Pseudomonas aeruginosa. We also briefly describe the challenges and limitations of the technique and conclude with a summary of future prospects for the field.Bacterial quorum sensing systems regulate the production of an ample variety of bioactive extracellular compounds that are involved in interspecies microbial interactions and in the interplay between the microbes and their hosts. The development of new approaches for enabling chemical detection of such cellular activities is important in order to gain new insight into their function and biological significance. In recent years, surface-enhanced Raman scattering (SERS) spectroscopy has emerged as an ultrasensitive analytical tool employing rationally designed plasmonic nanostructured substrates. This review highlights recent advances of SERS spectroscopy for label-free detection and imaging of quorum sensing-regulated processes in the human opportunistic pathogen  During their growth, bacteria secrete a large repertoire of chemical compounds that can function in the environment as signaling molecules, cues, virulence factors and agents of microbial warfare  systems  patients. Significantly, the number of multi-drug and pan-drug resistant strains of this pathogen is increasing worldwide, complicating therapeutics  and worse disease outcomes  spectroscopy is an analytical tool that combines the molecular specific information provided by Raman scattering with the signal-enhancing power of plasmonic nanostructures. Through SERS it is possible to harness chemical information of biomolecules without the need of any external labeling , as well as non-invasive analysis of biological samples and imaging of cells  excitation, which occurs when conduction electrons collectively oscillate in resonance with the frequency of incident light Figure . This inNanoparticles of noble metals, su ch as gold and silver, are optical enhancers of choice in SERS because they resonantly scatter and absorb light in the visible and near-infrared spectral region upon excitation Figure . The plain vivo applications. Gold is more chemically inert and robust, and offers better control of its particle size and shape, thereby enabling a wider range of synthetic possibilities, as well as its significantly higher biocompatibility. This is fundamental, since size, shape, composition and stability should be carefully controlled in order to achieve sensitive and reproducible SERS detection. It has been known for a long time that nanoparticle aggregates exhibit larger Raman signal enhancements than individual nanoparticles. This is due to the generation of hot spots within the interparticle gaps. Remarkably, the electromagnetic field enhancement in hot spots is highly sensitive to the detailed local structure and nature of nanoparticle assemblies . The first one involves plasmonic colloids, which are mixed with the sample and the SERS spectra are recorded upon aggregation of nanoparticles. The second approach entails the use of plasmonic platforms based on assemblies of plasmonic nanoparticles and plasmonic patterns over a surface , which offers the possibility to control nanoparticle clustering and the topological parameters of hot spots, leading to improved sensitivity and reproducibility of the SERS measurements. In Figure Different parameters such as the excitation laser wavelength and the microscope objective are important aspects that may be considered during SERS. The choice of the excitation laser line depends on the analyte and the optical properties of the plasmonic material. Regarding the analyte, an excitation laser wavelength overlapping or being very close to an electronic transition of the molecule is preferred so as to measure under SERRS conditions. Regarding the plasmonic material, it is important to consider an appropriate wavelength source to enable efficient excitation of the surface plasmons. For nanoparticle suspensions it is predicted that maximum SERS signal can be obtained when the plasmon frequency is tuned to be slightly red-shifted from the laser wavelength. For hot-spot containing plasmonic materials it has been demonstrated that depending on symmetry effects and differences in plasmonic coupling strength the highest SERS intensity could be independent of the excitation source  are employed as signaling molecules for many Gram-negative bacteria and have become a paradigm for bacteria intercellular signaling , has been successfully applied in a multimodal chemical imaging approach to evaluate the spatial distribution of quinolone QS molecules across P. aeruginosa biofilms throughout various states of organization  poly N-isopropylacrylamide (pNIPAM) hydrogel doped with gold nanorods (Au@pNIPAM), (2) mesoestructured Au@TiO2 thin film over a layer of gold nanospheres, and (3) micropatterned Au@SiO2 supercrystal arrays comprising gold nanorods assembled in micrometer-sized pedestal-like structures coated with a mesoporous silica thin layer. In their study, the authors focused on pyocyanin, a heterocyclic nitrogen containing metabolite that is regulated by QS. Pyocyanin functions as an intercellular signaling molecule in the QS network of P. aeruginosa   in complex biological environments still represents a significant challenge. One of these limitations is related to the intrinsic complexity of the biological matrix that may prevent the interaction of the target analyte with the metallic surface. In turn, this would hinder analysis by SERS, as other molecular species interacting with the metal would increase background signal . In a recent work Bodelón and coworkers developed an approach for label-free SERS detection and imaging of pyocyanin, as a proxy of QS in live biofilm communities of P. aeruginosa culture supernatants, achieving limits of detection (LOD) ranging from 10−10 M for Au@pNIPAM hydrogel, 10−9 M for mesoporous Au@TiO2 thin film and 10−14 M for the micropatterned mesoporous Au@SiO2 substrate. Interestingly, the hybrid plasmonic substrates were shown to facilitate in situ SERRS detection of pyocyanin produced by biofilms and small cellular aggregates of P. aeruginosa grown in droplets, and yielded spatially resolved 2D maps of the QS molecule with high spatial resolution. The Au@pNIPAM hydrogel, devised as a highly porous platform with enhanced diffusivity, led to plasmonic detection of pyocyanin throughout the growth of the colony-biofilm , the Au@SiO2 supercrystal platform enabled ultrasensitive SERRS detection of pyocyanin in low-density bacterial cultures at early stages of biofilm development, and imaging of bacterial communication triggered by small clusters of cells colonizing the micrometer-sized plasmonic features  substrates  that are involved in the production of pyocyanin , as opposed to strains deficient in the biosynthesis of this phenazine , compromised the growth of CV026. Therefore, this experimental evidence indicated that pyocyanin exerted a toxic effect to C. violaceum. As stated by the authors, although PA14 and CV026 bacteria can initially coexist, P. aeruginosa eventually overgrows C. violaceum, reducing the viability of its partner in extended co-cultures. In view of these results, it was suggested that the promiscuous CviR transcriptional receptor of CV026 can sense C4-AHLs produced by PA14 bacteria producing violacein, which in turn may contribute to pyocyanin down-regulation. This hypothesis points toward a potential defensive mechanism of C. violaceum CV026 in the chemical interplay between the bacterial species. This study illustrates the potential of SERS for non-invasive chemical analysis of microbial interactions on agar, which is the standard support matrix for culturing microbial cells, enabling to visualize the expression of two microbial metabolites in the co-culture taking place as a result of QS interspecies communication. In the context of polymicrobial diseases, similar SERS-based approaches could be applied for studying clinically relevant interactions between P. aeruginosa and other microbial species such as S. aureus, Burkholderia spp, C. albicans, etc.Notably, quantitative PCR analysis of gene expression indicated that the decreased levels of pyocyanin were, at least in part, due to the repression of the P. aeruginosa is a versatile bacterium that has evolved a set of regulatory mechanisms to adapt to nutritional changes and thrive in hostile environments. Recent studies have shown that carbon source has a high impact on bacterial QS signaling, virulence, biofilm formation and pyocyanin production  bearing a hexa-histidine tag and a cysteine in its carboxyl-terminus was expressed and affinity-purified in a soluble, ligand-free active form. By chemical crosslinking of purified LasRLBD with disuccinimidyl suberate (DSS) authors demonstrated the presence of dimeric complexes of LasRLBD at similar levels regardless of the presence or absence of its cognate C12-AHL ligand. This indicates that the polypeptide can exist in the form of homodimers even when it is expressed in the absence of cognate signal molecules , the origin of the SERS signal must be unequivocally ascertained by the use of mutant strains deficient in the production of the biological compound.As discussed above, SERS measurements are greatly influenced by the affinity between biomolecules and the metal surface, thereby label-free SERS analysis of target analytes in biological samples  may be dominated by vibrational bands originating from other “contaminating” biomolecular species, which may lead to complex SERS spectra. In this context, the Raman spectrum of the cell and the extracellular medium is characterized by many different vibrational modes of biomolecules, including nucleic acids, proteins, lipids, and carbohydrates, representing a complete biomolecular profile, making the interpretation of the SERS spectrum a challenge for most adsorbates. In order to maximally exploit the capabilities of SERS in microbiology for in situ measurements of living organisms  by SERS requires plasmonic devices that will have to withstand high ionic strength conditions, which may produce detrimental outcomes. Other significant issues are related with homogeneity and reproducibility of the SERS signal within the plasmonic substrate. They consist in the difficulty to generate uniform distributed enhancement factors, occurring only at localized positions  and the polydispersity of SERS-active colloidal clusters, which may hamper quantitative analysis. Although SERS often requires optimization of the plasmonic sensing system for each target analyte, new approaches have been developed to overcome these limitations and produce SERS-active substrates with high sensitivity, stability and reproducibility. The engineering of hot-spots and plasmonic supercrystals may circumvent some of the aforementioned problems (Shiohara et al., The main challenge to obtain reliable SERS measurements is represented by the performance of the plasmonic substrates. For analytical applications, the preparation of these structures has to be straightforward and reproducible, while at the same time the signal enhancement has to be homogenous. SERS may suffer from issues related to substrate degradation that results in signal decrease over time. For instance, P. aeruginosa, such as detection and quantification of QS signaling molecules, chemical analysis of biofilm formation, in situ imaging of QS-regulated metabolites, as well as the use of SERS as a potential tool for screening protein-ligand interactions. In spite some limitations and challenges that still must be overcome, this highly versatile technique offers great potential for the study of extracellular metabolites and other secreted factors produced by microbial populations. The ability to visualize these chemical substances is fundamental to provide new knowledge into their function, as well as the spatiotemporal dependencies required for the chemical interactions shaping microbial communities. In this context, revealing the extensive intercellular signaling potential of bacteria, and other microbial species, can prove breeding ground to yield valuable ecological insight and drug prospecting.Herein we have presented some recent applications of SERS spectroscopy for assessing QS in in situ characterization, applications for which SERS excels. In this framework, SERS is already being implemented in lab-on-a-chip and nano/microfluidics technologies for sensing in nanoliter volumes (Jahn et al., With the prevalence of multidrug resistant bacteria, new antibiotics and therapeutic approaches are urgently needed. Specifically, the capacity of SERS to non-invasively study microbial populations may open new avenues for understanding QS and for the development of new therapies targeting this form of bacterial communication. Microorganisms represent a depository for natural-product discovery, many of which have been shown to be under QS regulation. Holistic approaches for the cultivation of microorganisms are being actively investigated in the search for new antimicrobials and for the development of bioactive substances that can function as antitumor agents, immunosuppressants or cholesterol lowering agents to name just a few (Nai and Meyer, The advancements in nanotechnology and photonics have dramatically incremented the capabilities of SERS, by which this analytical tool is increasingly being adopted in microbiology studies for very diverse applications, including the sensitive detection of pathogenic bacteria (Liu et al., GB and IP-S conceived and wrote most of the work. VM-G and JP-J participated in the writing of the Raman scattering and SERS spectroscopy section. All listed authors actively contributed in the revision 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.


