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Vittrup Sanders posted an update 2 days, 10 hours ago
Multiple myeloma (MM) is a hematological malignancy with a poor prognosis while with a long and progressive outcome. To date, the therapeutic options are restricted to few drugs, including thalidomide or its derivates and autologous transplantation including stem-cell transplantation. More recently, the use of both proteasome inhibitors and monoclonal antibodies have been included in MM therapy, but the clinical results are still under evaluation. Unfortunately, death rates (within the 5-year overall survival rates) are still very high (45%), with no relevant improvement over the past 10 years. Here, we discuss data supporting a new therapeutic approach against MM, based on a common phenotype of tumor malignancies, which is the acidic microenvironment. Extracellular acidity drastically reduces the efficacy of both anti-tumor drugs and the immune reaction against tumors. Pre-clinical data have shown that anti-acidic drugs, such as proton pump inhibitors (PPIs), have a potent cytotoxic effect against human MM cells, thus supporting their use in the treatment of this malignancy. Here, we discuss also similarities between MM and type II diabetes mellitus (DM) with high risk of developing MM, suggesting that both anti-diabetic drugs and a hypocaloric diet may help in curing MM patients.Gravity in the head-to-toe direction, known as +Gz (G force), forces blood to pool in the lower body. Fighter pilots experience decreases in blood pressure when exposed to hypergravity in flight. Human centrifuge has been used to examine the G tolerance and anti-G straining maneuver (AGSM) techniques of military pilots. Some factors that may affect G tolerance have been reported but are still debated. The aim of this study was to investigate the physiological responses and anthropometric factors correlated with G tolerance. We retrospectively reviewed the training records of student pilots who underwent high G training. Variables were collected to examine their correlations with the outcome of 7.5G sustained for 15 s (7.5G profile). There were 873 trainees who underwent 7.5G profile training, 44 trainees (5.04%) could not sustain the test for 15 s. The group with a small heart rate (HR) increase (less than 10%) during the first 1-5 s of the 7.5G profile had a nearly ten-fold higher failing chance compared with the large HR increase group (adjusted odds ratio 9.91; 95% confidence interval 4.11-23.88). click here The chances of failure were inversely related to the HR increase percentage (p for trend less then 0.001). Factors, including body mass index, relaxed and straining G tolerance, and AGSM, were found to be negatively correlated with the outcome.The human eye is a specialized organ with a complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years, many in vitro models have been developed in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review, the ocular cell types and functionality are described, providing an overview about the scientific challenge for the development of three-dimensional (3D) in vitro models.The bonded lingual retainer (BLR) is considered a favorable choice for retaining lower incisors’ alignment post-orthodontic treatment; however, it may cause some unwanted effects such as inadvertent tooth movement and torque changes. These often result in gingival recession (Miller class III-type) with exposure of the root surface, which compromises the esthetics and hinders the comfort of the patient. Fifteen post-orthodontic patients presenting Miller class III-type recessions with BLR were examined. Two protocols were used the first included the removal of the BLR prior to surgery and the second included only a surgical approach. All patients underwent the same surgery of a modified tunnel double papilla procedure for root coverage. The gingival recession was measured using a dental probe before, and three to six months post-surgery. The average improvement in recession depth was significantly greater (p = 0.008) for the protocol that included removal of the BLR (4.0 ± 0.83 mm) with an improvement of 87.2% as compared to the second protocol that showed an improvement of 43.8% (1.88 ± 1.29 mm). Removing the BLR prior to surgery is beneficial for predictable root coverage in post-orthodontic Miller class III recessions.The efficacy of audiovisual (AV) integration is reflected in the degree of cross-modal suppression of the auditory event-related potentials (ERPs, P1-N1-P2), while stronger semantic encoding is reflected in enhanced late ERP negativities (e.g., N450). We hypothesized that increasing visual stimulus reliability should lead to more robust AV-integration and enhanced semantic prediction, reflected in suppression of auditory ERPs and enhanced N450, respectively. EEG was acquired while individuals watched and listened to clear and blurred videos of a speaker uttering intact or highly-intelligible degraded (vocoded) words and made binary judgments about word meaning (animate or inanimate). We found that intact speech evoked larger negativity between 280-527-ms than vocoded speech, suggestive of more robust semantic prediction for the intact signal. For visual reliability, we found that greater cross-modal ERP suppression occurred for clear than blurred videos prior to sound onset and for the P2 ERP. Additionally, the later semantic-related negativity tended to be larger for clear than blurred videos. These results suggest that the cross-modal effect is largely confined to suppression of early auditory networks with weak effect on networks associated with semantic prediction. However, the semantic-related visual effect on the late negativity may have been tempered by the vocoded signal’s high-reliability.