The changing temperature and rainfall patterns associated with climate change are expected to alter the distribution of environmental suitability for malaria transmission in West Africa.We use a mechanistic model of disease transmission to investigate the effects of climate change on village scale hydrology, entomology, and disease transmission. This highly detailed model explicitly simulates water pools that serve as mosquito breeding sites, the life cycle of individual mosquito agents, and the transmission of the malaria parasite between human agents.We simulate current malaria conditions ranging from the very low transmission region bordering the Sahara to the higher transmission Savanna zones, focusing on areas with high sensitivity to increases in vectorial capacity. We then consider predictions of future climate, and assess the impact these changes would on malaria transmission.The use of this mechanistic model allows us to translate projected changes in temperature and rainfall into changes in vectorial capacity and malaria transmission rates.


Migraine headaches and undesirable quality of sleep in patients with multiple sclerosis are very common.The aim of the present study is the effectiveness of sleep health training on improving sleep quality, and reduction of the symptoms of migraine headaches in individuals with multiple sclerosis.Therefore, to do this, 60 patients with MS peered selected and randomly put into two groups of experimental and control. They answered Pittsburg quality of sleep of the Najarian symptoms of migraine headache. Experimental group took part for four sessions of Sleep health training session. After completing the sessions both answered to two tests again.The results showed that sleep health training on improving the quality of sleep and reduction the symptoms of migraine headache has been effective in experimental group.Therefore, sleep health training to improve the quality of sleep and reduce the symptoms of migraine headache sufferers of MS, can be conducted along with other pharmaceutical and medical treatments.No conflict of interest.


The appropriate function of the nervous system relies on precise patterns of connectivity among hundreds to billions of neurons across different biological systems. Evolutionarily conserved patterns of neural circuit organization and connectivity between morphologically and functionally diverse sets of neurons emerge from a remarkably robust set of genetic blueprints, uniquely defining circuits responsible for planning and execution of behavioral repertoires (Arenkiel et al., This Research Topic comprises a wide variety of articles contributing to current views and understanding of different neural circuits, how they are organized in neural networks, and what are the functional outputs of this organization. Additionally, pioneering researchers in the field review novel high-throughput tools and analytical approaches, further describing how these methods have evolved to better explore neural circuits at different levels, covering a wide spectrum of analyses that range from the study of big volumes of brain tissue, to the functional properties of a given network.The Research Topic eBook is organized into three chapters that cover different aspects of our current knowledge of neural circuits. In chapter 1 the reader will find articles related to the architecture and structural definition of neural circuits. In this chapter Li et al.  use a coTogether, this Research Topic brings to the readers not only new neurobiological data and novel analytical tools, but also offers new perspectives about the way we think about neural circuits and networks, giving rise to important insights to be considered when exploring structural and functional features of micro- and macrocircuits.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.


We report a rare case of 50-year-old Moroccan woman with local recurrence of a subcutaneous hydatid cyst in proximity to the medial surface of the tibia and another cyst at the tibialis posterior muscle in the absence of liver, lung und spleen involvement. The first surgery was done in another hospital three years ago; no adjuvant treatment was performed after surgery. Recurrence was diagnosed according to the MRI appearance, serological and pathological findings. The patient underwent complete excision of the subcutaneous cyst with two centimeters of the medial gastrocnemius muscle; the tibialis posterior muscle cyst was intraoperatively drained and irrigated with scolicidal agent as it was next to the posterior tibial pedicle. A periopertive anthelmintic chemotherapy was administered. Two years after the patient showed no recurrence. This case report and literature review describe an approach to the diagnosis and management of this pathological entity. Echinococcosis has its highest prevalence in countries, where the common intermediate hosts, sheep and cattle, are raised  , 2. The A 50 year old Moroccan female patient of rural origin presented in Avicenna hospital Rabat-Morocco with history of pain and swelling of the medial aspect of the right leg for two years. The patient had been operated, in another hospital, three years earlier for echinococcosis of the subcutaneous tissue of the right leg with no adjuvant treatment. No history of trauma, fever and weight loss was reported. A painful mass  next theRecurrent disease is defined as the appearance of new active cysts after therapy. It occurs after surgical or radiologic intervention and manifests as reappearance of live cysts at the site of a previously treated cyst or the appearance of new disease resulting from procedure-related spillage . The reaDetermining the ideal therapeutic approach for a recurrent subcutaneous and muscular hydatid cyst can be quite challenging for the surgeon. Moreover, the rarity of the disease renders the decision making on the favorable treatment quite difficult. Nevertheless, once the diagnosis is established, the surgeon should consider performing a radical procedure with periopertive administration of anthelmathic chemotherapy aiming in minimizing the possibility of a recurrence. A long term follow-up is required in all cases.


This e-book is the culmination of countless hours of meticulous work by global scientists. We would like to thank the researchers for their great contributions to this hot topic. The combination of these studies reflects the importance of the topic amongst researchers and practitioners and the wide interest from numerous laboratories around the world. The contributions include a variety of formats including five original investigations, three review articles, one opinion article and a hypothesis and theory article. Notably, these contributions included both human and animal models that encompassed a range of techniques from molecular mechanisms to real life interventions thus reinforcing the translational approach for the understanding of cardiovascular responses to stress.The three review articles (Huang et al., Following the review articles, two interesting papers addressed novel and important aspects for stress management therapies. The opinion article by Stults-Kolehmainen  highlighAs mentioned previously, the variety of original research investigations included within this topic reinforced the importance of research translation. The cross-sectional study by Childs and de Wit  reportedOther important responses during different sources of stress were also included in this e-book. The study of Rauber et al.  was the The study of Franklin et al.  documentFinally, the study of Sasse et al.  presenteThis e-book has taken the initial action to integrate current research findings to stimulate further discussion and research. We would like to thank the authors for their significant contributions and the many reviewers who critiqued and improved the overall topic. Future studies will clarify the importance of physical fitness, exercise and PA to regulate cardiovascular responses during stress and such benefits for cardiovascular health.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.


Ligularia, an important genus of the Compositae family, has captured the interest of natural product chemists for years. Phytochemical investigations on the title genus have led to isolation of hundreds of secondary metabolites with various skeletons. Herein, we summarized the chemical constituents of this genus and their biological activities over the past few decades.


Throughout human history, complementary and alternative medicine in the form of folk medicine has emerged and flourished in every civilization, tribe, and continent. Some forms evolved to become traditional medicine and some disappeared to be forgotten, while others have been labeled untraditional medicine and are now regarded as complementary and alternative medicine. In the past half century, an increasing number of patients and health care providers in the West have become dissatisfied with aspects of traditional Western medicine and have turned their attention to these branches of untraditional medicine. The term integrative or integrated medicine was born recently as the popularity grew in incorporating complementary medicine to reinforce gaps to better fulfill the purpose of traditional medicine.Complementary and alternative medicine includes many branches such as herbal medicine which increasingly appears in the form of nutritional supplements to elude increasing governmental regulation as demand for these products grow. In an analysis by the International Trade Center that spanned 2010–2013, it was estimated that global medicinal plant production was $50 billion and is growing at a rate of almost 16% annually. The increasing use of various forms of traditional herbal medicine in combatting modern illnesses, particularly the dangerous side effects of pharmaceutical drugs, has proven to be valuable. However, the absence of proper warning labels concerning drug-herb interaction causes an alarming number of emergency clinic cases due to the unwanted consequences of some of these interactions.Impact of Chinese herbal medicine on American society and health care system: perspective and concern” reflected these issues and concerns. Also included are articles highlighting research into ginkgo biloba and cancer-related herbal research.Acupuncture is one of these aforementioned branches that has made major inroads into Western medicine. It, along with the increased interest and research in herbal medicine, is likely the most researched branch of alternative medicine in the West. Acupuncture has been recognized for its healing value by the National Institutes of Health in 1997. The subsequent creation of the National Institute of Complementary and Alternative Medicine within the NIH in the United States and the founding of European Congress of Integrative Medicine has promoted research into these various overlooked disciplines. Understanding the value and discovering the merits of each discipline using modern Western scientific methodology is integral in trying to incorporate desirable aspects into traditional medicine. This special issue reviewed and accepted merited articles ranging in topics from the current dilemma of Eastern medicine in the West to the problem of government oversight in the field of herbs that are frequently and misguidedly marketed as nutritional supplements. An article included in this special issue titled “Noting all these development, we turn our attention to a systematic way of doing traditional Chinese medicine research. All articles published in this special issue underscore the positive trend of returning to natural approaches for our health care and emphasize better treatment for all types of human sickness.There were three research articles, in this special issue, on the mechanisms of immune system and apoptosis for the therapeutic studies of antitumor activities. Both in vitro herbal drugs possess an enormous potential for the cure of certain types of cancer diseases.Anti-inflammatory effects of 81 Chinese herb extracts and their correlation with the characteristics of traditional Chinese medicine” which suggests that herbs with pungent flavors be considered the drugs of choice due to their effective anti-inflammatory agents which can be evaluated by their effects on nitrogen oxide (NO) production and cell growth in LPS/IFNγ-costimulated murine macrophage RAW264.7 cells. This discovery could be used as one of the criteria to select different Chinese herbs for anti-inflammatory purposes. Also included in this special issue is an intensive study on the effect of Cryptotanshinone, extracted from the Chinese herb Dan Shen  on reversing the reproductive and metabolic disturbances in polycystic ovary syndrome (PCOS) in rats. This study and its analysis into the possible regulatory mechanism would validate the clinical efficacy of this particular herb for the treatment of PCOS patients.It is important to have well-designed pharmaceutical studies to help explain the millennia old theory of Chinese herbology and the mechanism, pharmacodynamics, pharmacokinetics, and pharmacognostics that elucidate the efficacy of Chinese herbs and unlock its century-old mysteries. The traditional clinical application of traditional Chinese medicine has been based on the characteristics of taste, flavor, channel entering, and actions of the herbs. This special issue includes an article entitled “The guest editors of this special issue hope that, through the articles accepted and published, we can bridge the gap between Western and Eastern medicines and bring them closer in order to further understand the human body and to promote the advancement of health care. Western cancer treatments such as radiation and chemotherapy have adverse effect. Eastern medicine could help mitigate those side effects by minimizing the symptoms and reducing dosage requirements when used in conjunction with current Western treatment and therapies. Immunological, enzymatic molecular biology-related research could benefit from studies of effective Eastern medicinal treatments. Studies of the ways in which Western mainstream medicine and technology can be integrated with traditional Eastern medicine are the focus of this special issue.Dominic P. LuDominic P. LuYemeng ChenYemeng ChenLixian XuLixian XuLeo M. LeeLeo M. Lee