Aortic dissection (AD) represents a clinically uncommon aortic pathology which predicts a dismal prognosis if not promptly treated. In acute Debakey type I AD (ADIAD), aortic lesion extends from aortic root to even distal abdominal aorta among which aortic arch and its three main branches still remain a great surgical challenge for repair and reconstruction. Several decades have witnessed the painstaking efforts of cardiovascular surgeons across the globe for optimizing the surgical procedures, from total or hemi-arch replacement, “elephant trunk” technique to branched stent graft. However, operative mortality and morbidity still remain to be reduced and surgical strategy is to be advanced and simplified, particularly the repair and reconstruction of aortic arch and supra-aortic vessels.In this paper, we reviewed the relevant literature concerning recent advances in surgical intervention of aortic arch and summarized our opinions in the application of branched stent graft in ADIAD.The operative strategy for acute Debakey type I aortic dissection still remain to be advanced and simplified, especially the repair and reconstruction of aortic arch and supra-aortic vessels. For selection of branched stent grafts, the anatomic features and pathological changes of diseased arch are the crucial factors for clinical decision making.Branched stent graft is potentially an effective alternative for the treatment of type I AD with diseased aortic arch and supra-aortic vessels. The selection of branched stent grafts still remains to be further discussed in large-scale studies in the future. Aortic dissection (AD) is widely appreciated to be a catastrophic clinical event characteristic of intimal tear of aorta triggering influx of blood into the layers of aortic wall and denudation of the layers . The disUrgent or elective surgical intervention is indicated by principle for acute Debakey type I AD (ADIAD), for the purpose of repair and reconstruction of the impaired aorta and aortic valve in time . The verThe primary purpose of this paper was to summarize recent advancements in surgical repair and reconstruction of aortic arch in ADIAD and in the meantime, share our experience of single-center concerning the application of branched stent graft in ADIAD.The operative principle for ADIAD lies in: 1) resection of the aortic wall where the intimal tear situates or occlusion of intimal tear; 2) implantation of befitting artificial blood vessels; 3) restoration of blood flow of true lumen; 4) repair or replacement of aortic valve and transplantation of coronary artery if necessary . SpecifiHemi-arch replacement is indicated for patients in which the intimal flap is restricted to the ascending aorta and the aortic arch has a diameter in the normal range without distal malperfusion. The procedure is literally described as the resection of ascending aorta and elimination of, in the greater curvature the aortic arch wall to the orifice of innominate artery, and in the lesser curvature the wall as much as possible . Hemi-arThe indication of total-arch replacement for ADIAD includes: 1) extensive intimal tear in aortic arch, especially the involvement of supra-aortic orifices; and 2) aortic expansion. The Canadian Thoracic Aortic Collaborate (CTAC) recommends that an arch with a diameter of more than 45 mm should be given consideration for total-arch replacement. It is also recommended in ADIAD patients at younger age or with connective tissue disorders. Classical total-arch replacement comprises of two main types . The firAs early as the year of 1983, Borst and his colleagues have first proposed to implant an artificial blood vessel into the aneurysm lumen in the proximal descending aorta through the incision of aortic arch-soft elephant trunk technique-in order to isolate the aneurysm lumen, reinforce the aortic wall and simplify the anastomosis of second-stage operation of distal descending aorta . HoweverIn 2006, Herold et al. described an E-vita open hybrid prosthesis made out of a proximal polyester tube graft and a distal self-expandable nitinol stent graft –28. ReceNearly from the year of 2010 to date, Chen and his colleagues have consecutively reported the application of the triple-branched stent graft in the treatment of ADIAD and also the improved version of the stented grafts. The triple-branched stent graft includes a main graft and three sidearms with different diameters which consist of the self-expanding nitinol stent covered with polyester fabric. The proximal part of the main graft is a stent-free Dacron tube previously designed for anastomosis. The triple-branched stent graft can be inserted into the true lumen of aortic arch and descending aorta under direct vision with the aid of a transverse incision of distal ascending aorta , 30, 31.To resolve this issue, Chen and his team reported the updated version of the stented graft-the self-adaptive triple-branched stent graft. Its main differences with the first generation lies in that the proximal portion of the main graft is stent-free, the distance between two neighboring sidearms was larger than that between two neighboring supra-aortic vessels of Chinese patients, and the diameter of main tube is bigger than normal ranges of Chinese ethnicity. The second generation of stented graft was positioned with the help of an arch longitudinal incision, after which an independent arch stent was placed in the proximal portion of the main graft. Due to the soft fabric of the proximal main tube, the prosthesis can easily fit the anatomic features of different patients , 32.Not confined to the triple-branched stent graft, the stented grafts with one or two branches for supra-aortic vessels are also available for clinical application in ADIAD , 26. HowCompared to “the frozen elephant trunk” technique, implantation of branched stent comprises the advantages that include: 1) greatly simplifying the surgery in comparison with the complicated and sophisticated surgical skills challenging for cardiovascular surgeons to handle in the “the frozen elephant trunk” (such as bleeding control and anastomosis); 2) reducing the operation time, particularly the time course of circulatory arrest; 3) avoiding the potential damage of recurrent laryngeal nerve that may occur in the operation.Despite the refinements in surgical and perfusion techniques over several decades, the incidence of cerebral injury remain high in the surgery of the aortic arch contemporarily with the approaches that include hypothermia and antegrade and/or retrograde cerebral perfusion. Galvin and his team have recently highlighted the application of“branch-first” continuous perfusion aortic arch replacement in ADIAD for the purpose of improved cerebral outcomes in particular. The graft is essentially a modified triple-branched Dacron graft that harbors an additional limb for antegrade cerebral perfusion after each branch vessel anastomosis. Thus this feature saves the need for right axillary cannulation to sustain the blood supply for brain. In the process of“branch-first” aortic reconstruction, the innominate artery, left common carotid artery and left subclavian artery were connected to the branches of trifurcated graft in sequence and the blood perfusion is resumed after the completion of anastomosis of each vessels. Then the anastomosis of arch graft to the distal aorta finishes and connection of the trifurcated graft to the ascending graft continues without the interruption of perfusion –36.From 2011 to 2015, 46 consecutive patients with ADIAD were recruited from the Department of Cardiovascular Surgery of the Provincial Hospital Affiliated Shandong University, and were hospitalized for implantation of branched stent graft. Amongst these patients, 32 were male and 14 were female, with an average age of 48 . Among these patients, 40, 5 and 1 patients received the implantation of one-, triple- and two-branched stent graft, respectively. The patient characteristics and perioperative data were summarized in the Table A median sternotomy was performed under general anesthesia and total cardiopulmonary bypass (CPB) was established by positioning an arterial cannula in the right axillary artery and two venous cannulas through right atrium. After carefully dissecting the ascending aorta, aortic arch and supra-arch vessels, a longitudinal incision was performed subsequent to the clamping of the ascending aorta. The cold blood cardioplegia was used by perfusion through the left and right coronary arteries for myocardial protection. Repair and reconstruction of the aortic arch was performed under profound hypothermic, circulatory arrest and selective antegrade cerebral perfusion. During the core cooling, concomitant cardiac procedures were performed if necessary, such as aortic valve repair or replacement, sinus reconstruction, and root replacement.The patients were cooled till the nasopharyngeal temperature dropped to 15 °C. Then the systemic circulation was arrested and selective anterograde cerebral perfusion via the right axillary artery was established by clamping the innominate artery. The clamping of the ascending aorta was subsequently removed and the aortic arch was opened with the incision from the ascending aorta to the base of innominate artery. The location and extent of intimal tear and dissection in aortic arch, supra-aortic vessels and proximal descending aorta were explored in order to determine the choice of branched stent graft  the diameter and curvature of the arch; B) the diameters of arch vessels; C) the distance between arch vessels; and D) the angles between arch and arch vessels Fig. . For insAnother key factor for branched stent graft implantation relies on the situations of pathological changes of diseased aortic arch. We recommend not to implant the branched stent graft under the circumstances of the aortic lesions below: A) aortic aneurysm in aortic arch, supra-arch vessels or proximal descending aorta; B) evident dilation or widening of aortic arch, supra-arch vessels or proximal descending aorta; C) obvious edema, ischemia and degeneration of aortic arch, supra-arch vessels or proximal descending aorta; D) concomitant carotid artery or subclavian artery disease.On the premise of (1) and (2):Compared to triple- and one-branched stented graft, two-branched stented graft has seldomly been reported in retrospective observational studies and we once used a trimmed triple-branched stent graft (with the branch for innominate artery cut off) as an alternative. We proposed that two-branched stented graft could be applied in the cases in which the intimal tear is situated in the opening of innominate artery whereas no intimal tear is found in the other part of arch, supra-arch vessels and proximal descending aorta.Placement of a triple-branched stent graft has been proved to be more challenging than that of a one-branched stent graft because what we have discussed in . AlthougOne-branched stent graft has recently been recognized in ADIAD and it has wider indication than triple-branched stent. In our pool of cases, we also applied one-branched stent in the patients in whom the left subclavian artery was retained while the other parts of arch, innominate artery and left common carotid artery were removed because of aneurysm, edema and dilation.The operative strategy for acute Debakey type I aortic dissection still remain to be advanced and simplified, especially the repair and reconstruction of aortic arch and supra-aortic vessels. For selection of branched stent grafts, the anatomic features and pathological changes of diseased arch are the crucial factors for clinical decision making.


