The objective of this review was to present an update of the currently managed studies on the characterization physical, chemical, and sensory analysis of several tomato cultivars. This review has indicated the importance of farming system and genotype on sensory and biochemical characteristics. It is necessary to use selected genotypes responding positively to organic farming in terms of sensory, biochemical characteristics and productivity aspects and to evaluate systems over more than one year of sampling. Solanum lycopersicum L.) has a great importance in the world, and its production, in 2013, reached 163.9 million tons and average yield of 34.7 tons per hectare [The tomato crop  and Bostwick values of consistency .Other researchers showed a higher number of studies with favorable results to the organic system, mainly concerning to the lower level of nitrate when compared to the conventional system ,18. AnotO-glucoside), flavones (apigenin-7-O-glucoside) and hydroxycinnamic acids . The phytochemical concentration, including the level of flavonoids, showed higher value in the fruits produced in the organic system [Tomatoes fruits were bought from the same cultivar (“Daniella”), in two consecutive years (2010 and 2011), at the same degree of maturity and the same size to study the differences in the phenolic content of organic and conventional tomatoes in the flavonoids , flavonones , lycopene (+20%), total phenolics +24%), and flavonoids (+21%) . It also%, and flA review compared studies that evaluated nutritional value, food safety and sensorial quality. According to the authors, the nitrate level was statistically lower in food produced under the organic system than in the conventional system; however, the nutrient content did not show any difference .O-rutinoside, myricetin and quercetin) were evaluated. The organic tomatoes showed higher levels of these compounds, when compared with tomatoes derived from the conventional production system [In a two-year research, the total sugar content, organic acids, vitamin C and phenolic compounds  obtained the best scores in all sensorial traits evaluated  .i.e., leads of liking/disliking were identified. In addition, the results showed that tomatoes with a round shape and a red color (reddish) were the most liked cherry tomatoes [Another work evaluated 10 accessions of organic cherry tomatoes by a trained panel using the Quantitative Descriptive Analysis (QDA), and similarly by 80 tomato consumers for the acceptance of appearance and intention to purchase. Subsequently, the results reached of the integration of data from the trained panel and consumers made a multidimensional map that elucidated of consumer liking of tomatoes in relation to the appearance, tomatoes .In the literature, different authors revealed that growing methods had no statistically significant effect on sensory parameters, in particular on aroma , becauseThis review has indicated the importance of farming system and genotype on sensory and biochemical characteristics. It is necessary to use selected genotypes responding positively to organic farming in terms of sensory, biochemical characteristics and productivity aspects and to evaluate systems over more than one year of sampling.


In today’s nanoworld, there is a strong need to manipulate and process materials on an atom-by-atom scale with new tools such as reactive plasma, which in some states enables high selectivity of interaction between plasma species and materials. These interactions first involve preferential interactions with precise bonds in materials and later cause etching. This typically occurs based on material stability, which leads to preferential etching of one material over other. This process is especially interesting for polymeric substrates with increasing complexity and a “zoo” of bonds, which are used in numerous applications. In this comprehensive summary, we encompass the complete selective etching of polymers and polymer matrix micro-/nanocomposites with plasma and unravel the mechanisms behind the scenes, which ultimately leads to the enhancement of surface properties and device performance. T. T2 plasThis review attempted to outline the interdisciplinary applications of plasma etching and the selective etching of polymer-based materials from different branches of science. Moreover, it looks at the origin of selectivity and attempts to find answers bringing together an understanding of plasma properties with very diverse results of plasma–surface interactions through the note to nanomaterials. Among various plasma modifications, neutral dense and ion free cold plasmas are have been found to be efficient, especially for treating delicate polymeric and biomaterials to avoid unwanted surface damages and thermal effects. The plasma-induced functionalization and etching of polymer substrates is preferred to wet chemical etching and UV irradiation for designing the surface chemistry, surface morphology, and surface energy. These plasma induced modifications enable the attachment of various materials and biomolecules onto the surface. Additionally, plasma-induced hydrophobization of the surface can effectively increase the water-resistant behavior of the surface to improve anti-aging, anti-fouling, and corrosion-resistant properties. Such improvements in the surface properties are directly connected to structural and morphological changes.The high-energy particles inside the plasma are able to distinguish various bond types under controlled process parameters. Utilizing the difference in the chemical stability of various bond types on the same molecule, delicate materials such as GNRs have been fabricated. The comparison of etching rate for different classes of polymeric materials has revealed that the difference in the etch rate is connected with both physical and chemical properties of the material. The presence of aromatic moieties has reduced the etching rate by radical quenching, whereas the surface cross-linking has reduced the etching rate for branched polymers. Generally, the etch rates are lower for hydrocarbon polymers compared to functionalized macromolecules. Additionally, a higher extension of crystallinity has reduced the plasma etch rates for various polymers, presented through reports on a few examples, namely, PET, LDPE, and HDPE. Thus, existing differences in the etching rates for various polymeric substrates have been employed in the surface structuring of block copolymers in applications, especially for the semiconductor industry. The pronounced applications of plasma selective etching of composite materials have been found to be efficient for reducing the dimensionalities of materials such as CNT or graphene sheets for advanced applications in electronics, electrical, and sensing devises. Furthermore, the preferential etching of composite surfaces has been effectively used for a simple and low-cost synthesis of polymer NWs with a controlled aspect ratio.etc. In some of the presented examples, the involved wet chemistry had slight adverse effects on the properties of the final product. An additional challenge in front of the plasma community is the pinpoint control of various plasma species and their reactions on the atomic or molecular level. Such developments are important, especially for such remarkable applications as plasma nanoscience and plasma medicine.The plasma etching rate and etching selectivity of micro/macro molecules are well connected with the strength of the available bonds in the material. However, the side reactions such as radical quenching and surface cross-linking significantly affect the etching rate. Thus, the optimization of the process parameters is essential for achieving etching selectivity in different systems. Plasma is used as a single operating tool in only one/a few step(s) throughout multistep processes for demanding applications. More frequently used plasma has been found as one of the steps in multi-processing. This is clearly visible in many of the discussed examples, including the synthesis of GNR, graphene nanomesh, patterning the surface of block copolymers,


To report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome.Third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis.This is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism. However, from 1992 on, cohort studies started to be published, which broadened the scope of the syndrome through new evidence such as clinical variants of later onset and autonomic nervous system involvement in other organs, which expands the possibilities of associated clinical manifestations . Confirmation of familial recurrence emphasized the genetic component and the broad phenotypic spectrum.PHOX2B gene mutations were identified as responsible for CCHS. The PHOX2B gene (paired-like homeobox gene), located on chromosome 4p12, encodes a transcription factor responsible for the regulation of genes involved in the development of the autonomic nervous system.,,In 2003, PHOX2B gene. Mice mutated for the gene, with an increase of seven alanines, show 85% reduction of RTNN and can survive only on artificial ventilation.The central breathing control depends on chemoreceptors expressed in specialized neurons located in the retrotrapezoid nucleus in the brainstem bulbar region, sensitive to carbon dioxide levels in Cerebrospinal Fluid (CSF).,,,,,,-,,,,Most of the mutations responsible for CCHS are de novo mutations. Approximately 10-25% of parents are asymptomatic carriers, responsible for transmission to their offspring.Thus, the aim of this study was to report the case of a neonate with recurrent apnea episodes, diagnosed with congenital central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease, configuring Haddad syndrome.Male neonate, born at term to non-consanguineous parents  through vaginal delivery without complications, classified as appropriate for gestational age (birth weight 3390 g), had an Apgar score of 8 in the 1st minute and 9 in the 5th minute. The mother