The various bacterial communities in the gut have many functions including metabolic, barrier effect, and trophic and immunological functions. The gut microbiota therefore performs a large number of important roles that define the physiology of the host. Advances in the understanding of microbiota interaction with the host have irrevocably altered the view of mammalian metabolism and gut biology. As stated by Kinross et al. , “human The understanding of the gut microbiota and its activities is essential for the generation of future personalized healthcare strategies. In this regard, there is a growing body of evidence to support the potential use of selected bacterial strains in the prevention and treatment of various human and animal diseases. Numerous studies including different probiotic strains have been performed in humans and animal models to investigate their beneficial effects –4. Overa Bifidobacterium and Lactobacillus, in healthy individuals and IBDs patients. The authors found that IBD patients appeared to have different immune responses to food bacteria. The work could set the basis for developing systems for early detection of IBD, based on the association of high levels of antibodies developed against extracellular proteins from lactic acid bacteria. On the other hand, data from animal models of colitis have indicated that specific probiotic Lactobacillus and Bifidobacterium strains could prevent and treat intestinal inflammation. The study of R. Chauhan et al. was undertaken to evaluate the antioxidative potentials of Lactobacillus fermentum Lf1, a promising indigenous probiotic Lactobacillus strain, to manage oxidative stress and modulation of lipid peroxidation in vitro and in vivo. The authors showed in intestinal epithelial cells cultures and in a DSS colitis mouse model that the probiotic strain Lf1 was able to increase the expression of antioxidative enzymes and reduce colitis, indicating that probiotics could be explored as a new strategy for IBD management through activation of the antioxidant enzyme system. In addition, J. Breton et al. studied the direct immune responses to alimentary fibers in murine model of experimental colitis. The study strongly suggests that intrinsic, nonprebiotic-driven effects of selected oligosaccharide and polysaccharide fibers can influence immunomodulatory functions and that these fibers could be used to enhance dietary interventions for the treatment of inflammatory disorders such as IBD and other diseases with an immune component. The use of fibers alone or in combination with selected probiotics (symbiotic preparations) could be considered as a promise intervention tool for inflammatory diseases.Studies have provided insight into the mechanisms by which probiotic bacteria are able to regulate the colonization and eradication of pathogens in the gut, including competition for limited nutrients in the intestine and modulation of the mucosal immune system , 5. In a Caenorhabditis elegans as a simple animal model to evaluate the effects of a complex food-derived microbiota on well characterized metabolic pathways. Authors provide evidence that feeding C. elegans with a lactic acid bacteria consortium influences longevity, larval development, fertility, lipid accumulation, and gene expression related to obesity in this model organism, as supported by transcriptional analysis of some genes involved in fat metabolism. The work clearly demonstrates the applicability of C. elegans model in the field of host-microbiota interaction.Fermented dairy foods result from the metabolic activity of complex and heterogeneous bacterial communities; then these dairy fermented products contain a complex, live microbial consortium mostly represented by lactic acid bacteria, which enter the human body and reach the gastrointestinal tract, where they can transiently interact with the resident gut microflora of the host. The interplay between these two microbial communities can greatly contribute to human health. However, evaluation of the interaction between these microbial populations has the obstacle of the lack of simple model organisms suitable for these studies. In this special issue, the work of E. Zanni et al. tested the nematode E. coli 16 expressing Vitreoscilla hemoglobin gene, associated with bacterial respiration under microaerobic condition, on carbon tetrachloride induced toxicity in rats. The work showed that the presence of Vitreoscilla hemoglobin gene improved the growth and intestinal tract colonization of E. coli 16. Moreover, recombinant E. coli 16 enhanced catalase activity in rats, prevented absorption of carbon tetrachloride in the intestine, and ameliorated hepatotoxicity. On the other hand, S. Shigemori et al. developed a β-lactoglobulin-secreting Lactococcus lactis and demonstrated that this recombinant strain is able to inhibit dipeptidyl peptidase-IV (DPP-IV) activity. DPP-IV is a serine protease and its endogenous physiological substrates are incretins. The incretins are primarily glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, which drive insulin secretion in pancreatic β cells and suppress pancreatic glucagon production. Thus, DPP-IV inhibitors are used in the management of type 2 diabetes mellitus.Currently, the use of genetically modified commensal and lactic acid bacteria to deliver compounds of health interest is gaining importance as an extension of the probiotic concept . Most ofIn summary, this special issue covers a range of diverse topics related to microbiota and probiotic in gut health and disease, thus highlighting the potential beneficial role friendly bacteria in human health. We hope the papers published will serve to further highlight the potential application of probiotics for the prevention and treatment of gut diseases, as well as stimulating further research into the cellular and molecular mechanisms of probiotic actions.Haruki KitazawaSusana AlvarezAlexander SuvorovVyacheslav MelnikovJulio VillenaBorja Sánchez


Maytenus illicifolia, a medicinal species from Brazil.Pentacyclic triterpenes are secundary metabolites which are promising molecules in the pharmaceutical field and food and material industries. These compounds are formed by the cyclization of oxidosqualene catalyzed by oxidosqualene cyclases (OSC) . The aimM. ilicifolia and used in the synthesis of cDNA. The PCR amplification of core fragments of OSC genes was performed with partially degenerated primers designed to anneal to highly conserved regions among OSC genes. The cloned fragments were sequenced and specific primers were designed for the rapid amplification of cDNA end (RACE) of 3' regions and for a first round amplification of 5' extension. After sequencing, another set of specific primers were generated for the RACE of 5' regions. Finally, it was possible to clone the full-length cDNA of the OSCs and confirm the predicted identity of the genes by sequencing [For this purpose, we adopted the strategy of RT-PCR using degenerated primers obtained from sequences of known plant OSC genes. Total RNA was extracted from leaves of quencing .In silico assembly and sequencing of the full-length cDNA covered the ORF of two main different groups of OSCs with ~2500 bp. Multiple alignment of these genes showed identity of about 50% between those two groups. Comparison of M. ilicifolia OSC genes with those described in the Genebank revealed that one group showed high identity (~90%) with cycloartenol synthase enzymes, while the other one showed high identity (>75%) with triterpene synthases as beta-amyrin and lupeol synthases.M. ilicifolia demonstrated two main groups of OSC enzymes present: the cycloartenol synthase, which is part of the plant primary metabolism [Saccharomyces cerevisiae will further characterize the oxidosqualene cyclases from M. ilicifolia leaves.Cloning of OSC genes from the leaves of tabolism  and one tabolism . Future


Congenital sensorineural hearing loss is the most common sensory disorder, with approximately 1 in every 1000 newborns in developed countries suffering from severe-to-profound hearing loss. At least half of those cases are attributable to genetic causes with more than 90 causative genes identified to date reflecting the complex clinical and genetic landscapes of hereditary hearing loss .Recent advances in molecular genetics technologies, notably next-generation sequencing (NGS), have drastically accelerated the identification of novel genes involved in hearing mechanism and expanded the mutational spectrum of known deafness-causing genes –9. In adThis special issue is to exhibit the advances and recent progress in the fields of molecular genetics and molecular biology of hearing and deafness.The review paper by S. Kitajiri and T. Katsuno (Kyoto University) summarized the importance of the tricellular tight junction proteins  in the inner ear by acting as a barrier separating the endolymphatic and perilymphatic spaces, which is essential for the generation and maintenance of the endocochlear potential.Callithrix jacchus). KIAA1199 has been reported as a cause of progressive hearing loss, but its spatial expression showed different and distinct patterns in mouse and rat cochlea. In this report, M. Hosoya at al. showed a more widespread KIAA1199 protein expression in the marmoset. These results are of importance for further investigation and elucidation of the functional role of KIAA1199 in primate cochlea.M. Hosoya et al. described the cochlea distribution patterns of KIAA1199 proteins in a nonhuman primate, the common marmoset  is the most important and effective treatment for patients with profound sensorineural hearing loss. However, outcomes vary among patients due to several reasons, one being the heterogeneous nature of the clinical as well as genetic etiology of hearing loss. H. Koyama et al. reported the CI outcomes in five patients with Waardenburg syndrome. They showed that CI is a good and suitable treatment option for Waardenburg syndrome cases.Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase and widely used as cholesterol-lowering drugs. However, in the last decade, conflicting data about the effect of statins on neuronal cells and the auditory system has been published. K. Leitmeyer et al. studied the effect of simvastatin on spiral ganglion neurons explants in vitro and showed its neurotoxic effect that seems to be at least partially mediated by the mevalonate pathway.In this special issue, we collected both basic and clinical original research articles stimulating the continuing efforts to understand the mechanisms of deafness and hearing systems. It is our wish to increase interest in this field and further accelerate future treatment options based on solid basic research.


