Supramolecular spectrally encoded microgels with double strand probes for absolute and direct miRNA fluorescence detection at high sensitivity

We present novel microgels as a particle-based suspension array for direct and absolute microRNA (miRNA) detection. The microgels feature a flexible molecular architecture, antifouling properties, and enhanced sensitivity with a large dynamic range of detection. Specifically, they possess a core-shell molecular architecture with two different fluorescent dyes for multiplex spectral analyses and are endowed with a fluorescent probe for miRNA detection. Encoding and detection fluorescence signals are distinguishable by nonoverlapping emission spectra. Tunable fluorescence probe conjugation and emission confinement on single microgels allow for ultrasensitive miRNA detection. Indeed, the suspension array has high selectivity and sensitivity with absolute quantification, a detection limit of 10(-15) M, a dynamic range from 10(-9) to 10(-15) M, and higher accuracy than qRT-PCR. The antifouling properties of the microgels also permit the direct measurement of miRNAs in serum, without sample pretreatment or target amplification. A multiplexed assay has been tested for a set of miRNAs chosen as cancer biomarkers

Three workouts compared: interval training, intermittent training and steady state training for the improvement of VO2max and BMI

An optimal soccer training, among many objectives, should allow both the improvement of VO2max, or the maximum oxygen supply, and of the anthropometric data. The purpose of the study was to examine the effects of intermittent training, interval training and steady state training methodologies on VO2max and BMI of the players. The sample was made up of 30 young amateur players (age, Mean ± standard deviation [SD] = 16 ± 0.74 years old) randomly divided into three 3 groups of 10. Each group performed a different resistance training methodology for 3 months: group 1 performed intermittent training, group 2 interval training and group 3 steady state training. The parameters taken into consideration were BMI and VO2max, obtained from Gacon test. Paired Sample T Test was performed to check the difference between pre and post 12 training weeks of each group regarding VO2max and BMI. A 3x2 mixed ANOVA was used to test for differences in training programs induced changes in maximal strength and functional capacity variables. The independent variables included one between-subjects factor (training intervention) with three levels (IT, HIIT, and SST), and one within-subject factor (time) with two levels (pre- and post-intervention). A significant difference (p0.05) between pre and post all of the three training protocols on VO2max was found, but no significant interaction (p>0.05) between group and time. BMI had no significant improvement (p>0.05). Intermittent, interval and endurance training all were equally effective improving VO2max, but not BMI

Medidas clínicas estáticas do retropé e joelho não estão associadas à síndrome da dor patelofemoral

O objetivo deste estudo foi investigar se existe associação entre a síndrome da dor patelofemoral e as medidas clínicas estáticas: os ângulos do retropé e Q. Foi realizado um estudo observacional, transversal, caso-controle, no qual foram avaliados 77 adultos (ambos os sexos), 30 participantes com síndrome da dor patelofemoral e 47 controles. Foram medidos os ângulos do retropé e Q, por meio da fotogrametria. Testes t para amostras independentes foram usados para comparações dos resultados das variáveis contínuas entre os grupos. Os resultados das variáveis contínuas foram transformados em classificações clínicas categóricas, para verificar a associação estatística com a disfunção, e o teste do χ2 para respostas múltiplas também foi utilizado. Não houve diferença entre os grupos para o ângulo do retropé [média da diferença: 0,2º (IC95% -1,4-1,8)] e ângulo Q [média da diferença: -0,3º (IC95%-3,0-2,4). Não houve associação entre o ângulo do retropé [Odds Ratio: 1,29 (IC95% 0,51-3,25)], assim como entre o ângulo Q [Odds Ratio: 0.77 (IC95% 0,31-1,93)] e a ocorrência da síndrome da dor patelofemoral. Apesar de serem teoricamente justificadas e amplamente utilizadas na prática clínica fisioterapêutica, não pode-se afirmar que as medidas dos ângulos do retropé e Q, quando mensuradas em posição ortostática, estão associadas com a ocorrência da síndrome da dor patelofemoral. Essas medidas podem ter aplicabilidade limitada na triagem desta disfunção.The aim of the present study was to investigate the association between the patellofemoral pain syndrome and the clinical static measurements: the rearfoot and the Q angles. The design was a cross-sectional, observational, case-control study. We evaluated 77 adults (both genders), 30 participants with patellofemoral pain syndrome, and 47 controls. We measured the rearfoot and Q angles by photogrammetry. Independent t-tests were used to compare outcome continuous measures between groups. Outcome continuous data were also transformed into categorical clinical classifications, in order to verify their statistical association with the dysfunction, and χ2 tests for multiple responses were used. There were no differences between groups for rearfoot angle [mean differences: 0.2º (95%CI -1.4-1.8)] and Q angle [mean differences: -0.3º (95%CI -3.0-2.4). No associations were found between increased rearfoot valgus [Odds Ratio: 1.29 (95%CI 0.51-3.25)], as well as increased Q angle [Odds Ratio: 0.77 (95%CI 0.31-1.93)] and the patellofemoral pain syndrome occurrence. Although widely used in clinical practice and theoretically thought, it cannot be affirmed that increased rearfoot valgus and increased Q angle, when statically measured in relaxed stance, are associated with patellofemoral pain syndrome (PFPS). These measures may have limited applicability in screening of the PFPS development

