The findings of this study showed that although the papillary and reticular dermis could be clearly distinguished in normal skin, three tissue layers were identified in the keloid dermis. The superficial dermis of keloid was characterized by active fibroblasts and lymphocytes; the middle dermis contained dense extracellular matrix (ECM) with large numbers fibroblasts, and the deep dermis was poorly cellular and characterized by hyalinized collagen bundles. In the keloid samples, from the superficial to the deep dermis, type I collagen increased and type III collagen decreased, and fibroblasts from the superficial dermis of the keloid were found to migrate more rapidly. In conclusion, the findings of this study showed that different depths within the keloid dermis displayed different biological features. The superficial dermis may initiate keloid formation, in which layer intralesional injection of pharmaceuticals and other treatments should be performed for keloid.Several studies have reported on certain aspects of the characteristics of different sites within a keloid lesion, but detailed studies on the keloid dermis at different depths within a keloid lesion are scarce. The aim of this study was to investigate the histology of the keloid dermis at different depths. This study included 19 keloid tissue samples that were collected from 19 patients and 19 normal skin samples, which were harvested from subjects without keloids or hypertrophic scar. Samples were studied by light microscopy using routine hematoxylin and eosin histochemical staining, and immunohistochemistry to detect CD20-positive B-lymphocytes and CD3-positive T-lymphocytes. Sirius Red histochemical staining was used to determine the type of collagen in keloid tissue and normal skin samples. The migratory properties of fibroblasts within the keloid dermis at different depths was compared, using an  Keloid is a fibrotic skin condition that typically results from abnormal wound healing. Keloid is characterized by the deposition of an excess of extracellular matrix (ECM). Unlike normal or hypertrophic scars, keloids do not regress with time, but persist indefinitely and extend beyond the original wound margin to invade the surrounding normal skin tissue . Patients fulfilled the currently accepted criteria for keloid, defined as the presence of typical skin lesions confirmed by two plastic surgeons. None of the patients included in the study had treatment within the previous 6 months. All keloid lesions caused pain or itching or displayed redness. The duration of the skin keloids ranged from 1.5 to 5 years. Keloids were located on the anterior chest wall (six), shoulder (two), chin (one), ear (seven), arm (one) or abdomen (two), and resulted from surgery (two), acne (two), vaccination (two), trauma (two), piercing (six), or were spontaneous (five).Nineteen normal skin specimens were obtained from age-matched and sex-matched healthy control subjects who underwent surgical procedures for cosmetic or other reasons, of which eight biopsies were from periauricular skin, five were from the anterior chest wall, four were from the abdomen, one was from the shoulder and one was from the arm. Healthy control subjects had neither keloids nor hypertrophic scars. All patients and healthy control subjects were Asian.This study was carried out in accordance with the recommendations of the Plastic Surgery Hospital Research Guidelines. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The study protocol was approved by the Ethical Committee of the Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.Excised keloids were fixed in 10% formalin for 24 h and dehydrated by standard histological procedures  for 1 h, rinsed briefly in 0.01 M HCl solution and then in water for 1 min, counterstained with hematoxylin for 1 min, differentiated in acid alcohol solution, rehydrated and mounted. Slides were visualized under polarized light microscopy, and photomicrographs were taken with identical exposure settings for all sections, as previous described , mid-dermis (MD), and deep dermis (DD). The strip of skin tissue containing the keloid dermis was placed horizontally onto the bottom of a tissue culture dish and covered with a sterilized glass coverslip. Tissues were maintained in Dulbecco's modified Eagle's medium (DMEM), supplemented with 10% fetal bovine serum (FBS) and incubated in a carbon dioxide incubator at 37°C. After 7 days, fibroblast migration was observed under microscopy and the migration distance (the perpendicular distance between the farthest fibroblast and the border of dermis strip) was measured.P < 0.05.Statistical analysis was performed using SPSS version 16.0 . Data were presented as the mean ± SD (standard deviation). Data were analyzed using Fisher's Least Significant Difference test to compare data between individual experimental groups. The level of statistical significance was The histology of keloid skin tissues and normal skin were viewed by light microscopy following routine hematoxylin and eosin (H&E) histochemical staining. In the normal skin, two layers of the superficial papillary dermis and the deeper, thicker reticular dermis were clearly distinguished (data not shown). In the dermis of the normal skin, the ECM was less compact, with fine, loosely and irregularly arranged collagen bundles and few cells. Although the thickness of the dermis from different skin biopsies was different, they showed similar histology.The dermis in the keloid skin showed distinct histological features at different depths, with three tissue layers identified. The superficial dermis (SD), directly beneath the epidermis, was the thinnest tissue layer (643 ± 380 μm) and was morphologically similar to the granulation tissue observed in normal wound healing. In this layer, we found a heavy infiltrate of cells, including spindle-shaped fibroblasts and lymphocytes. The collagen bundles in the superficial dermis of the keloid were fine and organized parallel to each other Figure .The mid-dermis (MD) of the keloid was the thickest layer accounting for more than half of the thickness of the lesion, with compact collagen fibers and the most prominent fibroblast infiltration Figure . DiffereThe third layer in the keloid dermis was the deep dermis (DD), which featured prominent degeneration and necrosis of dermal cells Figure . AtrophiThough keloid lesions were harvested from different parts of the body, there were no obvious differences in their histology. In our study, keloid duration was also not related to the histology, which may have resulted from small sample size and short duration of disease.+ T-lymphocytes were mainly located in close association with vessels, whereas CD20+ B-lymphocytes formed large and compact aggregates in the SD of the keloid. However, few of CD3- positive T-lymphocytes or CD20-positive B-lymphocytes were found in the MD or DD of the keloid, or in the dermis of normal skin.To confirm whether those small round cells with large nucleus infiltrated in the SD of the keloid the markers of T-lymphocytes and B-lymphocytes, CD3 and CD20 were examined by immunohistochemistry staining  were the main component of ECM, while type III (green) comprised only a small portion. Also, the composition of collagen fibers did not display differences at different depths in normal skin. Consistent with the results of the H&E staining, type I and III collagen fibers were fine, as well as loosely and irregularly arranged in the normal dermis Figure .Compared with the normal skin, collagen fibers were thicker in the dermis of the keloid and the composition was different at different depths Figure . In the The migration of fibroblasts from keloid dermis at different depths was investigated using tissue culture Figure . Seven dIn the present study, different histological features were identified at different depths in the keloid dermis, which may explain the conflicting findings from different studies. Taking collagen fibers as an example, some studies have reported that collagen fibers are haphazardly oriented in keloid lesions (Santucci et al., A number of studies have indicated an important role for lymphocytes in the development of fibrosis. In a study we previously reported, we showed that B-lymphocytes and T-lymphocytes were present in keloid dermis (Jiao et al., The predominant collagen types in the human dermis are types I and III, which account for >95% of the bulk of all of the collagen, with approximately 85% being type I collagen (Uitto et al., One of the key features of keloids is the progressive invasion into the adjacent normal skin, exceeding the original wound margin. Migration is a cellular behavior commonly observed during wound healing and metastasis, where fibroblasts or cancer cells undergo dynamic responses featured by rapid focal adhesion turnovers, actin polymerizations and traction force generations (Footer et al., Our results suggest the SD may initiate keloid formation. In the SD, lymphocytes may produce certain cytokines in a paracrine manner and increase the proliferation of fibroblasts and the synthesis of collagen. With the deposition of ECM, fibroblasts are buried in the ECM, which reduces the effects of lymphocytes, and these fibroblasts produce more type I instead of type III collagen. In the deep layer of the keloid dermis, the disappearance of fibroblasts may be due to apoptosis or some other mechanism, decrease in ECM synthesis results in degeneration of collagen fibers, which may explain why few cells and hyalinized collagen fibers were found in the DD of keloid lesions.Because the SD is important for keloid formation and the infiltration of lymphocytes is increased in the margin of keloids, we would suggest that intralesional injection and other treatments should be performed in the superficial layer of the keloid dermis, especially in the margin of keloids. Because the superficial layer is easily accessed, the development of some medicine for external use feasible. Also, this study has shown that pathological changes were found in the surrounding normal skin, where treatment should also be performed. Our study provides a better understanding of the histological features of the keloid dermis to help guide such local therapeutic strategies.HJ conceived and performed the experiments, collected and analyzed the data, and drafted the manuscript. TZ assisted with the collection of data. JF helped in harvesting the keloids and normal skin specimens. RX conceived and designed the project, oversaw the collection of results and data interpretation, wrote the manuscript and had primary responsibility for final content. All authors read and approved the final manuscript.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.


