Decades of extensive research have matured the development of carbon nanotubes (CNTs). Still, the properties of macroscale assemblages, such as sheets of carbon nanotubes, are not good enough to satisfy many applications. This paper gives an overview of different approaches to synthesize CNTs and then focuses on the floating catalyst method to form CNT sheets. A method is also described in this paper to modify the properties of macroscale carbon nanotube sheets produced by the floating catalyst method. The CNT sheet is modified to form a carbon nanotube hybrid (CNTH) sheet by incorporating metal, ceramic, or other types of nanoparticles into the high-temperature synthesis process to improve and customize the properties of the traditional nanotube sheet. This paper also discusses manufacturing obstacles and the possible commercial applications of the CNT sheet and CNTH sheet. Manufacturing problems include the difficulty of injecting dry nanoparticles uniformly, increasing the output of the process to reduce cost, and safely handling the hydrogen gas generated in the process. Applications for CNT sheet include air and water filtering, energy storage applications, and compositing CNTH sheets to produce apparel with anti-microbial properties to protect the population from infectious diseases. The paper also provides an outlook towards large scale commercialization of CNT material. The strong interaction between the aerogel and catalyst and the high surface area of the support resulted in high catalytic activity [Over the last two decades, carbon nanotubes (CNT) have attracted attention in the fields of sensors , filteriactivity . The CVDactivity . The relactivity . The amoactivity .The unique properties of CNT materials include good current carrying capability ,18 good The porous nature of thin CNT sheet or sheet with particles, and the high surface area of CNTs, may be useful for air and water filtering applications. The conductive and antimicrobial properties of CNTs can be used for pathogen/virus capture and inactivation. To enhance the antimicrobial property, anti-viral nanoparticles  can be integrated into the CNT synthesis process . Sheet pThis paper discusses the synthesis of CNT using the floating catalyst approach and describes a new approach to integrate metal nanoparticles with the CNT sheet to improve its properties. Furthermore, applications for this improved carbon nanotube hybrid (CNTH) sheet are discussed, such as filtering and energy storage along with associated manufacturing obstacles and commercialization.In this study, we used the floating catalyst process to fabricate CNT sheet and carbon nanotube hybrid (CNTH) sheet. After the synthesis step, the vertically grown CNT is drawn to produce a CNT sheet. As can be seen in 2 carrier gas. Fuel is delivered by the syringe pump into the atomizer and then into a mixer at a rate between 30 and 60 mL/hr. As the fuel enters the atomizer, it is broken into droplets that are micron-size using about 3 watts of power. The power of the atomizer is self-controlled and depends on the load of the fuel which may contain metal NPs. NPs can also be carried by the gases. When fuel is injected into the mixer through a needle inside the atomizer, Ar gas and H2 gas carry the fuel into the mixer, and when the fuel mixture leaves the mixer it forms a sock that is transported out of the reactor. The gas flow can vary depending on the process.2 gas flow is 100 SCCM, and Ar gas is used in the range between 100 to 2400 SCCM while using a video camera to continuously check the state of the sock coming through the outlet of the ceramic tube. Gases are included among various variables that determine the state of the sock, and we have produced the optimal CNT and CNTH sheet within the limit of reducing the use of gas as much as possible. The process must be carefully tuned to prevent breaking of the sock. To increase electrical and thermal conductivity and mechanical properties of the CNT, metal, ceramic, or carbon NPs are injected with the Ar gas during the CNTH manufacturing process through a separate route, using a custom particle injector. The Ar gas and H2 gas flowing through the fuel injector and particle injector into the glove box are controlled by mass flow controllers. When the fuel supplied from the fuel injector and metal NPs supplied from the particle injector are mixed in the mixer and injected into the high-temperature ceramic tube, the sock is formed and enters the glove box within 1–1.5 s. The sock leaving the outlet is wound up by a rotating drum, as shown in In a typical synthesis process, H2 structure enables CNTs to possess unique electrical and mechanical properties for a sheet. CNTs have highly stable shells, a high specific surface area, a large length/diameter aspect ratio, and a high Young’s modulus. The carbon shells can be wet by other materials without affecting the stability of the nanotubes [Carbon nanotubes have extraordinary properties and are increasingly being used in various fields of engineering and research. The spanotubes . Althoug2 crystalline carbon from solid solutions. Apart from group VIII metals, other carbide-forming transition metals, such as TaC, TiC, WC, HfC, and LaB3, and those which have high coordination numbers are also capable of precipitating carbon to form graphene as well as nanotubes [How different types of NPs interact with CNTs is complicated and not well understood. Several methods and approaches are proposed in the literature that involve combining various metals and alloys with CNTs. To combine CNTs and metals requires understanding the theory of wetting and solubility of CNTs with other materials. Substances that are used to wet and fill CNTs usually have a low surface tension energy with an upper limit of 200 mN/m . This lianotubes . The outanotubes . DecoratIn this experiment, carbon nanotube sheets were synthesized using the floating catalyst chemical vapor deposition (FCCVD) method as discussed in CNT use in different applications has kept growing since its first discovery in 1991 by Iijima . ApplicaThe scanning electron microscope (SEM) provides a visual understanding of CNT hybrid materials at the nanometer scale. An SEM employs a narrow beam of electrons that interacts with the subject, reflecting energy back which is collected to produce an image of the surface. Depending upon the type of CNT hybrid material, the sample is prepared accordingly for better surface imaging. A CNT hybrid material with a non-conducting polymer coating generally needs a sputtered metal coating to enhance the image resolution. SEM images provide visual information regarding the presence of surface impurities and CNT fiber alignment and structure. The carbon nanotubes synthesized in this work use an iron catalyst and primarily exhibit the tip-growth mechanism, which is evident from the transmission electron microscopy (TEM) images in 2 bonds on the CNTs. The presence of the sp2 bond is depicted by the presence of a G-band peak at ~1580 cm−1 of the Raman scan on the sample  to the intensity of the D-band (ID). A higher IG/ID ratio indicates fewer defects in the CNT hexagonal structure. The presence of a radial breathing mode (RBM) peak at ~150 cm−1 indicates the presence of single-wall CNTs in the scanned sample. G/ID ratio of the scans represents the IG/ID of the sample. IG/ID ratio of 12 scans for CNT sheets synthesized at different temperatures.Raman spectroscopy depends on the Raman effect, which is the scattering of light on interaction with the sample. Based on the energy absorbed or given up by the molecule of the sample upon interaction with the incident photon, the phenomenon of photon interaction is classified as stokes scattering or anti-stokes scattering. Raman spectroscopy provides information about the spe sample . The preIG/ID ratio with an increase in synthesis temperature, as shown in It can be observed in Tensile testing of the CNT sheet samples was performed using an Instron 5948 machine. There were variations in measuring the tensile strength of the CNT sheet depending on the cutting, thickness, and size of the sheet. Here, the sheets were cut in strips 2-mm wide × 20-mm long using a laser micromachining system. The samples were bonded to a paper frame  Figure a. The teThe electrical conductivity of the CNT sheets was measured using the four-point potential measurement technique. CNT sheets synthesized by the floating catalyst method and by the substrate based chemical vapor decomposition method are primarily anisotropic . Therefore, a linear four-probe arrangement produces an average measure of the electrical conductivity of the anisotropic CNT sheets. A square four-probe arrangement measures the electrical conductivity of the anisotropic CNT sheets ,45 in twThe discovery of carbon nanotubes has stimulated immerse interest among researchers in academia and industry for next-gen energy applications. Although many different CNT synthesis methods have been developed, the problems inherent in CNT synthesis have become more prominent along the way, such as very limited batch-process throughput, low purity, and low production yield. Floating catalyst CVD (FCCVD) has the potential to reduce these problems. Additionally, due to the flexible reactor design and unique continuous FCCVD process, the porous, flexible, freestanding films as-synthesized possess many advantages, which include good electrical properties, high mechanical reliability, and ease of handling. As an example, the CNT sheet has a large surface area and can be used to form the electrodes of a compact supercapacitor .Charge storage has three mechanisms: the first involves an electrical double layer (EDL) capacitance, which stores charge on the surface of the electrode reversibly. The second is called the Nernstian process, also called a non-capacitive Faradaic process, which mainly follows the Nernst equation to describe the transfer of the localized valance electrons. The third is called the capacitive Faradaic process, which involves a pseudo-capacitor, the capacitive pathway based on the transfer of the delocalized valence electrons .Transition metals and conductive polymers have been widely used as pseudocapacitive materials, which can provide capacitive Faradaic charge storage from the transfer of delocalized valence electrons . ElectriSeveral groups have used CNTs and related hybrids for supercapacitors and battery applications, either in sheet form or in fiber form. Although CNT-based energy storage shows encouraging results, one of the main challenges remaining is preventing the reduction in the surface area during the fabrication of the device. The reduced surface area has an adverse effect on the electrochemical performance of the electrodes, as well as providing limited space for loading active materials into the sheet, and it causes poor electrolyte diffusion .2O2 and nitric acid showed 97% filtering efficiency for chromium. The removal efficiency of the modified filter was higher due to the large surface area and small nanotube diameter [Carbon nanotube bundles are held together by van der Waals forces and these entangled nanotubes in a thin sheet create a porous structure which can be used to trap and immobilize virus/pathogens. Thick CNT sheets become almost impermeable. The inner core diameter of the carbon nanotube and nanotube growth can be controlled by the catalyst particle ,53 and tdiameter .Carbon nanotubes have emerged as a promising solution for water purification due to their remarkably large surface area and their ability to be chemically functionalized to increase their affinity towards target molecules . MagnetiVolatile organic compounds (VOCs) present in the atmosphere lead to severe health issues. Carbon sorbents have high removal efficiency and are cost-effective. One study suggests that amorphous carbon provided more sorption capacity for organic chemicals and the curvature and topological defects affect the sorption process . PressurThe recent outbreak of COVID-19 prompted a global response to biological