Oxidative stress is a metabolic dysfunction that favors the oxidation of biomolecules, contributing to the oxidative damage of cells and tissues. This consequently contributes to the development of several chronic diseases. In particular, zinc is one of the most relevant minerals to human health, because of its antioxidant properties. This review aims to provide updated information about the mechanisms involved in the protective role of zinc against oxidative stress. Zinc acts as a co-factor for important enzymes involved in the proper functioning of the antioxidant defense system. In addition, zinc protects cells against oxidative damage, acts in the stabilization of membranes and inhibits the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NADPH-Oxidase). Zinc also induces the synthesis of metallothioneins, which are proteins effective in reducing hydroxyl radicals and sequestering reactive oxygen species (ROS) produced in stressful situations, such as in type 2 diabetes, obesity and cancer. Literature provides strong evidence for the role of zinc in the protection against oxidative stress in several diseases. Oxidative stress is characterized by an imbalance between oxidants and antioxidants, due to the excessive production of reactive oxygen species (ROS) and the reduction in the rate of its removal by the antioxidant defense system. This metabolic disturbance favors the oxidation of biomolecules, contributing to the oxidative damage in the cells and tissues and consequently to the development of several chronic diseases such as obesity, diabetes and cancer ,2,3.Several studies have examined the role of minerals in the antioxidant defense system. In particular, zinc is one of the essential minerals for human health because it serves as a co-factor for over 300 enzymes and 2000 transcription factors. Zinc is an important mediator of cellular signaling ,5. It acZinc acts as a co-factor for important enzymes that contribute to the proper functioning of the antioxidant defense system. In addition, this mineral protects cells against oxidative damage because it acts in the stabilization of membranes, inhibits the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NADPH-Oxidase), a pro-oxidant enzyme, and induces metallothionein synthesis. Metallothionein is involved in the reduction of hydroxyl radicals (OH) and in the sequestration of the reactive oxygen species produced under stress conditions ,10.Therefore, considering the complexity of oxidative stress and its detrimental effect on health in addition to the potent antioxidant properties of zinc, this review aims to provide the latest information on the mechanisms involved in the role of zinc in the protection against oxidative stress in chronic diseases.This is a narrative review and a bibliographical survey of articles in the databases PubMed and Science Direct without limit for the year of publication, selected from August to September 2016. The keywords used in the search were "zinc”, “oxidative stress”, “zinc transporters”, and “antioxidant”. The descriptors were used alone or combined using the Boolean operators “AND” and “OR”.Studies that presented relevant aspects of the mechanisms involved in the role of zinc in protection against oxidative stress were included. Dissertations, theses, articles in which only a summary was available, and those duplicated in different databases were excluded.Then, we proceeded with the analysis of the included articles, and started reading the titles, followed by summaries, and later the full text. The application of the exclusion criteria was performed at all stages, always by consensus of the reviewers. At the end, we selected 63 articles.The role of zinc in the antioxidant defense system has been widely investigated. Studies have highlighted its role in the regulation of glutathione peroxidase and in the expression of metallothionein, as well as its role as a co-factor for superoxide dismutase. Moreover, zinc competes with iron and copper in the cell membrane, inhibits the NADPH-oxidase enzyme, and reduces chronic inflammation and hyperglycemia ,12.Zinc is a structural component of the enzyme superoxide dismutase present in the cytoplasm of cells. Superoxide dismutase has an active center with a copper ion and a zinc ion. This enzyme promotes the conversion of two superoxide radicals to hydrogen peroxide and molecular oxygen, reducing the toxicity of ROS because it converts a highly reactive species to a less harmful one .Therefore, maintaining adequate concentrations of zinc in the cell compartments is essential for the proper functioning of the antioxidant defense system. Examining this function, Homma et al.  found thAnother mechanism by which zinc acts as an antioxidant is by affecting the expression of glutamate-cysteine ligase, which is the rate-limiting enzyme of glutathione de novo synthesis. This has a two-fold effect of zinc to neutralize free radicals directly by glutathione or indirectly as a glutathione peroxidase cofactor . Ha et aZinc is a potent metallothionein inducer. Zinc is bound to metallothionein under normal physiological conditions. In oxidative stress conditions, the micronutrient is released from its complex with metallothionein and is redistributed in the cells to exert antioxidant actions ,19. LianIt is noteworthy that metallothionein has the ability to effectively bind heavy metal ions, such as zinc, copper, chromium, cadmium, mercury ,22,23. TResponsive metal transcription factor 1 (MTF-1) also has an important role in coordinating cellular responses to metal homeostasis and oxidative stress. MTF-1 is a zinc-dependent transcription factor that stimulates the expression of metallothionein and zinc transporter-1 (ZnT-1) genes when the concentration of zinc increases. Zinc transporter ZnT-1 is located in cellular membranes and it allows the efflux of excess zinc from the cell. Through this function, it diminishes zinc toxicity in the cytosol. Furthermore, metallothionein also binds excess zinc ions in the cytosol. Thus, the induction of the expression of metallothionein and ZnT-1 is a mechanism that acts against elevated zinc levels ,25.MTF-1 also can protect cells from oxidative stress because this transcription factor is very sensitive to fluctuations in the redox cell status and promotes the expression of the target genes after stimulation. MTF-1 activates the expression of the Selenoprotein 1 (Sepw1) gene, which encodes an antioxidant glutathione-binding protein which scavenges free radicals . FurtherIt is important to note the ability of zinc to compete with iron and copper in the binding sites present in the cell membrane. Iron and copper ions can catalyze the production of radicals from lipid peroxides. In this way, the replacement of iron and copper by zinc could prevent the formation of highly reactive radicals because zinc is catalytically inert ,28.Linked to this, there is a close association between chronic low-grade inflammation and oxidative stress. Various pro-inflammatory transcription factors, including nuclear factor κB (NF-κB) and activator protein-1 (AP-1), can induce the production of ROS, causing the release of inflammatory cytokines. This in turn enhances oxidative stress, thus setting a vicious cycle . While iThe study conducted by Prasad et al.  using ceResearch has shown the role of zinc deficiency in causing oxidative damage and, consequently, endothelial dysfunction. Zinc deficiency in endothelial cells enhances the inflammatory response mediated by cytokines and lipids, possibly via mechanisms associated with increased cellular oxidative stress. In contrast, zinc supplementation exerts a protective role against damage to the vascular system. The mechanisms by which zinc protects the blood vessels include the regulation of Nrf2, a transcription factor important for the expression of genes encoding antioxidant enzymes and for the induction and expression of metallothionein ,33,34.d-aspartate (NMDA) receptors, involved in the transport of calcium from the extracellular environment to the cytosol. Through this function, zinc deficiency promotes the activation of NMDA receptors and increases intracellular calcium concentration [Studies have also demonstrated the role of zinc as an inhibitor of N-methyl-ntration . This inntration . Furtherntration  (Figure Zinc also improves insulin sensitivity and glycemic control because it contributes to reducing the synthesis of ROS under hyperglycemic conditions, thereby inhibiting the activation of oxidative stress pathways . In thisRecent research looking into the influence of zinc carrier proteins on cellular oxidative stress has shown the coordinated action of these carrier proteins in mitigating cellular damage. Liang et al.  demonstrMoreover, oxidative stress appears to be capable of altering the expression of zinc carrier proteins. Sun et al.  demonstrChronic exposure to ethanol also significantly reduces zinc levels in the endoplasmic reticulum and mitochondria of isolated liver cells. Accordingly, treatment with zinc supplementation promotes the increased expression of Zip-8 and Zip-13, which transport zinc from the mitochondria and endoplasmic reticulum to the cytosol. Zinc supplementation also increases the expression of ZnT-4, which transports zinc from the cytosol to the mitochondria . Zinc deZinc is a potent inducer of metallothionein and is bound to metallothionein. Zinc is released from its complex with metallothionein in oxidative stress conditions. MTF-1, a zinc-dependent transcription factor, activates metallothionein gene expression, which can protect cells against oxidative stress. Zinc is a structural component of the enzyme superoxide dismutase, which promotes the conversion of two superoxide radicals to hydrogen peroxide and molecular oxygen. Zinc influences the expression of glutamate-cysteine ligase, an enzyme involved in the synthesis of glutathione, which acts directly on the neutralization of free radicals. Zinc also inhibits the NMDA receptors involved in the transport of calcium from the extracellular environment to the cytosol. Thus, zinc deficiency promotes the activation of NMDA receptors, which increase the intracellular concentration of calcium. In conditions where zinc is deficient, the NADPH oxidase enzymes and nitric oxide synthase are activated, favoring the production of reactive species of oxygen and nitrogen.On the other hand, zinc also acts as a pro-oxidant when its concentration is either deficient or in excess and becomes pro-inflammatory and pro-apoptotic. Zinc excess also induces copper deficiency, which has been related to multiple adverse effects. These adverse effects include decreased expression of copper-dependent enzymes, such as superoxide dismutase and ceruloplasmin, which are important in antioxidant defense ,45. MoreResearch has shown that zinc status may be altered under pathophysiological conditions, such as diseases characterized by elevated oxidative stress, which impairs the control of these diseases. In particular, obese individuals may present with a deficiency of zinc, which aggravates the oxidative stress present in this disease ,49. A stChronic hyperglycemia in type 2 diabetes mellitus has been associated with lipid peroxidation and oxidative damage in cells, impairing the antioxidant defense in type 2 diabetes patients. Lima et al.  showed rZinc deficiency also can be found in chronic kidney disease, which has been attributed to reduced food intake and intestinal absorption of the mineral, interaction with calcium and iron and increased loss of minerals during dialysis. In this disease, zinc binds to proteins modified by uremia, such as albumin, thus aggravating its deficiency ,52. A stIn the study by Guo and Wang , supplemThe regulation of extracellular zinc concentrations is also extremely important for maintaining homeostasis of the neural network, because this mineral plays a role in both the physiology and pathophysiology of the brain . In synaMoreover, antioxidants and anti-carcinogenic mechanisms associated with zinc homeostasis appear to play an inhibitory role in the growth of neoplastic cells. Zinc acts in the protection against genomic instability and genetic mutations. In this sense, the superoxide dismutase is an anticarcinogenic enzyme. It inhibits the initiation, promotion, and progression phases in mammary carcinogenesis .Furthermore, dietary zinc deficiency has also been linked to an increased risk for breast cancer ,58. OxidIt is noteworthy that the expression of metallothionein is deregulated in breast cancer, which is correlated with resistance to chemotherapy and poor prognosis. Metallothionein participates in carcinogenesis via mechanisms that promote the development of tumor cells resistant to chemotherapy and radiation. High levels of metallothionein in cancer cells protect against damage by inhibiting free radicals, apoptosis and promoting cell proliferation. Thus, these functions support uncontrolled growth of these cancer cells. Moreover, the interaction of metallothionein with zinc ions is involved in the regulation of several transcription factors that contribute to carcinogenesis .In diseases, such as epilepsy, schizophrenia, and Alzheimer’s and Parkinson’s diseases, the deleterious effects of zinc can also be observed. In these conditions, zinc is released in excess by presynaptic neurons and astrocytes, resulting in neuronal death via the activation of microglia, NADPH oxidase and the production of ROS in neurons ,61,62. MResearch has still not fully elucidated the role of zinc in the molecular mechanisms involved in the pathophysiology of chronic diseases, such as obesity, diabetes and cancer. However, data in the literature show that a deficiency in zinc favors the manifestation of oxidative stress, promoting the development of these diseases. It is necessary to clarify the biochemical and molecular basis involved in this process. Therefore, further studies on the subject may elucidate the role of this nutrient in protecting against oxidative stress present in these diseases.