The gastrointestinal microbiota plays a critical role in nutritional, metabolic, and immune functions in infants and young children and has implications for future lung health status. Understanding the role of intestinal dysbiosis in chronic lung disease progression will provide opportunities to design early interventions to improve the course of the disease. Gut microbiota is established within the first 1 to 3 years of life and remains relatively stable throughout the life span. In this review, we report the recent development in research in gut-lung axis, with focus on the effects of targeting microbiota of infants and children at risk of or with progressive lung diseases. The basic concept is to exploit this approach in critical window to achieve the best results in the control of future health. Clinical research in the last decades focused on host-microbe crosstalk especially at intestinal level raising the hypothesis that the gut microbiota is one of the key factors that determine host health. The immune and metabolic functions are influenced by the colonization of intestine by friendly bacteria  and a grThe microbiome is established within the first 1 to 3 years of life and remains relatively stable throughout the life span . The neoIn this review, we analyze the main factors and phases of early microbial imprinting, gut-lung axis in the progression of chronic lung diseases in children, and the manipulation of early-life gut microbiota for modifying history of lung diseases in children.Environmental factors together with genetics and immune system activity influence microbial colonization pattern in newborns Lactobacillus, Bifidobacteria, and Bacteroides in infants born by cesarean section is delayed [The type of delivery influences the pattern of colonization in infant gut. Vaginally delivered infants are colonized with bacterial communities from the mother's vaginal and intestinal tract. Infants born to cesarean section lack such exposure, leading to the first establishment of bacteria similar to the human skin microbiota . In addi delayed .Infant feeding influences the gut microbial composition with long-lasting effects. Breastfeeding has been associated with a variety of long-term beneficial effects including lower incidence of obesity , diabeteBifidobacteria has consistently been associated with host health. The predominance of Bifidobacteria in breastfed infant stools was firstly found over 100 years ago, suggesting that breast milk contains specific molecules that stimulate the growth of these bacteria, defined as bifidus factors [Bifidobacteria. The latter dominate the microbiota of breastfed infants, whereas formula-fed infants had higher proportions of Bacteroides and members of the Clostridium coccoides and Lactobacillus groups [An infant gut microbiota dominated by  factors . Today, s groups . In addis groups .Antibiotics have a major impact on gut microbiome composition particularly in young infants. In the latter, the gut bacteria structure is very unstable, and the continuous and repeated use of antibiotics, especially if the antibiotic used is a broad-spectrum one, profoundly alters gut microbial structure with major late clinical consequences. Recent papers show that prenatal use of antibiotics is associated with an increased risk of subsequent asthma .Of course, antibiotics are often necessary for certain conditions, but their use should be considered in the light of the new data summarized in The gut and respiratory epithelia provide a physical barrier against microbial penetration, and colonization with the normal microbiota generates resistance to pathogens. The role of microbiota in lung homeostasis and immunity is supported by the poor outcomes of germ-free mice that were exposed to acute infections  and theiCystic fibrosis (CF) is a disease in which recurrent and chronic infection leads to a progressive decline of lung function and ultimately to death. In observational studies in humans, CF has been associated with aberrant microbial colonization of the intestinal and the respiratory tracts. These findings are the likely consequences of the loss of CF transmembrane conductance regulator (CFTR) function and the resulting altered microenvironment . MutatioStudies have demonstrated also a relationship between poor nutrition and the development of bronchopulmonary dysplasia in preterm infants who require prolonged supplemental oxygen therapy . No dataBifidobacterium longum, and a reduction in Bacteroides fragilis [Lachnospira, Veillonella, Faecalibacterium, and Rothia seems significantly decreased in children at risk of asthma, with consequent reduced levels of fecal acetate and dysregulation of enterohepatic metabolites [Children developing asthma have a reduced gut microbial diversity in the first year of life as compared to healthy children . In partfragilis  in the gabolites .Lactobacilli have profound immunoregulatory effects on the lung, but the results of clinical trials in humans have been highly variable. Strain differences may in part explain the observed variability.Oral administration of probiotics and prebiotics or a combination of both  could indirectly influence the composition of airway microbiota through the release of bacterial products or metabolites that reach the lung and promote the outgrowth of beneficial bacteria or directly, via microaspiration of the probiotic strain from the intestinal tract to the airways . These mLactobacillus GG (LGG) negatively influenced the incidence of ventilator-associated pneumonia [In humans, administration of neumonia  and reduneumonia .Asthma is a major potential target for probiotics, due to its frequency, related pathogenesis, and the lack of consistently effective preventive strategies. However, data on early intestine microbial manipulation are missing, because asthma develops progressively until school age, and the long-term follow-up of probiotic and prebiotic study is limited.Lactobacillus reuteri has been related with a reduction of episodes of pulmonary exacerbations in children with CF [Pseudomonas aeruginosa. Nineteen children were given LGG for 6 months followed by placebo  for the subsequent 6 months. In parallel, 19 children were given the placebo during 6 months then the probiotic for the same period of time. The patients on LGG had a significant reduction of intestinal inflammation and of episodes of pulmonary exacerbations and hospitalization rates, with a decrease in IgG, suggesting that there is a relationship between intestinal and pulmonary inflammation. The intake of this probiotic was associated with a significant increase of the maximal forced expiratory volume in 1 second (FEV1) compared to the placebo as well as to a significant increase of body weight [10 colony-forming units Lactobacillus reuteri per day or placebo for 6 months. Pulmonary exacerbations and the number of upper respiratory tract infections were significantly reduced in the treatment group compared with the placebo group [Manipulation of gut microbiota in CF by changing dietary content of indigestible carbohydrate and short-chain fatty acids, namely, butyrate, may improve undernutrition and play an anti-inflammatory effect on animals . Restora with CF –38. The y weight . In anotbo group .As for bronchopulmonary dysplasia, no studies on humans have been conducted with pre- or probiotics. Moreover, in intermittent hypoxia induced in animal models, the supplementation with probiotics may improve pulmonary status, by acting on the specific matrix metalloproteinases suggesting a beneficial effect on lung inflammation. In addition, prebiotic uses have been associated with arrested lung vascular endothelial growth factor signaling highly involved in lung microvascular development, suggesting preservation of angiogenesis .However, the effects of probiotics are likely to be time-dependent, indicating the need for comparative clinical trials evaluating early-life microbiota modulation impact on lung health status. In particular, future studies are required in order to analyze how gut microbial composition in early life influence lung disease occurrence and history, investigating also the role of functional foods in preventing and/or modifying lung health status in children.