aerosol exposure. SWNTs presented strong antibacterial activity. Direct interaction of bacteria with high purity, narrow-diameter nanotubes caused severe damage, and cell inactivation . A compaThe Environmental Protection Agency (EPA) classified sheets with long CNTs  as “articles” and not “particles,” meaning they are too large to be inhaled or absorbed by the skin . AnotherWhen a CNT sheet is tested in a tensile test machine, the CNT sheet fails by the bundles of CNT slipping apart. Individual CNTs are flexible and strong, and it is believed that CNTs do not fracture or release particles when they fail. CNT sheet that is rubbed can transfer CNT bundles to shear surfaces. Thus, in textile applications, a veil or outer layer can be used with CNT sheets for safety.2 = 100. Thus, the new reactor might produce 100 × 7.5 = 750 g/day (this prediction must be verified) of CNT sheet. Assuming 260 work days/yr, the scale-up reactor could produce 195 kg/yr. About six reactors  could produce a metric ton (1000 kg) per year of CNT sheet. Manufacturing cost is mainly due to capital (amortized over 7–10 years) and labor to operate the reactors. Raw materials, electricity, and facilities are smaller costs. Reactors larger than the example shown would be needed to further reduce costs. The new reactor offers a commercial opportunity to manufacture CNT and CNTH sheets. The commercial opportunity becomes greater if end products  are manufactured instead of just CNT sheets. The reactor design is based on the scale up of a research reactor using a different configuration of the furnace. The reactor design is compact and multiple reactors can be put in a small factory, and two operators might monitor the condition of the reactors using a central computer system. The reactors must be cleaned daily and this adds a labor cost to the manufacturing.Manufacturing of CNT sheets is done at grams per day levels at universities ,87,88 anThis paper described the synthesis of CNT sheets using a substrate-grown forest and by a floating catalyst method. Examples from the literature were reviewed. A new method was also presented for integrating nanoparticles via a custom particle injector to produce a carbon nanotube hybrid sheet in a one-step floating catalyst synthesis process. This CNTH sheet is multifunctional and has good electrical and mechanical properties. The integration of nanoparticles depends upon the wetting and solubility of the CNTs with other materials. Wetting of the nanotubes enables decoration of the nanoparticles on the outer surface of the nanotube which can be helpful in many applications such as composite materials. Chemical functionalization of CNT sheets is another way to improve the interaction with particulates and adsorption properties for filtering applications. Due to the great potential of CNTs, companies are investing in their various applications in textile, wastewater treatment, air filtration, sensors, and others. There are certain drawbacks as CNTs at the macroscale are expensive and the synthesis process has a low yield. To overcome these barriers, the need for the development of larger reactors, improving properties by improving the synthesis process, and better understanding the science behind CNT nucleation and growth are important.


Exosomes secreted by tumor cells, through the transport of bioactive molecules, reprogram the surroundings, building a microenvironment to support the development of the tumor. The discovery that exosomes carry genomic DNA reflecting that of the tumor cell of origin has encouraged studies to use them as non-invasive biomarkers. The exosome-mediated transfer of oncogenes suggested a new mechanism of malignant transformation that could play a role in the formation of metastases. Several studies have examined the role of tumor exosomes on the modulation of the tumor microenvironment, but relatively few have been directed to assess how stressful stimuli can influence their production and cargo. Understanding the changes in exosome loads and the production pattern of the stressed tumor cell may uncover actionable mechanisms responsible for tumor progression. Exosomes are a population of nanometer-sized extracellular vesicles (EVs) that originate from the multivesicular endosome and are released from all cells. Their secretion was first described as a mechanism for the elimination of excessive proteins or undesirable molecules from the cell  and for Exosomes are released by tumor cells and their role in tumor progression and metastasis has been largely investigated. Tumor exosomes, reflecting the content of their cell of origin, can transfer oncogenic molecules to recipient cells that will be functionally influenced by them . EvidencIn recent years, several studies have examined the role of tumor exosomes on the modulation of the tumor microenvironment, but relatively few have been directed at assessing how stressful stimuli can affect their production. This review will discuss the influence of the tumor microenvironment on the composition of the exosome, focusing in particular on DNA content and its possible role in promoting malignant transformation.2+ homeostasis contribute to endoplasmic reticulum (ER) dysfunction due to the accumulation of incompletely or incorrectly folded proteins. Exosomes released from ER-stressed liver cancer cells mediate the JAK2/STAT3 activation pathway and promote the release of cytokines by macrophages [It has been described that the molecular composition of exosomes, dictated by local microconditions and the stress state related to the tumor microenvironment, can induce an increase in the release of exosomes from cells and changes in the composition of their cargo ,10 Tabl. Cell curophages .Melanoma-derived EVs secreted under cytostatic, heat, and oxidative stress conditions show substantial differences in the miRNome and proteome, which results in several abnormalities in the recipient mesenchymal stem cells .It is known that DNA damage, irradiation, and activation of oncogenes can cause cellular senescence by the acquisition of a pro-inflammatory phenotype known as the senescence-associated secretory phenotype (SASP). EVs secreted by senescent cells appear to be a new SASP factor that can exert pro-tumorigenic activity for pre-malignant recipient cells ,15,16. RIt has been noted that the chemotherapeutic drug Paclitaxel may induce senescence in triple negative cancer cells accompanied by increased secretion of exosomes . SenesceHypoxia is an important feature of the tumor microenvironment. Tumor growth in low oxygen conditions exhibits more aggressive phenotypes and is associated with a poor patient outcome in a wide variety of cancers . SeveralHypoxia results in acidification of the tumor microenvironment, which may have a profound influence on the release and uptake of exosomes. The microenvironmental acidification of the melanoma cell culture conditions increases the intra-tumor production and uptake of exosomes, which leads to activation of the metabolic pathways related to tumor aggressiveness .Chronic inflammation plays a key role in the progression of cancer and in the development of interactions between host and tumor cells. Increasing evidence indicates that inflammasome activity is correlated with higher EVs production and modulation of their protein cargo . StimulaThe production of exosomes was initially proposed as a mechanism to maintain cellular homeostasis by removing excess or obsolete molecules from cells, but further studies have attributed them to a sophisticated role in cell–cell communication. Recently, it has been shown that exosomes, in addition to several types of nucleic acids , transport mitochondrial ,36 and sExosomes allow the elimination of damaged DNA accumulated in the cytoplasm and as proof of the importance of this function, it has been shown that inhibition of their production promotes cellular senescence by stimulating the cGAS/STING inflammatory pathway . AdditioUsing whole genome sequencing, it has been shown that serum exosomes from patients with pancreatic cancer contain > 10 Kb fragments of genomic dsDNA spanning all chromosomes . DNase tThe discovery of exosomal DNA has attracted considerable attention as a non-invasive source for early diagnosis of cancer and monitoring of treatment response. Exosomal DNA could be used as a genetic marker for the detection of mutations, since the same mutations as the parent cancer cells are found in the transported DNA. Exosomes are present in blood and other biological fluids in large numbers and cancer cells generally release many exosomes continuously. It has been estimated that more than 90% of cell-free DNA (cfDNA) in human blood is found in plasma exosomes . On the Exosomal DNA is stable under several storage conditions because its encapsulation provides it with enhanced stability than when it is outside the cells . On the Several studies have documented the presence of dsDNA in the exosomes analyzed in supernatants of various cancer cell lines  . The detection of EGFR mutations in exosomes isolated from malignant pleural effusions ,50 and KIt is important to note that the analysis of exosomal DNA has become particularly relevant when it is difficult to detect mutations prior to surgery, such as for neuronal tumors ,53. SeruG395A sequences, an essential biomarker in the current management of human glioma, was detected by conventional PCR in 80% of low-grade gliomas samples, matching results from IHC and conventional PCR on solid samples [All types of EVs  secreted by glioma cells in a xenograft mouse model cross the intact blood–brain barrier into the bloodstream. In addition, glioma-derived EVs could be detected in the peripheral blood of a small cohort of low and high grade glioma patients, regardless of the BBB integrity. The presence of IDH1 samples .Arabidopsis thaliana-DNA (A.t.-DNA) mediate the horizontal transfer of DNA into recipient cells. Sequencing analysis revealed that exogenous DNA was stably integrated into the genome of recipient cells, even if authors specify that this was a rare event [The exosomal DNA, as for other molecules contained in them, can be transferred from one cell to another (same cell type or even different) and translocated in the nucleus. EVs secreted by marrow-derived mesenchymal stromal cells (BM-hMSC) transfected with an exogenous re event .ras-driven xenografts. Tumor excision resulted in the disappearance of the leukocytes-associated gDNA signal within several days, which is in line with the expected half-life of these cells. In addition, the exposure of HL-60 myeloid cells to EVs from H-ras-driven cancer cells resulted in an increase in tissue factor procoagulant activity and interleukin 8 production [It has been proposed that horizontal DNA transfer from tumor cells to normal cells represents an important mechanism for tumorigenesis, tumor progression, and metastasis . Oncogenoduction .Circulating DNAs isolated from the blood of cancer patients are deleterious for normal cells as they can damage their DNA, integrating into the genome, and activate proteins of the DNA damage–repair response and apoptotic pathways. Fragmented DNA was readily taken up by culture cells, localized in their nuclei within minutes and the genomic integration, detected by FISH and NGS on recipient cells, led to dsDNA breaks, measured as activation of H2AX .ras transformed epithelial cells that contain dsDNA fragment covering the entire genome, including full length H-ras oncogene sequences which can be transferred to non-tumorigenic fibroblasts. H-ras signals were readily detected by PCR within 2 days of EV exposure, and were still present as long as 30 days later, albeit at diminished levels, with concomitant mitogenic response of recipient cells [The presence of active retrotransposon elements in the genetic material of exosomes suggests a possible role in the formation of genetic instability in recipient cells . Microarnt cells .ras-EVs, but these effects are transient and do not produce a permanent tumor transformation of these cells, even