was multiparous, with 6 pregnancies and no miscarriages, aged 34 years; the pregnancy was uneventful. The newborn presented, in the first hour of life, with bradypnea, bradycardia and cyanosis, underwent endotracheal intubation and antibiotics for suspected early neonatal sepsis. The echocardiography showed a patent foramen ovale without hemodynamic repercussions. The transfontanellar ultrasonography showed no abnormalities suggestive of central nervous system malformations. The patient had delayed meconium elimination, on the 4th day of life and only after rectal stimulation. He was assessed by the staff of pediatric surgery, which identified a circular stenosis at 3.5 cm of the rectum through digital rectal examination.During hospitalization in the Neonatal ICU, in the first month of life, the patient had difficulty to undergo extubation. Several attempts were made to withdraw mechanical ventilation with the use of noninvasive positive pressure ventilation, but he persisted with desaturation episodes during sleep and wakefulness. Additionally, there were recurrent episodes of metabolic acidosis and three episodes of respiratory acidosis during ambient air maintenance attempts. He also developed hypoglycemic episodes alternating with hyperglycemia, recurrent abdominal distention, leukocytosis and fluctuating increased C-reactive protein levels with negative blood cultures. Inborn errors of metabolism were suspected. The best option to offer nutrition was through continuous gavage, as had episodes of hypoglycemia approximately one hour after feeding. If the glucose infusion rate was increased, he soon showed hyperglycemia.There was a family history of a brother with a similar neonatal picture, who died at 10 months from respiratory complications, with an undefined etiological diagnosis, but managed as a carrier of organic acidemia (3-hydroxy-3-methylglutaryl-CoA lyase deficiency). Thus, tests were performed to screen for inborn errors of metabolism  and a leucine, isoleucine and valine-free formula was initiated empirically, associated with the use of high-dose vitamins t . There was no clinical improvement after the institution of dietary therapy and megavitamin. The newborn screening test with mass spectrometry and research of urinary organic acids were normal.At two months, he underwent a barium enema, which showed cone-shaped transition zone at the splenic flexure and dilatation upstream and Hirschsprung's disease was diagnosed. He underwent intestinal biopsy, affected segment resection and Hartmann's colostomy. Anatomopathological examination showed the presence of a nerve plexus, but absence of ganglion cells in the rectum, sigmoid, transition zone and descending colon; nerve plexus with ganglion cells was present only in the transverse and ascending colon.Given the suspicion of congenital central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease and after ruling out the hypothesis of inborn error of metabolism, genetic testing was performed using the molecular technique of polymerase chain reaction to screen for CCHS.,Congenital central hypoventilation syndrome (CCHS) is a rare, but probably underdiagnosed disorder. In 1999, there were approximately 160-180 known cases worldwide.,It was possible to make the diagnosis of CCHS due to a constellation of factors: the possibility of excluding organic acidemia; the previous experience of members of the multidisciplinary neonatal ICU team who hypothesized the presence of CCHS and persisted in their investigation; the finding of Hirschsprung's disease (HD) during evolution; and access to genetic testing. The patient's brother, also possibly affected by the syndrome, did not achieve diagnostic clarification in life. The doubt between the diagnosis of organic acidemia and CCHS persisted during his 10 months of life, mainly because the excretion of organic acids in urine was demonstrated and there was no access to genetic testing at the time. However, after reviewing the case, it is believed that the increase in acid metabolite excretion was related to the patient's critical condition and hypoxia.PHOX2B gene was demonstrated by the molecular technique of polymerase chain reaction, but the technique used does not quantify the number of polyalanine expansions, as it only identifies the presence of above than normal expansions. However, it seems to be the most severe phenotype, due to the onset of symptoms in the neonatal period and the association with Hirschsprung's disease. Approximately 87-100% of the cases caused by non-polyalanine repeat expansion mutations (NPARM) have Hirschsprung's disease.,,The presence of a mutated allele in the ,,,The parents have not been submitted to mutation screening, but considering the history of familial recurrence, it is likely that one of them is a carrier. There are no reports of other cases in the family. The mother has postural hypotension and chronic constipation, which may represent mild symptoms of autonomic nervous system dysfunction.cor pulmonale and hypoxic-ischemic lesions, caused by inadequate ventilatory support.,,,Central hypoventilation is the cardinal sign of CCHS and the characteristic with the highest morbimortality.,The diagnosis and management of these patients are quite challenging. The rarity of the disease, the broad differential diagnosis , restricted access to specific genetic tests, the need for ventilatory support at birth and follow-up with a multidisciplinary team  are the basis of the previous statement. The survival and quality of life can be improved through the planning of early tracheostomy and gastrostomy, efficient deinstitutionalization process, access to home care programs and even the possibility of diaphragmatic pacemaker implantation.


Metastatic spinal cord compression (MSCC) is a medical emergency that requires rapid diagnosis and treatment to reduce pain, to preserve neurological functioning, and to prolong survival. The diagnosis of liver cancer is often neglected in the differential diagnosis of MSCC. Treatment is usually palliative and evolution is often fatal. This is a case report of a 28-year-old patient living in Mauritania hospitalized in November 2014 at the neurology department of Fann national teaching hospital in Dakar, for the management of a chronic dorsal spinal cord compression. The radiological and laboratory investigations done revealed the metastatic compression originating from a liver cancer with elevated alpha-fetoprotein and aspartate transaminase, positive hepatitis B surface antigen, and multiple metastasis in the lungs, mediastinum, ribs, iliac, and peritoneum. The hip joint X-ray showed a spontaneous fracture of the right femoral neck. The multidisciplinary treatment was palliative and the evolution was fatal within the month of hospitalization. Earlier diagnosis and treatment of MSCC may not have saved the life of the patient but may have prevented much suffering and would likely have prolonged the life of a young man. Metastatic spinal cord compression (MSCC) is a medical emergency, requiring rapid diagnosis and treatment. Described for the first time by Spiller in 1925, it consists of an extrinsic compression of the epidural space by a metastatic tumor [This is the case of a 28-year-old patient living in Mauritania with no medical history, hospitalized in November 2014 at the neurology department of Fann national teaching hospital in Dakar , for a chronic dorsal pain and lower limbs progressive paralysis lasting for three months. On physical exam we found complete paraplegia, loss of sensation on both lower limbs to T6 level, loss of bladder and bowel control, jaundice, hepatomegaly, and weight loss. The diagnosis of spinal cord compression was made as well as the thorax, abdomen, and pelvic CT scan. The chest X-ray showed multiple pulmonary nodules of different sizes involving both lungs. The CT scan showed multiple hypodense and heterogenous masses of various sizes of the spinal cord at T6 and T9 and located in the lungs, mediastinum, ribs, iliac, and peritoneum and a hepatomegaly .This liver mass was large, heterogeneous, and partially necrotic and located in the right lobe . ElsewheDespite the absence of a histological confirmation, the combination of clinical history, radiology, and biochemical markers justified a diagnosis of MSCC from primary liver cancer with extensive metastases. The treatment was multidisciplinary based on palliative measures. The patient received corticosteroids (methyl-prednisolone), pain killer (tramadol and morphine), and supportive care such as psychotherapy, physiotherapy, and nursing. The pain was partially controlled but there was no improvement of neurological signs. The evolution was fatal within a month of hospitalization.Metastatic spinal cord compression (MSCC) from primary liver cancer metastases is rare and represents less than 1% of secondary locations . Liver cHepatitis B surface antigen and tumor markers were also positive in our patient. Magnetic resonance imaging (MRI) is the gold standard for the diagnosis of spinal cord compression but is not widely available in large parts of the world. However, conventional X-rays and CAT scan were, at least in this case, sufficiently clear in showing the large vertebral metastases to corroborate the clinical diagnosis of MSCC . The treWe presented a case of metastatic spinal cord compression (MSCC) in a young adult with primary liver cancer. MSCC is a common complication of cancer in adults with more common cancers. This rare case illustrates that MSCC can occur at any age in virtually any cancer. Unlike Western countries, liver cancer is very common in countries with a young population and with a high prevalence of hepatitis B and hepatitis C, such as in Senegal. Since appropriate diagnostic and therapeutic techniques will be increasingly available, early diagnosis and immediate treatment of MSCC will be an increasing challenge, not only to reduce pain, but also to prevent neurological deterioration and to improve survival.