The vertical gastrectomy indications for surgical treatment of morbid obesity haveincreased worldwide. Despite this increase, many aspects of surgical techniquestill remains in controversy. To contribute presenting surgical details in order to better realize the verticalgastrectomy technique in bariatric surgery.Technical systematization, patient preparation, positioning of the trocars,operative technique and postoperative care are presented in details. During 12 months were enrolled 120 patients undergoing GV according to thetechnique described herein. The results are published in another ABCD article:61-64) in this same volume and number.The surgical technique proposed here presented itself viable and facilitating thesurgeon's work on difficult points of the vertical gastrectomy.  The calibration of the remaining gastrictube, conducting oversuture reinforcing the staple line, distance from the pylorus tostart clipping, and resulting gastric amount in antrectomy, are in constant discussions.Besides the technical aspects, there is also no consensus on the indications, themetabolic effects and the long-term results. Regarding complications, fistula in theline of staples although with incidence rate similar to Roux-en-Y gastric bypass,generally carries higher morbidity and healing time; based on this, it is of greatconcern among surgeonsThus, despite the SG already is a common bariatric procedure also entails studiesneeding to clarify controversial aspects regarding the surgical technique. Therefore,this study aims to contribute with technical details that can improve and make easierthe use of SG in bariatric surgery.The operation is performed with the patient supine, with open legs in reverseTrendelenburg position (inclined) in operating table with angle of 30°. The mainsurgeon is positioned between the lower limbs; the assistant surgeon and the scrubnurse are on his right side. To prevent fall injuries and poor positioning, patientsare attached to the operating table with the use of special braces in the abdomen andlower limbs. Pneumoperitoneum is performed with direct abdominal puncture with aVeress needle in the left upper quadrant, along the costal margin in themidclavicular line, kept up with inflation pressure of 16 mmHg and flow 40 l/min ofcarbon dioxide. Before the operation is applied by subcutaneous enoxaparin 40 IU,antibiotic prophylaxis with 2 g of cefazolin and introduced gavage-caliber (32 Fr)orally, positioned a few centimeters below the gastroesophageal transition.Taking as reference the average anatomical xifoumbilical line, the first trocar  is inserted at the intersection of two thirds with the lower upperthird of about 3 cm to the left of the patient. This position allows frontal approachto gastroesophageal transition without the risk of puncture stand in the middle ofthe round ligament (trocar 1 - T1). The second trocar  is placednext to the xiphoid process (trocar 2 - T2) for removal of the liver. The third  is positioned on the right side of the patient, at the rightmidclavicular line in parallel to the T1 (trocar 3 - T3). The fourth  is placed in the left anterior axillary line along the costal margin(trocar 4 - T4). The last trocar  is placed at the level of theleft midclavicular line, also near the costal margin (trocar 5 - T5) .The operation begins with the dissection and removal of the fat pad of theesophagogastric junction , to alloUpon completion of the stapling and gastric tube production, is carried outcontinuous suture, transmural and transfixing with absorbable Caprofil(r) 3-0(Ethicon - Johnson & Johnson Corporation - USA), who started both by thetransition, as near the pylorus, with the completion of the suture in the middleportion of gastric tube body  and10. APatients are kept until they are hospitalized with adequate tolerance of oral fluids,no pain, no nausea and normal walking condition. Receive proton pump inhibitor for 90days and prophylaxis of thromboembolic events with enoxaparin for at least 10 daysbeyond the hospital. Vitamin-mineral and protein supplementation is recommended forone year. Revaluations with the surgeon and the entire multidisciplinary team areheld in the three months till complete two years. After this, an annual consultationis recommended.During 12 months were enrolled 120 patients undergoing SG according to the techniquedescribed herein. The results are published in another article ABCD :61-64) in this same volume/number.,,Several reasons, besides the good result of weight loss, have contributed to theworldwide acceptance of SG. It is considered operation technically easier and simpler;does not need anastomosis; none nutritional problems; and does not generatevitamin-mineral need for replacement for a long time, since there is no intestinalbypass. Although the SG was firstly proposed as a procedure with significant limits -reserved for severe cases with the intention to reduce the surgical risk - quickly theselimits have been expanded, especially in patients where the realization of the Roux-en-Ygastric bypass was controversial, such as in patients with inflammatory bowel disease,previous abdominal operations and before or after organ transplantation such as liverand kidney,,Perhaps the only consensual aspect is that the SG should preferably be done bylaparoscopy because the dissection of the great gastric curvature near the spleen isgreatly facilitated by direct vision that only laparoscopy can provide, avoidingiatrogenic splenic injury. Moreover, the correct stapler position near thegastroesophageal transition also can be performed by laparoscopic vision. Laparoscopicrelease of the greater curvature of the gastric fundus is faster and more secure withthe use of ultrasonic energy or bipolar electrocautery. In this study, the preference isfor the use of ultrasound (Ultracision Harmonic Ace Plus- Ethicon - Johnson &Johnson Corporation - USA) which by means of mechanical vibration energy enables thesealing of tissue by protein denaturation resulting in rapid and reliablehemostasis Among the technical controversies about SG is the diameter of the remaining stomach,especially in the gastric body region. In practice, surgeons use of a "template"intragastric for guiding the staple line, generally probe Nelaton(r) type "Fouchet".There is no consensus whether this probe should serve only as "anatomical" parameter forguidance of the staple line or whether it should be used as a calibration mold(diameter) of gastric tube. And, in case of serving as calibration template, there is noconsensus about what would be the ideal size for it.In this aspect, several evaluations have analyzed the outcome of surgery with differentgastric tube calibration standards, from 28 to more than 50 Fr. Calibrations over 40 Frhave been associated with poor performance or loss of important regained weight.Apparently, adjust the calibration to less than 36 Fr does not lead to better weightloss results, but increases significantly the risk of complications, especially theleackage transition and clinically symptomatic stenoses. Also over time,oesophagogastric fistula at the angle seemed much more related to the transitionfragility of local problems than in relationship with clipping too close to the angularnotch. What appears to be consensus among surgeons is the need to use this intragastric"mold" to guide the staple line, as well as offering greater technical security; theabsence of this parameter can result in inappropriately broad remaining stomachs andcompromise weight lossAn example of the technical details to be observed to achieve better results with lowcomplication rate is the care of the staple firing in the notch region because, althoughit was opted for calibration and adjusted to a 32 Fr catheter, it should be preventednarrowing too much this region, thus avoiding difficulties of stomach body emptying andconsequent increase in the pressure of the gastric tube, and an increased risk of leaksnear the esophagogastric junction.,,The use of some sort of reinforcement of the staple line is another controversial pointin the technical systematization of SG. It has been quite common to use synthetic,bioabsorbable and specifically designed for application on clipping lines inlaparoscopic surgery for the purpose of reducing the occurrence of bleeding and fistulas(Gore Seamguard(r); WL Gore & Associates, Inc., Flagstaff, AZ). However, the resultspublished in the biomedical literature is conflicting because some studies have notshown advantages of oversuture with surgical thread or stapling technique without anyreinforcementThe surgical technique proposed here presented itself viable facilitating the surgeon'swork on difficult points of the sleeve gastrectomy.


