric oxide-induced apoptotic and necrotic cell death.
The mechanisms that regulate nitric oxide (NO)-induced apoptosis, especially in T cell apoptosis, are largely uncharacterized. Here, we report that protection from NO-induced cell death by phorbol 12-myristate 13-acetate (PMA) is dependent on both p38 and extracellular signal-regulated kinase (ERK) activation. Exposure of Molt4 cells to NO donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) induced both apoptotic and necrotic modes of cell death along with a sustained increase in p38 kinase phosphorylation. However, the p38 inhibitor SB202190 only slightly protected Molt4 cells from NO toxicity. In contrast, PMA rapidly phosphorylated both p38 kinase and ERK, and the phosphorylation statuses were not altered in the presence of SNAP. Interestingly, although each mitogen-activated protein kinase (MAPK) inhibitor by itself had only a modest effect, the combination of inhibitors for both MAPKs almost completely abolished the protective effect of PMA. Furthermore, dominant negative or catalytically inactive variants that modulate p38 and ERK mimicked the effects of MAPK inhibitors. We located the action of p38 and ERK upstream of the p53/mitochondrial membrane potential loss and caspases cascade. Together, these findings suggest that the PMA-induced activations of ERK and p38 kinase are parallel events that are both required for inhibition of NO-induced death of Molt4 cells.


Serum neutralization of SARS coronavirus 2 Omicron sublineages BA.1 and BA.2 and cellular immune responses 3 months after booster vaccination.
We investigated serum neutralizing activity against BA.1 and BA.2 Omicron sublineages and T cell response before and 3 months after administration of the booster vaccine in healthcare workers (HCWs). HCWs aged 18-65 years who were vaccinated and received booster doses of the BNT162b2 vaccine were included. Anti-SARS coronavirus 2 IgG levels and cellular response (through interferon γ ELISpot assay) were evaluated in all participants, and neutralizing antibodies against Delta, BA.1, and BA.2 were evaluated in participants with at least one follow-up visit 1 or 3 months after the administration of the booster dose. Among 118 HCWs who received the booster dose, 102 and 84 participants attended the 1-month and 3-month visits, respectively. Before the booster vaccine dose, a low serum neutralizing activity against Delta, BA.1, and BA.2 was detectable in only 39/102 (38.2%), 8/102 (7.8%), and 12/102 (11.8%) participants, respectively. At 3 months, neutralizing antibodies against Delta, BA.1, and BA.2 were detected in 84/84 (100%), 79/84 (94%), and 77/84 (92%) participants, respectively. Geometric mean titres of neutralizing antibodies against BA.1 and BA.2 were 2.2-fold and 2.8-fold reduced compared with those for Delta. From 1 to 3 months after the administration of the booster dose, participants with a recent history of SARS coronavirus 2 infection (n = 21/84) had persistent levels of S1 reactive specific T cells and neutralizing antibodies against Delta and BA.2 and 2.2-fold increase in neutralizing antibodies against BA.1 (p 0.014). Conversely, neutralizing antibody titres against Delta (2.5-fold decrease, p < 0.0001), BA.1 (1.5-fold, p 0.02), and BA.2 (2-fold, p < 0.0001) declined from 1 to 3 months after the administration of the booster dose in individuals without any recent infection. The booster vaccine dose provided significant and similar response against BA.1 and BA.2 Omicron sublineages; however, the immune response declined in the absence of recent infection.


Particle size distributions and elemental composition of atmospheric particulate matter in southern Italy.
Three 2-wk seasonal field campaigns were performed in 2003 and 2004 at a sampling site on the southern Tyrrhenian coast of Italy with the aim to investigate the dynamics and characteristics of particle-bound pollutants in the Mediterranean area. Fine (PM(2.5)) and coarse particulate matter (PM(10-2.5)) size fractions were collected by a manual dichotomous sampler on 37-mm Teflon filters over a 24-hr sampling period. On average, 70% of the total PM(10) (PM(2.5) + PM(10-2.5)) mass was associated with the coarse fraction and 30% with the fine fraction during the three campaigns. The ambient concentrations of Pb, Ni, Cr, Zn, Mn, V, Cd, Fe, Cu, Ca, and Mg associated with both size fractions were determined by atomic absorption spectrometry. Ambient concentrations showed differences in their absolute value, ranging from few ng x m(-3) to microg x m(-3), as well as in their variability within the PM(2.5) and PM(10-2.5) size fractions. PM(10) levels were well below the European Union (EU) limit value during the study period with the exception of three events during the first campaign (fall) and five events during the third campaign (spring). Two main sources were identified as the major contributors including mineral dust, transported from North Africa, and sea spray from the Tyrrhenian Sea. Comparing the results with backward trajectories, calculated using the Hybrid Single-Particle Lagrangian Integrated Trajectory Model (HYSPLIT) and Total Ozone Mapping Spectrometer-National Aeronautics and Space Administration (TOMS-NASA) maps, it was observed that in central and eastern Europe, the Tyrrhenian Sea and North Africa were the major emission source regions that affected the temporal variations and daily averages of PM(2.5) and PM(10-2.5) concentrations.


