Repeated dose 28-day oral toxicity study of DEAE-Dextran in mice: An advancement in safety chemotherapeutics

Cancer has emerged as a global threat with challenges for safe chemotherapeutics. Most of the currently available anti-cancer drugs exhibit significant toxicity. Amongst novel agents, interferons have exhibited anti-proliferative and cytoprotective roles. However, due to stability drawbacks of interferons, we have identified an interferon inducer DEAE-Dextran, which resolves the stability issues. Based on the previous history of toxicity pertaining to the current chemotherapeutic agents, it is equally essential to determine the safety of DEAE-Dextran. In the present study, repeated dose 28 day oral toxicity of DEAE-Dextran has been evaluated in accordance to OECD-407. We found absence of any CNS behavioral changes related to self-mutilation, walking backwards, aggressiveness on handling or tonic-clonic seizures during the 28 day study. Neither the motor activity nor grip strength was altered during the treatment duration with DEAE-Dextran implying absence of any effect on the skeletal muscles. Interestingly, we also found that treatment with DEAE-Dextran did not present any significant cardiac, hepatic, renal, gastrointestinal, lymphatic or reproductive system toxicity or alteration in the body's normal physiology based upon the various organ function tests. Henceforth, it may be concluded that DEAE-Dextran is a safe anti-cancer agent devoid of any sub-acute toxicity.     

Mixing is required for uniform reconstitution of filter-dried protein antigens in a single-injection vaccine formulation

Ambient temperature filter dried vaccine formulations have been proposed to simultaneously achieve thermostability and offer a ready-to-use immunisation device that combines reconstitution and injection. Vaccine concentration should be uniform at the point of injection, but the uniformity following direct reconstitution of filter-dried vaccines has not been reported. We present here a study of vaccine mixing and release following dissolution of filter-dried model protein and toxoid antigens within a single syringe, filter and needle unit. Release was better for filters made from glass than cellulose. Without additional mixing, uniformity was poor and only 41% of input protein was released from protein filter-dried onto glass fiber. In contrast, adding a simple glass bead and mixing by inversion, 100% release antigen solution was achieved, with uniform concentration at exit from the needle throughout a simulated injection. Adsorption onto alum adjuvant had no detectable effect on vaccine dissolution and mixing. The uniformity and yield of low doses of diphtheria and tetanus toxoid was also improved by mixing, albeit with a lower yield of 60–68%. We conclude that uniformity and mixing should be studied to ensure safety and efficacy of directly reconstituted filter-dried vaccine formulations.     

Whole genome alignment based one-step real-time RT-PCR for universal detection of avian orthoreoviruses of chicken,pheasant and turkey origins

Newly emerging avian orthoreovirus (ARV) variants have been continuously detected in Pennsylvania poultry since 2011. In this paper, we report our recent diagnostic assay development of one-step real-time RT-PCR (rRT-PCR) for the rapid and universal detection of all ARVs or reference strains of chicken, pheasant and turkey origins and six σC genotypes of the newly emerging field ARV variants in Pennsylvania (PA) poultry. Primers and probes for the rRT-PCR were designed from the conserved region of the M1 genome segment 5′ end based on the whole-genome alignment of various ARV strains, including six field variants or novel strains obtained in PA poultry. The detection limit of the newly developed rRT-PCR for ARV was as low as 10 copies/reaction of viral RNA, and 10^0.50–10^0.88 tissue culture infectious dose (TCID₅₀)/100 μL of viruses. This new rRT-PCR detected all six σC genotypes from the 66 ARV field variant strains and reference strains tested in this study. There were no cross-reactions with other avian viruses. Reproducibility of the assay was confirmed by intra- and inter-assay tests with variability from 0.12% to 2.19%. Sensitivity and specificity of this new rRT-PCR for ARV were achieved at 100% and 88%, respectively, in comparison with virus isolation as the “gold standard” in testing poultry tissue specimen.     

Characteristics of pediatric invasive pneumococcal diseases and the pneumococcal isolates in Suzhou,China before introduction of PCV13

BackgroundData on characteristics of invasive pneumococcal diseases (IPD) is limited in China. We aimed to understand the clinical features and explore the molecular characteristics of the pneumococcal isolates in China.MethodsSince 2010, we prospectively collected the pneumococcal isolates and the IPD patients’ demographic and clinical information in Suzhou University Affiliated Children’s Hospital (SCH). The antibiotic susceptibility, serotypes, genotypes of Streptococcus pneumoniae strains were identified by E-test, quellung reaction and/or multiplex PCR, and multi-locus sequence typing, respectively.ResultsDuring the period from January 2010 to December 2015, a total of 80 IPD patients were identified. They were diagnosed as meningitis (31.3%), septicemia (27.5%), pneumonia (21.3%) and others (20.0%). About half of them required vancomycin treatment, 42.5% were admitted to ICUs, 36.2% had complications and 6.2% were hospitalized for over 1 year. The most common serotypes of the pneumococcal isolates were serotypes 6B and 14, the coverage of PCV13 was 92.5%, and CC236s and CC199s were the most common clone complexes.ConclusionsPediatric IPD patients had severe clinical symptoms, demanded intensive treatment, suffered poor prognosis and substantial burden. The pneumococcal isolates’ serotype coverage of PCV13 vaccine was high, which leads to implication of PCV vaccine usage among children in China.     

Transcranial Direct Current Stimulation Enhances Cognitive Control During Emotion Regulation

BackgroundThe ability to cognitively control emotions is critical for mental health. Previous studies have identified the dorsolateral prefrontal cortex (dlPFC) as a core region in cognitive reappraisal. However, there is only scarce evidence whether directly modulating dlPFC activity results in improved capacities for cognitive reappraisal.ObjectiveIn this study, we used anodal transcranial direct current stimulation (tDCS) over the right dlPFC to investigate the effects of increased dlPFC excitability on cognitive reappraisal as indexed by subjective emotional arousal ratings and skin conductance responses.MethodsThe study was designed as a double-blind, between-subjects, sham-controlled trial. Half of the healthy participants were randomly assigned to receive either active tDCS (n = 21, 1.5 mA for 20 min over the right dlPFC) or sham stimulation (n = 21). Participants viewed negative and neutral pictures from the International Affective Picture System while they were instructed to either downregulate, upregulate or maintain their emotions. After each picture presentation, participants rated the intensity of emotional arousal. Skin conductance responses and gaze fixation were assessed.ResultsOur results revealed that anodal prefrontal tDCS during downregulation resulted in decreased skin conductance responses and decreased emotional arousal ratings. The opposite pattern was observed for the upregulation condition in which anodal tDCS resulted in higher arousal ratings accompanied by marginally enhanced skin conductance responses.ConclusionOur data indicates that tDCS facilitates cognitive reappraisal in both directions by either increasing or decreasing emotional responsiveness depending on the regulatory goal. This provides further evidence for the potential use of tDCS as a tool to modulate cognitive reappraisal. However, given the limitations of the present study, our findings need to be replicated and complimented by further studies.