Demonstrating Agreement between Radio and Fluorescence Measurements of the Depth of Maximum of Extensive Air Showers at the Pierre Auger Observatory.

We show, for the first time, radio measurements of the depth of shower maximum (X_{max}) of air showers induced by cosmic rays that are compared to measurements of the established fluorescence method at the same location. Using measurements at the Pierre Auger Observatory we show full compatibility between our radio and the previously published fluorescence dataset, and between a subset of air showers observed simultaneously with both radio and fluorescence techniques, a measurement setup unique to the Pierre Auger Observatory. Furthermore, we show radio X_{max} resolution as a function of energy and demonstrate the ability to make competitive high-resolution X_{max} measurements with even a sparse radio array. With this, we show that the radio technique is capable of cosmic-ray mass composition studies, both at Auger and at other experiments.

Limits to Gauge Coupling in the Dark Sector Set by the Nonobservation of Instanton-Induced Decay of Super-Heavy Dark Matter in the Pierre Auger Observatory Data.

Instantons, which are nonperturbative solutions to Yang-Mills equations, provide a signal for the occurrence of quantum tunneling between distinct classes of vacua. They can give rise to decays of particles otherwise forbidden. Using data collected at the Pierre Auger Observatory, we search for signatures of such instanton-induced processes that would be suggestive of super-heavy particles decaying in the Galactic halo. These particles could have been produced during the post-inflationary epoch and match the relic abundance of dark matter inferred today. The nonobservation of the signatures searched for allows us to derive a bound on the reduced coupling constant of gauge interactions in the dark sector: α_{X}≲0.09, for 10^{9}≲M_{X}/GeV<10^{19}. Conversely, we obtain that, for instance, a reduced coupling constant α_{X}=0.09 excludes masses M_{X}≳3×10^{13} GeV. In the context of dark matter production from gravitational interactions alone, we illustrate how these bounds are complementary to those obtained on the Hubble rate at the end of inflation from the nonobservation of tensor modes in the cosmological microwave background.

Surface guided radiation therapy: An international survey on current clinical practice.

Introduction: Surface Guided Radiation Therapy (SGRT) is being increasingly implemented into clinical practice across a number of techniques and irradiation-sites. This technology, which is provided by different vendors, can be used with most simulation- and delivery-systems. However, limited guidelines and the complexity of clinical settings have led to diverse patterns of operation. With the aim to understand current clinical practice a survey was designed focusing on specifics of the clinical implementation and usage. Materials and methods: A 32-question survey covered: type and number of systems, quality assurance (QA), clinical workflows, and identification of strengths/limitations. Respondents from different professional groups and countries were invited to participate. The survey was distributed internationally via ESTRO-membership, social media and vendors. Results: Of the 278 institutions responding, 172 had at least one SGRT-system and 136 use SGRT clinically. Implementation and QA were primarily based on the vendors' recommendations and phantoms. SGRT was mainly implemented in breast RT (116/136), with strong but diverse representation of other sites. Many (58/135) reported at least partial elimination of skin-marks and a third (43/126) used open-masks. The most common imaging protocol reported included the combination of radiographic imaging with SGRT. Patient positioning (115/136), motion management (104/136) and DIBH (99/136) were the main applications.Main barriers to broader application were cost, system integration issues and lack of demonstrated clinical value. A lack of guidelines in terms of QA of the system was highlighted. Conclusions: This overview of the SGRT status has the potential to support users, vendors and organisations in the development of practices, products and guidelines.

Consensus paper on postural dysfunction: recommendations for prevention, diagnosis and therapy.

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.

Measurement of the Fluctuations in the Number of Muons in Extensive Air Showers with the Pierre Auger Observatory.

We present the first measurement of the fluctuations in the number of muons in extensive air showers produced by ultrahigh energy cosmic rays. We find that the measured fluctuations are in good agreement with predictions from air shower simulations. This observation provides new insights into the origin of the previously reported deficit of muons in air shower simulations and constrains models of hadronic interactions at ultrahigh energies. Our measurement is compatible with the muon deficit originating from small deviations in the predictions from hadronic interaction models of particle production that accumulate as the showers develop.

