Remarkable progress in a range of biomedical disciplines has promoted the understanding of the cellular components of the autonomic nervous system and their differentiation during development to a critical level. Characterization of the gene expression fingerprints of individual neurons and identification of the key regulators of autonomic neuron differentiation enables us to comprehend the development of different sets of autonomic neurons. Their individual functional properties emerge as a consequence of differential gene expression initiated by the action of specific developmental regulators. In this review, we delineate the anatomical and physiological observations that led to the subdivision into sympathetic and parasympathetic domains and analyze how the recent molecular insights melt into and challenge the classical description of the autonomic nervous system. The “great sympathetic”... “was the principal means of bringing about the sympathies of the body”. With these words Langley , 2 summaIn this review we first describe the anatomical and physiological findings that led to the formulation of the classical model of the autonomic nervous system, subdivided into sympathetic and parasympathetic subsystems, acting partly in antagonistic manner. The heart as a prime target of autonomic innervation is discussed with respect to the historical unfolding of the physiological function of both autonomic nervous pathways regulating heart activity, their anatomical trajectories and the positions of the neuron cell bodies involved. We then consider the electrophysiological and neurochemical features of autonomic neurons, to illustrate neuron diversity even within each of the autonomic subsystems and to compare the cranial, thoracolumbar and sacral autonomic domains, their constituent cells and targets. This paves the way to delineate neuron development and factors regulating the acquisition of neuron subtype- specific features determining functional properties. We highlight transcription factor fingerprints of preganglionic and postganglionic neurons at different axial levels that suggest a sympathetic rather than parasympathetic developmental profile of the sacral spinal cord outflow, which stands in stark contrast to the classical model of autonomic neuron domains. Then we discuss the limitations of our understanding of the mechanisms responsible for the selective innervation of postganglionic neuron populations by the appropriate preganglionic neurons. Together with the more detailed characterization of a range of autonomic neuron populations so far underrepresented in the molecular and developmental analysis, a comprehensive understanding of the cellular composition and connectivity of the autonomic nervous system is expected to emerge.During the last two decades of the 19th century a series of keystone publications on structure and function of autonomic nerves were released from the Gaskell and Langley labs that provided the foundation for the thinking about the “autonomic”  nervous Gaskell attempted to replace the nomenclature of the efferent nerves, which to him in part appeared entirely artificial or hypothetical, by fundamental divisions of the nervous system where physiological and structural properties can be grouped together. In a series of landmark papers on the nerves innervating the heart , the visFor Langley , 14 it aAn important issue in Langley’s synthesis  is the dThe classical model of the sympathetic and parasympathetic nervous system provided an amazingly constructive framework for results coming in from the biomedical disciplines at increasing speed. The division into two subsystems acting at least in part in an antagonistic manner based on two neurotransmitter systems provided a very attractive framework for considering system biological problems and to confront a vast range of therapeutic challenges. The opposite action of sympathetic and parasympathetic stimulation on the ciliary muscle, the heart and the reproductive organs were but three examples where the attraction of this approach became apparent. Histological, electrophysiological, pharmacological and neurochemical approaches became the main motors to complete an anatomical and physiological description of cellular structure and function of the autonomic nervous system and its target structures , 17 as wThe interrogation of the neural control of the heart at the turn of the 19th century resolved the problem of whether the heart was able to move independently of the presence of the nervous system and the question for the contribution of the nervous system to the modulation of heart activity . Work onThe first convincing report on antagonistic regulation of the heart activity by the vagus and the sympathetic nerve is attributed to the brothers Ernst Heinrich and Eduard Weber using the electromagnetic rotation apparatus for experiments performed in frogs and confirmed in birds and mammals. Ernst Heinrich Weber reported in 1845  that galvanic excitation of the vagus nerve weakens the heart and slows down or interrupts the heartbeat, while excitation of the sympathetic restores, enhances and enforces the movement of the heart.At the time Langley and Gaskell released their key papers, Bayliss and Starling  publisheA quantitative model for the regulation of heart rate by the parasympathetic – sympathetic antagonistic action was developed , yet theThe anatomical course and physiological impact of the cardio – inhibitor and cardio – accelerator fibers were studied in different mammalian species. They are exemplified by studies in dogs where electrical stimulation and surgical interruption of different cardiac nerve branches and the paravertebral sympathetic trunk were combined to determine the course of the preganglionic vagal and postganglionic sympathetic neurons –32. PostThe balanced interaction of the two tracks of the autonomic nervous system during regulation of heart function as reflex action under different stimulus settings and stressor regimes and its relation to heart dysfunction and autonomic conflict remain the focus of continuing interest , 48. UndEven though the anatomical connection of the vagus nerve, the sympathetic trunk and the heart was already recognized in the 18th century , anatomiLabeling of the entire vagus nerve or the target structures heart, lungs and stomach was performed in the cat by Kalia  and discUpon HRP application to the heart and aortic arch of the dog, the greatest number of labeled postganglionic cell bodies is detected in the medium cervical ganglia, in addition in the cranial poles of the stellate ganglia and occasionally in the superior cervical ganglia . Upon HRThe connectivity between preganglionic and postganglionic neurons was analyzed by electrophysiology in the superior cervical ganglia of the guinea pig . This prCharacterization of the electrophysiological properties of preganglionic sympathetic neurons and their reflex regulation by sensory stimuli demonstrated a diversity of neuron populations that may subserve different functions –68. ThisCharacterization of the electrophysiological properties in combination with morphometric analysis and histochemical classification  complemeIn addition to the location of the cell bodies of the autonomic neurons, their histological characterization provided increasing insight into their nature. In particular the neurons of the sympathetic ganglia became the subject of histological and molecular analysis that provided insight into the neurotransmitter phenotype –78, theiSuch a detailed knowledge is not yet available for preganglionic sympathetic or pre– and postganglionic parasympathetic neurons. Characterization of the postganglionic vagal neurons innervating the heart is still incomplete. Histochemical characterization of the heart ganglia demonstrated the presence of a cholinergic neuron population, considered to represent the postganglionic parasympathetic neuron population, and a population of small intensely fluorescent cells whose function is not fully characterized . The comOf similar interest will be the characterization of the preganglionic neurons in the sympathetic and parasympathetic systems. A very important finding was the discovery of the Phox2 transcription factors expressed in preganglionic motoneurons of the brainstem . In the Of note, application of HRP to the vagus nerve not only labels preganglionic parasympathetic neurons in the brainstem but also postganglionic sympathetic neurons in the cervical sympathetic ganglia. Even HRP application to the cervical vagus reveals labeling in the sympathetic trunk . MoreoveAfter HRP application to the duodenum and jejunum in the cat and the guinea pig, sympathetic neurons are not only labeled in the celiac ganglion but also in the cervical and stellate ganglia of the sympathetic trunk . Since cThus, the abdominal parts of the digestive tract are innervated by several domains of the sympathetic and of the parasympathetic nervous system. The cervical and thoracic domains of the sympathetic system target the duodenum and jejunum via postganglionic neurons from cervical and thoracic ganglia running in the vagus nerve. In addition, neurons from the celiac ganglia and the splanchnic nerves are involved. Lumbar domains of the sympathetic nervous system target the colon via postganglionic neurons in colonic nerves from the mesenteric ganglia –96. The Postganglionic sympathetic neurons innervating abdominal viscera are located in the paravertebral chain of ganglia, in prevertebral ganglia, in isolated clusters of neurons found in the aortic plexus and plexuses accompanying arterial vessels as well as the superior hypogastric plexus, and in the pelvic ganglion or pelvic plexus as it is called in species where the condensation into a well demarcated ganglion is not so prominent.The prevertebral ganglia – the celiac, superior and inferior mesenteric ganglia – were subject to morphological, neurochemical and electrophysiological characterization as described for the cervical and thoracic sympathetic ganglia , 105–107The pelvic ganglion or plexus is unique due to its dual composition  reflecteFostered by the remarkable progress in electrophysiological instrumentation, histochemical techniques and pharmacological approaches, research on the autonomic nervous system in particular during the second half of the 20th century established detailed knowledge of the cellularity and connectivity of the sympathetic and parasympathetic system. The technique of retrograde neuronal tracing by HRP application to sectioned nerves or into target tissues provided a breakthrough in the localization of preganglionic and postganglionic autonomic neurons. Extracellular recordings allowed the characterization of neuronal behavior under control and experimental conditions thus demonstrating the presence of different populations of preganglionic and postganglionic neurons providing pathways to distinct target tissues as exemplified by the sympathetic supply of different vascular beds and other targets. Intracellular recording techniques provided access to the electrical properties of neurons and again demonstrated the presence of different populations of postganglionic neurons in the accessible sympathetic ganglia. In addition they allowed the study of synaptic input from preganglionic neurons to address questions concerning the synaptic integration of autonomic neuronal activity. With these and other techniques a detailed picture of the cellular structure of the autonomic nervous system was developed for adult mammals and assembled into a model of functional organization of two partly antagonistic systems mediating a homeostatic control of key organs.During the first half of the 20th century the basic science approach towards the autonomic nervous system was largely restricted to mature mammalian organisms such as cats and dogs. This changed dramatically since the 1950‘s. The discovery of nerve growth factor (NGF) has put the development of postganglionic sympathetic as well as primary sensory neurons at center stage of Developmental Neuroscience. In the 1970s, immunohistochemical techniques provided specific access to the rate limiting enzyme of catecholamine biosynthesis. Developmental analysis at that time focused on postganglionic sympathetic neurons, expression of the noradrenergic marker enzyme tyrosine hydroxylase and the role of neurotrophic factors in their development. During the 1990s, this focus was considerably strengthened and widened by in situ hybridization for mRNA detection in developing tissues and the inclusion of different markers of neuron populations such as several enzymes of the noradrenaline biosynthesis cascade and transporter proteins. Growth factor receptor protein subunits and transcription factors responsible for cell type specific gene expression and its regulation during development could be analyzed. At the turn of the 21st century, this approach in combination with viral overexpression studies in chick embryos and mutational inactivation studies in mice provided critical insight into the differentiation of the noradrenergic transmitter phenotype in sympathetic neurons and the growth factors and transcription factors involved. In recent years this analysis has been extended to compare sympathetic neuron development at thoracolumbar levels to parasympathetic neuron development at cranial levels. In addition, autonomic neuron development was studied at sacral levels. This resulted in the critical finding that both preganglionic as well as postganglionic neurons at sacral levels are related in the regulation of their differentiation with thoracolumbar sympathetic but not cranial parasympathetic neurons.The discovery and characterization of NGF and its action on peripheral neurons initiated the molecular interrogation into the sympathetic nervous system –114. DifUncoupling of the survival function of NGF by deletion of the proapoptotic Bax2 gene allowed the analysis of additional functions in vivo . The finThe introduction of a range of histochemical and biochemical techniques