Brain-derived neurotrophic factor (BDNF) has been proposed as a biomarker of schizophrenia and, more specifically, as a biomarker of cognitive recovery. Unfortunately, it has only been tested once with cognitive remediation treatment (CRT).A randomized and controlled trial (NCT02341131) with 70 schizophrenia outpatients and 15 healthy volunteers was conducted. The participants with schizophrenia were randomly assigned to either CRT or the control group. All the participants were assessed in terms of cognition, quality of life, and their serum BDNF levels at both baseline and after the intervention. Additionally, comparisons of the effects of the different genotypes of the Val66Met polymorphism at the BDNF gene on the outcome variables were also performed.The patients in the CRT group presented with improvements in cognition. However, no significant changes were detected in the serum levels of BDNF. Interestingly, we found a significant positive interaction effect between the serum BDNF levels and the different BDNF genotypes. The Val/Val group showed significantly higher serum levels after the CRT treatment.The replication of the previous finding of increased serum BDNF levels after cognitive remediation in clinically stable individuals with schizophrenia was not achieved. However, our data indicated that genetic variability may be mediating serum BDNF activity in the context of CRT. All in all, the current consideration of BDNF as a biomarker of cognitive recovery in schizophrenia is promising but still premature.


Passiflora species in the southern limit of their geographical distributions. Climatic factors can drive genetic diversity, and their importance varies according to the marker. The primary predictors are variables representing higher temperatures during cold periods of the year and higher precipitation during dry periods. We concluded that, although these species are present in colder areas at the edge of their range, Tropical Niche Conservatism acts as a restraining force on genetic diversity in southern populations of Passiflora.The Tropical Niche Conservatism hypothesis is one of the most relevant theories to explain why tropical diversity is high, although the mechanisms underlying this hypothesis require further clarification. A possible research avenue to address the underlying mechanisms includes determining population-level processes associated with such a hypothesis, in particular by trying to identify how adaptation may occur in extreme niche conditions at the edges of species ranges. However, the determinants of molecular diversity at the edges of geographical distributions of tropical taxa are still poorly known. Here we assessed which environmental variables determine diversity in nuclear and plastid genetic markers for populations of four  Understanding the limits of geographical distribution of species and how these limits are determined is of special interest to answer several questions in evolution and population genetics . DistribThe Rapoport’s rule states that species can have narrower tolerances in more stable climates, leading to smaller ranges and allowing coexistence of more species . ConversThe tropical niche conservatism (TNC) hypothesis has frequently been used to explain why tropical ecosystems are biologically more diverse  is the extreme southern limit of 16 species of Figure S1) as described in Passiflora species occur in the extreme south of Brazil. We also sampled information from the east of Rio Grande do Sul, representing a more humid area at the southern limit of the distribution of many species within the Passiflora genus .We extracted environmental data and biogeographical information for the entire region where Passiflora to assess the degree of variance in different environmental factors in the studied region and search for multivariate environmental differentiation among major areas. We used altitude and bioclimatic variables obtained from http://www.worldclim.org/). More specifically, 19 variables representing distinct properties of climate such as temperature- and precipitation-specific niche characteristics were included in this study. These variables are widely used for modelling niches of species and other taxa because they represent specific environmental factors that can influence the geographical distribution of taxa on large and small scales. We used layers with a resolution of 2.5 arc minutes (~4.5 km) and extracted average values per grid cell. We transformed point data into grid files by implementing the re-sampling circular neighborhood technique . To avoid incorrect a priori definitions of populations, we included molecular richness grouping data from all four species, defined according to their occurrence in distinct spatial units, so that these data included all sequence types per marker  and the plastid intergenic spacer  genomes . DNA seqPassiflora to assess the degree of variance in different environmental factors in the studied region and search for multivariate environmental differentiation among major areas. The four resulting PCs were used to establish K-means clusters for two and three groups, consecutively. Biogeographical cluster analyses were implemented based on a presence/absence matrix of the species of Passiflora following occurrences reported by Mikania  based on the values of climate and altitude variables in each grid cell with occurrence of  Mikania , which aThe sequences of both genetic markers were automatically aligned using Muscle as implemented in MEGA 6.0  for the i.e., create homoscedasticity) by applying average environmental values per diversity class obtained in the diversity grids . We used Shapiro-Wilk, Jarque-Bera, Chi-square, and Anderson-Darling tests to assess the normality of the distributions, as implemented in We applied three spatial regression methods , which takes into account both predictive power and complexity . A distinction between eastern and western physiographical areas proposed by Passiflora , explained ~92% of the total environmental variance . PC 1 altrnH-psbA grid presented values of richness ranging from 1 to 24. A clear difference in coefficients was observed in a comparison of OLS and SAR models  conditions and do not present patterns driven by the temperate climate itself. Instead, they may be constrained by the typical temperate climate . The use of AIC allowed us to select the minimum adequate autoregressive models and suggested that increases in the values of temperature variables better predict diversity in the nuclear marker ITS, while the amount of precipitation is positively associated with plastid variability (Passiflora in the edge of its distribution. However, more species and markers within the genus should be tested in the future using methods that incorporate the effect of spatial autocorrelation to confirm this proposition.Although the studied areas belong to a region with a temperate climate, genetic patterns found based on molecular diversity of iability . All thePassiflora species. It is a region with high Passiflora species richness (L.B. Freitas, unpublished data; The division into western and eastern forests, previously suggested by Passiflora species is also most likely derived from historical migrations through the `Portal de Torres’ as well as from the diversification of molecular types that are autochthonous and resilient in the South and remained conserved in tropical-like niches. In fact, both niche suitability and migration appear to be the dominant causes of spatial patterns of species turnover and diversity of genetic markers in the region studied.Migration from typically tropical areas to areas with colder climatic conditions is not common and contributes to the accumulation of species in tropical regions (The suitability of this region for forest taxa is most likely a result of landscape patterns. The northwestern and eastern forest areas occupy the region surrounding the Brazilian plateau and are apparently dependent on the warm and moist characteristics of these large areas. Additionally, altitudes gradually increase toward the north and northwestern areas of the Rio Grande do Sul state, reaching approximately 900 meters above sea level in the north. In fact, altitude was the variable with the greatest contribution according to PCA . The forP. caerulea is known for its hardiness in the winter and resistance to temperate climates (P. caerulea, as well as those from P. tenuifila, exhibited higher diversity indices for both markers than P. misera or P. capsularis, indeed the diversity indices were similar to those obtained for P. actinia Hook. (subgenus Passiflora; P. contracta Vitta (subgenus Deidamioides; P. caerulea is one of the species reaching the southernmost areas of the distribution of the genus (Passiflora species, and this pattern may be amplified when breaks in the distribution are taken into account (The species Passiflora species (Passiflora populations at the southern limit of the species’ distribution.Stochasticity was cited as a relevant factor in determining distribution range limits  and our