Information transmission within the visual system is highly organized with the ultimate goal of accomplishing higher-order, complex visuo-spatial and object identity processing. Perception is dependent on the intactness of the entire system and damage at each stage—in the eye itself, the visual pathways, or within cortical processing—might result in perception disturbance. Herein we will review several examples of lesions along the visual system, from the retina, via the optic nerve and chiasm and through the occipital cortex. We will address their clinical manifestation and their cortical substrate. The latter will be studied via functional magnetic resonance imaging (fMRI) and Diffusion Tensor Imaging (DTI), enabling cortical, and white matter mapping of the human brain. In contrast to traditional signal recording, these procedures enable simultaneous evaluation of the entire brain network engaged when subjects undertake a particular task or evaluate the entirety of associated white matter pathways. These examples provided will highlight the importance of using advanced imaging methods to better understand visual pathologies. We will argue that clinical manifestation cannot always be explained solely by structural damage and a functional view is required to understand the clinical symptom. In such cases we recommend using advanced imaging methods to better understand the neurological basis of visual phenomena. In order for visual perception to occur, the physiological signal initiated by the photoreceptors in the retina must travel all the way to the visual cortex at the back of our brain. This long journey requires a set of long-range white matter tracts to communicate the signals.optic nerve, and there is a partial crossing of axons at the optic chiasm. After the chiasm, the axons (which now carry binocular information) are referred to as the optic tract. The optic tract wraps around the midbrain to get to the Lateral Geniculate Nucleus (LGN), where all the axons synapse. From there, the LGN axons fan out through the deep white matter of the brain as optic radiations, which will ultimately travel to the primary visual cortex. The occipital-callosal fiber tract that connects the two occipital lobes via the corpus callosum is a key pathway for the flow of information between the two hemispheres  located in the occipito-parietal and occipito-temporal regions is less sensitive to stimuli topography and more involved in processing the Retinotopic mapping is obtained by presenting simple visual stimuli to the different visual fields' portions. For example, in order to map the eccentricity axis from the central to the peripheral visual field, an expanding ring stimulus is used. The subject views an expanding flashing checkerboard circular stimulus that gradually expands from the center to the periphery of the visual field. This stimulus creates a wave of neuronal activity, which moves along the calcarine sulcus from the posterior to the anterior region  which utilizes the neuro-vascular coupling principle: in response to a visual task, neural activity in a specific cortical visual region will trigger change in the regional blood flow which will be captured in the MRI scan  served to explain the functioning of distributed systems, such as our visual pathways. This accumulated knowledge of the intact visual pathways provided the basis for understanding the neuronal substrate of unexplained visual dysfunctions, which cannot be addressed via standard anatomical imaging regime. fMRI has contributed, for example, to our understanding of the phenomenon of blindsight, in which a patient with cortical damage resulting in hemianopia retains some residual abilities within his blind field. fMRI studies in these patients demonstrated powerful activation in area MT, despite nearly complete destruction of the primary visual region (V1) . Using this method, information regarding localization and directionality of the fibers as well as evaluation of the quality of their cohesiveness and their ability to conduct the neuronal signal can be obtained . The method is based on diffusion, the random motion of water molecules in the extra- and intra-cellular spaces. When the motion of molecules is limited by Fibers' cohesiveness may be evaluated by four diffusion properties: mean diffusivity (MD); fractional anisotropy ; diffusion parallel to the principal fiber direction ; and diffusion perpendicular to the principal fiber direction  .Functional MRI, including retinotopy mapping and population receptive field (pRF) estimation revealed several differences between MM and sighted controls . Early in the course of the disease the inflammatory process causes a significant reduction or even blockage in the amount of information being transferred along the optic nerve. This is expressed clinically as deficits in visual field, visual acuity, contrast sensitivity, and color perception. Later on, when the inflammation is alleviating, these functions are usually restored. Nevertheless, due to damage to the myelin surrounding the nerve fibers, there is a continuing delay in conduction along the optic nerve; which can last for several months or even years following the acute attack. Consequently, patients that are reported to have recovered according to standard visual testing continue to complain about residual visual dysfunction in their daily visual abilities. Recently, we demonstrated that static visual functions  tend to recover shortly following the acute optic neuritis attack (weeks to months). Yet patients with optic neuritis continue to exhibit major deficiencies in dynamic visual functions (motion perception) even a year following the attack  rather than demonstrating cortical plasticity, as suggested previously.In recent years DTI and fiber tractography have been used to study the effect of focal damage to neighboring pathways. As was reported in animal studies, neuronal loss following damage is often greater than might be expected from the severity of the injury to the nerve itself. We utilized the visual pathways, which comprise a well-defined system, and optic neuritis, which is usually a spatially and temporally discrete event, to study the effect of focal demyelinative lesions on neighboring white matter.b = 0 and b = 1000 s/mm2. The high b-value was obtained by applying gradients along 64 different diffusion directions). Image processing was done using the open-source mrVista package . Fiber tractography was performed using the probabilistic Contrack algorithm  and 12 matched control subjects using DTI and fiber tractography methods and measured the directional diffusivities in those fibers. DTI data was acquired using a diffusion-weighted imaging sequence . As opposed to the optic tracts, AD within the optic radiations was similar among patients and controls . Furthermore, FA and RD levels were associated with the presence of demyelinative lesions within the optic radiations , suggesting that white matter damage in these fibers could be explained by local demyelinative damage in the optic radiations , or resulting from a mechanical compression of adjacent structures   showed a giant tuberculum sellae meningioma compressing the entire chiasm. The patient underwent right fronto-orbital craniotomy and the lesion was completely resected. Visual fields improved significantly, although some residual deficit was still evident Figure . To studCase 5: A 65-year-old- woman was admitted to the rehabilitation department following diffuse occipital and occipito-parietal damage due to Posterior Reversible Encephalopathy Syndrome (PRES) , which is known to be involved in processing topographical scenes, greater activity was evident when viewing pictures of places as compared with pictures of faces . In contrast, no specification for face recognition was evident in the ventral-temporo-occipital fusiform face area (FFA), responsible for face processing Figure . PPA andCase 6: A 64-year-old woman was admitted to our clinic following repeated occipital ischemic events. She reported no light perception and behaved as though she was blind. Standard MRI revealed damage in her right early visual regions. Flash visual evoked potential (VEP) testing demonstrated delayed but evident cortical responses. To reveal whether the visual cortex received and processed the visual input, an fMRI examination was performed. fMRI examination included viewing full-field flickering checkerboard to activate early visual regions; viewing visual objects (vs. scrambled images of these objects) to activate LOC; viewing pictures of faces (vs. scrambled images of these faces) to activate FFA; and viewing expanding-contracting rings (vs. stationary rings) to activate MT. In addition, resting-state fMRI was applied to assess the visual cortical network.Viewing flickering checkerboard resulted in intact activation at early visual regions within the undamaged left hemisphere. Intact activation was also evident within higher-order visual regions: activation of LOC in response to viewing objects, activation of the FFA in response to viewing faces, and activation of MT for viewing moving stimuli.Functional connectivity during resting-state fMRI revealed an intact visual cortical network Figure , accompaVision is a perceptual experience, which includes the retinal ability to perceive inputs as well as the cortical ability to process them. Vision is a complicated process of sorting, encoding, interpreting, and understanding the meaning of the visual input. Consequently, the image created in our awareness does not always reflect the optical reality. Areas devoted to visual information processing constitute a large portion of the human cortex, indicating their complexity. The visual cortex contains an impressively large number of distinct areas and specific functional networks that create the neuronal basis for perceiving different visual elements of the stimuli (Van Essen and Drury, In the past two decades, the use of non-invasive functional imaging and especially fMRI has dramatically expanded our knowledge about the functional visual human brain in healthy and disease states. Intact vision requires functioning of the entire visual system, starting at the eye, continuing through the visual pathways and ending at the visual cortex. Furthermore, the visual cortex is not isolated, and functioning separately from other areas won't achieve normal vision. Therefore, we should relate to the visual system with a holistic view, integrating imaging techniques for the eye, the visual pathways and the brain, in order to assess its overall functioning.Taking advantage of their ability to visualize the whole brain at once, DTI and fMRI are adequate tools to assess the consequences of focal lesions along the visual pathways on white matter integrity and cortical functioning in the entire system.As in the case of optic neuritis, DTI is useful for investigating the effect of focal lesions on neighboring white matter, modeling the relationships between intact and pathological white matter structures, or, as discussed in the case of chiasmal compression, DTI may explain residual visual loss after removal of the focal lesion.Evaluating the functional properties of the entire brain, fMRI is useful for differentiating between functioning and dysfunctioning cortical regions, and explaining specific visual dysfunctions, as was seen in the case of acquired brain damage.Regarding the system as a whole is important when developing advanced technologies to reconstruct the sensing organ. As the first case illustrates, cutting edge studies aimed at restoring vision such as retinal prosthesis or retinal stem cell transplant, cannot only focus on reconstruction of the sensing organ. They also have to account for the intactness or rehabilitation of the entire system.fMRI can bridge the gap between MRI-detected tissue damage and clinical manifestations, explaining behavioral phenomena even in the absence of a clear structural fingerprint (Filippi and Rocca, In the optic neuritis studies we emphasized the association between cortical activity and visual functioning, demonstrating motion perception deficits in both. In this way, the cortical activity reflects the behavioral phenomenon. In contrast, the last case demonstrated a mismatch between the behavior and the cortical activity pattern. Intact activation within the occipital visual cortex was evident despite the patient experiencing no light perception. These findings were used to leverage the rehabilitative process since the cortical residua indicated possible recovery.The examples reviewed above emphasize the importance of using functional imaging to understand visual system pathologies. In some cases, standard MRI scans do not have enough resolution to localize the specific pathology. The clinical picture cannot be explained by clear structural damage and an understanding of the pattern of cortical activity and connectivity between different cortical and subcortical areas is needed to explain the visual deficit. To that end we recommend using advanced imaging techniques to better understand the neuronal basis of the apparent neurological event.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.