This data article contains the statistical analysis of the total, percentage and distribution of editorial board composition of 111 Hindawi journals indexed in Emerging Sources Citation Index (ESCI) across the continents. The reliability of the data was shown using correlation, goodness-of-fit test, analysis of variance and statistical variability tests. Specifications tableValue of the data•The data could be helpful in the determination of the impact of journal indexing on scientific publications.•The analysis can be extended to other publishers.•The dataset can be helpful in bibliometric analysis.•The dataset can be helpful as a ranking analytics for journals and management of smart campuses.•Hindawi journals.The dataset can be helpful in monitoring the impact of editorial composition in the acceptance and rejection of manuscripts submitted to different •The dataset can provide insight to the following: stereotyping in academic publications, duration differences in acceptance or rejection of manuscript, bias in publication. See •The dataset can spur academic discourse on the effect of geographical distribution of editorial board membership on perceived research output using the journals indexed in ESCI as case study. This can be achieved when citation analysis is incorporated. See the conclusions of •Several statistical models and methods can be applied to the dataset for further analysis.1a.The dataset of editorial composition of 111 Hindawi journals indexed in ESCI. This can be assessed as b.The frequency of editorial board composition of the 111 Hindawi journals and their summary statistics. This is presented in c.a, b, c, d and e.The editorial board membership grouped into six continents. These are presented in bar charts. See Fig. 2d.The detailed statistical analysis such as correlation analysis, test of normality and analysis of variancee.The detailed dataset showing the Poisson distribution goodness-of-fit test of the data classified into six continents namely North America (NAM), Europe (EURO), Asia (ASIA), South America (SAM), Australia (AUST) and Africa (AFR).The dataset contained in this article are listed as follows:1.1Hindawi Publishing Corporation is one of the leading academic publishers of medical, technical, social and scientific peer-reviewed literature. Currently, they publish 302 journals that cut across different academic domains. The publisher operates on fully open access model under Creative Commons Attribution License (CC-BY). The editorial policies of the journals stipulate that they operate without editor-in-chief but rather through editorial boards. Manuscripts submitted to the journals are first processed at the editorial office and sent to an assigned editor chosen from the pool of editorial board members of the journal. The assigned editor is then saddled with the responsibility of sourcing for qualified reviewers for the manuscript. The decision to accept or reject solely rests on the shoulders of the editors. The business model used by the publisher is that indexing determines the article processing charges.Currently, Hindawi publishing Corporation publishes 111 journals indexed in emerging sources citation index (ESCI). ESCI is part of web of science owned and maintained by of Clarivate Analytics (formerly Thomson Reuters). ESCI has been in existence since 2015 and it includes peer reviewed academic journals.2The experimental design used in this paper is the application of statistical methods targeted at revealing the hidden patterns of the datasets. Text mining was used to extract the dataset from the publisher's website. Similar analysis on statistical methods and the applications in bibliometrics can be found in Ref. 2.1The editorial board membership of the publisher is classified into six continents. The summary statistics is as shown in 2.2Percentage editorial board membership composition of Hindawi journals indexed in ESCI was obtained to show the actual percentage composition across the continents. This is shown in 2.3The correlation results using Spearman, Pearson and Kendall correlation coefficient are obtained in form of matrices shown in The distances between the correlations are computed using the following;The application of the transformations and their percentages using The result of the partial correlation is presented in 2.4The uneven editorial board membership composition across the continents necessitated the conduct of goodness-of-fit test using Poisson distribution. The goodness-of-fit results are divided into two. Firstly, the detailed tests are shown in 2.5The data is subjected to analysis of variance (ANOVA) and the result is shown in 2.6Different variability measures are conducted for editorial board composition of ESCI indexed Hindawi journals across the continents. These are summarized in


To assess the influence of gender, time of the day and gestational age on fetal heart rate (FHR) parameters between appropriate-for-gestational-age (AGA) and small-for-gestational age (SGA) fetuses using a portable fetal ECG monitor employed in the home setting.We analysed and compared the antenatal FHR data collected in the home setting on 61 healthy pregnant women with singleton pregnancies from 24 weeks gestation. Of the 61 women, 31 had SGA fetuses  and 30 were pregnant with AGA fetuses. FHR recordings were collected for up to 20 h. Two 90 min intervals were deliberately chosen retrospectively with respect to signal recording quality, one during day-time and one at night-time for comparison.Overall, success rate of the fetal abdominal ECG in the AGA fetuses was 75.7% compared to 48.6% in the SGA group. Based on randomly selected episodes of heart rate traces where recording quality exceeded 80% we were able to show a marginal difference between day and night-time recordings in AGA vs. SGA fetuses beyond 32 weeks of gestation. A selection bias in terms of covering different representation periods of fetal behavioural states cannot be excluded. In contrast to previous studies, we neither controlled maternal diet and activity nor measured maternal blood hormone and heart rate as all mothers were monitored in the home environment.Based on clinically unremarkable, but statistically significant differences in the FHR parameters between the AGA and SGA group we suggest that further studies with large sample size are required to assess the clinical value of antenatal fetal ECG monitoring. Antepartum cardiotocography (CTG) is widely used for the assessment of fetal well-being, although there is no high-quality evidence to indicate that it improves perinatal outcomes , 2. SuchStudies have shown changes in CTG parameters with gestation in appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) fetuses –7. In adThe aim of our present study was to explore the effects of diurnal variation, gestational age and gender on computerized CTG in a cohort of healthy pregnant women carrying AGA and SGA fetuses in their home environment using a portable abdominal fetal ECG monitor .This work was undertaken to analyze and compare FHR data published separately on normal  and SGA th percentile to describe a fetus that has not reached its target weight. Patients were divided into two groups for comparison; fetuses with EFW below the 10th percentile for gestational age (SGA) and fetuses with EFW >10th percentile for gestation (AGA). Exclusion criteria were known fetal malformation, alcohol dependence and any pharmacologically treated co-morbid conditions . None of the participants used medications including β-blockers, central nervous system depressants, tocolytics or steroids which could possibly affect the FHR. Information about each pregnancy, the characteristics of deliveries and newborn outcomes were collected from the medical records.For the purpose of this study, we used the definition by the Royal College of Obstetricians and Gynaecologists (RCOG)  which inWomen provided informed, voluntary, written consent prior to participation. The fetal ECG monitor (Monica AN24) was attached to the participant’s abdomen by placing five skin electrodes in standardized positions . ParticiFetal electrophysiological data recorded by the monitor were downloaded later via USB connection. The methodology used for signal extraction and analysis has been described in detail by Cohen et al . In ordeBasal FHR: baseline heart rateLong-term FHR variation (LTV): overall: minute-by-minute range of pulse intervalsShort-term FHR variation (STV) overall: sequential epoch-to-epoch variation. Both the LTV overall and the STV overall are measured in milliseconds (ms).Accelerations: increase in FHR above the baseline that lasted longer than 15 s and had an amplitude greater than 10 bpm.Episodes of high FHR variation : episodes in which the LTV in at least 5 out of 6 consecutive minutes was equal to or greater than 32 ms.In contrast to the ultrasound-based CTG monitors, although the fetal ECG monitor (Monica AN24) uses different signals to acquire FHR data, the monitor relies on the same averaging algorithm as introduced by Dawes and Redman  to calcuIndependent sample t-tests were used to compare the characteristics of mothers and babies between the two groups.Mean differences in day and night time measurements of FHR parameters were calculated within the AGA and the SGA group. To compare differences between groups, linear models were fitted with FHR as the dependent variable and fixed factors for time of measurement and fetus size as independent variables. An interaction term between the two fixed factors was included to test if there was a difference in the day and night time measurements between the two groups. Generalised estimating equations were used to fit the models to allow for repeated measurements on individuals . DiffereMean differences between genders were calculated within the AGA and the SGA group. To compare differences between genders, linear models were fitted with FHR measurement as the dependent variable and fixed factors for gender and fetus size as independent variable. An interaction term between the two fixed factors was included to test if there was a difference in measurements between genders in the normal and the SGA group. Generalised estimating equations were used to fit the models to allow for repeated measurements on individuals.Linear models were used to examine the relationship between heart rate parameters measured at night and gestational age at time of recording. Models were fitted with FHR as the dependent variable and a fixed factor for fetus size and gestational age covariate as independent variables. An interaction term between the two independent variables was included to allow for different relationships in the normal and the SGA group. Step wise model selection was used to first test for the interaction, the difference between the two groups and finally the linear trend. At each step, non-significant terms were removed.A total of 61 maternal-fetal pairs were studied; 30 participants carried AGA and 31 carried SGA fetuses. The baseline characteristics of the participants and their fetuses are given in One hundred and twenty-two recordings (61 day and 61 night) made over 90min segments were analysed from 30 AGA and 31 SGA fetuses. All the parameters from both AGA and SGA fetuses were in the normal range at any times of the observations. Exact time of the day and maternal activity during the recordings could not be reconstructed retrospectively.With respect to gender, even though, the difference in STV between male and female fetuses was higher both in the AGA and the SGA groups than the diurnal variation described above, this observation did not reach statistical significance .Further analysis of the effect of gestational age on FHR parameters  showed nA significant negative correlation between gestational age and basal FHR  <10onal age . Howevertriction . SGA inctriction . Serial rcentile . In the In the current study, SGA fetuses demonstrated the widely reported phenomenon of maturational change and a similar trend of CTG parameters with increasing gestational age as do the normal fetus. Over the last couple of decades, it has become clear that fetal growth restriction can start early in pregnancy when it is termed as early onset of fetal growth restriction . FigueraLack of information on fetal body movements, rest and activity cycles, fetal breathing, maternal activity, diet intake and other physiological conditions that could influence FHR , 26, 27,Another possible limitation of this study was related to the methodology. To assess the day: night change in FHR parameter, we randomly selected the best 90 min FHR data from the day and night recording. This limitation was related to the overall success rate of the recording in the SGA group. The average overall success of acquiring fetal signals in the AGA group was 75.7%, however in the SGA group it was 48.6% which is lower than the success rate reported by Stampalija et al . One of The diurnal pattern of FHR and its variation exists from 20 to 22 weeks onwards . We obseTo date, only a few studies have evaluated the influence of gender on CTG parameters and these have produced conflicting results. Lange et al  suggesteThis study confirms that although SGA fetus with no evidence of Doppler velocimetry abnormalities exhibit similar changes in FHR pattern with gestation as do AGA fetuses, the CTG pattern seems to be differing between the two groups when the time of day is taken into consideration. Nonetheless, all our observations are in the range of normal findings. We did not follow up on perinatal outcome, nor we analysed beat-to-beat information on the acquired FHR data, implying that may be the underlying difference in the STV between the AGA and the SGA were masked by the use of averaged FHR data provided by the Monica AN24 leading to the loss in temporal resolution. We suggest that further studies should be undertaken to explore the value of true beat-to-beat information on FHR variability by employing Monica AN24 before its clinical utility and more widespread adoption can be ascertained.S1 Fig(XLSX)Click here for additional data file.


