Introduction: We have reported that a developed lower-positioned transverse ligament between the superior-medial orbital rim and the lateral orbital rim on the lateral horn in the lower orbital fat space antagonizes eyelid opening and folding in certain Japanese to produce narrow eye, no visible superior palpebral crease, and full eyelid. In this study, we confirmed relationship between development of the lower-positioned transverse ligament and presence of the superior palpebral crease. Methods: We evaluated whether (1) digital immobilization of eyebrow movement during eyelid opening and (2) a developed lower-positioned transverse ligament could classify Japanese subjects as being with or without visible superior palpebral crease. Results: Digital immobilization of eyebrow movement restricted eyelid opening in all subjects without visible superior palpebral crease but did not restrict in any subject with visible superior palpebral crease. Macroscopic and microscopic evidence revealed that the lower-positioned transverse ligament behind the lower orbital septum in subjects without visible superior palpebral crease was significantly more developed than that in subjects with visible superior palpebral crease. Conclusions: Since a developed lower-positioned transverse ligament antagonizes opening and folding of the anterior lamella of the upper eyelid in subjects without visible superior palpebral crease, these individuals open their eyelids by lifting the eyebrow with the anterior lamella and the lower-positioned transverse ligament owing to increased tonic contraction of the frontalis muscle, in addition to the retractile force of the levator aponeurotic expansions. In subjects with visible superior palpebral crease, the undeveloped lower-positioned transverse ligament does not antagonize opening and folding of the anterior lamella, and so they open their eyelids by folding the anterior lamella on the superior palpebral crease via the retractile force of the levator aponeurotic expansions. Since the absence of visible SPC indicates the anterior lamella of the upper eyelid to be unfoldable and require lifting of the eyebrow for maintenance of an adequate visual field, we considered this to be the key distinguishing trait of descendants of the Yayoi migrants in this study. In contrast, we presumed the presence of visible natural SPC to specifically indicate the anterior lamella of the upper eyelid as being foldable on the SPC without lifting the eyebrow for maintenance of an adequate visual field in Japanese stemming from Jomon native ancestry.Digital immobilization of eyebrow movement during eyelid opening from closed eyelid to primary gaze counteracts the contraction of the frontalis muscle to lift the eyebrow with the anterior lamella of the upper eyelid and is commonly used to exclude involvement of eyebrow lifting when impaired levator function is evaluated in congenital blepharoptosis c. This tTo verify our hypotheses, we evaluated whether (1) digital immobilization of eyebrow movement during eyelid opening and (2) a developed LTL that restricts eyelid opening and folding could classify Japanese subjects as being with or without visible SPC.We enrolled 66 Japanese subjects . Reasons for the surgery consisted of 10 blepharoplasties, 18 bilateral acquired blepharoptoses, and 5 unilateral congenital blepharoptoses in 33 subjects without visible SPC, and 8 blepharoplasties and 25 bilateral acquired blepharoptoses in 33 subjects with visible natural SPC. The nonptotic eyelids in 5 subjects with unilateral blepharoptosis were evaluated.We first evaluated whether digital immobilization of eyebrow movement by pressing on the anterior surface of the supraorbital margin, during movement from loosely closed eyelids following tight eyelid closure with relaxing the frontalis muscle2 square scale  and the size of retractors or forceps   was significantly larger than that in the visible SPC group (0.88 ± 0.45 mm) ( 0.0136) .Histological examination confirmed our macroscopic findings, whereby collagen fibers of the LTL in subjects without visible SPC a appeareMacro- and microscopic evidence obtained in the current study demonstrated that whereas subjects without visible SPC had a developed LTL behind the lower orbital septum in terms of not only the width of the lowest LTL and the number of LTLs a, those On the basis of our findings, it appears that variations in the LTL may determine the features of Yayoi migrants or the Jomon natives in the Japanese. A developed LTL between the superior-medial orbital rim and the lateral orbital rim on the lateral horn behind the lower orbital septum not only restricted eyelid opening and folding but also kept the orbital fat in a lower position. Subsequently, narrow eye, no visible SPC, and fullness of the upper eyelid ensued as specific features of the Yayoi migrants. They appeared to open the eyelid by not only the eyelid retraction but also the upward movement of the lateral canthus. On the contrary, an undeveloped LTL did not restrict eyelid opening and folding, resulting in the wide eye and visible SPC that are distinctive of the Jomon natives. Undeveloped LTL might allow the orbital fat to sink into the upper orbit like the Occidental eyelid . In the In subjects without visible SPC, because the developed LTL antagonizes opening and folding of the anterior lamella of the upper eyelid, these people open their eyelids not only by the retractile force of the levator aponeurotic expansions but also by lifting the eyebrow with the anterior lamella and developed LTL owing to increased tonic contraction of the frontalis muscle. Since their eyebrows had been lifted in normal primary gaze, the digital immobilization test in this study was performed during movement from loosely closed eyelids following tight eyelid closure with relaxing the frontalis muscle to eyelid opening for primary gaze. In subjects with visible SPC, because the undeveloped LTL did not antagonize opening and folding of the anterior lamella, they were able to open their eyelids by folding the anterior lamella on the SPC via the simple retractile force of the levator aponeurotic expansions.Our subjects who had no visible SPC and developed LTL may correspond to the Yayoi migrants with eyelid structures for cold tolerance. Because they always lift the eyebrows in primary gaze, their supraorbital margin may be high-positioned and round as a result of the lifting force by tonic contraction of the frontalis muscle, which mechanically presses on the supraorbital margin a. In conThe development of LTL restricts eyelid opening and folding and distinguishes Japanese as being with or without visible SPC, or rather being of Jomon native or Yayoi migrant ancestry. To compensate for the restriction of eyelid opening and folding in Japanese without SPC, tonic reflex contraction of the frontalis muscle to persistently lift the eyebrow with the anterior lamella of the upper eyelid and thick LTL serves as another eyelid-opening mechanism. From a surgical viewpoint, both the excision of LTLs behind the orbital septum and the creation of the functional SPC, on which the anterior lamella is folded, may reduce both tonic reflex contraction of the frontalis muscle and the eyebrow height. Further studies are needed on the differences in supraorbital margin shape between Japanese subjects without and with visible SPC, as well as on the relationship between LTL development and expansion of the levator aponeurosis to the pretarsal skin, both of which contribute to the formation of SPC.


