Connection between the duplication of the middle cerebral artery (DMCA) and the presence of multiple aneurysms has been described in a small number of cases.The presence of a rare type of DMCA associated with cerebral aneurysms was diagnosed in 56 year old woman after a rupture of an aneurysm on the dorsal segment of the DMCA. .. The presence of equal diameters of branches of the DMCA and anterior cerebral artery (ACA) could be recorded as trifurcation of the carotid internal artery (ICA). However, due to the anastomosis of the DMCA branches in the area of the M2 segment, the recorded anatomical change represented a segmental duplication of MCA. Three aneurysms that were directly related to the segmental DMCA were diagnosed.Anatomical variation by type of segmental DMCA is a rare subtype of DMCA. The presence of multiple aneurysms associated with this type of anatomical variation in MCA indicates their high hemodynamic instability. Anatomical variations of the middle cerebral artery (MCA) are significantly less common than those of other intracranial arteries , 2. The The presence of aneurysms directly related to anatomic variation by type of DMCA is rarely described, and they have an extremely high frequency of rupture , 9.A 56-year-old woman was admitted as an emergency, after a sudden loss of consciousness. The multislice CT (MSCT) of the brain performed in a local medical centre showed the presence of intracerebral hematoma 7x4cm in the temporobasal region, with the penetration of blood into the venticular system Fig. . On admiThe DMCA, as we know, is classified into two types. Type A is diagnosed when branches are separated from the very tip of the ICA together with the ACA, and Type B is diagnosed when one branch occurs between the top of the ICA and the onset of AchA , 6. The The association between the duplicated MCA and brain aneurysms has been described in 32 cases. Of these, 65% were detected after previous rupture of the brain aneurysm (9). If we know that the presence of cerebral aneurysms in the general population is between 5 and 9% and their rupture occurs in 10 out of 100,000 [The specificity of our case is that the segmental DMCA is associated with the presence of multiple brain aneurysms that are directly related to the anatomical variation itself. A ruptured aneurysm located in the middle segment of the dorsal branches DMCA indicates an extraordinary haemodynamic load in that area. Providing adequate perfusion in the parts of the brain supplying MCA through two anomalous blood vessels directly leads to increased hemodynamic stress on their walls. In addition, the wall structure of the anomalous DMCA segments will have greater sensitivity to increased perfusion requirements, which in the first part leads to aneurysmal extensions, and later to their rupture.The association between segmental DMCA with multiple aneurysms and their rupture points to high hemodynamic instability of such anatomical variation.


Surprisingly we remain ignorant of the function of the majority of genes in the human and mouse genomes. The dark genome is a major obstacle to the interpretation of the function of human genetic variation and its impact on disease. At the same time, pleiotropy, how individual variants influence multiple phenotypes, is key to understanding gene function and the role of genes and genetic networks in disease systems. Both understanding the genetics of disease and developing new therapeutic approaches and advances in precision medicine are all compromised by our limited knowledge of gene function and pleiotropic effects. Illuminating the dark genome and revealing pleiotropy across the genome requires a highly coordinated and international effort to acquire and analyse high-dimensional phenotype data from model organisms. We describe briefly how the International Mouse Phenotyping Consortium is addressing these challenges and the novel features of the pleiotropic landscape that are revealed by functional genomics programmes at genome-wide scale. Numerous studies have employed GWAS and genome sequencing approaches to identify loci involved with a wide variety of human traits and diseases  is building a catalogue of mammalian gene functions by generating and phenotyping a knockout mouse line for every protein-coding gene  enable an unprecedented view of the mammalian genome landscape, particularly in revealing novel loci, many of them thus far unstudied, associated with various disease states (Meehan et al. The plethora of new genetic disease models generated by IMPC and others, together with knowledge on basic gene function and pleiotropy, will inform and underpin studies on rare diseases and Mendelian disorders, illuminate GWAS studies and ultimately help provide a more profound understanding of the function of human genetic variation and its involvement in disease. The study of the dark genome alongside the generation of a comprehensive map of the pleiotropic functions of all genes is critical to informing a deeper understanding of the mammalian genome. Future advances in genomic and precision medicine will depend upon the success of this endeavour.


The torcular Herophili is formed by the joining of the straight sinus, superior sagittal sinus, and transverse sinus. The anatomic configuration of the torcular Herophili is highly variable. In the current literature, classification systems define up to nine subtypes of the torcular Herophili. The frequency of prevalence of these anatomical variants is also variable. Herein is a case report of a circularly-shaped torcular Herophili found during cadaveric dissection. The confluence of sinuses also called the torcular Herophili lies near the internal occipital protuberance and receives venous drainage from various regional dural venous sinuses . ClassicDuring the routine dissection of an adult male cadaver aged 87 years at death, an unusual arrangement of the dural venous sinuses was identified Figure . This spRecently, Matsuda et al. reexamined anatomical variations of the torcular, focusing on venous flow and the continuity of the superior sagittal and transverse sinuses. They reported that venous flow from the superior sagittal sinus to the transverse sinus could be either symmetric or asymmetric . The finRecently, a circular variant of the torcular was reported on magnetic resonance imaging from a patient suffering from chronic headaches and questionable papilledema . In the The embryology of the dural sinuses further elucidates the genesis of anatomical variants. The torcular Herophili is an area of interest for neurosurgical and interventional procedures. Given the high variability of the region, an awareness of normal anatomy and variations such as seen in the case presented herein is crucial for preoperative planning and during the interpretation of cranial imaging.


Editorial on the Research TopicEditorial: Intraoperative Radiotherapy (IORT)—A New Frontier for Personalized Medicine as Adjuvant Treatment and Treatment of Locally Recurrent Advanced MalignancyIntraoperative radiotherapy (IORT) is a treatment delivery technique with reports starting in the early twentieth century with the use of orthovoltage energy with limited applicability due to the energy characteristics . This tevia tumor bed devascularization, elimination of inter-fraction tumor cell repopulation, and possibly providing a systemic immune effect (There are numerous advantages of IORT in oncology. IORT has the benefit of delivering a tumoricidal radiation dose in a single treatment, while targeting the therapy to the region of highest risk of disease recurrence with direct visualization in the operating room. This provides a high relative biological effectiveness while limiting dose to normal tissue e effect . In addiSethi et al. describe the technical and dosimetric considerations for the various applicators now available to treat patients with disease intraoperatively in various locations including with flat, spherical, and even a needle applicator. Valente et al. discuss their experience with IORT from the surgical perspective and how their group decreased operative times in patients receiving breast IORT with increased utilization. Paunesku and Woloschak provide a review of the history of IORT as well as an engaging discussion of how IORT can be used in the future. Herskind et al. extend this discussion into the theoretical usage of large radiation fraction size in brain metastasis and the potential combination with immunotherapy. The series then reviews the use of IORT in various malignancies, including head and neck cancer, pancreas cancer, and brain metastasis. Three articles finally review the use of IORT in breast cancer a highly prevalent cancer with numerous radiation treatment options available. Jacobson and Sochi provide a review of the various types of partial breast therapy and the toxicities associated. Chin et al. describe their experience using IORT for patients with prior thoracic radiation exposure. Harris and Small provide a comprehensive review of the data in support of the use of breast IORT as well as the toxicities, cosmesis, and quality of life with use of this treatment modality touching on both the use of electron and photon-based IORT.In this series we focus on the use, radiobiology, and physics of IORT with an emphasis on the Intrabeam system. The Organization for Economic Cooperation and Development evaluated the spending, supply, utilization, and price of health care across 13 high income countries and found that as a percent of GDP from 1980 to 2013 health care spending is approximately 17% in the United States versus 10% in the other countries evaluated . In the Both authors contributed to the editorial.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.