in the second half of the 20th century boosted developmental analysis of autonomic neurons with particular emphasis on sympathetic neurons. Accessibility of catecholamines and the rate limiting enzyme in their synthesis, tyrosine hydroxylase (Th), by formaline– induced histofluorescence, enzyme activity measurements and immunohistochemistry established Th as phenotypic marker for catecholaminergic neurons, their biochemical activity state, protein expression and gene transcription. The histofluorescence technique  was applA remarkable advantage of the histofluorescence technique was the possibility for combination with nucleolus staining in “quail-chick” chimeras resulting in the breakthrough in the analysis of the neural crest contribution to the postganglionic sympathetic and parasympathetic system . TransplAnother critical finding was the observation that sympathetic neuroblasts are still able to divide after noradrenergic and neuronal differentiation. Combination of catecholamine detection by histofluorescence techniques and demonstration of cell division by incorporation of radiolabeled thymidine into newly synthesized DNA demonstrated that sympathetic neuroblasts in chick embryos are still dividing when they have already acquired neuronal and noradrenergic properties , 135. ThWith in situ hybridization a highly specific as well as selective method was introduced to allow detection of gene expression by mRNA labeling in tissues and even single cells. Comparison of gene expression onset for noradrenergic markers and transcription factors demonstrates an early onset of Th and dopamine beta – hydroxylase (Dbh) transcript detectability following the paired homeodomain protein transcription factors Phox2a and Phox2b in mice and in chick , 140. MuGene overexpression studies in chick embryos as well as mutational inactivation in mouse embryos demonstrates that a set of transcription factors including Phox2a and 2b, Gata2 and 3, Hand1, 2 and 3 and Ascl1 interact as a network to accomplish sympathetic neuronal differentiation , 145  are required for the initiation of differentiation in both systems , 156–158With short delay after initiation of the noradrenergic marker gene induction and several days before target tissue innervation expression of synaptic protein genes commences in chick sympathetic ganglia. This is shown for synaptotagmin I, a critical calcium sensor of the transmitter vesicle membrane, and neurexin 1, a crucial organizer of protein complexes within the pre-synaptic membrane and binding partner to post–synaptic neuroligins . During The development of synapses and transmission in chick ciliary ganglia has been investigated by electrophysiological and ultrastructural analysis . InitialThese studies outline aspects of synapse formation in a selected set of autonomic ganglia. They demonstrate induction of the genes coding for synaptic proteins before the onset of preganglionic and postganglionic contact formation. On the other hand they show the modulatory role of preganglionic innervation as well as target contact on the specification of the synaptic machinery. RNA sequencing analysis demonstrates enormous variation in transcript levels between neurons within sympathetic ganglia , which iPostganglionic parasympathetic neurons are generated later than sympathetic neurons and are located often at sites near their target tissues. The unexpected finding that these parasympathetic neurons are generated from glial progenitor-like cells associated with nerves , 171 expComparison of marker gene expression in autonomic postganglionic neurons of the mouse embryo from cranial to sacral levels discloses a similarity between cells in the paravertebral sympathetic chain and the pelvic ganglion and critical differences to those of cranial parasympathetic ganglia, strongly suggesting a homologous developmental origin of thoracolumbar and sacral postganglionic autonomic neurons . While nMutational inactivation of Olig2 required for motoneuron differentiation results in the lack of preganglionic nerves, which surprisingly did not affect the size of the pelvic ganglion . In addiAnalysis of marker genes at the sites of preganglionic neuron development in the mouse embryo demonstrates two distinct patterns of transcription factor expression at cranial as compared to thoracolumbar and sacral levels . While TBy electrophysiological recording and cell labeling techniques synaptic input from parasympathetic and sympathetic preganglionic neurons to individual postganglionic cells was quantified to study the features of ganglionic information processing. Analysis of the rodent submandibular ganglion , 179, thDuring postnatal development the number of preganglionic fibers innervating individual neurons in the submandibular ganglion decreases while the number of synaptic boutons increases resulting in ganglion cells innervated by single preganglionic neurons in the rat . CompariIn the guinea pig superior cervical ganglion, a preganglionic fiber is estimated to contact 50 to 200 postganglionic neurons . An indiCrucial progress came from NGF mutant mice where the loss of sympathetic neurons was prevented by the additional mutation of the proapoptotic gene Bax . In newbThus, innervation and synapse formation in sympathetic ganglia are controlled by different families of growth factors, in particular neurotrophin signaling. The corresponding factors involved in synapse formation in parasympathetic ganglia are not resolved. In addition, the factors that regulate the establishment of specific connections in different autonomic pathways are unknown.The question of how the specific connections from preganglionic neurons to the target tissue are brought about is unresolved. This entails a number of different problems of distinct interest. A very productive approach has been applied to somatic motoneuron development  where trMolecular understanding is, however, emerging concerning the question of the formation of the paravertebral sympathetic strands and their projections. Neuropilin 1 and 2, receptors for semaphorins and vascular endothelial growth factor, are expressed in postganglionic sympathetic neurons . MutatioTwo key unresolved problems are the transition from axon outgrowth to target innervation and the establishment, competition for and maintenance of synapses. These critical events during the development of a neural network composed of diverse target–specific pathways are incompletely understood for the autonomic nervous system. To what extent population specific cell surface markers may play a role in this process is still unknown. The critical issue of how the neural circuits to the different, in part closely associated autonomic targets such as sweat glands and the neighboring blood vessels are selectively innervated is still open for analysis.A range of cell biological, molecular and surgical techniques established a detailed knowledge of the development of the noradrenergic transmitter phenotype in postganglionic sympathetic neurons including the growth factor signaling systems and the transcription factors required for induction, differentiation and maintenance of the cells. The differentiation of the cholinergic postganglionic parasympathetic neurons is not characterized in its molecular mechanism. Yet, the transcription factors expressed in these neurons during development are known at least in part. This is also the case for the preganglionic neurons in both the sympathetic and parasympathetic system. With the increasing characterization of the transcription factors expressed and required in sympathetic and parasympathetic neurons, the close relation of thoracolumbar and sacral autonomic neurons and the difference from cranial autonomic neuronal development at both preganglionic and postganglionic levels is recognized and provokes the renaming of the sacral division of the autonomic nervous system as sympathetic.With electrophysiological and histochemical techniques, subpopulations of postganglionic sympathetic neurons have been characterized and their target tissues described. RNA sequencing techniques are now complementing this approach to molecularly specify the efferent sympathetic outflow pathways. This approach is still lacking for the postganglionic parasympathetic neurons and the preganglionic neurons of both branches of the autonomic nervous system.A major quest concerning the development of the autonomic nervous system remains the understanding of process outgrowth from both preganglionic and postganglionic neurons and the establishment of neuronal specificity. Some molecular players have been identified but the picture is far from complete. The question how the outgrowing neuronal processes are directed to and choose among alternative target structures and how the strength of the synaptic connections is established and regulated are key problems for the coming years.The classical scheme of the autonomic nervous system as delineated by Langley and Gaskell included a cranial and a sacral parasympathetic domain divided by a thoracolumbar sympathetic domain. One critical argument for the classical subdivision of the sympathetic and parasympathetic systems was the anatomical segregation along the body axes of the preganglionic outflow from the cranial, the thoracolumbar and the sacral level by gaps devoid of white communicating rami containing myelinated preganglionic fibers. In addition to the anatomical location of the preganglionic neuronal cell bodies, a range of arguments are brought forward which do not provide unequivocal criteria. These weaker arguments include the neurotransmitter phenotype, the distance from postganglionic cell bodies to target tissue and the opposite action of sympathetic and parasympathetic stimulation on a range of target organs. Yet, the classical subdivision of the domains in the autonomic nervous system is only partially supported by the molecular signatures specifying cellular differentiation.With the analysis of the transcription factors expressed in the precursors and differentiating neurons of the cranial, thoracolumbar and sacral domains involved in the generation of preganglionic and postganglionic autonomic neurons , strong Alternatively, the term spinal autonomic appears appropriate. Indeed, based on comparative anatomical analysis between vertebrate classes, the term “spinal autonomic” was proposed earlier to include the sympathetic and the sacral, then called parasympathetic, autonomic system  Fig. 3)3). It reAs already emphasized by Langley , the terThe recent description of developmental regulators involved in the differentiation of autonomic neurons and the proposed renaming of the “sacral autonomic outflow” initiated a heated dispute –208. TheFrom the rebuttal discussions , 209 it The visceral motoneurons at hindbrain level are derived from different progenitor populations than the somatic motoneurons whereas both are derived from the same progenitor population in the spinal cord . This isThe amazing progress with RNA sequencing techniques that allow quantitative detection of message transcribed from each gene within the cellular genome provided a quantum leap in the characterization of gene expression patterns within cell populations and single cells. Among autonomic neurons detailed data are available for postganglionic sympathetic neurons derived from stellate and thoracic ganglia , 83. GenMore challenging but at least as important will be the characterization by RNA sequencing of preganglionic sympathetic and parasympathetic neurons at all levels of the body axis. Again a host of questions will be addressed and the comparison to somatic motoneurons on the one hand and the subpopulations of preganglionic autonomic neurons on the other hand can be expected to provide crucial progress. A key problem linked to this approach is the molecular understanding of the pathways taken by preganglionic neurons from either system. Aspects of this topic are the understanding of the differences between preganglionic sympathetic neurons targeting postganglionic neurons in the paravertebral sympathetic chain, those targeting neurons in the prevertebral ganglia and those destined to innervate more distal plexuses. Another crucial point is the understanding of the molecular control of target innervation in cases where the sympathetic and the parasympathetic system innervate different sites within the same target tissue, i.e. the ciliary body, the heart and the pelvic organs.Already some 300 years ago the sympathetic paravertebral chain and vagus nerve, then called the great and the medium sympathetic , were cThe molecular and physiological characterization of the autonomic neurons has provided very refined knowledge of neuron subpopulations distinguished by their neurochemistry, electrical activity and reflex behavior upon sensory stimulation. The integration into autonomic networks is only partially understood, however. The molecular identity of the preganglionic and postganglionic neurons synaptically linked in distinct autonomic pathways is still undefined at the level of the molecular players mediating the specific synaptic connection. In addition, the postganglionic sympathetic neurons targeting major organs such as heart, lung and kidney are not yet characterized by their full transcriptional fingerprint. Thus, a significant gap remains between the cellular characterization of autonomic neurons and the understanding of their embedding in neural networks mediating homeostatic control. Two key systems coordinating organ functions, the cardio – respiratory balancing of respiration and perfusion , 214 andTaken together, the molecular and developmental characterization of selected autonomic neuron subgroups  awaits tThe synthesis of physiological characterization and molecular identification in combination with developmental analysis of autonomic neurons promises not only a comprehensive understanding of the neural networks underlying homeostatic regulation of the body functions but also of their emergence during vertebrate development and evolution.