Significant differences were observed between the glottic areas of the excised larynges in the initial state and following modified frontolateral partial laryngectomy with the cartilage closed. However, no significant differences were observed between the glottic areas of the excised larynx in the initial state and following modified frontolateral partial laryngectomy with the cartilage open. The glottic area of the larynges in vivo in the initial state and following right chordectomy via laryngofissure were not observed to be significantly different. Furthermore, no significant differences were observed between the glottic areas of the larynges in vivo in the initial state and following modified frontolateral partial laryngectomy without tracheotomy. In conclusion, modified frontolateral partial laryngectomy without tracheotomy is a feasible and efficacious means of eradicating early and selected invasive carcinomas of the larynx, which is supported by animal experiments.The aim of this study was to validate the feasibility of modified frontolateral partial laryngectomy without tracheotomy using animal experiments. The glottic area before and after surgery of 6 excised canine larynges and 10 canine larynges  Male and female mongrel dogs of various ages, weighing 9–15 kg were used for the experiment. A total of 16 dogs were divided into 2 groups denoted The dogs were sacrificed and their larynges were excised for anatomical study and placed in appropriate individual plastic vessels. The supraglottic tissue was removed to expose the true vocal folds. Stepwise procedures were performed and, after each step, the vocal folds were photographed from a superior perspective using a grid placed over the vocal folds to measure the glottal area.Photographic images of the glottis were captured prior to performing any procedures on the larynx. The thyroid laminae were then incised vertically 2–3 mm posterior to the anterior commissure and removed. In all larynges, ∼20% of the laryngeal cavity was excised. The incisal margins of the vocal folds were sutured to the ipsilateral thyroid perichondrium and the glottis was then photographed. Finally, the incisal edges of the thyroid laminae were sutured together to reconstruct the anterior commissure. The glottis was then photographed for the third time.The laryngeal cavity was isolated and adequately exposed. The epiglottis was captured and pulled forward and upward after the mucosa of the epiglottic vallecula was cut open. The mucosa of the lateral pharyngeal walls was cut to pull the whole larynx out. Photographic images of the glottis were then captured at the maximum phase to measure the maximum phase area of the untreated glottis. Right cordectomy was performed via laryngofissure and the incisal margins of the thyroid cartilage were sutured together; the glottis was then photographed again at maximum phase. Subsequently, modified frontolateral partial laryngectomy was performed according to the procedure described previously ,6 and thex vivo group were processed using AutoCAD2004 image software and the following data were obtained: i) area of the untreated glottis of the ex vivo larynx; ii) area of the glottis of the ex vivo larynx with the incisal margins of the thyroid cartilage sutured following frontolateral partial laryngectomy; and iii) area of the glottis of the ex vivo larynx following frontolateral partial laryngectomy with the incisal margins of the anterior commissure sutured to the homolateral perichondrium of the thyroid cartilage.Images of the in vivo group were processed using AutoCAD2004 image software and the following data were obtained: i) the maximum phase area of the untreated glottis of the in vivo larynx; ii) the maximum phase area of the glottis of the in vivo larynx following right cordectomy via laryngofissure; and iii) the maximum phase area of the glottis of the in vivo larynx following modified frontolateral partial laryngectomy.Images of the ex vivo experiments were compared by Student’s t-test, since the data were normally distributed. The data of the in vivo group was compared using ANOVA and Newman Keuls test.The data of ex vivo glottises were stationary and the areas were relatively constant without the effect of respiration and thus simple to measure. The distance and angle of the scales may greatly affect measurements of the glottic area. Therefore, in the present study the scales were placed strictly on the same plane as the vocal cords and photographed at a distance of 30 cm to provide accurate measurements.The The processing of all images was completed using AutoCAD2004 image software. An image of the primitive glottis is shown in ex vivo group are shown in ex vivo group, attempts were made to confirm whether changing the shape of the glottis (with the front part resected) to a trapezoid by suturing the sternohyoid muscle to the laryngeal lumen, significantly decreases the area of the glottis. The statistical data above show that area of the glottis was enlarged in certain cases by changing its shape to a trapezoid.The experimental results of the A glottis following modified frontolateral partial laryngectomy is shown in in vivo group are shown in The experimental results of the Conventionally, laryngofissure and cordectomy have been the primary means of eradicating early and selected invasive glottic squamous cell carcinomas . A numbeet al(et al(Tracheotomy is routinely performed in patients undergoing partial laryngectomy due to the high risk of postoperative dyspnea originating from a narrowed laryngeal lumen or laryngeal edema. Postoperative care for the tracheotomy is burdensome for the patient and provider and is associated with prolonged hospitalization and significant morbidity. Even temporary tracheotomy is associated with increased complication rates, suggesting that prophylactic tracheotomy at the time of surgery is less than ideal. Although Muscatello et al and Wolfet al have rep al(et al reported al(et al.The feasibility and effectiveness of the modified frontolateral partial laryngectomy are functions of the anatomical association between the laryngeal lumen and its surrounding structures. The interior of the larynx in cross-section is triangular due to the contour of the thyroid cartilage. Geometrically, the area of a triangle is less than that of a trapezoid or rectangle of equivalent base and height. In the present approach, we aimed to transform the natural triangular contour into a trapezoid to achieve a greater cross-sectional area. To achieve this, the sternohyoid muscle was sutured to the laryngeal lumen and the thyroid lamina was vertically incised, resulting in abduction of the anterior part of the thyroid cartilage. In addition, the muscular fascia was retroflexed and sutured to the contra-lateral side, bringing the larynx into the desired trapezoidal or rectangular conformation. To expand the breadth of the laryngeal cavity, the sternohyoid fascia was reverted, covering the anterior larynx and completing the ladder-shaped lumen. Although the anteroposterior diameter of the neolarynx was decreased, the cross-sectional area was sufficiently enlarged to allow normal respiration, even in the absence of an endotracheal tube.In the present study, on the basis of clinical study, animal model establishment and computer technology, it was demonstrated that expanding the anterior end of the laryngeal cavity and changing the shape from the original triangle into a trapezoid with equal bottom length and height was able to considerably increase the effective respiratory area. This result demonstrates the theoretical basis of modified frontolateral partial laryngectomy and validates its efficacy and feasibility.In conclusion, these animal experiments demonstrated the feasibility of modified frontolateral partial laryngectomy without tracheotomy. The present data indicate that it is a safe and reliable method for excising the anterior 20% of the vocal cord and thyroid cartilage without the necessity of tracheotomy. This procedure, therefore, represents a new, less invasive technique for the treatment of glottic squamous cell carcinoma.


Thyone, and the horseshoe crab Limulus. Any realistic future theories for filopodium stability are likely to rely on an accurate treatment of such steric effects, as analysed in this work.Filopodia are long, thin protrusions formed when bundles of fibers grow outwardly from a cell surface while remaining closed in a membrane tube. We study the subtle issue of the mechanical stability of such filopodia and how this depends on the deformation of the membrane that arises when the fiber bundle adopts a helical configuration. We calculate the ground state conformation of such filopodia, taking into account the steric interaction between the membrane and the enclosed semiflexible fiber bundle. For typical filopodia we find that a minimum number of fibers is required for filopodium stability. Our calculation elucidates how experimentally observed filopodia can obviate the classical Euler buckling condition and remain stable up to several tens of  ThyoneFilopodia are formed by the growth of bundles of biological fibers outwards from a biological cell surface that remain enclosed in a membrane tube. They are implicated in many processes vital to life, including sensing and motility In this work, we investigate the stability of filopodia, which involves the subtle interplay between a fluid membrane tube, and an enclosed semiflexible fiber bundle. The simplest physical picture of filopodia is one in which the membrane tube produces a longitudinal force and a transverse force on the enclosed fiber bundle. The longitudinal membrane force acts to try and shorten the end-to-end distance of the fiber bundle, while the transverse force is required to maintain fiber bundle enclosure. The energetics required to investigate the stability of filopodia thus necessitates us to consider the elasticity of both the membrane tube as well as the fiber bundle, subject to the constraint that the polymer bundle must remain enclosed by the membrane tube. The energetic ground state conformations of filopodia thus necessitate a careful theoretical treatment of both elastic and steric considerations. For example, one might ask if a filopodium ever buckles, or perhaps more intriguingly does the region of filopodium buckling exist in some small corner of a complicated energetic phase diagram, well outside the range of physiologically relevant parameters?A naive Euler buckling type estimate for the stability of filopodia that remained perfectly cylindrical, despite simulation snapshot evidence to the contrary In Typical experimental parameter values for biological membranes range from The ground-state configuration of a filopodium is determined by finding the minimum of the total energy per unit length Shown in We have calculated theoretically the ground state configurations of filopodia, and found ‘islands of stability’ for typical filopodia within physiologically relevant parameters. Our calculation elucidates how experimentally observed filopodia can obviate the classical Euler buckling condition and remain stable up to several tens of The work presented here differs from that presented in ThyoneLimulusExperimental observation of the results obtained in this work for the helical-like deformations of enclosing membrane tubes in filopodia would presumably be difficult. However, such helical membrane conformations are qualitatively supported by the snapshot pictures of simulation work carried out in We adopt a ground state approximation in which thermal fluctuations are assumed to be small. Since the amplitude of these fluctuations is small at the high tensions of interest to us here, perhaps a few nm or less without an enclosed stiff polymer has also recently been considered in Analogous steric constraints to those considered here are likely to be of relevance in other similar and important biological contexts, such as the packaging of semiflexible DNA in viral capsids, for example In order to describe the filament bundle, inside filopodia, we study the semi-flexible polymer Hamiltonian Any realistic deformation of the polymer must be able to pack a given contour length We have chosen to parameterise the polymer in terms of the In this way we can easily translate between the arc-length The polymer part In order to describe deformations of our membrane tube, we use:We parameterise our membrane given by The membrane contribution By inspection of Eqs. (2) and (6), we can see that the steric condition we need to apply to the membrane in order to guarantee polymer enclosure is given by:In order to find the ground-state configuration of our filopodium, we need to find the conformation which minimises the total energy Putting the result of Eq. (10) into By inspection of the Fourier coefficients Utilising the inextensibilty conditions outlined above, we can easily re-write


Here we propose a possible role of chaotic dynamics in the generation of two distinctive rhythm patterns of local field potential of the hippocampus; namely the theta rhythm and large irregular activity (LIA). The basic idea is that the rapid alternation of the state between theta rhythm and LIA can be described as bifurcation of the attractor between limit cycle and chaos.It is well known that the hippocampus has two distinctive states described by the characteristic activity of the local field potential, the theta rhythm and LIA. The theta rhythm is a highly periodic activity thought to play an important role in learning and retrieving process, whereas LIA is a irregular field activity with sharp ripple complex, which is thought to play an important role in the consolidation process of old memories. However, the underlying mechanism of realizing these two distinctive field oscillations embedded in the same network remains unknown. On the other hand, Katori et al. reported that transitions between synchronous and asynchronous oscillatory state can be realized with gap junction-coupled simple conductance-based model neurons . Further


Acute aortic dissection is one of the most dreaded clinical conditions during pregnancy. The limited experience reported in the literature does not allow the determination of guidelines for surgical management of aortic dissection in these cases. In this case presentation we successfully treated a 27-year-old woman with Marfan syndrome in the 36th week of pregnancy with acute type A aortic dissection, who underwent aortic repair with the fetus remaining in situ.After a review of the data reported in the literature, we present this case of acute aortic dissection in a pregnancy woman with Marfan syndrome and discuss some new perspective of surgical management and maternal-fetal outcome considering the peculiarities of this disease's manifestation.Surgery for acute aortic dissection during pregnancy has been described by other investigators and, in most cases; the fetal outcome was relatively poor. The review of the data suggests that, in cases of fetal maturity, Cesarean section should be performed before or in combination with aortic repair. However, the appropriate surgical management with an immature fetus in utero remains unclear. The cardiopulmonary bypass (CPB) with the fetus in utero may itself represent a risk factor, as already demonstrated by studies that hypothermia contributes for a worse prognosis. We present a case of a 36th weeks pregnancy patient with Marfan syndrome who had acute type A Aortic dissection and underwent operative repair with modified Bentall de Bono technique with the fetus remaining in situ, where during CPB was used high-flow, high pressure and mild hypothermia. The maternal-fetal outcome was excellent and an elective Cesarean of the fetus could be done one week later the aortic repair when the clinical conditions of the mother was completely stabilized and the fetus presented better maturity.Despite the controversies of surgical management of aortic dissection during pregnancy because the lack of data, it seems to be possible as established in this case presentation, with the development of CPB and surgical techniques, perform the aortic repair with the fetus remaining in situ.