Although various computer tools have been elaborately developed to calculate a series of statistics in molecular population genetics for both small- and large-scale DNA data, there is no efficient and easy-to-use toolkit available yet for exclusively focusing on the steps of mathematical calculation. Here, we present PopSc, a bioinformatic toolkit for calculating 45 basic statistics in molecular population genetics, which could be categorized into three classes, including (i) genetic diversity of DNA sequences, (ii) statistical tests for neutral evolution, and (iii) measures of genetic differentiation among populations. In contrast to the existing computer tools, PopSc was designed to directly accept the intermediate metadata, such as allele frequencies, rather than the raw DNA sequences or genotyping results. PopSc is first implemented as the web-based calculator with user-friendly interface, which greatly facilitates the teaching of population genetics in class and also promotes the convenient and straightforward calculation of statistics in research. Additionally, we also provide the Python library and R package of PopSc, which can be flexibly integrated into other advanced bioinformatic packages of population genetics analysis. D value for testing hypothesis of neutral evolution on basis of the observed DNA polymorphisms in 1989 [Theoretical framework of population genetics had been significantly promoted due to the accumulated evidence in molecular biology, which resulted in an interdisciplinary Molecular Population Genetics more than two decades ago . A prima in 1989 , which h in 1989 .Prior to the advent of high-throughput sequencing techniques, the common molecular data available for studies of population genetics always only involve a short DNA fragment directly sequenced with tens of thousands of base pairs in length or several hundreds of polymorphism loci individually genotyped. By aiming at these small-scale and standard molecular data, kinds of computer programs, such as the actively cited DnaSP  and ArleDespite the fact that there are various tools available for population genetics analysis on both small- and large-scale molecular data, we also found two limitations in this field deserving to be addressed. First, it is very inconvenient for using these existing tools, because all of them require strict format of input data, when you intend to compute certain statistics directly starting with the ready-made metadata of variants  instead of raw DNA sequences. So, we believe that the easy-to-use online calculator would be very helpful for conducting some trivial tasks in teaching as well as research of molecular population genetics. Second, there is no toolkit available yet for exclusively performing the calculation step of statistics, which, in expectation, should be able to be directly and flexibly employed and incorporated into an advanced bioinformatic package. Such toolkit, therefore, could facilitate the development of analysis packages for bioinformatists without good background in population genetics, and also for biologists only holding the elementary skills in bioinformatics. In the present study, we specially addressed the two issues.To address the issues as mentioned above, PopSc was designed to exclusively perform the calculation step of statistics of interest in molecular population genetics. Therefore, the initial input data into PopSc are these descriptive metadata, such as the allele or haplotype frequencies, number of segregating sites, counts of different mutation types, and mismatch distribution, etc., which must be generated from upstream raw DNA sequences or genotyping data in advance. After completing the computational duties, PopSc will directly pass the numerical output of statistic on to users. Such philosophy of design will promote the convenient calculation without requiring tedious input of raw DNA sequences and also guarantee the possibility of direct integration of PopSc toolkit into other advanced packages of bioinformatic analysis.Generally guided by the popularity in scientific literatures, we comprehensively collected a total of 45 basic statistics in molecular population genetics into PopSc . All of ab initio input of DNA sequences or other types of raw molecular data. Mathematical formulas and the related documentation for each statistic are also clearly shown on the respective web pages, which would be very helpful for teaching the molecular population genetics in class; and such teaching purpose had also been successfully addressed by the very popular tool of GENALEX, which is an add-in program for Microsoft Excel [Because the web browser is independent of operating system and requires no installation, PopSc was first implemented as online calculator . The webft Excel .http://pypi.python.org and http://cran.r-project.org, respectively) and could be installed by standard commands. The web-based calculator, source codes and reference manuals of PopSc could also be freely available at: http://chenshiyi.com/popsc.html.During the past years, programming languages of Python and R are becoming more and more popular in bioinformatic analyses. Therefore, PopSc was further independently implemented and provided as the Python library and R package, which can be easily integrated into other advanced bioinformatic packages in molecular population genetics. The Python library and R package of PopSc are deposited in official repositories (Of course, PopSc is not an upgrade or even a replacer to the exiting computer tools because it just performs the step of mathematical calculation for each statistic. Therefore, PopSc only accepts the descriptive metadata, which must be independently prepared from raw DNA sequences or genotyping data with the aid of the custom scripts or other computer tools, such as MEGA . PopSc c


Lynn Margulis in the 1960s elegantly proposed a shared phylogenetic history between bacteria and mitochondria; this relationship has since become a cornerstone of modern cellular biology. Yet, an interesting facet of the interaction between the microbiome and mitochondria has been mostly ignored, that of the systems biology relationship that underpins host health and longevity. Rickettsia) that entered  into a mutualistic partnership with ancient anaerobic microbes (likely Archaea). A stable symbiosis was established, given the metabolic versatility of the early mitochondria, which were capable of providing energy with or without oxygen, whereas nutrient gathering was the assumed responsibility of the host. While microbial relationships with single-cell protists must have occurred in the past, as they occur today, the evolution of multicellular organisms generated a new framework for symbiosis with the microbial world, taking the ancient partnership to an entirely new level. Cell-cell communication between microbes and single-cell protists was augmented through multicellularity to allow distant communication between the host cells and the microbiome, resulting in the development of complex metabolic relationships and an immune system to manage these interactions. Thus, the host is now the body and its resident mitochondria, and the microbiome is an essential supplier of metabolites that act at the level of mitochondria in skeletal muscle to stabilize host metabolism. We humans are caretakers of a profoundly vast and diverse microbiota, the majority of which resides in the gut. Indeed, the microbial genetic diversity of our microbiota outstrips our own by several orders of magnitude, and the cellular abundance is roughly equivalent to our somatic selves. Modern clinical science has elegantly highlighted the importance of the microbiome for metabolic health and well-being. This perspective underscores one fundamental facet of this symbiosis, the ancestral mitochondrion-microbiome axis.Lynn Margulis in the 1960s elegantly proposed a shared phylogenetic history between bacteria and mitochondria; this relationship has since become a cornerstone of modern cellular biology. Yet, an interesting facet of the interaction between the microbiome and mitochondria has been mostly ignored, that of the systems biology relationship that underpins host health and longevity. The mitochondria are descendants of primordial aerobic pleomorphic bacteria (likely genus  Clostridium and Butyrivibrio genera . Recent studies have highlighted the importance of three key microbiome metabolites: (i) the short-chain fatty acids (SCFA), (ii) the urolithins, and (iii) lactate. In particular, among these key metabolites is the SCFA butyrate, which is produced by microbial fermentation of indigestible fiber by a number of different bacterial lineages, including the o genera –3, and uand nuts , 5. Bothand nuts . As a miand nuts . A link and nuts –9. ThereClostridium spp. and lactobacilli  exerts potent effects over muscle performance and oxidative capacity (12–Clostridiaceae following exercise is positively correlated with blood lactate accumulation, which reflects fitness levels (Of particular interest, probiotic supplementation with capacity  as well tarum TWK exerts pcapacity , 18. Butcapacity , 12–14 as levels . These rThe ability of specified microbiome lactobacilli to metabolize polyphenols found in certain fruits  or fermeThe potential for precise therapeutic interventions that target microbial-mitochondrial metabolic communication provides a novel avenue for the treatment of many metabolic disturbances and could have profound implications for the future of medical treatments. From an ancient union, the dominance of the microbial world is redefining our perspective for health and wellness.


