Large-scale production of monoclonal antibodies in suspension culture.
Monoclonal antibodies are being manufactured for clinical trials in suspension culture at the 1300-L scale. Suspension culture offers some advantages relative to high-density mammalian cell culture methods; in particular, the ability to closely monitor the behavior of cells in a homogeneous environment. Computer control and on-line mass spectrography of exit gases provide instantaneous information about the culture metabolic activity. Air sparging and agitation by marine impeller provide aeration sufficient to maintain a constant dissolved oxygen tension at cell concentrations up to 5.0 x 10(6) cells/mL without causing apparent cell damage.


Prophylactic activity of dihydroheptaprenol, a synthetic polyprenol derivative, against Sendai virus infection in mice.
The effect of a chemically synthesized polyprenol derivative, dihydroheptaprenol (DHP), on the non-specific resistance of mice to Sendai virus infection was investigated. The mice that received 200 micrograms of DHP intranasally twice, at 3 days and 1 day before the infection, showed a significant protection against Sendai virus infection. Treatment of mice twice even with as much as 2000 micrograms of DHP through the subcutaneous route, however, had no protective effect against infection. Excess interferon and tumour necrosis factor production in intranasally DHP-treated mice was seen 1 day after the infection when compared with Sendai virus alone controls or with DHP alone controls. Variance analysis of these findings indicates a prophylactic activity of DHP in pulmonary viral infections.


Inhibition of quorum sensing-controlled virulence factor production in Pseudomonas aeruginosa PAO1 by Ayurveda spice clove (Syzygium aromaticum) bud extract.
Quorum sensing controls the virulence determinants in most proteobacteria. In this work, the hexane, chloroform and methanol extracts of an Ayurveda spice, namely clove (Syzygium aromaticum), shown anti-quorum sensing activity. Hexane and methanol extracts of clove inhibited the response of C. violaceum CV026 to exogenously supplied N-hexanoylhomoserine lactone, in turn preventing violacein production. Chloroform and methanol extracts of clove significantly reduced bioluminescence production by E. coli [pSB1075] grown in the presence of N-(3-oxododecanoyl)-L-homoserine lactone. We demonstrated that clove extract inhibited quorum sensing-regulated phenotypes in Pseudomonas aeruginosa PA01, including expression of lecA::lux (by hexane extract), swarming (maximum inhibition by methanol extract), pyocyanin (maximum inhibition by hexane extract). This study shows that the presence of natural compounds that exhibit anti-quorum sensing activity in the clove extracts may be useful as the lead of anti-infective drugs.


Gene mutations of esophageal squamous cell carcinoma based on next-generation sequencing.
Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore potential molecular targets in ESCC, we quantified the mutation spectrum and explored the relationship between gene mutation and clinicopathological characteristics and programmed death-ligand 1 (PD-L1) expression. Between 2015 and 2019, 29 surgically resected ESCC tissues and adjacent normal tissues from the Fourth Hospital of Hebei Medical University were subjected to targeted next-generation sequencing. The expression levels of PD-L1 were detected by immunohistochemistry. Mutational signatures were extracted from the mutation count matrix by using non-negative matrix factorization. The relationship between detected genomic alterations and clinicopathological characteristics and PD-L1 expression was estimated by Spearman rank correlation analysis. The most frequently mutated gene was TP53 (96.6%, 28/29), followed by NOTCH1 (27.6%, 8/29), EP300 (17.2%, 5/29), and KMT2C (17.2%, 5/29). The most frequently copy number amplified and deleted genes were CCND1/FGF3/FGF4/FGF19 (41.4%, 12/29) and CDKN2A/2B (10.3%, 3/29). By quantifying the contribution of the mutational signatures to the mutation spectrum, we found that the contribution of signature 1, signature 2, signature 10, signature 12, signature 13, and signature 17 was relatively high. Further analysis revealed genetic variants associated with cell cycle, chromatin modification, Notch, and Janus kinase-signal transducer and activator of transcription signaling pathways, which may be key pathways in the development and progression of ESCC. Evaluation of PD-L1 expression in samples showed that 13.8% (4/29) of samples had tumor proportion score ≥1%. 17.2% (5/29) of patients had tumor mutation burden (TMB) above 10 mut/Mb. All samples exhibited microsatellite stability. TMB was significantly associated with lymph node metastasis (r = 0.468, P = 0.010), but not significantly associated with PD-L1 expression (r = 0.246, P = 0.198). There was no significant correlation between PD-L1 expression and detected gene mutations (all P > 0.05). Our research initially constructed gene mutation profile related to surgically resected ESCC in high-incidence areas to explore the mechanism underlying ESCC development and potential therapeutic targets.


Utilization of wild Cressa cretica biomass for pectinase production from a halo-thermotolerant bacterium.
Halophytes are the native inhabitants of saline environment. Their biomass can be considered as a potential substrate for the production of microbial enzymes. This study was intended at feasible utilization of a halophytic biomass, Cressia cretica, for pectinase production using a halo- and thermo-tolerant bacterium, Bacillus vallismortis MH 10. The data from fractionation of the C. cretica biomass revealed presence of 17% pectin in this wild biomass. Seven different factors (temperature, agitation, pH, inoculum size, peptone concentration, substrate concentration, and incubation time) affecting pectinase production using C. cretica were assessed through a statistical tool, Plackett-Burman design. Consequently, two significant factors (incubation time and peptone concentration) were optimized using the central composite design. The strain produced 20 IU mL-1 of pectinase after 24 h under optimized conditions. The enzyme production kinetics data also confirmed that 24 h is the most suitable cultivation period for pectinase production. Fourier transform infrared spectroscopy and scanning electron microscopy of C. cretica biomass ascertained utilization of pectin and structural changes after fermentation. The purification of pectinase by using DEAE column yielded specific activity and purification fold of 88.26 IU mg-1 and 3.2, respectively. The purified pectinase had a molecular weight of >65 kDa. This study offers prospects of large-scale production of pectinase by halotolerant strain in the presence of economical and locally grown substrate that makes the enzyme valuable for various industrial operations.


Effects of intermittent aerobic training on exercise capacity, pulmonary functions, and gait parameters in asthmatic children with cerebral palsy: a randomized controlled trial.
There is no evidence that exercise training program is effective in improving aerobic capacity, musculoskeletal abnormalities, and quality of life in asthmatic children with cerebral palsy (CP). Therefore, the effects of intermittent aerobic training on exercise capacity, pulmonary function, and gait parameters in asthmatic CP children have been evaluated in the current study. This clinical trial included thirty-six asthmatic CP children between January and December 2021. Their ages were between 7 and 12 years old. They were randomly allocated to the intermittent aerobic exercise group (IAEG) and a control group (CG), with 18 per each group. The children have been recruited for the 10-week interventional program. The 6-minute walk test (6MWT), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), stride length, cadence, gait speed, and pediatric asthma quality of life (PAQLQ) were all measured before and after treatment. Pre-post analysis in the IAEG showed noteworthy changes (6MWT, p=0.005; FVC, p=0.002; FEV1, p<0.001; overall score of PAQLQ, p<0.001; stride length, p<0.001; cadence, p<0.001; and gait speed, p˂0.001), while the control group showed non-significant changes (p>0.05). There were noteworthy differences between IAEG and CG post-treatment (6MWT, p=0.019; FVC, p=0.031; FEV1, p<0.001; overall score of PAQLQ, p=0.031; stride length, p<0.001; cadence, p=0.009; and gait speed, p<0.001) in favor of the IAEG. Depending on the study findings, 10 weeks of intermittent aerobic exercise may improve exercise capacity, pulmonary function, gait parameters, and quality of life in asthmatic CP children. Based on what we found, this protocol should be used in pulmonary rehabilitation programs for children with CP who have breathing problems.


Pseudoxanthoma-elasticum-like papillary dermal elastolysis: another case.
Pseudoxanthoma-elasticum-like papillary dermal elastolysis is a rare acquired idiopathic non-inflammatory elastolytic disorder. This disease, described in aged females, is characterized by asymptomatic skin lesions of the neck and supraclavicular regions clinically resembling pseudoxanthoma elasticum. Histological and ultrastructural examinations show a total loss of the elastic fibres in the papillary dermis. We report another case of this entity in a 69-year-old Italian woman.


Inflammatory reaction in acute retinal artery occlusion: cytokine levels in aqueous humor and serum.
To investigate the role of inflammation in acute retinal artery occlusion (RAO). Levels of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) were measured in serum (n = 14) and aqueous humor (AqH) (n = 8) samples from patients with RAO. Findings were compared with 24 age- and disease-matched patients, 10 healthy subjects (serum), and 16 patients undergoing cataract surgery (AqH). Patients who arrived early (within 4-6 hours of occlusion) had higher serum IL-8 and IL-6 levels than controls; the IL-6 level in the AqH was lower than that of controls, while the IL-8 level was higher. In seven patients for whom both serum and AqH samples were available, serum IL-6 levels were higher than their corresponding AqH levels in most patients arriving within 10 hours of occlusion, and AqH IL-8 levels were higher than the corresponding serum levels in all but one. TNF-alpha levels were consistently higher in the serum than in the AqH at all time points. Serum IL-8 and IL-6 and AqH IL-8 are elevated immediately following acute RAO. The early local suppression of IL-6 may be related to ocular immune mechanisms.


IL-21 mediated Foxp3 suppression leads to enhanced generation of antigen-specific CD8+ cytotoxic T lymphocytes.
Efforts to reproducibly isolate tumor antigen-specific T cells from patients would be facilitated by removing immunoregulatory barriers. Using a human model for eliciting T-cell responses to tumor-associated antigens, we develop a novel strategy that eliminates nearly all Foxp3-expressing cells through the combination of CD25 depletion and IL-21 treatment resulting in a more than 150-fold decrease in Foxp3(+) cells to virtually undetectable levels and a more than 200-fold increase in antigen-specific cytotoxic T lymphocytes (CTLs). The extent of Foxp3 elimination and degree of expansion of antigen-specific CTLs shown in this study have not previously been achievable and are unique to IL-21. We demonstrate for the first time a possible mechanism for IL-21-mediated expansion of antigen-specific CTLs that involves suppression of Foxp3-expressing cells and reversal of inhibition to tumor-associated antigen-specific CTL generation in vitro. Taken together, the combination of CD25 depletion and IL-21 exposure, by releasing regulatory constraints, leads to markedly enhanced CTL induction and represents a robust strategy for the ex vivo generation of antigen-specific T cells for adoptive cellular therapy.


