Miracle-dz/UniFAR-FTUs huggingface dataset:
Ozone therapy is an effective therapy in chronic fatigue syndrome: result of an Italian study in 65 patients

The terms chronic fatigue syndrome and myalgic encephalomyelitis describe a complex physical illness characterized by debilitating fatigue, post-exertional malaise, pain, cognitive problems, sleep dysfunction and an array of other immune, neurological and autonomic symptoms. At the MEDE Clinic of Sacile, Italy, from February 2016 to December 2017, we have treated 65 patients, with auto hemo transfusion, according to the Scientific Society of Oxygen Ozone Therapy (SIOOT) protocols, twice a week for one month and twice a month as maintenance therapy. In conclusion, at our knowledge this is the largest study of patients with chronic fatigue syndrome treated with ozone therapy. Oxygen ozone therapy is an effective therapy in the treatment of chronic fatigue syndrome. However, more patients are needed and in particular a longer follow up is a necessary. In the meantime, ozone therapy seems a treatment that, also because without any side effect, is possible to be proposed to patients with chronic fatigue syndrome that are not obtaining sufficient results from available therapy.
Implementing the current knowledge of uptake and effects of nanoparticles in an adverse outcome pathway (AOP) framework

Unlike most other environmental pollution issues, safety assessments of nanoparticles (NPs) were meant to be the prime example on how to foresee and tackle predicted environmental concerns. For once, research efforts were ahead of mass production and potential release into environments. NPs' safety research focuses on the central question of whether the unique properties of NPs cause fundamentally different effects as compared to their larger counterparts. This chapter gives an overview of the present understanding of NP toxicity in aquatic organism. Briefly, state-of-the-art techniques to detect NPs in tissues are summarized and the present understanding of cellular and organismal NP uptake routes given. The location of NPs in tissues bears several challenges but is the first step in identifying target organs or cells and, thus, is important in the search for mechanisms of action. The evaluation of our current knowledge of cellular and organismal responses when exposed to NPs, ultimately, allows for the identification of key knowledge gaps and foresees research directions and the need to develop Adverse Outcome Pathways for NPs.
Point-of-Care Ultrasound in the Emergency Department

Point-of-care ultrasound (POCUS) is a useful diagnostic tool and has become an integral part of the care provided in the Emergency Department. It has evolved over the past two decades to include diagnostic and therapeutic skills. POCUS helps emergency physicians improve their diagnostic accuracy and provide better overall patient care. This chapter will summarize 13 core POCUS applications that are considered within the diagnostic armamentarium of all emergency physicians.
The effect of the SHR Y chromosome on voluntary running

This study tested the hypothesis that there is an increase in the amount of voluntary running performed by SHR/y vs.WKY rat strains. The SHR/y rat is a strain having the SHR Y chromosome in a normotensive WKY genetic background by backcrossing 19 generations of male offspring to a WKY female. Two groups of adult rats (WKY and SHR/y) (n=6/group) were established. Each rat was housed individually in cages connected with PVC tubing to a running wheel. Blood glucose and hematocrit of each rat was measured at baseline and every two weeks thereafter. Results of this ongoing study indicate that male SHR/y rats, when given access to a running wheel, voluntarily run significantly (p<0.05) longer distances/day (~80%) on average compared to WKY rats. Additionally, blood glucose and hematocrit were positively correlated with one another (p<0.05) and SHR/y rats had elevated hematocrit compared to WKY (p<.05) for the first two weeks of study. In conclusion, rats with the SHR Y chromosome have a higher voluntary running activity than rats with the WKY Y chromosome, which may be due to increased SNS activity and higher aerobic capacity.
Studies of protein complexes involved in the adenylation cascade of the nitrogen signalling pathway in Escherichia coli.