after several months of observation [To date, it is not yet clear whether EVs containing oncogenes exert regulatory rather than transforming influence on recipient cells. Primary and immortalized fibroblasts are susceptible to phenotypic transformation induced by H-ervation .On the other hand, cancer cell exosomes have been shown to contribute to malignant transformation when used as an initiator in combination with a promoter (TPA), which induce cell proliferation in the classic two-step cell transformation assay. Exosomes released from pancreatic cancer-derived cell lines, unlike those produced by normal pancreatic cells, introduce mutations in NIH/3T3 recipient cells that under proliferative stimulation, completely transform and induce the formation, in culture, of foci capable of inducing tumors when injected into mice . It was The mechanism for loading DNA into exosomes remains poorly understood. The formation of micronuclei (MN) in cancer cells, following the induction of genomic instability with genotoxic drugs, promotes the release of DNA-carrying exosomes by ovarian cancer cells. Collapsing of MN directly interacts with the molecular machinery for exosome biosynthesis via tetraspanins, suggesting that the cargo of disrupted MN is loaded into exosomes . On the Our preliminary data suggested that the activation of TLR4 modulates the packaging of mutated genes in exosomes, which are efficiently transferred into normal recipient cells. We observed that exosomes derived from SW480 cells are able to transfer TP53 dsDNA fragments and KRAS-mutated sequences, which are efficiently internalized by CCD841 colon epithelial and THL-2 hepatocytic cells. Copies of mutated DNA and relative mRNA were found in recipient cells up to one month after discontinuation of treatment with exosomes. Note that the activation of TLR4 with LPS stimulates the packaging of the mutated DNA in the exosomes and consequently, more mutated DNA was found in the recipient cells treated with exosomes released from cells activated by TLR4 stimulation .The study of the tumor microenvironment is improving our knowledge of the underlying mechanisms of tumor formation, progression, and metastasis. Exosomes play a key role in the modulation of the microenvironment by orchestrating changes on behalf of tumor cells. Oncogenic gDNA sequences are transported by the tumor exosomes and are delivered through the bloodstream to sites distant from the primary tumor location. There, exosomes could be internalized by receiving cells and induce a malignant transformation. In this process, microenvironmental stressors could play a crucial role in promoting DNA sorting within the exosomes . Further


A number of papers exist about post-traumatic silaocele. Iatrogenic sialocele has been described as complication of parotid surgery but there is no specific data about the cases of sialocele and salivary duct surgical injury in condylar fracture management.A 36-year-old man was reported to the maxillofacial emergency department for mandibular sub-condylar fracture and internal fixation of the sub-condylar fracture was planned. Postoperatively he presented a salivary cyst which was managed by conservative treatment.Iatrogenic injury to the salivary duct and sialocele formation observed in the post-operative period of surgical treatment of a condylar fracture by sub-angulomandibular approach. Maxillofacial surgeons should be aware of this complication and the importance of adopting a conservative treatment whenever it is possible. Botulinum toxin injections can be performed as a first-line treatment for these complications.A conservative management was adopted by pressure dressings and percutaneous needle aspiration of the swelling, which was useful to absorb cystic content and helped healing. •No specific data about the cases of sialocele and salivary duct surgical injury in condylar fracture management.•The iatrogenic lesion of the salivary gland is rarely observed in trauma surgery when the subcondylar fracture is revealed.•The principle of treatment is to dry up salivary secretion.•Maxillofacial surgeons should be aware of this complication and the importance of adopting a conservative treatment whenever it is possible. The iat2A 36 years-old man with no medical history was reported to the maxillofacial emergency department following severe facial trauma as a result of an automobile accident. He complained of pain in his jaw and was unable to open his mouth.Initial physical examination showed abrasions and lacerations on the facial skin and the lips. Limited opening of the mouth and lateral deviation of the mandible toward the right side on mouth opening was noted. Intraoral examination revealed no abnormalities.The Initial panoramic radiography revealed a displacement mandibular sub-condylar fracture with a decreased vertical height of the ramus in the fractured side.Based on the positive medical history and clinical examination, open reduction, and internal fixation of the sub-condylar fracture were planned. General anesthesia was administered through nasotracheal intubation. The sub-angulomandibular approach was used for the exposure of the fracture site On the third day of the postoperative period a fluctuating mass measured about 6 cm in length and 5 cm in width in the right parotid region appeared . There wOn bimanual palpation an ill-defined and resilient mass was noticed, the percutaneous puncture of the mass was performed obtaining 20cl of yellow liquid.At the 30-day follow-up visit, complete recovery was noticed, and the residual swelling had totally disappeared after multiple aspirations and compression dressings. Routine follow up 3, 6 and 12 months later showed no signs of recurrence.This case has been reported in line with the SCARE criteria .3Sialocele is an inflammatory pseudo-capsule that contains salivary secretions within the soft tissues of the cheek, without proper drainage . ClinicaThis is the complication especially of neglected parotid pleasures, without surgical exploration, the average time to their onset is seven days for fistula and 12 days for sialocele.trans-parotid approach and preauricular to the mandibular condyle. In our case, the salivary involvement can be explained by the involvement of the masseteric prolongation of the parotid artery which is demonstrated during the surgical intervention.In facial trauma, the sub-angulomandibular approach, which we used for our patient, the literature reports a large number of cases of facial nerve damage (up to 37% of operations in certain series ), usuallThe principle of treatment for this complication is to dry up salivary secretion to allow healing . PreservA variety of treatments have been proposed for parotid sialoceles . These i4The iatrogenic lesion of the salivary gland or the salivary duct is rarely observed in trauma surgery when the sub-condylar fracture is revealed. If not treated duct injury may result in such complications as sialocele or ductal cysts. Numerous techniques for the management of salivary duct injuries have been proposed, but botulinum toxin represents an excellent alternative for the treatment of sialoceles and salivary fistulas because of its effectiveness, its rare side effects and its low binding nature.Maxillofacial surgeons should be aware of this complication and the importance of adopting a conservative treatment whenever it is possible.5Not commissioned, externally peer reviewed


Thumb extensor injuries and bony avulsion in the distal phalanx of the thumb are rare compared with other fingers. The most reported complications are infection, nail deformity, joint incongruity, implant failure, recurrent flexion deformity, and residual pain. This report presents a case of 30-year-old man suffering from an injury in the left thumb distal phalanx with a displaced comminuted intra-articular fracture of the distal phalanx of the left thumb. The nail plate was interposed between the dorsal and palmar fragments. The interposition of the nail plate in the bony mallet thumb has not been described before. Surgical treatment and fixation with a 2-mm miniscrew resulted in successful treatment. Clinical suspicion of this complication is of great importance and can affect treatment outcomes. Traumatic injuries to the extensor mechanism at the distal interphalangeal (DIP) joint can lead to a mallet finger with or without bony avulsion.A mallet finger lesion is known as a variant of lesions such as skin wounds  and/or fractures of the distal phalanx involving more than one-third of the articular surface or displaced fractures of the distal phalanx growth plate (Seymour lesions).A few reports have addressed thumb extensor injuries. Depending on the size of the fragments, conservative treatment may result in satisfactory outcomes in less than 50% of the articular joints without dislocation. But surgical treatments are recommended in patients with fragment or distal phalanx dislocations.A case of 30-year-old man suffering from an injury to his left thumb distal phalanx after falling during a soccer game is presented in this report. Upon physical examination, the left thumb was swollen and painful; moreover, he could not actively extend his interphalangeal (IP) joint. The initial radiographs demonstrated a displaced comminuted intra-articular fracture of the distal phalanx of the left thumb . The doUnder digital block, the closed reduction and percutaneous pinning were initially attempted. However, intraoperative radiographs showed unsatisfactory reduction outcomes. Therefore, open reduction and internal fixation were implemented. At surgery, a relatively large dorsal osseous fragment attached to the EPL tendon lied on the proximal part of the nail plate, and the nail plate was interposed between the dorsal and palmar fragments . The frA bony mallet finger is a consequence of an avulsion of the extensor tendon from the distal phalanx with a bony fragment of the bone attached to the avulsed tendon.The readers may argue that our case is that of a comminuted fracture of the distal phalanx rather than a mallet injury; however, a mallet finger lesion can be considered a mirror lesion to an avulsion of FDP tendon.Some authors have extended the definition of mallet finger to fractures of the distal phalanx involving more than one or two-thirds of the articular surface or displaced fracture of the distal phalanx growth plate (Seymour lesion).Regarding the Al-Qattan type 5 FDP avulsion with a comminuted intra-articular fracture of the distal phalanx, we suggested a mirror concept in our case. In our opinion, the disruption of the extensor mechanism through a significant bone lesion, where the extensor tendon is still attached to the dorsal fragment and the patient is unable to actively extend the thumb's IP joint, can be considered as a type of mallet lesion rather than a comminuted intra-articular distal phalanx fracture.Compared with a mallet finger, a mallet thumb is an uncommon lesion since the thumb is shorter than the other fingers and its EPL is thicker than the terminal tendon of the extensor mechanism of the other fingers.Treatments of bony mallet thumbs may vary from splinting to surgical treatment.Only a few case reports and sporadic cases of bony mallet thumb have been described among the large case series describing the mallet fingers or mallet thumbs. The bony mallet thumbs can be surgically treated with tension band technique, pull-in suture, extension block pinning with one or two Kirschner wires, hook plate, screw, external fixation, compression pins, and biodegradable device.Although these various techniques resulted in excellent functional outcomes, the authors' successful experiences were limited to a few cases of bony mallet thumb.This case report described a bony mallet thumb lesion with interposition of the nail plate between the dorsal and volar fragments. The avulsed fragment was large enough to receive a 2-mm miniscrew. To the best of our knowledge, the interposition of the nail plate in the bony mallet thumb has not been described before.


