The allergenic activity and clinical impact of individual IgE-antibody binding molecules from indoor allergen sources.
A large number of allergens have been discovered but we know little about their potential to induce inflammation (allergenic activity) and symptoms. Nowadays, the clinical importance of allergens is determined by the frequency and intensity of their IgE antibody binding (allergenicity). This is a rather limited parameter considering the development of experimental allergology in the last 20 years and the criteria that support personalized medicine. Now it is known that some allergens, in addition to their IgE antibody binding properties, can induce inflammation through non IgE mediated pathways, which can increase their allergenic activity. There are several ways to evaluate the allergenic activity, among them the provocation tests, the demonstration of non-IgE mediated pathways of inflammation, case control studies of IgE-binding frequencies, and animal models of respiratory allergy. In this review we have explored the current status of basic and clinical research on allergenic activity of indoor allergens and confirm that, for most of them, this important property has not been investigated. However, during recent years important advances have been made in the field, and we conclude that for at least the following, allergenic activity has been demonstrated: Der p 1, Der p 2, Der p 5 and Blo t 5 from HDMs; Per a 10 from P. americana; Asp f 1, Asp f 2, Asp f 3, Asp f 4 and Asp f 6 from A. fumigatus; Mala s 8 and Mala s 13 from M. sympodialis; Alt a 1 from A. alternata; Pen c 13 from P. chrysogenum; Fel d 1 from cats; Can f 1, Can f 2, Can f 3, Can f 4 and Can f 5 from dogs; Mus m 1 from mice and Bos d 2 from cows. Defining the allergenic activity of other indoor IgE antibody binding molecules is necessary for a precision-medicine-oriented management of allergic diseases.


Minimally invasive salvage of infected breast tissue expanders: A continuous closed irrigation technique based on surface biofilm disruption.
Removal of the infected device has been the general treatment for device-associated infection in antibiotic failure. There have been anecdotal attempts to salvage infected medical devices by introducing a continuous closed irrigation system. This study examines whether continuous closed irrigation of an infected device is a successful alternative to removal in patients with recalcitrant device-associated infection. Patients who were diagnosed with recalcitrant periexpander infections during the course of expander-implant breast reconstruction from 2010 to 2018 were enrolled in a retrospective case-control study. Patients who failed antibiotics before 2017 underwent expander removal, but patients since 2017 underwent continuous closed irrigation of the infected expanders. Treatment details and clinical outcomes were compared. Rationale for expander irrigation was based on review of the current literature on biofilm research. During the study period, 21 out of the 1176 patients were diagnosed with periexpander infection recalcitrant to antibiotic therapy. Among the 21 patients, 16 underwent expander removal and five underwent expander irrigation. Clinical outcomes were comparable in terms of resolution of infection signs. The irrigation group showed fewer patients who abandoned reconstruction after infection treatment (removal = 11/16, irrigation = 1/5). Literature review revealed that expander irrigation might have induced hydrodynamic disruption of the biofilm structure. Expander irrigation was less invasive than removal and effective in suppressing severe recalcitrant periexpander infection. Continuous closed irrigation of infected expander devices may be a successful antibiofilm strategy in treating device-associated infections in select patients.


Locally advanced undifferentiated sarcomatoid carcinoma of the right maxillary sinus with PDCD6-TERT fusion: A rare case report.
Sarcomatoid carcinoma of maxillary sinus tumor is extremely rare in head and neck tumors and has poor prognosis and frequently occurs to relapse locally after surgery. We first reported a case of locally advanced undifferentiated sarcomatoid carcinoma of right maxillary sinus with PDCD6-TERT fusion gene. The patient with a previous history of moderate alcohol drinking and smoking. The patient underwent surgical treatment. The tumor tissue using NGS analysis, no other driver gene mutations, and the PD-L1 IHC was negative. He received TPF regimen induction chemotherapy combined with anti-PD1 inhibitor and radiotherapy. The effect of treatment was good.


Use of ultra pure nitric oxide generated by the reduction of nitrogen dioxide to reverse pulmonary hypertension in hypoxemic swine.
Inhaled nitric oxide (NO) has the capacity to selectively dilate pulmonary blood vessels, and thus enhance the matching of ventilation and perfusion, improve oxygenation and decrease pulmonary hypertension. However, existing approaches for the administration of inhaled NO are associated with the co-delivery of potentially toxic concentrations of nitrogen dioxide (NO2) due to the oxidation of NO in oxygen rich environments. We tested the ability of a novel methodology for generating highly purified NO through the reduction of NO2 by ascorbic acid to reverse pulmonary hypertension. In vitro testing demonstrated that the NO output of the novel device is ultrapure and free of NO2. An in vivo hypoxemic swine model of pulmonary hypertension was used to examine the dose response to NO in terms of pulmonary pressures and pulmonary vascular resistance. Pulmonary hypertension was induced by lowering inspired oxygen to 15% prior to treatment with inhaled ultra purified NO (1, 5, 20, and 80PPM). Hypoxemia increased mean pulmonary artery pressures and pulmonary vascular resistance. Inhaled ultra purified NO doses (down to 1PPM) show a marked reduction of hypoxemia-induced pulmonary vascular resistance. These experiments demonstrate a simple and robust method to generate purified inhaled NO that is devoid of NO2 and capable of reversing hypoxemia induced pulmonary hypertension.


Glycemic variability indices can be used to diagnose islet transplantation success in type 1 diabetic patients.
High glycemic variability (GV) is the major indication for islet transplantation (IT) in patients with type 1 diabetes (T1D). The actual criteria used to assess graft function do not consider GV improvement. Our study aimed to describe GV indices' evolution in T1D patients who benefited from IT during the TRIMECO trial and to evaluate if thresholds might be defined to diagnose IT success. We collected data from 29 patients of the TRIMECO trial, a clinical trial (NCT01148680) comparing the metabolic efficacy of IT with intensive insulin therapy. Based on CGM data, we analyzed mean glucose level and four GV indices (standard deviation, coefficient of variation, MAGE and GVP) before (M0) and 6 months (M6) after IT. Each GV index decreased significantly between M0 and M6: SD 53.9 mg/dL [44.6-61.5] versus 20.1 mg/dL [13.5-24.3]; CV 35.2% [30.6-37.7] versus 17.3% [12.0-20.5]; MAGE 134.9 mg/dl [111.2-155.8] versus 51.9 mg/dL [32.4-62.4]; GVP 35.3% [24.9-47.2] versus 12.2% [6.2-18.8] (p ≤ 0.0001). Thresholds diagnosing IT success at 6 months post-transplant were an SD at 22.76 mg/dL (sensibility 88.89%, specificity 80.00%), a CV at 17.47% (sensibility 88.89%, specificity 70.00%), a MAGE at 54.81 mg/dL (sensibility 88.89%, specificity 80.00%) and a GVP at 12.27% (sensibility 88.89%, specificity 70.00%). This study confirms a positive impact of IT on GV. The proposed thresholds allow an easy evaluation of IT success using only CGM data and may be a clinical tool for the follow-up of transplanted patients.


Nitric oxide enhances aluminum tolerance by affecting cell wall polysaccharides in rice roots.
Nitric oxide (NO) is a key signal molecule involved in many physiological processes in plants. To study the mechanisms of exogenous NO contribution to alleviate the aluminum (Al) toxicity, roots of rice (Oryza sativa) seedlings pre-treated with sodium nitroprusside (SNP, a NO donor) were used to investigate the effect of Al in this study. Results indicated that NO alleviated the lipid peroxidation induced by Al and promoted the root elongation, whereas butylated hydroxyanisole (BHA), an efficient lipophilic antioxidant, alleviated the lipid peroxidation only. Rice seedling roots pre-treated with SNP followed by Al treatment had lower contents of pectin and hemicellulose, lower Al accumulation in root tips and cell walls, higher degree of methylation of pectin and lower wall Al-binding capacity than the roots with Al treatment only. Therefore, the decreased Al accumulation in the cell walls of rice roots is likely to be the reason for the NO-induced increase of Al tolerance in rice, and it seems that exogenous NO enhanced Al tolerance in rice roots by decreasing the contents of pectin and hemicellulose, increasing the degree of methylation of pectin, and decreasing Al accumulation in root cell walls.


Characterization of a Novel Mannose Isomerase from Stenotrophomonas rhizophila and Identification of Its Possible Catalytic Residues.
D-Mannose has great value in the treatment of chronic diseases. D-Mannose isomerase can catalyze the bioconversion of D-fructose to D-mannose. Therefore, a novel D-mannose isomerase gene (Strh-MIase) from Stenotrophomonas rhizophila strain IS26 was expressed, purified, and characterized for the industrial production of D-mannose. The specific activities of the Strh-MIase for D-mannose and D-fructose were 437.5 ± 0.8 U/mg and 267.2 ± 0.7 U/mg. Its optimal temperature and pH were 50 °C and 7.0. The enzymatic bioconversion produced 25 g/L D-mannose from concentration D-fructose (100 g/L) in 6 h by recombinant Strh-MIase, resulting in a final yield of 25%. Sodium phosphate inhibition has little influence on D-mannose production when a high concentration of D-fructose is used as substrate. We demonstrate that the metal ions improve the efficiency of D-mannose isomerase because of the enhancement of its thermostability. Moreover, the possible catalytic residues of Strh-MIase were identified by site-directed mutagenesis.


Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is life-saving for severe hematological conditions. However, its outcomes need further improvement, and co-infusion of mesenchymal stem cells (MSCs) may show promise. A growing body of research on this subject exists, while the results of different trials are conflicting. A systematic review and meta-analysis is needed to appraise the real efficacy and safety of MSC co-transplantation in allo-HSCT. Studies comparing MSC co-transplantation in allo-HSCT with allo-HSCT alone were searched in six medical databases from inception to June 10, 2020. The primary outcomes were engraftment and graft-versus-host disease (aGVHD and cGVHD, respectively). Other outcomes included overall survival (OS), relapse rate (RR), non-relapse mortality (NRM), and immune reconstitution. Information was independently extracted by two investigators. Methodological quality was assessed using the Cochrane Collaboration tool. Meta-analysis was performed using RevMan 5.4. Six randomized controlled trials (RCTs) and 13 non-randomized controlled trials (nRCTs) were included. MSC co-infusion resulted in shorter times to neutrophil engraftment (RCTs: standardized mean difference (SMD) - 1.20, p = 0.04; nRCTs: SMD - 0.54, p = 0.04) and platelet engraftment (RCTs: SMD - 0.60, p = 0.04; nRCTs: SMD - 0.70, p = 0.01), a lower risk of cGVHD (RCTs: risk ratio (RR) 0.53, p = 0.01; nRCTs: RR 0.50, p < 0.01), and a slightly positive trend towards reducing the risk of aGVHD and NRM, without affecting RR and OS. Subgroup analyses revealed that when MSCs were co-transplanted, children and adolescents, and patients receiving human leukocyte antigen (HLA)-nonidentical HSCT showed improvements in engraftment and incidence of GVHD and NRM; adults and patients who received HLA-identical HSCT had lower cGVHD; patients with malignancies exhibited improvements in GVHD and NRM incidence; and patients with non-malignancies experienced accelerated engraftment. Notably, a reduced OS was observed in patients with hematological malignancies undergoing HLA-identical HSCT. MSC co-infusion generally improved engraftment and reduced cGVHD, without increasing mortality or relapse. Regarding aGVHD and NRM, the effects of MSCs were not quite significant. Specifically, our data support the utilization of MSC co-transplantation in children and young individuals with HLA-nonidentical HSCT, but not in adult patients with hematological malignancies undergoing HLA-identical HSCT.