The Canine Comparative Oncology and Genomics Consortium (CCOGC) was formed in 2004 in an effort to capitalize on the generation of a domestic dog genome sequence assembly , which cThe start-up costs to develop and maintain a repository of specimens from 3,000 dogs was estimated to be $2.1 million. This included the physical infrastructure, database development and management, and collection and maintenance of clinical specimens with assurance of stable sample quality during long-term storage. A lead gift of $1.1 million was received from Pfizer, and with it Pfizer received the naming rights to the biospecimen repository. Additional substantial donations were received from the Morris Animal Foundation and the American Kennel Club Canine Health Foundation. The National Cancer Institute (NCI) provided support for the physical infrastructure for the Pfizer-CCOGC biospecimen repository, which is housed at Fisher Bioservices in Frederick, Maryland. In 2007, the CCOGC was incorporated as a not for profit entity with 501c3 status. Two sustainable revenue streams were defined, the first being requests for samples from the research community following a predefined cost structure. The second proposed revenue stream was through targeted recruitment of prospective specimens on behalf of individual investigators, using the established CCOGC infrastructure.Standard operating procedures (SOPs) for sample collection were established by the CCOGC Bank Committee, which is composed of key leaders in the field of comparative oncology and representatives from each collecting institution. A universal SOP was implemented that applied to each of the seven histologies and outlined the collection of all required fluids , along with requirements for specimen labeling and shipping. Histology-specific SOPs were attached as appendices. These appendices included specific inclusion and exclusion criteria along with requirements for collection of representative tumor tissue, in addition to matched normal (non-neoplastic) tissue from the same case. Each submission required the provision of both formalin-fixed and OCT-fixed tumor and normal tissue samples, in addition to non-fixed specimens snap-frozen in liquid nitrogen. Tissue and blood samples were to be partitioned into multiple representative portions at the collection site, prior to transfer to the biorepository, for maintenance of sample integrity and to maximize their downstream utility. There were no restrictions placed on the breed, age or sex of the dog. All samples were to be collected from client-owned dogs prior to initiation of therapy and with informed owner consent.In 2006 the CCOGC issued an initial request for proposals from potential sample collection sites, which was circulated to veterinary academic institutions in the mainland USA. Essential criteria included having dedicated medical and surgical oncology services, pathology services with 52-week coverage, experience with tissue archiving and clinical trials, and a veterinary clinical caseload appropriate for achieving target collection numbers. Three sites  were selected in 2006 to pilot the SOPs for sample collection. Four additional sites  were added in 2007 and an eighth collection site (University of Tennessee) joined in 2009. The SOPs were approved by each Institutional Animal Care and Use Committee (IACUC).To date, the biospecimen repository has received over 60,000 specimens from almost 2,000 dogs. These include samples from 511 osteosarcomas, 446 lymphomas, 329 soft tissue sarcomas, 186 mast cell tumors, 184 hemangiosarcomas, 108 melanomas, and 100 pulmonary tumor cases. One hundred breeds are represented in the biospecimen repository, with golden retrievers (13%), Labrador retrievers (13%) and mixed breed dogs (22%) being highly represented. Patient age at time of collection ranged from <1 to 20 years with a majority being collected between at 7–10 years of age (51%). Patient demographics, pathology reports, treatment information, and clinical follow-up every six months (until time of death or a patient is lost to follow up) have been recorded for all cases. A web-based system, CCOGC DogBank Tissue Tracker, was developed by the NCI to enable entry of patient information at the collection sites. Queries of the biorepository inventory are made through Labmatrix, a CaBig-compliant web-accessible clinical and biological relational database that permits the application of dozens of filters to optimize sample selection.In 2012, an internally commissioned quality assessment of the Pfizer-CCOGC biospecimen repository was performed, prior to the release of specimens to the research community. Quality control and quality assurance parameters were assessed on a panel of biospecimens distributed randomly across the eight submitting institutions and the seven tumor histologies represented in the repository. The first phase consisted of a comprehensive histopathologic review of formalin-fixed and paraffin-embedded (FFPE) specimens from 331 tumors, representing 40–50 cases of each histology. A panel of board-certified veterinary pathologists from the NCI examined hematoxylin and eosin (H&E)-stained sections from each tumor, assigning a diagnostic classification that was subsequently compared with that associated with the original case submission. The proportion of cases for which the FFPE specimen examined at the NCI corroborated the original diagnosis ranged from 64% (hemangiosarcoma) to 100% (lymphoma and osteosarcoma), with a mean of 89% across the total of 331 cases. An alternative diagnosis was reached for 6% of all specimens, and the remaining 5% of specimens showed no conclusive evidence for the presence of a neoplastic process. The low value for hemangiosarcoma was due primarily to lack of sufficient tumor tissue in the submitted specimen to permit conclusive diagnosis. Hemangiosarcoma is associated with particularly extensive cellular, anatomical and clinical heterogeneity, which correlates with broad molecular variation both within and between tumors, and marked attenuation of tumor-associated genomic abnormalities by non-neoplastic cells [To this end, tumor heterogeneity was assessed in 132 cases from the three major histologies  through identification of stromal contamination in FFPE sections using routine histopathology, immunohistochemistry and a novel quantitative morphometry technique . The vasThe second component of the biospecimen repository assessment was carried out to assess the quality and yield of nucleic acid obtained from fresh-frozen tumor tissue and whole blood, since these represent the most commonly utilized reagents destined for downstream molecular studies. A total of 188 cases were selected at random from the biospecimen repository, providing proportional representation of each tumor histology and submitting institution. Routine techniques were used to extract total genomic DNA from tumor and blood specimens, and total RNA was isolated from tumor tissue. Certain histology-associated limitations were noted, such as reduced yields among hemangiosarcomas due to low cellularity and the presence of necrotic tissue, and in osteosarcoma due to challenges with effective tissue disruption. Pigmentation associated with melanotic lesions also impacted sample purity in a small proportion of melanomas. Overall, however, the quality scores for the majority of specimens fell in the highest category for nucleic acid yield and integrity , readily exceeding standard criteria for application in current molecular biology techniques. Conclusions from the quality assessment of the Pfizer-CCOGC biospecimen repository were presented at the 2013 American Association for Cancer Research Special Conference on the Translational Impact of Model Organisms on Cancer .In October 2013, after successful completion of the quality assessment phase, the CCOGC opened the biospecimen repository to the research community. A price structure was implemented to allow for the replenishment of the repository as samples are released. To date, the Pfizer-CCOGC biospecimen repository has released over 1,900 samples and completed one prospective collection. In an effort to maximize the future utility of the repository, the CCOGC recently eliminated the requirement for scientific review and project disclosure. Investigators apply online and include the number and nature of samples requested, along with any criteria required for additional sample filtering. Samples matching these criteria are then identified within the specimen inventory and a request is made to the repository for those samples to be retrieved and shipped to the investigator. The average turnaround time from completion of sample request to shipment is 2–3 weeks.Through generous donations and the efforts of the CCOGC officers and collection sites the Pfizer-CCOGC Biospecimen Repository has become one of the most valuable resources in the field of comparative oncology. The CCOGC has laid the groundwork for biobanking in the comparative oncology community, and the comprehensive quality assurance evaluation of the repository reinforces its tremendous potential to advance canine and comparative cancer studies. Indeed, this effort has spawned additional ongoing biobanking efforts at both CCOGC-participating and non-participating institutions.www.ccogc.org.Additional information about the CCOGC can be found at


The brown tumor or osteitis fibrosacystica is a benign bone lesion that caused by hyperparathyroidism. This complication has been decreased by diagnosis and successful treatment of hyperparathyroidism. The brown tumor of hyperparathyroidism results from a metabolic disorder that affects long bones, ribs, and pelvis. The maxillary involvement is rare. Parathyroidectomyis a good choice for patients with high parathyroid hormone (PTH) levels and diffuse brown tumor leading to a gradual decrease in the maxillary tumors. We report the case of a 50-year-old woman with chronicrenal failure presented with one-year history of slowly enlarging mass of the left cheek after 17 years of maintenance hemodialysis. The physical examination revealed a mass of the left jaw and the infraorbital region associated with a left exophtalmia. The mass was soft in consistency and tender on palpation. Her serum PTH concentration was 4830 pg/ml and her calcemia was normal. The computed tomography (CT) of the facial skeleton showed multiple osteolytic lesions of the maxillary sinuses and mandibular bone suggestive of brown tumors. The expansive lesion of the left maxillary bone found an extensive involvement of the left maxilla and the maxillary sinus. The patient underwent a subtotal parathyroidectomy. The PTH concentration taken 1 hour after the surgery confirmed a level within the normal range. At 12-month follow-up, there was an improvement of the exophtalmia and partial regression of the tumors.