Walking animals produce adaptive interlimb coordination during locomotion in accordance with their situation. Interlimb coordination is generated through the dynamic interactions of the neural system, the musculoskeletal system, and the environment, although the underlying mechanisms remain unclear. Recently, investigations of the adaptation mechanisms of living beings have attracted attention, and bio-inspired control systems based on neurophysiological findings regarding sensorimotor interactions are being developed for legged robots. In this review, we introduce adaptive interlimb coordination for legged robots induced by various factors . In addition, we show characteristic properties of adaptive interlimb coordination, such as gait hysteresis and different time-scale adaptations. We also discuss the underlying mechanisms and control strategies to achieve adaptive interlimb coordination and the design principle for the control system of legged robots. Animals produce adaptive motor behaviors by skillfully manipulating their complicated and redundant musculoskeletal systems. Locomotion is an important behavior required in daily life. Gait selection in accordance with the situation, such as speed and environment, is a prominent adaptive motor function. Humans walk bipedally and use walking and running gaits. Quadruped animals use four legs and produce walking, trotting, and galloping gaits. Hexapod insects use six legs and create metachronal (wave), tetrapod, and tripod gaits as well as intermediate stepping patterns forming a continuum. These gaits, including the transitions and the intermediate stepping patterns for hexapods, are generated through the intralimb and interlimb coordination of leg movements. Intralimb coordination is the relationship between segments or joints within one leg, whereas interlimb coordination is the relationship between legs. For example, in the adaptive control of intralimb coordination, peak timings of ankle plantar flexion, knee extension, and hip extension are out of phase during the human walking gait, but they are shifted and almost in phase during the human running gait , which are located in the spinal cord of vertebrates and in the thoracic ganglia of invertebrates, are an important factor for elucidating the locomotion mechanism . In addition, we show characteristic properties of adaptive interlimb coordination in animals and robots, such as gait hysteresis and different time-scale adaptations. Finally, we discuss the underlying mechanisms and control strategies to achieve adaptive interlimb coordination and the design principle for the control system of legged robots.The most general adaptive interlimb coordination appears when varying the locomotion speed in legged animals. This has been observed even in spinal cats on treadmills . Such a task is mainly generated by modulating the leg movements, and thus adaptive control of intralimb coordination is important. However, also important is adaptive control of interlimb coordination. To step over an obstacle, the leading limb first clears the obstacle and then the trailing limb follows it. The foot of the leading limb must be raised higher than usual to avoid collision with the obstacle, and this motion delays foot contact. Especially for bipedal and quadrupedal animals, the foot of the trailing limb must be raised after foot contact of the leading limb; otherwise, the obstacle avoidance task will fail because the contralateral limb does not support the body at the onset of raising the trailing limb , which are usually applied to independent control of individual legs or joints, most of the studies explicitly design complete interlimb connections to obtain the desired locomotor behaviors. This results in limitations of adaptive and flexible interlimb coordination (e.g., Kirchner et al., Although walking animals create adaptive locomotor behavior by skillfully manipulating their complicated and redundant musculoskeletal systems, the underlying mechanisms are still unclear. Designing the control architecture for legged robots to autonomously achieve such adaptability is still a challenge. Although some legged robots produced adaptive locomotor behaviors by purely engineering approaches without inspiration from biological systems, neurophysiological findings such as CPG organizations and sensorimotor interactions are useful for designing the control system of legged robots. Robot experiments with CPG models and sensory feedbacks are insightful from a dynamic viewpoint for understanding gait generation and adaptation in a self-organizing manner among neural dynamics, body dynamics, and environment. In this review, we showed adaptive interlimb coordination in the locomotion of animals and legged robots induced by various factors, such as locomotion speed, environmental situation, body properties, and tasks. We also showed characteristic properties of adaptive interlimb coordination, such as gait hysteresis and different time-scale adaptations. Legged robots are becoming a valuable tool for understanding the locomotion mechanism including interlimb coordination. In the future, together with the improvement of robotics systems, such as actuators and sensors, it will be important to enhance biological plausibility and feasibility by the integration with sophisticated models of neural and musculoskeletal systems, such as the Hodgkin-Huxley model and the muscle-tendon unit model, and to extract dynamical features by integration with simple models, such as the template model (Full and Koditschek, SA and PM contributed to the conception and design of the paper. SA, PM, and YA reviewed the relevant literature and wrote the paper. FM and FW revised the paper critically for important intellectual content. All authors approved the paper 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.


