Retinoic acid reduces staurosporine-induced apoptotic damage in chick embryonic neurons by suppressing reactive oxygen species production.
The effect of all-trans retinoic acid (RA), which is known as a regulator of cell growth and differentiation, was studied during neuronal apoptosis. Apoptosis was induced in primary cultures of chick embryonic neurons by treatment with staurosporine (200 nM) for 24 h which led to a reduction of cellular viability to 40% compared to 83% in untreated cultures as well as to an increase in the number of apoptotic neurons (determined by nuclear staining with Hoechst 33258) to 60% compared to 15% in untreated cultures. RA (1 nM-10 microM) reduced the number of non-viable and apoptotic cells in a concentration-dependent manner and the maximal response was seen at 1 microM RA with 60% cellular viability and 38% apoptotic neurons. The production of mitochondrial reactive oxygen species (ROS, determined by the fluorescent indicator dihydrorhodamine) was elevated 4.4-fold after 4 h of staurosporine-treatment which was reduced to a 2-fold increase in the presence of 10 microM RA. The results indicate that RA was able to reduce apoptotic damage in staurosporine-treated chick embryonic neurons by suppressing the production of ROS.


Inhibition of polyclonal B-cell activation by suppressor monocytes in patients with sarcoidosis.
The present study employed a direct plaque-forming cell (PGC) assay following pokeweed mitogen (PWM) induced polyclonal activation of B lymphocytes in sarcoidosis to evaluate the in vitro humoral immune response in this disease and to delineate the immunoregulation of this response. Sarcoidosis lymphocytes had a suppressed PFC response to polyclonal activation, but were unable to suppress normal B-cell PFC responses in allogeneic co-cultures. Removal of a cell type, which was corticosteroid-resistant, radio-resistant, adherent and a non-T cell, from sarcoidosis mononuclear cell suspensions reversed the suppressed PFC response, indicating the presence of a suppressor monocyte. Thus in vitro suppressor cell activity has now been demonstrated in this disease, which is characterized by multiple immunological aberrancies.


Polymer multilayer tattooing for enhanced DNA vaccination.
DNA vaccines have many potential benefits but have failed to generate robust immune responses in humans. Recently, methods such as in vivo electroporation have demonstrated improved performance, but an optimal strategy for safe, reproducible, and pain-free DNA vaccination remains elusive. Here we report an approach for rapid implantation of vaccine-loaded polymer films carrying DNA, immune-stimulatory RNA, and biodegradable polycations into the immune-cell-rich epidermis, using microneedles coated with releasable polyelectrolyte multilayers. Films transferred into the skin following brief microneedle application promoted local transfection and controlled the persistence of DNA and adjuvants in the skin from days to weeks, with kinetics determined by the film composition. These 'multilayer tattoo' DNA vaccines induced immune responses against a model HIV antigen comparable to electroporation in mice, enhanced memory T-cell generation, and elicited 140-fold higher gene expression in non-human primate skin than intradermal DNA injection, indicating the potential of this strategy for enhancing DNA vaccination.


Coevolution in temporally variable environments.
Many potentially mutualistic interactions are conditional, with selection that varies between mutualism and antagonism over space and time. We develop a genetic model of temporally variable coevolution that incorporates stochastic fluctuations between mutualism and antagonism. We use this model to determine conditions necessary for the coevolution of matching traits between a host and a conditional mutualist. Using an analytical approximation, we show that matching traits will coevolve when the geometric mean interaction is mutualistic. When this condition does not hold, polymorphism and trait mismatching are maintained, and coevolutionary cycles may result. Numerical simulations verify this prediction and suggest that it remains robust in the presence of temporal autocorrelation. These results are compared with those from spatial models with unrestricted movement. The comparisons demonstrate that gene flow is unnecessary for generating empirical patterns predicted by the geographic mosaic theory of coevolution.


SLC9A2, suppressing by the transcription suppressor ETS1, restrains growth and invasion of osteosarcoma via inhibition of aerobic glycolysis.
Recent studies have shown that Solute Carrier Family 9 Member A2 (SLC9A2) could serve as a biomarker for cancer. However, its mechanism of action in osteosarcoma (OS) was still unclear. In this study, the data sets GSE154530 and GSE99671 were downloaded from the Gene Expression Omnibus (GEO) database, and 31 differentially expressed genes (DEGs) related to methylation were screened by bioinformatics analysis tools. Subsequently, SLC9A2 was screened as a candidate gene from DEGs, which was significantly downregulated in OS. CCK-8, transwell, western blotting and Seahorse XFe24 Cell Metabolic Analyzer assays demonstrated that overexpression of SLC9A2 could constrain OS cell proliferation, invasion, and aerobic glycolysis. Dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assays indicated ETS proto-oncogene 1 (ETS1) was a transcription suppressor of SLC9A2, and overexpression of ETS1 could promote methylation levels in specific regions of the SLC9A2 promoter. ETS1 could promote the proliferation, invasion, and aerobic glycolysis ability of OS cells, as well as tumor growth in vivo by inhibiting the expression of SLC9A2. In addition, SLC9A2, suppressing by ETS1, restrains growth and invasion of OS via inhibition of aerobic glycolysis. Thus, SLC9A2 can function as a key inhibitory factor in the aerobic glycolysis to inhibit proliferation and invasion of OS. This indicated that SLC9A2 has a potential targeted therapeutic effect on OS.


Use of vitamin D and infection in patients with chronic kidney disease.
To evaluate the effectiveness of vitamin D supplementation as protection factor against infection of patients with chronic kidney disease on conservative treatment. Retrospective cohort study carried out between 2013 and 2016 in the Conservative Treatment Outpatient Clinics (Ambulatório de Tratamento Conservador) of the Hypertension and Kidney Hospital (Hospital do Rim e Hipertensão) of the Universidade Federal de São Paulo. Data on sociodemographic factors, comorbidity, infection episodes and use or nonuse of vitamin D supplementation for at least 6 months were collected from medical records. The primary outcomes considered in both groups were: presence or absence of infection anywhere on the body (bloodstream, urinary, respiratory and surgical sites). A total of 263 patients were included and those who received (n=43) vitamin D had 59% less chance of developing infections (OR=0.41; 95%CI; 0.15-0.99), when compared to those who did not receive. Vitamin D supplementation was a protective factor against infections of all causes.


[Electronic prescription for Primary Care: a reliable tool to conceal medication at hospital admission?].
To analyze the reliability of an electronic prescription software at primary care (Medoracyl®) to conceal the medication at hospital admission. Prospective, comparative study of the home-based validated treatment of patients admitted to the hospital as compared to the one prescribed through Medoracyl®. The medi cation at admission was gathered by medical interview, medi cal records, and revision of the medication brought by the patients; the medication active in Medoracyl® by consulting the application the admission day. The discrepancies between both therapies were analyzed. 47 patients were included with 273 lines of home validated treatments and 274 lines of Medoracyl® treatment. 48 out of 273 lines were in discrepancy (17.6% [95% CI: 13.1- 21.6]). 27 out of 48 were justified, whereas 7.8% represented a discrepancy risk [95% CI: 4.6-11.0]. Medoracyl® is a useful tool and easy to access that allows knowing more than 90% of the home medication of the patients.


Determination of somatostatin receptor subtype 2 in carcinoid tumors by immunohistochemical investigation with somatostatin receptor subtype 2 antibodies.
We have shown previously that expression of mRNA for somatostatin receptor subtype 2 (sst2) detected by in situ hybridization correlates to therapeutic outcome in patients with carcinoid tumors treated with somatostatin analogues. However, in situ hybridization is laborious and not practical in clinical routine work. We have, therefore, developed polyclonal antibodies directed against sst2 that may be used for immunohistochemistry on tissue specimens. The staining is specific and is highly correlated to expression of mRNA for sst2 (P < 0.01) as well as to tracer uptake at somatostatin receptor scintigraphy (P < 0.01). There is also a good correlation to the therapeutic response in carcinoid patients treated with somatostatin analogues (P < 0.05). Of 35 patients with carcinoid tumors included in this investigation, 25 stained positive with the antibodies. Twenty-two of these were investigated by somatostatin receptor scintigraphy and showed tracer uptake in metastases. An additional two patients that did not stain with the antibodies showed pathological uptake of the tracer in metastases, which might indicate binding to somatostatin receptor subtype 5. None of the 10 patients without positive immunostaining responded to somatostatin analogue treatment, whereas patients with a positive stain had a biochemical response or remained stable during treatment. Thus, these antibodies may be used to determine the presence of sst2 in carcinoid tumors and to select patients suitable for somatostatin analogue treatment. The method is easily applicable in clinical practice.


Ca2+ uptake and Cd2+ accumulation in larval tilapia (Oreochromis mossambicus) acclimated to waterborne Cd2+.
The present study compares the rates of Ca2+ uptake and Cd2+ accumulation in tilapia (Oreochromis mossambicus) between larvae preexposed to Cd2+ and naive larvae. Preexposure to Cd2+ induces some form of adaptation that attenuates the effects of Cd2+ later on. Exposure to Cd2+ decreased the uptake of Ca2+ but did not suppress the accumulation rate of Cd2+. A 12-fold increase in 96-h half-maximal lethal concentration was found in tilapia larvae preexposed to 0.45 microM Cd2+ from hatching for 3 days in comparison with naive 3-day-old larvae. The effects of Cd2+ on Ca2+ influx kinetics in larvae preexposed to 0.18 microM Cd2+ for 3 days were examined. The Michaelis constant for Ca2+ in the 0.18 microM Cd2+ preexposed larvae did not change significantly in the presence of Cd2+, whereas maximal velocity increased by approximately 23%. An enhanced Ca2+ uptake efficiency ( approximately 18%) was found in these Cd2+-acclimated larvae. The criterion that determines the survival of tilapia larvae encountering Cd2+ challenge is the degree of interference with Ca2+ homeostasis instead of the absolute amount of Cd2+ accumulated.