Non-polio enteroviruses are emerging viruses known to cause outbreaks of polio-like infections in different parts of the world with several cases already reported in Asia Pacific, Europe and in United States of America. These outbreaks normally result in overstretching of health facilities as well as death in children under the age of five. Most of these infections are usually self-limiting except for the neurological complications associated with human enterovirus A 71 (EV-A71). The infection dynamics of these viruses have not been fully understood, with most inferences made from previous studies conducted with poliovirus.Non-poliovirus enteroviral infections are responsible for major outbreaks of hand, foot and mouth disease (HFMD) often associated with neurological complications and severe respiratory diseases. The myriad of disease presentations observed so far in children calls for an urgent need to fully elucidate the replication processes of these viruses. There are concerted efforts from different research groups to fully map out the role of human host factors in the replication cycle of these viral infections. Understanding the interaction between viral proteins and human host factors will unravel important insights on the lifecycle of this groups of viruses.This review provides the latest update on the interplay between human host factors/processes and non-polio enteroviruses (NPEV). We focus on the interactions involved in viral attachment, entry, internalization, uncoating, replication, virion assembly and eventual egress of the NPEV from the infected cells. We emphasize on the virus- human host interplay and highlight existing knowledge gaps that needs further studies. Understanding the NPEV-human host factors interactions will be key in the design and development of vaccines as well as antivirals against enteroviral infections. Dissecting the role of human host factors during NPEV infection cycle will provide a clear picture of how NPEVs usurp the human cellular processes to establish an efficient infection. This will be a boost to the drug and vaccine development against enteroviruses which will be key in control and eventual elimination of the viral infections. Enterovirus (consisting of 15 species); family Picornaviridae pyrimidines have also been evaluated against enteroviruses; CV-B3 and EV-A71 virus infections where they inhibited their infections but the exact mechanism was not established . More reNatural products have recently gained much interest in drug development studies. Of these; plant secondary metabolites; flavonoids have been of interest in drug therapy screens against viral infections given that they are freely available and form better part of human dietary. Screening of plant metabolites for possible use as antiviral therapy has been reported as reviewed by Zakaryan and colleagues  and theiLittle success has been achieved in terms of antiviral therapy against enteroviruses. Given that drug discovery process is an expensive and time-consuming venture, most researchers have relied on the FDA approved drugs or drugs that are already in use for possible re-purposing. Not much success on drug therapy has been recorded in viral infections due to the high mutation rates observed during viral replication. Combination therapy of the drugs with different mode of actions targeting different stages of viral infections would be an alternative in targeting different stages of the enteroviral infection cycle. This will only be achieved with a complete map out of the human host factors hijacked by these viruses during infections. Thus, there is need for continued elucidation of molecular mechanisms of the already postulated viral targets as well as identifying other underlying factors and process. Vaccines have shown much success against viral infections and the success story of vaccination against poliovirus infection in the world which is a picornavirus; points for the need of continued studies towards identifying vaccine candidates against the enteroviral infections. With outbreaks of enteroviruses being recorded in different parts of the world, if not checked they might have a potential threat to the global health; just soon after near- eradication of poliovirus infection.The emergence of outbreaks of enteroviral infections in different parts of the world point to the need of mapping all the host factors involved in the infection paradigm. Given that viruses need host factors in every step of their infection from attachment, entry, replication, virion assembly and eventual entry, there is need to elucidate all the host factors involved for an improved understanding of the molecular dynamics of enteroviral infections. This will be a big boost towards the long overdue antiviral and vaccine development against these epidemiologically important viruses. There is much to be elucidated on the formation of NPEV replication complex formation as the existing mechanisms do not wholly explain the processes and steps involved in this important process during viral replication. The nuclear host factors involved in the enteroviral replication also needs to be fully described as this is a vital step in maintaining viral replication and eventual life cycle. Viral entry studies need to be carried out as the known receptors and viral entry requirements do not fully explain the myriad of disease features observed during viral infections. The role of cellular processes such as autophagy, apoptosis, necroptosis, pyroptosis as well as post-translational modifications in enteroviral infections also needs to be fully elucidated. This will be specifically important in explaining the little-known stages of viral infections such as non-lytic egress for continuous viral cycle within the host.The paucity of information on the infection dynamics of these viruses calls for concerted efforts to elucidate the viral-human cell interactions. There is still a lot to be investigated to fill the gaps that exist on the life cycle of non-polio enteroviruses. With new cases emerging in different parts of the world, it is just a matter of time before we have a global outbreak of non-poliovirus enteroviral infections in different parts of the world. There is also an urgent need for further studies especially in the field of vaccine developments as well as antiviral therapy against enteroviruses.


Asbestos is classified as a hazardous pollutants between the airborne particles that cause diseases such as lung fibrosis (asbestosis). This protocol describes an integrated method for determination of asbestos fibres concentration and its temporal-spatial trends in the air of urban areas. To do this, 60 samples were gathered from various areas of Yazd city with low, moderate and high traffic. For analysis of asbestos fibres in the samples scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) were utilized. The spatial and temporal variation of asbestos fibres concentration was carried out by ArcGIS 10 analysis. The Inverse Distance Weighting (IDW) method was used to draw asbestos fibres distribution maps. The interpolation of asbestos fibre by IDW method indicated that the distribution of the fibres in summer and winter were followed almost the similar pattern. However, the distribution of asbestos fibre concentrations in the direction of southeast to the northwest of the city was higher than that in the other areas due to high vehicular traffic. Specifications TableValue of the Protocol2 and an altitude of 1230 m above the sea level located in the center of Iran   was used . After tThe geometric mean of asbestos fibres concentrations in the sampling stations is presented in The morphology and chemical component of asbestos fibres obtained by EDX showed that about 70% of all identified fibres were asbestos and 30% were non-asbestos fibres. For example, the specific peaks of the elements such as silica, magnesium, calcium, and iron correspond to the chemical properties of the tremolite type of asbestos fibres . Also, t


The disappearance of the soft-bodied Ediacara biota at the Ediacaran–Cambrian boundary potentially represents the earliest mass extinction of complex life, although the precise driver(s) of this extinction remain unresolved. The ‘biotic replacement’ model proposes that an evolutionary radiation of metazoan ecosystem engineers in the latest Ediacaran profoundly altered marine palaeoenvironments, resulting in the extinction of Ediacara biota and setting the stage for the subsequent Cambrian Explosion. However, metazoan ecosystem engineering across the Ediacaran–Cambrian transition has yet to be quantified. Here, we test this key tenet of the biotic replacement model by characterizing the intensity of metazoan bioturbation and ecosystem engineering in trace fossil assemblages throughout the latest Ediacaran Nama Group in southern Namibia. The results illustrate a dramatic increase in both bioturbation and ecosystem engineering intensity in the latest Ediacaran, prior to the Cambrian boundary. Moreover, our analyses demonstrate that the highest-impact ecosystem engineering behaviours were present well before the onset of the Cambrian. These data provide the first support for a fundamental prediction of the biotic replacement model, and evidence for a direct link between the early evolution of ecosystem engineering and the extinction of the Ediacara biota. Untangca 550 Ma) and the Ediacaran–Cambrian boundary [In summary, our study provides the first robust test for a key prediction of the biotic replacement model for the Ediacaran–Cambrian transition—namely, an increase in metazoan ecosystem engineering in the latest Ediacaran. Our trace fossil data from the Nama Group of southern Namibia illustrate a gradual increase in bioturbation intensity throughout the Nama Group, but a dramatic increase in the EEI of trace fossils in the latest Ediacaran. These increases in diversity and EEIs pre-date or are at least contemporaneous with the appearance of low-diversity and potentially ecologically stressed communities of soft-bodied Ediacara biota in the same basin ,28 and aboundary –73. TherFinally, our findings highlight that further work is needed to spatially constrain Nama Group trace fossils in the context of the contemporaneous soft-bodied Ediacara biota, to understand changes in bioturbation during the Avalon and White Sea assemblages and to determine a precise biogeochemical mechanism(s) associated with bioturbation that could have led to, or arisen from, environmental changes. Despite this, our study provides a link between ecosystem engineering and the extinction of the Ediacara biota, provides insights into the evolution of bioturbation prior to the Cambrian and illustrates that early metazoans were capable of achieving levels of ecosystem engineering approaching those that appear in the earliest Cambrian by the latest Ediacaran.


The role of the cytochrome P450 superfamily of heme-thiolate enzymes in oxidative metabolism is discussed in the context of evolutionary development. Concordances between the rise in atmospheric oxygen content, elaboration of the P450 phylogenetic tree and the accepted timescale for the emergence of animal phyla are described. The unique ability of the P450 monooxygenase system to activate molecular oxygen via the consecutive input of two reducing equivalents is explored, such that the possibility of oxygen radical generation and its toxic consequences can be explained in mechanistic terms, together with an appreciation of the ways in which this oxygen activating ability has been utilized by evolving biological systems in their adaptation to an increasing atmospheric oxygen concentration over the past two billon years.


This Special Issue on lung diseases is aimed at giving emergent researchers and clinicians an important forum to share their original research and expert reviews on key topics within respiratory diseases. This Special Issue will be of interest to general physicians and respiratory specialist and will equip the reader with up-to-date knowledge on a wide array of lung diseases, including interstitial lung diseases, COPD, and Asthma. Journal of Clinical Medicine. Our objectives are to showcase emergent researchers working at the cutting edge of scientific and clinical advances in the broad field of respiratory diseases.Lung diseases are amongst the leading causes of mortality worldwide. One-sixth of total deaths are attributed to lung disease, accounting for over 9.5 million deaths worldwide. This burden of disease is the prime reason for this timely Special Issue on lung diseases in the Here, we provide the reader with comprehensive reviews that would interest those with general medical and specialist respiratory interests. We have two reviews covering chronic obstructive pulmonary disease (COPD), the leading cause of respiratory mortality worldwide. Dey et al.  discuss Journal of Clinical Medicine.This Special Issue on lung diseases also presents a number of primary research articles spanning all aspects of respiratory diseases showcasing emergent researchers at the forefront of advances in respiratory medicine. We present a variety of themes from novel aspects of lung physiology testing in pulmonary hypertension to the prevalence of fatigue in asthmatic patients and the use of macrolide therapies during hospitalisation of children with childhood disease, amongst other interesting primary research articles, which would be of interest to our growing number of readers of the