Neuroergonomics  at any given moment or how much mental effort it will cost for brain to meet given task demands . Fortunately, the demand for high-metabolic energy of the brain tissue is mainly regulated by complex but adequate energetic substrate delivery via a dense and redundant network of microvessels. Hence, metabolic demands are orchestrated by the blood supply hemodynamic response.The absence of consideration of the neurophysiological mechanisms in Neuroergonomics is certainly due to the difficulty in investigating them. Yet, there are real energy mobilizations that occur within the operator's neurovascular coupling (NVC). Simply, NVC is a tight temporal association of the neuronal activity with regional cerebral blood flow delivery. Understanding the fundamental cellular mechanisms underlying NVC is necessary to measure a dimension of the local brain machinery expenditure at work. The appraisal of the energetic costs required by NVC implies the assessment of mental resources. For instance, when an operator is engaged in a task, the mobilization of the neural pathways needs a synergistic support of massive astrocyte glial cells to fuel neurons and interneurons with oxygen and nutriments furnished by close capillaries.Since the first discoveries by Roy and Sherrington , it has NVC is observable due to changes in neuronal-astroglial and microvasculature activities, which occur in several steps. First, the measurable electrical neuronal activity  is accompanied by synaptic neurotransmitter release  with a neuronal-astroglial regional cerebral metabolic rate of oxygen consumption, mainly for regional cerebral metabolic rate of glucose demand. Second, this activity induces a cascading pathway involving the production and the release of powerful vasodilator metabolites by neurons and astrocytes and drives a chemical signal up to the vascular smooth muscle and pericytes cells along the microvessels which dilate the microvasculature. Third, the microvessels dilatation significantly modulates the regional cerebral blood activity  which greatly exceeds the neuronal-astroglial oxygen requirements, and results in a measurable overabundance of blood flow, hence, a local hyperoxygenation. Yet, the role of NVC as it contributes to the comprehension of the energy mobilization in response to mental resources is not common knowledge. The cellular measures of energy production, delivery, and utilization are crucial to understanding and interpreting NVC activity. How to clearly establish the role of NVC into the operator's brain machinery? One possible way would be to associate the level of correlates of NVC while interpreting the degree of task demand. It seems thus fairly possible that an accurate measurement of NVC, spatially and temporally and in terms of amplitude, would be a valuable neurophysiological marker for quantifying changes in brain activation. Although this statement is still reductionist , this approach links the concept of human MWL and mental resources to objective neurophysiological measures for Neuroergonomics purposes.Recent Neuroergonomics research has progressed in neurocognitive or neuroimaging-sensing instrumentation for determining operator states through the measurement of NVC activity associated with the degree of mental processes . fNIRS provides a continuous monitoring of the hemodynamic activity using near-infrared light transmitted between optodes. It infers the changes in the concentrations of oxygenated and deoxygenated hemoglobin in the cortical regions from scattering and absorption properties of light probing beneath the surface of the skull Perrey, . These tOn the other hand, EEG offers a fine temporal resolution (milliseconds) thus enabling detection of brief neuronal processes, but is limited in its capacity for spatial resolution, at least in real time even though dense array EEG permits source propagation localization. EEG uses scalp electrodes to capture weak electrical current fluctuations generated by inhibitory or excitatory postsynaptic potentials of a pool of neurons firing simultaneously in response to a stimulus. The electrophysiological roots of these signals correspond to the summation of the spontaneously and synchronously recruited neuronal population that contributes to the neuronal activity of the superficial layers of the cortex. EEG waves and event-related potentials signals are particularly strong candidates for objective measures of operator's brain activity at the workplace  and methods for its assessment in work settings  wrote the majority of the manuscript. The other authors  have extensively reviewed and revised the manuscript from the first draft before giving final approval of the version to be submitted.This work was funded by the French Research National Agency, the French Defence Procurement Agency (ASTRID), and the AXA Research Fund.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.


Osprioneides kampto borings were found in bryozoan colonies of Sandbian age from northern Estonia . The Ordovician was a time of great increase in the quantities of hard substrate removed by single trace makers. Increased predation pressure was most likely the driving force behind the infaunalization of larger invertebrates such as the Osprioneides trace makers in the Ordovician. It is possible that the Osprioneides borer originated in Baltica or in other paleocontinents outside of North America.The earliest  Trypanites reported in Early Cambrian archaeocyathid reefs in Labrador Trypanites and PalaeosabellaPetroxestes), bryozoan etchings , sponge borings (Cicatricula), Sanctum (a cavernous domichnium excavated in bryozoan zoaria by an unknown borer) and GastrochaenolitesThe oldest macroborings in the world are the small simple holes of GastrochaenolitesTrypanites borings are known from brachiopods of the Arenigian Trypanites and Sanctum, in bryozoans of Middle and Upper Ordovician strata of northern Estonia.The bioerosion trace fossils of Ordovician of North America are relatively well studied The aims of this paper are to: 1) determine whether the shafts in large Sandbian bryozoans belong to previously known or a new bioerosional ichnotaxon for the Ordovician; 2) determine the systematic affinity of the trace fossil; 3) discuss the ecology of the trace makers; 4) discuss the paleobiogeographic distribution of the trace fossil; and 4) discuss the occurrence of large borings during the Ordovician Bioerosion Revolution.During the Ordovician, the Baltica paleocontinent migrated from the temperate to the subtropical realm The total thickness of the Ordovician in Estonia varies from 70 to 180 m Mastopora), brachiopods , conulariids, gastropods , ichnofossils , sponges, receptaculitids (Tettragonis), rugosans (Lambelasma), bryozoans, and asaphid trilobites. The Alliku Ditches are located in Harju County near the village of Alliku. Clayey limestones with interlayers of marls are exposed here. The fauna includes algae, brachiopods, bryozoans , echinoderms, gastropods, ostracods, rugosans, receptaculitids and trilobites according to Rõõmusoks The material studied here was collected from the Hirmuse Creek  and AlliOsprioneides borings are deposited at the Institute of Geology, Tallinn University of Technology (GIT), Ehitajate tee 5, Tallinn, Estonia, with specimen numbers GIT-398-729, GIT 665-18 and GIT 665-19.No permits were required for the described study, which complied with all relevant Estonian regulations, as our study did not involve collecting protected fossil species. Three described bryozoan specimens with the Trypanites borings occur inside the large boring with oval cross section. The apertures of the large borings occur on both the upper and lower surfaces of the bryozoans .Numerous unbranched, single-entrance, large deep borings with oval cross sections were found in three large trepostome bryozoan colonies , 4, 5, 6Petroxestes known from Late Ordovician bryozoans and hardgrounds of North America Petroxestes the aperture width is much greater than the boring’s depth. In contrast, the depth of the borings in bryozoans is much greater than their apertural width. Unlike Petroxestes, the Sandbian borings examined here have a tapering terminus and somewhat sinuous course. The axial ratio of Petroxestes borings aperture (major axis/minor axis) is also much greater than observed in these borings.The borings in these bryozoans resemble somewhat Osprioneides, which is known from the Silurian of Baltica, Britain and North America Osprioneides kampto because of their similar general morphology. They have a single entrance, an oval cross section, and significant depth similar to Osprioneides kampto. Their straight, curved to somewhat sinuous shape also resembles that of Osprioneides. Both Osprioneides and these borings in bryozoans have a tapered to rounded terminus.The other similar large Palaeozoic boring is Osprioneides trace maker was a soft-bodied animal similar to polychaete worms that used chemical means of boring as suggested by Beuck et al. Osprioneides means bivalves were very unlikely to have been the trace makers.Most likely the Osprioneides borings were made post mortem because the growth lamellae of the bryozoan do not deflect around the borings. There are also no signs of skeletal repair by the bryozoans. Several Osprioneides borings truncate other Osprioneides borings that were likely abandoned by the trace maker by that time. Similarly, empty Osprioneides borings were colonized by Trypanites trace makers. This indicates that the Osprioneides borings may have appeared relatively early in the ecological succession. Overturning of the bryozoan zoaria can explain the occurrence of Osprioneides borings apertures on both upper and lower surfaces. There is no sign of encrustation on the walls of the studied Osprioneides borings, suggesting relatively rapid burial of the host bryozoans shortly after the Osprioneides colonization.Osprioneides trace makers were suspension feeders similar to the Trypanites animals due to their stationary life mode Osprioneides comprise stromatoporoids and tabulate corals. This new occurrence of Osprioneides borings in large bryozoans shows that the trace maker possibly selected its substrate only by size of skeleton because the traces are not found in smaller fossils. However, they are not found in any Ordovician hardgrounds that provide more area than do the bryozoan colonies. Wyse Jackson and Key It is likely that Gastrochaenolites from the Early Ordovician of Baltica Petroxestes borings appeared in North America. At the same time the Osprioneides borings described here appeared in Baltica. Thus the Ordovician was also the time of great increase in quantities of hard substrate removed by single trace makers. The biological affinities of Ordovician Gastrochaenolites are not known Petroxestes was almost certainly produced by the facultatively boring bivalve Corallidomus scobinaOsprioneides trace makers, which is suggested by the somewhat sinuous shape of some borings. This indicates that more than one group of animal was involved in the appearance of large bioerosional traces during the Ordovician Bioerosion Revolution. Increased predation pressure Osprioneides trace makers in the Ordovician. On the other hand in echinoids, for example, infaunalization was presumably the result of colonization of unoccupied niche space Morphological diversification was not the only result of the Ordovician Bioerosion Revolution. Most of the large bioerosional traces of the Paleozoic had their earliest appearances in the Ordovician Osprioneides is a relatively rare fossil compared to the abundance of Trypanites in the Silurian of Baltica Osprioneides borings also occur outside of Baltica. They are known from the Llandovery of North America and Ludlow of the Welsh Borderlands Osprioneides is presumably absent in the Ordovician of North America because Ordovician bioerosional trace fossils of North America are relatively well studied Osprioneides trace maker originated in Baltica or elsewhere and migrated to North America in the Silurian. This may well be connected to the decreased distance between Baltica and Laurentia (the closing of the Iapetus Ocean) and the loss of provinciality of faunas in the Silurian.