Maintenance of testicular temperature below body temperature is essential for the process of spermatogenesis. This process of thermoregulation is mainly achieved by testicular veins through pampiniform venous plexus of the testis by absorbing the heat conveyed by the testicular arteries. However, this mechanism of thermoregulation may be hampered if an abnormal communication exists between the testicular vessels. We report herewith a rare case of arteriovenous communication between testicular artery and testicular vein on left side. The calibre of the communicating vessel was almost similar to left testicular artery. Such abnormal communication may obstruct the flow of blood in the vein by causing impairment in the perfusion pressure with the eventual high risk of varicocele. Testicular arteries are long, slender vessels originating from abdominal aorta slightly below the origin of renal arteries. Testicular arteries reach the deep inguinal ring and pass through spermatic cord in the inguinal canal and finally enter the scrotum to supply testis . VenulesMaintaining the suitable temperature for the crucial stages of spermatogenesis is priority of the body. The specialised venous network in the form of pampiniform plexus of the testicular veins allows countercurrent heat exchange with the testicular artery and maintains the thermoregulation.Occasionally there may be parallel collaterals to the gonadal veins at different locations of its extent . Very raDuring routine cadaveric dissection for the undergraduate medical students, we observed a prominent communicating vascular channel between testicular artery and testicular vein on the left side of the male adult cadaver aged about 65 years. The calibre of the communicating vessel was almost similar to testicular artery. The communicating channel was found to be connecting the vessels between 1.5 and 2 inches at the commencement of the testicular artery and termination of testicular vein . The skiVariation in testicular artery and vein is not uncommon. Studies show that the testicular artery variations are more common on right side as compared to left side . CicekciThe present case is second extremely rare report of arteriovenous communication between the left testicular artery and the vein. Only one case report by Nayak et al. has been found in literature regarding such variation . There iEtiological factors of varicocele and male infertility are numerous and in rare cases it is difficult for the clinician to pinpoint the exact cause of the disease. Testicular arteriovenous communication can be one of the etiological causes for the abovementioned diseases. Even though the cases of testicular arteriovenous communication are rare, cases of male infertility due to oligospermia and varicocele should be investigated with the help of Doppler ultrasound and arteriogram to rule out any vascular anomaly such as described in the present case. During the procedure for varicocele embolisation to treat varicocele on left side, the catheter is passed through the renal vein and then into testicular vein. The catheter or probe during such procedure may accidently pass in the testicular arteriovenous communication reaching the testicular artery. Thus during left varicocele embolisation, presence of testicular arteriovenous communication should be noted.Arteriovenous communication of testicular vessels should be kept in mind by the clinicians and surgeons treating the varicocele and male infertility.


Assessment of the lateral wall thickness of the maxillary sinus is very important in decision making for many surgical interventions. The association between the thickness of the lateral wall of the maxillary sinus and the dental status is not well identified.To compare the thickness of the lateral wall of the maxillary sinus in individuals with and without teeth to determine if extraction of the teeth can lead to a significant reduction in the thickness of the maxillary sinus lateral wall or not.In a retrospective study on fifty patients with an edentulous space, the thickness of the lateral wall of the maxillary sinus,one centimeter above the sinus floor in the second premolar (P2), first molar (M1) and second molar (M2) areas was determined by cone beam computed tomography scans(CBCTs) and a digital ruler in Romexis F software (Planmeca Romexis 2.4.2.R) and it was compared with values measured in fifty dentated individuals. Three way analysis of variance was applied for comparison after confirmation of the normal distribution of data.The mean of the wall thickness in each of these points was lower in patients with edentulous spaces; however it was not significant. There was no association between gender and the thickness of the lateral wall of the maxillary sinus, but location was associated with different thicknesses.The differences in the thickness based on the location and dental status necessitates assessment of the wall thickness of the maxillary sinus in addition to the current evaluation of bone thickness between the sinus floor and the edentulous crest before maxillary sinus surgery. Assessment of the thickness of the lateral wall of the maxillary sinus is very important in decision making for many surgical interventions such as Caldwell-Luc surgery, Lefort I osteotomy, open sinus lift, facial and jaw bone fracture fixation and mini-screw insertion in orthodontics as well as the diagnosis of chronic sinusitis -5. It isWe designed a study to compare the thickness of the lateral wall of the maxillary sinus in individuals with and without teeth to determine if extraction of the teeth can lead to a significant reduction in the thickness of the maxillary sinus lateral wall or not. The number of years that had passed after teeth extraction was not considered in this study.In this retrospective study, we assessed the thickness of the lateral wall of the maxillary sinus one centimeter above the sinus floor by cone beam computed tomography scan (CBCT) in fifty patients with edentulous spaces who were candidates for dental implant placement (the edentulous space group) and we compared the results with CBCTs of fifty maxillofacial trauma patients who had no maxillary bone and teeth problem (the dentate group). This area was chosen because the majority of surgical procedures that need bone removal to get access inside the maxillary sinus or osteotomy cuts and osteosynthesis devices are all involved with this location. The main inclusion criteria were the tooth absence and presence in the posterior maxilla in the coronal axis of CBCTs in the first and second groups, respectively. In addition, as the maxillary sinus fully develops in 15 year olds  and age Multivariate analysis was used for comparison of lateral wall thickness of the maxillary sinus as the effects of gender and dental status were considered in the analysis. It showed that both of them and their interaction had no significant effect on the wall thickness (P>0.05). For comparison between the three bony locations , repeated measure ANOVA was used. There were significant differences between these three locations. Bonefferoni correction showed significant differences between all three pairwise locations (P<0.05). The thickest bone was thefirst molar region followed by the second premolar and finally the second molar . While the anatomy of the maxillary sinus septa is well-identified -10, therThe thickness of the maxillary sinushas previously showed to have association with the difficulty of sinus surgeries.The differences inthe thickness based on the location and dental status necessitates CBCT assessment of the wall thickness of the maxillary sinus in addition to the current evaluation of the bone thickness between the sinus floor and the edentulous crest or dental roots before sinus surgeries.


Mobile elements including retrotransposons are implicated in the organization of the epigenetic landscape, the progression of tumorigenesis, and the enhancement of genetic diversity. Despite the importance of repetitive and transposable elements these sequences are traditionally ignored in high-throughput sequencing analysis due to the technical difficulty of uniquely mapping reads from repeat DNA sequences. Here we report a new computational method for the analysis of repetitive elements from high-throughput sequencing datasets that accounts for all mapping reads. In our approach, we examine reads that map uniquely and to multiple locations of the genome using two separate strategies to determine a complete estimate of enrichment for repetitive elements. Included in our computational method is an output defined by reads per kilobase of repeat element per million mapped reads (similar to RPKM definition for the exon model) . The callt mouse . We comp [et al. , and dem


Schwannomas are rarely seen on the sciatic nerve and can cause sciatica. In this case report we aimed to present an unusual location of schwannoma along sciatic nerve that causes sciatica. A 60-years-old-man was admitted to us with complaints of pain on his thigh and paresthesia on his foot. Radiography of the patient revealed a solitary lesion on the sciatic nerve. The lesion was excised and the symptoms resolved after surgery. Schwannomas are derived from Schwann cells of neuroectoderm. They serve for the formation of myelin sheaths of nerves that insulate nerve and facilitate the transmission of an impulse . It is aSciatica is defined as pain along the course of the sciatic nerve and its branches. Characteristically the patients report gluteal pain radiating down the posterior thigh and leg with paresthesia in the calf and foot along the route of the sciatic nerve . In this report we aimed to present a patient with the symptoms of sciatica for five years due to unrecognized eight-centimetre schwannoma of sciatic nerve at the sciatic notch of pelvis. A 60-years-old patient with long standing symptoms of pain and paresthesia was referred to algology and physical therapy departments for finding out the possible etiology as his symptoms of sciatica increased. His past medical history revealed that he had been treated with the diagnosis of lumbosacral degenerative pathology for a long period of time although he had irrelevant lumbosacral magnetic resonance imaging (MRI). He had been further investigated with electromyography (EMG) that revealed decrease peroneal and tibial motor and sensory nerve conduction velocity. Sural and superficial peroneal sensory action potentials were decreased. Pelvic MRI was taken for the possible lesion compressing the sciatic nerve which displayed the noncontrast enhancing mass on the sciatic nerve at the sciaitc notch section .Surgery was planned with the possible diagnosis of schwannoma or neurofibroma. An incision was made through the route of sciatic nerve and the nerve was explored till the sciatic notch beginning proximally. The soft tissue mass on the sciatic nerve was seen and removed from the nerve sheath . The patSciatica is most commonly caused by herniated disc compressing the nerve roots or lumbosacral degenerative pathology, although very infrequent entrapment of sciatic nerve along its course within the pelvis or the lower extremity due to heterotopic ossification, misplaced intramuscular injections, myofascial bands in the thigh, myositis ossificans of biceps muscle, posttraumatic or anticoagulant-induced hematomas, compartment syndrome, and bone and soft tissue tumors can cause sciatica –5. Schwannomas are common, slow-growing benign tumors of the sheath of peripheral nerves arising from the schwann cells and involvement of sciatic nerve is very rare. Most are solitary lesions and multiplicity or malignant transformation occurs very rarely , 7. Alth Pain not responding to rest or activity, sensory and motor dysfunction along the nerve distribution are the most common manifestations. Surgical intervention should be the treatment of choice in order to prevent neurological deficits and exclude the possibility of malignancy. Sciatic nerve schwannomas should be kept in mind as a causative factor of sciatica and magnetic resonance imaging of the sciatic nerve in case of suspicion especially in patients with irrelevant lumbosacral MRI is important for diagnosis.


