Circulating miR-26b-5p and miR-451a as diagnostic biomarkers in medullary thyroid carcinoma patients.

PURPOSE/METHODS: The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis is still challenging. The aim of this study was to identify non-invasive circulating biomarkers in MTC. To achieve this goal, paired MTC tissue and plasma extracellular vesicle samples were collected from multiple centres and microRNA (miRNA) expression levels were evaluated. RESULTS: The samples from a discovery cohort of 23 MTC patients were analysed using miRNA arrays. Lasso logistic regression analysis resulted in the identification of a set of circulating miRNAs as diagnostic biomarkers. Among them, miR-26b-5p and miR-451a, were highly expressed and their expression decreased during follow-up in disease-free patients in the discovery cohort. Circulating miR-26b-5p and miR-451a were validated using droplet digital PCR in a second independent cohort of 12 MTC patients. CONCLUSION: This study allowed the identification and validation of a signature of two circulating miRNAs, miR-26b-5p and miR-451a, in two independent cohorts reporting a significant diagnostic performance for MTC. The results of this study offer advancements in molecular diagnosis of MTC proposing a novel non-invasive tool to use in precision medicine.

Correction to: Flow-mediated dilation and heart failure: a review with implications to physical rehabilitation.

The scholarship support information in Acknowledgement was missing.

Bioactivity of volatile organic compounds by Aureobasidium species against gray mold of tomato and table grape.

Aureobasidium strains isolated from diverse unconventional environments belonging to the species A. pullulans, A. melanogenum, and A. subglaciale were evaluated for Volatile Organic Compounds (VOCs) production as a part of their modes of action against Botrytis cinerea of tomato and table grape. By in vitro assay, VOCs generated by the antagonists belonging to the species A. subglaciale showed the highest inhibition percentage of the pathogen mycelial growth (65.4%). In vivo tests were conducted with tomatoes and grapes artificially inoculated with B. cinerea conidial suspension, and exposed to VOCs emitted by the most efficient antagonists of each species (AP1, AM10, AS14) showing that VOCs of AP1 (A. pullulans) reduced the incidence by 67%, partially confirmed by the in vitro results. Conversely, on table grape, VOCs produced by all the strains did not control the fungal incidence but were only reducing the infection severity (< 44.4% by A. pullulans; < 30.5% by A. melanogenum, and A. subglaciale). Solid-phase microextraction (SPME) and subsequent gas chromatography coupled to mass spectrometry identified ethanol, 3-methyl-1-butanol, 2-methyl-1-propanol as the most produced VOCs. However, there were differences in the amounts of produced VOCs as well as in their repertoire. The EC50 values of VOCs for reduction of mycelial growth of B. cinerea uncovered 3-methyl-1-butanol as the most effective compound. The study demonstrated that the production and the efficacy of VOCs by Aureobasidium could be directly related to the specific species and pathosystem and uncovers new possibilities for searching more efficient VOCs producing strains in unconventional habitats other than plants.

Flow-mediated dilation and heart failure: a review with implications to physical rehabilitation.

Endothelial dysfunction plays as an important role on mismatch responses that occur during exercise in patients with congestive heart failure (CHF). However, cardiac rehabilitation, a core component of management of CHF patients, can improve endothelial function, contributing to reduce the morbidity and mortality of these patients. The primary aims of this review were to describe the importance of flow-mediated dilatation (FMD) as a non-invasive validation tool to assess endothelial dysfunction and to highlight the relevance of scientific studies that evaluated the effects of exercise interventions on peripheral vascular endothelial function as measured by FMD in patients with CHF with both preserved and reduced ejection fraction.

Active multilayered capsules for in vivo bone formation.

Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled.

Sudden Vegetation Dieback in Atlantic and Gulf Coast Salt Marshes.

Salt marshes rank as the most productive ecosystems on the planet. Biomass production can be greater than 3 kg dry matter/m2/year, which is 40% more biomass than tropical rainforests produce. Salt marshes provide multiple benefits to mankind. For example, coastal communities receive protection from storm surges and wave erosion. Salt marshes absorb excess nitrogen and phosphorus from sewage and fertilizer run-off into rivers, which, in turn, prevents algal blooms and hypoxia in coastal waters. In addition, these unique ecosystems provide habitat and shelter for many hundreds of species of shellfish, finfish, migratory and sedentary birds, and other marine animals. Despite the richness in animal species, the intertidal marshes of the salt marsh ecosystem are dominated by only a few plant species. Of these, the most prevalent plant species in a marsh are the tall and short forms of smooth cordgrass (Spartina alterniflora). The first recorded account of a dieback in a U.S. salt marsh was in the early 1990s in the Florida panhandle where patches of Sp. alterniflora as large as 1 ha died. This article explores possible causes of Sudden Vegetation Dieback.