In the process of treating scoliosis essence of treatment is to maintain normal patterns of attitudes through appropriate antigravity muscle tone. Stimuli proper posture pattern in the period in which the child does not perform exercises provide appropriately selected and made corset. The use of dynamic slicing applications - Kinesiology Taping at the surface of the skin also stimulates the child to maintain proper muscle tone shaping correct posture.Evaluated in a group of 40 children diagnosed with idiopathic scoliosis in age from 10 to 15 years residing in the treatment by the Fed at the Centre for Rehabilitation in Zgorzelec. Each child before treatment, the day of admission to the ward had made an assessment method Diers. Then an application of Kinesiology Taping. Used applications ligamentous took the form of V and were used on curves thoracic and lumbar scoliosis. Next, a re-image method Diers assessing mathematical representation of the body surface after the application of Kinesiology Taping.The results obtained after the application of Kinesiology Taping show that the image of body posture changes, which record the images method Diers.Kinesiology Taping techniques are useful in the treatment of idiopathic scoliosis. Alter the tension of the skin and muscles make it easy to maintain the correct posture pattern


In this article we investigate the heat and mass transfer analysis in mixed convective radiative flow of Jeffrey fluid over a moving surface. The effects of thermal and concentration stratifications are also taken into consideration. Rosseland's approximations are utilized for thermal radiation. The nonlinear boundary layer partial differential equations are converted into nonlinear ordinary differential equations via suitable dimensionless variables. The solutions of nonlinear ordinary differential equations are developed by homotopic procedure. Convergence of homotopic solutions is examined graphically and numerically. Graphical results of dimensionless velocity, temperature and concentration are presented and discussed in detail. Values of the skin-friction coefficient, the local Nusselt and the local Sherwood numbers are analyzed numerically. Temperature and concentration profiles are decreased when the values of thermal and concentration stratifications parameters increase. Larger values of radiation parameter lead to the higher temperature and thicker thermal boundary layer thickness. The boundary layer flow of non-Newtonian fluids gains a special attention of the researchers because of its wide occurrence in the industrial and engineering processes. The most commonly involved fluids in industry and technology are categorized as non-Newtonian. Many of the materials used in biological sciences, chemical and petroleum industries, geophysics etc. are also known as the non-Newtonian fluids. The non-Newtonian fluids are further divided into three main classes namely differential, rate and integral types. The simplest subclass of non-Newtonian fluids is the rate type fluids. The present study involves the Jeffrey fluid model which falls into the category of rate type non-Newtonian fluids. This fluid model exhibits the properties of ratio of relaxation to retardation times and retardation time. This model is very popular amongst the investigators. Few studies regarding Jeffrey fluid model are mentioned in the references The better cooling rate in the manufacturing processes is very essential for the best quality final product. For such processes, a controlled cooling system is required. An electrically polymeric liquid seems to be a good candidate for such applications of polymer and metallurgy because here the flow can be controlled by an applied magnetic field. Further the magnetohydrodynamic (MHD) flows are quite prominent in MHD power generating systems, cooling of nuclear reactors, plasma studies, geothermal energy extraction and many others. Interesting investigations on MHD flows can be seen in the references Influence of stratification is an important aspect in heat and mass transfer analysis. The formation or deposition of the layers is known as the stratification. This phenomenon occurs due to the change in temperature or concentration, or variations in both, or presence of various fluids or different densities. It is quite important and interesting to examine the effects of combined stratifications  in mixed convective flow past a surface when heat and mass transfer analysis is performed simultaneously. Investigation of doubly stratified flows is a subject of special attention nowadays because of its broad range of applications in industrial and engineering processes. Few practical examples of these applications include heat rejection into the environment such as rivers, seas and lakes, thermal energy storage systems like solar ponds, mixture in industrial, food and manufacturing processing, density stratification of the atmosphere etc. Having all such applications in view, Hayat et al. Here our main theme is to study the influences of thermal and concentration stratifications in mixed convection flow of Jeffrey fluid over a stretching sheet. Heat and mass transfer characteristics are encountered. Further, we considered the thermal radiation effect. Mathematical modelling is presented subject to boundary layer assumptions and Roseland's approximation. The governing nonlinear flow model is solved and homotopic solutions 0B is applied normal to the flow direction (see We consider the mixed convection flow of an incompressible Jeffrey fluid over a stretching surface. Thermal and concentration stratifications are taken into account in the presence of thermal radiation. The vertical surface has temperature tion see . The effThe subjected boundary conditions are The radiative flux is accounted by employing the Rosseland assumption in the energy equation SettingHere The skin friction coefficient, the local Nusselt number and the local Sherwood number areTo develop the homotopic procedure When variation of The general solutions are derived as follows:The coupled nonlinear ordinary differential equations are solved via homotopy analysis method. The convergence of derived homotopic solutions depend on the suitable values of auxiliary parameters The dimensionless velocity profile The variations in the non-dimensional temperature distribution function The effects of magnetic parameter ness see .The numerical values of We examined the effects of thermal and concentration stratifications in mixed convective radiative flow of Jeffrey fluid in this attempt. The main observations that we found in this investigation are as follows:We have to compute 28th-order of HAM deformations for the convergent solutions.Deborah number The effects of thermal buoyancy parameters on the velocity field An increase in thermal stratification parameter The temperature profile and thermal boundary layer thickness are enhanced when radiation parameter The concentration field and its associated boundary layer thickness are decreasing functions of concentration stratification parameter Numerical values of skin-friction coefficient are increased by increasing The larger values of