Obesity has become a worldwide epidemic and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease (CKD). A high body mass index is one of the strongest risk factors for new-onset CKD. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing CKD in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year, the World Kidney Day will promote education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option. In 2014, over 600 million adults (18 years and older) worldwide were obese. Obesity is a potent risk factor for the development of kidney disease. It increases the risk of developing major risk factors for chronic kidney disease (CKD), like diabetes and hypertension, and it has a direct impact on the development of CKD and end-stage renal disease (ESRD). In individuals affected by obesity, a compensatory mechanism of hyperfiltration likely occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidney structure and raise the risk of developing CKD in the long-term.The good news is that obesity, as well as the related CKD, are largely preventable. Education and awareness of the risks of obesity and a healthy lifestyle, including proper nutrition and exercise, can dramatically help in preventing obesity and kidney disease. This article reviews the association of obesity with kidney disease on the occasion of the 2017 World Kidney Day.2) worldwide has increased substantially  to be normal weight, a BMI between 25 and 30 kg/m2 as overweight, and a BMI of >30 kg/m2 as obese. Although BMI is easy to calculate, it is a poor estimate of fat mass distribution, as muscular individuals or those with more subcutaneous fat may have a BMI as high as individuals with larger intra-abdominal  fat. The latter type of high BMI is associated with substantially higher risk of metabolic and cardiovascular disease. Alternative parameters to more accurately capture visceral fat include waist circumference (WC) and a waist hip ratio (WHR) of >102 and 0.9 cm, respectively, for men and >88 and >0.8 cm, respectively, for women. WHR has been shown to be superior to BMI for the correct classification of obesity in CKD.Definitions of obesity are most often based on BMI . A BMI between 18.5 and 25 kg/mNumerous population-based studies have shown an association between measures of obesity and both the development and the progression of CKD . Higher Higher visceral adipose tissue measured by computed tomography has been associated with a higher prevalence of albuminuria in men . The obs2 higher BMI was associated with a 25% higher risk of kidney cancers, with 10% of all kidney cancers attributable to excess weight   .Obesity results in complex metabolic abnormalities, which have wide-ranging effects on diseases affecting the kidneys. The exact mechanisms whereby obesity may worsen or cause CKD remain unclear. The fact that most obese individuals never develop CKD, and the distinction of as many as 25% of obese individuals as “metabolically healthy” suggests that increased weight alone is not sufficient to induce kidney damage . Some ofThese various effects result in specific pathological changes in the kidneys , which cObesity is associated with a number of risk factors contributing to the higher incidence and prevalence of nephrolithiasis. Higher body weight is associated with lower urine pH  and incThe mechanisms behind the increased risk of kidney cancers observed in obese individuals are less well characterized. Insulin resistance, and the consequent chronic hyperinsulinemia and increased production of insulin-like growth factor 1 and of numerous complex secondary humoral effects may exert stimulating effects on the growth of various types of tumor cells . More revs deleterious longer-term effects of higher BMI  and those receiving suboptimal care, to inform these patients of the potential risk for CKD to which they are exposed, is the first step towards developing public health interventions. Acquiring evidence showing that current interventions to reduce CKD risk in the obese are efficacious and deployable is an urgent priority to set goals and means for risk modification. Appropriate documentation of existing knowledge distilling the risk and the benefits of primary and secondary prevention interventions in obese people, and new trials in this population to fill knowledge gaps (see below) are needed. Finally, surveillance programs that monitor progress on the detection of at-risk individuals and the effectiveness of prevention programs being deployed  constituA successful surveillance system for CKD has already been implemented in some places such as the UK . A campaper se predicts a higher risk for incident CKD . In overweight or obese diabetic patients, a lifestyle intervention including caloric restriction and increased physical activity reduced the risk for incident CKD by 30%, compared to a standard follow-up based on education and support to sustain diabetes treatment; although it did not affect the incidence of cardiovascular events  study showed that the nephron-protective effect of angiotensin-converting enzymes (ACE) inhibition in proteinuric CKD patients was maximal in obese CKD patients, but minimal in CKD patients with normal or low BMI (Observational studies in metabolically healthy obese subjects show that the obese phenotype unassociated with metabolic abnormalities dent CKD , suggestr events . Such a r events . In a rer events . A thoro low BMI . Of note low BMI –87.Globally, these experimental findings provide a proof of concept for the usefulness of weight reduction and ACE inhibition interventions in the treatment of CKD in the obese. Studies showing a survival benefit of increased BMI in CKD patients, however, remain to be explained . These fThe worldwide epidemic of obesity affects the Earth’s population in many ways. Diseases of the kidneys, including CKD, nephrolithiasis and kidney cancers are among the more insidious effects of obesity, but which nonetheless have wide ranging deleterious consequences, ultimately leading to significant excess morbidity and mortality and excess costs to individuals and the entire society. Population-wide interventions to control obesity could have beneficial effects in preventing the development or delaying the progression of CKD. It is incumbent upon the entire healthcare community to devise long-ranging strategies towards improving the understanding of the links between obesity and kidney diseases, and to determine optimal strategies to stem the tide. The 2017 World Kidney Day is an important opportunity to increase education and awareness to that end.


Several studies have shown the association between affective dysregulation and severity of psychotic symptoms in schizophrenic patients. Attentional biases, which operate automatically to favor the processing of emotionally negative information in early stages of information processing, are known to play a causal role in the etiology of anxiety and other negative affective states. This study was conducted to evaluate the association between selective attention bias for fear stimuli and psychotic symptoms in patients with schizophrenia.A total of 66 patients with schizophrenia were included in the study. Attentional biases were measured with the dot-probe task with facial expression of neutral and fear emotional. To measure the psychotic features of the participants, the Positive and Negative Symptom Scale (PANSS), Psychotic Symptom Rating Scale (PSYRATS), the Scale to Assess Unawareness of Mental Disorder (SUMD), and Clinical Global Impression–Severity scale (CGI-S) were used.Attentional vigilance scores were calculated by subtracting the median RT in congruent trials (dot at the position of the fear face) from the median RT in incongruent trials  Attentional vigilance scores was moderately correlated with the hallucination subscale of PSYTATS  in the participants. No correlation was found between selective attention bias and the scores of PANSS, PSYTATS-delusion, SUMD, and CGI-S. When the participants were divided into biased and non-biased groups by the attentional vigilance scores of +40 msec, no significant difference was found in the clinical measures. However, a statistical trend was found in hallucination severities between the biased and non-biased groups (p=0.092).As a pilot study, the results suggest that the emotional information processing might affect the subjective severity of psychotic features in schizophrenia. Further study would be needed to clarify this association.