Adenylyl transferase (ATase), the glnE gene product from Escherichia coli, is a bifunctional enzyme that catalyses the opposing adenylylation and deadenylylation of glutamine synthetase (GS). The overall aim of this thesis was elucidation of the molecular mechanisms of the adenylylation cascade. A new central domain has been identified using ATase truncation constructs in activity assays and solubility trials. This new regulatory domain is flanked by two flexible Qlinkers, Q1 and Q2. Thus the topology of ATase can be represented as N-Q1-R-Q2-C. The N domain was PII-UMP independent in in vitro deadenylylation assays, and had 1000 fold less activity then entire ATase, suggesting PII-UMP binding impacts on the conformation of the deadenylylation active site. Monoclonal antibodies (mAbs) generated in this work against ATase were characterised using ATase mutants and the truncated proteins. Two mAbs, 5A7 (binds residues 502- 548) and 39G11 (binds residues 466-501) both binding in the R domain, blocked the binding of PII, GlnK, PII-UMP and GlnK-UMP to ATase. This is the first report that pinpoints the effector-protein binding sites to within the R domain of ATase. Both PII and ATase bound α-ketoglutarate (α-kg) in direct binding assays. Several lines of evidence suggested that PII contains the high affinity α-kg binding site and ATase the low affinity site. This study demonstrates for the first time that the two small effector-molecules α-kg and glutamine (gln) probably bind in the last 340 residues of ATase (Q2-C domain), possibly near the adenylylation active site. The demonstration that the ATase mutant W694G presented a gln independent phenotype suggests that the bulky side chain of Trp 694 must move out of the adenylylation active site, so that GS can dock and be modified. Surface plasmon resonance (SPR) data suggested the binding of gln within Q2-C is transmitted to the R domain as an allosteric inhibitor of PII-UMP binding, and consequently deadenylylation. A panel of mAbs was also produced against PII and characterised using a series of PII mutants. Two of the PII mAbs 19G4 (binds PII/GlnK) and 24H2 (binds PII) were used further to demonstrate that heterotrimers are formed between PII and GlnK in vivo in nitrogen starved cells. It is well documented that the T-loops of PII and GlnK are probably the principal regions used by these signalling proteins to bind to the various receptor-proteins such as ATase, UTase and NRII. This study suggests PII and GlnK also interact with GS. Using PII mutants carrying specific GlnK residues at positions 43, 52 and 54 in the T-loop this study demonstrated the Asp at position 54 was the critical determinant of PII T-loop binding to GS, whereas the interaction with UTase involved both Asp54 and Thr43.
Recent developments in Phytophthora diseases of trees and natural ecosystems in Europe

Phytophthora diseases of trees is a fast moving field: considerable research progress and further unexpected disease developments have occurred since our last European review of 2001 (see Brasier and Jung, 2003). These developments include accumulating evidence that Phytophthoras are spreading from infested nursery stock into forests; advances in the taxonomy and phylogeny of European forest Phytophthoras; an upsurge in Phytophthora activity on European beech and sycamore; surveys of Phytophthora populations on chestnut and oaks; and elucidation of a possible mechanism of pathogenesis of P. cinnamomi. Developments on the ‘sudden oak death’ front include the spread of P. ramorum onto trees; progress in assessing the potential host range of P. ramorum on European tree species; characterisation of EU and US populations of P. ramorum for phenotypes and isozymes; further elucidation of the P. ramorum breeding system; and the discovery of another new ‘aerial’ invasive, P. kernoviae, in the UK. Here we review these developments and consider some of their implications.
Ultrasonography as a Diagnostic Aid in Evaluating Cystic Lesions, Benign Tumors and Malignancies of Maxillofacial Region: A Clinical Study

To evaluate the accuracy of Ultrasonography as a diagnostic aid in cysts, benign tumors and malignancies of maxillofacial region. This study was conducted to evaluate the accuracy of ultrasonography in the diagnosis of the osseous lesions of the jaws including cysts, benign tumors and malignant tumors. All the findings obtained by ultrasonography were compared and correlated with the clinical diagnosis, radiographic diagnosis and histopathological findings. The study was conducted on 42 patients with osseous maxillofacial swellings. The clinical and radiographic examination was carried out for all the patients who were afterward subjected to ultrasonography with color Doppler followed by histopathology. All the findings obtained were then statistically analyzed. The utility of ultrasonography was evaluated considering histopathology as a gold standard. The diagnostic accuracy of ultrasound was found to be 100% in cystic lesions, 80% in benign tumors, and 85.71% in malignant tumors. Ultrasonography provides an accurate imaging of the head and neck region and does provide information about the nature of the lesion, its extent, and relationship with the surrounding structures. We propose the use of ultrasonography as an adjunctive examination for osseous lesions of the jaws before any invasive treatment.
Large Scale Gene Expression Profiling during Adipogenesis of Murine Bone Marrow Stromal Cells