Mild-to-moderate COVID-19 impact on the cardiorespiratory fitness in young and middle-aged populations.

The goal of the present study was to compare pulmonary function test (PFT) and cardiopulmonary exercise test (CPET) performance in COVID-19 survivors with a control group (CG). This was a cross-sectional study. Patients diagnosed with COVID-19, without severe signs and symptoms, were evaluated one month after the infection. Healthy volunteers matched for sex and age constituted the control group. All volunteers underwent the following assessments: i) clinical evaluation, ii) PTF; and iii) CPET on a cycle ergometer. Metabolic variables were measured by the CareFusion Oxycon Mobile device. In addition, heart rate responses, peak systolic and diastolic blood pressure, and perceived exertion were recorded. Twenty-nine patients with COVID-19 and 18 healthy control subjects were evaluated. Surviving patients of COVID-19 had a mean age of 40 years and had higher body mass index and persistent symptoms compared to the CG (P<0.05), but patients with COVID-19 had more comorbidities, number of medications, and greater impairment of lung function (P<0.05). Regarding CPET, patients surviving COVID-19 had reduced peak workload, oxygen uptake (V̇O2), carbon dioxide output (V̇CO2), circulatory power (CP), and end-tidal pressure for carbon dioxide (PETCO2) (P<0.05). Additionally, survivors had depressed chronotropic and ventilatory responses, low peak oxygen saturation, and greater muscle fatigue (P<0.05) compared to CG. Despite not showing signs and symptoms of severe disease during infection, adult survivors had losses of lung function and cardiorespiratory capacity one month after recovery from COVID-19. In addition, cardiovascular, ventilatory, and lower limb fatigue responses were the main exercise limitations.

Effect of continuous positive airway pressure associated to exercise on the breathing pattern and heart rate variability of patients undergoing coronary artery bypass grafting surgery: a randomized controlled trial.

Continuous positive airway pressure (CPAP) has been used to improve gas exchange and diaphragmatic function, among others benefits. Moreover, it can be used to increase exercise tolerance and positively influence ventilatory function and breathing pattern (BP) during exercise. However, there is no information about the long-term effects of CPAP, as an adjunct to an inpatient cardiac rehabilitation (CR) program, on BP and heart rate variability (HRV) of patients after coronary artery bypass grafting surgery (CABG). Twenty patients were allocated to receive, after randomization, standard inpatient CR without CPAP (control group - CG) or CR with CPAP between 10 to 12 cmH2O (CPAP group - CPG) associated with the exercises. Participants were assessed preoperatively and on the discharge day, in the sitting rest position. Outcome measurements included BP variables, collected by respiratory inductive plethysmography, and HRV, collected by polar precision performance. The CPG presented lower values of percent rib cage inspiratory and expiratory contributions to tidal volume (%RCi and %RCe) at discharge time, compared to CG. No statistical differences between groups were observed for HRV variables and both groups presented lower values of these indices, compared to preoperative ones. In this context, the patients who received CPAP throughout the whole rehabilitation program were discharged with a better BP, which could indicate more synchronized breathing. CPAP did not influence cardiac autonomic modulation in the long term.

Reliability and validity of six-minute step test in patients with heart failure.

Exercise intolerance is the hallmark consequence of advanced chronic heart failure (HF). The six-minute step test (6MST) has been considered an option for the six-minute walk test because it is safe, inexpensive, and can be applied in small places. However, its reliability and concurrent validity has still not been investigated in participants with HF with reduced ejection fraction (HFrEF). Clinically stable HFrEF participants were included. Reliability and error measurement were calculated by comparing the first with the second 6MST result. Forty-eight hours after participants underwent the 6MST, they were invited to perform a cardiopulmonary exercise test (CPET) on a cycle ergometer. Concurrent validity was assessed by correlation between number of steps and peak oxygen uptake (V̇O2 peak) at CPET. Twenty-seven participants with HFrEF (60±8 years old and left ventricle ejection fraction of 41±6%) undertook a mean of 94±30 steps in the 6MST. Intra-rater reliability was excellent for 6MST (ICC=0.9), with mean error of 4.85 steps and superior and inferior limits of agreement of 30.6 and -20.9 steps, respectively. In addition, strong correlations between number of steps and CPET workload (r=0.76, P<0.01) and peak V̇O2 (r=0.71, P<0.01) were observed. From simple linear regression the following predictive equations were obtained with 6MST results: V̇O2 peak (mL/min) = 350.22 + (7.333 × number of steps), with R2=0.51, and peak workload (W) = 4.044 + (0.772 × number of steps), with R2=0.58. The 6MST was a reliable and valid tool to assess functional capacity in HFrEF participants and may moderately predict peak workload and oxygen uptake of a CPET.