Thus, the objective of thissystematic review is to verify the effectiveness of the therapy protocol foralternate rapid maxillary expansion and constriction (Alt-RAMEC) in the earlytreatment of Class III malocclusion. in vivo studies conducted with earlyintervention  with the use of theAlt-RAMEC protocol. Reviews, case reports, editorials, and studies with syndromicpatients or under use of systemic drug were excluded. Duplicates were alsoexcluded. The studies were assessed for methodological quality using the Cochranetool for assessment of risk of bias, and classified as high or low risk of bias.searches were performed in the following electronic databases: Cochrane Library,Medline (EBSCO and PubMed), SciELO, LILACS and Scopus. The following inclusioncriteria were used: 53 articles were found. Duplicates exclusion was thus performed and 35 articlesremained. After inclusion analysis, only 5 matched the criteria. Two articles wereclassified as low risk of bias and three as high risk of bias. It was observedthat the Alt-RAMEC enable protraction in less time and with better results,promoting greater effectiveness in the protraction treatment of Class IIImalocclusion. Although there is positive evidence of the effectiveness of early treatment withthe Alt-RAMEC protocol in patients with Class III malocclusion, further studiesare needed to confirm its effectiveness using long-term methodology.  Thus, asalternative, early treatment by means of non-surgical procedures can be employed. Thesecan be conducted by different types of protocols, providing a dynamic developmentprocess which may change its direction during the treatment, allowing some maxillaryadjustments.,The Alt-RAMEC protocol confers alternate movements of rapid maxillary expansions andconstrictions. The expander device used in the protocol consists of double-hingedintraoral maxillary protraction springs made of beta-titanium alloy. The main goal ofthis protocol is to generate the greatest maxillary expansion, allowing largestmaxillary protraction, since the effectiveness of protraction depends on the opening ofthe circumaxillary sutures. An adequate opening of these sutures is the basicprerequisite for a good amount of maxillary protraction.However, this new treatment protocol for Class III malocclusion is still controversial.Thus, the objective of this systematic review is to assess by scientific evidences theeffectiveness of early therapy for Class III malocclusion using maxillary protractionand disjunction, with the alternate expansion and contraction movements of Alt-RAMECprotocol.Journal of Craniofacial Research. The searchstrategy included appropriate changes in the keywords, following syntax rules of eachdatabase (The review was conducted according to the PRISMA guidelines(www.prisma-statement.org). To identify relevant studies from 1900 to February 2016,a language-independent search was conducted in the following databases: CochraneLibrary, Medline EBSCO and PubMed, SciELO, LILACS and Scopus. Independent searchesthroughout the reference lists of the retrieved articles were also conducted, inaddition to the database .The articles were selected based on title and abstract, and had to match thefollowing inclusion criteria: controlled clinical studies with patients in the growthphase  with Class III malocclusion (P-participants),who were submitted to the Alt-RAMEC protocol for maxillary expansion and protractionas early treatment (I-intervention). The articles also had to compare individuals ofsame gender and age, and also with the traditional method of maxillary expansion(C-comparison), establishing from the results whether there was a greatereffectiveness of Alt-RAMEC or not (O-outcome) . Were exThe initial analysis excluded articles with titles and abstracts not related to thestudied issue and presenting at least one of the exclusion criteria. The next stepwas a detailed analysis of selected articles, to examine those who respected allinclusion criteria or presented exclusion criteria. When the information in the titleor abstract was insufficient to decide about the inclusion or exclusion, the fullarticle was read and then decided about its inclusion or exclusion. Articles withoutabstract were read entirely to define their eligibility.Article selection was performed by two researchers based on critical analysesregarding the inclusion and exclusion criteria. If discrepancies were found betweenthe two researchers, a new reviewer was added, to eliminate the discrepancies betweenthe other two evaluators. When consensus was obtained among the reviewers regardingthe articles that met the inclusion criteria, these were finally included in thesystematic review. In cases where additional data were needed, authors were contactedvia email to obtain these additional information.To assess the methodological quality and risk of bias of the included studies, it wasused the The Cochrane Collaboration’s Tool for Assessing Risk of Bias, published inthe Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0).The selection bias consists in the systematic difference between the baseline groupand the other groups, composed by the domains of sequence generation and allocationconcealment. The performance bias comprises systematic differences between the groupsin which the care is provided, or submitted to other factors than the interventionsof interest, including the domains of blinding of participants and staff and otherpotential threats to validity.The detection bias was assessed by the blinding of outcome assessment, which consistsof systematic differences of how are defined the results between the groups. Theattrition bias was evaluated by the domain of incomplete outcome data, comprisingsystematic differences between the groups that were drawn from the study. And thereporting bias includes the systematic differences between the reported andunreported results, being evaluated by the domains of selective reporting. For each assessed domain the articles could be classified as low risk  or the Alt-RAMEC protocol followed by another method of maxillarytraction. It is noteworthy that meta-analysis was tried, but it was not possible to beperformed due to the high degree of heterogeneity between the studies.Comparative studies developed by Liou and TsaiRegarding quantification of the force applied in the treatment with Alt-RAMEC, Liouand TsaiAs regards to the activation periods, Liou and TsaiIn regard to the follow-up period, only the study of Liou and TsaiUsing a modified Alt-RAMEC protocol, without the use of intraoral springs, Isci, Turkand Elekdag-TurkIsci, Turk and Elekdag-TurkAlthough a study was conducted with patients with cleft lip and palate, it did notdetect any difference in treatment in non cleft patients, with exception to themaking of the piece that was modeled so that the jackscrew stayed orientedperpendicularly to the alveolar fissure.Analyzing the results from the Alt-RAMEC protocol associated to TADs, the studypointed the effectiveness to treat Class III malocclusion patients. On the otherhand, the authors postulate that the Alt-RAMEC alone does not increase the amount ofmaxillary forward movement, thus other factors such as age of the patient, durationof the mask use and treatment exposure should be considered. Therefore, furtherstudies are needed to clarify the stability of this protocol.It may be seen throughout this review that all selected studies comparing the use ofAlt-RAMEC and other traditional expansion protocols concluded that there aresignificantly different results, with better results for the group treated with theAlt-RAMEC protocol. However, there is a gap in the literature, since there were nostudies focusing on assessing the stability of the results on the long-term (over twoyears). Further studies, with long-term design, are necessary to evaluate thestability maintenance, which is important for Class III malocclusion treatmentprotocols.From the analysis of the articles, it was concluded that:» The use of Alt-RAMEC protocol is effective to early treatment of Class IIImalocclusion patients.» The stability of the correction of Class III malocclusion could not beverified, because of the lack of studies designed to assess this issue.» Although the scientific evidence point to a greater effectiveness of theprotocol using Alt-RAMEC in the early treatment of Class III malocclusion, morestudies are needed with longer follow-up period, as well as better definitionof the test and control groups.


In maxillofacial surgery, every patient presents special problems requiring careful evaluation. Conventional methods to study the deformities are still reliable, but the advent of tridimensional (3D) imaging, especially computed tomography (CT) scan and laser scanning of casts, created the opportunity to better understanding the skeletal support and the soft tissue structures. Nowadays, virtual technologies are increasingly employed in maxillofacial surgery and demonstrated precision and reliability. However, in complex surgical procedures, these new technologies are still controversial. Especially in the less frequent cases of three-part maxillary surgery, the experience is limited, and scientific literature cannot give a clear support. This paper presents the case of a young patient affected by a complex long face dentofacial deformity treated by a bimaxillary surgery with three-part segmentation of the maxilla. The operator performed the surgical study completely with a virtual workflow. Pre- and postoperative CT scan and optical scanning of plaster models were collected and compared. Every postoperatory maxillary piece was superimposed with the presurgical one, and the differences were examined in a color-coded map. Only mild differences were found near the osteotomy lines, when the bony surface and the teeth demonstrated an excellent coincidence. A satisfying outcome in orthognathic surgery depends on the surgical technique and the accuracy of the orthodontic-surgical treatment plan. Surgical decisions are based on complex clinical and instrumental data. Until today, at the end of the presurgical orthodontic treatment, the surgeon simulates the desired bony movements on the casts and creates dental splints to be employed during the surgery. This process demonstrated reliability both for common clinical situations  and for A 19-year-old female was referred to the Maxillofacial Department of Parma University Hospital for a complex long face dentofacial deformity. The face of the patient demonstrated an important vertical height excess with lips incompetence and a severe dental anterior open-bite malocclusion. As well known, correcting the vertical dimension of the face always involves difficult decisions, for both long and short face situations –46. The The anterior portion of the color-coded map demonstrated a good correspondence between the prediction and the final result . A smallIn the right portion, also for the right maxillary piece, the large green area demonstrated an excellent coincidence . Only miIn the left portion, the outcome was similar  showing Virtual planning for maxillofacial surgery is increasingly emerging as a useful procedure in the clinical routine. In our experience, it represents now a routine tool for both single- and double-jaw surgeries. However, virtual surgery planning is less common in cases of maxillary segmentation, due to the lower frequency of the pathologies requiring this procedure and the difficulties in programming the surgery on the computer. A two-piece maxillary surgery is generally limited to special clinical situations, that is, in the transversal defect  when a t