Miniaturized and integrated analytical devices, including chemical sensors, are at the forefront of modern analytical chemistry. The construction of novel analytical tools takes advantage of contemporary micro- and nanotechnologies, as well as materials science and technology. Two electrochemical techniques were used in experiments: electrochemical impedance spectroscopy and cyclic voltammetry. The goal of this study was to investigate electron transfer resistance in a model solution containing  Over the years, many methods were invented or used in the investigation of protein layers immobilized on the surface. The most commonly used are the techniques based on immunological and fluorescent tests. Presently the most popular method is Enzyme-Linked Immunosorbent Assay (ELISA) . ELISA iElectrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) are electrical techniques in which the electrochemical cells are used. They consist of three individual electrodes  placed inside the vessel. In EIS the electrical response of the investigated system to the small amplitude periodic small amplitude alternating voltage (AC) signal is measured . The anaIntegration of the electrochemical cell electrodes on the surface of the common substrate allows for the cell miniaturization and facilitates the increase of the number of simultaneously conducted experiments in multiplexed measurement system. Integrated electrochemical cells can be fabricated on various substrates such as silicon , Low TemIntegrated electrochemical cells (IEC) used in our measurements were fabricated using LTCC technology. The devices made using LTCC technology can be characterized by their chemical inactivity, hermeticity, high reliability and high temperature stability. This technology allows fabrication of microfluidic systems such as flow sensors, micropumps, microvalves, micromixers, microreactors and polymerase chain reaction (PCR) devices ,18,19.Electrochemical cells fabricated using LTCC technology were used in many chemical and biological measurements such as devices for the detection of cortisol , heavy mIn this work, the preliminary experiments with the integrated electrochemical cells fabricated in the LTCC technology were conducted. The results of the test measurements with model solution containing IEC were fabricated using LTCC technology. Schematic drawing depicting the LTCC manufacturing process steps is shown in The IECs used in the experiments presented in this paper were made on rectangular substrate (20 × 3.5 mm) and were formed using three layers of green tape . Nine types of IECs were fabricated with electrodes varying in size  which diFabricated IECs are meant to be used in the protein adsorption measurements done in the presence of the  surface . Results surface ,25. It a surface .The eight-channel potentiostat of our own design was used in the measurements. It was designed as the EIS extension of the IMP-STM32 impedance analyzer . Its simOur system was designed to be fully compatible with the integrated electrochemical cells. IECs dimensions and contact pads placements were designed in such way that they fit into typical micro-USB connectors. The measurement head connected to the multichannel potentiostat has eight such connectors and may be placed on top of the titrate plate with sensors positioned vertically in eight of 24 wells. Impedance analyzer IMP-STM32 was used in the measurements and the range of the frequency sweep was from 1 Hz to 100 kHz. The measurement system is shown in the Q (expressed in n (dimensionless) are the parameters and The EIS spectra were analyzed using the Electrical Equivalent Circuit (EEC) method with the circuit shown in requency . The infThe SEM images of the IEC electrodes are shown in The preliminary tests of the Ag/AgCl reference electrode on LTCC ceramic formed using both highly concentrated NaCl solution  and elecThe Bode and Nyquist graphs —dots shoAll types of the IECs were tested using EIS in the experiments which were carried out in the PBS solution with the presence of various concentrations of cFe2+/3+ . It can The influence of the electrode geometry on the components of the Equivalent Electrical Circuit  is shown in Protein adsorption to the WE surface was investigated using EIS for five type of sensors (k calculated as:It was observed that the obtained value of the electrical double layer capacitance The CV experiments were conducted in two steps. In the first step the cyclic voltammograms for five type of sensors (Cyclic voltammetry is a simple and easy means of showing the changes of electrode behavior after each assemble step and CV experiments further confirmed that the BSA was successfully adsorbed on gold WE surface. The results of experiments of k for the same reason as mentioned in The normalized cyclic voltammograms of Miniature integrated electrochemical cells fabricated using LTCC technology were used in measurement with model solution containing The results of the presented preliminary work confirmed that the IECs were used in the measurement with the presence of


Hort and Simpson and in the SMGL supplement.See related articles by On behalf of the Saving Mothers, Giving Life (SMGL) Technical Working Group, we would like to thank Holt and SimpsonWe agree with the authors on the importance of bringing attention to the valuable experiences and lessons learned during the implementation and course of the SMGL activities, including the activities directly related to health systems strengthening (HSS). We generally agree with the points raised regarding a lesser focus on the evaluation of the process of implementation of the SMGL initiative in the supplement in favor of highlighting the outcomes and impacts of the initiative on maternal and newborn health. However, we beg to differ that the implementation experiences of SGML are “not well documented.”The articles constituting the supplement do not represent an exhaustive account of all aspects of the SMGL initiative. The select articles published in the supplement have largely focused on the outcomes of the initiative at its conclusion after 5 years of implementation. They add to already published accounts about the initial planning, implementation, and monitoring and evaluation of the SMGL interventions, including a comprehensive external evaluation of inputs and processes undertaken during the first year of the initiative.In the context of describing extraordinary, effective, multisectoral, and large-scale interventions that reduced maternal mortality in the SMGL-supported districts, the supplement includes numerous examples of HSS. The articles describing the comprehensive district system strengthening approaches that led to reductions in the “Three Delays” give ample details about strategies employed at the individual, community, health facility, and district levels. Successes and challenges to implementation of these strategies and increased accountability demanded by the initiative are thoroughly documented.The fact that the authors were able to identify examples in the supplement to discuss SMGL’s successes at the macro, meso, and micro levels attests to the wealth of implementation details provided by the articles in the supplement. We echo the value of examining HSS through a more structured and formalized lens, though “there is little consensus on what health systems strengthening (HSS) entails, what the drivers of successful HSS initiatives are, and how they can be measured.”We thank Holt and Simpson for noting the importance of HSS in global health programming and research and recognize the value of continuing to share the experiences and lessons learned during the course of planning, implementing, and evaluating the SMGL initiative. We echo their thoughts on the need for future research to tease out more firmly the critical components of HSS in Uganda and Zambia. There is a wealth of qualitative and quantitative evidence that captured these crucial experiences. Continued analyses and documentation of these aspects may include bringing forward country- and district-level insights and experiences of the SMGL initiative related to HSS. Uganda and Zambia have already embarked on a road of scaling up components of the SMGL model. Policy makers and program managers in other low- and middle-income settings where similar approaches could be used to rapidly reduce maternal mortality may greatly benefit from learning about the SMGL’s role in improving health systems.


We read with great interest the review article written by Bibbò et al.  entitledNASH has become one of the most common causes of liver disease in industrialized countries  and is cConsidering that gut microbiota dysbiosis is a driver of inflammation in the development of NAFLD, the reverse modulation of intestinal dysbiosis may alter the disease process. There is emerging interest in the modulation of gut microbiota to induce benefits in inflammatory intestinal disorders, such as probiotic use, antibiotic treatment, and fecal microbiota transplantation. Although diet can significantly influence the composition of gut microbiota, clinical trials investigating the effects of dietary interventions on the gut microbiota of NAFLD patients are lacking. To ascertain the exact mechanisms of action of gut microbiota in NAFLD, additional human studies with larger patient populations and animal studies are needed. Unraveling the relationship between gut microbiota and the development of NAFLD may then allow for the identification of relevant targets for future therapeutic intervention.