Parascolymia bracherti has been identified as a new species in spite of the dissolved skeleton. In the recent era, Parascolymia like all Lobophylliidae is restricted to the Indo-Pacific region, where it is represented by a single species. The new species proves the genus also in the Miocene Mediterranean reef coral province. A review of the spatio-temporal relationships of fossil corals related to Parascolymia indicates that the genus was probably rooted in the Eastern Atlantic‒Western Tethys region during the Paleocene to Eocene and reached the Indo-Pacific region not before the Oligocene. The revealed palaeobiogeographical pattern shows an obvious congruence with that of Acropora and tridacnine bivalves reflecting a gradual equatorwards retreat of the marine biodiversity center parallel to the Cenozoic climate deterioration.Palaeobiogeographical and palaeodiversity patterns of scleractinian reef corals are generally biased due to uncertain taxonomy and a loss of taxonomic characters through dissolution and recrystallization of the skeletal aragonite in shallow marine limestones. Herein, we describe a fossil lobophylliid coral in mouldic preservation from the early middle Miocene Leitha Limestone of the Central Paratethys Sea . By using grey-scale image inversion and silicone rubber casts for the visualization of the original skeletal anatomy and the detection of distinct micromorphological characters   Scolymia Haime, 1852, once thought to be cosmopolitan . Th. ThParasdbridge”  [13,14,2 Optimum ,63, whic Optimum . This shhat time ,64. Thertruncata  in West Parascolymia shows obvious parallels with that of the reef coral Acropora and tridacnine bivalves  farquharsoni in the Oligocene of Somali and its association with P. (Parascolymia) vitiensis in the early Miocene of Makran [P. (Parascolymia) used the East African‒Arabian bioprovince as stepping stone into the Indo-Polynesian bioprovince and became typical elements of the entire Indo-West Pacific region after the closure of the Tethyan Seaway  the late Eocene‒early Miocene Arabian hotspot acting as stepping stone for Parascolymia into the Indo-West Pacific; and (3) the early Miocene‒recent Indo-Australian Archipelago hotspot in the center of the recent distribution of Parascolymia  in the Vienna Basin  based on the mould of a single corallum. In order to overcome the mouldic preservation grey-scale inversion images and silicone rubber casts were applied for the identification of original macro- and micromorphological features . The results show that coral moulds potentially prove the chance to study micromorphological characters of reef corals from shallow water limestones where skeletal aragonite is usually dissolved. This is important since the highest diversity of zooxanthellate corals occurs in pure carbonate shallow-water environments, but the fossil record of the Scleractinia is significantly biased in favour of well-preserved isolated corals from argillaceous lithologies representing unfavorable habitats of reduced coral diversity [Acanthophyllia ampla, which occurred associated with the new species in the Central Paratethys, is placed in synonymy with Parascolymia. Before this evidence, Parascolymia was considered as strictly Indo-Pacific coral genus. The records from the Central Paratethys occur roughly 7 million years after the complete isolation of the Mediterranean from the Indian Ocean coral faunas by the restriction of the Tethyan Seaway. This finding and a review of the temporal and spatial distribution of other fossil corals related to Parascolymia indicate that the lineage originated in the Eastern Atlantic‒Western Tethys region during the Paleocene‒Eocene, corresponding to the former center of marine biodiversity. It also reveals an obvious temporal and spatial coincidence between the dispersal of Parascolymia and the displacement of the marine biodiversity hotspot into the present Indo-West Pacific region. Parascolymia is thus an example of a successful transformation of an originally Tethyan element contributing to the present biodiversity in the Indo-West Pacific. The gradual nature of this palaeobiogeographic change implies an important climatic control contrasting the hypothesis of a primarily tectonically driven hopping of geographically distinct biodiversity hotspots in the Cenozoic.iversity . Acantho


Functional, esthetic and endodontic restoration of a pulpally involved permanent incisor with root dilaceration often presents a daunting clinical challenge. The outcome of conventional treatment modalities like surgical removal of the tooth followed by orthodontic closure of the space is time consuming and esthetically compromising. Even the prosthetic and implantalogical rehabilitation after extraction is not possible until the patient reaches certain age; while the compliance is a problem with the use of removable partial denture in young children. Autoalloplastic anterior tooth transplantation can lead to physical and psychological trauma in a young individual.Thus endo-esthetic management of such teeth helps in maintaining both morphology and esthetics in a growing child until the permanent long lasting prosthetic solution is sought after the complete development of the dentition and jaws. This treatment option for a pulpally involved permanent incisor with root dilaceration involves completing the endodontic treatment in a partially calcified and aberrantly located root canal followed by the use of light transmitting fiber post and core build up using composite resin. One of the sequelae to trauma to the primary dentition is the possibility of damaging permanent successor tooth buds.Intrusive displacement of deciduous teeth is the most frequent cause of sequelae involving teeth of the second dentition, with damage ranging from coronal changes in color and shape to radicular malformation and distinct root anomalies.1The creasing or bending of the crown axis with respect to the root axis, as commonly observed in these cases, is also termed dilaceration. This results from the displacement of the crowns of the incisors, usually still without roots, in a vestibular direction while root growth is still progressing in a cranial direction4137The incidence of root dilacerations amounts to approximately 3% of all the damage to permanent teeth following trauma to deciduous teeth. In the literature a distinction is made between vestibular and lateral root bending. Whether the trauma is the sole cause of vestibular root bending is a subject of controversy. In the majority of the cases it has been observed only in the upper central incisor. In many cases the roots are by then malformed and root growth has come to an end prematurely.When such dilacerated teeth gets involved pulpally due to caries, it poses a challenging endo-esthetic problem.A 12-year-old healthy male child with no contributory medical history visited the Dept. of Pediatric and Preventive Dentistry, Dr DY Patil Dental College Pune, with the chief complaint of pain in the upper front tooth since 15 days and history of intermittent dull ache in upper right and left back region for a couple of months.On examination, the upper left lateral incisor showed a gross carious involvement of crown. Upper right and left second premolars showed severe carious destruction of crown rendering them clinically nonrestorable . The upper left lateral incisor was tender on vertical percussion. The child had mandibular prognathism and angles class III molar relation ship .Radiographic examination of the upper anterior region revealed tortuous root canals suggestive of severe root dilacerations of upper left central and lateral incisor. In case of lateral incisor the root tortuousity does not seem to be as complicated as of a central incisor. This is because of the buccopalatal angulation of the root of lateral incisor which is not evident on radiograph very clearly .Patient’s parents revealed history of traumatic episode at the age four which involved avulsion of two deciduous teeth from upper front region. Electric pulp testing of the involved lateral incisor exhibited delayed response compared to the contralateral tooth.Various treatment modalities were explained to the parents of the child with their pros and cons and it was finally decidedto go ahead with the present treatment approach.As the pulp chamber was calcified and root canal was patent only in the middle and apical third, the negotiation of the root canal was not an easy task .Profound anesthesia was achieved by administering 2% Lignocaine with Adrenaline (1:200000) and access cavity preparation was done using round carbide bur.In an attempt to gain an access to radicular portion, a perforation occurred in coronal one third of the distal aspect of root.Upon further exploration, a very unusual location of the root canal was found on the palatal wall of the root .An immediate diagnostic radiograph was made to ensure the correct positioning and the length of the root canal .Upon confirming the canal position, thorough biomechanical preparation was carried out using rotary protaper system and pulp space was obturated with gutta percha points using AH-26  as a root canal sealer .The perforation on coronal one third of the distal aspect of root was sealed using mineral trioxide aggregate  .The affected tooth was kept isolated using cotton rolls, 2 × 2 gauze and high vacuum suction all throughout the procedure.The entire endodontic treatment and sealing of the perforation was carried out in a single visit. In the subsequent visit the post space was prepared using peeso reamers. Considering the length of the root canal and crown-root ratio and the disadvantages associated with cast posts, the light transmitting fiber post  was used .It was cemented using dual cure adhesive cement  .The core structure was built around the post using nano filled composite resin (Z-350 3M ESPE USA) .Finishing and polishing of the composite was done using contouring and polishing discs (Sof-Lex-3M ESPE USA) which ultimately resulted into a fairly acceptable esthetics .Considering the dental and chronological age of the child the decision of giving a final extracoronal ceramic restoration is deferred until the eruption of all permanent teeth.Trauma to primary incisors may lead to lasting damage to the permanent teeth. The patient’s age, and the degree and the direction of the malposition of the primary teeth are some of the factors.Possible sequelae to permanent teeth following trauma involving primary teeth includeDiscoloration and hypoplasia of the enamelBending and malformation of the anatomic crown and rootHypoplasia of the rootRetarted eruption.The maximum incidence of accidents to primary teeth occurs in children aged 3 to 4 years.For this reason sequelae to accidents occurring at this time particularly affect root growth. Even in the presented case the parents gave history of trauma at the age of 4 years and avulsion of two primary maxillary anterior teeth.In such cases various treatment options that would be thought of are surgical removal of the tooth.10Just as the above mentioned treatment options have drawbacks, the autoalloplastic transplantation also does inherit disadvantage of a surgical approach in a young individual.Even an extraction of a tooth with carious crown and a dilacerated root, would pose a traumatic problem.Less time consumingLeast traumatic physically and psychologically to a childMore estheticVery much predictable in a young childMore economical when compared to other treatment modalities.It remains to be seen the extent of the longevity of the restoration prior to the final permanent restoration in the form of a ceramic extracoronal restoration after the complete eruption of all the permanent teeth.Considering the drawbacks associated with above mentioned approaches we thought of endo-esthetic management approach with following advantages,Although the endodontics and prefabricated post and core build up restoration is an established procedure in dentistry, the prognosis of the same needs to be assessed on the basis of long-term periodic recalls.