Anatomic variations involving arterial supply of the large intestines are of clinical significance. Variations range from the pattern of origin, branching and territorial supply. The colon, the part of the large intestine, usually receives its arterial blood supply from branches of the superior and inferior mesenteric arteries. However, anatomic variation in this vascular arrangement has been reported, with vascular anatomy of the right colon being described as complex and more variable compared with the left colon. During routine cadaveric dissection of the supracolic and infracolic viscera, we encountered an additional mesenteric artery originating directly from the anterior surface of the abdominal aorta between the origins of the superior and inferior mesenteric arteries. This additional “inferior mesenteric artery” ran obliquely superiorly toward the left colon giving rise to two branches supplying the distal part of the ascending colon, the transverse colon and the proximal part of the descending colon. Awareness and knowledge of this anatomic variation are important for radiologists and surgeons to improve the quality of surgery and avoid both intra- and postoperative complications during surgical procedures of the colon. The abdominal aorta usually gives rise to three anterior unpaired branches, the celiac artery (CA), superior mesenteric artery (SMA) and inferior mesenteric artery (IMA). The SMA through the ileocolic, right colic and middle colic arteries supplies structures derived from the midgut. These structures include the cecum, ascending colon and proximal two-thirds of the transverse colon. The IMA through its branches, the left colic, sigmoid and superior rectal arteries supplies structures derived from the hindgut, including the distal third of the transverse colon, descending and sigmoid colon and rectum. Anatomical variation in this classical arrangement has been reported , 7. VariAwareness of these and other vascular variations is of clinical significance during various surgeries involving the colon to avoid complications such as intraoperative hemorrhage and colonic ischemia .The variant artery described in the present case report arose from the ventral aspect of the aorta, between the SMA and IMA and gave rise to several branches that supplied the distal part of the ascending colon, the transverse colon and the proximal part of the descending colon. Normally, these colonic regions are supplied by the middle and left colic arteries from the SMA and IMA, respectively. We discuss the possible embryological basis and the surgical implications of this vascular variation.In this case report, we describe a variant mesenteric artery originating directly from the abdominal aorta between the origin of the SMA and IMA in a 85-year-old Caucasian female body donor during routine dissection of the supracolic and infracolic regions. The cause of death in the donor was indicated as myocardial infarction. No past medical records were available for review.During the exposure of the celiac artery, superior and inferior mesenteric arteries, the intestinal loops were moved to the right and the peritoneum covering the posterior abdominal wall removed. The celiac artery and the superior mesenteric artery originated independently from the ventral surface of the abdominal aorta about 1 cm apart (Fig. Between the SMA and IMA, an additional mesenteric artery was found to originate from the ventrolateral surface of the distal aorta, about 2 cm proximal to the origin of the IMA (Fig. The finding in this case reports a variation in the branching pattern of the arteries supplying parts of the colon. The branches supplying the distal part of the ascending colon, the transverse colon and the descending colon were found to originate from a variant branch of the abdominal aorta. Usually, the middle and left colic arteries, branches of the superior and inferior mesenteric arteries, respectively, supply these parts of the colon. The variant artery reported in this case took its origin from the abdominal aorta between the SMA and IMA before giving rise to two branches that correspond to the middle and left colic arteries. Case reports of variant arteries arising directly from the aorta between the SMA and IMA have previously been documented , 8.The variations in the vascular supply of the small and large intestines can best be understood by appreciating the early development of the small and large intestines and their vascular supply. During the embryological period, each of the paired dorsal aortae gives rise to three sets of paired arterial branches: the dorsal, lateral and ventral intersegmental vessels . With suThere is great similarity in the origin, course and the branching pattern of the third mesenteric artery observed in our case report and a similar case reported by Benton and Cotter . Other cThe pattern of blood supply to the colon has implications on the surgical techniques and treatment outcomes on various pathological conditions involving the colon. In the surgical treatment of invasive colonic malignancies, for example, resection of the involved colon is usually accompanied with ligature of the accompanying arterial branches , 6. AcciAn in-depth knowledge of the vascular anatomy of the colon and the associated pattern of collateral variation is necessary for surgeons to avoid both intra- and postoperative complications in surgical procedures involving the colon. Making sure that patients undergo radiological investigations such as selective angiography, CT and MDCT angiography that provide better visualization of vascular variations can avert some of these complications.