Anaphylaxis is the most severe form of allergic reaction, resulting from the effect of mediators and chemotactic substances released by activated cells. Mast cells and basophils are considered key players in IgE-mediated human anaphylaxis. Beyond IgE-mediated activation of mast cells/basophils, further mechanisms are involved in the occurrence of anaphylaxis. New insights into the potential relevance of pathways other than mast cell and basophil degranulation have been unraveled, such as the activation of the contact and the coagulation systems. Mast cell heparin released upon activation provides negatively charged surfaces for factor XII (FXII) binding and auto-activation. Activated FXII, the initiating serine protease in both the contact and the intrinsic coagulation system, activates factor XI and prekallikrein, respectively. FXII-mediated bradykinin (BK) formation has been proven in the human plasma of anaphylactic patients as well as in experimental models of anaphylaxis. Moreover, the severity of anaphylaxis is correlated with the increase in plasma heparin, BK formation and the intensity of contact system activation. FXII also activates plasminogen in the fibrinolysis system. Mast cell tryptase has been shown to participate in fibrinolysis through plasmin activation and by facilitating the degradation of fibrinogen. Some usual clinical manifestations in anaphylaxis, such as angioedema or hypotension, or other less common, such as metrorrhagia, may be explained by the direct effect of the activation of the coagulation and contact system driven by mast cell mediators. Mediators of human mast cells comprise pro-inflammatory molecules, such as histamine, leukotriene (LT) B4 and LTC4, or prostaglandin D2 (PGD2), cytokines, vascular endothelial growth factor (VEGF), proteases such as tryptase and chymase, and the highly sulfated polysaccharides, heparin and chondroitin sulfate, being the last two especially abundant in mast cell secretory granules , the respiratory tract , the digestive , or the cardiovascular systems (dizziness and hypotension) can be present during an anaphylactic episode . Unusualin vitro contact system activation have been elucidated, the in vivo effects of this complex system in some instances are still unclear.The contact system integrates the plasma bradykinin (BK) formation pathway  and the intrinsic coagulation cascade. In addition, it is involved in thrombus formation, fibrinolysis, and complement activation . The conThe effects of BK include peripheral vasodilatation, enhancement of vascular permeability and subsequent vascular leakage, and the contraction of gastrointestinal and uterine smooth muscle, resulting in angioedema, hypotension, and abdominal pain , all cliIn vivo, this proteoglycan is exclusively synthesized in mast cells , present in the circulation and expressed by cells around the vessels when the endothelial layer is compromised. The intrinsic pathway is activated by FXII, which activates both the contact system polymers . Fibrinopolymers   that measures intrinsic coagulation pathway, and a significant anti-Xa activity, with extremely low fibrinogen level with only a slight increase of D-dimer was observed . The autThe coagulation system has also been assessed in relation to conditions which share some features with anaphylaxis, and in which, mast cells plays a crucial role, such as urticaria. In chronic spontaneous urticaria it was found that coagulation factors  were increased compared to controls and were significantly correlated with disease severity .In a murine model, the tetramer-forming β-tryptases cleaved the α and β-fibrinogen chains and, therefore, the thrombin-initiated clot formation was inhibited . This isvia proteolytic degradation (Moreover chymase, a protease exclusively of mast cell origin, has also been shown to affect the coagulation pathway. Mast cell chymase, whose activity depends on heparin , is respradation . In addiradation .Histamine has been shown to induce the expression of TF in vascular cells activating the H1, but not the H2, receptor , 60, revThus, as it occurs with the contact system, several mast cell mediators have a potential role in the regulation of coagulation and fibrinolysis. When a massive release of mast cells mediators occurs, as in anaphylaxis, the activation of these two systems may contribute to the pathophysiology of the multisystemic reaction. In addition, depending on the relative release of each mediator, the clinical effects may differ.Currently, the only biomarkers that can be measured routinely in anaphylaxis are histamine and tryptase. Reliable biomarkers to assess contact system activation and the generation of BK have not been established.in vivo is practically impossible due to its rapid degradation by kininases once released. As BK is present in the circulation for only few seconds, the measurement of activation products of the contact system can be valuable biomarkers as they may reflect recent BK production. Thus, we speculate that the most suitable biomarkers to assess contact activation are circulating cleaved HK and kallikrein activity but these measurements are very labor intensive since standardized assays are lacking. To assess the coagulation system, the observation of prolonged aPTT reveals activation of the intrinsic coagulation pathway. Increased levels of anti-Xa reflect the possible effect of heparin and the inhibition of the common coagulation pathway. Regarding the fibrinolytic system, increased levels of plasmin complexes and also increased levels of D-dimer, in patients without a thromboembolic event, should raise the suspicion that the contact and fibrinolytic systems are activated.Measurement of BK Anaphylaxis is a complex allergic reaction where multiple biological systems are involved. Further mechanistic studies to discern the involvement of molecules from the contact and coagulation systems are warranted to completely understand the pathophysiology and subsequent clinical effects during anaphylaxis. In order to assess all these complex connections between mast cell mediators and the activation of the contact and coagulation systems, a wide array of potential biomarkers are needed and should be monitored at multiple time-points together with their functional effects. Only then, will we be able to have a complete overview of the interactions and subsequent effects of each mediator and pathway, and maybe also offer a closer insight to new potential diagnostic markers or therapeutic targets for anaphylaxis.All authors made substantial contributions to conception and design of the review. MG and AS-C drafted the manuscript. ML-H, OL, and VC participated in revising it critically for important intellectual content. All authors approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Compositional analysis of the luminal fluids collected from the epididymis of a variety of species has revealed the complexity of this milieu, with a diversity of inorganic ions, proteins, and small non-coding RNA transcripts having been identified to date. Notably, both the quantitative and qualitative profile of each of these different luminal elements display substantial segment-to-segment variation, which in turn contribute to the regionalized functionality of this long tubule. Thus, spermatozoa acquire functional maturity in the proximal segments before being stored in a quiescent state in the distal segment in preparation for ejaculation. Such marked division of labor is achieved via the combined secretory and absorptive activity of the epithelial cells lining each segment. Here, we review our current understanding of the molecular mechanisms that exert influence over the unique intraluminal environment of the epididymis, with a particular focus on vesicle-dependent mechanisms that facilitate intercellular communication between the epididymal soma and maturing sperm cell population.The testicular spermatozoa of all mammalian species are considered functionally immature owing to their inability to swim in a progressive manner and engage in productive interactions with the cumulus–oocyte complex. The ability to express these key functional attributes develops progressively during the cells’ descent through the epididymis, a highly specialized ductal system that forms an integral part of the male reproductive tract. The functional maturation of the spermatozoon is achieved  The mammalian epididymis is an exceptionally long, convoluted ductal system that serves to connect the ductuli efferentes, which drain the testes, to the ductus deferens. Anatomically, this highly specialized organ is generally divided into four broad segments: the initial segment, caput, corpus, and cauda epididymides Figures A,B 1); ; 1); altIt is well established that the combined secretory and absorptive activities of the epididymal epithelial cells are responsible for the creation of the highly specialized luminal microenvironment that promotes the gradient of increasing fertility in the sperm population held therein . SystemaThe process of post-testicular sperm maturation is reliant on the highly specialized intraluminal microenvironment of the epididymis, arguable one of the most complex milieus produced by any endocrine gland. Accordingly, the selective ablation of genes that lead to dysregulation of the epididymal microenvironment commonly results in male infertility/subfertility phenotypes Table . The oriPrincipal cells represent the major cell type throughout the entire epididymis, constituting as much as 80% of the peritubular interstitium . These cThe remaining cell types comprising the epididymal epithelium are predominantly related to immune functions , an impovia the uptake, repositioning, and posttranslational modification of a significant portion of proteins. Such changes are mediated by direct exposure to the proteins secreted into the epididymal luminal environment, with a majority of these originating in the proximal segments of the caput and corpus epididymis  class of RNA molecules (~21–25 nucleotides) that hold a key regulatory role in the repression of mRNA translation. Indeed, the use of microarray and next generation sequencing methodologies has led to the identification of a total of 545 and 370 miRNAs in the human and mouse epididymis, respectively , 29. A lididymis . The bioectively . Thus, tectively . Alternaectively .In any case, it is therefore perhaps not surprising that intraluminal proteome of the epididymis ranks among the most complex produced by any endocrine gland. In addition to a diversity of soluble proteins, electron-dense proteinaceous complexes have also been described in the epididymal lumen of rodents, rams and, recently humans –40. Thesvia indirect mechanisms involving delivery of regulatory cargo  to epithelial cells downstream of their site of genesis.In addition to amyloids/dense bodies, the epididymal lumen also features an impressive population of extracellular vesicles. Indeed, as early as 1985, Yanagimachi identified a population of small membranous vesicles residing near the surface of epididymal spermatozoa in the Chinese hamster, and subsequently predicted their potential role in cholesterol transfer to the maturing spermatozoa . The exiin vitro co-incubation studies between spermatozoa and epididymosomes focusing on protein complexes such as the MCA4a–PMCA4b–CASK complex, which has been directly co-immunoprecipitated from epididymosomes , and −. This change is sensed by purinergic receptors in adjacent clear cells where it leads to activation of bicarbonate-sensitive adenylyl cyclase and the downstream re-localization of proton pumping ATPases to the apical region of these cells. These pumps subsequently secrete H+  that are located in the principal piece of the sperm flagellum. Accordingly, blocking Ca2+ influx via CatSper knockout strategies leads to impaired sperm motility   . Accordi (LRP-2) . This pr (LRP-2) . Epididy (LRP-2) . Another (LRP-2) . The epi (LRP-2) .Despite recognition of the importance of bidirectional epithelial transport in regulating the epididymal luminal environment, little is currently known about the molecular machinery that controls these complementary pathways. Key elements are likely to include Soluble NSF Attachment Protein Receptor (SNARE) proteins, which have well-described roles in the regulation of membrane fusion activity in alternative tissue models. This activity requires the complementary action of different SNARE proteins contributed by vesicles (v-SNARE proteins) and target (t-SNARE proteins) membranes. Initiated by nucleation of the SNARE complex in response to calcium fluxes, the two opposing membranes are brought into close apposition and are thereafter able to engage in membrane fusion . The firvia uptake into the surrounding epithelial cells  including miRNA and tRNA fragments  does not overtly influence the transfer efficacy of the alternative population (collected from cauda segment) during simultaneous co-incubation with spermatozoa . As an evia the docking of GPI anchor(s) to the outer leaflet of the sperm surface lipid bilayer (via trypsin/pronase proteolysis, leads to a significant reduction in the efficacy of epididymosome cargo transfer to the sperm cells (At present, however, the molecular mechanisms underpinning the biogenesis of different populations of epididymosomes, as well as those responsible for their interaction with spermatozoa remain to be established. Recent work has suggested the latter process may be initiated  bilayer . Such do bilayer , 113. Su bilayer . Notably bilayer . Owing t bilayer , these m bilayer  that therm cells . Howeverin vitro (Adding to this controversy is the suggestion that the interaction between epididymosomes and spermatozoa may not involve a complete fusion of their respective membranes . Rather,in vitro . Such inin vitro , thus inThe epididymal milieu is undoubtedly crucial for promoting sperm maturation as well as supporting their storage. Indeed, since sperm are transcriptionally and translationally silent cells, their functional transformation relies entirely on the creation and maintenance of a highly specialized epididymal luminal milieu. The establishment of this unique epididymal microenvironment features the varied endocytotic and exocytotic contributions of the epithelial cells that line the duct. Unfortunately, our understanding of the molecular machinery the epididymal epithelial cells employ to facilitate these processes remains incomplete, as does our knowledge of how these cells are precisely regulated in different segments. Resolving these questions promises to inform our understanding of male fertility regulation with implications for contraceptive intervention and infertility diagnostics.All authors made substantial contributions to the conception of this review and the critical appraisal of the literature summarized herein. WZ generated the initial draft of the manuscript, and this was critically revised by BN, GD, and MD. All authors approved the final version and submission of this article.The authors declare that this manuscript was prepared in the absence of any commercial or financial relationships or activities that could be construed as a potential conflict of interest.