Non-contact anterior cruciate ligament (ACL) injuries occur with rapid decelerations and pivoting. A recent injury to a high-level National Basketball Association (NBA) player demonstrated neuromuscular control and injury-sparing mechanisms that resulted in only minor ligament injury to the medial collateral ligament. We analyzed biomechanical mechanisms via publically available orthogonal 2-D video to demonstrate how this potential ACL injury was averted. Analysis of the knee injury mechanism demonstrated that the NBA player experienced low ground reaction force, high sagittal plane flexion, and maintenance of frontal plane stability with neuromuscular control. The outcome of these factors inhibited dynamic valgus collapse of the knee throughout the fall, avoiding ACL injury – a potentially career-altering injury. Many athletes, professional and recreational, will be subjected to similar mechanisms of injury and will have improved outcomes if they can successfully utilize preventive strategies of neuromuscular control to limit injury mechanisms. Non-contact ACL injuries are common in competitive-level sports, such as basketball, with movements of rapid decelerations and pivoting. Many athletes are subjected to injurious mechanisms and forces that could potentially cause ACL injury. Proper neuromuscular control can potentially avert ACL injury occurrence. This case study demonstrates:The neuromuscular control and biomechanical factors that averted a potentially career-altering ACL injury for a high-level athlete.That a dynamic valgus collapse of the knee is a vital characteristic in ACL injury.nd quarter during Game 4 of the opening round series. Moments prior to the injury, an opposing player, rushing down the court, tripped and slid across the floor, leaving a wet residue of sweat on the playing surface. This residue was directly in the path of the starting point guard who was moving at a fast pace down the court in an attempt to take a defensive position and prevent an opposing score in the remaining seconds of the half. The player the point guard was defending pulled up to shoot, leading the point guard to plant his left leg on the slick surface in an attempted rapid deceleration. Immediately, the point guard lost traction causing his left foot to slide out distally from his body. The resultant attempt to hinder the fall with his right leg caused him to incur a right knee injury as he collapsed to the court.During an exceptional season in which a starting National Basketball Association (NBA) point guard demonstrated remarkable skill on the court , won the league MVP title, and assisted his team to the 2016 NBA Playoffs, the said player experienced a potentially tragic injury at the close of the 2With any high-force knee injury , an anterior cruciate ligament (ACL) or medial collateral ligament (MCL) injury is a reasonable diagnosis to assess. Partial MCL tears (Grade II) are painful, but heal well in the extra-articular environment as clotted blood forms a fibrous network for mending the ligamentous tissue . Even a However, by a series of fortunate injury-sparing mechanisms for this potentially ACL-injurious incident, the point guard in question only demonstrated a Grade I MCL sprain diagnosed via MRI. Grade I means that the ligament was stretched, but not torn. The team stated that he would be re-evaluated two weeks post injury. During this re-evaluation, the team physicians would determine whether the player was capable of returning to play without likelihood of causing further harm or injury to his knee. The point guard was sidelined for a total of 15 days and missed four playoff games prior to receiving permission from team physicians to return to the court. Although he could not contribute to his team’s playoff run during a brief two week period, both team and player were assured he was not undertaking the intensive physical therapy and surgical reconstruction of his right knee. Such aggressive treatment would equate to the definitive sidelining of the point guard until at least the mid-point of the 2016–2017 basketball season.From both a biomechanical and neuro-mechanical viewpoint, 2-D video can be analyzed for determining mechanism of injury(11) as well as the factors that spared the starting point guard from an ACL rupture  12]. Th. Th12]. The most prevalent mechanisms of ACL injury entail 1) high ground reaction force; 2) valgus collapse; 3) planted foot (often flat-footed); and 4) the knee near full extension ,13. An aThe biomechanical construct of the knee allows for ab-/adduction in the coronal plane, flexion/extension in the sagittal plane, and internal/external rotation in the transverse plane. The knee has both extra- and intracapsular ligamentous structures to limit undesirable motion that could lead to injury. The MCL passively limits knee abduction and the lateral collateral ligament passively limits knee adduction. Further passive restraints of knee motion include the ACL, the posterior cruciate ligament (limiting posterior translation of the tibia in relation to the femur) and the knee capsule. Beyond ligamentous stability, the screw-home mechanism of the knee provides mechanical restraint to knee mobility. The screw-home mechanism is provided by a combination of asymmetric femoral condyles and muscular activation, effectively limiting the internal/external rotation of the knee at or near full extension ,16. The in sim and in vitro testing has demonstrated that knee abduction significantly loads the ACL to strain levels that are not sufficient to compromise the MCL [As an intracapsular ligament in the femoral notch, the ACL originates on the medial side of the lateral femoral condyle and attaches near the intercondyloid eminence of the tibia, often blending with the anterior horn of the lateral meniscus. With these points of attachment, the ACL passively limits not only the anterior translation of the tibia in relation to the femur, but can also limit knee abduction and internal rotation . These s the MCL ,20. In a the MCL ,22. In r the MCL , and the the MCL ,24. With the MCL ,19,25,26Beyond passive restraints of the knee, the neuromuscular system is vital to providing both reflexive and feedforward signaling to the active muscle restraints of joint stabilization. The contractile and elastic musculature is the preferred tissue to inhibit injurious forces to the passive ligamentous structures and joint capsule. The major musculature of the knee (quadriceps and hamstrings) allow for flexion and extension of the joint. Whereas the hamstrings are agonists to the ACL and will spare anterior tibial translation, the quadriceps are antagonistic and will increase anterior tibial translation and further extend the knee . In addiGiven the potential injurious situation the NBA point guard in question was subjected to, it is apparent that beyond the unmodifiable factors (i.e. slipping on the floor), he employed protective mechanisms to prevent rupture of the ACL. These included 1) distribution of forces across both legs; 2) high flexion of the knee with likely inhibition of quadriceps contraction; and 3) neuromuscular control to maintain ab-/adduction stability and internal/external rotation of the right knee which allowed for internal rotation to occur at the hip. The kinematic angles measured demonstrated an absence of dynamic valgus knee collapse with associated sparing knee flexion angle. These neuromuscular responses reduced knee abduction, anterior tibial translation, and internal tibial rotation, significantly reducing his risk for sustaining an ACL injury.


The aim of this article is to describe the clinical case of the non-surgical retreatment of a failed revascularization/revitalization treatment (RRT). The retreatment was preceded by two sessions including an interim medication with calcium hydroxide and a modified irrigation protocol containing a highly-concentrated sodium hypochlorite and prolonged usage of ethylenediaminetetraacetic acid (EDTA) to reverse unacceptable side effects of hypochlorite. During a 15- month follow-up, the healing of the periapical lesion, increased thickening of root canal walls and maturation of root was apparent. The repeated RRT represents a possible treatment modality for s failed RRT. Key words:Retreatment, revascularization, revitalization, maturogenesis, immature tooth. The treatment of immature permanent teeth with necrotic pulp presents many challenges that place demands on dental specialists and compromise the prognosis of teeth. Disinfection of the root canals introduces several problems such as cleaning and shaping large canals with open apices, the obturation and potential root fractures due to thin root canal walls . During et al. , and an access cavity was adhesively restored. Palpation was mildly painful but responses to percussing and probing the pocket depth were all within normal limits. A diagnostic x-ray from a referral dentist showed that the tooth was in the second stage of root development and revealed a periapical lesion and radiopaque material in the pulp chamber. The access cavity was inadequate because the mesial pulp horn was not included in the access cavity design Fig. . The tooet al. . InteresMany complications of regenerative endodontic procedures have been described, such as discoloration of the clinical crown, inability to induce bleeding from apical papilla or the collapse of MTA into the blood clot . Scienti


The aim of this study was to obtain a Brazilian transcultural adaptation ofan instrument developed in the United Kingdom for assessing the knowledgeand attitudes towards dementia by physicians.The "Knowledge Quiz" (KQ) contains 14 items on epidemiology, diagnosis andmanagement of dementia, while the "Attitude Quiz" contains 10 sentencesabout physicians' thoughts on the management of demented patients. TheQuizzes were translated, back-translated and the resultant version appliedto five physicians.The transcultural equivalence process was performed and four items of the KQneeded adapting to the Brazilian context. After changes suggested by a panelof specialists, the final version was applied to another five physicians andthe transcultural equivalence considered adequate.The Brazilian version of the instrument was successfully transculturallyadapted for future validation and application in Brazil. According to the same group, cases of dementia are setto double every 20 years, rising to 81.1 million by 2040. Currently, 61% of allcases of dementia are found in underdeveloped countries.2TThe prevalence of dementia in Brazil has increased in the last three decades amidsta rapidly aging population.6 umber of countries. In Brazil, only one Brazilianstudy has investigate this issue.7Considering evidence-based medicine, it is unclear whether early detection ofdementia improves patients' outcomes, although cognitive impairment assessment ispart of the global geriatric assessment.9Physicians often overlook cognitive impairment (CI) in the elderly, especially in itsearly stages.13 have identified dementia knowledge deficits amonghealth workers and caregivers. Basically, two instruments designed for this purposehave been used in these studies: the Alzheimer's Disease Knowledge Scale14 and the "Knowledge Quiz andAttitude Quiz".10 It is importantfor this type of instrument to be short and easy to answer. Instruments should alsohave good reliability in measuring what they propose to assess. International use ofthe instrument is also of importance since it enables comparisons between differentmedical educational systems. Of the two instruments cited, the "Knowledge Quiz andthe Attitude Quiz" by Turner et al.10 seems a promising tool for