Charlson Comorbidity Index Is Related to Organ Damage in Systemic Lupus Erythematosus: Data from KORean lupus Network (KORNET) Registry.
The aim of this study was to identify whether comorbidity status is associated with organ damage in patients with systemic lupus erythematosus (SLE). A total of 502 patients with SLE enrolled in the KORean lupus Network were consecutively recruited. Data included demographics, age-adjusted Charlson Comorbidity Index (CCIa), disease activity indexes, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), the Medical Outcomes Study Short Form-36 health survey (SF-36) score, and the Beck Depression Inventory (BDI) score. Of the total patients, 21.1% (n = 106) experienced organ damage (SDI ≥ 1). Univariate correlation analysis revealed that SDI was not statistically correlated with any clinical variables (correlation coefficient r < 0.3 of all). There were significant differences in the BDI, mental component score of the SF-36, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), CCIa, C-reactive protein, and mean dose of corticosteroid between non-damage (SDI = 0) and damage (SDI ≥ 1) groups. The presence of damage to at least 1 organ in patients with SLE was found to be closely related with higher CCIa, higher SLEDAI, and mean dose of corticosteroid (OR 1.884, 95% CI 1.372-2.586, p < 0.001; OR 1.114, 95% CI 1.041-1.192, p = 0.002; OR 1.036, 95% CI 1.004-1.068, p = 0.026; respectively) in binary logistic regression analysis. This study suggests that organ damage as assessed by the SDI in Korean patients with SLE is related to comorbidities together with disease activity and corticosteroid exposure.


Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans.
Preventing germline stem cell proliferation extends lifespan in nematodes and flies. So far, studies on germline-longevity signaling have focused on daf-16/FOXO and daf-12/VDR. Here, we report on NHR-80/HNF4, a nuclear receptor that specifically mediates longevity induced by depletion of the germ line through a mechanism that implicates fatty acid monodesaturation. nhr-80/HNF4 is induced in animals lacking a germ line and is specifically required for their extended longevity. Overexpressing nhr-80/HNF4 increases the lifespan of germline-less animals. This lifespan extension can occur in the absence of daf-16/FOXO but requires the presence of the nuclear receptor DAF-12/VDR. We show that the fatty acid desaturase, FAT-6/SCD1, is a key target of NHR-80/HNF4 and promotes germline-longevity by desaturating stearic acid to oleic acid (OA). We find that NHR-80/HNF4 and OA must work in concert to promote longevity. Taken together, our data indicate that the NHR-80 pathway participates in the mechanism of longevity extension through depletion of the germ line. We identify fat-6 and OA as essential downstream elements although other targets must also be present. Thus, NHR-80 links fatty acid desaturation to lifespan extension through germline ablation in a daf-16/FOXO independent manner.


Valuing ecosystem services of sustainable urban drainage systems: A discrete choice experiment to elicit preferences and willingness to pay.
Sustainable urban drainage systems (SUDS) address stormwater management issues and provide a variety of benefits to residents in terms of ecosystem services. Economically valuing the non-monetary ecosystem services often proves difficult, as limited markets for SUDS measures exist, rendering revealed preference methods inapplicable. We conducted a discrete choice experiment to elicit the preferences and willingness to pay of the ecosystem services of SUDS in Berlin, Germany. Results from a latent class model indicated how residents weigh the different ecosystem services and that they garner the highest utility in improved water quality from reduced fish die-offs. With these results, practitioners and policy makers can better prioritize measures and make strong economic arguments for SUDS implementation and increasing the provision of ecosystem services.


Serious menstrual bleeding associated with use of TNF alpha blocker: two cases.
Menstrual disorders associated with the use of TNF alpha blocker have been rarely reported. Herein, we reported two cases aged 31 and 41, presenting with excessive menstrual bleeding occured after adalimumab administration which was subsequently discontinued.


Using children's humor to clarify the relationship between linguistic awareness and early reading ability.
This study uses linguistic humor to show that an awareness of only those linguistic units transcribed by the orthography bears a special relation to early reading success. The subjects were 48 second-grade children tested on ten "phoneme/morpheme" riddles which manipulate phonemes and bound morphemes and ten "control" riddles which depend on awareness of other aspects of linguistic structure and "common sense". Each child also received the Word Identification and Word Attack subtests of the Woodcock Reading Mastery Tests and the Peabody Picture Vocabulary Test. Reading ability was significantly related to correct resolution of the phoneme/morpheme riddles but not to correct resolution of the control riddles. PPVT scores were significantly related to performance on both types of riddles but not to reading ability. Thus, while IQ is related to the resolution of riddles in general, reading ability has a special relation to riddles which manipulate phonemes and morphemes, consistent with the morphophonological nature of English orthography.


[Kinetics of the reactions of glycosylation in the biosynthesis of glycoproteins: ordered bi-bi mechanism of glycosyltransferases and cooperativity].
Glycosyl-transferases respond to a Bi-Bi ordered mechanism, with two substrates and two products, completed by positive or negative cooperativity in relation to substrates concentration.


Both network architecture and micro cracks effects on lacuno-canalicular liquid flow efficiency within the context of multiphysics approach for bone remodeling.
When physical forces are applied to bone, its mechanical adaptive behaviors change according to the microarchitecture configuration. This leads to changes in biological and physical thresholds in the remodeling cell population, involving sensor cells (osteocytes) interacting with each other and changes in osteocyte shape due to variation in lacunar shape. The resulting alterations in fluid flow leads to changes in the membrane electrical potential and shear stress. Eventual creation of microcracks, may lead in turn to modify cell activity. In contrast, the redundancy in the lacuno canalicular network (LCN) interconnectivity maintains partial flow. Our goal was to investigate the role of fluid flow in LCN by proposing a model of electro-mechanical energy spread through inhomogeneous microarchitectures. We focused on mechano-sensitivity to changes in load-induced flow impacted by neighboring micro cracks and quantifying its critical role in changing, velocity, shear stress and orientation of liquid mass transportation from one cell to another. To enhance the concept of intricacy LCN micro-structure to fluid flow, we provide a new combined effects factor considered as osteocytes sensor efficiency. We customized an influence function for each osteocyte, coupling: in one hand, the spatial distribution within remodeling influence areas, conducting a significant fluid spread, leading hydro-dynamic behavior and impacted further by presence of micro cracks and; in other hand, the fluid electro kinetic behavior. As an attempt to fill the limitations stated by many of the recent studies, we reveal in numerical simulation, some results which cannot be measured in vitro/in vivo studies. Numerical calculations were performed in order to evaluate, among many others, how liquid flow conditions changes between lacunas, how the orientation and the magnitude of the governing flow in LCN can regulate osteocytes efficiency. In addition to be regulated by osteocytes, a direct effects of fluid flow are also acting on osteoblast activity. In summary, this new approach considers mechano-sensitivity in relation to liquid flow dynamic and suggests additional pathway for Osseo integration via osteoblast regulation. However, this novel modeling approach may help improve the mapping and design bone scaffolds and/or selection of scaffold implantation regions.


Complications after oral surgery in patients with congenital or drug-induced bleeding disorders.
Bleeding disorders (BD) can cause significant problems during or after surgical procedures of the oral cavity. The aim of this study was to explore the risk of bleeding following oral surgery in patients with BD. The medical records of all BD patients referred to the department of cranio- and maxillofacial surgery were reviewed. Ninety-five patients (26 inherent BD, 69 taking antithrombotic drugs) were reviewed for this study. Interestingly, patients taking oral anticoagulants presented more bleeding complications than patients with inherent BD. During simple tooth extraction procedures, patients taking antithrombotic drugs had a higher risk of bleeding than patients with inherent BD. The currently available treatment protocols for surgical treatment of dental patients with inherent BD suffice. However, our data indicates that there is still a need for clear guidelines for the treatment of patients taking antithrombotic drugs, especially phenprocoumon.


Pathologic complete response of hepatoid adenocarcinoma of the stomach after chemo-immunotherapy: A rare case report and literature review.
Hepatoid adenocarcinoma of the stomach (HAS) is a highly malignant subtype of gastric carcinoma with specific clinicopathological features and extremely poor prognosis. We present an exceedingly rare case of complete response after chemo-immunotherapy. A 48-year-old woman with highly elevated serum alpha-fetoprotein (AFP) level was found to have HAS verified by pathological examination based on gastroscopy. Computed tomography scan was done and TNM staging of the tumor was T4aN3aMx. Programmed cell death ligand-1 (PD-L1) immunohistochemistry was performed, revealing a negative PD-L1 expression. Chemo-immunotherapy including oxaliplatin plus S-1 and PD-1 inhibitor terelizumab was given to this patient for 2 months until the serum AFP level decreased from 748.5 to 12.9 ng/mL and the tumor shrank. D2 radical gastrectomy was then performed and histopathology of the resected specimen revealed that the cancerous cells had disappeared. Pathologic complete response (pCR) was achieved and no evidence of recurrence has been found after 1 year of follow-up. We, for the first time, reported an HAS patient with negative PD-L1 expression who achieved pCR from the combined chemotherapy and immunotherapy. Although no consensus has been reached regarding the therapy, it might provide a potential effective management strategy for HAS patient.


