We here compared results achieved by applying popular methods for reducing artifacts in magnetoencephalography (MEG) and electroencephalography (EEG) recordings of the auditory evoked Mismatch Negativity (MMN) responses in healthy adult subjects. We compared the Signal Space Separation (SSS) and temporal SSS (tSSS) methods for reducing noise from external and nearby sources. Our results showed that tSSS reduces the interference level more reliably than plain SSS, particularly for MEG gradiometers, also for healthy subjects not wearing strongly interfering magnetic material. Therefore, tSSS is recommended over SSS. Furthermore, we found that better artifact correction is achieved by applying Independent Component Analysis (ICA) in comparison to Signal Space Projection (SSP). Although SSP reduces the baseline noise level more than ICA, SSP also significantly reduces the signal—slightly more than it reduces the artifacts interfering with the signal. However, ICA also adds noise, or correction errors, to the waveform when the signal-to-noise ratio (SNR) in the original data is relatively low—in particular to EEG and to MEG magnetometer data. In conclusion, ICA is recommended over SSP, but one should be careful when applying ICA to reduce artifacts on neurophysiological data with relatively low SNR.  Recordings of evoked-responses  with electroencephalography (EEG) or magnetoencephalography (MEG) are widely used methods in cognitive and clinical neuroscience. One of the major challenges in research and clinical applications of evoked-responses is the prevalent strongly interfering electromagnetic signals from external objects and devices in the surrounding MEG or EEG measurement environment as well as nearby mechanical and biological electromagnetic sources originating from the head and other parts of the body of the subject. Since the interfering environmental noise from, for example, laboratory mechanics and electronic devices may be several orders of magnitude stronger than the brain signals of interest , it is In the clinical routine, data from patients having a limited control of muscular activity (such as stroke or dementia patients or preterm infants) or with ferromagnetic implants (such as cochlear implantees) typically contain a considerable amount of artifacts. The time constraints of experiments and tests on clinical populations exclude the possibility of a large number of trials that would allow discarding the artefactual ones. A viable alternative to simply rejecting parts of the recorded data is that of correcting the data. Both in clinical patient recordings and in experimental settings with healthy subjects, strong electromagnetic noise from electronic devices, static electricity, and in particular with regard to EEG also the 50/60-Hz power-line noise may interfere significantly with the measurements . When reApart from external artifact sources, it is important to reduce the influence of the internal artifacts originating from the head and the rest of the body of the subject. Typically, MEG and EEG recordings are contaminated by relatively strong artifacts caused by the eyes , 7–9. Th™ software [Different methods have been developed to reduce the influence of externally and internally originating artifacts. The externally originating interference can be minimized by applying physical shielding techniques in the laboratory , by usinsoftware . The SSSsoftware –18. Sincsoftware . HoweverThe tSSS method is additionally able to filter out interferences from artifactual sources in the space between the brain and the MEG sensor array, by reducing signals in the common subspace through comparisons of the time series in the internal and external spaces. For instance, it has been shown that tSSS makes it possible to locate brain sources on the cortex with beamformer methods in clinical patients, although these patients wore strongly magnetically interfering dental braces; thereby, tSSS seems to allow extending the clinical population compatible with MEG .The internally originating artifacts can be reduced by applying band-pass filtering  and compTo investigate the performances and risks of using different popular artifact correction methods, we compared here results achieved by applying SSS, tSSS, ICA, and SSP. We chose to study the performance of the correction methods on the Mismatch Negativity (MMN) response, which is a well-known evoked-response , 51. In A sample of ten volunteers from a larger database named “Tunteet” was chosen . The participants were six females and four males. Three participants were nonmusicians, three were amateur musicians, and four were professional musicians. All participants were right-handed, and their average age was 24.8 years (range 18–35 years). Written informed consent was obtained from each participant, and the study was approved by the local ethics committee.The participants listened to a melody pattern of 2100 ms, repeated with variations during ~25 minutes. The melody patterns were created from digital piano tones (McGill University Master Samples) and followed the rules of Western tonal music. All melodies started with a triad (300 ms) followed by four single tones (two of 125 ms and two of 300 ms) and an ending tone (575 ms) all separated by 50 ms silent gap. Between all melodies there was a silent gap of 125 ms. Deviations of six types were inserted into the melody patterns to evoke MMN responses to a deviant tone as compared with corresponding unaltered standard. The deviants are explained in In total, the tested sample contained 120 brain responses, which comprised the responses to the six standard and six deviant conditions from each of the ten participants.™ 306-channel MEG system  equipped with a compatible EEG system. The MEG system had 102 triple-sensor elements, each comprising two orthogonal planar gradiometers and one magnetometer. A 64-channel EEG electrode cap was used. The reference electrode was placed on the nose tip and the ground electrode was on the right cheek. Blinks, as well as vertical and horizontal eye movements, were measured with four electrodes attached above and below the left eye and close to the external eye corners on both sides. Four head position indicator coils were placed on top of the EEG cap. Their positions were determined with respect to the nasion and preauricular points by an Isotrak 3D digitizer . MEG and EEG data were recorded with a sample rate of 600 Hz.The simultaneous MEG and EEG data were collected at the BioMag Laboratory of the Helsinki University Central Hospital. The measurements were performed in an electrically and magnetically shielded room  with VectorviewDuring the measurement, subjects were comfortably seated and watched a silenced movie with subtitles. The stimuli were presented with Presentation software . The sound was delivered through a pair of pneumatic headphones at individually adjusted loudness. Elekta Neuromag MaxFilter 2.2 Signal Space Separation (SSS) and temporal Signal Space Separation (tSSS) , 16 wereCorrection for internal artifacts with Signal Space Projection (SSP) was performed with the MNE Python version 0.11.0 released with the MNE software version 2.7.4-3485 , 56. We  runica function [Independent Component Analysis- (ICA-) based correction for internal artifacts was achieved by applying the logistic infomax algorithm implemented in thefunction  for MATLEvent-related EEG and MEG responses were extracted as single-trial epochs with a time window of 0 to 400 ms after the standard or deviant tone onset. The trials were baseline-corrected by applying a baseline of −100 to 0 ms before the tone onset. Since the planar gradiometer sensors measure along two orthogonal directions, the data from each pair of longitudinal and latitudinal sensors were combined by applying the Pythagorean distance formula, as implemented in the FieldTrip toolbox for MATLAB  ; d=longiFor the sake of clarity, we performed the subsequent analyses on one channel of each sensor type, those in which the highest MMN amplitude was measured within a typical MMN latency range of 75–200 ms. In this case, we analyzed the event-related waveforms from EEG channel 012 , magnetometer channel MEG 1341 , and the combined planar gradiometer channels MEG 2222 and 2223  see . These ax is the measured value, i is the trial number, and N is the total number of trials [We measured the MMN amplitude in response to each type of deviant tone by taking the average value across the time window from 125 to 155 ms after the tone onset. To compare the noise levels after utilizing each artifact correction method, we first used a baseline standard deviation measure. Since a flat baseline is desirable, we applied a baseline standard deviation (STD) measure to show the flatness of the baseline in a single trial (where lower baseline STD means a more flat baseline) . We calcf trials  and we atude/σx- .The Mismatch Negativity (MMN) evoked-response is analyzed by comparing the average response to the deviant stimulus with the average response to the standard stimulus , 51. AlsStatistical comparisons were made with SPSS version 20 . Since the resulting values were not normally distributed, we applied the Wilcoxon signed-rank test to compare the values achieved after utilizing the different artifact correction methods.A statistically significant and slightly better reduction of the signal standard deviation (STD) is achieved by applying tSSS in comparison to SSS for for both the MEG magnetometer and gradiometer data see . ImportaFrom grand average waveforms of the event-related responses , it can be seen that the SSP-based artifact correction reduces the signal amplitude, whereas the signal amplitude is similar before and after the artifact correction based on ICA see .The SSP method results in lower baseline standard deviation (STD) and signal STD in comparison to the ICA method see . The basThe SNR achieved by applying the ICA-based artifact correction is similar to that achieved by applying the SSP method with respect to the EEG and magnetometer channels. However, for the gradiometers applying the ICA method results in statistically significantly and slightly better SNR than that achieved by applying the SSP method see .We compared the noise suppression results achieved with SSS and tSSS on healthy subjects not wearing magnetized material. MaxFilter with tSSS resulted in better suppression of artifacts from external and nearby noise sources in comparison to SSS. In particular, the application of tSSS instead of SSS was important with respect to the MEG gradiometers, since SSS correction in 6% of the cases resulted in an increase of the noise level in the MEG gradiometer data, and thus the reliability of the gradiometer data decreased in comparison to that before SSS. We also compared the performance of ICA and SSP in reducing internal electrophysiological artifacts, originating from eye movements and heart beats of the participants. The ICA-based artifact correction performed better than the SSP method. The SSP method reduced part of the signal of interest along with the artifacts, and the SNR was slightly higher after applying the ICA method than after applying the SSP method. However, after ICA-based artifact correction the baseline noise level increased, in particular in the EEG and magnetometer channels, which have relatively low SNR in the original data. These findings support both the importance of reducing the bias on measures of evoked-responses with EEG and MEG caused by artifacts and the importance of minimizing the bias introduced by errors in artifact correction methods.With regard to the suppression of external noise, we here observed that the averaged MMN evoked-response in 6% of the cases with the MEG gradiometers even became more unreliable after applying SSS correction than before. Possibly, the influence of nearby artifacts on the evoked-response can become stronger after the external artifacts have been reduced with the SSS. When tSSS is applied the influence of such nearby artifacts on the evoked-responses would be reduced. In general, it seems relevant to further investigate whether correction methods for reducing one type of artifact, such as SSS, in some cases might enhance the influence of other artifacts on the averaged event-related waveform.The comparisons of the ICA and SSP methods for suppression of internal artifacts revealed particular biases appearing after the corrections. For the SSP method, there is a risk that the artifacts and signals of interest are not described by orthogonal components . We obseIn summary, our test results suggest that tSSS is recommendable for reducing the influence of artifacts originating from external and nearby sources instead of SSS only. We find that the noise level decreases more with tSSS than with SSS in this sample of EEG and MEG data from healthy participants despite the fact that they were not wearing strongly magnetized materials. For the reduction of internal physiological artifacts, we showed that the highest signal-to-noise ratio (SNR) is achieved with ICA-based artifact correction on the tested sample. However, both ICA- and SSP-based artifact corrections are subject to certain limitations. In particular, one must be aware of the risk when processing data with relatively low SNR, such as EEG and MEG magnetometer data, that artifact correction based on ICA may decrease the interference from artifacts while simultaneously increasing the noise level, due to increasing errors in estimating the mixing matrix in the context of data with lower SNR levels.