[Visual hallucination in the hemianopic field caused by dural arteriovenous malformation].
We presented a 65-year-old man with the right occipital dural arteriovenous malformation (AVM) who first experienced photopsia in his left inferior quadrantanopic field and then developed formed hallucinations 8 days later. His visual hallucinations disappeared with saccadic eye movements. EEG showed no epileptic discharge. MRI revealed hyperintensity in the right medial occipital lobe on proton density image. 123I-IMP SPECT during the hallucinations revealed decrease of regional cerebral blood flow (r-CBF) not only in the right medial occipital lobe but also in the right lateral occipital and in the right medial temporal lobe. Both left inferior quadrantanopia and visual hallucinations disappeared following the treatment of the dural AVM by transarterial embolizations. Because the lesion on MRI improved after the treatment, we considered that the lesion was brain edema, not infarction. Additionally decreased r-CBF in the temporo-occipital lesion on SPECT improved after the treatment, we emphasized the role of the temporo-occipital lesion as the cause of visual hallucinations in the hemianopic field.


Radiologic bone assessment in the evaluation of osteoporosis.
Osteoporosis affects nearly 28 million elderly Americans. Its major clinical manifestation is fragility fractures of the spine, hip, and distal radius. Low bone mass is the most important risk factor for a fragility fracture. In 1994, the World Health Organization defined osteoporosis on the basis of a bone mineral density that is 2.5 standard deviations below that in peak young normal persons. Three common imaging modalities used to assess bone strength are dual-energy x-ray absorptiometry, quantitative computed tomography, and calcaneal ultrasonography. The first two modalities measure bone mineral density in both the lumbar spine and peripheral sites. It is thought that calcaneal ultrasonography measures bone architecture and density. Unlike the other studies, ultrasonography currently cannot be used for monitoring skeletal changes over time or evaluating response to therapy.


Treatment of hip dislocation in Kabuki syndrome: a report of three hips in two patients.
The incidence of hip dislocation in Kabuki syndrome (KS) is thought to be between 18% and 40%. Although hip dislocation is apparently well recognized in KS, to our knowledge, its management and outcome have not previously been addressed in the literature. We report 2 children (3 hips) with KS and hip dislocation who underwent surgical treatment with a minimum of 24-month follow-up. In addition, we review the current literature on the treatment of orthopaedic problems in KS.


Phosphinoborenium cations stabilized by N-heterocyclic carbenes: synthesis, structure, and reactivity.
Phosphinoborenium cations stabilized by N-heterocyclic carbenes (NHCs) were synthesized via the reaction of bromo(phosphino)boranes with NHCs. Their structures were investigated by heteronuclear magnetic resonance spectroscopy, X-ray diffraction, and density functional theory calculations. They possess a planar trigonal boron center directly bonded with the pyramidal phosphanyl group (PR2) and can be treated as cationic phosphinoboranes. The reactivity of the selected NHC-phosphinoborenium cation was tested toward AuCl·SMe2 and Ph2PCl. In both reactions, the titled compound acted as a phosphido group donor under heterolytic cleavage of the P-B bond. Control experiments with parent phosphinoborane emphasized differences between the reactivity of low-coordinate neutral and cationic species with P-B functionality.


Elucidating the Molecular Interactions between Lipids and Lysozyme: Evaporation Resistance and Bacterial Barriers for Dry Eye Disease.
Dry eye disease (DED) is a chronic condition characterized by ocular dryness and inflammation. The tear film lipid layer (TFLL) is the outermost layer composed of lipids and proteins that protect the ocular surface. However, environmental contaminants can disrupt its structure, potentially leading to DED. Although the importance of tear proteins in the TFLL functionality has been clinically recognized, the molecular mechanisms underlying TFLL-protein interactions remain unclear. In this study, we investigated tear protein-lipid interactions and analyzed their role in the TFLL functionality. The results show that lysozyme (LYZ) increases the stability of the TFLL by reducing its surface tension and increasing its surface pressure, resulting in increased TFLL evaporation and bacterial invasion resistance, with improved wettability and lubrication performance. These findings highlight the critical role of LYZ in maintaining ocular health and provide potential avenues for investigating novel approaches to DED treatment and patient well-being.


The np Rydberg series of boron monohydride: l-uncoupling and Rydberg electron interactions with the rovibrational motion of the ion core.
A simple two-channel quantum defect theory approach accounts for resonance positions in the np Rydberg series of (11)BH. The transition from Hund's case (b) to (d) in the interacting levels of this np series represents a fundamental example of electron orbital ⇔ cation core rotational coupling, and frame transformation theory offers a means to connect close-coupled electronically excited-state potentials and l-uncoupled Rydberg positions. This evolving interaction of the np Rydberg electron with the rotational and the vibrational motion of the (11)BH(+) core is formulated in terms of quantum defects, μ(λ)(v(+)).