The health state of rotating machinery directly affects the overall performance of the mechanical system. The monitoring of the operation condition is very important to reduce the downtime and improve the production efficiency. This paper presents a novel rotating machinery fault diagnosis method based on the improved multiscale amplitude-aware permutation entropy (IMAAPE) and the multiclass relevance vector machine (mRVM) to provide the necessary information for maintenance decisions. Once the fault occurs, the vibration amplitude and frequency of rotating machinery obviously changes and therefore, the vibration signal contains a considerable amount of fault information. In order to effectively extract the fault features from the vibration signals, the intrinsic time-scale decomposition (ITD) was used to highlight the fault characteristics of the vibration signal by extracting the optimum proper rotation (PR) component. Subsequently, the IMAAPE was utilized to realize the fault feature extraction from the PR component. In the IMAAPE algorithm, the coarse-graining procedures in the multi-scale analysis were improved and the stability of fault feature extraction was promoted. The coarse-grained time series of vibration signals at different time scales were firstly obtained, and the sensitivity of the amplitude-aware permutation entropy (AAPE) to signal amplitude and frequency was adopted to realize the fault feature extraction of coarse-grained time series. The multi-classifier based on the mRVM was established by the fault feature set to identify the fault type and analyze the fault severity of rotating machinery. In order to demonstrate the effectiveness and feasibility of the proposed method, the experimental datasets of the rolling bearing and gearbox were used to verify the proposed fault diagnosis method respectively. The experimental results show that the proposed method can be applied to the fault type identification and the fault severity analysis of rotating machinery with high accuracy. Rotating machinery is one of the most common mechanical equipment, which plays an important role in industrial applications. It generally operates under tough working environments, which can eventually result in mechanical breakdown that lead to high maintenance costs, severe financial losses, and safety concerns ,2. As roThe vibration signal is widely used in fault diagnosis of rotating machinery because it is easy to collect and monitor online. For example, when there is a local fault in the running process of the rolling bearing, each contact causes an instantaneous shock and stimulates the rolling bearing to conduct high-frequency free vibration attenuation according to its inherent frequency. The instantaneous impact caused by the failure has obvious periodicity, the impact frequency depends on the bearing speed, and the impact amplitude depends on the bearing fault size. Therefore, the impact characteristics caused by local damage should be extracted by signal analysis technology and then, fault identification should be conducted by the artificial classifier.As rotating machinery works in the industrial environment, its vibration signal often contains the inherent vibration signal of rotating machinery, the fault impact signal and background noise. The vibration signals collected by the accelerometers have the characteristics of non-linearity, non-stationarity and impact . TherefoDue to the nonlinearity and non-stationarity of the vibration signals of rotating machinery a time-frequency analysis method is often used to solve the problem of feature extraction of the vibration signals of rotating machinery. The fast Fourier transform (FFT) is a classical time-frequency analysis method, but it is only suitable for solving the problem of stationary signal analysis. The wavelet transform (WT) is also a classical time-frequency analysis method that can preset the time and frequency window of interest. However, the WT is not an adaptive signal decomposition method, and it requires the kernel function and its parameters to be set in advance. The wavelet packet transform (WPT) can select the frequency resolution and the WPT is more flexible than the WT. However, the WPT is still not an adaptive time-frequency analysis method. The empirical mode decomposition (EMD) is a self-adaptive time-frequency method that can adaptively decompose the vibration signal into a set of intrinsic mode functions (IMFs) that contain the amplitude and frequency characteristics. However, the EMD has the end effect and mode mixing problem in that the stability of the IMFs is poor, which affects the subsequent feature extraction process. In order to solve the problems existing in EMD, EEMD and a complete ensemble empirical mode decomposition (CEEMD) are proposed .In recent years, due to the fact that fault information contained in the vibration signals can be extracted more effectively at different time scales, a large number of scholars have applied a multiscale entropy (MSE) algorithm and its variants to fault feature extraction of rotating machinery ,11. In aAfter the fault features are extracted from the vibration signals of rotating machinery, a high performance classifier is needed to identify the fault types and fault severity. Many artificial intelligence techniques have been adopted to realize the fault diagnosis of rotating machinery, such as the artificial neural network (ANN) , supportIn view of the above problems in fault diagnosis of rotating machinery based on the pattern recognition method, this paper presents a novel fault diagnosis method based on the improved multiscale amplitude-aware permutation entropy (IMAAPE) and the mRVM for rotating machinery. The main contributions of this paper are summarized as follows:(1) As the AAPE is very sensitive to the amplitude change of the vibration signal, the vibration of rotating machinery needs to be pre-processed before the feature extraction to minimize the interference of external noise to the vibration signal. The intrinsic time-scale decomposition (ITD) was used to decompose the vibration signal of rotating machinery into a group of proper rotation components stably, among which the optimum PR component can highlight the main time-frequency characteristics of the vibration signal so as to facilitate the subsequent fault feature extraction.(2) The performance of the AAPE improved. A fault feature extraction method of rotating machinery based on the IMAAPE is proposed for the first time. The IMAAPE improves the coarse-graining procedure in a multiscale analysis and adopts the characteristics of the AAPE sensitive to the amplitude and frequency changes of the vibration signal. The IMAAPE can calculate the AAPE values in different time scales and construct the feature vectors, which can effectively describe the fault features contained in the vibration signals of rotating machinery.(3) The mRVM multi-classifier is trained to realize fault identification and fault severity analysis of rotating machinery. In this paper, two different realization methods of the mRVM and the effect of parameter selection on the identification accuracy of rotating machinery fault types are discussed by comparing experiments.The organization of the rest of this paper is as follows. The ITD is an algorithm for the efficient and precise time-frequency-energy (TFE) analysis of signals. The ITD can decompose a complex time series into a series of proper rotation (PR) components and accurately extract the intrinsic instantaneous amplitude, frequency information and other morphological characteristics of the complex time series, which is suitable for the analysis of non-stationary and nonlinear signals .Let The main steps of the ITD algorithm are as follows:Assuming that  α∈ .According to Equation (2) and Equation (3), the PR component The baseline signal ith PR component and ith PR component and After the ITD, the time series The entropy analysis of the time series from a single scale may lose some important information of the original signal. The multiscale entropy (MSE) was proposed by Costa M. to represent the complexity of a signal. The MSE relies on the computation of the sample entropy over a range of scales to extract the characteristic information of the complex signal in different time scales . The MSE(1) The coarse-graining procedure derives a set of time series representing the system dynamics on different time scales. The coarse-graining procedure for scale (2) Then, the sample entropy of each coarse-grained time series is calculated and Bandt put forward the concept of basic permutation entropy in 2002 . At presd-dimensional space to obtain the reconstruction vectors ith permutation is called as Assume the given time series However, there are two main problems in describing the complex time series by the PE. First, the traditional PE only considers the ordinal structure of a time series, but ignores the amplitude information of the corresponding elements in the time series. Second, the effect of the elements with equal amplitude on the PE value in the time series is not clearly explained. In view of these, Azami and Escudero proposed the amplitude-aware permutation entropy (AAPE) to improve the sensitivity of the PE to the amplitude and frequency of the time series. The flow chart of the AAPE algorithm is shown in Assuming that the initial value of The AAPE calculation of the time series can be expressed as follows:The traditional RVM is a binary classifier which cannot directly solve the multi-classification problem. The multiclass relevance vector machine (mRVM) effectively solves the multi-classification application problem of the traditional RVM. The basic principle of the mRVM is described below.The input training data sample set is denoted as The continuous nature of In order to ensure the sparsity of the mRVM, similar to the RVM, a normal prior distribution with mean value of 0 and variance of The regressors When category For a certain category, the posterior expectation of auxiliary variables is:For The posterior probability distribution of the prior parameters of the weight vector is:1 follows the construction process, starting with an empty sample set, gradually adding samples according to their contribution to the method, or deleting samples with a low contribution to the method. The mRVM1 has two convergence principles: conv1 and conv2. The mRVM1_conv1 follows the principle described by [1_conv2 adds the limit of the minimum number of iterations to the mRVM1_conv1. The mRVM2 follows a top-down process, first loading the entire training sample set and then removing the unnecessary samples during the training process. The mRVM2 has two convergence principles: convA and convN. For the mRVM2_convA principle, 2_convN, the number of iterations is limited to Psorakis proposed two training methods of the mRVM in the literature  and the ribed by . The mRVThe main process of the proposed fault diagnosis method of rotating machinery includes signal preprocessing, fault feature extraction and fault identification. The principle of the fault diagnosis method proposed in this paper is introduced below.Due to the fault of rotating machinery, the vibration signal has impact characteristics and the impact amplitudes are obviously different with different fault severity. In order to reduce the influence of external interference on the vibration signals and highlight the fault features of the vibration signals, it is necessary to preprocess the vibration signals before the feature extraction.Although different from the time-frequency analysis method such as the EMD, EEMD and LMD, the ITD is used to highlight the major amplitude variations in the vibration signals. The ITD algorithm is adopted to decompose the vibration signal into a sum of proper rotation components, for which instantaneous frequency and amplitude, as well as a monotonic trend, are well defined. The ITD can effectively suppress the mode mixing and end effect. The optimum proper rotation component is selected for further fault feature extraction because it contains the most obvious fault features. The calculation process of signal preprocessing based on the ITD can be referred to In order to effectively extract fault features of the vibration signals, an improved multi-scale amplitude-aware permutation entropy (IMAAPE) algorithm is proposed in this paper. This method improves the coarse-graining procedures in a multi-scale analysis and improves the stability of the fault feature extraction. In the classical MSE algorithm, when the scale factor rocedure .Supposing that the time series to be analyzed is For each scale factor The high-performance multi-classifier can realize the fault type identification and further, a fault severity analysis of rotating machinery. The mRVM is adopted to analyze and identify the fault features of rotating machinery in this paper. After the feature extraction of the vibration signal samples with different fault types and fault severity by IMAAPE, a fault feature set is formed to model the mRVM classifier. The established mRVM classifier can identify the fault type and analyze the fault severity of rotating machinery by extracting the IMAAPE fault feature from the vibration signals.The fault diagnosis procedure of rotating machinery proposed in this paper is shown in In order to verify the feasibility and effectiveness of the fault diagnosis method of rotating machinery proposed in this paper, the rolling bearing and gearbox are taken as examples to carry out the experiments and analysis. The rolling bearing experiment adopts the famous public data set provided by Case Western Reserve University Bearing Data Center . The geaThe experimental platform designed by Case Western Reserve University Bearing Data Center is shown in A vibration signal waveform of the rolling bearing with ball elements fault under the fault diameter of 7 mils with the load 0 hp is shown in The three dimensions of the IMAAPE feature vectors for different fault types under different fault diameters with load 0 hp is shown in 1_conv1 is higher than other classification methods, and at the same time, this method has reasonable operation efficiency. Therefore, the mRVM1_conv1 was used as the multiple classifier of the rolling bearing fault diagnosis method in this paper.In order to illustrate the fault identification accuracy of the fault diagnosis method based on the IMAAPE and the mRVM proposed in this paper, the samples under different loads were used to verify the effectiveness of the proposed method. The selection of the experimental samples is shown in 1_conv1 under different fault severity with the load 0 hp is shown in The fault identification accuracy of mRVMIn this paper, the effectiveness of the different fault extraction methods combined with the mRVM classifier for the rolling bearing were compared. The experimental results are shown in The experimental platform QPZZ-II was manufactured by Jiangsu Qingpeng Diagnosis Engineering Co., Ltd. A picture of QPZZ-II is shown in The vibration signal waveforms of the gearbox in different fault conditions are shown in The vibration signal is decomposed by the ITD and the ITD decomposition results (PR components) are shown in As shown in This paper presents a novel diagnosis method for rotating machinery, which can further analyze the fault severity of rotating machinery on the basis of accurately identify the fault types. The experiments were conducted to illustrate the validity and feasibility of the fault diagnosis method for rotating machinery. This paper can summarize the following conclusions:(1) The improved multiscale amplitude-aware permutation entropy (IMAAPE) proposed in this paper improves the coarse-graining process of the MSE and the problems existing in the PE, and can effectively extract the fault information contained in the vibration signals. Moreover, compared with other fault feature extraction methods, the IMAAPE has higher execution efficiency.(2) The multiclass relevance vector machine (mRVM) is suitable for the multi-classification of rotating machinery and has high identification accuracy on the basis of reasonable selection of nuclear parameters.(3) The rolling bearing experiments and gearbox experiments show the effectiveness of the proposed method. The experimental results on the rolling bearing and gear box show that the proposed fault diagnosis method for rotating machinery has a high fault identification accuracy of over 99%. In particular, the rolling bearing experiments show the potential application of the proposed method in fault severity analysis.