Facial trauma that results in fractured, displaced or lost teeth can have significant negative functional, esthetic and psychological effects on children. An acute dental trauma may imply impact to the hard dental tissues and damage to the pulp and periodontium, ultimately leading to partial or total pulp necrosis and/or root resorption. Apexification is a commonly used procedure for treating and preserving immature permanent teeth that have lost pulp vitality. Immature teeth undergoing apexification were earlier filled with calcium hydroxide paste for the purpose of disinfection and induction of an apical calcific barrier. However, certain drawbacks led to the use of mineral trioxide aggregate (MTA) to fill the apical end without the need for calcific barrier formation. This article demonstrates the use of MTA as an apical barrier material for root-end closure in the permanent teeth of five patients.How to cite this article: Gupta S, Goswami M. Use of Mineral Trioxide Aggregate in Surgical and Conventional Endodontics: A Report of Five Cases. Int J Clin Pediatr Dent 2013;6(2): 134-139. One of the treatment modality for apexification of immature teeth with severely inflamed or necrotic pulps is utilization of calcium hydroxide as an intracanal medication.3The presence of healthy pulp is essential for root development and apical closure. An injury sustained between the ages of 6 and 14 can adversely affect a patient's pulpal health and interrupt or arrest root development.4 In some cases, root resorption5 possibly caused by trauma and increased risk of root fracture6 due to dressing the root canal for an extended time with calcium hydroxide have been reported in teeth undergoing apexification.While the advantage of calcium hydroxide lies in the fact that it has been widely studied and has shown success, the disadvantages are its prolonged treatment time, the need for multiple visits and radiographs.4 MTA offers the option of a two-visit apexification procedure, which has the benefit of better compliance and reduced number of radiographs over the multiple visit calcium hydroxide apexification, particularly in younger patients.4 This article presents five case reports involving use of MTA for successful management of various types of traumatic injuries to immature maxillary incisors.Over the last decade, mineral trioxide aggregate (MTA) has been researched extensively and reported as a possible answer to many clinical endodontic challenges.An 11-year-old female reported to the Department of Pediatric Dentistry with a chief complaint of unsightly appearance due to broken right upper front tooth due to trauma 2 years back. The patient gave a history of undergoing treatment from a general dental practitioner before reporting to the present department. Clinical examination revealed right maxillary central incisor with horizontal fracture at the junction of middle and coronal third of crown . PatientObturation of the root canal was done after placement of MTA apical plug and the tooth was then restored with esthetic composite restoration  and 4.A 9-year-old male reported to the Department of Pediatric Dentistry with the chief complaint of a broken and a missing upper front tooth due to trauma. Clinical examination revealed oblique crown fracture of right maxillary central incisor and severe intrusion  with complicated crown fracture of left maxillary central incisor . All theThe intruded incisor was surgically extruded and brought into arch alignment after raising a full thickness mucoperiosteal flap. Hydroxyapatite granules were placed over the bony defect caused by associated alveolar fracture of labial cortical plate. The flap was sutured back and stabilization was achieved using arch bar for the whole maxillary arch. Suture removal and arch bar removal were done after 1 and 6 weeks respectively. Endodontic treatment of the intruded incisor was initiated and calcium hydroxide-iodoform paste  was placed in the root canal for a week. This was followed by placement of MTA apical plug in the next visit and obturation . EndodonA 10-year-old male reported to the Department of Pediatric Dentistry with a chief complaint of loose and elongated right upper front tooth and broken left upper front tooth due to sports trauma. Clinical examination revealed extrusive luxation of right maxillary central incisor, crown fracture of left maxillary central incisor at the level of middle third and missing right maxillary lateral incisor . The patThree weeks later, the patient complained of spontaneous and severe pain in the region of the traumatized central incisors. It was planned to perform periapical curettage and retrograde MTA filling for this patient. For this, after obtaining adequate anesthesia, a full thickness mucoperiosteal flap was raised and periapical curettage and apicoectomy was done. MTA was packed in a retrograde manner to seal the pathways of the root canal from the periradicular tissues. The flap was replaced back and sutured. Orthograde obturation was done using gutta-percha after access opening and thorough cleaning of the root canal . The tooAn 8-year-old male was referred to the Department of Pediatric Dentistry with the chief complaint of loosening of upper front teeth due to trauma. The patient gave a history of loss of his right upper front tooth which was reimplanted back into its socket about 20 minutes after trauma. Clinical examination revealed marked swelling of upper lip and extrusion of right maxillary central incisor with moderate mobility. The reimplanted tooth had been stabilized by packing gauze pieces in the labial vestibule by the referring dentist . IntraorSplinting was done using acid etch composite and wire for 4 weeks. Endodontic treatment of the reimplanted central incisor was initiated 1 week after splinting. The canal was filled with Metapex for 1 week for disinfection. This was followed by placement of MTA apical plug and obturation with gutta-percha . The patAn 8-year-old female reported to the Department of Pediatric Dentistry with the chief complaint of pain on biting in relation to her inward displaced upper front teeth due to trauma 3 weeks back. However, there was no mobility in relation to the traumatized teeth. Clinical examination revealed the crowns of maxillary central incisors to be firm in position but palatally displaced . SensibiIt was planned to perform apexification with MTA for her traumatized incisors. Access was opened for both the teeth and after thorough cleaning and debridement of the root canals; calcium hydroxide-iodoform paste  was inserted in the canals for a week to achieve an aseptic environment. This was followed by placement of apical MTA plugs in both the teeth and subsequent obturation using gutta-percha .In all the patients, MTA was mixed with distilled water as per the manufacturer's instructions and filled in apical third of the root canal using rear end of a size 80 gutta-percha cone. A moist cotton pellet was placed in the remaining root canal and the access opening was sealed. The patient was recalled the next day and obturation of the canal was done using gutta-percha with lateral condensation technique. All the patients have been kept on regular follow-up.7The case 1 reports the treatment of an immature tooth initially treated with calcium hydroxide apexification technique. When the patient subsequently sought treatment for esthetic concerns, the presence of deficient calcium hydroxide filling and a defective coronal seal required revision of the endodontic procedure. The use of MTA as an apical filling material and restoration with chemically cured composite resin aid in preventing further contamination of the root canal system and restoring the esthetics. The advantages of a one-step MTA procedure were cited as reduced treatment time, reduced risk of calcium hydroxide-induced changes to dentine, and consequently reduced fracture risk, and the early placement of a sealing and possibly reinforcing coronal/intraradicular restoration.in vitro study8reported that surgical repositioning of severely intruded permanent teeth with complete root development resulted in more normal orientation of the periodontal fibers and consequently less replacement resorption as the fibers are under less tension with respect to the cementum and bone walls. In addition, Andreasen et al9 favored surgical repositioning of moderate to severely intruded teeth with complete root development as it is potentially less time consuming, requiring fewer patient visits. Prior to use of MTA, it is necessary to remove the bacteria and their byproducts from the canal using irrigation with sodium hypochlorite and intracanal medication with calcium hydroxide for a minimum of 1 week; the latter has been demonstrated to eliminate bacteria in the root canal when applied for this period.10 Thus Metapex  was placed in the root canal as intracanal dressing for a week.Because of the severity of intrusion and completed root development, immediate surgical repositioning of intruded incisor was planned in case 2. Arch bar was used in this case because of associated alveolar fracture and extreme mobility of the adjacent teeth. An animal 11In case 3, as there was marked root resorption and periapical radiolucency of the extruded tooth, retrograde MTA filling was done after apicoectomy and periapical curettage. An ideal orthograde or retrograde filling material should seal the pathways of communication between the root canal system and its surrounding tissues. It should also be nontoxic, noncarcinogenic, nongenotoxic, biocompatible, insoluble in tissue fluids, and dimensionally stable. MTA was developed and recommended because existing root-end filling materials did not have the ‘ideal’ characteristics.In case 4, endodontic treatment of the avulsed tooth was initiated even though it had open apex as no attempts were made by the referring dentist to achieve disinfection of the tooth and it had not been stored in an appropriate medium prior to reimplantation. Thus, calcium hydroxide-iodoform based intracanal medicament was placed in the root canal for this purpose prior to apexification by MTA. The patient has been kept on regular follow-up to assess the outcome of the procedure.12 Development of pulp necrosis after trauma can be associated with symptoms, such as spontaneous pain or tenderness to percussion.13 Thus, endodontic treatment of the traumatized teeth was followed in case 5 after the patient complained of pain on biting in these teeth.Several authors have highlighted the unpredictable response of a tooth to pulp testing following trauma. The irregular response is caused by injury, inflammation, pressure or tension to apical nerve fibers.7 Despite its many advantages, MTA has some drawbacks such as discoloration potential, presence of toxic elements in the material composition, difficult handling characteristics, long setting time, high material cost, an absence of a known solvent for this material, and the difficulty of its removal after setting.1415 Although the standardized clinical approach for apexogenesis or apexification has been widely practiced, the fate of apexification as a first-line treatment for immature teeth with nonvital pulps is affected by the shifting paradigm of the management and the coming era of pulp/dentine tissue regeneration. The progress of pulp/dentine regeneration so far has been promising and is likely to work in the not so distant future.16The diverse application of MTA in the practice of pediatric dentistry is evident in its use as an apical barrier in immature nonvital teeth and in the coronal fragment of fractured roots, as a pulpotomy medicament in primary and permanent teeth, a pulp-capping agent in young permanent teeth, and as a repair material for perforation and resorptive defects.