Important complications have been reported, including cerebrovascularaccidents, pulmonary vein stenosis and atrioesophageal fistula.5 We report here a case of superior vena cava syndrome afterradiofrequency ablation for AF.Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinicalpractice. Its prevalence increases with age, and it is commonly associated withstructural heart diseases, leading to hemodynamic and thromboembolic complicationswith significant economical implications and increasing morbimortality.Female patient, 60 years old, with mild chronic obstructive pulmonary andpre-syncope episodes, had her first AF episode in July, 2012 and remainedasymptomatic until January, 2013, when she had a new AF episode, reversed withamiodarone. Since then, she had recurrent AF episodes, in spite of the use ofamiodarone and beta blockers. She was referred for invasive treatment of AF(radiofrequency ablation of the pulmonary veins) and was thus admitted tohospital to undertake the procedure. Transesophageal echocardiography wasperformed prior to the procedure and showed mild to moderate dilation of theleft atrium, thickened mitral valve with prolapse of both cusps and moderate toimportant regurgitation. There was mild tricuspid regurgitation, with a maximalsystolic pulmonary pressure estimated at 46 mmHg; Both atria and respectiveappendages were free from thrombi, with the left atrial appendage contractingnormally ; pulmonaryvenous anatomy and drainage was normal. The electrophysiological procedure wascarried out as usual, with the patient under general anesthesia and with theplacement of an esophageal thermometer. After the introduction of 3 multi-polecatheters through the femoral vein, they were placed in the coronary sinus andin the left atrium, after a double transeptal puncture. The patient, who was inAF at the start of the procedure, underwent circumferential isolation of thepulmonary veins using an irrigated catheter under the guidance of an electroanatomic mapping system (CARTO®). Duringthe applications of radiofrequency (RF) to the right pulmonary veins, the AF wasreversed to sinus rhythm. After the isolation of the pulmonary veins, it wasdecided to attempt isolation of the superior vena cava (SVC). The applicationson the superior vena cava were carried out using irrigated catheter, with apotency of 30w. These applications were made in a segmented manner, guided by aLasso catheter. The phrenic nerve was mapped out with high output stimulationand no applications were made to the capture sites. After the procedure, thepatient was awaken from the anesthesia and sent to her room.One day after the procedure, the patient presented with facial edema and flushingof the cheeks and edema of the upper limbs. She also reported pressure on herhead and neck, with the symptoms exacerbated when laying horizontally andleaning her head forward, suggesting a superior vena cava syndrome (SVCS). Atransthoracic echocardiogram (TTE) was carried out, with similar preproceduralfindings, except for the presence of turbulent flow in the SVC at its entry inthe right atrium, with Doppler velocity at 136 cm/s , confirmA year later, the patient underwent a new procedure, that showed evidence ofelectric reconnection of the superior vena cava and the pulmonary veins, thusisolating pulmonary veins was again attempted . An atrial tachycardiaoriginating from the left atrial appendage was mapped out, with no need forapplications to the superior vena cava. No difficulty in manipulating cathetersat the superior vena cava was observed.6SVCS results from any condition that leads to the obstruction of its blood flow. Theobstruction may be caused by the invasion or external compression of the SVC by apathological process involving the right side of the lung, the lymph nodes and otherstructures of the mediastinum, or due to thrombosis inside the SVC. In some cases,both external compression and thrombosis may coexist.More recently, the incidence of SVCS due to thrombosis has increased especially dueto the use of intravascular devices, such as central venous catheters and pacemakerwires. Benign causes currently represent 20 to 40% of the SVCS cases.The rapidity of onset of symptoms and signs from SVC obstruction is dependent uponthe rate at which complete obstruction of the SVC occurs in relation to therecruitment of venous collaterals.Interstitial edema of the head and neck is visually impressive, but usually of verylittle clinical importance. However, the edema may obstruct the lumen of the nasalcavity and of the larynx, and potentially compromise the function of the larynx andpharynx, causing dyspnea, wheezing, cough, hoarseness and dysphagia.Vascular complications are among the most common adverse events related to AFablation, most likely due to the need for anticoagulation during and immediatelyafter the procedure. These complications include hematoma at the site of catheterinsertion, pseudo-aneurysm, arteriovenous fistula, or retroperitoneal bleeding.7 with no reports of this complication resulting from catheterablation of AF ablation yet. It is assumed that the mechanisms associated with theRF-induced venous occlusion leads to intimal proliferation, substitution of thenecrotic muscle by collagen, endovascular contraction and rupture and thickening ofthe internal elastic lamina.8Transitory occlusion of the SVC is rare, and has only been reported after catheterablation of inappropriate sinus tachycardia,9Venous structures of smaller diameter, such as the coronary sinus and the pulmonaryveins, may be subject to an even greater risk of occlusion as a result of ablationprocedures carried out in the adjacent tissue.8 Even though the complete occlusion of the SVC wasnot observed in this patient, the characteristics of the Doppler flow observed inthe junction between the SVC and the right atrium lead to the conclusion that theedematous tissue induced by the RF is a plausible mechanism for suchcomplication.In this patient, the RF application inside the superior vena cava, performed toeliminate this possible trigger, probably caused the formation of a significantedema in the junction of the SVC with the right atrium. This edema is more marked inthe area that receives the RF, but it also occurs throughout its entirecircumference, presumably by the propagation of the interstitial edema through thecontiguous tissue. This edema of the tissues, resulting in the narrowing of theSVC-right atrium junction, may persist throughout the entire period of time of theablation procedure, but seems to be resolved within weeks or months. Studies inanimals have shown that the thickening of the atrial tissue after RF applicationincreases with time, and persists for at least 150 min.


The development of smart nanocarriers for the delivery of therapeutic drugs has experienced considerable expansion in recent decades, with the development of new medicines devoted to cancer treatment. In this respect a wide range of strategies can be developed by employing liposome nanocarriers with desired physico-chemical properties that, by exploiting a combination of a number of suitable soft interactions, can facilitate the transit through the biological barriers from the point of administration up to the site of drug action. As a result, the materials engineer has generated through the bottom up approach a variety of supramolecular nanocarriers for the encapsulation and controlled delivery of therapeutics which have revealed beneficial developments for stabilizing drug compounds, overcoming impediments to cellular and tissue uptake, and improving biodistribution of therapeutic compounds to target sites. Herein we present recent advances in liposome drug delivery by analyzing the main structural features of liposome nanocarriers which strongly influence their interaction in solution. More specifically, we will focus on the analysis of the relevant soft interactions involved in drug delivery processes which are responsible of main behaviour of soft nanocarriers in complex physiological fluids. Investigation of the interaction between liposomes at the molecular level can be considered an important platform for the modeling of the molecular recognition processes occurring between cells. Some relevant strategies to overcome the biological barriers during the drug delivery of the nanocarriers are presented which outline the main structure-properties relationships as well as their advantages (and drawbacks) in therapeutic and biomedical applications. Liposomes composed of surfactants, natural or synthetic (phospho)lipids, and block copolymer vesicles represent a versatile platform for the development of improved drug delivery therapies in a wide range of biomedical applications . The abiHerein, we analyze how the efficacy of liposomes depends on their physicochemical properties as well as on the nature of their components, on their size, lipid organization, and surface interactions . In addition, we aim to highlight the main liposome properties that strongly influence their colloidal stability during their employment in drug delivery applications and their interaction with cells. We also describe some strategies developed to overcome the limitations of the biological barriers, and how those approaches have been crucial for the development of advanced smart drug delivery approaches.Liposomes and vesicle-like nanocarriers are hollow spherical structures formed by the self-assembly of surfactants and natural and/or synthetic lipids or block copolymers in aqueous solution. Due to their loading capacity, good biocompatibility, and the facile inclusion of tissue-recognition ligands, liposomes are suitable soft nanocarriers for a wide number of therapeutic applications. Nanocarriers formed by the self-association of phospholipids are versatile prototypes for drug delivery applications ,7. Phosp, stirring, sonication, extrusion, microfluidification, or electroformation) 2+ to the cytoplasm and subsequent photoinduced interaction. This approach demonstrates that prominent tumour selectivity and therapeutic ability can be achieved by the successful combination of tumour specificity of folate-conjugated liposomes with the imaging and therapeutic potential rendered by [Ru(phen)2(dppz)]2+. Although several innovative configurations for targeted delivery of drugs have been developed in nanomedicine at a preclinical level, up to now few have been admitted in clinical trials, while none of them have been approved for the market yet, as we will see later -N,N,N-trimethylammonium methyl-sulfate (DOTAP) and DOPC lipids) employed in anti-angiogenesis, breast, and pancreatic cancers treatments. Finally, Lipoplatin and SPI-077, which are liposomal formulations for the Cisplatin chemotherapy drugs, are in clinical trials for the treatment of head/neck and lung cancers [Other important liposome nanocarriers include liposomal formulations for the  cancers ,111. Two cancers ,111.Liposome-based nanocarriers have been the longest-studied platform and have attracted considerable attention for their extensive applications in biotechnology, drug, and gene delivery. Recent developments in nanoscience stimulated the combination of the simple approaches of liposome technology with the advanced concept of supramolecular self-assembly for the development of more complex, hierarchical nanostructures ,112,113.Owing to a facile modulation of their size, hydrophobic/hydrophilic character, low toxicity, and biocompatibility, liposomal nanocarriers still represent one of the best platforms that continues to attract the renewed interest of researchers who, through combining basic principles of soft-matter assembly with the more advanced concepts of supramolecular (bio-)chemistry, work towards designing and developing complex theranostic nanocarriers ,114. TheWe presented recent advances in liposome based drug nanocarriers, by analyzing the relevant soft interactions involved in drug delivery processes which are responsible for the main behaviour of soft nanocarriers in complex physiological fluids. Relevant strategies to overcome the biological barriers during nanocarrier drug delivery are presented, outlining the main structure-properties relationship as well as their advantages (and drawbacks) in therapeutic and biomedical applications. The investigation of the soft interactions between liposomes at the molecular level can be considered to be an important framework for the modeling of the molecular recognition processes occurring between cells. These relatively weak interactions can be amplified by multiple binding at the liposome surface in multivalent complexes. While considerable research effort on the theoretical side is certainly necessary, further investigations of physico-chemical properties are required with different/complementary experimental methods in order to critically evaluate the stability of the nanocarriers in simulated environmental solutions which are close to the physiological fluid conditions.