The world of osseointegration has moved forward as a courtesy of the recent technological revolution which has presented itself in many forms, one of which is the introduction of new implant geometries and surfaces which is changing the surgical protocols, making everything easier, faster, and more predictable.In fact, new implant macrotopographies have been introduced aiming to allow clinicians to obtain better and more predictable primary stability, therefore using dental implants as a solution to more challenging cases , with the possibility of anticipating nonconventional loading scenarios of the prosthetic superstructure, with the aim to provide positive patients outcome based on obtaining predictable short- and long-term results. Immediate placement of dental implants in fresh extraction sockets is usually highly appreciated protocol by patients, as it can provide satisfactory restorations at fraction of trauma, time, and cost. Similarly, the possibility of speeding up fitting the prosthetic superstructure is appreciated by patients, because it reduces treatment time and the related costs; in addition, it allows patients to avoid the discomfort and embarrassment of having to use provisional removable dentures during the healing period, with functional and aesthetic benefits.In order to accelerate the bone healing processes, new implant micro- and nanotopographies have been introduced in the market. In fact, new surface treatments allow us to obtain micro- and nano-rough implant surfaces, characterized by a controlled micro- and nanotopography, able to geometrically stimulate and accelerate the bone healing processes: this can effectively enhance osseointegration, reducing healing times. These are important applications, in dentistry, of the tissue engineering concepts.in vitro studies on cell cultures, in vivo animal histologic/histomorphometric studies, in vivo human histologic/histomorphometric studies, and clinical studies) on the effects of new macro-, micro-, and nanotopographies on osseointegration. Finally, we are delighted that this issue includes the first human histologic article in the dental literature, reporting on the 5-year results with an innovative strategy for enhancing aesthetics in implant treatment in the anterior maxilla utilising the root membrane/socket shield technique.In the present thematic special issue, we have gathered several well conducted scientific and clinical papers that examine and describe the above concepts. This thematic special issue features a series of clinical studies on the effects of new implant macrotopographies on the implant stability, survival, and success in the short and long term. Moreover, we have collected a series of scientific articles (Only high quality research and clinical papers have been selected and published in the present thematic special issue. We really hope you will enjoy the reading and find it very interesting.Francesco ManganoHassan MaghairehJosè Calvo-Guirado


Neurodevelopmental disorders (NDDs) include a huge variety of pathologies characterised by varying degrees of intellectual disability and behavioural dysfunction. Research during the last years has underlined the genetic nature of the aetiological factors involved in most NDDs, identifying in some cases  single gene mutations as the unique pathological cause, while determining in others multiple genetic risk factors ). The high interindividual variability in several key pathological aspects of NDDs, such as the severity of the behavioural symptoms and the age-related progression, has motivated researchers to direct their attention to environmental factors that may critically influence the expression of the genetic “determinants” of these pathologies. This research has led to several theoretical models describing the relationships between genetic and environmental insults in NDDs: these models have in turn emphasised the additive or synergistic interactions between genes and environment and increased the interest in better understanding the specific contributions of these interactions in the aetiopathology of NDDs.Gene-environment interactions are obviously of relevance to most disorders of the nervous system but are especially important for developmental pathologies, because of the considerable plasticity of the developing brain and its critical responsiveness to environmental changes. Indeed, a large body of human and animal data has demonstrated that environmental stimulation/deprivation can, respectively, ameliorate or exacerbate the symptoms of many NDDs. Nonetheless, animal studies combining both genetic and environmental manipulations are still scarce, at least compared to the huge amount of research work that concentrates only on genetic effects. This special issue aims to attract attention to the importance of gene-environment interactions, which so far have often been ignored. Review and original research articles are combined to discuss the impact of the interactions between genetic and environmental interventions in both clinical and preclinical studies. A variety of NDDs are included, such as ASDs, schizophrenia, Fragile X, Down syndrome, and ADHD, and a multitude of genetic and environmental manipulations are discussed. Several environmental factors were studied, such as nutritional manipulations, immunological changes, environmental enrichment, stress, or social deprivation. These sometimes implied environmental adversity, but in other cases environmental stimulation, possibly supporting nonpharmacological therapies based on sensory-social or nutritional enrichment.The review by C. Madore et al. investigates the relevance of nutritional factors in the aetiopathology of neurodevelopmental disorders. This article is focused in particular on the role of polyunsaturated fatty acids (PUFAs), because of the association between imbalances in PUFA levels and NDDs. Preclinical and clinical data are summarised, highlighting the anti-inflammatory properties of PUFAs and their impact on the microbiota, which is suggested as the main factor potentially linking inflammation, environmental adversity, and NDDs. P. Moran et al. instead provide a review of preclinical studies on gene-environment interactions in schizophrenia using genetic animal models. This review discusses the synergistic effects of genetic and environmental risk factors on the expression of those endophenotypes that are relevant to schizophrenia, thus supporting the validity of multifactorial preclinical models.μ-opioid receptor gene (Oprm1/−−). Early environmental stimulation of the highly immature mouse pups using an enrichment protocol providing additional maternal care was applied and both short- and long-term behavioural effects of this manipulation were detected. The research article by E. Burrows et al. focuses its attention instead on environmental adversity, evaluating the behavioural effects of social isolation housing in a mouse model for autism, the Neuroligin-3 (NL3) mouse. The data presented here also highlight the importance of the choice of the procedures for behavioural testing in research on genetic models of neurodevelopmental disorders, since the effects of the environmental and genetic manipulations differed depending on the specific social test used.The research article by E. Aronoff et al. provides original clinical data on the therapeutic impact of environmental enrichment in autistic children. Indeed, a therapy based on daily sensory enrichment is shown to ameliorate children's behavioural problems in multiple domains, including cognitive, emotional, social, and sensorial abilities. Interestingly, these effects were largely independent of the subjects' gender, nationality, or initial severity levels of the pathology. The article by L. Garbugino et al. parallels this human study, providing original data on the effects of early enrichment in an animal model of social dysfunction, the KO mouse for the The review by I. De Toma et al. expands the evaluation of the effects of gene-environment interactions in NDDs by assessing the role of epigenetic mechanisms in the aetiopathology of these diseases. The link between global and local epigenetic alterations, such as anomalies in DNA methylation, histone modifications or chromatin remodelling, and developmental disorders, is discussed, with a focus on two examples of developmental pathologies characterised by cognitive impairments, Down syndrome (DS) and Fragile X syndrome (FXS). This article also directly describes therapeutic approaches using epigenetic drugs that can act as cognitive enhancers in DS and FXS.In conclusion, this special issue emphasises the importance of continuing and extending neurobehavioural studies on NDDs combining genetic with environmental manipulations and suggests that a multifactorial approach is most likely to identify novel therapeutic approaches and to advance our understanding of the aetiopathology of these complex disorders.Susanna PietropaoloWim E. CrusioJoram Feldon


Rhizobium bacteria. Additionally, like most vascular flowering plants, legumes are able to form a mutualistic endosymbiosis with arbuscular mycorrhizal (AM) fungi. These beneficial associations can enhance the plant resistance to biotic and abiotic stresses. Understanding how symbiotic interactions influence and increase plant stress tolerance are relevant questions toward maintaining crop yield and food safety in the scope of climate change. Proteomics offers numerous tools for the identification of proteins involved in such responses, allowing the study of sub-cellular localization and turnover regulation, as well as the discovery of post-translational modifications (PTMs). The current work reviews the progress made during the last decades in the field of proteomics applied to the study of the legume-Rhizobium and -AM symbioses, and highlights their influence on the plant responses to pathogens and abiotic stresses. We further discuss future perspectives and new experimental approaches that are likely to have a significant impact on the field including peptidomics, mass spectrometric imaging, and quantitative proteomics.Legume plants are key elements in sustainable agriculture and represent a significant source of plant-based protein for humans and animal feed worldwide. One specific feature of the family is the ability to establish nitrogen-fixing symbiosis with  Glycine max L. Merr.), common bean (Phaseolus vulgaris L.), chickpea (Cicer arietinum L.), lentil (Lens culinaris Medik.), pea (Pisum sativum L.), or alfalfa (Medicago sativa L.). However, given the large size and genome complexity of these major crops, the scientific community has focused its efforts in the development of tools and protocols for other legume plants, commonly referred to as model legumes, namely Medicago truncatula Gaertn. and Lotus japonicus L. For many of these legume species there is genomic sequence information available, which greatly facilitates protein identification using mass spectrometry-based proteomic approaches. Many species within the family are able to establish endosymbiotic relationships with nitrogen-fixing Rhizobium bacteria and arbuscular mycorrhizal (AM) fungi. These symbiotic interactions involve complex signal exchanges between both symbionts and an intimate communication to allow the establishment of the bacteria or fungi inside root cells. These interactions are considered mutualistic associations, with Rhizobium bacteria providing a source of reduced nitrogen inside specialized root organs named nodules, and AM fungi facilitating the capture of important nutrients for the plant such as phosphorous or sulfur, and even improving the plant responses to biotic and abiotic stress conditions  studies focused on the characterization of the legume plant proteome, and (ii) works focused on the er Table . In the i et al.  identifii et al. . FurtherVigna unguiculata, although at the time the lack of genomic sequence information limited protein identification. The availability of expressed sequence tags (ESTs) and, subsequently, genomic sequences of several legume plants have led to greatly improve the number of identified proteins. For instance, the model legume M. truncatula has been subjected to detailed proteomic characterization in terms of symbiotic responses. One of the first studies in nodules identified two leghemoglobin isoforms and one enolase protein as some of the proteins that most accumulated in roots upon inoculation with symbiotic bacteria  and around 80 other abundant membrane or membrane-associated proteins such as the hypersensitive response protein and remorin . The identification of proteins present in this specialized membrane is of key relevance, since it represents the direct interface where nutrient and signal exchange occurs between the legume host plant and r et al.  carried r et al. . In thisRhizobium symbiotic interaction. The reason behind this interest is that a number of protein kinases have been shown essential for rhizobial infection and/or nodule development. These include LysM-domain-containing receptor kinases, implicated in the binding of Nod factors, as well as other membrane receptor-like kinases and calcium/cadmodulin-dependent protein kinases .One of the strengths of mass spectrometry-based proteomic approaches is that it allows the identification of post-translational modification (PTM) sites in proteins, something that cannot be accurately predicted with genomic information alone. PTMs have a huge impact on plant signaling and metabolism, contributing to the regulation of protein activity, stability/degradation, interactions, and ultimately gene expression. In recent years, the number of studies focused on the identification of PTMs in plants has considerable grown  is the most extensively observed association with roots of land plants  varieties with contrasting tolerance to water deficit have shown a relation between plant tolerance to the stress and the abundance of proteins involved in stress signaling and wax biosynthesis in leaves -free and Cd-contaminated substrates. Authors identified nine out of 15 proteins changing under Cd treatment in non-mycorrhizal roots that were not observed in Cd-treated, colonized roots. In shoots Cd induced the accumulation of proteins related to photosynthesis in plants under symbiotic conditions. As a conclusion, when exposed to Cd, symbiotically grown plants partially escaped metal toxicity through a concerted increase in shoot biomass and thanks to allocation plasticity strategies compared to non-symbiotic plants.The plant-AM symbiosis has been shown to have a positive impact on the plant nutritional status, thus, improving growth and crop productivity. In legumes, an overall enhanced tolerance to abiotic stress has been also reported  proteins, Kunitz-type proteinase inhibitors, a lectin, and proteins related to primary carbohydrate metabolism. Interestingly, the induction of these pathogen responses occurred to a lesser extent in plants under mixed infections , which indeed reinforces the idea of the beneficial effects of symbiosis toward pathogenic infections. A similar observation was made when analyzing the leaf proteome and metabolome of pea plants after the co-inoculation with R. leguminosarum and AM fungi, or either of those combined with the pathogenic fungi Didymella pinodes  or even of mass spectrometry spectral identification like ProMEX  offers a tool for the automatic annotation of several legume proteomes including these of M. truncatula, G. max and L. japonicus. One of the strengths of this database is that it allows for the rapid identification of orthologous genes/proteins across different legume species, simplifying the task of tracking down proteins with multiple IDs. Recently, Lotus Base an integral information portal providing genomic, proteomic, and expression resources for the model legume L. japonicus has been also made available  and B. japonicum (157 entries).In terms of databases focused on the microsymbionts, one useful platform is the RhizoGATE (M. truncatula and soybean root nodule proteome in response to drought. Authors found that the nodule proteome in response to stress in grain and forage legumes was very similar, suggesting that proteome research conducted on the model legume might be extended to other economically relevant crop legumes.One major challenge of proteomic data is that the vast amount of information generated is difficult to present in a convenient, accessible way, thus mostly ending up in huge lists of metadata that are difficult to access for further work. Additionally, transfer of knowledge from one organism to another is very restricted; even if protein functions can be estimated based on sequence similarity, their localization and specific responses to stress varies depending on the plant species. One example of such comparative approach can be found in Gil-Quintana et al. , who comA. thaliana (Joshi et al., Taken together, there are several legume-specific proteomic databases available. The development of a platform gathering and allowing the analysis of this proteomic information in legumes, similarly to the MASCP gator for the visualization and extraction of proteomic information in Rhizobium and -AM symbiosis and their interactions with abiotic and biotic stresses. It has become evident that symbiotic interactions have a significant, positive impact on the plant fitness levels, improving their tolerance to stress conditions and pathogen attack. Although, supplementation based on nitrogen fertilizers under optimal conditions may still lead to higher crop yield in global terms, the positive influence of the microsymbiont should be taken into consideration for future breeding programmes, particularly now under the predicted climatic change scenarios.This work reviews some of the most important outcomes of proteomic analysis of the legume-M. truncatula (Ye et al., During the last decade, improvements in terms of speed and accuracy of mass spectrometric instruments has led to about one order of magnitude increase in the amount of high-throughput proteomic data obtained, with the identification of >1,000 different proteins per experiment. However, these improvements have not yet been fully exploited in the field of the legume-microbial symbiosis. There is, for instance, growing interest in extending the work on endogenous plant peptides described to act as signaling molecules and shown to be involved in plant-microbe communication (van de Velde et al., Taking into account the large number of proteins involved in response to abiotic and biotic stresses that have been identified, it is now necessary to integrate and compile this information in an accessible way so that this proteomic data and the numerous potential markers identified are analyzed in terms of their contribution to symbiotic and pathogen signaling, nodule formation and nitrogen-fixation efficiency, as well as in improved stress tolerance. The growing application of CRISPR/Cas9 technology and the availability of mutant lines for several model legumes will most likely contribute to this end. Interactions between plant genomic and proteomic specialists and integration of their techniques are key aspects that need to be strengthened in the future.EL and SW performed the literature review, analysis, drew conclusions, and wrote the article.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The objective of this review is to explore interactions between physicians and the pharmaceutical industry including sales representatives and their impact on physicians’ attitude and prescribing habits.PubMed, Embase, Cochrane Library and Google scholar electronic databases were searched from 1992 to August 2016 using free-text words and medical subject headings relevant to the topic.Studies included cross-sectional studies, cohort studies, randomised trials and survey designs. Studies with narrative reviews, case reports, opinion polls and letters to the editor were excluded from data synthesis.Two reviewers independently extracted the data. Data on study design, study year, country, participant characteristics, setting and number of participants were collected.Pharmaceutical industry and pharmaceutical sales representative (PSR) interactions influence physicians’ attitudes and their prescribing behaviour and increase the number of formulary addition requests for the company’s drug.Physician–pharmaceutical industry and its sales representative’s interactions and acceptance of gifts from the company’s PSRs have been found to affect physicians’ prescribing behaviour and are likely to contribute to irrational prescribing of the company’s drug. Therefore, intervention in the form of policy implementation and education about the implications of these interactions is needed. Large up-to-date systematic review of studies exploring the impact of pharmaceutical industry representative interactions on physicians.This systematic review used the recommendations outlined in the Cochrane Handbook for conducting systematic reviews and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to assess the quality of the evidence by outcome.PubMed, Embase, Cochrane Library and Google Scholar electronic databases were searched from 1992, as well as grey literature.Most studies identified were observational and of varying methodological design.Some studies did not provide evidence for the significance of their findings.The relationship between physicians and the pharmaceutical industry has evoked heated debate for many decades.We followed a detailed methodology that we described in our review protocol, which is available on request to the corresponding author. Two independent reviewers assessed selected articles as per inclusion/exclusion criteria, shortlisted them for writing the review and cross-checked their decisions about inclusion/exclusion with each other. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines .10.1136/bmjopen-2017-016408.supp1types of studies: observational study design, such as cross-sectional studies and cohort studies, but also (non-)randomised trials and survey designs comparing at least one facet that are mentioned below on the impact on behaviour and attitude;types of participants: physicians, pharmaceutical representatives and physicians in training/residents;types of exposure: any type of interaction between physicians and the pharmaceutical industry where there is direct interaction with the physician, such as meeting with drug representatives, participating in pharmaceutical-sponsored Continuing Medical Education (CME) events, receiving travel funding, free drug samples, industry-provided meals, gifts and presentations of industry-related information;types of outcome: knowledge, beliefs and/or attitudes of physicians regarding physician–industry interactions and (prescribing) behaviour of physicians;type of control: no interaction.Exclusion criteria were: qualitative, ecological, econometric studies, editorials, letters to the editor, studies on other health professionals , small samples sizes, studies assessing indirect interactions and research funding.The eligibility criteria were:We did not exclude studies based on risk of bias. We took risk of bias into account when grading the quality of evidence using GRADE approach.The search strategy included PubMed, Embase, Cochrane Library and Google Scholar electronic databases (January 1992 to August 2016). Databases were not searched before 1992, as these studies were already investigated in an earlier review.10.1136/bmjopen-2017-016408.supp2Two reviewers assessed in duplicate and independently the risk of bias in each eligible study. Disagreements were resolved by discussion or adjudication by a third reviewer. We used the recommendations outlined in the Cochrane Handbook to assess the risk of bias in randomised studies. We graded each potential source of bias and rated the studies as high, low or unclear risk of bias.The information extracted from the selected studies included type of study, study design, type of pharmaceutical industry and PSR