Hospital Inpatient Costs for Single Ventricle Patients Surviving the Fontan Procedure.
We estimated the inpatient resource use for a Fontan patient from birth to adulthood and explored factors that might induce cost differences (2014 US dollar). Inpatient costing records from 4 hospitals with greatest numbers of Fontan patients in Australia and New Zealand were linked with the Fontan registry database. Inpatient records between July 1995 and September 2014 for 420 Fontan patients were linked, and the most frequent primary diagnoses were hypoplastic left heart syndrome (20.7%), tricuspid atresia (19.7%), and double inlet left ventricle (17.1%). The mean hospital cost for a Fontan patient from birth to 18 years of age was estimated to be $390,601 (95% confidence interval [CI] $264,703 to $516,499), corresponding to 164 (95% CI 98 to 231) inpatient days. The cost incurred from birth through to Fontan completion (the staged procedures period) was $219,482 (95% CI $202,410 to $236,553) and the cost thereafter over 15 years was $146,820 (95% CI $44,409 to $249,231), corresponding to 82 (95% CI 72 to 92) and 65 (95% CI 18 to 112) inpatient days, respectively. Costs were higher in male and hypoplastic left heart syndrome patients in the staged procedures period (p <0.001). Having fenestration was associated with higher costs in the staged procedures period (p <0.001) and lower cost after Fontan over 15 years (p = 0.66). In conclusion, patients with single ventricle congenital heart disease continue to demand considerable inpatient resources after the staged procedures period. Over 40% of the pediatric hospital costs for Fontan patients were estimated to occur after the last planned surgery.


The prevalence of erythromycin resistance in group B streptococcal isolates at a University Hospital in Taiwan.
Due to reduced antibiotic consumption in Taiwan, erythromycin resistance rate had decreased in Streptococcus pyogenes, but it increased in Streptococcus pneumoniae. The objectives of the present study were (1) to determine the erythromycin and clindamycin resistance rate and minimum inhibitory concentration (MIC) of the group B streptococcus (GBS) clinical isolates, and (2) to investigate the mechanism responsible for the macrolide, lincosamide, and group B streptogramin (MLS(B)) resistance. A total of 1,395 GBS isolates were collected from June 2001 to April 2007. Forty-four percent of the GBS isolates were resistant to erythromycin, and 39% were resistant to clindamycin. The annual erythromycin resistance rate increased from 32% in 2001 to 51% in 2004; a significant decrease was observed in 2005 (47%), 2006 (42%), and 2007 (38%). Percentage of erythromycin-resistant isolates with erm(B) gene significantly increased from 72% in 2001 to 90% in 2007. We found that the plasmid encoded zeta gene was present in 13% of the resistant isolates, along with erm(B). When compared to our previous study (1991 to May 2001), the overall erythromycin resistance rate increased from 30% to 44%. erm(B) was the major resistant determinant, and zeta toxin encoding plasmid has a limited role in mediating erythromycin resistance unlike in GAS isolates as reported earlier.


Effect of glucose on pHin and [Ca2+]in in NIH-3T3 cells transfected with the yeast P-type H(+)-ATPase.
NIH-3T3 cells transfected with yeast H(+)-ATPases (RN1a cells) are tumorigenic (Perona and Serrano, 1988, Nature, 334:438). We have previously shown that RN1a cells maintain a chronically high intracellular pH (pHin) under physiological conditions. We have also shown that RN1a cells are serum-independent for growth, maintain a higher intracellular Ca2+ ([Ca2+]in), and glycolyze more rapidly than their non-transformed counterparts (Gillies et al., Proc. Natl. Acad. Sci., 1990, 87:7414; Gillies et al., Cell. Physiol. Biochem., 1992, 2:159). The present study was aimed to understand the interrelationships between glycolysis, pHin, and [Ca2+]in in RN1a cells and their non-transformed counterparts, NIH-3T3 cells. Our data show that the higher rate of glycolysis observed in RN1a cells is due to the presence of low affinity glucose transporters. Consequently, the higher rate of glycolysis is exacerbated at high glucose concentration in RN1a cells. Moreover, the maximal velocity (Vmax) for glucose utilization is up to sixfold higher in RN1a cells than in the NIH-3T3 cells, suggesting that the number of glucose transporters is higher in RN1a than NIH-3T3 cells. Glucose addition to NIH-3T3 cells results in modest decreases in both pHin and [Ca2+]in. In contrast, RN1a cells respond to glucose with a large decrease in pHin, followed by a large decrease in [Ca2+]in. The decrease in [Ca2+]in observed upon glucose addition is likely due to activation of Ca(2+)-ATPase by glycolysis, since the Ca2+ decrease is abolished by the Ca2+ ATPase inhibitors thapsigargin and cyclopiazonic acid. Glucose addition to ATP-depleted cells results in a decrease in [Ca2+]in, suggesting that ATP furnished by glycolysis is utilized by this pump.


Effects of surface activation on the structural and catalytic properties of ruthenium nanoparticles supported on mesoporous silica.
Using colloid-based methods to prepare supported catalytic metallic nanoparticles (NPs) often faces the challenge of removing the stabilizer used during synthesis and activating the catalyst without modifying the particles or the support. We explored three surface activation protocols (thermal oxidation at 150 °C, thermal reduction at 350 °C, and argon-protected calcination at 650 °C) to activate ruthenium NPs supported on mesoporous silica (MSU-F), and assessed their effects on the structural and catalytic properties of the catalysts, and their activity by the aqueous phase hydrogenation of pyruvic acid. The NPs were synthesized by polyol reduction using poly-N-vinyl-2-pyrrolidone (PVP) as a stabilizer, and supported on MSU-F by sonication-assisted deposition. The NPs maintained their original morphology on the support during activation. Ar-protected calcination was the most efficient of the three for completely removing PVP from particle surfaces, and provided the highest degree of particle crystallinity and a metal dispersion comparable to commercial Ru/SiO2. Its catalytic performance was significantly higher than the other two protocols, although all three thermally activated catalysts achieved higher activity than the commercial catalyst at the same Ru loading. Post-reaction analysis also showed that the supported catalyst activated at 650 °C retained its morphology during the reaction, which is an important requirement for recyclability.


Long non-coding RNA SNHG16, binding with miR-106b-5p, promoted cell apoptosis and inflammation in allergic rhinitis by up-regulating leukemia inhibitory factor to activate the JAK1/STAT3 signaling pathway.
Allergic rhinitis (AR) is a type I hypersensitive disease. Long non-coding RNA (lncRNA) SNHG16 acts as an oncogene in a variety of tumors and promotes the occurrence of inflammation in many inflammatory diseases. The study aims to investigate the expression of SNHG16 and its potential biological functions in AR. RT-qPCR results showed that the expression of SNHG16 in AR was up-regulated. The AR cell model was constructed by stimulating primary nasal mucosal epithelial cells from AR patients with IL-13. After knocking down the expression of lncRNA SNHG16, cell apoptosis was detected by flow cytometry, and the expression of inflammatory factors was detected by ELISA. The results showed that SNHG16 promoted cell apoptosis and inflammation. Then, bioinformatics analysis was used to screen miRNAs bound with SNHG16. Luciferase reporter gene assay and RNA pull-down experiment were used to verify the relationship. We found that the expression of miR-106b-5p was down-regulated and leukemia inhibitory factor (LIF) expression was up-regulated in the AR cell model. The expression of phospho-Janus kinase 1 and p-signal transducer and activator of transcription 3 (STAT3) were detected by Western blotting. Silencing the expression of LIF could inhibit the activity of JAK1/STAT3 pathway and further inhibit cell apoptosis and the occurrence of inflammation. Then transfected SNHG16 shRNA alone or together with miR-106b-5p antagomir into the AR cell model, we found that silencing the expression of SNHG16 down-regulated the expression of LIF and inhibited the activity of the JAK1/STAT3 pathway, cell apoptosis, and inflammation. However, miR-106b-5p antagomir weakened its inhibitory effects. The role of SNHG16 in AR was further verified by the ovalbumin-induced AR mouse model in vivo. In conclusion, SNHG16 up-regulates LIF expression by binding with miR-106b-5p, thus promoting the activity of JAK1/STAT3 pathway, and promoting the development of AR. These results provide new targets for the treatment of AR and may help reduce the damage caused by AR.


Understanding Hospital Volume-Outcome Relationship in Severe Traumatic Brain Injury.
The hospital volume-outcome relationship in severe traumatic brain injury (TBI) population remains unclear. To examine the relationship between volume of patients with severe TBI per hospital and in-hospital mortality, major complications, and mortality following a major complication (ie, failure to rescue). In a multicenter cohort study, data on 9255 adults with severe TBI were derived from 111 hospitals participating in the American College of Surgeons Trauma Quality Improvement Program over 2009-2011. Hospitals were ranked into quartiles based on their volume of severe TBI during the study period. Random-intercept multilevel models were used to examine the association between hospital quartile of severe TBI volume and in-hospital mortality, major complications, and mortality following a major complication after adjusting for patient and hospital characteristics. In sensitivity analyses, we examined these associations after excluding transferred cases. Overall mortality was 37.2% (n = 3447). Two thousand ninety-eight patients (22.7%) suffered from 1 or more major complication. Among patients with major complications, 27.8% (n = 583) died. Higher-volume hospitals were associated with lower mortality; the adjusted odds ratio of death was 0.50 (95% confidence interval: 0.29-0.85) in the highest volume quartile compared to the lowest. There was no significant association between hospital-volume quartile and the odds of a major complication or the odds of death following a major complication. After excluding transferred cases, similar results were found. High-volume hospitals might be associated with lower in-hospital mortality following severe TBI. However, this mortality reduction was not associated with lower risk of major complications or death following a major complication.


IDENTITY OF TARICHATOXIN AND TETRODOTOXIN.
Tarichatoxin (C(11)H(17)N(3)O(8)), a potent neurotoxin recently isolated in pure form from the eggs of the California newt, Taricha torosa, has been found to be identical to tetrodotoxin from the ovaries of Sphoeroides rubripes, the Japanese Fugu or puffer fish. As yet this substance has been detected only in a single family of fish, Tetraodontidae, and in a single family of amphibia, Salamandridae.