Silver-coated (Agluna®) tumour prostheses can be a protective factor against infection in high risk failure patients.
Endoprostheses in the treatment of extremity sarcomas are associated with late complications including periprosthetic infection. This study analysed the incidence of infection in patients undergoing endoprosthetic replacement (EPR) with a silver-coated prosthesis. The study comprised a retrospective single centre study of 394 consecutive patients treated with resection and EPR for primary extremity bone tumours. 89 patients at risk for infection were treated with a silver-coated (Agluna®) EPR (22.6%), compared to 305 patients treated with a non-silver EPR (77.4%). The incidence of periprosthetic infection, requiring revision as the primary endpoint was 34/394 (8.6%); 11 patients (12.4%) in the silver group and 23 patients (7.5%) in the non-silver group (p = 0.154). Overall implant survival was 90.9% and 95.3% at 1-year and 86.8% and 91.8% at 5-years in the silver-coated and non-silver coated group, respectively (p = 0.193). Infection was treated in the silver group by washout of the prosthesis in 2/11, debridement and implant retention (DAIR) in 1/11 and single-stage revision in 1/11, and in the non-silver group by washout in 1/23 or DAIR in 2/23. Two-stage revision was successful in 2/11in the silver group, and in 11/23 in the non-silver group. Amputation was required in 4/11 in the silver group and 9/23 in the non-silver group. One patient in the silver group died due to disease with an infected EPR. Silver-coated prostheses in high risk patients show similar infection free survival as non-silver coated prosthesis in standard sites in primary bone tumours of the extremities.


Chronic pseudophakic endophthalmitis versus saccular endophthalmitis.
A retrospective survey of 1456 cataract operations done at one hospital from 1991 to 1994 found three cases of chronic pseudophakic endophthalmitis. In two of these cases and one referred from another center, microbiological studies from aqueous humor, capsular bag, and vitreous humor were performed using an identical technique. The histopathology in the three cases showed the presence of microorganisms in the capsular wall, although the cultures were only positive in one case (for corynebacterium species).


Outside of the intensive care unit: the safety and effectiveness of an insulin-dextrose infusion protocol.
A review of patients who were on an insulin-dextrose (I-D) infusion protocol in general hospital wards over a 6-month period was conducted to compare glycaemic control before, during and following I-D infusion. Among the 34 cases identified, blood glucose levels during the period of I-D infusion were significantly better than those before or after I-D infusion. This I-D infusion protocol was shown to be effective and safe in maintaining good glycaemic control for patients outside intensive care unit.


T cells are unresponsive to transgenic MHC class II molecules expressed on pancreatic beta cells.
It has been proposed that the autoimmune attack on the pancreatic beta cells leading to insulin-dependent diabetes mellitus can be caused by the expression of MHC class II molecules on the beta cells. Transgenic mice expressing normal levels of allogeneic MHC class II Ak on the beta-cell surface (IP-Ak) do not develop either insulitis or diabetes, yet these mice are not tolerant to Ak when expressed on normal antigen-presenting cells. The authors have stimulated T cells from IP-Ak mice in vitro with Ak-expressing beta cells. Mice were also primed in vivo in order to facilitate the antiallogeneic response. The authors found that neither IP-Ak positive nor IP-Ak negative mice were able to respond to Ak-expressing beta cells, and that in vivo priming does not overcome this inability. They suggest that beta cells do not act as antigen-presenting cells, probably due to inability of delivering costimulatory signals. This strengthens the notion that MHC class II expression per se is not sufficient to induce an autoimmune attack on the beta cells.


Changes in pH and dissolved inorganic carbon in water affect the growth, saxitoxins production and toxicity of the cyanobacterium Raphidiopsis raciborskii ITEP-A1.
Raphidiopsis raciborskii is a widely distributed, potentially toxic cyanobacterium described as a tropical-subtropical species. However, its occurrence in temperate regions has been expanding. Understanding the environmental factors underlying the expansion and colonization success of Raphidiopsis has been the object of numerous studies. However, less is known regarding its responses to pH and inorganic carbon in water. Thus, the aim of the present study was to investigate the effects of changes in pH and dissolved inorganic carbon on growth and saxitoxins production in the strain R. raciborskii ITEP-A1. We incubated batch cultures with different unbuffered and buffered pH (neutral-acid and alkaline) and inorganic carbon availability (CO2-rich air bubbling and the addition of NaHCO3) to assess the effect of these factors on the growth, toxin production as well as saxitoxins composition of the cyanobacterium. The carbon concentrating mechanism (CCM) system of ITEP-A1 was also characterized by an in silico analysis of its previously sequenced genome. The growth and saxitoxins production of R. raciborskii were affected. The addition of sodium bicarbonate and air bubbling enhanced the growth of the cyanobacterium in alkaline pH. In contrast, saxitoxins production and relative toxicity were decreased. Moreover, significant changes in the cellular composition of saxitoxins were strongly related to pH changes. ITEP-A1 potentially expresses the low-flux bicarbonate transporter BicA, an efficient CCM which uptakes most of its carbon from HCO3-. Hence, increasing the diffusion of CO2 in alkaline eutrophic lakes is likely to increase R. raciborskii dominance, but produce less toxic blooms.


Eliciting Patient Experiences About Their Care After Cardiac Surgery.
Experience surveys provide an opportunity for patients to give their feedback about health care processes and services. Unfortunately, the most current surveys have been designed as "one-size fits-all" tools, and thus, do not take into account items pertaining to specific clinical groups. The objective of this study was to gain a deeper understanding of the specific aspects of care deemed important to cardiac surgery patients. Individual semistructured telephone interviews were conducted with a cohort of patients who had previously underwent cardiac surgery. Interviews were recorded and transcribed. Using a phenomenological approach, a thematic analysis was used to generate a list of themes and subthemes deemed important by participants. Eight interviews were conducted in July and August 2019. Participants included 7 men and 1 woman, ranging from 55 to 84 years of age. Five key themes emerged from the data: (1) overall experience; (2) communication; (3) the physical hospital environment; (4) care needs and ongoing management; and (5) person-centred care. Our interviews revealed that participants had many overwhelmingly positive experiences with care. Through reports of their own experiences, participants highlighted important areas that might be improved. Our results confirm and expand upon those highlighted in quantitative research by our group. Findings and knowledge derived from this study might be used to inform quality improvement activities. These might also play a key role in the development of a patient experience survey, specifically for those who undergo cardiac surgery; thus addressing a potential limitation of surveys currently in use.


Photochemically induced colonic ischaemic lesions: a new model of ischaemic colitis in rats.
Recent clinical studies suggest that ischaemic colitis is caused by a microcirculatory disturbance that involves thrombosis of the colon. To establish a new model of photochemically induced ischaemic colitis in rats. Thirty male Wistar rats were anaesthetised with amobarbital, the femoral veins were cannulated and laparotomies were performed. The serosal surface of the proximal colon was irradiated by using a krypton laser (wavelength 568 nm, 20 mW) for four minutes. An intravenous infusion of a photosensitising dye, rose bengal (20 mg/kg body weight), was administered over 90 seconds, beginning at the start of irradiation. Rats were killed immediately (n = 4), 12 hours (n = 2), 24 hours (n = 10), three days (n = 4), seven days (n = 4), 14 days (n = 2), or 28 days (n = 2) after irradiation. Two control rats received laser irradiation without dye infusion. Specimens of the irradiated sites were examined by using histopathology. Localised ulcers of the colon were present in rats killed at 12 hours, 24 hours, three days, and seven days after irradiation. Microscopy findings were consistent with the features of human ischaemic colitis. Reproducible ulcerative lesions were produced by photothrombosis of microvessels in the colon. This model may be useful for further investigation of the pathophysiology of ischaemic colitis.


Production systems--an example from Brazil.
Important information about the Brazilian agribusiness, population and economy are presented in this paper, as well as details of beef production, market, industry and production system, to inform people involved in meat industry about details on demography, production, economy and production systems of a country that is the largest player in beef exports in the world and that uses, mostly, Bos indicus based bovine population, reared under pasture conditions, for meat production purposes. Herd size, genetic evaluation programs, quantity of beef produced and market is informed, with figures about the global and major players' production. Some discussion related to environmental concerns, methane emission and carbon fixation is also presented, as well as meat quality. Meat quality of fed animals is also compared with beef from animals that are raised in pasture conditions.


Th-1, Th-2, Th-9, Th-17, Th-22 type cytokine concentrations of critical COVID-19 patients after treatment with Remdesivir.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the world causing a pandemic known as coronavirus disease 2019 (COVID-19). Cytokine storm was directly correlated with severity of COVID-19 syndromes. We evaluated the levels of 13 cytokines in ICU hospitalized COVID-19 patients (n = 29) before, and after treatment with Remdesivir as well as in healthy controls (n = 29). Blood samples were obtained from ICU patients during ICU admission (before treatment) and 5 days after treatment with Remdesivir. A group of 29 age- and gender-matched healthy controls was also studied. Cytokine levels were evaluated by multiplex immunoassay method using a fluorescence labeled cytokine panel. In comparison to cytokine levels measured at ICU admission, serum levels were reduced of IL-6 (134.75 pg/mL vs. 20.73 pg/mL, P < 0.0001), TNF-α (121.67 pg/mL vs. 10.15 pg/mL, P < 0.0001) and IFN-γ (29.69 pg/mL vs. 22.27 pg/mL, P = 0.005), whereas serum level was increased of IL-4 (8.47 pg/mL vs. 12.44 pg/mL, P = 0.002) within 5 days after Remdesivir treatment. Comparing with before treatment, Remdesivir significantly reduced the levels of inflammatory (258.98 pg/mL vs. 37.43 pg/mL, P < 0.0001), Th1-type (31.24 pg/mL vs. 24.46 pg/mL, P = 0.007), and Th17-type (36.79 pg/mL vs. 26.22 pg/mL, P < 0.0001) cytokines in critical COVID-19 patients. However, after Remdesivir treatment, the concentrations of Th2-type cytokines were significantly higher than before treatment (52.69 pg/mL vs. 37.09 pg/mL, P < 0.0001). In conclusion, Remdesivir led to decrease levels of Th1-type and Th17-type cytokines and increase Th2-type cytokines in critical COVID-19 patients 5 days after treatment.


Removal of selected pharmaceuticals from aqueous solution using magnetic chitosan: sorption behavior and mechanism.
A novel-modified magnetic chitosan adsorbent was used to remove selected pharmaceuticals, i.e., diclofenac (DCF) and clofibric acid (CA) and carbamazepine (CBZ), from aqueous solutions. The characterization of magnetic chitosan was achieved by scanning electron and transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, vibrating sample magnetometer, and nitrogen sorption analysis. The magnetic chitosan had effective sorption affinity for DCF and CA but no sorption of CBZ was observed. The sorption capacities of CA and DCF in the individual solutions were 191.2 and 57.5 mg/g, respectively. While in mixed solution, DCF showed higher sorption affinity. Sorption kinetics indicated a quick equilibrium reached within 2 min. Lower solution pH values were found to be advantageous for the adsorption process. The sorption efficacy of CA declined significantly with increasing inorganic salt concentration. However, sorption performance of DCF was stable under different ionic strength conditions.