Purpose. This study aimed to evaluate the effects of prosthetic foot types on the postural stability among transtibial amputees when standing on different support surfaces. Materials and Methods. The postural stability of 10 transtibial amputees wearing solid ankle cushion heel (SACH) foot, single-axis (SA) foot, and energy-saving and return (ESAR) foot was assessed. Results were compared with able-bodied participants. Anterior-posterior stability index (APSI), mediolateral stability index (MLSI), and overall stability index (OSI) were measured by computed posturography in an upright stance on firm, foam, and unstable support surfaces. Results. The mean OSI score of SACH foot was significantly lower than that of an ESAR foot when the participants were standing on a compliant surface. When compared to able-bodied group, MLSI score was significantly higher for each of the prosthetic foot groups while OSI score was significantly higher for ESAR foot only in foam condition. Conclusions. Differences between prosthetic foot types and groups (amputees versus able-bodied) can only be distinguished when individuals were standing on a compliant surface. Amputees exhibited an increased postural instability in the mediolateral direction than able-bodied individuals. Hence, the restoration of stability in the frontal plane and the enhancement of proprioception at the residual limb should be the basis of rehabilitation programs. Postural stability is achieved by maintaining an upright body alignment against gravitational force and preserving the equilibrium of the center of mass (CoM) in an individual's base of support . SuccessAnkle and hip strategies are considered responsible for the control of horizontal CoM movements in anterior-posterior and mediolateral directions, respectively , 11. HowFor amputees to return to their daily life activities, the ability to maintain postural balance is essential while adapting to various support surface conditions. Balance can be relatively well managed in the comfort of an individual's house but may be very challenging when outdoor terrains are considered. For example, compliant  or unstable surfaces reduce the ability to detect body orientation accurately . Horak  also recAlthough prosthetic foot has been hypothesized to influence standing stability, knowledge about how or to what extent it controls stability remains unclear because of variations in the types of prosthetic feet tested in studies that may have determined the balance performance. Hence, it is vital for the clinician to understand the mechanism underlying integration of prosthesis limb into the balance system to compensate for the limb loss. This study aimed to determine the effect of different prosthetic foot types on the control of postural stability under various support surface conditions. This study was also designed to compare the results with those of able-bodied control subjects.Using convenience sampling method, we enrolled 10 male unilateral below-knee amputees. All of the amputees were recruited from the University of Malaya Medical Centre rehabilitation clinics. Inclusion criteria were listed as follows: age > 20 years, unilateral below-knee amputation, with at least one year of experience in the current prosthesis, and able to walk without the use of an assistive device. Exclusion criteria for the amputees were described as follows: poor fittings of prosthesis and residuum pain. The participants with visual or vestibular impairment, lower limb musculoskeletal injury, and other neurological deficits were also excluded. A comparison control group consisting of nine male able-bodied participants were also included. This study was approved by the Institutional Ethics Committee Board, and written informed consent was obtained from each of the participants.The subjective measure of prosthetic use and function was determined using a Houghton Scale questionnaire, which consists of four questions with a maximum possible score of 12 points . To ensuThe study employed a repetitive crossover study in which all of the amputees underwent a total of three testing sessions for three weeks. The control group was subjected to only one session for the completion of data collection. The amputees wore their corresponding prostheses that allowed the interchange of foot components. The same socket and suspension components were used throughout the study to eliminate any confounding effect of these variables. The amputees' current prosthetic sockets and components were optimally aligned using a laser liner before the assessment by the same registered prosthetist. The three prosthetic feet that were tested in this study included a solid ankle cushion heel (SACH) foot, a single-axis (SA) foot, and energy-saving and return (ESAR) foot Talux. All of the tested feet were prescribed according to the subject's foot size and body weight in addition to the activity level of the Talux foot. All subjects wore identical covered shoes and the same shoes were used in all the experiments.The subjects familiarized themselves of the test procedures during their first visit. At the end of the first session, the prosthetic foot in the subject's prosthesis was exchanged for the first test foot. The subjects then returned to the laboratory to undergo postural stability assessment after one week of accommodation period . The secY is the total anterior-posterior deviation in the sagittal plane and X is the total medial-lateral deviation in the frontal plane.Postural stability test was conducted using a Biodex stability system  for its known reliability in objective assessment of postural stability . The sysPostural control was assessed under three different surface conditions: rigid, compliant, and unstable. For the rigid condition, the participants were asked to stand directly on a rigid and static platform. To simulate a compliant surface, we placed low-density polyethylene foam with a circular radius of 22 cm and a thickness of 2.5 cm on the platform . Platfort-test was employed to compare the able-bodied control group with each prosthetic foot group. P ≤ 0.05 was considered significant. The effect size was also determined to indicate the significance of the results because of the small sample size used in this study. On the basis of Cohen's guidelines, we considered the effect size values > 0.14 to be significantly different [A total of 27 data sets from nine conditions (three support surface conditions and three prosthetic feet) for each of the stability indexes  were obtained. All of these data were initially screened to determine the normality of distribution and homogeneity of variance by using Shapiro-Wilk test. All of the data showed normal distribution. A 3 × 3 (support surface × prosthetic foot) repeated-measures analysis of variance (ANOVA) was used to examine the significance of differences between stability indexes. After the differences between groups were identified, post hoc HSD Tukey's test was applied to detect the specific area in which statistical differences were observed. Independent ifferent . StatistThe demographics summary of the participants is presented in P = 0.04) when the subjects were standing on a foam surface compared with a firm and unstable support surface. A large effect size of 0.38 indicated that the differences were significant. Nevertheless, there was a noticeable trend of stability indexes being the lowest for SACH foot and the highest for ESAR foot in most of the conditions. Postural stability of the amputees as measured from the OSI, APSI, and MLSI indexes was not significantly affected by the interaction between prosthetic foot types and sensory conditions .The average values of OSI, APSI, and MLSI and the corresponding significant differences are shown in P = 0.05 and P = 0.03, resp.) when the subjects were standing on a foam surface. The OSI (P = 0.04) and MLSI (P = 0.04) of ESAR were significantly higher than those of able-bodied subjects standing on a foam surface. The effect size under all of the conditions was large (ranged from 0.20 to 0.39). No significant difference was evident in the APSI scores of the three prosthetic groups and the able-bodied group under all of the support surface conditions.Although the stability indexes in prosthetic feet were higher than those of the able-bodied participants, significant differences were observed only in several conditions. For instance, the MLSI scores of the SACH foot and the SA foot were significantly higher than those of the able-bodied subjects (This study investigated the effect of a prosthetic foot on the control of postural stability by comparing three types of prosthetic feet using the Biodex stability system. In addition, the importance of proprioception sensory information was examined by comparing the postural stability of able-bodied and below-knee amputee groups. Following amputation, complete loss of cutaneous, muscle, and joint receptors of the residual limb as well as distorted sensory feedback from the intact limb could affect postural stability . HoweverOur results provided evidence that different prosthetic ankle mechanisms provided by various designs may influence postural stability in different support surface configurations. The stiffness of a prosthetic ankle has been proposed as the basis of stability in the unperturbed standing of amputees . In partIn normal subjects, postural instability during quiet standing is resisted by muscle contraction to control ankle joint stiffness and counterbalance of the destabilizing gravitational torque in anterior-posterior and mediolateral directions . For theWe found that different postural stability characteristics can be determined between prosthetic foot types as well as between amputees and able-bodied groups when individuals are standing on a compliant surface. This was because the firm and flat surface provides accurate orientation information of body from the intact limb and residual limb while the compliant and tilting surface reduced the accuracy of information . When stLimitations in our study are acknowledged. We noted that the lack of significant differences under firm and unstable conditions may be caused by an increase in the dependence on other accurate sensory inputs from visual and vestibular systems. Therefore, future studies should occlude more than two sensory modalities for the differences between feet and groups to become apparent. Furthermore, the absence of prosthetic foot effect may be attributed to a less challenging nature of the task during quiet standing on firm and unstable platforms because the amputees were experienced and skilled prosthetic users. In addition, the small number of the subjects in this study may provide great differences between prosthetic feet and between groups, but such differences may not be statistically significant. Results in this study represent balance performance of transtibial amputees in general, which did not specifically distinguish between dysvascular and nondysvascular amputees. Although static balance has become an essential skill in rehabilitation process for the amputee populations to achieve independent standing and walking , furtherThe results suggest that prosthetic foot design affected the overall stability of below-knee amputees, particularly when subjects were standing on a compliant surface. Therefore, clinicians should consider this factor when prosthetic feet are prescribed to amputees who ambulate mostly on soft surfaces. Furthermore, amputees utilised the hip strategy to control postural stability in mediolateral directions in an upright stance on a compliant surface. These findings can be utilised to develop intervention during rehabilitation using different support surfaces which may lead to improvement in postural stability and reduce risk of falls in a person with lower limb amputations.


Dear Editor,, together withenhancement after administration of paramagnetic contrast, as well as restricteddiffusion of water at the levels studied. Cranial MRI revealed acute lesions  in the right middle cerebral artery. The patient underwent surgeryto treat the aortic dissection, and her neurological function was monitored.A 52-year-old female with aortic dissection presented with neurological symptoms andsigns, in a markedly acute presentation, of flaccid paraplegia and painful hypoesthesiaof the lower limbs. She also presented postoperative monoplegia of the left arm.Computed tomography angiography of the chest confirmed the diagnosis of type Adissection (Stanford classification), with extension to the infrarenal abdominal aorta,associated with extensive subocclusive thrombus in the thoracoabdominal transition ofthe aorta . On T2-w-4. In the case presentedhere, neurological findings were associated with aortic dissection, and the MRI findingswere consistent with the diagnosis of spinal cord infarction with ischemic stroke in theright middle cerebral artery. Although spinal cord infarction is not a rareevent, the subtlety of thefindings and the wide range of differential diagnoses can make its diagnosis difficult.Spinal cord ischemia can be attributed to several causes, including aortic dissection(as in the case presented) and thoracolumbar sympathectomy, or can even occur as apostpartum complication. The single anastomotic segment that irrigates the anterior twothirds of the spinal cord (mainly by the artery of Adamkiewicz) is more susceptible toischemia than is the posterior segment, which has several levels of vascularsupply. A high degree ofclinical suspicion of neurological involvement of the spinal cord is indicative of thediagnosis. Symptoms vary depending on the extent of the affected area and the level ofspinal injury. Cerebral ischemic lesion is also a possible complication of aorticdissection and can result from reduced blood flow to the brain caused by the surgicalprocedure or even from carotid involvement caused by dissection or embolism from thethrombus in the aorta. In addition, data in the literature indicate that there is aright-side dominance of lesions, which is explained by different mechanical dynamics inthe progression of the dissecting hematoma.The evaluation of the aorta by imaging methods has been the subject of a series of recentpublications in the Brazilian radiology literature. Diffusion sequences can show restriction in theischemic area. In fact, diffusion sequences can provide early detection, although this technique is not alwaysapplied in routine MRI scans of the spinal cord. Therefore, we have presented a case ofaortic dissection with a rare combination of neurological complications of brain andspinal cord ischemia.MRI is particularly sensitive in the detection of aortic dissection and can reveal signalabnormality in the anterior horns of the spinal cord, which can be associated withenhancement after contrast agent injection. The spinal segment most often affected isthe thoracic segment, due to the border arterial supply


In 1985 the World Health Organization (WHO) stated: "There is no justification for any region to have Caesarean Section (CS) rates higher than 10-15%",3.dysbiosis of the gut microbiota which in turn leads to immune dysfunction and increased tendency for immune-mediated diseases such as allergies [Emerging evidences indicate that the early composition of neonatal gut microbiota is responsible for shaping of immune response since there is a complex interaction between the intestinal microbiome and the immune system (Gut-Associated Lymphoid Tissue) and this cross-talk is involved in maintaining normal immune homeostasis . The micllergies ,6 and aullergies .Upon delivery, the neonate is exposed to a wide variety of microbes, many of which are provided by the mother during and after the passage through the birth canal, a heavily colonized ecosystem. The neonatal colonization pattern is further influenced by several post-natal environmental factors such as the place and mode of delivery, the level of affluence, the number of siblings, the use of antibiotics and infant feeding.Bacteroides, E. coli, and bifidobacteria and a higher presence of facultative anaerobes such as Clostridium species, compared with vaginally born infants [The reduced microbial exposure and delayed colonization occurring in caesarean born infants have been associated with the development of allergic disease. CS delivered infants, deprived of contact with the maternal vaginal microbiota, experience a deficiency of strict anaerobes such as  infants .Clostridia) for the increasing incidence of allergic disease [It is debated whether a low total diversity of the gut microbiota during infancy is more important than an altered prevalence of particular bacterial species  -15. Clin


