Abstract: In small clinical studies, the application of transcranial photobiomodulation (PBM), which typically delivers low-intensity near-infrared (NIR) to treat the brain, has led to some remarkable results in the treatment of dementia and several neurodegenerative diseases. However, despite the extensive literature detailing the mechanisms of action underlying PBM outcomes, the specific mechanisms affecting neurodegenerative diseases are not entirely clear. While large clinical trials are warranted to validate these findings, evidence of the mechanisms can explain and thus provide credible support for PBM as a potential treatment for these diseases. Tubulin and its polymerized state of microtubules have been known to play important roles in the pathology of Alzheimer's and other neurodegenerative diseases. Thus, we investigated the effects of PBM on these cellular structures in the quest for insights into the underlying therapeutic mechanisms. In this study, we employed a Raman spectroscopic analysis of the amide I band of polymerized samples of tubulin exposed to pulsed low-intensity NIR radiation (810 nm, 10 Hz, 22.5 J/cm2 dose). Peaks in the Raman fingerprint region (300-1900 cm-1)-in particular, in the amide I band (1600-1700 cm-1)-were used to quantify the percentage of protein secondary structures. Under this band, hidden signals of C=O stretching, belonging to different structures, are superimposed, producing a complex signal as a result. An accurate decomposition of the amide I band is therefore required for the reliable analysis of the conformation of proteins, which we achieved through a straightforward method employing a Voigt profile. This approach was validated through secondary structure analyses of unexposed control samples, for which comparisons with other values available in the literature could be conducted. Subsequently, using this validated method, we present novel findings of statistically significant alterations in the secondary structures of polymerized NIR-exposed tubulin, characterized by a notable decrease in alpha-helix content and a concurrent increase in beta-sheets compared to the control samples. This PBM-induced alpha-helix to beta-sheet transition connects to reduced microtubule stability and the introduction of dynamism to allow for the remodeling and, consequently, refreshing of microtubule structures. This newly discovered mechanism could have implications for reducing the risks associated with brain aging, including neurodegenerative diseases like Alzheimer's disease, through the introduction of an intervention following this transition.

Abstract: BackgroundNon-melanoma skin cancer is one of the most common types of cancer and one of the main approaches is brachytherapy. For small lesions, the treatment of this cancer with brachytherapy can be done with two commercial applicators, one of these is the Large Field Valencia Applicators (LFVA).PurposeThe aim of this study is to test the capabilities of the LFVA to use clinically 60Co sources instead of the 192Ir ones. This study was designed for the same dwell positions and weights for both sources.MethodsThe Penelope Monte Carlo code was used to evaluate dose distribution in a water phantom when a 60Co source is considered. The LFVA design and the optimized dwell weights reported for the case of 192Ir are maintained with the only exception of the dwell weight of the central position, that was increased. 2D dose distributions, field flatness, symmetry and the leakage dose distribution around the applicator were calculated.ResultsWhen comparing the dose distributions of both sources, field flatness and symmetry remain unchanged. The only evident difference is an increase of the penumbra regions for all depths when using the 60Co source. Regarding leakage, the maximum dose within the air volume surrounding the applicator is in the order of 20% of the prescription dose for the 60Co source, but it decreases to less than 5% at about 1 cm distance.ConclusionsFlatness and symmetry remains unaltered as compared with 192Ir sources, while an increase in leakage has been observed. This proves the feasibility of using the LFVA in a larger range of clinical applications.

Abstract: We consider a flavour conserving two Higgs doublet model that consists of a type I (or X) quark sector and a generalized lepton sector where the Yukawa couplings of the charged leptons to the new scalars are not proportional to the lepton masses. The model, previously proposed to solve both muon and electron g – 2 anomalies simultaneously, is also capable to accommodate the ATLAS excess in pp -> S -> tau(+)tau(-) with gluon-gluon fusion production in the invariant mass range [0.2; 0.6] TeV, including all relevant low and high energy constraints. The excess is reproduced taking into account the new contributions from the scalar H, the pseudoscalar A, or both. In particular, detailed numerical analyses favoured the solution with a significant hierarchy among the vevs of the two Higgs doublets, t(beta)similar to 10, and light neutral scalars satisfying m(A) > m(H) with sizable couplings to tau leptons. In this region of the parameter space, the muon g – 2 anomaly receives one and two-loop (Barr Zee) contributions of similar size, while the electron anomaly is explained at two loops. An analogous ATLAS excess in b-associated production and the CMS excess in ditop production are also studied. Further New Physics prospects concerning the anomalous magnetic moment of the tau lepton and the implications of the CDF M-W measurement on the final results are discussed.