Assessing the utility and efficacy of e-OSCE among undergraduate medical students during the COVID-19 pandemic.
The outbreak of coronavirus disease 2019 (COVID-19) and its quick progression to a global pandemic has urged medical schools to shift from didactic to distance learning and assessment approaches. The quality of clinical training and assessment have been jeopardized due to the regulatory restrictions and potential hazards to human lives. The aim of this paper is to evaluate the utility and efficacy of an electronic Objective Structured Clinical Examination (e-OSCE), which attempted to transform the format of a face-to-face OSCE to an e-OSCE. We conducted three end of clerkship e-OSCEs for final year medical students in Surgery, Medicine and Family Medicine using the teleconferencing application of Microsoft Teams (MST). The e-OSCE blueprint included the assessment of all clinical skills except physical examination and procedural skills. Examiners supervised e-OSCE from the college campus, while all students were remotely assessed through the MST channels. During the exam, the students stayed in their specified MST channel and examiners rotated across all students. The utility and efficacy of e-OSCE was evaluated using a self-administered questionnaire for students, examiners and e-OSCE team. The data analysis showed that 93.4% students and 92.2% examiners agreed with the quality and process of e-OSCE. Similarly, 83.6% students and 98% examiners agreed with the seamless organization of e-OSCE. As many as 45.9% students and 74.5% examiners agreed that e-OSCE was close to real life practice. Approximately one fifth of students and one third of examiners preferred e-OSCE over the face-to-face OSCE. The analysis of qualitative data generated the themes of e-OSCE structure and technology. While majority of participants were satisfied with e-OSCE, students were concerned about examiners' training and e-OSCE contents. Examiners and e-OSCE team recognized the paper-less, tech-savy, fast and reliable format of e-OSCE. During and beyond COVID- 19 era, e-OSCE is a strong substitute to standard OSCE for assessing clinical competence except for physical examination and procedural skills. The planning and implementation of e-OSCE reflects an ingenuity in the assessment of clinical competencies of medical students.


Kinetics of the oxidation of p-coumaric acid by prostaglandin H synthase and hydrogen peroxide.
Steady-state kinetics of the oxidation of p-coumaric acid (CA) by prostaglandin H synthase and hydrogen peroxide was studied at 25 degrees C in 0.1 M phosphate buffer, pH 8.0, using a stopped-flow apparatus. The following evidence supports a mechanism in which CA serves as a reducing substrate for prostaglandin H synthase through two one-electron oxidation steps: (a) the oxidation product of CA is the same in the prostaglandin H synthase/hydrogen peroxide and the horseradish peroxidase/hydrogen peroxide systems; (b) an identical steady-state enzyme intermediate (compound II) is present in both systems; (c) CA stimulates the cyclooxygenase activity of prostaglandin H synthase; the concentration of CA that produces 50% stimulation, A50, is 350 +/- 30 microM. On the time scale of our experiments, the inactivation of prostaglandin H synthase by hydrogen peroxide was insignificant when CA was present. A molar absorptivity of 17.2 +/- 0.9 mM-1 cm-1 at 300 nm was determined for CA which was used to follow the initial rate of disappearance of CA. The reaction of CA with hydrogen peroxide catalyzed by prostaglandin H synthase showed saturation behavior. An irreversible reaction mechanism for the steady-state kinetics of prostaglandin H synthase is proposed which is consistent with all of our experimental results. Under steady-state conditions, the second-order rate constants for the reactions of prostaglandin H synthase with hydrogen peroxide and prostaglandin H synthase-compound II with CA are (9.2 +/- 0.1) x 10(5) and (2.5 +/- 0.1) x 10(6) M-1 s-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Use of a murine secreted alkaline phosphatase as a non-immunogenic reporter gene in mice.
The development of any vector system as a gene delivery system requires its optimization in vitro and in vivo. Preliminary studies frequently involve the use of a reporter gene, which allows for the rapid and simple assay of vector function through monitoring expression levels of the reporter gene. However, evaluation of vector efficacy can be compromised by immune responses directed against immunogenic reporter proteins. We have cloned a murine secreted alkaline phosphatase (mSEAP), and explored its use as a reporter gene in the context of an early region 1 (E1)-deleted adenovirus (Ad) vector. Studies involved characterization of gene expression in vitro and in vivo, and immunological responses after gene delivery to mice. In tissue culture, we show that mSEAP is easily measured quantitatively using a sensitive, commercially available chemiluminescent assay, or visualized directly using histological staining. The level of transgene expression from AdmSEAP was similar to that observed for an Ad vector encoding the human placental secreted alkaline phosphatase (hSEAP). After intravenous administration in mice, AdmSEAP continued to express at high levels for the duration of the experiment (1 month), whereas expression from AdhSEAP declined to background levels over the course of the experiment. Although cytotoxic T-lymphocytes were not detected against either the murine or human SEAP proteins in mice, antibodies were readily detected against the human protein. No antibodies were detected to mSEAP. Taken together, these data illustrate that mSEAP is a sensitive, non-immunogenic reporter gene for preclinical mouse studies.


Quantitative interferon-gamma responses predict future disease progression in badgers naturally infected with Mycobacterium bovis.
The diagnosis and control of Mycobacterium bovis infection (bovine tuberculosis: TB) continues to present huge challenges to the British cattle industry. A clearer understanding of the magnitude and duration of immune response to M. bovis infection in the European badger (Meles meles) - a wildlife maintenance host - may assist with the future development of diagnostic tests, and vaccination and disease management strategies. Here, we analyse 5280 diagnostic test results from 550 live wild badgers from a naturally-infected population to investigate whether one diagnostic test (a gamma interferon release [IFNγ] assay, n = 550 tests) could be used to predict future positive results on two other tests for the same disease (a serological test [n = 2342 tests] and mycobacterial culture [n = 2388 tests]) and hence act as an indicator of likely bacterial excretion or disease progression. Badgers with the highest IFNγ optical density (OD) values were most likely to subsequently test positive on both serological and culture tests, and this effect was detectable for up to 24 months after the IFNγ test. Furthermore, the higher the original IFNγ OD value, the greater the chance that a badger would subsequently test positive using serology. Relationships between IFNγ titres and mycobacterial culture results from different types of clinical sample suggest that the route of infection may affect the magnitude of immune response in badgers. These findings identify further value in the IFNγ test as a useful research tool, as it may help us to target studies at animals and groups that are most likely to succumb to more progressive disease.


Implementation fidelity: a framework for evaluation in the health information technology field.
Health information technology evaluators need to distinguish between intervention efficacy as assessed in the ideal circumstances of clinical trials and intervention effectiveness as assessed in the real world circumstances of actual practice. We have developed a framework for implementation fidelity evaluation with methods for estimating intervention effectiveness and efficacy. We apply this framework to evaluate an ongoing health information technology clinical trial.


[Effect of skull acupuncture and scalp acupuncture on serum vascular endothelial growth factor in the patient of acute cerebral infarction].
To investigate effect of skull suture acupuncture (skull acupuncture) and scalp acupuncture on serum vascular endothelial growth factor (VEGF) in the patient of acute cerebral infarction (CI). Twenty cases of CI were treated with skull suture acupuncture at coronal suture, sagittal suture, lambdoid suture, etc. combined with medication (group B), group C (n=20) with scalp acupuncture at contralateral Dingnie Qian-xiexian (MS 6) and Dingnie Houxiexian (MS 7) plus medication, and group A (n=20) with medication. Changes of serum VEGF contents were investigated in the three groups. After treatment, the serum VEGF content did not significantly change in group A (P > 0.05), and significantly increased in group B and group C (P < 0.01, P < 0.05), with significant difference as group B and C compared with that of group A (P < 0.05), and with no significant difference between group B and group C (P > 0.05). Skull suture acupuncture combined with medication and scalp acupuncture plus medication have a similar effect on serum VEGF in the patient of acute cerebral infarction.


Retargeted and Stealth-Modified Oncolytic Measles Viruses for Systemic Cancer Therapy in Measles Immune Patients.
Measles viruses (MV) are rapidly inactivated by anti-measles neutralizing antibodies, which has limited their clinical performance as oncolytic agents. Here, by substituting the H and F surface glycoproteins of MV with those from the homologous canine distemper virus (CDV) and engineering the CDV H attachment protein to target EGFR or CD38, we generated a fully retargeted MV capable of resisting neutralization by measles-immune human serum. The resultant recombinant MVs encoding retargeted CDV envelope glycoproteins had similar growth kinetics as the control MV, showed the expected engineered receptor specificities for cell entry, intercellular fusion, and target cell killing, and were blind to native CDV receptors. In contrast to the control MV, recombinant MVs incorporating CDV F and H glycoproteins retained full infectivity when exposed to high concentrations of pooled measles-immune human serum. Comparing viruses bearing MV or CDV glycoproteins in the SKOV3ip.1 model, only the virus bearing an EGFR-retargeted CDV envelope glycoprotein complex was capable of limiting tumor growth and extending the survival in measles immune mice. MV, "stealthed" and retargeted using engineered CDV surface glycoproteins, may be a promising platform to advance for systemic cancer therapy in measles immune patients.


Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ß-Thalassemia: A Meta-Analysis.
At present, the main therapies for ß-thalassemia patients include regular blood transfusion and iron chelation, associating with a number of limitations. Thalidomide, a fetal hemoglobin (HbF) inducer that promotes γ-globin gene expression, has been reported to be effective for ß-thalassemia. Thus, this meta-analysis was conducted to assess the efficacy and safety of thalidomide for treating patients with ß-thalassemia. We searched the related studies from eight databases published from inception until December 1, 2021. The R 4.0.5 language programming was used to perform meta-analysis. After screening of retrieved articles, 12 articles were included that enrolled a total of 451 patients. The Cochrane Collaboration risk assessment tool was used to evaluate the quality and the bias risk of the randomized controlled trials (RCTs), and non randomized trials were assessed using Newcastle-Ottawa Scale (NOS). After treatment with thalidomide, the pooled overall response rate (ORR) was 85% (95% confidence interval (CI): 80-90%), and the pooled complete response rate (CRR) was 54% (95% confidence interval: 31-76%). Compared with the placebo group, the thalidomide group had higher odds of overall response rate (odds ratio = 20.4; 95% CI: 6.75-61.64) and complete response rate (odds ratio = 20.4; 95% CI: 6.75-61.64). A statistically significant increase in hemoglobin level and HbF level after treatment, while there was no statistically significant difference in adult hemoglobin (HbA) level, spleen size, and serum ferritin. According to the results of ORR and CRR, transfusion-dependent thalassemia (TDT) patients showed remarkable efficacy of thalidomide, 83 and 52% respectively. So we analyzed 30 transfusion-dependent thalassemia patients from three studies and found that the most frequent ß-globin gene mutations were CD41-42 (-TCTT), while response to thalidomide did not show any statistically significant relationship with XmnI polymorphism or CD41-42 (-TCTT) mutation. About 30% of patients experienced mild adverse effects of thalidomide. Collectively, thalidomide is a relatively safe and effective therapy to reduce the blood transfusion requirements and to increase Hb level in patients with ß-thalassemia.