Our knowledge of the modular organization of the cerebellum and the sphere of influence of these modules still presents large gaps. Here I will review these gaps against our present anatomical and physiological knowledge of these systems. Advances in our knowledge of the functional anatomy of the cerebellum have raised new questions. In this review I will draw attention to some of, what I consider, the main flaws in our knowledge of the anatomy and physiology of cerebellar modules and their connections.My main questions are:The anatomical organization of the cerebellum is based on modules, defined by their projection to a specific cerebellar or vestibular nucleus, their climbing fiber input and the physiological and neurochemical properties of their Purkinje cells. Why do the modules in motor regions of the cerebellum alternate between those connected with motor pathways and those connected with wide regions of the cerebral cortex?The cerebello-rubral pathway, the cerebello-thalamo-cortical projections and the corticorubral-olivary climbing fiber system seem to be organized as closed loops. What is the function of these loops and of the convergence of cortical and cerebellar nuclear input to the parvocellular red nucleus and other intercallated nuclei at the meso-diencephalic junction?Which are the tractable behaviors with which to evaluate the hypothesis that each Purkinje cell zone constitutes a basic functional unit of the cerebellum Simpson, ?What are the topographical and functional relations between mossy and climbing fibers in the cerebellar cortex?Are mossy and climbing fiber pathways organized according to the same anatomical principles?What are the topographical interrelations of different mossy fiber system in the cerebellum?The cerebellum is known to be organized in a modular fashion. Cerebellar modules consist of one or more Purkinje cell zones that project to a particular cerebellar or vestibular nucleus, their climbing fiber input from a subdivision of the contralateral inferior olive with a collateral projection to the cerebellar target nucleus and reciprocal connections of this target nucleus with the contralateral inferior olive. Seven to nine of these modules originally were distinguished on both sides of the cerebellum in carnivores, rodents and primates Figures .(A) and (D)). Purkinje cell zones, therefore, are either zebrin-positive or negative  and lateral (LIP) intraparietal areas and prefrontal areas 9l, 46d, preSMA and the rostral dorsal premotor area  can be subdivided into microzones. Microzones are narrow longitudinal strips of Purkinje cells that receive climbing fiber input sharing the same receptive field (Andersson and Oscarsson, Mossy fibers, initially, follow a transverse course through the cerebellar white matter Figure . At reguIn the studies of Voogd et al.  and PijpDifferent ideas have been proposed for the functional relations of mossy fiber terminal aggregates and the climbing fiber microzones. Llinás  hypothesGibson et al.  and otheIt has been suggested that the efferent thalamocortical and the cortico-ponto-cerebellar mossy fiber systems are organized as closed loops (Kelly and Strick, Cerebellar-cortical connections and the cortico-cerebellar mossy fiber projections in monkeys have been found to be reciprocally organized (Kelly and Strick, Where individual mossy fibers emit collaterals bilaterally at specific medio-lateral positions, entire mossy fiber systems all terminate in bilaterally distributed discrete aggregates of mossy fiber rosettes Figure . This paAnother feature of the distribution of mossy fibers in motor regions of the cerebellum is their concentric arrangement Figure . CorticoLength and synaptic size of parallel fibers differ for the upper and lower molecular layer (see Van der Want et al.  for refeRepairing gaps in our knowledge on cerebellar systems asks for a collaborative effort of anatomists and physiologists. Noninvasive techniques for the tracing of axonal pathways will have to be developed to collect information in non-human primates. MRI technology will have to be improved to visualize climbing fiber paths and Purkinje cell activity. The alternation of Purkinje cell zones receiving peripheral and cortical climbing fiber input, and the contribution of the mutiple narrow Purkinje cell zones to cerebellar function should be evaluated in suitable animal models. But even when we know the precise interrelations of different cortical areas and brainstem centers with the cerebellum, the contribution of the cerebellum to the information processing in these structures remains incompletely known.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Our ICU is a general mixed ICU with 9 beds in a trauma centre. We admit over 300 patients/year. We have started using thromboelastometry (ROTEM) in 2009. Thromboelastometry is used to guide the therapy of massive bleeding and therapy of coagulopathy in ICU patients. The usage of thromboelastometry has been increasing since 2009 and in January 2014 we have implemented POC thromboelastometry guided factor concentrate based coagulation algorithm for the treatment of coagulopathy in massive bleeding [Analysis of transfusion requirements of packed red blood cells (PRBC), plasma (FFP), platelet concentrates and the usage of fibrinogen and prothrombin complex concentrate (PCC) in ICU patients before and after the introduction of thromboelastometry guided factor concentrate based coagulation algorithm for the treatment of coagulopathy in massive bleeding and its influence on cost of therapy.Retrospective analysis of the utilisation of blood products  and fibrinogen and PCC before and after the introduction of thromboelastometry guided factor concentrate based coagulation algorithm.The usage of all allogenic blood products has decreased in our unit after the introduction of thromboelastometry guided factor concentrate based coagulation algorithm by 46,7%.The reduction of PRBC was 16,6%, platelet concentrate usage decreased by 43,6 % and FFP usage decreased by 81,8%.The usage of fibrinogen and PCC has increased after the implementation of algorithm.The cost of therapy of bleeding and coagulopathy in our ICU  has not significantly changed after the implementation of algorithm.We have achieved a major reduction in allogenic blood products after the introduction of a thromboelastometry guided factor concentrate based coagulation algorithm in our intensive care unit. The usage of fibrinogen and PCC has increased, but the cost has not significantly changed. Implementation of thromboelastometry guided factor concentrate based coagulation algorithm reduces the exposure of intensive care patients to allogenic blood products and does not increase cost of therapy of bleeding and coagulopathy.Our study was supported by a grant from Scientific Board of Regional Hospital Liberec


The etiology of most joints' inflammations is unknown. Arthritis in children can have a diversified course. Various parameters useful in diagnosis and treatment of different forms of inflammations of the joints are being researched. Reactive oxygen species in large concentrations are toxic and cause, among others, the phenomenon of polyunsaturated fatty acids lipid peroxidation, which results in the formation of aldehyde compounds. Non enzymatic antioxidants include: lipid peroxides (LHP = LOOH), lipophuscin (LF). An important part of non enzymatic antioxidative defense are sulfhydryl groups-SH. Total oxidative status (TOS) is used as an indicator of the overall oxidative potential of cells.The aim of the study was to find how the level of the selected oxidative parameters changes in serum in children with inflammation of the joints. The correlation between the selected oxidative parameters and disease's relapses is also studied.The studied parameters were measured in blood serum of 59 patients with JIA, aged from 2 to 18 years old, hospitalized in the Rheumatology Division of the Department of Pediatrics, Silesian Medical University. The control group consisted of 25 healthy children.See Table The studied parameters of oxidative status differ between children with arthritis and healthy ones. Lipid peroxide levels are dependent on the type of arthritis. The LOOH and lipofuscin concentrations in healthy children as compared with a group of children with JIA differ. Higher values occur in the acute forms of JIA, but the difference is not statistically significant. There is no correlation in the total oxidative status (TOS) and the inflammation's level in the joints.None declared.