Metabolism of 3-hydroxychrysene by rat liver microsomal preparations.
3-Hydroxychrysene, a metabolite of the polycyclic aromatic hydrocarbon (PAH) chrysene, was metabolised by rat liver microsomal preparations obtained from Arochlor 1254-pretreated rats. Eight major metabolites were isolated by high performance liquid chromatography and characterised by u.v. spectroscopy and a variety of mass spectrometric techniques. The metabolites were unambiguously identified as 9-hydroxy-trans-1,2-dihydroxy-1,2-dihydrochrysene and 9-hydroxy-r-1,t-2,t-3,c-4-tetrahydroxy-1,2,3,4-tetrahydrochrysene and tentatively identified as 3-hydroxy-trans-5,6-dihydroxy-5,6-dihydrochrysene (since chrysene is a symmetrical molecule the 3- and 9-positions are equivalent), 9-hydroxy-trans-3,4-dihydroxy-3,4-dihydrochrysene, 1,2,3-trihydroxy-1,2,3,4-tetrahydrochrysene, an oxidised phenol and two diphenols. These results indicate that 3-hydroxychrysene can be further metabolised via a number of different pathways including those involving the formation of phenol- and triol-epoxides.


Dose-response curve of glutamate applied by superfusion to crayfish muscle synapses.
Single muscle fibers were space clamped to a membrane potential of -75 to -80 mV, and the synaptic currents elicited by L-glutamate (gEPSCs) were recorded. The bathing solutions flowing across the fibers at high speed could be switched rapidly and repeatedly through valves actuated by solenoids. Glutamate solutions were applied for periods of 7 s or 1 s, and the responses to repeated applications were averaged. For glutamate concentrations of 10-50 mumol/l, applied for 7 s, the gEPSCs reached a steady state. In this concentration range the amplitude of the gEPSC rose steeply proportional to the power n=2.5 to n=6 (average of 12 experiments n=4.0) of the glutamate concentration. At higher concentrations, after rising for a few seconds the gEPSC was reduced by desensitization. At 500 mumol/l glutamate complete desensitization was reached with an approximate time constant of less than 1 s. The glutamate concentration that elicited a half maximum gEPSC was K=70 mumol/l. If glutamate was superfused only for 1 s, similar dose-response curves were observed. In these experiments n was between 4 and 6. The results obtained by superfusion agree quantitatively with those published for electrophoretic applications.


The role of PACAP in gonadotropic hormone secretion at hypothalamic and pituitary levels.
The presence of pituitary adenylate cyclase-activating polypeptide (PACAP) and its mRNAin the three levels of the hypothalamo-hypophyseal-ovarian axis was previously demonstrated using immunohistochemistry, in situ hybridization, and reverse transcriptase polymerase chain reaction (RT-PCR). In the hypothalamus, PACAP is present in neuroendocrine effector cells and in the median eminence. In the anterior pituitary and ovary, PACAP is transiently present during the proestrous stage of the estrous cycle. In the pituitary, PACAP was observed in gonadotropes. In the ovary, PACAP was demonstrated in the granulosa cells of the preovulatory ovarian follicles. The effect of PACAP on luteinizing hormone (LH) secretion was demonstrated in in vivo and in vitro models. In our work we have studied the role of PACAP in gonadotropic hormone secretion at hypothalamic and pituitary levels. At the hypothalamic level, PACAP, administered intracerebroventricularly to female rats before the critical period of the proestrus stage, can inhibit LH release and ovulation. Its inhibiting effect is mediated through corticotropin-releasing factor (CRF) and endogenous opioids. PACAP administered to neonatal female rats delayed the onset of puberty by influencing the luteinizing hormone-releasing hormone (LHRH) neuronal system. In the pituitary gland, the release of PACAP depended on the stage of the estrous cycle and on the time of day the animals were sacrificed. On the day of proestrus, the number of PACAP-releasing cells showed a diurnal change with two peaks (in the morning and in the evening). The peak was much higher in the evening at the end of the LH surge than in the morning.


Comparison of aflatoxin B1-DNA binding and glutathione conjugate formation by liver preparations from rats of different ages.
The capability of the newborn rat liver to detoxify aflatoxin B1 (AFB1), a potent hepatocarcinogen is not well understood. Our present results show that immature rats are deficient in the hepatic key factors involved in biotransformation of AFB1. The activities of cytosolic glutathione S-transferases and microsomal cytochrome P-450 along with cellular glutathione (GSH) content show postnatal developmental changes. The ability of hepatic subcellular preparation from newborn rats to convert AFB1 to its reactive epoxide form, is reported for the first time in this communication. Epoxidation of [3H]AFB1 in the presence of liver microsomes from different age-groups as measured by its adduct formation to calf thymus DNA in vitro shows that newborn rats are capable of catalyzing only minimal AFB1-DNA binding compared with that of adults. Addition of cytosolic fraction of various age groups to the system suggests that young rats are less efficient in modulating the binding as compared with adults. The amount of AFB1-GSH conjugate formed is also significantly higher when adult GSH S-transferase is involved in the system. These observations show that immature liver is less efficient than a mature organ in handling a chemical carcinogen and the metabolism of AFB1 by neonatal liver differs from that in the adult.


Metabolic effects of telmisartan in spontaneously hypertensive rats.
The favorable metabolic effects of telmisartan are supposedly related to the changes in carbohydrate and lipid metabolism driven by peroxisome proliferators-activated receptor-gamma (PPARgamma). The fatty acid translocase CD36 is one of the PPARgamma targets that mediate these actions. We studied the metabolic effects of telmisartan in the NIH-derived strain of spontaneously hypertensive rats (SHR/NIH), which harbors a deletion mutation in CD36, in comparison to the original SHRs (SHR/Izm), which express wild-type CD36. In SHR/Izm, administration of telmisartan was associated with significantly lower serum levels of free fatty acids (42%), triglycerides (29%), glucose (11%), insulin (31%), and lower hepatic triglyceride (17%) levels, as well as larger epididymal fat pads (1.19-fold) than in SHR/NIH. Additionally, insulin-stimulated glucose incorporation into epididymal fat tissues was significantly augmented in SHR/Izm (1.33-fold) compared with SHR/NIH. In the epididymal fat pads of SHR/Izm treated with telmisartan, CD36 mRNA transcript (1.55-fold) and protein expression (1.37-fold) were also significantly enhanced. However, after 4 weeks of treatment with telmisartan, in SHR/NIH only serum free fatty acid levels were slightly reduced (20%). Overall, these results showed marked discrepancies in the metabolic actions of telmisartan in SHR/Izm and SHR/NIH and further supported the involvement of CD36 in the actions of this drug, suggesting that this pharmacogenetic interaction may be of particular importance in CD36-deficient patients.


Construct and discriminant validity testing of the FACE-Q Head and Neck Cancer Module for assessing speech and swallowing outcomes for patients undergoing maxillectomy or mandibulectomy.
The FACE-Q H&N is a patient reported outcome measure covering multiple constructs for patients with head and neck tumors. Additional testing is needed to determine suitability in assessing speech- and swallowing-related quality of life and function. FACE-Q H&N, The M. D. Anderson Dysphagia Inventory (MDADI), and Speech Handicap Index (SHI) scores were collected from two patient cohorts who had undergone jaw reconstruction. Construct validity was assessed using convergent validity testing and known groups testing to assess discriminant validity. A priori hypotheses testing demonstrated strong correlations (ρ > 0.6, p < 0.05) between FACE-Q H&N eating and drinking, swallowing and eating distress scales with MDADI subscales, and between FACE-Q H&N speech function and distress scales and the SHI. Known groups testing demonstrated all instruments could delineate outcomes among patients who had radiation, advanced tumors, and tracheostomy. The FACE-Q H&N may be an alternative for the SHI and MDADI in this patient cohort.


Evidence for independent osmosensitivity of lateral preoptic and lateral hypothalamic neurons.
The purpose of the present study was to determine if a functional or modulatory relationship exists between osmosensitive neurons of the lateral preoptic (LPO) and lateral hypothalamic (LHA) areas. Unit activity was recorded from one neural area (LPO or LHA) following bilateral destruction of the opposite area, i.e., LPO recording site with LHA lesion site, and vice-versa. Bilateral destruction of the LPO or LHA did not eliminate the osmosensitivity characteristics of LPO or LHA units, demonstrating that units of either area do not require input from the opposite area for osmosensitivity.


Tetra-kis(benzyl-amino)-phospho-nium chloride.
The title salt, [P(NHCH(2)C(6)H(5))(4)](+)·Cl(-), crystallizes with the P atom and Cl(-) anion lying on a twofold rotation axis. The P atom has a slightly distorted tetra-hedral geometry with two classes of N-P-N angles [101.15 (10) and 100.55 (11)° and 113.07 (9) and 114.83 (8)°] and the environments of sp(2)-hybridized N atoms are essentially planar (sum of angles = 359.9 and 360.1°). In the crystal, the phospho-nium ion inter-acts with each neighboring chloride ion via two approximately equal N-H⋯Cl inter-actions, forming parallel chains along the c axis.


"Having a non-normative body for me is about survival": Androgynous body ideal among trans and nonbinary individuals.
The present study focused on trans and nonbinary (TNB) individuals who have an androgynous or non-stereotypical body ideal, with attention to how their body ideal is conceptualized and maintained. Data were collected online from 76 TNB individuals. Based on responses to two open-ended prompts, a two-tiered analysis was conducted. First, thematic analysis was used to develop four central themes describing the way TNB individuals conceptualized their androgynous body ideal: 1) Attaining Neutrality and De-Categorizing Gender; 2) Disaggregating Gender Expression; 3) Managing Gender Dysphoria; and 4) Achieving Authenticity. Second, content analysis was used to document 12 behaviors engaged in or actions taken for the purpose of approaching or maintaining an androgynous or non-stereotypical body ideal. These were grouped into 3 main categories: gender expression (clothes, hair, make-up, body modifications), body shape (weight, muscularity, eating/diet), and sex characteristics (hormone therapy, body hair, vocal, chest, genitals). Results of the present study expand the current body ideal literature by including TNB narratives and by focusing specifically on the ways an androgynous body ideal is conceptualized and maintained. Research and clinical implications are discussed.