Use of a mineralized collagen membrane to enhance repair of calvarial defects in rats.
The aim of the present study was to evaluate mineralized collagen membranes for enhancement of bone regeneration in calvarial defects. Forty adult female Sprague-Dawley rats received calvarial full thickness defects with a diameter of 8 mm. In 20 animals, the defects were covered with a mineralized collagen membrane, and 20 animals served as controls. After 6, 13, 26 and 52 weeks, bone regeneration was evaluated using undecalcified thick-section histometry. There was no clear enhancement of bone regeneration during the first 26 weeks after the operation. Bone regeneration underneath the membrane produced consistently thicker bone, albeit without statistical significance. Accumulation of membrane material occurred in the center of the defects surrounded by multinuclear giant cells during early stages of healing. After complete resorption of the membrane, significantly increased bone formation was seen after 52 weeks in the defects that had received membrane coverage. It was concluded that mineralization in the present form did not increase mechanical strength of the membrane to prevent interference of the membrane with bone regeneration in the defect. The reason for the increase in bone formation after resorption of the membrane after 26 weeks remains to be clarified.


Essential role of B7-H1 in double-stranded RNA-induced augmentation of an asthma phenotype in mice.
Clinical and epidemiological studies have shown the contribution of viral infection to the development of allergic asthma. Many RNA viruses, pathogenic for the respiratory tract, generate double-stranded (ds)RNA during their replication. Typical innate immune responses triggered by dsRNA involve the endosomal and cytoplasmic pathways. The former is mediated by Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF), and the latter by IFN-β promoter stimulator 1 (IPS-1). We explored the effect of polyinocinic polycytidilic acid, a synthetic dsRNA, on the development of an asthma phenotype in mice. Administration of dsRNA during ovalbumin sensitization augmented airway eosinophilia and airway hyperresponsiveness after an antigen challenge, which was associated with enhanced induction of IL-13-producing CD8(+) T cells. The augmentation was induced in IPS-1-deficient mice but not in TRIF-deficient mice. The interactions between dendritic cells (DCs) and T cells are regulated by B7-family costimulatory molecules, including B7-H1 (also known as PD-L1), a putative ligand for programmed death-1 (PD-1). Treatment of bone marrow-derived DCs with dsRNA enhanced B7-H1 expression in a TRIF-dependent manner. Additionally, dsRNA increased B7-H1 expression on DCs in the draining lymph nodes of ovalbumin-sensitized mice. The augmentation of the asthma phenotype was prevented by the treatment of mice with anti-B7-H1 mAb but not with anti-PD-1 mAb. The augmentation was not induced in B7-H1-deficient mice. These results suggest that dsRNA-triggered activation of the innate immune system in sensitization leads to augmentation of the asthma phenotype via IL-13 mainly from CD8(+) T cells. B7-H1 plays a crucial role in the process without requiring interaction with PD-1.


Non-occupational exposure of Malay women in Kuala Lumpur, Malaysia, to cadmium and lead.
Abstract Peripheral blood and 24-h total food duplicate samples were obtained from 49 adult Malay women in Kuala Lumpur, Malaysia, in July, 1995. Samples of boiled and uncooked (raw) rice were also collected from the subjects. The blood samples, homogenates of each food duplicates and rice samples (both cooked and raw) were digested by heating in the presence of mineral acids, and the digests were subjected to analysis for cadmium (Cd) and lead (Pb) with a system composed of a fully automated liquid sampler, a graphiie furnace atomic absorption spectrometer and a data processor. The geometric mean metal concentrations in blood were 0.71 ng Cd per ml and 45.6 ng Pb per ml, and the dietary metal intakes were 7.31 μg Cd per day and 10.1 μg Pb per day. The metal intake via rice accounted for 53% and 13% of total dietary intake of cadmium and lead, respectively. When the absorption from the air and foods was compared, the cadmium burden came almost exclusively from foods, whereas the lead burden came both from air (44%) and foods (56%).


Validation of the Alopecia Areata Patient Priority Outcomes (AAPPO) Questionnaire in Adults and Adolescents with Alopecia Areata.
Individuals with alopecia areata (AA) may experience significant impacts on their health-related quality of life. The novel Alopecia Areata Patient Priority Outcomes (AAPPO) questionnaire has been developed to assess hair loss signs, emotional symptoms, and activity limitations associated with AA. The objective of this study was to evaluate psychometric properties and establish scoring of the AAPPO in adults and adolescents with AA. Scoring and measurement properties of the AAPPO were examined using baseline and 2-week follow-up data from a prospective, noninterventional, web-based study of 121 patients with AA (85 adults aged ≥ 18 years, 36 adolescents aged 12-17 years) with Severity of Alopecia Tool (SALT) ≥ 25% scalp hair loss. Exploratory and confirmatory factor analysis supported four single Hair Loss (HL) items, an Emotional Symptoms domain (ES; 4 items), and an Activity Limitations domain (AL; 3 items). Among all patients, the multi-item ES and AL domains had strong internal consistency (α ≥ 0.87); all HL items and domain scores had strong test-retest reliability (weighted kappa or intraclass correlation coefficients ≥ 0.78). All HL item scores demonstrated strong construct validity (r ≥ 0.52) compared with the patient-reported Alopecia Areata Symptom and Impact Scale (AASIS) hair loss subscale score; ES and AL domain scores exhibited strong construct validity (r ≥ 0.66) compared with the SF-36 Mental Component Summary (MCS) score. Using SALT scores, HL mean item scores were better (lower) in the 25-49% SALT subgroup versus those with highest SALT scores (76-100%); however, ES mean domain scores were better in the SALT 76-100% subgroup in the same comparison (p < 0.0001). Using AASIS and MCS score-created subgroups, ES and AL mean domain scores demonstrated hypothesized differences across subgroups (all p values < 0.0001). The AAPPO questionnaire is a reliable, valid disease-specific measure of hair loss severity and impact in individuals with AA.


Massively parallel sequencing reveals an accumulation of de novo mutations and an activating mutation of LPAR1 in a patient with metastatic neuroblastoma.
Neuroblastoma is one of the most genomically heterogeneous childhood malignances studied to date, and the molecular events that occur during the course of the disease are not fully understood. Genomic studies in neuroblastoma have showed only a few recurrent mutations and a low somatic mutation burden. However, none of these studies has examined the mutations arising during the course of disease, nor have they systemically examined the expression of mutant genes. Here we performed genomic analyses on tumors taken during a 3.5 years disease course from a neuroblastoma patient (bone marrow biopsy at diagnosis, adrenal primary tumor taken at surgical resection, and a liver metastasis at autopsy). Whole genome sequencing of the index liver metastasis identified 44 non-synonymous somatic mutations in 42 genes (0.85 mutation/MB) and a large hemizygous deletion in the ATRX gene which has been recently reported in neuroblastoma. Of these 45 somatic alterations, 15 were also detected in the primary tumor and bone marrow biopsy, while the other 30 were unique to the index tumor, indicating accumulation of de novo mutations during therapy. Furthermore, transcriptome sequencing on the 3 tumors demonstrated only 3 out of the 15 commonly mutated genes (LPAR1, GATA2, and NUFIP1) had high level of expression of the mutant alleles, suggesting potential oncogenic driver roles of these mutated genes. Among them, the druggable G-protein coupled receptor LPAR1 was highly expressed in all tumors. Cells expressing the LPAR1 R163W mutant demonstrated a significantly increased motility through elevated Rho signaling, but had no effect on growth. Therefore, this study highlights the need for multiple biopsies and sequencing during progression of a cancer and combinatorial DNA and RNA sequencing approach for systematic identification of expressed driver mutations.


Pediatric patients' views regarding smoke-free hospital grounds compared to those of adults: A survey study.
Children are important stakeholders in discussions about regulation of smoking and protection from secondhand smoke, but are rarely acknowledged as such. We explored the opinion of pediatric patients and other key stakeholders regarding the planned smoke-free zone around the Erasmus MC, a large university hospital in the Netherlands. In 2019, we conducted a survey among pediatric patients and their parents, Erasmus MC employees, visitors, and adult patients, before implementation of the outdoor smoke-free zone, to assess their opinions on smoking and the planned smoke-free policy. Qualitative and quantitative data were collected and analyzed mostly using descriptive statistics and thematic analysis. In all, 91 parent-child dyads and 563 employees, visitors, patients and students filled in the questionnaires. Over 90% of children reported that they were regularly exposed to tobacco smoke, most often on the streets. Many underlined the exemplary role of healthcare providers, and 89% felt that nobody should be allowed to smoke near the hospital. Among parents, 89% were (very) positive towards the planned implementation of the smoke-free zone. In addition, 70% of adult patients, 81% of employees, 65% of visitors, 89% of students and 75% of 'others' were (very) positive about the new smoke-free policy. Smokers and former smokers generally were less positive about the policy. Children generally disapproved smoking around a hospital and felt that healthcare providers should be a good example concerning not smoking. The majority of adult patients, employees and visitors support a smoke-free zone surrounding the hospital, and virtually all pediatric patients and their parents do. Children should be acknowledged as important stakeholders in smoke-free policies and should be involved in planning and implementation.


Peripheral endothelial cells are not reliable in differentiating primary benign and malignant hepatocellular lesions in fine needle aspirates of the liver.
The distinction of hepatocellular carcinoma (HCC) from benign lesions of the liver in fine needle aspiration (FNA) specimens can be problematic. In an attempt to separate well-differentiated HCC from benign hepatocellular lesions, the presence of tissue fragments displaying peripheral endothelial cells (PE) has been proposed in a previous study as a useful feature in favour of malignancy. In this study, we evaluated slides from 59 cases of liver masses undergoing FNA (19 HCC, 40 benign) and evaluated them for the presence of tissue fragments containing PE. We found that 90% of cases of HCC contained tissue fragments in which PE were either focally present or abundant. However, 68% of cases containing only benign hepatocytes also contained tissue fragments in which PE were at least focally present. In addition, it appears that within the group of benign lesions, the presence of PE was related to the overall cellularity of the specimen rather than the specific nature of the lesion. Thus, the presence of PE in tissue fragments does not, in isolation, appear to be a useful morphological feature for the separation of benign and malignant hepatocellular lesions in FNA material.