Elicitors of biological origin, especially those that are able to control plant pathogens by induction of plant systemic resistance are being intensively investigated because of their great potential for crop protection and environmental compatibility. Since the range of induced defense responses can depend on the elicitor used, the plant treated and the target pathogen, a detailed study of the modes of action of biogenic elicitors is required prior to their use.Control of plant pathogens by biogenic elicitors and possible mechanisms of action was a better understanding of the mechanisms underlying the protective effect of microorganisms with a potential or already established role in biocontrol. Interestingly, works included in the topic report that a biocontrol agent is simultaneously able to activate both SAR and ISR defense pathways in the same plant . Thus, tomato root colonization with the arbuscular mycorrhizal fungus Funneliformis mosseae induced a range of plant defense reactions, and primed defense responses, including the activation of some enzymes and the up-regulation of PR genes associated with SAR upon challenge with Alternaria solani. At the same time, it was also shown that JA-dependent signaling was necessary for mycorrhiza-primed systemic resistance to this pathogen .In this context, an important aim of the Research Topic on Fusarium oxysporum or Trichoderma strains protects tomato against vascular wilt and other diseases via distinct mechanisms including induction of local and systemic resistance. Proteins, such as CS20EP produced by F. oxysporum strain CS-20  as well as Sm1 and Epl1 from Trichoderma spp.  strongly contribute to the activation of defense-responsive genes in the pretreated plants. Experiments on systemic tomato protection with wild, epl1- and sm1-deletion or overexpression strains against necrotrophic  and hemibiotrophic (Pseudomonas syringae pv. tomato) pathogens indicate that Sm1 and Epl1 induce both ISR and SAR, affecting different specific targets in the same pathway depending on the life style of the pathogen . CS20EP identified as a new fungal small cysteine-rich protein is considered as a likely candidate for elicitation of the ion exchange response in plant cells and enhanced PR-1 expression, both of which may result in a mitigation of Fusarium wilt severity on tomato seedlings . Another research related to protein- and peptide-containing elicitors and their possible mode of action  focuses on studying the applicability of such elicitors under field conditions. The authors show that a natural derivative from meat and yeast effectively controls powdery mildew on grapevine in field, and provide data that the crop protection level is comparable to the level achieved after plant treatment with sulfur used as a standard fungicide. Importantly, expression of grapevine defense-related genes induced with the tested elicitor was observed not only prior to infection but also at early stages of the disease, and the protection was effective over the period of three-year field trials .Plant disease resistance is triggered by various elicitors, which are widely presented in pathogenic and non-pathogenic fungi, bacteria and oomycetes. Biogenic elicitors  as well as microbial proteins and peptides triggering defense responses play an important role in the development of local and systemic resistance. In the current research topic, several publications confirm the importance of such proteins for plant-mediated interactions of biocontrol fungi with soil or foliar pathogens of various life styles. They report both common features and individual specificity concerning the mechanisms of action of various proteinaceous elicitors. For instance, colonization of plant roots with saprophytic FocVel1 in the cucumber wilt pathogen (F. oxysporum f. sp. cucumerinum), which disruption reduces the fungal pathogenicity, growth and reproduction .Li and colleagues presented the work on identification and functional study of the velvet gene Pseudomonas bacteria by different changes in apoplastic phenolics. Some of these changes are specifically caused by pathogen infection and suggest weakening of the apoplast/symplast barrier .The apoplast is the first line of defense, where various scenarios of the plant-microbe battle take place. Saprotrophic or pathogenic microorganisms can induce alterations in the biochemical pattern of apoplastic metabolites, thereby influencing the outcome of relationships with host or non-host plants. Research by Baker and co-workers covers some aspect of plant-microbe interactions in the apoplast, viz. redox/phenolic events, which are induced by pseudomonads. The authors report that tobacco plants respond to saprophytic, virulent or avirulent Meloidogyne incognita induced the transcription of JA- and NO-related genes in tomato, and also demonstrated that leaf spraying with JA and NO suppressed nematode development in tomato roots and decreased the negative influence of the pathogen on photosynthesis. According to the authors' suggestion, NO-involving defense against RKN is likely associated with the JA-dependent signaling pathway. The key role of PI2 (protease inhibitor 2 encoding gene) in tomato resistance to RKN is also emphasized .New findings about mechanisms resulting in basal resistance against root-knot nematodes (RKN) are presented by Zhou and colleagues. They showed that plant inoculation with Collectively, the articles published in the topic confirm a high potential of biogenic elicitors for plant pathogen control, promote in-depth analyses of elicitation mechanisms and evidence that biogenic elicitors may become a powerful tool in the protection of crop plants from diseases.All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


We report here a rare case of undifferentiated carcinoma of the pancreas mimicking main-duct intraductal papillary mucinous neoplasm. In an 80-year-old woman, an approximately 8-mm papillary mass was incidentally detected at the downstream edge of a dilatated main pancreatic duct lumen on CT and MRI. Main pancreatic duct dilatation in the pancreatic body and tail and parenchymal atrophy were observed in the upstream of the mass. Histopathologically, the tumor protruded into the downstream edge of the dilatated main pancreatic duct lumen in the pancreatic body. The tumor cells had highly atypical nuclei and abundant polymorphic structures, and showed positive staining for granulocyte colony-stimulating factor, which led to the diagnosis of undifferentiated carcinoma. A total of 13 cases of undifferentiated carcinoma with intraductal tumor growth have been reported to date. The case report by Bergmann et al. has been the smallest in histopathological specimen, and the present case is the smallest in size detected by radiological images. Since early undifferentiated carcinoma of the pancreas can resemble those of main-duct intraductal papillary mucinous neoplasm in cross-sectional images, we have to consider undifferentiated carcinoma in the differential diagnosis of the solitary and papillary mass with low contrast enhancement in early phase in the main pancreatic duct. Undifferentiated carcinoma of the pancreas is a subtype of pancreatic ductal carcinoma . In geneAn 80-year-old woman underwent a medical examination for hematuria, and a left renal pelvic tumor was detected on computed tomography (CT). Meanwhile, a mass was incidentally found in the pancreatic body, and a close examination was conducted. Her past medical history was colon cancer , uterine leiomyoma, appendicitis, and hypertension, but her family history was unremarkable. In the laboratory examination, the white blood cell (WBC) count and tumor markers  were within the normal limits.On CT, the main pancreatic duct was dilatated to 12 mm in largest diameter in the pancreatic body and tail, and an approximately 8-mm papillary mass was observed at the downstream edge of the dilatated duct lumen. The mass showed slight enhancement between the pancreatic phase and delayed phase on dynamic CT and its border with the surrounding parenchyma was irregular. The pancreatic parenchyma in the body and tail showed atrophy, with prolonged contrast enhancement. Main pancreatic duct dilatation was not seen in the downstream of the mass Fig. .Fig. 1AMain-duct IPMN with an associated invasive carcinoma was suspected on the grounds that the dilated main pancreatic duct accompanied a solidary nodule, and distal pancreatectomy was performed. Meanwhile, left nephrectomy was performed for the left renal pelvic tumor.In the loupe findings, the tumor protruded papillary into the downstream edge of the dilatated main pancreatic duct lumen in the pancreatic body. The maximum diameter of the papillate region of the tumor was 8 mm and the region of interstitial infiltrate was 7 mm. The entire epithelium of the main pancreatic duct was substituted by atypical cells. Histopathologically, the tumor cells had highly atypical nuclei and abundant scattered polymorphic structures, and numerous multinucleated giant cells were also observed. The tumor cells showed positive staining for granulocyte colony-stimulating factor (G-CSF) Fig. . The patUndifferentiated carcinoma is a subtype of pancreatic ductal carcinoma that exhibits sarcomatous proliferation of severe mononuclear tumor cells and multinuclear giant cells. It accounts for 2–7% of all pancreatic cancers and frequently occurs in older men . AbdominTo the best of our knowledge, 13 cases of undifferentiated carcinoma with intraductal tumor growth into the main pancreatic duct have been reported to date –18. MostAlthough the debate on the histogenesis of the tumor has been controversial, Bergmann et al. provided the evidence for a ductal origin of the tumor histopathologically . FurtherIPMN and ITPN  are categorized as intraductal pancreatic tumors, and are representative of pancreatic tumors with intraductal tumor growth into the main pancreatic duct . Some caSince early undifferentiated carcinoma of the pancreas can resemble those of main-duct IPMN in cross-sectional images, we have to consider undifferentiated carcinoma in the differential diagnosis of the solitary and papillary mass with low contrast enhancement in early phase in the main pancreatic duct.We report a rare case of undifferentiated carcinoma of the pancreas mimicking main-duct IPMN. We have to consider undifferentiated carcinoma in the differential diagnosis of the solitary and papillary mass with low contrast enhancement in early phase in the main pancreatic duct.


