Effect of electron and X-ray irradiation on microbiological and chemical parameters of chilled turkey

The purpose of this work was to compare the effect of electron and X-ray irradiation on microbiological content and volatile organic compounds in chilled turkey meat. Dose ranges which significantly suppress the pathogenic microflora while maintaining the organoleptic properties of the turkey meat are different for electron and X-ray irradiation. According to the study it is recommended to treat chilled turkey using X-ray irradiation with the dose ranging from 0.5 to 0.75 kGy, while in electron irradiation permissible doses should be within 0.25–1 kGy. Three main groups of volatile compounds: alcohols, ketones, and aldehydes—were found in irradiated and non-irradiated samples of turkey meat. It was found that the total amount of aldehydes, which are responsible for the formation of a specific odor of irradiated meat products, increases exponentially with the increase in the absorbed dose for both types of irradiation. It was established that acetone can be used as a potential marker of the fact of exposure of low-fat meat products to ionizing radiation.

Pharmacokinetics and Pharmacodynamics of Vancomycin derivative LYSC98 in a Murine Thigh Infection Model against Staphylococcus aureus

LYSC98 is a vancomycin derivative used for gram-positive bacterial infections therapy. We reported the pharmacokinetic/pharmacodynamic (PK/PD) targets of LYSC98 against Staphylococcus aureus using a murine thigh infection model. Three Staphylococcus aureus strains were utilized. Single-dose plasma pharmacokinetics of LYSC98 were determined in infected mice after the tail vein injection of 2, 4, and 8mg/kg. The results showed maximum plasma concentration (Cmax) 11466.67 -48866.67 ng/mL, area under the concentration-time curve from 0 to 24 h(AUC0-24) 14788.42 -91885.93 ng/mL·h, and elimination half-life(T1/2) 1.70-2.64 h, respectively. The Cmax (R2 0.9994) and AUC0-24 (R2 0.981) were positively correlated with the dose of LYSC98 in the range of 2-8 mg/kg. Dose fractionation studies using total doses of 2 to 8 mg/kg administered with q6h, q8h, q12h, and q24h were performed to evaluate the correlation of different PK/PD indices with efficacy. Sigmoid model analysis showed Cmax/MIC (R2 0.8941) was the best PK/PD index to predict the efficacy of LYSC98. In the dose ranging studies, two Methicillin-resistant Staphylococcus aureus (MRSA) clinical strains were used to infect the mice and 2-fold-increasing doses (1 to 16 mg/kg) of LYSC98 were administered. The magnitude of LYSC98 Cmax/MIC associated with net stasis, 1, 2, 3 and 4 - log10 kill were 5.78, 8.17, 11.14, 15.85 and 30.58, respectively. The results of this study showed LYSC98 a promising antibiotic with in vivo potency against MRSA, and will help in the dose design of phase one study for LYSC98.

Zircon (U-Th)/He Closure Temperature Lower than Apatite Ther-Mochronometric Systems: Reconciliation of a Paradox

We present here seven new zircon (U-Th)/He (ZHe) ages and three new zircon fission track ages (ZFT) analyzed from an age-elevation profile (Machu Picchu, Peru). ZFT data present older ages in comparison with the other thermochronological data, whereas the ZHe data interestingly present similar ages than the ones obtained with apatite (U-Th)/He (AHe). It has been proposed that He retention in zircon is linked to the damage dose, with an evolution of the closure-temperature from low values associated to low α-dose (<1016 α/g), subsequently increasing before decreasing again at very high α-dose (>1018 α /g). Studies have been focused on the He diffusion behavior at high α-dose, but little is known at low dose. We propose that the ZHe closure temperature at α-dose ranging from 0.6×1015 to 4×1016 α/g is in the range of ~60-80°C. This value is lower than the one proposed in the current damage model ZRDAAM and demonstrates that the ZHe and AHe methods could have similar closure temperatures at low α-dose (i.e. similar ages). These new data strengthen our previous geological conclusions and even highlight an about twice more important cooling rate than the one deduced from AHe and apatite fission-track data alone registered at Machu Picchu.