the assessment of CI by BrazilianGeneral Practitioners, having been used for this purpose in the United Kingdom.Few studies10 previouslyused in the United Kingdom for assessing the knowledge and the attitudes towardsdementia of Brazilian physicians.The aim of this study was to obtain a cross-cultural adaptation of aninstrumentEscola Paulista de Medicina,Universidade Federal de São Paulo.The translation of the instrument comprising the Knowledge Quiz (KQ) and AttitudeQuiz (AQ) questionnaires was authorized by their authors and this project wasapproved by the Ethics Committee of the Subjects. Numerous cross-cultural adaptation studies have shown that theinstrument's final version can be applied to a small sample of subjects since itscharacteristics accommodate diversity of individuals.15 In this study, the participants of thecross-cultural adaptation of the KQ and AQ were five recently graduated physiciansfrom different Brazilian medical schools. Five other physician could be assessed ifnecessary, in a second application of the instrument. The inclusion criterion was tobe on the first year of a medical residence program of the "Escola Paulista deMedicina, Universidade Federal de São Paulo". There were no exclusioncriteria.The physicians were invited to participate in the study during a "Welcome section" ofthe residence programs run by the institution. The physicians were randomly selectedand asked to fill out the instrument. None of the physicians refused toparticipate.Instruments. The Knowledge Quiz  Question 1 , from "a general practitioner with a list of 1,500–2,000people can expect to have the following number of people with dementiaon their list" to "a general practitioner with a list of 1,000 peopleaged 60 years or older can expect to have the following number of peoplewith dementia on their list";(ii) Question 2, from "by 2021, the prevalence of dementia in the generalpopulation in the UK is expected to" to "from 65 years of age, theprevalence of dementia...".An explanation was included (in brackets) about the meaning of "stepwise diseasecourse" on answer "c" of question 11.On question 14, Alzheimer's Disease Society was changed to Brazilian Alzheimer'sDisease Association.After these changes, the KQ was reapplied to another five physicians and thecross-cultural equivalence was performed with no doubts raised. The definitiveBrazilian version of the KQ is given in Descriptive analyses of the subjects in both applications were performed.2, representing an issue of concernacross all spheres of Medicine. Straight-forward instruments that can better trainphysicians to deal with dementia are fundamental. The internationality of theseinstruments is also important to allow comparisons of medical education, thuscross-cultural adaptation is a method of promoting this exchange of experience.In terms of public health, physicians' knowledge about dementia in elderly and theattitude they have toward demented patients is important to guarantee reliableclinical care for patients with dementia. Dementia cases have been increasing inBrazil and worldwide17The importance of dementia as an epidemic issue in public health was the priority tobe emphasized in questions 1 and 2. These questions address basic information aboutdementia prevalence that all physicians in Brazil should know. Question 14 alsounderwent adaptation to the Brazilian context, reflecting the role of a Brazilianequivalent of the Alzheimer Disease Society. On the other hand, the change inquestion 11 was more straight-forward, entailing adaptation to include a linguisticexplanation of the term "stepwise disease course".There were no apparent difficulties translating and back-translating the instrument,but the conceptual and semantic equivalence raised more doubts for the KQ than theAQ. Ultimately, both questionnaires were successfully cross-culturally adapted, andthe Brazilian version of the KQ about dementia and the AQ toward dementia patientscan be used to compare Brazilian physicians to other physicians worldwide. The panelof specialists contributed to the cultural equivalence of KQ by changing somequestions about epidemiology. Brazilian studies on prevalence express these numbersas percentages according to age.A limitation of this study was the profile of the physicians to whom the Brazilianversion was applied. These physicians were young and recently graduated which mayhave facilitated comprehension of the instrument, as compared to older doctors.Nevertheless, these recently graduated physicians represent the next generation ofphysicians to attend as general practitioners in public health.In the dementia field, primary care physicians in the United Kingdom have beenstudied periodically by the KQ and AQ instrument. The authors of the present studyintend to discuss the quality of teaching on this issue in Brazil.In conclusion, the Brazilian version of the instrument was successfullycross-culturally adapted for future validation and application in Brazil, serving toimprove health-care assistance in primary care.


Prestige being the last one. After the accident, a big human mobilisation took place in order to clean beaches, rocks and fauna, trying to reduce the environmental consequences of this serious catastrophe. These people were exposed to the complex mixture of compounds contained in the oil. This study aimed at determine the level of environmental exposure to volatile organic compounds (VOC), and the possible damage induced on the population involved in the different cleaning tasks by applying the genotoxicity tests sister chromatid exchanges (SCE), micronucleus (MN) test, and comet assay. Four groups of individuals were included: volunteers (V), hired manual workers (MW), hired high-pressure cleaner workers (HPW) and controls. The higher VOC levels were associated with V environment, followed by MW and lastly by HPW, probably due to the use of high-pressure cleaners. Oil exposure during the cleaning tasks has caused an increase in the genotoxic damage in individuals, the comet assay being the most sensitive biomarker to detect it. Sex, age and tobacco consumption have shown to influence the level of genetic damage, while the effect of using protective devices was less noticeable than expected, perhaps because the kind used was not the most adequate.Petroleum is one of the main energy sources worldwide. Its transport is performed by big tankers following some established marine routes. In the last 50 years a total amount of 37 oil tankers have given rise to great spills in different parts of the world,


In recent years, an increasing number of studies incorporated biogeography with phylogenetic analyses to reveal the origin and evolutionary history of specific floras. In this study, we constructed the mega-phylogeny of the floras of three representative regions across Yunnan, southwestern China. We analyzed the phylogenetic structure and beta diversity based on the presence/absence of species (genus or family) data to investigate the phylogenetic patterns of regional floras. We found conspicuous divergence at the genus and species level in the pattern of phylogenetic structures, which most likely related to historical biogeography. The flora of southern Yunnan was shaped by the strike-slip extrusion of Indochina and the regional climatic stability, while the flora of northwestern Yunnan was shaped by the uplift of the Himalaya-Tibetan Plateau and the oscillations of the glacial-interglacial periods. The flora of central Yunnan had nearly equal proportions of the northern and southern floras that may be derived from a common Tertiary tropical or subtropical flora. Geological events fit well with the floristic and phylogenetic patterns across Yunnan. This study highlighted the importance of linking phylogenetic analyses to biogeographic interpretations to improve our understanding of the origin, evolution and divergence of regional floras. It is widely accepted that geological history, evolutionary events and processes, and current climatic conditions are significant factors in the formation of contemporary biogeographic patterns145The collision between India and Eurasia, which began in the early Cenozoic, may be the largest active orogenic event on earth797121415In this study, we investigated the floristic phylogenetic patterns of three representative regions in southern, central, and northwestern Yunnan. The present study aimed to examine the significance of key geological events, particularly the plate collision-induced uplift of the Himalaya-Tibetan Plateau and the strike-slip extrusion of Indochina, on contemporary patterns of biogeography using a comprehensive method combining floristic geography with phylogenetic information. Several factors made these regions ideal for this research. First, the Yunnan region is located at a sutural zone between Laurasia and Gondwana in geological history1714151519201415We constructed mega-phylogenies of the regional floras and then analyzed the phylogenetic assemblage structure in each flora, as well as the phylogenetic beta diversity between floras from three taxonomical hierarchies . These phylogenetic analyses were also conducted among different geographical elements  for more detailed phylogenetic investigations of these floras. Specifically, we addressed the following questions: (i) What is the pattern of the phylogenetic structure in three floras across Yunnan ? (ii) What is the phylogenetic beta diversity between these floras? and (iii) Do the results integrated with phylogenetic information agree with previous biogeographic hypotheses in terms of the biogeographical divergence of the flora across Yunnan initiated by the uplift of Himalaya and extrusion of Indochina? Based on the biogeographic history described above and predicted patterns for community phylogenetic structure, we proposed three hypotheses. (i) The assemblages of flora in northwestern Yunnan are clustered, especially to temperate floristic elements, due to the quick speciation and divergence of abundant closely related taxa with the uplift of Himalaya. (ii) In contrast, the southern flora is more phylogenetically overdispersed, especially to tropical floristic elements, in response to the collision between India and Asia. This geological event resulted in southern Yunnan as a sutural zone, where distantly related taxa from Indo-Malesian flora (from Gondwana) and East Asia flora (from Laurasian) came together. (iii) The phylogenetic similarity between central and northwestern flora is nearly identical to the similarity between central and southern flora, which could derive from a common flora in geological time.NRI), while genera and species in central and northwestern Yunnan were clustered (NTI).At the family level, the patterns of phylogenetic structure in these three regions were less divergent  but distlustered . Genera lustered , NTI.p-values of all NRI and NTI measures and the taxonomic richness of these groups are available in the The S.E.S. Dnn in the tropical families and genera than temperate families and genera suggested that tropical and temperate taxa had smaller phylogenetic beta diversity than expected, and tropical taxa had a lower diversity than temperate taxa among these regions (The floras of the three regions at the family level were very similar (over 0.837), followed by those at the genus level (0.624–0.747), but fairly dissimilar at the species level (0.324–0.530) . The phy regions .In this study, we extended traditional species-centric floristic analyses and phylogenetic analyses of certain taxa or local floras to incorporate phylogenetic information and focus on regional floras. We used presence/absence floristic data of