Solitary extranodal Rosai-Dorfman disease of the mandible: an exceedingly rare presentation.
Sinus histiocytosis with massive lymphadenopathy, generally known by the name of Rosai-Dorfman disease is a rare benign condition principally affecting cervical lymph nodes. Concurrent extra-nodal disease frequently occurs, however, solitary extra-nodal disease involving the mandible is exceedingly rare with less than five reported cases in the English literature. We describe a case of primary involvement of the mandible in a 27-year-old female, and discuss the differential diagnosis of this disease with other histiocytic lesions.


IL-13 production by regulatory T cells protects against experimental autoimmune encephalomyelitis independently of autoantigen.
Treatment with an anti-inflammatory Salmonella vaccine expressing enterotoxigenic Escherichia coli colonization factor Ag 1 (CFA/I) proved effective in stimulating protective, potent CD25(+)CD4(+) regulatory T (T(reg)) cells in susceptible mice challenged with experimental autoimmune encephalomyelitis (EAE). Because the Salmonella vector was considerably less protective, we questioned whether altering fimbrial subunit expression to resemble conventional Salmonella expression may impact T(reg) cell potency. The Salmonella-CFA/I vaccine was modified to limit fimbrial subunit expression to the intracellular compartment (Salmonella-CFA/I(IC)). SJL mice were challenged with proteolipid protein peptide 139-151 to induce EAE and orally treated with one of three Salmonella vaccines 6 days postchallenge. Treatment with Salmonella-CFA/I(IC) greatly reduced clinical disease, similarly as Salmonella-CFA/I, by subduing IL-17 and IL-21; however, mechanisms of protection differed as evident by increased IL-13 and IFN-gamma but diminished TGF-beta production by T(reg) cells from Salmonella-CFA/I(IC)-treated mice. Adoptive transfer of T(reg) cells from both CFA/I-expressing constructs was equivalent in protecting against EAE, showing minimal disease. Although not as potent in its protection, CD25(-)CD4(+) T cells from Salmonella-CFA/I(IC) showed minimal Th2 cells, but vaccination did prime these Th2 cells rendering partial protection against EAE challenge. In vivo IL-13 but not IFN-gamma neutralization compromised protection conferred by adoptive transfer with Salmonella-CFA/I(IC)-induced T(reg) cells. Thus, the Salmonella-CFA/I(IC) vaccine elicits T(reg) cells with attributes from both the Salmonella vector and Salmonella-CFA/I vaccines. Importantly, these T(reg) cells can be induced to high potency by simply vaccinating against irrelevant Ags, offering a novel approach to treat autoimmune diseases independently of the autoantigen.


Hyperpolarization induces differentiation in human cardiomyocyte progenitor cells.
In the past years, cardiovascular progenitor cells have been isolated from the human heart and characterized. These cells can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells and are therefore of great value for investigation of the mechanisms that drive progenitor cell function and plasticity, drug testing and, potentially, therapeutical purposes. In this respect, most studies have focused on enhancing differentiation with chemicals or growth factors, or co-culture with other cell types. Although they have revealed important mechanisms, protocols need to be established that exclude the need for such factors when one considers using progenitor cells to repair the human heart. In this study we tested whether we could induce cardiomyogenic differentiation of human cardiomyocyte progenitor cells (CMPCs) by altering their membrane potential. We induced hyperpolarization in CMPCs by either co-culturing them with a K(ir)2.1-overexpressing cell line or by overnight culture in medium containing low potassium concentrations. Hyperpolarization led to increased intracellular calcium concentrations, activation of calcineurin signaling, increased cardiac-specific gene and protein expression levels and, ultimately, to the formation of spontaneously beating cardiomyocytes. Thus, hyperpolarization is sufficient to induce differentiation of CMPCs, thereby revealing a novel mechanism for cardiomyogenic differentiation of heart-derived progenitor cells.


5D Analysis of Capacity Degradation in Battery Electrodes Enabled by Operando CT-XANES.
For devices encountering long-term stability challenges, a precise evaluation of degradation is of paramount importance. However, methods for comprehensively elucidating the degradation mechanisms in devices, particularly those undergoing dynamic chemical and mechanical changes during operation, such as batteries, are limited. Here, a method is presented using operando computed tomography combined with X-ray absorption near-edge structure spectroscopy (CT-XANES) that can directly track the evolution of the 3D distribution of the local capacity loss in battery electrodes during (dis)charge cycles, thereby enabling a five-dimensional (the 3D spatial coordinates, time, and chemical state) analysis of the degradation. This paper demonstrates that the method can quantify the spatiotemporal dynamics of the local capacity degradation within an electrode during cycling, which has been truncated by existing bulk techniques, and correlate it with the overall electrode performance degradation. Furthermore, the method demonstrates its capability to uncover the correlation among observed local capacity degradation within electrodes, reaction history during past (dis)charge cycles, and electrode microstructure. The method thus provides critical insights into the identification of degradation factors that are not available through existing methods, and therefore, will contribute to the development of batteries with long-term stability.


Chemically induced disseminated pythiosis in BALB/c mice: A new experimental model for Pythium insidiosum infection.
Pythiosis is a severe and life-threatening disease that affects humans and various animal species. We report a model of vascular/disseminated pythiosis occurring after subcutaneous inoculation of 2 x 104 Pythium insidiosum zoospores/mL in immunocompromised BALB/c mice. For this model, we carried out two rounds of experiments. First, we evaluated two protocols of immunosuppression before inoculation: cyclophosphamide at 150 mg/kg (CYP group) and cyclophosphamide 200 mg/kg plus hydrocortisone acetate at 250 mg/kg (CYP+HCA group). It was not possible to obtain mortality in the CYP group; however, the combination of CYP+HCA altered disease outcomes, with mortality rates reaching 60%. Second, we used the CYP+HCA immunosuppression protocol to analyze the histological and immunological statuses triggered by disease. When we inoculated immunocompetent mice with P. insidiosum zoospores, self-healing occurred via increased levels of IL-2, IFN-γ and IL-17A, which are characteristic of the Th1/Th17 cytokine response. For infected and immunosuppressed mice, the cytokine profiles showed high levels of IL-10, IL-6 and TNF-α. Increased IL-10 values are related to fungal infection susceptibility and led us to speculate that infection may be established through suppression of the host immune response. In addition, histopathological evaluation of the kidneys and liver demonstrated the presence of hyphae and the cellular findings suggested an acute vascular inflammation that mimics vascular/disseminated pythiosis in humans. This is the first murine model for pythiosis that is useful both for understanding the pathogenesis of this disease and for evaluating new treatment approaches.


Identification of two novel promelacacinidin dimers from Acacia nigrescens.
Two new flavanol-flavonol C(4)(C) to C(5)(D) linked promelacacinidin dimers were isolated from the heartwood of Acacia nigrescens. Their structures were elucidated by extensive (1)H and (13)C NMR spectroscopic studies, and the main conformational features are discussed.


A Review of Metal Exposure and Its Effects on Bone Health.
The presence of metals in the environment is a matter of concern, since human activities are the major cause of pollution and metals can enter the food chain and bioaccumulate in hard and soft tissues/organs, which results in a long half-life of the metal in the body. Metal intoxication has a negative impact on human health and can alter different systems depending on metal type and concentration and duration of metal exposure. The present review focuses on the most common metals found in contaminated areas (cadmium, zinc, copper, nickel, mercury, chromium, lead, aluminum, titanium, and iron, as well as metalloid arsenic) and their effects on bone tissue. Both the lack and excess of these metals in the body can alter bone dynamics. Long term exposure and short exposure to high concentrations induce an imbalance in the bone remodeling process, altering both formation and resorption and leading to the development of different bone pathologies.


Persistence of selected organophosphate and carbamate insecticides in waters from a coastal watershed.
Organophosphate and carbamate compounds are among the most widely used pesticides. Contamination of surface water by these compounds is of concern because of potential toxicity to aquatic organisms, especially those at lower trophic levels. In this study we evaluated the persistence of diazinon, chlorpyrifos, malathion, and carbaryl in waters from various sites in the Newport Bay-San Diego Creek watershed in southern California (USA). The persistence of diazinon and chlorpyrifos was much longer than that of malathion or carbaryl and was further prolonged in seawater. Microbial degradation contributed significantly to the dissipation of diazinon and chlorpyrifos in freshwater, but was inhibited in seawater, leading to increased persistence. In contrast, degradation of malathion and carbaryl was rapid and primarily abiotic. A greater temperature dependence was observed for carbaryl degradation in all waters and for diazinon degradation in freshwater. The interactions of pesticide persistence with water location, temperature, and type of pesticides suggest that site- and compound-specific information is needed when evaluating the overall ecotoxicological risks of pesticide pollution in a watershed. Because the persistence of diazinon and chlorpyrifos may increase significantly in seawater, mitigation should occur before the pesticides reach seawater. The relatively short persistence of these compounds in freshwater suggests that practices aimed at extending residence time (e.g., diversion to wetlands) may effectively reduce pesticide output to downstream water bodies.


Lack of retrovirus gene expression in somatic cell hybrids of friend cells and teratocarcinoma cells with a teratocarcinoma phenotype.
Two types of hybrids between cells with erythroid phenotype (Friend cells) and teratocarcinoma cells can be distinguished: cell hybrids with an erythroid phenotype, which release or can be induced to release large amounts of Friend spleen focus-forming virus (F-SFFV) on exposure to bromodeoxyuridine and cell hybrids with a teratocarcinoma phenotype, which do not release Friend virus and are not inducible for F-SFFV release. In this paper, we attempted to relate these differences to the expression of F-SFFV and Friend murine leukemia virus (F-MuLV) functions. Teratocarcinoma phenotype hybrids retained F-SFFV-and F-MuLV-related provirus sequences. They did not express F-SFFV- or F-MuLV-related RNA or proteins. The hybrids differentiated to endoderm-like cells on exposure to retinoic acid or hexamethylene-bis -acetamide. These cells, in contrast to the teratocarcinoma phenotype (uninduced) cells expressing SSEA-1-like antigens, did not express SSEA-1-like antigens; they formed typical, prekeratin-staining cytoskeletal structures and could be induced to release mouse interferon. The differentiating cells, but not the uninduced teratocarcinoma hybrids, were infected productively with F-MuLV or the F-MuLV--F-SFFV complex. They, however, did not express endogenous F-SFFV. Endogenous F-SFFV functions could not be rescued by infection with F-MuLV. Induction of teratocarcinoma hybrids with retinoic acid did not activate endogenous F-MuLV or F-SFFV transcription or protein synthesis. These data demonstrated two control mechanisms of Friend virus repression: one which acted trans during formation of the cell hybrids and was maintained only in teratocarcinoma phenotype cells and the other which acted cis and was still operative during induction of endodermal differentiation.