Obesity is an increasing health problem for many western countries, manifested in a heterogeneous group of associated disorders. Obesity itself is defined as a disorder of energy balance, where energy intake exceeds energy expenditure. Understanding the molecular mechanisms and environmental cues which drive a somatic stem cell to a preadipocyte and further to a mature adipocyte may enable us to fight obesity on a molecular level by designing effective drug treatments to reduce adipose tissue mass with small or no side effects for the patients. The microarray technology is a powerful means to generate a gene expression profile, which allows to simultaneously observe the activity of thousands of genes in one experiment. The objective was to establish a cell culture model system to study the transcriptional mechanisms which are involved in adipogenesis in vitro. A cell line of murine bone marrow stromal (BMS) cells has been proven to be capable of undergoing adipogenesis upon proper induction. A supplementation of growth medium with dexamethasone and indomethacin massively induced adipogenesis. This was evidenced by oil red O staining. BMS cells are known to have somatic stem cell character, being able to differentiate into osteocytes, chondrocytes, adipocytes, haematopoiesis-supporting cells and even non-mesodermal cells. The established cell line was investigated for its in vivo properties via an in vivo transplantation assay. The results show that these cells are able to form bone, adipocytes and a complete haematopoietic microenvironment. Further, the reciprocity of the cells was tested, by means of re-differentiating a mature adipocytic culture into a culture showing an osteogenic phenotype. Finally, microarray assays were performed in order to delineate transcriptional regulatory networks.
MHC-UNRESTRICTED MUC1-SPECIFIC T CELL RECEPTOR FOR CANCER IMMUNOTHERAPY/GENE THERAPY

MUC1 glycoprotein is overexpressed on the surface of a variety of epithelial tumors and has been under investigation as a target for immunotherapy. A number of cytotoxic lymphocyte clones were generated in our laboratory from breast and pancreatic cancer patients that recognized MUC1 on the surface of tumor cells in a TCR-mediated MHC-unrestricted manner. The purpose of this study was to test the feasibility, efficacy and safety of using MHC-unrestricted MUC1-specific T cell receptor (TCR) gene transfer as a tool for cancer immunotherapy. The TCR £ and £] chains were cloned from one MHC-unrestricted MUC1-specific CTL clone (MA). Various configurations of chimeric TCRs were constructed and were expressed on the surface of a variety of cell lines in vitro. The TCR-deficient T cell line, Jurkat JRT3.5, transfected with the TCR £ and £] chains from MA CTL clone fluxed calcium in response to stimulation by a MUC1+ pancreatic human tumor, HPAF. BWZ murine thymoma cells transfected with a single-chain TCR (scTCR) consisting of the TCR extracellular domain and the CD3 ƒe signaling domain) were triggered to secrete IL-2 in response to stimulation with different MUC1+ tumor cells. The tumor recognition and rejection functions of this scTCR were tested in vivo when SCID mice were reconstituted with bone marrow (BM) cells transduced with scTCR-MFG retroviral supernatant and challenged with HPAF tumor cells. Tumor growth in mice reconstituted with scTCR-transduced BM cells was significantly slower (P<0.05) than that seen in the control group. Tumor sections from TCR-reconstituted mice were infiltrated by neutrophils and macrophages, and to lesser extent, by NK cells. FACS analyses showed that BM cells transduced with scTCR-MFG could differentiate in vivo into multiple immune lineages including T cells, B cells, granulocytes, monocytes and NK cells that express the scTCR. The scTCR was expressed on higher percentages of cells of the innate immune system when compared to T and B cells. Human MUC1 transgenic (Tg.) mice reconstituted with BM cells transduced with this MUC1-specific TCR did not show any signs of autoimmunity, abnormal cellular infiltration or destruction of MUC1-expressing tissues. Transduction of BM with tumor-specific TCR represents a potentially efficacious gene therapy/immunotherapy approach. MUC1-specific MHC-unrestricted TCR will make this treatment applicable to all cancer patients with MUC1+ tumors, regardless of their HLA type.
A enzima 2-trans-enoil-ACP (COA) redutase de Mycobacterium tuberculosis : inibição por um novo composto e estudos espectroscópicos do seu mecanismo de resistência à hidrazida do ácido isonicotínico

