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  • Gustafsson McCallum posted an update 1 year, 6 months ago

    009). The Cox proportional hazard regression analysis revealed a lower rate of osteoporosis for the metformin group (adjusted hazard ratio of 0.820; 95% confidence interval = 0.691-0.972, p = 0.022). Diabetic patients with CIS under metformin therapy presented lower osteoporosis rate than those who were not receiving metformin therapy.The genus Enterococcus comprises a ubiquitous group of Gram-positive bacteria that can cause diverse health care-associated infections. Their genome plasticity enables easy acquisition of virulence factors as well as antibiotic resistances. Urinary tract infections (UTIs) and catheter-associated UTIs are common diseases caused by enterococci. In this study, Enterococcus strains isolated from UTIs were characterized, showing that the majority were E. faecalis and contained several virulence factors associated to a better colonization of the urinary tract. Their susceptibility against the bacteriocin AS-48 and several antibiotics was tested. AS-48 is a potent circular bacteriocin that causes bacterial death by pore formation in the cell membrane. The interest of this bacteriocin is based on the potent inhibitory activity, the high stability against environmental conditions, and the low toxicity. AS-48 was active at concentrations below 10 mg/L even against antibiotic-resistant strains, whereas these strains showed resistance to, at least, seven of the 20 antibiotics tested. Moreover, the effect of AS-48 combined with antibiotics commonly used to treat UTIs was largely synergistic (with up to 100-fold MIC reduction) and only occasionally additive. These data suggest AS-48 as a potential novel drug to deal with or prevent enterococcal infections.Mitochondrial transplantation therapy is an innovative strategy for the treatment of mitochondrial dysfunction. The approach has been reported to be useful in the treatment of cardiac ischemic reperfusion injuries in human clinical trials and has also been shown to be useful in animal studies as a method for treating mitochondrial dysfunction in various tissues, including the heart, liver, lungs, and brain. On the other hand, there is no methodology for using preserved mitochondria. Research into the pharmaceutical formulation of mitochondria to promote mitochondrial transplantation therapy as the next step in treating many patients is urgently needed. In this review, we overview previous studies on the therapeutic effects of mitochondrial transplantation. We also discuss studies related to immune responses that occur during mitochondrial transplantation and methods for preserving mitochondria, which are key to their stability as medicines. Finally, we describe research related to mitochondrial targeting drug delivery systems (DDS) and discuss future perspectives of mitochondrial transplantation.Lifting and carrying heavy objects is a major aspect of physically intensive jobs. Wearable sensors have previously been used to classify different ways of picking up an object, but have seen only limited use for automatic classification of load position and weight while a person is walking and carrying an object. In this proof-of-concept study, we thus used wearable inertial and electromyographic sensors for offline classification of different load positions (frontal vs. unilateral vs. bilateral side loads) and weights during gait. Ten participants performed 19 different carrying trials each while wearing the sensors, and data from these trials were used to train and evaluate classification algorithms based on supervised machine learning. The algorithms differentiated between frontal and other loads (side/none) with an accuracy of 100%, between frontal vs. unilateral side load vs. bilateral side load with an accuracy of 96.1%, and between different load asymmetry levels with accuracies of 75-79%. While the study is limited by a lack of electromyographic sensors on the arms and a limited number of load positions/weights, it shows that wearable sensors can differentiate between different load positions and weights during gait with high accuracy. In the future, such approaches could be used to control assistive devices or for long-term worker monitoring in physically demanding occupations.Prostate cancer is the second most frequent malignancy in men worldwide. Unfortunately, current therapies often lead to the onset of metastatic castration-resistant prostate cancer (mCRPC), causing significant mortality. Therefore, there is an urgent need for new and targeted therapies that are advantageous over the current ones. Recently, the PSMA-targeted radioligand therapy of mCRPC has shown very promising results. In line with this, we described the synthesis of a new radioimmunoconjugate, 223RaA-silane-PEG-D2B, for targeted mCRPC therapy. The new compound consists of a NaA zeolite nanocarrier loaded with the α-particle emitting Ra-223 radionuclide, functionalized with the anti-PSMA D2B antibody. Physicochemical properties of the synthesized compound were characterized by standard methods (HR-SEM, TEM, XRD, FTIR, EDS, NTA, DLS, BET, TGA). The targeting selectivity, the extent of internalization, and cytotoxicity were determined in LNCaP C4-2 (PSMA+) and DU-145 (PSMA-) cells. Our results supported the 223RaA-silane-PEG-D2B synthesis and revealed that the final product had a diameter ca. 120 nm and specific activity 0.65 MBq/1mg. The product was characterized by a high yield of stability (>95% up to 12 days). The conjugation reaction resulted in approximately 50 antibodies/nanoparticle. The obtained radioimmunoconjugate bound specifically and internalized into PSMA-expressing LNCaP C4-2 cells, but not into PSMA-negative DU-145 cells. 223RaA-silane-PEG-D2B demonstrated also potent cytotoxicity in LNCaP C4-2 cells. These promising results require further in vivo evaluation of 223RaA-silane-PEG-D2B with regard to its toxicity and therapeutic efficacy.ZnO and carbon quantum dots (CQDs) were synthesized by a hydrothermal method, and CQDs were doped into ZnO by a grinding method to fabricate a ZnO/CQDs composite. The X-ray diffraction and the scanning electron microscope revealed that the as-prepared ZnO has a structure of wurtzite hexagonal ZnO and a morphology of a flower-like microsphere which can provide more surface areas to adsorbed gases. The ZnO/CQDs composite has a higher gas sensitivity response to NO gas than ZnO microspheres. A gas sensitivity test of the ZnO/CQDs composite showed that the sensor had a high NO response (238 for 100 ppm NO) and NO selectivity. DNA-PK inhibitor The detection limit of the ZnO/CQDs composite to NO was 100 ppb and the response and recovery times were 34 and 36 s, respectively. The active functional group provided by CQDs has a significant effect on NO gas sensitivity, and the gas sensitivity mechanism of the ZnO/CQDs composite is discussed.