Overexpression of a Novel ROP Gene from the Banana (MaROP5g) Confers Increased Salt Stress Tolerance.
Rho-like GTPases from plants (ROPs) are plant-specific molecular switches that are crucial for plant survival when subjected to abiotic stress. We identified and characterized 17 novel ROP proteins from Musa acuminata (MaROPs) using genomic techniques. The identified MaROPs fell into three of the four previously described ROP groups (Groups II⁻IV), with MaROPs in each group having similar genetic structures and conserved motifs. Our transcriptomic analysis showed that the two banana genotypes tested, Fen Jiao and BaXi Jiao, had similar responses to abiotic stress: Six genes (MaROP-3b, -5a, -5c, -5f, -5g, and -6) were highly expressed in response to cold, salt, and drought stress conditions in both genotypes. Of these, MaROP5g was most highly expressed in response to salt stress. Co-localization experiments showed that the MaROP5g protein was localized at the plasma membrane. When subjected to salt stress, transgenic Arabidopsis thaliana overexpressing MaROP5g had longer primary roots and increased survival rates compared to wild-type A. thaliana. The increased salt tolerance conferred by MaROP5g might be related to reduced membrane injury and the increased cytosolic K⁺/Na⁺ ratio and Ca2+ concentration in the transgenic plants as compared to wild-type. The increased expression of salt overly sensitive (SOS)-pathway genes and calcium-signaling pathway genes in MaROP5g-overexpressing A. thaliana reflected the enhanced tolerance to salt stress by the transgenic lines in comparison to wild-type. Collectively, our results suggested that abiotic stress tolerance in banana plants might be regulated by multiple MaROPs, and that MaROP5g might enhance salt tolerance by increasing root length, improving membrane injury and ion distribution.


On the causal structure of information bias and confounding bias in randomized trials.
Randomized trials are undoubtedly different from observational studies, but authors sometimes propose differences between these designs that do not exist. In this article we examine two claims about randomized trials: first, a recent claim that the causal structure of exposure measurement (information) bias in a randomized trial differs from the causal structure of that bias in an observational study. Second, a long-standing claim that confounding bias cannot operate in a randomized trial - if randomization was perfectly implemented. Using causal diagrams (causal directed acyclic graphs), we show that both claims are false in the context of an intention-to-treat analysis. We also describe a previously unrecognized mechanism of information bias, and suggest that the term 'information bias' should replace the terms 'measurement bias' and 'observation bias'.


Nogo-A expresses on neural stem cell surface.
Nogo-A, as a myelin-associated molecule to inhibit axon regeneration in the injured adult central nervous system (CNS), has been detected to be enriched in numerous populations of cells in CNS. In this study, we found that Nogo-A was also expressed on the surface of neural stem cells (NSCs). The possible effects of NSCs-expressed Nogo-A on the NSC transplantation for CNS repair were discussed.


Utilization of Lemon Peel for the Production of Vinegar by a Combination of Alcoholic and Acetic Fermentations.
Lemon peel is the major by-product of lemon juice processing and is currently underutilized. In this study, we explored the feasibility of using lemon peel as a raw material for making vinegar. Lemon peel was homogenized, treated with pectinase (30,000 U/g, 0.1%) at 50 °C for 4 h, and then filtered. The obtained lemon peel juice was first subjected to alcoholic fermentation by Saccharomyces cerevisiae var. FX10, and then acetic fermentation by an acid tolerant Acetobacter malorum, OQY-1, which was isolated from the lemon peels. The juice yield of the lemon peel was 62.5%. The alcoholic fermentation yielded a lemon peel wine with an alcoholic content of 5.16%, and the acetic acid fermentation produced a vinegar with a total acid content of 5.04 g/100 mL. A total of 36 volatile compounds were identified from the lemon vinegar, with some compounds such as esters and some alcohols that increased significantly during alcoholic fermentation while alcohols, terpenoids, and some esters decreased significantly during the fermentations. E-nose and E-tongue analyses coupled with principal component and discriminant factor analyses (PCA and DFA) were able to discriminate the samples at different fermentation stages. Overall, this work demonstrates the potential to transform lemon peel into a valuable product, thus reducing the waste of lemon processing and adding value to the industry.


[Protective mechanism on the vascular pathological process in diabetes mellitus rats by Rheum officeinale].
To explore the protective mechanism of officeihale on the vascular pathological process in diabetes mellitus (DM) rats. After the DM rat model was established, 24 DM rats were randomly divided into model group (12 DM rats) and Rheum officeinale group (12 DM rats). Rheum officeinale was orally given in 10 g kg(-1) per day, and the other two groups were given equal pure water. 8 weeks later, blood samples were collected to determine the level of nitric oxide (NO) and endothelin-1 (ET-1). Thoracic aortic rings was prepared to observe the inhibiting effect of Ach with different concentration on contraction caused by NE. Another part of aorta was made to observe the expression of ICAM-1 and VCAM-1 by method of SP immunohistochemistry staining, Rheum officeinale group obviously decreased the level of ET-1 and increased the NO compared with model group (P <0.05). The expression of ICAM-1 and VCAM-1 could be obviously inhibited in Rheum officeinale group compared with model group. (P <0.05). Rheum officeinale could decrease the level of ET-1 with increased the NO in diabetes rats, and inhibit the expression of ICAM-1 and VCAM-1, which may be mechanisms of protecting the endothelium of vessel in diabetes rats.


Emerging molecular targets for the treatment of asthma.
Current therapeutic approaches for the treatment of asthma have limitations in their ability to target all the features of the disease. Indeed, existing pharmacological asthma therapies are based on decades old strategies that were developed prior to the rapid growth in knowledge stemming from cell and molecular biology in the past decade. Thus, there is an unmet need for developing new drugs to target these features along with improved efficacy and safety. In the present review, the limitations of prevalent pharmacological asthma therapy are discussed briefly, and some explanations are suggested as to why new therapeutic targets are required to treat asthma, and finally directions for novel asthma therapies are proposed.


Impacts of rising atmospheric carbon dioxide on model terrestrial ecosystems
In model terrestrial ecosystems maintained for three plant generations at elevated concentrations of atmospheric carbon dioxide, increases in photosynthetically fixed carbon were allocated below ground, raising concentrations of dissolved organic carbon in soil. These effects were then transmitted up the decomposer food chain. Soil microbial biomass was unaffected, but the composition of soil fungal species changed, with increases in rates of cellulose decomposition. There were also changes in the abundance and species composition of Collembola, fungal-feeding arthropods. These results have implications for long-term feedback processes in soil ecosystems that are subject to rising global atmospheric carbon dioxide concentrations.


The Donut Island Flap: Avoiding Stoma Relocation in Patients With Intractable Chronic Ileostomy Leakage.
Severe skin scarring after multiple abdominal surgeries may lead to serious difficulties in stoma care, especially in patients with IBD. We demonstrate the technique of Donut Island Flap that we used in a female patient with colonic Crohn's disease that presented with intractable chronic ileostomy leakage. A relocation of the ileostomy was not possible because an alternative stoma site was not available anymore. The scarred peristomal skin was radially excised up to a diameter of 10 cm. A pedicled anterolateral thigh perforator island flap was elevated from the right leg and was passed behind the rectus femoris muscle and through the inguinal tunnel into the defect. The ileostomy was passed through a small opening in the middle of the flap. The donor site at the thigh was closed primarily. No postoperative complications occurred. Three months after surgery, the ostomy care is providing no difficulties for the patient. The Donut Island Flap is a reliable and relatively simple technique to provide an adequate surrounding for ileostomy whose care is seriously impeded by severe skin scarring.


Platelet function testing in acute cardiac care - is there a role for prediction or prevention of stent thrombosis and bleeding?
The role of platelet function testing in acute coronary syndrome patients undergoing percutaneous coronary intervention remains controversial despite the fact that high platelet reactivity is an independent predictor of stent thrombosis and emerging evidence suggests also a link between low platelet reactivity and bleeding. In this expert opinion paper, the Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association and the Working Group on Thrombosis of the European Society of Cardiology aim to provide an overview of current evidence in this area and recommendations for practicing clinicians.


[An elderly case of acute myelocytic leukemia complicated with bleeding gastric angiodysplasia, successfully treated with topical endoscopic polidocanol injection].
A 72-year-old man with acute myelocytic leukemia (AML) suffered relapsing massive bleeding from gastric angiodysplasia. He was referred to our hospital in February 2000 because of anemia and thrombocytopenia. He had hypercellular (nucleated cell count 42 x 10(4)/microl) bone marrow with 90% myeloblasts, and AML (FAB: M1) was diagnosed. Remission induction therapy by BHAC/DM regimen failed. While considering subsequent regimens, massive hematemesis from a solitary gastric angiodysplasia developed. In April, after re-remission induction by CAG regimen, hematemesis from the same lesion reccurred. Hemostasis was achieved by topical transendoscopic injection of polidocanol. After achievement of complete remission by CAG therapy, he was treated on an outpatient basis. In July, his AML relapsed and he was treated mainly by transfusion therapy. In September, hematemesis recurred resulting in hemostasis with the same procedure. In the course of endoscopic injections, his mucosal lesion became difficult to observe. Gastric angiodysplasia is occasionally observed in the elderly, but massive bleeding is a rare complication. In this case, topical injection of polidocanol was an effective procedure for the massive bleeding from it even in an elderly patient with the complication of thrombocytopenia due to AML.


Pyropia yezoensis Extract Suppresses IFN-Gamma- and TNF-Alpha-Induced Proinflammatory Chemokine Production in HaCaT Cells via the Down-Regulation of NF-κB.
Pyropia yezoensis, a red alga, is popular and harvested a lot in East Asia and is famous for its medicinal properties attributable to its bioactive compounds including amino acids (porphyra-334 and shinorine, etc.), polysaccharides, phytosterols, and pigments, but its anti-inflammatory effect and mechanism of anti-atopic dermatitis (AD) have not been elucidated. In this study, we investigate the anti-AD effect of P. yezoensis extract (PYE) on mRNA and protein levels of the pro-inflammatory chemokines, thymus, and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), in human HaCaT keratinocyte cells treated to interferon (IFN)-γ or tumor necrosis factor (TNF)-α (10 ng/mL each). The effect of the PYE on extracellular signal-regulated kinase (ERK) and other mitogen-activated protein kinases (MAPKs) was related to its suppression of TARC and MDC production by blocking NF-κB activation in HaCaT cells. Furthermore, astaxanthin and xanthophyll from P. yezoensis were identified as anti-AD candidate compounds. These results suggest that the PYE may improve AD and contained two carotenoids by regulating pro-inflammatory chemokines.