Epigenetic reprogramming mechanisms of immunity during influenza A virus infection.
This paper reviews epigenetic mechanisms by which influenza viruses affect cellular gene activity to control their life cycles, aiming to provide new insights into the complexity of functional interactions between viral and cellular factors, as well as to introduce novel targets for therapeutic intervention and vaccine development against influenza infections.


Urban solid waste management in Chongqing: challenges and opportunities.
The dual influences of the resource supply and protection in ecological environments will pose a significant challenge to China's sustainable development. Solid waste management offers opportunities to improve profits by conserving resources and improving environmental performance. This paper examines municipal solid waste (MSW) management in urban Chongqing, the nation's fourth largest municipality after Beijing, Shanghai and Tianjin. In this paper, we will provide information on the quantity and composition of MSW, as well as give an overview of different methods for collection, transport, treatment and disposal of MSW. At present the daily amount of MSW generated per person is about 1.08 kg; food waste accounts for about 59% of total MSW. MSW in Chongqing has a higher moisture content (64.1%) and a lower LHV (3728 kJ/kg) than other cities in Asia, which is an obstruction for incineration. Landfills are the main method of disposal in Chongqing, but pollution caused by simple landfills and lack of backup MSW disposal capacity are becoming major problems in the main districts of Chongqing. In this paper, the challenges being faced and opportunities to MSW in Chongqing are analyzed and some suggestions are given for improving the MSW system in the future.


Determination of Deposition Order of Toners, Inkjet Inks, and Blue Ballpoint Pen Combining MeV-Secondary Ion Mass Spectrometry and Particle Induced X-ray Emission.
Determination of the deposition order of different writing tools is very important for the forensic investigation of questioned documents. Here we present a novel application of two ion beam analysis (IBA) techniques: secondary ion mass spectrometry using MeV ions (MeV-SIMS) and particle induced X-ray emission (PIXE) to determine the deposition order of intersecting lines made of ballpoint pen ink, inkjet printer ink, and laser printer toners. MeV-SIMS is an emerging mass spectrometry technique where incident heavy MeV ions are used to desorb secondary molecular ions from the uppermost layers of an organic sample. In contrast, PIXE provides information about sample elemental composition through characteristic X-ray spectra coming from greater depth. In the case of PIXE, the information depth depends on incident ion energy, sample matrix and self-absorption of X-rays on the way out from the sample to the X-ray detector. The measurements were carried out using a heavy ion microprobe at the Ruđer Bošković Institute. Principal component analysis (PCA) was employed for image processing of the data. We will demonstrate that MeV-SIMS alone was successful to determine the deposition order of all intersections not involving inkjet printer ink. The fact that PIXE yields information from deeper layers was crucial to resolve cases where inkjet printer ink was included due to its adherence and penetration properties. This is the first time the different information depths of PIXE and MeV-SIMS have been exploited for a practical application. The use of both techniques, MeV-SIMS and PIXE, allowed the correct determination of deposition order for four out of six pairs of samples.


Massive binge eating, gastric dilatation and unsuccessful purging in a young woman with bulimia nervosa.
This report describes the case of a young woman with bulimia nervosa who developed acute gastric dilation that was diagnosed by computerized tomography. The patient had no history of factors associated with delayed gastric emptying. The treatment course is reviewed, as is the pathophysiology of acute gastric dilation.


Synthesis of iron oxide nanoparticles with control over shape using imidazolium-based ionic liquids.
Ionic liquid (IL)-coated iron oxide nanoparticles (IONs) were synthesized by the thermal decomposition of Fe(CO)(5) in an IL/DMF solvent system in the absence of stabilizing surfactants at 90 degrees C for 1 h. The IL, [omim][BF(4)], could regulate the shape and allow the preparation of anisotropic IONs, such as barlike and wirelike nanoparticles. The barlike IONs prepared using this method showed good superparamagnetic behavior in a magnetic field and a MR contrast enhancement effect in a MR scanner.


1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in the rat: characterization and age-dependent effects.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent dopaminergic toxin that has been found to produce Parkinson's disease-like symptoms in humans and monkeys. The neurotoxic effects of MPTP appear to be reduced in rodents where multiple dosing procedures are required to demonstrate long-lasting neuronal deficits. In the present study, the neurotoxic effects of MPTP were further characterized in the rat. Following the repeated administration of MPTP, pronounced (60-80%) and dose-dependent depletions of striatal dopamine and serotonin concentrations were found in the rat brain. Time-course studies revealed that while striatal dopamine concentrations remained consistently reduced for at least 8 weeks following MPTP treatment, striatal serotonin depletions as well as MPTP-induced monoamine depletions in other brain regions were transient in nature. Pretreatment with the MAO-B inhibitor pargyline afforded a selective and complete protection of striatal dopamine levels without significantly affecting MPTP-induced striatal serotonin depletions. Similarly, treatment with ascorbic acid was found to selectively attenuate MPTP-induced dopamine depletions in rats. The neurotoxic effects of MPTP were also found to increase in the developing rat. No significant brain monoamine depletions were observed in neonatal rats following the repeated administration of MPTP. However, MPTP-induced neurotoxicity progressively increased in older rats. The present results indicate that when appropriate treatment procedures are used, a pronounced, selective, age-dependent, and long-lasting MPTP-induced reduction in striatal dopamine concentrations can be observed in the rat brain. The present results are discussed in reference to the putative mechanisms and species differences of MPTP-induced neurotoxicity.


Minimum doses of ultraviolet radiation required to induce murine skin edema and immunosuppression are different and depend on the ultraviolet emission spectrum of the source.
Many photo immunological studies have used UV radiation sources that emit nonsolar UV spectral energy and UV doses based on nonimmunological endpoints, e.g. erythema and skin edema. Interpretation of these data has led to misunderstanding when extrapolated to hypothetical effects in humans exposed to solar UV. The purpose of this study was to: (1) establish UV dose response relationships for murine skin edema and immunosuppression, and (2) determine how different UV spectra affect these relationships. Back skin and ear minimum edema doses (MEdD) for Kodacel-filtered FS20 sunlamp UV (290-400 nm) were greater than two-fold higher than those for unfiltered FS20 sunlamp UV (250-400 nm). Xenon are solar simulator UV (295-400 nm) MEdD were > 10-fold higher than those for unfiltered sunlamp UV. Back skin and ear MEdD differed two- to five-fold between C3H/HeN, SWR/J and HRA/Skh-1 mice. The minimum immunosuppression doses (MISD) in C3H mice showed similar UV source spectrum dependence. The solar simulator UV MISD was 5.4- and 1.5-fold higher than for unfiltered and Kodacel-filtered sunlamp UV MISD, respectively. Furthermore, MISD were from 3- to 50-fold higher than the MEdD for the three UV sources. The UV bioeffectiveness spectra indicated that UVC energy (250-290 nm) contributed 12% and 18%, respectively, of the total skin edema and immunosuppression UV energy. These data demonstrate the variability in UV sensitivity among mouse strains, the significant differences between murine MEdD and MISD and how these differences are influenced by nonsolar regions (below 295 nm) of the UV spectrum.


Follow-up of chronic paediatric hepatitis C virus in a low-/middle-income country.
Follow-up of chronic hepatitis C virus (HCV) infection following Interferon (IFN) plus Ribavirin (RBV) or direct-acting antiviral (DAA) drug therapy in a cohort of paediatric outpatients as confirmed by a sustained virologic response (SVR). This study included a cohort of 60 patients (6-18 years), divided into 2 groups: Group 1:21 patients who completed treatment with IFN/RBV. Group 2:39 treated with dual DAA therapy: 19 with Sofosbuvir/Ledipasvir (SOF/LED) and 20 with Sofosbuvir/Daclatasvir (SOF/DCV). Group 1:12 (57.1%) were cured, six were IFN/RBV treatment failure then subsequently treated with DAAs successfully, and three had liver transplants. IFN/RBV side effects were reported in all patients; however, fibrosis regressed in two cured patients. Group 2: all were cured. HCV RNA became negative in all DAAs-treated patients at weeks 2, 4 and 12 of treatment (100%) as well as SVR after 12 weeks (100%). Thirty patients reported no adverse side effects whereas only nine suffered minor side effects. In our cohort, SOF/LED therapy and SOF/DCV therapy were extremely safe and effective with 100% SVR and negligible short-term side effects. IFN/RBV therapy was much less effective (SVR 57.1%) and accompanied with short-term side effects. Fibrosis might stop and even regress with successful treatment.


Mapping the Lineage Relationship between CXCR5+ and CXCR5- CD4+ T Cells in HIV-Infected Human Lymph Nodes.
CXCR5 is a key marker of follicular helper T (TFH) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5- CD4+ T cells with TFH-cell-like features. This CXCR5- subset becomes expanded in severe HIV infection and is characterized by the upregulation of activation markers and high PD-1 and ICOS surface expression. Integrated analyses on the phenotypic heterogeneity, functional capacity, T cell receptor (TCR) repertoire, transcriptional profile, and epigenetic state of CXCR5-PD-1+ICOS+ T cells revealed a shared clonal relationship with TFH cells. CXCR5-PD-1+ICOS+ T cells retained a poised state for CXCR5 expression and exhibited a migratory transcriptional program. TCR sequence overlap revealed a contribution of LN-derived CXCR5-PD-1+ICOS+ T cells to circulating CXCR5- CD4+ T cells with B cell help function. These data link LN pathology to circulating T cells and expand the current understanding on the diversity of T cells that regulate B cell responses during chronic inflammation.


Antiepileptic intranasal Amiloride loaded mucoadhesive nanoemulsion: development and safety assessment.
Current investigation aimed to develop a novel Amiloride loaded mucoadhesive nanoemulsion formulation for nose-to-brain delivery. Furthermore, nasal irritation study and histopathological examination of the nasal mucosa were also carried out to assess nonirritant nature of the nanoemulsion. The optimized formulation, surface epithelium lining and the granular cellular structure of the nasal mucosa were totally intact, whereas KCl caused major changes in the ultrastructure of mucosa. Amiloride loaded mucoadhesive nanoemulsion formulations are non toxic on nasal mucosa and can be administered by intranasal route for effective treatment of epilepsy.