Stroke patients commonly have impairments associated with reduction infunctionality. Among these impairments, the motor impairments are the mostprevalent. The functional profile of these patients living in the communitywho are users of the primary health-care services in Brazil has not yet beenestablishedTo describe the functional profile of stroke patients who are users of theprimary health-care services in Brazil, looking at one health-care unit inthe city of Belo Horizonte, Brazil.From medical records and home visits, data were collected regarding healthstatus, assistance received following the stroke, personal and environmentalcontextual factors, function and disability, organized according to theconceptual framework of the International Classification of Functioning,Disability and Health (ICF). Test and instruments commonly applied in theassessment of stroke patients were used.wereperceived as obstacles. The majority of the patients used thehealth-care unit to renew drug prescriptions, and did not receive anyinformation on stroke from health professionals, even though patientsbelieved it was important for patients to receive information and to provideclarifications.Demographic data from all stroke patients who were users of the health-careunit participated of this study. Most subjects presented with disabilities, aschanges in emotional function, muscle strength, and mobility, risks offalling during functional activities, negative self-perception of quality oflife, and perception of the environment factors Stroke patients who used primary health-care services in Brazil have chronicdisabilities and health needs that require continuous health attention fromrehabilitation professionals. All of these health needs should be consideredby health professionals to provide better management as part of the integralcare of stroke patients, as recommended by the clinical practice guidelinesfor stroke rehabilitation. Stroke patients who use the primary health-care services in Brazil showedseveral disabilities.Impairments in emotional and motor functions were common in thesepatients.Changes in mobility and risks of falling were common in these patients.Environmental factors were perceived as obstacle by these patients.Primary health-care services were primarily used by these patients to renewdrug prescriptions.,,,Stroke has a very high incidence and prevalence, and is one the main causes ofdisability worldwide,,.Clinical practice guidelines for stroke rehabilitation recommend the following:systematic follow-up of patients by a multiprofessional team, provision ofrehabilitation servicesIdentification of the health and function profile of the population of a certainregion may enable identifying the common needs of these patients. This allows for abetter orientation of the care offered to people living in the same area who havesimilar conditions, and the identification of possible improvement or modificationin the treatment strategies for this population,-In this context, there has been great interest in information related to the functionand health profile of Brazilian stroke patients. Although previous studies haveaimed to describe this profile, they either included convenience samples,A descriptive study was used in which all stroke patients who used the selectedhealth-care unit were invited to participate. The health-care unit was selected onthe basis of the criteria established by the Brazilian Ministry of Health (BMH), asfollows: a multi professional team responsible for a maximum of 4,000 persons in adefined area; composed of a doctor, a nurse, a nursing assistant, and health-carecommunity agents (HCAs); and with sufficient HCAs to cover 100% of the registeredpopulationAt the time of data collection, the selected health-care unit assisted a totalpopulation of 16,363 users including stroke patients, and had four familyhealth-care teams, in addition to a team from the Family Health-Care Support Centre,comprising a social worker, a physical educator, two physical therapists, one speechtherapist, one nutritionist, one psychologist, one psychiatrist, and oneoccupational therapist. One of the physical therapists in the Family Health-CareSupport Centre worked exclusively at the health-care unit.At least once a month, for 1 year, one of the members of the research groupparticipated in the meetings of the family health-care teams to identifypotential participants in the study, using the the following inclusion criteria:suffered a primary stroke or a clinical diagnosis of recurring stroke for >6months; lived in the community serviced by the health-care unit; used the SUSwhile being registered at the health-care unit, as verified by an employee ofthe health-care unit; age ≥20 years; and had freely signed the clarified consentterm approved by the research ethics committee of the Universidade Federal deMinas Gerais (UFMG), Belo Horizonte, MG, Brazil and the health-care secretariatof Belo Horizonte (state of Minas Gerais) (CAAE: 14038313.4.0000.5149). Allparticipants signed the consent term.All data were collected by an examiner, a previously trained physical therapist,with the aid of another examiner, between May 2013 and May 2014 within 2 days(i.e. data from each patient was collected over a period of 2 days). Initialdata were collected from the medical charts of the health-care unit; then,additional data were collected during a home visit. A previously elaboratedassessment sheet was used to register the following:Variables related to health conditions and the assistance received at thehealth-care unit: date of stroke occurrence, associated diseases, namesand number of drugs used, the services of the health-care unit used inthe last 6 months before the assessment date, and whether or not theparticipant had received any information or guidance from a professionalof the health-care unit about stroke management .Variables related to personal factors such age, sex, educationalbackground, socioeconomic status,,Variables related to environmental factors such as those surveyed in theMeasure of the Quality of the Environment (MQE) questionnaire, in aversion with 26 items translated and adapted for Brazilians withadequate measurement properties---Variables of function and disability, organized according to the ICF,including body structure and function, activity, and participationFor the ordinal and nominal categorical variables, absolute and relativefrequencies were calculated (%). For normally distributed quantitative variables, medians andstandard deviations (SDs) were calculated. For all other variables, the mediansand interquartile differences were calculated .The sample was comprised of post-stroke patients who used the health-care unitidentified by the family health-care teams and by the Family Health-Care SupportCentre. Forty-four patients were assessed, with a predominance of women 54.5%,n=24). The patients average age was 69.23 years  and the time sincethe stroke was 67 months . Owing to the different limitations ordisabilities presented by the participants, not all of them were able to undergo alltests and measurements . The number of participants assessedto obtain each end point is presented in the related tables -4..5%,n=24The features of the stroke episode , associated diseases, and number of drugs used are presentedin By using the 6 months before the data collection as a reference, it wasdetermined that the participants used the services of the health-care unitmainly to renew their drug prescriptions . Other services usedincluded appointments scheduled with a health-care professional ,routine checkups , and vaccinations .Most participants, 72.7% (n=32), reported never having received information aboutstroke and the care associated with this condition at the health-care unit, norduring home appointments with professionals from the health-care unit nor fromthe Family Health-Care Support Centre. However, 79.5% (n=35) of participantsstated that they believed it was important to receive information andclarifications in order to improve the health care they receive.