Tuberculosis (TB) resurged in the late 1980s and now kills approximately 3 million people a year. The reemergence of tuberculosis as a public health threat has created a need to develop new anti-mycobacterial agents. The shikimate pathway is an attractive target for herbicides and anti-microbial agents development because it is essential in algae, higher plants, bacteria, and fungi, but absent from mammals. Homologs to enzymes in the shikimate pathway have been identified in the genome sequence of Mycobacterium tuberculosis. Among them, the shikimate kinase I encoding gene (aroK) was proposed to be present by sequence homology. Accordingly, to pave the way for structural and functional efforts towards anti-mycobacterial agents development, here we describe the molecular modeling ofM. tuberculosis shikimate kinase that should provide a structural framework on which the design of specific inhibitors may be based. 2002 Elsevier Science (USA). All rights reserved.
Evaluation of surgical outcomes of arthroscopic subtalar arthrodesis performed through two lateral portals

Objective: The purpose of this study is to present the surgical outcomes of twelve patients undergoing arthroscopic subtalar arthrodesis using two lateral portals (anterior and medial) in the sinus tarsi. Methods: A retrospective study was conducted with twelve patients (7 men and 5 women) with a mean age of 55.1 (36-74) years who underwent arthroscopic subtalar arthrodesis through the sinus tarsi between May 2015 and December 2016. The post-surgical follow-up was 12 months. Consolidation time and postoperative complications were evaluated, and a validated functional questionnaire from the American OrthopedicFoot and Ankle Society (AOFAS) and the visual analog scale (VAS) for pain were applied both before and after surgery. Results: The mean bone fusion time was 11.5 weeks. Bone consolidation was observed in all analyzed patients. Four patients developed late complications, three of which were related to screw positioning in the calcaneus, while one was related to residual hindfoot varus deformity. Screw-related complications are common with all subtalar arthrodesis techniques, and such complications are considered less relevant when evaluating the effectiveness of the presented technique. The mean preoperative AOFAS score was 42.3 (27-66) points, while the mean postoperative score was 83 (73-94) points. The mean preoperative VAS score for pain was 8.1 (5-10) points, and the mean postoperative score was 2.1 (0-5) points. The above data are similar to those reported in other published studies and reflect high bone consolidation rates. Conclusion: Arthroscopic subtalar arthrodesis through two lateral portals in the sinus tarsi is a safe and effective technique for the treatment of primary and secondary disorders of the subtalar joint. Correct positioning of screws and hindfoot alignment must be carefully ensured to avoid complications related to the synthesis material and hindfoot varus deformity. Level of Evidence IV; Therapeutic Studies; Case Series.
Incremental nonlinear stability analysis of stochastic systems perturbed by Lévy noise

We present a theoretical framework for characterizing incremental stability of nonlinear stochastic systems perturbed by either compound Poisson shot noise or finite‐measure Lévy noise. For each noise type, we compare trajectories of the perturbed system with distinct noise sample paths against trajectories of the nominal, unperturbed system. We show that for a finite number of jumps arising from the noise process, the mean‐squared error between the trajectories exponentially converge toward a bounded error ball across a finite interval of time under practical boundedness assumptions. The convergence rate for shot noise systems is the same as the exponentially stable nominal system, but with a tradeoff between the parameters of the shot noise process and the size of the error ball. The convergence rate and the error ball for the Lévy noise system are shown to be nearly direct sums of the respective quantities for the shot and white noise systems separately, a result which is analogous to the Lévy–Khintchine theorem. We demonstrate both empirical and analytical computation of the error ball using several numerical examples, and illustrate how varying the parameters of the system affect the tightness of the bound.
Overexpression of GRP78/BiP in P-Glycoprotein-Positive L1210 Cells is Responsible for Altered Response of Cells to Tunicamycin as a Stressor of the Endoplasmic Reticulum