Emotion guided threat detection: expecting guns where there are none.
Five experiments examine whether the ability of emotions to influence judgments of threat extends to a very basic process inherent in threat detection: object recognition. Participants experiencing different emotions were asked to make rapid judgments about whether target individuals were holding guns or neutral objects. Results across 4 experiments supported the hypothesis that anger increases the probability that neutral objects will be misidentified as ones related to violence, but not the converse. Of import, the findings demonstrate that this bias is not a simple function of the negative valence of an emotional state, but stems from specific threat-relevant cues provided by anger. Direct manipulation of participants' expectancies for encountering guns in the environment is shown not only to remove the bias among angry individuals when set to be low but also to produce a corresponding bias among neutral participants when set to be high. A 5th study demonstrates that the bias is amenable to correction given sufficient ability.


Galactose-Anchored Gelatin Nanoparticles for Primaquine Delivery and Improved Pharmacokinetics: A Biodegradable and Safe Approach for Effective Antiplasmodial Activity against P. falciparum 3D7 and in Vivo Hepatocyte Targeting.
Primaquine phosphate (PQ) is mainly used as a radical cure therapy to eradicate relapse of malaria at the liver stage, which is particularly caused by P. falciparum and P. vivax. In the present study, PQ-loaded galactosylated gelatin nanoparticles (Gel-LA-PQ-NPs) were formulated using a one-step desolvation technique. The mean particle size of Gel-LA-PQ-NPs was found to be 93.48 ± 6.36 nm with a zeta potential of 4.80 ± 0.20 mV having 69.90 ± 1.53% encapsulation efficiency. Electron microscopy demonstrated that the NPs were spherical in shape and uniformly distributed without any cluster formation. The in vitro release of PQ from Gel-LA-PQ-NPs has been facilitated in sustained manner, and the release was three times slower than the naïve drug. The prepared nanoparticles (Gel-LA-PQ-NPs) were significantly (p < 0.0001) less hemolytic than the pure drug PQ. The hematological ex vivo study further supported that the developed Gel-LA-PQ-NPs were safer than PQ. The in vitro antiplasmodium assay revealed that the IC50 value against the blood stage of asexual P. falciparum 3D7 strains was significantly (p < 0.01) less (2.862 ± 0.103 μM) for Gel-LA-PQ-NPs than naïve PQ (3.879 ± 0.655 μM). In vivo pharmacokinetic parameters of Gel-LA-PQ-NPs such as half-life and AUC were significantly higher for Gel-LA-PQ-NPs, i.e., with higher bioavailability. Galactosylation of the NPs led to liver targeting of the PQ in animal studies. Approximately eight-fold higher accumulation of PQ was observed in liver compared to pure drug (i.e., PQ). Conclusively, the prepared galactosylated gelatin nanocarrier holds the promising potential and hepatic targetability of an antimalarial, maintaining its safety and biocompatibility.


Cognitive and Affective Risk Beliefs and their Association with Protective Health Behavior in Response to the Novel Health Threat of COVID-19.
The COVID-19 global pandemic is an unprecedented health threat for which behavior is critical to prevent spread and personal factors could contribute to decisions for protective action. The purpose of this study was to describe associations of COVID-19 related behaviors capturing a snapshot in time during the height of the first wave of the pandemic. We tested perceptions of likelihood and severity of infection, worry, and their associations with behavior. We further explored relationships by demographic characteristics, and tested main and interactive relationships between these characteristics and beliefs and protective behaviors. Using an online cross-sectional survey, U.S. adults (N = 795) reported their perceptions of likelihood and severity of, and worry about, contracting COVID-19 for self and others, and engagement in protective behaviors. In bivariate tests, all cognitive and affective beliefs were positively associated with hygiene behaviors, but only worry and personal and others' severity were associated with greater likelihood of social distancing. Controlling for other beliefs and demographic factors, perceived personal severity remained associated with social distancing, and worry with hygiene behaviors. How people think and feel about risk could have implications for communicating information about this novel health threat and motivating action to mitigate its spread.


Synergism Effects of Ursolic Acid Supplementation on the Levels of Irisin, C-reactive Protein, IL-6, and TNF-α During High-intensity Resistance Training in Low Activity Men.
Ursolic Acid (UA) is a pentacyclic triterpenoid carboxylic acid which is extracted from plants. UA may enhance the effect of Resistance Training (RT) in human. Current research was designed to show the effect of High-Intensity Resistance Training (HIRT) in the presence or absence of UA on the serum levels of irisin, CRP, IL-6 and TNF-α in the low activity men. The study included twenty-two healthy male HIRT with placebo, supplementation, and HIRT in the presence of UA supplementation. The two groups received eight-week intervention including 2 sets of 8 exercises, with 8~10 repetitions at 70~75% of 1 repetition maximum and a 2 min rest interval between sets, performed 3 times/week. Placebo or UA orally was evaluated as 1 capsule 3 times/day during 8 weeks. The subsequent factors were measured post- and preintervention: C-Reactive Protein (CRP), Irisin, Tumor Necrotic Factor (TNF-α) and Interleukin-6 (IL-6). UA supplementation significantly increased the plasma levels of irisin in the HIRT+UA group versus the HIRT+P group (p<0.05). UA treatment also dramatically decreased the plasma levels of CRP, IL-6, and TNF-α in the HIRT+UA group versus the HIRT+P group (p<0.05). The current data showed that UA-induced an increase in serum irisin and reduction of CRP, IL-6, and TNF-α may have beneficial effects as a chemical for increasing of the effects of HIRT in low activity men.


Sickle cell disease at the dawn of the molecular era.
Recent investigations have identified a syndrome of hemolysis-associated vasculopathy in patients with sickle cell disease (SCD), which features severe hemolytic anemia that leads to scavenging of nitric oxide (NO) and its biochemical precursor arginine. This diminished bioavailability of NO promotes several clinical sequelae, which includes pulmonary hypertension, cutaneous leg ulceration, priapism, and ischemic stroke. Additional correlates of this vasculopathy include activation of endothelial cell adhesion molecules and leukocytes, as well as oxidative stress-related pathways. Some known risk factors for atherosclerosis are also associated with sickle cell vasculopathy, including low levels of apolipoprotein AI and high levels of asymmetric dimethylarginine, an endogenous inhibitor of NO synthase. Our current understanding of the dysregulated vascular biology pathways in SCD provides a basis for new clinical trials investigating promising targeted therapeutics.


Species-specific differences in translational regulation of dihydrofolate reductase.
We have observed that rodent cell lines (mouse, hamster) contain approximately 10 times the levels of dihydrofolate reductase as human cell lines, yet the sensitivity to methotrexate (ED(50)), the folate antagonist that targets this enzyme, is similar. Our previous studies showed that dihydrofolate reductase protein levels increased after methotrexate exposure, and we proposed that this increase was due to the relief of feedback inhibition of translation as a consequence of methotrexate binding to dihydrofolate reductase. In the current report, we show that unlike what was observed in human cells, dihydrofolate reductase (DHFR) levels do not increase in hamster cells after methotrexate exposure. We provide evidence to show that although there are differences in the putative mRNA structure between hamster and human mRNA in the dihydrofolate reductase binding region previously identified, "hamsterization" of this region in human dihydrofolate reductase mRNA did not change the level of the enzyme or its induction by methotrexate. Further experiments showed that human dihydrofolate reductase is a promiscuous enzyme and that it is the difference between the hamster and human dihydrofolate reductase protein, rather than the DHFR mRNA, that determines the response to methotrexate exposure. We also present evidence to suggest that the translational up-regulation of dihydrofolate reductase by methotrexate in tumor cells is an adaptive mechanism that decreases sensitivity to this drug.


A Rapid One-Pot Synthesis of Novel High-Purity Methacrylic Phosphonic Acid (PA)-Based Polyhedral Oligomeric Silsesquioxane (POSS) Frameworks via Thiol-Ene Click Reaction.
Herein, we demonstrate a facile methodology to synthesis a novel methacrylic phosphonic acid (PA)-functionalized polyhedral oligomeric silsesquioxanes (POSSs) via thiol-ene click reaction using octamercapto thiol-POSS and ethylene glycol methacrylate phosphate (EGMP) monomer. The presence of phosphonic acid moieties and POSS-cage structure in POSS-S-PA was confirmed by Fourier transform infrared (FT-IR) and nuclear magnetic resonance (¹H, 29Si and 31P-NMR) analyses. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrum of POSS-S-PA acquired in a dithranol matrix, which has specifically designed for intractable polymeric materials. The observed characterization results signposted that novel organo-inorganic hybrid POSS-S-PA would be an efficacious material for fuel cells as a proton exchange membrane and high-temperature applications due to its thermal stability of 380 °C.


Circular RNA THBS1 promotes proliferation and apoptosis of non-small cell lung cancer cells by sponging miR-129-5p and regulating SOX4 expression.
To investigate the influence of circular ribonucleic acid thrombospondin-1 (circTHBS1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells by sponging miR-129-5p and regulating the expression of SRY-box transcription factor 4 (SOX4). Carcinoma and para-carcinoma specimens were collected from 40 NSCLC patients, and 25 pairs of specimens were obtained from patients with metastatic and non-metastatic NSCLC. After NSCLC cells were cultured, the proliferation was detected via cell counting kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) assays, and the cell cycle and apoptosis rate were analyzed through flow cytometry. Finally, the action targets of circTHBS1 were determined using dual-luciferase reporter gene assay, and Western blotting assay was applied to measure the changes in protein levels. The expression of circTHBS1 was markedly higher in NSCLC patients than that in control group, and it was increased in patients with metastatic NSCLC compared with that in patients with non-metastatic NSCLC. Moreover, the proliferative ability of the cells was weakened notably after transfection with small interfering (Si)-CircTHBS1, but it was enhanced remarkably after transfection with CircTHBS1-overexpression vector (OE). There were complementary sites in circTHBS1 for the 3'-UTR of miR-129-5p, and the fluorescence intensity of wild-type circTHBS1 declined evidently after interacting with miR-129-5p. Besides, there was a putative binding site between miR-129-5p and SOX4, and SOX4 expression was decreased obviously after overexpressing miR-129-5p but increased following overexpression of circTHBS1. CircTHBS1 promotes the proliferation and inhibits the apoptosis of NSCLC cells through targeting miR-129-5p and regulating SOX4 expression.


Circulation policies in health science libraries.
There is general agreement that library policies have considerable influence on the use of libraries. Medical school (health science) libraries of this country were surveyed as to their policies in respect to whether faculty and student use were regulated by a single policy, circulation regulations, hours library was accessible to users, accessibility of reserve material, interlibrary loan, policy on overdue material, and exit control. THE LIBRARIES WERE THEN DIVIDED INTO THREE GROUPS, HIGH, MIDDLE, AND LOW ACCORDING TO THE FOLLOWING CHARACTERISTICS: size of student body, size of faculty, size of holdings, size of library staff, annual budget, and annual circulation. Our findings would indicate that schools falling in a high category based upon these criteria tend to be more restrictive in their policies and to have different regulations for faculty and students than do schools in the low category.These findings warrant further study.