Coactosin-like 1 antagonizes cofilin to promote lamellipodial protrusion at the immune synapse.
Actin depolymerizing factor-homology (ADF-H) family proteins regulate actin filament dynamics at multiple cellular locations. Herein, we have investigated the function of the ADF-H family member coactosin-like 1 (COTL1) in the regulation of actin dynamics at the T cell immune synapse (IS). We initially identified COTL1 in a genetic screen to identify novel regulators of T cell activation, and subsequently found that it associates with F-actin and localizes at the IS in response to TCR+CD28 stimulation. Live cell microscopy showed that depletion of COTL1 protein impaired T cell spreading in response to TCR ligation and abrogated lamellipodial protrusion at the T cell - B cell contact site, producing only a band of F-actin. Significantly, re-expression of wild type COTL1, but not a mutant deficient in F-actin binding could rescue these defects. In addition, COTL1 depletion reduced T cell migration. In vitro studies showed that COTL1 and cofilin compete with each other for binding to F-actin, and COTL1 protects F-actin from cofilin-mediated depolymerization. While depletion of cofilin enhanced F-actin assembly and lamellipodial protrusion at the IS, concurrent depletion of both COTL1 and cofilin restored lamellipodia formation. Taken together, our results suggest that COTL1 regulates lamellipodia dynamics in part by protecting F-actin from cofilin-mediated disassembly.


Validation of a theoretically motivated approach to measuring childhood socioeconomic circumstances in the Health and Retirement Study.
Childhood socioeconomic status (cSES) is a powerful predictor of adult health, but its operationalization and measurement varies across studies. Using Health and Retirement Study data (HRS, which is nationally representative of community-residing United States adults aged 50+ years), we specified theoretically-motivated cSES measures, evaluated their reliability and validity, and compared their performance to other cSES indices. HRS respondent data (N = 31,169, interviewed 1992-2010) were used to construct a cSES index reflecting childhood social capital (cSC), childhood financial capital (cFC), and childhood human capital (cHC), using retrospective reports from when the respondent was <16 years (at least 34 years prior). We assessed internal consistency reliability (Cronbach's alpha) for the scales (cSC and cFC), and construct validity, and predictive validity for all measures. Validity was assessed with hypothesized correlates of cSES (educational attainment, measured adult height, self-reported childhood health, childhood learning problems, childhood drug and alcohol problems). We then compared the performance of our validated measures with other indices used in HRS in predicting self-rated health and number of depressive symptoms, measured in 2010. Internal consistency reliability was acceptable (cSC = 0.63, cFC = 0.61). Most measures were associated with hypothesized correlates (for example, the association between educational attainment and cSC was 0.01, p < 0.0001), with the exception that measured height was not associated with cFC (p = 0.19) and childhood drug and alcohol problems (p = 0.41), and childhood learning problems (p = 0.12) were not associated with cHC. Our measures explained slightly more variability in self-rated health (adjusted R2 = 0.07 vs. <0.06) and number of depressive symptoms (adjusted R2 > 0.05 vs. < 0.04) than alternative indices. Our cSES measures use latent variable models to handle item-missingness, thereby increasing the sample size available for analysis compared to complete case approaches (N = 15,345 vs. 8,248). Adopting this type of theoretically motivated operationalization of cSES may strengthen the quality of research on the effects of cSES on health outcomes.


Perioperative outcomes in minimally-invasive versus open surgery in infants undergoing repair of congenital anomalies.
This study compared perioperative outcomes among infants undergoing repair of congenital anomalies using minimally invasive (MIS) versus open surgical approaches. The ACS NSQIP Pediatric (2013-2018) was queried for patients undergoing repair of any of the following 9 congenital anomalies: congenital lung lesion (LL), mediastinal mass (MM), congenital malrotation (CM), anorectal malformation (ARM), Hirschsprung disease (HD), congenital diaphragmatic hernia (CDH), tracheoesophageal fistula (TEF), hepatobiliary anomalies (HB), and intestinal atresia (IA). Inverse probability of treatment weights (IPTW) derived from propensity scores were utilized to estimate risk-adjusted association between surgical approach and 30-day outcomes. 12,871 patients undergoing congenital anomaly repair were included (10,343 open; 2528 MIS). After IPTW, MIS was associated with longer operative time (difference; 95% CI) (16 min; 9-23) and anesthesia time (13 min; 6-21), but less postoperative ventilation days (-1.0 days; -1.4- -0.6) and shorter postoperative length of stay (-1.4 days; -2.4- -0.3). MIS repairs had decreased risk of any surgical complication (risk difference: -6.6%; -9.2- -4.0), including hematologic complications (-7.3%; -8.9- -5.8). There was no significant difference in risk of complication when hematologic complications were excluded (RD -2.3% [-4.7%, 0.1%]). There were no significant differences in the risk of unplanned reoperation (0.4%; -1.5-2.2) or unplanned readmission (0.2%; -1.2-1.5). MIS repair of congenital anomalies is associated with improved perioperative outcomes when compared to open. Additional studies are needed to compare long-term functional and disease-specific outcomes. In this propensity-weighted multi-institutional analysis of nine congenital anomalies, minimally invasive surgical repair was associated with improved 30-day outcomes when compared to open surgical repair. III.


Tyrosine derivatives assembled on gold.
Two different tyrosine derivatives, one with the OH group free and one with the OH group phosphorylated, linked to 3-mercaptopropionic acid through an amide bond are adsorbed to gold surfaces. The adsorbates are studied by means of X-ray photoelectron spectroscopy (XPS) and infrared reflection-absorption spectroscopy (IRAS). The techniques are used to investigate the coordination to the surface and the molecular orientation of adsorbates relative to the surface. Molecular surface interactions, causing chemical shifts in the core level XPS spectra of the adsorbates on gold, are investigated using multilayer films as references. Angle-dependent XPS, XPS(theta), and IRAS are used to estimate molecular orientation relative to the surface. The tyrosine derivatives adsorb chemically to the surface through the sulfur atoms and highly organized monolayers are formed with the OH and the PO(2-)(3) exposed to the air/vacuum interface.


[Hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia].
Chronic myelogenous leukemia (CML) is a malignant hematological disease.CML patients are commonly treated with hematopoietic stem cells transplantation (HSCT). This study was designed to evaluate the effect of HSCT on the patients with CML. Forty-four patients with CML were treated by HSCT, including 8 cases treated with purging autologous transplantation, 30 cases with related donor allogeneic HSCT (allo-HSCT), and 6 cases with unrelated donor allo-HSCT. The conditioning regimen was TBI (total-body irradiation)+CY (CTX) protocol in 31 patients and modified BuCY (hydroxyurea, busulfan, Ara-C, CTX) protocal in 12 patients, and MACC (Melphalan, Ara-C, CTX and CCNU) protocol in one patient. CsA (cyclosporine) and MTX were used in the patients with related donor allo-HSCT, and CsA and MTX added to mycophenolate mofetil (MMF) and antithymocyte globulin (ATG) were used in the patients with unrelated donor all-HSCT for graft versus host disease (GVHD) prophylaxis. Otherwise, CsA was only used in the patients with accelerated phase(AP) and blast crisis(BC) for GVHD prophylaxis. Kaplan-Meier survival analysis model was used to estimate the overall survival (OS) and the disease-free survival (DSF) at 5 years after transplantation. Eight patients with autologous transplantation, except one case died of transplantation-related-complication, obtained part or complete cytogenetic remission within 3 months after transplantation. One patient, who was BC and obtained complete remission (CR) in hematology before transplantation,obtained complete molecular remission for 81 months after autologous transplantation. All patients obtained CR, except one patient died of hepatic veno-occlusive disease (VOD) and one case did not obtained CR, in 36 patients with allo-HSCT after transplantation. The incidence of infection and VOD during transplantation were 38.6% and 9.1%, respectively. The incidences of hemorrhagic cystitis (HC) and cytomegalovirus (CMV) pneumonia after transplantation were 15.9% and 11.4%, respectively. VOD, HC, and CMV pneumonia did not occur in the patients with autologous transplantation. The incidence of acute GVHD in the patients with related and unrelated donor transplantation were 40.0% and 33.3%, respectively. The incidence of chronic GVHD was 43.4% in the patients with related donor transplantation. The rates of transplant-related mortality (TRM) in the patients with autologous and allogeneic transplantation were 12.5% and 16.7%, respectively. The rates of relapse in patients with autologous and related donor transplantation were 37.5% and 13.3%, respectively. The DFSs at 5 years in patients with autologous and related donor transplantation after transplantation were 18.7% and 53.7%, respectively. The DFS at 5 years in patients with CP (chronic phase) or AP and BC before transplantation were 66.4% and 26.7%, respectively. all-HSCT shows higher clinical cure rate to CML patients with CP. CsA+MTX+MMF+ATG protocol is more effective for acute GVHD prophylaxis and can decrease the incidence and severity of acute GVHD in patients with unrelated donor transplantation. Autologous transplantation with bone marrow purged can prolong the survival time and a few patients may be cured with autologous transplantation in CML.


Vocational and social adjustment after laryngectomy.
This study examined the vocational and social adjustment of 62 persons with cancer of the larynx. Predisability data were obtained by interview on 14 measures which assessed the vocational, social, and home adjustment prior to cancer. Post-disability data were obtained after laryngectomy by interview on 21 measures of adjustment. Additional measures include severity of laryngeal cancer classified by clinival stages, total or partial laryngectomy, presence of radiation therapy, presence of speech, months since surgery, age, sex, education, and marital status. The best predictors of vocational and social adjustment after laryngectomy were: removation, realism, rehabiltation outlook, previous vocational plans, highest educational grade, educational plans, and acquisition of speech. There were no significant differences in adjustment among patients in different clinical stages.


A device for single leaf labelling with CO2 isotopes to study carbon allocation and partitioning in Arabidopsis thaliana.
Plant biomass consists primarily of carbohydrates derived from photosynthesis. Monitoring the assimilation of carbon via the Calvin-Benson cycle and its subsequent utilisation is fundamental to understanding plant growth. The use of stable and radioactive carbon isotopes, supplied to plants as CO2, allows the measurement of fluxes through the intermediates of primary photosynthetic metabolism, long-distance transport of sugars in the vasculature, and the synthesis of structural and storage components. Here we describe the design of a system for supplying isotopically labelled CO2 to single leaves of Arabidopsis thaliana. We demonstrate that the system works well using short pulses of 14CO2 and that it can be used to produce robust qualitative and quantitative data about carbon export from source leaves to the sink tissues, such as the developing leaves and the roots. Time course experiments show the dynamics of carbon partitioning between storage as starch, local production of biomass, and export of carbon to sink tissues. This isotope labelling method is relatively simple to establish and inexpensive to perform. Our use of 14CO2 helps establish the temporal and spatial allocation of assimilated carbon during plant growth, delivering data complementary to those obtained in recent studies using 13CO2 and MS-based metabolomics techniques. However, we emphasise that this labelling device could also be used effectively in combination with 13CO2 and MS-based techniques.