OBJECTIVES/SPECIFIC AIMS: The objective of this research is to determine under what conditions endpoints based on estimated glomerular filtration rate (eGFR) slope or on relatively small declines in eGFR provide valid and useful surrogate endpoints for pivotal clinical trials in chronic kidney disease (CKD) patients. METHODS/STUDY POPULATION: We consider 2 classes of surrogate endpoints. The first class includes endpoints defined by the average rate of change in eGFR during defined portions of the follow-up period of the trial, following initiation of the randomized treatment interventions. The second class includes composite endpoints defined by the time from randomization until the occurrence of a designated decline in eGFR or kidney failure. The true clinical endpoint is considered to be the time from randomization until kidney failure, irrespective of the trajectory in eGFR measurements prior to kidney failure. We apply statistical simulation to determine conditions under which alternative endpoints within the 2 classes are (1) valid surrogate endpoints, in the sense of preserving a low probability of rejecting the null hypothesis of no treatment effect on the surrogate endpoint when there is no treatment effect on the clinical endpoints and are also (2) useful surrogate endpoints, in the sense of providing increased statistical power that allows significant reductions in sample size and/or duration of follow-up. Input parameters for the simulations include (a) characteristics of the joint distribution of the longitudinal eGFR measurements and the time to occurrence of renal failure, (b) characteristics of the short-term and long-term effects of the treatment, and (c) design parameters, including the duration of accrual and follow-up and the spacing of eGFR measurements during the follow-up period. We use joint analyses of 19 treatment comparisons across 13 previous clinical trials of CKD patients to guide the selection of input parameters for the simulations. We apply longitudinal mixed effects models for analysis of endpoints based on eGFR slope, and Cox regression for analyses of the composite time-to-event endpoints. RESULTS/ANTICIPATED RESULTS: We have previously shown that surrogate endpoints defined by eGFR declines of 30% or 40% can provide valid and useful alternative endpoints in CKD clinical trials for interventions that do not produce short-term effects on eGFR which differ from the longer-term effects of the interventions. Other factors influencing the validity and utility of these endpoints include the average baseline eGFR, the mean rate of change in eGFR, and the extent to which the size of the treatment effect depends on the patient’s underling rate of eGFR decline. We will extend these results by presenting preliminary results describing conditions under which outcomes based on eGFR slope provide valid and useful alternatives to the clinical endpoint of time until occurrence of kidney failure. DISCUSSION/SIGNIFICANCE OF IMPACT: The statistical simulation strategy described in this research can be used during the design of clinical trials of chronic kidney disease to assist in the selection of endpoints that maximize savings in sample size and duration of follow-up while retaining a low risk of producing a false positive conclusion in the absence of a true effect of the treatment on the time until kidney failure.


Special Issue on the topic of Electron Crystallography, now available in the August 2019 issue of Acta Crystallographica, Section B, contains contributions which we hope will interest readers of IUCrJ.A  IUCrJ has published 111 articles with the term ‘electron crystallography’ as one of the keywords, with these articles attracting 450 citations a year and comparable activity continuing into 2019. This level of relevant activity provides the context and justification for the more specialized, in-depth, Special Issue on Electron Crystallography now available in the August 2019 issue of Acta Crystallographica, Section B, which contains important contributions from many of the major players in the field. We therefore believe that this Special Issue will prove attractive and relevant to the readership of IUCrJ and we wish to recommend the articles therein, as described in the Guest Editors’ Introduction reproduced below.Since its launch in 2014, Introduction by the Guest Editors of the Special Issue on Electron Crystallography Structure analysis of micro- and nanocrystalline materials has witnessed immense progress in the last decade thanks to the development of electron diffraction techniques. The automation of data collection, development of new data collection modes and improvements in the data treatment have allowed unprecedented progress in most aspects of crystallography dealing with very small crystals. Probably the most notable change of paradigm is observable in the structure determination of unknown phases by electron diffraction. Three-dimensional diffraction techniques now allow almost routine solution and refinement of structures from single crystals as small as a few tens of nanometres, providing access to hitherto unsolvable crystal structures or to previously unattainable levels of structural detail. Scanning diffraction techniques allow phase and orientation mapping with nanometre resolution and even three-dimensional reconstruction of phase and orientation distributions.et al., 2019et al., 2019et al., 2019et al., 2019This special issue features a collection of original contributions covering a broad range of aspects of electron crystallography. An interested reader will find papers describing the foundations and methodological basis of structure solution by electron diffraction (Eggeman, 2019The collection of contributions in this special issue showcases the diversity of applications of current electron diffraction techniques, demonstrates the state of the development of the technique and also features work that further advances the electron diffraction methods. We believe that this special issue can serve as a starting point for anybody interested in electron crystallography and we are convinced that the contributions in this issue will become reference points for future research in this exciting field.


This study attempts to establish the relationships that exist between the different variables of organizational climate and job satisfaction among academic staff in some selected private Universities in South-West Nigeria, to ascertain related factors in organizational climate that can cause dissatisfaction among academics; and to determine if there is a significant difference in the way senior academics and junior academics perceive the existing organizational climate. A total of 384 copies of questionnaires were administered to selected five (5) private Universities in the South-West Zone of Nigeria but a total of 293 questionnaires were returned fully and appropriately filled. The study made use of appropriate statistics such as measurement model  and Multiple Regression to obtain results. Specifications TableValue of the Data•The data can produce useful highlight on the factors that university lecturers view as enhancing job satisfaction within the organizational climate.•The management of schools will find the data helpful in improving staff morale and bringing about job satisfaction of their employees.•The data will be of great value in recommending policies and strategies for mitigating organizational correlates of job dissatisfaction.•To help in gaining understanding that the climates of an organization and job satisfaction vary together.•The questionnaire attached can be modified, adopted or adapted for further comparative researches in private and public universities and other industries aside from educational industry.1Survey method was used mainly by questionnaire to collect the data from University lecturers in Southwest Nigeria. Respondents were requested to respond to questions with self-administered and structured questionnaire. The researcher utilized one structured questionnaire for both the senior academics and junior academics. This was presented personally to all respondents by the researcher in the sampled universities. This enhanced uniformity of response bearing in mind the degree of variations in perception of what the organizational climate may be referred to The study populations from which the sample was drawn consist of eighteen (18) private universities in the Southwest Nigeria. Out of these private universities, five (5) were taken as the study sample through judgmental sampling method and questionnaires were administered to the academic staff ranging from the Professors, Associate Professors, Senior lecturers, Lecturers 1, Lecturers 2, Assistant lecturers and Graduate Assistants. The total number of academic staff in the selected private universities is 754. The private universities chosen for this study are Covenant University, Bells University of Technology, Crawford University, Babcock University and Bowen University.2The evolving competition in the higher education environment in Nigeria brought about by increase in the number of new Universities has necessitated the need for good organisational climate that will enable these Universities retain their best employees. Reports by NUC (2008) revealed that though Universities are increasing, yet the number of qualified teachers is not increasing proportionately. Thus, surveys are necessary to establish the relationships that exists between the different variables of organisational climate and job satisfaction among academic staff of selected private Universities in Southwest Nigeria.Out of 384 copies of questionnaire administered, only 293 copies of questionnaires were returned representing 76.30%. Majority of the questions used were adapted with some modifications from a job satisfaction questionnaire. Questionnaire for the study were sorted and those that were not properly filled were removed. To minimize errors, data from questionnaire were coded so as to pave way for editing of data before the use of SPSS-Statistical package for Social Sciences-software.For the purpose of efficiency and thoroughness two field assistants were recruited and trained. The training focused on the pertinent objectives and importance of the study, how to administer/conduct the study instruments and how to secure respondents’ informed consent. The researchers ensured that respondents were well informed about the study and the objectives of this research and they were encouraged with the participation process. Respondents were offered the opportunity to stay anonymous and their responses were treated confidentially.Hence, this study has extensive implications for the institutions, academic staff, government, educators and researchers in this regard. It can be concluded that the success of these universities depend on the ability to impact on the motivation and job satisfaction of academic staff with a wide range of benefits to promote retention and reduce job-hopping. To this end, the data presented in this article is imperative for more comprehensive analysis as presented in