The immune cell landscape of metastatic uveal melanoma correlates with overall survival

Uveal melanoma (UM) represents the most common primary intra-ocular malignancy in adults. Up to 50% of the patients develop distant metastases within 10\u2009years from diagnosis, with the liver as the most common site. Upon metastatization, life expectancy strongly reduces and immune checkpoint inhibitors that prove effective in cutaneous melanoma do not modify clinical outcome. To date, few studies have focused on deciphering the immunomodulatory features of metastatic UM microenvironment, and there are no prognostic models for clinical use. This highlights the urgent need to understand the delicate interplay between tumor and immune cells acting at the site of metastasis

How to Process Sputum Samples and Extract Bacterial DNA for Microbiota Analysis

Different steps and conditions for DNA extraction for microbiota analysis in sputum have been reported in the literature. We aimed at testing both dithiothreitol (DTT) and enzymatic treatments of sputum samples and identifying the most suitable DNA extraction technique for the microbiota analysis of sputum. Sputum treatments with and without DTT were compared in terms of their median levels and the coefficient of variation between replicates of both DNA extraction yield and real-time PCR for the 16S rRNA gene. Treatments with and without lysozyme and lysostaphin were compared in terms of their median levels of real-time PCR for S. aureus. Two enzyme-based and three beads-based techniques for DNA extraction were compared in terms of their DNA extraction yield, real-time PCR for the 16S rRNA gene and microbiota analysis. DTT treatment decreased the coefficient of variation between replicates of both DNA extraction yield and real-time PCR. Lysostaphin (either 0.18 or 0.36 mg/mL) and lysozyme treatments increased S. aureus detection. One enzyme-based kit offered the highest DNA yield and 16S rRNA gene real-time PCR with no significant differences in terms of alpha-diversity indexes. A condition using both DTT and lysostaphin/lysozyme treatments along with an enzymatic kit seems to be preferred for the microbiota analysis of sputum samples

Recent progress with hot carrier solar cells

Hot carrier solar cells offer one of the most promising options for high performance “third generation” photovoltaic devices. For successful operation, these need to be thin, strongly absorbing, radioactively efficient devices in a simple 2-terminal configuration. Nonetheless, they offer potential performance close to the maximum possible for solar conversion, equivalent to a multi-cell stack of six or more tandem cells possibly without some of the limitations, such as spectral sensitivity. However, hot carrier cells offer some quite fundamental challenges in implementation that our team is addressing in an internationally collaborative effort

Rationale and protocol of a double-blind, randomized, placebo-controlled trial to test the efficacy, safety, and tolerability of dimethyl fumarate in Friedreich Ataxia (DMF-FA-201)