Fence technique for localized three-dimensional bone augmentation: a technical description and case reports.
This study presents a novel bone reconstructive technique based on guided bone regeneration for localized three-dimensional hard tissue augmentation. This two-stage technique utilized a titanium osteosynthesis plate and a collagen membrane to form a physical barrier resembling a fence that contains bone graft biomaterial composed of a combination of deproteinized bovine bone matrix and autologous bone grafted from intraoral sites. Six patients were treated. At 6 months postsurgery, an increase in bone volume of 953 mm³ was shown. Mean maximum linear augmentation in the vertical direction was 6.75 mm. Histologic analysis of the regenerated area revealed the presence of compact newly formed bone with no sign of inflammation. A total of 13 implants were placed. Peri-implant marginal bone level was 0.94 mm at implant placement and 1.30 mm after 6 months. The patients were satisfied with the procedure and no complications were observed.


Lack of levamisole effect on experimental herpes keratitis.
Levamisole, which is an anthelminthic, can restore depressed cell-mediated immunity (CMI) under some circumstances. In a controlled trial of experimental herpetic keratis in rabbits, levamisole was found to have no significant effect on acute herpetic keratitis or its recurrence rate. This is consistent with previous findings that other nonspecific CMI stimulation had no effect on recurrences of experimental herpes keratitis. Because of the known tendency of levamisole to produce agranulocytosis, we believe it should not be used in man unless proven effective in a carefully controlled double-blind study.


Anti-tumor and anti-carcinogenic activities of triterpenoid, beta-boswellic acid.
Boswellin (BE), a methanol extract of the gum resin exudate of Boswellia serrata, contains naturally occurring triterpenoids, beta-boswellic acid and its structural related derivatives, has been used as a traditional medicine for the treatment of inflammatory and arthritic diseases. Topical application of BE to the backs of mice markedly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in skin inflammation, epidermal proliferation, the number of epidermal cell layers, and tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mice. Feeding 0.2% of BE in the diet to CF-1 mice for 10-24 weeks reduced the accumulation of parametrial fat pad weight under the abdomen, and inhibited azoxymethane (AOM)-induced formation of aberrant crypt foci (ACF) by 46%. Addition of pure beta-boswellic acid, 3-O-acetyl-beta-boswellic acid, 11-keto-beta-boswellic acid or 3-O-acetyl-11-keto-beta-boswellic acid to human leukemia HL-60 cell culture inhibited DNA synthesis in HL-60 cells in a dose-dependent manner with IC50 values ranging from 0.6 to 7.1 microM. These results indicate that beta-boswellic acid and its derivatives (the major constituents of Boswellin) have anti-carcinogenic, anti-tumor, and anti-hyperlipidemic activities.


Homodyne Solid-State Biased Coherent Detection of Ultra-Broadband Terahertz Pulses with Static Electric Fields.
We present an innovative implementation of the solid-state-biased coherent detection (SSBCD) technique, which we have recently introduced for the reconstruction of both amplitude and phase of ultra-broadband terahertz pulses. In our previous works, the SSBCD method has been operated via a heterodyne scheme, which involves demanding square-wave voltage amplifiers, phase-locked to the THz pulse train, as well as an electronic circuit for the demodulation of the readout signal. Here, we demonstrate that the SSBCD technique can be operated via a very simple homodyne scheme, exploiting plain static bias voltages. We show that the homodyne SSBCD signal turns into a bipolar transient when the static field overcomes the THz field strength, without the requirement of an additional demodulating circuit. Moreover, we introduce a differential configuration, which extends the applicability of the homodyne scheme to higher THz field strengths, also leading a two-fold improvement of the dynamic range compared to the heterodyne counterpart. Finally, we demonstrate that, by reversing the sign of the static voltage, it is possible to directly retrieve the absolute THz pulse polarity. The homodyne configuration makes the SSBCD technique of much easier access, leading to a vast range of field-resolved applications.


Peripheral blood biomarkers correlate with outcomes in advanced non-small cell lung Cancer patients treated with anti-PD-1 antibodies.
Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies. We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester. White blood cell count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC (ANC: ALC) ratio, absolute eosinophil count, absolute monocyte count (AMC), platelet counts, and myeloid to lymphoid (M:L) ratio at baseline and throughout treatment were assessed. Kaplan-Meier method and Cox proportional hazards model were performed. We treated 146 patients with nivolumab and 11 with pembrolizumab between January 1, 2015 and April 15, 2017. At median follow-up of 20 months, median OS and PFS were 6.0 and 2.6 months, respectively. Higher baseline ANC, AMC, ANC: ALC ratio and M: L ratio correlated with worse clinical outcomes in patients who underwent anti-PD-1 treatment. A baseline ANC: ALC ratio of 5.9 or higher had a significantly increased risk of death (hazard ratio [HR] =1.94; 95% confidence interval [CI], 1.24-3.03; P = 0.004) and disease progression (HR, 1.65; 95% CI, 1.17-2.34; P = 0.005) compared with patients with lower ratio. Similarly, a baseline M: L ratio of 11.3 or higher had significantly increased risk of death (HR, 2.5; 95% CI, 1.54-4.05; P < 0.001), even after a multivariate analysis (HR, 2.31; P = 0.002), compared to those with lower ratio. Increased baseline ANC: ALC ratio and M: L ratio before initiation of anti-PD1 antibodies were associated with poor PFS and OS in advanced NSCLC patients. The potential predictive value of these readily available biomarkers might help with risk stratification and treatment strategies. These findings warrant further investigation in a larger, prospective study.


Neuroleptic malignant syndrome in an elderly patient with normal pressure hydrocephalus overlapping corticobasal degeneration.
In this case report, neuroleptic malignant syndrome (NMS) in an elderly patient with normal pressure hydrocephalus overlapping corticobasal degeneration was reported. The case highlights the need for clinicians to be cautious when using dopaminergic medication in the elderly patients, since these agents have risks for NMS which is a life-threatening complication. Additionally, co-occurrence of primary and secondary parkinsonian dementia syndromes should be kept in mind to avoid additional complications in the elderly patients.


Effector Antitumor and Regulatory T Cell Responses Influence the Development of Nonmelanoma Skin Cancer in Kidney Transplant Patients.
Chronic immunosuppression promotes nonmelanocytic squamous cell carcinoma (SCC) after kidney transplantation. Adaptive and innate immunity play a key role controlling tumor growth and are influenced by different immunosuppressive agents. We hypothesized that functional impairment of tumor-specific T cell responses due to calcineurin inhibitors (CNI) could contribute to SCC development, whereas conversion to mammalian target of rapamycin inhibitors (mTOR-i) could recover this protective immune response. Peripheral tumor-specific T cell responses against main SCC-derived antigens using the IFN-γ enzyme-linked immunospot assay and intratumor (IT) and circulating immune phenotypes (CD4 + T, CD8 + T, CD20 + B, CD56 + NK, FOXP3 + regulatory T [Treg] cells) were explored in a cross-sectional analysis in 59 kidney transplant patients with SCC on CNI (KT-CNI-SCC) or mTOR-i (KT-mTORi-SCC), 25 nontransplants developing SCC (NoKT-SCC) and 6 healthy controls. Moreover, 25 KT-CNI-SCC were switched to mTOR-i and evaluated after 12 months. Kidney transplant patients showed lower IT infiltrates and tumor-specific T cell responses than NoKT-SCC, and intratumoral and circulating FOXP3 + Treg cells were higher in KT-mTORi-SCC (P < 0.05). Tumor-specific T cell responses were significantly lower in KT-CNI-SCC than KT-mTORi-SCC and NoKT-SCC and predicted SCC relapses (area under the curve = 0.837; P < 0.05). One-year after mTOR-i conversion, a significant increase in FOXP3 + Treg cell numbers and tumor-specific T cell responses were observed, reaching similar levels than KT-mTORi-SCC and NoKT-SCC patients. Tumor-specific T cell responses are strongly impaired in CNI-treated patients but recover after mTOR-i conversion, reducing SCC relapses.


Sensitivity of biologically active UV radiation to stratospheric ozone changes: effects of action spectrum shape and wavelength ranges.
Biological action spectra are commonly used to assess health and ecosystem responses to increases in spectral ultraviolet (UV) irradiances resulting from stratospheric ozone (O3) reductions. For each action spectrum, a normalized sensitivity coefficient (the radiation amplification factor [RAF]) can be calculated as the relative increase in biologically active UV irradiance for a given relative decrease in the atmospheric O3 column amount. We use a detailed radiative transfer model to calculate the dependence of RAF on the O3 column amount and the solar zenith angle (and, therefore, implicitly on latitude and season) for several commonly used action spectra. A simple analytical model is used to interpret the results in terms of the semilogarithmic slope of the action spectra in the UV-B and UV-A wavelength ranges. We also show that RAF may be overestimated substantially if the UV-A portion of an action spectrum is significant but is neglected. This is illustrated using several idealized action spectra as well as published action spectra for plant responses to UV irradiation. Generally, if the portion of an action spectrum measured longward of approximately 300 nm spans less than about two orders in magnitude in its sensitivity, significant errors in the estimated RAF may ensue, and the use of this action spectrum in O3-related studies can be compromised.


Multiplication theory for dynamically biased avalanche photodiodes: new limits for gain bandwidth product.
Novel theory is developed for the avalanche multiplication process in avalanche photodiodes (APDs) under time-varying reverse-biasing conditions. Integral equations are derived characterizing the statistics of the multiplication factor and the impulse-response function of APDs, as well as their breakdown probability, all under the assumption that the electric field driving the avalanche process is time varying and spatially nonuniform. Numerical calculations generated by the model predict that by using a bit-synchronous sinusoidal biasing scheme to operate the APD in an optical receiver, the pulse-integrated gain-bandwidth product can be improved by a factor of 5 compared to the same APD operating under the conventional static biasing. The bit-synchronized periodic modulation of the electric field in the multiplication region serves to (1) produce large avalanche multiplication factors with suppressed avalanche durations for photons arriving in the early phase of each optical pulse; and (2) generate low avalanche gains and very short avalanche durations for photons arriving in the latter part of each optical pulse. These two factors can work together to reduce intersymbol interference in optical receivers without sacrificing sensitivity.