[Pyogenic Spinal Infections in Adults: A 5-Year Experience from a Tertiary Care Centre].
PURPOSE OF THE STUDY To describe epidemiological and clinical features of pyogenic spinal infections in patients treated at the Department of Infectious, Parasitic and Tropical Diseases of the Hospital Na Bulovce in 2010-2014, and to analyse a predictive significance of selected variables. MATERIAL AND METHODS A single-centre retrospective cohort study carried out from 1.1.2010 to 31.12.2014 enrolled adult patients with septic spondylitis, discitis and facet joint infections. Recorded parameters included: demographics, chronic comorbidities, time to diagnosis, radiological work-up, anatomical level of spinal infection, source of infection, etiological agent, complications, treatment and outcomes. RESULTS Fifty-four patients were enrolled, 35 men (65%) and 19 women (35%), age range 33-90, mean age 63 years. Forty patients (74.1%) had a chronic comorbidity, 20 patients (37%) were obese. Time to diagnosis ranged between 1-90 days, mean 16.3 days. The diagnosis was assessed with MRI in 41 (75.9%) and CT in 11 patients (20.4%). Lumbosacral spine was affected in 38 (70.4%), thoracic in 14 (25.5%), cervical in 8 patients (14.8%), and 6 patients (11.1%) had a multilevel disease. Epidural abscess developed in 28 (51.9%), paravertebral oedema or abscess in 41 patients (75.9%). Endocarditis was diagnosed in 8 patients (14.8%). Aetiology was identified in 45 patients (83.3%), with Staphylococcus aureus isolated in 29 patients (53.7%). Twenty-two patients (40.7%) were treated surgically in addition to antibiotics. The mean length of hospital stay, parenteral antibiotic treatment and total antibiotic treatment was 48.7, 38.2 and 71.5 days, respectively. Thirty-six patients (66.6%) recovered with no or mild sequelae, 7 (13%) with severe sequelae, and 11 patients (20.4%) died. None of the analysed variables proved to be a statistically significant predictive factor of clinical outcome. DISCUSSION In accordance with previous studies pyogenic spinal infections were diagnosed mainly in elderly with chronic internal comorbidities, mostly with magnetic resonance imaging, they were often localized in lumbar spine, with staphylococci being the leading agents. In spite of unavailable CT-navigated biopsy, the aetiology was discovered in majority of patients. In contrast, this study found a more frequent posterior segments involvement, a shorter time to treatment, no tuberculous cases, a relatively high case fatality ratio, but less sequelae and no relapse. CONCLUSIONS The study confirmed an increasing incidence of pyogenic spinal infections, known predisposing factors, importance of MRI in diagnostics, disease predilection in lumbar spine, staphylococcal predominance in causative pathogens, and a relatively high case fatality ratio. Although time to treatment was not proved to be a negative predictive factor of clinical outcome, it is an imperative to strive for an early diagnosis and treatment. Predictors of clinical outcome have to be evaluated in a more extensive cohort of patients. Key words: spinal infection, discitis, spondylitis, spondylodiscitis, epidural abscess, psoas muscle abscess.


PD-L1/LAG-3 bispecific antibody enhances tumor-specific immunity.
Anti-programmed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) treatments are effective in a fraction of patients with advanced malignancies. However, the majority of patients do not respond to it. Resistance to cancer immunotherapy can be mediated by additional immune checkpoints. We hypothesized that co-targeting of PD-L1 and lymphocyte-activation gene 3 (LAG-3) could provide an alternative therapeutic approach. Here, we developed IBI323, a dual blockade bispecific antibody targeting PD-L1 and LAG-3. We assessed the binding affinity, blocking activity, cell bridging effect, and immunomodulation function of IBI323 using in vitro assays. We also evaluated, in two humanized mouse models, anti-tumor effects and antitumor T cell immunity induced by IBI323. IBI323 bound to PD-L1 and LAG-3 with similar potency as its parental antibodies and blocked the interaction of PD-1/PD-L1, CD80/PD-L1, and LAG-3/MHC-II. Moreover, IBI323 mediated the bridging of PD-L1+ cells and LAG-3+ cells and demonstrated superior immune stimulatory activity compared to each parent antibody in mixed leukocyte reaction. In PD-L1/LAG-3 double knock-in mice bearing human PD-L1 knock-in MC38 tumors, IBI323 showed stronger anti-tumor activity compared to each parental antibody. The better antitumor response correlated with increased tumor-specific CD8+ and CD4+ T cells. IBI323 also induced stronger anti-tumor effect against established A375 tumors compared with combination in mice reconstituted with human immune cells. Collectively, these data demonstrated that IBI323 preserved the blockade activities of parental antibodies while processing a novel cell bridging function. Based on the encouraging preclinical results, IBI323 has significant value in further clinical development.


Surface modification by poly(ethylene glycol) with different end-grafted groups: Experimental and theoretical study.
Dihydroxyphenylalanine (DOPA) is extensively reported to be a surface-independent anchor molecule in bioadhesive surface modification and antifouling biomaterial fabrication. However, the mechanisms of DOPA adsorption on versatile substrates and the comparison between experimental results and theoretical results are less addressed. We report the adsorption of DOPA anchored monomethoxy poly(ethylene glycol) (DOPA-mPEG) on substrates and surface wettability as well as antifouling property in comparison with thiol and hydroxyl anchored mPEG (mPEG-SH and mPEG-OH). Gold and hydroxylated silicon were used as model substrates to study the adsorptions of mPEGs. The experimental results showed that the DOPA-mPEG showed higher affinity to both gold and silicon wafers, and the DOPA-mPEG modified surfaces had higher resistance to protein adsorption than those of mPEG-SH and mPEG-OH. It is revealed that the surface wettability is primary for surface fouling, while polymer flexibility is the secondary parameter. We present ab initio calculations of the adsorption of mEGs with different end-functionalities on Au and hydroxylated silicon wafer (Si-OH), where the binding energies are obtained. It is established that monomethoxy ethylene glycol (mEG) with DOPA terminal DOPA-mEG is clearly favored for the adsorption with both gold and Si-OH surfaces due to the bidentate Au-O interactions and the bidentate O-H bond interactions, in agreement with experimental evidence.


Fusion of Low-Level Descriptors of Digital Voice Recordings for Dementia Assessment.
Digital voice recordings can offer affordable, accessible ways to evaluate behavior and function. We assessed how combining different low-level voice descriptors can evaluate cognitive status. Using voice recordings from neuropsychological exams at the Framingham Heart Study, we developed a machine learning framework fusing spectral, prosodic, and sound quality measures early in the training cycle. The model's area under the receiver operating characteristic curve was 0.832 (±0.034) in differentiating persons with dementia from those who had normal cognition. This offers a data-driven framework for analyzing minimally processed voice recordings for cognitive assessment, highlighting the value of digital technologies in disease detection and intervention.


Effects of n-3 fatty acid supplements on glycemic traits in Chinese type 2 diabetic patients: A double-blind randomized controlled trial.
To investigate the effects of n-3 fatty acid supplements, both marine and plant-based, on glycemic traits in Chinese type 2 diabetes patients. In a double-blind randomized controlled trial, 185 recruited Chinese type 2 diabetes patients were randomized to either fish oil (FO, n = 63), flaxseed oil (FSO, n = 61), or corn oil group (served as control group, n = 61) for 180 days. The patients were asked to take corresponding oil capsules (four capsules/day), which totally provided 2 g/day of eicosapentaenoic acid + docosahexaenoic acid in FO group and 2.5 g/day of alpha-linolenic acid in FSO group. No group × time interaction was observed for homeostatic model assessment of insulin resistance, fasting insulin, or glucose. Significant group × time interaction (P = 0.035) was observed for glycated hemoglobin A1c (HbA1c), with HbA1c decreased in FO group compared with corn oil group (P = 0.037). We also found significant group × time interactions for lipid traits, including LDL cholesterol (P = 0.043), total cholesterol (P = 0.021), total cholesterol/HDL cholesterol (P = 0.009), and triacylglycerol (P = 0.003), with the lipid profiles improved in FO group. No significant effects of FSO on glycemic traits or blood lipids were observed. Marine n-3 PUFA supplements may improve glycemic control and lipid profiles among Chinese type 2 diabetic patients.


Documenting individual differences in the propensity to hold attitudes with certainty.
The certainty with which people hold their attitudes is an important consideration because attitudes held with certainty better predict judgment and behavior than attitudes held with doubt. However, little is known about whether people's assessments of their certainty reflect a disposition to hold attitudes with confidence. Adapting methods used to document individual differences in people's attitudes, the present research demonstrates that the certainty with which people hold any given attitude is in part a reflection of a relatively stable disposition. Across 5 studies and 6 samples (total N = 106,050), we demonstrate dispositional variability in attitude certainty and show that it is related to but distinct from confidence in other judgmental domains. We also demonstrate that dispositional attitude certainty may be useful in predicting certainty in newly formed evaluations (Study 3) and an important consequence of certainty-attitude-behavior correspondence (as indicated by reports of behavioral intentions and recent behavior; Study 4 and Student Sample in Study 5). Furthermore, we demonstrate that dispositional attitude certainty is relatively stable over time (Study 5). Results are discussed with respect to potential mechanisms and boundary conditions relating to dispositional attitude certainty, the implications of these individual differences for attitudes and persuasion, as well as the potential origins of dispositional attitude certainty. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Photosynthetic characteristics of the subtending leaf of cotton boll at different fruiting branch nodes and their relationships with lint yield and fiber quality.
To investigate photosynthetic characteristics of the subtending leaf at the 2-3rd and 10-11th fruiting branch (FBN, FB2-3, and FB10-11), and their relationship with cotton yield and quality, field experiments were conducted using two cotton cultivars, Kemian 1 and Sumian 15. The results showed that with FBN increasing, chlorophyll (Chl) components, Pn and non-photochemical quenching (NPQ) in the subtending leaf significantly declined, while soluble sugar, amino acid and their ratio (C SS/C AA) as well as F v/F m increased. These results indicated that (1) non-radiative dissipation of excess light energy at FB2-3 was reduced to improve solar energy utilization efficiency to compensate for lower Pn, (2) higher NPQ at FB10-11 played a role in leaf photo-damage avoidance, (3) boll weight was related to the C SS/C AA ratio rather than carbohydrates content alone, (4) with FBN increasing, lint biomass and lint/seed ratio increased significantly, but lint yield decreased due to lower relative amount of bolls, and (5) the decreases in Pn, sucrose content and C SS /C AA in the subtending leaf at FB2-3 resulted in lower boll weight and fiber strength.