The cholinergic system is a potent neuromodulatory system that plays critical roles in cortical plasticity, attention and learning. In this review, we propose that the cellular effects of acetylcholine (ACh) in the primary visual cortex during the processing of visual inputs might induce perceptual learning; i.e., long-term changes in visual perception. Specifically, the pairing of cholinergic activation with visual stimulation increases the signal-to-noise ratio, cue detection ability and long-term facilitation in the primary visual cortex. This cholinergic enhancement would increase the strength of thalamocortical afferents to facilitate the treatment of a novel stimulus while decreasing the cortico-cortical signaling to reduce recurrent or top-down modulation. This balance would be mediated by different cholinergic receptor subtypes that are located on both glutamatergic and GABAergic neurons of the different cortical layers. The mechanisms of cholinergic enhancement are closely linked to attentional processes, long-term potentiation (LTP) and modulation of the excitatory/inhibitory balance. Recently, it was found that boosting the cholinergic system during visual training robustly enhances sensory perception in a long-term manner. Our hypothesis is that repetitive pairing of cholinergic and sensory stimulation over a long period of time induces long-term changes in the processing of trained stimuli that might improve perceptual ability. Various non-invasive approaches to the activation of the cholinergic neurons have strong potential to improve visual perception. Boosting the brain’s functioning during rehabilitation paradigms might help individuals with cognitive or sensory deficits to better recover their abilities. In this review, we will examine how the cholinergic system might help in this regard by specifically focusing on visual function. Recent knowledge about the cellular and functional organization of the primary visual cortex (V1) is particularly interesting for the deciphering of the neurobiological mechanisms of perceptual learning and its modulation by the cholinergic system. V1 is the first cortical step of the integration of complex visual stimuli and is decisive in the selection of specific stimuli from the visual field. This process further orients processing in higher cognitive cortical areas involved in elaboration of fine visual conscious perception. Thus, cholinergic modulation of visual processing in V1 would have strong effects on the fine-tuning of perception and the acquisition of memory traces.Perceptual learning is the long-term improvement of the ability to detect or discriminate specific sensory stimuli without interfering with or diminishing other skills that results from training over a sustained period of time  as a neurotransmitter, is particularly relevant because it widely innervates V1 and alters the efficiency of neurons. The injection of ACh or its analogs into V1 has been shown to increase neuronal responses and trigger synaptic plasticity Gu,  and cortOur research hypothesis proposes that cholinergic effects in V1 contribute to perceptual learning and can thus be used to voluntarily develop one’s brain capacity and aid the restoration of visual function. In the present review, we will discuss how ACh might improve perceptual capacities, particularly during repetitive stimulation paired with visual stimulation, which are related to its roles in the long-term enhancement of cortical responsiveness and cortical plasticity Figure .Cholinergic fibers are distributed throughout the cortical layers of V1  and Ca2+ (α7)  Rang,  and in tStimulation of the cholinergic system in V1 can be achieved via the administration of ACh analogs , cholinergic receptor agonists  or cholinesterase inhibitors or through electrical or optogenetic stimulation of the cholinergic neurons that project to V1. The cholinergic neurons that project to V1 are located in the basal forebrain (BF), particularly the ventral pallidum, substantia innominata and the horizontal limb of the diagonal band of Broca  while lowering interference from the background . Several animal studies have described deficits of attention following cholinergic lesions or injections of cholinergic antagonists  balance Figure . The excThe cholinergic modulation of V1 thus promotes cortical plasticity through LTP-like long-term enhancement of synaptic responses to subsequent presentations of a visual stimulus and through control of the excitatory-inhibitory balance that regulate the strength of cortical output and internal connectivity. The cortical plasticity induced by cholinergic stimulation could transfer the acute cholinergic effect into long-term scale to produce visual precision.In summary, acute effects of cholinergic activation might amplify the thalamocortical response that promotes the transmission of sensory inputs. Intensive release of ACh might also inhibit intracortical interactions and relieve the internal brake on processing in the sensory cortices. Simultaneously, neurons with similar tuning characteristics  are co-activated via lateral connections to enhance the transfer of visual information. This cholinergic alternation might contribute to gain control modulation in both stimulus-dependent or and -independent manners and prioritize the processing of selected visual stimuli; this process might be linked to attention and is the first step of perceptual learning. The cholinergic activation also induces the NMDAR-dependent LTP-like long-term enhancement  and relief of the brakes on plasticity by altering the E-I balance. The repetitive coupling of visual and cholinergic stimulation results in reinforcement of all of these acute mechanisms and generate gamma-band synchronization. This would result in the consolidation of the synaptic strengths of new and existing neuronal connections, facilitation of the processing of certain thalamocortical inputs while suppressing others. It has been shown that increases in the cortical responses by expanding the number of neurons to a stimulation (via increases in the strength of the connections) would improve perceptual capacity  the use of the layer II/III GABAergic system to filter the pre-amplified response from layer IV; (2) NMDAR-dependent modification at the postsynaptic level to induce long-term augmentations of individual neurons, and an increase in the numbers of cholinergic varicosities to facilitate ACh release; and (3) changes in the efficiency of the connectivity between cortical areas and bottom-up and top-down control.Similar with experimental data, some clinical studies have demonstrated that enhancing cholinergic system improves perception (Furey et al., Some pharmacological approaches have been developed to increase the perceptual learning in healthy humans. Performance improvements following the use of donepezil during a motion direction discrimination task have confirmed that systemic blockade of ACh esterase can induce perceptual learning (Rokem and Silver, In this review, we proposed that the neuromodulator ACh, which is known for its involvement in attention and learning, might participate in and promote perceptual learning. We proposed that, via the inhibition of intracortical feedback, ACh can render V1 more sensitive to incoming thalamocortical information and enhance sensory performance. During visual processing, ACh acts on different layers to amplify the encoding of weak stimuli by strengthening synaptic connectivity, which leads to behavioral improvements. Furthermore, ACh might not only facilitate task-relevant perceptual learning via attention but also facilitate task-irrelevant learning via reward reinforcement. However, much remains to be uncovered regarding whether the cholinergic system has the potential to be used as a key mechanism for improving the function of the brain and speeding rehabilitation. Specifically, because perceptual learning occurs easily under conditions of attentional control, the development of a method to improve one’s brain capacity through improved attention and cholinergic stimulation is very attractive.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


An ectopic tonsil is defined as tonsillar tissue that develops in areas outside of the four major tonsil groups: the palatine, lingual, pharyngeal, and tubal tonsils. The occurrence of tonsillar tissue in the oral cavity in ectopic locations, its prevalence, and its developmental mechanisms that belong to its formation remain unclear. In this report, we describe a rare case of bilateral symmetric ectopic oral tonsillar tissue located at the ventral surface of the tongue along with two solitary cases arising from the floor of the mouth. The role of immune system and its aberrant response leading to ectopic deposits desires further studies. As an ectopic tonsil may simulate a benign soft tissue tumor, this case series highlights the importance of this entity in our clinical differential diagnosis of oral soft tissue masses. The tonsils form part of a circular band of adenoid tissue known as Waldeyer's ring, which guard the opening of the digestive and respiratory tracts. This circular band is comprised of four major tonsil groups: the palatine, lingual, pharyngeal, and tubal tonsils. An ectopic tonsil is tonsillar tissue that develops in areas outside of these regions. The existence of ectopic oral tonsils was described by Knapp in 1970 [Ectopic tonsils have been reported in different anatomic locations of the oral cavity, for example, on the floor of the mouth –6, ventrHere we report a rare case of bilateral symmetric ectopic oral tonsillar tissue observed on the ventral surface of the tongue and two other solitary cases arising from floor of the mouth along with a review of the literature.A 53-year-old Japanese male, referred by his general dental practitioner, presented with small, bilaterally symmetric masses on the ventral surface of the tongue, noticed during a routine dental examination 2 months ago. The areas affected were painless and remained unchanged in size over the previous 2 months. Intraoral examination revealed hard masses of 8 mm diameter (right) and 6 mm diameter (left) on the ventral surface of the tongue . The surA 63-year-old Japanese female presented at our hospital with a small swelling on the left side of the floor of the mouth. She first noticed this lump 10 days previously. The affected area was painless and its size remained unchanged. Intraoral examination revealed a well-circumscribed mass (5 mm diameter) on the left side of the floor of the mouth . The masA 38-year-old Japanese female visited our clinic complaining of a small painless lump on the right side of the floor of the mouth. She first noticed this lesion 2 days ago. Intraoral examination revealed a well-circumscribed mass (6 mm diameter) covered by intact normal-appearing mucosa . The masEctopic tonsils are comprised of a single or branched crypts containing lymphoid follicles lined with stratified squamous epithelium. In As a result only 62 cases have been reported in the English language. The most frequently affected area is the floor of the mouth (59% of cases), followed by the soft palate (24.6%) and ventral surface of the tongue (9.8%). In the clinical findings, the size of the lesions ranged from 3 to 28 mm with rounded shape, and the surface covering of the lesions was occasionally and slightly red. Therefore, they may cause diagnostic confusion, especially when found around the floor of the mouth. It may be misdiagnosed as tumors that arise from the sublingual gland.According to Knapp, lymphoepithelial cyst that originates from lymphoid tissue following obstruction of these crypts also may have similar presentation. Clinically, these lesions appear yellowish and comprise a cystic cavity that appears as a dilated crypt lined with a stratified squamous epithelium . In the The pathogenesis of ectopic tonsils in this region remains unclear. Lymphoid tissue is also found in fetal salivary glands, and occasionally remnants of lymphoid tissue are found in adult salivary glands . The masThese cases reported by us highlight the possibility of ectopic oral tonsillar tissue and raise the need to consider them when making a differential diagnosis of soft tissue lumps found on the floor of the mouth and/or the ventral surface of the tongue. Further cadaveric study is required to clarify the presence of ectopic tonsillar tissue on these anatomical sites, particularly with regard to its developmental mechanisms, and to assess its prevalence and to study the clinical significance of the immune system and its response.Ectopic tonsils appear to occur more frequently than are generally recognized, probably because they are usually asymptomatic and are thus easily overlooked. We have described these three cases of ectopic tonsils to propose that clinicians may consider inclusion of this entity in the clinical differential diagnosis, often not encountered in reference text books in oral medicine and pathology.


