Validating the total illness burden index for prostate cancer (TIBI-CaP) in men with castration-resistant prostate cancer: data from TRUMPET.

AIM: To validate the total illness burden index for prostate cancer (TIBI-CaP) in castration-resistant prostate cancer (CRPC) patients. PATIENTS & METHODS: Baseline comorbidity scores collected using the TIBI-CaP were compared with the baseline patient-reported health-related quality of life using the SF-12v2 and FACT-P questionnaires in 302 patients enrolled in the Treatment Registry for Outcomes in CRPC Patients (TRUMPET). RESULTS: Baseline TIBI-CaP scores were negatively correlated with all baseline SF-12v2 domain/composite (p < 0.001) and FACT-P subscale/total (p < 0.020) scores. There was a significant decreasing linear trend in SF12v2 and FACT-P scores over the categories based on TIBI-CaP quartiles of comorbidity burden (from 'least' to 'severe'). CONCLUSION: The TIBI-CaP is a valid measure of comorbidity burden in patients with CRPC in the real world.

Benzimidazole inhibitors of protein kinase CK2 potently inhibit the activity of atypical protein kinase Rio1.

Benzimidazole derivatives of 5,6-dichlorobenzimidazole 1-ß-D-ribofuranoside (DRB) comprise the important class of protein kinase CK2 inhibitors. Depending on the structure, benzimidazoles inhibit CK2 with different selectivity and potency. Besides CK2, the compounds can inhibit, with similar activity, other classical eukaryotic protein kinases (e.g. PIM, DYRK, and PKD). The present results show that a majority of the most common CK2 inhibitors can affect the atypical kinase Rio1 in a nanomolar range. Kinetic data confirmed the mode of action of benzimidazoles as typical ATP-competitive inhibitors. In contrast to toyocamycin-the first discovered small-molecule inhibitor of Rio1-the most potent representative of benzimidazoles TIBI (IC50 = 0.09 µM, K i  = 0.05 µM) does not influence the oligomeric state of the Rio1 kinase. Docking studies revealed that TIBI can occupy the ATP-binding site of Rio1 in a manner similar to toyocamycin, and enhances the thermostability of the enzyme.

Validation of the transcranial Doppler rescue criteria for mechanical thrombectomy.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) identifies acute stroke patients with arterial occlusion where treatment may not effectively open the blocked vessel. This study aimed to examine the clinical utility and prognostic value of TCD flow findings in patients enrolled in a multicenter prospective study (CLOTBUST-PRO). METHODS: Patients enrolled with intracranial occlusion on computed tomography angiography (CTA) who underwent urgent TCD evaluation before intravenous thrombolysis was included in this analysis. TCD findings were assessed using the mean flow velocity (MFV) ratio, comparing the reciprocal ratios of the middle cerebral artery (MCA) depths bilaterally (affected MCA-to-contralateral MCA MFV [aMCA/cMCA MFV ratio]). RESULTS: A total of 222 patients with intracranial occlusion on CTA were included in the study (mean age: 64 ± 14 years, 62% men). Eighty-eight patients had M1 MCA occlusions; baseline mean National Institutes of Health Stroke Scale (NIHSS) score was 16, and a 24-hour mean NIHSS score was 10 points. An aMCA/cMCA MFV ratio of <.6 had a sensitivity of 99%, specificity of 16%, positive predictive value (PV) of 60%, and negative PV of 94% for identifying large vessel occlusion (LVO) including M1 MCA, terminal internal carotid artery, or tandem ICA/MCA. Thrombolysis in Brain Ischemia scale, with (grade ≥1) compared to without flow (grade 0), showed a sensitivity of 17.1%, specificity of 86.9%, positive PV of 62%, and negative PV of 46% for identifying LVO. CONCLUSIONS: TCD is a valuable modality for evaluating arterial circulation in acute ischemic stroke patients, demonstrating significant potential as a screening tool for intravenous/intra-arterial lysis protocols.

An update on water kefir: Microbiology, composition and production.

Water kefir is a sparkling, slightly acidic fermented beverage produced by fermenting a solution of sucrose, to which dried fruits have been added, with water kefir grains. These gelatinous grains are a symbiotic culture of bacteria and yeast embedded in a polysaccharide matrix. Lactic acid bacteria, yeast and acetic acid bacteria are the primary microbial members of the sugary kefir grain. Amongst other contributions, species of lactic acid bacteria produce the exopolysaccharide matrix from which the kefir grain is formed, while yeast assists the bacteria by a nitrogen source that can be assimilated. Exactly which species predominate within the grain microbiota, however, appears to be dependent on the geographical origin of the grains and the fermentation substrate and conditions. These factors ultimately affect the characteristics of the beverage produced in terms of aroma, flavour, and acidity, for example, but can also be controlled and exploited in the production of a beverage of desired characteristics. The production of water kefir has traditionally occurred on a small scale and the use of defined starter cultures is not commonly practiced. However, as water kefir increases in popularity as a beverage - in part because of consumer lifestyle trends and in part due to water kefir being viewed as a health drink with its purported health benefits - the need for a thorough understanding of the biology and dynamics of water kefir, and for defined and controlled production processes, will ultimately increase. The aim of this review is to provide an update into the current knowledge of water kefir.

Microstructure, mechanical properties, castability and in vitro biocompatibility of Ti-Bi alloys developed for dental applications.

In this study, the microstructure, mechanical properties, castability, electrochemical behaviors, cytotoxicity and hemocompatibility of Ti-Bi alloys with pure Ti as control were systematically investigated to assess their potential applications in the dental field. The experimental results showed that, except for the Ti-20Bi alloy, the microstructure of all other Ti-Bi alloys exhibit single α-Ti phase, while Ti-20Bi alloy is consisted of mainly α-Ti phase and a small amount of BiTi2 and BiTi3 phases. The tensile strength, hardness and wear resistance of Ti-Bi alloys were demonstrated to be improved monotonically with the increase of Bi content. The castability test showed that Ti-2Bi alloy increased the castability of pure Ti by 11.7%. The studied Ti-Bi alloys showed better corrosion resistance than pure Ti in both AS (artificial saliva) and ASFL (AS containing 0.2% NaF and 0.3% lactic acid) solutions. The concentrations of both Ti ion and Bi ion released from Ti-Bi alloys are extremely low in AS, ASF (AS containing 0.2% NaF) and ASL (AS containing 0.3% lactic acid) solutions. However, in ASFL solution, a large number of Ti and Bi ions are released. In addition, Ti-Bi alloys produced no significant deleterious effect to L929 cells and MG63 cells, similar to pure Ti, indicating a good in vitro biocompatibility. Besides, both L929 and MG63 cells perform excellent cell adhesion ability on Ti-Bi alloys. The hemolysis test exhibited that Ti-Bi alloys have an ultra-low hemolysis percentage below 1% and are considered nonhemolytic. To sum up, the Ti-2Bi alloy exhibits the optimal comprehensive performance and has great potential for dental applications.