Teaching Point: Kommerell aneurysm is a rare differential diagnosis of mediastinal enlargement on a chest radiograph that requires CT for accurate diagnosis. A frontal and lateral chest radiograph was obtained in a 73-year-old man with hemoptysis Figure . It reveA chest computed tomography (CT) was performed the same day, confirming a pulmonary mass in the left upper lobe with lymphadenopathy in the aortopulmonary window. The right paratracheal lesion, however, proved to be an unsuspected aneurysm developed on an arteria lusoria  named “Kommerell aneurysm.”The positron emission tomography (PET) CT Figure  was posiAberrant right subclavian artery is an anatomical variant, affecting 1% of the population. Kommerell diverticulum is present in about 60% of cases and is described as a diverticulum at the origin of an aberrant right or left subclavian artery in a left-sided or in a right-sided aortic arch, respectively [Aneurysms of this diverticulum (Kommerell aneurysm) are seen in 3–8% of cases. These aneurysms present as a fusiform dilation of the diverticulum at the origin of the aberrant subclavian artery .Most patients are asymptomatic but can present with dysphagia, dyspnea, or chest pain. These symptoms depend on the location and size of the aneurysm .Kommerell aneurysm requires surgical treatment because of the risk of rupture and dissection. Rupture can occur in approximately 19% of cases [Uncomplicated diverticulum of Kommerell, saccular aneurysm of the thoracic aorta and ductus diverticulum are mimics of Kommerell aneurysm. The differential diagnosis is based on the origin of the aneurysm, outpoutching contents, and morphology. The Kommerell diverticulum arises from the aortic arch and the Kommerell aneurysm from the Kommerell diverticulum. Saccular aneurysms of the aortic arch do not involve the origin of the aberrant right subclavian artery. Ductus diverticulum is located at the level of the ligamentum arteriosum . The Kommerell aneurysm may be saccular or fusiform. The Kommerell diverticulum is always fusiform.


Disease states are often linked to large scale changes in microbial community structure that obscure the contributions of individual microbes to disease. Establishing a mechanistic understanding of how microbial community structure contribute to certain diseases, however, remains elusive thereby limiting our ability to develop successful microbiome-based therapeutics. Human microbiota-associated (HMA) mice have emerged as a powerful approach for directly testing the influence of microbial communities on host health and disease, with the transfer of disease phenotypes from humans to germ-free recipient mice widely reported. We developed a HMA mouse model of the human vaginal microbiota to interrogate the effects of Bacterial Vaginosis (BV) on pregnancy outcomes. We collected vaginal swabs from 19 pregnant African American women with and without BV (diagnosed per Nugent score) to colonize female germ-free mice and measure its impact on birth outcomes. There was considerable variability in the microbes that colonized each mouse, with no association to the BV status of the microbiota donor. Although some of the women in the study had adverse birth outcomes, the vaginal microbiota was not predictive of adverse birth outcomes in mice. However, elevated levels of pro-inflammatory cytokines in the uterus of HMA mice were detected during pregnancy. Together, these data outline the potential uses and limitations of HMA mice to elucidate the influence of the vaginal microbiota on health and disease. The vagina houses a numerically immense and functionally consequential microbiota   mouse model of BV using germ-free mice. While the natural microbiota of mice differs greatly to that of humans , while patient demographics, health status, pregnancy complications and birth outcomes were recorded as well . SpecifiThe patients' vaginal microbiota was swabbed at the hospital and the swabs were transported immediately to the Emory Gnotobiotic Animal Core (EGAC). The vaginal tract of female germ-free C57BL/6 mice was inoculated by physically wiping the vaginal swab on the mouse, concentrating the swab to the vaginal opening. This process was typically completed within 2 h of collecting the vaginal swab from the patient. Mice were then housed within bioexclusion husbandry cages for the vaginal microbiota to establish and colonize. After 2 weeks, a male germ-free mouse was introduced into the bioexclusion cages of each HMA female mouse, and conception date recorded by the appearance of a viscous copulatory plug. At 18.5 days post-coitum (18.5 dpc) and before delivery of litters, mice were sacrificed and the uterus, vagina, and fecal pellet collected under sterile conditions . Charactin utero among the HMA mice and sought to determine whether the microbiota harbored in the vaginal canal correlated with litter size. We determined litter size in HMA mice by recording the number of pups within the uterine horns at 18.5 dpc. This was done before birth in order to obtain a faithful count of viable pups and to mitigate the prospect that the new moms' cannibalize their newborn offspring, which often occurs postpartum in C57BL/6 mice and could affect our data. We compared the litter size at 18.5 dpc with the Nugent score of the corresponding patient described in Despite no similarity between donor and HMA mouse vaginal microbiota, we recorded considerable variation in the number of pups Inflammation in the uterus, or endometritis is commonly associated with pregnancy complications. We examined the extent to which the colonizing microbes influenced levels of inflammation in the uterus of HMA mice. Although the uterus has considerably lower levels of bacteria compared to the vaginal tract, it may be possible that certain bacterial species in the vaginal tract have negative impacts on the physiology of the entire reproductive system. Linear regression analysis of cytokine concentrations in the uterus of HMA mice described in In order to better understand the effect of the vaginal microbiota on health, we assessed the utility of the HMA mouse approach, which has been widely employed in the study of host cell and intestinal microbe interactions  African American by self-report; (2) Between 8 and 14 weeks' gestation  and expecting a singleton pregnancy; (3) Able to comprehend written and spoken English; (4) Between 18 and 40 years of age; (5) Experiencing no chronic medical condition or taking prescribed chronic medications . For enrolled women, data collection consisted of completing a sociodemographic questionnaire as well as self-collecting vaginal and rectal swabs during the study visit and giving permission to complete a medical record abstraction at the end of the pregnancy. For the swab collection, participants were provided verbal and pictorial instructions directing them to obtain (in a private exam room) self-collected vaginal swabs  and one rectal swab (for DNA extraction and 16S rRNA gene sequencing). The swabs for microbiota sequencing were Sterile Catch-All™ Sample Collection Swabs  which were immediately plunged into MoBio bead tubes  and frozen upright on dry ice until transported to the lab, to be stored at −80°C until DNA extraction and preparation for vaginal microbiota measurement occurs. The swabs for vaginal Gram staining were dacron swabs that were stored in a sterile tube until transport to the Emory Clinical Microbiology Laboratory for Gram staining for Nugent criteria scoring for evaluation of BV  and/or early ultrasound, given enrollment criteria. Gestational age at birth is determined from the delivery record, based upon the date of delivery in relation to the estimated date of confinement established during the 8–14 week prenatal visit. Complications/Type and Mode of Delivery. Gestational diabetes, preeclampsia/eclampsia, etc., type and mode of delivery are ascertained from record review after delivery and defined according to standard clinical definitions of the American College of Obstetricians and Gynecologists. Medication use, including any antibiotic use, in the month prior to sampling was also ascertained.Maternal Medical Chart Abstraction was completed by the research team using a standardized chart abstraction tool to ascertain for the following: After collection of the human vaginal swabs by hospital staff the swabs were immediately transferred to research staff who inoculated 10 week-old germ-free female single-housed in a bioexclusion microisolator cage at the Emory Gnotobiotic Animal Core (EGAC). Germ-free status of mice was confirmed by bacterial 16S rDNA PCR assay paired with anaerobic culture testing, undertaken by IDEXX BioAnalytics . To handle the mice contained in the bioexclusion cages, the cage was saturated in disinfectant and placed in a sterile biosafety hood. Gloves and forceps for mouse handling were sterilized in disinfectant before opening the cage. Inoculation was achieved by physical wiping of the vaginal swab at the vaginal opening of the mouse for several seconds, ensuring adequate transfer of microbes from the swab onto the vaginal opening of the mouse. Inoculated females were housed for 2 weeks before introduction of a germ-free male. Evidence of copulation was monitored by inspection for a vaginal copulatory plug every morning after inoculation. Observance of a vaginal plug was designated as 0.5 days post-coitum (dpc). After identification of a vaginal plug the male mouse was removed to prevent the possibility of multiple copulations. The day before expected delivery (18.5 dpc) the female mouse was sacrificed and the uterine horns, vagina and fecal pellet were collected under strict sterile conditions. The number of developing pups in the uterus were enumerated and removed. The vaginal canal was immediately processed for microbial DNA isolation and the uterine horn was flash frozen for future cytokine analysis.http://www.ncbi.nlm.nih.gov/bioproject/655465.After sterile collection the vaginal canal from the HMA mouse was placed in a MagnaLyser tube . Protein concentrations were quantified using the Pierce BCA assay kit and the protein concentrations were diluted and normalized for cytokine quantification using the V-PLEX Proinflammatory Panel 1 Mouse Kit  following manufacturer's protocol with the help of the Emory Multiplexed Immunoassay Core .PRJNA655465.The original contributions presented in the study are publicly available. This data can be found in the NCBI short read archive (SRA) under the accession number The studies involving human participants were reviewed and approved by Emory University Institutional Review Board and the Grady Research Oversight Committee. The patients/participants provided their written informed consent to participate in this study. The animal study was reviewed and approved by Emory University IACUC committee.RJ and AD conceived and oversaw the project. AD and EC oversaw patient sample collections. AW and TS performed the experiments. DV, AW, and TS analyzed the data and produced the figures. RJ, AW, AD, and AN wrote the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The skin represents the exterior interface between the human body with the environment while providing a home to trillions of the commensal microorganisms—collectively referred to as the skin microbiota. These microbes that coexist in an established balance play a pivotal role in the protection of cutaneous health and the orchestration of skin homeostasis. However, the well-controlled but delicate balance can be perturbed by alterations in the skin