Moyamoya disease is a vascular dysplasia clinically characterized by a combination of ischemic and hemorrhagic strokes. The Research Committee on Moyamoya disease in 1979 classified the initial attacks into 6 types; subsequently, the asymptomatic and the headache type were also added in 2003. In fact headache is common in Moyamoya disease and can be the first symptom especially in childhood; its characteristics and classification are largely unknown because of the uncertainty and probably multifactorial nature of the mechanism[A seven-year-old Romanian girl, presented to the Emergency Department of the L'Aquila Hospital suffering from drop attacks, dysarthria, choreic movements and headache. Neurologic symptoms had appeared for four days and headache onset had started a year ago, with daily onset, especially in the evening, more pronounced in the frontal region, with oppressive and binding features, often triggered by physical exertion and requiring daily assumption of ketoprofene. The brain magnetic resonance imaging showed: bilateral cortical ischemic areas involving the fronto-mesial regions and the right perirolandic region, complete occlusion of the medium and posterior cerebral arteries, and lenticulostriate and thalamostriate arteries dilated with a “puff of smoke” appearance. The patient was sent to the Pediatric Neurosurgery of the A. Gemelli Hospital in Rome where she underwent cerebral arteriography and surgical operation. Indirect revascularization of the right (December 2014) and the left side (February 2015) was done by means of encephalo-myo-synangiosis and accessory burr holes. At first follow-up: the drop attacks had disappeared, and there was significant improvement of the hemiparesis and the steppage. Current therapy is cardioaspirin 50 mg/die. The girl refers considerable improvement of the headache with weekly recurrence and mild intensity.Diagnostic classification of headache associated with Moyamoya disease is controversial: the characteristics of headache vary and may be migraine-like throbbing pain or the dull headache noted in tension-type headache. In most of the studies headache is suggested to be an important symptom of ischemic cerebrovascular diseases and surgery bypass seems to be an effective therapy in most patients. Other studies report that headache can persist or develop after indirect bypass surgery despite successful prevention of cerebral ischemia; thus, progressive recruitment and redistribution of blood flow should be considered another cause of headache. The efficacy of surgery revascularization, even on the headache symptom, clarified that her headache was probably related to cerebral hypoperfusion.Written informed consent to publication was obtained from the patient(s).


Optic nerve dural ectasia is a rare cause of optic nerve sheath enlargement due to the accumulation of CSF around the optic nerve with no associated pathology. It diagnosed by MRI studies and can follow benign or sometimes an unfavorable course. We describe the case of a 24-day-old female referred for a visual blurring, which we diagnosed as a dural ectasia of the optic nerve sheath by MRI and confirmed in surgical intervention. We present this case report to illustrate the classic imaging features of the disease. Dural ectasia of the optic nerve is a rare cause of optic nerve sheath enlargement due to the accumulation of CSF around the optic nerve with no associated pathology . The terA 24-year-old woman presented with a 8 month history of visual blurring with a slow decrease in visual acuity, and headache. Humphrey's visual field analysis revealed an enlarged blind spot. Dilated funduscopy showed an elevation of the left optic disc and choroidal folds above the nerve extending into the macula. General physical examination was normal.A magnetic resonance imaging (MRI) with fat-suppression and an off-axis, coronal and sagittal views were performed, a tubular-cystic enlargement of the optic nerve sheath was identified as containing a CSF -intensity lesion that was hyperintense on T2-weighted images . There wThe subject was therefore, diagnosed as having dural ectasia of the optic nerve sheath, which is also known as optic nerve meningocoele, without intracranial hypertension. Once the diagnosis had been confirmed in surgical intervention. The patient remained stable over the next 4 months with the same visual acuity.Dural ectasia of the optic nerve sheath  is a saccular dilatation of the meninges surrounding the orbital portion of the optic nerve . The lumThe radiological examination of choice is MRI with high spatial resolution, fat-suppression with contrast techniques in off-axis, cronal and sagittal views . Dural eOptic nerve dural ectasia is a saccular dilatation of the optic nerve sheath. It can be suspected based on the evidence of visual blurring or retrobulbar pressure. The radiological investigation of choice is MRI with techniques to emphasize high spatial resolution and optic nerve anatomy. Surgical intervention is reserved for severe cases of optic nerve decompression.


Insect locomotion presents a type of pattern adaptation in which the phase relations change with the speed of walking. In forward walking, the protraction of legs progresses sequentially one after the other from posterior to anterior: a metachronal wave gait. The duration of protraction is roughly invariant to the speed of locomotion, and the duration of retraction is linearly dependent on the step period . These cK2).We described a model of insect locomotion employing the cornerstone Shilnikov bifurcation ,3. This In the model, each leg was controlled by one oscillator consisting of two mutually inhibitory interneurons: protraction and retraction interneurons. The model central pattern generator (CPG) contains three coupled oscillators: PP-PR, MsP-MsR, MtP-MtR labeling protractor and retractor interneurons each for the prothoracic, mesothoracic, and metathoracic segments, respectively. The bifurcation-generated mechanisms make quantitative predictions on the CPG activity. The duration of the burst was governed by the inverse-square-root law Figure . The burThe burst duration of the retractor interneuron determined the period of the network. The retractor burst duration determined what type of gait was exhibited by network activity. As such, we were able to control the smooth transition from metachronal wave to tripod gait. While the duty cycle of retractor interneurons was greater than 50%, we observed a gait comprised of metachronal progression of bursts from posterior to anterior. When the duty cycle became 50%, we observed the tripod gait, where the activity in the prothoracic and metathoracic protractor interneurons was synchronous.In conclusion, we constructed a locomotor CPG model using a mechanism generated by the cornerstone bifurcation. This mechanism controls the duration of pulse-triggered bursts in endogenously silent neurons and governs a smooth transition from a metachronal gait to a tripod gait.


Multiple myeloma (MM) is a hematologic cancer characterized by the accumulation of malignant plasma cells in the bone marrow, which causes bone destruction and marrow failure . Despite(1) Diagnosis, Monitoring, and Prognosis of MM. Extensive gene expression profile analysis has provided interesting insight into the disease biology, and its correlation with clinical outcome has opened a new direction for risk stratification as well as novel target and therapy identification. Prognostic models such as the Durie-Salmon staging system and International Staging System (ISS) are available and account for the disease burden [e burden ; howeverMinimal residual disease (MRD) has emerged as one of the most relevant prognostic factors in MM and should be included in a new definition of complete response (CR) . In the (2) Role of the Bone Marrow Milieu. The bone marrow (BM) microenvironment plays a crucial role in MM pathogenesis. MM cells reside in and dynamically interact with various subsets of cells in the BM including mesenchymal cells (MSCs), osteoclasts (OCLs), osteoblasts (OBLs), and vascular endothelial cells, which support growth and survival of the tumor cells and lead to development of drug resistance [sistance . These csistance .The review by F. Accardi et al. summarizes the preclinical and clinical evidence on the effects of bortezomib and other new Proteasome Inhibitors (PIs) on myeloma bone disease. Osteoclastic formation and activity are inhibited by PIs, mainly through the blockade of RANKL signaling pathway in the osteoclast progenitors. However, the more significant impact of the bone remodeling by this class of drugs is the capacity to stimulate either the osteogenic differentiation of MSC or the osteoblastic function, leading to the consequent bone formation with a considerable anabolic effect. Osteocytes are also possible targets of PIs with a stimulatory effect on their viability. The preclinical evidence, thus, is confirmed in MM patients treated with bortezomib and more recently with carfilzomib. An improvement of the bone remodeling markers was observed in the patients treated with PIs. The histomorphometric data in MM patients treated with bortezomib prominently indicated that PIs can stimulate the bone formation process and induce the bone regeneration process. Bone healing, as well as an increase in the BMD, has also been reported in some of the patients treated with bortezomib. Overall, the literature data support the use of these drugs to restore bone integrity in MM patients.MM cells are cradled within the BM microenvironment by an array of adhesive interactions between the BM extracellular matrix (ECM) components and a variety of adhesion molecules on the surface of MM cells, which results in the “cell adhesion-mediated drug resistance” (CAM-DR) thought to be one of the major mechanisms by which MM cells escape the cytotoxic effects of therapeutic agents . MM is cAngiogenesis is fundamental to tumor growth and spread in many hematological disorders, particularly MM . The ang(3) Genetic and Epigenetic Abnormalities. MM cells accumulate various genetic and epigenetic abnormalities that drive the malignant phenotype and confer distinct biologic sequelae and disease outcomes [outcomes .miRNA are important transcriptome modifiers that play important role in myeloma tumor progression, survival, and development of drug resistance . In theiMoreover, S.-F. Lin and W.-C. Yang review molecular mechanisms underlying MM development, progression, and resistance to treatment, further highlighting the relevance of microRNAs as well as immune dysfunctions and conventional or novel therapies targeting such vulnerabilities. Overall, authors advocate that understanding the genomic landscape of MM deserves more attention in the prospect of developing personalized and effective targeted therapies that overcome resistance to currently used anti-MM drugs.In addition to microRNAs, dysregulation of transcription factors (TFs) features prominently in the biology of MM and B cell malignancies. TFs are the downstream effectors of signaling pathways within cells, which receive growth and other signals from the microenvironment; they also regulate cellular homeostasis as well as cell survival and proliferation. On this basis, mutations in TF genes or dysregulation of TFs' expression could play a significant role in cancer pathogenesis and drug resistance. The TF EBF1 is the master regulator of the specification, development, and maintenance of the B-lymphoid lineage, and perturbations of EBF1 expression and/or functions have been associated with the development of B cell malignancies . In thisGenome instability, defined by higher rate of genomic changes acquisition per cell division compared to normal cells, represents a prominent feature of MM cells . M. Cea Altogether, the data presented in this special issue may contribute to increasing our current knowledge of the biology of MM and B cell malignancies.Mariateresa FulcinitiNicola AmodioMichele CeaPatricia MaisoAbdel Kareem Azab


A 34-year-old man with history of stress presented to the emergency department with blurred vision in the left eye for the past week. There has been no vision change in his right eye. The vision acuity of the left eye was 20/100. The fundus examination revealed a localized serous detachment of the macula (A). The fluorescein angiography (B) and the ocular coherence tomography (OCT) (C) confirmed the diagnosis of Central serous chorioretinopathy. Central serous chorioretinopathy (CSCR) is characterized by the accumulation of subretinal fluid at the posterior pole of the fundus, causing a retinal detachment. When the detachment spreads into the macula, patients typically describe decreased vision acuity, metamorphopsia and a scotoma. CSCR is predominant in caucasians men between 20 to 45 years of age, and is highly linked to stress and the use of corticosteroid. The diagnosis is based on the ophthalmoscopic findings and results of fluorescein angiography, which shows single or multiples leakage points. The ocular coherence tomography (oct) contribute in the diagnosis by demonstrating the neurosensory detachment and is an objective way of surveillance. Generally, CSCR has a good prognosis for spontaneous visual recovery. However, some patients develop chronic CSCR or subretinal fibrosis.