The dissemination of cancer cells from the primary tumor to a distant site, known as metastasis, is the main cause of mortality in cancer patients. Metastasis is a very complex cellular process that involves many steps, including the breaching of the basement membrane (BM) to allow the movement of cells through tissues. The BM breach occurs via highly regulated and localized remodeling of the extracellular matrix (ECM), which is mediated by formation of structures, known as invadopodia, and targeted secretion of matrix metalloproteinases (MMPs). Recently, invadopodia have emerged as key cellular structures that regulate the metastasis of many cancers. Furthermore, targeting of various cytoskeletal modulators and MMPs has been shown to play a major role in regulating invadopodia function. Here, we highlight recent findings regarding the regulation of protein targeting during invadopodia formation and function. Although epithelial cancers are one of the leading causes of death, the mechanisms regulating the development and metastasis of carcinomas are not fully understood. Multiple studies suggest that the progression of tumors is dependent on the intrinsic properties of cancer cells, such as their ability to migrate and invade. Furthermore, many extrinsic factors, such as extracellular matrix (ECM) proteins, are also crucial for regulation of cancer metastasis. The ECM proteins that make up the specialized basement membrane (BM) serve as a barrier for cell invasion. However, the BM which is rich in laminin and collagen IV, also provides the substrate for adhesion of the migrating tumor cells. Furthermore, BM degradation results in the release/activation of various growth factors required for angiogenesis, tumor growth, and metastasis Kalluri, . ECM degBM disruption involves a localized degradation of the ECM via the secretion of MMPs  and inhibition of the active enzyme by tissue inhibitors of MMPs or tissue inhibitors of metalloproteinases (TIMPs) P2, thus forming the site for invadopodia formation  promotes ECM proteolysis  kinase have recently emerged as important players in invadopodia formation and maturation (Beaty et al., The final maturation stage of the invadopodia involves targeted delivery and exocytosis of MMP2, MMP9, and MMP14. The appearance of these MMPs is generally considered to be a mark of functional mature invadopodia. As the result, much effort has been invested in understanding the regulation of MMP targeting to invadopodia, leading to recent studies defining the machinery governing MMP transport during cancer cell invasion.in vitro (Nakahara et al., MMP14 is a membrane embedded MMP whose extracellular proteolytic activity is regulated by a balance between exocytosis and internalization via clathrin and/or caveolar mediated endocytosis (Remacle et al., 2+ oscillations regulate MMP14 recycling to the plasma membrane (Sun et al., Transport vesicle targeting and fusion with its destination membranes often relies on specific tethering factors that impart specificity to membrane transport. The tethering factors regulating MMP14 targeting remain to be identified. However, Tks4, a scaffolding factor related to Tks5, has been shown to be required for the formation and function of invadopodia (Buschman et al., MMP2 and MMP9 are gelatinases that possess fibronectin type II repeats that allow them to degrade collagen and gelatin. Gelatinolytic degradation can cause the release of signaling molecules from the ECM that aid cell migration and angiogenesis. A lot of effort has been focused on understanding the transport and targeting of gelatinases because they are overexpressed in a variety of tumors and are associated with tumor aggressiveness and poor patient prognosis (Pacheco et al., in vitro, the formation and function of invadopodia in vivo is less well understood due to challenges associated with visualizing and distinguishing these structures in animal models. Cancer invasion usually occurs deep in tissues and these events are highly dynamic and unpredictable making it difficult to visualize invadopodia during primary tumor metastasis. Though the majority of invadopodial studies have been conducted in 2D tissue culture systems, some groups have studied invadopodia formation in 3D matrices as they better simulate the physiological in vivo environment. Such studies of invadopodia in complex 3D matrices have shown that the matrix degrading activity is localized to the base rather than the tip of the invadopodia (Wolf et al., in vivo and provide a good model to study formation of invadopodia.Although there is an increasing amount of evidence demonstrating the existence of invadopodia in vivo experiments that confirm that invadopodia are not just in vitro artifacts. Recently, the chorioallantoic membrane of the chicken embryo was used to visualize the intravascular formation of invadopodia and the extravasation of tumor cells into the stroma (Leong et al., Caenorhabditis elegans, the anchor cell breaches the uterine and vulval basement membranes by making an invadopodium (Hagedorn et al., meltdown forms invadopodia-like protrusions that invade into the stromal tissue in response to cues from the surrounding smooth muscle layer (Seiler et al., Despite the challenges mentioned above, there is some compelling evidence drawn from elegant in vivo and understand how widespread the use of invadopodia by cells is. Many questions regarding the importance of invadopodia in cancer invasion and metastasis still exist. Future studies in the field of invadopodia will need to focus on detection of invadopodia in human cancer samples as well as to identify the role of invadopodia in the different steps of the metastatic cascade. The other areas that require focus are the identification of components specific to invadopodia that can be targeted and the development of compounds that can specifically inhibit invadopodia formation and function. These issues will need to be addressed before invadopodia can become a candidate for development of new cancer therapies.Significant advances have been made in understanding the formation and function of invadopodia. However, there are still a lot more unknowns regarding this subcellular structure. While all of the above mentioned studies have helped to confirm the physiological role of invadopodia as a structure used by invasive cells to penetrate the basement membrane, more evidence is required to elucidate the functional role of invadopodia 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 lateral accessory lobe (LAL) mediates signals from the central complex to the thoracic motor centers. The results obtained from different insects suggest that the LAL is highly relevant to the locomotion. Perhaps due to its deep location and lack of clear anatomical boundaries, few studies have focused on this brain region. Systematic data of LAL interneurons are available in the silkmoth. We here review individual neurons constituting the LAL by comparing the silkmoth and other insects. The survey through the connectivity and intrinsic organization suggests potential homology in the organization of the LAL among insects. The lateral accessory lobe (LAL) is a neuropil that is highly associated with the central complex (CX). The LAL is thought to facilitate communication between the CX and the motor centers. For example, it is proposed that the LAL receives input from the CX and selects the activity of descending output  that originate in the brain and project to the thoracic motor centers.Male moths orient to conspecific females by the use of sex pheromones. The circuit within the LAL generates pheromone-evoked persistent firing in the silkmoth  is thought to mediate sensory-motor pathways for phonotaxis  cell bodies belong to the cluster located on the anterior surface beside the anterior optic tubercle, (2) they descend the ipsilateral side of the neck connective, and (3) they have smooth processes in the LAL. The neurons that meet these morphological features have been reported in other species, including the sphinx moth Manduca sexta  and locust (Homberg, The LAL is classified into two subdivisions that are delineated by the LAL commissure that is the prominent bundle connecting the bilateral LALs: upper division and lower division (Iwano et al., Homberg, . The intHomberg, . This suBombyx (Supplementary Figure Drosophila (Lin et al., Bombyx and Drosophila. The lobula complex also supplies biased inputs to the LAL (Supplementary Figure Drosophila (Namiki et al., Drosophila seems to be biased toward the lateral side of the LAL (Nässel and Elekes, The inputs from the CX terminate in specific sub-regions within the LAL (Heinze et al., The dendritic innervation of LAL DNs is biased to the lower division (Supplementary Figure Bombyx group-I DNs in Drosophila show similar features (VGlut-F-500726, VGlut-F-000150; FlyCircuit Database; Chiang et al., Putative homologous neurons of From these anatomical observations, we propose the modular organization of the LAL is common across insects. The upper division integrates the information from multiple protocerebral regions in addition to the CX, while the lower division produces the premotor signal output via DNs Figure .Drosophila and other insects. There are plentiful examples for their potential homology at the level of individual neurons, suggesting the presence of a ground pattern organization. Insects adapt to various environments in different ways, but the same basic design of the nervous system may underlie diverse behavioral repertoire. Expanding the application of a comparative neurobiological approach provides a powerful clue to explore these mechanisms.We reviewed the neuronal components of the LAL in the silkmoth and described the neurons with similar morphology in All authors listed, have made substantial, direct, and intellectual contribution to the work, and approved it for publication.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.


Gastroesophageal Reflux (GER) is a common condition in childhood characterized by the rise of gastric contents into the esophagus. According to the International Consensus of the Montreal, gastroesophageal reflux disease (GERD) is defined as "the condition that develops when the retrograde passage of gastric contents causes troublesome symptoms and/or complications that result in an impairment of the quality of life of these patients" . In pedi


