Combination of Extrusion and Fermentation with Lactobacillus plantarum and L. uvarum Strains for Improving the Safety Characteristics of Wheat Bran

Processed wheat bran (W) is of great importance for food and feed. Consequently, the biosafety of W should be evaluated and improved with valorisation strategies. This study tested a design combining extrusion (at temperature of 115 and 130 °C; screw speeds of 16, 20, and 25 rpm) and fermentation with Lactobacillus plantarum and L. uvarum strains for the valorisation of W to provide safer food and feed stock. The influence of different treatments on biogenic amine formation, mycotoxin content, and free amino acids, as well as acidity, microbiological parameters, and sugar concentration, were analysed. This research showed that a combination of extrusion and fermentation with selected strains can change several aspects of W characteristics. There was a significant effect of applied treatments on acidity and the microbiological parameters of W, as well as biogenic amines content. The lowest total mycotoxin concentration (29.8 µg/kg) was found in extruded (130 °C; 25 rpm) and fermented with L. uvarum sample. Finally, the combination of the abovementioned treatments can be confirmed as a prospective innovative pre-treatment for W, capable of potentially enhancing their safety characteristics and composition.     

Resensitising proteasome inhibitor-resistant myeloma with sphingosine kinase 2 inhibition

The introduction of the proteasome inhibitor bortezomib into treatment regimens for myeloma has led to substantial improvement in patient survival. However, whilst bortezomib elicits initial responses in many myeloma patients, this haematological malignancy remains incurable due to the development of acquired bortezomib resistance. With other patients presenting with disease that is intrinsically bortezomib resistant, it is clear that new therapeutic approaches are desperately required to target bortezomib-resistant myeloma. We have previously shown that targeting sphingolipid metabolism with the sphingosine kinase 2 (SK2) inhibitor K145 in combination with bortezomib induces synergistic death of bortezomib-naïve myeloma. In the current study, we have demonstrated that targeting sphingolipid metabolism with K145 synergises with bortezomib and effectively resensitises bortezomib-resistant myeloma to this proteasome inhibitor. Notably, these effects were dependent on enhanced activation of the unfolded protein response, and were observed in numerous separate myeloma models that appear to have different mechanisms of bortezomib resistance, including a new bortezomib-resistant myeloma model we describe which possesses a clinically relevant proteasome mutation. Furthermore, K145 also displayed synergy with the next-generation proteasome inhibitor carfilzomib in bortezomib-resistant and carfilzomib-resistant myeloma cells. Together, these findings indicate that targeting sphingolipid metabolism via SK2 inhibition may be effective in combination with a broad spectrum of proteasome inhibitors in the proteasome inhibitor resistant setting, and is an approach worth clinical exploration.     

Exploring IL-17 in spondyloarthritis for development of novel treatments and biomarkers

Spondyloarthritis (SpA) is an umbrella term describing a family of chronic inflammatory rheumatic diseases. These diseases are characterised by inflammation of the axial skeleton, peripheral joints, and entheseal insertion sites throughout the body which can lead to structural joint damage including formation of axial syndesmophytes and peripheral osteophytes. Genetic evidence, preclinical and clinical studies indicate a clear role of interleukin (IL)- 23 and IL-17 as mediators in SpA pathogenesis. Targeting the IL-23/?17 pathways seems an efficient strategy for treatment of SpA patients, and despite the remaining challenges the pathway holds great promise for further advances and improved therapeutic opportunities. Much research is focusing on serological markers and imaging strategies to correctly diagnose patients in the early stages of SpA. Biomarkers may facilitate personalised medicine tailored to each patient's specific disease to optimise treatment efficacy and to monitor therapeutic response. This narrative review focuses on the IL-17 pathway in SpA-related diseases with emphasis on its role in pathogenesis, current approved IL-17 inhibitors, and the need for biomarkers reflecting core disease pathways for early diagnosis and measurement of disease activity, prognosis, and response to therapy.     