P-glycoprotein (P-gp, ABCB1 member of the ABC (ATP-binding cassette) transporter family) localized in leukemia cell plasma membranes is known to reduce cell sensitivity to a large but well-defined group of chemicals known as P-gp substrates. However, we found previously that P-gp-positive sublines of L1210 murine leukemia cells (R and T) but not parental P-gp-negative parental cells (S) are resistant to the endoplasmic reticulum (ER) stressor tunicamycin (an N-glycosylation inhibitor). Here, we elucidated the mechanism of tunicamycin resistance in P-gp-positive cells. We found that tunicamycin at a sublethal concentration of 0.1 µM induced retention of the cells in the G1 phase of the cell cycle only in the P-gp negative variant of L1210 cells. P-gp-positive L1210 cell variants had higher expression of the ER stress chaperone GRP78/BiP compared to that of P-gp-negative cells, in which tunicamycin induced larger upregulation of CHOP (C/EBP homologous protein). Transfection of the sensitive P-gp-negative cells with plasmids containing GRP78/BiP antagonized tunicamycin-induced CHOP expression and reduced tunicamycin-induced arrest of cells in the G1 phase of the cell cycle. Taken together, these data suggest that the resistance of P-gp-positive cells to tunicamycin is due to increased levels of GRP78/BiP, which is overexpressed in both resistant variants of L1210 cells.
Modulations of Insular Projections by Prior Belief Mediate the Precision of Prediction Error during Tactile Learning

Awareness for surprising sensory events is shaped by prior belief inferred from past experience. Here, we combined hierarchical Bayesian modeling with fMRI on an associative learning task in 28 male human participants to characterize the effect of the prior belief of tactile events on connections mediating the outcome of perceptual decisions. Activity in anterior insular cortex (AIC), premotor cortex (PMd), and inferior parietal lobule (IPL) were modulated by prior belief on unexpected targets compared with expected targets. On expected targets, prior belief decreased the connection strength from AIC to IPL, whereas it increased the connection strength from AIC to PMd when targets were unexpected. Individual differences in the modulatory strength of prior belief on insular projections correlated with the precision that increases the influence of prediction errors on belief updating. These results suggest complementary effects of prior belief on insular-frontoparietal projections mediating the precision of prediction during probabilistic tactile learning. SIGNIFICANCE STATEMENT In a probabilistic environment, the prior belief of sensory events can be inferred from past experiences. How this prior belief modulates effective brain connectivity for updating expectations for future decision-making remains unexplored. Combining hierarchical Bayesian modeling with fMRI, we show that during tactile associative learning, prior expectations modulate connections originating in the anterior insula cortex and targeting salience-related and attention-related frontoparietal areas (i.e., parietal and premotor cortex). These connections seem to be involved in updating evidence based on the precision of ascending inputs to guide future decision-making.
Proteins and Peptides as Important Modifiers of the Polymer Scaffolds for Tissue Engineering Applications—A Review

Polymer scaffolds constitute a very interesting strategy for tissue engineering. Even though they are generally non-toxic, in some cases, they may not provide suitable support for cell adhesion, proliferation, and differentiation, which decelerates tissue regeneration. To improve biological properties, scaffolds are frequently enriched with bioactive molecules, inter alia extracellular matrix proteins, adhesive peptides, growth factors, hormones, and cytokines. Although there are many papers describing synthesis and properties of polymer scaffolds enriched with proteins or peptides, few reviews comprehensively summarize these bioactive molecules. Thus, this review presents the current knowledge about the most important proteins and peptides used for modification of polymer scaffolds for tissue engineering. This paper also describes the influence of addition of proteins and peptides on physicochemical, mechanical, and biological properties of polymer scaffolds. Moreover, this article sums up the major applications of some biodegradable natural and synthetic polymer scaffolds modified with proteins and peptides, which have been developed within the past five years.
Parents' experiences of health visiting for children with Down syndrome

Children with Down syndrome have an increased likelihood of experiencing serious health conditions. Health visitors can have an important role in monitoring and promoting health and development for young children with Down syndrome. This study aimed to explore parents' experiences of health visiting services for children with Down syndrome. Twenty-four parents of children with Down syndrome aged 0–5 years completed a brief questionnaire about the number and nature of visits from health visitors in the previous 12 months and their support needs. Some parents commented that other professionals met the needs of their child, whereas others said that they would like more advice and support from health visitors. A further exploration of broader health service provision, including health visiting, for young children with Down syndrome is needed.