Drosophila melanogaster—provides an opportunity to explore circuit functions using genetic manipulations, which, along with high-resolution microscopic techniques and lipid membrane interaction studies, will be able to verify the structure–function details of the presented mechanism of perception.Perception is a first-person internal sensation induced within the nervous system at the time of arrival of sensory stimuli from objects in the environment. Lack of access to the first-person properties has limited viewing perception as an emergent property and it is currently being studied using third-person observed findings from various levels. One feasible approach to understand its mechanism is to build a hypothesis for the specific conditions and required circuit features of the nodal points where the mechanistic operation of perception take place for one type of sensation in one species and to verify it for the presence of comparable circuit properties for perceiving a different sensation in a different species. The present work explains visual perception in mammalian nervous system from a first-person frame of reference and provides explanations for the homogeneity of perception of visual stimuli above flicker fusion frequency, the perception of objects at locations different from their actual position, the smooth pursuit and saccadic eye movements, the perception of object borders, and perception of pressure phosphenes. Using results from temporal resolution studies and the known details of visual cortical circuitry, explanations are provided for (a) the perception of rapidly changing visual stimuli, (b) how the perception of objects occurs in the correct orientation even though, according to the third-person view, activity from the visual stimulus reaches the cortices in an inverted manner and (c) the functional significance of well-conserved columnar organization of the visual cortex. A comparable circuitry detected in a different nervous system in a remote species—the olfactory circuitry of the fruit fly  Helmholtz proposed that visual perception is mediated by unconscious inferences using cognitive resources  is one of the different spiking activities observed at different neuronal processes. Others include dendritic spikes and axonal spikes . The third-person observed neuronal firing is comparable across different excitatory neuronal populations. However, severe variabilities exist in both the number of input connections  and the sets of sensory inputs that can trigger a single neuronal firing. The number of inputs of a neuron ranges from one  to many approximately 5600  to 60,000 (as in a monkey’s motor cortex) Cragg .The observed firing of a neuron cannot be directly attributed to the induction of first-person internal sensory elements of the various higher brain functions due to the following reasons. (1) Since different sets of dendritic spine inputs  can lead to the same action potential, neuronal firing is non-specific with regards to its inputs. For example, in a pyramidal neuron with thousands of inputs, the arrival of nearly any set of 40 excitatory postsynaptic potentials (EPSPs) at the axonal hillock can lead to its firing , a total delay ranging from 6 to 11 ms is expected for the activity to propagate from the retina to reach the dendritic spines of the cortical neurons Fig. . The perHuman observers perceive visual stimuli as continuous above the flicker fusion frequency . Among all the sensory stimuli, light has the maximum velocity. In this regard, for both the predator and the prey, the visual details are of paramount importance for their survival. Therefore, the structural features of the visual cortex are expected to be optimized to obtain the finest visual details of the object and the organization of cortical columns is likely to have a functional role. Similarly, the nocturnal life of rodents necessitates touch perception via whiskers, which can provide the finest surface details of objects so that the rodents can retrieve memories of the remaining qualities of the object. In this regard, the structural organization of the barrel cortex is expected to have a functional role. How can the columnar organization provide the finest details for the internal sensation of object perception?In contrast to the different higher brain functions, the internal sensation of perception occurs in real time at the arrival of the sensory stimuli. From the earlier sections, it can be seen that two essential features are associated with the formation of the internal sensation of perception. One is the need for an overlapping of the units of perception for achieving homogeneity of the percept above the flicker fusion frequency. The second is the limitations imposed by the functional perimeter of the cortical columns that necessitate the arrival of only a few input stimuli from the object at a given column. Since it was found that neurons within a column are selectively sensitive to straight-line visual stimuli at limited angles of orientation . Since the lateral spread of activity through the inter-postsynaptic functional LINKs contributes a horizontal component to the oscillating potentials for the systems function of percepton formation, horizontal connections between the columns are essential. Since the induction of perceptons takes place only at the level of the inputs from the LGN neurons to the abutting postsynaptic terminals at different neuronal layers, it is not affected by several non-matching findings detected when neuronal firing is given a central role in sensory perception . The eyeball indentation leads to a non-uniform tangential stretch of the retina that exerts a locally variable depolarization of horizontal cells Brindley , providiPressure phosphenes are perceived at the field of vision opposite to the location of application of pressure. This indicates that pressure phosphenes are perceived at a direction opposite to the direction of arrival of pressure stimuli over the posterior aspect of the eyeball similar to that of the normal visual perception. In this regard, the mechanism of percept formation of pressure phosphenes and normal visual perception has similarities in the direction at which percepts are formed. Since light-emitting cells were not observed in the retina Bokkon , how doeIn patients with visual hallucinations due to the pathological accumulation of Lewy bodies in the inferior temporal cortex  shows an alpha frequency background in the posterior occipital regions when the eyes are kept closed. These alpha waves change to beta frequency waves when the eyes are opened and light stimuli reach the visual cortex. This indicates that there is relative increase in the vertical trans-synaptic spread of activity between different neuronal orders compared to the increase in the horizontal component of oscillating potentials contributed by the reactivation inter-postsynaptic functional LINKs between the dendritic spines of the visual cortical neurons that synapse with the LGN axonal terminals. Extracellularly-recorded gamma oscillatory responses in the visual cortex were shown to be important in visual perception  activates only one glomerulus  and the lateral horn (LH). PN axons innervate the MB by terminating in large boutons  inhibit all the remaining glomeruli (Hong and Wilson The reactivation of a maximum number of inter-postsynaptic functional LINKs evokes the peak quality of percept for smell. A given odor is not expected to activate non-specific receptors even at the highest concentrations. It is observed that many odors are attractive at low concentrations but aversive at higher concentrations (Wang et al.  Since a large number of postsynapses is expected to be inter-LINKed by innate mechanisms that enable the fly to smell food and survive, the presence of islets of LINKed inter-postsynapses is anticipated at the time of birth. It may be noted that perceptons can be formed even if the inter-postsynaptic functional LINKs occur between the postsynapses that belong to the same PN. A comparable location in mammals is the dendritic excrescences on the dendritic tree of individual CA3 neurons in the hippocampus. The present circuit can provide a mechanism for inducing internal sensation of perception at the inter-LINKed postsynapses of the PNs at the ORN-PN synaptic junctions and its correlation with the spiking of GABAergic ILNs and possibly the latter’s phase-locking with the LFP oscillations in the MB (Tanaka et al. Oscillating potentials and the arrival of background sensory stimuli are expected to induce non-specific semblances and were explained to contribute to C-semblance for consciousness Vadakkan . Even thIt is known that ORNs spike even in the absence of ligands Wilson  with an  Based on the present work, limiting the number of inter-LINKable postsynapses is essential to provide visual perception properties similar to that of the pixilation in a digital image. This is achieved by limiting the lateral borders of the possible expansion of the islets of inter-postsynaptic functional LINKs by the vertically arranged cortical columns. It is described in a previous section that by increasing the number of cortical columns, the pixilation effect by the perceptons is increased. However, the number of different types of smell percepts induced is expected to be much smaller than the number of visual percepts. This is evident from the presence of only 50 different types of ORNs Wilson  among thBased on the present work, innately determined and pre-existing inter-postsynaptic functional LINKs form the major mechanism responsible for percept formation. The pre-existing ones are expected to have inter-postsynaptic membrane hemifusions likely stabilized by trans-membrane proteins. Evidence for these can be examined in the visual cortex and olfactory glomerulus by using advanced high-resolution microscopes.The second possible mechanism of percept formation by rapid removal of hydration repulsion at the inter-postsynaptic locations and its rapid reversal by rehydration can be examined in the visual cortex and olfactory glomerulus. This is likely to require developing novel techniques.By changing the frequency of oscillating potentials in the glomerulus, the net semblance for olfactory perception can be changed. This will alter olfactory perception.Blocking large number of inter-postsynaptic functional LINKs either in the visual cortex or in the glomerulus is expected to alter the horizontal component of oscillating potentials, which will alter the frequency of oscillating potentials and disrupt visual or olfactory perception respectively.The present framework used third person observations to construct a feasible mechanism for the first-person internal sensation of perception and has explained a large number of findings made at different levels. In a state of background semblances induced by oscillating patterns of activation of several postsynapses that contributes to the internal sensation of awareness, the arrival of sensory stimuli induces perceptons that are basic units of perception. The lack of orientation for the perceptons indicates their likely mechanism of integration to form the percept is likely similar to that of pixels in a digital image. The present work has provided a new explanation for the spatial restriction of the cortical columns that can provide mechanisms for accommodating the requirements for the induction of perceptons, and incorporating a pixilation-like effect in the percepts. The presented framework has also provided answers to a large number of questions arising when the circuitry for perception is examined from a third-person frame of reference Wilson .Drosophila supports the view that unitary elements for the formation of the internal sensation exist across different members of the animal species and across different sensations. As the complexity of the nervous system varies, the nature of the basic quality of percepts is likely to change. Drosophila genetics can be used to design experiments to perturb the functioning of the circuitry at different levels to understand the details of the mechanism. A similar mechanism is expected to operate for the perception of other sensations in the nervous system.The percept of the smell of nutritious food that is deemed attractive is likely evolved from an evolutionary selection process due to the survival of flies that fed on those food items. Even though light travels much faster than smell, odorant molecules can reach the fly even from hidden locations from where visual inputs won’t reach the fly. Therefore, perceiving smell is much more efficient than visual stimuli for detecting the presence of food. Flying towards the direction of increasing stimulus gradient of odorants can lead the fly towards the source of food. The presence of a circuitry for the first-person visual perception in mammals and olfactory perception in the fly


Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), have evolved a remarkable ability to evade the immune system in order to survive and to colonize the host. Among the most important evasion strategies is the capacity of these bacilli to parasitize host macrophages, since these are major effector cells against intracellular pathogens that can be used as long-term cellular reservoirs. Mycobacterial pathogens employ an array of virulence factors that manipulate macrophage function to survive and establish infection. Until recently, however, the role of mycobacterial cell envelope lipids as virulence factors in macrophage subversion has remained elusive. Here, we will address exclusively the proposed role for phthiocerol dimycocerosates (DIM) in the modulation of the resident macrophage response and that of phenolic glycolipids (PGL) in the regulation of the recruitment and phenotype of incoming macrophage precursors to the site of infection. We will provide a unique perspective of potential additional functions for these lipids, and highlight obstacles and opportunities to further understand their role in the pathogenesis of TB and other mycobacterial diseases.Mycobacterial pathogens, including  Mycobacterium tuberculosis (Mtb), and its close pathogenic relative M. marinum , and its structurally-related compound, phenolic glycolipids (PGL). In an elegant study, Cambier et al. proposed an exciting mechanism for their role in immune evasion strategies evolved by Mtb to evade immune surveillance  and the subsequent recruitment of microbicidal macrophages , a truncated form of PGL containing just the saccharide domain and the phenol ring, which may also have biological activities  induced increased secretion of the pro-inflammatory cytokines TNF-α, IL-6 and IL-12p40  receptor 2 (CCR2)-dependent recruitment of macrophages by inducing the expression of the chemokine CCL2 through a molecular mechanism still unknown  for diverting macrophages from their natural function and for establishing infection. Most of the research has focused on the macrophage because its dialog with mycobacteria is thought to be the seminal step of the immune response. The study of Cambier et al. marks an important step in understanding the functions of lipids, as it takes into account the full repertoire of the innate immune system (Cambier et al., Mtb lipid effects will lead to the characterization of signaling pathways that are modulated for the benefit or detriment of mycobacteria survival in the host. Therefore, we would like to provide a framework to study the molecular mechanisms governing mycobacterial DIM and PGL activity at the direct interface with macrophages (Figure Mtb PAMPs (Cambier et al., We anticipate that the identification of the molecular mechanisms involved in s Figure . We propmar in the context of zebrafish infection (Cambier et al., M. bovis BCG as surrogate might be a valuable tool to enable the direct comparison of the effects of the PGL variants in the context of a relevant mycobacterial envelope and within the same genetic background (Tabouret et al., For the purpose of conciseness, we focused the current perspective on DIM and PGL, but we believe that in the near future there will be a need for a broad assessment of mycobacterial lipids and their overall effects in the immune system. Novel strategies need to be devised in order to deal with the redundant role as virulence or immunomodulatory factor among mycobacteria cell envelope lipids. In this aspect, our group has undertaken the construction of single and multiple lipid mutants to assess the role of trehalose-derived lipids, sulfolipids, diacyltrehaloses and polyacyltrehaloses, and their respective contribution to the virulence together with DIM (Passemar et al., In conclusion, we believe that the development of microbiological tools and adequate research models, in combination with multidisciplinary strategies, should open up new venues to achieve a better understanding of the ever-evolving relationship between host and pathogen. In many ways, the lipid at the mycobacteria wall is just a starting point!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 new EU project TRANS-FUSIMO (http://www.trans-fusimo.eu) aims at the translation of this software demonstrator into a fully integrated system for the FUS treatment of the liver.The movement of the target challenges the application of high intensive focused ultrasound (HiFU/MRgFUS) for the treatment of malignancies in moving abdominal organs such as liver and kidney. Moreover, the anatomical location of the lesion is often behind the rib cage. The physiology of the organs, the dynamic and complex blood perfusion impairs the energy disposition in the tissue due to the heat transfer within the organ. To explore the full potential of extracorporeal FUS to safely and precisely destroy tissue in the depth of a moving organ requires sophisticated software and advanced hardware. In the EU project FUSIMO  for human patients with metastases or HCC will show the feasibility of the TRANS-FUSIMO system for the clinical setting.The FUSIMO software demonstrator based on MeVisLab incorporates a set of dynamic organ models for the physical and biophysical processes involved in MR guided FUS treatment: (i) an organ motion model simulates the patient specific deformation of the relevant anatomical structures during breathing; (ii) a patient specific tissue model represents the ultrasound propagation, the energy distribution as well as the tissue heating and cooling; (iii) an organ/tumour model captures the patient specific tissue’s response to the therapy. These model components are integrated into a software demonstrator, which orchestrates the interplay between the models and feeds them with model parameters that are extracted from patient specific MR and/or US imaging data. The system and the model components are being validated in phantom and ex vivo experiments show that the FUSIMO system is capable of compensating organ motion through real-time motion detection, motion modelling and real-time beam steering.The FUSIMO/TRANS-FUSIMO software demonstrator comprises specific models for the simulation of FUS application in moving organs based on imaging data derived from volunteers. It supports the assessment of the feasibility of the intervention, predicting and optimizing the outcome, detecting potential risks and avoiding them, as well as monitoring the progress and tracking deviations from the planned procedure. Our in vivo animal studies and first patient study shall show that MRgFUS in moving organs can be performed safely, efficaciously and effectively.In TRANS-FUSIMO a fully integrated system will be developed for which