[Contemporary control of biological warfare].
Biological pathogens actually are in the focus of interest as a potential biological weapon in bioterrorist's disposition. In the study the main pathogens and their activity spectrum have been presented. The special attention has been paid upon aerosol way of transmission and its consequences. The possibilities of prevention and treatment of diseases caused by biological pathogens have been also discussed.


Clinical implications of seizures in neurosarcoidosis.
Seizures are a recognized manifestation of neurosarcoidosis, but their clinical relevance is not well established. We reviewed the characteristics, clinical correlations, and prognosis of seizures in 79 patients with neurosarcoidosis. Thirteen (15%) of the 79 patients had seizures, and in eight patients (10%) a seizure was the first manifestation of neurosarcoidosis. These seizures were generalized tonic-clonic seizures in 12 patients (92%) and partial seizures in four patients (31%). The patients with neurosarcoidosis with seizures were more likely to have a progressive or relapsing clinical course and intracranial mass lesions (four patients [31%]), encephalopathy or vasculopathy (eight patients [62%]), or hydrocephalus (five patients [38%]). These central nervous system disorders, rather than the seizures per se, were responsible for most of the serious morbidity and the two deaths (15%) among our patients with seizures. Indeed seizure control was good in 11 (85%) of 13 patients treated with combinations of steroids and antiepileptic medications. Seizures are an important sign in neurosarcoidosis because they are associated with more severe and progressive or relapsing forms of central nervous system sarcoidosis and may be an early manifestation of such disorders.


Evolution and assembly of an extremely scrambled gene.
The process of gene unscrambling in hypotrichous ciliates represents one of nature's ingenious solutions to the problem of gene assembly. With some essential genes scrambled in as many as 51 pieces, these ciliates rely on sequence and structural cues to rebuild their fragmented genes and genomes. Here we report the complex pattern of scrambling in the DNA polymerase alpha gene of Stylonychia lemnae. The germline (micronuclear) copy of this gene is broken into 48 pieces with 47 dispersed over two loci, with no asymmetry in the placement of coding segments on either strand. Direct repeats present at the boundaries between coding and noncoding sequences provide pointers to help guide assembly of the functional (macronuclear) gene. We investigate the evolution of this complex gene in three hypotrichous species.


[Upper extremity deep venous effort thrombosis : management of the Paget-Schroetter syndrome in the emergency department].
We report a case of upper extremity deep venous effort thrombosis complicating a thoracic outlet syndrome in a 44-year-old patient. The appearance of this complication was sudden. A clinical examination followed by imaging with phlebography leads to a quick diagnosis. Effort thrombosis is a classic example of an entity which, if treated correctly, has minimal long-term sequelae but, if ignored, is associated with significant long-term morbidity. An appropriate medical and interventional care has been implemented as soon as possible. Once primary thrombosis is recognized, catheter-directed thrombolytic therapy is usually successful if initiated early, but often unmasks an underlying problem.


[Crohn disease: initial experiences with cyclosporin A in an adolescent girl].
The diagnosis of Crohn's disease with extensive involvement of small intestine and colon was first made in a 12 3/4-year-old girl, now 15 1/2 years old. Despite continued treatment with prednisolone and salazosulfapyridine, as well as azathioprine and metronidazole, no lasting remission was obtained. Widespread severe osteoporosis with vertebral fractures made it necessary to discontinue the prednisolone, despite endoscopically and biochemically confirmed signs of activity of the disease. Administration of cyclosporin A in this situation produced phases of improved clinical and biochemical parameters. Regular control of biochemical levels failed to reveal any drug-specific acute side-effects. Because of the increased incidence of malignant lymphoma under cyclosporin A this drug should be held in reserve in the treatment of Crohn's disease, until results from controlled studies have become available.


Factors associated with hospital and intensive care admission in paediatric SARS-CoV-2 infection: a prospective nationwide observational cohort study.
Coronavirus disease 2019 (COVID-19) is usually less severe in children compared to adults. This study describes detailed clinical characteristics, treatment and outcomes of children with COVID-19 in a non-hospitalised and hospitalised setting and quantifies factors associated with admission to hospital and intensive care unit in children with SARS-CoV-2 infection on a nationwide level. Data were collected through the Swiss Paediatric Surveillance Unit from children < 18 years with confirmed SARS-CoV-2 infection. All 33 paediatric hospitals in Switzerland reported non-hospitalised and hospitalised cases from March 1 to October 31, 2020 during both pandemic peaks. In total, 678 children were included. The median age was 12.2 years (IQR 5.0-14.6), 316 (46.6%) were female and 106 (15.6%) had comorbidities. Overall, 126 (18.6%) children were hospitalised of whom 16 (12.7%) required ICU admission. Comorbidities were the only factor associated with hospital admission in a multivariable regression analysis (odds ratio 3.23, 95%CI 1.89 to 5.50; p-value < 0.01). Children with preexisting comorbidities did not require ICU admission more often. Hospitalised children more often presented with fever (96 [76.2%] vs 209 [38.1%], p-value < 0.01) and rash (16 [12.8%] vs 6 [1.1%], p-value < 0.01). Anosmia/dysgeusia was more prevalent in non-hospitalised children (73 [13.3%] vs 3 [2.4%], p-value < 0.01). In hospitalised children, oxygen treatment was required in 34 (27.0%), inotropes in nine (7.3%) and mechanical ventilation in eight (6.3%) cases. Complications were reported in 28 (4.1%) children with cardiovascular complications being most frequent (12 [1.8%]). Three deaths were recorded.Conclusion: This study confirms that COVID-19 is mostly a mild disease in children. Fever, rash and comorbidities are associated with higher admission rates. Continuous observation is necessary to further understand paediatric COVID-19, guide therapy and evaluate the necessity for vaccination in children. What is Known: • Clinical manifestations of SARS-CoV-2 infection in children vary from asymptomatic to critical disease requiring intensive care unit admission. • Most studies are based on hospitalised children only; currently, there is limited data on non-hospitalised children. What is New: • The clinical spectrum and severity of COVID-19 is influenced by age: in children less than 2 years, fever, cough and rhinorrhoea are the most common symptoms and in adolescents, fever, cough and headache are more common. • Hospitalised children more often presented with fever and rash, while anosmia/dysgeusia is more prevalent in non-hospitalised children. • Children with pre-existing comorbidities are more frequently hospitalised but do not require ICU admission more often.


Modulation of JA signalling reveals the influence of StJAZ1-like on tuber initiation and tuber bulking in potato.
Phytohormones and their interactions play critical roles in Solanum tuberosum (potato) tuberization. The stimulatory role of jasmonic acid (JA) in tuber development is well established because of its significant promotion of tuber initiation and tuber bulking. However, the dynamics and potential function of JA signalling in potato tuberization remain largely unknown. The present study investigated the role of the JAZ1 subtype, a suppressor of JA signalling, in potato tuberization. Using 35S:StJAZ1-like-GUS as a reporter, we showed that JA signalling was attenuated from the bud end to the stem end shortly after tuber initiation. Overexpression of StJAZ1-like suppressed tuber initiation by restricting the competence for tuber formation in stolon tips, as demonstrated by grafting an untransformed potato cultivar to the stock of StJAZ1-like-overexpressing transgenic potato plants (StJAZ1-like ox). In addition, transcriptional profiling analysis revealed that StJAZ1-like modulates the expression of genes associated with transcriptional regulators, cell cycle, cytoskeleton and phytohormones. Furthermore, we showed that StJAZ1-like is destabilised upon treatment with abcisic acid (ABA), and the attenuated tuberization phenotype in StJAZ1-like ox plants can be partially rescued by ABA treatment. Altogether, these results revealed that StJAZ1-like-mediated JA signalling plays an essential role in potato tuberization.


Hepatic gluconeogenesis and the activity of PDH in individual tissues of GTG-obese mice following adrenalectomy.
Adrenalectomy (ADX) lowers circulating glucose levels in animal models of non-insulin dependent diabetes (NIDDM) and obesity. To investigate the role of hepatic glucose production (HGP) and tissue glucose oxidation in the improvement in glucose tolerance, hepatocyte gluconeogenesis and the activity of pyruvate dehydrogenase (PDH) were examined in different tissues of gold thioglucose (GTG) obese mice 2 weeks after ADX or sham ADX. GTG-obese mice which had undergone ADX weighed significantly less than their adrenal intact counterparts (GTG ADX: 37.5 +/- 0.7 g; GTG: 44.1 +/- 0.4; p < 0.05), and demonstrated lower serum glucose (GTG ADX: 22.5 +/- 1.6 mmol/L; GTG: 29.4 +/- 1.9 mmol/L; p < 0.05) and serum insulin levels (GTG ADX: 76 +/- 10 microU/mL; GTG: 470 +/- 63 microU/mL; p < 0.05). Lactate conversion to glucose by hepatocytes isolated from ADX GTG mice was significantly reduced compared with that of hepatocytes from GTG mice (GTG ADX: 125 +/- 10 nmol glucose/10(6) cells; GTG: 403 +/- 65 nmol glucose/10(6) cells; p < 0.05). ADX also significantly reduced both the glycogen (GTG ADX: 165 +/- 27 mumol/liver; GTG: 614 +/- 60 mumol/liver; p < 0.05) and fatty acid content (GTG ADX: 101 +/- 9 mg fatty acid/g liver; GTG: 404 +/- 40 mg fatty acid/g liver; p < 0.05) of the liver of GTG-obese mice. ADX of GTG-obese mice reduced PDH activity by varying degrees in all tissues, except quadriceps muscle. These observations are consistent with an ADX induced decrease in hepatic lipid stores removing fatty acid-induced increases in gluconeogenesis and increased peripheral availability of fatty acids inhibiting PDH activity via the glucose/fatty acid cycle. It is also evident that the improvement in glucose tolerance which accompanies ADX of GTG-obese mice is not due to increased PDH activity resulting in enhanced peripheral glucose oxidation. Instead, it is more likely that reduced blood glucose levels after ADX of GTG-obese mice are the result of decreased gluconeogenesis in the liver.


Complete exon structure of the ALL1 gene.
The ALL1 gene is found rearranged in approximately 10% of acute lymphoblastic leukemias and in over 5% of acute myeloid leukemias. The gene undergoes fusion with either a variety of partner genes located on different chromosomes or with itself. To further characterize the role of the ALL1 gene in the leukemogenic process, and possibly in solid malignancies, we defined its complete genomic structure. The gene, which spans a region on chromosome band 11q23 approximately 90 kb in length, consists of 36 exons, ranging in size from 65 bp to 4249 bp. The determination of intronic sequences flanking the exon boundaries will allow the determination of whether point mutations may be responsible for inactivation of the gene in solid tumors showing loss of heterozygosity at region 11q23.