Endocytic pathways constitute an evolutionarily ancient system that significantly contributed to the eukaryotic cell architecture and to the diversity of cell type–specific functions and signaling cascades, in particular of metazoans. Here we used comparative proteomic studies to analyze the universal internalization route in eukaryotes, clathrin-mediated endocytosis (CME), to address the issues of how this system evolved and what are its specific features. Among 35 proteins crucially required for animal CME, we identified a subset of 22 proteins common to major eukaryotic branches and 13 gradually acquired during evolution. Based on exploration of structure–function relationship between conserved homologs in sister, distantly related and early diverged branches, we identified novel features acquired during evolution of endocytic proteins on the way to animals: Elaborated way of cargo recruitment by multiple sorting proteins, structural changes in the core endocytic complex AP2, the emergence of the Fer/Cip4 homology domain-only protein/epidermal growth factor receptor substrate 15/intersectin functional complex as an additional interaction hub and activator of AP2, as well as changes in late endocytic stages due to recruitment of dynamin/sorting nexin 9 complex and involvement of the actin polymerization machinery. The evolutionary reconstruction showed the basis of the CME process and its subsequent step-by-step development. Documented changes imply more precise regulation of the pathway, as well as CME specialization for the uptake of specific cargoes and cell type-specific functions. One of the principal features of the eukaryotic cell that distinguishes it from prokaryotic cell is complex endocytic system. According to the current view, the role of this system in evolution lies in its impact on actuation of the eukaryotic cell plan . FurtherClathrin-mediated endocytosis (CME) is a universal internalization route in eukaryotes  and the Despite extensive investigation of CME over the last three decades, a number of fundamental questions still remain. What is the very basis of CME that could be observed in extant eukaryotes? To what extent are the CME of animals and yeast related regarding the latter as widely used model for CME studies? How was CME linked to other cellular processes, in particular signaling? These questions could be answered by reconstruction of CME evolution. Advances over the past decade in genome sequencing have led to the elaboration of comparative and evolutionary studies in molecular and cell biology. The availability of complete genomes and proteomes allowed the investigation of evolutionary changes in proteins and their families; however, what is more intriguing is the possibility of evolutionary reconstructions of cellular pathways and systems.To date, several reports described the evolutionary histories of individual endocytic proteins  or the dHere we provide data on the evolutionary history of CME typical of animals. We traced the emergence of essential animal endocytic proteins and their modifications during evolution of eukaryotes from the last eukaryotic common ancestor (LECA) to metazoans. The role of these evolutionary events is discussed in relation to their possible impact on the mechanism of CME, thereby shaping endocytosis to that observed in extant animals, particularly in mammals.www.broadinstitute.org, last accessed August 16, 2015) databases  and UniProt  (the other organisms). To find potential homologs of animal endocytic proteins, we first constructed Hidden Markov Models (HMMs) for each of the 35 endocytic proteins using HMMER . Coiled-coil regions were predicted with ncoils .Accession numbers of the homologs identified for each endocytic component throughout the eukaryotes together with supplementary table S8, Supplementary Material online). We took into account only motifs in the protein “tails,” C-terminal regions lacking globular domains, and in the case of stonin (STON) we counted the motifs in the N-terminal region.Motifs that potentially bind core endocytic proteins were predicted using regular expressions: DP[WF]|F.D.F|WV.F|F.F.[FL] for AP2 binding , L and NUMB [protein numb homolog]) or the muHD domain of the AP2 mu subunit (such as for STON) C. These Thus, LECA possessed sorting proteins essential for engagement of cargoes necessary for vesicle fusion and signal transduction processes. Starting from opisthokonts, endocytic accessory proteins gained ability of cargo recruitment via acquisition of cargo-binding regions. The most evolutionary recent CLASPs specific of metazoans were based on domains typical of signaling pathways.The late stage of CME requires constriction of the vesicle neck, recruitment of the DNM GTPase, and coordinated polymerization of actin to promote vesicle scission .supplementary table S1, Supplementary Material online) and previously published data . We followed transformation of DRP to DNM analyzing its key functional regions. The three crucial interfaces for dimer and tetramer formation . However, DNM had a specific interaction interface between the PH domain and middle domain (MD) in contrast to DRPs . The other domains, GTPase and GTPase effector domain, of identified nucleariid protein were typical of DRP (B and Csupplementary fig. S4), suggesting that transformation of DRP to DNM was initiated in the MD.According to our results . Within the transitional DRP-to-DNM protein of F. alba, a long C-terminus with PxxP motifs necessary for SH3 domain interactions was documented. The distribution across eukaryotes of SH3-containing proteins, SNX9 and AMPH, that are important recruiters of DNM . These proteins were first found in the apusomonad T. trahens that belongs to a group that branched prior to Opisthokonta . Within opisthokonts, SNX9 and AMPH as well as DRP with a proline-enriched C-terminus were poorly conserved or lost in fungi. However, these SH3 domain proteins together with their target motifs in DNM became conserved in holozoans. Noteworthy, another SH3-containing regulator of this GTPase, the ITSN protein, underwent expansion of its SH3 domains from two to five in this taxon . A high level of aldolase conservation as well as its residues involved in SNX9 binding .In the cytosol, DNM persists in a repressed state in complex with SNX9 and the glycolytic enzyme aldolase, AldoA E. Aldola binding  was obseThus, multiple concurrent changes contributed to the emergence of novel mechanism of vesicle fission based on the mechanochemical GTPase DNM and included regulators of membrane curvature and actin polymerization. The emergence of DNM from DRP occurred in several steps: The first transformation apparently was initiated in the MD, then the C-terminus gained multiple linear motifs for SH3 domain binding, and the PH domain and corresponding interaction interface emerged. The distribution and conservation of SH3-containing interactors of DNM overlap with the presence of PxxP motifs within the C-terminal tail of the GTPase. Thus, apparently, the mechanism of negative regulation and bringing DNM to endocytic sites via the SH3-containing recruiters was accomplished in holozoans.The complexity of modern organisms is a result of long-term evolution. All the features of living creatures are based on sophisticated interplay of events at the molecular level. Yet, how was the molecular basis of known processes gained, which steps did it take, and what was its relative timing? Trying to answer these questions in the field of endocytosis, we followed transformation of the CME machinery during the course of eukaryotic evolution. The most ancient core endocytic proteins typical of most eukaryotes were defined as well as gains of novel components together with their links to existing components. The results showed that CME underwent many-sided changes affecting early and late stages of CCV formation, and the way of loading the endocytic cargoes.The analysis revealed that LECA possessed a subset of 22 of 35 proteins crucial for animal CME that apparently were sufficient to form CCVs. The core CME proteins clathrin and AP2, as well as proteins involved in membrane deformation, clathrin assembly, recruitment of the actin cytoskeleton, and vesicle uncoating were found in major eukaryotic branches. These data are in line with previous studies that reported the ubiquitous nature of CME in eukaryotes .N. gruberi that belongs to the earliest branch of extant eukaryotes  were derived from conserved ancestral molecules. The proteins mentioned constitute the FEI functional complex, needed for early and intermediate steps of CME in animals. Ancestors of the FEI components, the EEC and muHD-containing proteins, were found in eukaryotic branches beyond opisthokonts, in particular in excavate karyotes . Moreovekaryotes . All EECkaryotes , the funkaryotes , as wellkaryotes  are invokaryotes . DespiteAddition of novel components to the CME machinery led to modifications of the endocytic PIN. We propose that FEI functional network became the third endocytic hub along with AP2 and clathrin that integrate the vesicle-forming machinery and CLASPs recruiting specific cargoes to the nascent pits. The existence of functionally distinct groups relies on the universal role of accessory proteins in vesicle formation and on the specific function of CLASPs in the selection of a certain cargo. Both AP2 complex and FEI proteins are required for initial steps of CME . The FEIInvolvement of animal AP2 in CME is controlled by the FEI proteins. The latter recruits AP2 to the PM  and shifin vivo will reveal new components of cargo selection and recruitment  and DNM (PxxP) accomplished the formation of the regulatory complex. Other components, SNX9 and AMPH, were gained earlier but became conserved in holozoans concomintantly with acquisition of linear motifs in DNM. This assumption is in line with the notion that linear motifs are important switchers of evolution of molecular complexes and interaction networks .Polymerization of actin was shown to precede vesicle fission in animal cells . Two essRecently, DNM was suggested to be a central component of the CME checkpoint in mammals capable of defining abortive and productive CCPs. The prolin-enriched C-terminus of DNM mediated numerous decisive interactions with SH3 domain-containing proteins capable of sensing membrane curvature, the presence of coat protein and cargo . FormatiOne of the last prominent changes of the CME machinery described was the generation of multiple paralogs in metazoans. Thus, 60% of the endocytic components studied were presented as protein families in vertebrates. Paralogs are often characterized by distinct expression profiles in tissues  or could differ in cellular localization . However, in most cases the precise functional role of paralogous proteins remains so far unresolved. Paralogs specialized in different tissues or cellular compartments could reflect the need for fine-tuned specific regulation developed by endomembrane system during its evolution.The major documented alterations in CME are summarized in Our better understanding of the evolution of CME is currently limited by the lack of data for the period between the first and the LECAs that remains largely a black box for investigations. Another constraint is poor structure-to-function and sequence data for under-represented groups, that is, choanozoans, apusomonads, and others. The lack in certain species or taxonomic groups of CME components that are homologous to those specific of animals could suggest alternative scenarios of endocytosis. The function of a missing homolog could either be performed by a highly related protein as reported for the beta subunit of AP2  or a CMESupplementary tables S1–S11, figures S1–S5, and file S1 are available at Genome Biology and Evolution online .