“Critérios de ClassificaçãoEconômica da Associação Brasileira de Empresas dePesquisa-ABEP)The results related to personal factors are presented in Considering the environment as a facilitator or obstacle, the average scores were1.30  points for facilitating factors and –2.40  points forobstacles.The results for functioning and disability variables are provided in Concerning body structure and function variables, most participants testednegative for potential alteration of cognitive function (97.3%), positive forsuspected depression (61.1%), severe to moderate motor impairment (67%), lack ofchanges in muscular tonus (>55%), and, on average, muscles weakness on theparetic side .Concerning activity and participation variables, most participants showed goodself-perception of manual ability , were classified ashaving limited walking ability (88%), with the ability to improve natural gaitspeed, having a change in balance (51.43%), and functional mobility (54.16%),with indications of fall risks, and low perception of quality of life . These results aresummarized in This study determined the function, disability, and health profile of stroke patientswho were users of a primary health-care unit of the SUS located in the city of BeloHorizonte, Brazil. The participants showed chronic disabilities related toimpairments in body structure and function, such as changes in motor function,limitations in certain activities, changes in mobility, increased risk of fallingduring functional activities, and restriction of participation. In addition, theyperceived their environment to be an obstacle, which indicates requirement formultidisciplinary and continuous health care. For most participants, their healthcare was directed toward medical practices such as drug prescriptions, withoutaccess to practices related to health education and function.,,,,,,,,The sociodemographic characteristics of the participants in this study, such as thepredominance of women,,Following a stroke, patients usually develop motor impairments,One of the main impairments that occur after a stroke is hemiparesis. The assessedparticipants showed this alteration, characterized by a decrease in handgripstrength (HS) on the affected side. In stroke patients, the impairments in HS hasbeen associated with worse performances in activities of daily living,,Despite the importance of physical activity in preventing a worsening of their healthcondition, decreasing the complications caused by the chronicity of stroke,improving patient functioning, controlling the risk factors associated with a newoccurrence of stroke, and promoting health and functionality,,,For most patients, functional independence and community participation mean havingthe capacity for ambulation,Another measure used to assess mobility was the timed “up and go” (TUG) test,SSQOL-Brazil is the most recommended life quality instrument for assessing theparticipation of stroke patients,Body structure and function, activity, and participation are variables that interactwith each other and are associated with contextual factors, determining thefunctioning and/or disability of patients,,Most of the participants in this study (54.5%) used the services of the assignedhealth-care unit in the 6 months preceding the data collection, to renew theirmedical prescriptions. This result reflects the reality of the medicalization ofcare, in which the use of drugs is considered as the main therapeutic action by bothphysicians and patients. It also reflects the orientation of care to medicaldiagnosis only,,,-,Although the health-care unit selected for this study complied with the criteriaestablished by the MH, and had adequate resources and rehabilitation professionals,including a dedicated physical therapist from the Family Health-Care Support Centre,the results showed that the participants still had relevant disabilities and healthneeds that were not met. This poses the question of why the clinical practicerecommendations for the rehabilitation of stroke patients :11.The results of this study clearly showed the potential importance of the role ofhealth-care professionals in the functional recovery and systematic follow-up ofstroke patients. However, it is extremely important that the primary actions aredirected to preventing the risk factors for the development of stroke and otherdisabling chronic diseases, and to promoting health targeted toward the entirepopulation. The need for these actions are clearly highlighted in the basics ofprimary care, family health-care teams, and the Family Health-Care Support Centre,in addition to the list of goals of the “Guidelines for the Care of People withChronic Disease in Health-Care Networks and Priority Care Lines” of the MH,“contributing to the promotion of health in the population and preventing thedevelopment of chronic diseases and their complications”A relevant limitation of this study was the inclusion of participants from only onehealth-care unit. However, as this is the first study to describe the functionalprofile of patients considering the biopsychosocial model of a nonconveniencesample, the results add important information that can guide future studies andactions related to the function and health of stroke patients.Stroke patients who use the SUS primary health-care services, specifically onehealth-care unit in the city of Belo Horizonte, Brazil showed chronic disabilitiesrelated to impairments in body structure and function, limitations in activities,and restriction in participation. Their health care was directed toward medicationtreatment rather than practices related to health education, assistance inrecovering functionality, and promotion of health and functionality. The healthneeds presented by these patients should be taken into consideration by health-careprofessionals, in order to organize the continuous health care process for strokepatients, and by researchers, in order to develop future evidence based studies. Theresults of this study are expected to enable the discussion, planning, andimplementation of strategies for health care that involve follow-up and caredirected specifically to the stroke patient population, on the basis of currentevidence that complies with the recommendations in the guidelines of clinicalpractices and care of the MH. In this study, such strategies were not observed,despite including a sample from a population that attended a health-care unit withthe potential for providing such assistance. Furthermore, the results of this studyare also expected to reinforce the importance of disease-preventing andhealth-promoting actions directed toward all individuals, in order to decrease theoccurrence of chronic and debilitating diseases such as stroke.


Epigenetic modifications, which are programmed across the individual’s lifespan by the genetic background but also modulated by environmental and lifestyle factors, are widely studied to identify biomarkers of human aging. Indeed, Garagnani et al. identified three genes whose methylation level strongly correlates with age . SubsequOn the other hand, most of the scientists involved with research on aging are willing to identify epigenetic modifications correlated with biological rather than with chronological age. Such markers may be important firstly because the definition of biological age in the elderly may be much more useful than chronological age to identify the subjects needing  care; secondly, because the identification of genes the methylation of which is correlated with biological aging may give important clues on the aging process and, possibly, on how to modulate it. Many hints suggest that these markers are likely to exist. For instance, global methylation showed to be correlated with biological and not with chronological age .Ribosomal RNA (rRNA) genes consist of highly evolutionary conserved tandem and clusters of units within nucleolar organizer regions, distributed, in humans, on the short arms of acrocentric chromosomes. The expression of rRNA genes is regulated during different stages of lifetime by several factors, including nutrients, transcription factors and epigenetic marks as well ,5. PreviWe evaluated the methylation levels of 19 CpGs located within the upstream control element (UCE) and 8 CpGs in the core promoter of rDNA in three groups of unrelated humans, each including subjects of different ages. For each subject the data regarding the cognitive, functional, and psychological status were collected and analysed. In addition, a follow up study allowed us to consider the vital status after nine years. Although a slight association between the methylation levels of some of the CpGs analysed and chronological age was observed, the methylation status of rRNA promoter appeared highly correlated with the cognitive performance and the survival chance. In fact, a significant negative correlation between the methylation levels of a specific CpG site (CpG_5) and the results of two test of episodic memory, that consist in the immediate and delayed recall of a 12-word list , was observed. In addition, subjects of 60-89 years old and displaying higher methylation levels at CpG_5 have a mortality risk increased of about two fold with respect to age-matched subjects with low methylation levels in a 9-year follow-up period . The results were consistently replicated in the three independent population samples, making these results quite reliable.Being the rDNA a highly evolutionary conserved region, we extended the characterization of its methylation levels to the homologous region of rats by analysing 9 CpGs in DNA samples extracted from blood, heart, liver, kidney, and testis of 3, 28, 40, 88, and 96 weeks old. A linear regression analysis of the methylation levels as a function of age  revealed that, regardless of the tissue type, the methylation of the rRNA promoter region exhibits a progressive and general increase, with the most important variation occurring in blood, where an about tenfold increase has been observed from weaning to old age.The analysis of rRNA in tissues of both humans and rats with different levels of methylation, confirmed the inverse correlation between the methylation and the transcription levels of rDNA and, then, the suppressive role of DNA methylation in silencing gene expression.These results, provide an interesting biomarker of the biological aging but they are also useful to understanding one of the most important age related process, that is the (in some cases dramatic) decline in the overall protein synthesis, which may have important effects, such as sarcopenia. If this decline has so far being justified as the result of a reduced translation frequency, our findings demonstrate an epigenetically-driven negative regulation of ribosomal RNA gene expression.