This study aims to present the feasibility of the open approach of hemilevator excision (HLE) as a promising alternative of the laparoscopic and/or robotic ones for the treatment of low rectal cancer extending to the ipsilateral puborectalis muscle.A 60-year-old male patient with a high-grade differentiated rectal adenocarcinoma at the right side of the lower rectum invading puborectalis muscle. The proposed operation consists of a combination of extralevator abdomino-perineal excision (ELAPE), intersphicteric resection (ISR), and low anterior resection (LAR) since it resects the ipsilateral to tumor levator ani muscle (LAM) from its attachment at the internal obturator fascia and the deep part of ipsilateral external anal sphincter (EAS), while the distal part of dissection is completed in the intersphincteric space taking out the internal anal sphincter (IAS). At the contralateral side of the tumor, the dissection plane follows the classic route of LAR.Pathology proved the oncologic adequacy of resection. MRI at the fourth postoperative week showed clearly the right aspect of anorectal junction free of tumor. Anorectal manometry revealed a fair anorectal function which is in accordance with the findings of clinical assessment of patient after restoring large bowel continuity .This is the first case of the open HLE that seems to be a good alternative compared to ELAPE or conventional APR, as it offers oncologic adequacy and a fair anorectal function. The treatment of cancer of the rectal lower third has been a challenging issue over time. Back in 1908, Ernest Miles first described the abdomino-perineal excision (APE) . HoweverA 60-year-old male patient was referred to our hospital with a high-grade differentiated rectal adenocarcinoma. The pelvic MRI revealed a tumor at the lower rectum  that invaded puborectalis muscle to a length of 9 mm on the right side. Moreover, the CT scan proved the absence of any distant metastasis. Given the tumor location and the absence of distant metastases, the patient went through manometric evaluation of anorectal function and clinical assessment with the Wexner scale score for incontinence . MRI at the fourth postoperative week showed clearly the right aspect of anorectal junction free of tumor and the absence of ipsilateral LAM Fig. .Fig. 3a In the earlier days of colorectal surgery for malignant tumors of the lower third of rectum, the operation of choice was the abdomino-perineal resection (APR) in which the sigmoid, the rectum, and the anus were excised leaving the levator ani muscle complex intact in both sides. In this way, the specimen resembles an hourglass due to the characteristic “waist” in the middle . HoweverThis is the first attempt at Greece to perform a technique which targets the saving of anal sphincter for very low rectal cancers with extension to the puborectalis muscle. This is the first procedure with removal of puborectalis muscle and partial excision of external sphincter with preservation of anal function. This innovative procedure requires full knowledge of pelvic anatomy. The surgical team must have experience to the standard TME. This procedure is the hope for a life without colostomy for patients with these tumors. Undoubtedly, a larger number of cases is demanded to draw firm conclusions since we have to take into account that anatomic characteristics such as gender, body mass index, etc. might affect the feasibility of the procedure.


The paper aims to present the reconstructive surgical approach in the case of a patient with complex soft tissue lesions of the calf. The patient was the victim of a road accident resulting in the fracture of the right tibia for which screw-plate osteosynthesis was performed. The chosen therapeutic solution was represented by covering the soft tissue defects using a complex algorithm that involved the use of a reverse sural flap associated with a medial hemisoleus muscle flap and a split-thickness skin graft.Considering functional recovery and the degree of patient satisfaction, the result of the therapeutic conduct was appreciated as very good. The association of the reverse sural flap with the medial hemisoleus flap can be a solution for solving complex cases with multiple soft tissue defects located in the middle and lower third of the calf. Fractures of the calf caused by road accidents often raise problems regarding the reduction and fixation of the fragments through the use of osteosynthesis materials. The intensity of the traumatizing agent, the high degree of contamination, and the associated lesions represent negative prognostic factors, which must be carefully integrated into the therapeutic protocol to avoid the structural, septic, and functional complications.The material presents the case of a 60 years old polytraumatized patient, the victim of a road accident that resulted in multiple injuries including minor cranial-cerebral trauma, thoracic and abdominal trauma with multiple rib fractures and fracture of the right tibia for which reduction and fixation were performed by using a plate and screws. The patient was admitted to the hospital 12 months after the trauma with calf infections associated with the exposure of the osteosynthesis material in the middle and inferior parts of the calf and local contamination with worms.The therapeutic protocol consisted of surgical debridement in order to eliminate the worm contamination, in combination with the administration of the specific antibiotic therapy after obtaining the result from the antibiogram . The next step was the ablation of the osteosynthesis material, followed by the surgical reconstruction in one stage with a medial hemisoleus flap for the coverage of the soft-tissue defect located in the middle third of the calf and a reverse sural fasciocutaneous flap for the defect in the lower third of the calf, finally the muscular flap being covered by split-thickness skin graft.The patient was reassessed periodically for 15 months, during the consults being determined that the flaps were integrated and that the functional recovery was completed, demonstrated by the socio-professional reintegration without limitations.Eradication of the septic outbreak and worm contamination was achieved within seven days after the osteosynthesis material ablation by surgical excisional debridement, daily dressing changes with antiseptic solutions (chlorine-based compounds) and administration of a drug combination that included a third-generation cephalosporin and gentamicin.A medial hemisoleus flap was used for the coverage of the soft-tissue defect from the middle third of the calf that was associated with bone exposure . In the The soft tissue defect in the lower third of the calf was covered with a reverse sural fasciocutaneous flap, followed by grafting the donor site with a free split-thickness skin graft . The locThe hospitalization time in the plastic surgery department was 14 days, the patient being discharged during the healing process with a fully functional lower limb, subsequently being reassessed regularly for 15 months after the intervention. Postoperative follow-up showed that the flaps were fully integrated  without The reconstructive options for covering the soft-tissue defects of the calf have been carefully studied within the international scientific community, the specialized literature presenting a multitude of interesting articles in this respect. The current approach is to cover the defects with flaps based on the perforating arteries, which offers structural similarity with the anatomical region to be reconstructed, in the conditions of an increased safety profile and reduced morbidity of the donor site . HoweverThe hemisoleus muscle flap represents a durable solution to cover the soft-tissue defects, especially in the lesions associated with bone exposure after the healing of a septic outbreak. The generous vascular component characteristic to this type of flap -6, constThe reverse sural flap represents a firm solution for the coverage of the soft-tissue defects located in the lower third of the pelvic limb , the redThe association of reconstructive techniques that involves the usage of the reverse sural flap and the hemisoleus flap is a feasible solution for solving cases that associate multiple soft tissue defects of the calf.In this case, the use of the medial hemisoleus flap for the coverage of the soft-tissue defect located in the middle third of the calf was not associated with a significant impairment of the patient’s locomotor capacity, the patient being able to move normally and carry out his daily and professional activity without limitations.The association between the hemisoleus muscle flap and the reverse sural flap may be a solution for complex cases where the use of perforator flaps is not possible.Muscle flaps represent the “safety belt” in the cases that require complex reconstructions of the calf, often being the optimal solution for patients with complex fractures associated with neglected septic processes and soft tissue defects of considerable size.The authors confirm that there are no conflicts of interest.


Since understanding how the human brain generates neural commands to control muscles during motor tasks still remains an untapped question, great interest is shown in the validation and application of muscle synergies among research groups focused on the electromyography (EMG). In the last decades, the factorization of the EMG signals by means of muscle synergies has been proposed to understand the neurophysiological mechanisms related to the central nervous system ability in reducing the dimensionality of muscle control. For this reason, we planned a special issue on validation and application of the muscle synergy theory to discuss the methodological issues and to propose novel applications in clinics, robotics, and sports. The special issue achieved success among researchers as demonstrated by the large amount of submitted papers and the scientific impact of the published ones.The special issue is composed of twelve manuscripts. Three systematic reviews are included: (i) the first one is focused on the meaning of the muscle synergy theory to understand its applicability as a neurorehabilitation tool ; (ii) the second one is useful to understand the applications of muscle synergies in the investigation of muscle coordination during walking of poststroke patients ; and (iii) the third one offers a complete overview on the tangible applications of muscle synergies in clinics, robotics, and sports .As concerns clinics, the effects of upper limb weakness and task failure, which is the inability to maintain a certain level of force during a task, on the muscle synergies are evaluated by Roh et al. and Castronovo et al., respectively. As regards robotics, the feasibility to use a muscle synergy approach to implement the control system of an upper limb exoskeleton is presented by Chiavenna et al. Moving to the sports, two papers are focused on understanding the muscle synergy organization during the execution of specific technical actions of the badminton , one paper shows the muscle synergy structure involved in stability exercises of rhythmic gymnastics , while the motor control underlying the throwing movement is studied by Cruz-Ruiz et al. Finally, two papers investigate some fundamental methodological issues; in particular concerning the influence of initialization techniques for the application of non-negative matrix factorization  and the reliability and repeatability of the methodology for extracting muscle synergies during daily life activities .We hope that this special issue can represent an important step to strengthen the use of muscle synergies to explain how the human brain organizes the muscle activation both in clinics and robotics, as well as in sports applications.