Teleportation-induced correlated quantum channels.

Quantum teleportation of an n-qubit state performed using as an entangled resource a general bipartite state of 2n qubits instead of n Bell states is equivalent to a correlated Pauli channel. This yields a new characterization of such channels in terms of many-body correlation functions of the teleporting media. It provides a relatively simple method for determining whether a correlated quantum channel is able to reliably convey quantum messages by studying the entanglement properties of the teleportation mediating system. Our model is then generalized to the continuous-variable case.

Inhibitory activity of cranberry extract on the bacterial adhesiveness in the urine of women: an ex-vivo study.

Strains of uropathogenic E. coli are responsible for approximately 90% of community-acquired, uncomplicated cystitis, and fimbriae represent the adhesive factors enabling E. coli to be anchored to uroepithelial cells in the first step of the infectious process. Recently, a few studies have shown that a correlation between the consumption of cranberry (Vaccinium macrocarpon) and prevention of UTI is related to the ability of proanthocyanidins to reduce the bacterial adhesion to uroepithelial cells. In this study we evaluate the inhibitory activity of urine of healthy women treated with tablets containing cranberry extract on the adhesiveness of E. coli to uroepithelial human cells. Two groups of 12 female volunteers each, aged between 18 and 65 years, were enrolled, one group with negative history and one group with positive history of recurrent cystitis. Subjects were treated with the active product or placebo in a random, cross-over, double-blinded sequence for one week in each of the two treatment sequences. Urine samples were collected at the beginning and the end of each study period. Tests of bacterial adhesiveness were performed with two strains of E. coli (ATCC 25922 and ATCC 35218) on HT1376 human bladder carcinoma cells. Significant reductions of bacterial adhesiveness were observed in women who received cranberry extract (-50.9%; p less than 0.0001), regardless of their medical history and the treatment period in the cross-over sequence. No changes were observed with placebo (-0.29%; n.s.). This ex-vivo study showed that the assumption of cranberry extract in suitable amounts can have an anti-adhesive activity on uropathogenic E. coli.

Effects of toluidine blue-mediated photodynamic therapy on periopathogens and periodontal biofilm: in vitro evaluation.

Photodynamic therapy (PDT) is a selective modality of killing targeted cells, mostly known for its application in neoplasms. PDT can be considered to be an alternative method for the elimination of periodontal bacteria from the pocket without harms for the resident tissues. Therefore, PDT may replace systemic antibiotics and enhance the effect of mechanical treatments of periodontal defects. This effort focused on the in vitro sensitization of periopathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia ) Toluidine Blue mediated and on the use of a Diode laser emitting source. The objective of this research was to evaluate the bactericidal in vitro effect of laser diodes 830 nm (as the light source) after photosensitization with Toluidine Blue (TBO) on the following periopathogenic bacteria: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and Prevotella intermedia. After evaluating the effect on the single bacterial strain, the ability of Diode Laser to disrupt the structure of biofilms produced by A. actinomycetemcomitans after photosensitization with TBO was also analyzed. The study suggests that the association of TBO and diode laser light 830 nm is effective for the killing of bacteria strains and determines the photoinactivation of Aggregatibacter biofilms. In summary, photodynamic therapy has effectively shown its capabilities and, therefore, it can be considered a valid alternative approach to antimicrobial therapy of periodontitis.

Impact of chronic obstructive pulmonary disease on linear and nonlinear dynamics of heart rate variability in patients with heart failure.