Clinical and biochemical observations on three cases of hypoxanthine-guanine phosphoribosyltransferase deficiency.
Clinical and enzymatic studies on two brothers with severe deficiencies of erythrocyte hypoxanthineguanine phosphoribosyltransferase (HGPRTase) are described, and are compared with similar studies of a classical case of the Lesch-Nyhan syndrome from another family. The two brothers have no neurological abnormalities, only traces of erythrocyte HGPRTase, erythrocyte adenine phosphoribosyltransferase activities approaching the high levels found in the Lesch-Nyhan patient, and similarly raised plasma and urinary concentrations of uric acid. Despite these strong biochemical similarities between the three patients, there were wide differences in the clinical case histories. In both families the enzyme deficiency appeared to be inherited as an X-linked character through asymptomatic carrier females. The relationship of HGPRTase deficiencies to the Lesch-Nyhan syndrome is discussed. Some observations relating to techniques are reported. Cellulose acetate has been found to give much better separations of labelled reaction products in low-level phosphoribosyltransferase assays than filter paper, when used as a supporting medium for electrophoresis. The analysis of hair follicles gives indications of individuals heterozygous for the enzyme deficiency, but the proportion of enzyme-deficient follicles was very small, and the test needs support from studies of other cell types. Using haemolysates, there were signs of a slow indirect conversion of hypoxanthine to inosinic acid, via inosine. Inosine appears to be labelled by a ribosyl-transfer reaction.


Health-related quality of life (HRQoL) from HIV patients' perspective: comparison of patient-reported outcome (PRO) measures among people living with hiv (PLWH) and other chronic clinical conditions.
People living with HIV (PLWH) are generally known to suffer from a lower quality of life compared to the one of general population, but still very few is known about the self-perception of quality of life when comparing HIV to non-communicable diseases. We performed a comprehensive assessment of patient's reported outcomes measures (PROMs) among PLWH and patients affected by other chronic conditions (OC) such as diabetes mellitus type 1, rheumatoid arthritis, breast cancer in hormonal therapy, in order to investigate differences in PROMs outcomes between PLWH and other pathologies. A cross-sectional observational study was performed by using questionnaires investigating health-related quality of life (Medical Outcomes Study Short Form 36-item Health Survey), work productivity (WPI), and global health status (EQ-5D-3L). They were administered to patients affected by chronic diseases consecutively observed at a single University Hospital during a 10 months period, with comparable disease related aspects. Logistic regression analysis was used to analyze the association between disease group (HIV vs OC) and PROMs. 230 patients were enrolled (89 PLWH, 143 OC). Mean age: 49 years (SD 10), mean time of disease 12 years (10), 96% were Caucasian, 35% assumed polypharmacy, 42% of male were PLWH versus 16% OC (p < 0.001), 19% PLWH versus 6% OC had clinical complications (p < 0.001). HIV infection was independently associated to a better health-related quality of life in several domains compared with the other conditions, except in mental health, whereas a worst health-related quality of life in most domains was reported by older patients and those experiencing polypharmacy. In this cohort of patients with chronic conditions followed within the same health setting, PLWH showed better self-reported health outcomes compared to other chronic conditions with comparable characteristics of chronicity. The potential detrimental role of older age and polypharmacy in most outcomes suggests the need of longitudinal assessment of PROMs in clinical practice.


The C-terminal tail of aquaporin-2 determines apical trafficking.
Aquaporin-2 (AQP-2) proteins are mainly expressed at the apical region of the collecting duct cells. We previously reported three different mutations in the C-terminus of AQP-2 that all-cause autosomal-dominant nephrogenic diabetes insipidus. When one of these mutant AQP-2s was expressed in Madin-Darby canine kidney (MDCK) cells, it was mistargeted to the basolateral membrane, suggesting a critical role of the C-terminal tail in the apical trafficking of AQP-2. Portions of the AQP-2 C-terminal tail (residues 226-271) were mutated by the polymerase chain reaction (PCR) technique and inserted into the pcDNA3.1 vector. Constructs were transfected into MDCK cells to examine the localization of mutated AQP-2 proteins by immunofluorescence microscopy. Cell surface expression was detected by biotinylation assay. The wild-type AQP-2 was localized at the apical membrane, whereas mutants lacking residues 262-271 (the last 10 amino acids) were predominantly distributed in the endoplasmic reticulum. Deletion mutants of the initial (226-240del) and middle (241-252del) portions of the C-terminal tail were identified at the apical membrane, suggesting that residues 226-252 have no involvement in apical targeting. An AQP-4-AQP-2 chimera in which a portion of the AQP-4 C-terminal tail was replaced by the corresponding site in AQP-2 (residues 256-271) was found at the apical membrane. The sequence of the last 4 amino acids of AQP-2 (G-T-K-A) corresponds to a PDZ-interacting motif. Our investigations identified a mutant of this portion mostly localized to the subapical region. Further, apical expression was found to be significantly decreased in mutants lacking a consensus sequence for cyclic adenosine monophosphate (cAMP)-dependent phosphorylation (residues 253-256). The sequence at 256-271 is sufficient for apical trafficking in AQP-2. The putative PDZ-interacting motif (G-T-K-A, residues 268-271) plays a key role in apical membrane expression. In addition, cAMP-dependent phosphorylation was found to be critical for apical targeting.


Leucocytoclastic vasculitis following influenza vaccination.
Influenza vaccinations are commonly administered and effectively prevent influenza. Most vaccine reactions are mild and self-limiting with few reported cases of vasculitis. We present a case of vasculitis post-vaccination unique for its dramatic visual presentation and rapid response to treatment with the aim to emphasise possible causation and timely treatment. This is a case of a 60-year-old man with chronic idiopathic pulmonary fibrosis, with fever, arthralgias and rash characterised by extensive erythematous plaques on his limbs and trunk 5 days after influenza vaccination. Skin biopsy revealed leucocytoclastic vasculitis. Rash and symptoms resolved 10 days after initiating treatment with oral prednisone. Influenza vaccines can potentially precipitate cutaneous vasculitis, and timely treatment reduces morbidity in the elderly.


Fucoidan modulates cytokine production and migration of THP‑1‑derived macrophages via colony‑stimulating factor‑1.
Fucoidan is known for its various biological activities, including immunomodulatory effects on immune cells. However, the effect of fucoidan on the functions of macrophages remains to be elucidated. The present study examined the effects of fucoidan on cytokine production and migration of THP‑1‑derived macrophages and its potential mechanisms. Fucoidan was added during the differentiation process of THP‑1‑derived macrophages along with lipopolysaccharide and interferon‑γ for 42 h, and then macrophages were harvested for functional assays. Fucoidan altered the morphology of THP‑1‑derived macrophages, and also attenuated their migration activity and pro‑inflammatory cytokine production. Additionally, THP‑1‑derived macrophages intensively produced colony‑stimulating factor‑1 (CSF‑1), which was significantly decreased by fucoidan. CSF‑1 neutralizing antibody attenuated the basic production level of pro‑inflammatory cytokines in macrophages. Furthermore, when recombinant human CSF‑1 was added along with fucoidan, the attenuating effects of fucoidan on migration and cytokine production were significantly reversed. In conclusion, the present study suggests that macrophages appear to be a potential target in the immunomodulatory action of fucoidan, and CSF‑1 may be involved in this modulation.


Isolation and partial characterization of an antigen-specific T-cell factor associated with the suppression of delayed type hypersensitivity.
Antigen-specific factors associated with immunosuppressive activity, released by cultured T cells from mice tolerant to the haptens trinitrophenyl, dinitrophenyl and oxazolone, were purified by hapten affinity chromatography. Their binding specificity for antigens paralleled their immunoregulatory activity. Like some immunoglobulin molecules, these factors had blocked NH2 termini and could be bound to Fc-like receptors on macrophages. However, neither immunoglobulin constant region determinants (isotypes) nor antigens encoded by the major histocompatibility complex were detected on the suppressive factors. The purified factors occurred as 68,000-dalton proteins and non-covalently linked dimers. No associated immunoglobulin light chain molecules were detected. The factors showed a marked propensity toward degradation with major breakdown products of 45,000-50,000 and 25,000-30,000 daltons. These results suggest that these molecules are the T-cell products analogous to B-cell immunoglobulin (equivalent to heavy chains) and that they may be the antigen-specific components which act in conjunction with major histocompatibility-controlled gene products to perform antigen-specific suppression.


Specific cellular and humoral immune responses induced by different antigen preparations of Echinococcus multilocularis metacestodes in patients with alveolar echinococcosis.
A specific proliferation of the peripheral blood mononuclear cells (PBMC) stimulated by antigens of Echinococcus sp. has been shown in patients with cystic as well as alveolar echinococcosis. However, the development of a major granulomatous reaction around the parasitic larvae is a characteristic feature of the local immune response to E. multilocularis while humoral immune responses seem to predominate in E. granulosus infection. The aim of this study was to analyse the specific proliferation of the PBMC from 36 patients with alveolar echinococcosis, and 23 controls, induced by a crude preparation of E. multilocularis (EmcAg) as well as by two E. multilocularis specific antigen preparations, the Em2 antigen and the protoscolex (ESAg) antigen. The significant correlation observed between the proliferation index either by Em2 and ES or by Emc suggests that both antigens account for an important part of the lymphocyte proliferative response. The strong effect of these species specific antigens on lymphocyte proliferation is confirmed by the comparison of the results obtained in this study to those obtained in a previous study of specific cellular immunity to E. granulosus antigens in patients with cystic echinococcosis. The proliferation indices were significantly elevated in all those 7 patients with a proven AE who were sero-negative using the Emc ELISA as well as in the 12 patients also seronegative, but using the Em2 ELISA. In 5 seronegative patients who had had a complete resection of the parasitic lesions two years before the lymphocyte proliferation evaluation, the PI was above the threshold value for two dilutions of EmcAg. PI under the threshold values were obtained only in patients with residual lesions. These results suggest that E. multilocularis specific antigens promote the proliferation of lymphocytes which could be TH1 cells, responsible for the intense periparasitic granulomatous reaction characteristic of alveolar echinococcosis.