Variability raises considerable interest as a promising and sensitive marker of dysfunction in physiology, in particular in neurosciences. Both internally  and/or externally  generated perturbations and the neuro-mechanical responses to them contribute to the fluctuating dynamics of locomotion. Defective internal gait control in Parkinson's disease (PD), resulting in typical timing gait disorders, is characterized by the breakdown of the temporal organization of stride duration variability. Influence of external cue on gait pattern could be detrimental or advantageous depending on situations . As well as being an interesting rehabilitative approach in PD, treadmills are usually implemented in laboratory settings to perform instrumented gait analysis including gait variability assessment. However, possibly acting as an external pacemaker, treadmill could modulate the temporal organization of gait variability of PD patients which could invalidate any gait variability assessment. This study aimed to investigate the immediate influence of treadmill walking (TW) on the temporal organization of stride duration variability in PD and healthy population. Here, we analyzed the gait pattern of 20 PD patients and 15 healthy age-matched subjects walking on overground and on a motorized-treadmill (randomized order) at a self-selected speed. The temporal organization and regularity of time series of walking were assessed on 512 consecutive strides and assessed by the application of non-linear mathematical methods . A more temporally organized and regular gait pattern seems to emerge from TW in PD while no influence was observed on healthy gait pattern. Treadmill could afford the necessary framework to regulate gait rhythmicity in PD. Overall, the results support the hypothesis of a greater dependence to regulatory inputs as an explanatory factor of treadmill influence observed in PD. Also, since treadmill misrepresents the gait as more healthy than it is, the present findings underline that gait analysis using treadmill devices should be cautiously considered in PD and especially for gait variability assessment in gait lab. Human movement is intrinsically dynamic and complex. Continuous integration of multiple sensory inputs and coordination of motor outputs are needed to achieve efficient, stable, and adaptable locomotion , the randomness of gait pattern observed in neurodegenerative diseases such as Parkinson's or Huntington's disease compromises adaptive gait control  or the over-regularity  indicate the loss of the adaptive capabilities of the system  and the fear of falling . For PD participants, the disease severity  and the patient's functional status (MDS-UPDRS) were also determined. All assessments were carried out during the ON state.Each participant performed two walking sessions of 10 min for obtaining 512 consecutive strides that is required to adequately apply mathematical methods described below , data acquisition started and the 512 first gait cycles were extracted for further analysis. In each of the two walking conditions, a unidimensional accelerometer was taped in the antero-posterior direction on the lateral malleolus of the most affected side in PD participants and the dominant side in healthy controls. Acceleration data were recorded at 512 Hz using the Vitaport 3 ambulatory recorder , and next transferred to a computer. Heel strike was detected in the raw acceleration signal with a peak detection method designed to minimize the risk of false step detection  and coefficient of variation (CV), and in terms of its organization, which provides complementary information about how stride duration evolves with time across consecutive strides  series by computing for each t the accumulated departure from the mean of the whole series . The series X(t) is then locally detrended by subtracting the theoretical values Xn(t) given by the regression. For a given interval length n, the characteristic size of fluctuation for this integrated and detrended series is calculated by Delignieres et al.  and log (n) determined H exponent.The Detrended Fluctuation Analysis (DFA) requires to initially integrate the x of the time series was calculated with Fourier transform analysis, and α exponent was estimated from the slope of a linear regression on a log (power) vs. log (frequency) plot  is computed. If σ > 2, then the difference between the original data set and the surrogate data set is considered statistically different. It does not prove the presence of long-range autocorrelations in the original time series but it can reject the null hypothesis that the series under investigation has no temporal structure .Further analyses were applied when r et al. . For eacm  and r (similarity criterion) were set according to the recommendations of Yentes et al. Values of 2 and 0.2 were respectively used for m and r  was also calculated on 512 consecutive strides to assess the regularity or predictability of the lower-limb movement. Smaller value is associated with the greater regularity whereas a system with high SampEn appears less predictable; generating more non-redundant information over time. Since SampEn values were influenced depending on input parameter, For further details, these methods are described elsewhere , the total number of steps can be determined from the raw acceleration signals. The step length was assessed following the relationship between the gait speed and gait cadence. During overground walking, lap times, laps number and the total distance were measured. Following the relationship between total walking distance and acquisition duration, mean gait speed, mean gait cadence and mean step length were assessed as follow:t-test. The treadmill influence in PD was also further investigated with respect to clinical factors such as disease severity, balance performance or fear of falling using Spearman's correlation coefficients. The results were considered statistically different for p < 0.05.Data were analyzed with the Sigmaplot 13.0 software . Standard measures of statistical dispersion  were computed to describe the study populations. Normality of data distribution was verified (using the Shapiro-Wilk test) for all variables, except for the gait cadence and the CV of stride duration that required the use of a log-transformation. A two-way repeated measures ANOVA  was applied to examine the influence of walking condition, as well as one of the pathological condition on LRA exponents, CV of stride duration and spatiotemporal gait variables. The effect size of TW as compared to OW was expressed in standardized terms (Hedge's g). Most of gait variables are speed- and/or age-dependent. Thus, to further identify the walking condition-caused gait modulations as opposed to changes arising solely from the age of subjects or from different walking speeds, all gait variables were age- and speed-normalized using a Z-score transformation. Andriacchi et al. and Winter's reference works provided normative data of spatiotemporal gait variables  is depicted for the PD participants and healthy controls in Figure Absolute and normalized values of stride duration variability measures and spatio-temporal gait variables are summarized in Figures d were below 0.10 in healthy population and both walking conditions  while it reached values higher than 0.10 in PD population . Using the surrogate data tests, the presence of a specific temporal structure in original time series can still be suggested for time series that did not verify the H, α, and/or d criteria. Across all conditions, the number of standard deviations between the original scaling exponent and the scaling exponent of the surrogate series (σH and σα) were on average clearly superior to 2 for both populations. Higher magnitude of stride duration variability  was also induced by the TW. Importantly, significant  interactions were demonstrated for LRA exponents, and the gait speed and step length confirming that TW influenced differently the gait pattern of PD and healthy participants  were used to refine previous observations and draw adequate conclusions by taking into account gait speed differences observed between the two walking sessions Table . Interesp-values. The temporal organization appeared highly related to the patient's functional status, and in particular its balance performance, while the magnitude of the stride duration variability was related to the gait speed changes . H and α exponents were respectively moderately and highly correlated to the disease severity . MDS-UPDRS III and BESTest were moderately correlated to H and α exponents . Similarly, the step length was correlated to both balance performance and confidence . The balance status could be thus the explanatory factor of the important changes observed between the two walking sessions in some patients.As depicted on Figures The aim of the present study was to investigate the immediate influence of treadmill walking compared to overground ambulation on both gait variability and spatiotemporal gait variables in Parkinson's disease and healthy controls. Firstly, our study demonstrated a more regular and temporally organized gait pattern in PD participants while healthy controls remained insensitive. A second observation was the highlighting of a reduced gait speed and a concomitant decreased step length, suggesting a cautious gait pattern adopted by PD participants walking on a treadmill. Finally, greater influence of TW was demonstrated among instable patients.Complexity and regularity of stride time signals may reveal insight into the neurophysiological organization of locomotion and into the regulation of the interacting subsystems, constituting the locomotor system . Descendent supraspinal signals and afferent input of the limbs are suggested to regulate the CPG activity. In this way, lower limbs that are rhythmically moved backwards and behind the trunk can constitute a regulatory input from the environment that could restore some interaction within the locomotor system. Efficient, stable, and adaptable locomotor pattern requires complex dynamic sensorimotor interactions depending on highly complex processes including efferent-type  and afferent-type information coming from different peripheral feedbacks.The use of regulatory inputs from the environment appears crucial to overcome the defective internal rhythm of the basal ganglia disorders  as an efficient and promising rehabilitative approach to improve classical spatiotemporal gait disorders even over the long-term (Mehrholz et al., The present study has some limitations that should be addressed. A safety harness was used to ensure the patient's security while some studies have highlighted influences of TW on vertical trunk acceleration and lower limb kinematics (Aaslund and Moe-Nilssen, In conclusion, the present study highlights that the treadmill could afford the necessary framework to regulate gait rhythmicity in PD while precautious gait pattern seems to be adopted with such type of walking. A more temporally organized and more regular gait pattern emerges from treadmill walking in PD while no influence was observed in healthy gait pattern. Those observations support the hypothesis of a greater dependence to regulatory inputs as an explanatory factor of treadmill influence observed in PD. Our results may form a further step toward a better understanding of the effect of treadmill on PD gait. Also, the present findings underline that gait analysis using treadmill devices should be cautiously considered in PD and especially for gait variability assessment.TW assisted with participant recruitment and data collection; participated in data analyses and interpretation of results; did literature searches; and drafted and wrote the manuscript. CD provided methodological and statistical inputs to the study, largely contributed to the good application of reference mathematical methods; participated in the interpretation of results; helped to draft the manuscript; and revised the manuscript. GS and TL provided methodological input to the study; participated in the interpretation of results; and revised the manuscript. AJ was the chief investigator who oversaw and coordinated all study activities; assessed participant eligibility; provided advice and input to all methodological issues; participated in the interpretation of results; helped to draft the manuscript; and revised the manuscript. All authors read and approved the final 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.