Bacillus thuringiensis toxins: an overview of their biocidal activity.
Bacillus thuringiensis (Bt) is a Gram positive, spore-forming bacterium that synthesizes parasporal crystalline inclusions containing Cry and Cyt proteins, some of which are toxic against a wide range of insect orders, nematodes and human-cancer cells. These toxins have been successfully used as bioinsecticides against caterpillars, beetles, and flies, including mosquitoes and blackflies. Bt also synthesizes insecticidal proteins during the vegetative growth phase, which are subsequently secreted into the growth medium. These proteins are commonly known as vegetative insecticidal proteins (Vips) and hold insecticidal activity against lepidopteran, coleopteran and some homopteran pests. A less well characterized secretory protein with no amino acid similarity to Vip proteins has shown insecticidal activity against coleopteran pests and is termed Sip (secreted insecticidal protein). Bin-like and ETX_MTX2-family proteins (Pfam PF03318), which share amino acid similarities with mosquitocidal binary (Bin) and Mtx2 toxins, respectively, from Lysinibacillus sphaericus, are also produced by some Bt strains. In addition, vast numbers of Bt isolates naturally present in the soil and the phylloplane also synthesize crystal proteins whose biological activity is still unknown. In this review, we provide an updated overview of the known active Bt toxins to date and discuss their activities.


Incursion pathways of the Asian tiger mosquito (Aedes albopictus) into Australia contrast sharply with those of the yellow fever mosquito (Aedes aegypti).
Understanding pest incursion pathways is critical for preventing new invasions and for stopping the transfer of alleles that reduce the efficacy of local control methods. The mosquitoes Aedes albopictus (Skuse) and Ae. aegypti (Linnaeus) are both highly invasive disease vectors, and through a series of ongoing international incursions are continuing to colonize new regions and spread insecticide resistance alleles among established populations. This study uses high-resolution molecular markers and a set of 241 reference genotypes to trace incursion pathways of Ae. albopictus into mainland Australia, where no successful invasions have yet been observed. We contrast these results with incursion pathways of Ae. aegypti, investigated previously. Assignments successfully identified China, Japan, Singapore and Taiwan as source locations. Incursion pathways of Ae. albopictus were entirely different to those of Ae. aegypti, despite broad sympatry of these species throughout the Indo-Pacific region. Incursions of Ae. albopictus appeared to have come predominantly along marine routes from key trading locations, while Ae. aegypti was mostly linked to aerial routes from tourism hotspots. These results demonstrate how genomics can help decipher otherwise cryptic incursion pathways. The inclusion of reference genotypes from the Americas may help resolve some unsuccessful assignments. While many congeneric taxa will share common incursion pathways, this study highlights that this is not always the case, and incursion pathways of important taxa should be specifically investigated. Species differences in aerial and marine incursion rates may reflect the efficacy of ongoing control programmes such as aircraft disinsection. © 2020 Society of Chemical Industry.


Eucalcemia during lipopolysaccharide challenge in postpartum dairy cows: I. Clinical, inflammatory, and metabolic response.
Hypocalcemia induced by immune activation is a conserved response across mammalian species; however, administration of Ca is discouraged in other species as it is associated with increased morbidity and mortality. Early postpartum cows experience a decrease in circulating Ca concentration following acute inflammation. Corrective Ca therapy during the transition period, particularly in dairy cows experiencing acute disease, is common practice. However, the effect of Ca administration on the inflammatory response during acute immune activation is unknown. Our objective was to compare the clinical, inflammatory, and metabolic response to an intravenous (IV) lipopolysaccharide (LPS) challenge between postpartum cows infused, or not, with IV Ca to maintain eucalcemia. Cows (n = 14, 8 ± 1 d in milk) were enrolled in a matched-pair randomized controlled design to receive IV Ca (IVCa) or sterile 0.9% NaCl (CTRL) during an IV LPS challenge (0.040 or 0.045 µg of LPS/kg of body weight over 1 h). Ionized Ca (iCa) was monitored cow-side, and IV Ca infusion was adjusted in a eucalcemic clamp for 12 h following the start of LPS infusion. Cows were monitored during the 24 h following challenge and serial blood samples were collected to quantify concentrations of glucose, β-hydroxybutyrate, nonesterified fatty acids, urea nitrogen, cytokines, acute-phase proteins, and cortisol. Blood iCa concentration decreased to 0.87 ± 0.03 mM in CTRL during challenge, and by design, iCa concentration was maintained within 3% of baseline in IVCa. Body temperature, heart rate, and respiratory rate were monitored for 24 h following the start of challenge and did not differ between groups. A treatment × time interaction was identified such that serum cortisol concentrations increased in both groups at 2 h but decreased to a greater extent at 6 h in IVCa compared with CTRL. Rumination time (min/h) over the first 12 h following challenge was greater in IVCa, but total rumination time in the 24 h following challenge did not differ from CTRL. Serum glucose and nonesterified fatty acid concentrations decreased, and β-hydroxybutyrate and urea nitrogen concentrations increased over time, but did not differ between groups. Acute leukopenia occurred in both groups at 4 h before leukocytosis was observed at 24 h with total white blood cell counts returning to baseline within 72 h. Plasma concentrations of tumor necrosis factor (TNF) and interleukin-10 (IL-10) increased within 1 h following the start of challenge and did not differ between groups. Serum haptoglobin and serum amyloid A concentrations increased within the 24 h following challenge and were elevated through 72 h but did not differ between groups. Eucalcemia during the acute systemic inflammatory response did not alter the TNF or IL-10 cytokine response, or the acute-phase protein SAA and haptoglobin response in this LPS challenge model; however, eucalcemia was associated with a more rapid decline in cortisol response and greater rumination time in the first 12 h following challenge. We did not find evidence that eucalcemia exacerbated the inflammatory response in early postpartum cows, but Ca administration may alter the clinical response to acute systemic inflammation.


Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin.
Parkinson's disease (PD) is a common neurodegenerative disorder caused by loss of midbrain dopaminergic neurons, the pathogenetic mechanisms of which remain unclear. Mitochondrial dysfunction, which has long been implicated in sporadic PD, has recently been highlighted as a key pathological cause, particularly with the identification of mutations in the PTEN-induced putative kinase (pink1), parkin and htrA2 (also known as omi) genes that are linked to PD. Studies in Drosophila melanogaster have shown that pink1 and parkin act in a common genetic pathway that maintains mitochondrial integrity, but other upstream or downstream components of this pathway are currently unknown. Using ectopic expression in the Drosophila eye as an assay, we have investigated the involvement of the mitochondrial protease encoded by omi in the Pink1/Parkin pathway and found that it acts genetically downstream of pink1 but functions independently of Parkin. Using the same approach, we also found that Rhomboid-7, a mitochondrial protease not previously implicated in PD, acts as an upstream component of this pathway, and showed that it is required to cleave the precursor forms of both Pink1 and Omi. These data further elucidate the composition of the Pink1 pathway and suggest that regulated intramembrane proteolysis is involved in its regulation.


Basic principles of intravenous immunoglobulin (IVIg) treatment.
The original rationale for the therapeutic application of immunoglobulins was prevention and treatment of infectious diseases. With the description of agammaglobulinemia, substitution therapy became the primary indication for the use of immunoglobulins. Limitations and side effects of the intramuscular administration of immunoglobulins led to the development of preparations for intravenous use (IVIg). In the early 1980s an immunomodulatory effect of IVIg was described. Since then, the efficacy of IVIg has been established in controlled trials for diseases like idiopathic thrombocytopenic purpura, Kawasaki disease, Guillain-Barré syndrome, dermatomyositis, and many others. There is a large body of evidence that IVIg can modulate an immune reaction at the level of T cells, B cells, and macrophages, interferes with antibody production and degradation, modulates the complement cascade, and has effects on the cytokine network. However, the precise mechanism of action is not yet clear.


Intra- and Intersubject Variability in Audiometric Measures and Loudness Judgments in Older Listeners with Normal Hearing.
This research was to document intra- and intersubject variability in measures of pure tone thresholds, loudness discomfort levels, and the Contour test of loudness for tonal and speech stimuli across 8 to 10 repeated test sessions over a period of almost 1 year in a group of 11 normal-hearing, older middle-aged adults (39 to 73 years, mean of 56 years). The measured pure tone thresholds and loudness discomfort levels were determined to be stable across sessions, with variability on the order of 5 dB. The categorical judgments for the Contour test for both warbled tones and spondaic speech stimuli decreased over time in level required for categories greater than comfortable. This result contrasts with reports of a slight increase over time when young, normal-hearing adults were tested in comparable measures. The intrasubject variability in the Contour test results was greatest for the 4,000-Hz tonal stimulus for which the largest time effects were observed. The intersubject variability was typically greater than the intrasubject variability and typically increased as the loudness category increased, with some exceptions. The results from this study can be used to aid in power and sample size analyses using these measures in future studies designed to compare effects of treatments based on changes in loudness judgments over time.


Tailoring Metalloporphyrin Frameworks for an Efficient Carbon Dioxide Electroreduction: Selectively Stabilizing Key Intermediates with H-Bonding Pockets.
The electrocatalytic reduction of carbon dioxide (CO2ER) is a great challenge within the field of energy and environmental research. Competing reactions, including hydrogen evolution reactions (HER) and surface oxidation, limit the conversion of CO2ER at low overpotentials. This is because these competing reactions produce intermediates (adsorbed H and OH) with chemical bonds similar to those formed in CO2ER (adsorbed COOH and OCHO). Here, we report the adsorption free energies of CO2ER and competitive intermediates within H-bonding functionalized metalloporphyrin frameworks using first-principles calculations. The functionalized frameworks shift the scaling relation of adsorption free energies to favor the CO2ER intermediates rather than the HER. Inspired by molecular catalysts, we proposed and studied H-bonding interfaces that specifically stabilize the target intermediates of the CO2ER. The selective H-bonding stabilization reduced the limiting potential for CO2ER by up to 0.2-0.3 V. Our results agree with previous experiments that found that cobalt- and iron-based metalloporphyrins exhibited the most promising catalytic activity in CO2-to-CO reduction, with small potential barriers for the adsorbed COOH intermediate. In addition, embedding the functionalized metalloporphyrin moieties in a rigid framework structure acted to enhance the CO2ER selectivity by preventing the porphyrin from stacking and keeping H-bonding interfaces in close proximity to only CO2ER intermediates. Improved selectivity to the desired CO2ER was achieved through three steps: first by systematically screening for metal centers, second by creating an ideal H-bonding environment, and finally by using a rigid macrocycle ring structure.