Features of the Energy Spectrum of Cosmic Rays above 2.5×10

We report a measurement of the energy spectrum of cosmic rays above 2.5×10^{18} eV based on 215 030 events. New results are presented: at about 1.3×10^{19} eV, the spectral index changes from 2.51±0.03(stat)±0.05(syst) to 3.05±0.05(stat)±0.10(syst), evolving to 5.1±0.3(stat)±0.1(syst) beyond 5×10^{19} eV, while no significant dependence of spectral features on the declination is seen in the accessible range. These features of the spectrum can be reproduced in models with energy-dependent mass composition. The energy density in cosmic rays above 5×10^{18} eV is [5.66±0.03(stat)±1.40(syst)]×10^{53} erg Mpc^{-3}.

New approach in Auger elemental relative sensitive factor calculation by using TEM-EDS analysis based on bi-layers of pure elements.

In fabrication of microelectronic devices two important steps are often recognized: i) all the processes performed on the wafer in order to build the active part of the devices and, ii) the assembly and packaging processes, typically performed on a chip, in order to fabricate interconnections between active part and exterior. The wafer back side is an active part of power devices and is normally coated with a stack of Ti-Ni-Au or Ti-Ni-Ag layers to ensure the best electrical contact with the frame on which the device is attached prior to the packaging. An important failure mechanism related to this particular process step is related to the diffusion of Ni to the surface of the stack that causes its oxidation on the back metal surface, inhibiting the correct connection to the metallic frame. Auger Electron Spectroscopy (AES) is a powerful analytical technique that can be used to detect this failure mechanism for its very high sensitivity in the characterization of surface layers. Unfortunately, its results are mainly qualitative. Quantitative extrapolations can be inaccurate using library Elemental Relative Sensitive Factor (ERSF) because they are mainly referred to a silicon substrate and could be not valid for a different matrix. A most accurate evaluation of the ERSF is based on the analysis, under identical experimental condition, of standard materials (with known concentration) that should be similar to the unknown sample and having the same matrix. However, the production of this kind of standard is not easy due to the mobility of Ni in Au and Ag. Another commonly used technique is the Energy Dispersive X-ray Spectrometry (EDS) which is less sensitive than the Auger and not sufficiently adequate for a quantitative analysis due to the limitation of the matrix correction methods. Recently, a new method to perform quantitative analysis by using Transmission Electron Microscopy (TEM) EDS was proposed, starting from bi-layers of pure elements. In this work we show how the use of TEM-EDS quantification of Ni in Ag could be a successful method for ERSF evaluation in order to overcome matrix effect in Auger quantification. For this purpose suitable foils of Ag/Al and Ni/Al were used. The validation of the method was performed on a sample with a tri-metal stack of Ti/Ni/Ag previously stimulated by means of a thermal budget to induce Ni migration on Ag surface. The quantitative analysis allowed us to use this characterized sample as AES standard for ERSF calculation.

Functional and molecular outcomes of the human masticatory muscles.

The masticatory muscles achieve a broad range of different activities such as chewing, sucking, swallowing, and speech. In order to accomplish these duties, masticatory muscles have a unique and heterogeneous structure and fiber composition, enabling them to produce their strength and contraction speed largely dependent on their motor units and myosin proteins that can change in response to genetic and environmental factors. Human masticatory muscles express unique myosin isoforms, including a combination of thick fibers, expressing myosin light chains (MyLC) and myosin class I and II heavy chains (MyHC) -IIA, -IIX, α-cardiac, embryonic and neonatal and thin fibers, respectively. In this review, we discuss the current knowledge regarding the importance of fiber-type diversity in masticatory muscles versus supra- and infrahyoid muscles, and versus limb and trunk muscles. We also highlight new information regarding the adaptive response and specific genetic variations of muscle fibers on the functional significance of the masticatory muscles, which influences craniofacial characteristics, malocclusions, or asymmetry. These findings may offer future possibilities for the prevention of craniofacial growth disturbances.