Older Americans living in the community who need help with basic activities of daily living overwhelmingly rely on unpaid care provided most commonly by working-age family members. Because unpaid family care limits the demand for nursing facilities and reduces expenses paid by Medicaid and other government programs, previous estimates of its economic value have mostly focused on estimating the benefits of unpaid family care. However, to assess accurately the overall economic value of unpaid family care and define better the scope for policy intervention, it is also important to account for the costs of such care, yet our knowledge of their magnitude remains limited. This study assesses the impact of unpaid family caregiving on the likelihood of working and hours worked for caregivers, and calculates the related cost of forgone earnings today and in 2050. To do so, it matches family caregivers from the National Study of Caregiving with non-caregivers from the Panel Study of Income Dynamics, and uses projections from the Urban Institute’s DYNASIM microsimulation model to inform calculations of future costs of foregone earnings. Results suggest that the cost of foregone earnings attributable to caregiving is currently about $67 billion. By mid-century, it will likely more than double, outpacing the growth of disabled older population as the share of better-educated caregivers with higher earning capacity increases. Policymakers can use these results to inform their current and future policy efforts aimed at assisting family caregivers who are facing the challenge of balancing work and caregiving responsibilities.


Plant breeding is based on phenotyping, not only because of tradition but also because of essence. A plant phenotype is the result of the interactions between the genome of a stationary plant and all the micro- and mega-environments encountered during its life span. Over the recent years, we have witnessed an explosion in state-of-the-art technologies developed through collaborative efforts of multidisciplinary teams to assist the process of high-throughput plant phenotyping in plant breeding , first oYet, plant phenotyping is still the bottleneck for breeding and farming  and the What so far has not been seriously considered, but we assert it should occupy a central part in the relevant discussions, is the choice of the appropriate unit of plant phenotyping in the field, so that the efficiency of selection in plant breeding programs and the corresponding measurable genetic gain are maximized. Should the community continue using the multi-plant, densely grown field plot as the unit of phenotyping and evaluation for plant breeding purposes or should we consider more efficient approaches based on the maximization of a plant’s phenotypic expression and differentiation?To increase efficiency in plant breeding, we advocate that the most appropriate unit of plant phenotyping for selection purposes should correspond to the individual plant grown unhindered in the absence of competitive interactions so that phenotypic expression and the corresponding phenotypic variance are maximized, the coefficient of variation (CV) of single-plant yields is minimized, and spatial heterogeneity is effectively controlled. These conditions are met when plants are allocated in the field according to one of the honeycomb selection designs (HSD) . In this opinion paper, we present a list of some commonly encountered barriers during a plant breeding program, including the so-called pre-breeding activities that exploit the potential of crop wild relatives (CWR), and discuss how these are successfully faced once the unit of plant phenotyping becomes the individual plant grown as described. Results from our long-term research focusing on the application and further development of the principles related to the HSD and the prognostic breeding paradigm  in varioex situ materials in gene banks need to be phenotyped. Seed supplies are not an issue when working with individual plants in HSDs  until enough homogeneous seed is gradually generated during the next few years, so as to permit replications, ranging between two and six, of densely grown plots. Additional testing locations are possible to be included only in the latter stages of the program. A similar problem of limited seed supply is encountered when crop wild relatives and  in HSDs Figure 1This barrier refers to the masking effects of interplant competition on selection efficiency  and the per se and the plant stability index, the latter being quantified on a single-plant basis for the first time. The whole-plant prognostic equation PPE incorporates the two components:Barrier 2 is overcome through a) the partitioning of CYP into components measured concurrently and precisely at the single-plant level under conditions excluding interplant competition  and b) twhere x is the plant yield in grams, ensities .We advocate that the critical question is not whether the entry ranking in densely grown plots corresponds to the ranking of individual plants in wide distances, but whether we truly need genotypes that behave differently under the two conditions. New varieties should have the genetic makeup that renders them density-neutral or density-independent . This isThis barrier relates to the masking effects of soil and spatial heterogeneity. The development of HSDs enables the effective sampling of soil heterogeneity, ensuring that all plants and sibling lines are allocated under comparable growing conditions in both fertile and non-fertile spots. In all HSDs, each plant in the trial is found in the middle of a i) circular, ii) complete, and iii) moving replicate and each sibling line belongs to a moving and triangular grid that covers uniquely the whole spectrum of spatial heterogeneity  plants advanced to the next generation, the higher will be the response R to selection. The same is expected when decreasing the generation time interval that is also related to the greater number of progenies.Barrier 5 relates to the conditions that satisfy the so-called breeder’s equation, originally derived from the practice of animal breeding , that deIn the practice of animal breeding, the unit of evaluation for selection has always been the individual animal raised with no competitive interactions for resources , as eachThis important barrier  concernsThis barrier relates to the reasons underlying the lack of automation in plant breeding coupled with the lack of standards in the phenotyping trials. The adoption of automated phenotyping in plant breeding is still in its infancy . The neeEach plant in a HSD trial possesses a unique position identification number, for example 8-12-7, where number 8 gives the number of the horizontal row, number 12 gives the plant position on the row, and number 7 gives the number of the design code corresponding to the particular sibling line. Attached to this number is the corresponding unique value of the plant phenotyping or prognostic equation. The intrinsic properties of the designs that provide a matrix of standardized motifs across environments and the wide distances between plants facilitate the use of geo-referencing methods. Plants are ranked according to the value of their phenotyping equation and selection of the “best” in each environment is an unbiased process, rendering the same results regardless of the person performing the analysis. It is thus amenable to full automation and robotization.Following the discussion on the barriers, we would also like to draw some attention to some recent references and work that support the above and highlight the novel possibilities that unfold. There is a recent acknowledgment that “it has become measurably harder to generate ideas and new approaches that result in real gains”  and the Importantly, there is good convergence of the concepts described above and the highly successful agronomic practices of the System of Rice Intensification (SRI) . Thus, tThe field phenotyping community can benefit by giving due consideration to the suggested innovations towards overcoming current barriers in plant phenotyping and phenomics, while serving also the developments in plant (epi)genomics. The involvement of international, multidisciplinary teams will contribute to the deeper understanding of the methodology. This will, in turn, unfold additional options and facilitate the successful automation, standardization, and robotization of large-scale phenotyping for plant breeding.DF and MO conceived the work and all authors contributed to the final form of the manuscript and securing relevant funding.The Cyprus Research Promotion Foundation in the frame of the research project MAGNET (INFRASTRUCTURES/1216/0032) supported this work.The authors declare that the opinion article was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


J Dent Res Dent Clin Dent Prospect 2017; 11(3):189-194, the name of the first author was misspelled. The correct name of the first author is Farzad Esmaeili. The authors’ affiliation with Dental & Periodontal Research Center of Tabriz University of Medical Sciences was also missing from the article. The original version of the article has been updated to reflect these corrections.In the article entitled "Efficacy of radiographic density values of the first and second cervical vertebrae recorded by CBCT technique to identify patients with osteoporosis and osteopenia" which appeared in


The systematic review published by Naylor et al. in April 2018 highlights methodological assumptions and biases that occur in studies investigating the burden of antimicrobial resistance (AMR). They note that, due to both the large diversity of statistical approaches and perspectives chosen, the current evidence base of the burden of AMR is highly variable. Certainly, these conclusions are valid and the authors present a very thorough analysis of the currently published literature with a broad array of drug-bug combinations. But readers are left with limited direction of estimating the current best available estimate of the health and economic burden of AMR. Such estimates are desperately needed to inform clinical management and for priority setting activities and initiative to curbing the global threat of AMR. It was with great interest that I read the recent systematic review by Naylor et al.(2018). This comprehensive systematic review investigated the approaches to estimating the burden of AMR for both gram negative and gram positive bacteria. They found 214 articles, comparing cases with resistant infections to both susceptible and uninfected controls.n = 7; 63%) show odds ratio (OR) of mortality to cross the line of significant (OR < =1), compared to the other groups which show greater odds when compared to un-exposed controls. Hence, selections of comparator groups that will answer the research question best should be clearly stated and be consistent to ensure estimates remain comparable between studies.The systematic review visualizes the eligible studies in a forest plots without performing a meta-analysis, which appears appropriate given the large heterogeneity of study design and outcomes measured. Despite this, authors go on to state that the majority of studies ‘..found resistance to be associated with higher mortality .” Figure 2a depicts 24 comparison groups with only 11 studies directly measuring the impact of resistance on mortality, by comparing resistant cases with susceptible. From these direct comparisons, majority , demonstrate the variety of methodologies used in studies  generating excess length of stay (LOS) estimates ranging from as little as an additional 2.5 days 8, demons. Timing All studies investigating the burden of AMR should be assessed for risk of bias. We have developed a tool to prioritize the quality of studies based on previously identified methodological caveats when measuring the burden of AMR . This toIn combination to the recommendations listed by Naylor et al. (2018) a prioritization of the quality of included studies would provide the reader with an appreciation of the strength of the estimates and allow a more informed judgement of the validity of AMR-attributable mortality , excess length of stay  and costs (Table 3). Such solutions should be in place to ensure the higher up the hierarchy the study design is positioned, the more rigorous the methodology and hence the more likely it is that the study design can minimize the effect of bias on the results. This would provide a level of clarity as to the ideal methodologies to use when designing studies and to guide the readers in the direction of deciding the best currently available estimates of burden of AMR.


This dataset focuses on the causes and effects of sick building syndrome among users of selected facilities in Lagos. A mixed research approach of field measurement and cross-sectional survey was adopted. Descriptive statistics were implemented on the data acquired and are reported on tables and figures. The significance of this data leverages on providing insight and consciousness of sick building syndrome to users and occupants of constructed facilities. The survey dataset when analyzed can show direction on physical quantities levels that can be experienced in public buildings in tropical region. In achieving the objectives of the dataset, opinions of 30 staff of three different banks and 46 users and worshippers in the university׳s worship centers in different locations on campus were sampled through structured questionnaire. Personal data characteristics of the respondents are shown and summarized in 2The dataset adopted cross-sectional survey design and physical measurement methods. The data purposively sampled 100 respondents who were users and worshippers in the church and mosque and staff of three commercial banks within the University of Lagos, Akoka campus. The sample frame consists of 76 valid questionnaires comprising 30 bank staffers and 46 worshipers. Recent studies


Systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) are frequently discussed together and perceived as two closely related diseases . Indeed,Caneparo et al.; Han et al.; Knight et al.; Sakata et al.; Weeding and Sawalha) report pathogenic pathways which appear to operate primarily in patients with SLE. The discussed mechanisms  suggest that multiple heterogeneous pathways operate preferentially in patients with SLE rather than in patients with primary APS. For example, the clinical and histological characteristics of renal involvement in patients with APS definitely differentiate the two entities. In particular, a thrombotic vasculopathy involving medium/large and in some cases small vessels is the main pathogenic mechanism in renal APS in contrast with the inflammatory vasculitis which is characteristic of lupus nephritis . Furthermore, involvement of the central nervous system (CNS) is frequent in patients with APS and is mainly linked to vascular thrombotic events while a heterogeneous panel of pathogenic mechanisms contribute to the expression of CNS manifestations in patients with SLE including the presence of NMDR antibodies and the activation of microglia by interferon type I . It is obvious that patients need tailored treatment to address the involved pathogenetic mechanisms.In this collection five manuscripts (Rekvig). Therefore, the classification of patients along the lines of clinical manifestations cannot serve the patient and definitely has not served the multitude of failed clinical trials .The complexity of the pathogenesis of lupus looms even larger in children with SLE in whom hormonal or extensive environmental factors are not yet major contributors but distinct single gene defects explain the development of SLE. Indeed, as discussed by Lo the list of monogenic SLE patients continues to expand (Radic and Pattanaik).In contrast, the clinical manifestations of patients with APS are easily attributed to thrombophilic events orchestrated by aPL although additional non-thrombotic mechanisms may account for the increased rate of miscarriages . SLE “molecular characterization” would be useful for clinicians for a personalized medicine and for better inclusion criteria in clinical trials. In fact, the common biomarkers are not informative enough and we need to enroll more homogenous, along molecular and biochemical lines, populations in the studies and to identify more specific tools for the evaluation of the efficacy of the therapy .A lot of attention has been paid to aberrant T cell activation pathways in SLE in addition to the tissue damage mediated by immune complex deposition. Several manuscripts in the session of the Journal have actually addressed this issue .Complement is central in SLE pathogenesis at two levels: luck of the early components C2 and C4 account for the incomplete elimination of autoreactive B cells and lack of C1q for the poor clearance of apoptotic debris whereas excessive activation and generation of the membrane attack complex and the production of C3a and C5a are directly responsible for the execution of tissue damage. APS experimental models support that complement activation takes place in APS as well and it represents a critical step for both aPL-mediated thrombosis and miscarriages. Moreover, there is preliminary evidence for complement activation also in patients. However, the characteristics of complement activation are quite different in SLE and APS further supporting the differences between these two disorders  had a substantial contribution to the conception or design of the work, or the acquisition, analysis or interpretation of data for the work; (ii) drafted the work or revised it critically for important intellectual content; (ii) provided approval for publication of the content, and (iii) agreed to be accountable for all aspects of the work.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 presence of a new type of brain cannabinoid receptor is also indicated. Important advances have been made in our understanding of cannabinoid receptor signaling pathways, their modulation of synaptic transmission and plasticity, the cellular targets of cannabinoids in different central nervous system (CNS) regions and, in particular, the role of the endogenous brain cannabinoid (endocannabinoid) system. Cannabinoids have widespread actions in the brain: in the hippocampus they influence learning and memory; in the basal ganglia they modulate locomotor activity and reward pathways; in the hypothalamus they have a role in the control of appetite. Cannabinoids may also be protective against neurodegeneration and brain damage and exhibit anticonvulsant activity. Some of the analgesic effects of cannabinoids also appear to involve sites within the brain. These advances in our understanding of the actions of cannabinoids and the brain endocannabinoid system have led to important new insights into neuronal function which are likely to result in the development of new therapeutic strategies for the treatment of a number of key CNS disorders.Cannabis has a long history of consumption both for recreational and medicinal uses. Recently there have been significant advances in our understanding of how cannabis and related compounds (cannabinoids) affect the brain and this review addresses the current state of knowledge of these effects. Cannabinoids act primarily via two types of receptor, CB


Photoluminescence detection of latent fingerprints has over the last quarter century brought about a new level of fingerprint detection sensitivity. The current state of the art is briefly reviewed to set the stage for upcoming new fingerprint processing strategies. These are designed for suppression of background fluorescence from articles holding latent prints, an often serious problem. The suppression of the background involves time-resolved imaging, which is dealt with from the perspective of instrumentation as well as the design of fingerprint treatment strategies. These focus on lanthanide chelates, nanocrystals, and nanocomposites functionalized to label fingerprints.


Aim: to determine the values of biomechanical parameters  in patients with keratoconus and their first degree family members. The purpose of the present study was to investigate the importance of assessing corneal biomechanics in subjects at risk of developing the primary ectasia. Materials and methods: 48 participants divided into three groups were analyzed in an observational study after a complete ophthalmological exam with the primary focus on Ocular Response Analyzer.Results: The mean values of CH, CRF, and KMI in the group of relatives were lower compared with the controls but higher when compared with keratoconus patients. We noted significant differences of CH and CRF between all three groups, while in the case of KMI, only the keratoconus group presented statistically significant differences compared with the relatives, respectively with the healthy subjects. Conclusions: the decreased values of CH and CRF may raise the question whether corneal biomechanics could be an adjuvant tool in the screening of a first-degree family member of a keratoconus patient in the attempt of the early detection of a possible forme fruste keratoconus. Keratoconus is a progressive, mostly bilateral disorder which results in the thinning of the corneal stroma, thus modifying its normal architecture into a conical shape [3]. The disease starts to develop usually in the early puberty and continues to progress until approximately the fourth decade of life [4]. Described as a noninflammatory disease, the pathophysiology of keratoconus remains enigmatic. It is considered to be a multifactorial corneal ectasia triggered by external factors such as eye-rubbing or contact lens wear and endogenous stimuli through the interplay of inflammatory tear mediators, a dysregulation of oxidative stress and proteolytic enzymes resulting in corneal remodeling and keratocytes apoptosis, as well as the presence of atopic patient history [5-8]. Furthermore, the condition has also a genetic pathway, most cases being sporadic, isolated, or associated with other ocular or systemic diseases like Down, Marfan, Ehler-Danslos syndromes [9]. Many studies reported an important number of cases with familial inherited keratoconus, either through an autosomal dominant or recessive transmission, suggesting the higher risk in first-degree family members of developing the disease [10-12].This can lead to irregular astigmatism and corneal scarring with a significant impact on the visual acuity [13-16]. Classically, keratoconus was defined as a noninflammatory corneal condition, yet in the last decade, many authors have debated the possible role of inflammation. Recent studies have published results that highlight the cytokine overexpression in the tear film of keratoconus patients [17]. From a histopathological point of view, a keratoconic cornea has certain changes such as the thinning of the epithelium, the presence of breaks in Bowman’s layer, disorganized and reduced collagen fibrils that have repercussions on the corneal biomechanics [18]. The cornea is a viscoelastic material and exhibits the property of recovering the initial form after the applied stress with a lag between the application of the force and the response. This property is called hysteresis [19].An essential parameter in monitoring the disease progression is the corneal biomechanics, which offers in vivo measurements of the cornea while being deformed when a mechanical stress is applied [20-23].Given the fact that the corneal stroma and Bowman’s layer are responsible for the corneal strength, their disintegration may cause instability of the tissue. Proteolytic enzymes and inflammatory cytokines released in the tear film of keratoconus patients generate a corneal thinning through the alterations produced at the level of the extracellular matrix and collagen fibrils. These factors interfere in the mechanical stability and imbalance the viscous behavior of the cornea [24-26]. In the last years, ORA has been used in the attempt of early detection of subclinical keratoconus and for monitoring its progression. According to many studies, both parameters (CH and CRF) have been reported to be lower in keratoconic corneas compared to healthy ones .Multiple methods have been used to measure corneal biomechanics beginning with the ex vivo studies reflected by Young’s modulus and continuing with the in vivo assessment of biomechanical properties. The Ocular Response Analyzer  is a noncontact tonometer that indents the cornea through an air puff producing two distinct peaks: P1 moving inwards and P2 outwards, representing the necessary pressures to deform the cornea respectively to recover from the applanation while the air pulse decreases. The difference between P1 and P2 is an indicator of the corneal viscosity and is called hysteresis (CH). As for the other parameter, the corneal resistance factor (CRF) highlights the overall resistance and is referred to as the indicator of corneal elasticity [28-30].Another waveform analysis is represented by the keratoconus match index (KMI), which is believed to be a reliable index in keratoconus diagnosis and staging, especially in the early diagnosis of a subclinical keratoconus and results from the comparison of the waveform of the patient’s eye compared with the waveform of the normal population in the database . The findings highlighted the altered viscoelastic capacities in keratoconic corneas as well as in the group of relatives.Taking into account the higher risk of developing keratoconus in relatives, we compared corneal hysteresis, corneal resistance factor and keratoconus match index in patients with keratoconus with their first-degree family members and a control group and observed lower values in the relatives when compared with the controls. These results were in accordance with the study conducted by Kara et al., which stated that these biomechanical properties could be used in assessing a subject at risk, suggesting that these may detect early changes of a diseased cornea even before the topographic indices [32]. Transposing this hypothesis into our study, the group of relatives presented decreased values of CH, CRF, and KMI compared with the controls, indicating that even though the topographic indices were inside normal limits, the corneal biomechanical properties may be affected in some degrees. Many studies evaluated the dynamics of biomechanical properties after corneal collagen crosslinking (CXL) using ORA and observed an improvement of some parameters after the intervention but no significant changes in CH or CRF long-term after CXL [33-35].Furthermore, Schwitzer et al. evidenced the finding of the lower values of CH and CRF in forme fruste keratoconus compared with healthy corneas with the hope of detecting subclinical keratoconus [The screening in keratoconus remains a clinical challenge, especially in the case of first-degree family members of the keratoconus patients who are at higher risk of developing the disease. These subjects should be closely and regularly assessed not only by corneal topography but also by Ocular Response Analyzer, since even a discretely modified biomechanical parameter could be an indicator of corneal sufferance and implicitly an early premonitory sign of a subclinical keratoconus.