Endurance exercise in seniors: Tonic, toxin or neither?
Cardiac adaptation to sustained exercise in the athletes is established. However, exercise-associated effect on the cardiac function of the elderly has to be elucidated. The aim of this study was to analyse left (LV) and right ventricular (RV) characteristics at different levels of chronic exercise in the senior heart. We studied 178 participants in the World Senior Games (mean age 68 ± 8 years, 86 were men; 48%). Three groups were defined based on the type and intensity of sports: low-, moderate- and high-intensity level. Exclusion criteria were coronary artery disease, atrial fibrillation, valvular heart disease or uncontrolled hypertension. LV and RV size and function were evaluated with an echocardiogram. LV trans-mitral inflow deceleration time decreased in parallel to the intensity of chronic exercise: 242 ± 54 ms in low-, 221 ± 52 ms in moderate- and 215 ± 58 ms in high-intensity level, p = .03. Left atrial volume index (LAVI) was larger in high-intensity group, p = .001. The LAVI remained significantly larger when adjusting for age, gender, heart rate, hypertension and diabetes (p = .002). LV and RV sizes were larger in the high-intensity group. LV ejection fraction and RV systolic function evaluated by tissue Doppler velocity, atrioventricular plane displacement and strain did not differ between groups. Left ventricular diastolic filling is not only preserved, but may also be enhanced in long-term, top-level senior athletes. Moreover, LV and RV systolic function remain unchanged at different levels of exercise. This supports the beneficial effects of endurance exercise participation in senior hearts.


Tips from the toolkit: 2--assessing organisational strengths.
'SWOT' is a familiar term used in the development of business strategy. It is based on the identification of strengths, weaknesses, opportunities and threats as part of a strategic analysis approach. While there are a range of more sophisticated models for analysing and developing business strategy, it is a useful model for general practice as it is less time consuming than other approaches. The following article discusses some ways to apply this framework to assess organisational strengths (and weaknesses). It is based on The Royal Australian College of General Practitioners' "General practice management toolkit".


Are exergames an option to cope with sleep disorders during the COVID-19 outbreak?
During the COVID-19 pandemic, factors related to the isolation and quarantine period increased psychobiological distress in the general population around the world, increasing anxiety, emotional stress, and depression, as well as worsening of the quality of sleep. Seeking alternatives to provide support for the implementation of some interventions for well-being and health under pandemic conditions, exergames (active video games) seem to be a feasible alternative to keep people physically active and to positively impact sleep health. In this overview article, we discussed the feasibility of exergames as an option to cope with sleep disorders and improve sleep quality during the COVID-19 outbreak through increasing physical exercise and physical fitness levels.


Full Wavefield Analysis and Damage Imaging Through Compressive Sensing in Lamb Wave Inspections.
One of the main challenges faced by the structural health monitoring community is acquiring and processing huge sets of acoustic wavefield data collected from sensors, such as scanning laser Doppler vibrometers or ultrasonic scanners. In fact, extracting information that allows the estimation of the damage condition of a structure can be a time-consuming process. This paper presents a damage detection and localization technique based on a compressive sensing algorithm, which significantly allows us to reduce the acquisition time without losing in detection accuracy. The proposed technique exploits the sparsity of the wavefield in different representation domains, such as those spanned by wave atoms, curvelets, and Fourier exponentials to recover the full wavefield and, at the same time, to infer the damage location, based on comparison between the wavefield reconstructions produced by the different representation domains. The procedure is applied to three different setups related to an aluminum plate with a notch, a glass fiber reinforced polymer plate with a notch, and a composite plate with a delamination. The results show that the technique can be applied in a variety of structural components to reduce acquisition time and achieve high performance in defect detection and localization by removing up to 80% of the Nyquist sampling grid.


Hidden diversity and phylogeographic history provide conservation insights for the edible seaweed Sargassum fusiforme in the Northwest Pacific.
Understanding the evolutionary processes that have created diversity and the genetic potential of species to adapt to environmental change is an important premise for biodiversity conservation. Herein, we used mitochondrial trnW-L and cox3 and plastid rbcL-S data sets to analyze population genetic variation and phylogeographic history of the brown alga Sargassum fusiforme, whose natural resource has been largely exterminated in the Asia-Northwest Pacific in the past decades. Phylogenetic trees and network analysis consistently revealed three major haplotype groups (A, B, and C) in S. fusiforme, with A and B distributed in the Japan-Pacific coast. Group C consisted of three subgroups (C1, C2, and C3) which were distributed in the Sea of Japan, the Yellow-Bohai Sea, and East China Sea, respectively. Isolation-with-migration (IM a) analysis revealed that the three groups diverged approximately during the mid-Pleistocene (c. 756-1,224 ka). Extended Bayesian skyline plots (EBSP) showed that groups A and B underwent relatively long-term stable population size despite a subsequent rapid demographic expansion, while subgroups C2 and C3 underwent a sudden expansion at c. 260 ka. FST and AMOVA detected low population-level genetic variation and high degrees of divergence between groups. The cryptic diversity and phylogeographic patterns found in S. fusiforme not only are essential to understand how environmental shifts and evolutionary processes shaped diversity and distribution of coastal seaweeds but also provide additional insights for conserving and managing seaweed resources and facilitate predictions of their responses to future climate change and habitat loss.