Image-guided ablations are nowadays applied in the treatment of a wide group of diseases and in different organs and regions, and every day interventional radiologists have to face more difficult and unusual cases of tumour ablation. In the present case review, we report four difficult and unusual cases, reporting some tips and tricks for a successful image-guided treatment. In recent years, interventional radiology has had a rapidly increasing diffusion worldwide, being recognised as the therapeutic modality of choice in several fields: vascular and biliary procedures, management of post-surgical complications and treatment of cancer patients –6. In thIn the present case review, some difficult and unusual cases, treated using tips and tricks, are presented and discussed.A 58-year-old male with history of resection of colorectal cancer two years earlier and percutaneous image-guided thermal ablation of a hepatic metastasis at segment VIII 10 months earlier was referred to our institution for possible local treatment of a 4 cm recurrence on the cranial side of the previously ablated area, which was detected by 18-FDG-PET/CT . Given tA 58-year-old male was referred to us for the evaluation of a possible percutaneous treatment for an adrenal metastasis from a previously resected lung cancer. The patient underwent 4 years before right upper lung lobe resection for a high-grade lung papillary adenocarcinoma. One year later, he developed a new lung lesion in the right lower lobe, and brain and left adrenal metastases, treated with repeated sessions of radiation therapy. The treatments achieved a good disease control at the brain level, meanwhile the adrenal lesion relapsed. The patient was referred to our Department of Interventional Radiology for local ablative treatment as radiation therapy was considered no more feasible. When the patient was evaluated for ablation, the adrenal lesion measured 31 mm . The pat2) was planned in order to displace the sensible structure from the adrenal gland. A protective manoeuver, such as the injection of fluid, gas or dedicated gel, has been successfully reported in order to displace the surrounding structure from the target of an image-guided ablation [2, and manual gas injection was performed. CO2 is particularly helpful in some cases, as it displaces the surrounding structures and also allows the achievement of a thermal insulation between the sensitive structures and of the area to be treated, as, compared to fluid materials, gas conduces by far less the heating. On the contrary, gas is compressible and easily diffuses into the soft tissues following the less resistance plane and may not be sufficient to achieve the planned displacement. Thus, it is important to exactly understand where to place the small needle in order to reach the desired displacement. In our case, we planned to place the needle as close as possible to the adrenal gland, with the aim of achieving a gas distribution exactly around the gland. After the injection of CO2, we were able to achieve a good distribution of the gas around the gland and a good displacement of the surrounding structures  as a bridge to transplantation. One HCC was located in segment VII and measured 36 × 28 mm, the other one was located in segment VI strictly close to the liver capsule and measured 12 × 11 mm . Based o antenna .According to the same proposed algorithm , laser tBoth MWA and LTA procedures were performed under ultrasonography (US) guidance and under conscious sedation. MWA was carried out by using a generator with a frequency of 2450 MHz and a 16-G internally cooled minichoked antenna , with power output of 70 W and duration of energy delivery of 12 min. LTA was performed by using a diode laser unit . Two 21-gauge Chiba needles spaced 12 mm each other were placed in the anterior border of the tumour, and two bare-tip, 300 μm in diameter laser fibres were introduced through the needles and advanced until the tip of the fibres was placed into the tumour 1 cm beyond the tip of the needle, and 1800 Joules per fibre was delivered in 6 min. Contrast-enhanced US (CEUS) performed about 5 min after the end of the procedures depicted a coagulation area of 44 × 32 mm in segment VII with no evidence of residual hyper-enhancing foci, suggesting complete necrosis of the nodule treated with MWA. Conversely, a viable, hyper-enhancing focus of 5 mm in diameter was observed in the posterior portion of the nodule in segment VI treated with LTA . ImmediaThe treatment was immediately repeated, and two laser fibres spaced 6 mm next to each other were placed into the residual tumour under CEUS guidance . A furthA 57-year-old female was diagnosed with endometrial adenocarcinoma two years previously and was treated with total laparoscopic hysterectomy, bilateral salpingo-oophorectomy and complete pelvic and limited peri-aortic lymphadenectomy. Histopathology revealed carcinosarcoma of the uterus. The patient subsequently received chemotherapy including carboplatin and taxol. One year later, a recurrent pelvic mass was detected on CT and patient underwent pelvic tumour resection including resection of the terminal ileum and anterior rectum. This was followed by pelvic external beam radiation therapy and concurrent cisplatin.A follow-up FDG PET/CT was performed to evaluate for residual pelvic metastases and new lesions. PET/CT revealed a markedly FDG avid lesion, hypodense on CT, along the posterolateral border of the spleen suggestive of metastatic peritoneal disease . Pelvic In view of the presence of a solitary peritoneal metastasis located at the posterolateral border of spleen  and consThe patient was injected with 5 mCi of F18 FDG one hour prior to initiation of the procedure. The cryoablation procedure was carried out using a PET/CT scanner is equipped with CT fluoroscopy . The patient was under general anaesthesia. Cryoablation has been used for successfully treating a wide variety of tumours , 39–42. The position and size of the lesion presents several challenges. The presence of bowel so close to the anterior margin of the tumour in the prone treatment position presents a risk of injuring the bowel during cryoablation which may lead to bowel perforation. In order to avoid this complication, infusion of saline with iodinated contrast in the space between the tumour and the bowel was planned so as to displace the bowel wall away from the tumour and avoid the bowel contact with the cryoablation ice ball. Protective manoeuvres can be applied to increase the feasibility and safety of percutaneous ablations , 44. TheBased on the fused PET/CT images, a plan was made for the cryoablation procedure including selection of the entry point, as well as the direction and depth of cryoablation probe insertions to achieve complete ablation of the entire tumour with margins. Needle placement for the instillation of saline with contrast for bowel displacement was also determined from the planning PET/CT.Following a small skin incision, the saline infusion needle was inserted under CT fluoroscopic guidance to reach the space between the anterior margin of the tumour and the bowel wall and a small volume of saline mixed with CT contrast was infused , e and eFollowing instillation of saline and CT fluoroscopic confirmation of increased separation of bowel wall from the tumour, two cryoablation probes  were inserted based on PET/CT-based plan into the superior and inferior parts of the tumour using fluoroscopic guidance. Following probe placement and prior to cryoablation, a single-bed position PET/CT was performed using a 35-s suspension of ventilation to acquire both CT and PET without respiratory motion related blurring or misregistration. After PET/CT confirmation of proper placement of both cryoablation probes and hydro displacement needle, the cryoablation was started . PET/CT Cryoablation freezes the tumour and creates an iceball involving the tumour and adjacent tissues; the FDG within tumour remains trapped even after ablation. This helps confirm that the cryoablation iceball, represented by the hypodense zone on CT extends beyond the FDG-avid tumour, thus ensuring adequate coverage of tumour plus a safety margin with cryoablation , 46.The patient was discharged the following day after an uneventful recovery. She underwent a follow-up MRI the next day to assess the results of the cryoablation and to provide a baseline for future follow-up .A follow-up CT scan after 2 weeks showed the hypo-enhancing ablation zone without enhancing residual tumour. In cases of poor visibility at US, the use of contrast-enhanced ultrasound (CEUS) with the administration of dedicated contrast agent has been reported to be extremely helpful to enhance the conspicuity of a lesion in order to better depict it and to enhance the accuracy of image-guided targeting.PET/CT-guided ablations have been reported to be feasible and effective.In cases of lesions invisible at US and not completely depictable with CEUS, the use of virtual navigations systems and fusion imaging have been reported to be a safe, feasible, and effective strategy to perform percutaneous ablationsInternal markers, such as vessels bifurcations, are the preferred markers to achieve registration and fusion of two imaging modalities.The use of CEUS immediately after the treatment during the same session allow for identify incomplete ablations, thus offering the chance of performing a subsequent ablation in the same sessionPercutaneous image-guided ablations have been reported to be feasible for the treatment of adrenal gland metastasesProtective manoeuver, such as injection of fluid, gas or dedicated gel, has been successfully reported in order to displace surrounding structure from the target of an image-guided ablationMicrowaves represent one of the most rapidly spreading technique for performing ablation, as it allow to deliver high energy in quite a short time, thus offering the possibility of achieving larger ablation volumes in shorter time in comparison with other techniques, such as radiofrequency.The diameter of LA needles is smaller than RFA electrodes and MWA antennas, making LTA safer and more suitable to ablate lesions with at-risk location and/or difficult to be reachedLTA has also been proposed as the ablation technique of choice in patients with multiple and small tumours variable in sizeImmediate post-procedural CEUS is strongly recommended to assess the completeness of the ablation treatment and to guide the immediate re-treatment in case of residual viable tissuePercutaneous image-guided ablation can be proposed as a safe and effective treatment for limited peritoneal metastases.Cryoablation has been used for treating successfully a wide variety of tumours.PET/CT can be effectively used to guide percutaneous biopsies and ablation.A single breath hold period has been reported as sufficient for good visualisation of the target lesion.Iceballs formed during cryoablation can be very well detected with CT.Cryoablation freezes the tumour and creates an iceball involving the tumour and adjacent tissues; the FDG within tumour remains trapped even after ablation. This helps confirm that the cryoablation iceball, represented by the hypodense zone on CT extends beyond the FDG-avid tumour, thus ensuring adequate coverage of tumour plus a safety margin with cryoablation.With the technical improvements of ablative devices, and the increasing evidence of clinical effectiveness of image-guided percutaneous ablations, an increasing number of cases will be referred to the interventional radiologist for a minimally invasive treatment. In this scenario, the number of more complex and unusual cases is also expected to grow. A good knowledge of all the technical options and of some tips and tricks is crucial for performing an effective and safe ablation. Availability of different ablative devices, with the possibility of choosing alterative solutions for image guidance and treatment monitoring, including virtual navigation, fusion imaging and CEUS, could help in the future to further increase the application of minimally invasive ablations to a larger series of patients. Good collaboration with referring physicians and oncologists, and larger dissemination of the knowledge of possible treatments provided by interventional radiologists are crucial for offering a dedicated multidisciplinary and multimodality treatment to oncological patients.


Median raphe cyst is a very rare, benign congenital lesion occurring mainly on the ventral aspect of the penis, but can develop anywhere in the midline between the external urethral meatus and anus. We report a case of median raphe cyst in the perineum presenting as a perianal polyp in a 65-year-old, English white male with exceptionally rare ciliated epithelium. According to our knowledge, this is the third such case of ciliated median raphe cyst in the English literature. This case, also the first case of ciliated median raphe cyst in the perineum location, focuses on pathogenesis of median raphe cyst.