Inter-hemispheric Claustral Connections in Human Brain: A Constrained Spherical Deconvolution-Based Study.

PURPOSE: Complex claustral connection network was widely demonstrated both in humans and animals. Moreover, several studies have suggested that claustral connections directly involve also the contralateral hemisphere. Detection of contralateral cortico-claustral and inter-claustral connections was reported mainly in animals and only partially in humans. The main purpose of this study was to provide more robust tractography-driven support of the existence of inter-hemispheric claustral connections in humans, by means of a dedicated optimized tractographic protocol. METHODS: Fifteen healthy subjects were examined by means of an advanced magnetic resonance imaging-based probabilistic constrained spherical deconvolution tractographic protocol. Moreover, quantitative diffusion parameters were extracted by each reconstructed pathway. RESULTS: In this study, further imaging-based support on the possible existence in humans of contralateral cortico-claustral and inter-claustral connections was provided. These connections were found to involve almost all the superior portion of each claustrum, showing a topographical organization. Moreover, the detection of inter-claustral connections passing through the anterior commissure was reported, for the first time, in humans. CONCLUSIONS: The possible existence of inter-claustral and cortico-claustral contralateral pathways might provide the morphological basis for the complex functional phenomena observed in previous studies. Furthermore, these connections might have several important clinical implications, since they might explain how the inter-hemispheric coordination governed by the claustrum, as well as the functional recovery subsequent to damages involving one claustrum, takes place.

Testing Hadronic Interactions at Ultrahigh Energies with Air Showers Measured by the Pierre Auger Observatory.

Ultrahigh energy cosmic ray air showers probe particle physics at energies beyond the reach of accelerators. Here we introduce a new method to test hadronic interaction models without relying on the absolute energy calibration, and apply it to events with primary energy 6-16 EeV (E_{CM}=110-170 TeV), whose longitudinal development and lateral distribution were simultaneously measured by the Pierre Auger Observatory. The average hadronic shower is 1.33±0.16 (1.61±0.21) times larger than predicted using the leading LHC-tuned models EPOS-LHC (QGSJetII-04), with a corresponding excess of muons.

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy.

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8±0.7(stat)±6.7(syst) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principles calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.

Histochemical and morphological aspects of fresh frozen bone: a preliminary study.

Bone graft are used in dentistry for the reconstruction of severely atrophic jaws. Fresh frozen bone has no osteogenic property but it has osteoconductive and osteoinductive properties because its matrix contains growth factors such as vascular endothelial growth factor. The purpose of the present study was to evaluate morphological and protein expression characteristics of fresh frozen bone before graft and after six months of graft in patients who needed maxillary reconstruction. After 6 month of graft we observed the presence of viable bone as evidenced by full osteocyte lacunae and by the presence of RANKR, osteocalcin positive cells and vascular endothelial growth factor. In conclusion, our findings show that the fresh frozen bone after six month of graft is for the most part viable bone, encouraging its use as an alternative to autogenous bone for reconstructing maxillary bone defects prior to implant.

High-Dose Robotic Stereotactic Body Radiotherapy in the Treatment of Patients With Prostate Cancer: Preliminary Results in 26 Patients.