Intracellular calcium concentration of acinar cells in feline tracheal submucosal glands.
We measured the intracellular free calcium ion concentration [( Ca2+]i) of acinar cells in isolated feline tracheal submucosal glands in response to secretagogues using the Ca2(+)-sensitive fluorescent dye fura-2. The secretagogues included cholinergic, adrenergic agonists, substance P (SP), and vasoactive intestinal polypeptide (VIP) which induce mucus glycoprotein secretion from feline tracheal submucosal glands. Methacholine (MCh) produced a significant increase in [Ca2+]i of up to 9.8 times that of control in a dose-dependent fashion at concentrations of 10(-8) to 10(-3) M. [Ca2+]i increase by MCh reached a peak within 30 s after stimulation and thereafter showed a sustained rise. In Ca2(+)-free medium, MCh produced an initial transient rise, which was less than 30% of that in a Ca2(+)-containing solution, and which lasted for 60 s with no prolonged sustained rise in [Ca2+]i. Atropine abolished MCh-evoked [Ca2+]i increase. Phenylephrine and SP produced a prolonged increase in [Ca2+]i without an initial transient increase. Phenylephrine (up to 10(-4) M) evoked an increase in [Ca2+]i by up to 240% that of control, which was abolished by prazosin. SP (up to 10(-4) M) also evoked an increase in [Ca2+]i by 155% that of control, which was abolished by atropine. By contrast, both isoproterenol (up to 10(-5) M) and VIP (up to 10(-5) M) failed to alter [Ca2+]i. These findings indicate that the mucus glycoprotein secretion evoked by muscarinic cholinergic, alpha-adrenergic agonist or SP can be mediated by intracellular Ca2+, whereas that by beta-adrenergic agonists or VIP cannot.


Key features of a trauma-informed public health emergency approach: A rapid review.
COVID-19 is a major threat to public safety, and emergency public health measures to protect lives (e.g., lockdown, social distancing) have caused widespread disruption. While these measures are necessary to prevent catastrophic trauma and grief, many people are experiencing heightened stress and fear. Public health measures, risks of COVID-19 and stress responses compound existing inequities in our community. First Nations communities are particularly at risk due to historical trauma, ongoing socio-economic deprivation, and lack of trust in government authorities as a result of colonization. The objective of this study was to review evidence for trauma-informed public health emergency responses to inform development of a culturally-responsive trauma-informed public health emergency framework for First Nations communities. We searched relevant databases from 1/1/2000 to 13/11/2020 inclusive, which identified 40 primary studies (and eight associated references) for inclusion in this review. Extracted data were subjected to framework and thematic synthesis. No studies reported evaluations of a trauma-informed public health emergency response. However, included studies highlighted key elements of a "trauma-informed lens," which may help to consider implications, reduce risks and foster a sense of security, wellbeing, self- and collective-efficacy, hope and resilience for First Nations communities during COVID-19. We identified key elements for minimizing the impact of compounding trauma on First Nations communities, including: a commitment to equity and human rights, cultural responsiveness, good communication, and positive leadership. The six principles guiding trauma-informed culturally-responsive public health emergency frameworks included: (i) safety, (ii) empowerment, (iii) holistic support, (iv) connectedness and collaboration, (v) compassion and caring, and (vi) trust and transparency in multi-level responses, well-functioning social systems, and provision of basic services. These findings will be discussed with First Nations public health experts, together with data on the experiences of First Nations families and communities during COVID-19, to develop a trauma-integrated public health emergency response framework or "lens" to minimize compounding trauma for First Nations communities.


Mechanical and circulating biomarkers in isolated clinic hypertension.
1. This review examines the current evidence for altered mechanical and circulating biomarkers in isolated clinic hypertension and their potential significance. 2. Arterial stiffness, as assessed by central pulse wave velocity, is influenced by multiple cardiovascular risk factors; however, an independent association with isolated clinic hypertension (ICHT) has not been convincingly shown in four small studies. 3. Endothelial dysfunction, as assessed by brachial artery flow-mediated vasodilation, circulating levels of endothelial markers (e.g. nitrite/nitrate, von Willebrand factor, endothelin-1) and/or circulating levels of inhibitors of vascular nitric oxide (plasma asymmetric dimethylarginine, homocysteine), has been shown to be present in established hypertension and to a variable and inconsistent extent in subjects with ICHT. 4. Evidence of increased oxidative stress in ICHT versus normotensive subjects was found in two of three studies. 5. Circulating inflammatory markers C-reactive protein and plasminogen activator inhibitor-1 were significantly increased in two of three and two of two studies, respectively, in ICHT compared with normotensive subjects. 6. Urinary albumin excretion is a marker of both arterial and renal disease. The consensus from seven studies in patients with ICHT is that albuminuria is not an independent marker for ICHT. 7. Studies to date assessing biomarkers in ICHT have been small and cross-sectional. Larger, long-term longitudinal studies of arterial functional and circulating biomarkers are required to assess the potential vascular impact of ICHT.


Systemic lupus erythematosus presenting as parotitis and secondary Sjogren's syndrome.
A 38-year-old woman presented with right-sided parotid swelling, dry mouth and dry eyes of one year duration. Her Schirmer's test and sialometry were positive and histopathology showed lymphoplasmacytic infiltration. She also had concomitant normochromic , normocytic anaemia and mild haematuria. Her anti-nuclear antibody titre was also positive, 1:640, with a speckled pattern on immunofluorescence. We discuss the atypical presentation of systemic lupus erythematosus, particularly parotitis and secondary Sjogren's syndrome.


The impact of domestication on the chicken optical apparatus.
Domestication processes tend to release animals from natural selection and favour traits desired by humans, such as food-production and co-operative behaviour. A side effect of such selective breeding is the alteration of unintended traits. In this paper, we investigate how active selection for egg production in chickens has affected the visual system, in particular the optical sensitivity that relates to the ability of chickens to see in dim light. We measured eye dimensions as well as the pupil diameter at different light intensities (the steady state pupil dynamics), in adult male and female White Leghorns and the closest relatives to their ancestor, the Red Junglefowls. With this information, we calculated the focal length and optical sensitivity (f-number) of the eyes. Males have larger eyes than females in both breeds and White Leghorn eyes are larger than those of Red Junglefowls in both sexes. The steady state pupil dynamics is less variable, however, the combination of pupil dynamics and eye size gives a higher optical sensitivity in Red Junglefowl eyes than in White Leghorns at light intensities below approximately 10 cd/m(2). While eye size and focal length match the larger body size in White Leghorns compared to Red Junglefowls, the steady state pupil dynamics do not. The reason for this is likely to be that eye morphology and the neuro-muscular control of the pupil have been affected differently by the strong selection for egg production and the simultaneous release of the selection pressure for high performing vision. This study is the first description of how optical sensitivity has changed in a domesticated species and our results demonstrate important considerations regarding domestication processes and sensory ability.


Differences in quality of life among college student electronic cigarette users.
The purpose of this study was to explore an association between e-cigarette use and Quality of Life (QOL) among college students. During February 2016, 1,132 students completed an online survey that included measures of tobacco use and the WHOQOL-BREF instrument. Differences were tested using Chi-square, Fisher's exact test, and ANOVA, and regression was used to assess possible relationships. E-cigarettes were used by 6.97% of the participants, either solo or along with traditional cigarettes. Bivariate analyses suggest that male college students are more likely than females to use e-cigarettes, either solo or in combination with traditional cigarettes (χ2 =19.4, P < .01). Lesbian, gay, and bisexual students are more likely than heterosexual students to use traditional cigarettes, either solo or in combination with e-cigarettes (χ2 = 32.9, P < .01). Multivariate models suggest that for every 10-unit increase in overall QOL, psychological well-being, social relations or environmental health the adjusted odds of being a sole cigarette user were significantly lower (all, P < .01), respectively. For every 10-unit increase in psychological well-being the adjusted odds of being a dual user was significantly lower (OR = .83, P = .026). Findings indicate that lower quality of life appears to be connected to tobacco use.


Geometrical factors in the cardiac nuclear probe.
The design of the collimator for the assessment of left ventricular function with a non-imaging detector is considered. When certain simplifying assumptions are made concerning the distribution of the background and the ventricular activity, the statistical variation in the calculated ventricular count rate is examined for various detector-collimator combinations. For detectors with sufficient diameter to give reasonably low counting errors it is shown that the focused multihole type of collimator is preferable and the optimum parameters of this are given. It is shown that when the simplifying assumptions are relaxed there is still a preference for the use of a focused multihole collimator.


Recycling of bowel content: the importance of the right timing.
Extracorporeal stool transport (recycling of chyme discharged from the proximal stoma end to the distal end of a high jejunostomy or ileostomy) is thought to be beneficial in preventing malabsoprtion, sodium loss, cholestasis and atrophy of the distal intestine until restoration of the intestinal continuity becomes possible. However little is known about its adverse effects. Our aim was to investigate the microbiological safety of recycling. Native samples were taken from the proximal stoma in 5 premature neonates who underwent an ileostomy or a jejunostomy due to necrotising enterocolitis, for qualitative culture. The first sample was drawn immediately after the change of the stoma bag, further samples were sent from the stoma bag at 30, 60, 90, 120, 150, and 180min later. The samples were inoculated by calibrated (10 μl) loops onto blood agar (5% sheep blood), eosin-methylene blue agar and anaerobic blood agar, respectively (Oxoid). The aerobic plates were incubated for 18-20 h at 5% CO2, whereas the anaerobic plates were incubated for 24-48 h in an anaerobic chamber (Concept 400). The bacterial strains were identified to species level by specific biochemical reactions, RapID-ANA II system (Oxoid) and ID32E, Rapid ID 32 Strep ATB automatic system cards (bioMérieux). The number of colony forming unit (CFU) of Gram-negative bacteria (mainly E. coli) exponentially increased after 30 min and reached 10(5)/ml after 120 min. Gram-positive strains (primarily E. faecalis) were detected after 60 min and CFU increased to 10(5)/ml after 120 min. The number of anaerobic (principally Bacteroides fragilis) CFU started to increase after 120 min. In two cases coagulase negative Staphylococcus strains were isolated the earliest in the chyme. The average of total CFU approached 10(5)/ml after 90 min and exceeded 10(5)/ml after 120 min. The chyme in the stoma bag is colonized by commensal facultative pathogenic enteral/colonic as well as skin flora species after 120 min. Recycling of stoma bag content may be dangerous after 90 min.


Vistech VCTS 6500 charts--within- and between-session reliability.
The aim of the study was to measure the reliability of the Vistech VCTS 6500 charts, in test score units, in order to allow clinicians to derive estimates of what constitutes a clinically meaningful change in performance over time. The reliability of a more familiar test, Bailey-Lovie high contrast visual acuity, was also measured to provide a comparison. Patients with normal vision and with early or subtle eye disease were recruited so that the results would be representative of the population likely to present for primary vision screening. Patients were tested on all three VCTS charts on two separate occasions at least 3 weeks apart to give estimates of within- and between-session reliability. Reliability was found to be low in all circumstances; between-session reliability could be improved by using the mean score for the three charts, but the 95% range of difference scores still encompassed at least one-half of the total performance range of the test. It was concluded that Vistech charts are unlikely to be of use for clinical measurements or for research studies.