Echinococcus granulosus and commonly manifests as hepatic and pulmonary cysts. When feasible, based on cyst size and location, surgical resection is potentially curative. Post-surgical recurrence of disease is encountered in up to 25% of patients. Secondary peritoneal contamination is a recognized complication in 5-10% of cases. Disseminated disease is usually palliated using systemic anti-parasitic agents such as benzimidazoles, albendazole and mebendazole but worsening of disease post-systemic treatment is frequent in 14-25% of patients. In this report, we share our experience of a patient with long-standing, chronic disseminated hydatidosis and subsequent diagnosis of non-small cell lung cancer who manifested evidence of reduced activity of the echinococcal disease following institution of chemotherapy for his new diagnosis of lung cancer. There was significant reduction in the serum level of anti-echinococcal antibody titers in tandem with chemotherapy administration. There was also minimal but notable decrease in the size of the cysts on serial cross-sectional imaging obtained for monitoring cancer response to chemotherapy. This intriguing observation of a possible benefit of anticancer chemotherapy against echinococcal disease in this index case may provide new insights for therapeutic exploration in disseminated echinococcal disease.Hydatid cystic disease is a parasitic infestation caused by  Echinococcus granulosus. While rare in the US and Western Europe, echinococcal disease is endemic in the Middle East and Mediterranean regions and South America where the incidence is as high as 220 per 100,000 [Cystic echinococcosis is a zoonotic disease caused by the parasitic cestode  100,000 . Thus th 100,000 .Hydatidosis is diagnosed based on clinical characteristics along with imaging and confirmatory immunodiagnostic studies . Abdominal ultrasound is the gold standard for diagnosing peri-hepatic cysts because of low cost and availability in addition to ability to characterize extent of disease. The serologic antibody titer, IgG-ELISA, has high sensitivity of approximately 95% in diagnosing echinococcal disease but it is comparatively non-specific and therefore, has limited use in confirmation of diagnosis or tracking disease activity in response to treatment . Due to There is currently no consensus on the best treatment approach for echinococcal hydatidosis . ManagemSystemic anti-parasitic therapy is used for short-term peri-interventional treatment and in cases of inoperable liver echinococcosis or multiple organ involvement . The benThe patient is a 68-year-old male, immigrant to the US from Iraq, where he was a sheepherder. He has a long-standing medical history of echinococcal hydatidosis and known hepatic cystic disease for more than 30 years. He had been treated previously with cystectomies and hepatic lobectomy in his native country. Prior surgical treatment was complicated by intraoperative contamination and dissemination of the disease to the peritoneum and pelvis secondary . Repeat Following recurrence of his cancer approximately 10 months later, patient was restarted on chemotherapy using a combination of carboplatin and pemetrexed. There was a similar reduction in the echinococcal titer with the resumption of chemotherapy. Due to treatment-related side effect, the patient elected to discontinue further chemotherapy following which the antibody titer gradually increased, reaching a peak of 6.32 within 4 months of the last dose of chemotherapy despite continued maintenance on albendazole. The patient is now approximately 6 years out from his original diagnosis of locally advanced lung cancer and remains alive and of chemotherapy.in vitro and in vivo efficacy of chemotherapeutic agents against echinococcus [Cystic hydatidosis is a rare parasitic disease associated with significant morbidity and diminished quality of life. Treatment of localized disease is infrequently curative while symptom palliation and control of disease remain the achievable goals of systemic treatment for disseminated infection. Our experience with this index patient with peritoneal hydatidosis and concomitant lung cancer is intriguing because of the observed reduction in markers of echinococcal activity and the administration of chemotherapy. The echinococcal IgG titer is regarded as the gold standard for assessing disease burden and activity . The signococcus .The cross-species activity of cytotoxic anticancer agents is plausible and perhaps not surprising. Neoplastic cells and echinococcal cellular subunits are similar in their increased proliferative capacity and in their metastatic ability that is dependent on secreted proteolytic enzymes . There iAnother interesting angle in this case is the prolonged survival past 6 years post-diagnosis recorded in this patient with advanced stage lung cancer despite the fact that he only received two different lines of chemotherapy regimens, i.e. platinum doublet and single agent pemetrexed. The median survival for patients with stage IIIB non-small cell lung cancer treated with chemotherapy and radiation is approximately 20 months , 24. WheListeria monocytogenes, and Corynebacterium parvum [However, it has been previously noted that active infection can modulate the course of cancer. An idea was first mooted in the mid-1800s based on the observation of a high rate of regressions of soft tissue sarcoma in patients whose disease was complicated by acute streptococcal infections , 26. Simm parvum , 28. Them parvum . There am parvum , 33.In conclusion, we report an interesting observation of potential efficacy of established anticancer chemotherapy agents against echinococcal disease. Serendipitous observations such as this have the potential to stimulate novel approaches to the treatment of patients with recalcitrant echinococcal disease.


The suitability of stacked thin films for next-generation display technology was analyzed based on their properties and geometrical designs to evaluate the mechanical reliability of transparent conducting thin films utilized in flexural displays. In general, the high bending stress induced by various operation conditions is a major concern regarding the mechanical reliability of indium–tin–oxide (ITO) films deposited on polyethylene terephthalate (PET) substrates; mechanical reliability is commonly used to estimate the flexibility of displays. However, the pattern effect is rarely investigated to estimate the mechanical reliability of ITO/PET films. Thus, this study examined the flexible content of patterned ITO/PET films with two different line widths by conducting bending tests and sheet resistance measurements. Moreover, a stress–strain simulation enabled by finite element analysis was performed on the patterned ITO/PET to explore the stress impact of stacked film structures under various levels of flexural load. Results show that the design of the ITO/PET film can be applied in developing mechanically reliable flexible electronics. Flexible electronic devices based on polymer substrates, such as organic light-emitting diodes (OLED), cholesteric liquid crystal displays (ChLCDs), and thin film transistors (TFT) are generally regarded as promising candidates for next-generation electronic devices. The brittle indium–tin–oxide (ITO) film is the transparent conducting material that is most widely used as anode in OLED devices. The advantages of this material include low electrical resistance, high light transmission characteristics, and easy manufacture in large areas by roll-to-roll sputter-coating and printing techniques ,2,3. TraThe bending testing mechanism utilized in this study is shown in As shown in R and sR refer to the calculated resistance and sheet resistance, respectively. Symbols L and W are separately denote the pattern length and width.To explore the pattern effect of ITO coating, test samples with two different patterns were cut along the length direction of the ITO lines, as shown in The experiment details of the patterned ITO/PET films proposed in this study are listed in The fracture of brittle transparent conducting films on flexible substrates is a critical reliability issue in the structure of stacked thin films. The stress–strain distribution of the patterned ITO/PET film was simulated to estimate the failure possibility and critical locations of the ITO/PET film under various bending loads. The FEA models of the patterned ITO/PET films are presented in M refers to the bending moment, and y and I denote the distance to the neutral axis and area moment of inertia, respectively. From Equation (2), the bending stress difference of the pattern 1/pattern 2 ITO/PET films was confirmed by the analytical results. Thus, decent and reliable simulation results were obtained for the estimation of the stress–strain-induced failure of the ITO/PET films.To explore the stress distribution of the patterned ITO/PET film, a bending load with 10 mm radius of curvature was applied on the bottom plane of the 50 µm-thick patterned ITO/PET FEA model. As shown in The influence of various ITO thicknesses was investigated to evaluate the thickness effect of the induced ITO bending strain. A similar investigation was applied to explore the pattern and PET substrate thickness influence of induced ITO bending strain under various PET substrate thicknesses . As depicted in An electrical resistance experimental method and a stress–strain simulation approach was proposed for ITO/PET films to examine the effects of the pattern and the thickness effect of stacked films under various bending loads. The calculated electrical resistance value agrees well with the experimental data of each patterned ITO/PET film, ensuring measurement accuracy and sample testing without damage. Moreover, the electrical resistance of the patterned ITO/PET film was significantly increased when a bending radius of curvature below 10 mm was considered. According to the experimental data, a narrow line width tends to accelerate the brittle failure of the ITO film. Thus, a wider line width was suggested for the ITO film to avoid failure. Furthermore, this study also evaluates how the thickness of the PET substrate affects the changes in electrical resistance under a bending load. The results indicated that the patterned ITO film deposited on a thicker PET substrate was easily cracked because of the significant increase in the distance from the neutral axis to the surface of the ITO film. Moreover, the experimental data of the critical tensile strain were analyzed by stress–strain simulation to determine the mechanical reliability of the ITO film coated on a PET substrate. The significant ITO bending strain obtained when the bending radius of curvature ranged from 10 to 2 mm dominated the stress–strain magnitude on the surface of the ITO film. Meanwhile, the pattern influence of the ITO film clarified that the narrow line width tends to induce a larger bending strain because of the reduction of the moment of inertia. In addition, ITO and PET thickness also play important roles in enhancing the mechanical reliability. Thus, a thicker ITO and thinner PET thickness was preferred to avoid the brittle failure of the ITO film.


The objective of this study was to determine the prevalence of depressive symptoms in Jamaican adolescents and examine its association with individual and family factors. We used an abbreviated form of the Beck's Depression Inventory II (BDI-II) to assess depressive symptoms among 748 students, attending public high schools in the parish of Hanover Jamaica. In the analysis, we classified adolescents with scores in the upper quartile of the depressive symptom score as having depressive symptoms. Multivariate logistic regression was used to determine the predictors of depressive symptoms. 14.2% of participants reported depressive symptoms. There was association between engagement in sexual activity , parental monitoring of adolescent activity , maternal affection and support , and paternal affection and support  with self reported depressive symptoms at the bivariate level. In the final model, depressive symptoms was associated with perceived lack of maternal affection and support  and showed marginal association with being sexually experienced . As most homes are female-headed, establishing support systems for the mother to take care of their adolescent children may decrease the odds of depressive symptoms. Sexually experienced adolescents may require screening for depression. Further research is required to fully explore all factors that could predispose Jamaican adolescents to depression.