Additionally, there are reports that suggest possible claustral involvement in focal epilepsy, including MRI findings of bilaterally increased T2 signal intensity in patients with status epilepticus (SE). Although its cytoarchitecture and connectivity have been studied extensively, the precise role of the claustrum in consciousness processing, and, thus, its contribution to the semiology of dyscognitive seizures are still elusive. To investigate the role of the claustrum in rats, we studied the effect of high-frequency stimulation (HFS) of the claustrum on performance in the operant chamber. We also studied the inter-claustral and the claustro-hippocampal connectivity through cerebro-cerebral evoked potentials (CCEPs), and investigated the involvement of the claustrum in kainate (KA)-induced seizures. We found that HFS of the claustrum decreased the performance in the operant task in a manner that was proportional to the current intensity used. In this article, we present previously unpublished data about the effect of stimulating extra-claustral regions in the operant chamber task as a control experiment. In these animals, stimulation of the corpus callosum, the largest interhemispheric commissure, as well as the orbitofrontal cortex in the vicinity of the claustrum did not produce that same effect as with claustral stimulation. Additionally, CCEPs established the presence of effective connectivity between both claustra, as well as between the claustrum and bilateral hippocampi indicating that these connections may be part of the circuitry involved in alteration of consciousness in limbic seizures. Lastly, some seizures induced by KA injections showed an early involvement of the claustrum with later propagation to the hippocampi. Further work is needed to clarify the exact role of the claustrum in mediating alteration of consciousness during epileptic seizures.The neural mechanisms of altered consciousness that accompanies most epileptic seizures are not known. We have reported alteration of consciousness resulting from electrical stimulation of the claustrum  The neural correlates of consciousness are not fully understood. Altered consciousness is the hallmark of focal dyscognitive seizures, which are characterized by loss of perception of external and internal stimuli during wakefulness  with functional MRI (fMRI) assessing interictal epileptiform discharges in individuals with focal epilepsy found increased blood-oxygen-level-dependent (BOLD) signal in the piriform area in association with spikes , and the direct clinical evidence through electrical stimulation, as well as the animal data we have collected so far all continue to be insufficient to formulate a solid hypothesis about the function of the claustrum. Therefore, more controlled experiments in animals and prospective data in humans need to be collected before a clearer picture about the function of the claustrum can be attained.Also, the KA model focuses on focal epilepsy and thus studies using a wide-range of animal models as well as a genetic model for generalized epilepsy are required to extend the generalizability of the findings. Future studies should also focus on the selection of different stimulation parameters and assessing whether low-frequency stimulation of the claustrum can have anti-seizure effects. With the advancement of direct access to the claustrum using modern techniques such as optogenetics (Wang et al., MK outlined the manuscript and all authors contributed equally. LK generated the first draft.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.


This data article contains information on a new intelligent bandwidth allocation model for future network (Smart Allocation). The included data describe the topology of the network testbed and the obtained results. Obtained data show the effectiveness of the proposed model in comparison with the MAM and RDM bandwidth allocation models. In relation to the performances evaluation, a variety of flows are used such as: voice over IP (VoIP), video, HTTP, and Internet Control Message Protocol (ICMP). The evaluation criteria are: VoIP latency and jitter, Peak Signal to Noise Ratio (PSNR) video, retransmission video, goodput, HTTP response page, and the Round-Trip Time (RTT) ICMP delay. The presented data are extracted based on simulation. Specifications TableValue of the data•Dynamic bandwidth allocation is one of the major concerns in the networking and telecommunications sector.•The proposed model allows equitable distribution of bandwidth resources over different flows with different priorities.•The proposed model is tested for the next generation computer networks. It can be deployed in industrial networks.•These simulation data can be used as references for future work related to adaptive bandwidth management.•The proposed model is deployed at a controller; this allows researchers in the Software-Defined Network (SDN) axis to adopt it in order to optimize the performance of their networks.1With the emergence of new flows , optimal bandwidth management has become one of the major concerns for both the telecommunication industry actors and the researchers. The Quality of Service (QoS) has become a necessity in the Next Generation Networks (NGN). Several algorithms have been proposed for dynamic bandwidth management while offering clients the solicited QoS level and guaranteeing operators the optimal use of their network infrastructures. The Maximum Allocation Model (MAM) 2The materials used in the experiment are the Cisco XR and Cisco 7200 IOS routers. The Smart Allocation model was deployed on a centralized controller, connected to routers through a 100 Megabit UTP link. The server contains a video sequence of 720 pixels’ resolution. This video will be broadcast to the users to measure the quality of the video in the three bandwidth adaptation models.•VoIP latency: the delay between sending a packet and receiving it.•VoIP jitter: the duration between the sending of two successive packets.•Page response time: the session opening delay and the delivery of all web content.•Round-Trip Time (RTT): the delay since sending an ICMP packet to the receipt acknowledgment.The experimental data shown in The values are represented in milliseconds. The evaluation methodology consists of activating IP SLA probes on routers and programming fully meshed communications. The results were obtained by repeating the same measures ten times in order to ensure the relevance of the obtained results. The parameters of the data used in the experiments are: the G.711 alaw codec for VoIP, version 1.1 of the HTTP protocol, and ICMP Echo type with the Don’t Fragment (DF) flag set.We cannot talk about the QoS without dealing with the video quality. The data in In order to qualitatively evaluate the data, Other data was generated to compare the QoS adaptation models; we mention the goodput and the retransmission. The goodput means the amount of information received by the application layer of the OSI model without including the size of the lower layer headers. The higher the goodput data, the better the quality of the intercepted video. The packets retransmission is one of the factors that influence the transmissions quality in general and specifically the video quality. The effective retransmission represents the number of packets successfully retransmitted.


A reference is omitted from the second sentence of the third paragraph in the Introduction section.The sentence should read: The hard palate of DS adolescents is often described as high arched and constricted or narrow , but data in the literature are contradictory , depending on patient age [23] of the studied DS group.


This is an interesting case that highlights the variability of the clinical course of sarcoidosis and the importance of the knowledge of the clinical and radiologic features of the disease for its diagnosis and management. The patient also reported dyspnea under moderate stress. Physical examination showed hepatomegaly and erythematous plaques on the face Figure A and lefSarcoidosis is an immune‐mediated systemic inflammatory disease of unknown etiology, characterized by noncaseating epithelioid‐cell granulomas. Sarcoidosis may affect virtually any organ system, although 90% of patients present with pulmonary involvement.Extrapulmonary disease is reported in 30% of patients, with the liver and spleen being the most frequently affected abdominal organs. Homogeneous hepatomegaly often associated with splenomegaly and enlarged lymph nodes is the typical imaging feature of abdominal sarcoidosis.All the authors made substantial contribution to the preparation of this manuscript and approved the final version for submission. YMR: contributed to write the case and identify the images. GZ: performed literature search and helped in identifying appropriate images. EM: reviewed and edited the case report and helped in identifying appropriate images.Consent was obtained from the patient for publication of case details.The authors declare that they have no conflict of interests to express.