Conjunction revisited.
The aim of this note is to revisit the analysis of conjunctions in imaging data. We review some conceptual issues that have emerged from recent discussion (Nichols, T., Brett, M., Andersson, J., Wager, T., Poline, J.-B., 2004. Valid Conjunction Inference with the Minimum Statistic.) and reformulate the conjunction of null hypotheses as a conjunction of k or more effects. Analyses based on minimum statistics have typically used the null hypothesis that k = 0. This enables inferences about one or more effects (k > 0). However, this does not provide control over false-positive rates (FPR) for inferences about a conjunction of k = n effects, over n tests. This is the key point made by Nichols et al., who suggest a procedure based on supremum P values that provides an upper bound on FPR for k = n. Although valid, this is a very conservative procedure, particularly in the context of multiple comparisons. We suggest that an inference on a conjunction of k = n effects is generally unnecessary and distinguish between congruent contrasts that test for the same treatment and incongruent contrasts of the sort used in cognitive conjunctions. For congruent contrasts, the usual inference, k > 0, is sufficient. With incongruent contrasts it is sufficient to infer a conjunction of k >u effects, where u is the number of contrasts that share some uninteresting effect. The issues highlighted by Nichols et al., have important implications for the design and analysis of cognitive conjunction studies and have motivated a change to the SPM software, that affords a test for the more general hypothesis k >u. This more general conjunction test is described.


Physical structure and absorption properties of tailor-made porous starch granules produced by selected amylolytic enzymes.
Porous starch granules (PSGs) with various pores and cavity sizes were prepared by amylolysis enzymes. The greatest hydrolysis rate on corn starch granule was observed with α-amylase, followed by gluco- and β-amylases. Temperature increase enhanced glucoamylase reaction rate more drastically than other enzyme treatments. Final hydrolysis level with glucoamylase reached to 66.9%, close to 67.5% of α-amylolysis. The α-amylase-treated PSGs displayed the greatest pore size and ratio of cavity-to-granule diameters. Gelatinization onset temperatures of PSGs increased to 72.1 (α-), 68.7 (β-), and 68.1°C (gluco-amylolysis) after 8 h; enthalpy changes of β- and gluco-amylase-treated PSGs increased to 13.4, and 13.1 J/g but α-amylase-treated one showed slightly reduced value of 8.5 J/g. Water holding capacities of PSGs were 209.7 (α-), 94.6 (β-), and 133.8% (gluco-amylolysis), and the untreated control had 89.1%; oil holding capacities of them showed 304.5, 182.7, and 211.5%, respectively, while the untreated control had 161.8%. Thus, enzyme types and their reaction conditions can be applied to generate desirable cavity and pore sizes in starch granules. This biocatalytic approach could contribute to develop tailor-made PSGs with distinct internal structure for specific uses in wide range of food, pharmaceutical and other industrial applications.


Aerosolized pentamidine as primary prophylaxis for Pneumocystis carinii pneumonia: efficacy, mortality and morbidity.
Primary prophylaxis against Pneumocystis carinii pneumonia (PCP) for patients with HIV infection has been recommended by the Centers for Disease Control and Prevention. We evaluated alternatives to routine primary PCP prophylaxis with aerosolized pentamidine. A total of 121 HIV-infected patients with CD4+ cell counts < or = 200 x 10(6)/l or an AIDS diagnosis were enrolled in a controlled study of aerosolized pentamidine as primary PCP prophylaxis. Patients were randomly assigned to treatment (n = 61) with aerosolized pentamidine once every month or to no treatment (n = 60). Patients were evaluated for PCP, mortality, morbidity and progression of HIV disease. Morbidity was estimated from the number of days patients were unable to work due to illness, number of days hospitalized and AIDS events. Baseline characteristics were similar in the treatment and control groups and mean CD4+ cell counts were 116 and 107 x 10(6)/l, respectively. Eight incidents of PCP and 19 deaths were observed in the treatment group during a median follow-up of 16.4 months (range, 2.3-32.4 months). Nineteen incidents of PCP and 13 deaths, of which one was related to an acute episode of PCP, were noted in the control group. Median follow-up of controls was 18.5 months (range, 3.1-32.9 months). Patients in the treatment group were unable to work 19% of the observation time and were hospitalized for 4.3% of that time. Corresponding figures were 20 and 3.0%, respectively, in the control group. Aerosolized pentamidine had significant prophylactic efficacy, but we could not detect any major effect on mortality and morbidity. The overall mortality and morbidity were not markedly influenced by PCP. Clinical check-ups and treatment of acute PCP could be a justifiable alternative to drug prophylaxis with aerosolized pentamidine in selected patients.


2,2'-Spirobi(1,3-benzodithiole).
The X-ray structure analysis of 2,2'-spirobi(1,3-benzodithiole), C(13)H(8)S(4), has been performed. The molecule has crystallographic twofold rotation symmetry, the axis passing through the spiro-C atom. The four S atoms are arranged around the spiro-C atom in two almost orthogonal CS(2) planes. However, because of large bending of the two five-membered rings, close contact is present between two connected C atoms on the benzo group of each 1,3-benzodithiole ring and one S atom on the other 1,3-benzodithiole ring.


Structure and Dynamics of Ferrocyanide and Ferricyanide Anions in Water and Heavy Water: An Insight by MD Simulations and 2D IR Spectroscopy.
Combined computational and experimental techniques were employed to investigate at the microscopic level the structural and dynamic properties of ferro- and ferricyanide ions in aqueous solution. The characterization of the structural patterns and multiscale dynamics taking place within the first solvation spheres in water and heavy water solvents was first achieved through extensive molecular dynamics simulations, performed with refined force fields, specifically parametrized for the cyanide ions under investigation. The information gained about the solute-solvent interactions is then validated through the successful comparison of computed and measured waiting-time-dependent 2D IR spectra. The vibrational patterns resulting from 2D IR measurements were rationalized in terms of the interaction between the ion and the neighboring water molecules described by simulation. It was found that, within the first solvation sphere, the stronger interactions of the solvent with the ferro species are responsible for a delay in the relaxation dynamics, which becomes more and more evident on longer time scales.


Distribution of extracellular signal-regulated protein kinases 1 and 2 in the rat adrenal and their activation by angiotensin II.
The adrenal gland of the rat is continuously regenerated through proliferation of a stem cell population in the outer part of the gland. To clarify the location of proliferative events within the adrenal gland, and the factors that stimulate them, rat adrenal capsule preparations, consisting of capsule, zona glomerulosa (ZG) and the outer zona fasciculata (ZF) were maintained in vitro under different conditions of stimulation, for varying periods. Sites of proliferation were identified by 5-bromo-2'-deoxy-uridine (BrdU) staining, and the distribution of classical MAP kinase (MAPK) family members, extracellular signal-regulated kinase (ERK) 1 and 2, immunoreactivity was determined using immunocytochemistry. BrdU staining was limited to the outer glomerulosa and the capsule, where it was enhanced by angiotensin II, but not by a high potassium ion concentration nor by ACTH. In contrast, ERK1/2 immunoreactivity was distributed throughout the ZG and in the medulla, with none detectable in the ZF and reticularis. Furthermore, angiotensin II, potassium ions and ACTH were all shown to induce ERK1 and ERK2 phosphorylation in the ZG. Treatment of adrenal capsule tissue with the specific MAPK kinase inhibitor PD98059 revealed inhibition of ERK1/2 phosphorylation, but no effect on angiotensin II-induced aldosterone secretion. Although the distribution and activation of the MAPK pathway suggest a link with proliferation, the findings clearly designated only the outer part of the glomerulosa and capsule as a potential stem cell population. Further functions should be sought for the apparently silent major part of the glomerulosa.


Alemtuzumab improves contrast sensitivity in patients with relapsing-remitting multiple sclerosis.
Alemtuzumab is a monoclonal antibody directed against CD52 that depletes T and B lymphocytes. To evaluate the treatment effect of alemtuzumab on low-contrast vision in relapsing-remitting multiple sclerosis (RRMS) patients. This was a pre-defined exploratory analysis within a randomized, rater-blinded trial (CAMMS223) that was run at 49 academic medical centers in the US and in Europe. Patients with untreated, early, RRMS (McDonald, n = 334) were randomized 1:1:1 to subcutaneous interferon beta-1a (IFNB-1a), or alemtuzumab 12 mg or 24 mg. Visual contrast sensitivity was measured for each eye at baseline and quarterly, with Pelli-Robson charts. The eyes of patients in the pooled alemtuzumab group (versus IFNB-1a) had a greater than 2-fold higher rate of both 3-month and 6-month sustained visual improvement, of at least 0.3 log units (2 triplets, 6 letters) (At 3 months the hazard ratio (HR) = 2.26; CI = 1.19 to 4.31; P = 0.013; and at 6 months the HR = 2.44; CI =1.16 to 5.15; P = 0.019), and they had a lower risk of 3- and 6-month sustained worsening of at least 0.15 log units (1 triplet, 3 letters) (At 3 months the HR = 0.58; CI = 0.38 to 0.89; P = 0.012; and at 6 months HR = 0.55; CI=0.35 to 0.87; P = 0.010). Over the 36-month study period, the eyes of patients in the pooled alemtuzumab group improved in mean contrast sensitivity to a greater extent than those in the IFNB-1a group (0.080 log units versus 0.038 log units; P = 0.0102). Alemtuzumab was associated with a greater chance of improved contrast sensitivity in patients with RRMS and may delay the worsening of visual function. Contrast sensitivity testing was sensitive to treatment effects, even within an active comparator study design. These results support the validity of low-contrast vision testing as a clinical outcome in MS trials.


Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.
The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.


The impact of alcohol hand sanitizer use on infection rates in an extended care facility.
Nosocomial infections are a major problem in health care facilities, resulting in extended durations of care and substantial morbidity. Since alcohol gel hand sanitizers combine high immediate antimicrobial efficacy with ease of use, this study was carried out to determine the effect of the use of alcohol gel hand sanitizer by caregivers on infection types and rates in an extended care facility. Infection rate and type data were collected in a 275-bed extended care facility for 34 months (July 1997 to May 2000), during which an alcohol gel hand sanitizer was used by the caregivers in 2 units of the facility. The primary infection types found were urinary tract with Foley catheter, respiratory tract, and wound infections. Comparison of the infection types and rates for the units where hand sanitizer was used with those for the control units where the hand sanitizer was not used showed a 30.4% decrease in infection rates for the 34-month period in the units where hand sanitizer was used. This study indicates that use of an alcohol gel hand sanitizer can decrease infection rates and provide an additional tool for an effective infection control program.