An educational intervention on based information, motivation and behavior skills model and predicting breast self-examination.
Breast self-examination recommend as a breast screening method in developing countries where there are limited access to other screening methods. Therefore promoting breast self-examination required to identify effective interventions and relevant factors. This study was a quasi-experimental design carried out among 314 women 20-69 years in community cultural centers in Isfahan city, Iran. Sampling was conducted from April to 10 August, 2016. A structured questionnaire was used for data collection in before and after the educational intervention. Then participants were followed by phone call after one month for breast self-examination performance. We used descriptive statistical analysis (mean, standard division, frequency distribution), and also other statistical methods (Paired t-test, Pearson's correlation and logistic regression).The data were analyzed using SPSS version 18 with considering a significant level less than 0.05. There was significant difference between mean scores of information, motivation and behavior skill before and after intervention (P < .0001). After one month following 205 of women (72.2%) reported to perform breast self-examination. Pearson's correlation showed that breast self-examination significantly correlated with information (r = .305, p = .000), motivation (r = .128, p = .031) and behavior skills (r = .161, p = .006). Also the logistic regression results demonstrated that information (p < .001, OR = 1.071), motivation (p = .045, OR = .978) and behavior skills (p = .001, OR = 1.033) predicted breast self- examination. Considering the results of this study, it appears that the use of educational interventions based on three constructs of information, motivation and behavior skills can be used to promote breast self-examination. Moreover these results can apply to improve breast self-examination among women by health care providers.


Removal of nutrient limitations in forest gaps enhances growth rate and resistance to cavitation in subtropical canopy tree species differing in shade tolerance.
A 4-year fertilization experiment with nitrogen (N) and phosphorus (P) was carried out in natural gaps of a subtropical forest in northeastern Argentina. Saplings of six dominant canopy species differing in shade tolerance were grown in five control and five N + P fertilized gaps. Hydraulic architectural traits such as wood density, the leaf area to sapwood area ratio (LA : SA), vulnerability to cavitation (P50) and specific and leaf-specific hydraulic conductivity were measured, as well as the relative growth rate, specific leaf area (SLA) and percentage of leaf damage by insect herbivores. Plant growth rates and resistance to drought-induced embolisms increased when nutrient limitations were removed. On average, the P50 of control plants was -1.1 MPa, while the P50 of fertilized plants was -1.6 MPa. Wood density and LA : SA decreased with N + P additions. A trade-off between vulnerability to cavitation and efficiency of water transport was not observed. The relative growth rate was positively related to the total leaf surface area per plant and negatively related to LA : SA, while P50 was positively related to SLA across species and treatments. Plants with higher growth rates and higher total leaf area in fertilized plots were able to avoid hydraulic dysfunction by becoming less vulnerable to cavitation (more negative P50). Two high-light-requiring species exhibited relatively low growth rates due to heavy herbivore damage. Contrary to expectations, shade-tolerant plants with relatively high resistance to hydraulic dysfunction and reduced herbivory damage were able to grow faster. These results suggest that during the initial phase of sapling establishment in gaps, species that were less vulnerable to cavitation and exhibited reduced herbivory damage had faster realized growth rates than less shade-tolerant species with higher potential growth rates. Finally, functional relationships between hydraulic traits and growth rate across species and treatments were maintained regardless of soil nutrient status.


Taming a Vinyl Cation with a Simple Al(OTf)3 Catalyst To Promote C-C Bond Cleavage.
A detailed mechanistic investigation identified the stepwise nature of the 1,3-aryl shift, which enables our recently disclosed Al3+ -catalyzed insertion of unactivated alkynes into the sp2 -sp3 C-C bond of benzyl alcohols. The selectivity for the rearranged product was found to be induced by the continued coordination of the aluminum catalyst to the rearranging species, which is encouraged by a reversible background reaction. This participation of the catalyst beyond the ionization step is unique in the realm of carbocation driven reactions and opens up the possibility of a catalyst-induced chiral induction in the future. Furthermore, the study represents a rare example of detailed mechanistic analysis of a reaction with a product selectivity that changes with increasing conversion.


Identification of Specific Oral and Gut Pathogens in Full Thickness Colon of Colitis Patients: Implications for Colon Motility.
Impaired colon motility is one of the leading problems associated with inflammatory bowel disease (IBD). An expanding body of evidence supports the role of microbiome in normal gut function and in progression of IBD. The objective of this work is to determine whether diseased full thickness colon specimens, including the neuromuscular region (critical for colon motility function), contain specific oral and gut pathogens. In addition, we compared the differences in colon microbiome between Caucasians (CA) and African Americans (AA). Thirty-nine human full thickness colon (diseased colon and adjacent healthy colon) specimens were collected from Crohn's Colitis (CC) or Ulcerative Colitis (UC) patients while they underwent elective colon surgeries. We isolated and analyzed bacterial ribosomal RNA (rRNA) from colon specimens by amplicon sequencing of the 16S rRNA gene region. The microbiome proportions were quantified into Operational Taxonomic Units (OTUs) by analysis with Quantitative Insights Into Microbial ecology (QIIME) platform. Two hundred twenty-eight different bacterial species were identified by QIIME analysis. However, we could only decipher the species name of fifty-three bacteria. Our results show that proportion of non-detrimental bacteria in CC or UC colon samples were altered compared to adjacent healthy colon specimens. We further show, for the first time in full thickness colon specimens, that microbiome of CC and UC diseased specimens is dominated by putative oral pathogens belonging to the Phyla Firmicutes (Streptococcus, Staphylococcus, Peptostreptococcus), and Fusobacteria (Fusobacterium). In addition, we have identified patterns of differences in microbiome levels between CA and AA specimens with potential implications for health disparities research. Overall, our results suggest a significant association between oral and gut microbes in the modulation of colon motility in colitis patients.


Impact of Climate Change on Vibrio vulnificus Abundance and Exposure Risk.
Vibrio species are marine bacteria that occur in estuaries worldwide; many are virulent human pathogens with high levels of antibiotic resistance. The average annual incidence of all Vibrio infections has increased by 41% between 1996 and 2005. V. vulnificus (Vv), a species associated with shellfish and occurring in the US Southeast, has ranges of temperature (16-33 °C) and salinity (5-20 ppt) dependencies for optimal growth. Increased water temperatures caused by atmospheric warming and increased salinity gradients caused by sea level rise raise concerns for the effect of climate change on the geographic range of Vv and the potential for increased exposure risk. This research combined monthly field sampling, laboratory analysis, and modeling to identify the current occurrence of Vv in the Winyah Bay estuary (South Carolina, USA) and assess the possible effects of climate change on future geographic range and exposure risk in the estuary. Vv concentrations ranged from 0 to 58 colony forming units (CFU)/mL, salinities ranged from 0 to 28 ppt, and temperature from 18 to 31 °C. A significant empirical relationship was found between Vv concentration and salinity and temperature that fit well with published optimal ranges for growth for these environmental parameters. These results, when coupled with an existing model of future specific conductance, indicated that sea level rise has a greater impact on exposure risk than temperature increases in the estuary. Risk increased by as much as four times compared to current conditions with the largest temporally widespread increase at the most upriver site where currently there is minimal risk.


The language of dissociation.
Three case studies of inner-city elementary school children illustrate the connection between speech-language disorders and dissociative disorders in children who have known or suspected trauma histories. The role of speech language pathologists in identifying and responding to dissociative symptoms in children is explored. Lack of adequate training concerning the impact of trauma and scarce literature on the communication profiles of dissociative children contributes and greatly impacts the diagnosis, referral, and treatment of these children. The case studies demonstrate how unusual speech and language symptoms and awareness of dissociative features may aid in identifying trauma-related problems and instituting effective treatment. Grounding techniques and specific language interventions can assist children in acquiring the vocabulary needed for communicating both their daily experiences and traumatic histories. The nature of the relationship between dissociation and communication disorders is explored, and the importance of future research, interdisciplinary collaboration, and trauma training in the speech-language curriculum is emphasized.


Tissue-specific differences in human transfer RNA expression.
Over 450 transfer RNA (tRNA) genes have been annotated in the human genome. Reliable quantitation of tRNA levels in human samples using microarray methods presents a technical challenge. We have developed a microarray method to quantify tRNAs based on a fluorescent dye-labeling technique. The first-generation tRNA microarray consists of 42 probes for nuclear encoded tRNAs and 21 probes for mitochondrial encoded tRNAs. These probes cover tRNAs for all 20 amino acids and 11 isoacceptor families. Using this array, we report that the amounts of tRNA within the total cellular RNA vary widely among eight different human tissues. The brain expresses higher overall levels of nuclear encoded tRNAs than every tissue examined but one and higher levels of mitochondrial encoded tRNAs than every tissue examined. We found tissue-specific differences in the expression of individual tRNA species, and tRNAs decoding amino acids with similar chemical properties exhibited coordinated expression in distinct tissue types. Relative tRNA abundance exhibits a statistically significant correlation to the codon usage of a collection of highly expressed, tissue-specific genes in a subset of tissues or tRNA isoacceptors. Our findings demonstrate the existence of tissue-specific expression of tRNA species that strongly implicates a role for tRNA heterogeneity in regulating translation and possibly additional processes in vertebrate organisms.


Effect of indomethacin on the antihypertensive efficacy of valsartan and lisinopril: a multicentre study.
To compare the effect on antihypertensive efficacy produced by the addition of indomethacin to the angiotensin II (Ang II) antagonist, valsartan, or to the angiotensin-converting enzyme inhibitor, lisinopril, in hypertensive patients with chronic osteoarthritis. One hundred and twenty-eight patients (52 men and 76 women) aged 25-82 years (mean age 55.7 years), with diastolic blood pressure (DBP) > 100 mmHg at the end of a 2-week placebo washout period were allocated randomly to groups to receive valsartan (80-160 mg once daily) or lisinopril (10-20 mg once daily). At the end of 10 weeks of treatment, patients with DBP < 90 mmHg, while continuing to receive valsartan or lisinopril treatment, were allocated randomly to groups to receive either indomethacin (50 mg three times a day) or the corresponding placebo for 2 weeks, with a 1-week washout period between the two treatments, according to a double-blind, crossover design. After the initial washout period, patients were examined at the end of the 4th, 8th and 10th weeks of randomized treatment with valsartan and lisinopril, at the end of the first crossover period and then at the beginning and at the end of the second crossover period. At each visit, sitting and standing blood pressure were measured by standard mercury sphygmomanometer. The addition of indomethacin blunted the blood pressure-decreasing effect of both antihypertensive drugs. Although indomethacin produced greater increases in both systolic and DBP values in the lisinopril-treated patients (5.45/3.22 mmHg) than in the valsartan-treated ones (2.12/1.87 mmHg), no significant difference between the two drugs was found. From a theoretical standpoint, these findings suggest that prostaglandins may play a part in the antihypertensive action of Ang II antagonists. From a practical standpoint, hypertensive patients treated with valsartan or with lisinopril should be monitored to detect changes in blood pressure control while receiving indomethacin.


Compact continuous-wave solid-state Raman lasers at 707 and 714 nm for laser trapping and cooling of atomic strontium and radium.
Two compact laser sources at 707 and 714 nm are realized efficiently by using a diode-pumped a-cut Nd:YVO4 laser with intracavity stimulated Raman scattering and sum-frequency generation (SFG). The fundamental wave at 1342 nm is generated by the 4F3/2 → 4I13/2 transition in Nd:YVO4 crystal. The Raman Stokes waves at 1496 and 1526 nm were obtained by placing the c-axis of the Nd:YVO4 crystal along the Ng and Nm axes of an Np-cut KGW crystal, respectively. LBO crystals with critical phase matching are used to perform the intracavity SFG of fundamental and Stokes waves. At a pump power of 36 W, the maximum output powers at 707 and 714 nm can reach 2.72 and 3.14 W, corresponding to light-to-light conversion efficiencies of 7.5% and 8.7%, respectively. The developed 707 and 714 nm laser sources are practically useful in laser trapping and cooling related to atomic strontium and radium.


Engineering of monobody conjugates for human EphA2-specific optical imaging.
In a previous study, we developed an E1 monobody specific for the tumor biomarker hEphA2 [PLoS ONE (2015) 10(7): e0132976]. E1 showed potential as a molecular probe for in vitro and in vivo targeting of cancers overexpressing hEphA2. In the present study, we constructed expression vectors for E1 conjugated to optical reporters such as Renilla luciferase variant 8 (Rluc8) or enhanced green fluorescent protein (EGFP) and purified such recombinant proteins by affinity chromatography in E. coli. E1-Rluc8 and E1-EGFP specifically bound to hEphA2 in human prostate cancer PC3 cells but not in human cervical cancer HeLa cells, which express hEphA2 at high and low levels, respectively. These recombinant proteins maintained >40% activity in mouse serum at 24 h. In vivo optical imaging for 24 h did not detect E1-EGFP signals, whereas E1-Rluc8 showed tumor-specific luminescence signals in PC3 but not in HeLa xenograft mice. E1-Rluc8 signals were detected at 4 h, peaked at 12 h, and were undetectable at 24 h. These results suggest the potential of E1-Rluc8 as an EphA2-specific optical imaging agent.


Silencing of the mitochondrial ascorbate synthesizing enzyme L-galactono-1,4-lactone dehydrogenase affects plant and fruit development in tomato.
L-Galactono-1,4-lactone dehydrogenase (EC 126.96.36.199) catalyzes the last step in the main pathway of vitamin C (L-ascorbic acid) biosynthesis in higher plants. In this study, we first characterized the spatial and temporal expression of SlGalLDH in several organs of tomato (Solanum lycopersicum) plants in parallel with the ascorbate content. P(35S):Slgalldh(RNAi) silenced transgenic tomato lines were then generated using an RNAi strategy to evaluate the effect of any resulting modification of the ascorbate pool on plant and fruit development. In all P(35S):Slgalldh(RNAi) plants with reduced SlGalLDH transcript and activity, plant growth rate was decreased. Plants displaying the most severe effects (dwarf plants with no fruit) were excluded from further analysis. The most affected lines studied exhibited up to an 80% reduction in SlGalLDH activity and showed a strong reduction in leaf and fruit size, mainly as a consequence of reduced cell expansion. This was accompanied by significant changes in mitochondrial function and altered ascorbate redox state despite the fact that the total ascorbate content remained unchanged. By using a combination of transcriptomic and metabolomic approaches, we further demonstrated that several primary, like the tricarboxylic acid cycle, as well as secondary metabolic pathways related to stress response were modified in leaves and fruit of P(35S):Slgalldh(RNAi) plants. When taken together, this work confirms the complexity of ascorbate regulation and its link with plant metabolism. Moreover, it strongly suggests that, in addition to ascorbate synthesis, GalLDH could play an important role in the regulation of cell growth-related processes in plants.


Determination of methylene blue and leucomethylene blue in male and female Fischer 344 rat urine and B6C3F1 mouse urine.
A liquid chromatographic method for the determination of methylene blue and leucomethylene blue in male and female Fischer 344 rat urine and male and female B6C3F1 mouse urine was developed for use in supporting toxicokinetic studies, validated, and used to analyze urine samples for a preliminary dose level range-finding study. The method was validated for a concentration range of 10.0 to 20,000 ng/mL in urine. Samples up to 75,000 ng/mL demonstrated good recoveries when diluted into the range of the calibration curve. Six sets of calibration standards were prepared in F344 male rat urine for analysis to demonstrate reproducibility and ruggedness. The stability of sample extracts was determined under various storage conditions. During the course of analyses of the animal samples, a possible metabolic process was observed. Although Azure B is a significant impurity in methylene blue trihydrate, the amount of Azure B seen in urine samples collected from rodents dosed with methylene blue trihydrate is significantly greater than the amount seen in rodent urine spiked directly with methylene blue. This observation suggests possible N-demethylation of the methylene blue as a metabolic transformation to Azure B.


The relationship between adiposity and bone density in U.S. children and adolescents.
In adults, obesity has been associated with several health outcomes including increased bone density. Our objective was to evaluate the association between percent body fat and fat mass with bone mineral density (BMD) in a nationally representative population of children and adolescents. A total of 8,348 participants 8-18 years of age from the National Health and Nutrition Examination Survey (NHANES) 1999-2006 had whole body DXA scans performed. We conducted linear regressions to examine the relationship between percent body fat and fat mass with outcome variables of total body, pelvic and lumbar spine areal BMD (aBMD), controlling for lean body mass and assessing for gender and race/ethnicity interactions. We found evidence of gender and race/ethnicity interactions with percent body fat and total fat mass for the different BMD areas. Generally, there were decreases in total body aBMD (p<0.001) and lumbar spine aBMD (p<0.001) with increasing percent body fat and total fat mass, with less consistent patterns for pelvic aBMD. Our findings of regional differences in the relationship of adiposity to aBMD in children and adolescents with significant interactions by gender and race/ethnicity emphasizes the need for further investigations to understand the impact of adiposity on bone health outcomes.


Global HIV neurology: a comprehensive review.
: Neurological conditions associated with HIV remain major contributors to morbidity and mortality and are increasingly recognized in the aging population on long-standing combination antiretroviral therapy (cART). Importantly, growing evidence shows that the central nervous system (CNS) may serve as a reservoir for viral replication, which has major implications for HIV eradication strategies. Although there has been major progress in the last decade in our understanding of the pathogenesis, burden, and impact of neurological conditions associated with HIV infection, significant scientific gaps remain. In many resource-limited settings, antiretrovirals considered second or third line in the United States, which carry substantial neurotoxicity, remain mainstays of treatment, and patients continue to present with severe immunosuppression and CNS opportunistic infections. Despite this, increased global access to cART has coincided with an aging HIV-positive population with cognitive sequelae, cerebrovascular disease, and peripheral neuropathy. Further neurological research in low-income and middle-income countries (LMICs) is needed to address the burden of neurological complications in HIV-positive patients, particularly regarding CNS viral reservoirs and their effects on eradication.


Atopic patients with genital warts have a more protracted clinical course and a greater probability of recurrences.
The factors predicting an unfavourable response of genital warts to treatment have not been determined. The disease characteristics were recorded for 390 patients with genital warts and treated by cryotherapy. The time to achieve clearance was recorded. A personal and family history of asthma, hay fever or eczema, as well as a personal history of common warts and number of recurrences was obtained by telephone four to five years after the clinical visits. In multiple regression analysis, the number of lesions (P < 0.001), extent of the disease (P = 0.003) and personal history of atopy (P = 0.001) were found to influence the time until response to treatment. Similar results were obtained for family history of atopy. The number of sexual partners (P = 0.007), extent of the disease (P = 0.009) and personal history of atopy (P < 0.001) were the main factors influencing the probability of recurrence in multiple logistic regression. The results for family history of atopy were again similar. The study concludes that atopy is a major factor influencing the time frame of the therapeutic response and the probability of recurrence in patients with genital warts.


Fluorescence determination of glyphosate based on a DNA-templated copper nanoparticle biosensor.
A rapid and convenient fluorescence glyphosate (GLYP) biosensor was developed based on DNA-templated copper nanoparticles (DNA-CuNPs). In the absence of GLYP, the DNA-CuNPs were formed through the reduction of Cu2+ by vitamin C (Vc). The DNA-CuNPs emitted intense fluorescence at 615 nm when being excited at 340 nm. In the presence of GLYP, GLYP can strongly chelate with Cu2+ by the phosphate and carboxyl groups to decrease the amount of free Cu2+. Due to the lack of free Cu2+, DNA-CuNPs cannot be formed, which caused the fluorescence to decrease. The whole detection process of this proposed GLYP biosensor can be completed within 14 min. Titration experiments showed that this biosensor had a linear relationship for GLYP in the range 1 to 18 µM with a limit of detection (LOD) of 0.47 µM. This biosensor showed obvious selectivity among other pesticides, even between GLYP and organophosphorus pesticides. This biosensor performed well for GLYP detection in real samples with recoveries of 88.0-104.0%.


MoP Quantum Dot-Modified N,P-Carbon Nanotubes as a Multifunctional Separator Coating for High-Performance Lithium-Sulfur Batteries.
Lithium-sulfur batteries (LSBs) have the advantages of high energy density and low cost and are considered promising next-generation energy storage systems, but the shuttle effect and slow sulfur redox kinetics severely limit their practical applications. Herein, MoP quantum dot-modified N,P-doped hollow PPy substrates are adopted as separator modification coatings for LSBs. The MoP quantum dots exhibit excellent chemisorption and catalytic conversion capabilities for polysulfides, while the N,P-doped PPy substrates can provide flexible channels for Li+/electron transport and act as a physical barrier to suppress the shuttle effect. As a result, LSBs assembled with modified separators exhibit excellent rate capability (739 mAh/g at 3 C) and cycle performance (600 mAh/g at 1 C after 600 cycles, 0.052% decay per cycle). Moreover, even under a high sulfur loading of 3.68 mg/cm2, areal capacities of 3.58 and 2.92 mAh/cm2 for the 1st cycle and 110th cycle are achieved. In addition, according to density functional theory calculations, MoP quantum dots have large adsorption energy for S8 and Li2Sn, which further confirms the possibility of lowering the initial nucleation energy barrier of Li2S and helps to improve the kinetics of the subsequent Li2S reaction. This study proposes a novel method for using transition-metal phosphides as catalysts in high-performance LSBs.


