Notes

Successful manufacture of n-caproate from syngas with a co-culture involving Clostridium aceticum along with Clostridium kluyveri.
Moreover, the extracted genomic DNA using this method is suitable for phage genomic analysis such as restriction enzyme studies, preparation of DNA library, and also next-generation sequencing.Feline astrovirus (FeAstV), an enteric RNA virus of recent concern that is associated with diarrheal illness in cats, has been described in several countries throughout the world. However, no scientific and sensitive diagnostic method against FeAstV was reported up to now. Here, we developed a specific, sensitive and repeatable TaqMan fluorescence quantitative PCR (qPCR) assay to investigate the prevalence of FeAstV in domestic cats from China, especially low copy numbers in clinical sample. Specific assay showed that no cross-reactivity was observed with other non-FeAstV cat-derivied pathogens, suggesting this method was highly specific for FeAstV. The lowest detection limit of this assay was 3.52 copies/μl, and 1000-times more sensitive than conventional PCR. Intra- and inter-assay variability was less than 1.72%, means a high degree of repeatability. A total of 578 clinical fecal samples were collected from northeast China, and were tested for FeAstV using our developed qPCR assay. 105 samples were positive for FeAstV with an overall prevalence of 18.17%. Moreover, a higher positive rate was found in cats with diarrhea (32.26%, 80/248) than that in asymptomatic cats (7.58%, 25/330), further demonstrating that FeAstV infection was associated with diarrhea in cats. In brief, our developed assay showed high specificity, sensitivity, reproducibility for detecting FeAstV, and can be used for clinical diagnosis and epidemiological investigation of FeAstV.Pre-existing heart failure (HF) in diagnosed patients with coronavirus disease 2019 (COVID-19) is associated with a close to two-fold increased mortality rate compared to COVID-19 patients without prior HF history. Moreover, based both on biomarker as well as imaging findings, widespread endothelial and cardiac injury seems to be present in many patients presenting with COVID-19, associated with adverse outcomes including new onset HF. Systematic echocardiographic studies in patients with COVID-19 indicate that the most common cardiac pathology is right ventricular (RV) dilatation (39%) over and above both left ventricular (LV) diastolic dysfunction (16%) and LV systolic dysfunction (10%). In addition, myocardial injury, assessed by magnetic resonance imaging (MRI), is observed in some 55% to 70% of patients recently recovered from COVID-19 even in those who didn't get very sick during the acute illness. GSK2334470 These observations seem to indicate a potentially rather high risk of clinical HF emerging in patients post-COVID-19, warranting close long-term monitoring of patients during recovery. On the other hand, given the established adverse prognostic role that pre-existing HF plays as a comorbidity in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it not only seems important in the still ongoing COVID-19 pandemic that all patients with known HF should proactively be well controlled and treated according to current guidelines, but also additionally be considered for priority vaccination against the SARS-CoV-2 infection if not yet vaccinated.Occupational asthma is an important health problem that can include exacerbation of existing asthma, or induce new asthma either through allergic sensitisation, or non-immunological mechanisms. While allergic sensitisation of the respiratory tract can be acquired to proteins, or to low molecular weight chemicals (chemical respiratory allergens) this article is on the latter exclusively. Chemical respiratory allergy resulting in occupational asthma is associated with high levels of morbidity and there is a need, therefore, that chemicals which can cause sensitisation of the respiratory tract are identified accurately. However, there are available no validated, or even widely accepted, predictive test methods (in vivo, in vitro or in silico) that have achieved regulatory acceptance for identifying respiratory sensitising hazards. For this reason there is an important reliance on human data for the identification of chemical respiratory allergens, and for distinguishing these from chemicals that cause occupational asthma through non-immunological mechanisms. In this article the reasons why it is important that care is taken in designating chemicals as respiratory allergens are reviewed. The value and limitations of human data that can aid the accurate identification of chemical respiratory allergens are explored, including exposure conditions, response characteristics in specific inhalation challenge tests, and immunological investigations.This paper compares the phase-specific inhalation toxicity of the cyclic semi-volatile methylsiloxanes (cVMSs) D4, D5 and D6. The objectives of this paper are to re-analyze information from acute to chronic inhalation studies on rats with these cVMSs to identify the unifying principles of phase-specific toxicity at the portal-of-entry and if they depend on acute, acute-on-chronic or chronic mechanisms. This re-analysis supports the hypothesis that concentrations must be high enough to exceed the vapor saturation at any given temperature for stabilizing the aerosol phase and evoking phase-specific effects at sites of the respiratory tract susceptible to the cVMSs-specific physicochemical properties amphiphilicity and surface tension. In summary, the portal-of-entry effects and related findings appear to be acute in nature and specific to liquid aerosol. The repeated inhalation exposure studies with D4 and D5 up to two years in duration did not reveal chronic aggravations of portal of entry outcomes. Findings at a pulmonary location where amphiphilic surfactant molecules are present appear to be caused by the acute adaptation to deposited dose. Such outcome should better be described as a high-dose liquid aerosol phenomenon imparted by the physicochemical properties "liquid" and "hydrophobic". This calls for a phase-specific human risk characterization of cVMSs.The aim of this paper was to provide a comprehensive toxicological and safety evaluation of a yeast cell wall preparation (YCWP) for use as an animal feed ingredient. The following toxicological assessments were carried out the mutagenic activity was tested using the Ames' Test in five Salmonella typhimurium strains; clastogenic activity was investigated using the mammalian micronucleus test in Swiss ICO OF1 (IOPS Caw) mice; genotoxic activity was assessed using the in vitro mammalian chromosomal aberration test in human lymphocytes; acute oral toxicity was tested by administration of a single dose of 2000 mg/kg BW. Eye and skin irritation were assessed in rabbits according to OECD guidelines; skin sensitivity was established in guinea pigs by means of the Buehler test, while acute dermal and inhalation studies in rats were further completed, also according to OECD guidelines. All conducted tests were considered valid under the experimental conditions. No significant mutagenic activity or genotoxic activity was observed, and it was concluded that the test article did not induce any clastogenic effect. YCWP was found to be mildly irritating to the eye, slightly irritating to the skin but was found to be non-sensitizing in the guinea pig. The acute oral, dermal and inhalation studies did not yield any evidence of gross toxicity or pharmacological effects.
Accelerated partial breast irradiation (APBI) represents a validated technique for low-risk breast cancer. Recently, ultra-APBI (uAPBI) using fewer than 5 fractions was described in the literature. We compared clinical outcomes and late toxicity after APBI or uAPBI in older patients.