A quantitative comparison of cellular motile systems.
Cellular motile systems as diverse as muscle and the mitotic spindle have been compared by their specific power output: the maximum power they develop per unit of engine volume. Striated muscles and flagella have high specific output; their performance is comparable to that of typical automobile engines. The cytokinetic furrow and the mitotic spindle have very much lower specific power output. The furrow's output is 7,000 times lower than muscle and the spindle's is 300,000 times lower. Different macromolecules have been used to generate power in systems with similar output (muscles and flagella) and, conversely, the same macromolecular motor has been used in systems with very different output (muscles and cytokinetic furrows). The common feature amid this diversity is adaptation to a particular biological role, which specific power output reflects very well. High values are found where a powerful, compact engine should be advantageous, while low values are found where precision, not power, matters most.


Supporting organizational learning: a comparative approach to evaluation in action research.
For well over a decade, the organizational context of nursing in the United Kingdom has been one of change and reform with a policy shift towards primary and community led health care. Such a major shift in policy provides nurses with an opportunity to re-think their approaches towards the individuals and communities they serve in order to promote self-care, recognize achievable health goals and provide family and community support. Although there is a growing appreciation of action research as an useful approach to this kind of development, it can be difficult to evaluate published studies because of the diverse nature of the literature. This paper will present and evaluate two case studies using a particular conceptual device (The Normative Information Model-based Systems Analysis and Design) in order to explore a possible alternative to the interpretative narrative or positivistic hypothesis-testing models used to report other kinds of nursing research and enlarge the debate about process evaluation.


X-ray pelvimetry of the pregnant adolescent. Pelvic size and the frequency of contraction.
Pelvic dimensions by x-ray of 282 pregnant adolescents and 181 adult women were compared to ascertain if the pelvis of the adolescent was smaller and contracted with greater frequency. The majority of 10 pelvic dimensions for black and white adolescents were significantly smaller or contracted with significantly greater frequency. The pattern of signifcant differences suggests that the adolescent pelvis has yet to mature fully by age 16. As a consequence of physiologic events during puberty, described by several authors, the adolescent pelvis grows at an accelerated rate and typically changes from an anthropoid to a gynecoid configuration. Caution must be taken in applying these results since pelvic size is not synonymous with obstetric outcome.


Detection of RNA complementary to herpes simplex virus DNA in human cervical squamous cell neoplasms.
Nonneoplastic and neoplastic cervical biopsy specimens were examined by in situ hybridization to 125I-labeled DNA of herpes simplex virus (HSV), adenovirus, and bacteriophage lambda DNA's, and quantitative hybridization data were obtained using a Video Image Analyser. HSV-specific RNA was detected in 72% of cervical intraepithelial neoplasia, 60% of squamous cervical carcinomas, 2% of nonneoplastic cervices, and 9% of primary adenocarcinomas of the cervix. None of the tissues gave positive hybridization with adenovirus or lambda DNA probes. In paired biopsies of cervical intraepithelial neoplasia and nonneoplastic epithelium from 29 individuals, HSV-specific RNA was detected only in the epithelium of the neoplastic sample and not in the nonneoplastic control. Infectious HSV-2 was isolated from a low proportion (2%) of both ectocervical swabs and cell-free tissue extracts of patients examined, suggesting that the HSV-specific RNA detected in squamous cell neoplasms was not due to overt infections.


Impact of positive margins on outcomes of oropharyngeal squamous cell carcinoma according to p16 status.
Currently, positive surgical margins in head and neck cancer are considered to be an indicator for postoperative chemoradiotherapy (CRT) over radiotherapy (RT) alone. However, there are less data regarding the impact of margin status on human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC). We performed a retrospective review of 55 patients with oropharyngeal SCC undergoing primary surgical treatment. The impact of margin status on disease-specific survival (DSS) was studied according to p16 status. Twenty-one patients had positive margins. Adjuvant treatment in these cases was CRT (n = 6), RT alone (n = 14), and none (n = 1). Among p16-negative patients, positive margins and dysplasia at margins predicted significantly worse DSS. Among patients with p16-positive disease, margin status had no impact on DSS. Patients with p16-positive oropharyngeal SCC and positive margins after excision maintain a low risk of recurrence despite most receiving RT alone as adjuvant treatment. These findings raise questions regarding the additional benefit of postoperative CRT in this group.


EATING PATTERNS, PHYSICAL ACTIVITY AND THEIR ASSOCIATION WITH DEMOGRAPHIC FACTORS IN THE POPULATION INCLUDED IN THE OBESITY STUDY IN ROMANIA (ORO STUDY).
Four major modifiable behavioral risk factors are considered responsible for the current burden of the non-communicable diseases: tobacco use, physical inactivity, unhealthy diet and excessive alcohol consumption. Limited data on the lifestyle habits in Romanian population is currently available. To assess the eating patterns and physical activity habits and other lifestyle components in various age groups in the population included in the ORO study. ORO was a cross-sectional, epidemiologic, multicenter non-interventional study conducted from January 2014 until August 2014 in 8 study centers spread in the main historical regions of Romania. Eating 3 meals/day every day was more frequently reported in the 60-79 years and ≥ 80 years age groups (53.0% and 51.7%) than in the 18-39 years and 40-59 years age groups (26.8% and 35.8%), p <0.001. The frequency of eating breakfast every day increased with age from 43.5% in the youngest age group to 79.3% in the oldest one (p <0.001). Intense and moderate leisure-time physical activity was more frequent among participants in the 18- 39 years age group. Leisure time physical activities were associated with younger age groups, male sex, rural area, higher educational level and non-smoking status. Regular breakfast and regular consumption of 3 meals/day was associated with older age group, male sex and non-smoking status. Our analysis showed a high frequency of unhealthy lifestyle habits among the younger age groups as compared to the older ones, with the highest frequency of these unhealthy behavior reported in the 18-39 years age group.


Ultrastructure in resolving a diagnosis of poorly differentiated clear cell sarcoma of soft parts in an adolescent male.
Clear cell sarcoma of soft parts is a rare tumor in children and it requires a high index of suspicion for accurate diagnosis. Early diagnosis leads to radical surgical excision and limits the aggressive behavior of this tumor. We report a case of a 12-year-old boy with a recurrent soft-tissue tumor in the scalp, misdiagnosed on three occasions as epitheloid sarcoma owing to the poorly differentiated appearance of cells. In spite of focal S-100 expression, this tumor was not recognized as a tumor of melanocytic origin till melanosomes were demonstrated on electron microscopy (EM). Detection of melanosomes on electron microscopy helped in clinching the histology diagnosis, reiterating the definite role of EM in diagnosing these tumors. Failure to accurately diagnose this tumor resulted in institution of preoperative chemotherapy, delayed surgical excision, tumor progression and death of patient within a year and half of presentation.


Nitrogen dioxide exposure and alveolar macrophage elastase in hamsters.
Adult male hamsters were exposed to 30 +/- 5 ppm nitrogen dioxide (NO2) for periods as long as 30 days. Alveolar macrophages obtained by lung lavage at 0, 2, 5, 14, and 30 days of exposure were present in increased amounts, with the greatest increase 8 times the control amount at 14 days of NO2 exposure. No elastolytic activity was observed in the cell-free lavage fluid. Alveolar macrophages were cultured in serum-free medium for 1 to 6 days. The mediums were collected and assayed for elastolytic activity using Sepharose-coupled [3H] soluble elastin as substrate. Elastolytic activity in the secretions increased significantly at days 2 and 5 but was greatest after 14 days of NO2 exposure. These observations indicate that the secretions of alveolar macrophages from hamsters exposed to NO2 increased elastolytic activity. This activity correlates with the duration of NO2 exposure for periods as long as 14 days. The increased elastolysis observed appears to be dependent on increased numbers of macrophages rather than on increased elastolytic secretion per cell. Inhibition studies with a battery of elastase inhibitors indicated that the elastase(s) secreted from NO2 and control alveolar macrophages have identical properties. The response of hamster macrophage elastase to inhibitors differs from that observed in the mouse and in humans in that it is not inhibited by EDTA, human serum or 1,10-phenanthroline.


Community-Based, Preclinical Patient Navigation for Colorectal Cancer Screening Among Older Black Men Recruited From Barbershops: The MISTER B Trial.
To test the effectiveness of a preclinical, telephone-based patient navigation intervention to encourage colorectal cancer (CRC) screening among older Black men. We conducted a 3-parallel-arm, randomized trial among 731 self-identified Black men recruited at barbershops between 2010 and 2013 in New York City. Participants had to be aged 50 years or older, not be up-to-date on CRC screening, have uncontrolled high blood pressure, and have a working telephone. We randomized participants to 1 of 3 groups: (1) patient navigation by a community health worker for CRC screening (PN), (2) motivational interviewing for blood pressure control by a trained counselor (MINT), or (3) both interventions (PLUS). We assessed CRC screening completion at 6-month follow-up. Intent-to-treat analysis revealed that participants in the navigation interventions were significantly more likely than those in the MINT-only group to be screened for CRC during the 6-month study period (17.5% of participants in PN, 17.8% in PLUS, 8.4% in MINT; P < .01). Telephone-based preclinical patient navigation has the potential to be effective for older Black men. Our results indicate the importance of community-based health interventions for improving health among minority men.


Improving alignment in total knee arthroplasty: a cadaveric assessment of a surgical navigation tool with computed tomography imaging.
To investigate the accuracy of an imageless, optical surgical navigation tool to assist with femoral and tibial bone cuts performed during TKA. Six board-certified orthopedic surgeons participated in a laboratory cadaver investigation, performing femoral and tibial bone cuts with the assistance of a computer navigation tool. Femoral and tibial varus/valgus, tibial slope, femoral flexion, and both femoral and tibial rotation measurements from the device were compared with angular measurements calculated from computed tomography (CT) images of the knees. Measurements with the navigation tool were highly correlated with those obtained from CT scans in all three axes. For the distal femoral cut, the absolute mean difference in varus/valgus was 0.83° (SD 0.46°, r = 0.76), femoral flexion was 1.91° (SD 1.16°, r = 0.85), and femoral rotation was 1.29° (SD 1.01°, r = 0.88) relative to Whiteside's line and 0.97° (SD 0.56°, r = 0.81) relative to the posterior condylar axis. For the tibia, the absolute mean difference in varus/valgus was 1.08° (SD 0.64°, r = 0.85), posterior slope was 2.78° (SD 1.40°, r = 0.60), and rotation relative to the anteroposterior axis (posterior cruciate ligament to the medial third of the tibial tuberosity) was 2.98° (SD 2.54°, r = 0.79). Utilization of an imageless navigation tool may aid surgeons in accurately performing and monitoring femoral and tibial bone cuts, and implant rotation in TKA and thus, more accurately align TKA components.