[Preparation of a monoclonal antibody against polyhedrin of Ectropis obliqua nucleopolyhedrovirus].
To develop a method based on immunoreactions for detection of Ectropis obliqua Nucleopolyhedrovirus (EoNPV), the polyhedra of the virus were purified and used to immunize the mouse BALB/c. The spleen cells from the immunized mice were then fused with the myeloma cell line Sp2/0. A hybridoma cell line which can stably secrete the monoclonal antibody against EoNPV was achieved by using indirect ELISA screening and cloning methods, and was named as 7D3. Meanwhile, the polyhedrin gene was cloned from EoNPV and expressed in E. coli. Western blotting analysis showed that the monoclonal antibody prepared from 7D3 could specifically react with the recombinant polyhedrin. An indirect ELISA method based on this monoclonal antibody for detecting EoNPV in infected tea looper was developed.


p-Nitrophenol degradation via 4-nitrocatechol in Burkholderia sp. SJ98 and cloning of some of the lower pathway genes.
Microbial degradation studies have pointed toward the occurrence of two distinct PNP catabolic pathways in Gram positive and Gram negative bacteria. The former involves 4-nitrocatechol (4-NC), 1,2,4-benzenetriol (BT), and maleylacetate (MA) as major degradation intermediates, whereas the later proceeds via formation of 1,4-benzoquinone (BQ) and hydroquinone (HQ). In the present study we identified a Gram negative organism viz. Burkholderia sp. strain SJ98 that degrades PNP via 4NC, BT, and MA. A 6.89 Kb genomic DNA fragment of strain SJ98 that encompasses seven putatively identified ORFs (orfA, pnpD, pnpC, orfB, orfC, orfD, and orfE) was cloned. PnpC is benzenetriol dioxygenase belonging to the intradiol dioxygenase superfamily, whereas PnpD is identified as maleylacetate reductase, a member of the Fe-ADH superfamily showing NADH dependent reductase activity. The in vitro activity assays carried out with purified pnpC and pnpD (btd and mar) gene products transformed BT to MA and MA to beta-ketoadipate, respectively. The cloning, sequencing, and characterization of these genes along with the functional PNP degradation studies ascertained the involvement of 4-NC, BT, and MA as degradation intermediates of PNP pathway in this strain. This is one of the first conclusive reports for 4-NC and BT mediated degradation of PNP in a Gram negative organism.


Bone health in the prostate cancer patient receiving androgen deprivation therapy: a review of present and future management options.
Osteoporosis and bone fractures are frequently overlooked complications of androgen deprivation therapy in men with nonmetastatic prostate cancer. All such patients should have their bone mineral density (BMD) monitored and be offered preventive measures, such as calcium and vitamin D supplementation; patients with low BMD should be offered treatment. Several agents, including bisphosphonates, are available (although this use is currently off-label), and upcoming treatments, such as denosumab and toremifene, have shown promise in reducing fracture risk in these patients.


Liquid chromatography/tandem mass spectrometry analysis of chloramphenicol in cooked crab meat.
A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method is described for the extraction, cleanup, determination, and confirmation of chloramphenicol (CAP) in cooked crab meat. The method involves pulverization of cooked crab meat with dry ice; extraction of the CAP into ethyl acetate (EtOAc); evaporation (by N2) of the EtOAc; addition of methanol, aqueous NaCl, and heptane; extraction of the lipids into the heptane, followed by extraction of the aqueous phase with EtOAc; evaporation (by N2) of the EtOAc; dissolution into methanol-water; filtration; and separation/detection/confirmation using LC/MS/MS. Crab meat was fortified at 0.25, 0.50, and 1.0 ng/g (ppb) chloramphenicol. Average absolute recoveries were 67, 84, and 86%, respectively, with relative standard deviation values all less than 1%. Four daughter ions (m/z 152, 176, 194, and 257) were monitored off the m/z 321 precursor ion. Determination was based on a standard curve using the peak areas of the m/z 152 daughter ion (the base peak) for standard solutions equivalent to 0.10, 0.20, 0.50, and 1.0 ppb in tissue (made with control crab extract). A set of 6 matrix controls (unfortified crab meat) was also analyzed, in which no chloramphenicol was detected. For identification purposes, the ion ratios (of each daughter ion versus the base daughter ion) of the fortified crab versus those of the chloramphenicol standards agreed within 10% (relative) at fortified chloramphenicol concentrations of 0.25-1.0 ppb.


Total water, phosphorus relaxation and inter-atomic organic to inorganic interface are new determinants of trabecular bone integrity.
Bone is the living composite biomaterial having unique structural property. Presently, there is a considerable gap in our understanding of bone structure and composition in the native state, particularly with respect to the trabecular bone, which is metabolically more active than cortical bones, and is readily lost in post-menopausal osteoporosis. We used solid-state nuclear magnetic resonance (NMR) to compare trabecular bone structure and composition in the native state between normal, bone loss and bone restoration conditions in rat. Trabecular osteopenia was induced by lactation as well as prolonged estrogen deficiency (bilateral ovariectomy, Ovx). Ovx rats with established osteopenia were administered with PTH (parathyroid hormone, trabecular restoration group), and restoration was allowed to become comparable to sham Ovx (control) group using bone mineral density (BMD) and µCT determinants. We used a technique combining (1)H NMR spectroscopy with (31)P and (13)C to measure various NMR parameters described below. Our results revealed that trabecular bones had diminished total water content, inorganic phosphorus NMR relaxation time (T1) and space between the collagen and inorganic phosphorus in the osteopenic groups compared to control, and these changes were significantly reversed in the bone restoration group. Remarkably, bound water was decreased in both osteopenic and bone restoration groups compared to control. Total water and T1 correlated strongly with trabecular bone density, volume, thickness, connectivity, spacing and resistance to compression. Bound water did not correlate with any of the microarchitectural and compression parameters. We conclude that total water, T1 and atomic space between the crystal and organic surface are altered in the trabecular bones of osteopenic rats, and PTH reverses these parameters. Furthermore, from these data, it appears that total water and T1 could serve as trabecular surrogates of micro-architecture and compression strength.


Complete genome sequence analysis of duck circovirus strains from Cherry Valley duck.
To investigate molecular epidemiology of DuCV in Cherry Valley ducks in China, the complete genomes of six DuCV strains, which were detected from Cherry Valley ducks in China between 2007 and 2008, were sequenced. Sequence and phylogenetic analysis were carried out to compare these six strains with another 27 DuCV strains from Mulard duck, Muscovy duck, Pekin ducks and Mule duck. The analysis showed that the six DuCV strains exhibited typical genetic features of the family of DuCV, such as a stem-loop structure, three major open reading frames (Rep, Cap and ORF3), four intergenic repeats and the conserved motifs for rolling circle replication and for the dNTP binding domain located in the Rep protein. Phylogenetic analysis of the nucleotide sequences of the complete genome and Cap gene of these strains together with those that have been previously published demonstrated two distinct DuCV genotypes. The DuCV strains with complete genomes containing 1988 and 1989 nucleotides clustered in genotype A, whereas the strains with complete genomes containing 1991, 1992, 1995 and 1996 nucleotides lay in genotype B. The six DuCV strains from Cherry Valley ducks were divided into the two groups. The results of the study provides some insight into the variation of DuCVs in Cherry Valley ducks.


Assessment of the classical MDR phenotype in epithelial ovarian carcinoma using primary cultures: a feasibility study.
This in vitro feasibility study has assessed a number of techniques and their applicability when looking at the role of multidrug resistance (MDR) in solid tumours. Fresh tumour material was obtained from 34 patients, (11 previously treated, 23 untreated) with ovarian adenocarcinoma. Doxorubicin sensitivity was measured using the MTT assay +/- the cyclosporins, Pgp expression was assessed by immunocytochemistry with the MRK-16 MoAb and flow cytometry was used to assess intracellular drug accumulation +/- PSC 833. 85% of samples showed some evidence of modest chemosensitisation by the cyclosporins (median 1.74-fold). We saw a marked variation in the number of Pgp positive cells between patients (1-87%, median 31%). 63% of samples tested showed an enhancement of DNR accumulation in the presence of PSC 833, with a median increase of 7% (sample range 0-29%). The present study highlights some of the technical difficulties encountered when working with fresh tumour material ex vivo. We conclude that screening of patients for their suitability to enter clinical trials incorporating MDR modulating agents is technically demanding, but feasible.


Prehospital emergency physicians' experiences with advance directives in Germany: a questionnaire-based multicenter study.
Palliative medical emergencies and end-of-life decisions resulting from the exacerbation of cancer account for approximately 3% of all out-of-hospital emergency applications in Germany. Therefore, prehospital emergency physicians (EP) may be confronted with advance directives and ethical and end-of-life decisions. The purpose of the study was to identify EPs' knowledge about ethical and end-of-life decisions and their legal education and experiences concerning advance directives. Over a six-month period, we questioned all 150 EPs from three emergency medical services (Braunschweig, Göttingen und Kaiserslautern). An anonymous, self-administered questionnaire with a mixed-methods design was used. The main outcome measures included responses regarding experiences related to advance directives and end-of-life decisions in palliative care patients. For statistical assessment, EPs were divided into three categories: competent, skilled, and unskilled. A total of 104 EPs returned the questionnaire (response rate 69%). Eighty-nine percent of the respondents treated patients who had advance directives. The existence of an advance directive influenced the EP's therapy decision in about 77% of their encounters. Eighty-seven percent of the EPs reported the need for defined end-of-life care pathways and/or standard operating procedures. Eighty-two percent desired educational training concerning end-of-life decisions and the validity of advance directives. The prehospital emergency treatment of palliative care patients can be particularly challenging for any EP. A high percentage of the EPs in our study felt insecure in dealing with advance directives and ethical and end-of-life decisions in palliative care patients. Our results suggest that EPs may need more information and education about palliative medical care, legal issues and ethical and end-of-life decisions to provide adequate patient-oriented palliative care in prehospital emergency situations.