Topical retinoid treatment for dry eye disorders.
We have demonstrated the clinical efficacy of topical all-trans retinoic acid ointment in the treatment of four severe cases of the following dry eye disorders: Keratoconjunctivitis sicca, Stevens-Johnson syndrome, drug-induced pseudopemphigoid, surgery-induced dry eye. In all four cases, impression cytology confirmed that improvements in symptoms, visual acuity, keratopathy, and Schirmer test resulted from reversal of the process of squamous metaplasia. This treatment represents the first nonsurgical approach with action directed specifically at the diseased ocular surface epithelia.


Conventional spinal radiography as a supplement to the neurologic assessment in myelomeningocele.
In patients born with a myelomeningocele early assessment of the severity of the anomaly is mandatory for planning of therapy. Conventional spinal radiography, although a routine examination, in many hospitals has been regarded as less rewarding. However, in this retrospective investigation of 92 patients, a reasonable conformity was found between conventional radiograms and neurologic deficit at follow-up. There was no significant difference between the results of radiologic examinations carried out during the first 1 to 10 weeks after birth and the later neurologic findings. Hence, the simple radiologic assessment has proved a valuable baseline examination in these patients. In cases with discrepancy between the conventional radiologic and the neurologic findings, and in cases with a course diverging from the anticipated, more sophisticated methods of imaging are recommended.


Modeling integrated cellular machinery using hybrid Petri-Boolean networks.
The behavior and phenotypic changes of cells are governed by a cellular circuitry that represents a set of biochemical reactions. Based on biological functions, this circuitry is divided into three types of networks, each encoding for a major biological process: signal transduction, transcription regulation, and metabolism. This division has generally enabled taming computational complexity dealing with the entire system, allowed for using modeling techniques that are specific to each of the components, and achieved separation of the different time scales at which reactions in each of the three networks occur. Nonetheless, with this division comes loss of information and power needed to elucidate certain cellular phenomena. Within the cell, these three types of networks work in tandem, and each produces signals and/or substances that are used by the others to process information and operate normally. Therefore, computational techniques for modeling integrated cellular machinery are needed. In this work, we propose an integrated hybrid model (IHM) that combines Petri nets and Boolean networks to model integrated cellular networks. Coupled with a stochastic simulation mechanism, the model simulates the dynamics of the integrated network, and can be perturbed to generate testable hypotheses. Our model is qualitative and is mostly built upon knowledge from the literature and requires fine-tuning of very few parameters. We validated our model on two systems: the transcriptional regulation of glucose metabolism in human cells, and cellular osmoregulation in S. cerevisiae. The model produced results that are in very good agreement with experimental data, and produces valid hypotheses. The abstract nature of our model and the ease of its construction makes it a very good candidate for modeling integrated networks from qualitative data. The results it produces can guide the practitioner to zoom into components and interconnections and investigate them using such more detailed mathematical models.


[Postoperative urinary retention].
Retention of urine is a common postoperative problem. We present two patients with postoperative urinary retention. Current opinions on monitoring and treatment are reviewed. One male postoperative patient was transferred from the postanaesthesia care unit after orthopaedic surgery under spinal anaesthesia. Shortly thereafter he collapsed. Hypotension and bradycardia were treated with intravenous ephedrine and atropine. Urinary retention was suspected and the bladder catheterised for 1,000 ml urine. A follow-up examination revealed no sequelae. A female patient was operated for haemorrhoids under epidural anaesthesia. The second postoperative day she was catheterised for 1,500 ml of urine. Two years later she had an ovarian cyst removed under general anaesthesia. Postoperative urinary retention developed with bladder overdistension (volume > 1,000 ml). A follow-up examination showed rest urine of 25 to 75 ml, and a chronic bladder dysfunction. The incidence of postoperative urinary retention varies depending upon type of surgery, gender, age, and preoperative history of urinary tract dysfunction. Method of anaesthesia or postoperative pain treatment is not correlated to incidence of urinary retention, but excessive intravenous volume load during the operation is. Postoperative urinary retention should be monitored in all patients after surgery. All patients with history of difficulties with micturition need close supervision to avoid urinary bladder overdistention.


Clinical impact of diarrhea during enteral feeding after esophagectomy.
Enteral feeding (EF) is recommended to enhance nutritional status after esophagectomy; however, diarrhea is a common complication of EF. We investigated the clinical and prognostic impact of diarrhea during EF after esophagectomy. One hundred and fifty-two patients who underwent transthoracic esophagectomy were enrolled. The King's stool chart was used for stool characterization. The short- and long-term outcomes were compared between a non-diarrhea (Group N) and diarrhea group (Group D). A higher dysphagia score (≥ 1) was observed more frequently in Group D than in Group N (45.7% vs. 19.8%, p = 0.002). Deterioration of serum total protein, serum albumin, serum cholinesterase, and the prognostic nutritional index after esophagectomy was greater in Group D than in Group N (p = 0.003, 0.004, 0.014, and 0.001, respectively). Patients in Group D had significantly worse overall survival (OS) and recurrence-free survival (RFS) than those in Group N (median survival time (MST): OS, 21.9 vs. 30.6 months, p = 0.001; RFS, 12.4 vs. 27.7 months, p < 0.001). In stratified analysis due to age, although there was no difference in OS with or without diarrhea in young patients (MST: 24.1 months in a diarrhea group vs. 33.6 months in a non-diarrhea group, p = 0.218), patients in a diarrhea group had significantly worse OS than those in a non-diarrhea group in elderly patients (MST: 17.8 months vs. 27.9 months, p < 0.001). Diarrhea during EF can put elderly patients at risk of postoperative malnutrition and a poor prognosis after esophagectomy.


Proteasome-dependent degradation of intracellular carbamylated proteins.
Carbamylation, which corresponds to the binding of isocyanic acid to the amino groups of proteins, is a nonenzymatic post-translational modification responsible for alterations of protein structural and functional properties. Tissue accumulation of carbamylation-derived products and their role in pathological processes such as atherosclerosis or chronic renal failure have been previously documented. However, few studies have focused on the carbamylation of intracellular proteins and their subsequent role in cellular aging. This study aimed to determine the extent of intracellular protein carbamylation, its impact on cell functions and the ability of cells to degrade these modified proteins. Fibroblasts were incubated with cyanate or urea and the carbamylation level was evaluated by immunostaining and homocitrulline quantification. The results showed that carbamylated proteins accumulated intracellularly and that all proteins were susceptible. The presence of intracellular carbamylated proteins did not modify cell proliferation or type I collagen synthesis nor did it induce cell senescence, but it significantly decreased cell motility. Fibroblasts were able to degrade carbamylated proteins through the ubiquitin-proteasome system. In conclusion, intracellular proteins are susceptible to carbamylation but their accumulation does not seem to deeply affect cell function, owing largely to their elimination by the ubiquitin-proteasome system.


Cardiopulmonary bypass and dual antiplatelet therapy: a strategy to minimise transfusions and blood loss.
Patients with preoperative dual antiplatelet therapy prior to coronary artery bypass surgery are at risk of bleeding and blood component transfusion. We hypothesise that an optimised cardiopulmonary bypass strategy reduces postoperative blood loss and transfusions. In total, 60 patients admitted for coronary artery bypass grafting with ticagrelor and aspirin medication withdrawn <96 hours before surgery were prospectively randomised into two equal sized groups. Cardiopulmonary bypass combined a closed Cortiva® heparin-coated circuit with low systemic heparinisation (activated clotting time < 250 seconds) and intraoperative cell salvage in the study group, whereas the control group used a Balance® coated open circuit, full systemic heparinisation (activated clotting time > 480 seconds) and conventional cardiotomy suction. This perfusion strategy was evaluated by the chest drain volume after 24 hours, perioperative haemoglobin and platelet loss accompanied by global coagulation assessments. Patients in the study group demonstrated significantly better outcomes signified by lower blood loss 554 ± 224 versus 1,100 ± 989 mL (p < 0.001), reduced packed red cell transfusion 7% versus 53% (p < 0.001), reduced haemoglobin -28 ± 15 versus -40 ± 14 g/L (p = 0.004) and platelet loss -35 ± 36 versus -82 ± 67 × 109/L (p = 0.001). Indices of rotational thromboelastometry indicated shorter clotting times within the internal and external pathways. Adenosine diphosphate activated platelet function was within normal range based on Multiplate® aggregometry, while ROTEM® platelet analyses indicated inhibited function both preoperatively and post-bypass. Platelet inhibition by aspirin was verified throughout the perioperative period. Platelet function showed no intergroup differences. A stringent perfusion strategy reduced blood loss and transfusions in dual antiplatelet therapy patients requiring urgent surgery.


A case report of aspergillosis accompanied by saccular bronchodilation after bronchial thermoplasty in a 19-year-old woman.
Fungal infections are rarely reported as a complication of bronchial thermoplasty (BT) in patients without immunosuppressive comorbidity. A 19-year-old woman college student was admitted to our hospital owing to uncontrolled severe asthma despite using the maximum dose of steroid inhalation. She experienced asthmatic attacks more frequently while cheerleading, which is an extracurricular activity. She received BT because she wanted to continue cheerleading. After the second BT session, she developed more sputum and cough. During the third session, white secretion and saccular bronchodilation appeared in the left lower bronchus. Aspergillus fumigatus was detected in the culture of the bronchial lavage sample, and saccular bronchodilation in the affected bronchus was observed on computed tomography (CT). Five months after the start of oral itraconazole, her subjective symptoms as well as her CT findings improved. Her asthma condition improved enough for the patient to continue cheerleading without exacerbation. It is necessary to consider the possibility of respiratory tract infections including fungal infections after BT. Detailed observations of the entire bronchus and sample collection for microbial culture are highly recommended.


Genetic regulation of sn-glycerol-3-phosphate dehydrogenase in brown adipose tissue.
The levels of sn-glycerol-3-phosphate dehydrogenase (GPDH) were determined in the brown adipose tissue (BAT) of different inbred strains of mice. The BAT of the BALB/cJ strain contains twice as much enzyme activity per milligram protein as do other strains. The appearance of this difference is developmentally dependent, since it is not detected in BAT until 25-30 days postpartum. Genetic analysis of this strain difference has shown that the mechanism of inheritance involves at least two genes, one of which is linked to the Gdc-1 structural locus on chromosome 15. Determinations of GPDH synthesis by immunoprecipitation of GPDH protein labeled in vivo with [3H]leucine, and of GPDH mRNA by Northern blot analysis, establish that in BALB/cJ mice higher rates of enzyme synthesis are determined by elevated levels of GPDH mRNA. It was also found that cold stress increases GPDH mRNA levels in all the strains examined.