Due to the lack of anatomical studies concerning complexity of the tibiofibular syndesmosis blood supply, density of blood vessels with further organization of syndesmotic vascular variations is presented in clinically relevant classification system. The material for the study was obtained from cadaveric dissections. We dissected 50 human ankles observing different types of arterial blood supply. Our classification system is based on the vascular variations of the anterior aspect of tibiofibular syndesmosis and corresponds with vascular density. According to our study the mean vascular density of tibiofibular syndesmosis is relatively low (4.4%) and depends on the type of blood supply. The highest density was observed among ankles with complete vasculature and the lowest when lateral anterior malleolar artery was absent . Awareness of various types of tibiofibular syndesmosis arterial blood supply is essential for orthopedic surgeons who operate in the ankle region and radiologists for the anatomic evaluation of this area. Knowledge about possible variations along with relatively low density of vessels may contribute to modification of treatment approach by the increase of the recommended time of syndesmotic screw stabilization in order to prevent healing complications. There is a lack of studies presenting the complexity of its arterial blood supply. Only McKeon et al. provided detailed anatomical description of the vessels supplying syndesmotic area5. However, this study is focused mainly on the supply of the anterior aspect of the tibiofibular syndesmosis with the consideration of the caliber of the vessels. Huber (1941) in his study mentioned a perforating (anterior) branch of the fibular artery , which pierces the interosseous membrane and runs across the anteroinferior region of the tibiofibular syndesmosis6. Bartonicek also reported a perforating branch of the peroneal artery that penetrates the interosseous membrane1. According to most studies the popliteal artery gives rise to anterior tibial artery and common tibiofibular trunk, which divides into posterior tibial artery and fibular artery. In most cases origin of the fibular artery is described as just below the level of the neck of fibula, about 5 cm below the bifurcation of the popliteal artery. Fibular artery in its distal part gives rise to anterior branch, posterior branch and communicating branch joining posterior tibial artery, and then continues its passage, finally spreading into the calcaneal branches. In general, three main arteries of the leg may have contribution in tibiofibular syndesmosis blood supply: posterior tibial, anterior tibial and fibular artery11. Understanding the anatomical variations in blood supply of tibiofibular syndesmosis is crucial for orthopedic surgeons operating in the ankle region and may contribute to the modification of the surgical technique to avoid complications as a direct consequence of accidental vessel injury. Among the most common complications is the malreduction resulting with decreased joint motion and chronic pain, both can lead to long-term disability. Another less prominent complication with yet poorly understood pathophysiology is heterotopic ossification. It can lead to ankle synostosis, resulting in pain and abnormal ankle kinematics12. Injury of the tibiofibular syndesmosis is associated with slower healing time in comparison with injuries of other ankle ligaments. Typically it results in significantly longer time away from ambulation and sport activities. The limited blood supply is the commonly recognized factor which may have a negative impact on healing of number of anatomical structures. Knowledge about this limitation is essential at the time of preoperative planning and selection of the potentially most successful treatment17. Insufficient vascular supply to an area of injury usually leads to delay in the healing process and increased overall morbidity5. The management of injury to the distal tibiofibular syndesmosis remains controversial in the treatment of ankle fractures. Operative fixation usually involves the insertion of a metallic diastasis screw. There are a variety of options for the position and characterization of the screw, the type of cortical fixation, and whether the screw should be removed prior to weight-bearing18. This paper reviews the relevant anatomy, the clinical and radiological diagnosis and the mechanism of trauma and alternative methods of treatment for injuries to the syndesmosis. The complex nature of vascular anatomy of the distal tibiofibular syndesmosis results with variation and disagreement in treatment strategies. The aim of this study is to present the complexity of the tibiofibular syndesmosis blood supply, further organization of its vascular variations into classification system and examination of vascular density of this region with clinical correlation.Tibiofibular syndesmosis is a fibrous connection localized between the fibular notch of the tibia and medial surface of the lateral ankle. It is stabilized by two ligaments: anterior and posterior tibiofibular ligament. Some authors distinguish three ligaments stabilizing this joint: anterior, posterior and interosseous tibiofibular ligament5 and our findings, variants of tibiofibular syndesmosis blood supply were organized into unified and clinically useful classification system  was described in 36 cases 72%). Its characteristic feature was complete blood supply of anterior aspect of the syndesmosis by lateral anterior malleolar artery from anterior tibial artery and by anterior branch of fibular artery. Type I was divided into three subtypes: IA when lateral anterior malleolar artery was present and supplied anterior aspect of syndesmosis indirectly connecting to the anterior branch of fibular artery. It occurred in 26 cases (52%) Fig. . In type%. Its chType II was found in 14 cases (28%). In this type, anterior aspect of tibiofibular syndesmosis was supplied exclusively by anterior branch of fibular artery, with lack of lateral anterior malleolar artery. Similarly to type I, type II was divided into three subtypes. In type IIA which was represented by 12 cases (12%), there was lack of lateral anterior malleolar artery but anterior tibial artery was present Fig. . In typeAccording to our analysis, mean vascular density of tibiofibular syndesmosis was relatively low (4.4%) and closely correlated with the specific type of its blood supply according to the classification system introduced in this study. The percentage of combined lumen of the blood vessel was 4.5% in type IA, 5.8% in type IB, 4.2% in type IC, 3.8% in type IIA and 3.5% in type IIB. The highest density was observed in type IB and the lowest in type IIB .19. Despite the amount of syndesmotic injuries, there is a lack of presentations in literature of all possible variations of its fairly complex vascular anatomy. Attinger et al. in his study of utilization of angiosomes of the foot in order to salvage the limb presented, that anterior tibial and fibular arteries are connected by anterior branch of fibular artery and lateral anterior malleolar artery20. According to authors of this study, disruption of that connection can put the lateral ankle soft tissue at risk. In our study this kind of connection was observed in 56% of cases (in types IA and IC)18. McKeon et al. study seems to be the most complete description5. In this analysis anatomical variations of tibiofibular syndesmosis blood supply were divided into three main types. In type I (63% of cases) – anterior branch of fibular artery was the main source of blood supply, with occasional anastomoses with anterior tibial artery. This type corresponds to our type IA (52% of cases enrolled in our study). In the second pattern (21%) the fibular artery gave rise of multiple branches to the anterior ligaments of syndesmotic area and was supplemented by branches of a lesser caliber arising from the anterior tibial artery which supplied syndesmosis directly5. In the third pattern (16%) the anterior tibial artery supplied branches of a larger caliber than that of the branches from the perforating branch of the fibular artery5. Second and third pattern of McKeon et al. study are similar to our type IB (16% of cases)5. In the classification system presented in our study we did not take into consideration the caliber of the vessels, only the total density of vessels calculated as the percentage of combined blood vessel lumen in the syndesmosis. Observations presented in McKeon’s study are complement with our findings that blood supply to the posterior aspect of syndesmosis is rather constant. However due to the limited number of specimens, cases with predominantly posterior blood supply, as the consequence of the lack of branches supplying anterior aspect of the syndesmosis, were omitted in McKeon’s study. This aspect is described in our study and completes the description proposed by McKeon et al.5.Tibiofibular syndesmosis in majority of cases is supplied by three branches of two main arteries of the leg. Anterior aspect of tibiofibular syndesmosis is supplied by lateral anterior malleolar artery from anterior tibial artery together with anterior branch of fibular artery, whereas posterior aspect by posterior branch of fibular artery. In the following study this complex vascular anatomy was organized into clinically useful classification system along with examination of vascular density of this area. Awareness of various types of tibiofibular syndesmosis arterial blood supply is crucial for orthopedic surgeons who operate in the ankle region and radiology specialists for the anatomic evaluation of this commonly injured structure. Approximately 5% to 10% of all ankle sprains and 23% of ankle fractures involve trauma to the tibiofibular syndesmosiset al. the vascular supply to the posterior syndesmotic area originated completely from the fibular artery in 63% of cases5. In 37% of cases the posterior tibial artery also provided small branches to supply the posterior syndesmosis. According to our study blood supply to posterior aspect of tibiofibular syndesmosis was rather constant and was supplied by posterior branch of fibular artery in 96% of cases  and in 4% of cases by branch of posterior tibial artery (type IC). McKeon et al.5 reported that there were no specimens in which due to the lack of anterior tibial artery, the posterior tibial artery contribution was the dominant supply to the posterior syndesmotic region. According to our study branch from posterior tibial artery was dominant in 4% of cases (type IC). Our classification system which is complement with McKeon et al.5 corresponds well with syndesmotic vascular density  in order to obtain general estimation of vascular density. Although this approach was enough for general orientation in density of blood vessels in examined area, further analysis of syndesmotic composition is needed. As the next step authors would like to examine histologic composition of tibiofibular syndesmosis utilizing specific tissue staining for better visual differentiation in order to increase the accuracy of estimations and provide detailed structure of tibiofibular syndesmosis.A clear understanding of arterial blood supply of the tibiofibular syndesmosis is essential for proper identification and avoidance of accidental injury of the arteries during procedures in the ankle region. Although fairly complex vasculature, the overall density of blood vessels in tibiofibular syndesmosis is low and is one of the factors which make surgical treatment of this area highly challenging.The material for the following study was obtained from routine cadaveric dissections in the Anatomy Department and Forensic Medicine Department, Jagiellonian University Medical College, Krakow, Poland. We dissected 50 human ankles of both sexes in the age from 35 to 76, observing different types of tibiofibular syndesmosis arterial blood supply Table . ImmediaAccess for proper visualization of the arterial blood supply of the tibiofibular syndesmosis was obtained by remove of the fibula. For this purpose a vertical incision on the posterior aspect of the leg was done, from the region of popliteal fossa to the plantar tendon. The incision was made along the axis of the bone, a finger breadth posterior to the fibula and was similar to the incision made in order to harvest fibular flap for reconstruction purposes. The skin, the muscles of posterior and lateral groups of the leg and a distal part of fibula were removed. The small vessels supplying lateral malleolar region were shown and described. Images of dissected specimens presented in this study, were recorded with digital camera  and then analyzed with Photoshop software .In order to examine the vascular density of tibiofibular syndesmosis material was evaluated under microscope in the Department of Pathology, Jagiellonian University Medical College, Krakow, Poland. Three sections were taken from upper, middle and lower part of tibiofibular syndesmosis Fig. . Tissue Regarding the experiments involving human participants (including the use of tissue samples) we have obtained informed consent for study participation and approval from the Jagiellonian University Medical College Bioethics Committee (registry no. KBET/167/B/2009) for routine cadaveric dissections in the Anatomy Department and Forensic Medicine Department, Jagiellonian University Medical College, Krakow, Poland. This study adhered to the Declaration of Helsinki and its later amendments. Due to the limited number of enrolled specimens statistical analysis was withdrawn.