Schwann cells are the glial cells of the peripheral nervous system (PNS). They insulate axons by forming a specialized extension of plasma membrane called the myelin sheath. The formation of myelin is essential for the rapid saltatory propagation of action potentials and to maintain the integrity of axons. Although both axonal and extracellular matrix (ECM) signals are necessary for myelination to occur, the cellular and molecular mechanisms regulating myelination continue to be elucidated. Schwann cells in peripheral nerves are physiologically exposed to mechanical stresses , occurring during development, adulthood and injuries. In addition, there is a growing body of evidences that Schwann cells are sensitive to the stiffness of their environment. In this review, we detail the mechanical constraints of Schwann cells and peripheral nerves. We explore the regulation of Schwann cell signaling pathways in response to mechanical stimulation. Finally, we provide a comprehensive overview of the experimental studies addressing the mechanobiology of Schwann cells. Understanding which mechanical properties can interfere with the cellular and molecular biology of Schwann cell during development, myelination and following injuries opens new insights in the regulation of PNS development and treatment approaches in peripheral neuropathies. Peripheral nerves are remarkable tissues of tremendous elasticity that propagate action potentials despite developmental growth , Schwann cells (SCs) produce the myelin sheath. They are among the largest known cells, with 0.6 mmPeripheral nerves and SCs have adapted to sustain constant mechanical constraints. In peripheral nerves, myelinated fibers are surrounded by 6–15 layers of connective tissues . In this disease caused by the haploinsufficency of Mechanobiology refers to how physical and mechanical signals can be sensed by organs, tissues or cells and are converted in specific cellular responses. Many fundamental aspects of cell behavior depend on mechanobiology, including adhesion, spreading, migration, gene expression and cell-cell interactions in multiple cell-types , glycoproteins and numerous proteoglycans. In addition, like epithelial cells, SCs secrete a basal lamina, an ECM component composed of laminin and collagen networks cross-linked with proteoglycans and nidogens, which links the extracellular environment to the plasma membrane of SCs (Bunge et al., Major adhesion complexes are formed by CAMs and are implicated at various stages of SC development (Poliak and Peles, Integrins are central to mechanosensation as they are connected both to the ECM and the actomyosin cytoskeleton, in clusters called focal adhesions. The structure of focal adhesions is complex and constitutes of numerous proteins. Thus, it is difficult to integrate the contribution of each one during mechanosensation. However, possible mechanically-induced stimulation of the focal adhesion complexes, could regulate important signaling pathways for SC biology, (i.e., downstream of FAK or ILK; Grove et al., Although incompletely understood, the responses of the actomyosin cytoskeleton together with the activation of focal adhesion signaling induce several mechanotransducing pathways. The most notables are YAP and TAZ, two transcriptional activators of the Hippo pathway. Indeed, several works have shown that YAP can be activated through the Hippo pathway in SCs by Crb/Amolt proteins (Colciago et al., Although much emphasis has been placed on cell adhesion complexes as force sensors, mechanosensitive ion channels contribute both to mechanosensation and transduction. Over the past few years, a number of advances have been made through the identification of new ion channels, expressed in nearly all cell types, such as mechanosensitive potassium channels and Piezo ion channels (Coste et al., in vivo environment of peripheral nerves. During adult life, peripheral nerves are constantly subjected to mechanical stresses. In addition, the elasticity of peripheral nerves varies greatly along development, from 6 kPa after birth, when myelination is starting, to 50 kPa in adult nerves (Urbanski et al., Experimental approaches to study SC mechanobiology need to account for a variety of factors to model accurately the in vivo confirmed that both mechanotransducers are active in SCs during axon-SC recognition, while SCs are myelinating and after completion of myelination (Poitelon et al., The first reports that studied YAP/TAZ in SCs in vitro appears to promote SC proliferation and prevent SC differentiation (Zhang et al., In vivo application of ultrasound after axonotmesis, also showed that SCs appeared to be affected, promoting an acceleration of peripheral nerve regeneration (Chang and Hsu, An exceptional quality of SCs is their ability to dedifferentiate from myelinated SCs to become repair SCs. After neurotmesis or axonotmesis, repair SCs are able to remyelinate newly regenerated axons, but most importantly, they provide the necessary tracks for axon guidance and support axonal regeneration. The function of repair SCs is highly considered in peripheral nerves injuries, but also in spinal cord injuries (Xu et al., SCs are poised to be the target of non-invasive mechanical therapies. Mechanically stimulating SCs could be of interest in traumatic neuropathies and demyelinating peripheral neuropathies, such as Charcot-Marie-Tooth disease, chronic inflammatory demyelinating polyradiculoneuropathy or Guillain-Barré syndrome. Yet, there is first a critical need to better understand SC mechanobiology. Determining the identity of the SC mechanosensors and mechanotransducers will define the signaling pathways and biochemical targets downstream of mechanical stress and help establish multidisciplinary approaches toward remyelination. Such research will also have the potential to be extended to strategies at reducing aberrant proliferation of SCs occurring in Schwannomas or neurofibromas.SB and YP wrote the manuscript; SB, KLZ and YP revised the manuscript; YP created the figures. All authors approved the final version of the manuscript 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.