Discrete structural rearrangements emerge as a series of abrupt discontinuities in stress-strain curves. We obtain the theoretical dependence of the yield stress on system size and geometry and elucidate the statistical properties of plastic deformation at such scales. Our results show that the absence of dislocation storage leads to crucial effects on the statistics of plastic events, ultimately affecting the universal scaling behavior observed at larger scales.Nanoindentation techniques recently developed to measure the mechanical response of crystals under external loading conditions reveal new phenomena upon decreasing sample size below the microscale. At small length scales, material resistance to irreversible deformation depends on sample morphology. Here we study the mechanisms of yield and plastic flow in inherently  Over the past years, experimental investigations have gathered increasing evidence that plastic deformation of crystalline materials proceeds through intermittent bursts of activity small systems. We propose a simple geometry, which can be reproduced in experiments on two-dimensional micrometer colloidal crystals, and provide robust input for mechanical testing of crystalline thin films below the micrometer scale. Our aim is to show that at very small scales the irreversible deformation of materials proceeds in a novel way, deviating from the allegedly universal behavior observed in larger systems. To this end, we investigate the dependence of the yield stress on system size and geometry and the statistical properties of plastic deformation and energy dissipation in uniaxially compressed two-dimensional small crystals, by means of atomistic simulations and analytical modeling.While several nanoindentation techniques have been developed to measure material resistance to irreversible deformation and plastic flow, the experimental observation of plasticity at the nanoscale still represents an enormous challenge We first consider the compression of perfect crystals of various sizes and aspect ratios. Crystals are simulated as two-dimensional aggregates of short-range interacting monodisperse particles in their lowest energy configuration, that is a triangular lattice in the free see . Uniaxials as in . Particlwhere anes see . In dispThe coupled Eqs. (1) for In both protocols, the response is initially elastic. In a perfect crystal, the elastic limit is reached as soon as the motion of a pair of opposite sign edge dislocations is activated, as in By moving, dislocations allow the system to slip plastically and emit/dissipate part of the stored elastic energy. The value of both the yield stress dislocation starvation mechanism. According to the literature, in larger systems the dependence of the yield stress on the system size follows a power law The connection between the yield stress and the boundary effects can be easily visualized in our simple model system. Up to values of the stress very close to where Equation (3) establishes a connection between the yield stress and dislocation strain distribution. It also bears implicitly the information about the dependence of the yield stress on the system size and geometry.The essence of our problem then lies in the stress distribution that accounts for By means of elasticity theory, we can demonstrate that the stress fields produced inside the sample by an edge dislocation close to a rigid boundary are long ranged and decay as with boundary conditions such that the full where From the above result, the elastic strain tensor In the case of our simulations, however, Eq. (6) may seem of limited help in calculating the strain energy We can conclude that the configuration in As soon as the yield point is reached, the response of the system to further loading differentiates depending on the deformation protocol. Under conditions of displacement control, stress-strain curves are characterized by serrated yielding, while they assume a staircase shape under conditions of stress control. We emulate realistic realizations of compressed samples by introducing randomness at free boundaries as follows. The initial state of each realization is obtained from the perfect crystal by extracting a random number of particles from one free surface and relocating them at random positions on the opposing surface. In this way both the number of particles and the linear size of all simulated specimens are kept constant, while the morphologies of their free surfaces are allowed to vary stochastically. Strain plateaus ases see . Remarkaases see  reveals Due to the limited system size, moving dislocations easily leave the sample through free boundaries. Pioneering studies have shown that in sub-micrometer Ni samples, pure mechanical loading can induce dislocation depletion within the sample Plastic event sizes are commonly quantified in experiments by looking at the amount of energy Here the dissipated energy Let us first consider the case of force control. If focusing on a single platen displacement event, we have Under displacement control conditions, instead, the statistical analysis of plastic flow and dissipated energy can be performed by looking at the distribution of stress drops . In Fig.Compared to numerical studies of size effects in dislocation dynamics at the microscale As for the origin of the anomalous avalanche exponents, we should remark that the novel behavior is related to the inability of the system to store large numbers of dislocations. In the absence of collective behavior, plastic flow departs from the traditional picture of cooperative dislocation organization. In fact our simulations show a behavior which approximately recalls a sequence of load-unload events, much in the spirit of stick-slip dynamics or fracture/failure mechanics. We notice that an energy release exponent very close to universal mean-field behavior observed at larger scales. Our results are thus a significant example of source-limited deformationIn conclusion, we have shown that the onset of plasticity at small scales is mediated by few dislocations. The number and arrangement of nucleated dislocations must account for the distribution of stress stored inside the crystal during the elastic-loading regime, allowing one to estimate the dependence of the yield stress on sample size and geometry. Our results confirm that both size and shape are crucial factors in determining the strength of materials at these scales. We find that plastic flow occurs in an intermittent manner reminiscent of irreversible deformation at larger length scales. Plastic avalanches of broadly distributed sizes are still observed, however, the absence of dislocation storage has important effects on the scaling characteristics of viscoplastic dynamics, which ultimately violate the Video S1The first appearance of a dislocation pair signals the onset of yield for the perfect system. As soon as each dislocation reaches the opposite rigid boundary, plastic activity stops and the the first event is over. The animation consists of 7 snapshots of the dynamics. Top: dislocations are represented as pairs of 5- and 7-coordinated particles, in blue and red respectively. Bottom: velocity field corresponding to the dislocation configuration above. The modulus of the velocity vector is represented. Lower velocities are in red, higher in violet, according to the color scheme of the visible spectrum.(MOV)Click here for additional data file.Video S2Time evolution of the velocity field at the time-steps shown in Video 1. Moving dislocations trigger particle motion and thus elastic energy dissipation.(MOV)Click here for additional data file.Video S3Dislocation dynamics in the flow regime. Plastic events correspond to the activation of few dislocations at a time. Dislocation storage is not observed for such small systems. The animation consists of 20 snapshots of the dynamics. Conventions are as in Video 1.(MOV)Click here for additional data file.


After publication of this work , we noteThe authors declare that they have no competing interests. GF declares no competing interests.RP did the primary data analysis and prepare the initial and subsequent versions of the manuscript; SA supervised the data analysis and preparation of the results table and commented on versions of the manuscripts. GF supervised the data analysis and statistical evaluation; KM conceived the study, reviewed the data and draft versions of the manuscript.


In the Funding Statement, an organization providing funding to the last author (HDO) is incorrectly omitted. The Funding Statement should read:"This work was supported by a grant by the Bundesministerium für Bildung und Forschung  and the LOEWE excellence initiative of the State of Hesse within the framework of the Cluster for Integrative Fungal Research (IPF) to HDO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."