Hypertrophic cardiomyopathy (HCM) has a wide clinical spectrum. An important subgroup of patients are at risk of major complications and sudden cardiac death. However risk stratification in these patients is still a challenge. The degree of hypertrophy and myocardial fibrosis are important predictors of prognosis. There are several papers showing the possibility of areas of abnormal left ventricular (LV) perfusion in patients with HCM. Some studies focused on stress-induced perfusion defects , demonstrating the presence of epi-endocardial gradients of perfusion in the LV due to microvascular dysfunction. Some other studies  have focused the attention on LGE-related rest perfusion abnormalities. These are due to areas of microvascular disruption and do not contribute necessarily towards the LV ischemic burden. Mixed defects are also possible. The aim of the study was to analyse in retrospective a group of patients with HCM that underwent stress perfusion and LGE-CMR and to describe the prevalence of perfusion defects of each type.This study included 33 consecutive patients with HCM. The images were analysed by consensus of 2 expert CMR readers. The results were reported on segmental basis, indicating the presence or absence of perfusion abnormalities on stress perfusion scans, the presence of a perfusion gradient, the presence of areas of scar related perfusion abnormalities or the presence of mixed perfusion defects.Hypertrophy, LGE and perfusion defects involved more frequently the inter-ventricular septum. No patients in this group had severe LV hypertrophy (max LV thickness > 30 mm). LGE had a prevalence of 76%, while perfusion abnormalities with a gradient pattern were seen in 87% of patients in at least 1 LV segment. Perfusion abnormalities were present with a pure gradient pattern in 55% of the LV segments. LGE-correlated abnormalities were seen alone in 15% of the segments. Mixed perfusion abnormalities were seen in 30% of the segments.Our results demonstrate that CMR is a useful tool to identify perfusion abnormalities in patients with HCM. Stress-induced perfusion defects are frequently present in patients with HCM also in the absence of severe LV hypertrophy. The intrinsic high spatial resolution allowed by perfusion and LGE-CMR enables the differential diagnosis of perfusion abnormalities indicative of microvascular dysfunction, contributing to the LV ischemic burden, and those related to the presence of scar. Combined perfusion and LGE-CMR has the potential to increase the accuracy of quantification of the true LV ischemic burden in patients with HCM.The Centre of Excellence in Medical Engineering is funded by the Wellcome Trust and EPSRC under grant number WT 088641/Z/09/Z. The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London.


Biodeterioration of historic monuments and stone works by microorganisms takes place as a result of biofilm production and secretion of organic compounds that negatively affect on the stone matrix.Escherichia coli Z1. The antimicrobial activity of CuNPs was evaluated against the bacterial strains Bacillus subtilis, Micrococcus luteus, Streptomyces parvulus, Escherichia coli, Pseudomonas aeruginosa as well as some fungal strains Aspergillus niger, Aspergillus flavus, Penicillium chrysogenum, Fusarium solani and Alternaria solani.Copper nanoparticles (CuNPs) were prepared biologically using the headspace gases generated by the bacterial culture E. coli, S. parvulus and B. subtilis in addition to an improvement in the physical and mechanical characters of the treated stones. Furthermore, the elemental composition of CuNPs was elucidated using electron dispersive x-ray system connected with the scanning electron microscope.Biological CuNPs demonstrated antibacterial and antifungal activities higher than those of the untreated copper sulfate. At the same time, limestone and sandstone blocks treated with consolidation polymers functionalized with CuNPs recorded apparent antimicrobial activity against Consolidation polymers impregnated with CuNPs could be used to restrain microbial deterioration in addition to the refinement of physico-mechanical behavior of the historic stones. Nanoparticles demonstrate vast array of properties such as optical, electrical, catalytic, magnetic and biological activities which are diverged from those of the original constituents , 2. The Micrococcus luteus, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, + + . In fact3)2]+ .2+ is the motivating force behind the antimicrobial properties of polymers containing Cu-nanocomposites [2+ or CuNPs against bacteria and fungi makes them perfect antimicrobial agents with low possibility of developing microbial resistance [This study clarified a marked antimicrobial efficacy of CuNPs against various bacterial and fungal species. The biocidal activity of CuNPs could be attributed to the effect of the CuNPs and/or the copper ions discharged from CuNPs. Because of the great surface area of the nanoparticles, it could be tightly adsorbed onto the surface of the microbial cells resulting in; i) disruption of cell permeability and release of integral components , ii) denmposites . At the mposites , 36. Obvsistance , 33.In the current study, the silicon and acrylic polymers that were loaded with the copper nanoparticles showed a positive influence on the treated stones through suppressing the growth of tested bacterial strains at various levels. At the same time, the antimicrobial activity of the biosynthesized CuNPs was not changed by merging with consolidation polymers. These results are in agreement with our preceding study  that revIn addition to the antimicrobial task of the functionalized polymers, they demonstrated an apparent perfection in the physical and mechanical properties of the treated stones. The consolidation polymers especially silicone polymer decreased the level of water absorption and porosity of stones through the formation of a protective layer. This layer is formed due to the penetration of the polymer molecules into voids and pores of the stone matrix. Moreover, the mechanical measurements indicated that both types of polymers increased the compressive strength which reflects the importance of using these polymers in the consolidation processes of the limestone monuments. These results are in harmony with Ahmed  who recoEscherichia coli to aggregate Cu ions into nanometal structures away from the bacterial cells. This bioprocess is inexpensive and eco-friendly. Besides, uncontaminated bacterial biomass could be used safely in different applications. The incorporation of CuNPs into polymer matrix produced nanocopper composites with remarkable antimicrobial capability. The functionalized consolidation polymers could be used not only to inhibit the microbial growth on the surfaces of historical stones but also to improve physical and mechanical properties of the treated stones. Additional research is required to evaluate the application of consolidation polymers loaded with nanoparticles of copper in situ treatment.Copper has strong biocidal activity with non-specific mode of action against microbial cells that make it ideal antimicrobial agent. CuNPs were prepared through novel bioprocess that utilizes volatile metabolites of