An increase in the accuracy of identification of Activities of Daily Living (ADL) is very important for different goals of Enhanced Living Environments and for Ambient Assisted Living (AAL) tasks. This increase may be achieved through identification of the surrounding environment. Although this is usually used to identify the location, ADL recognition can be improved with the identification of the sound in that particular environment. This paper reviews audio fingerprinting techniques that can be used with the acoustic data acquired from mobile devices. A comprehensive literature search was conducted in order to identify relevant English language works aimed at the identification of the environment of ADLs using data acquired with mobile devices, published between 2002 and 2017. In total, 40 studies were analyzed and selected from 115 citations. The results highlight several audio fingerprinting techniques, including Modified discrete cosine transform (MDCT), Mel-frequency cepstrum coefficients (MFCC), Principal Component Analysis (PCA), Fast Fourier Transform (FFT), Gaussian mixture models (GMM), likelihood estimation, logarithmic moduled complex lapped transform (LMCLT), support vector machine (SVM), constant Q transform (CQT), symmetric pairwise boosting (SPB), Philips robust hash (PRH), linear discriminant analysis (LDA) and discrete cosine transform (DCT). The identification of Activities of Daily Living (ADL)  is of utDespite the increasing complexity of ADL identification systems, the recognition of the surrounding environment is limited because of the restrictions of some location sensors. For instance, Global Positioning System (GPS) sensors, can only be reliably and accurately used in outdoor scenarios. Likewise, proximity sensors, radar sensors, Passive Infra-Red (PIR) sensors and alike require significant installation effort, thus are not widely used in real scenarios which require ADL identification. As proposed in previous works ,10,11, aMost mobile devices are equipped with a microphone that can capture an acoustic signal. This signal can be processed using audio fingerprinting techniques, allowing the system to find a match between the collected signal and a database of well-known audio fingerprints. This might facilitate an increase in the accuracy of recognition of the environment where ADLs are performed.Several methods may be used to carry out audio fingerprinting, performing the pre-processing of the acoustic data ), extracting relevant features, and after that, obtaining a classification or recognition ).This review summarizes the existing methods in the literature related to audio fingerprinting techniques for the application in a system that uses mobile technology for the recognition of the environment. While acknowledging that the methods here presented are very diverse and have been tested with different data sets and different feature extraction techniques, in order to estimate which method may provide better results in a mobile computational device, this paper also presents a comparison between the different methods and features.The remainder of this paper is organized as follows: The primary questions of this review were as follows: (RQ1) What is audio fingerprinting? (RQ2) Which audio fingerprinting techniques are useful to identify the environment of daily activities? (RQ3) Which are the audio fingerprinting techniques feasible for their use in mobile devices?Studies assessing ADLs using audio fingerprinting techniques were included in this review if they met the following criteria: (1) audio fingerprinting techniques adapted to mobile devices; (2) audio fingerprinting techniques used for the detection of the environment of ADL; (3) using mobile devices; (4) the accuracies of the audio fingerprinting techniques presented are reported; (5) were published between 2002 and 2017; and (6) were written in English.The team searched for studies meeting the inclusion criteria in the following electronic databases: IEEE Xplore, and ACM Digital Library. Every study was independently evaluated by eight reviewers , and its suitability was determined with the agreement of all parties. The studies were examined to identify the characteristics of audio fingerprint and its suitability for application with mobile devices for the identification of ADL.The following data was extracted from the studies and tabulated see : year ofAs illustrated in We suggest that interested readers refer to the original cited works to find relevant information about the details of the methods analyzed in this review. In , the autIn , severalTsai et al.  presenteAnother audio feature named local energy centroid (LEC) is used in  to obtaiIn , the autAnother algorithm is presented in  that conIn , the audIn , the autIn  is propoThe authors of  proposedThe authors of  presenteIn , the autThe authors of  proposedThe authors of  presentsIn  an audioThe authors of  presenteIn , the autThe authors of  created The authors of  exploredThe authors of  created The authors of  presenteIn , the autThe authors of  proposedThe work presented in  reviews In , an audiThe authors of  proposedThe authors of  proposedThe authors of  presenteThe authors of  implemenIn , the autIn , the autThe authors of  proposedThe authors of  used a sIn , the autThe authors of  created In , the autIn , the autThis review confirms the findings of previous studies related to the use of audio fingerprinting techniques for identification of the environment related to the different ADLs. We consider that many of the reviewed works raise important issues regarding the concept of Open Science, including, but not limited to, Reproducibility and Verifiability of the research results, and Comparability of similar research. Many of them were evaluated on unpublished data and did not publish their source code, although when commercial solutions are in perspective, a necessary degree of confidentiality is understandable. Regarding validation and comparability, only six studies used raw data available online or published its research data online. Likewise, only three studies presented some parts of the code used of the experiments. In addition, the studies that used data that is now publicly available, did not publish the research source code, making the validation of the results and further comparative research an impossible task. Therefore, we suggest to the audio fingerprinting community to become better at sharing raw data and algorithms, so as to be able to recreate and evaluate the soundness of previous studies.Nevertheless, assuming the results of the presented research studies are comparable, For On the other hand, as verified in Taking For a particular use, the methods to be implemented must be chosen according to their complexity, the computational power of the use case scenario, and to the purpose of its intended use. This review is focused on the use of mobile devices, but only three of the reviewed works argue that they use methods that need low resources see . Only 19According to the results of this review, the use of the mobile devices for the application of audio fingerprinting techniques is limited, because of the restrictions these devices impose, i.e., low power processing and battery capacity. Thus, only 10 of the analyzed studies utilize mobile devices with local processing or server-side processing of the data acquired from the mobile devices. In the case of the server-side processing, the use of the mobile devices implies a constant and stable network connection, which is not a trivial requirement both from technical perspective, but also because of battery life implications. To some extent, the using Fog and Mist Computing paradigms could overcome the challenges of the client-server architectures. The creation of lightweight techniques should be explored, as they could be executed on mobile devices . The models could be recalibrated offline on the server occasionally, and then, as pre-trained models to be seamlessly redeployed on mobile devices.In conclusion, only one of the reviewed studies  can achi(RQ1) the audio fingerprinting is defined as the ability to recognize the scenario in which a given audio was collected and involved in, based on various methods.(RQ2) Several techniques have been applied to implement audio fingerprinting methods, including Fast Fourier Transform (FFT). Support Vector Machine (SVM), QUery Context (QUC)-tree, spectral subband centroid (SSC), Streaming Audio Fingerprinting (SAF), Human Auditory System (HAS), Gaussian mixture models (GMM) modelling, likelihood estimation, linear discriminant analysis (LDA), Compressive Sampling (CS) theory, Philips robust hash (PRH), Asymmetric Fingerprint Matching, and TO-Combo-SAD (Threshold Optimized Combo SAD). These techniques yield high accuracy, and the use of mobile devices does not influence the predictive performance, allowing the use of these techniques anywhere, anytime.(RQ3) All of the methods presented in RQ2 can be implemented on mobile devices, but the methods that require lower computational resources are FFT with the CUFFT library, divide and locate (DAL) audio fingerprint method, and sub-fingerprint masking based on the predominant pitch extraction.This review identified and described the methodologies used for audio fingerprinting that can be applied to mobile technologies. Forty-seven studies were examined and the main findings are summarized as follows:In addition, this review highlights the application of audio fingerprinting techniques on mobile or other devices with limited computational and battery resources. Some limitations of this review should be mentioned. First, the authors chose to exclude studies that are not focused on audio fingerprinting techniques. Second, the studies that do not utilize mobile devices have been excluded. These exclusions were performed with the analysis of the abstract and then, the full text of the papers. Finally, only English-language publications were included.Based on the analysis, we conclude that the most used methods are undifferentiated methods, two level search algorithms, likelihood estimation, Principal Component Analysis (PCA), and Hamming distances between each fingerprint. The conclusion is that the use of statistical methods reports results with an accuracy higher than 80%. Furthermore, the most used features are Fast Fourier Transform (FFT), Thresholding, normalized spectral subband centroid (SSC), Mel-frequency cepstrum coefficients (MFCC), maximum, local peaks and landmarks, Shannon entropy, Rényi entropy, MPEG-7 descriptors, Spectral bandwidth, Spectral flatness measure. Modified discrete cosine transform (MDCT), Constant Q Transform (CQT), Short-time Fourier transform (STFT), average, and minimum, which also result in accuracies greater than 80%.As future work, the extraction of features based on audio fingerprinting will be implemented in order to develop a system for the recognition of ADLs and their environments, presented in ,10,11. A