Although the maximum human life span of 122 years is well established, the genetic and biochemical changes that influence the ability to reach old age in good physical and mental health are not very well understood. Both multiple environmental (~70%) and genetic (~30%) factors seem to play a role in attaining longevity [Clues to the role of FOXO3A in controlling longevity may be available through the comparative study of organisms which show no sign of aging. One of the very few examples of animals which appear to be truly immortal is the freshwater polyp Hydra . Tissue With technological advances including the development of genomic resources  and noveIn the new study , a literThe findings have captured the imagination of the popular press, and raised the skeptic's eyebrows. What lessons can actually be learned from the Hydra study? What does this mean for understanding human longevity? First, the Hydra results have moved the longevity-enabling FOXO3A gene from reported association to possible functions, corroborating and extending beyond previous observations in C. elegans and Drosophila. Second, the link between FoxO and components of the innate immune system  is of pa


The gonadotropin-releasing hormone (GnRH) system is well known as the main regulator of reproductive physiology in vertebrates. It is also part of a network of brain structures and pathways that integrate information from the internal and external milieu and coordinate the adaptive behavioral and physiological responses to social and reproductive survival needs. In this paper we review the state of knowledge of the GnRH system in relation to the behavior, external, and internal factors that control reproduction in one of the oldest lineage of vertebrates, the lampreys. Neuro-endocrine integration is defined as the process whereby a neuro-endocrine system converts signals received from the external and internal media into adaptive physiological and/or behavioral changes . ReproduGeotria and Mordacia) can be found in the southern hemisphere as well. Lampreys (Petromyzontidae) and hagfishes (Mixini) are the only members of the monophyletic vertebrate group of Cyclostomes and the only agnathans surviving in the actual fauna. The overall body morphology of lampreys seems to have been surprisingly well conserved over the 400–500 millions years of evolution as suggested by paleontological evidence  factors known to influence lamprey reproductive behavior and physiology.Petromyzon marinus) and the Pacific lamprey (Entosphenus tridentatus). Sea lamprey is represented by two varieties: the landlocked lampreys in the Great Lakes and the anadromous variety in the Atlantic Ocean seaboard. Due to the extraordinary measures that were taken for the control of the lamprey population in the Great Lakes  larSexual maturation  in lampreys is initiated during the parasitic phase of its life cycle. Final maturation takes place during upstream migration. Three main stages were identified for the upstream migration of reproductively mature lamprey: (i) initial migration from the ocean or lake to coastal rivers usually during the winter that precedes spawning, (ii) pre-spawning animals swim upstream the river, and (iii) spawning stage when sexual organs are fully matured and which includes specific reproductive behaviors like nest building, nest fanning, inter-male aggression, and the spawning act itself.Among the environmental factors that influence the upstream migration and their behavior during the final spawning phase the most important are photoperiod and temperature. Hydrological factors may also impact migration , 13 althP. marinus. The relative genetic homogeneity of the anadromous Atlantic sea lamprey on the North American east coast also suggests that mature animals do not return to their home streams for spawning  and landlocked sea lamprey (up to 10%) . This wenervus terminalis  is present in a majority of species with the exception of some fish. The type 2 GnRH (or “chicken” GnRH) shows the widest pattern of distribution, an identical GnRH type 2 was found in all major Gnathostome lineages. Type 3 is characteristic to teleosts . Most sprminalis .Therefore, in a very simplified GnRH type on biological function mapping scheme GnRH 1 is the hypophysiotropic form, GnRH 2 is considered mostly a neuromodulatory peptide with role in behavior while the teleost GnRH 3 could play various roles as mentioned, many times being found in the telencephalic area where some evidence suggests that it plays an olfactory modulatory role. The GnRH type 2 peptides are very well conserved in all vertebrates species with the exception of some of the mammalian groups where this peptide is absent, as it is the case of rodents and some primates. Behavioral control function hypothesized to be played by midbrain GnRH 2 seems to be supplanted by other systems in these species. Interestingly, in monkeys as well as in humans both GnRH type 1 and GnRH type 2 are present and show hypothalamic distribution albeit in distinct neuronal populations. This and the evidence collected mainly in monkeys on their hypophysiotropic role and differential estrogen neuronal sensitivity suggests that both isoforms are components of the HPG axis in these species with functions tuned to respond to different physiological contexts . The mai2 respectively) are common with the Gnathostome GnRH. Tyr3 and Leu5 in lGnRH-I, Asp6 in lGnRH-III, and Glu6 in lGnRH-I as well as Phe or Lys in position 8 are characteristic to lamprey sequences  in lamprey brains is much more restricted. Lamprey GnRH immunoreactive nerve fibers originate from cells in the arc-shaped hypothalamic/preoptic areas and end at the neurohypophysis forming the preoptico-hypophyseal GnRH tract , 26. Thenscripts . Presenchemistry . This ishemistry , 29.Gonadotropin-releasing hormone receptors are G-protein coupled receptors acting primarily through interaction with Gq/11 G-proteins followed by activation of the IP3 second messenger signal transduction pathway . ActivatIn vitro autoradiography followed by Scatchard analysis of binding of a mammalian GnRH analog to lamprey pituitary identified two classes of high affinity binding of the ligand. These binding sites were located in the proximal pars distalis and in a lesser extend in the rostral pars distalis of the pituitary. The labeled analog was displaced by the lamprey GnRH peptides I and III which suggested that the detected high affinity binding was due to the presence of at least two types of GnRH receptors expressed in the pituitary tissue of lamprey  and a steroid receptor orthologs were demonstrated as well. Regulatory changes in the expression of these genes during spawning suggest that these steroid hormones might play a role in gonadal maturation and reproductive function in this animal. However, the existence of a central neuro-endocrine control mechanism in Cephalochordates is still in the stage of unconfirmed hypothesis as no GnRH or other gonadal steroidogenic factor originating in their central nervous system was found . Treatmein vitro release of estradiol from isolated lamprey gonads which demonstrates a direct action of GnRH on the reproductive organs in vitro. This effect strongly increases in co-culture systems where the gonads are exposed to GnRH treatment in the presence of pituitary tissue which convincingly supports the hypothesis of a hypophyseal gonadotropin-like factor with a GnRH-dependent release and having a steroidogenic effect on the gonads  negative feedback – neuro-endocrine homeostatic mechanism of control of gonadal steroidogenesis, (2) positive feedback – has a physiologic role during the LH surge and ovulation in the estrous cycle of mammals, and (3) behavioral neuromodulators upon binding to a multitude of steroid sensitive brain areas. In female vertebrates gonadal steroid hormones regulate activity on the HPG axis via both positive and negative central feed-back mechanisms, these mechanisms being the most prominent and most studied during the estrous cycle of mammals .The neuromodulatory role of steroids depends on the spatial and temporal pattern of expression of different types of steroid receptors in the brain tissue. First evidence of steroid feed-back action in lamprey was provided by estrogen brain tissue autoradiography experiments . Early ein situ hybridization by Sower and Baron The first type of interaction can be described as a pheromone priming effect on GnRH secretion. Recent evidence suggests that chemosensory input induce upregulation of GnRH expression in the lamprey brain followed by the downstream activation of HPG pathway and increase in plasma steroid level . The pat(2)nervus terminalis and olfactory sensory epithelium: the neurons of the nervus terminalis ganglia were shown to express GnRH and send projections peripherally to the olfactory epithelium neurons that express GnRH receptors  effect of GnRH on olfactory sensory pathways. In most vertebrates, this role is studied in connection with the GnRH system attached to eceptors . Centriftructure . In the hemistry . More rehemistry .In Gnathostomes there are two sides of the relationships between olfactory input and GnRH system, related to the hypophysiotropic versus non-hypophysiotropic (neuromodulatory) roles of GnRH: (1) in the first case the olfactory input with reproductive relevance modulates the secretion of the GnRH from the preoptic area of the hypothalamus and consequently the activity on the HPG axis and (2) non-hypophysiotropic GnRH regulates the receptivity to olfactory stimuli via centrifugal projections to the peripheral olfactory structures:In conclusion, the influence of pheromonal signals on lamprey behavior has been well established at different stages of its reproductive cycle and they also seem to induce priming effects on GnRH. The neural pathway that mediate these actions are largely unknown in both of cases. Moreover, no evidence of a non-hypophysiotropic, neuromodulatory role of lamprey GnRH on olfaction has been found to date.The key players in photoperiod neuro-endocrine regulation in vertebrates are the pineal gland and its hormone, melatonin. In adult mammals the pineal does not directly respond to light stimuli, this information if received at the central level from the retina via a specialized retinofugal pathways, the retinohypothalamic tract [see for example Ref. ]. This cIn lamprey both retinofugal projections to hypothalamus and optic tectum as well as retinopetal FMRF-amide immunoreactive projections connecting the visual centers in the brain with the eye have been described . SimilarLamprey behavior during the last, reproductive phase of their life cycle is sensitive to the dark/light cycle. Observations of animals during their migration and spawning suggest they swim upstream mostly at night while spawning takes place during the day . As descin vitro cultured lamprey pineal glands under different light and temperature regimes has shown that under an alternating light:dark regime at 20°C the melatonin secretion was completely inhibited during the light cycle and peaked in the dark  and internal hormonal stimuli.Measurement of the melatonin release from the dark , 87. The125I]-melatonin was detected in the lamprey optic tectum and in the parvocellular and magnocellular cells of the preoptic nucleus (Photoperiod affects the neuro-endocrine reproductive axis at different levels [reviewed for example in Ref. ]. Intera nucleus . Co-loca nucleus . GnRH re nucleus . HoweverIn summary, light and temperature are important environmental factors that directly impact the behavior of the animals during their reproductive phase, possibly through mechanisms that involve the pineal and its melatonin secretion. The effect of these factors are sensitive to the combined influence of gonadal maturation stage and the presence of olfactory signals. As in many other cases in lamprey, there is only a limited understanding of how these interrelations are determined at the central level possibly through interplay between the melatonin and steroid sensitive brain pathways.Our goal was not to give an exhaustive presentation of the research in lamprey reproduction as there is not enough room for that in the space of a short review. Nor are we attempting to provide a comprehensive model for the control of reproduction in lamprey as this would be condemned to be highly speculative at this time given the rather fragmentary information available on molecular mechanisms that drive reproduction in this animal. Instead we adopted here a perspective on lamprey reproduction as an integrated system that in its most basic organization is an input/output system reflective to a certain extent of the primordial neuro-endocrine system that governed reproduction at the beginning of the vertebrate radiation. We briefly surveyed some of the most important channels through which the organism collects information about the internal and external media. This information is processed to generate an output represented by a sequence of stereotyped behaviors and stages of maturation of reproductive organs. The data accumulated to date suggests that lamprey share many of the neuro-endocrine characteristics of Gnathostomes like the existence of a HPG axis, the role of the sex steroid hormones, and the sensitivity of reproduction to light and temperature. These processes are coordinated at the central level by mechanisms that in lamprey are likely genetically encoded and inscribed into the morphological and chemical makeup of the brain during the embryonic and metamorphic development. Aside from the central role of the GnRH however, much less is understood from reproductive neurobiology of lamprey and of agnathans in general. There is an important body of information available on chemical neuroanatomy of lamprey brain, collected more recently through the efforts of research groups like Pombal in Spain  or GrillThe 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.