The prevalence of postoperative pain in the first 48 hours following day surgery at a tertiary hospital in Nairobi.
Day case surgery services are increasing all over the world. The prevalence of postoperative pain after day surgery is found to be high. Little is known about the prevalence of postoperative pain, in Kenya, after day case surgeries. To investigate the prevalence of postoperative pain after day surgery at Aga Khan University Hospital (AKUH), Nairobi, to determine the severity/intensity of postoperative pain following day case surgery. Consecutive sampling was carried out until sample size of one hundred and fifty patients was achieved. The purpose and nature of the study was explained to patients before informed consent was obtained. They were shown how to score their pain using a visual analogue scale prior to the surgical procedure. A questionnaire was used to collect data from the patients. Follow up information was obtained through telephone interviews at 24 and 48 hours, after discharge from the day surgery unit. The prevalence of postoperative pain after day care surgery was found to be 58% within 30 minutes postoperatively, 55.3% after 24 hours, and 34.7% after 48 hours following surgery. The prevalence of moderate to severe postoperative pain was 13% after 24 hours, and 11.7% after 48 hours. The overall prevalence of postoperative pain after day surgery at the Aga Khan University Hospital, Nairobi was noted to be different from what has been reported in the literature. The prevalence of moderate and severe pain however, is less than reported in the literature.


Nobiletin ameliorates hepatic ischemia and reperfusion injury through the activation of SIRT-1/FOXO3a-mediated autophagy and mitochondrial biogenesis.
Hepatic ischemia and reperfusion injury are characterized by impaired autophagy, mitochondrial dysfunction, and subsequent compromise of cellular homeostasis following hepatic surgery or transplantation. Nobiletin, a natural flavonoid, is a beneficial antioxidant that possesses anti-inflammatory and anti-cancer activities. We investigated the effect of nobiletin on hepatic IR injury and described the underlying mechanisms. C57BL/6 mice were subjected to 60 min of partial hepatic ischemia, treated with nobiletin (5 mg/kg) or vehicle at the start of reperfusion, and killed at 5 h of reperfusion. Hepatic ischemia and reperfusion increased hepatocellular oxidative damage, inflammation, and cell death, but these changes were alleviated upon nobiletin treatment. Nobiletin increased the expression of proteins that control autophagy, mitochondrial dynamics, and biogenesis. Specifically, the SIRT-1/FOXO3a and PGC-1α pathways were activated by nobiletin. IR-induced AKT activation was associated with FOXO3a phosphorylation, which resulted in a significant reduction in the nuclear FOXO3a levels and potentially attenuated autophagy-regulatory gene expression. Nobiletin increased FOXO3a expression and its nuclear translocation via the inhibition of AKT. Specific inhibition of SIRT-1 abolished the protective effect of nobiletin, causing decreased FOXO3a expression, followed by autophagy induction and decreased PGC-1α expression and mitochondrial dynamics. Taken together, our data indicate that SIRT-1 directly mediates the protective effect of nobiletin against hepatic ischemia and reperfusion injury. The activation of autophagy and mitochondrial function through the SIRT-1/FOXO3a and PGC-1α pathways indicate that nobiletin could have therapeutic potential for treating hepatic ischemia and reperfusion injury.


Astrocyte-mediated ischemic tolerance.
Preconditioning (PC) using a preceding sublethal ischemic insult is an attractive strategy for protecting neurons by inducing ischemic tolerance in the brain. Although the underlying molecular mechanisms have been extensively studied, almost all studies have focused on neurons. Here, using a middle cerebral artery occlusion model in mice, we show that astrocytes play an essential role in the induction of brain ischemic tolerance. PC caused activation of glial cells without producing any noticeable brain damage. The spatiotemporal pattern of astrocytic, but not microglial, activation correlated well with that of ischemic tolerance. Interestingly, such activation in astrocytes lasted at least 8 weeks. Importantly, inhibiting astrocytes with fluorocitrate abolished the induction of ischemic tolerance. To investigate the underlying mechanisms, we focused on the P2X7 receptor as a key molecule in astrocyte-mediated ischemic tolerance. P2X7 receptors were dramatically upregulated in activated astrocytes. PC-induced ischemic tolerance was abolished in P2X7 receptor knock-out mice. Moreover, our results suggest that hypoxia-inducible factor-1α, a well known mediator of ischemic tolerance, is involved in P2X7 receptor-mediated ischemic tolerance. Unlike previous reports focusing on neuron-based mechanisms, our results show that astrocytes play indispensable roles in inducing ischemic tolerance, and that upregulation of P2X7 receptors in astrocytes is essential.


THE STRUCTURE OF THE INTESTINAL MICROBIOTA AND THE FREQUENCY OF DETECTION OF PATHOGENICITY GENES (STXI, STX2, BFP) IN ESCHERICHIA COLI WITH NORMAL ENZYMATIC ACTIVITY ISOLATED FROM CHILDREN DURING THE FIRST YEAR OF LIFE.
E. coli is an intestinal commensal of vertebrates. The ability to produce Shiga toxins (Stx) is the major virulence feature of Shiga toxin-producing E. coli (STEC). These potent cytotoxins block the protein synthesis by inactivating ribosomes. Their action on the target cells is responsible for the most severe forms of STEC-induced disease, such as hemorrhagic colitis and the life-threatening hemolytic uremic syndrome (HUS). Enteropathogenic E. coli (EPEC) also continues to be an important cause of infantile diarrhea in developing countries. Bundle-forming pili (bfp) are essential for the full virulence of enteropathogenic E. coli (EPEC). Exchange of genetic material between different types of bacteria, as well as with other members of the family Enterobacteriaceae in the intestinal ecosystem, leads to the appearance of normal variants of E. coli with phenetic features of pathogenicity that can serve as a theoretical basis for attributing these strains to pathobionts. PCR was used to examine 68 strains of E. coli (E. coli with normal enzymatic activity) for the presence of genes encoding the synthesis of Shiga toxins (stxl and stx2) and genes encoding the bundle-forming pilus (bfp). They were isolated from children with functional disorders of the gastrointestinal tract. The presence of the desired amplicon specific for stxl and bfp genes has resulted in formation of E. coli strains with more intense pathogenicity.


Association of Endothelial Glycocalyx and Tight and Adherens Junctions With Severity of Plasma Leakage in Dengue Infection.
The role of vascular endothelial (VE) components in dengue infection with plasma leakage is unknown. Therefore, we conducted a study to determine the adjusted association of the endothelial glycocalyx layer (EGL) and tight and adherens junction markers with plasma leakage. A prospective observational study was conducted at Cipto Mangunkusumo Hospital and Persahabatan Hospital, Jakarta, Indonesia. Adult dengue patients admitted to the hospital on the third day of fever from November 2013 through August 2015 were included in the study. Multiple regression analysis was used to determine the adjusted association of the VE biomarkers with the severity of the plasma leakage. A total of 103 dengue-infected patients participated in the study. In the critical phase, levels of syndecan-1 (odds ratio [OR] = 1.004; 95% confidence interval [CI] = 1.001-1.007) and chondroitin sulfate (OR = 1.157; 95% CI = 1.025-1.307) had an adjusted association with plasma leakage, whereas levels of syndecan-1 (OR = 1.004; 95% CI = 1.000-1.008) and claudin-5 (OR = 1.038; 95% CI = 1.004-1.074) had an adjusted association with severe plasma leakage. In dengue-infected patients, elevated levels of syndecan-1 and chondroitin sulfate are strongly associated with plasma leakage, and elevated levels of syndecan-1 and claudin-5 are strongly associated with severe plasma leakage.


Haemofiltration: how to do it.
Haemofiltration and its variants are simple procedures which allow the management of patients with renal failure in intensive therapy units without the need for continual support from renal specialists. In order for non-renal specialists to manage the practical aspects of these treatments logically, safely and successfully it is important to understand the basic principles involved.


Shyness, aggression, and empathy in children of shy mothers: Moderating influence of children's psychophysiological self-regulation.
Maternal psychological factors are known to play a critical role in children's socioemotional development, particularly in pro- and anti-social behaviors. Although shyness is a ubiquitous phenomenon and associated with social anxiety, relatively few have examined the relation between maternal shyness and children's socioemotional development. We explored the moderating influence of children's resting respiratory sinus arrhythmia (RSA) and RSA change on the relation between maternal shyness and children's shyness, empathy, and aggression in 129 (62 males) typically developing 4- (n = 81) and 6- (n = 48) year-olds. We found that 6-year-olds' RSA change score from baseline to a cognitive challenge task acted as a moderator on the relation between mother's shyness and child observed empathy but not for maternal report of child aggression or child's observed shyness. These results were not found in the 4-year-olds. Six-year-olds with relatively high RSA change and relatively low maternal shyness displayed the highest levels of empathy. These results suggest that the maternal caregiving environment and biological characteristics of the child may confer individual differences in prosocial behaviors in children. Findings are discussed in terms of age-related differences in socioemotional behaviors in children of shy mothers.


A Molecular Approach on the Protective Effects of Mangiferin Against Diabetes and Diabetes-related Complications.
Diabetes and its related complications are now a global health problem without an effective therapeutic approach. There are many herbal medicines which have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets. The aim of this study is to review available knowledge of mangiferin focusing on its mode of action. Mangiferin was extensively reviewed for its antidiabetic activity using online database like Scopus, PubMed, and Google Scholar as well as some offline textbooks. A critical discussion based on the mechanism of action and the future perspectives is also given in the present manuscript. Mangiferin is a natural C-glucoside and mainly obtained from its primary source, the leaves of mango tree (Mangifera indica L.). Therapeutic and preventive properties of mangiferin include antimicrobial, anti-inflammatory, antioxidative, antiallergic, neuroprotective, and cognition-enhancing effects. It dissolves well in water, so it can be easily extracted into infusions and decoctions and hence, a number of researches have been made on the therapeutic effect of this molecule. Recently, mangiferin has been proved to be an effective remedy in diabetes and diabetes-related complications. It is a beneficial natural compound for type 2 diabetes mellitus as it improves insulin sensitivity, modulates lipid profile and reverts adipokine levels to normal. This study concludes that mangiferin has the potential to treat diabetes and it can be developed as a therapeutic agent for diabetes and the complications caused by diabetes.


Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response.
Protective immunity to enterotoxigenic Escherichia coli (ETEC) is antibody (Ab) dependent; however, oral immunization with purified ETEC fimbriae fails to elicit protective immunity as a consequence of antigenic alteration by the gastrointestinal (GI) tract. Unless unaltered ETEC fimbriae can reach the inductive lymphoid tissues of the GI tract, immunity to ETEC cannot be induced. To produce immunity, live vectors, such as Salmonella typhimurium, can effectively target passenger antigens to the inductive lymphoid tissues of the GI tract. By convention, oral immunizations with Salmonella vectors induce CD4(+) T helper (Th) cell responses by gamma interferon (IFN-gamma)-dominated pathways both to the vector and passenger antigen, resulting in serum immunoglobulin G2a (IgG2a) and modest mucosal IgA Ab responses. In the present study, mice orally immunized with a Salmonella vector engineered to stably express ETEC colonization factor antigen I (CFA/I) showed initially elevated serum IgG1 and mucosal IgA anti-CFA/I Ab responses. As expected, mice orally immunized with an E. coli-CFA/I construct elicited poor anti-CFA/I Ab responses. In fact, the addition of cholera toxin during oral E. coli-CFA/I immunization failed to greatly enhance mucosal IgA Ab responses. Seven days after immunization with the Salmonella-CFA/I construct, cytokine-specific ELISPOT showed induction of predominant Th2-type responses in both mucosal and systemic immune compartments supporting the early IgG1 and IgA anti-CFA/I Abs. By 4 weeks, the Th cell response became Th1 cell dominant from the earlier Th2-type responses, as evidenced by increased mucosal and systemic IFN-gamma-producing T cells and a concomitant elevation of serum IgG2a Ab responses. This biphasic response offers an alternative strategy for directing Salmonella vector-induced host immunity along a Th2 cell-dependent pathway, allowing for early promotion of mucosal and systemic Abs.


Strength and Similarity Guided Group-level Brain Functional Network Construction for MCI Diagnosis.
Sparse representation-based brain functional network modeling often results in large inter-subject variability in the network structure. This could reduce the statistical power in group comparison, or even deteriorate the generalization capability of the individualized diagnosis of brain diseases. Although group sparse representation (GSR) can alleviate such a limitation by increasing network similarity across subjects, it could, in turn, fail in providing satisfactory separability between the subjects from different groups (e.g., patients vs. controls). In this study, we propose to integrate individual functional connectivity (FC) information into the GSR-based network construction framework to achieve higher between-group separability while maintaining the merit of within-group consistency. Our method was based on an observation that the subjects from the same group have generally more similar FC patterns than those from different groups. To this end, we propose our new method, namely "strength and similarity guided GSR (SSGSR)", which exploits both BOLD signal temporal correlation-based "low-order" FC (LOFC) and inter-subject LOFC-profile similarity-based "high-order" FC (HOFC) as two priors to jointly guide the GSR-based network modeling. Extensive experimental comparisons are carried out, with the rs-fMRI data from mild cognitive impairment (MCI) subjects and healthy controls, between the proposed algorithm and other state-of-the-art brain network modeling approaches. Individualized MCI identification results show that our method could achieve a balance between the individually consistent brain functional network construction and the adequately maintained inter-group brain functional network distinctions, thus leading to a more accurate classification result. Our method also provides a promising and generalized solution for the future connectome-based individualized diagnosis of brain disease.


The effect of gel structure on the in vitro digestibility of wheat starch-Mesona chinensis polysaccharide gels.
The digestibility of wheat starch gels in the presence of Mesona chinensis polysaccharide (MCP) was studied. MCP was found to be the most effective polysaccharide in reducing wheat starch digestion in comparison to starch gels of similar hardness containing xanthan, guar, locust bean gum (LBG) and agar. A 33% reduction in the digestibility of intact starch gels containing 5% w/w MCP (after 120 minutes of digestion) was observed and this was attributed to the strengthening of the gels in the presence of high concentration of the polysaccharide. In contrast, despite a reduction in the firmness of the gel when 2% w/w MCP was present, there was a 7% reduction in starch digestibility and hence, firmness was deduced to be not solely responsible for the digestibility of the gels. When these gels were macerated, starch digestibility was reduced regardless of the MCP concentration. Starch digestion in the macerated samples seemed to cease after 10 minutes with about 30% more starch remaining when 5% w/w MCP was present, suggesting that the amount of starch available for digestion was reduced in the presence of MCP. The reduced availability of starch for digestion was hypothesised to be due to starch-MCP interactions, which formed amylose-MCP complexes that are likely to be resistant to enzymatic digestion. Overall, this work shows the potential for MCP to be utilized as an ingredient to reduce the glycaemic index.


Neural blockade for persistent pain after breast cancer surgery.
Persistent pain after breast cancer surgery is predominantly a neuropathic pain syndrome affecting 25% to 60% of patients and related to injury of the intercostobrachial nerve, intercostal nerves, and other nerves in the region. Neural blockade can be useful for the identification of nerves involved in neuropathic pain syndromes or to be used as a treatment in its own right. The purpose of this review was to examine the evidence for neural blockade as a potential diagnostic tool or treatment for persistent pain after breast cancer surgery. In this systematic review, we found only 7 studies (n = 135) assessing blocks directed at 3 neural structures-stellate ganglion, paravertebral plexus, and intercostal nerves-but none focusing on the intercostobrachial nerve. The quality of the studies was low and efficacy inconclusive, suggesting a need for well-designed, high-quality studies for this common clinical problem.


Recalibration of the NBS Glass Standards of Spectral Transmittance.
In 1934, Gibson, Walker, and Brown developed sets of four colored glass filters to serve as working standards of spectral transmittance for checking the reliability of spectrophotometers. Several sets of these glasses were measured carefully and reserved and designated as future reference standards. Duplicate standards evaluated by comparison with the reference standards are available by purchase to the public. The current set of reference standards was established in the years 1945 to 1947, and one of these reference standards (selenium-red) was recalibrated in 1952. This paper reports a recalibration, made in 1961 and 1962, of all four glasses (selenium-red, carbon-yellow, copper-green, cobalt-blue) on three spectrophotometers (Cary 14, Beckman DU, König-Martens). Except for the cobalt-blue standard, the values of spectral transmittance found differ from those previously assigned by amounts differing at some wavelengths by as much as or slightly more than the uncertainties estimated for the present values, though not by amounts exceeding the combined uncertainties of the present and previous determinations. The indicated changes for these three standards are fairly regular, however, and support the view that the selenium-red and carbon-yellow standards are changing chiefly by formation of a reflectance-reducing film on the surfaces. The indicated rate of upward drift is slow, and suggests that it takes about 10 years for the drift to exceed the assigned uncertainity.


Unusual Presentation of Postradiation Sarcoma With Subsequent Intestinal Metastasis Revealed by 18F-FDG PET/CT.
Radiation-related sarcoma is a rare but serious complication for patients after receiving radiation therapy initially for their primary malignancy. However, it usually takes several years and needs enough in-field radiation dose to develop this sarcoma. We describe a 60-year-old man with right axillary sarcoma revealed by whole-body F-FDG PET/CT 1 year after chemoradiotherapy, which presented ultrashort latency period and did not match the consensus definition of radiation-related sarcoma. Besides, metastatic sarcoma to small intestine was accidentally noted in the F-FDG PET/CT image.


Conditions for reservoir computing performance using semiconductor lasers with delayed optical feedback.
Photonic implementations of reservoir computing (RC) have been receiving considerable attention due to their excellent performance, hardware, and energy efficiency as well as their speed. Here, we study a particularly attractive all-optical system using optical information injection into a semiconductor laser with delayed feedback. We connect its injection locking, consistency, and memory properties to the RC performance in a non-linear prediction task. We find that for partial injection locking we achieve a good combination of consistency and memory. Therefore, we are able to provide a physical basis identifying operational parameters suitable for prediction.


Modified guanidinium thiocyanate method for human sperm DNA isolation.
Mammalian sperm chromatin is highly condensed, so isolating DNA from such chromatin can be a formidable task. The procedures that produce high quality DNA from somatic cells fail to yield quality sperm DNA. In this study we have modified the previously used guanidinium method to make it simple and efficient in isolating human sperm DNA. In our method, the lysis buffer contained guanidinium, sodium citrate, sarkosyl, proteinase K and mercaptoethanol. Proteinase K was not used in the original guanidinium method but was included in our protocol. CsCl centrifugation of the lysate, as described in the original procedure, was omitted. Instead, isopropyl alcohol was added directly to the lysis buffer to harvest the DNA. This modified guanidinium method generated high molecular weight DNA while the other two methods resulted in considerable DNA degradation. There was no difficulty in restriction enzyme digestion of DNA prepared by the modified method as revealed by Southern blot analysis. Since the modified guanidinium method is a simple one-step procedure which avoids homogenization, organic solvents, centrifugation and, more importantly, produces degradation-free DNA, it could be the method of choice when DNA from mature germ cells is needed.


Design and Prototyping of an Underactuated Hand Exoskeleton With Fingers Coupled by a Gear-Based Differential.
Exoskeletons and more in general wearable mechatronic devices represent a promising opportunity for rehabilitation and assistance to people presenting with temporary and/or permanent diseases. However, there are still some limits in the diffusion of robotic technologies for neuro-rehabilitation, notwithstanding their technological developments and evidence of clinical effectiveness. One of the main bottlenecks that constrain the complexity, weight, and costs of exoskeletons is represented by the actuators. This problem is particularly evident in devices designed for the upper limb, and in particular for the hand, in which dimension limits and kinematics complexity are particularly challenging. This study presents the design and prototyping of a hand finger exoskeleton. In particular, we focus on the design of a gear-based differential mechanism aimed at coupling the motion of two adjacent fingers and limiting the complexity and costs of the system. The exoskeleton is able to actuate the flexion/extension motion of the fingers and apply bidirectional forces, that is, it is able to both open and close the fingers. The kinematic structure of the finger actuation system has the peculiarity to present three DoFs when the exoskeleton is not worn and one DoF when it is worn, allowing better adaptability and higher wearability. The design of the gear-based differential is inspired by the mechanism widely used in the automotive field; it allows actuating two fingers with one actuator only, keeping their movements independent.