interaction and type of outcome. We did not conduct a meta-analysis due to the heterogeneity of study design, types of interventions, outcomes assessed and outcome measures used. Instead, we summarised the data narratively. We assessed the quality of evidence by outcome using the GRADE methodology.We independently screened the titles and abstracts of the 2170 identified records for potential eligibility. Out of 2170, the full text of 49 eligible citations that matched the inclusion criteria were retrieved and used for qualitative assessment during the writing of the review , table 1The identified studies were published between 1992 and August 2016. Most of the studies included were cross-sectional studies.We found that PSR interactions are a regular feature in the daily lives of physicians across the world.We found that physicians have a positive attitude towards PSRsMost studies found that physicians do not believe that PSR interactions impact their prescribing behavoir,We found that better scores on knowledge and attitudes were significantly associated with fewer interactions with representatives and their gifts.Most of the physicians who accepted drug samples had a positive attitude towards the pharmaceutical representatives.Sponsored lectures/symposia of pharmaceutical companies influenced behaviour of the attendees leading to the attendees prescribing more drugs from the sponsoring companies without sufficient evidence supporting superiority of those drugs.Physicians who received money to attend pharmaceutical symposia or to perform research requested formulary addition of the company’s drug more often than other physicians. This association was independent of many confounding factorsPharmaceutical company-sponsored conference travels to touristic locations have quantifiable impact on the prescribing rational of attendees. A significant increase (three times) in the prescribing rate of two company drugs was observed after the physicians attended a company-sponsored symposium with all their expenses covered. Despite this significant difference in the prescribing patterns, physicians insisted there was no impact on their prescribing behaviour.Most physicians received invitations for dinnersPhysicians who attended company-sponsored CME events had more positive attitudes towards and inclination to prescribe the branded drugs.We report that there is widespread interaction between the pharmaceutical industry and physicians.The relationship of physicians with patients is of a fiduciary nature. Hence, activities that might affect that relationship by altering physicians’ clinical behaviour are not acceptable. Physician–pharmaceutical industry and PSR interactions may put the trust of patients in physicians at risk. Interaction with pharmaceutical industry and PSRs begins early in the physicians’ career. Trainees are exposed to pharmaceutical industry marketing and promotional techniques from the initial years of their medical education, which impact their prescribing behaviour in future. Overall, trainees, that is, residents and interns, are more vulnerable to pharmaceutical industry and PSR interactions than senior physiciansA major strength of this study is that it is a large, up-to-date systematic review of studies exploring the effects of physician and pharmaceutical industry representative interactions and residents in different settings . Another strength of this study is the use of Cochrane and GRADE methodologies for conducting a review and assessing the quality of the studies. Moreover, we performed an extensive search in three databases and the grey literature. Some of the limitations of this review are related to the included studies, as some did not provide evidence for the significance of their findings or had varying study designs and outcomes, which made it impossible to conduct a meta-analysis. Also, the included studies were subject to risk of bias related to the lack of validity of outcome measurement and inadequate handling of significant potential confounders.Pharmaceutical industry and PSR interactions compromise the objectivity of the physicians. Educating physicians and increasing regulation of pharmaceutical industry and PSR interactions may lower the likelihood of prescribing new non-superior industry drugs and irrational prescription behaviour. Further studies are required to evaluate the impact of pharmaceutical industry and PSR interactions on physicians over time and the benefits of various intervention-based education programmes on the clinical and ethical behaviour of the physicians.


For decades of biomedical research, scientists have been enchanted by, and relentlessly hunted for, powers of modifying the inheritable genomic information in particular cell types or in living organisms. Such technological capabilities, generally known as gene- or genome-editing, hold great promises for both scientific research and medicine. Indeed, the discovery of restriction enzymes in 1960s has led to the birth of recombinant DNA technique and the bloom of modern biotechnology, and the development of TALEN and CRISPR systems in the past few years have launched the new era of genome-editing research and raised the hope for therapeutic applications.Despite such exciting achievements we have witnessed, enormous challenges still remain for further advances of genome-editing techniques, in particular, to enhance the editing efficiency and to eliminate the off-target events. In May 2016, Gao et al. reported that an archaebacterium-derived DNA nuclease named NgAgo could precisely recognize and efficiently edit the genomic DNA of mammalian cells in a DNA oligonucleotide-guided manner. Given the researchers’ desire for new genome-editing tools, it is not unexpected that this report has drawn immediate attentions and generated broad enthusiasms in the scientific community. For instance, it was suggested that NgAgo could perform as an important, or an even superior alternative to the CRISPR system whose editing process is guided by a short sequence of RNA instead of DNA.Protein & Cell has decided to publish in this issue a scientific letter, jointly composed by 20 independent research groups from different institutions worldwide, that refutes the initial report by Gao et al. In this letter, the authors show that NgAgo exhibits little, if any, editing activities towards the genomic DNA of mammalian cells under a range of experimental conditions. Protein & Cell notes that, although this controversy of NgAgo technique has been fermenting for months, most of criticisms were not presented in formal and scholarly manners, particularly, in a peer-reviewed scientific journal, which has significantly limited the research community from assessing the dueling claims from the two sides. The editors, therefore, believe and wish that publication of this collection of contradicting results could set off the momentum in the research community to scrutinize the potentials of NgAgo, and to venture forwards to further expanding the toolbox of genome-editing technique.However, as a bitter twist of the initial excitements, concerns of the reproducibility of NgAgo genome-editing technique have been accumulating in the past few months. Criticisms that NgAgo did not work in genome-editing experiments as originally reported can be found on many online scientific forums. Also, researchers have begun to discuss, openly or in private, their failures to reproduce the key findings of Gao et al. With this ongoing controversy of NgAgo genome-editing technique,


This paper presents an EEG-based brain-computer interface system for classifying eleven motor imagery (MI) tasks within the same hand. The proposed system utilizes the Choi-Williams time-frequency distribution (CWD) to construct a time-frequency representation (TFR) of the EEG signals. The constructed TFR is used to extract five categories of time-frequency features (TFFs). The TFFs are processed using a hierarchical classification model to identify the MI task encapsulated within the EEG signals. To evaluate the performance of the proposed approach, EEG data were recorded for eighteen intact subjects and four amputated subjects while imagining to perform each of the eleven hand MI tasks. Two performance evaluation analyses, namely channel- and TFF-based analyses, are conducted to identify the best subset of EEG channels and the TFFs category, respectively, that enable the highest classification accuracy between the MI tasks. In each evaluation analysis, the hierarchical classification model is trained using two training procedures, namely subject-dependent and subject-independent procedures. These two training procedures quantify the capability of the proposed approach to capture both intra- and inter-personal variations in the EEG signals for different MI tasks within the same hand. The results demonstrate the efficacy of the approach for classifying the MI tasks within the same hand. In particular, the classification accuracies obtained for the intact and amputated subjects are as high as  Nowadays, many individuals are suffering from hand motor impairments due to strokes, hand amputations, and spinal cord injuries. Developing a system that can recover a significant part of the lost or disabled hand functionality is crucial to improve the quality of life of those individuals. Recently, we have witnessed substantial advancements in designing and developing wearable assistive devices, such as robotic prosthetic hands and exoskeletal orthotic hands. These assistive devices can be of great benefit for individuals who are cognitively intact and suffering from motor impairments. In particular, an individual with amputated hand can utilize a prosthetic hand to recover part of the missing hand functionality . MoreoveBCI systems translate the neural signals of the human brain into control commands for peripheral and assistive devices, which in turn can improve the communication capabilities of the individuals who suffer from severe motor impairments. Several noninvasive neuroimaging modalities have been utilized in BCI systems, such as functional magnetic resonance imaging (fMRI) , electroOver the past two decades, motor imagery (MI) has been used to design EEG-based BCI systems that enable individuals with motor impairments to control various assistive devices, such as wheelchairs ,17, prosLiterature reveals that the vast majority of the existing MI EEG-based BCI systems were focused on differentiating between MI tasks that are associated with four different body parts ,25,26,27Recently, a few studies have been reported to utilize EEG signals in order to discriminate between flexion/extension movements of the fingers ,33 as weThe aim of the current study is to contribute to the ongoing research in the field of EEG signal analysis by introducing an EEG-based BCI system that employs an extracted set of time-frequency features (TFFs) to discriminate between eleven MI tasks within the same hand. In fact, we hypothesize that the use of time-frequency distribution (TFD) as joint time-frequency representation of EEG signals enables the extraction of salient TFFs that comprise discriminative information about different MI tasks within the same hand. The MI tasks considered in the present study range from basic wrist and fingers tasks, such as flexion/extension tasks, to complex hand tasks, such as functional grasping tasks. This diverse set of MI tasks makes the problem of classifying the MI tasks challenging, due to the substantial inter- and intra-personal variations of the EEG signals associated with different MI tasks.In order to discriminate between the EEG signals associated with the eleven MI tasks, a sliding window approach is employed to decompose each EEG signal into overlapping segments. Then, we utilize the Choi-Williams TFD (CWD) to construct a time-frequency representation of the EEG segments that can describe the dynamic changes in the EEG signals during different MI tasks. Using the time-frequency representation, we extract five categories