regions in southern, central, and northwestern Yunnan to analyze the phylogenetic structure and beta diversity of the three regional floras to quantify how closely related pairs of taxa were within or between floras. Our results showed a conspicuous divergence at the genus and species level in the pattern of phylogenetic structures among the three representative floras. We integrated these results with the influence of geological historical events on the biogeographical divergence of regional floras to assist with interpretation.NRI), and the same was found for the tropical genera, especially with tropical Asia and tropical Asia to tropical Australia distributions (NRI). This pattern aligned with the geological and biogeological events, which was the collision between India and Asia that displaced Indochina southeastward along the Ailao Shan-Red River shear zone717The pattern of phylogenetic structure in the flora of southern Yunnan was overdispersed. The assemblages of species (or genera) in southern Yunnan were more phylogenetically dispersed across the whole phylogeny . This pattern may relate to the evolution and reproduction of species under a stable tropical climate. Phylogenetic clustering at a regional scale may result from the rapid speciation rates or slow extinction rates in evolutionary time231425NRI and NTI were due to the different identification and measurements, which emphasized the importance of the simultaneous use of two indices providing diverse information from the whole phylogeny and the more recent divergences.However, the lustered , NTI. ThNRI) and with respect to the more recent divergences (NTI), and the same was found for the temperate genera (27SaussureaPedicularisMeconopsisThe floristic composition of northwestern Yunnan showed significant phylogenetic clustering. The species (or genera) in northwestern Yunnan were clustered across the entire phylogeny (NRI) , which includes 3 counties located at the center of the Hengduan Mountains, has a temperate climate and an alpine-deep valley topography, with altitudes ranging from 1,900 m to 6,740 m across an area of 23,870 km2. Its main vegetation consists of temperate sclerophyllous oak forests and cold temperate coniferous forestsYunnan province is located in southwestern China, between 21°09′–29°15′N and 97°32′–106°12′E. The present analyses utilized the floras of three representative regions in southern, central and northwestern Yunnan . Southerhttp://www.theplantlist.org), which is an international standard database for plant nomenclature. This process aimed to maximize the match between names in the local lists and those in the backbone phylogenetic hypothesis for construction of the phylogeny. All the names in the species list that were considered synonyms were replaced with their accepted names from the TPL. We assigned each species to a family using the R package ‘plantlist’41Comprehensive synonymized inventories of the total angiosperms in southern, central and northwestern Yunnan were obtained based on checklists from several monographs151920et al.45Furthermore, to explore the phylogenetic information concerning taxa with different patterns of geographical distribution in the study areas, patterns of angiosperms distribution were quantified at the genus and family levels based on WuWe built a presence/absence matrix at each level  based on the presence or absence of each angiosperm in each region for the following calculation of phylogenetic structure and beta diversity.et al.’s species-level phylogenyWe constructed phylogenies by grafting the families, genera and species included in the study onto a backbone phylogenetic hypothesis in the R package ‘S. PhyloMaker’NRI) and the nearest taxon index (NTI). In general, NRI is considered more sensitive to tree-wide patterns of phylogenetic clustering and overdispersion, while NTI is more sensitive to patterns of overdispersion and clustering closer to the tips of the phylogenetic treeNRI and NTI are defined as the measure of standardized effect size of mean pairwise distance (MPD) and mean nearest taxon distance (MNTD), respectively. These indices describe the difference in phylogenetic distance  between observed and null communities generated with some randomization methods divided by the standard deviation of phylogenetic distance in the null communitiesThe phylogenetic structure of each flora was quantified using two indices: the net relatedness index (MPDobserved (or MNTDobserved) is the observed MPD (or MNTD), mean (MPDnull) [or mean (MNTDnull)] is the average MPD (or MNTD) of randomly generated assemblages, and sd (MPDnull) [or sd (MNTDnull)] is the standard deviation of MPD (or MNTD) in the null assemblages. We randomly shuffled the tip labels of the constructed phylogeny 999 times to generate null communities. A positive NRI (or NTI) value indicated a smaller phylogenetic distance among co-occurring taxa than expected . Conversely, a negative NRI (or NTI) value indicated a greater phylogenetic distance among co-occurring taxa than expected .where In this study, we used all the species in the three floras as a species pool and each study area as a plant community at the regional scale.Dpw (mean pairwise phylogenetic distance) was unsuitable for large-scale studies, because it did not vary significantly along environmental and distance gradientsPhyloSor (phylogenetic Sørensen index) and Dnn (nearest neighbor phylogenetic distance) to evaluate the phylogenetic relationships between floras. PhyloSor is defined as the ratio of branch length between shared taxa to the total branch length of all taxa in two ecological communitiesPhyloSor value indicates closer community relationshipsDnn is defined as the mean phylogenetic distance between a species in community A and its most-related species in community B. We used a null model analysis to test whether regional floras were more or less phylogenetically similar than expected by chancePhyloSor and the standardized effect size (S.E.S.) of Dnn can be quantified as follows:Phylogenetic beta diversity provides insights into the phylogenetic relationships between communities. Previous studies demonstrated that BLij is the branch length between taxa shared by two communities, and BLi (or BLj) is the branch length between all taxa of community i (or j). Dnnobserved is the observed dissimilarity between floras. Dnnnull is the mean of Dnn of the null distributions generated by randomly shuffling the tip labels of the phylogeny 999 times. sd (Dnnnull) is the standard deviation of Dnn in the null distributions.where Analyses of phylogenetic structure and beta diversity were performed using the R packages ‘picante’How to cite this article: Liu, S. et al. A Phylogenetic Perspective on Biogeographical Divergence of the Flora in Yunnan, Southwestern China. Sci. Rep.7, 43032; doi: 10.1038/srep43032 (2017).Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


The average yield harvested worldwide amounts to roughly half of the yield obtained potentially given optimal conditions for crop growth. The difference between actual and potential yield, known as the yield gap  and leaf senescence (cytokinins) under stress conditions : “YR, MK and GC had the original idea. YR and MK: Bridging the yield gap: a question of sustainability. YR and GC rootstock-mediated tolerance to biotic and abiotic stressors. MK Confronting the combinatorial effects of multiple stressors. All authors: Challenges ahead. MK and YR contributed significantly to improve the final version of the article.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.


More than one third of nurses experience musculoskeletal pain several times during a normal work week. Consistent use of assistive devices during patient transfers is associated with a lower risk of occupational back injuries and low back pain (LBP). While uncertainties exist regarding which type of assistive devices most efficiently prevent LBP, exposure assessments using technological advancements allow for quantification of muscle load and body positions during common work tasks.The main objectives of this study are (1) to quantify low back and neck/shoulder muscle load in Danish nurses during patient transfers performed with different types of assistive devices, and (2) to combine the exposure profile for each type of assistive device with fortnightly questionnaires to identify the importance of muscle load (intensity and frequency of transfers) and body position (degree of back inclination and frequency) on LBP intensity and risk of back injury during a patient transfer.A combination of technical measurements (n=50) and a prospective study design (n=2000) will be applied on a cohort of female nurses in Danish hospitals. The technical measurements will be comprised of surface electromyography and accelerometers, with the aim of quantifying muscle load and body positions during various patient transfers, including different types of assistive devices throughout a workday. The study will thereby gather measurements during real-life working conditions. The prospective cohort study will consist of questionnaires at baseline and 1-year follow-up, as well as follow-up via email every other week for one year on questions regarding the frequency of patient transfers, use of assistive devices, intensity of LBP, and back injuries related to patient transfers. The objective measurements on muscle load and body positions during patient handlings will be applied to the fortnightly replies regarding frequency of patient transfer and use of different assistive devices, in order to identify risk factors for back injuries related to patient transfers and intensity of LBP.Data collection is scheduled to commence during the winter of 2017.The design of this study is novel in its combination of technical measurements applied on a prospective cohort, and the results will provide important information about which assistive devices are associated with intensity of LBP and risk of back injury related to patient transfers. Furthermore, this study will shed light on the dose-response relationship between intensity, duration, and frequency of patient transfers and the intensity of LPB in Danish nurses, and will thereby help to guide and improve electronic health practices among this population. Musculoskeletal disorders (MSDs) represent a widespread occupational disease as well as a major socioeconomic burden on public health systems in Europe and North America ,2. Low bOne occupation that is commonly associated with MSDs as a result of physically demanding job tasks is the health care profession. The annual prevalence of MSDs among nurses and nurses’ aides is high . FurtheIt is well-known that the utilization of various assistive devices during patient transfers decreases the risk of back injuries and intensity of LBP ,11. FurtPrevious research has used biomechanical measurements to identify peak loading during various job-related tasks among health care workers -19. For The primary aim of this project is therefore to quantify muscular loads during different patient transfers. By following Danish nurses during a full work day, this study seeks to obtain real-life measurements during patient transfers. The key aspect of this project is the measurement of muscle load and body positions during a number of patient transfers, with and without the use of assistive devices. These technical measurements, using surface electromyography (EMG) and accelerometers to quantify muscle activity and body movements, respectively, will allow for identification of the biomechanical characteristics of various patient transfers. As preparatory work to ensure high quality data