Attempted suicide in Denmark. III. Assessment of repeated suicidal behaviour.
Ninety-nine patients, randomly chosen among hospital admitted suicide attempters, were initially interviewed at the Department of Psychiatry, Odense University Hospital, Denmark, and then followed up for a period of about 3 years. Half of the patients repeated the attempt in the follow-up period, mostly in the first year. Ten patients committed suicide, half of them in the first 3 months after the interview, shortly after discharge from hospital. The majority of the repeaters were living alone, while those that committed suicide were mostly married women aged 50-60 years. Other characteristic features for the repeaters were previous suicidal behaviour and suicidal behaviour among relatives. Many had a psychiatric record and expressed chronic somatic complaints. Around the time of the attempt, many expressed hopelessness, isolation and suicidal ideation. Pierce's Suicide Intent Scale performed poorly due, in particular, to low specificity. Future work will focus on objective risk factors, those indicated here and others, in order to establish an up-to-date background for assessment and management.


Comparison of discrete and continuous motion in scanning probe microscopy monitored via confocal Raman microspectroscopy.
Confocal Raman imaging is a relatively new analytical technique that combines the strengths of Raman microspectroscopy and confocal optics. The images collected by the microscope are obtained by monitoring specific bands in the Raman spectra that are collected at many points in a sample, with the number of spectra usually numbering in the hundreds or thousands. Some commercially available systems acquire data while the sample is continuously moving with respect to the microscope objective. The distance that the stage moves during a single acquisition is a parameter that can be set prior to data acquisition. Data in this report was acquired with both a static and continuously moving sample for comparison, utilizing the 520 cm(-1) Si phonon of a silicon wafer to monitor an edge. Scattering collected from each discrete step, i.e., no motion during spectral acquisition, showed excellent precision of location, but a loss in resolution was observed as the pixel size was increased beyond the maximum theoretical resolution of the instrument. A continuously moving stage contributed to erroneous position data as the pixel size was increased beyond the maximum theoretical resolution of the instrument.


Electrospun 3D Structured Carbon Current Collector for Li/S Batteries.
Light weight carbon nanofibers (CNF) fabricated by a simple electrospinning method and used as a 3D structured current collector for a sulfur cathode. Along with a light weight, this 3D current collector allowed us to accommodate a higher amount of sulfur composite, which led to a remarkable increase of the electrode capacity from 200 to 500 mAh per 1 g of the electrode including the mass of the current collector. Varying the electrospinning solution concentration enabled obtaining carbonized nanofibers of uniform structure and controllable diameter from several hundred nanometers to several micrometers. The electrochemical performance of the cathode deposited on carbonized PAN nanofibers at 800 °C was investigated. An initial specific capacity of 1620 mAh g-1 was achieved with a carbonized PAN nanofiber (cPAN) current collector. It exhibited stable cycling over 100 cycles maintaining a reversible capacity of 1104 mAh g-1 at the 100th cycle, while the same composite on the Al foil delivered only 872 mAh g-1. At the same time, 3D structured CNFs with a highly developed surface have a very low areal density of 0.85 mg cm-2 (thickness of ~25 µm), which is lower for almost ten times than the commercial Al current collector with the same thickness (7.33 mg cm-2).


Seabird-Transported Contaminants Are Reflected in the Arctic Tundra, But Not in Its Soil-Dwelling Springtails (Collembola).
Arctic-breeding seabirds contain high levels of many anthropogenic contaminants, which they deposit through guano to the tundra near their colonies. Nutrient-rich soil in vicinity to seabird colonies are favorable habitats for soil invertebrates, such as springtails (Collembola), which may result in exposure to seabird-derived contaminants. We quantified a wide range of lipid-soluble and protein-associated environmental contaminants in two springtail species (Megaphorura arctica and Hypogastrura viatica) and their respective habitats (soil/moss) collected underneath seabird cliffs. Although springtails are commonly used in laboratory toxicity tests, this is the first study to measure concentrations of persistent organic pollutants (POPs) and mercury (Hg) in springtails from the field, and to study biotransportation of contaminants by seabirds to soil fauna. We categorized the sites a priori as of low, medium, or high seabird influence, based on the seabird abundance and species composition. This ranking was reflected in increasing δ15N values in soil/moss and springtails with increasing seabird influence. We found clear indications of seabirds impacting the terrestrial soil environments with organic contaminants, and that concentrations were higher in soil and moss close to the bird cliff, compared to farther away. However, we did not find a relationship between contaminant concentration in springtails and the concentrations in soil/moss, or with level of seabird influence. Our study indicates a low uptake of contaminants in the soil fauna, despite seabird-derived contamination of their habitat.


One-Dimensional Confinement Inhibits Water Dissociation in Carbon Nanotubes.
The effect of nanoconfinement on the self-dissociation of water constitutes an open problem whose elucidation poses a serious challenge to experiments and simulations alike. In slit pores of width ≈1 nm, recent first-principles calculations have predicted that the dissociation constant of H2O increases by almost 2 orders of magnitude [ Muñoz-Santiburcio and Marx, Phys. Rev. Lett. 2017 , 119 , 056002 ]. In the present study, quantum mechanics-molecular mechanics simulations are employed to compute the dissociation free-energy profile of water in a (6,6) carbon nanotube. According to our results, the equilibrium constant Kw drops by 3 orders of magnitude with respect to the bulk phase value, at variance with the trend predicted for confinement in two dimensions. The higher barrier to dissociation can be ascribed to the undercoordination of the hydroxide and hydronium ions in the nanotube and underscores that chemical reactivity does not exhibit a monotonic behavior with respect to pore size but may vary substantially with the characteristic length scale and dimensionality of the confining media.


Renal proximal tubule function is preserved in Cftr(tm2cam) deltaF508 cystic fibrosis mice.
1. Changes in proximal tubule function have been reported in cystic fibrosis patients. The aim of this study was to investigate proximal tubule function in the Cftr(tm2cam)deltaF508 cystic fibrosis (CF) mouse model. A range of techniques were used including renal clearance studies, in situ microperfusion, RT-PCR and whole-cell patch clamping. 2. Renal Na(+) clearance was similar in wild-type (1.4 +/- 0.3 microl min(-1), number of animals, N = 12) and CF mice (1.6 +/- 0.4 microl min(-1), N = 7) under control conditions. Acute extracellular volume expansion resulted in significant natriuresis in wild-type (7.0 +/- 0.8 microl min(-1), N = 8) and CF mice (9.3 +/- 1.4 microl min(-1), N = 9); no difference between genotypes was observed. 3. In situ microperfusion revealed that fluid absorptive rate (Jv) was similar under control conditions between wild-type (2.2 +/- 0.4 nl mm(-1) min(-1), n = 10) and CF mice (1.9 +/- 0.3 nl mm(-1) min(-1), n = 11). Addition of a forskolin-dibutyryl cAMP (db-cAMP) cocktail to the perfusate caused no significant change in Jv in either wild-type (2.6 +/- 0.7 nl mm(-1) min(-1), n = 10) or Cftr(tm2cam)deltaF508 mice (2.0 +/- 0.5 nl mm(-1) min(-1), n = 10). 4. CFTR expression was confirmed in samples of outer cortex using RT-PCR. However, no evidence for functional CFTR was obtained when outer cortical cells were stimulated with protein kinase A or forskolin-db-cAMP using whole-cell patch clamping. 5. In conclusion, no functional deficit in proximal tubule function was found in Cftr(tm2cam)deltaF508 mice. This may be a consequence of a lack of whole-cell cAMP-dependent Cl(-) conductance in mouse proximal tubule cells.


The neurotoxin MPTP increases calbindin-D28k levels in mouse midbrain dopaminergic neurons.
The calcium-binding protein calbindin-D28k (CALB) has been localized in high concentrations in several neuronal populations within the central nervous system (CNS) and is believed to act as an intracellular calcium (Ca2+) buffer. There has been much interest and speculation concerning its potential neuroprotective function. However, there is little direct evidence linking CALB content of individual neurons to Ca2+ buffering ability, resistance to Ca(2+)-mediated excitotoxicity, or vulnerability to Ca(2+)-mediated degeneration. It is necessary to demonstrate these relationships on a cellular level so that more definitive conclusions can be made. We have utilized immunocytochemical and Western blot techniques to determine whether cellular CALB content is altered in the nucleus A10 dopaminergic region of the midbrain following administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our data demonstrate a significant increase in the CALB content of nucleus A10 neurons (up to 227 +/- 23% above control) 3 and 6 h after MPTP treatment. CALB elevation demonstrated both time and dosage dependence as 6-h groups exhibited larger increases than 3-h groups, and a 60 mg/kg dosage induced a larger increase than a 20 mg/kg dosage. These data support the hypothesis that MPTP is neurotoxic by causing increases in free intracellular Ca2+ and that increased CALB in the midbrain dopaminergic neurons is a protective response to elevated intracellular free Ca2+.


Radioimmunoassay of antibiotics and chemotherapeutic agents.
Theapeutic monitoring of drugs has become of major importance and has stimulated development of new assay systems. Chemotherapeutic agents, many of which are toxic, have until recently been assayed by microbiological systems or other complex techniques that are impractical for a clinical laboratory. Radioimmunoassays have now been developed for some of these agents. We review the techniques for producing hapten protein conjugates and radiolabeling at specific sites on the drug molecule, and the use of these assays in clinical medicine and pharmacology.


Persistent eNOS in lung hypoplasia caused by left pulmonary artery ligation in the ovine fetus.
Because increased flow and shear stress upregulate endothelial (e) nitric oxide synthase (NOS) in adult endothelial cells in vivo and in vitro, we hypothesized that decreased pulmonary blood flow would decrease eNOS content in the late-gestation ovine fetus. To investigate the effects of decreased blood flow and the potential role of altered eNOS content in lung hypoplasia, we studied an animal model of lung hypoplasia after left pulmonary artery (LPA) ligation in nine fetal lambs (114-124 days gestation; term = 147 days). After at least 14 days, animals were killed, and lungs were harvested for histology, immunostaining, Western blot analysis for eNOS protein content, and biochemical assays of NOS activity. LPA ligation markedly reduced left lung size. Histology demonstrated loose connective tissue and airway immaturity in the left lungs. eNOS immunostaining demonstrated equal staining in the left pulmonary vessels compared with the right. Solitary endothelial cells staining for eNOS and factor VIII-related antigen were observed throughout the mesenchyme of left, but not right, lungs. eNOS protein content and activity were similar in left and right lungs. We conclude that, despite the absence of pulmonary blood flow and marked lung hypoplasia, eNOS content and NOS activity were not reduced after LPA ligation in the late fetal lung. We speculate that low pulmonary blood flow does not downregulate fetal pulmonary vascular eNOS expression and that other factors, such as paracrine or autocrine stimuli, may account for the persistence of eNOS in the developing lung circulation.