Exploitation of two siderophore receptors, BauA and BfnH, for protection against Acinetobacter baumannii infection.
Iron uptake system is expressed in early stages of Acinetobacter baumannii infections under iron-restricted conditions. This study is aimed at the evaluation of immuno-protectivity of BfnH in comparison with BauA in both mature and selected fragmental proteins. The study was designed in single and combined forms of antigens. BfnH is presented in 3472 strains of A. baumannii with more than 97% identity. The preliminary immune-informatics analysis of this protein indicated a region from the β-barrel domain including exposed loops 2-5, with antigenic score comparable to that of BfnH. There was a significant rise in the specific IgG response in all test groups. The bacterial challenge with a lethal dose of A. baumannii demonstrated partial protection of whole proteins which coincides with a significant reduction in the bacterial population colonized in the main organs and an increase in the survival level. Passive immunization of the mice brought about 50% survival in the mice groups immunized with BfnH and with a combination of BfnH and BauA. The protectivity of siderophore receptors suggests their potential immunogenic role that could be considered as a component of multivalent subunit vaccine candidates against A. baumannii.


A brainstem map for visceral sensations.
The nervous system uses various coding strategies to process sensory inputs. For example, the olfactory system uses large receptor repertoires and is wired to recognize diverse odours, whereas the visual system provides high acuity of object position, form and movement1-5. Compared to external sensory systems, principles that underlie sensory processing by the interoceptive nervous system remain poorly defined. Here we developed a two-photon calcium imaging preparation to understand internal organ representations in the nucleus of the solitary tract (NTS), a sensory gateway in the brainstem that receives vagal and other inputs from the body. Focusing on gut and upper airway stimuli, we observed that individual NTS neurons are tuned to detect signals from particular organs and are topographically organized on the basis of body position. Moreover, some mechanosensory and chemosensory inputs from the same organ converge centrally. Sensory inputs engage specific NTS domains with defined locations, each containing heterogeneous cell types. Spatial representations of different organs are further sharpened in the NTS beyond what is achieved by vagal axon sorting alone, as blockade of brainstem inhibition broadens neural tuning and disorganizes visceral representations. These findings reveal basic organizational features used by the brain to process interoceptive inputs.


Ontogeny of corticosteroid receptors in the brain.
1. In the brain, glucocorticoids bind to both the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). These receptors show clearly distinct developmental patterns in the infant rat. 2. Low levels of GRs are present around the time of birth throughout the brain. Concentrations rise slowly, and do not achieve adult levels until the third week of life, approximately. GR affinity for corticosterone is higher perinatally than at later ages. Receptor microdistribution changes dramatically during ontogeny. In particular, certain regions, such as the suprachiasmatic nucleus of the hypothalamus, express high levels of receptor only during the first week of life. GRs may show impaired capacity to undergo transformation and/or nuclear translocation during the second postnatal week. Environmental manipulations during early ontogeny (e.g., early handling) may have permanent effects on GR capacity. 3. MRs are present at very low concentrations in the first days of life. Binding capacity rises rapidly thereafter and resembles that found in the adult by the end of 1 week. Neither binding affinity in vitro nor overall distribution changes with age. As in the adult, low doses of corticosterone, in vivo, bind mainly to the MRs. Levels of corticosterone are low and relatively unperturbable in the intact infant rat. It is likely, therefore, that most of the physiological actions of this hormone during this period are mediated by the MR.


The incidence of recurrence and hypothyroidism following treatment with antithyroid drugs, surgery or radioiodine in all patients with thyrotoxicosis in Malmö during the period 1970-1974.
The incidence of recurrence and of hypothyroidism was determined in all new patients treated for thyrotoxicosis during the period 1970-1974 in an unselected, well-defined urban population. A total of 309 patients were followed up for a median time period of 108 (1-192) months. There was a cumulative incidence of 51% recurrence in patients who were treated with antithyroid drugs for Graves' thyrotoxicosis, whereas after surgery or radioiodine treatment there were few recurrences, but 32% and 78% cumulative incidences of hypothyroidism. There were no recurrences after surgery or radioiodine treatment in patients with toxic multinodular goitre or solitary toxic adenoma, but 29% and 40% cumulative incidences of hypothyroidism following radioiodine treatment. Late hypothyroidism occurred after surgery for Graves' thyrotoxicosis, and in all groups treated with radioiodine. Thus it is advisable that all patients with Graves' thyrotoxicosis, regardless of treatment, and all patients with toxic multinodular goitre or solitary toxic adenoma treated with radioiodine, should be followed up for many years, and probably for life.


Note: Improved sensitivity of magnetic measurements under high pressure in miniature ceramic anvil cell for a commercial SQUID magnetometer.
Two modifications have been made to a miniature ceramic anvil high pressure cell (mCAC) designed for magnetic measurements at pressures up to 12.6 GPa in a commercial superconducting quantum interference (SQUID) magnetometer [N. Tateiwa et al., Rev. Sci. Instrum. 82, 053906 (2011); ibid. 83, 053906 (2012)]. Replacing the Cu-Be piston in the former mCAC with a composite piston composed of the Cu-Be and ceramic cylinders reduces the background magnetization significantly smaller at low temperatures, enabling more precise magnetic measurements at low temperatures. A second modification to the mCAC is the utilization of a ceramic anvil with a hollow in the center of the culet surface. High pressures up to 5 GPa were generated with the "cupped ceramic anvil" with the culet size of 1.0 mm.


Analysis of Polymorphism rs1900004 in Atonal bHLH Transcription Factor 7 in Saudi Patients with Primary Open Angle Glaucoma.
To investigate the association between the rs1900004 polymorphism in the atonal bHLH transcription factor 7 (ATOH7) gene and primary open angle glaucoma (POAG) in Saudi patients. Eighty-seven unrelated POAG cases and 94 unrelated control subjects of Saudi origin were genotyped utilizing a TaqMan® assay. The association between mutant genotypes and POAG and its related clinical indices was investigated. The genotype and allele frequencies of the polymorphism in ATOH7 did not show any statistically significant association with POAG compared to controls. The minor allele frequency was 0.32 in both cases and controls. None of the demographic, systemic diseases nor glaucoma-specific clinical indices such as intraocular pressure (IOP), cup/disc ratio, and number of antiglaucoma medication, showed any significant association with genotypes. Binary logistic regression analysis (adjusted for age and gender) showed that age was a marginally significant risk factor for the development of glaucoma (adjusted odds ratio = 1.1; 95% confidence interval = 1.079-1.158; p < 0.0001). The study did not detect any direct link between genotype/allele frequency of rs1900004 in ATOH7 and POAG or its related clinical indices such as IOP and cup/disc ratio indicating that this polymorphism is not a risk factor for POAG in a Saudi cohort.


Lipid Head Group Charge and Fatty Acid Configuration Dictate Liposome Mobility in Neurofilament Networks.
Intermediate filaments constitute a class of biopolymers whose function is still poorly understood. One example for such intermediate filaments is given by neurofilaments, large macromolecules that fill the axon of neurons. Here, reconstituted networks of purified porcine neurofilaments are studied and the diffusion behavior of different nanoparticles in the biopolymer network is evaluated. A strong dependence of particle diffusion on the charge state of the particles, and - for liposomes - also on the fatty acid configuration of lipids is observed. The results suggest that both electrostatic and hydrophobic interactions contribute to nanoparticle trapping in neurofilament networks, and that the latter is enabled by lipids with an inverted cone geometry which grant access to the hydrophobic core of the liposome shell.


A comparison between the crystal and solution structures of Escherichia coli asparaginase II.
The small angle X-ray scattering (SAXS) pattern of the homotetrameric asparaginase II from Escherichia coli was measured in solution in conditions resembling those in which its crystal form was obtained and compared with that calculated from the crystallographic model. The radius of gyration measured by SAXS is about 5% larger and the maximum dimension in the distance distribution function about 12% larger than the corresponding value calculated from the crystal structure. A comparison of the experimental and calculated distance distribution functions suggests that the overall quaternary structure in the crystal and in solution are similar but that the homotetramer is less compact in solution than in the crystal.


Ventriculoperitoneal shunt placement with ultrasound guidance and laparoscopic assistance: 2-dimensional instructional video.
Postoperative communicating hydrocephalus has been described in the literature commonly associated with treatment of ruptured intracranial aneurysms; however, it is also reported to occur following other intracranial interventions such as meningioma resection and decompressive hemicraniectomy. In 2011, Burkhardt et al. reported the incidence of postoperative hydrocephalus following skull base meningioma resection was twice as high as resection of meningiomas in other regions.[1] They found that age and increased length of surgery were associated with higher rates of postoperative hydrocephalus. Our patient, a 76-year-old man, initially presented with the left-hand paresthesias and numbness before the revelation of a large sphenoid planum meningioma on workup imaging. He underwent surgical resection due to developing cranial nerve deficits and personality changes in an extensive procedure that required approximately 8 h to complete. His postoperative course, given the factors above, included the development of hydrocephalus. He was taken to the operating room for ventriculoperitoneal shunt placement, as displayed in this video case report, which highlights our surgical and sterile techniques, intraoperative ultrasound to ensure appropriate ventricular placement, and a single-port laparoscopic technique for direct visualization of placement of the abdominal catheter. After shunt placement, his course was complicated by a small tract hemorrhage, which resolved without further treatment. He was observed to have an improvement in mental function that occurred over the following 2-3 days before being discharged to an outpatient rehabilitation facility for continued care. Ventriculoperitoneal shunt placement is an effective and safe procedure for the treatment of postoperative communicating hydrocephalus when performed with appropriate techniques as displayed in the associated video case report. The patient gave informed consent for surgery and video recording. Institutional Review Board approval was deemed unnecessary.


Association between angiotensinogen gene M235T polymorphism and mitral valve prolapse syndrome in Taiwan Chinese.
It has been reported that patients with mitral valve prolapse syndrome (MVPS) also have a disorder in autonomic or neuroendocrine function which can cause many related symptoms. Although a potential role of the reninangiotensin system in the pathogenesis of MVPS has been addressed, the role of the angiotensinogen (AGT) genetic variant in MVPS has not been studied. Thus, a case-controlled study was performed to investigate the possible relationship between AGT gene polymorphisms and MVPS. A total of 100 patients with MVP diagnosed by echocardiography and 100 age- and sex-matched normal control subjects was studied. AGT gene M235T and T174M polymorphisms were identified by polymerase chain reaction-based restriction analysis. There was a significant difference in the distribution of AGT gene M235T genotypes (p <0.001) and allelic frequencies (p <0.001) between MVPS cases and controls. An Odds Ratio (OR) for risk of MVPS associated with M235T TT genotype was 8.55 (95% CI 4.51-16.18). An OR for risk of MVPS associated with the T allele at the M235T locus of the AGT gene was 3.27 (95% CI 2.05-5.22). The T174M polymorphism of AGT gene showed no association with MVPS (p = 0.94). These findings suggest that the M235T polymorphism of the AGT gene is associated with MVPS in the Chinese population of Taiwan. The association of the TT genotype with MVPS is more noteworthy than an overall increase in the frequency of the T allele at the M235T locus.