Evidence accumulating the past decades indicates that human populations are exposed to environmental chemicals interfering with endocrine systems. There is growing concern of the potential adverse impact of exposure to such endocrine disrupting chemicals (EDCs) on human health, based on observations in wildlife, animal model systems and reports of yet unexplained increased incidences of hormone related disorders in humans. Exposure in fetal and neonatal age may be associated with developmental and reproductive disturbances due to interference with the programming of normal hormone signaling and metabolic pathways. Boys are conceived to be more vulnerable than girls due to their more complicated and androgen driven prenatal sex differentiation.Male prenatal sex differentiation is crucially dependent on the functioning of fetal Leydig cells. Exposure of these cells to EDCs at critical time windows of development may result in undermasculinization and disorder(s) of sex development (DSD), such as hypospadias, cryptorchidism and ambiguous genitalia. Furthermore, a novel trend of earlier start of puberty has been found during the past few decades, at least in some regions and mostly affecting girls. Among plausible causes behind this phenomenon it has been suggested that exposure to EDCs affecting the programming or triggering of the pubertal clock could result in premature activation of gonadotropin secretion. Another hypothesis is that gonadotropin independent effects of EDCs are associated with an earlier start of puberty.Proof of principle of such potential roles of EDCs has been obtained from a multitude of studies in experimental animals and gained some support by case studies, exposure data and epidemiological investigations in humans. This presentation will review recent data and ongoing studies on the mechanism(s) of action of EDCs, including effects of mixtures, on the hypothalamus- pituitary-gonadal axis in experimental animals and humans. The impact of genetic susceptibility on the degree of disrupting activity caused by certain EDCs will be discussed on the basis of ongoing animal studies.


Rhythmic activity in the brain has been known since Berger's discovery of the alpha rhythm in the 1920's. Numerous mechanisms have been proposed for various rhythms but in the past half-century no consensus has been reached on the mechanism of any major rhythm. The recent development of high-throughput imaging methods enable us for the first time to rigorously and quantitatively test ideas about the dynamics of brain rhythms.The aim of this project is to characterize the contributions of intrinsic dynamics of brain regions and network connections in generating the global dynamics of cortical activity using a mouse model.2 of mouse cortex by voltage-sensitive dyes, in both anesthetized and awake animals. We have instantiated current ideas about delta rhythm in models for the dynamics of such activity and we measure the fit of these models quantitatively in predicting this data, thus shedding light on the relative contributions of these processes in the delta rhythm. We include in the model intrinsic regional oscillations, thalamic input, and communication between cortical regions. We specify the form of the model and then estimate the parameters by fitting the dynamical behavior to high-resolution time series of cortical activity in mouse cortex. We try to estimate the relative contributions of each of the major components of the model to the fluctuations.We have generated high-resolution data on neural activity over 40 mmWe show that a potassium-current mechanism for intrinsic oscillations does in fact fit the data well, and we estimate some of the effective connectivity between different cortical regions under anesthesia.


Insects are able to find their mates from the sparse pheromone patches transported by turbulent air streams. This source-finding ability is remarkable because the pheromone patches don't point towards the source and because the temporal and concentration statistics encountered during the search are highly irregular. The knowledge of the coding dynamics at the single ORN level is presently incomplete and it seems mandatory to decipher these dynamics before further investigating the integration of the signal at higher levels of the olfactory system.A receptor that would attempt to infer the distance of a source from the detection dynamics of the pheromone patches would obviously benefit from the complete evolution of the pheromone concentration with time. Yet, it is possible to build a Bayesian model based on the known dynamics of the plume propagation  and to iAgrotis ipsilon, stimulated by puffs of pheromone (cis-7-dodecenyl acetate) of variable duration delivered at constant concentration. The spiking responses of ORNs to single puffs varying over four decades of durations (1ms-10s) were recorded and decoded. In the absence of precise knowledge on the decoding mechanism inside the antennal lobe and in higher neural structures of the insect brain, 3 decoding schemes were utilized, based on logistic regression, support vector machine and signal dependent Poisson firing model designed to include bursting dynamics. With this protocol the relative selectivity of ORNs coding with the variation of puff duration and thus the relative information transfer could be analyzed. Then, in order to investigate the possible coding dependency of the currently detected pheromone patch on previous patch detections, double puffs coding were investigated, similarly over four decades of durations. The evolution of the ORN coding showed that the detection of previous puffs influenced the coding of the current puff and hence that instantaneous decoding could bring information on the previous puff duration and timing. Furthermore, we quantified the relative  sensitivity of the instantaneous coding with respect to the duration and spacing of the previous puff. Interestingly, we also show that the "random spiking" dynamics bears a non-negligible amount of information on the past patch dynamics detection.As a simplified framework, we investigated the dynamical olfactory coding of ORNs of a moth, The coding and decoding procedures were then evaluated on signals mimicking the temporal dynamics of patches in a turbulent stream. We found that training based on one patch and two patches allowed efficient and reliable decoding of patch dynamics in turbulent air streams. Finally, we quantified the amount of information encoded by ORNs about the duration, timing, and most importantly waiting time between consecutive pheromone puffs.