Despite multiple advantages, subclavian vein (SCV) cannulation via the traditional landmark approach has become less used in comparison to ultrasound (US) guided internal jugular catheterization due to a higher rate of mechanical complications. A growing body of evidence indicates that SCV catheterization with real-time US guidance can be accomplished safely and efficiently. While several cannulation approaches with real-time US guidance have been described, available literature suggests that the infraclavicular, longitudinal “in-plane” technique may be preferred. This approach allows for direct visualization of needle advancement, which reduces risk of complications and improves successful placement. Infraclavicular SCV cannulation requires simultaneous use of US during needle advancement, but for an inexperienced operator, it is more easily learned compared to the traditional landmark approach. In this article, we review the evidence supporting the use of US guidance for SCV catheterization and discuss technical aspects of the procedure itself. Since its original description over 60 years ago by Aubaniac, the subclavian vein (SCV) has been an important vessel for central venous cannulation.Wide availability and improved technology have made bedside US a valuable tool for establishing vascular access. It allows for direct visualization of and evaluation for the vessel of choice in addition to precise needle positioning during cannulation.15At first glance, the SCV seems difficult to visualize on US because it travels beneath the highly reflective clavicle bone. This, along with the higher complication rate of the LM-guided approach, has resulted in the SCV falling out of favor for elective central vein cannulation in many modern clinical settings. To explore this notion, recent studies have compared the use of US to the LM approach in SCV cannulation  and resuPositioning the long footprint of the US probe perpendicular to the course of the vessel gives rise to a short axis view . This viA single-center randomized crossover control trial including 57 emergency medicine residents and attending physicians of varying US experience compared the short axis versus long axis approach for axillary vein cannulation using a torso phantom model.16Multiple studies have demonstrated the advantages of a supraclavicular approach to SCV cannulation, but results have been dependent on operator experience.20There are limited published data comparing supraclaviclar to infraclavicular approaches with real-time US guidance. In one prospective anatomical study of normovolemic patients, Stachura et al demonstrated that identifying the SCV in the supraclavicular region using US is technically easier compared to the infraclavicular region.The axillary vein courses medially and becomes the SCV at the lateral border of the first rib. It continues its path under the clavicle, arching upward across the superior surface of the first rib and then inclines medially, downwards and across the insertion of the anterior scalene muscle. At this point, it enters the thorax as it unites with the IJV behind the sterno-clavicular joint.27The procedure begins with the patient placed in a supine position, prepared and draped in a sterile fashion. The subclavian and axillary veins are visualized by placing a high frequency linear transducer in the infraclavicular fossa , in ordeThis longitudinal, real-time, US-guided infraclavicular SCV cannulation approach offers several advantages to the LM technique. Using this approach, the operator can control the advancement of the needle, identify adjacent anatomical structures, including the pleura and posterior wall of the vessel. This in turn allows for a decreased risk of posterior vessel wall puncture, lowering the subsequent risk of pneumothorax.The SCV offers multiple advantages as a target for central venous access in the appropriately selected patient. The use of real-time US guidance for infraclavicular placement of SCV catheters allows for direct visualization of needle insertion and adjacent anatomical structures, as well as guidewire location and directionality, all of which can lead to decreased mechanical complications and improved cannulation success, compared to a LM technique. Although more research is needed, in our opinion the current literature supports the use of the infraclavicular longitudinal US-guided SCV catheterization as the preferred technique for cannulation of SCV when compared to LM approach and a solid alternative to cannulation of IJVs.


A fourth production region for the globally important Antarctic bottom water has been attributed to dense shelf water formation in the Cape Darnley Polynya, adjoining Prydz Bay in East Antarctica. Here we show new observations from CTD-instrumented elephant seals in 2011–2013 that provide the first complete assessment of dense shelf water formation in Prydz Bay. After a complex evolution involving opposing contributions from three polynyas (positive) and two ice shelves (negative), dense shelf water  is exported through Prydz Channel. This provides a distinct, relatively fresh contribution to Cape Darnley bottom water. Elsewhere, dense water formation is hindered by the freshwater input from the Amery and West Ice Shelves into the Prydz Bay Gyre. This study highlights the susceptibility of Antarctic bottom water to increased freshwater input from the enhanced melting of ice shelves, and ultimately the potential collapse of Antarctic bottom water formation in a warming climate. Antarctic bottom water (AABW) production is critical to the global ocean overturning circulation. Here, the authors show new observations of AABW formation from seal CTD data in Prydz Bay, East Antarctica that highlights its susceptibility to increased freshwater input from the melting of ice shelves. Antarctic bottom water (AABW) production is vital to the Earth's climate system and biogeochemical cycles12783 per year)14Mirounga leonina). This led to the conclusion that the primary DSW source of CDBW was the Cape Darnley polynyaDecades of speculation about a DSW source in Prydz Bay1112Here we focus on the role of the Prydz Bay polynyas and ice shelves in the formation of DSW to clarify Prydz Bay's contribution to CDBW. We use a further 2 years of salinity and temperature observations from instrumented seals in 2012–2013 that expand both the spatial and seasonal coverage of DSW in Prydz Bay. Extended periods of concentrated profiling of the water column around the periphery of the Prydz Bay Gyre (PBG) are now available. These unique observations in the key polynyas of Barrier Bay, Davis and MacKenzie Bay, and across the outflow region through Prydz Channel upstream of Cape Darnley, allows us to present a comprehensive picture of the evolution of DSW formation and export from Prydz Bay. Documenting the impact of ice shelves on polynya-driven AABW production, this study is timely given the growing evidence of widespread thinning of both West and East Antarctic coastal ice sheet margins171819The ocean circulation in Prydz Bay consists of a large cyclonic gyre, centred in a deep channel, known as the Amery Depression122224n<28.27) is the dominant water mass from April through May, intruding at intermediate depths and moving southeastward over the Four Ladies Bank towards Davis Station and the eastern Amery Ice Shelf frontIn the eastern region of Prydz Bay, mCDW  has been observed outflowing through the western flank of the calving frontDSW at depths between 50 and 500 m  in the polynyas around Prydz Bay following the PBG circulation, from the northeast at the Barrier Bay polynya, followed by the Davis, MacKenzie Bay and Cape Darnley polynyas (S<34.55), to the MacKenzie Bay polynyas (S<34.7). The latter is also observed along the western flank of Prydz Bay through Prydz Channel. As previously reportedS>34.8).We examine the presence of DSW . It seems likely that a combination of both processes is occurring, given the low-salinity signal detected in the overflows of mSW north of Cape DarnleyThere are two possible pathways for the DSW from Prydz Bay Recently, a warming trend  has been documented in AABW properties downstream of the Prydz Bay–Cape Darnley system, due to increased entrainment of CDWAs observational data sets expand into previously unexplored regions of the East Antarctic coastline, provided largely by animal-borne sensors, we are finding that each newly discovered polynya-based DSW region varies dynamically from the previous ones. In the Mertz Polynya, the large storage volume of the Adélie Depression aids the build-up of DSWThe dual system of DSW contributions detailed in this paper for Cape Darnley and Prydz Bay is similar to other key AABW production regions around Antarctica. In the Ross Sea, there is high-salinity DSW input from Terra Nova Bay polynyas, together with a less dense, fresher variety of DSW from the Ross Ice Shelf−1)−1)A modelling study tested the impact of Antarctic ice shelf basal melting on deep ocean properties and showed that glacial basal melting stabilized the water column in front of an ice shelf as well as downstream, reducing the volume of DSW and thus of AABWTo conclude, we provide novel evidence of dense shelf water export from Prydz Bay, demonstrating that it makes an important secondary contribution to Cape Darnley bottom water. The salinity of DSW leaving the MacKenzie Bay polynya is greater than 34.67, in the range of DSW exported from the Mertz Glacier region (∼142° E) in the production of Adélie Land bottom water. Cape Darnley DSW is the highest in salinity (34.8) and is clearly the primary source of CDBW, nonetheless, Prydz Bay makes a vital contribution to it, through the direct export of DSW through Prydz Channel and the potential pre-conditioning of the CDP beneath the Cape Darnley ice barrier. This study highlights the complex nature of DSW formation around Antarctica, in particular the importance of upstream regions on local water mass transformations and the likely impacts of enhanced ocean/ice shelf interactions. In the broader context of Antarctica's role in global climate, we find that despite strong sea ice production from three polynyas in the region, freshening from ocean/ice shelf interactions limits the overall formation of DSW in Prydz Bay.There has been a lot of attention recently on the decadal-scale impact of icescape changes to AABW, resulting from major ice front calving events in polynyas regions, such as along Adélie Land after the calving of the Mertz Glacier35www.meop.net)Instrumented elephant seals have been providing an invaluable additional source of oceanographic measurements to global databases, with particularly strong impact in data-poor regions such as around Antarctica163839http://www.meop.net). All relevant data are available from the authors.The marine mammal data were processed and made freely available by the International MEOP Consortium and the national programs that contribute to it .Supplementary Figures 1-4 and Supplementary Table 1


Modern electrophysiology is developing fast and it sometimes provides more data than available algorithms and methods can handle and process. In particular, there is an increasing demand for methods which provide the possibility to study similarity patterns of activity across many neurons. Accordingly, a wide variety of approaches to quantify the similarity (or dissimilarity) between two or more spike trains has been suggested. Recently, the ISI- and the SPIKE-distance ,2 have bn)N2). By selecting a pair of spike trains one obtains a bivariate dissimilarity profile whereas the selection of a time instant yields an instantaneous matrix of pairwise spike train dissimilarities which can be used to divide the spike trains into instantaneous clusters, i.e., groups of spike trains with low intra-group and high inter-group dissimilarity. Another way to reduce the information is averaging. The spatial average over spike train pairs yields a dissimilarity profile for the selected (sub)population, whereas temporal averaging leads to a bivariate distance matrix for the selected interval or the selected trigger points. Finally, application of the remaining average results in one distance value which describes the overall level of synchrony for a group of spike trains over a given time interval.For both the regular and the real-time SPIKE-distance, there are several levels of information reduction . The sta. This interactive program facilitates the application of the ISI- and the SPIKE-distance to both simulated and real data. Once given a set of spike train data (importable from many different formats), SPIKY calculates the desired measure and allows visualization of different representations such as measure profiles and pairwise dissimilarity matrices. SPIKY also includes the possibility to generate movies which are very useful in order to track the varying patterns of (dis)similarity. Finally, SPIKY has been optimized with respect to both computation speed  and memory demand (by taking advantage of the piecewise linear nature of the dissimilarity profiles).The Matlab source codes for calculating and visualizing both the ISI- and the SPIKE-distance have been made publicly available and have already been widely used in various contexts. However, the use of these codes is not very intuitive and their application requires some basic knowledge of Matlab. Thus it became desirable to provide a more user-friendly and accessible interface. Here we address this need and present an advanced version of the graphical user interface SPIKY ,5. This