microbial communities, namely, dysbiosis, often due to commensals defeated by pathogens competing for space and nutrients, which leads to the occurrence of multiple cutaneous disorders. In view of this, the analysis of skin microbiota constituents in skin diseases is crucial for defining the role of commensal microbes and treatment of skin diseases. Emerging evidence shows that the ecology-based therapy of microbial transplantation has been proven as a valid therapeutic strategy for cutaneous disorders caused by skin microbial dysbiosis. Although its mechanism is not well-understood, there are already some applications for ecology-based therapy with the aim of correcting the imbalances on the cutaneous ecosystem. In this review, we summarize the interactions between dysbiosis and the cutaneous disorders, including homeostasis and dysbiosis of skin microbiota, microbial composition in skin diseases, and the mechanisms and applications of reversing or ameliorating the dysbiosis by the targeted manipulation of the skin microbiota, which may contribute to aid development of therapeutic modality for ecology-based therapy. Cutibacterium (formerly Propionibacterium)  species  infection , makes it possible to thoroughly characterize skin microbiota constituents   is a paradigmatic chronic inflammatory cutaneous disease that affects 10–30% of children in industrialized countries and has a lifetime prevalence of up to a fifth of the population in the developed world  state  state . In addie) state . For exaMalassezia is a typically dominant skin-dwelling fungal class comprising 17 species and linked with AD  were enriched in AD-prone skin by whole metagenome profiling  is one of the most ubiquitary non-communicable inflammatory dermatoses of the pilosebaceous unit  in the skin-residing microorganisms of healthy adults, has been viewed as an important pathogenic factor accompanying the development of AV , replacing a state of previous skin homeostasis in childhood  encoding a tight adhesion (Tad) locus in relation to virulence affecting bacterial adhesion and host immune responses and two unique loci of genomic islands (loci 1 and 2) encoding a Sag gene cluster in association with hemolytic activity in pathogens , which are present in health-associated type II C. acnes phenotypes, confer protective immunity against the invasion of viruses, phages, and plasmids or other exotic DNA, and avoid the acquisition of extra genetic elements that foster virulence and acne pathogenesis  and synergizing with microbiota-produced AMPs and the human AMP LL-37 or/and DCD-1(L) to selectively kill or inhibit S. aureus  signaling molecule. The full length of AIP is composed of 7–12 amino acids with the last 5 amino acids forming a cyclic (thio)lactone ring between the C-terminal and a cysteine or serine side chain  that could block the agr-mediated quorum sensing of all classes of S. aureus (type I–IV) to prohibit their colonization and skin infection. Although a number of animal CoNS species have been identified to have inhibitory effects on S. aureus quorum sensing, there are still few studies on quorum sensing between CoNS species on human skin. In a more recent study, Williams et al.  to murine skin resulted in potent inhibition of S. aureus agr activity, demonstrating that the human skin microbiota can contribute to epithelial barrier homeostasis by using quorum sensing to dampen S. aureus virulence factors  quorum sensing system plays a pivotal role in the orchestration of cellular behavior between CoNS species and k et al.  found ths et al.  applied Fusobacterium nucleatum in the gut has been linked to colorectal cancer through their adherence and invasion into intestinal epithelial cells, ultimately resulting in increased oncogenic and inflammatory responses  that has selective antiproliferative activity against tumor lines by interfering with the essential process of DNA replication but did not inhibit primary keratinocytes. A single application of S. epidermidis strain producing 6-HAP to mouse impaired the incidence of ultraviolet-induced skin tumors. However, further research is needed to validate whether the dysbiosis caused by the loss of such strains elevates the risk of human skin cancer.Previous studies have illustrated that dysbiosis may lead to carcinogenesis. For instance, the abnormal proliferation of Roseomonas mucosa is one particular commensal found on the skin of healthy and AD individuals  are produced by keratinocytes and sebocytes to potentiate the skin resistance against pathogens. Except for the constitutively expressed AMPs, others can be agitated by cues from certain members of the skin microbiota, a phenomenon known as heterologous protection. For example, these cues can be directly stimulated by athogens . FurtherPs Otto, . In anotC. acnes on 18 subjects in the first 3 days, the observation demonstrated that the level of engraftment was positively correlated with the presence of several different strains in the probiotic solution, implicating that different strain combinations have synergistic effects on colonization of recipient skin surface and modulation of the C. acnes population at the strain level is feasible by microbiome transplantation. Notably, patients with C. acnes subtype H1 and Leifsonia being more abundant showed a markedly higher transplantation by using a multistrain donor solution, suggesting that different microbiota might have a synergistic effect  that differ immunologically and structurally from the human cutaneous milieu. As investigations in the field grows, efforts will be needed to identify the efficacy of long-term application of living microbiota onto epidermal models (Williams et al., in vitro model for human therapeutic applications (Summerfield et al., Moving forward, it is clear that the technique of skin microbiome transplantation is only at the initial stages. A temporary modulation of the skin microbiota population at the species and strain level is feasible in patients with skin disorders without an adverse event. The application of living microbiota is largely limited by WL and ZL conceived the structure of the review. HZ drafted the manuscript. LS, YR, and XT carried out revisions of the manuscript. All authors read and approved the final manuscript. All authors contributed to the article and approved the submitted version.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.


In the mammalian adult hippocampus, new neurons are continuously generated throughout life in the subgranular zone of the dentate gyrus. Increasing evidence point out the contribution of adult-born hippocampal granule cells (GCs) to cognitive processes such as learning and memory, indicating the relevance of understanding the molecular mechanisms that control the development of these new neurons in the preexisting hippocampal circuits. Cell proliferation and functional integration of adult-born GCs is a process highly regulated by different intrinsic and extrinsic factors. In this review, we discuss recent advances related with cellular components and extrinsic signals of the hippocampal neurogenic niche that support and modulate neurogenesis under physiological conditions. Several studies provide evidences indicating that hippocampal neurogenesis is needed for the integration of new information into pre-existing context promoting flexible learning and adaptive behaviors. Physiological experiences such as learning, physical exercise and exposition to enrich environment (EEs) have been associated with an increase in survival, proliferation and differentiation of adult-born hippocampal cells. Moreover, others pathophysiological conditions, such as aging, stress, and degenerative disorders  have been described to impair and decrease adult neurogenesis . These eUnderstanding the signals derived from this specific microenvironment results essential to enhance the process of neuronal integration in the aged and diseased brain. In this minireview, we focus our attention in the complexity of the adult hippocampal neurogenic niche, which provides multiple signals that are integrated by the neural stem cells (NSCs) and the newborn neurons to respond adequately in different circumstances.Adult hippocampal neurogenesis has been confirmed in the majority of mammals, but whether it is present in humans has been the issue of an intense recent debate . MethodoThe general pattern of hippocampal neurogenesis is conserved across different mammalian species. Hippocampal NSCs give rise to GCs throughout a highly regulated process, which involves the exit of the quiescence state, posterior divisions, specification to a neuronal fate, neuronal differentiation, and the physiological integration in the preexisting hippocampal circuits. Along this period morphological, intrinsic electrical properties and synaptic connections evolve in parallel toward a mature neuronal phenotype. All the process is tightly controlled by physiological stimuli, that modify the hippocampal niche .The adult hippocampal neurogenic niche is a specialized and dynamic microenvironment, which involves both cellular and non-cellular components of the DG. Altogether, cells and the signals produced by them can regulate the neurogenic process acting at different levels from proliferation to functional integration .Astrocytes represent one of the main modulators of the neurogenic niche . They coSeveral studies have shown the relevance of microglia in adult hippocampal neurogenesis. They are involved in phagocytosis of apoptotic adult-born GCs . TherefoA growing body of data indicates that blood vessels are essential components of hippocampal NSC niches. Vascular cells can impact neurogenesis directly by producing neurogenic factors or indirectly, transporting neurogenic substances produced by other cells. Many studies indicate that endothelial cells secrete different trophic factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and chemokines such as CCL11, which affect NSCs proliferation and maturation of these cells . A recenIncreasing evidence shows an important role for NSCs as regulators of their own niche, influencing the development of their progeny at different neurogenic stages. VEGF, neurotrophin-3 (NT3), Pleiotrophin (PTN), and BDNF are some of the factors released by the NSCs .Neuronal activity regulates multiple stages of adult neurogenesis from proliferation, survival, neuronal maturation, and synaptic integration. Local interneurons, hilar inhibitory neurons, mossy glutamatergic neurons and mature GCs from the DG control different stages of newborn GCs integration. Extensive literature has demonstrated an essential role of neurotransmitters locally released by DG neurons or by axons arising from projecting neurons in the modulation of adult-born GCs development . This toThe cellular components of the subgranular zone (SGZ) provide a complex regulatory architecture that allow the correct development of the adult-born GCs, promoting their correct integration in the preexisting hippocampal circuits. Neural activity triggered by physiological experiences is essential to govern the interaction between the different cellular components that control the neurogenic process by secreting specific signals. An interesting example of the signal integration in the hippocampal neurogenic niche was evidenced in a recent study which shows that hippocampus-associated behaviors increase microvascular blood-flow velocity in the DG and enhance hippocampal neurogenesis. The authors proved that this effect is mediated by parvalbumin-expressing