Ungulates like sheep and goats have, like many other mammalian species, two complementary olfactory systems. The relative role played by these two systems has long been of interest regarding the sensory control of social behavior. The study of ungulate social behavior could represent a complimentary alternative to rodent studies because they live in a more natural environment and their social behaviors depend heavily on olfaction. In addition, the relative size of the main olfactory bulb (MOB) [in comparison to the accessory olfactory bulb (AOB)] is more developed than in many other lissencephalic species like rodents. In this review, we present data showing a clear involvement of the main olfactory system in two well-characterized social situations under olfactory control in ungulates, namely maternal behavior and offspring recognition at birth and the reactivation of the gonadotropic axis of females exposed to males during the anestrous season. In conclusion, we discuss the apparent discrepancy between the absence of evidence for a role of the vomeronasal system in ungulate social behavior and the existence of a developed accessory olfactory system in these species. The sense of smell is of primary importance for social recognition among mammals and is mediated by the main and the accessory olfactory systems. These olfactory systems differ both in their organization and in their function. The main olfactory system is involved in the processing of volatile odors detected at the level of the main olfactory epithelium in the nasal cavity. Sensory neurons send axons to glomerular cell layer of the main olfactory bulb (MOB) where they synapse with dendrites of mitral and tufted cells. The olfactory information is then conveyed to several primary olfactory structures including the anterior olfactory nucleus, the olfactory tubercle, the piriform cortex, the posterolateral cortical amygdala, or the entorhinal cortex  and we then discuss the general involvement of both systems in the regulation of ungulates social behavior and in comparison to rodents.In sheep, the establishment of maternal behavior is under the major influence of amniotic fluids which cover the lamb at birth. An important shift toward amniotic fluid is observed across pregnancy and parturition: while repelled by amniotic fluid throughout pregnancy, ewes become highly attracted to amniotic fluid around parturition  and the excitatory glutamate within the MOB. Once ewes establish a selective bond with their lambs after parturition, the odors of familiar lambs, but not those of unfamiliar ones, increase the release of both transmitters. Infusion of the GABAa receptor antagonist bicuculline in the MOB prevents lamb recognition once it has been formed. Therefore, it is hypothesized that the general increase of GABA refines the olfactory signal by inhibiting MOB mitral cells with the exception of those processing the odor of the familiar lamb.A dramatic increase of noradrenaline release also occurs during the learning of lamb odor  without being in contact with a lamb has been performed. It showed an increase in Fos expression that was mainly restricted to the main olfactory processing regions, i.e., the MOB, the piriform cortex, the frontal medial cortex and the orbitofrontal cortex in females exposed to lambs  activation around parturition Keller,  and thatIn ungulates, the introduction of a male among seasonally anoestrous females results in activation of LH secretion (short-term response) leading later to ovulation and sexual receptivity (long-term response; Delgadillo et al., The chemosignal responsible for the reactivation of the female gonadotropic axis seems to be a mixture of various compounds which have only been partially identified. It has been shown that the biological activity of the chemosignal requires the simultaneous presence of compound retained in both acid and neutral fractions (Cohen-Tannoudji et al., The role of the main and the accessory olfactory systems have been evaluated through lesioning or inactivating different regions of the main or the accessory olfactory pathways. Destruction of the main olfactory epithelium through intranasal administration of zinc sulfate or inactivation of the cortical nucleus of the amygdala by infusion of the anaesthetic lidocaine completely blocks the neuroendocrine response to ram odor (Gelez and Fabre-Nys, Correlational studies using Fos immunocytochemistry to reveal central activations triggered by male odors support the view that the main olfactory system primarily conveys the male odor. In sheep, when comparing groups exposed to a male, male fleece, female fleece or no odor, the male or its odor significantly increases Fos expression in the main olfactory system, especially the MOB and the cortical nucleus of the amygdala (Gelez and Fabre-Nys, In goats, neuroendocrine activations by male odor involve the kisspeptin system in the arcuate nucleus of the hypothalamus (Hamada et al., In summary, it has been shown that in sheep, contrary to many other species, the main olfactory system is primarily involved in the processing of the olfactory signal emanating from the male and that mediates a physiological response, while the accessory olfactory system seems to be less engaged. This is in contrast to rodents, where pheromonal cues are usually processed by the vomeronasal system (Keller et al., The data presented in the context of maternal behavior as well as those related to the male effect clearly support a key role for the main olfactory system in ungulate social behavior. Evidence showing an involvement of the vomeronasal system is scarce and the only experiment claiming a role of the VNO in sheep offspring recognition has raised methodological concerns.However, ungulates are one of the animal taxa where a specific olfactory behavior that is thought to be dependent upon the vomeronasal system, namely flehmen response, is widely reported (Melese-d'Hospital and Hart, At the neuroanatomical level, the VNO, the AOB, and the “vomeronasal” amygdala have been identified and are quite well developed in many wild and farm ungulate species (Kratzing, As in other species, in sheep the chemosignals are thought to contact vomeronasal receptors in the VNO epithelium through a pumping mechanism (Meredith et al., The downstream organization of the vomeronasal system also seems to be perfectly functional, even if some slight differences with rodents can be noticed. First, the respective zone to zone projection from the apical and basal sensory epithelium of the VNO to the anterior and posterior part of the AOB, typical in rodents, is not present in adult sheep (Salazar et al., Finally, at the level of the central projections of the vomeronasal system, it seems that the vomeronasal amygdala of the sheep is as extensive as that of rodents (Jansen et al., In conclusion, the current knowledge on the regulation of social behavior by the accessory olfactory system leads to an apparent contradiction. Indeed, neuroanatomical characterizations suggest that despite a reduced relative size, the vomeronasal system seems to be perfectly functional. By contrast, the behavioral evidence regarding its function in social olfaction is scarce, therefore advocating for further investigations in this area. Particularly, the use of other behavioral situations than the ones explored so far could lead to a re-evaluation of the role of the vomeronasal olfaction in the control of social behavior in ungulates. For example, it is likely that vomeronasal olfaction could play a more developed role in wild ungulates such as antelopes or moose than in domesticated species (Deutsch and Nefdt, The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The Gambia Hepatitis Intervention Study (GHIS) consisted in the progressive introduction of HBV plasma-derived vaccine in different zones of this African country during the period 1986-1990. The study was launched and coordinated by IARC and is one of the most effective examples of an intervention project that both substantially contributed to our knowledge and to the health of local populations. Similar intervention studies have been carried out in South-East Asia. The studies indicate that the natural history of HBV infection differs in different populations , having a direct relevance for the implementation of HBV vaccination programmes in various parts of the world. Recent estimations provided by GloboCa 2008  indicateAll the children vaccinated within the Gambia Hepatitis Intervention Study (GHIS) were registered, resulting in two cohorts of approximately 60,000 children, one of which received only the routine EPI vaccination and the other the HBV vaccine in addition. To determine the response to HBV vaccine and the persistence of vaccine-induced immunity, some 1000 children were recruited consecutively and these have been followed annually to assess their HBV serological status. A cross-sectional survey was carried out at the ages of 4 and 9 years of a similar number of unvaccinated children to determine the vaccine efficacy against HBV carriage status and infection.The vaccine efficacy shows an 84% protection against infection and 94% against HBV chronic carriage at 9 years of age , clearly show that exposure to aflatoxins affects the entire population and that exposure to both HBV infection and aflatoxins results in a prominent increase risk of developing HCC.In The Gambia the high incidence of HCC is also associated with exposure to the carcinogen aflatoxin Brasiticum. ComprehIn summary, these studies show that HBV vaccination programmes have been successfully implemented in various parts of the world. In addition, molecular epidemiological studies in The Gambia and in South-East Asia have clearly shown the relevance of other major risk factors, namely aflatoxin exposure , in the The author declare that has no competing financial or non-financial interest.


The TB screening algorithm used in the study to identify individuals with symptoms indicative of active tuberculosis is actually based on reporting ANY of three primary symptoms, not ALL three primary symptoms, thus the number of individuals with symptoms indicative of active tuberculosis should have been 79%, not 23%. This finding appears once in the Abstract, once in the Results, and once in the Discussion.


Hip arthroscopies are often used in the treatment of intra-articular hip injuries. Patient-reported outcomes (PRO) are an important parameter in evaluating treatment. It is unclear which PRO questionnaires are specifically available for hip arthroscopy patients. The aim of this systematic review was to investigate which PRO questionnaires are valid and reliable in the evaluation of patients undergoing hip arthroscopy.A search was conducted in Pubmed, Medline, CINAHL, the Cochrane Library, Pedro, EMBASE and Web of Science from 1931 to October 2010. Studies assessing the quality of PRO questionnaires in the evaluation of patients undergoing hip arthroscopy were included. The quality of the questionnaires was evaluated by the psychometric properties of the outcome measures. The quality of the articles investigating the questionnaires was assessed by the COSMIN list.Five articles identified three questionnaires; the Modified Harris Hip Score (MHHS), the Nonarthritic Hip Score (NAHS) and the Hip Outcome Score (HOS). The NAHS scored best on the content validity, whereas the HOS scored best on agreement, internal consistency, reliability and responsiveness. The quality of the articles describing the HOS scored highest. The NAHS is the best quality questionnaire. The articles describing the HOS are the best quality articles.This systematic review shows that there is no conclusive evidence for the use of a single patient-reported outcome questionnaire in the evaluation of patients undergoing hip arthroscopy. Based on available psychometric evidence we recommend using a combination of the NAHS and the HOS for patients undergoing hip arthroscopy. Hip arthroscopy is a relatively new procedure in the management of hip disorders ,2. It haThe number of hip arthroscopies is rising because of improvements in surgical technique and a better understanding of the pathology associated with the hip joint . TherefoA number of PRO questionnaires have been developed for individuals with hip pathology, especially osteoarthritis -14. The The aim of this systematic review was to investigate which PRO questionnaires are valid and reliable in the evaluation of patients undergoing hip arthroscopy.A systematic review was performed 1) to identify all PRO questionnaires used in the evaluation of patients undergoing hip arthroscopy 2) to evaluate the quality of these questionnaires based on their psychometric evidence 3) to determine the methodological quality of the studies into the psychometric evidence of these questionnaires.A health-related PRO questionnaire is a measurement of any aspect of a patient's health status that is directly assessed by the patient, thus without interpretation of the patient's responses by a physician or anyone else .Psychometric properties are part of psychometrics, which is the discipline concerned with the construction and validation of measurement instruments, such as questionnaires and tests . The psyA computerized literature search was performed using Pubmed, Medline, CINAHL (via EBSCO), the Cochrane Library, Pedro, EMBASE (via OVID) and Web of Science to identify relevant articles published between January 1931 and 1 October 2010. The search was conducted by two reviewers (NM and MT). The following terms were used:Hip AND arthroscopyHip AND arthroscopy AND questionnaires OR outcome assessment OR self assessment OR outcomeHip AND rehabilitation OR treatment AND questionnaires OR outcome assessment OR self assessment OR outcomeTerms were searched as key words or 'free-text' terms in all databases except for Pubmed in which they were searched as MESH terms. The reference lists of the retrieved articles were searched for more relevant studies. The search was completed with a separate search for the identified questionnaires as well as for authors of these questionnaires.The two reviewers (NM and MT) independently assessed all collected publications on title and abstract for possible inclusion in the study. All selected publications were retrieved in full and in- and exclusion criteria were applied by the two reviewers. Inclusion criteria are presented in Table Two assessment procedures were used to assess the quality of the identified questionnaires and the methodological quality of the articles describing the questionnaires.Terwee et al.  developeNo overall score is calculated, but a conclusion is drawn based on the information of the properties combined with the aim of the questionnaire . This crThe methodological quality of the studies into the psychometric evidence of these questionnaires was determined by the Consensus-based Standards for the selection of health Measurement Instruments list (COSMIN) . This liThe total search identified 3025 articles. A total of 2971 articles were excluded based on title and abstract which left 54 articles that were read in full text. Of these 54 articles 49 were excluded based on the remaining exclusion criteria which left five articles to be included in the study with a total of 830 subjects. None of the articles used the same group of subjects for their data collection. An overview of the descriptive data of the articles is shown in Table Any disagreement between the two reviewers (NM and MT) was resolved by consensus.The psychometric properties per questionnaire are shown in Table The MHHS scored high on construct validity because it correlated well with the domains bodily pain and physical functions of the Short Form-36 (SF-36) . Some inThe quality of the articles investigating the psychometric evidence of the PRO questionnaires were rated by the COSMIN checklist and presented in Table This systematic review included five articles on hip arthroscopy using three different questionnaires . The MHHS is a modification of the Harris Hip Score which is an observer-administrated score . Potter The overall quality of the articles investigating the measurement properties as rated by the COSMIN list was fair to good. Remarkably, in most cases the generalisability per box was better than the quality of the assessed properties per article. Only one article scored excellent on hypothesis testing of the correlation between the MHHS and SF-36 . FurtherThe NAHS has been developed for a young population with orthopedic, non arthritic hip pain and not specifically for patients undergoing hip arthroscopy, like the HOS . TherefoThe COSMIN list we used in this review was recently developed. At present no other checklists for the assessment of articles on the methodological quality of questionnaires are available ,16,19. TThis systematic review shows that there is no conclusive evidence for the use of a single patient-reported outcome questionnaire in the evaluation of patients undergoing hip arthroscopy. A limitation of this study is the small number of studies that could be included. Based on available psychometric evidence we recommend using a combination of the NAHS and the HOS for patients undergoing hip arthroscopy. In order to provide a conclusive recommendation more studies on the validity and reliability of these questionnaires are warranted.The authors declare that they have no competing interests.MT participated in the design of the study, carried out the literature search, selection and evaluation of articles and writing of the review. RC participated in the design of the study and revising the manuscript. NM carried out the literature search, selection and evaluation of articles. EV participated in the design of the study and revising the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/117/prepubDefinitions and scoring criteria of the psychometric properties. Definitions and scoring criteria of the psychometric properties developed by Terwee et al. Note: Important for other authors in order to get a clear image of the research performed. Not important enough to be placed in manuscript.Click here for fileQuality of the questionnaires based on psychometric properties rated by article. Quality of the questionnaires based on psychometric properties and displayed by article. Note: Important for other authors in order to get a clear image of the research performed. Not important enough to be placed in manuscript.Click here for file