On-chip assessment of human primary cardiac fibroblasts proliferative responses to uniaxial cyclic mechanical strain.
Cardiac cell function is substantially influenced by the nature and intensity of the mechanical loads the cells experience. Cardiac fibroblasts (CFs) are primarily involved in myocardial tissue remodeling: at the onset of specific pathological conditions, CFs activate, proliferate, differentiate, and critically alter the amount of myocardial extra-cellular matrix with important consequences for myocardial functioning. While cyclic mechanical strain has been shown to increase matrix synthesis of CFs in vitro, the role of mechanical cues in CFs proliferation is unclear. We here developed a multi-chamber cell straining microdevice for cell cultures under uniform, uniaxial cyclic strain. After careful characterization of the strain field, we extracted human heart-derived CFs and performed cyclic strain experiments. We subjected cells to 2% or 8% cyclic strain for 24 h or 72 h, using immunofluorescence to investigate markers of cell morphology, cell proliferation (Ki67, EdU, phospho-Histone-H3) and subcellular localization of the mechanotransduction-associated transcription factor YAP. Cell morphology was affected by cyclic strain in terms of cell area, cell and nuclear shape and cellular alignment. We additionally observed a strain intensity-dependent control of cell growth: a significant proliferation increase occurred at 2% cyclic strain, while time-dependent effects took place upon 8% cyclic strain. The YAP-dependent mechano-transduction pathway was similarly activated in both strain conditions. These results demonstrate a differential effect of cyclic strain intensity on human CFs proliferation control and provide insights into the YAP-dependent mechano-sensing machinery of human CFs.


Gluconolactone Alleviates Myocardial Ischemia/Reperfusion Injury and Arrhythmias via Activating PKCε/Extracellular Signal-Regulated Kinase Signaling.
Gluconolactone (D-glucono-1,5-lactone or GDL) is a food additive which presents in dietary products such as tofu, yogurt, cheese, bread, wine, etc. GDL has long been considered as a free radical scavenger; however, its role in cardioprotection remains elusive. In this study, using a mouse model of myocardial ischemia/reperfusion (I/R) injury and a model of hypoxia/reoxygenation (H/R) in neonatal rat cardiomyocytes (NRCM), we explored the role of GDL in I/R injury. We found that GDL (5 mg/kg, i.p.) attenuated myocardial I/R injury as evidenced by decreased infarct size, release of cardiac injury markers and apoptosis. Additionally, GDL decreased reperfusion-induced arrhythmias and oxidative stress. These effects were also observed in parallel in vitro studies. Mechanistically, we found that GDL treatment was strongly associated with activation of pro-survival extracellular signal-regulated kinase (ERK) signaling both in vivo and in vitro, and pharmacological inhibition of ERK signaling via U0126 attenuated GDL-induced cardioprotection against H/R injury in NRCM cells. To reveal how GDL regulates ERK signaling, we predicted the putative targets of GDL by Swiss Target Prediction, and protein kinase C (PKC) emerged as the most promising target for GDL. By pharmacological intervention and immunofluorescence, we found that PKCε, an important member of the PKC family, was activated after GDL treatment in heart, thereby leading to ERK activation and cardioprotection against I/R injury. Taken together, our results demonstrated that GDL acts as a potent activator of PKCε and, thus, provides cardioprotection against I/R injury via activation of ERK signaling.


Perineal groove-a case report.
The perineal groove is a rare congenital anomaly of the perineum. We present a case of this uncommon condition that had been misinterpreted as irritant dermatitis following treatment for diaper rash. To our knowledge this is the first report of this condition is the dermatology literature.


Cardio-respiratory values during recovery from exercise in soccer Spanish leagues.
In this cross-sectional study, we compared Spanish division one (n = 114) and division two (n = 80) soccer players in terms of their cardio-respiratory response during recovery following a maximum laboratory effort test. Following the maximum laboratory effort protocol, we measured oxygen consumption ([Formula: see text]), heart rate (HR), and ventilation ([Formula: see text]) during recovery. Over the first 60 s of recovery, no significant differences were seen in either [Formula: see text] (28.7 versus 28.3 ml/kg/m, in division one and two players, respectively), HR, or [Formula: see text] (p > 0.05). After 90 s, however, significant differences appeared between the players of the two divisions (p < 0.01), although not among playing positions. Significant differences in [Formula: see text] (21.1 versus 26.0 ml/kg/m, in division one and two players, respectively) and HR were still apparent at 180 s into the recovery period. The change in professional soccer players' cardio-respiratory values over the recovery period following maximum effort are independent of the position played, but are associated with the division in which a player competes. Second division players show significantly higher [Formula: see text] and HR values than first division players at 180 s into the recovery period. These differences might influence performance in soccer and in other athletes whose sports require intermittent bouts of maximum effort and consequently times to repeat high-intensity efforts as short as possible.


Practice patterns for the radical treatment of nasopharyngeal cancer by head and neck oncologists in the United Kingdom.
Advances in radiation delivery, imaging techniques, and chemotherapy have significantly improved treatment options for non-metastatic nasopharyngeal cancers (NPC). However, their impact on the practice in the United Kingdom (UK), where this tumour is rare, is unknown. This study examined the current attitudes of UK head and neck oncologists to the treatment of NPC. UK head and neck oncologists representing 19/23 cancer networks were sent an invitation email with a personalised link to a web-based survey designed to identify the influence of tumour and nodal staging on current NPC management practices. 26/42 (61%) of clinicians responded. Induction chemotherapy followed by concomitant chemoradiation was the treatment of choice for Stage III (69%) and IVa/b (96%), with cisplatin and 5-fluorouracil combination being the most commonly used induction chemotherapy regimen (88%). 16 centres (61%) used a geometric approach, adding variable margins of 0-10 mm to the gross tumour volume to define their therapeutic dose clinical target volume. 54% of respondents used 3 radiotherapy (RT) prescription doses to treat NPC. Retropharyngeal nodal region irradiation policy was inconsistent, with nearly one-quarter treating the entire group to a radical dose. Significant heterogeneity currently exists in the RT practice of NPC in the UK. A consensus regarding the optimal curative, function-sparing treatment paradigm for NPC is necessary to ensure cancer survivors have satisfactory long-term health-related quality of life. Advances in knowledge: This is the first study to highlight the significant variation in RT practice of NPC in the UK.


[Self-reported prevalence of fructan food hypersensitivity in university students from the State of Mexico].
To determine the self-reported prevalence of fructans food hypersensitivity in a sample of Mexican university students and to investigate the most frequent symptoms, the related foods involved, risk factors and gastrointestinal function status. A cross-sectional, descriptive study was conducted in a convenience sample of 412 university students aged from 18 to 35 years. Data were collected about their personal and family history of gastrointestinal diseases, the presence of symptoms after consumption of certain foods, and the severity of their symptoms. The prevalence of fructans food hypersensitivity was 31.1 %; it was higher in women than in men. The most frequent gastrointestinal symptoms were bloating and flatulence. The most frequent extra-intestinal symptoms were fatigue and stress. The food groups related to the occurrence of symptoms were legumes, vegetables, and fruits. Significant association was found between female sex, personal and family history of gastrointestinal diseases and the presence of fructans food hypersensitivity (p < 0.05). Most individuals with fructans food hypersensitivity had mild gastrointestinal dysfunction (67.2 %). FFH is a common condition, it was found in one third of university students and occurs mainly in women. More research and diffusion about this pathology is required.


Cloning and expression in Escherichia coli of a Klebsiella ozaenae plasmid-borne gene encoding a nitrilase specific for the herbicide bromoxynil.
An enzyme (nitrilase) that converts the herbicide bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) to its metabolite 3,5-dibromo-4-hydroxybenzoic acid was shown to be plasmid encoded in the natural soil isolate Klebsiella ozaenae. The bromoxynil-specific nitrilase was expressed in Escherichia coli by direct transfer and stable maintenance in E. coli of a naturally occurring 82-kilobase K. ozaenae plasmid. Irreversible loss of the ability to metabolize bromoxynil both in E. coli and K. ozaenae was associated with the conversion of the 82-kilobase plasmid to a 68-kilobase species. In E. coli this conversion was the result of a host recA+-dependent recombinational event. A gene, designated bxn, encoding the bromoxynil-specific nitrilase was constitutively expressed in K. ozaenae and E. coli and subcloned on a 2.6-kilobase PstI DNA segment. The polarity and the location of the gene were determined by assaying hybrid constructs of the bromoxynil-specific nitrilase gene fused with the heterologous lac promoter.


Prediction and Global Sensitivity Analysis of Long-Term Deflections in Reinforced Concrete Flexural Structures Using Surrogate Models.
Reinforced concrete (RC) is the result of a combination of steel reinforcing rods (which have high tensile) and concrete (which has high compressive strength). Additionally, the prediction of long-term deformations of RC flexural structures and the magnitude of the influence of the relevant material and geometric parameters are important for evaluating their serviceability and safety throughout their life cycles. Empirical methods for predicting the long-term deformation of RC structures are limited due to the difficulty of considering all the influencing factors. In this study, four popular surrogate models, i.e., polynomial chaos expansion (PCE), support vector regression (SVR), Kriging, and radial basis function (RBF), are used to predict the long-term deformation of RC structures. The surrogate models were developed and evaluated using RC simply supported beam examples, and experimental datasets were collected for comparison with common machine learning models (back propagation neural network (BP), multilayer perceptron (MLP), decision tree (DT) and linear regression (LR)). The models were tested using the statistical metrics R2, RAAE, RMAE, RMSE, VAF, PI, A10-index and U95. The results show that all four proposed models can effectively predict the deformation of RC structures, with PCE and SVR having the best accuracy, followed by the Kriging model and RBF. Moreover, the prediction accuracy of the surrogate model is much lower than that of the empirical method and the machine learning model in terms of the RMSE. Furthermore, a global sensitivity analysis of the material and geometric parameters affecting structural deflection using PCE is proposed. It was found that the geometric parameters are more influential than the material parameters. Additionally, there is a coupling effect between material and geometric parameters that works together to influence the long-term deflection of RC structures.