IntroductionFriedreich Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder that causes gait and limb ataxia, dysarthria, and impaired vibratory sense, with cardiomyopathy being the predominant cause of death. There is no approved therapy, which results in the use of symptomatic treatments and the chronic support of physiotherapy. Dimethyl fumarate (DMF) is a fumaric acid ester used for the treatment of psoriasis and Multiple Sclerosis (MS). It induces Nrf2 in vitro and in vivo, and it increases frataxin in FRDA patient lymphoblasts, in mouse models, and in MS treated patients.MethodsThe aim of our study is to investigate if DMF can increase the expression of the FXN gene and frataxin protein and ameliorate in-vivo detectable measures of mitochondrial dysfunction in FRDA. The study is composed of a screening visit and two sequential 12-week phases: a core phase and an extension phase. During the first phase (core), patients will be randomly assigned to either the DMF or a placebo group in a 1:1 ratio. During the first week, patients will receive a total daily dose of 240 mg of DMF or placebo; from the second week of treatment, the dose will be increased to two 120 mg tablets BID for a total daily dose of 480 mg. During the second phase (extension), all patients will be treated with DMF. EudraCT number 2021-006274-23.EndpointsThe primary endpoint will be a change in FXN gene expression level after 12 weeks of treatment. Secondary endpoints will be frataxin protein level, cardiopulmonary exercise test outputs, echocardiographic measures, Nrf2 pathway and mitochondrial biogenesis gene expression, safety, clinical scales, and quality of life scales.ConclusionsThis is the first study aimed at exploring the ability of DMF, an already available treatment for MS and psoriasis, to correct the biological deficits of FRDA and potentially improve mitochondrial respiration in-vivo

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

Rationale: Up to one-third of patients hospitalized with pneumococcal pneumonia experience major adverse cardiac events (MACE) during or after pneumonia. In mice, Streptococcus pneumoniae caninvade themyocardium, induce cardiomyocyte death, and disrupt cardiac function following bacteremia, but it is unknown whether the same occurs in humans with severe pneumonia. Objectives: We sought to determine whether S. pneumoniae can (1) translocate the heart, (2) induce cardiomyocyte death, (3) causeMACE, and (4) induce cardiac scar formation after antibiotic treatment during severe pneumonia using a nonhuman primate (NHP) model. Methods: We examined cardiac tissue from six adult NHPs with severe pneumococcal pneumonia and three uninfected control animals. Three animals were rescued with antibiotics (convalescent animals). Electrocardiographic, echocardiographic, and serum biomarkers of cardiac damage were measured (troponin T, N-terminal pro-brain natriuretic peptide, and heart-type fatty acid binding protein). Histological examination included hematoxylin and eosin staining, immunofluorescence, immunohistochemistry, picrosirius red staining, and transmission electron microscopy. Immunoblots were used to assess the underlying mechanisms. Measurements and Main Results: Nonspecific ischemic alterations were detected by electrocardiography and echocardiography. Serum levels of troponin T and heart-type fatty acid binding protein were increased (P,0.05) after pneumococcal infection in both acutely ill and convalescent NHPs. S. pneumoniae was detected in the myocardium of all NHPs with acute severe pneumonia. Necroptosis and apoptosis were detected in the myocardium of both acutely ill and convalescent NHPs. Evidence of cardiac scar formation was observed only in convalescent animals by transmission electron microscopy and picrosirius red staining. Conclusions: S. pneumoniae invades the myocardium and induces cardiac injury with necroptosis and apoptosis, followed by cardiac scarring after antibiotic therapy, in anNHP model of severe pneumonia

Transplantation of human fetal biliary tree stem/progenitor cells into two patients with advanced liver cirrhosis.

Efforts to identify cell sources and approaches for cell therapy of liver diseases are ongoing, taking into consideration the limits recognized for adult liver tissue and for other forms of stem cells. In the present study, we described the first procedure of via hepatic artery transplantation of human fetal biliary tree stem cells in patients with advanced cirrhosis.MethodsThe cells were immune-sorted from human fetal biliary tree by protocols in accordance with current good manufacturing practice (cGMP) and extensively characterized. Two patients with advanced cirrhosis (Child-Pugh C) have been submitted to the procedure and observed through a 12 months follow-up.ResultsThe resulting procedure was found absolutely safe. Immuno-suppressants were not required, and the patients did not display any adverse effects correlated with cell transplantation or suggestive of immunological complications. From a clinical point of view, both patients showed biochemical and clinical improvement during the 6 month follow-up (Table1), and the second patient maintained a stable improvement for 12 months.ConclusionThis report represents proof of the concept that the human fetal biliary tree stem cells are a suitable and large source for cell therapy of liver cirrhosis. The isolation procedure can be carried out under cGMP conditions and, finally, the infusion procedure is easy and safe for the patients. This represents the basis for forthcoming controlled clinical trials