Transient Visual Loss in a Hepatitis C Patient Treated With Pegylated Interferon Alfa-2a and Ribavirin

Introduction:

Patients with Hepatitis C are commonly treated with combination of Pegylated Interferon alfa-2a and Ribavirin. Less than 1% of patients receiving this treatment experience very uncommon ophthalmological side effects such as optic neuropathy and vision disorder, which are usually subclinical, mild and reversible, not requiring the withdrawal of the treatment. Retinopathy is the most commonly reported ocular side effect of interferon use, usually presenting with cotton wool spots and retinal hemorrhages.

Case Presentation:

We represent a case of severe retinopathy and optic neuropathy in a patient with chronic hepatitis C genotype 3a infection, treated with the combination of PEG-IFN alfa-2a (180 mkg once weekly) and Ribavirin (1200 mg daily). Bilateral visual loss of both eyes developed at 11th week of therapy and changes in retina and optic nerve were observed. Fluorescein angiography and optical coherence tomography showed bilateral anterior ischemic optic neuropathy and macular edema. Visual acuity improved 1 month and fundoscopic changes were no longer present 6 months after the urgent permanent discontinuation of PEG-IFN treatment and the pulse steroid therapy followed by a 2 week course of oral prednisone.

Discussion:

In case of interferon-associated retinopathy discontinuation of the therapy and treatment with high dose steroids can be beneficial. The prognosis of interferon-associated opthalmological side effects remains uncertain: in some patients visual acuity improves, other continues with poor visual outcome. Considering that, all patients should undergo ophthalmologic examination before treatment with interferon and their ophthalmological status should be monitored regularly while receiving this therapy.     

Performance of the Prototype NovioSense Noninvasive Biosensor for Tear Glucose in Type 1 Diabetes

Introduction:We recently published the results of a pilot study measuring glucose in tear fluid. We now show the results of an additional 24 patients.Methods:Twenty-four subjects were recruited from Haaglanden Diabetes Centre. The patients reported in a fasting state and were given a meal with half the usual dose of insulin during the test. The device was applied under the lower eyelid. Glucose levels from capillary blood and interstitial fluid with a flash glucose measurement device were recorded every 15 minutes; the current from the tear glucose sensor was recorded continuously. The eye surface and tolerability were regularly checked. A calibration algorithm to convert tear glucose to blood values was built using a neural network regression model and validated.Results:No adverse events were attributed to the sensor coil placed under the lower eyelid. The mean absolute relative difference for the 24-patient subset was 16.7 (after 6 hours total time in the eye). The median absolute relative difference was 13.3. Compared to published data from Abbott (15.7 on day 1), the present device is comparable to Libre, considering that the device was allowed only one hour of equilibration time before the measurements were made.Conclusion:The NovioSense Tear glucose sensor measures blood glucose values with an acceptable accuracy and may become a good alternative to invasive devices.     

Exposure to urban nitrogen dioxide pollution and the risk of myocardial infarction

OBJECTIVES: This study attempted to determine whether long-term exposure to nitrogen dioxide (NO2), an indicator of motor vehicle exhaust, increases the risk of myocardial infarction (MI). METHODS: A population-based case-control study was conducted among men aged 25-64 years and residing in Kaunas, Lithuania. The study included all cases of first-time myocardial infarction in 1997-2000. Interviews with patients treated in hospitals elicited information on smoking and other risk factors, including residential histories. A high response rate (77.4%) resulted in 448 cases and 1777 controls. Nitrogen dioxide (NO2) was selected for analysis as an indicator of traffic-related air pollution. The annual air pollution levels were estimated for the residential districts; thereafter the data were linked to the home addresses of the cases and controls. RESULTS: After adjustment for age, education, smoking, blood pressure, body mass index, marital status, and psychological stress, the risk of myocardial infarction was higher for the men exposed to medium [odds ratio (OR) 1.43, 95% confidence interval (95% CI) 1.04-1.96] and high (OR 1.43, 95% CI 1.07-1.92) NO2 levels. The data suggested a stronger association among 55- to 64-year-old men. The risk of myocardial infarction increased by 17% among the 25- to 64-year-old men (OR 1.17, 95% CI 1.01-1.35) and by 34% among those aged 55-64 years (OR 1.34, 95% CI 1.08-1.67) from the first to the third tertile of NO2 exposure. CONCLUSIONS: The results indicate that urban NO2 pollution may increase the risk of myocardial infarction and that vehicle emissions may be of particular importance.