The objective of this study was to investigate the impact of chronic obstructive pulmonary disease (COPD)-heart failure (HF) coexistence on linear and nonlinear dynamics of heart rate variability (HRV). Forty-one patients (14 with COPD-HF and 27 HF) were enrolled and underwent pulmonary function and echocardiography evaluation to confirm the clinical diagnosis. Heart rate (HR) and R-R intervals (iRR) were collected during active postural maneuver (APM) [supine (10 min) to orthostasis (10 min)], respiratory sinus arrhythmia maneuver (RSA-M) (4 min), and analysis of frequency domain, time domain, and nonlinear HRV. We found expected autonomic response during orthostatic changes with reduction of mean iRR, root mean square of successive differences between heart beats (RMSSD), RR tri index, and high-frequency [HF (nu)] and an increased mean HR, low-frequency [LF (nu)], and LF/HF (nu) compared with supine only in HF patients (P<0.05). Patients with COPD-HF coexistence did not respond to postural change. In addition, in the orthostatic position, higher HF nu and lower LF nu and LF/HF (nu) were observed in COPD-HF compared with HF patients. HF patients showed an opposite response during RSA-M, with increased sympathetic modulation (LF nu) and reduced parasympathetic modulation (HF nu) (P<0.05) compared with COPD-HF patients. COPD-HF directly influenced cardiac autonomic modulation during active postural change and controlled breathing, demonstrating an autonomic imbalance during sympathetic and parasympathetic maneuvers compared with isolated HF.

Secondary breast angiosarcoma: A multicentre retrospective survey by the national Italian association of Breast Surgeons (ANISC).

BACKGROUND: Breast angiosarcoma is a malignant mesenchymal neoplasm, which accounts for approximately 2% of all soft tissue sarcomas. Secondary breast angiosarcoma (SBA) may be related to chronic lymphedema after a mastectomy with lymph node dissection (Stewart Treves syndrome) and previous radiotherapy for complications from breast radiation treatment. It is a very rare condition; therefore, diagnosis and management are still a challenge. METHODS: The ANISC collected SBA data by means of a survey sent to all Italian breast centres in the ANISC. The clinicopathological characteristics and the management of this disease were analysed. RESULTS: Twenty-four centres participated in this survey in which 112 cases of SBA were analysed. The median age of the women with SBA was 68.9 years and it appeared approximately 90 months after the first irradiation for breast cancer. In 92% of cases, a mastectomy was performed without axillary dissection for those patients having a high grade of SBA (74.2%). The prognosis was worse in the high-grade cases (overall survival-OS: 36 months) as compared with the low-grade cases (OS: 48 months). After a follow-up of 5 years, 50.5% of the patients were still alive. Disease-free survival (DFS) was 35 months, and there were no differences between the groups of patients with either high- or low-grade histology. CONCLUSIONS: Secondary breast angiosarcoma is a very aggressive disease associated with a short survival outcome. The surgical approach still remains an important step in the course of treatment; furthermore, an accurate histological examination is helpful in establishing the prognosis of the patient. A mastectomy is mandatory. A longer OS was observed in patients with low-grade angiosarcoma as compared to high-grade angiosarcoma (C.I. 40-57 vs. 31-41 months).

Cardiorespiratory and metabolic determinants during moderate and high resistance exercise intensities until exhaustion using dynamic leg press: comparison with critical load.

The objective of this study was to assess cardiovascular, respiratory, and metabolic responses during a commonly used dynamic leg press resistance exercise until exhaustion (TEx) at different intensities and compare with critical load (CL). This was a prospective, cross-sectional, controlled, and crossover study. Twelve healthy young men (23±2.5 years old) participated. The subjects carried out three bouts of resistance exercise in different percentages of 1 repetition maximum (60, 75, and 90% 1RM) until TEx. CL was obtained by means of hyperbolic model and linearization of the load-duration function. During all bout intensities, oxygen uptake (VO2), carbon dioxide production (VCO2), ventilation (VE), and respiratory exchange ratio (RER) were obtained. Variations (peak-rest=Δ) were corrected by TEx. In addition, systolic and diastolic blood pressure (SBP and DBP), blood lactate concentration [La-] and Borg scores were obtained at the peak and corrected to TEx. CL induced greater TEx as well as number of repetitions when compared to all intensities (P<0.001). During CL, Borg/TEx, ΔSBP/TEx, ΔDBP/TEx, and [La-] were significantly lower compared with 90% load (P<0.0001). In addition, VO2, VCO2, VE, and RER were higher during CL when compared to 90 or 75%. TEx was significantly correlated with VO2 on CL (r=0.73, P<0.05). These findings support the theory that CL constitutes the intensity that can be maintained for a very long time, provoking greater metabolic and ventilatory demand and lower cardiovascular and fatigue symptoms during resistance exercise.

Ultra-short-term heart rate variability during resistance exercise in the elderly.