The epimutation concept, that is, malignancy is a result of deranged patterns of gene expression due to defective epigenetic control, proposes that in the majority of adult cancers the primary (initiating) lesion adversely affects the mechanism of vertical transmission of the epigenetic pattern existing in the stem cells of differentiated tissue. Such an error-prone mechanism will result in deviant gene expression capable of accumulation at each mitosis of the affected stem cell clone. It is argued that a proportion of these proliferation products will express combinations of genes which endow them with malignant properties, such as the ability to transgress tissue boundaries and migrate to distant locations. Since the likelihood of this occurrence is dependent on the proliferation of cells manifesting the defective epigenetic transmission, the theory predicts that cancer incidence will be strongly influenced by factors regulating the turnover rate of the stem cells of the tissue in question. Evidence relating to this stipulation is examined. In addition, it would be anticipated on the basis of the selection of genes involved that the susceptibility to malignant transformation will vary according to the tissue of origin and this is also discussed. Recently there has been considerable interest in the role of epigenetic mechanisms in cancer –3 and itThe cardinal abnormality exhibited by the majority of adult cancers is chromosomal instability (CIN) with widespread alterations in gene expression  accompanSome of the relevant factors involve obvious differences such as the number of susceptible cells and the degree of mutagenic exposure. For each tissue the probability of the initiation phase taking place is influenced by the size of the population, the number of genes that have to be mutated to bring about the defect, the exposure to mutagenic events, and the elimination or repair efficiency of the relevant stem cells, i.e., stem cell numbers, the number of crucial genes, and their effective mutation rate , 10. DifAn important question with regard to the epigenetic theory of carcinogenesis concerns the problem of which genes are necessary and sufficient to bring about the defective copying of the epigenetic pattern and whether the same genes are involved in all cases. It can be argued that in developmental neoplasms the underlying problem is the failure of evocation of some gene silencing mechanism involved in differentiation, and in these cases reversal is possible . In adulHowever, assuming that the initiation stage has been accomplished, the factors implicated in the secondary carcinogenic events, i.e., the failure of fidelity of epigenetic copying resulting from the initiating lesion, have hitherto received relatively little discussion. In essence the likelihood of the acquisition of epigenetic errors that result in malignancy will depend on two criteria: (1) the rate of stem cell proliferation and (2) the ease of activation of the genes that determine the metastatic phenotype. In the absence of clear evidence of which genes are involved in the processes that result in the manifestation of the malignant phenotype, the second factor is difficult to assess. Possibly, if reactivation of the most recently silenced genes occurs more readily, it might be speculated, for example, that migratory properties would be more likely to be expressed in melanocytes, thus accounting for the earlier age-specific incidence of melanoma . An inteFrom the theoretical point of view, the proposed central role of stem cell proliferation in bringing about the epigenetic errors that lead to the malignant phenotype makes a number of testable predictions, several of which are known to be the case. For example, it follows that malignant tumours are not found in nonproliferating tissues such as the central nervous system and rarely occur in slowly proliferating cells such as striated muscle. Moreover, since the greatest turnover occurs in epithelia, it accounts for the high proportion of epithelial cancers. The central significance of stem cell proliferation has been emphasised by the statistical association between cancer risk and the total number of stem cell divisions in different tissues as shown by Tomasetti and Vogelstein  and the Also consistent with the epigenetic model is the evidence of increased risk of malignancy associated with factors increasing the proliferation rate of tissues. This includes the stimulatory effects of chronic inflammation and specific growth factors such as hormones, e.g., the increased breast cancer risk associated with hormone replacement therapy . At the The influence of the stem cell proliferation rate on the acquisition of malignant characteristics importantly predicts that initiated cells can be prevented from becoming malignant by suppression of proliferation. This phenomenon has been described in the case of hepatocytes experimentally initiated by aflatoxin –30.In brief, the preventative possibilities presented by the epimutation model of cancer concern the identification of mutant genes responsible for the error-prone epigenetic copying and their repair or selective elimination of cells bearing these mutations. In this respect the scenario differs from the conventional theories of carcinogenesis only in focusing on genes implicated in the epigenetic copying mechanism. It is a moot point which genes might be most significant in this respect but possible candidates include genes involved in regulating the activities of DNA methylases, histone deacetylases, p53 and related processes involved in apoptosis, and other possible gatekeeping and editing functions. For example, polycomb group proteins such as EZH2 the H3K29 methylase UTX and components of the chromatin remodelling complex such as SWI/SNF are modified in several cancers  and therAssuming that malignant behaviour in all cases is derived from a specific genetic composition, a promising approach might lie in the identification of the genes giving rise to the crucial malignant properties. This would potentially enable the design of agents causing epigenetic suppression of these malignant genes or drugs to selectively eliminate cells expressing those genes. At present, the nature of such crucial genetic targets is not clear and, moreover, it seems probable that the route to malignancy varies according to the tissue of origin. For the present it appears that the most accessible target is the evidence that the carcinogenic risk is a function of the stem cell proliferation rate of the tissue in question. Hence, if a tissue has undergone carcinogenic induction, any means that diminishes the rate of stem cell proliferation will suppress the emergence of a malignant variant clone and, of course, many of the currently effective chemotherapeutic agents target the proliferation rate of the affected tissue.The epigenetic theory of carcinogenesis proposes that the acquisition of the malignant phenotype results from error-prone copying of the epigenetic pattern when tissue stem cells divide. This failure of fidelity of epigenetic transmission is due to initiating mutations affecting the set of crucial genes involved in the normally stable copying of the epigenetic pattern. The manifestation of error-prone epigenetic copying is the generation of clones showing a diversifying range of abnormalities including structural and functional anomalies, abnormal mitoses, alterations of ploidy, and the occurrence of bizarre cytological features. It is argued that these anomalies give rise to cells some of which exhibit malignant characteristics and are able to transgress tissue barriers and spread to distant sites.Whilst it may be impossible to avoid the initiating mutagenesis, in principle cancer could be prevented if cells bearing the initiating lesion(s) could be identified and the faulty epigenetic process corrected or the affected cells eliminated. This eventuality remains a hope for the future.However, in view of the important role of mitosis in enabling the perpetuation of epigenetic errors, ensuring the minimum turnover rate of tissue stem cells seems to offer a basis for a general cancer prevention strategy.


Epiphytic bryophyte communities in the Amazon forest show a vertical gradient in species composition along the trunk of the host trees. The investigation of species traits related to this pattern has focused on the physiology of selected taxa with a clear preference for one of the extremes of the gradient. Although some species are indeed only found on the tree base or in the outer canopy, the vertical gradient is composed mainly by the variation in the abundances of species with a broader occurrence along the height zones. Therefore, this study approaches the differences among community assemblages, rather than among species, to test the role of morphological and dispersal traits on the establishment of the vertical gradient in species composition.A character state matrix was built for 104 species of the family Lejeuneaceae recorded as epiphytes in the Amazonian terra firme forests, and six binary traits supposed to influence species occurrence: dark pigmentation on leaves; ability to convolute leaves when drying; possession of thickened cell walls; reproduction mode (monoicous or dioicous); occurrence of asexual reproduction; and facultative epiphyllous habit. Based on a previous dataset on community composition along the vertical gradient, trait occurrences in random draws of the metacommunity was compared to trait occurrences in field data, in order to detect significant deviations in the different height zones.Four out of the six traits tested showed significantly higher or lower occurrence in the species composition of canopy and/or understory communities. Traits related to high dispersal ability did not vary much along the vertical gradient; although facultative epiphylls were overrepresented on tree base. Dark pigmentation and convolute leaves were significantly more frequent in the canopy communities, but also significantly less frequent in communities at the base of the tree.Dark pigmentation and convolute leaves seem to be advantageous for the establishment in the canopy zones. They may, respectively, prevent light damage and allow longer periods of photosynthesis. Interestingly, these traits occur randomly along the trunk, but are wiped out of communities on the tree base. In the relatively deep shade of the first meters of the understory, they possibly hamper net carbon gain, the first by darkening the leaf surface and the second by delaying desiccation—which can be damaging under high temperatures and low light. The fact that production of asexual propagules is not overrepresented in the most dynamic microenvironment along the gradient, the canopy, challenges current views of bryophyte life strategy theory. Watson’s implicit assumption of niche assembly—in the broad sense that species features have a role on species occurrence—as well as his emphasis on environmental filtering, rather than on species interactions, illustrates the common sense in bryophyte ecology , but not in the outer canopy (zone 6) or along the trunk (zones 2 and 3). The occurrence of this trait in communities at the base of the tree (zone 1) was significantly lower than expected by chance. Convolute leaves were significantly more represented in the outer canopy (zone 6), and significantly less in the first two understory zones (zones 1 and 2). Both the monoicous reproduction system and the facultative epiphylly were significantly more represented only in communities at the base of the tree (zone 1), with the latest significantly less represented only in communities in the bifurcation zone.For bryophytes, the vertical gradient along the host trees reflects the two extremes of a water balance axis: in the canopy, plants may die from desiccation due to evaporation and to the unavailability of water for photosynthesis and growth; in the understory, from the lack of enough light to achieve net carbon gain, given the relatively high temperature. Interestingly, in this study, the traits supposed to protect against the harsh conditions of the canopy were not only significantly more frequent there, but showed also significantly lower occurrence in the darkest zone of the understory, the tree base.Sphagnum species due to photoinibition (Bryophytes show light saturation of photosynthesis at modest irradiance when compared to most vascular plants , and lignibition . It was nibition , but thenibition .In the Amazonian lowlands, low light levels during the day combined with moist and warm conditions at night promotes high respiration rates, which in turn causes a limitation of net carbon gain . That isThe reproductive traits supposed to be relevant for the assembly of canopy communities met the expectations poorly, which could be a shortcoming of the data, because the characters treated in this study are only indirectly related to high dispersal ability. Still, I believe that a better explanation for the results obtained is that dispersal features have simply little influence on community assemblage. This relatively less deterministic role of dispersal in bryophyte assemblages has been supported especially by recent studies with a mechanistic approach of species assemblage that take into account the relationship between metacommunity and local communities . For insProduction of asexual propagules and dioicous reproductive mode are frequently taken as associated features , and eveSeveral relevant traits that play a role on plant dispersal, establishment and growth are not represented by presence/absence data. For instance, the responses of photosynthesis to irradiance of epiphytic bryophytes show compensation points over a wide range among species , as muchThe presence of dark pigmentation and the presence of convolute leaves seem to have a relevant influence on the occurrence of species at both extremes of the forest vertical microenvironmantal gradient, either favouring—in the canopy—or hampering—at the base of the tree—the number of individuals assembled in the communities. Species traits related to morphological features showed greater influence on the occurrence of species than traits related to reproduction and dispersal. Further advances in this field will profit from the study of traits with continuous variation, such as the ones mentioned in the discussion.