Neurofibromas of the common bile duct are extremely rare. The lack of specific clinical or radiological features makes preoperative diagnosis in the absence of histology difficult. We report the case of a female patient who presented with obstructive jaundice and evidence of a common bile duct stricture on imaging. She underwent an exploratory laparotomy, and intraoperative frozen section confirmed clear margins and a benign lesion. Excision of the extrahepatic bile duct and A Roux-en-Y hepaticojejunostomy was performed. We discuss the clinical features and management of neurofibromas of the bile duct in light of the literature. Neurofibromas of the common bile duct are extremely rare. The lack of specific clinical or radiological features makes preoperative diagnosis in the absence of histology difficult.A 70-year-old Caucasian woman with no significant alcohol consumption presented with a 4-week history of painless jaundice, anorexia and pruritus. She did not have any significant past medical history or family history of hereditary diseases. Clinical examination revealed she was jaundiced with no palpable masses or skin lesions. There was a right subcostal surgical scar from an open cholecystectomy performed two years previously. Laboratory analysis revealed deranged liver function tests suggestive of an obstructive presentation, with an elevated bilirubin level of 74μmol/l  and alkaline phosphatase of 379iu/l . Contrast enhanced computed tomography (CT) of the abdomen and pelvis identified a stricture at the mid-common bile duct  with no Following case discussion at the multidisciplinary team meeting, the patient underwent an exploratory laparotomy. At laparotomy, thickening of the mid-upper third of the common bile duct suspicious of malignancy was observed. There were no palpable lymph nodes or surrounding fibrosis suggestive of local invasion and no evidence of distant metastases. Intraoperative frozen sections were performed, both proximal and distal to the stricture to ensure margin clearance, which demonstrated characteristics of a benign lesion. The patient underwent excision of the extrahepatic bile duct and a Roux-en-Y hepaticojejunostomy.The postoperative histological findings were consistent with a neurofibroma, with the presence of long spindle cells  and posiNeurofibromas are rare benign tumours arising from Schwann cells of nerve sheaths. Solitary neurofibromas may occur but they occur most frequently as part of neurofibromatosis, an autosomal dominant disease characterised by multiple tumours throughout the nervous system with or without skin lesions. Bile duct neurofibromas arise from the sympathetic and parasympathetic nerve fibres in the wall of the common bile duct and are extremely rare, with a limited number of cases reported in the literature. These tumours are characterised pathologically by the presence of long spindle cells, whose neurogenic properties are demonstrated by positive immunohistochemistry for S100, a marker for neurofilament protein.The most common primary tumours of the biliary tract are cholangiocarcinomas, most of which are adenocarcinomas. Surgery is the only curative treatment with a 9–18% five-year survival rate for proximal bile duct lesions and a 20–30% five-year survival for distal lesions.In the absence of neurofibromatosis, almost all cases of neurofibromas of the common bile duct are secondary to operative trauma following a cholecystectomy,Symptomatic neurofibromas usually present with jaundice, with or without abdominal pain and/or fever. Such patients are investigated radiologically with CT as in this case, with or without endoscopic ultrasonography (EUS).Neurofibromas of the bile duct are rare, and the lack of specific clinical and radiological features makes preoperative diagnosis difficult. The diagnosis should be considered in patients presenting following previous bile duct trauma such as a cholecystectomy. An exploratory laparotomy should include the use of intraoperative frozen section to ensure clear margins and confirm benign disease, to enable the most appropriate surgical management to be instituted.


Numerical methods and applications in biomechanical modeling have continued to play increasingly important roles in biomedical research and applications. This special issue, following the very successful one in 2013, provides a snapshot of the emerging biomedical applications and research. The main focus of this special issue was on the interface between numerical methods and biomedical applications especially for cardiovascular dynamics and biomechanics problem in the human body. The goal of this special issue was to bring together experts in related fields of computational biomedical engineering like multiscale flow modeling , blood flow propagation, boundary conditions, fluid-solid coupling, inverse problems in biomechanics, high-performance computing of multiphysics discretization schemes, cardiovascular biomechanics, and porous media. Then, the details of these papers are summarized as follows.The work of M. Klous et al. attempts to compare ankle and knee joint loading at the steering leg between carved ski and snowboard turns. The authors showed higher forces along the longitudinal axis in skiing and similar forces for skiing and snowboarding in anterior-posterior and mediolateral direction. This study can help the clinician to improve understanding of how forces are distributed in the ankle and knee joint when these sports are done.X. Liu et al. present the deformation and haptic feedback of soft tissue in virtual surgery based on a liver model by using a force feedback device. This paper introduces a kind of mesh-free method for deformation simulation of soft tissue and force computation based on viscoelastic mechanical model and smoothed particle hydrodynamics (SPH). The results reveal that SPH methodology is suitable for simulating soft tissue deformation and force feedback calculation, and SPH based on dynamic local interaction area has a higher computational efficiency significantly compared with the usual SPH.A. Belwadi and K. H. Yang show an interesting paper about how the occupant-seating position, bumper profile height, and the principal direction of force of impact play a crucial role in the generation of strain and pressure in the aorta and a potential injury mechanism responsible for traumatic rupture of the aorta in automobile crashes. In their study, 16 design of computer experiments were carried out with varying levels of principal direction of force, impact velocity, impact height, and impact position of the bullet vehicle combined with occupant-seating positions in the case vehicle to determine the effects of these factors on aortic injury. Simulation results showed that, in simulated near side left lateral crashes, peak average maximum principal strain mainly took place in the isthmus of the aorta. Their design of computer experiments using finite element vehicle models has identified the key factors responsible for aortic injury.N. Mijailovic et al. combine within biomechanical model different sensor measurements to determine the knee cartilage deformation ratio and the knee cartilage stress distribution to predict when it is necessary to perform surgery on a patient. The model includes the impact of ground reaction forces, contact force between femur and tibia, patient body weight, ligaments, and muscle forces. Despite introduction of a new approach and presentation of some preliminary findings, their proposed method shows great potential for preoperative and postoperative surgical planning and treatment of patients with knee injuries.The paper by M. Jahangiri et al. compares different turbulent models over a stenosed artery considering an elastic wall. The results were compared with those of the laminar flow assumption and the rigid artery wall and show the effects of turbulent blood flow over the velocity profiles. in vivo and discuss their potential for uptake into sports training and rehabilitation. The review introduces the different computational techniques and outlines their advantages and disadvantages for the informed usage by nonexperts. With sufficient validation and widespread application, muscle force calculations during strength exercises in vivo are expected to provide biomechanically based evidence for clinicians and therapists to evaluate and improve 20 training guidelines.F. Schellenberg et al. present a review of existing computational techniques to determine muscle forces in the lower limbs during strength exercisesR. Rockenfeller et al. compare two models of mammalian striated muscle activation dynamics proposed by Hatze and Zajac and perform a sensitivity analysis for investigating the influence of model parameters on the solution of the mathematical equations. The authors also used a global sensitivity analysis approach to factor in finite ranges of parameter values. The authors demonstrate that the findings of global sensitivity analysis must be treated with caution because the whole dynamics of a system is condensed to a single average function per whole parameter range.The work of S. Khalafvand et al. studies the blood flow characteristics in the normal left ventricle. The authors show the vortices produced (generation and growth) and their correlation with flow acceleration and deceleration during the mitral valve opening and closing. This work can help the cardiologist to understand how the vortices are produced in the heart movement, thus contributing to understanding of pathogenesis of cardiac disease.The objective of the work by Þ. Pétursson et al. describes a novel preliminary methodology for patient evaluation before total hip replacement surgery as a first step towards creating a patient-specific, presurgical application for determining the optimal prosthesis procedure. Ten patients were studied using finite element analysis and bone mineral density to estimate the status of hip before surgery; after that a fracture risk index is defined and compared with the patient's age, sex, and average proximal bone mineral density. Findings of this study showed a high degree of variability between patients grouped according to implant procedure, with age and gender being the poor indicators for determining total hip replacement procedure. Their results could be used as a basis to develop a clinical database for correlating bone mineral density and fracture risk index to total hip replacement patient outcomes.G. Saborit and A. Casinos present a mathematical model to predict the optimum gradient for a minimum energetic cost. The model focuses on the variation in mechanical energy during gradient walking. The authors show that kinetic energy plays a marginal role in low speed gradient walking. Consequently, the optimal negative gradient depends on the individual step length.In this special issue, we have provided examples of recent progress in computational and mathematical methods in biomedicine, for the benefit of students, researchers, healthcare professionals, and teachers.