BACKGROUND: Stereotactic body radiotherapy (SBRT) can emulate high dose rate brachytherapy (HDR-BRT) dose fractionation. We report our preliminary results using SBRT in monotherapy or pre-external-beam radiotherapy (EBRT) boost in patients with localized prostate cancer (LpC). The primary end point was the evaluation of both acute and late toxicities; secondary end point was the observation of prostate-specific antigen (PSA) nadir. PATIENTS AND METHODS: Patients with LpC having prostate volume ≤90 cm(3) were enrolled in the present study. Patients were treated with SBRT alone or in combined modality (SBRT + EBRT). SBRT was performed using a CyberKnife System (Accuray Incorporated, Sunnyvale, California) and fiducial tracking system. RESULTS: From February 2008 to July 2013, 21 patients for monotherapy (38 Gy/4 fractions) and 5 for combined modality (9.5 Gy/2 fractions plus 46 Gy/23 fractions EBRT) were enrolled. Androgen deprivation therapy (ADT) was administered in 16 of the 26 patients. The median pretreatment PSA was 9.4 (range, 4.5-14.3) ng/mL. All patients completed the planned therapy. Acute Grade 1 toxicity was observed in 18 patients, genitourinary (GU) in 12 / 26 patients, and gastrointestinal (GI) in 6 / 26 patients. Acute Grade 2 GU toxicity was reported in 1 / 26 patients, and Grade 2 GI toxicity was observed in 2 / 26 patients. The median PSA nadir was 0.15 (range, 0.02 = 1.4) ng/mL. Late toxicities were observed in 5 / 26 patients: Grade 1 GU (3 of 26), Grade 2 GU (1 of 26), and Grade 1 GI (1 of 26). Median follow-up was 21.5 (range, 8-65) months. CONCLUSIONS: Our preliminary results of SBRT "simulating" HDR for LpC confirm a minimal toxicity and an optimal PSA response. The PSA nadirs appear comparable with HDR-BRT.

Sarcoglycan complex in masseter and sternocleidomastoid muscles of baboons: an immunohistochemical study.

The sarcoglycan complex consists of a group of single-pass transmembrane glycoproteins that are essential to maintain the integrity of muscle membranes. Any mutation in each sarcoglycan gene causes a series of recessive autosomal dystrophin-positive muscular dystrophies. Negative fibres for sarcoglycans have never been found in healthy humans and animals. In this study, we have investigated whether the social ranking has an influence on the expression of sarcoglycans in the skeletal muscles of healthy baboons. Biopsies of masseter and sternocleidomastoid muscles were processed for confocal immunohistochemical detection of sarcoglycans. Our findings showed that baboons from different social rankings exhibited different sarcoglycan expression profiles. While in dominant baboons almost all muscles were stained for sarcoglycans, only 55% of muscle fibres showed a significant staining. This different expression pattern is likely to be due to the living conditions of these primates. Sarcoglycans which play a key role in muscle activity by controlling contractile forces may influence the phenotype of muscle fibres, thus determining an adaptation to functional conditions. We hypothesize that this intraspecies variation reflects an epigenetic modification of the muscular protein network that allows baboons to adapt progressively to a different social status.

Can scanning near-field optical microscopy be compared with confocal laser scanning microscopy? A preliminary study on alpha-sarcoglycan and beta1D-integrin in human skeletal muscle.

The dystrophin-glycoprotein complex and the vinculin-talin-integrin system constitute, together a protein machinery, called costameres. The dystrophin-glycoprotein complex contains, among other proteins, also dystrophin and the sarcoglycans subcomplex, proteins playing a key role in the pathogenesis of many muscular dystrophies and linking the cytoplasmic myofibrillar contractile elements to the signal transducing molecules of the extracellular matrix, also providing structural support to the sarcolemma. The vinculin-talin-integrin system connects some components of the extracellular matrix with intermediate filaments of desmin, forming transverse bridges between Z and M lines. In our previous reports we always studied these systems by confocal laser scanning microscopy (CLSM). In this paper we report on the first applications of optical near-field fluorescence microscopy to the spatial localization of alpha-sarcoglycan and beta1D-integrin in human skeletal muscle fibres in order to better compare and test the images obtained with conventional CLSM and with scanning near-field optical microscopy (SNOM). In addition, the analysis of the surface morphology, and the comparison with the fluorescence map is put forward and analyzed for the first time on human muscle fibres. In aperture-SNOM the sample is excited through the nanometre-scale aperture produced at the apex of an optical fibre after tapering and subsequent metal coating. The acquisition of the topography map, simultaneously to the optical signal, by SNOM, permits to exactly overlap the fluorescence images obtained from the two consecutive scans needed for the double localization. Besides, the differences between the topography and the optical spatial patterns permit to assess the absence of artefacts in the fluorescence maps. Although the SNOM represented a good method of analysis, this technique remains a complementary method to the CLSM and it can be accepted in order to confirm the hypothesis advanced by CLSM.

Sarcoglycan subcomplex in normal and pathological human muscle fibers.

Sarcoglycans are a sub-complex of transmembrane proteins which are part of the dystrophin-glycoprotein complex (DGC). They are expressed above all in the skeletal, cardiac and smooth muscle. Although numerous studies have been conducted on the sarcoglycan sub-complex in skeletal and cardiac muscle, the manner of distribution and localization of these proteins along the non-junctional sarcolemma is still not clear. Furthermore, there are unclear data about the actual role of sarcoglycans in human skeletal muscle affected by sarcoglycanopathies. In our studies on human skeletal muscle, normal and pathological, we determined the localization, distribution and interaction of these glycoproteins. Our results, on normal human skeletal muscle, showed that the sarcoglycans can be localized both in the region of the sarcolemma over the I band and over the A band, hypothesizing a correlation between regions of the sarcolemma occupied by costameres and the metabolic type of the fibers (slow and fast). Our data on skeletal muscle affected by sarcoglycanopathy confirmed the hypothesis of a bidirectional signaling between sarcoglycans and integrins and the interaction of filamin2 with both sarcoglycans and integrins. In addition, we have recently demonstrated, in smooth muscle, the presence of alpha-SG, in contrast with data of other Authors. Finally, we analyzed the association between contractile activity and quantitative correlation between alpha- and epsilon-SG, in order to better define the arrangement of sarcoglycan subcomplex.

Sarcoglycan immunoreactivity is lacking in infantile hypertrophic pyloric stenosis. A confocal laser scanning microscopic study.

OBJECTIVES: The Dystrophin-Glycoprotein Complex (DGC) is a large multisubunit complex that plays a crucial role in maintaining the structural integrity and physiology of muscle fibers. Dystrophin has been reported to be absent in the pyloric muscle of infantile hypertrophic pyloric stenosis (IHPS) patients. The present study was designed to investigate the other two patterns of DGC (dystroglycan and sarcoglycan complexes) in normal pyloric muscle and their possible modifications in IHPS patients. METHODS: Ten pyloric muscle biopsies were obtained from babies operated for IHPS and five control pylorus biopsy taken at autopsy from cases without gastrointestinal disease. The DGC sub-complexes (beta-dystroglican and beta, delta- sarcoglycans) were localized immunohistochemically using specific monoclonal antibodies. The results were evaluated using a confocal laser scanning microscope. RESULTS: Positive immunolocalization of the two DGC sub complexes was demonstrated in the smooth muscle cells (SMCs) of the pyloric region of control patients. Similarly, a positive immune expression of beta-dystroglican was observed in the pyloric SMCs of IHPS patients. On the other hand a negative immunoreaction for sarcoglycans was recorded within the full thickness of the pyloric SMCs of these patients. CONCLUSIONS: The absence of sarcoglycans within the hypertrophied pyloric muscle may be a predisposing factor in the pathogenesis of IHPS since it could alter the normal physiology of SMCs through the modifications of structural integrity of sarcolemma and signaling between the extracellular and intracellular compartment.

Integrins, muscle agrin and sarcoglycans during muscular inactivity conditions: an immunohistochemical study.