Following publication of the original article , the autIn this Correction the incorrect and corrected version of Fig. Originally Fig. The corrected version of Fig.


Peripheral neuropathies of the shoulder are common and could be related to traumatic injury, shoulder surgery, infection or tumour but usually they result from an entrapment syndrome. Imaging plays an important role to detect the underlying causes, to assess the precise topography and the severity of nerve damage. The key points concerning the imaging of nerve entrapment syndrome are the knowledge of the particular topography of the injured nerve, and the morphology as well signal modifications of the corresponding muscles. Magnetic Resonance Imaging best shows these findings, although Ultrasounds and Computed Tomography sometimes allow the diagnosis of neuropathy. Peripheral neuropathies of the shoulder are common and represent an important cause of morbidity and disability in patients. They could be related to traumatic injury, shoulder surgery, infection or tumour, but usually they result from an entrapment syndrome, a condition in which the nerve is stretched into an incompressible space .Although all the nerves of the shoulder could be affected, we will focus our topic on the major nerves that could be involved in this area, principally suprascapular nerve, followed by the axillary, musculocutaneous, spinal accessory and long thoracic nerves. The sensory and motor innervations of these nerves as well as the etiology and usual site of entrapment are summarized in Table edema signal of the denervated muscle. This finding is related to an increased extracellular free water and muscle blood volume. In acute and subacute stages, high signal intensity fluid is found in T2-weighted with fat suppression sequences associated with normal signal in T1-weighted sequences  could add more information than X-ray by allowing morphologic evaluation of suprascapular and spinoglenoid notches, assessing the muscular trophicity and fatty degeneration, and showing extrinsic compression of the injured nerve by labral, mucoid cysts or tumours. Ultrasonography (US) is a useful, non-invasive modality that allows bilateral with dynamic comparison of the periscapular soft tissue. US does sometimes allow morphologic assessment of the nerves, essentially on the basis of focal thickening, and can also guide diagnosis on the basis of atrophy and fatty degeneration, characterized by a loss of muscle volume and muscle hyperechogenicity. The key points concerning the imaging of nerve entrapment syndrome are the morphology and the signal changes of the innervated muscles, best demonstrated by Magnetic Resonance Imaging (MRI). The earliest MRI sign of an impairment of the relationship between motor neurons and muscle fibers is the The suprascapular nerve is a mixed nerve providing motor innervation to the supraspinatus and infraspinatus muscles and sensory innervation of the coracohumeral ligament, the coracoclavicular ligament, the subacromial bursa, the acromioclavicular joint and upper and posterior glenohumeral joint. The nerve arises from the upper trunk of the plexus brachial and is formed by the ventral rami of C5 and C6 roots and occasionally from the C4 root. Then, it crosses the posterior cervical triangle in the supraclavicular fossa, deep to the omohyoid muscle Figure  23]. In3. In23].The clinical presentation of suprascapular neuropathy may be various. The pain is usually chronic and dull, in the superior and posterior shoulder often radiation to the neck or lateral arm. Weakness, loss of function and atrophy of the shoulder are other clinical manifestations.The causes of the nerve entrapment are multiple. The suprascapular notch is the most frequent point for the suprascapular nerve to be entrapped by compression or traction. In addition, the anatomic configuration of the suprascapular notch may represent a predisposing factor to the development of entrapment. Several morphologic variations in size and shape of the suprascapular notch have been reported. Rengachary et al., described six types of suprascapular notch and their incidence, based on the shape of the notch . Natsis 911Extrinsic compression by labral or mucoïd cyst Figure , tumour Microtraumatisms by repetitive movements, especially with overhead activities, for example in volleyball and baseball athletes, expose the nerve to tension especially with a predisposing anatomy. As the shoulder is in extreme external rotation and abduction, the muscles of supraspinatus and infraspinatus impinge upon the scapular spine compressing the motor branch of the infraspinatus, resulting to an isolated infraspinatus muscle weakness .At the level of the spinoglenoid notch, the nerve entrapment may be due to an increased tension in adduction and internal rotation with a hypertrophied inferior transverse scapular ligament .A possible association between the suprascapular nerve entrapment and extensive rotator cuff tears has been reported. The mechanism of this entrapment is based on cadaveric study that showed that the medial retraction of supraspinatus tendon stretches the nerve by changing the angle between the nerve and its first motor branch . This re16bullseye sign as an indicator of peripheral nerve constriction in Parsonage Turner syndrome [Imaging, especially MRI, plays an important role to detect the underlying causes of nerve damage , the precise topography of injury  MRI is also useful to determine the severity of the nerve injury (edema and/or atrophy) and to diagnose other cause of neuropathy such as cervical radiculopathy or Parsonage Turner syndrome. This syndrome is a rare idiopathic disorder, often attributed to viral infections or immunological reaction after vaccination, characterized by a sudden onset of pain of the shoulder girdle affecting one or several nerves of brachial plexus . There isyndrome .The axillary nerve is a mixed nerve, providing motor innervation of the deltoid and teres minor muscles, supplying collateral branches to the subscapularis and coracobrachialis muscles. This nerve provides also sensory innervation of the shoulder joint capsule (shared with suprascapular nerve), the inferior glenohumeral ligament and the posterolateral skin of the shoulder and the arm. The nerve is the terminal branch of posterior cord of the plexus brachial and is formed by the ventral rami of C5 and C6 roots, lying superior to the radial nerve and behind the axillary artery and vein 22. Five 23The quadrilateral space, also called quadrangular space or lateral axillary hiatus, is bounded by the teres minor muscle superiorly, the upper border of the teres major muscle inferiorly, the long head of the triceps brachii medially, and the surgical neck of humerus laterally . In most22The differences in innervation between the anterior and posterior branches of the axillary nerve explain the occurrence of an isolated palsy of the deltoid or the teres minor muscles with or without sensory loss in the axillary nerve distribution .unhappy triad is the condition in which multiple peripheral nerves injury occurs in combination with rotator cuff tear. In this triad, the axillary nerve is the most commonly affected  [The axillary nerve injury is one of the most commonly injured nerves during surgical procedures of the shoulder making up to 10% of all brachial plexus injuries. The anterior branch of the nerve, ascending around the surgical neck of humerus is at risk during deltoid splitting or humeral nailing or prosthetic procedures . It may  nerves) .Extrinsic compression by hematoma, posteroinferior labral cyst, bone callus, tumour, and accessory subscapularis muscle are other common etiologies of axillary nerve injury 28.Chronic compression of the axillary nerve, known as quadrilateral space syndrome is a rare and misdiagnosed neurovascular syndrome. This syndrome is defined as compression or mechanical injury of the axillary nerve or posterior circumflex artery as they pass through the quadrilateral space. The clinical manifestation is various including nondermatomal neuropathic pain, numbness and weakness in the shoulder or vascular manifestations such as thrombosis, digital or hand ischemia. The electromyography is often normal. This syndrome has been reported in overhead or throwing athlete including volleyball, baseball, swimming but also in yoga or window cleaning that involve abduction and external rotation . ImagingThe musculocutaneous nerve is a mixed nerve, providing motor innervation to the coracobrachialis, biceps brachii, and brachialis muscles and sensory innervation of lateral forearm. The nerve arises from the lateral cord of the plexus brachial and is formed by the ventral rami of C5 and C6 roots and occasionally from the C4 or C7 roots. There are numerous anatomical variations. Located lateral to the median nerve and axillary artery, the nerve runs frequently downward and passes through the coracobrachialis muscle and descends obliquely between the biceps brachii and the brachialis muscles, which it innervates. Then, the nerve emerges along the lateral margin of biceps aponeurosis and continues in the forearm as the lateral antebrachial cutaneous nerve .Weakness of biceps brachii muscle and, sometimes, sensory deficit in the forearm are the main symptoms of musculocutaneous neuropathy. Isolated musculocutaneous nerve injuries are rare and the reported causes are penetrating traumas, anesthetic blocks, anterior shoulder surgery especially in coracoid abutment (Latarjet procedure), and sport related entrapment such as windsurfing, rowing or weightlifting athletes. Proximal nerve injury can occur when the nerve pierces the coracobrachialis muscle during violent extension of the arm in throwing athletes or by entrapment between the biceps brachii and the brachialis muscles, in forced abduction and external rotation 3031. Ima30The long thoracic nerve (Charles Bell nerve) is a pure motor nerve arising directly from the ventral rami of C5, C6, and C7 roots and occasionally from the C4 root. The roots from C5 and C6 runs downward and pierce through the scalenus medius, while the root from C7 runs over this muscle. In the supraclavicular region, the upper division of the long thoracic nerve runs parallel and posterior to the brachial plexus close to the supra- scapular nerve. In the axilla, the upper and lower portion merge and extends along the side of the thorax to the lower border of the serratus anterior, supplying filaments to each digitation of this muscle .Traumatic injuries to the nerve after motor vehicle accidents, or after falls have been reported . The ner34Imaging shows denervation signs (edema and atrophy) of the serratus anterior and may help to eliminate other causes of scapular winging. In case of multiple muscle denervation sites, imaging could suggest a Parsonage Turner syndrome.The spinal accessory nerve  provides motor innervation of the trapezius and sternocleidomastoid muscles. It is a motor nerve arising from both the medulla and the spinal cord. The cranial fibers innerve the pharyngeal and laryngeal muscles and the spinal fibers arise from the anterior horn of the upper five (or six) cervical vertebra. The spinal fibers enter the posterior cranial fossa, merge with the cranial fibers and then exit the skull via the jugular foramen, along with the vagus and glossopharyngeal nerves. The nerve passes deep into the posterior belly of the digastric muscle to supply the sternocleidomastoid muscle. Then, it passes through this muscle and runs obliquely across the posterior cervical to end in the deep surface of trapezius muscle via several terminal branches to supply upper, middle and lower trapezius muscle 37.droopy shoulder characterized by the inability to raise the affected arm above the level of the shoulder.The nerve is vulnerable in the posterior triangle of the neck, during radical neck surgery, tumour dissection and cervical lymph node biopsy. Traumatic injury by direct impact or deep tissue massage and water-skiing injuries has been reported but occurs rarely. These injuries lead to a Imaging of this nerve is quite challenging but MRI shows denervation of the trapezius and sternocleidomastoid muscles Figure . In patiDiagnosis of shoulder neuropathy is difficult and challenging because of overlapping symptoms with various origins. Imaging plays an important role to detect the underlying causes to assess the precise topography and the severity of nerve damage. The key points concerning the imaging of nerve entrapment syndrome are the knowledge of the precise topography of the injured nerve and the morphological and signal change of the innervated muscle, best shown by MRI, although US and CT may allow the diagnosis of neuropathy.