Genome-Wide Transcriptional Responses of Marine Nematode Litoditis marina to Hyposaline and Hypersaline Stresses.
Maintenance of osmotic homeostasis is essential for all organisms, especially for marine animals in the ocean with 3% salinity or higher. However, the underlying molecular mechanisms that how marine animals adapt to high salinity environment compared to their terrestrial relatives, remain elusive. Here, we investigated marine animal's genome-wide transcriptional responses to salinity stresses using an emerging marine nematode model Litoditis marina. We found that the transthyretin-like family genes were significantly increased in both hyposaline and hypersaline conditions, while multiple neurotransmitter receptor and ion transporter genes were down-regulated in both conditions, suggesting the existence of conserved strategies for response to stressful salinity environments in L. marina. Unsaturated fatty acids biosynthesis related genes, neuronal related tubulins and intraflagellar transport genes were specifically up-regulated in hyposaline treated worms. By contrast, cuticle related collagen genes were enriched and up-regulated for hypersaline response. Given a wide range of salinity tolerance of the marine nematodes, this study and further genetic analysis of key gene(s) of osmoregulation in L. marina will likely provide important insights into biological evolution and environmental adaptation mechanisms in nematodes and other invertebrate animals in general.


Arteriovenous Malformation Presenting as Symptomatic, Enlarging and Contrast-Enhancing Mass 12 Years After Being Treated with Embolization and Radiotherapy.
Gross total resection of arteriovenous malformations (AVMs) of the central nervous system confirmed by formal angiography is accepted as a cure for patients. In some cases, this may not be possible. Even though in these cases other treatment modalities such as endovascular embolization and radiotherapy can be used, long-term follow-up is lacking in the literature. Here we report a case of a 57-year-old woman with history of a right-sided parieto-occipital/periatrial AVM, initially treated with a combination of endovascular embolization and radiotherapy. The patient subsequently presented (12 years later) with a symptomatic, enlarging, contrast-enhancing mass at the same location that was angiographically occult but ultimately proven to be an AVM on a background of reactive changes on pathology.


Hepatitis C virus NS4B protein induces epithelial-mesenchymal transition by upregulation of Snail.
Chronic hepatitis C virus (HCV) infection is an important cause of hepatocellular carcinoma (HCC). Epithelial to mesenchymal transition (EMT) is a key process associated with tumor metastasis and poor prognosis. HCV infection, HCV core and NS5A protein could induce EMT process, but the role of NS4B on EMT remains poorly understood. We overexpressed HCV NS4B protein in HepG2 cells or Huh7.5.1 cells infected by HCVcc, the E-cadherin expression, N-cadherin expression and the EMT-associated transcriptional factor Snail were determined. The migration and invasion capabilities of the transfected cells were evaluated using wound-healing assay. Additionally, we used Snail siRNA interference to confirm the relation of HCV NS4B and Snail on EMT promotion. HCV NS4B increased the expression of EMT related markers and promoted cell migration and invasion. Snail knock-down almost completely eliminated the function of NS4B protein in EMT changes and reversed cell migration capacity to lower level. HCV NS4B protein could reduce the expression of Scribble and Hippo signal pathway were subsequently inactivated, resulting in the activation of PI3K/AKT pathway, which may be the reason for the up-regulation of Snail. This study demonstrates that HCV NS4B protein induces EMT progression via the upregulation of Snail in HCC, which may be a novel underlying mechanism for HCV-associated HCC development, invasion and metastasis.


Quaternary naltrexone reverses morphine-induced behaviors.
This study explored the relative role of the peripheral and central nervous systems (CNS) in the production of morphine-induced behavioral changes. Toward this end we used a quaternary derivative of an opiate antagonist (naltrexone methobromide, NM) that presumably does not cross the blood-brain barrier. Naltrexone methobromide (20, 40 and 80 mg/kg, IP) was used to challenge the stereotypic locomotion, analgesia and elevated "Straub" tail response observed in C57BL/6J mice after a 30-mg/kg (IP) injection of morphine. The quaternary derivative of naltrexone reversed the locomotor hyperactivity, "Straub" tail and analgesia normally observed in the opiate-treated C57BL/6J mouse. The data reported here, if taken at face value, suggest an important role for peripheral opiate receptors in morphine-induced behavioral changes. However, these conclusions are contingent on further research to more fully evaluate NM's capacity to cross the blood-brain barrier of the C57BL/6J mouse.


Apo B/Apo A-I ratio in central and peripheral arterial diseases.
The apo B/apo A-I ratio represents the balance between atherogenic particles, rich in apo B, and the antiatherogenic ones, apo A-I rich. This study investigated the association between atherosclerotic diseases in different anatomical sites and apo B/apo A-I ratio. Lipids, lipoproteins, and apolipoproteins A-I and B were assessed in 30 subjects with coronary artery disease (CAD), 26 with ischemic stroke (IS), 30 with peripheral arterial obstructive disease (PAOD), and 38 healthy subjects (controls). HDLc and Apo A-I were significantly lower in PAOD and CAD groups, respectively, than in other groups. Significantly higher levels of triglycerides were observed for CAD and PAOD groups than for controls. Apo B was significantly higher in IS group than in control and PAOD groups. The apo B/apo A-I ratio showed significantly higher in CAD and IS groups when compared to control and PAOD groups (p < 0.001). The apo B/apo A-I ratio was important for identifying an increased trend for coronary and cerebral atherosclerosis. In spite of the increased trend for apo B/apo A-I ratio in IS and CAD groups, the studied variables cannot be considered in an isolated way, given as those parameters were analyzed together by a binary logistic regression, no association has been demonstrated.


Barcelona Clinic Liver Cancer staging and transplant survival benefit for patients with hepatocellular carcinoma: a multicentre, cohort study.
Allocation of deceased-donor livers to patients with chronic liver failure is improved by prioritising patients by 5-year liver transplantation survival benefit. The Barcelona Clinic Liver Cancer (BCLC) staging has been proposed as the standard means to assess for prognosis of patients with hepatocellular carcinoma. We aimed to create a prediction model linking the BCLC stage of patients with hepatocellular carcinoma to their 5-year liver transplant benefit. A large cohort of consecutive patients with hepatocellular carcinoma (n=1328) from the ITA.LI.CA database (n=2951) were judged as potentially eligible for liver transplantation according to the following criteria: absence of macroscopic vascular invasion or metastases, age 70 years or younger, and absence of relevant extra-hepatic comorbidities. To assess the correlation between BCLC staging and non-liver transplantation survival, we did Cox univariate and multivariate analyses including the following covariates: BCLC stage, year of diagnosis, age, sex, cause of cirrhosis, model for end-stage liver disease score, α-fetoprotein concentrations, and treatment. Liver-transplantation survival benefit for patients was calculated, using Monte Carlo simulation analysis, as the patient's 5-year life expectancy with liver transplantation (estimated by the Metroticket model) minus the 5-year life expectancy without liver transplantation according to BCLC stage. 83 (6%) of 1328 patients had BCLC 0 stage disease, 614 (46%) had BCLC A, 500 (38%) had BCLC B-C, and 131 (10%) had BCLC D. In the Cox non-liver transplantation survival multivariate model, hazard ratios associated with increasing BCLC stages were 1.530 (95% CI 1.107-2.116) for BCLC A versus BCLC 0, 1.572 (1.350-1.830) for BCLC B-C versus BCLC A, and 1.470 (1.164-1.856) for BCLC D versus BCLC B-C. Results of the Monte Carlo simulation analysis confirmed the significant effect of BCLC classification on transplant benefit; in the adjusted model, a median 5-year transplant benefit of 11.19 months (IQR 10.73-11.67) for BCLC 0, 13.49 months (11.51-15.57) for BCLC A, 17.36 months (15.06-19.28) for BCLC B-C, and 28.46 months (26.38-30.34) for BCLC D. Liver transplantation could result in survival benefit for patients with hepatocellular carcinoma and advanced liver cirrhosis (BCLC stage D) and in those with intermediate tumours (BCLC stages B-C), regardless of the nodule number-size criteria (ie, Milan criteria), provided that macroscopic vascular invasion and extra-hepatic disease are absent. None.


Influence of high power ultrasound on natural microflora, pathogen and lactic acid bacteria in a raw meat emulsion.
Raw meat emulsions may have natural, spoilage and pathogenic microorganisms due to the origin and characteristics of this food matrix. All of these microorganisms must be minimized during industrial processing to make food consumption safe and meet quality regulations. Therefore, in this research, the effect of probe ultrasound on the inactivation of three kinds of microorganisms in a raw meat emulsion is evaluated. The microorganisms are: natural microflora NAM, Listeria monocytogenes LIS, and Lactobacillus delbrueckii LAC. A high-intensity probe ultrasound system was used, during 1.0, 2.5, 5.0, 7.5 and 10 min, with pulsed waves of 0.0, 10, 20 and 30 seg, and 200, 250, 300, 350 and 400 W of power. The interrelation between time, wave pulse cycle, and power factors was assessed. The results showed a positive linear independence effect in the treatments without wave pulse for each microorganism, and a quadratic interaction with the time and the ultrasound power for the inactivation of the three kinds of microorganisms. Besides, the desirability function for the inactivation reached up to 60% of the microbial population with the probe ultrasound treatment, with 10 min, a 7.56 s wave pulse and 400 W of power. Thus, these results could be useful to decide the incorporation of mild and emerging technologies in a meat industry line process.


High Efficiency Removal of Cytokines and HMGB-1 by Continuous Hemofiltration With a Dual Layered Polyethersulfone Membrane: An Ex Vivo Study.
Cytokines and high mobility group box chromosomal protein-1 (HMGB-1) play key roles in inflammatory conditions. While hemofiltration has been shown to remove cytokines, removal of cytokines and HMGB-1 by hemofiltration using a polyethersulfone membrane has not been reported. This study aimed to test the hypothesis that the polyethersulfone membrane will achieve higher removal performance for substances including inflammatory cytokines compared to other hemofilters, while retaining low albumin removal capacity. Subjects were eight healthy volunteers. We collected 400 mL each of blood samples into containers with heparin and added 30 mg of lipopolysaccharide to spike cytokines and HMGB-1. After incubation at 39ºC for 12 h, each blood sample was circulated through a hemofiltration circuit with a polyethersulfone hemofilter (2.1 m2 or 1.1 m2 ) at a filtration flow rate of 2 L/h. Measurement samples were collected from arterial, venous, and ultrafiltrate sampling points. Concentrations of cytokines (IL-1ß, IL-4, IL-6, IL-8, IL- 10, and tumor necrosis factor [TNF-a]), HMGB-1, and albumin were determined at each time point (1, 4, 8, 12, and 24h). High sieving coefficients (SCs) above 0.8 were obtained for all cytokines except for TNF-a as well as HMGB-1, whereas the SC for albumin was less than 0.04 with both hemofilters. The hemofilter with a larger membrane area achieved significantly higher clearances for TNF-a and HMGB-1, and slower decreases in SCs over time for IL-1ß, IL-6, IL-8, TNF-a, and albumin. Continuous hemofiltration with a polyethersulfone membrane achieved high efficiency removal of cytokines and HMGB-1, without excessive removal of albumin.