collection, the most common types of patient transfers in Danish hospitals have been identified and a pilot-study that primarily served to test the EMG and actigraphy equipment has been performed (manuscript in preparation). Furthermore, another novel aspect of this project will combine the technical measurements described above with the results from fortnightly emails received from nurses in Danish hospitals. These emails will include answers to a short questionnaire regarding the weekly intensity, frequency, and duration of patient transfers, as well as the number of back injuries (defined as a sudden and unexpected accident during a patient transfer) and the intensity of LBP .The combination of technical measurements (EMG and actigraphy) and the prospective aspect of this project will allow for the development of a detailed exposure profile . TherefoThis study follows a cross-sectional  design as well as a prospective cohort design (questionnaires and fortnightly electronic follow-up). The technical measurements will be performed on full-time nurses from hospitals in Denmark. Therefore, by following nurses during a work day, the measurements will reflect real-life patient transfer scenarios with and without the use of appropriate assistive devices. Data collection is expected to take place from autumn 2017 to spring 2018, and baseline questionnaires were sent out in March 2017. Referring to the Helsinki Declaration, all participants will be informed about the content of the study before providing written informed consent. This information will be given both written and verbally. The study  is approved by the Danish National Committee on Biomedical Research Ethics  and the Danish Data Protection Agency (j.nr. 2015-41-4232).Approximately 50 female nurses will be recruited from Danish hospitals. To achieve a sufficient number of measurements of patient transfers during each individual work day, prospects will be approached by the lead nurse who knows the schedules. The generalizability of this study will therefore only apply to female nurses, as this constitutes a homogenous group and represents the vast majority of health care personnel in Denmark. Inclusion criteria will be an expected number of 10 or more patient transfers during the work day. Exclusion criteria are life-threatening diseases, pregnancy, and hypertension. The two former criteria will be evaluated by asking the nurse prior to the day of testing, whereas the latter will be measured on the day and is defined as readings >160/100 mmHg.Each participant will be equipped with wireless surface EMG equipment , allowing for continuous measurements. Before electrode placement, the skin will be prepped and cleaned. EMG signals will be recorded using a bipolar EMG configuration  with an interelectrode distance of 2 centimeters -28. The Before the beginning of a work day, the participant will enter the room designated for equipment application and testing. The EMG electrodes will be positioned bilaterally on: (1) the upper trapezius, 2 centimeters lateral from the middistance between the C7 vertebra and the acromion; (2) on the lower trapezius, 2/3 on the line from the trigonum spinea to the eighth thoracic vertebra; (3) on erector spinae longissimus, two finger widths lateral from L1; and (4) on erector spinae iliocostalis, one finger width medial from the line from the posterior spinae iliaca superior to the lowest point of the rib, at the level of L2 ,31. The The two accelerometers will be positioned on the lower back (just above the sacroiliac joint) and on the upper back (just below C7 vertebra). The equipment listed will be fixated with adhesive tape , and the strength of the signal will be confirmed. After successful application, normalization procedures will be performed. These procedures will consist of: (1) maximal isometric voluntary contractions (MVICs); and (2) submaximal isometric contractions, which will be performed in the morning and again in the afternoon. We will include both procedures as the latter has recently shown greater reliability for the erector spinae muscle . Two triFollowing the initialization and normalization procedures described above, the participant will start her work day. The test leader will follow the participant as she is performing various patient transfers. Given the nature of the wireless equipment, the test leader will be able to visually monitor the live EMG signals on a laptop. To ensure an adequate level of detail of all patient transfers using this setup, the test leader will observe and note the type of patient transfer and associated assistive devices, the number of nurses involved, as well as patient characteristics . Using this methodology, it will be possible to differentiate each patient transfer into its partial lifts that together constitute the whole. This approach will provide a level of detail novel to this field and will allow for more precise measurements of exposure during patient transfers. After finishing her shift, the nurse will return to the test room for end-day normalizations. By using the average value from the standardized normalizations performed before and after the work day, as well as EMG temporal and spectral changes , we aim The main outcomes of this project will be the association between low back muscle activity intensity  and body position (position and frequency), on the risk of back injury related to patient transfer and change in intensity of LBP during a one-year period.The first article will be descriptive in terms of muscle load and body position while using different assistive devices. The following articles will apply the results of technical measurements to the cohort (n=2000) with main outcomes, which are LBP intensity and risk of back injury during patient transfers.All statistical analyses will be performed using SAS statistical software for Windows . Poisson regression (injury) and linear regression (LBP) models will be performed using generalized estimating equations (Proc Genmod) and linear mixed models (Proc Mixed). An alpha level of 0.05 will be accepted as significant.Data collection is scheduled to commence during the winter of 2017.This is the first project to investigate the effect of using assistive devices during patient transfers via a combination of technical measurements and a prospective cohort design. Whereas previous research has either used biomechanical measurements to identify musculoskeletal loads during work or questionnaire-based designs to quantify work-related MSDs, this combination of research methodologies enables us to create exposure matrices regarding the dose-response relationship and importance of load, intensity, frequency, and type of patient transfer, in addition their individual associations with LBP back injuries related to patient transfers. In contrast to the job-exposure matrix commonly used in epidemiological studies, this exposure matrix will provide much greater detail as it assigns job exposure according to the specific tasks performed by the nurse. Furthermore, this is the first study to perform real-life measurements on nurses during a work day and will undoubtedly result in more realistic identification of potential risk factors, which can be made readily available as part of the electronic learning material currently used by nurses. Therefore, the present study has the potential to provide essential and detailed knowledge regarding the use of assistive devices during patient transfers in hospitals, and  to better guide the workplaces’ efforts to reduce the number of back injuries and the occurrence of MSDs among female nurses.


Bacilli class, genera Bacillus and Lactobacillus, colonize epithelium blurring the boundaries between resident and transient microbiota. Despite their minor proportion in the microbiome composition, these bacteria can significantly affect both the intestinal microbiota and the entire body thanks to a wide range of secreted compounds. Recently, insufficiency and limitations of pure genome-based analysis of gut microbiota became known. Thus, the need for intense functional studies is evident. This review aims to characterize the Bacillus and Lactobacillus in GIT, as well as the functional roles of the components released by these members of microbial intestinal community. Complex of their secreted compounds is referred by us as the “bacillary secretome.” The composition of the bacillary secretome, its biological effects in GIT and role in counteraction to infectious diseases and oncological pathologies in human organism is the subject of the review.Current studies of human gut microbiome usually do not consider the special functional role of transient microbiota, although some of its members remain in the host for a long time and produce broad spectrum of biologically active substances. Getting into the gastrointestinal tract (GIT) with food, water and probiotic preparations, two representatives of  A decrel cancer . Microbious ones . Bacillidiabetes . The posdiabetes .Viability is by definition a prerequisite for probiotic effectiveness as it is essential for colonization of intestinal mucosa, displacement of pathogens and immunomodulation. Viable bacteria demonstrate adhesive and antagonistic properties and produce a large number of extracellular enzymes and biologically active compounds . NeverthDespite more than a century of active use of probiotics, initiated by I. Mechnikov in 1907, the majority of modern reviews assessing the effectiveness of these drugs confirm the need for further studies to determine the exact mechanisms of positive effects of probiotics on the human body. Both live probiotic bacterial cells and their metabolites can be useful in treatment of intestinal diseases . The molCARD9) failed to metabolize tryptophan that increased host susceptibility to colitis , SCFAs , neurotransmitters , hormones, bacterial antigens, pathogen-associated molecular patterns, and toxins , minerals  and energy metabolites , while lactobacilli produce 100s of compounds , and identify the stage responsible for actually registered “influence.” Bacilli introduced into the GIT through the consumption of fermented food do integrate the resident microbiome  secreted by Bacilli aid in digestion of food components in GIT -lactonase help to modulate the microbiota content by decreasing the number of quorum-sensing pathogenic bacteria in the GIT through direct disruption of their signal molecules Hydrogen peroxide , which plays a central role in regulation of intestinal inflammation and homeostasis  are essential for the protection of these bacteria from predation and antibiotics produced by other species  (B. subtilis (se (JNK) . Many sisubtilis . Sideropsubtilis  and theisubtilis .extracellular vesicles have emerged as prominent vehicles of biological signals. Intense research on that topic revealed that EVs play important roles in bacterial physiology and pathogenesis, ranging from secretion and delivery of biomolecules  over stress response and biofilm formation to immunomodulation and adherence to host cells  were identified (B. subtilis (B. subtilis is hypothesized to guard bacilli from alien EVs and disrupt cell signaling by means of EVs in competing populations (Extracellular vesicles carry hydrolytic enzymes for nutrient acquisition from extracellular complex substrates or key nutrients to feed sibling cells and contain specific agents for antagonizing competing species. In EV important for survival compounds are protected from damage retaining activities much longer and can be transported in concentrated amounts for long distances from producing cells. Among these compounds are antibiotics and hydrolytic