Despite the appeal of ultra-short-term heart rate variability (HRV) methods of analysis applied in the clinical and research settings, the number of studies that have investigated HRV by analyzing R-R interval (RRi) recordings shorter than 5 min is still limited. Moreover, ultra-short-term HRV analysis has not been extensively validated during exercise and, currently, no indications exist for its applicability during resistance exercise. The aim of the present study was to compare ultra-short-term HRV analysis with standard short-term HRV analysis during low-intensity, dynamic, lower limb resistance exercise in healthy elderly subjects. Heart rate (HR) and RRi signals were collected from 9 healthy elderly men during discontinuous incremental resistance exercise consisting of 4-min intervals at low intensities (10, 20, 30, and 35% of 1-repetition maximum). The original RRi signals were segmented into 1-, 2-, and 3-min sections. HRV was analyzed in the time domain (root mean square of the of differences between adjacent RRi, divided by the number of RRi, minus one [RMSSD]), RRi mean value and standard deviation [SDNN] (percentage of differences between adjacent NN intervals that are greater than 50 ms [pNN50]), and by non-linear analysis (short-term RRi standard deviation [SD1] and long-term RRi standard deviation [SD2]). No significant difference was found at any exercise intensity between the results of ultra-short-term HRV analysis and the results of standard short-term HRV analysis. Furthermore, we observed excellent (0.70 to 0.89) to near-perfect (0.90 to 1.00) concordance between linear and non-linear parameters calculated over 1- and 2-min signal sections and parameters calculated over 3-min signal sections. Ultra-short-term HRV analysis appears to be a reliable surrogate of standard short-term HRV analysis during resistance exercise in healthy elderly subjects.

Crossover from lattice to plasmonic polarons of a spin-polarised electron gas in ferromagnetic EuO.

Strong many-body interactions in solids yield a host of fascinating and potentially useful physical properties. Here, from angle-resolved photoemission experiments and ab initio many-body calculations, we demonstrate how a strong coupling of conduction electrons with collective plasmon excitations of their own Fermi sea leads to the formation of plasmonic polarons in the doped ferromagnetic semiconductor EuO. We observe how these exhibit a significant tunability with charge carrier doping, leading to a polaronic liquid that is qualitatively distinct from its more conventional lattice-dominated analogue. Our study thus suggests powerful opportunities for tailoring quantum many-body interactions in solids via dilute charge carrier doping.

Neoadjuvant systemic treatment for breast cancer in Italy: The Italian Society of Surgical Oncology (SICO) Breast Oncoteam survey.

The Italian Society of Surgical Oncology (SICO) Breast Oncoteam developed a survey to explore the state of the art of neoadjuvant treatment for breast cancer in Italy, specifically focusing on cases treated during the two-year period 2014-2015. A questionnaire was sent to Italian Breast Units with a minimum of 150 new breast cancer cases treated/year according to the Senonetwork directory and to the SICO Breast Oncoteam Breast Unit network. A total of 23/107 Breast Units submitted the survey, reporting a total amount of 20156 cases of breast carcinoma (17241 invasive, 2915 in situ) treated in the biennium, corresponding approximately to 20% of newly diagnosed breast cancers in Italy. In the United States, medical treatment before surgery for breast cancer is indicated in about 22.7% of newly diagnosed cases according to the National Cancer Database, while a German study reported approximately 20% of cases treated with neoadjuvant therapy. In our survey, a total of 1673/17241 cases (9.7%) were treated with neoadjuvant therapy, ranging from 2.9% to 23.6% according to different centres, showing heterogeneity in neoadjuvant treatment indications, even in multidisciplinary breast units. Better resources should be engaged to achieve a standardised quality indicator for neoadjuvant treatment, and this indicator could be included among the European Society of Breast Cancer Specialists (EUSOMA) quality indicators. In the near future, we plan to develop a second survey to better test improvements in the employment of neoadjuvant therapy after the expiry of the 2016 European Parliament deadline and after the 2017 St. Gallen Conference recommendations.

Analysis of self-organized criticality in the Olami-Feder-Christensen model and in real earthquakes.

We perform an analysis on the dissipative Olami-Feder-Christensen model on a small world topology considering avalanche size differences. We show that when criticality appears, the probability density functions (PDFs) for the avalanche size differences at different times have fat tails with a q-Gaussian shape. This behavior does not depend on the time interval adopted and is found also when considering energy differences between real earthquakes. Such a result can be analytically understood if the sizes (released energies) of the avalanches (earthquakes) have no correlations. Our findings support the hypothesis that a self-organized criticality mechanism with long-range interactions is at the origin of seismic events and indicate that it is not possible to predict the magnitude of the next earthquake knowing those of the previous ones.