Two cohorts of older patients (aged ≥70 years) with low-risk breast cancer treated with APBI (interstitial brachytherapy) were analyzed retrospectively. A total dose of 34 Gy in10 fractions (APBI) or 16 Gy in 1 fraction (uAPBI) was delivered from 2004 to 2012 and from 2013 to 2018, respectively. Oncologic outcome analyzed the cumulative incidence of local relapse, regional relapse, and distant metastases with disease-free survival, cause-specific survival, and overall survival. Late toxicity and cosmetic results were investigated.

One hundred fifty-seven patients (APBI, n=109 patients; uAPBI, n=48 patients) underwent APBI according to the same selection criteria. Apart from the median follow-up (97 vs 72 months for APBI andsult. uAPBI based on a single fraction of brachytherapy represents an attractive option for therapeutic de-escalation in older patients with breast cancer.
We report the first study comparing APBI versus uAPBI in a cohort of older patients with low-risk breast cancer. No significant difference was found between the 2 treatment groups regarding oncologic outcome, late toxicity, and cosmetic result. uAPBI based on a single fraction of brachytherapy represents an attractive option for therapeutic de-escalation in older patients with breast cancer.Needle-free jet injections are actuated by a pressure impulse that can be delivered by different mechanisms to generate high-speed jets (Vj~O102 m/s). During filling and transportation of disposable cartridges and ampoules, bubbles can form, which can be problematic especially for viscous fluids. Here, we report on the effect of location and size of entrapped air pockets in cartridges used in spring-powered jet injections. As air bubbles pass through the orifice, they undergo depressurization, which results in intermittent atomization and spray formation, temporarily increasing the jet dispersion. Atomization and dispersion of the jet can lead to product loss during an injection. We find that the effect of bubble location on the jet exit speed, delivery efficiency, and the projected area of the blebs formed after the injection was statistically significant (p less then 0.05). The findings of this study have implications for the development of pre-filled cartridges for jet injection applications.As part of early drug development, preformulation studies are used to comprehensively explore the properties of new drugs. In particular, this includes the biopharmaceutical characterization and evaluation of impacting factors (e.g. excipients, microenvironmental conditions etc.) by permeation studies. To overcome the limitations of current studies, a novel standardized ex vivo procedure using esophageal mucosa as surrogate has been established successfully and applied to preformulation studies for oromucosal delivery of cyclobenzaprine hydrochloride, a tricyclic muscle relaxant with potential for psychopharmacotherapeutic use. By using the standardized ex vivo permeation process, a twofold enhancement of permeability (0.98 ± 0.16 to 1.96 ± 0.10 * 10-5 cm/s) was observed by adjustment and controlling of microenvironmental pH, empowering a targeted and effective development of sublingual formulations. Predictivity and suitability were superior compared to in vitro experiments using artificial biomimetic membranes, revealing a determination coefficient (R2) of 0.995 vs. 0.322 concerning pH-dependent permeability of cyclobenzaprine. In addition, diffusion properties were extensively examined (e.g. influence of mucosal thicknesses, tissue freezing etc.). The alignment of the study design regarding physiologically/clinically relevant conditions resulted in ex vivo data that allowed for the estimation of plasma AUC levels in the extend of reported in vivo ranges.
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