Assessing the trophic state of Linhos lake: a first step towards ecological rehabilitation.
Lack of recognition of the value of wetlands has led to the loss of considerable areas of these ecosystems in the past. Linhos lake (Figueira da Foz, Portugal) is a good example of one of these ecosystems, in which human intervention was responsible for its environmental degradation and led to its precocious terrestrialization. Physico-chemical conditions and zooplankton community structure were studied in Linhos lake, in order to evaluate ecosystem functioning and to acquire baseline information. The system is characterised by high oxygen depletion. Spatial heterogeneity was confirmed by the existence of significant differences in total densities for the three zooplanktonic groups. Rotifers were the most abundant group attaining their maximum density in April (2251 x 1 ind/l). Keratella quadrata, K. cochlearis, Polyarthra vulgaris, Filinia terminalis and Hexarthra mira were the main abundant species. Correspondence analysis suggested temperature as the main controlling factor in species seasonality. In order to prevent the precocious disappearance of the lake some restoration measures were proposed based on zooplankton community structure.


Cyclosporine A protects against arachidonic acid toxicity in rat hepatocytes: role of CYP2E1 and mitochondria.
Diets high in polyunsaturated fatty acids (PUFA) are important for the development of alcoholic liver injury. The goal of this report was to characterize toxicity by arachidonic acid (AA), its enhancement by salicylate, and the role of mitochondrial injury in the pathway leading to toxicity in hepatocytes from pyrazole-treated rats. AA caused toxicity that was increased by sodium salicylate. This synergistic toxicity was reduced by diallyl sulfide (DAS), an inhibitor of CYP2E1; Trolox ([+/-] 6-hydroxy, 2, 5, 7, 8-tetramethylchroman-2-carboxylic acid), an inhibitor of lipid peroxidation; Z-Val-Ala-Asp(OMe)-fluoromethylketone (ZVAD-FMK), a pan caspase inhibitor; and by cyclosporine A (CsA), an inhibitor of the mitochondrial permeability transition. Mitochondrial membrane potential also was reduced, and this was prevented by cyclosporine, diallyl sulfide, and Trolox. There was release of mitochondrial cytochrome c into the cytosol and activation of caspase 3, which were prevented by cyclosporine, diallylsulfide, and Trolox. Toxicity was prevented by expression of catalase either in the cytosolic or the mitochondrial compartment. Levels of CYP2E1 rapidly declined, and this was partially prevented by salicylate. These results are consistent with a model in which CYP2E1-dependent production of reactive oxygen species enhances lipid peroxidation when AA is added to hepatocytes. This results in damage to the mitochondria, with initiation of a membrane permeability transition and a decline in membrane potential, followed by release of cytochrome c, caspase 3 activation, and cellular toxicity. In conclusion, damage to mitochondria appears to play an important role in the CYP2E1 plus AA toxicity.


A prototype diagnostics system to detect ultraviolet emission for plasma turbulence.
A system to detect ultraviolet emissions from plasma is developed for multi-point measurement, the target of which is the imaging of turbulence with a high temporal resolution. A fluorescent glass, which converts ultraviolet emissions to visible light with a wavelength of approximately 540 nm, is utilized in the system. Following the conversion, the fluorescent light is transferred with fibre optics, and is converted to electric signals in a location that is sufficiently distant from an electrically noisy environment around the plasma device. This paper describes a prototype system of this diagnostic method and discusses the spectral analysis obtained using a low-aspect-ratio reversed field pinch RELAX.


Divergent cell cycle kinetics of midgestation ventricular cells entail a higher engraftment efficiency after cell transplantation.
Cardiac progenitor cells (CPCs) in the primary and secondary heart fields contribute to the formation of all major cell types in the mammalian heart. While some CPCs remain undifferentiated in midgestation and postnatal hearts, very little is known about their proliferation and differentiation potential. In this study, using an Nkx2.5 cell lineage-restricted reporter mouse model, we provide evidence that Nkx2.5(+) CPCs and cardiomyocytes can be readily distinguished from nonmyocyte population using a combination of Nkx2.5 and sarcomeric myosin staining of dispersed ventricular cell preparations. Assessment of cell number and G1/S transit rates during ventricular development indicates that the proliferative capacity of Nkx2.5(+) cell lineage gradually decreases despite a progressive increase in Nkx2.5(+) cell number. Notably, midgestation ventricles (E11.5) contain a larger number of CPCs (∼2-fold) compared with E14.5 ventricles, and the embryonic CPCs retain cardiomyogenic differentiation potential. The proliferation rates are consistently higher in embryonic CPCs compared with myocyte population in both E11.5 and E14.5 ventricles. Results from two independent cell transplantation models revealed that E11.5 ventricular cells with a higher percentage of proliferating CPCs can form larger grafts compared with E14.5 ventricular cells. Furthermore, transplantation of embryonic ventricular cells did not cause any undesirable side effects such as arrhythmias. These data underscore the benefits of donor cell developmental staging in myocardial repair.


Neurologic dysfunction after major thoracic surgery in a patient with severe arteriosclerotic disease receiving epidural analgesia.
We present a patient who underwent pulmonary lobectomy with thoracic epidural analgesia and developed postoperative sensory-motor symptoms of the lower limbs. Radiological investigation indicated ischemia of the conus medullaris as the likely cause. The motor deficit disappeared gradually and the patient was mobilizing independently when discharged on postoperative day 21.


Cerebellar and Prefrontal Structures Associated With Executive Functioning in Pediatric Patients With Congenital Heart Defects.
Children, adolescents, and young adults with congenital heart defects (CHD) often display executive dysfunction. We consider the prefrontal and cerebellar brain structures as mechanisms for executive dysfunction among those with CHD. 55 participants with CHD (M age = 13.93) and 95 healthy controls (M age = 13.13) completed magnetic resonance imaging (MRI) of the brain, from which we extracted volumetric data on prefrontal and cerebellar regions. Participants also completed neuropsychological tests of executive functioning; their parents completed ratings of their executive functions. Compared to healthy controls, those with CHD had smaller cerebellums and lateral, medial, and orbital prefrontal regions, they performed more poorly on tests of working memory, inhibitory control, and mental flexibility, and their parents rated them as having poorer executive functions across several indices. Across both groups, there were significant correlations for cerebellar and/or prefrontal volumes with cognitive assessments of working memory, mental flexibility, and inhibitory control and with parent-completed ratings of task initiation, working memory, and planning/organization. Greater prefrontal volumes were associated with better working memory, among those with larger cerebellums (with group differences based on the measure and the prefrontal region). Greater prefrontal volumes were related to better emotional regulation only among participants with CHD with smaller cerebellar volumes, and with poorer inhibition and emotional regulation only among healthy controls with larger cerebellar volumes. The cerebellum not only contributes to executive functioning among young individuals with CHD but may also modulate the relationships between prefrontal regions and executive functioning differently for pediatric patients with CHD vs. health controls.


N-acetylcysteine delivery with silica nanoparticles into 3T3-L1 adipocytes.
Background: The addition of 5 mM N-acetylcysteine (NAC) to 3T3-L1 adipocytes culture inhibits the accumulation of triglycerides (Tg) by 50%, but after 48 h uptake was only 16% of total NAC available. Based on these results, the aim of this study is to increase the NAC cellular uptake by encapsulating it in silica nanoparticles (NPs). Materials & methods: Silica NPs, 20 ± 4.5 nm in size, were developed, with an inner cavity loaded with 5 mM NAC. At 48 h after treatment, there was a dose-dependent cytotoxic effect. We attempted to reduce the cytotoxicity of silica NPs by coating them with bovine serum albumin. Results: While we obtained nontoxic bovine serum albumin coated NPs, their effect on Tg cellular accumulation was also reduced.


Gender-selective neural populations: evidence from event-related fMRI repetition suppression.
Accurate recognition of gender in another individual is integral to successful human social interaction and to mate selection. When we encounter another person, we are effortlessly able to identify their gender, most often through the information conveyed by their facial features. Faces comprise the most abundantly encountered cue used to classify human gender. Considering the importance of facial information in gender perception, relatively little is known about the mechanisms involved in perceiving gender through human facial cues. We used an event-related fMRI repetition suppression paradigm to explore the neural circuitry underlying gender perception from facial information. Participants viewed brief consecutive images consisting of either gender-same face pairings (two male faces or two female faces) or images of gender-different face pairings (a male face preceded or followed by a female face), while attending to facial attractiveness in both conditions. Using a region-of-interest approach, we found repetition suppression on gender-same trials within the left ventral temporal fusiform gyrus and in the right collateral sulcus. Whole-brain voxel-wise analyses revealed selectivity for face gender again in the right collateral sulcus, in addition to the left cuneus and the right lateral occipital gyrus. Our results indicate that in addition to the face-selective FFA, cortical areas that are not traditionally considered to be "face-selective" are involved in the perception of gender-based facial cues.


Aegean wall lizards switch foraging modes, diet, and morphology in a human-built environment.
Foraging mode is a functional trait with cascading impacts on ecological communities. The foraging syndrome hypothesis posits a suite of concurrent traits that vary with foraging mode; however, comparative studies testing this hypothesis are typically interspecific. While foraging modes are often considered typological for a species when predicting foraging-related traits or mode-specific cascading impacts, intraspecific mode switching has been documented in some lizards. Mode-switching lizards provide an opportunity to test foraging syndromes and explore how intraspecific variability in foraging mode might affect local ecological communities.Because lizard natural history is intimately tied to habitat use and structure, I tested for mode switching between populations of the Aegean wall lizard, Podarcis erhardii, inhabiting undisturbed habitat and human-built rock walls on the Greek island of Naxos. I observed foraging behavior among 10 populations and tested lizard morphological and performance predictions at each site. Furthermore, I investigated the diet of lizards at each site relative to the available invertebrate community.I found that lizards living on rock walls were significantly more sedentary-sit and wait-than lizards at nonwall sites. I also found that head width increased in females and the ratio of hindlimbs to forelimbs in both sexes increased as predicted. Diet also changed, with nonwall lizards consuming a higher proportion of sedentary prey. Lizard bite force also varied significantly between sites; however, the pattern observed was opposite to that predicted, suggesting that bite force in these lizards may more closely relate to intraspecific competition than to diet.This study demonstrates microgeographic variability in lizard foraging mode as a result of human land use. In addition, these results demonstrate that foraging mode syndromes can shift intraspecifically with potential cascading effects on local ecological communities.


