Functional Hair Cell Mechanotransducer Channels Are Required for Aminoglycoside Ototoxicity

Aminoglycosides (AG) are commonly prescribed antibiotics with potent bactericidal activities. One main side effect is permanent sensorineural hearing loss, induced by selective inner ear sensory hair cell death. Much work has focused on AG's initiating cell death processes, however, fewer studies exist defining mechanisms of AG uptake by hair cells. The current study investigated two proposed mechanisms of AG transport in mammalian hair cells: mechanotransducer (MET) channels and endocytosis. To study these two mechanisms, rat cochlear explants were cultured as whole organs in gentamicin-containing media. Two-photon imaging of Texas Red conjugated gentamicin (GTTR) uptake into live hair cells was rapid and selective. Hypocalcemia, which increases the open probability of MET channels, increased AG entry into hair cells. Three blockers of MET channels (curare, quinine, and amiloride) significantly reduced GTTR uptake, whereas the endocytosis inhibitor concanavalin A did not. Dynosore quenched the fluorescence of GTTR and could not be tested. Pharmacologic blockade of MET channels with curare or quinine, but not concanavalin A or dynosore, prevented hair cell loss when challenged with gentamicin for up to 96 hours. Taken together, data indicate that the patency of MET channels mediated AG entry into hair cells and its toxicity. Results suggest that limiting permeation of AGs through MET channel or preventing their entry into endolymph are potential therapeutic targets for preventing hair cell death and hearing loss

Exploring anomalous HZγ couplings in γ-proton collisions at the LHC

The HZγ coupling, which is highly sensitive to the new physics beyond the standard model, is studied through the process pp→pγp→pHX at the LHC. To this purpose, an effective Lagrangian, in a model independent approach, with dimension six operators is considered in this paper. New interaction terms regarding beyond the standard model physics include the Higgs boson anomalous vertices in both CP-even and CP-odd structures. A detailed numerical analysis is performed to scrutinize the accurate constraints on the effective HZγ couplings and to discuss how far the corresponding bounds can be improved. This is achieved by testing all the efficient Higgs decay channels and increasing the integrated luminosity at three different forward detector acceptance regions. The numerical results propose that the Higgs photoproduction at the LHC, as a complementary channel, has a great potential of exploring the HZγ couplings

Bio-oss in Treatment of Furcation Class II Deffects and Comparison with Coronally Positioned Flap

Statement of Problem: Among periodontal defects, the furcation involvement represents one of the most chalenging scenarios due to the difficulty of achieving a predictable improvement regardless of the type of periodontal therapy. Moreover, the presence of furcation involvement has been demonstrated to considerably affect tooth prognosis. Thus, treatment of furcation defects is a challenge in clinical periodontics. The aim of periodontal treatment is not only to control infection but also to regenerate periodontal tissues lost as a consequence of periodontal disease.Purpose: The purpose of this study was to compare Bio-oss (Bo), an anorganic bovine bone Xenograft, in combination with coronally positioned flap to open flap debridment surgery with coronally positiond flap alone in human mandibular class II furcation defects.Materials and Methods: In this clinical trial and interventional study 24 furcations, which provided 12 pairs of similar periodontal defects were evaluated. Each defect was randomly assigned to treatment with Bio-Oss in combination coronally positioned flap or open flap debridment and coronally positioned flap alone. Following basic therapy, baseline measurements were recorded including probing depth (PDD), clinical attachment level (CAL),gingival recession (REC), keratinized gingiva (KG) and closed horizontal probing depth(CHPD). After 6 months, all sites were re-entered and hard tissue measurements were recorded.Hard tissue measurements were performed during surgery to determine open horizontal probing depth (OHPD) and open vertical probing depth (OVPD). The data was analyzed using t-test paired sample.Results: Vertical probing depth reduction of 3.17±1.32 mm and horizontal probing depth reduction of 4.42±1.02 mm were noted for the BO group, with 2.87±0.83 mm and 2.31±0.49 mm reductions, respectively, noted for CPF alone. Both surgical procedures resulted in statistically significant probing depth reduction and gain clinical attachment levels, with no significant difference between groups. Recession didn't have significant differences betweengroups. Hard tissue measurements (after Re-entry) showed 4.17±1.66 mm of vertical furcation bone fill (OVPD) for test group (BO) and 0.83±0.72 mm for CPF alone. The test (BO) group had 3.87±0.88mm of horizontal furcation bone fill (OHPD), and the CPF group had1.21±0.8mm.Conclusion: There was a statistically significant difference between test (BO) group and CPF group in all soft and hard tissue measurements with the exception of attachment level, recession,and keratinized gingiva. The use of Bio-oss improved horizontal and vertical defect resolution in mandibular class II furcation defects

Predicting Factors of Radiosensitivity in Individual Radiotherapy

BACKGROUND AND OBJECTIVE: Radiation dose in oncology protocols is different for each patient according to the type and grade of the tumor, as well as adjuvant therapies. In the current treatment regimens, some predicting factors of individual radiosensitivity have not been considered. Individual radiotherapy can lower side effects through radiation dose reduction with respect to tumor control. In this study, the most determining factors for predicting radiosensitivity, used for individual radiotherapy, were reviewed. METHODS: Data were retrieved through searching Sciencedirect, PubMed, Google scholar, Iranmedex and SID databases. The titles and abstracts of Persian and English articles were searched using keywords including: radiotherapy, the rate of cell proliferation, tumoral hypoxia, inherent radiosensitivity, tumor cell cycle, inhibitor factors of tumor, cancer stem cells, field dose radiation, apoptosis and predicting factors of radiosensitivity. FINDINGS: Out of 90 articles, 25 original articles and reviews on predicting factors of the rate of radiosensitivity were thoroughly studied. Multiple factors, such as the presence of hypoxic zone and its size, inherent radiosensitivity and apoptosis, are crucial in determining individual radiation dose. Other factors, including previous history of exposure, blood type, left-or right-handedness and physical factors, should also be considered. CONCLUSION: With respect to the physical, chemical, and biological parameters influencing individual radiosensitivity, radiotherapy individualization can promote tumor treatment and diminish side effects of radiotherapy on normal tissue