Incidence of upper respiratory tract Mycoplasma pneumoniae infections among outpatients in Rhône-Alpes, France, during five successive winter periods.
In this prospective study, nasal swab samples from patients with acute respiratory infections were evaluated for the presence of Mycoplasma pneumoniae. This PCR-plus-hybridization-based detection was associated with the detection of other viral agents. During the five winter surveillance periods, 3,897 samples were collected by 75 medical practitioners participating in the Groupe Régional d'Observation de la Grippe surveillance network in Rhône-Alpes (France). M. pneumoniae was detected in 283 samples (7.3%); its rate of detection ranged from 10.1 to 2.0% over the five periods, and it was the second most frequently isolated pathogen during the survey, after influenza A. Three high-prevalence winters were observed, yielding an early winter peak of M. pneumoniae infection which was observed in all age groups. No statistically significant difference was detected between rates of infections in the different age groups, but M. pneumoniae infection was significantly related to lower respiratory tract infection during periods of high prevalence. This study defined the frequency of M. pneumoniae detection from nasal swab specimens in patients with acute respiratory infections, confirming its high prevalence and the presence of large outbreaks due to this pathogen.


Proteins and enzymes in uterine lavage fluid of postpartum and nonparturient mares.
Uterine lavage fluids from postpartum and nonparturient mares were compared to determine when the normal secretory capacity of the postpartum uterus is restored. Lavage fluids were obtained from cyclic nonparturient mares on the second, fourth or fifth day of oestrus, and 3, 8, or 14 days after ovulation (seven mares/sampling day). Twelve intact postpartum mares were sampled 1 to 28 days postpartum (group A: 1, 6, 12 and 20; group B: 2, 8, 14 and 24; group C: 4, 10, 16 and 28 days postpartum; four mares/group). Three ovariectomized (OVX) postpartum mares were sampled as mares in group C. Samples were analysed for neutrophils, bacteria, total protein concentration, proteolytic and antiproteolytic activities and for various lysosomal enzyme activities. In nonparturient mares, activities of acid phosphatase, beta-glucuronidase (B-Gase), and N-acetyl-beta-D-glucosaminidase (NAGase) in uterine lavage fluids were significantly higher in mid- and late-dioestrus than in mid- to late-oestrus (p < 0.05). Lysozyme concentration, trypsin-inhibitor capacity (TIC), and plasmin activity were below the detection limit in nonparturient mares. One to four days postpartum, total protein, acid phosphatase, B-Gase, and NAGase were high but declined rapidly thereafter. Lysozyme and plasmin activities were high 1 to 6 days postpartum. TIC peaked around day 6 postpartum. On day 16 postpartum, acid phosphatase, B-Gase, and NAGase, being progesterone-dependent, tended to be higher in intact mares than in OVX ones (p < 0.1). Total protein and lysozyme concentrations, TIC, and B-Gase (p < 0.01) and acid phosphatase (p < 0.05) activities were significantly higher in parturient mares during postpartum oestrus than in oestrous nonparturient mares. High total protein concentration and TIC, and detectable lysozyme and plasmin activities during postpartum oestrus were associated with uterine inflammation. During dioestrus, differences between postpartum and nonparturient mares were not statistically significant and suggested that the endometrium of postpartum mares had resumed its normal secretory capacity by this time.


G708E mutation in the androgen receptor results in complete loss of androgen function.
End-organ resistance to androgens, called androgen insensitivity syndrome (AIS), is a rare disorder. The most common cause of AIS is mutations(s) in the androgen receptor (AR) gene; however, a significant number of these mutations have not been functionally analyzed. In the present study, we analyzed a case of complete AIS for mutations in the AR gene. Sequencing of the entire coding region of the AR gene revealed a 2650G>A mutation (mRNA sequence reference) in exon 4 of the gene, resulting in replacement of glycine with glutamate at codon 708 in the ligand-binding domain of the AR protein. The mutation was absent in 200 normal male individuals analyzed to look at its occurrence in general population. In vitro androgen-binding and transactivation assays showed that the mutation resulted in approximately 65% loss of ligand binding and almost complete loss of transactivation function. Complete AIS in this individual was due to a G708E substitution in the AR protein.


[Effects of HMGB1 inhibition on endoplasmic reticulum stress after myocardial ischemia/reperfusion injury in rats].
To investigate the effect of high mobility group protein B1 (HMGB1) inhibition on endoplasmic reticulum stress (ERS) after myocardial ischemia/reperfusion (I/R) in rats. Forty male Sprague-Dawley (SD) rats were randomly divided into four groups (n = 10): sham operation group, I/R model group, Gene silencing (HMGB1-siRNA) group, and empty vector (Scrambled-siRNA) group. Coronary blood flow of the rats were ligated for 30 minutes, relaxed the ligament line for 2 hours, to establish I/R injury model; not ligation with the sham operation group. Each group was injected 1 mL phosphate buffer (PBS), HMGB1-siRNA mixture or Scrambled-siRNA mixture preoperative by tail vein 0 hour, 12 hours, and 24 hours before surgery. After 2 hours reperfusion, the levels of tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-8) in the serum were detected by enzyme linked immunosorbent assay (ELISA); the expression of HMGB1 protein in myocardium was detected by immunohistochemistry; the protein and mRNA expressions of HMGB1, GRP78, CHOP and caspase-12 in myocardium were detected by Western Blot and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR). Compared with sham operation group, the levels of serum inflammatory factor, HMGB1 positive cells, and the protein and mRNA expressions of GRP78, CHOP, caspase-12 were significantly increased in I/R model group. The levels of serum inflammatory factor in HMGB1-siRNA group were significantly lower than those in the I/R model group [TNF-α (ng/L): 783.4±203.4 vs. 963.9±214.1, IL-6 (ng/L): 358.8±94.8 vs. 452.3±103.7, IL-8 (ng/L): 180.5±73.6 vs. 347.3±90.3, all P < 0.05], HMGB1 positive cells, and the protein and mRNA expressions of GRP78, CHOP, caspase-12 in HMGB1-siRNA group were significantly lower than I/R model group (HMGB1 protein: 1.59±0.26 vs. 3.21±0.40, GRP78 protein: 2.59±0.28 vs. 4.21±0.42, CHOP protein: 2.01±0.23 vs. 3.21±0.43, caspase-12 protein: 1.48±0.22 vs. 3.01±0.48; HMGB1 mRNA: 2.35±0.26 vs. 4.67±0.45, GRP78 mRNA: 6.59±0.26 vs. 11.21±0.40, CHOP mRNA: 2.01±0.43 vs. 5.21±0.63, caspase-12 mRNA: 4.48±0.32 vs. 8.41±0.52, all P < 0.05). There was no significant difference between the Scrambled-siRNA group and the I/R model group. HMGB1 may be involved in the activation of ERS in myocardial I/R injury and increase the damage of myocardial cells.


[Study on the mechanism of hepatocytic insulin signal transduction defects in severely scalded rats].
To investigate the mechanism of hepatocytic insulin signal transduction defects in severely scalded rats, so as to clarify the molecular basis of postburn insulin resistance. Wistar rats inflicted by 30% III degree scalding on the back were employed as the model. The rat hepatocytic insulin receptor was partially purified by wheat-germ agglutinin (WGA)-sepharose 4B affinity chromatography. The change of receptor tyrosine protein kinase (TPK) activity, the receptor beta-subunit autophosphorylation and the hepatocytic insulin receptor binding behavior of scalded rats during early stage of scalding were observed by means of insulin receptor binding test, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) autoradiography of phosphorylation of insulin receptor and phosphorylation of exogenous substrate. There exhibited no evident changes of hepatocytic insulin receptor maximal binding capacity and affinity at 3 postburn days (PBDs) in scalded rats. The autophosphorylation capacity of the receptor beta-subunit decreased significantly. And the receptor TPK activity decreased obviously and its reaction to insulin stimulation decreased markedly. The defects of the insulin receptor signal transduction in hepatocyte leading to the post-receptor defects of insulin biological effects might be molecular mechanism of postburn insulin resistance.


Transcriptome analysis in endothelial progenitor cell biology.
The use of endothelial progenitor cells (EPCs) is a promising new treatment option for cardiovascular diseases. Many of the underlying mechanisms that result in an improvement of endothelial function in vivo remain poorly elucidated to this date, however. We summarize the current positions and potential applications of gene-expression profiling in the field of EPC biology. Based on our own and published gene-expression data, we demonstrate that gene-expression profiling can efficiently be used to characterize different EPC types. Furthermore, we highlight the potential of gene-expression profiling for the analysis of changes that EPCs undergo during culture and examine changes in gene transcription in diseased patients. Transcriptome profiling is a powerful tool for the characterization and functional analysis of EPCs in health and disease.


[Glucocorticoid pathway mediated the inhibition of testosterone in rats exposed to dibutyl phthalate].
To investigate the inhibitory mechanisms of testosterone (T) biosynthesis in rats exposed to dibutyl phthalate (DBP). Male Wistar rats were randomly divided into five groups by weight, including 0.25, 0.50, 1.00, 2.00 g/kg DBP groups and corn oil control group, with 16 rats in each group. DBP was administered by gavage once a day. After 30 days exposure, eight rats in each group were killed and the others were killed after 15 days without DBP administration. The levels of T and glucocorticoid (GC) in serum were determined by radioimmunoassay. The expression levels of 11 beta-dedroxysteriod dehydrogenase (11 beta-HSD) mRNA and steroidogenesis acute regulatory protein (StAR) mRNA were determined by RT-PCR. The protein expression level of glucocorticoid receptor (GR) was investigated by Western blotting. During exposure period, in 1.00 and 2.00 g/kg DBP groups, the levels of T were (0.260 +/- 0.218) ng/ml and (0.260 +/- 0.342) ng/ml, the levels of GC were (13.470 +/- 5.661) ng/ml and (13.740 +/- 3.977) ng/ml, the levels of T and GC in control group were (1.045 +/- 1.222) ng/ml and (9.224 +/- 3.496) ng/ml. There were statistic differences between 1.00 and 2.00 g/kg DBP groups and control group (t(T) values were -2.295 and -2.295, t(GC) values were 2.159 and 2.296, respectively, P < 0.05). The expression level of StAR mRNA was significantly down-regulated in 1.00 and 2.00 g/kg DBP groups, while StAR/beta-Actin values were 0.657 +/- 0.060 and 0.407 +/- 0.033, and compared to control group (0.871 +/- 0.081), there was statistic difference (t values were -3.707 and -8.037, P < 0.05). In 1.00 and 2.00 g/kg DBP groups, the expression of 11 beta-HSD mRNA and the expression of GR protein were increased in DBP dose-dependent manner, while 11 beta-HSD/beta-Actin values were 0.538 +/- 0.138 and 0.988 +/- 0.133, and GR/beta-Actin were 0.785 +/- 0.106 and 0.956 +/- 0.076, respectively. There were statistic difference, as compared to the controls (0.285 +/- 0.106 and 0.275 +/- 0.035) (t(11 beta-HSD/beta-Actin) values were 2.829 and 7.860, t(GR/beta-Actin) values were 8.064 and 10.77, respectively, P < 0.05).Linear correlation and regression revealed that there were positive correlation between DBP dose and the expression levels of 11 beta-HSD mRNA and GR protein, with r values of 0.766 and 0.790, respectively. In post-exposure period, there were no statistic differences of all above index among DBP groups and control group. DBP might inhibit T production in rats through GR mediation.