Constitutive and hyperresponsive signaling by mutant forms of Saccharomyces cerevisiae amino acid sensor Ssy1.
Sensing of extracellular amino acids results in transcriptional induction of amino acid permease genes in yeast. Ssy1, a membrane protein resembling amino acid permeases, is required for signaling but is apparently unable to transport amino acids and is thus believed to be a sensor. By using a novel genetic screen in which potassium uptake was made dependent on amino acid signaling, we obtained gain-of-function mutations in SSY1. Some alleles confer inducer-independent signaling; others increase the apparent affinity for inducers. The results reveal that amino acid transport is not required for signaling and support the notion that sensing by Ssy1 occurs via its direct interaction with extracellular amino acids.


Progesterone receptors on human spermatozoa.
Progesterone, primarily recognized as a female steroid hormone, is reported to affect several sperm functions especially capacitation, motility and acrosome reaction. These effects of progesterone on the spermatozoa are mediated via the progesterone binding sites/progesterone receptor (PR) on the acrosomal membrane. These receptors in response to progesterone increase the intercellular Ca2+ levels and stimulate Ca2+ influx in the mature human spermatozoa via non-genomic mode of actions. Characterization of this receptor reveals that the sperm PR is masked protein and is exposed to the surface by some non-ionic detergents. Localized on to the acrosome region of the spermatozoa, these receptors are recognized by most antibodies directed towards the C-terminal region of the conventional PR. The estimated molecular weight of PR on spermatozoa varies from 27 kDa to 85 kDa. At the molecular level, sequences encoding for the entire DNA and hormone binding domains of the conventional PR are detected in the mRNA derived from spermatozoa. No insertions, deletions or mutations are detected in this region. These results are suggestive of the fact that at least the C terminal region of the conventional PR is conserved in the sperm. It is hypothesized that post-translational modifications or peptide splicing of the conventional PR in spermatozoa may possibly lead to the variant of the steroid hormone receptor. Detailed characterization of the sperm PR will be important in understanding the alternate non-genomic mode of action of steroid hormone receptors.


The control of microtubule stability in vitro and in transfected cells by MAP1B and SCG10.
In neurons, the regulation of microtubules plays an important role for neurite outgrowth, axonal elongation, and growth cone steering. SCG10 family proteins are the only known neuronal proteins that have a strong destabilizing effect, are highly enriched in growth cones and are thought to play an important role during axonal elongation. MAP1B, a microtubule-stabilizing protein, is found in growth cones as well, therefore it was important to test their effect on microtubules in the presence of both proteins. We used recombinant proteins in microtubule assembly assays and in transfected COS-7 cells to analyze their combined effects in vitro and in living cells, respectively. Individually, both proteins showed their expected activities in microtubule stabilization and destruction respectively. In MAP1B/SCG10 double-transfected cells, MAP1B could not protect microtubules from SCG10-induced disassembly in most cells, in particular not in cells that contained high levels of SCG10. This suggests that SCG10 is more potent to destabilize microtubules than MAP1B to rescue them. In microtubule assembly assays, MAP1B promoted microtubule formation at a ratio of 1 MAP1B per 70 tubulin dimers while a ratio of 1 SCG10 per two tubulin dimers was needed to destroy microtubules. In addition to its known binding to tubulin dimers, SCG10 binds also to purified microtubules in growth cones of dorsal root ganglion neurons in culture. In conclusion, neuronal microtubules are regulated by antagonistic effects of MAP1B and SCG10 and a fine tuning of the balance of these proteins may be critical for the regulation of microtubule dynamics in growth cones.


Logarithmic coarsening and glassy behavior in a polymer model with mass-dependent diffusion.
We present a model of polymer growth and diffusion with frustration mechanisms for density increase and with diffusion rates of Arrhenius form with mass-dependent energy barriers Gamma(m) approximately (m-1)gamma. It shows nonuniversal logarithmic coarsening involving the exponent gamma. Strong-glass behavior is found in the typical times for disappearance of all polymers up to a given length, without reference to the equilibrium states of the macroscopic system. These features are predicted by numerical simulations, scaling theories, and an analytic solution of the master equation within an independent interval approximation, which also provides the cluster size distribution.