A STUDY TO EVALUATE THE SAFETY OF ARIPIPRAZOLE IN TREATMENT OF SCHIZOPHRENIA

Objectives: Aripiprazole is recommended in a dose of 10 and 15 mg/day, with a dose ranging between 10 and 30 mg/day in the treatment of schizophrenia. The primary objective of the study is to evaluate the safety profile of Aripiprazole in low dose of 15 mg versus high dose of 30 mg in the treatment of Schizophrenia. Methods: A total of 60 patients (not on treatment) between age 18-60 years of either gender who meet the diagnostic criteria as per DSM-IV classification for schizophrenia and schizoaffective disorder. All patients were randomly divided into two groups on single-blind study criteria. Group-I: Aripiprazole 15 mg once a day, morning dose for 6 weeks. Group-II: Aripiprazole 30 mg once a day, morning dose for 6 weeks. The ESRS includes 12 questionnaire items; each item is rated on a 7-point scale. Efficacy assessment included at baseline and at 6 weeks end study scoring on PANSS, EPRS, and CGI. Results: The total number of patients showed the ESRS (total symptoms) in group-I was 09 patients (35%) out of 26 and in group II, 13 patients (59%) out of total 22 showed the ESRS (total symptoms). In both the groups aripiprazole showed the comparable efficacy by improving overall symptoms in the number of patients. In group I, 20 patients have shown the improvement in overall scores of all scales. In group II, 16 patients have shown the improvement in overall scores in different scales. Conclusions: Aripiprazole is effective in schizophrenia and schizoaffective disorders, doses of 15 mg are equally effective as doses of 30 mg, side effects like EPS are more with higher doses of Aripiprazole.

MVA vector expression of SARS-CoV-2 spike protein and protection of adult Syrian hamsters against SARS-CoV-2 challenge

Numerous vaccine candidates against SARS-CoV-2, the causative agent of the COVID-19 pandemic, are under development. The majority of vaccine candidates to date are designed to induce immune responses against the viral spike (S) protein, although different forms of S antigen have been incorporated. To evaluate the yield and immunogenicity of different forms of S, we constructed modified vaccinia virus Ankara (MVA) vectors expressing full-length S (MVA-S), the RBD, and soluble S ectodomain and tested their immunogenicity in dose-ranging studies in mice. All three MVA vectors induced spike-specific immunoglobulin G after one subcutaneous immunization and serum titers were boosted following a second immunization. The MVA-S and MVA-ssM elicited the strongest neutralizing antibody responses. In assessing protective efficacy, MVA-S-immunized adult Syrian hamsters were challenged with SARS-CoV-2 (USA/WA1/2020). MVA-S-vaccinated hamsters exhibited less severe manifestations of atypical pneumocyte hyperplasia, hemorrhage, vasculitis, and especially consolidation, compared to control animals. They also displayed significant reductions in gross pathology scores and weight loss, and a moderate reduction in virus shedding was observed post challenge in nasal washes. There was evidence of reduced viral replication by in situ hybridization, although the reduction in viral RNA levels in lungs and nasal turbinates did not reach significance. Taken together, the data indicate that immunization with two doses of an MVA vector expressing SARS-CoV-2 S provides protection against a stringent SARS-CoV-2 challenge of adult Syrian hamsters, reaffirm the utility of this animal model for evaluating candidate SARS-CoV-2 vaccines, and demonstrate the value of an MVA platform in facilitating vaccine development against SARS-CoV-2.

New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy

Around 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade. Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments. What is Known:• Therapeutic hypothermia is beneficial in neonatal hypoxic-ischemic encephalopathy.• Neonates with moderate or severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia still experience severe sequelae. What is New:• Erythropoietin, allopurinol, melatonin, cannabidiol, and exendin-4/exenatide show promise in conjunction with therapeutic hypothermia.• There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials.