The psychophysiological effects of different tempo music on endurance versus high-intensity performances

The use of music during training represents a special paradigm for trainers to stimulate people undertaking different types of exercise. However, the relationship between the tempo of music and perception of effort during different metabolic demands is still unclear. Therefore, the aim of this research was to determine whether high intensity exercise is more sensitive to the beneficial effects of music than endurance exercise. This study assessed 19 active women (age 26.4 \ub1 2.6 years) during endurance (walking for 10' at 6.5 km/h on a treadmill) and high intensity (80% on 1-RM) exercise under four different randomly assigned conditions: no music (NM), with music at 90-110 bpm (LOW), with music at 130-150 bpm (MED), and with music at 170-190 bpm (HIGH). During each trial, heart rate (HR) and the rating of perceived exertion (RPE) were assessed. Repeated analysis of variance measures was used to detect any differences between the four conditions during high intensity and low intensity exercise. RPE showed more substantial changes during the endurance exercises (11%), than during high intensity exercise (6.5%), between HIGH and NM conditions. The metabolic demand during the walking exercise increased between NM and HIGH bpm conditions. This study indicates the benefits of music under stress conditions as well as during endurance and high intensity training. The results demonstrate that the beneficial effects of music are more likely to be seen in endurance exercise. Consequently, music may be considered an important tool to stimulate people engaging in low intensity physical exercise

Analysis of blood-based markers as predicting tools of pathologic tumour response in rectal cancer patients receiving neo-adjuvant chemoradiotherapy

Neo-adjuvant chemo-radio therapy (pCRT) has been accepted as a standard care in the treatment of patients with locally advanced rectal cancer. The multimodality treatment has been established to improve tumour downstaging, pathological complete response, and local disease control. However, the response of individual tumors to the treament is not uniform and ranges from complete response to complete resistance. The discovery of new molecular markers that predict the tumour response is surely of wide interest for personalizing the therapy and reducing time, costs and side effects in the patients with resistant tumours. Many potential biomarkers have been evaluated in order to predict the response to pCRT, and to implement targeted therapeutics. However, single-marker or multi-markers analyses, based on pre-treatment tissue biopsies, often obtained conflicting results demonstrating the heterogeneity of the individual tumour response. Moreover, the prediction of histopathological response to neo-adjuvant treatment is complicated by the interaction and the involvement of the microenvironment in modulating the sensitivity to pCRT. In this study, we developed blood-based methods of biomarker analysis in order to evaluate the histopathological response to treatment in a broad contest that can take into account not only the signalling pathway of tumour cells but also the microenvironment as a part of a unique system. Indeed, the non-invasive nature and the dynamism for which different molecules could be detected according with physiological and pathological states has given us the possibility to monitor the response along the administration of the treatment. In particular, we focused on two different kind of circulating molecules: the cell-free DNA (cfDNA) and the circulating low molecular weight (LMW) peptides. In particular, we investigated the presence, the quantity of cfDNA and its integrity (cfDNA integrity = non apototic cfDNA / total cfDNA) along the chemo-radio treatment. For this purpose we measured the cfDNA concentration and cfDNA integrity in a prospective study of locally advanced rectal cancer patients plasma collected before the pCRT, after two weeks from initiation of the pCRT and after the pCRT. We evaluated the association of these markers with the histological response to the chemo-radio therapy, demonstrating a different kinetic of cfDNA integrity in association with the tumour response. Then we studied the LMW peptidome circulating in plasma, in order to find evidences of possible differences in the peptide profile that could reflect the tumour response. To overcome the technical difficulties in harvesting LMW species, we have employed the mesoporous chip-based technology, developed by the Nanomedicine Department of The Methodist Hospital Research Institute in Houston, Texas. This mesoporous device, in combination with matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS), allows the isolation and the detection of small peptides from the large proteins. We analyzed plasma of rectal cancer patients, with positive or negative response to the therapy, at the same time points as the cfDNA: before, during, after the chemo-radio therapy. Multivariate analyses of the LMW peptide profile at different time points identified combinations of peptides that revealed high discriminating capacity of the different tumour responses. In particular, before the pCRT, a pattern of five ionic species showed a sensitivity and a specificity of 80% and after the pCRT, a pattern of other five specific ionic species showed a sensitivity of 80% and a specificity of 85% to cluster patients on the basis of histopathologic response to pCRT. Moreover the identification of the amino acids sequences of the response-specific ionic species revealed the presence of protein fragments that could be directly or indirectly valuable for further investigation on the resistance mechanisms of the rectal tumour to the neo-adjuvant chemo-radio therapyLa radiochemioterapia neoadiuvante (pCRT) è un protocollo standard accettato per il trattamento di pazienti con cancro rettale localmente avanzato. Il trattamento preoperatorio multimodale è stato introdotto per la riduzione dello stadio del tumore, per l’aumento della risposta completa patologica e per il controllo locale della malattia. Tuttavia la risposta patologica al trattamento non è uniforme e varia da una risposta completa alla resistenza totale. La scoperta di nuovi marcatori molecolari in grado di predire la risposta del tumore è sicuramente di grande interesse al fine di personalizzare la terapia, riducendo così i tempi, i costi e gli effetti collaterali nei pazienti con tumori resistenti. Molti potenziali biomarcatori sono stati valutati con l’obiettivo di prevedere la risposta alla pCRT, e di attuare terapie mirate. Finora molti studi su singolo o multi-marcatore sono stati eseguiti prevalentemente su biopsie di tessuto pre-trattamento. I risultati ottenuti, tuttavia, erano spesso contrastanti dimostrando l'eterogeneità individuale della risposta tumorale al trattamento. Inoltre, la predizione della risposta istopatologica alla pCRT è complicata dall’interazione e dal coinvolgimento del microambiente che può modulare la sensibilità del tumore al trattamento. In questo studio, abbiamo sviluppato metodi di analisi di biomarcatori su sangue, al fine di valutare la risposta del tumore al trattamento in un contesto più ampio, che rende conto non solo dell’ambiente strettamente tumorale, ma che prende in considerazione anche il microambiente come parte di un sistema unico. Infatti, la natura non invasiva del materiale biologico analizzato e il dinamismo per cui molecole differenti possono essere rilevate secondo lo stato fisiologico e patologico dell’organismo, ci hanno permesso di monitorare la risposta lungo il tempo di somministrazione del trattamento. In particolare, ci siamo concentrati su due diversi tipi di molecole circolanti: il DNA libero da cellule (cfDNA) e i peptidi a basso peso molecolare (Low Molecular Weight, LMW). In particolare, abbiamo studiato la presenza, la quantità e l’integrità del cfDNA durante il trattamento radio-chemioterapico. A questo scopo abbiamo misurato la concentrazione e l'integrità del cfDNA (cfDNA integrity=cfDNA apoptotico/cfDNA totale) in uno studio prospettico di plasma di pazienti con carcinoma rettale localmente avanzato, raccolto prima della pCRT, dopo due settimane dall'inizio del trattamento e dopo la pCRT. Abbiamo valutato l'associazione di questi marcatori con la risposta istologica alla chemio-radio terapia, dimostrando la presenza di diversa cinetica nell’integrità del cfDNA, in associazione con la risposta tumorale. Nel plasma, abbiamo quindi studiato il peptidoma circolante a basso peso molecolare, al fine di trovare potenziali differenze nel profilo peptidico che potessero riflettere la risposta tumorale. Per superare le difficoltà tecniche nella rilevazione dei peptidi circolanti a basso peso molecolare, abbiamo utilizzato una strategia basata sull’esclusione dimensionale di un chip di silice mesoporosa (MSC), sviluppato dal Dipartimento Nanomedicina del The Methodist Hospital Research Institute di Houston, Texas. Questo dispositivo mesoporoso, in combinazione con l’utilizzo dello spettrometro di massa MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization-Time Of Flight Mass Spectrometry), consente l'efficiente rimozione di grandi proteine e l'isolamento del peptidoma circolante da campioni di fluidi corporei. Abbiamo analizzato il plasma di pazienti con cancro rettale, prelevato in diversi tempi (prima, durante, dopo la chemio-radio terapia) e stratificati secondo la risposta positiva o negativa alla pCRT. L'analisi multivariata del profilo peptidico nei diversi tempi di analisi ha identificato combinazioni di peptidi che evidenziavano un’elevata capacità discriminante della risposta tumorale. In particolare, il modello di regressione logistica ha evidenziato, prima della pCRT, una combinazione di cinque specie ioniche capace di identificare i pazienti che non rispondono al trattamento, con una sensibilità e una specificità del 80%; mentre la stessa analisi con i campioni raccolti dopo la pCRT, ha identificato un'altra combinazione di cinque specie ioniche che evidenziano una sensibilità del 80% e una specificità del 85%. Inoltre, l'identificazione delle sequenze amminoacidiche di alcune tra le specie ioniche discriminanti la risposta alla pCRT, hanno rivelato la presenza di frammenti proteici che possono essere direttamente o indirettamente utili per ulteriori indagini sui meccanismi di resistenza del tumore rettale alla radio-chemio terapia neo-adiuvant

Clinical correlation between retinal sensitivity and foveal thickness in retinitis pigmentosa patients

PURPOSE: To investigate the relationship between retinal structure and retinal sensitivity comparing data obtained using spectral-domain optical coherence tomography (SD-OCT) and microperimetry in retinitis pigmentosa (RP) and healthy patients. METHODS: A total of 49 patients (98 eyes) with RP were divided into 4 groups according to the OCT findings: group A, patients with no macular changes; group B, patients with cystoid macular edema (CME); group C, patients with vitreomacular traction (VMT); group D, patients with retinal thinning. As a control group, we enrolled 27 healthy subjects. All subjects underwent a complete ophthalmologic examination, including SD-OCT and microperimetry. For the statistical analysis, Pearson correlation test and linear regression analysis were used. A p value <0.05 was considered statistically significant. RESULTS: We did not find any significant difference in best-corrected visual acuity (BCVA), foveal thickness, or retinal sensitivity between group A and the healthy subjects (p>0.05). In group B, linear regression of logMAR versus foveal thickness and retinal sensitivity versus foveal thickness gave r values of 0.931 and 0.786, respectively. In group C, r values were 0.786 and 0.842, respectively, while in group D they were 0.816 and 0.795. CONCLUSIONS: This article shows the first application of the new microperimeter MP3 in patients with RP, which has proven to be very sensitive in detecting functional abnormalities in all the patients. Future studies should investigate the relationships among photoreceptor cell loss, retinal sensitivity, and fixation in patients with RP

The Wnt/\u3b2-catenin pathway in human fibrotic-like diseases and its eligibility as a therapeutic target

The canonical Wnt signaling pathway is involved in a variety of biological processes like cell proliferation, cell polarity, and cell fate determination. This pathway has been extensively investigated as its deregulation is linked to different diseases, including various types of cancer, skeletal defects, birth defect disorders (including neural tube defects), metabolic diseases, neurodegenerative disorders and several fibrotic diseases like desmoid tumors. In the "on state", beta-catenin, the key effector of Wnt signaling, enters the nucleus where it binds to the members of the TCF-LEF family of transcription factors and exerts its effect on gene transcription. Disease development can be caused by direct or indirect alterations of the Wnt/\u3b2-catenin signaling. In the first case germline or somatic mutations of the Wnt components are associated to several diseases such as the familial adenomatous polyposis (FAP) - caused by germline mutations of the tumor suppressor adenomatous polyposis coli gene (APC) - and the desmoid-like fibromatosis, a sporadic tumor associated with somatic mutations of the \u3b2-catenin gene (CTNNB1). In the second case, epigenetic modifications and microenvironmental factors have been demonstrated to play a key role in Wnt pathway activation. The natural autocrine Wnt signaling acts through agonists and antagonists competing for the Wnt receptors. Anomalies in this regulation, whichever is their etiology, are an important part in the pathogenesis of Wnt pathway linked diseases. An example is promoter hypermethylation of Wnt antagonists, such as SFRPs, that causes gene silencing preventing their function and consequently leading to the activation of the Wnt pathway. Microenvironmental factors, such as the extracellular matrix, growth factors and inflammatory mediators, represent another type of indirect mechanism that influence Wnt pathway activation. A favorable microenvironment can lead to aberrant fibroblasts activation and accumulation of ECM proteins with subsequent tissue fibrosis that can evolve in fibrotic disease or tumor. Since the development and progression of several diseases is the outcome of the Wnt pathway cross-talk with other signaling pathways and inflammatory factors, it is important to consider not only direct inhibitors of the Wnt signaling pathway but also inhibitors of microenvironmental factors as promising therapeutic approaches for several tumors of fibrotic origin

Long term results of no-alcohol laser epithelial keratomileusis and photorefractive keratectomy for myopia

<b>RESULTS:</b> Twenty-one eyes and 22 eyes completed follow-up of 60mo in LASEK and PRK group respectively. Manifest refraction at 60mo follow-up was -0.01 and 0.26 in LASEK and PRK group respectively. In the LASEK group mean UDVA and mean CDVA after 60mo were 20/22 and 20/20 respectively (<i>P</i>&gt;0.01). In the PRK group mean UDVA and mean CDVA at 60mo follow-up were 20/20 and 20/20 after 60mo (<i>P</i>&gt;0.01). The efficacy indexes were 0.87 and 0.95, and the safety indexes were 1.25 and 1.4 respectively for LASEK group and PRK group.<b>CONCLUSION:</b>Both standard PRK and no-alcohol LASEK offer safe and effective correction of low-moderate myopia in the long term without any statistically significant difference between the two groups

When is a multidisciplinary surgical approach required in sinonasal tumours with cranial involvement?

The term "sinonasal tumours" includes a large spectrum of diseases, which are characterized by heterogeneous biological behavior and prognosis, and located in a critical anatomic area. Diagnosis and treatment of sinonasal tumours require the contribution of different disciplines. A narrative review was performed to highlight the role of surgeons in contributing to a multidisciplinary approach to sinonasal tumours. Diagnosis and staging of sinonasal tumours is challenging and requires collaboration between surgeons, radiologists, and pathologists. The identification and management of critical extensions (orbital or intracranial encroachment, vascular abutment or encasement) is fundamental for successful treatment. Most cases of advanced sinonasal tumours can undergo surgical intervention by an adequately trained otorhinolaryngological team. The contribution of neurosurgeons and oculoplastic surgeons is required in selected scenarios. In rare circumstances, multidisciplinary reconstructive strategies can be indicated for complex tissue defects. Furthermore, a multidisciplinary approach is pivotal in the management of perioperative complications. While surgery remains the mainstay of treatment, the role of non-surgical adjuvant or even exclusive treatments is constantly expanding

Diagnostic and prognostic role of cell-free DNA testing for colorectal cancer patients

Circulating cell-free DNA (cfDNA) was found in increased amounts in cancer patients and tumor-associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU-based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n=114) in comparison to healthy subjects (n=56) and patients with adenomatous lesions (n=22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type-specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease. 2016 UICC

Growth rate and myofibroblast differentiation of desmoid fibroblast-like cells are modulated by TGF-\u3b2 signaling

Abstract Desmoid-like fibromatosis (DF) is a rare myofibroblastic benign tumor, often associated with local and repeated injuries, spontaneous regression and stabilization of disease progression suggesting the involvement of altered Wnt/-catenin signaling activation and/or aberrant response of the DF cells to external environmental stimuli. The aim of this study was to investigate the response of DF cells to microenvironmental factors such as inflammatory and growth factors or hormones. We observed that the inflammatory cytokine, transforming growth factor- (TGF-1) stimulated cell growth and myofibroblast differentiation of DF cells regardless of the presence of a -catenin mutation. The role of TGF-1 in cell growth and myogenic differentiation of in vitro cultures of primary DF cells and normal fibroblasts was investigated by gene and protein expression analyses. We demonstrated that TGF-1 exerted its role via the canonical Smad pathway with the phosphorylation of Smad3 being crucial for TGF-1 dependent DF cell growth and myofibroblastic differentiation. Furthermore we demonstrated that cell confluence is a critical determinant of TGF-1 inducing the DF myofibroblast differentiation, implying that the intercellular communications have an important role on the DF myofibroblast behavior. We observed the formation of an increased stress-fiber pattern in DF cells with increased projected cell area and stronger cell-cell contacts in presence of TGF-1. These results demonstrated that TGF-1 plays a crucial role in the DF cells growth and, together with cell-cell interactions, in DF myofibroblast conversion; we also highlighted that the cellular sensitivity to this cytokine was an intrinsic feature of the DF cells

Modulation of masseter exteroceptive suppression by non-nociceptive upper limb afferent activation in humans

The effects induced by non-noxious electrical stimulation of upper limb nerves on exteroceptive suppression (ES) of masseter muscle EMG activity were studied in 15 healthy subjects. EMG activity of masseter muscles was recorded bilaterally and great care was taken to minimise the activation of afferents other than the stimulated ones. Masseter ES was elicited by applying a non-noxious electrical stimulus to the skin above the mental nerve (Mt) of one side, during a voluntary contraction of masseter muscles at a prescribed steady clenching level. Onset and offset latencies and duration of early and late components of masseter ES (ES1 and ES2, respectively) were evaluated in control conditions and compared to those obtained when a non-noxious electrical stimulation was delivered separately to Med or Rad or simultaneously to both nerves (Med-Rad) of one side. Upper limb nerve stimulation could be simultaneous or it could precede or follow Mt stimulation by various time intervals. In control conditions, ES1 latency onset and duration values (mean ± SD) were 11.3±2.9 ms and 16.9±2.1 ms, respectively, and ES2 latency onset and duration values were 44.5±6.0 ms and 28.6±11.1 ms, respectively. No significant differences were observed which were related to the side being recorded. Two types of effects, opposite in nature, were shown on masseter ES, depending on the time intervals between Mt and upper limb nerve stimulation. The first effect, which was facilitatory, consisted of a significant increase in ES1 and ES2 duration. A maximal increase in ES1 duration (134–155% compared to control value) occurred when upper limb nerve stimulation preceded that of Mt by 18–30 ms. Maximal ES2 lengthening (115–145%) was observed when upper limb nerve stimulation followed that of the Mt by 10 ms. The second effect was inhibitory and affected only ES2, which appeared completely eliminated when Med stimulation preceded that of Mt by 40–80 ms. By contrast, ES1 was never suppressed at any interstimulus interval. These data might reflect the different action of the central outflow, following the upper limb-induced effects, on the different neuronal circuits mediating ES1 and ES2