Local Pharmacy Pharmacists' Responses to the Prescription of Drugs That Influence Driving.
In 2013, the Ministry of Health, Labour, and Welfare issued a notification regarding drugs that influence driving. Afterward, a questionnaire survey of these drugs was conducted involving health insurance pharmacies in Tokyo and Shiga Prefectures. As a result, 503 (Tokyo) and 116 (Shiga) pharmacies provided completed questionnaires. The notification was sufficiently and slightly recognized by 20% and 44% of the surveyed pharmacies, respectively, and drugs with a driving-related warning were recognized by 31% of the pharmacies. In addition, 23% of the pharmacies reported that they always asked patients whether they drive. The influence on driving of antianxiety drugs, hypnotics, antiepileptics, and smoking-cessation drugs was always explained to patients by 74%, 72%, 64%, and 40% of the pharmacies, respectively. Concerning responses to the prescription of drugs influencing driving, the proportion of surveyed pharmacies in Tokyo and Shiga Prefectures that directed patients not to drive was 71% and 53%, respectively, and that directed patients to stop driving on developing any symptom was 32% and 49%. Tokyo and Shiga Prefectures showed a significant difference in the reason for not prohibiting driving; the proportion of pharmacies that regarded strict medication adherence as of major importance to treat patients' primary diseases was 22% and 43%, respectively. This difference might have been attributable to a high percentage of patients (80%) driving to pharmacies in Shiga Prefecture. To facilitate the prescription of drugs influencing driving, it is recommended to design drug-specific pharmaceutical education manuals that also give consideration to patients' QOL.


Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI).
Mild traumatic brain injury (mTBI) is recognized as a common injury among children, sportsmen, and elderly population. mTBI lacks visible objective structural brain damage but patients frequently suffer from long-lasting cognitive, behavioral and emotional difficulties associated with biochemical and cellular changes. Currently there is no effective treatment for patients with mTBI. The thioredoxin reductase/thioredoxin pathway (TrxR/Trx1) has both anti-inflammatory and anti-oxidative properties. If the system is compromised, Trx1 remains oxidized and triggers cell death via an ASK1-Trx1 signal transduction mechanism. We previously showed tri and tetra peptides which were derived from the canonical -CxxC- motif of the Trx1-active site, called thioredoxin mimetic (TXM) peptides, reversed inflammatory and oxidative stress damage mimicking Trx1 activity. Here, TXM-peptides were examined for protecting cognitive function following weight drop closed-head injury in a mouse model of mTBI. TXM-CB3 (AcCys-Pro-CysNH2), TXM-CB13 (DY-70; AcCys-Met-Lys-CysNH2) or AD4 (ACysNH2) were administered at 50 mg/kg, 60 min after injury and cognitive performance was monitored by the novel-object-recognition and Y-maze tests. Behavioral deficits subsequent to mTBI injury were reversed by a single dose of TXM-CB3, TXM-CB13 and, to a lesser extent, by AD4. TXM-CB13 similar to TXM-CB3 and AD4 reversed oxidative stress-induced phosphorylation of mitogen-activated kinases, p38MAPK and c-Jun N-terminal kinase, (JNK) in human neuronal SH-SY5Y cells. We conclude that significantly improved cognitive behavior post mTBI by the TXM-peptides could result from anti-apoptotic, and/or anti-inflammatory activities. Future preclinical studies are required to establish the TXM-peptides as potential therapeutic drugs for brain injuries.


The long noncoding RNA NR_045363 involves cardiomyocyte apoptosis and cardiac repair via p53 signal pathway.
Long noncoding RNAs (lncRNAs) can participate in various biological behaviors, including regulating cell differentiation, proliferation, and apoptosis. The investigators have previously confirmed that highly conserved lncRNA NR_045363 controls cardiomyocyte (CM) proliferation and cardiac repair. The present study investigates the effects of NR_045363 on CM apoptosis. Seven-day-old mice were subjected to permanent left anterior descending coronary artery ligation (LAD), and the NR_045363 expression was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of NR_045363 in the MI group significantly exceeded the Sham group during the first week after the operation. The NR_045363 expression was knocked down in primary cultured CMs using an NR_045363-targeting lncRNA Smart silencer, and the apoptosis of CMs was analyzed by terminal-deoxynucleoitidyl transferase mediated nick end labeling and Annexin-V/PI double staining. These present results indicate that the NR_045363 knockdown significantly promoted the apoptosis of CMs. In order to investigate the underlying mechanism, RNA-sequencing (RNA-seq) was performed, and ingenuity pathway analysis (IPA) was used to analyze the RNA-seq results. The RNA-seq data revealed that a total of 2,291 genes were upregulated or downregulated in NR_045363 knockdown CMs, and the IPA analysis indicated that tumor protein 53 (p53) was the upstream regulator. In vivo, the NR_045363 overexpression through the AAV9 system improved the heart function after MI in 7-day-old mice and inhibited the CM apoptosis. These data suggest that NR_045363 is involved in CM apoptosis and that NR_045363 overexpression exerts positive effects on cardiac repair by alleviating CM apoptosis through the inhibition of the p53 pathway.


The 'straight mouse': defining anatomical axes in 3D embryo models.
A primary objective of the eMouseAtlas Project is to enable 3D spatial mapping of whole embryo gene expression data to capture complex 3D patterns for indexing, visualization, cross-comparison and analysis. For this we have developed a spatio-temporal framework based on 3D models of embryos at different stages of development coupled with an anatomical ontology. Here we introduce a method of defining coordinate axes that correspond to the anatomical or biologically relevant anterior-posterior (A-P), dorsal-ventral (D-V) and left-right (L-R) directions. These enable more sophisticated query and analysis of the data with biologically relevant associations, and provide novel data visualizations that can reveal patterns that are otherwise difficult to detect in the standard 3D coordinate space. These anatomical coordinates are defined using the concept of a 'straight mouse-embryo' within which the anatomical coordinates are Cartesian. The straight embryo model has been mapped via a complex non-linear transform onto the standard embryo model. We explore the utility of this anatomical coordinate system in elucidating the spatial relationship of spatially mapped embryonic ' Fibroblast growth factor ' gene expression patterns, and we discuss the importance of this technology in summarizing complex multimodal mouse embryo image data from gene expression and anatomy studies. www.emouseatlas.org.