Using neural networks for (13)c NMR chemical shift prediction-comparison with traditional methods.
Interpretation of (13)C chemical shifts is essential for structure elucidation of organic molecules by NMR. In this article, we present an improved neural network approach and compare its performance to that of commonly used approaches. Specifically, our recently proposed neural network (J. Chem. Inf. Comput. Sci. 2000, 40, 1169-1176) is improved by introducing an extended hybrid numerical description of the carbon atom environment, resulting in a standard deviation (std. dev.) of 2.4 ppm for an independent test data set of approximately 42,500 carbons. Thus, this neural network allows fast and accurate (13)C NMR chemical shift prediction without the necessity of access to molecule or fragment databases. For an unbiased test dataset containing 100 organic structures the accuracy of the improved neural network was compared to that of a prediction method based on the HOSE code (hierarchically ordered spherical description of environment) using SPECINFO. The results show the neural network predictions to be of quality (std. dev. = 2.7 ppm) comparable to that of the HOSE code prediction (std. dev. = 2.6 ppm). Further we compare the neural network predictions to those of a wide variety of other (13)C chemical shift prediction tools including incremental methods (CHEMDRAW, SPECTOOL), quantum chemical calculation (GAUSSIAN, COSMOS), and HOSE code fragment-based prediction (SPECINFO, ACD/CNMR, PREDICTIT NMR) for the 47 (13)C-NMR shifts of Taxol, a natural product including many structural features of organic substances. The smallest standard deviations were achieved here with the neural network (1.3 ppm) and SPECINFO (1.0 ppm).


Sterilization and reprocessing of materials and medical devices--reusability.
Problems associated with reprocessing of disposable medical devices such as hemodialysers with resterilization for reuse and changes in material properties with resterilization of polymeric (PVC, polypropylene, polyester, polycarbonate) materials intended for development of disposable devices are reviewed. Reprocessing of hospital supplies, polystyrene microtiter plate and angiographic catheter for reuse is also discussed.


Short report: peak period of filarial transmission.
This study was designed to determine the peak period of infective mosquito biting and thus the greatest potential for filarial transmission to occur. It was found that biting density, natural infection, and infectivity rates of Culex quinquefasciatus were significantly higher in the third quadrant of the night (from midnight to 3:00 AM) than at other times. This was true in both an urban and a rural environment. Avoidance of mosquito bite by any means during this time period might reduce and limit filarial transmission to a great extent.


Surgical results in Brown syndrome.
Surgical treatment for Brown superior oblique tendon sheath syndrome, now called Brown syndrome, has been advocated for patients with abnormal head posture or manifest hypotropia in primary gaze. Several surgical procedures with variable results and complications have been reported without consensus. Techniques and results of treatment for Brown syndrome at two institutions were reviewed. Charts of all patients who had undergone surgical treatment at Texas Children's Hospital, Houston, Tex, and Riley Hospital for Children, Indianapolis, Ind, between 1965 and 1989 were reviewed. The review yielded 38 patients. Superior oblique tenectomy was the most efficacious initial procedure. Surgery was successful in the treatment of anomalous head posture associated with Brown syndrome. There was no loss of sensory function as a result of surgery, but surgery did not inevitably lead to improved sensory function. We do not advocate superior oblique weakening combined with simultaneous surgery for iatrogenic superior oblique palsy as an initial procedure for Brown syndrome, since nearly one-half of our patients did not develop superior oblique palsy when followed for more than 1 year.


[Epidemiological features of human brucellosis in the rural areas in Shandong during 1990-1996].
Epidemiologic features of Brucellosis in the rural areas in Shandong in the 90's were studied and analysed by means of epidemiological and statistical methods. Results indicated an increasing trend in incidence of the disease (Trend tast: chi 2 = 76.06, P < 0.01). Cases mainly concentrated in few economically poor regions connecting Jinan, Zibo, Binzhou and Weifang cities or prefectures. The patients showed serious and classical clinical symptoms. More cases under 14 years and over 60 years old were seen than before. The epidemic peak has been advanced with the epidemic strain B. melti. III identified. Mismanagement on animal quarantine, eradication of infected animals and vaccination in those poor areas accounted for the major reasons of the recurrence.


Application of genetic algorithm on optimization of laser beam shaping.
This study proposes a newly developed optimization method for an aspherical lens system employed in a refractive laser beam shaping system, which performs transformations on laser spots such that they are transformed into flat-tops of any size. In this paper, a genetic algorithm (GA) with multipoint search is proposed as the optimization method, together with macro language in optical simulation software, in order to search for ideal and optimized parameters. In comparison to a traditional two-dimensional (2D) computational method, using the one-dimensional (1D) computation for laser beam shaping can search for the optimal solution approximately twice as fast (after experiments). The optimal results show that when the laser spot shrinks from 3 mm to 1.07 mm, 88% uniformity is achieved, and when the laser spot increases from 3 mm to 5.273 mm, 90% uniformity is achieved. The distances between the lenses for both systems described above are even smaller than the thickness for the first lens, enabling us to conclude that our design objectives of extra light and slimness in the system are achieved.


Microvascular Permeability and Texture Analysis of the Skeletal Muscle of Diabetic Rabbits With Critical Limb Ischaemia Based on DCE-MRI.
We evaluated skeletal muscle vascular permeability in diabetic rabbits with critical limb ischaemia using quantitative dynamic contrast agent-enhanced (DCE) magnetic resonance imaging (MRI) and explored the feasibility of using DCE-MRI Ktrans-based texture analysis for assessing early slight ischaemia-related skeletal muscle structural changes. Twenty-four male New Zealand white rabbits (2.7 ± 0.3 kg; n = 12 each in sham-operated and experimental groups) underwent axial MRI of the vastus lateralis muscle at 1, 2, and 3 weeks after alloxan injection. Between-group and intra-group postoperative permeability and texture parameters were compared. Texture features of experimental groups in the third week were modelled by receiver operating characteristic (ROC) curve analysis. Correlations of permeability and of statistical texture parameters with peripheral blood endothelial progenitor cells (EPCs) and microvascular density (MVD) were analysed. In the experimental group, the transfer constant (Ktrans) was statistically significant at all time-points (F = 5.800, P = 0.009). Their vastus lateralis muscle Ktrans was significantly lower in the third than in the first week (P = 0.018) and correlated positively with peripheral blood EPCs in the experimental group [r = 0.598, (95% CI: 0.256, 0.807)]. The rate constant was negatively associated with vastus lateralis muscle MVD [r = -0.410, (95% CI: -0.698, -0.008)]. The area under the ROC curve of texture parameters based on Ktrans in ischaemic limbs was 0.882. Quantitative DCE-MRI parameters could evaluate microvascular permeability of ischaemic limb skeletal muscle, and texture analysis based on DCE-MRI Ktrans allowed evaluation of early slight skeletal muscle structural changes.


Bovine retained placenta: hormonal concentrations in fetal and maternal placenta.
The aim of this study was to evaluate the relationship between the occurrence of retention of the fetal membranes (RFM) and the hormonal concentrations of progesterone, estradiol-17beta, prostaglandin E(2) (PGE(2)), prostaglandin F(2alpha) (PGF(2alpha)), oxytocin (OT), oxytocin receptor (OT-R), endothelin-1 and angiotensin II (Ang II) in the placental tissues of cattle. Parturition was induced in nine Holstein cows by a single injection of PGF(2alpha) on Day 274 of gestation. Six out of nine cows in the induced group did not release the fetal membranes within 12 h after parturition and served as the RFM group, and the remaining three cows in that group, which released their fetal membranes within 12 h, served as the non-RFM group. Five other cows calved spontaneously and served as controls. The placental tissues were collected immediately (0 h) and at 6 h after parturition. The hormonal concentrations were measured by enzyme immunoassay in maternal and fetal placental tissues from RFM, non-RFM and control cows. There were no differences in P4 and E2 concentrations among the RFM, non-RFM and control groups. The mean PGF(2alpha) concentration of the RFM group was lower than those of the non-RFM and control groups in the maternal part of the placenta. In maternal tissues, the OT and OT-R concentrations in the RFM group were lower than those at 0 and 6 h after parturition in the non-RFM group. Additionally, the Ang II concentration of the RFM group in both the maternal and fetal parts of placental tissues tended to be higher than those of the other groups. In conclusion, the present results suggest that ET-1 and Ang II may play differential tissue-specific roles in the placental unit that may amplify the local endocrinological cascade involving OT, OT-R and PGF(2alpha) interactions which are necessary for normal placental separation in the cow.


5-Fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole, and irradiation for brain stem gliomas: a pilot study of the Brain Tumor Research Center and the Childrens Cancer Group.
Twenty-eight evaluable children with the diagnosis of brain stem glioma were treated with 5-fluorouracil and CCNU before posterior fossa irradiation (5500 rads); during irradiation, the children received hydroxyurea and misonidazole. The treatment was well tolerated, and minimal toxicity was produced. The median relapse-free survival was 32 weeks, and the median survival was 44 weeks. Analysis of covariates showed that, in patients between the ages of 2 and 19 years, survival was longest in the older children (P less than 0.02). Tumor histology, sex, extent of operation (if any), Karnofsky score, and radiation dose did not correlate with survival.