E. coli causing urinary tract infections (UTI) in the community in the West of Ireland was mapped. All adult patients consulting with a suspected UTI in 22 general practices in the West of Ireland over a nine-month study period were requested to supply a urine sample. Those with a laboratory confirmed E. coli infection were included (n = 752) in the study. Antimicrobial susceptibility testing was performed by standardized disc diffusion. Patient addresses were geocoded. The diameters of the zone of inhibition of growth for trimethoprim (5 μg) and ciprofloxacin (5 μg) for the relevant isolate was mapped against the patient address using ArcGIS software. A series of maps illustrating spatial distribution of AMR in the West of Ireland were generated. The spatial data demonstrated a higher proportion of isolates with AMR from urban areas. Some rural areas also showed high levels of resistant E. coli. Our study is the first to demonstrate the feasibility of using a geographical information system (GIS) platform for routine visual geographical analysis of AMR data in Ireland. Routine presentation of AMR data in this format may be valuable in understanding AMR trends at a local level. The use of antimicrobials over the past six decades has been associated with the emergence and dissemination of antimicrobial-resistant bacteria. To explore local geographical patterns in the occurrence of acquired antimicrobial resistance (AMR), AMR of  The spread of acquired antimicrobial resistance (AMR) in bacteria represents a significant public health threat, with growing limitations on the availability of effective drug treatment options for many common infections ,2. StudiThe use of maps for analyzing and illustrating the occurrence of AMR in bacterial pathogens at a national level has been employed on a European-wide basis since 1999 . This caDifferences in the levels of AMR in bacteria at the regional level have been reported in numerous countries, and practitioners are advised in many countries to consult local resistance data when prescribing antimicrobials for bacterial infections ,5,11,12.Geographical information systems (GIS) have been used as a means of conveying health care related data to a wide audience, as they facilitate the visualization of disease patterns in a specified geographic region . GIS areInvestigations into the spread of resistant pathogens in the wider community represent a major challenge for public health. Community based investigations generally involve broad geographical regions, and there are currently no established regional AMR reporting systems in place in Ireland. The appropriate medium would need to convey relevant health information, such as resistance data, to health care professionals at all levels, in particular general practitioners, on a routine basis. The ideal platform for this type of data would give an easy to understand, clear and concise overview of bacterial AMR on local, regional and national levels. This platform should also support analysis of spatial variation in the occurrence of AMR in the context of spatial data on antimicrobial consumption and other health indicators . This information would promote health care professionals’ and communities’ awareness of the local occurrence of resistance and ultimately to understand to what extent factors such as local antimicrobial consumption impact on local resistance levels. The routine provision of AMR data in the primary care setting in this format could support a positive change in antimicrobial prescribing practices, as prescribing would be guided by local resistance patterns. Staphylococcus aureus (MRSA) [Streptococcus pneumoniae [E. coli [E. coli causing UTI from a prospective study in a region in the West of Ireland, details of which have been previously reported [E. coli isolates associated with UTI in the community during the study period were mapped against the geo-coordinates of the patients. Since Ireland does not have postal codes, geocoding was done by hand, based on the townland address. This process aided a feasibility assessment for the routine use of GIS in analyzing and reporting AMR information. GIS are currently underutilized for studying AMR in the community and have not been used previously for this purpose in Ireland. Previous research elsewhere applied GIS to study meticillin-resistant s (MRSA) , Streptoeumoniae  and E. c[E. coli . The prereported . The agereported . AntimicThe current study included 682 females (91%). The overall patient mean age was 55 (±21) years . OverallE. coli UTI cases, study practices and nursing homes in the study region are outlined in n ≥ 10) of E. coli cases per electoral divisions (ED) are indicated with a red or orange color. A low number (n ≤ 5) of cases are indicated with blue or green. Practices and nursing home locations are identified in each ED. High numbers of UTI cases are observed in more urban areas with a higher population density. The distribution of E. coli to ciprofloxacin and trimethoprim are presented in Heat maps showing the mean antimicrobial diameter of the zone of inhibition results for A choropleth map a,b displE. coli UTI isolates occurring in many individual EDs contributes to potential differences in AMR that occur by chance. Nevertheless, the results of the current study suggest spatial clustering of resistance and potential areas of high-risk for antimicrobial-resistant E. coli.The present study demonstrates the feasibility of the application of GIS for studying the dissemination of acquired AMR in a common bacterial pathogen in the wider community at a local level. GIS software allows for the analysis and visual representation of data in the form of a geographical map, which can be easily interpreted by health care professionals, members of the public and policy makers . ResultsThe study uses both clinically interpreted (EUCAST) and non-interpreted (zone diameter) results to present the data, which also allows for the visualization of a summative quantitative measure of resistance (mean zone diameter) in addition to the more commonly used percentage of isolates categorized as resistant by defined interpretive breakpoint criteria. E. coli in a locality and the presence of a nursing home in the area, although this is both unconfirmed and difficult to interpret. The inclusion of isolates from nursing homes in the current study introduced bias. UTIs are very common in nursing home residents and urine samples are regularly taken to check for infection. A higher proportion of UTIs is therefore to be expected in areas with a nursing home. The proportion of resistant E. coli UTIs is also higher due to a combination of high antimicrobial consumption by the residents and interpersonal spread. The inclusion of isolates from nursing homes will inflate the overall AMR level of a particular area compared to townlands where no nursing home is present, in particular with the low numbers included in this study. Previous research has identified household and community risk factors for the acquisition of resistant bacterial pathogens. The role of the wider environment in the spread of AMR is now better understood [n = 27) from patients within a specific area of a city [The results suggest spatial clustering of resistance to trimethoprim and ciprofloxacin and therefore the possibility of local high-risk areas of resistant bacteria. The use of GIS allows one to examine spatial variations at the level of resistance in the context of particular geographical information, for example urban compared with rural areas or the occurrence at a nursing home in the locality. There is a subjective impression, for example, of a link between higher resistance among derstood . A studyf a city . The autE. coli as a urinary tract pathogen and correlated high-level resistance with antimicrobial consumption expressed as defined daily doses (DDD). Similar to the current study, clustered hot-spots of resistance were observed along with significant spatial variation. Resistance hot spots correlated to higher usage  of ciprofloxacin in the community. General practitioners (GPs) could benefit from the routine use of GIS for displaying AMR data by aiding in the prescription choice of antimicrobial drugs for common infections. The maps could indicate if the GP is in an area where high or low resistance to certain drugs is prevalent in the bacterial population. This would result in less use of newer, reserve antimicrobials (particularly in areas of low resistance), hence more appropriate and better treatment outcomes for patients (particularly in areas of high resistance). Conversely, GIS could be used to show antimicrobial prescribing patterns as a direct measure of antimicrobial resistance in a specified region; however this was not carried out in the present study. The use of GIS to visually present the association between antimicrobial consumption and antimicrobial prescribing was previously carried out in Sao Paulo, Brazil . This prE. coli information at the townland level. This is particularly apparent with the inclusion of isolates from nursing home residents, where a greater number of E. coli isolates with increased AMR can inflate the observed levels of resistance in that area, as previously discussed.While there are numerous advantages of using GIS to display health care information, appropriate precautions must be adhered to. When inferring a relationship based on the results of spatial analysis, caution should be used in applying the appropriate areal units  and analysis should be carried out at numerous scales to evaluate the effect . The useThe use of GIS for mapping health care data based on patient addresses in Ireland on a routine basis has several limitations. Geocoding of patient addresses can be a time-consuming task, in particular where postal codes are not in use, as is the case in Ireland. Numerous discrepancies exist between the spellings of various townlands, in particular where Irish is the first language (Gaelic-speaking areas). The introduction of postal codes in Ireland, or the automatic linking of patient addresses with x, y coordinates, would alleviate this problem and allow for automated patient data retrieval and subsequent analysis. This is the first study to report the use of GIS for the investigation of patterns of antimicrobial resistance in pathogenic bacteria in Ireland. The study highlights the potential of GIS to present antimicrobial resistance data for routine communication of current epidemiological trends in bacterial pathogens. As piloted in this study, this can allow the investigation into the impact of possible risk factors associated with antimicrobial resistance, such as the presence of a health care center such as a nursing home in the region. While not evaluated in the current study, the software can also be used to investigate the impact of other potential risk factors such as social deprivation or agricultural use in the region , as well2). Patient data from a previous prospective case-control study analyzing AMR (trimethoprim and ciprofloxacin) in E. coli causing UTI in the community was used [The study area covered two counties in the West of Ireland, namely Galway and Roscommon . Antimicrobial susceptibility zone diameters (mm) to two antimicrobials (trimethoprim and ciprofloxacin) and patient townland addresses were geocoded with assignment of specific latitude and longitude coordinates, for use with ArcGIS software as described below.n = 342) were used as base scale features (polygons). EDs are the smallest legally defined administrative areas in Ireland, of which there are 3,440 [n = 22) was manually geolocated on a base map in ArcGIS. Patient townland data was converted to a vector point Shapefile by extracting the centroid  of each townland polygon. Following this, a spatial join was carried out in ArcGIS to link the patient data with the geographic townland dataset. Electoral divisions (ED)  . The diai.e., a minimum zone diameter of 6 mm) to the antimicrobial. Color themed maps were created to visually display the number of UTI cases per ED. Where an isolate originated from a nursing home patient, the nursing home was indicated in an ED. Heatmaps were generated by extracting the average zone diameter for each ED, while choropleth maps were generated using proportions of resistance for each ED. Heatmaps use varying degrees of color  to represent a scale. In this study, a lighter yellow color indicates a larger zone diameter result and less resistance to the specific antimicrobial studied. A deeper orange color indicates a smaller zone diameter result indicating increased resistance to an antimicrobial, while a red color indicates complete resistance (The spatial extent of heatmaps a,b does This research demonstrates that it is possible to spatially analyze community antimicrobial resistance in common bacterial pathogens. This suggests a potential application of geo-mapping to optimize antimicrobial prescribing practices across large geographical regions.