neurons which increase blood flow via nitric-oxide signaling. This increase in the microvascular hemodynamics enhances IGF-1 signaling promoting the newborn cell survival .The different cellular components of the neurogenic niche can modulate neurogenesis by multiple signaling mechanisms . Here weDirect cell–cell interaction is critical in stem cell maintenance. A known membrane molecule, Notch, and its ligands can mediate direct interaction between NSCs and neighboring cells, and thus play an important role in neurogenesis. Ablation of Notch in hippocampal NSCs during adulthood promotes cell cycle exit and neuronal fate determination . The impEprhrin/Eph signaling has also been involved as important players regulating stem cell behavior. Initial studies showed that Ephrin-B2 presented by astrocytes interacts with EphB4 receptors on NSCs, promoting neuronal differentiation . A recenAll cell types in the SGZ niche are in contact with the ECM, a complex and dynamic network of macromolecules with different physical and biochemical properties. The ECM acts providing a physical supportive structure and also molecular signals to regulate NSC development. The contribution of the ECM molecules to the modulation of hippocampal neurogenesis is complex, as they can act by interacting directly with cellular receptors or indirectly as modulators of the availability of soluble factors present in the neurogenic niche . Among EThe different cells that constitute the DG neurogenic niche regulate stem cell activity by secreting diffusible signaling molecules, which represent the majority of extracellular cues that regulate neurogenesis . Among tTrophic factors, such as IGF-1 and VEGF are relevant players involved in adult neurogenesis at different developmental stages that have previously been deeply analyzed .During the last years new soluble molecules known for other functions, have emerged as modulators of the neurogenic process. Thus, the Globule-epidermal growth factor (EGF) 8 (MFGe8), a molecule involved in the phagocytosis of apoptotic cells, was found to be expressed by quiescent NSCs and astrocytes in the SGZ. Recently, it was shown that adult specific deletion of MFGe8 in NSCs promotes the increase in NSC proliferation and depletion of the neurogenic pool causing a decreased neurogenesis at later developmental stages . AnotherThe role of the neurotrophins in hippocampal adult neurogenesis is well documented. Particularly, BDNF is expressed in SGZ by NSCs, mature DG granule neurons and also by non-neuronal cells, while its receptor, TrkB, is broadly expressed by NSCs at different developmental stages . Brain-dOther member of the neurotrophin family, NT-3 is highly expressed in the adult DG. Conditional ablation of NT-3 in the brain throughout development shows normal proliferation in the SGZ, a reduction in the number of newly generated granule neurons and an increase in the proportion of cells that do not express differentiation markers, indicating a role of NT3 in maturation of neural progenitor cells .A more recent work has demonstrated that the protein PTN secreted by hippocampal NSCs from the SGZ niche is important for the correct development and integration of the new neurons in the DG. Ablation of PTN leads to defects in neuronal integration and synaptic activity of the newborn neurons in the hippocampus without affecting the production or survival of them. This effect is mediated by one of the PTN receptors, ALK, which is expressed by NSCs. Interestingly, this study showed that the expression of PTN is reduced with aging but that the administration of PTN is able to ameliorate the age-induced defects of hippocampal neurogenesis .Recently, glial-derived neurotrophic factor (GDNF), a neurotrophic factor initially described for its potent effect on the survival of dopaminergic nigrostriatal neurons was described as a novel regulator of newborn GCs integration . The recAs growth factors involved in hippocampal neurogenesis acts through different receptors triggering specific downstream signaling pathways, the remaining question is how newborn neurons integrate this information. One possibility is that the same cell expresses all the receptors but need to integrate the different signals in order to respond appropriately. A second possibility is the existence of subpopulations of adult-born GCs each of which respond to different growth factors expressing specific receptor repertoires. Moreover, the presence and the abundance of receptors and the downstream signaling partners can be modified during the maturation process. Thus, the expression of different arrays of trophic factor receptors in the adult-born GCs deserve further analysis.These small membrane extracellular vesicles have emerged as one of the major mediators of intercellular communication . DiverseOver the last years, lipids have gained attention in the regulation of adult neurogenesis . Lipids The large literature about the different cells and the nature of signals which modulate adult hippocampal neurogenesis indicates that extrinsic control of this process is much more complex than previously envisioned. The distribution of different factors in the neurogenic niche, the precise signaling pathways that they trigger, the interaction with other intrinsic and extrinsic signals and their function in pathological process deserves further investigation.The great diversity of signals present in the niche should be appropriately integrated by the adult-born GCs to promote the proper maturation and integration of them into preexisting circuits. The different factors derived from the microenvironment induce specific transcriptional programs that drive the maturation of the new cells and determine the morphological and physiological properties of GCs at the different stages during neuronal development and their response to external stimuli.In parallel to the great diversity of signals that have been described as modulators of the hippocampal neurogenesis, different studies pointed out to the heterogeneity of NSCs. This idea indicates that not all NSCs or immature GCs respond similarly to the different extracellular signals that are present in the niche . CellulaThe identification of the array of factors present in the SGZ niche during neurogenesis represents a crucial knowledge because it opens the possibility to combine them in order to improve the development of adult-born neurons in physiopathological conditions. In this context a recent study reported that mimicking the beneficial effects of exercise by pharmacological induction of neurogenesis, combined with elevation of BDNF levels in the DG revert the negative effects of Alzheimer’s disease on newborn hippocampal neurons in a mouse model of the disease .Thus, understanding the complexity of the SGZ neurogenic niche becomes essential for the development of novel therapeutic strategies for the treatment of cognitive impairments associated with aging and brain disorders in which adult hippocampal neurogenesis is affected.All authors contributed equally to this mini-review.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.


They can help to assess the value of new treatments and may provide insights to inform the design of future clinical trials.6The European Hematology Association (EHA) has observed the development of the ESMO-MCBS with interest, since no oncology frameworks have yet been validated for assessing treatments for hematologic malignancies. Given the increasing number of treatments available for these types of malignancy, that often target small, well-defined patient populations, availability of an appropriate validated assessment for hematologic malignancies is of pressing importance. Consequently, experts from EHA and ESMO tested the latest version of ESMO-MCBS (version 1.1) in several hematologic malignancies, and their findings have recently been published.6 Their gradings were then reviewed by the ESMO-MCBS Working Group to ensure applicability and correctness. The hematologic malignancies considered included acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), Hodgkin and non-Hodgkin lymphomas, multiple myeloma (MM) and myelodysplastic syndromes (MDS). For each of these diseases, the scoreability of the studies and the reasonableness of the derived scores were evaluated so that any shortcomings in the current version of ESMO-MCBS, when applied to each hematological malignancy, could be identified. Clinical benefit was graded for treatments with curative intent and for treatments with non-curative intent.Experts from relevant EHA Scientific Working Groups identified and graded 80 studies of recently approved treatments for hematologic malignancies using the ESMO-MCBS version 1.1 forms.The ESMO-MCBS version 1.1 was widely applicable to the overwhelming majority of studies analyzed by EHA experts. Of the 80 studies analyzed, 72 (90%) could be scored, and the scores generated were generally considered to correspond with expert assessment of the magnitude of clinical benefit obtained for the treatments under evaluation. This is encouraging but suggests that more work is needed to increase this further.6A key aim of this project was to probe the ESMO-MCBS more deeply, to identify key differences between sold tumors and hematological malignancies in order to isolate the most important shortcomings that would need to be addressed and amended in order to develop a version that is applicable more robustly to the full spectrum of hematologic malignancies. Due to the high degree of cooperation that existed between the scientific leadership of the ESMO-Magnitude of Clinical Benefit Working Group and the European Hematology Association over the past 2 years, this project has resulted in the completion of this work, which has recently been published in ESMO Open.Some shortcomings in the capacity of ESMO-MCBS to grade the magnitude of clinical benefit appropriately were identified for almost all types of hematological malignancies (with the exception of AML); these shortcomings are summarized in Table 7 that underlie the integrity of this endeavor which is critical to both EHA and ESMO and to the use of the tool in public health policy.This critical accomplishment is now facilitating the next phase of this ongoing collaboration between our organizations, the development of a robustly validated version of the ESMO-MCBS for hematological malignancies: ESMO-MCBS:H. This process is underway: a draft version of ESMO-MCBS:H has been prepared which will undergo scientific review, statistical validation, extensive field testing and a process of expert peer review for reasonableness. These methodological stringencies are essential to meet the standards of “accountability for reasonableness”We look forward to this important challenge with the secure knowledge that we now have an established track record of tremendous cooperation. We believe that the ESMO-MCBS:H will make a major contribution to the word of malignant hematology.The ESMO-MCBS version 1.1 is widely applicable to studies of recently approved treatments for hematological malignancies analyzed by EHA experts. However, a number of modifications are necessary to enable hematological malignancies to be validated within the ESMO-MCBS framework. Based on the findings of this EHA analysis, EHA and ESMO are committed to develop a version of the scale that is robustly validated to grade studies of new treatments for hematological malignancies. Collaboration between these organizations is ongoing in order to achieve this in a timely manner.