Sarcoglycans are transmembrane proteins that seem to be functionally and pathologically as important as dystrophin. Sarcoglycans cluster together to form a complex, which is localized in the cell membrane of skeletal, cardiac, and smooth muscle. It has been proposed that the dystrophin-glycoprotein complex (DGC) links the actin cytoskeleton with the extracellular matrix and the proper maintenance of this connection is thought to be crucial to the mechanical stability of the sarcolemma. The integrins are a family of heterodimeric cell surface receptors which play a crucial role in cell adhesion including cell-matrix and intracellular interactions and therefore are involved in various biological phenomena, including cell migration, and differentiation tissue repair. Sarcoglycans and integrins play a mechanical and signaling role stabilizing the systems during cycles of contraction and relaxation. Several studies suggested the possibility that integrins might play a role in muscle agrin signalling. On these basis, we performed an immunohistochemical analyzing sarcoglycans, integrins and agrin, on human skeletal muscle affected by sensitive-motor polyneuropathy, in order to better define the correlation between these proteins and neurogenic atrophy due to peripheral neuropathy. Our results showed the existence of a cascade mechanism which provoke a loss of regulatory effects of muscle activity on costameres, due to loss of muscle and neural agrin. This cascade mechanism could determine a quantitative modification of transmembrane receptors and loss of alpha7B could be replaced and reinforced by enhanced expression of the alpha7A integrin to restore muscle fiber viability. Second, it is possible that the reduced cycles of contraction and relaxation of muscle fibers, during muscular atrophy, provoke a loss of mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix. Consequently, these mechanical changes could determine modifications of chemical signals through variations of pathway structural integrins, and alpha7A could replace alpha7B.

Non-invasive assessment of motor unit anatomy in jaw-elevator muscles.

The estimation of fibre length in jaw-elevator muscles is important for modelling studies and clinical applications. The objective of this study was to identify, from multi-channel surface EMG recordings, the main innervation zone(s) of the superficial masseter and anterior temporalis muscles, and to estimate the fibre length of these muscles. Surface EMG signals were collected from 13 subjects with a 16-electrode linear array. The innervation zones of the masseter and anterior temporalis were identified and their variability intra- and inter-subject outlined. More than one main innervation zone location was identified in the masseter of all subjects and in the temporalis anterior of 12 subjects. Average estimated fibre lengths, for the right (left) side, were (mean+/-SD) 27.3+/-2.4 mm (27.0+/-1.7 mm) and 25.9+/-2.3 mm (26.6+/-1.6 mm), for the superficial masseter and temporalis anterior muscle, respectively. The range of innervation zone locations was up to approximately 50% of the fibre length, both within and between subjects. Fibre length estimates well matched with published data on cadavers. It was concluded that multi-channel surface EMG provides important and reliable information on the anatomy of single motor units in jaw-elevator muscles.

Pre-surgical finasteride therapy in patients treated endoscopically for benign prostatic hyperplasia.

INTRODUCTION: Transurethral resection of the prostate is considered the standard technique for patients with moderate or severe lower urinary tract symptoms related to benign prostatic hyperplasia (BPH). Pathologically BPH is characterized by an increased proliferation of stromal and acinar cells, sustained by increased vascularization (neoangiogenesis). Recent studies have also shown that finasteride reduces angiogenesis and prostatic bleeding associated with BPH. Reducing the volume as a final step in reducing neoangiogenesis could thus represent a fundamental advance in limiting intra- and postoperative bleeding in patients undergoing transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Our study included 60 patients undergoing TURP between January 2001 and January 2002. Of the patients, 30 received pretreatment with finasteride while 30 did not undergo any pretreatment (control group). In all the patients we evaluated the degree of peri-surgical bleeding, intended as a reduction in hemoglobin values in the 24 h following surgery. RESULTS AND CONCLUSIONS: In the group of patients pretreated with finasteride, blood loss, evaluated as a reduction in hemoglobin values, was minimal, and none of the patients required blood transfusion. The average hemoglobin loss in the 24 h following surgery was 0.9%. In the control group (average age 67 years), 4 patients (12%) required blood transfusion. The loss of hemoglobin was 2.36%. Finasteride, therefore, seems to play a fundamental role in the pretreatment of TURP patients, since by reducing dihydrotestosterone synthesis, it interacts with endothelial growth factors, thus reducing angiogenesis and preventing bleeding.