A multicentre randomised controlled pilot study of fluid resuscitation with saline or Plasma-Lyte 148 in critically ill patients.
Normal saline (NS) is the most commonly used crystalloid solution worldwide but contains an excess of chloride and may cause metabolic acidosis and hyperchloraemia. Such abnormalities may be attenuated by the use of a balanced solution such as Plasma-Lyte 148 (PL-148). To assess the feasibility, safety and biochemical and physiological effects of resuscitation with NS versus PL-148 in critically ill patients. An exploratory, multicentre, doubleblind, randomised controlled trial involving patients aged ≥ 18 years who were prescribed crystalloid fluid resuscitation by the treating clinician between 16 July and 22 October 2015, in three multidisciplinary intensive care units in Melbourne, Victoria, Australia. Random allocation of NS or PL-148 was concealed, and all fluids were delivered in indistinguishable bags. NS or PL-148 was administered for all fluid resuscitation and for all subsequent crystalloid fluid therapy until Day 4 of ICU admission. The treating intensivist determined the rate and frequency of fluid administration. Primary outcome was daily base excess (BE). Relevant secondary outcomes included the incidence of acute kidney injury (AKI), change in serum creatinine and serum chloride levels, and mortality. Seventy patients were recruited, with 34 in the NS group and 33 in the PL-148 group available for analysis. Baseline characteristics of study patients were well balanced; the mean ages were 64 and 62 years, respectively, and nearly two-thirds of the patients in each group were men. The median Acute Physiology and Chronic Health Evaluation III scores were 64 for the NS group (interquartile range [IQR], 48-73) and 55 for the PL-148 group (IQR, 44-81). After treatment, there was no significant difference in the worst (most negative) median BE between the NS and PL-148 groups (-4 mEq/L [IQR, -7 to -2 mEq/L] v -3 mEq/L [IQR, -7 to 2 mEq/L]; P = 0.42). Chloride levels were significantly higher with NS therapy (median, 111 mmol/L [IQR, 108-116 mmol/L] v 108 mmol/L [IQR, 106-110 mmol/L]; P = 0.01). There was no significant difference in the incidence of AKI (P = 0.48), peak creatinine levels (P = 0.92) or ICU or hospital mortality between the two groups. In our exploratory, double-blind, randomised controlled trial, when compared with NS, PL-148 did not significantly increase BE values in critically ill patients requiring fluid resuscitation, but decreased peak chloride concentrations.


Characterization of recA genes and recA mutants of Rhizobium meliloti and Rhizobium leguminosarum biovar viciae.
DNA fragments carrying the recA genes of Rhizobium meliloti and Rhizobium leguminosarum biovar viciae were isolated by complementing a UV-sensitive recA- Escherichia coli strain. Sequence analysis revealed that the coding region of the R. meliloti recA gene consists of 1044 bp coding for 348 amino acids whereas the coding region of the R. leguminosarum bv. viciae recA gene has 1053 bp specifying 351 amino acids. The R. meliloti and R. leguminosarum bv. viciae recA genes show 84.8% homology at the DNA sequence level and of 90.1% at the amino acid sequence level. recA- mutant strains of both Rhizobium species were constructed by inserting a gentamicin resistance cassette into the respective recA gene. The resulting recA mutants exhibited an increased sensitivity to UV irradiation, were impaired in their ability to perform homologous recombination and showed a slightly reduced growth rate when compared with the respective wild-type strains. The Rhizobium recA strains did not have altered symbiotic nitrogen fixation capacity. Therefore, they represent ideal candidates for release experiments with impaired strains.


A Novel Method for Deposition of Multi-Walled Carbon Nanotubes onto Poly(p-Phenylene Terephthalamide) Fibers to Enhance Interfacial Adhesion with Rubber Matrix.
In order to enhance the interfacial adhesion of poly(p-phenylene terephthalamide) (PPTA) fibers to the rubber composites, a novel method to deposit multi-walled carbon nanotubes (MWCNTs) onto the surface of PPTA fibers has been proposed in this study. This chemical modification was performed through the introduction of epoxy groups by Friedel⁻Crafts alkylation on the PPTA fibers, the carboxylation of MWCNTs, and the ring-opening reaction between the epoxy groups and the carboxyl groups. The morphologies, chemical structures, and compositions of the surface of PPTA fibers were characterized by scanning electron microscope, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The results showed that MWCNTs were uniformly deposited onto the surface of PPTA fibers with the covalent bonds. The measurement of contact angles of the fibers with polar solvent and non-polar solvent indicated that the surface energy of deposited fibers significantly increased by 41.9% compared with the untreated fibers. An electronic tensile tester of single-filament and a universal testing machine were utilized to measure the strength change of the fibers after modification and the interfacial adhesion between the fibers and the rubber matrix, respectively. The results showed that the tensile strength had not been obviously reduced, and the pull-out force and peeling strength of the fibers to the rubber increased by 46.3% and 56.5%, respectively.


Na+ transport in normal and CF human bronchial epithelial cells is inhibited by BAY 39-9437.
To test the hypothesis that Na+ transport in human bronchial epithelial (HBE) cells is regulated by a protease-mediated mechanism, we investigated the effects of BAY 39-9437, a recombinant Kunitz-type serine protease inhibitor, on amiloride-sensitive short-circuit current of normal [non-cystic fibrosis (CF) cells] and CF HBE cells. Mucosal treatment of non-CF and CF HBE cells with BAY 39-9437 decreased the short-circuit current, with a half-life of approximately 45 min. At 90 min, BAY 39-9437 (470 nM) reduced Na+ transport by approximately 70%. The inhibitory effect of BAY 39-9437 was concentration dependent, with a half-maximal inhibitory concentration of approximately 25 nM. Na+ transport was restored to control levels, with a half-life of approximately 15 min, on washout of BAY 39-9437. In addition, trypsin (1 microM) rapidly reversed the inhibitory effect of BAY 39-9437. These data indicate that Na+ transport in HBE cells is activated by a BAY 39-9437-inhibitable, endogenously expressed serine protease. BAY 39-9437 inhibition of this serine protease maybe of therapeutic potential for the treatment of Na+ hyperabsorption in CF.


Phase behavior of large unilamellar vesicles composed of synthetic phospholipids.
Large unilamellar vesicles (LUV) have been prepared by three procedures from several synthetic and natural phosphatidylcholines. Reverse-phase evaporation vesicles (REV) and fusion vesicles were prepared by established procedures. A published procedure for the preparation of dialyzed octyl glucoside vesicles (DOV) was modified to allow its use with synthetic phospholipids. Negative-staining and freeze--fracture electron microscopy was used to determine the vesicle size distribution (mean diameters 800-1000 A) and extent of oligolamellar contamination in DOV preparations. Trapping of 6-carboxyfluorescein yielded measurements of the internal volume (2.6 +/- 0.3 microL/mumol of Pi) consistent with the size distributions determined by electron microscopy. An upper limit of less than 3 mol % oligolamellar vesicle contamination was indicated by calorimetric heat capacity profiles. The phase behaviors of large multilamellar vesicles and all three types of LUV were compared by using high-sensitivity differential scanning calorimetry and fluorescence depolarization of the membrane probe diphenylhexatriene. The most remarkable feature was the increased breadth of the main transition of DOV and of REV relative to the multilamellar species and to fusion vesicles. Both the main transition and the pretransition occurred at nearly the same temperatures in unilamellar and multilamellar species, but the unilamellar pretransition involved less than half the enthalpy observed in the multilamellar transition. Additional experiments indicated that the broadened main phase transition associated with DOV and REV reflected bilayer impurities resulting from preparation. It is concluded that LUV prepared by procedures that avoid impurities undergo a highly cooperative phase transition, as demonstrated here for fusion vesicles.


Exceptional CO2 adsorbing materials under different conditions.
In this article we discuss those materials that have recorded the highest adsorption capacities for the greenhouse gas CO2 under ambient conditions as well as at different temperatures and pressures. For convenience, the materials have been categorized under four categories, viz., porous carbon, metal-organic, zeolite and mesoporous silica, and porous organic frameworks. It has been found that the gas adsorption property significantly relies on several factors such as high surface area and pore volume and the presence of N-, O- and S-containing moieties. The presence of a microporous structure and strong interaction between the CO2 molecules with the framework through H-bonding or dipole-quadrupole interactions facilitates adsorption of the gas.


Inference of the ancestral vertebrate phenotype through vestiges of the whole-genome duplications.
Inferring the phenotype of the last common ancestor of living vertebrates is a challenging problem because of several unresolvable factors. They include the lack of reliable out-groups of living vertebrates, poor information about less fossilizable organs and specialized traits of phylogenetically important species, such as lampreys and hagfishes (e.g. secondary loss of vertebrae in adult hagfishes). These factors undermine the reliability of ancestral reconstruction by traditional character mapping approaches based on maximum parsimony. In this article, we formulate an approach to hypothesizing ancestral vertebrate phenotypes using information from the phylogenetic and functional properties of genes duplicated by genome expansions in early vertebrate evolution. We named the conjecture as 'chronological reconstruction of ohnolog functions (CHROF)'. This CHROF conjecture raises the possibility that the last common ancestor of living vertebrates may have had more complex traits than currently thought.


Identification of the aromatase inhibitor aminoglutethimide in urine by gas chromatography/mass spectrometry.
Aminoglutethimide is used therapeutically as an aromatase inhibitor in the treatment of metastatic breast cancer in post-menopausal women. For doping purposes, aminoglutethimide may be used for treatment of adverse effects of an extensive abuse of anabolic androgenic steroids (gynaecomastia) and to increase the testosterone concentration and stimulation of testosterone biosynthesis. The use of aromatase inhibitors has been prohibited for male athletes since September 1, 2001. The purpose of this study was to develop methods for the identification of the parent compound or its main metabolite and the inclusion of this information into established screening procedures in doping analysis. An excretion study was conducted using oral application of one single therapeutic dose (500 mg) of Orimeten. The analysis was performed by gas chromatography/mass spectrometry (GC/MS). Aminoglutethimide is excreted almost totally as unconjugated parent compound and is detectable by different screening procedures for up to 165 h. Most suitable for the detection of aminoglutethimide is the screening procedure for heavy volatile nitrogen-containing drugs ('Screening 2'). However, since only competition samples are analysed in that screening procedure, the additional inclusion of aminoglutethimide in the screening procedure for anabolic androgenic agents ('Screening 4') is recommended. Full mass spectra and diagnostic ions for the analysis of aminoglutethimide are presented.


A better index for analysis of co-occurrence and similarity.
Scientists often need to know whether pairs of entities tend to occur together or independently. Standard approaches to this issue use co-occurrence indices such as Jaccard, Sørensen-Dice, and Simpson. We show that these indices are sensitive to the prevalences of the entities they describe and that this invalidates their interpretability. We propose an index, α, that is insensitive to prevalences. Published datasets reanalyzed with both α and Jaccard's index (J) yield profoundly different biological inferences. For example, a published analysis using J contradicted predictions of the island biogeography theory finding that community stability increased with increasing physical isolation. Reanalysis of the same dataset with the estimator [Formula: see text] reversed that result and supported theoretical predictions. We found similarly marked effects in reanalyses of antibiotic cross-resistance and human disease biomarkers. Our index α is not merely an improvement; its use changes data interpretation in fundamental ways.