Glomerular diseases including diabetic nephropathy are the leading cause of ESRD worldwide. Proteinuria, the hallmark of renal damage in glomerular diseases, is dependent on two main factors: the alteration of the glomerular filtration barrier and its three layers ), and the impairment of proteins reabsorption by proximal tubular epithelial cells. In recent years there has been a great increase of knowledge of the molecular structure of glomerular filtration barrier and of the molecular mechanisms involved in tubular reabsorption of proteins.In this special issue the structure of the glomerular filter and the importance of glomerular talk in maintaining the integrity of the glomerular filtration barrier are reviewed by M. Menon et al. A. Tojo and S. Kinugasa reviewed the albumin glomerular permeability in normal and disease status and present their views of a possible mechanism of selective proteinuria in nephrotic syndrome of minimal change disease. A. Zhang and S. Huang summarized several molecular defects responsible for dysfunction of the glomerular filtration barrier. J. E. Toblli et al. overviewed the alterations of glomerular endothelial cells, basement membrane and podocytes, the possible relationship between glomerular proteinuria and tubulointerstitial damage, and described less and more recent approaches to reduce proteinuria. The review of J. R. Machado et al. summarizes the most important molecules involved in the pathogenesis of nephrotic syndrome. Galactose-deficient IgA1 is the hallmark of IgA nephropathy; in a cohort of 40 pediatric patients with biopsy-proven IgAN, a research group from the Le Bonheur Children's Hospital found no association between albuminuria and the galactose-deficiency, a finding that may question the pathologic role of galactose-deficiency in IgAN. The possible therapeutic efficacy of inhibition of mammalian target of rapamycin (mTOR) in primary mesangioproliferative glomerulonephritis was discussed by H. Trimarchi et al. who suggested prospective clinical trials. B. Zhang and W. Shi reviewed the therapeutic effects of cyclosporine A (CsA) in glomerulonephritis and evaluated the data in support of a nonimmunologic antiproteinuric effect of CsA dependent on a direct stabilization of podocyte cytoskeleton. The review by A. Cohen-Bucay and G. Viswanathan discusses nine additional urine biomarkers that may offer better prediction for the course of diabetic kidney disease progression than urinary albumin. The authors call for further longitudinal studies to validate the clinical value of these biomarkers to overcome the limitations of albuminuria.The great increase in knowledge of molecular biology of glomerular filtration barrier and tubular reabsorption of proteins has not been matched as yet by outcome prediction improvement and therapeutic advances. There is a need for further studies for better understanding the pathogenesis of proteinuria and the clinical value of the different urine biomarkers in diagnosis and management of patients with chronic glomerular diseases.Finally special thanks to the authors and the reviewers for their efforts to provide to the nephrology community a concise up-to-date knowledge on the pathogenesis and management of proteinuric kidney disease.Claudio BazziOmran BakoushLoreto Gesualdo


Environmental Policy and Household Behaviour is a collection of studies on household behavior in environment-related areas originated from a multidisciplinary research program carried out by four Swedish universities between 2003 and 2008 under the financial support of the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, and the Swedish Environmental Protection Agency.The book’s contributions can be best appreciated within the context of recent shifts in environmental policy. Over the past decade, much of the focus of environmental policy has moved away from industrial production as the main source of pollution and from the implementation of cleaner processes toward an integrated approach that considers the life-cycle environmental impacts of goods and services involving all actors along the product chain, including consumers. Environmental policy-making bodies have also recognized the importance of a better understanding of these decision-making processes and households within a broader social science framework.For environmental policy, then, the main contribution lies in the focus on incorporating consumption-based measures into environmental policy and management and promoting more sustainable patterns of consumption a better understanding of the role and drives of consumption. For household behavior, the main contribution lies in the focus on capturing a wider range of policy influences through the inclusion of noneconomic explanations of behavior—from those grounded on noncognitive foundations of everyday life to those embedded in the collective, cultural, and social view of both choice and action.Overall, the book is a valuable source of information for both researchers and policy makers interested in or working on environmental issues that arise in household decisions, although it may not readily appeal to researchers engaged in theoretical or methodologically sophisticated empirical analyses. It can also serve as a supplementary text in an upper-level undergraduate course in environmental policy, particularly in interdisciplinary programs such as environmental studies.s that policies should facilitate comparison across the effects of different environmental activities. The book addresses the question of policy legitimacy, which requires that policies reflect society’s core values and attitudes, and how financial rewards and punishments may be inconsistent (and thus viewed as lacking legitimacy) with a moral willingness to do the right thing.Through its comprehensive approach to household behavior, the book provides insight into the complexity of designing environmental policies to achieve environmentally sustainable lifestyles and offers guidelines as to how such a complexity can be simplified. It begins with a discussion of the potential tension between individual freedom of choice and environmental obligations and how such a conflict is avoided through market-based policy instruments that place environmental responsibility on individuals as consumers in the marketplace. It explores how households handle the complexities and challenges of making environmentally informed decisions through compensatory measures and simplifications. To help households, the authors suggestThe book provides a thorough review of four types of determinants of behavior  within a broad framework of analysis. The discussion of the various types of determinants of behavior is most enlightening in bringing together insights about human behavior from many academic disciplines and fields and also encompassing linkages between different types of factors, particularly between attitudinal factors and contextual factors and habits. Hence, inner motivation to “act green” is not likely to result in green behavior if the perceived cost of sustainable behavior is high and/or habits of nonsustainable behavior are strong.In a series of case studies, the book analyzes the interplay of the four types of casual factors in specific environment-related household consumption areas: waste management, eco-consumption, and transportation. The three areas are cleverly selected to stress how policy challenges differ across areas as the relevance of the different casual factors and strength of interaction between them vary across different household activities. The specific reference to Sweden and the Swedish experience is most telling in illuminating another layer of complexity in the pursuit of sustainable consumption patterns that arises when nonenvironmental policies  and other public initiatives  are at odds with promoting environmental sustainable household behavior.Despite the relevance of combining elements about human nature and behavior from various social sciences, the book tends to overly discount, at least implicitly, the importance of economic motives and instruments. One of the three key implications summarized in the concluding chapter does speak of the need for policy packages as a potentially effective way to respond to morality-based motivations for green behavior while providing economic incentives. Nevertheless, the theoretical part of the book tends to emphasize the political, social, and psychological dimensions of household decision making, pointing to an excessive reliance on economic instruments; and the empirical part tends to overlook the impact of market-based policies even though such policies have received much attention, especially in the transport area, for their efficiency and their financial transparency.Environmental Policy and Household Behaviour makes a significant contribution to our understanding of the incentives and constraints households face when formulating judgments and making decisions. This understanding is a key requirement for the design of policies that are both effective and acceptable. The book does not offer specific policy prescriptions but suggests a framework that allows for the inclusion of a wider range of motives for environmentally responsible behavior and gives the opportunity of examining and rethinking the interaction between different types of motivation.In sum,