Fractures of the lateral end of the clavicle are common in pediatric patients; most of these fractures occur at the physeal level representing Salter Harris injuries. The vast majority of fractures of the lateral end of the clavicle are managed nonoperatively. In this report, we describe a unique type of fracture of the distal end of the clavicle in the pediatric patients in which the fracture occurs in the metaphyseal lateral clavicle with the proximal edge of the fracture displaced posteriorly through the trapezius muscle causing obvious deformity. It is similar in pathology to type IV AC joint dislocation. In this study we report this injury in eleven-year-old boy. Literature review showed that similar injuries were described before three times (two of them in pediatric patients). Due to the significant clinical deformity of this category with entrapment of the bone through the trapezius muscle, reduction (open or closed) of the fracture is the recommended treatment. The clavicle ranks among the most frequently fractured bones in the immature skeleton. It is prone to fracture as it resides subcutaneously along the majority of its length and distributes almost all forces from the upper extremity to the trunk. Fractures of the clavicle are categorized according to anatomic location, medial third, middle third, and distal third, the bulk of which involves the middle third, while distal fractures only represent 10–20% [As fusion of the distal epiphysis is not complete until the mid-twenties, fractures of the lateral end in children usually result in a physeal separation of the distal clavicle, rather than a true acromioclavicular (AC) separation –4. AdditThe purpose of this report is to describe a new category of distal clavicular fracture in children that occurs in the distal metaphysis and behaves like AC joint disruption type IV (posterior displacement). This category requires special attention as it needs reduction and not mere observation as in the majority of distal clavicular fractures. We present our case in addition to review of the literature for possible similar published cases. Pubmed search was used with cross reference of the articles. Studies describing distal clavicular fractures in children were assessed for possible similar cases.An 11-year-old male was unconstrained in a motor vehicle collision. No loss of consciousness was reported. He presented to the emergency room with significant left shoulder pain. There was tenderness to palpation at the left shoulder and clavicle with minor overlying abrasion, erythema, and prominent posterior bony mass over his posterior shoulder. He was neurovascularly intact but was unable to move the shoulder due to significant pain. Radiography and CT revealed an oblique fracture of the distal third of the left clavicle with posterior displacement of the distal end of the proximal  fragment . The fraPatient underwent surgery one week following the initial injury. A small transverse incision was made over the distal clavicle. The periosteal sleeve around the distal end of the clavicle was disrupted; however, the attachment of the coracoclavicular ligament into the inferior part of the periosteal sleeve surrounding the clavicle was still intact. The distal end of the proximal  fragment was observed to have disrupted the periosteal sleeve with significant posterior displacement into the trapezius muscle. Multiple attempts were required to free the distal end of the medial segment of the fracture from the trapezius muscle. Then, the fracture ends were reduced together. Once good reduction was achieved, three K-wires were inserted percutaneously from the lateral end of the acromion to the clavicle traversing both ends of the fracture . The patInjuries involving the distal clavicle in children are classically “pseudodislocations” of the AC joint in which the joint and the coracoclavicular ligaments are usually intact, and fracture involves the lateral physis of the clavicle with displacement of the bone through a split in the periosteal sleeve. True dislocation typically does not occur because the AC joint is maintained by the trapezius and the deltoid muscles .In the skeletally immature patient, ligamentous attachment by the coracoclavicular (CC) ligaments is biomechanically stronger than the physeal-metaphyseal region, thus allowing the lateral portion of the clavicle to be displaced from its periosteal tube, giving the radiographic impression of a dislocation of the AC joint due to radiolucent cartilaginous lateral physis.The excellent remodeling capacity in immature bone allows most distal clavicular injuries to be treated nonoperatively. It is widely accepted that nondisplaced or minimally displaced fractures can be managed conservatively with sling immobilization and early rehabilitation with range-of-motion exercises , 5. KubiPediatric injuries that involve the AC joint have been classified by Dameron and Rockwood in a scheme that mirrors the classification of adult AC joint injuries. Type IV injury includes a posterior displacement of the distal clavicle in relation to the acromion with buttonholing of the shaft through the trapezius . The injLiterature review revealed three other similar cases with type IV-like fractures of the distal clavicle; two of these cases were in the pediatric age group , 11. ItoIn conclusion, our case and the three other cases presented previously in the literature suggest that there is a separate category of distal clavicular fracture (more common in pediatric population) that involves the metaphysis of the distal clavicle with posterior displacement of the medial end of the proximal fracture segment through the trapezius. This fracture is similar to type IV AC joint injury, yet the fracture is entirely through the metaphysis of the distal clavicle. Due the significant clinical deformity of this category with entrapment of the bone through the trapezius muscle, reduction (open or closed) of the fracture is the recommended treatment.


Rac GTPases are regulators of the cytoskeleton that play an important role in several aspects of neuronal and brain development. Two distinct Rac GTPases are expressed in the developing nervous system, the widely expressed Rac1 and the neural-specific Rac3 proteins. Recent experimental evidence supports a central role of these two Rac proteins in the development of inhibitory GABAergic interneurons, important modulatory elements of the brain circuitry. The combined inactivation of the genes for the two Rac proteins has profound effects on distinct aspects of interneuron development, and has highlighted a synergistic contribution of the two proteins to the postmitotic maturation of specific populations of cortical and hippocampal interneurons. Rac function is modulated by different types of regulators, and can influence the activity of specific effectors. Some of these proteins have been associated to the development and maturation of interneurons. Cortical interneuron dysfunction is implicated in several neurological and psychiatric diseases characterized by cognitive impairment. Therefore the description of the cellular processes regulated by the Rac GTPases, and the identification of the molecular networks underlying these processes during interneuron development is relevant to the understanding of the role of GABAergic interneurons in cognitive functions. Inhibitory γ-aminobutyric acid (GABA)ergic interneurons modulate brain functions  of the telencephalon causes several defects, including a failure of the tangential migration of interneurons from the GEs  with the conditional deletion of Rac1 in postmitotic neurons by the Synapsin-I-Cre results in mice that are neurologically impaired, with spontaneous epileptic seizures  in the development of interneurons. The secreted factor neuregulin-1 (NRG1) interacts with its transmembrane tyrosine kinase receptor ErbB4 to promote the growth of dendrites in mature interneurons. Evidence has been produced that Kalirin-7, a major dendritic Rac GEF (guanine nucleotide exchange factor) of the Trio/Kalirin family, mediates the effects of NRG1/ErbB4 activation on the growth of dendrites in interneurons, and that the phosphorylation of the carboxy-terminus of kalirin-7 is critical for these effects  pathway that produces phosphatidylinositol 3,4,5-trisphosphate (PIP3) at the plasma membrane. How the activation of PI3-kinase affects the migration of the precursors and their later differentiation into mature inhibitory neurons is unknown. One possibility is that PIP3 engages the GEFs to activate the Rac’s at the plasma membrane  can be regulated by Rac GTPases , which together with GIT2 is part of a family of scaffold proteins with Arf GTPase activating protein (GAP) activity. GIT proteins form stable complexes with the Rac/Cdc42 GEFs of the PIX family, αPIX, and βPIX (Totaro et al., Less is known about the role in neuronal development of the widely expressed GIT2 protein. GIT2 knockout mice have no evident brain defects, but show anxiety-like behavior as a major neurological symptom (Schmalzigaug et al., Interestingly, it has been recently shown that knockout of GIT1 causes a strong and specific reduction in the inhibitory input and in the number of PV-positive interneurons in the hippocampal CA1 region, where the GIT1 protein is normally expressed (Won et al., in vitro highlight the importance of flanking the studies in vivo with reductionistic approaches entailing explants or primary cultures of interneurons from the GEs, to address the machinery required for their development in simplified experimental systems. The identification of the molecular sets involved in the different phases of interneuron development is expected to give an important contribution to the understanding of different neurological and psychiatric disorders where defects in cortical GABAergic cell development appears to importantly contribute to the pathogenesis.The role of Rac1 and Rac3 in the development of cortical and hippocampal GABAergic interneurons has been confirmed by recent studies. Still, substantial work remains to characterize the distinct effects of the two Rac proteins in different developmental steps required for the formation of mature interneurons. Moreover, a number of players has been identified that may regulate or mediate the action of the Rac GTPases in these cells. The wide variety of GABAergic cell types required for normal brain function suggests that specific combinations of regulators and effectors for these GTPases are expected to take part in the maturation and function of distinct types of interneurons. Most of the work on developing interneurons has been performed using mice models, but the fewer studies The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.