Dear Editor,Postgraduate Medical Journal,1 suggesting the potential harms associated with the use of unproven antimicrobials for the management of COVID-19. We appreciate the efforts of authors to underscore the potential drug safety concerns during the ongoing health crisis. In align with these suggestions, we felt inclined to share another potential hazard associated during the current phase of drug repurposing.We read with great interest a recent editorial published in 2 carrying the potential to cure COVID-19. Most of these reports primarily rely on invitro investigations and lack firm clinical evidences from human studies.3  4  5 Though such a hypothesis, generations for the treatment of COVID-19 are the need of hour, but uncontrolled amplified dissemination of news or information by the lay press, electronic and social media may trigger self-medication of candidate drugs among general community. It is pertinent to mention that every news channel or agency is efficiently engaged to break any new findings or studies related to the treatment and prevention of COVID-19. Such news reports may influence the people who are searching for appropriate measures to save themselves from the virus.COVID-19 has encompassed more than 200 countries with unprecedented rise in infected cases along with mortalities. Healthcare professionals and researchers around the globe are battling hard to combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and taking all possible measures to reduce the growing encumbrance of the disease. Since most of the countries have imposed lockdown and people are confining to their homes with restricted movements, they are more vigilant for the updates on COVID-19, particularly on treatments and preventive measures. Most of the people are relying on electronic media and social networking to get latest and updated information related to the disease. On the other hand, increasing numbers of COVID-19-related deaths are creating panic among the general public. In such circumstances, both general and healthcare communities are anxiously waiting to receive any positive news regarding the treatment and prevention of infection. Literature has reported several medications such as hydroxychloroquine (HCQ) and chloroquine (CQ)6 It must be noted that Nigeria is endemic for Malaria, and shortage of CQ or HCQ may result in another parasitic catastrophe. Moreover, sudden interest in HCQ has led to reports of shortages for patients who rely on the drug to treat their autoimmune diseases that could place these patients at risk for severe and even life-threatening flares; some may require hospitalisation when hospitals are already at capacity.6 7The discovery of new candidates for the treatment of COVID-19 is improving the clinical management of infected cases but at the same time portending potential risks of self-medication among the general public. Despite the absence of firm evidences, attempts to self-medicate with the repurposed drugs have been observed in the public. HCQ can have life-threatening side effects if the dose is not carefully controlled, and cases of CQ poisoning have been reported in Nigeria and the USA. Nigerian health authorities have already issued several warnings amid CQ poisoning, which immediately occurred after the media reports.8 During the current environment of global panic, such endorsements may result in widespread use of drugs for prophylaxis and overly optimistic perception related to the effectiveness of CQ and HCQ among the public. Widespread use of HCQ may expose some patients to rare but potentially fatal harms, including serious cutaneous adverse reactions, fulminant hepatic failure and ventricular arrhythmias . Furthermore, overdose of these drugs is hazardous and difficult to treat.3 Recent recommendations of FDA limit the use of these drugs in hospital setting to treat COVID-19 in adults and adolescents who weigh at least 50 kg and are not able to participate in clinical trials. Moreover, FDA also insisted to obtain these drugs from the national stockpile to protect the supply for other patients who have relied on the drugs for years to control autoimmune diseases including lupus and rheumatoid arthritis. Despite these recommendations, an immediate surge in demand was observed resulting in shortage of both drugs.9 The situation of drug shortage in India is not different, probably indicating widespread self-medication. Similar problem is observed in Pakistan, where most of the pharmacies in major cities ran out of these medications immediately after the announcement of their effectiveness in COVID-19. Although both drugs are inexpensive and abundantly available in the market, several companies have also hiked their price.6Both CQ and HCQ have been approved by the US Food and Drug Administration (FDA) under emergency use authorization and subsequently advocated by the Indian Council for Medical Research. Indian health ministry has also endorsed the prophylactic use of these drugs among healthcare professionals.4 This antiparasitic drug also carries substantial odds to be self-medicated attributing to its low price and easy accessibility. Although ivermectin has an established safety profile for human use and is FDA-approved for several parasitic infections,2 this drug poses risks of serious neurotoxicity, which can be even fatal in some cases. Moreover, there is no enough evidence to claim this drug is safe for pregnant women.10 Azithromycin is another repurposed drug, which is easily accessible at community level and can be self-medicated alone or in combination with HCQ.Ivermectin is another easily available and accessible drug, which has been recently repurposed for the immediate use in treatment in SARS-CoV-2.11 These patterns underscore that any news regarding the effectiveness of a particular drug for the management of COVID-19 may pose substantial risks of self-medication, which may either result in adverse outcomes, deaths or drug shortage. Even 0.1% drug-associated complications would be thousands in number, which will be difficult to cope by healthcare system currently engaged to combat the COVID-19. Moreover, increased demand for these drugs by the general public may halt the supply and availability of these agents for their approved indications and may also relate to price gouging. These factors may collapse the existing fragile healthcare system in most of the developing or underdeveloped countries during the ongoing pandemic. We believe that careful or responsible reporting and addressing of these potential factors by the health authorities is of paramount importance. We felt inclined to share few suggestions in this regard which should be considered in haste to facilitate the already overwhelmed healthcare system.The association of serious risks of widespread self-medication and media announcements can be evident by the public interest in CQ and HCQ as demonstrated by the data of Global Google Trends where search for these drugs spiked following the press conference acknowledging the benefits of these drugs for COVID-19.Since repurposing of most of the drugs for COVID-19 is based on either in vitro investigations or findings from small uncontrolled case series, both electronic and paper media should avoid any claim of cure for the general public.Media should avoid any exaggerated or amplified statements which could act as triggers for self-medication among general community.During the current pandemic, numerous TV channels are hosting talks or live shows on the disease by inviting various stakeholders. These shows or programmes must avoid any discussion on drug use or on the benefits of under-investigated drugs of COVID-19.The most reasonable and ethical approach would be limiting the COVID19-related discussions in TV shows to healthcare professionals rather than political or business figures.Media regulatory authorities must issue guidelines to host or break any statement on the prevention and treatment of COVID-19.Community pharmacists can play a crucial role in current circumstances and may limit the sale of under-investigation drugs by prescription only.Pharmacies should control bulk selling of repurposed drugs, even to the patients who are already relying on these drugs for other indications.Pharmacists may counsel general community regarding the harms of self-medication and encourage customers to adopt quarantine and control measures for the prevention of disease.Pharmacists should vigilantly observe and report any unusual activities in the supply chain, doubted sale pattern in the market and unethical promotion of these drugs.The role of drug regulatory authorities is of utmost importance to control the self-medication during current pandemic. Drug regulators can ensure appropriate supply of these drugs particularly in areas of high demand such as hospitals receiving patients with COVID-19 and centers treating malaria or autoimmune diseases. They can strictly observe unusual selling trends of these drugs and may take necessary actions wherever required.Self-medication during the current pandemic may aggravate the ongoing health crises for which none the country is readily prepared. We believe that restricted and careful media announcements, active involvements of pharmacists and drug regulators with positive support from the national health authorities will mitigate the potential risks of self-medication and subsequent drug shortage and price hike during the current pandemic.