The implants failure may be caused by micromotion and stress exerted on implants during the phase of bone healing. This concept is especially true in case of implants placed in atrophic ridges. So the primary stabilization and fixation of implants are an important goal that can also allow immediate loading and oral rehabilitation on the same day of surgery. This goal may be achieved thanks to the technique of welding titanium bars on implant abutments. In fact, the procedure can be performed directly in the mouth eliminating possibility of errors or distortions due to impression. This paper describes a case report and the most recent data about long-term success and high predictability of intraorally welded titanium bar in immediate loading implants. The technique of welding portions of intraoral prosthesis has demonstrated many advantages in clinical practise. In fact, the procedure can be performed directly in the mouth eliminating the possibility of errors or distortions due to impressions. In particular, the intraoral welding is very effective in immediate loading of dental implants positioned in atrophic edentulous ridges. So, in case of immediate loading, adequate fixation and stability of implants are very important conditions to prevent the risk of micromovements and loss of implants. In this context, a rigid splinting seems to have an important role in response of peri-implant tissues, since it is able to reduce stress exerted on implants.The immediate fixation of more implants can be achieved by intraoral welding of abutments. Intraoral welding allows getting immediate retention of osseointegrated implants. The method consists in welding a titanium bar directly to the abutments in the oral cavity before the immediate loading.The main advantage of intraoral welding consists in placing definitive restoration on the same day of surgery, or few days later. In fact, the lack of stability and retention of denture is the main discomfort complained about by totally edentulous patients.Degidi and coll –8 have pIn 2006 Degidi and coll  publisheHere we describe a case of atrophic mandible treated with five implants and a welded bar.A 67-year old female came to our clinic for an examination. The medical history did not reveal any systemic diseases and the patient confirmed she did not take any kind of medication. The orthopantomography showed periodontal teeth which subsequently were extracted . Before Patient was very satisfied and no adverse effect was detected in the subsequent 1 year follow-up .The lack of stability and retention is responsible for oral complains associated with dentures. Besides, sometime implant rehabilitation of atrophic mandible may be impossible because of insufficient bone. Immediate loading implants with definitive denture have demonstrated long-term success and high predictability. Other studies confirm successful oral rehabilitation of edentulous atrophic maxilla with a fixed, definitive restoration supported by an intraorally welded titanium bar on the same day of implant placement surgery , 3.Avvanzo demonstrated that dental abutments, intraorally welded with a titanium bar, allow immediate loading implants and provisional or definitive restoration during healing of bone, without problems of micromovements and implants loss. Immediate denture improves patient's compliance due to a more comfortable prosthesis .Immediate loading of implants may be successfully achieved with intraoral welding technique when they are positioned in zygomatic bone too. In fact it is possible to successfully rehabilitate the edentulous atrophic maxilla with a permanently fixed prosthesis supported by an intraorally welded titanium framework attached to standard and zygomatic implants on the day of surgery. They show stability and prosthetic success rate at the 12-month  and 3-yeAnother method to connect the abutments to the bars is represented by the laser welding. Kuo et al. in 2006 described a new technology for immediate loading implants using laser welded bars applicable to various implant systems and clinical situations .In today's dental literature, most frequently, esthetics are addressed with fixed restorations. This technique gives the opportunity to provide patients with very good esthetic outcomes with a hopeless dentition utilizing dental implants, laser-welded titanium components, and characterized acrylic resin prostheses. The definitive prostheses provide excellent facial support, phonetics, esthetics, smile line, and function. Laser-welded titanium frameworks offer many advantages for the patient, clinician, and dental technician . SupportA study by Silva investigated the influence of laser welding and electroerosion procedure on the passive fit of fixed implant-supported titanium frameworks, concluding that frameworks may show a more precise adaptation if they are sectioned and laser welded. In the same way, electroerosion improves the precision in the framework adaptation , 14.De Aguiar in his study compared the accuracy of fit of three types of implant-supported frameworks cast in Ni-Cr alloy: specifically, a framework cast as one piece compared to frameworks cast separately in sections to the transverse or the diagonal axis and later laser welded. Results of this study showed that casting diagonally sectioned frameworks lowers misfit levels of prosthetic implant-supported frameworks and also improves the levels of passivity to the same frameworks when compared to structures cast as one piece .Lack of passivity has been associated with biomechanical problems in implant-supported prosthesis. De Castro evaluated the passivity of three techniques to fabricate an implant framework from a Co-Cr alloy by photoelasticity. It was concluded that there were no differences in forces exerted on implants .Rigid splinting of multiple implants with intraoral welding technique results in a predictable fixation in the early stage for bone healing with a significant reduction of the micromovement problem and implants loss.


The efficacy of lamotrigine in the treatment of focal epilepsies have already been reported in several case reports and open studies, which is thought to act by inhibiting glutamate release through voltage-sensitive sodium channels blockade and neuronal membrane stabilization. However, recent findings have also illustrated the importance of lamotrigine in alleviating the depressive symptoms of bipolar disorder, without causing mood destabilization or precipitating mania. Currently, no mood stabilizers are available having equal efficacy in the treatment of both mania and depression, two of which forms the extreme sides of the bipolar disorder. Lamotrigine, a well established anticonvulsant has received regulatory approval for the treatment and prevention of bipolar depression in more than 30 countries worldwide. Lamotrigine, acts through several molecular targets and overcomes the major limitation of other conventional antidepressants by stabilizing mood from “below baseline” thereby preventing switches to mania or episode acceleration, thus being effective for bipolar I disorder. Recent studies have also suggested that these observations could also be extended to patients with bipolar II disorder. Thus, lamotrigine may supposedly fulfill the unmet requirement for an effective depression mood stabilizer. Management of bipolar disorders has given main focus on the treatment of acute mania, while neglecting the treatment of bipolar depression, both of which constitutes the extreme poles of the bipolar disorder . HoweverOver the past few years, lamotrigine has also been found effective in the treatment of bipolar disorder being more efficacious in treating the depressive phase of the illness . For theLamotrigine, an anticonvulsant drug is one such widely studied medication whose therapeutic efficacy has been extended even beyond its use as a mood stabilizer . Lamotrin = 66), lamotrigine 200 mg/d (n = 63), or placebo (n = 66) were given to the patients showing 17-item HDRS score ≥18. After 7 weeks of treatment, primary measures were not significantly different secondary measures, had a significantly superior response rate on mean ± SD observed scores on 17-item HDRS, CGI-Severity of Illness, and CGI-Improvement in lamotrigine 200 mg/d group. In the four other studies subjects diagnosed with bipolar I disorder  which may alternate from depressive episode lasting for several weeks or months to intense maniac symptoms lasting for about the same duration. In patients with bipolar II disorder, the clinical data for the long term use of lamotrigine is very limited . PatientIn various clinical trials lamotrigine use as an augmentation agent was explored for bipolar disorder with depressive episodes not responsive to typical mood stabilizers. In a randomized, double-blind, 7-week pilot trial, lamotrigine augmentation was compared with citalopram augmentation for bipolar I and II depression . Total MThe antidepressant drug lamotrigine is found to be therapeutically more effective in the treatment of depressive phase of the bipolar disorder than in treating hypomania or mania . The usein vivo evaluations in various regions of the brain were conducted to understand the effect of lamotrigine on serotonin 1A-receptor-mediated adenyl cyclase responses in various brain areas in the mice. The results, which were obtained thereafter, suggested a new pathway which reflected the therapeutic efficacy of various classes of mood stabilizers. This in vivo study was therefore successful in explaining lamotrigine’s mode of action that was eventually a result of downregulation of cortical 5-HT1A-receptor-mediated adenyl cyclase responses. Thus showing significant role of 5-HT in the physiopathology of maniac depressive disorder  which was used in combination with functional magnetic resonance imaging (fMRI) for monitoring the response. This is a significant non-invasive method for the assessment of motor cortex excitability which also helps in the stimulation of the cerebral cortex. This method is also found to be useful in the pharmacological examination of neuroactive drugs on specific brain circuits . It was The detailed investigations in the study showed that anticonvulsant activity of the antiepileptic drugs such as lamotrigine and valproic acid is conferred to the inhibition of the brain activation caused by the reduced excitability of the motor cortex induced by TMS stimulation. However, lamotrigine exerts a different action in the prefrontal corticolimbic system on TMS stimulation which shows that lamotrigine differs from valproic acid in molecular mechanisms of action as increased TMS-induced BOLD response was observed in corticolimbic circuits when TMS was applied over the dorsolateral prefrontal cortex . This coin vitro activity of the hippocampus in response to the drug /Akt intracellular signaling pathways are known for its important role played in the regulation of multiple cellular processes such as apoptosis, metabolism, proliferation, differentiation, synaptogenesis, and resilience/cellular plasticity . In 19969 . However9 . One intnsferase . Lamotrinsferase . Comparansferase  whereas nsferase .N-methyl-D-aspartate receptors (NMDAR’s). These receptors allow the extracellular flow of calcium into the cell, which causes the membrane phospholipid to selectively release arachidonic acid, via the activation of cPLA2 type IV  responsible for the conversion of arachidonic acid to pro-inflammatory Prostaglandin E2, greater expression of vesicular glutamate transporter I, as well as elevated levels of protein and m RNA in the rat frontal cortex (2 and thromboxane (TXB2) concentrations (Bipolar disorder is characterized by hyperglutamatergic neurotransmission and by upregulated arachidonic acid cascade, which forms a new profound therapeutic target in the treatment of the disorder . The mecl cortex . It was trations . Lamotritrations . Besidestrations . Lamotritrations . In the trations .After vigabatrin and felbamate, the third ever new generation antiepileptic to be commercialized was lamotrigine. However, out of these two drugs only lamotrigine for studied for its utility as a mood stabilizer, while the other two were not studied as after its commercialization as antiepileptics they showed idiosyncratic side-effects namely aplastic anemia and visual field problems which has limited their use for treating very special epilepsy cases. Undoubtedly, lamotrigine has given the best results as compared to all other third-generation anticonvulsants in the treatment of bipolar disorder being more therapeutically effective in treating the depressive episodes encountered in a bipolar disorder . DespiteTreatment of bipolar II depression with adjunctive lamotrigine may also be associated with a history of suicide-attempts and a number of depression-related prior hospitalization in case of poor response to the adjunctive lamotrigine therapy, as per the data from the 52-week follow-up study. In case of a history of previous hospitalization, an increased risk of re hospitalization, treatment resistance, and depressive relapse was reported . The risVarious studies regularly reported partial rather than full response for lamotrigine in bipolar depression, both acute and maintenance. For depressive symptoms lamotrigine can serve as first choice drug for augmentation to a primary mood stabilizer for depressive symptoms. Since lamotrigine has certain limitations it can be supported with a second drug or non-drug intervention . FurtherThis review highlights the importance of understanding the different mechanisms and pathways contributing to the therapeutic use of the well-established antiepileptic drug lamotrigine in the management of bipolar disorder, being more effective in treating the depressive phase of the disorder as well as how it differs from other clinically relevant mood stabilizers, conventional antidepressants and anticonvulsants in exerting its efficacy over bipolar depression. A large double-blind study showed that lamotrigine monotherapy was far more superior over placebo in the patients presented with mild to very severe bipolar depression. It was also demonstrated that lamotrigine was used either as sole therapy or in adjunct with lithium or valproic acid in the treatment of bipolar depression, which is usually well tolerated. Data provided in this review also focus on the effectiveness of lamotrigine in alleviating bipolar depression without resulting in mood destabilization and in showing significant improvements in both depressive as well as maniac phases of the bipolar disorder. Prefrontal cortex of the brain which plays an important role in processing emotions as well as in reward processing has been shown to be disrupted in bipolar disorder, which was found to be overcome by lamotrigine by increasing BOLD-response in the hippocampus contrasting the effects of lamotrigine produced on the motor circuits which could provide future highlights in the improved therapeutic targets for bipolar disorder. The value of investigating the effects of psychoactive drugs on the neural circuits was also reviewed thereby providing better understanding of lamotrigine’s efficacy in treating bipolar depression. Lamotrigine is also shown to possess some limitation, encountered during the course of the treatment though infrequent. Thus, in comparison with the mood stabilizers which currently lack the ability to cause stabilization from “below baseline” lamotrigine is considered to be given a welcome addition to the treatment options available in the management of bipolar disorder and the emerging results from the previous studies also extends its usefulness in patients with bipolar II disorder and in rapid-cycling disorder, however more placebo-controlled trials would be required for the complete confirmation of the efficacy of lamotrigine, an antiepileptic mood stabilizer in the treatment of bipolar depression.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.