Management of Breast Cancer during the COVID-19 Pandemic.
The novel coronavirus disease (COVID-19) arises from the virus SARS-CoV-2 which is similar to the original SARS virus. The most common symptoms of the COVID-19 infection are fever, coughing and shortness of breath. According to the current data, the primary mode of transmission for the COVID-19 virus is between people through respiratory droplets and contact routes. The virus may lead to worse respiratory complications, including pneumonia, especially in older patients and patients with pre-existing illnesses, such as cancer. Cancer patients are at a significantly higher risk of getting infected with COVID-19 since their immune system can be compromised and that reality has to do with both that they have cancer and that they are on therapy for their cancer. COVID-19 crisis has impacted every aspect of the practice, including outpatient, elective, wards, emergency care, conferences, teaching and research. We should make sure cancer patients on active treatment are treated appropriately. In this review, we tried to explain how to prevent the negative effects of the COVID-19 pandemic on the diagnosis and treatment of breast cancer patients.


Coming of age: a review of embodiment and the neuroscience of semantics.
Over the last decade, there has been an increasing body of work that explores whether sensory and motor information is a necessary part of semantic representation and processing. This is the embodiment hypothesis. This paper presents a theoretical review of this work that is intended to be useful for researchers in the neurosciences and neuropsychology. Beginning with a historical perspective, relevant theories are placed on a continuum from strongly embodied to completely unembodied representations. Predictions are derived and neuroscientific and neuropsychological evidence that could support different theories is reviewed; finally, criticisms of embodiment are discussed. We conclude that strongly embodied and completely disembodied theories are not supported, and that the remaining theories agree that semantic representation involves some form of convergence zones (Damasio, 1989) and the activation of modal content. For the future, research must carefully define the boundaries of semantic processing and tackle the representation of abstract entities.


[Primary molecular changes and secondary biological problems in Bartter and Gitelman syndrome].
Bartter syndrome and Gitelman syndrome are primary hereditary diseases characterized by hypokaliemia, alkalosis, hypertrophy of the juxtaglomerular complex with secondary hyperaldoteronism and normal blood pressure. They result from molecular disorders leading to a defect of sodium reabsorption in respectively the Henle's loop and the distal convoluted tubule. Biological adaptations of downstream tubular segments, i.e. distal convoluted tubule and collecting duct, are responsible for hypokaliemia, alkalosis, renin-aldosterone activation, prostaglandins hypersecretion and dysregulation of the urinary excretion of calcium and magnesium, illustrating the close integration of the regulation of different solutes in the distal tubular structures.


The importance of solvent quality on the modification of conjugated polymer conformation and thermodynamics with illumination.
Device efficiency in key organic electronic devices such as organic photovoltaics, field transistors, and light emitting diodes has long been known to be closely tied to the conformation of the conjugated polymer chains which make up the active layers. Our previous results show that light exposure can have a profound effect on the structure and assembly of these optoelectronic materials in solution. In order to advance our understanding of the role which solvent quality plays in this phenomenon, we have further studied the modulation of these illumination dependent structural changes on the key benchmark conjugated polymers P3HT and MEH-PPV as a function of solvent quality over a wide range of polymer solubilities. Analysis of this data indicates that use of poorer conjugated polymer solvents ultimately results in larger absolute alterations to polymer conformation, denoting the crucial role which solution thermodynamics plays in this generic effect. This discovery opens the door to controlling final device morphology through careful manipulation of solvent composition during solution based device casting techniques, moving our efforts closer to the development of a powerful, non-destructive, and tunable method for light-driven control of polymer conformation in novel light-responsive organic materials.


Stochastic modeling and simulation of reaction-diffusion system with Hill function dynamics.
Stochastic simulation of reaction-diffusion systems presents great challenges for spatiotemporal biological modeling and simulation. One widely used framework for stochastic simulation of reaction-diffusion systems is reaction diffusion master equation (RDME). Previous studies have discovered that for the RDME, when discretization size approaches zero, reaction time for bimolecular reactions in high dimensional domains tends to infinity. In this paper, we demonstrate that in the 1D domain, highly nonlinear reaction dynamics given by Hill function may also have dramatic change when discretization size is smaller than a critical value. Moreover, we discuss methods to avoid this problem: smoothing over space, fixed length smoothing over space and a hybrid method. Our analysis reveals that the switch-like Hill dynamics reduces to a linear function of discretization size when the discretization size is small enough. The three proposed methods could correctly (under certain precision) simulate Hill function dynamics in the microscopic RDME system.


Choroidal epithelial cyst. Case report.
A supratentorial cyst in the leptomeninges of an 8-month-old infant was studied with the electron microscope. The lining of the cyst consisted of a single layer of peg-shaped epithelial cells rich in organelles and glycogen. Their free border had numerous microvilli but no cilia, and their basal portions rested on a basement membrane. Tight junctions and interdigitations were frequent between contiguous cells. The blood vessels were fenestrated. Since these features characterize developing choroidal epithelial cells, we felt the diagnosis of choroidal epithelial cyst was justified. Cysts lined by choroidal epithelium may continue to secrete cerebrospinal fluid after surgical extirpation when this is incomplete. Accumulation of the fluid in the partially excised cyst bed may therefore account for recurrence of symptoms.


Attenuation of oxalate-induced nephrotoxicity by eicosapentaenoate-lipoate (EPA-LA) derivative in experimental rat model.
Hyperoxaluria is one of the major risk factors for the formation of urinary calcium oxalate stones. Calcium oxalate crystals and their deposition have been implicated in inducing renal tubular damage. Lipoic acid (LA) and eicosapentaenoic acid (EPA) have been shown to ameliorate the changes associated with hyperoxaluria. This prompted us to investigate the nephroprotectant role of EPA-LA, a new derivative, in vivo in hyperoxaluric rats. Elevation in the levels of calcium, oxalate and phosphorus, the stone-forming constituents, were observed in calculogenic rats as a manifestation of crystal deposition. Tubular damage to the renal tissue was assessed byassaying the excretion of marker enzymes in the urine. Damage to the tubules was indicated by increased excretion of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transferase (gamma-GT), beta-Glucuronidase (beta-GLU) and N-Acetyl beta-D glucosaminidase (NAG). Fibrinolytic activity was found to be reduced. Administration of EPA, LA and EPA-LA reduced the tubular damage and decreased the markers of crystal deposition markedly, which was substantiated by the reduction in weight of bladder stone formed. Our results highlight that EPA-LA is the most effective drug in inhibiting stone formation and mitigating renal damage caused by oxalate toxicity, thus confirming it as a nephroprotectant. Further work in this direction is warranted to establish the therapeutic effectiveness of this new derivative.


A bright future: innovation transforming public health in Chicago.
Big cities continue to be centers for innovative solutions and services. Governments are quickly identifying opportunities to take advantage of this energy and revolutionize the means by which they deliver services to the public. The governmental public health sector is rapidly evolving in this respect, and Chicago is an emerging example of some of the changes to come. Governments are gradually adopting innovative informatics and big data tools and strategies, led by pioneering jurisdictions that are piecing together the standards, policy frameworks, and leadership structures fundamental to effective analytics use. They give an enticing glimpse of the technology's potential and a sense of the challenges that stand in the way. This is a rapidly evolving environment, and cities can work with partners to capitalize on the innovative energies of civic tech communities, health care systems, and emerging markets to introduce new methods to solve old problems.


Persistence and variation of Mangosta street rabies virus antigens during adaptation into mice.
A Mangosta street rabies virus strain antigen not shared by the challenge virus standard (CVS) was identified by counterimmunoelectrophoresis. This strain antigen persisted following nine mouse passages of the virus, during which the CVS strain antigen was not acquired. These observations suggest that the antigen composition of the two virus strains is different. Antigenic differences during the course of adaptation of Mangosta virus were also revealed by crossed serum neutralization tests. The findings are discussed in terms of the occurrence of variations in the number and localizaion of antigen sites in the virus and of the possible existence of antigenic competition by non-infective viral antigens in serum neutralization tests for rabies.


X-Linked Hypophosphatemic Rickets: Multisystemic Disorder in Children Requiring Multidisciplinary Management.
X-linked hypophosphatemic rickets (XLH) is the commonest inherited form of rickets. It is caused by an impaired regulation of fibroblast growth factor 23 (FGF23) due to a PHEX gene mutation, which leads to reduced tubular reabsorption of phosphate and renal 1α-hydroxylase activity and increased renal 24-hydroxylase activity. Hypophosphatemia associated with renal phosphate wasting, normal serum levels of calcium, parathyroid hormone, and 25-hydroxyvitamin D represents the main biochemical sign in affected patients. Patients with XLH show rickets and osteomalacia, severe deformities of the lower limbs, bone and muscular pain, stunted growth, and reduced quality of life. However, XLH is a multisystemic disorder requiring multidisciplinary approaches in specialized subdisciplines. Severe complications may occur in patients with XLH including craniosynostosis, hearing loss, progressive bone deformities, dental and periodontal recurrent lesions, and psychosocial distress. Moreover, long-term conventional treatment with active vitamin D metabolites and oral inorganic phosphate salts may cause endocrinological complications such as secondary or tertiary hyperparathyroidism, and adverse events in kidney as hypercalciuria, nephrocalcinosis, and nephrolithiasis. However, conventional treatment does not improve phosphate metabolism and it shows poor and slow effects in improving rickets lesions and linear growth. Recently, some trials of treatment with recombinant human IgG1 monoclonal antibody that targets FGF23 (burosumab) showed significant improvement of serum phosphate concentration and renal tubular reabsorption of phosphate that were associated with a rapid healing of radiologic signs of rickets, reduced muscular and osteoarticular pain, and improved physical function, being more effective for the treatment of patients with XLH in comparison with conventional therapy. Therefore, a global management of patients with XLH is strongly recommended and patients should be seen regularly by a multidisciplinary team of experts.


Specific inhibition of N-methyl-D-aspartate receptor function in rat hippocampal neurons by L-phenylalanine at concentrations observed during phenylketonuria.
Hippocampal N-methyl-D-aspartate receptors (NMDARs) are thought to be involved in the regulation of memory formation and learning. Investigation of NMDAR function during experimental conditions known to be associated with impaired cognition in vivo may provide new insights into the role of NMDARs in learning and memory. Specifically, the mechanism whereby high concentrations of L-phenylalanine (L-Phe) during phenylketonuria (>1.2 mM) cause mental retardation remains unknown. Therefore, the effects of L-Phe on NMDA-activated currents (I(NMDA)) were studied in cultured hippocampal neurons from newborn rats using the patch-clamp technique. L-Phe specifically and reversibly attenuated I(NMDA) in a concentration-dependent manner (IC(50) = 1.71 +/- 0.24 mM). In contrast, L-tyrosine (L-Tyr), an amino acid synthesized from L-Phe in normal subjects, did not significantly change I(NMDA). Although the L-Phe-I(NMDA) concentration-response relationship was independent of the concentration of NMDA, it was shifted rightward by increasing the concentration of glycine. Consistent with an effect of L-Phe on the NMDAR glycine-binding site, L-Phe (1 mM) did not attenuate I(NMDA) in the presence of D-alanine (10 microM). Furthermore, L-Phe significantly attenuated neither glutamate-activated current in the presence of MK-801, nor current activated by AMPA. The finding that L-Phe inhibits specifically NMDAR current in hippocampal neurons by competing for the glycine-binding site suggests a role for impaired NMDAR function in the development of mental retardation during phenylketonuria and accordingly an important role for NMDARs in memory formation and learning.