Identification and assessment for cognitive impairment is a difficult task further complicated by the need to determine capacity. Issues related to cognitive impairment and capacity create ethical dilemmas potentially spanning all four ethical principles: autonomy, beneficence, non-malfeasance, and justice. This paper uses a case scenario to describe different types of cognitive impairment and demonstrate ethical issues that commonly arise when treating patients with cognitive impairment in the clinical setting. The authors also recognize the complexity of capacity as an issue that spans both the medical and legal fields and provides explanations and distinctions. The overall goal of this paper is to raise awareness of the impact of cognitive impairment on the vulnerability of older adults, describe the complex ethical issues that cognitive impairment and capacity raise and the importance of defining capacity in the context of the legal and medical fields.


Objective: The impact of substance abuse on violent behavior in patients suffering from schizophrenia is well-known. However, the association between the pattern of substance abuse and certain aspects of criminal behavior like the severity of offense, the previous history of violence and the age at onset of the criminal career is still unclear.Method: To assess the relationship between substance abuse, schizophrenia and violent behavior we examined healthy non-offenders; healthy offenders; non-offenders suffering from schizophrenia; and offenders suffering from schizophrenia, with respect to different patterns of substance abuse .Results: Healthy offenders as well as offenders and non-offenders suffering from schizophrenia are characterized by increased rates of alcohol and illicit drug abuse. Especially multiple substance abuse appears to lower the threshold of aggression and illegal behavior. This effect is more pronounced in subjects suffering from schizophrenia. In both offender groups the abuse of psychoactive substances is associated with an earlier onset of the criminal career, but has no impact on the severity of the offenses.Conclusion: Our results point to the need for a differentiated view on the contribution of substance abuse to the criminality of subjects suffering from schizophrenia. During the last 20 years various studies have confirmed a moderate though statistically significant association between schizophrenia and violence –9. Most However, the aforementioned association remains unclear for several reasons:Compared with the general population, subjects suffering from schizophrenia exhibit significantly higher rates for substance abuse. This primarily concerns alcohol and cannabis, while opiates and hallucinogens are of minor importance –40. SubjIndependent of a subject's mental health status, substance abuse is by itself a major criminogenic factor –47. A meSince 1996 the World Health Organization (WHO) has compiled the Global Alcohol Database to provide a standardized reference source of information for a global epidemiological survey of alcohol use and its related problems . Since 1Our study addresses the following questions:Are there differences concerning the prevalence rates and patterns of substance abuse between offenders suffering from schizophrenia and non-offenders suffering from schizophrenia?Are there differences concerning the prevalence rates and patterns of substance abuse between offenders with schizophrenia and healthy offenders?Do the rates of substance abuse in these three groups differ from the rates in healthy controls?Is there an association between substance abuse and patterns of criminal behavior independent of the mental status of the offenders?In order to assess the impact of the patterns of substances abuse on criminal behavior of male patients with schizophrenia, we used a case-control-study-design with four groups.One hundred and three male offenders suffering from schizophrenia (OS) according to DSM-IV , admitteOne hundred and three healthy male offenders (OH), matched for age and severity of offense with the offenders suffering from schizophrenia.One hundred and three male non-offenders suffering from schizophrenia according to DSM-IV (NoS) matched for age and duration of illness with the offenders NGRI.One hundred and three male non-offenders without major mental disorders or personality disorders (NoH), matched for age with the other groups. The social stratification and the town/rural distribution of this group are representative for the overall population of Eastern Austria .The protocol of the study was approved by the ethic commission of the Medical University Vienna. All patients gave written informed consent in accordance with the Declaration of Helsinki.All subjects underwent the Structured Clinical Interview for DSM Disorders (SCID 1 + 2). The Inter-rater reliability tested for 25 patients was very satisfying . We distinguished three types of harmful substance abuse:AlcoholIllicit DrugsMultiple substances The assignment to social classes was done according to Kleining and Moore . The patThe frequency of substance abuse was analyzed by means of Chi-Square Tests, associations between the patterns of violent behavior  and the different types of substance abuse  by means of One-Way ANOVA (df = 3).The social and clinical data of the four groups are listed in Table Table Finally we compared the relationship between the different types of substance abuse and the patterns of criminal behavior of the two offender groups, which showed substantial similarities Table . By meanComparison of the four groups shows that a statistically significantly higher prevalence of substance abuse is associated with both psychiatric illness and offending behavior Table . Only 4.Non-offending patients with schizophrenia differ from the other groups by a relatively high prevalence of illicit drug abuse (25.2%) which is nearly exclusively confined to cannabis. This is in line with previous findings of studies on the use of cannabis in schizophrenic patients , 55, 56.Compared with the offenders suffering from schizophrenia, significantly fewer cases of multiple substance abuse were identified among the non-offenders suffering from schizophrenia  allows to draw robust and differentiated conclusions concerning the impact of substance abuse on criminal behavior in offenders suffering from schizophrenia. However, Eisner  stated tTherefore we have to take into account the globally different rates of criminality and substance abuse. As they are substantially higher in the USA compared to Europe, the results of US-studies apply only partly to European countries. Austria with its low rates of criminality and substance abuse  is in line with most of the other Western European countries. As a consequence, methodologically similar studies in other regions are necessary to investigate the variations of the impact of the culture-specific types of substance consumption on the criminal behavior of patients suffering from schizophrenia.TS and HS planned the study and collected the data of the offender groups. TS did the statics and wrote the paper. KR collected the data of both non-offending groups.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The aim of this paper is the discussion of quality control (QC) criteria for environmental monitoring of organic contaminants at trace levels in water. In addition, QC criteria in the identification and confirmation of target analytes have been considered.


FRC), in the absence and presence of piracetam (gHSAFRC-PIR), was performed by fluorescence quenching of macromolecules. On the basis of obtained data we concluded that under the influence of glycation, association constant (Advanced Glycation End-Products (AGEs) are created in the last step of protein glycation and can be a factor in aging and in the development or worsening of many degenerative diseases . Albumin is the most susceptible to glycation plasma protein. Modified albumin by AGEs may be more resistant to enzymatic degradation, which further increases the local accumulation of AGEs in tissues. The aim of the present study was to analyze in vitro glycation of serum albumin in the presence of piracetam (PIR) and the gliclazide (GLZ)-glycated albumin interaction. The analysis of PIR as an inhibitor and GLZ interaction with nonglycated human albumin (HSA) and glycated by fructose human albumin (gHSA The tangent to the Scatchard curve at the intersection with the X-axis represents the average number of moles of ligand bound to one mole of albumin in the analyzed binding site. A linear Scatchard curve indicates the existence of one, independent class of binding sites in the albumin molecule. The Scatchard curve can also have a nonlinear curve. The course of the curve similar to hyperbole indicates the nonspecific nature of ligand binding, negative cooperativeness or the existence of many classes of binding sites. A “conical” curve indicates positive cooperativity or instability of the ligand .Hill’s coefficient was determined on the basis of Hill’s method (Equation (5)) :(5)log(rThe primary objective and novelty of this study was to estimate the inhibition properites of piracetam (PIR) and its impact on the gliclazide (GLZ)–glycated albumin interaction. Based on the conducted in vitro data we concluded that piracetam (PIR) used in eldery simultaneously with gliclazide (GLZ) inhibits the formation of Advanced Glycation Ends Products (AGEs) and increases the binding strength of GLZ to glycated albumin that weakens its therapeutic effect. Although the studies are preliminary and cannot be directly used in clinical practice, the results highlight the novelty and validity of the studies and suggest using other research methods as a continuation of this work.