[Mediastinal pathology: pathological treatment of frozen section].
Tumoral pathology of the mediastinum is extremely varied, with different prognoses and treatments. The pathological examination is essential, both etiologically and prognostically. Mediastinoscopy is generally used to check for lymph node metastases, bronchopulmonary carcinoma, but also, to a lesser degree, for the exploration of isolated mediastinal adenopathy. Finally, this technique enables a diagnostic approach to mediastinal tumours. The frozen section has its place, at the first indication, making it possible to prescribe neoadjuvant chemotherapy, and in the other situations to make sure that the quantity of material removed is sufficient or even to carry out complementary techniques.


New observations on midline defects: coincidence of anophthalmos, microphthalmos and cryptophthalmos with hypothalamic disorders.
Four children with severe congenital eye anomalies are described of which three had related symptoms. Two had bilateral anophthalmia, the optic nerves not detectable by computed cranial tomography and magnetic resonance imaging, and the third child had bilateral microphthalmia and coloboma iridis. The fourth patient had bilateral cryptophthalmia as part of Fraser syndrome. All four patients were of small stature. In three of them growth hormone deficiency was demonstrated which was of hypothalamic origin as shown by growth hormone releasing hormone tests. In the fourth child hypogonadotropic hypogonadism and tertiary thyroid deficiency were diagnosed which responded well to thyroxine treatment. Pathogenetically the described disorders are due to congenital defects of midline structures as a common "developmental field".


Identification of selective ligands targeting two GPCRs by receptor-affinity chromatography coupled with high-throughput sequencing techniques.
The rapid growth of demands for drug discovery has necessitated the ongoing pursuit of new methods for specific ligands screening and identification. This work combined receptor-affinity chromatography (RAC) with high-throughput sequencing techniques to rapidly screen and identify the specific ligands. By this method, immobilized angiotensin II type I receptor (AT1R) and endothelin receptor A (ETAR) based on RAC were utilized for lead screening from a DNA-encoded library. The specific ligands of AT1R (ligand A1, A2) and ETAR (ligand B1, B2) were synthesized after decoding by high-throughput sequencing techniques. The dissociation rate constants (kd) of ligand A1, A2 to AT1R and B1, B2 to ETAR were 9.65 × 10-4, 31.1 × 10-4 and 0.66, 1.22 s-1 by peak profiling assay. The association constant (KA) to the receptors of four ligands was 5.4 × 106, 3.3 × 106 and 1.6 × 106, 2.2 × 105 by injection amount dependent method. The kinetic and thermodynamic parameters of the four specific ligands are similar to those of the positive drugs. This indicates that they are promising to drug candidates. The druggability of the four ligands through pharmacokinetic investigation by HPLC-MS/MS presented desired pharmacokinetic behavior including the fast absorption, the relatively slow elimination. These results, taking together, indicated that the RAC combined with high-throughput sequencing techniques can screen and identify the specific ligands according to various proteins, thus creating a general strategy for rapid discovery of promising drug candidates.


Evidence that production of autoantibody to the alternative pathway C3 convertase is a normal physiologic event.
The origin of autoantibody production was studied with the use of antibody to the alternative pathway C3 convertase (C3 nephritic factor (C3NeF), as a model. Pokeweed mitogen stimulation of peripheral mononuclear cells from newborn infants, normal adults, and patients with membranoproliferative glomerulonephritis indicated that the ability to make C3NeF is apparently present in everyone from the time of birth. In addition, C3NeF appeared to express a single or very limited idiotope (21/21 isolates). The data also suggest that the elaboration of C3NeF may approximate an antibody response after immunization. Thus the C3NeF fraction of the total IgG or IgM produced in culture by pokeweed mitogen-stimulated mononuclear cells from normal neonates and adults, as well as from patients, was in the range of the production of specific antibody. Further, both IgG and IgM C3NeF produced by cells from these normal individuals, including newborn infants, had an affinity for antigen (10(8) to 10(9) L/mol) that was also in the range of specific antibody. Most of the autoantibody molecules (5/7) from serum were IgG3; two B cell clones producing C3NeF were CD5-negative. These experiments indicate that unmutated germline genes are used in the production of C3NeF and that a limited spectrum of antiidiotypic antibodies regulate its production.


Education and the moderating roles of age, sex, ethnicity and apolipoprotein epsilon 4 on the risk of cognitive impairment.
We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies, with an average follow-up ranging between 2 and 10 years. Pooled hazard ratios were obtained from multilevel parametric survival analyses predicting cognitive impairment (CI) from education and its interactions with baseline age, sex, APOE*4 and ethnicity. In separate models, education was treated as continuous (years) and categorical, with participants assigned to one of four education completion levels: Incomplete Elementary; Elementary; Middle; and High School. Compared to Elementary, Middle (HR = 0.645, P = 0.004) and High School (HR = 0.472, P < 0.001) education were related to reduced CI risk. The decreased risk of CI associated with Middle education weakened with older baseline age (HR = 1.029, P = 0.056) and was stronger in women than men (HR = 1.309, P = 0.001). The association between High School and lowered CI risk, however, was not moderated by sex or baseline age, but was stronger in Asians than Whites (HR = 1.047, P = 0.044), and significant among Asian (HR = 0.34, P < 0.001) and Black (HR = 0.382, P = 0.016), but not White, APOE*4 carriers. High School completion may reduce risk of CI associated with advancing age and APOE*4. The observed ethnoregional differences in this effect are potentially due to variations in social, economic, and political outcomes associated with educational attainment, in combination with neurobiological and genetic differences, and warrant further study.


Green technology for sustainable biohydrogen production (waste to energy): A review.
Perceiving and detecting a sustainable source of energy is very critical issue for current modern society. Hydrogen on combustion releases energy and water as a byproduct and has been considered as an environmental pollution free energy carrier. From the last decade, most of the researchers have recommended hydrogen as one of the cleanest fuels and its demand is rising ever since. Hydrogen having the highest energy density is more advantageous than any other fuel. Hydrogen obtained from the fossil fuels produces carbon dioxide as a byproduct and creates environment negative effect. Therefore, biohydrogen production from green algae and cyanobacteria is an attractive option that generates a benign renewable energy carrier. Microalgal feedstocks show a high potential for the generation of fuel such as biohydrogen, bioethanol and biodiesel. This article has reviewed the different methods of biohydrogen production while also trying to find out the most economical and ecofriendly method for its production. A thorough review process has been carried out to study the methods, enzymes involved, factors affecting the rate of hydrogen production, dual nature of algae, challenges and commercialization potential of algal biohydrogen.


Attitudes to prescribing compression stockings for patients with acute DVT: the MASTER registry.
Compression therapy is still not widely used for patients with deep vein thrombosis (DVT). This report provides information on Italian doctors' use of elastic stockings (ES) after acute DVT and identifies some predictors of prescription. The MASTER multicenter registry collected information about clinical characteristics and management of patients with venous thromboembolism (VTE). In patients with objectively confirmed acute VTE, information about clinical presentation, diagnostic methods, temporary and permanent risk factors, pre-event prophylaxis and treatment, including ES prescription, were captured by an electronic data network at the time of the index event. Of 2119 patients enrolled, 1913 had DVT, 1772 in the legs; 1277 were prescribed ES at hospital discharge. The following conditions were associated with more frequent prescription: edema, in-hospital management, known thrombophilia; younger age. In multivariate analysis these factors all remained significantly associated with more frequent use of ES. Italian clinicians' attitudes to prescribing ES still appear suboptimal. Special attention is needed for patients treated at home, where organizational problems can interfere with the use of ES.


Data on the relationship between traveller perceived value and traveller intention to revisit a destination.
Data was collected at the OR Tambo Airport in Johannesburg South Africa from 503 willing international tourists. The survey was self-administered over a two-month period. Due to the absence of a sampling frame, non-probability sampling was adopted in selecting participants. A unique conceptual model was developed to test the causal effect of traveller perceived value on cognitive and affective destination image as well as on traveller intention to revisit. In addition, the direct effect of cognitive and affective destination image on traveller intention to revisit was also measured. Analysis of data involved descriptive statistics and structural equation modeling conducted in the Statistical Package for the Social Sciences (SPSS) 25 and Analysis of Moment Structures (AMOS) 25 respectively. Descriptive statistics produced frequencies on gender, age, travels, purpose of trip and holidays associated with each respondent. Structural equation modeling was conducted following a two-step process. First, confirmatory factor analysis followed by hypothesis testing. Further research could assess the possibility of a link between affective and cognitive destination image.


Bipolar affective disorder, type II, apparently precipitated by donepezil.
There is considerable evidence that pro-cholinergic agents can cause depressed mood. However, there are also published case reports of a rare association between cholinesterase inhibitors and mood elevation in patients with pre-existing major functional psychiatric disorders, or organic disorders other than dementia. This report adds to the literature by describing a case of mood elevation in a patient without pre-existing psychiatric disorder.


Characterization of two new human leukocyte antigen alleles: HLA-A*02:982 and HLA-C*04:441.
Two new alleles were identified during routine next generation sequencing.


Protection of salivary function by concomitant pilocarpine during radiotherapy: a double-blind, randomized, placebo-controlled study.
To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dose distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.


Phenotypic characterization of canine intestinal intraepithelial lymphocytes in dogs with inflammatory bowel disease.
Many dogs suffering from inflammatory bowel disease (IBD) are presented to veterinary clinics. These patients are diagnosed based on a history of chronic gastrointestinal signs and biopsy-confirmed histopathologic intestinal inflammation. Intestinal intraepithelial lymphocytes (IEL) are part of the first line of defense in the gastrointestinal immune system. Alterations in IEL subsets may play a role in the pathogenesis of IBD. The aim of this study was to characterize the phenotypes of IEL in dogs with IBD compared with healthy control dogs. Intestinal intraepithelial lymphocytes subpopulations of control dogs (n = 5) obtained from endoscopic biopsies (EB) were compared to those obtained from full thickness biopsies (FTB) on the same day. In addition, the phenotypes of IEL from FTB of control dogs (n = 10) were compared with EB of IBD dogs (n = 10). Each participant was scored clinically using the canine inflammatory bowel disease activity index (CIBDAI), and all samples were graded histopathologically. Three-color flow cytometry of isolated IEL was performed using monoclonal antibodies against T- and B-lymphocyte subpopulations. No significant differences in the composition of IEL subpopulations were found in control dogs based on method of biopsy. The IBD dogs had significantly higher CIBDAI and histopathologic scores compared with control dogs and their IEL contained a significantly higher frequency TCRγδ T-cells. Endoscopic biopsies provide suitable samples for 3-color flow cytometry when studying canine intestinal IEL and IBD patients show significant changes of major T-cell subsets compared to healthy control dogs.