How can Fullerenes Help in the Treatment of Diseases? A Review Article on Pharmaceutical Usage of Fullerenes as Carriers.
Drug degradation is a process that can render pharmaceuticals inactive without causing any visible distortion. This can disrupt the therapeutic process, and on occasion, when the process produces toxic metabolites, it can have much more fatal consequences. Light is one of the most significant components that might cause deterioration, and several attempts have been made to improve and increase the practical photosensitizing of nano-scaled pharmaceuticals. Considering this, the insolubility and aggregating qualities of fullerenes have received significant attention. Fullerene is considered to have a unique carbon structure. In order to gain improved water solubility and biocompatible properties, fullerenes have been combined with water-soluble, biodegradable, and adjustable polymers. More specifically, these linkers exhibit increased tumor cell identification and greater tumor cell suppression when linked to therapeutic ligands (tumor-targeting) or stimuliresponsive polymers. According to scientific studies, fullerene-drug combinations can be used in certain complex diseases, like infectious and viral types. Several studies have combined fullerenes into nano-emulsions or liposomes for various pharmacological objectives. In the current work, fullerene/polymer nanomaterials are discussed for potential therapeutic techniques for the treatment of various diseases, particularly cancer and AIDS. According to the research studies, fullerene is a suitable element with outstanding physical and chemical properties that has a wide range of potential applications in the pharmaceutical industry, including drug delivery system design, photodynamic cancer therapy, and antioxidant therapy.


Retinoic acid inducible gene-I mediated detection of bacterial nucleic acids in human microglial cells.
Bacterial meningitis and meningoencephalitis are associated with devastating neuroinflammation. We and others have demonstrated the importance of glial cells in the initiation of immune responses to pathogens invading the central nervous system (CNS). These cells use a variety of pattern recognition receptors (PRRs) to identify common pathogen motifs and the cytosolic sensor retinoic acid inducible gene-1 (RIG-I) is known to serve as a viral PRR and initiator of interferon (IFN) responses. Intriguingly, recent evidence indicates that RIG-I also has an important role in the detection of bacterial nucleic acids, but such a role has not been investigated in glia. In this study, we have assessed whether primary or immortalized human and murine glia express RIG-I either constitutively or following stimulation with bacteria or their products by immunoblot analysis. We have used capture ELISAs and immunoblot analysis to assess human microglial interferon regulatory factor 3 (IRF3) activation and IFN production elicited by bacterial nucleic acids and novel engineered nucleic acid nanoparticles. Furthermore, we have utilized a pharmacological inhibitor of RIG-I signaling and siRNA-mediated knockdown approaches to assess the relative importance of RIG-I in such responses. We demonstrate that RIG-I is constitutively expressed by human and murine microglia and astrocytes, and is elevated following bacterial infection in a pathogen and cell type-specific manner. Additionally, surface and cytosolic PRR ligands are also sufficient to enhance RIG-I expression. Importantly, our data demonstrate that bacterial RNA and DNA both trigger RIG-I-dependent IRF3 phosphorylation and subsequent type I IFN production in human microglia. This ability has been confirmed using our nucleic acid nanoparticles where we demonstrate that both RNA- and DNA-based nanoparticles can stimulate RIG-I-dependent IFN responses in these cells. The constitutive and bacteria-induced expression of RIG-I by human glia and its ability to mediate IFN responses to bacterial RNA and DNA and nucleic acid nanoparticles raises the intriguing possibility that RIG-I may be a potential target for therapeutic intervention during bacterial infections of the CNS, and that the use of engineered nucleic acid nanoparticles that engage this sensor might be a method to achieve this goal.


Changes in plasma gonadotropins, inhibin and testosterone concentrations and testicular gonadotropin receptor mRNA expression during testicular active, regressive and recrudescent phase in the captive Japanese black bear (Ursus thibetanus japonicus).
Male Japanese black bears (Ursus thibetanus japonicus) have an explicit reproductive cycle. The objective of this study was to clarify the variation of plasma testosterone, FSH, inhibin, LH levels and testicular gonadotropin receptor mRNA expression of male bears associated with their testicular activity. Notably, this study investigated peripheral FSH concentration and localization of gonadotropin receptor mRNAs for the first time in male bears. Blood and testicular tissue samples were taken from captive, mature, male Japanese black bears during testicular active, regressive and recrudescent phases. Plasma hormone concentrations were measured by immunoassays, and gonadotropin receptor mRNA expression in the testis was investigated by in situ hybridization technique and also by real-time PCR. There were significant variations in plasma testosterone and inhibin concentrations. Changes in FSH concentration preceded these hormones with a similar tendency. Hormones started to increase during denning, and achieved the highest values at the end of the recrudescent phase for FSH and in the active phase for testosterone and inhibin. These changes in hormone concentrations were accompanied by testicular growth. In situ hybridization analysis revealed that FSH and LH receptor mRNA was possibly expressed in Sertoli cells and Leydig cells, respectively, as they are in other mammals. However, neither plasma LH concentration nor testicular gonadotropin receptor mRNA expression level varied significantly among the sampling months. These results suggest that FSH, inhibin and testosterone have roles in testicular activity in male bears. This study provides important endocrine information for comprehending seasonal reproductivity in male Japanese black bears.


Survey of resuscitation practices at emergency medical service agencies in the U.S.
Survival for out-of-hospital cardiac arrest (OHCA) varies across emergency medical service (EMS) agencies. Yet, little is known about resuscitation response and quality improvement activities at EMS agencies. We describe herein a novel survey to EMS agencies in a U.S. registry for OHCA. Using data from the Cardiac Arrest Registry to Enhance Survival (CARES), we identified 577 EMS agencies with ≥10 OHCA cases annually between 2015 and 2019 that remained active in CARES. We administered a survey to EMS directors regarding agency characteristics, cardiac arrest response, relationships with first responders and dispatchers, quality improvement activities and perceived barriers in the community. Of eligible EMS agencies, 470 (81.5%) completed the survey. The high completion rate was likely due to frequent personalized emails and phone calls, liaising with CARES state coordinators to encourage survey response, and multiple periodic drawings of an automated external defibrillator during the survey period for participating EMS agencies. The survey examined rates of resuscitation training modalities; use of resuscitation equipment and devices in the field; frequency of simulation; non-EMS stakeholder response to OHCA (dispatchers, fire, police); quality improvement; and community factors affecting bystander response to OHCA. In this study design paper on the RED-CASO survey, we provide summary data on EMS agency characteristics in the U.S. Upon linkage to CARES patient-level data, this survey will provide critical insights into 'best practices' at EMS agencies with the highest OHCA survival rates as well as provide insights into current disparities in outcomes.


Multifunctional Carbon Nanostructures for Advanced Energy Storage Applications.
Carbon nanostructures-including graphene, fullerenes, etc.-have found applications in a number of areas synergistically with a number of other materials. These multifunctional carbon nanostructures have recently attracted tremendous interest for energy storage applications due to their large aspect ratios, specific surface areas, and electrical conductivity. This succinct review aims to report on the recent advances in energy storage applications involving these multifunctional carbon nanostructures. The advanced design and testing of multifunctional carbon nanostructures for energy storage applications-specifically, electrochemical capacitors, lithium ion batteries, and fuel cells-are emphasized with comprehensive examples.


The immediate effects of intra-articular injections of osmic acid.
One hundred mg of osmic acid (with corticosteroid and lidocaine) was injected for therapeutic purposes into the knee in 10 patients suffering from various types of recalcitrant synovitis (mostly rheumatoid arthritis). The effects of this injection were followed by examination of synovial fluid, blood, and urine of these patients, collected at various intervals after intra-articular injection. As a control, a group of 3 patients (5 knees) received corticosteroid and lidocaine intra-articularly, and another group (6 patients, 7 knees) was injected with lidocaine only, both with the same total volume as the first group. Blood and urine examinations revealed essentially no effects of osmic acid, whereas in synovial fluid a strong inflammatory reaction was observed up to the second day after the injection, though the effusion soon disappeared. In a group treated with lidocaine + corticosteroid, a mild, early inflammatory reaction was noted, while lidocaine alone produced only a dilution effect, and the exudate remained relatively longer. Thus, the early local inflammatory reaction due to osmic acid is an expression of the necessary drastic effect of this beneficial therapeutic agent.


Regulation of Bax activation and apoptotic response to microtubule-damaging agents by p53 transcription-dependent and -independent pathways.
Microtubule-damaging agents (MDA) are potent antineoplastic drugs that are widely used in clinical treatment for a variety of cancers. However, the precise mechanisms underlying MDA-induced cell death are largely unknown. Here, we report that both p53 and Bax are central participants in the MDA-mediated cell death machinery in HCT116 human colon cancer cells. MDA, including epothilone B analogue (BMS-247550) and vinblastine, induced apoptosis of Bax-positive HCT116 cells in a p53-dependent manner; p53 was required for MDA-induced Bax conformational change. In response to MDA treatment, the BH3-only proapoptotic protein PUMA was up-regulated in p53-positive but not in p53 knockout HCT116 cells. Moreover, PUMA knockout HCT116 cells were resistant to MDA-induced Bax conformational change and apoptosis. In addition, introducing p53 plasmid DNA into p53-deficient HCT116 cells restored PUMA expression and apoptotic response to MDA treatment. However, ectopic expression of the p53 point mutation L22Q/W23S, but not the proline-rich domain deletion mutants 83-393 and DeltaProAE, could also sensitize p53 knockout HCT116 cells to MDA-induced Bax activation and apoptosis, although all mutants failed to restore PUMA expression. Together, these findings suggest that p53 acts upstream of Bax to promote MDA-mediated cell death in a proline-rich domain-dependent manner through both transcription-dependent (by up-regulating PUMA expression) and -independent mechanisms in human colon cancer HCT116 cells.