Characterization of polydisperse macrogols and macrogol-based excipients via HPLC and charged aerosol detection.
Macrogol-based emulsifiers and their respective precursor substances, i.e. macrogols (PEG), fatty acids (FA), and fatty alcohols (FAA), are widely used excipients which are usually characterized by a series of tests described within the European Pharmacopoeia (Ph. Eur.). Examples are bulk parameters such as the hydroxyl value, the peroxide value, and the determination of fatty acids composition by gas chromatography. The choice of tests depends on the emulsifier considered and its possible precursors. Though all methods are well established, most of them are time consuming and, in some cases, prone to errors and exhibit a low reproducibility. Here, an alternative and supplemental method was developed, using a HPLC-system coupled to a charged aerosol detector (CAD). Seven PEG samples, five saturated as well as two nonsaturated FA samples, and two FAA samples were analyzed. Together with these precursors, 13 macrogol-based emulsifiers of 3 different groups, i.e. macrogol ethers with FAA, macrogol esters with FA, and polysorbates, were successfully analyzed for oligomeric distribution and free precursor molecules in one run.


Phase transitions in Schloegl's second model for autocatalysis on a Bethe lattice.
Schloegl's second model (also known as the quadratic contact process) on a lattice involves spontaneous particle annihilation at rate p and autocatalytic particle creation at empty sites with n≥2 occupied neighbors. The particle creation rate for exactly n occupied neighbors is selected here as n(n-1)/[z(z-1)] for lattice coordination number z. We analyze this model on a Bethe lattice. Precise behavior for stochastic models on regular periodic infinite lattices is usually surmised from kinetic Monte Carlo simulation on a finite lattice with periodic boundary conditions. However, the persistence of boundary effects for a Bethe lattice complicates this process, e.g., by inducing spatially heterogenous states. This motivates the exploration of various boundary conditions and unconventional simulation ensembles on the Bethe lattice to predict behavior for infinite size. We focus on z=3, and predict a discontinuous transition to the vacuum state on the infinite lattice when p exceeds a threshold value of around 0.053.


Antineutrophil cytoplasmic autoantibodies: how are they detected and what is their use for diagnosis, classification and follow-up?
Antineutrophil cytoplasmic antibodies (ANCA) are traditionally detected by an indirect immunofluorescence technique. According to the international consensus on ANCA testing, ANCA should also be tested by antigen-specific tests for myeloperoxidase-ANCA and proteinase 3-ANCA. The direct noncompetitive enzyme-linked immunosorbent assay (ELISA) used to be the method of choice. Nowadays, these assays are called "first-generation" assays. Second-generation tests (capture ELISA) or third-generation tests (anchor ELISA) are more sensitive and specific for ANCA testing. We postulate that ANCA as detected by these newer ANCA tests may replace the need to perform indirect immunofluorescence-based assays. For classification of patients, ANCA serotype seems more important than classifying patients according to their clinical subtype, since genetics, clinical manifestations and response to therapy are more related to ANCA serotype than to clinical subtype. Detection of ANCA to monitor disease activity is still a controversial issue. Treatment based on ANCA levels is at present only experimentally performed in those patients who are treated with B-cell depletion therapy with rituximab. Future studies are needed to establish whether this way of monitoring patients is warranted.


CCL2 promotes metastasis and epithelial-mesenchymal transition of non-small cell lung cancer via PI3K/Akt/mTOR and autophagy pathways.
In non-small cell lung cancer (NSCLC), metastasis is the most common phenotype, and autophagy plays a vital role in its regulation. However, there are limited data on how autophagy-related genes and metastasis-related genes affect NSCLC progression. Our goal was to identify the genes that regulate autophagy and metastasis in NSCLC, and to assess the underlying mechanisms in this current study. RNA sequencing data from public databases were used to screen differentially expressed autophagy- and metastasis-associated genes. Enrichment analyses and immune correlations were conducted to identify hub genes and potential regulating pathways in NSCLC. In this study, we found that CCL2 expression was highly expressed in NSCLC tissues and high CCL2 level was correlated with strong infiltration in lung tissues from NSCLC patients. Overexpression of CCL2 can enhance the metastasis of NSCLC cells in nude mice. Furthermore, CCL2 activated the PI3K/Akt/mTOR signalling pathway axis, promoted epithelial-mesenchymal transition (EMT), and blocked the autophagic flux in NSCLC cells. Therefore, our results indicate that CCL2 promotes metastasis and EMT of NSCLC via PI3K/Akt/mTOR axis and autophagy signalling pathways. We believe that CCL2 could be a probable target for the diagnosis and therapeutics of NSCLC, and this study may expand our understanding of lung cancer.