The emergence of infectious diseases pose major global health threats. Estimates of total in-country human pathogen diversity, and insights as to how and when species were described through history, could be used to estimate the probability of new pathogen discoveries. Data from the Lao People’s Democratic Republic (Laos) were used in this proof-of-concept study to estimate national human pathogen diversity and to examine historical discovery rate drivers.A systematic survey of the French and English scientific and grey literature of pathogen description in Laos between 1874 and 2017 was conducted. The first descriptions of each known human pathogen in Laos were coded according to the diagnostic evidence available. Cumulative frequency of discovery across time informed the rate of discovery. Four distinct periods of health systems development in Laos were identified prospectively and juxtaposed to the unmodelled rate of discovery. A model with a time-varying rate of discovery was fitted to these data using a Markov-Chain- Monte-Carlo technique.From 6456 pathogen descriptions, 245 discoveries of known human pathogens in Laos, including repeat discoveries using different grades of evidence, were identified. The models estimate that the Laos human pathogen species diversity in 2017 is between 169 and 206. During the last decade, there has been a 33-fold increase in the discovery rate coinciding with the strengthening of medical research and microbiology.Discovery curves can be used to model and estimate country-level human pathogen diversity present in a territory. Combining this with historical assessment improves the understanding of the factors affecting local pathogen discovery.A protocol of this work was registered on PROSPERO (ID:CRD42016046728). Discovery curves have been used to estimate the diversity of diverse taxa such as trees, ants, birds and ferns. They have also been used to estimate global virus species diversity.Estimates of country-level pathogen diversity are needed to inform policy on potential of emergence, guide appropriate investment of resources in the skills, facilities and technologies necessary for aetiological discovery, particularly in resource limited setting like Laos.A historical analysis of the local context is needed to build on past experience of pathogen discovery to identify factors that facilitate discovery and encourage appropriate investment.From 6455 pathogen description records, 244 first descriptions of known human pathogens in Laos, including repeat discoveries using different grades of evidence, were identified.Four distinct periods of health systems in Laos were prospectively identified and juxtaposed to the unmodelled rate of discovery.The models estimate that the human pathogen species diversity in 2017 in Laos was between 169 and 206.A 33-fold increase in the discovery rate was observed during the last decade, reflecting greatly increased investment in medical research.Our finding show that it is possible, with sparse and historically varied infectious disease surveillance, to model pathogen discovery and estimate pathogen species diversity The time-varying rate discovery curve model is a useful proof-of-concept to estimate how many pathogens may be present in territories with sparse infectious disease surveillance and can be tested prospectively. This type of analysis could be used to guide appropriate investment in resources necessary for aetiological discovery, especially in scarce-resource settingsCountry-level historically linked discovery curve investigations elsewhere could improve our understanding of pathogen diversity between countries and estimate the probabilities of new discoveries and our understanding of the factors influencing such discoveries in different health systems.Human pathogens are defined as species-level organisms associated with disease or clinical infection in humans.The emergence and re-emergence of human pathogens is influenced by numerous demographic, historical, sociological, population and environmental factors.Discovery curves have been used to estimate the global diversity of diverse taxa such as trees, ants, birds, ferns and viruses.2), bordered by Thailand and Myanmar to the west, Vietnam to the east, China to the north and Cambodia to the south. Laos’ population is approaching 7 million; the rural population comprises 49 recognised ethnic groups reflecting the social and cultural heterogeneity of the region.16 17Laos is a small mountainous land-linked country  national health reports, accounts from medical personnel, case reports, journals, theses and other published documents were searched. Only paper health reports from pre-1990 were included as reports after then could be assumed to be identified through internet searches. Using Adobe Professional  documents were converted into readable-text-format and searched according to the search strategy. Mendeley  was used to manage references. Uncertain entries were re-examined by PN, TR and collaborators (see the acknowledgements).Every human pathogen referenced in the source documents was given a new line item in the dataset and accompanied by variables for the date of identification and publication, the source and type of document it came from and a measure of certainty in the diagnosis. Pathogens are defined as potential causes of human disease and are listed in Laos irrespective as to whether they were described as causing disease. Three grades of evidence were used to stratify the dataset into measures of certainty in the discovery specificity.Grade 1 includes culture and/or molecular assays (which includes PCR diagnosis) and/or direct microscope observation, grade 2 is serology-based diagnosis and grade 3 a clinical diagnosis without aetiological laboratory assays. For most pathogens, grade 3 represents the lowest grade of diagnostic confidence available. The perceived prestige of being the first to identify the presence of a pathogen in Laos may lead to confirmation bias and the graded data helps to account for this.et al.Discovery curves are used to estimate the total number of species in a specified area,The geographical region is defined by Laos’ borders that have remained relatively unchanged since the 1893 Siam-France treaty, when Siam (modern Thailand) surrendered territories east of the Mekong to France.Discovery curves comprised cumulative frequency plots of the identified organisms against their year of description.The first discovery curve (level 3) used the minimum year value (earliest date) from the set containing all grade data. The second curve (level 2) the minimum year value from the set containing only grade 1 and 2 data. The final discovery curve (level 1) used only data from grade 1. Thus the three discovery curves, by incrementally excluding lower quality graded evidence, reflected an increase of certainty in our estimate of pathogen diversity see .Previous time-based discovery-curve analyses assumed a constant-rate of pathogen discovery. The historical discussion supported a time-variant approach by suggesting four distinct periods of public health experienced in Laos; the French era of colonisation (1893–1953), the postcolonial (1953–1975), the socialist (1975–1990) and the post-Soviet periods (1990 to the present).The total number of species available for discovery is given by the parameter The probability of discovery at time Where the parameters The parameters were fitted to the data using MCMC Bayesian inference simulation with a standard Metropolis-Hastings parameter sampling algorithm adjustment and a 5000-iteration burn-in period. The MCMC simulations were run for each level of evidence using 1 million runs. All parameters received uniform priors except Confidence Intervals around the mean estimates were calculated using the 5th and 95th percentiles of the posterior distributions for each parameter. A sensitivity analysis was conducted using a 1000 bootstrap samples of the posterior parameter distributions (after burn-in) to reflect the estimated uncertainty around the mean estimated model.Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.The final pre-exclusion dataset consisted of 6456 entries and the final dataset comprised 5127 entries . Each enThe year of description and grade of evidence for each of the 244 identified species was used to develop the grade stratified We fitted the time-varying discovery rate model to the cumulative curves in The changing diagnostic capabilities of Laos are reflected in the granularity of pathogen discoveries over time. The majority of human pathogens recorded from Laos to date are bacteria . Bacteri25Over the last 150 years Laos’ path of pathogen discovery has been disrupted by political unrest and conflict and undergone an ideological transformation from a loosely ruled monarchy to a socialist state . MappingThe first written French description of a pathogen in Laos was in 1874 (a cholera outbreak), recorded in a 1904 French publication.An increase in laboratory capabilities is matched by a decline in the frequency of clinical discovery (grade 3). Post-1924 laboratory developments include, enhanced microscopical capacities (a grade 1 recognised level of evidence) and limited serological testing (grade 2), influencing the shapes of grades 1 and 2 curves, respectively . During During the postcolonial period the all-grade flattening of the discovery curves continued until the late 1960s and early 1970s. Early into this period two competing forms of nationalism emerged in Laos: the Royal Lao Government (RLG) and the prosocialist Pathēt Lao.An increasing foreign presence and Cold-War conflicts amplified the political divisions within Laos and in 1975, the USA, who had supported the RLG, left Laos. The Pathēt Lao gained political control of the country, heralding the socialist period.13 26A Soviet model of socialism was maintained from 1975 until the 1990s. The adopted Soviet-model of primary healthcare was set up to provide free nationwide healthcare.In the 1990s, Laos incorporated elements of free-market trade into policy, creating a new era of post-Sovietism.This changing politics and health of Laos forms a useful backdrop for the developed models. In the context of Laos narrative the plateauing off of the curves suggests that French colonial era years had a limited impact on the future discovery rate. However, this era was still responsible a large proportion of, mostly clinical, early first descriptions of pathogens.These early clinical descriptions are still important as in some instances, for example, Epstein-Barr virus in 1966 or chicken pox virus in 1927,The estimates from the models suggest that between 11 (level 3), 12 (level 2) and 13 (level 1) new species are currently available for discovery in Laos, reflecting estimated total species diversity of 169, 185 and 206, respectively . AlthougThe differences in the estimated diversity are greatest between the levels 1 and 3 models, due in part to Although there is a 16 species difference between the level 2 and level 1 models, there is only a difference of 1 between their baseline Despite a slight decline in rate of discovery in the second decade of this century, the models are not asymptotic, suggesting that data informing the model is incomplete and/or that the key modelling assumption of a finite number of pathogens available for discovery in Laos is not met. Accounting for emergent and imported pathogens will be crucial for further modelling of these data.The majority of emergent zoonotic diseases are viral, of which there are comparatively fewer recorded discoveries in Laos .30 AlthoThe gradient change is captured in the model by the parameter,  model 1  suggestsSalmonella enterica that includes both typhoid and non-typhoidal Salmonella. This research does not investigate the risk of associated morbidity or mortality predicted with the emergence of new infections. However, there is potential to use these data to develop a model that considers the evolutionary stages, as identified by Wolfe et al,Important limitations of this study include the exclusion of languages other than French and English, and not searching archives in Vietnam and Russia. The use and definition of species represents difficulty for some pathogens, such as for Despite the recent increase in pathogen discovery rate, Laos has among the lowest health-science outputs of countries in the Association of South East Asian Nations.35Despite the uncertainties in the model, the observed recent great increase in the discovery rate should inform national policy and investment, to understand what human pathogens are present, and how much further investment in pathogen description is needed, to ensure that strategies are in place to protect public health. Accompanying these investigations with local historical analysis builds on past experience of pathogen discovery to identify factors that influence discovery and encourage investment. Comparative country-level historically linked discovery curve investigations could improve our understanding of diversity variability, estimate the probabilities of new descriptions and our understanding of the factors influencing such discoveries in different health systems.


A 19-year-old Asian male presented to our emergency department with atraumatic right hip pain radiating to the right groin associated with pain on ambulation. Magnetic resonance imaging of the right hip with and without contrast revealed the diagnosis. Pigmented villonodular synovitis is a rare, monoarticular benign tumor originating from the synovium of the joint. The treatment is synovectomy of the pathological joint to prevent further disease progression. A 19-year-old Asian male presented to our emergency department (ED) with a one-day history of atraumatic right hip pain radiating to the right groin associated with pain on ambulation. The patient denied weakness or numbness of his extremity, fever, chills, or recent illness. Physical examination only revealed decreased range of motion and pain with internal rotation and flexion of the right hip. ED labs consisting of complete blood count, complete metabolic profile, C-reactive protein, and erythrocyte sedimentation rate were within normal limits. Ultrasound with Doppler of the patient’s scrotum was unremarkable. Computed tomography of the abdomen and pelvis with intravenous contrast demonstrated a right hip fluid collection consistent with inflammation or infection. Magnetic resonance imaging (MRI) of the right hip with and without contrast suggested the diagnosis .Pigmented villonodular synovitis (PVNS) is a rare, monoarticular benign tumor originating from the synovium of the joint.What do we already know about this clinical entity?Pigmented villonodular synovitis (PVNS) is a rare, monoarticular benign tumor originating from the synovium of the joint.What is the major impact of the image(s)?The image demonstrates the hypointense lesion caused by the hemosiderin deposition in the hyperplastic synovium characteristic of PVNS.How might this improve emergency medicine practice?This case illustrates the necessity of a broad differential diagnosis in a very common patient chief complaint  for optimum patient outcome.