IFN-gamma regulates the expression of B7-H1 in dermal fibroblast cells.
Programmed cell death ligand 1 (B7-H1) was recently cloned in antigen presenting cells (APCs) and represents a third member of the B7 family. Thus, B7-H1 may be a novel target for clinical intervention in human inflammatory disease. The aim of this study is to investigate the signal transduction mechanism and transcriptional regulation of B7-H1 expression in human dermal fibroblasts. We performed reverse transcription PCR (RT-PCR) for the detection of mRNA expression, luciferase reporter assays with B7-H1 promoter constructs, and Western blot analysis. From RT-PCR analysis, IFN-gamma can induce the expression of B7-H1 mRNA in dermal fibroblast. This expression is similar to the results of luciferase reporter assay with B7-H1 promoter. Western blot analysis and EMSA revealed that NF-kappaB transcription factors mediate the induction of B7-H1 expression via the transient phosphorylation of ERK1/2 and PI3K when cells are stimulated by IFN-gamma. Also, Specific destruction of the NF-kappaB binding site abolished the induction of the promoter activity by IFN-gamma. Our data not only provides the first evidence to demonstrate that dermal fibroblast express the B7-H1 mRNA in the process of skin inflammation, but also suggests the involvement of NF-kappaB and MAPK and PI3K, that may play some important roles in inflammation process in human skin diseases.


Psychologists' views of inter-disciplinary psychosocial communication within the cancer care team.
Little is known about how psychologists working in cancer care centres communicate clinical information to other members of the multidisciplinary team or what information is communicated. This study surveyed Australian cancer care psychologists regarding their communication practices and their views on barriers to and facilitators of effective inter-disciplinary communication. Psychologists were invited to complete an online survey containing purpose-designed items that addressed study aims. Forty-four psychologists completed the survey. Psychologists' most common method of recording initial consultations was in patient medical records, with 69 % of respondents recording notes in either most of the time or all of the time. Twenty-two percent of psychologists said they did not regularly feedback the results of an initial assessment to a referrer and more than 40 % used verbal and e-mail communication to do so. This study provides data that will assist in the development of guidelines for inter-professional communication between psychologists and other members of the cancer care team.


Margins of stability of persons with transtibial or transfemoral amputations walking on sloped surfaces.
Gait is a complex motor skill. However, most falls in humans occur during gait, and people with lower limb amputation have an increased risk of falls. Thus, this study evaluated the stability of persons with unilateral amputation by quantifying the margin of stability (MoS) during gait, to contribute to understanding the strategies adopted by these people to reduce falls. The participants were divided into 3 groups: persons with transtibial amputations (n = 12, 32.27 ± 10.10 years, 76.9 ± 10.3 kg, 1.74 ± 0.06 m); persons with transfemoral amputations (n = 13, 32.21 ± 8.34 years, 72.55 ± 10.23 kg, 1.73 ± 0.05 m); and controls (n = 15, 32.2 ± 10.17 years, 75.4 ± 9.25 kg, 1.75 ± 0.05 m), who walked for 4 min on a level and sloped (8% down and up) treadmill. The pelvic and foot marker kinematic data were used to estimate the center of mass and base of support, and from these, the MoS was estimated. Although both groups of persons with amputations showed higher values for the ML MoS than did the control group (transtibial: 8.81 ± 1.79, 8.97 ± 1.74, 8.79 ± 1.76, transfemoral: 10.15 ± 2.03, 10.60 ± 1.98, 10.11 ± 1.75, control: 8.13 ± 1.30, 7.18 ± 1.85, 8.15 ± 1.57, level, down, and up, respectively), only the transfemoral group presented a significant higher value compared to the control group. Our findings suggest that the documented limitations in persons with amputations, especially with transfemoral amputation, are exacerbated in situations that require more skills, such as walking on sloped surfaces, triggering protective mechanisms.


Evaluation and treatment of the asymptomatic patient with a positive exercise tolerance test.
A positive exercise study in an asymptomatic patient presents a clinical dilemma. Many of these asymptomatic positive studies are false-positive, but a subset of these patients have silent coronary artery disease. Other noninvasive tests can be used in conjunction with exercise testing to help identify this subset of patients, but coronary angiography is often ultimately necessary to ensure an accurate diagnosis. An algorithm for the evaluation and treatment of the patient with an asymptomatic positive exercise study is proposed.


Reliable stability prediction to manage research or marketed vaccines and pharmaceutical products. "Avoid any doubt for the end-user of vaccine compliance at time of administration".
A major challenge for the pharmaceutical/vaccine industry is to anticipate and test/control product stability, regardless of the time/temperature profile of the product, from release to administration. Current empirical stability protocols performed to ensure product stability remain limited to the prediction of product stability in a thermal excursion (cold chain break) during their long-term storage. As recently recommended by the World Health Organization, mathematical models can be used for shelf-life and stability predictions. Therefore, various approaches have been published with good performance for simple chemical reactions. However, for biomolecules/vaccines, more complex reaction profiles require more complex models to predict their stability with a good level of confidence. This complexity constitutes a real scientific challenge because the number of model parameters increases with model complexity and need to be balanced with the limited number and quality of the available experimental data. We have developed a dedicated method/software based on different vaccines/pharmaceutical case studies. This predictive method considers phenomenological models, five levels of model confidence assessment, predictive quality value and simulated designs of experiment to improve and define the limits within which the prediction models can be used, and to increase model/prediction confidence to the required regulatory and scientific levels. This artificial intelligence system should help to avoid any doubt of stability at time of vaccine injection.


PHF14 enhances DNA methylation of SMAD7 gene to promote TGF-β-driven lung adenocarcinoma metastasis.
Aberrant activation of TGF-β signaling plays a pivotal role in cancer metastasis and progression. However, molecular mechanisms underlying the dysregulation of TGF-β pathway remain to be understood. Here, we found that SMAD7, a direct downstream transcriptional target and also a key antagonist of TGF-β signaling, is transcriptionally suppressed in lung adenocarcinoma (LAD) due to DNA hypermethylation. We further identified that PHF14 binds DNMT3B and serves as a DNA CpG motif reader, recruiting DNMT3B to the SMAD7 gene locus, resulting in DNA methylation and transcriptional suppression of SMAD7. Our in vitro and in vivo experiments showed that PHF14 promotes metastasis through binding DNMT3B to suppress SMAD7 expression. Moreover, our data revealed that PHF14 expression correlates with lowered SMAD7 level and shorter survival of LAD patients, and importantly that SMAD7 methylation level of circulating tumor DNA (ctDNA) can potentially be used for prognosis prediction. Together, our present study illustrates a new epigenetic mechanism, mediated by PHF14 and DNMT3B, in the regulation of SMAD7 transcription and TGF-β-driven LAD metastasis, and suggests potential opportunities for LAD prognosis.


Spatial attention in children with perinatal stroke.
Spatial neglect is a common feature of right hemisphere damage in adults, but less is known about spatial inattention following early brain damage. We used a Posner-based cueing task to examine hemispatial neglect and aspects of attention in children with perinatal stroke in either left (LH) or right hemisphere (RH) and controls. A visual perception task assessed the speed of visual perception. A spatial attention cueing task (the E-task) measured the ability to discriminate the direction of a target stimulus ("E"), when presented on the left or right side of the screen. This task provided indices of performance for attention orienting, disengagement and reorienting. Children with LH lesions had slowed visual perception compared to controls. Children with RH lesions did not demonstrate similar deficits. On the E-task, groups with both LH and RH lesions demonstrated lower accuracy on both left and right sides compared to controls. Children with LH lesions also showed impaired attention orienting and disengagement on left and right sides compared to controls, while children with RH lesions were most impaired in orienting and disengagement on their contralesional side. Children with LH lesions demonstrated more extensive attentional deficits than children with RH lesions. These results suggest that development of spatial attention may require different neural networks than maintenance of attention.


Inactivation of medium-chain acyl-CoA dehydrogenase by oct-4-en-2-ynoyl-CoA.
Mitochondrial medium-chain acyl-CoA dehydrogenase is a key enzyme for the beta-oxidation of fatty acids, which catalyzes the FAD-dependent oxidation of a variety of acyl-CoA substrates to the corresponding trans-2-enoyl-CoA thioesters. Oct-4-en-2-ynoyl-CoA was identified as a new irreversible inhibitor of acyl-CoA dehydrogenase, and kinetic parameters K(I) and k(inact) were determined to be 11 microM and 0.025 min(-1), respectively. Triple bond between C2 and C3 of the inhibitor was identified as the functional group responsible for enzyme inactivation, and Michael addition is proposed as the mechanism for this inactivation, which is a new pathway for inactivation of MCAD by inhibitors. The inhibitor may become a lead for further development for treating non-insulin-dependent diabetes mellitus.


Vascularized bone grafting in a canine carpal avascular necrosis model.
Limited experimental research has been performed on the treatment of avascular necrosis (AVN) by vascularized bone grafting. A new model simulating carpal AVN was created to investigate surgical revascularization of necrotic bone. In seven mongrel dogs, AVN was induced by removal of the radial carpal bones bilaterally, deep-freezing, coating in cyanoacrylate, and reimplantation. A reverse-flow vascularized bone graft from the distal radius was implanted in the avascular radial carpal bone. The contralateral side served as an untreated ischemic control. Bone blood flow, bone volume, radiography, histomorphometry, histology, and MRI were analyzed at 4 weeks. Blood flow was substantially higher in grafted bones when compared with controls (14.68 ± 15.43 versus 0.27 ± 0.28 mL/minute/100 g). Blood flow correlated with increased osteoid formation and higher levels of bone turnover. T1 and T2 signals on MRI did not correlate with quantitative bone blood flow measurements. Necrotic bones with no blood flow had normal T1 and T2 signals, whereas revascularized bones had signal changes when compared with adjacent carpal bones. No major collapse occurred in any radiocarpal bone. In a canine experimental model, investigation of carpal AVN shows the ability of vascularized bone grafting to revascularize and remodel avascular bone. Surgical revascularization of necrotic bone induced by vascularized bone grafting results in increased bone perfusion and bone remodeling as compared with untreated necrotic bone. MRI T1 and T2 signals can be normal in necrotic avascular bone.