of TFFs, including log-amplitude-based category, amplitude-based category, statistical-based category, spectral-based category, and spectral entropy-based category. The extracted TFFs are utilized to construct a hierarchical classification model that classifies each EEG segment into one of the eleven MI tasks considered in this study. Specifically, the hierarchical classification model consists of four layers. The first layer classifies the EEG segments into rest or movement segments. In the second layer, the EEG segments that were identified as movement segments at the first layer are further classified into functional or basic wrist and finger movements. The third layer classifies the EEG segments that comprise functional movements into small diameter grasp, lateral grasp, and extension-type grasp, and the EEG segments that comprise basic wrist and fingers movements into wrist-related movements and finger-related movements. Finally, the fourth layer classifies the EEG segments that comprise wrist-related movements into wrist flexion/extension, wrist ulnar/radial, and the EEG segments that comprise finger-related movements into index flexion/extension, middle flexion/extension, ring flexion/extension, little flexion/extension, and thumb flexion/extension.In order to evaluate the performance of the proposed approach, we have recorded EEG data for both intact and amputated subjects while imagining to perform the eleven hand MI tasks. Two performance evaluation analyses are conducted to evaluate the performance of the proposed TFD-based approach in identifying the eleven different MI tasks. The two performance evaluation analyses are: the channel-based performance evaluation analysis and the TFF-based performance evaluation analysis. These performance evaluation analyses quantify the effect of the utilized EEG channel locations and TFFs on the capability of the proposed system to decode different MI tasks within the same hand. Furthermore, within each evaluation analysis, the hierarchial classification model is trained using two different procedures, namely subject-dependent and subject-independent training procedures. These two training procedures measure the ability of the proposed TFD-based system to capture both intra- and inter-personal variations of the EEG signals for different MI tasks within the same hand. To the best of our knowledge, this is the first study that explores the use of TFD for classifying MI tasks within the same hand for both intact and amputated subjects.The remainder of this paper is organized as follows: In The EEG dataset employed in the current study is composed of two databases, namely The experimental procedure adopted in the current study is similar to the experimental procedures employed in several previous studies related to EEG-based MI tasks classification, such as ,34,35,36The experimental procedure consists of a training phase and recording phase. In the training phase, each subject was asked to watch a set of videos displaying each of the movements depicted in Raw EEG data was acquired using the Biosemi ActiveTwo EEG recording system . The Biosemi ActiveTwo system employs the 10–20 international EEG electrode placement system to localize 16 Ag/AgCl electrodes at the following locations: Fp1, Fp2, C3, C4, Cz, F3, F4, Fz, T7, T8, O1, O2, Oz, P3, P4, and Pz, referenced to the common mode sense (CMS)/ driven right leg (DRL) at C1/C2 locations for noise cancelation see . In thisThe EEG signals were acquired at a sampling frequency of 2048 Hz. The acquired signals were filtered using a band pass filter with a bandwidth of 0.5–35 Hz to reduce low-frequency noise  and ensuThe non-stationary nature of the EEG signals implies that the frequency contents of the EEG signals are rapidly changing over time . This imW and N represent the number of time-domain samples of W and N are set to 256 and 512, respectively.In this study, we propose a time-frequency representation for analyzing EEG signals that is based on computing the time-frequency distribution (TFD) of the EEG signals. Specifically, TFD can be viewed as a transformation that maps the EEG signals from the one-dimensional time-domain into a two-dimensional time-frequency plane (TFP), which allows capturing the spectral changes in the EEG signals occurring over time . In ordeentation ,45,46. S follows :(1)sx(t)ransform . The timn, Cohen ,45 provi follows ,45:(3)AFthe TFDs . When thon (WVD) . The WVDon (WVD) . Therefoon (WVD)  in orderon (WVD) ,43. The on (WVD) :(4)ψTF2=1This category of features consists of the mean  . The nor of TF11 ,56,57. T of TF12 . In thisAs indicated by Edelman et al. , the EEGTo address this limitation, we propose a four-layer hierarchical classification model to classify each EEG segment into one of the eleven HMITs considered in our study. The four-layers in our classification model convert the original complex classification task  into a sequence of simpler classification tasks that are performed at each layer. In particular, the first layer consists of a classification node, namely n is the number of classes. In particular, for In this study, the input to the hierarchical classification model is a feature vector that consists of the TFFs extracted from the CWD computed for an EEG segment. Moreover, the classification nodes in the four layers are implemented using support vector machine (SVM) classifiers with radial basis function (RBF) kernel ,62. Preve scheme ,66, in wC for each classification node. In the first direction, we vary the value of the parameter C. Then, the best SVM model is selected such that its parameters maximize the average classification accuracy.The performance of the SVM classifier with RBF kernel depends on the selected values of the RBF kernel parameter Procedure  to constrocedure . This prIn this section, we present the performance evaluation results of the proposed approach for the channel-based and TFF-based evaluation analyses obtained for the intact and amputated subjects using the SDTP and SITP.In this section, we evaluate the performance of the proposed approach based on In p values for p values for p values, for both SDTP and SITP, demonstrate that the performance of the classification nodes achieved based on the TFFs extracted from the EEG channels of To compare between the performance of the proposed approach using each group of EEG channels, we have conducted paired t-tests with significance level of In p values for p values for p values, for both SDTP and SITP, indicate that the performance of the classification nodes based on the TFF of To compare the performance of the proposed approach obtained using each of the five TFFs categories, we have conducted paired t-tests with significance level of In this section, we evaluate the performance of the proposed approach based on the acquired EEG signals of the amputated subjects recruited in In p values for p values for p values, for both SDTP and SITP, demonstrate that the performance of the classification nodes based on the TFFs that are extracted from the EEG channels of To evaluate the performance of the proposed approach using each group of EEG channels, we have conducted paired t-tests with significance level of The SDTP results reported in p values computed for p values computed for p values calculated for the SDTP and SITP indicate that the performance of the classification nodes based on the TFF of To evaluate the performance of the proposed approach obtained using the five categories of TFFs, we have conducted paired t-tests with significance level of This study aims to investigate the feasibility of using the CWD, which enables the extraction of TFFs from the EEG signals, along with a hierarchical classification model to discriminate between eleven HMITs, including: rest, basic finger and wrist movements, and grasping and functional movements. The results demonstrate that our proposed approach can classify the eleven HMITs and achieve promising performance in both subject-dependent and subject-independent evaluation scenarios.In order to study the effect of the utilized different EEG channels on the capability of the proposed approach to classify the eleven HMITs, channel-based analyses were carried out using four groups of EEG channels that overlay the motor cortex regions in the brain. The results of the channel-based analyses for both intact and amputated subjects, which are provided in The TFF-based analyses aimed to investigate the effect of utilizing different categories of TFFs on the classification accuracy of the eleven HMITs. Furthermore, the results of the TFF-based analyses indicate that the proposed approach is significantly degraded for the SITP compared to the SDTP. This is mainly due to the large variations in the EEG signals of various HMITs across different subjects. Despite the reduction in the accuracies, the performance of the proposed approach based on the SITP is still significantly higher than the average random classification accuracy, which suggests the feasibility of applying the proposed approach to optimize the number of training sessions required to control neural prosthetic devices.Literature reveals that the majority of the existing studies have focused on classifying MI tasks associated with different limbs, such as feet, right hand, and left hand . DespiteRecently, few studies have investigated the possibility of applying EEG signal analysis to classify different MI tasks and actual movements within the same hand. In this vein, few researchers have investigated the possibility of decoding actual movements performed by each finger in one hand using EEG signals. For example, Liao et al.  proposedented in , our proIn another related study, Quandt et al.  proposedt et al. , Figure ented in , taking Other groups of researchers focused on investigating the possibility of classifying different wrist MI movements within the same hand using EEG signals. In this vein, Vuckovic and Sepulveda  developen et al.  utilizedIn comparison with the studies presented in ,9, for tIn another study, Yong and Menon  proposedIn this paper, we investigated the capability for decoding eleven MI tasks within the same hand using EEG signals. In particular, the CWD was employed to extract a set of TFFs from the EEG signals. The extracted TFFs are processed using a four-layer hierarchical classification model to classify each EEG segment into one of the eleven MI tasks. Two different performance evaluation analyses were conducted to quantify the effect of utilizing different combinations of EEG channels and TFFs on the capability of the proposed approach to decode MI tasks within the same hand. These performance evaluation analyses were applied to the EEG signals obtained from eighteen intact subjects and four amputated subjects. For the intact subjects, the results of the channel-based and TFF-based analyses show that the proposed system achieved average accuracies of Although the main goal of our proposed approach is to investigate the possibility of classifying MI tasks within the same hand using EEG signals, the current study did not consider the problem of describing the kinematic information of the MI tasks based on EEG signals. The kinematic information of the hand’s joints, such as the fingers and wrist joint angles, is important to effectively control the prosthetic hand in performing dexterous tasks. Therefore, we believe that combining the MI tasks classification, which is considered in the current study, and the hand kinematic information, which we plan to investigate in the near future, would enable better real-time control of prosthetic hands. Moreover, our future research directions include comparing the performance of our proposed approach in recognizing different MI tasks based on EEG signals that are acquired from closed-eyes subjects with the performance achieved when the eyes are open. Such a comparison can be of great benefit to assess the performance of real-world applications that involve subjects controlling prosthetic hands while their eyes are open.