TextA 78-year-old woman was referred for coronary angiography with the chief complaint of exertional angina and dyspnea of a very long duration during routine daily physical activities. She had a history of poorly controlled hypertension and dyslipidemia. Coronary angiography revealed diffuse three-vessel disease. Interestingly, an unusual branch was noted originating from the mid shaft of the left main trunk with a funnel-shaped root and travelling the course of a left atrial (LA) branch  and 2. The left main coronary artery (LMCA) usually bifurcates into two major branches: the left anterior descending (LAD) and left circumflex (LCx) arteries. In some patients, the LMCA trifurcates into the LAD, LCx, and a branch artery named ramus intermedius. This third branch arises between the LAD and LCx arteries. The LCx artery gives rise to one or two left atrial circumflex branches which supply the lateral and posterior aspects of the left atrium. According to our extensive search of the literature, this is the first case to be reported with the LA branch originating from the LMCA.


An 73-year-old man, with no abdominal surgical history, presented to the emergency in an array of acute intestinal obstruction. Abdominal CT-Scan axial (A) and coronal (B) sections were performed objectifying hernia sac containing intestinal structure hail externalized through a collar on the outer edge of the rectus muscle on Spiegel's line with no sign of digestive sufferance. The laparoscopic total extraperitoneal mesh repair of the Spiegel hernia was performed. The postoperative course was uneventful and the patient left the hospital on the seventh postoperative day after resumption of normal intestinal transit. Spiegelian hernia is a rare type of ventral abdominal hernia. It occurred in patients in the 6th and 7th decade of life, with an equal sex prevalence. The pathogenesis often involves a dehiscence of the transverse and internal oblique muscle aponevrosis. The diagnosis of Spiegelian hernia is difficult because no characteristic symptoms are identified and often there is no palpable mass, therefore only 50% of cases are diagnosed preoperatively. The abdominal CT scan is helpful in the description of hernia's topography and sometimes in diagnostic confirmation. Surgical treatment is recommended due to the high risk of complications like incarceration and strangulation.


Corynebacterium pseudotuberculosis, which is an intracellular facultative pathogen. In Brazil, the high prevalence occurs principally in northeast and southwest, where has the major herd of sheep and goat causing important economic losses. The actual commercial vaccine confers some level of protection and as based in attenuated or inactive bacteria. The third generation of vaccine includes the DNA vaccine, which can give some advantages as does not cause infection and the stability [C. pseudotuberculosis. For this, we cloned on eukaryotic expression pTARGET vector, gene fragments of C. pseudotuberculosis namely Cp1002_1957 and Cp1002_1802, which encoded for the LipY protein and transferase B protein, respectively. After PCR using specific primers to each gene, the encode sequence were ligated on pTARGET vector (Promega) and the ligation reaction was used to transform Escherichia coli Top10 by eletroporation. The transformation was plated in LB with ampicilin and X-gal substrate. After incubation, the white colonies were select for a screening by digestion with the enzyme EcoRI to confirm gene insertion on vector. Five clones of each gene are selected to transfection of the CHO cells in order to confirm the expression level of proteins by indirect immunofluorescence using sera of mice immunized with the recombinant proteins (rCP1957 and rCP1802). The immunofluorescence analysis show high levels of protein expression (CP1957 and Cp1802) in CHO cells in all clones tested. Both DNA vaccines (pTARGET/1802 and pTARGET/1957) are able to express the proteins in CHO cells in vitro. On the next step, we will perform the animal immunization to confirm the protection level  and the immunomodulatory response.The caseous lymphadenitis (CLA) is a common disease that affects ruminants around the world. The CLA is caused by gram-positive bacteria known as tability -3. Thus


Sustainable development aims to maintain utilization of finite resources without exhausting them and meet the demand of present and future generations . SustainTraditional Chinese Medicine (TCM) has a long history of application and has attracted more and more world-wide attention for its significant effect in prevention and treatment of diseases. Wild medicinal resource is the basis of TCM and accounts for nearly 80% of all the sources of Chinese herbs. With the development of the modern TCM industry and gradual degradation of the natural environment, natural reserves of medicinal resources face a tremendous amount of pressure. Many medicinal plants are at risk of extinction and some adulterants have appeared on the market bringing to attention the need to ensure sustainable utilization of medicinal resources. More and more measures have been taken to guarantee the supply  and idenBungarus Parvus), using ITS2 to identify Ferula species and indirubin-containing medicinal plants, are included. Rapid identification of plants in the Asteraceae with improved RBF-ANN classification models based on MOS-sensor E-nose is also provided.In this special issue, a total of 15 papers have been devoted to sustainable utilization of TCM resources. Identification of Radix Astragali using DNA barcoding, DNA barcode-based PCR-RFLP, and diagnostic PCR for authentication of Jinqian Baihua She ( Rheum tanguticum by multilevel remote sensing. Traceability based on chemical two-dimensional barcode for controlling quality in the whole process of the industrial chain of TCM is included. Finally, measuring Agarwood formation ratio quantitatively by fluorescence spectral imaging technique and determining oleanolic and ursolic acids using hyphenated ultrasound-assisted supercritical carbon dioxide extraction and chromatography are introduced.Introduction and cultivation can supply raw medicinal materials in short supply and play an important role in the sustainable utilization of TCM. Prevention and cure of diseases and insect pests and characteristics of soil microbial community in ginseng cultivation are offered. A systematic review on the production mode of Chinese herbal medicines is also presented. This special issue also reports natural resource monitoring ofReaders of this special issue will find not only different identification methods and updated reviews on cultivation, but also some important issues influencing quality control. The industrial chain of TCM, from the production of raw materials to the sale of the finished products, is a complicated multilink process. There are still some key questions to be resolved in the whole process including but not limited to breeding, prevention and cure of diseases and insect pests, quality traceability, exploiting new medicinal resources, and the mechanism of drug metabolism.Shilin ChenShilin ChenYitao WangYitao WangZhongzhen ZhaoZhongzhen ZhaoChristine J. LeonChristine J. LeonRobert J. HenryRobert J. Henry