Pathophysiological study of chronic necrotizing pulmonary aspergillosis.
The aim of the present study is to define the characteristics of the clinical and histopathological features of chronic necrotizing pulmonary aspergillosis (CNPA) cases with severe hemoptysis. We conducted a histological study of three patients clinically diagnosed as having CNPA who had hemoptysis for 5 years. A tuberculosis sequelae was found as the underlying disorder in all three cases. All patients had fever, general fatigue, and hemoptysis, and their chest computed tomographic images revealed fungus balls, cavity wall thickening, consolidation surrounding the cavity, and satellite foci. All had been treated with anti-fungal drugs and corticosteroids. However, all patients died from respiratory failure due to massive hemoptysis. Histopathological examination revealed that the cavity wall consisted of three layers comprised of necrotic, granulation, and fibrous tissue layers. Aspergilli were found in both the fungus ball and necrotic tissue comprising the inner layer of the cavity. In addition, most of the vessels were incompletely occluded with thrombosis and were necrotic, as well as showing local invasion of Aspergilli. Surgical intervention should be considered as a prior procedure for CNPA patients, because vessels at the cavity wall, whether occluded completely or incompletely, are usually necrotic and/or show local invasion of Aspergilli.


[The diagnostic value of fluorescence quantitative PCR in screening of influenza A virus].
To discuss the the diagnostic value of fluorescence quantitative PCR in screening of influenza A virus. Influenza A virus RNA in 150 cases of suspected influenza patients with throat swab was measured by fluorescence quantitative RT-PCR. The white blood cell count was measured by XT-1800 automated hematology analyzer in patients' anticoagulant EDTA whole blood. 45 cases of influenza A virus RNA-positive patients were detected with influenza A virus core protein by colloidal gold. In 150 patients, 54 cases were detected influenza A virus RNA positive, the positive rate was 36%.The 54 cases of influenza A virus RNA-positive patients were detected with influenza A virus core protein by colloidal gold, the results were all negative.The white blood cell count is (6.81+/-2.12) x 10(9)/L in the influenza A virus RNA-positive patients, and (6.64+/-3.13) x 10(9)/L for the negative cases. White blood cell count in patients with influenza A and non-influenza patients have no significant difference. Fluorescence quantitative RT-PCR in the detection of influenza A virus RNA has a better positive rate, its sensitivity and specificity are better than colloidal gold and white blood cell count, and it can be screened quickly and efficiently in patients with influenza to prevent disease outbreaks.


[Application of septal extension graft with autogenous septal cartilage and auricular cartilage in rhinoplasty].
Objective: To explore the feasibility of reconstruction of nasal tip with septal cartilage and auricular cartilage. Methods: From September 2018 to October 2019, 17 patients (two males and fifteen females) with low noses underwent rhinoplasty under general anesthesia. The age of the patients ranged from 19 to 39, with an average of 27 years old. Among them, all the 17 cases were primary rhinoplasty. During the operation, autologous nasal septum cartilage was used as septal extension graft to extend the caudal septum, and the auricular cartilage was used to enhance the stability of the strut and to elevate the tip for adjusting the shape of nose by making into spreader graft, columellar strut graft, derotation graft and onlay graft. The nasal dorsum was filled with polytetrafluoroethylene. Digital scanning technology was used to evaluate the nasal structure before and after operation. SPSS 22 software was used to analyze the data with paired t-test. Results: The follow-up was from 6 to 12 months, with an avaerge of 7.6 months. Seventeen patients were satisfied with postoperative nasal morphology and height. There was no infection, prosthesis displacement, skin flap necrosis, no auricle deformation and other complications. Statistical software SPSS 22 performed paired t-test on the preoperative and postoperative data obtained by digital technology: postoperative nasal length and nasal tip protrusion increased compared with that before surgery, and it was statistically significant(length:(3.60±0.77)mm, tip protrusion:(3.61±0.64)mm, t value was -19.203 and -23.132 respectively, both P<0.001). The nasolabial Angle was smaller than that before surgery, and the data were statistically significant(3.40°±2.11°,t=6.635, P<0.001). Conclusion: The nasal tip and nasal septum extension complex constructed by autogenous nasal septal cartilage combined with auricular cartilage can increase the length of nasal tip, increase the height of nasal tip and reduce the angle of nasolabial angle.


The Food Contaminant Deoxynivalenol Exacerbates the Genotoxicity of Gut Microbiota.
An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food-especially cereal products-in Europe and North America. This study investigates the effect of the food contaminant DON on the genotoxicity of the E. coli strains producing colibactin. In vitro, intestinal epithelial cells were coexposed to DON and E. coli producing colibactin. In vivo, newborn rats colonized at birth with E. coli producing colibactin were fed a DON-contaminated diet. Intestinal DNA damage was estimated by the phosphorylation of histone H2AX. DON exacerbates the genotoxicity of the E. coli producing colibactin in a time- and dose-dependent manner in vitro Although DON had no effect on the composition of the gut microbiota, and especially on the number of E. coli, a significant increase in DNA damage was observed in intestinal epithelial cells of animals colonized by E. coli strains producing colibactin and coexposed to DON compared to animals colonized with E. coli strains unable to produce colibactin or animals exposed only to DON. In conclusion, our data demonstrate that the genotoxicity of E. coli strains producing colibactin, increasingly present in the microbiota of asymptomatic human beings, is modulated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gut microbiota with regard to intestinal carcinogenesis.IMPORTANCE An increasing number of human beings from developed countries are colonized by Escherichia coli strains producing colibactin, a genotoxin suspected to be associated with the development of colorectal cancers. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food-especially cereal products-in Europe and North America. Our in vitro and in vivo results demonstrate that the intestinal DNA damage induced by colibactin-producing E. coli strains was exacerbated by the presence of DON in the diet. This raises questions about the synergism between food contaminants and gut microbiota with regard to intestinal carcinogenesis.


The Application of Biphasic Extrathoracic Cuirass-Assisted Ventilation in Normal Subjects Wearing Chemical-Biological-Radiological-Nuclear (CBRN) Gas Masks.
Mobile RTX (MRTX), a portable light-weighted ventilator, provides noninvasive respiratory support using biphasic extrathoracic cuirass-assisted ventilation. Despite the effectiveness of chemical-biological-radiological-nuclear (CBRN) gas masks, they cause respiratory loading as a result of added dead space and resistance. This prospective comparative pilot study was conducted to investigate the safety and efficacy of assisted ventilation provided by MRTX in healthy adult volunteers wearing CBRN gas masks at rest. Cardiorespiratory parameters were monitored in 11 healthy adult volunteers breathing spontaneously or with assisted ventilation provided by MRTX, freely or with the mask on. Comparisons were made by single-factor analysis of variance. AV significantly increased minute ventilation (p < 0.001). MRTX increased minute ventilation by 6.4 L/min (mean, 95% confidence interval: 3.1, 9.8; p < 0.005) and by 4.7 L/min (1.8, 7.5; p < 0.01) during spontaneous breathing and with the mask on, respectively. Simultaneously, end-tidal carbon dioxide partial pressure decreased by 3.6 mmHg (2.2, 5.1; p < 0.001) and by 6.5 mmHg (3.8, 9.1; p < 0.001). Biphasic extrathoracic cuirass assisted ventilation provided by MRTX is safe and effective in supporting adequate needs at rest even when wearing protective masks. MRTX should be further assessed as a possible adjunct to currently used field ventilation in CBRN scenarios.


Epidural abscess T5T8 due to methicillin-resistent staphylococcus aureus in an immunocompetent patient.
A 28-year-old man was admitted with severe thoracic pain, a body temperature of 37.20, paraplegia and sphincter disturbances. MRI revealed an epidural abscess T5T8. A decompressive laminectomy T5T8 was performed and the abscess was removed. A methicillin-resistent Staphylococcus aureus was cultured. Vancomycin was administered. Six months later muscle testing showed values from 3/5 to 4/5. MRI is the first choice diagnostic tool. Laminectomy, drainage and intravenous antibiotics constitute the basic treatment. Antibiotics alone can be sufficient in case of whole spine involvement, lumbosacral localization without neurological symptoms, fixed neurological deficit, complete paralysis for more than 72 hours, or severe concomitant medical problems.


Protection against Staphylococcus aureus and tetanus infections by a combined vaccine containing SasA and TeNT‑Hc in mice.
In developing countries, trauma patients and neonates are vulnerable to Staphylococcus aureus (S. aureus) and Clostridium tetani infections. It has been suggested that a combined vaccine against the two infections may be a reliable and cost‑effective strategy. Previous studies have indicated that the S. aureus surface protein A (SasA) and the C fragment of tetanus neurotoxin (TeNT‑Hc) may be suitable candidates for a vaccine against S. aureus and tetanus infections, respectively. In the present study, mice were immunized with a combined vaccine containing SasA and TeNT‑Hc, which induced a robust immune response to both antigens, and mutual interference between SasA and TeNT‑Hc was not observed. In the S.aureus challenge model, the combined vaccine fully protected BALB/c mice against lethal intraperitoneal challenges with 3x109 colony‑forming units of a methicillin‑resistant S. aureus USA300 strain. In the TeNT challenge model, the combined vaccine conferred complete protection against a lethal dose of (2x103) xLD50 tetanus toxin. These results implied that SasA and TeNT‑Hc promising components for a combined vaccine against S. aureus and tetanus infections.


Accuracy of ventriculostomy catheter placement using a head- and hand-tracked high-resolution virtual reality simulator with haptic feedback.
The purpose of this study was to evaluate the accuracy of ventriculostomy catheter placement on a head- and hand-tracked high-resolution and high-performance virtual reality and haptic technology workstation. Seventy-eight fellows and residents performed simulated ventriculostomy catheter placement on an ImmersiveTouch system. The virtual catheter was placed into a virtual patient's head derived from a computed tomography data set. Participants were allowed one attempt each. The distance from the tip of the catheter to the Monro foramen was measured. The mean distance (+/- standard deviation) from the final position of the catheter tip to the Monro foramen was 16.09 mm (+/- 7.85 mm). The accuracy of virtual ventriculostomy catheter placement achieved by participants using the simulator is comparable to the accuracy reported in a recent retrospective evaluation of free-hand ventriculostomy placements in which the mean distance from the catheter tip to the Monro foramen was 16 mm (+/- 9.6 mm).