enzymes including peptidoglycan-degrading hydrolases . EVs isoabolites . Proteinabolites . In EVs entified . Sunl prsubtilis . The tarulations . EVs werulations .C. elegans with EVs originated from L. plantarum WCFS1 led to increased transcription of host defense genes, cpr-1 and clec-60, and thus provided protection against vancomycin-resistant Enterococcus faecium. Moreover, in human Caco-2 cells these EVs had similar effect, leading to the upregulation of REG3G, which is functionally similar to clec-60, and CTSB, the human ortholog of cpr-1 (B. lentus isolated from Korean soybean fermented food induced apoptosis of human colon carcinoma cells HCT116 (L. rhamnosus GG are likely to be implicated in the anti-cancer activity as they induce apoptosis in the hepatic adenocarcinoma cell line HepG2 via augmentation of the expression ratio between pro- and anti-apoptotic genes bax/bcl-2 (Interaction of EVs with the host is specific to the microorganism from which the EVs were produced and is based on the lipid content and cargo of the EVs . Gram-poof cpr-1 . The EVss HCT116 . EVs derax/bcl-2 .Bacillus genus are much less abundant but are capable of producing several times more extracellular molecules than lactobacilli. Many of them still require exploration. Further deep studies are needed for better understanding of the complex interactions between human organism and its microbiota, clarification of the particular mechanisms underlying remarkable beneficial properties of probiotic Bacilli, and the specific action of innumerous secreted low- and high-molecular weight compounds and their vesicular transportation.Now, it has become clear that studies on phylotype profiling are limited to the identification of microbial constituents, where information is lacking about the molecular interaction of bacterial communities with the host. Lactobacilli are well-represented in the human GIT and secrete a number of compounds which have direct and indirect effects on the health of GIT and organism as a whole. Species of Bacillus and the components of their secretome belongs to VVU. She structured the review and created the scheme summarizing the main idea of the review on the diversity of components secreted by the representatives of Bacilli class. DRY, being a specialist in the field of probiotic activity of lactobacilli, analyzed data on the influence of Lactobacillus and their metabolites on intestinal functions and microbiota, and host organism. IGG collected literature data on the microflora of the human intestine. On the basis of his analysis of epithelial biopsy samples obtained during the operations of patients with diagnosed colorectal cancer, a conclusion about the contribution of Bacilli class to the microbiota closely associated with the epithelium was made.The basis of this review was the experimental work of the group led by ONI, in which a variety of biological activities of bacilli and lactobacilli secretome was established. ONI developed the main idea of this review, collected literature data, verified the text and coordinated it with co-authors carrying out the general guidance of the review. The part of the review devoted to the properties of representatives of the genus 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 surgical management of both early and advanced stage germ cell tumors of the testis remains a complex process of surgical decision making to maximize oncologic control while minimizing morbidity. Over the past 5 decades, the evolution of the surgical template for retroperitoneal lymphadenectomy (RPLND) has resulted in important modifications to achieve these goals. In this review, we will characterize the historical motivating factors that led to the modified template, outline patient and clinical factors in selecting these approaches in both early and advanced stage disease, and briefly discuss future horizons for their implementation. Few topics generate more discussion and consideration than the extent and laterality of the surgical template when managing the retroperitoneum (RP) in germ cell tumor (GCT) patients. The implications of limiting the surgical template inappropriately leave patients at risk for RP relapses. Conversely, extending the template beyond necessary boundaries increases the risk of surgical complications and long-term side effects. Several modifications have been incorporated that allow for an optimization between functional and oncologic outcomes. Understanding the historical rationale for these alterations and the clinical scenarios in which implementation of a limited dissection can be safely integrated is imperative. For the purposes of this review, our goal is to highlight the motivating factors and clinical experience that led to changes in the surgical boundaries for retroperitoneal lymph node dissection (RPLND).Prior to effective chemotherapy for metastatic GCT, wide surgical resection of retroperitoneal (RP) disease was necessary to provide patients their only chance for durable, cancer-free survival. Additionally, cross-sectional imaging was unavailable and staging of disease limited. Accordingly, the burden of disease in this era was great; therefore, suprahilar and bilateral retroperitoneal dissections were routinely performed. With the development of curative, platinum-based chemotherapy regimens  along wiSeveral surgical advancements improved our understanding of nodal dissemination of disease to the RP and neural pathways that impacted ejaculatory function were discovered, setting the stage for surgical modifications and refinement. Preceded by cadaveric and lymphangiographic studies elucidating the primary and secondary lymphatic drainage of the testicle –10, Ray Weissbach and Boedefeld reported on a prospective, multi-institutional trial of 214 consecutive patients undergoing a bilateral dissection for clinical stage II disease . The goaDespite data from several published series, incorporation of these template modifications into clinical guidelines has remained controversial. Patient selection remains key for maximizing the cancer control and limiting the morbidity. In the primary setting, the risk of contralateral spread increases with increasing tumor burden. For patients with residual disease after chemotherapy, locations of disease both pre- and postchemotherapy, IGCCCG risk classification, along with tumor size have been suggested as criteria to consider when selecting patients for template modifications. Included in Several institutions have assessed oncologic and functional outcomes with modifications in the surgical template over time. While significant variability exists among groups as to the type of modifications made to the template, outcomes regarding RP relapse rate, and recovery of ejaculatory function are uniformly reported. In one of the earliest studies out of Italy, Pizzocaro et al. reported on 61 CSI patients, of which 10 experienced relapse in the absence of adjuvant therapy. None of these occurred in the RP and 87% reported preservation of antegrade ejaculation with template modification alone . SimilarProponents of bilateral, infrahilar dissections with unilateral or bilateral nerve-sparing have suggested that limited templates subject patients to higher rates of unresected disease in the RP, leaving them at greater risk for late relapse, higher burdens of chemotherapy, and potentially a greater risk of death. Eggener et al. reported upon 191 cases of pathologic node-positive cases undergoing primary RPLND for early stage NSGCT . CompariEarly experience in using full bilateral templates following cisplatin-based chemotherapy was reported by Donohue et al. in 1982 . PatientOthers have published on the pathologic findings of disease outside the boundary of a modified template. For example, Carver et al. published the results of 269 patients who had a full bilateral template performed and described the pathologic findings outside the bounds of a modified template . They deHistorical comparisons for bilateral RPLND are associated with loss of seminal emission and ejaculation in the majority of patients. With the incorporation of unilateral templates, preservation of antegrade ejaculation was attributable to the exclusion of any dissection or disruption of the contralateral efferent, postganglionic sympathetic nerve fibers as they course to the hypogastric plexus. Donohue reported ejaculatory rates of 90% with modified, unilateral templates without any compromise in oncologic efficacy . Similarp < 0.001). Additional clinical outcomes are also improved with a modified template dissection in the appropriately selected patient, such as shorter operative times, less blood loss, less transfusions, and fewer postoperative complications [While data exist describing the safety of template surgery in the postchemotherapy setting from an oncologic standpoint, functional data also support an improved ejaculatory status in modified template surgery. In the Indiana series with 10-year follow-up data, antegrade ejaculation occurred in 97.7% of patients, who were contacted . Additioications .The majority of the current data supports the oncologic safety of modified template surgery in strictly defined cohorts. Efforts to determine the safety in other patient populations such as poor-risk disease and late relapse offer areas of potential study. These studies would require meticulous design to ensure patient safety. For example, patients with a late relapse 10 years following their primary tumor with a small solitary recurrence in the ipsilateral landing zone could be reasonable to apply modified template principles. The assumption here would be that the disease has declared itself to the ipsilateral landing zone of the primary tumor and there has been a 10-year lag time to monitor the contralateral side with no recurrence.Data surrounding the use of minimally invasive surgery and template dissection is limited particularly in the postchemotherapy setting, but this should and will be held to the same standards of the open approach. Oncologic outcomes regarding the therapeutic value of template surgery in laparoscopic and robot-assisted primary RPLND are significantly lacking due to small numbers of patients, even smaller numbers with true pathologic disease, and the majority of patients with pathologic stage II disease receiving adjuvant chemotherapy. While some early reports of nerve-sparing success in the robotic settings are promising in the primary RPLND setting , this isWith more than 35 years of experience, several studies have confirmed the safety of modified templates for RPLND both in the primary and postchemotherapy setting. Benefits include limiting the morbidity of surgery, without compromising the therapeutic impact among appropriately selected patients. Expansion of its use within other patient populations warrants exploration but must be integrated in a thoughtful manner to ensure patient outcomes are not compromised.


Chemical proteomics has emerged as an integrated research engine for the discovery of new drugs and the agnostic identification of drug targets. It involves the development and combination of chemical tools, bioorthogonal techniques, phenotypic screens, target identification and validation, mode of action and chemoinformatics that together provide robust and high-throughput workflows for exploring drug-target-phenotype relationships. In particular, the focus is on the application of small molecules in proteomics and genome-wide techniques for the rapid identification of drug targets.The special issue of Proteome Science highlights the state-of-the-art for workflows and applications of chemical proteomics with 3 review articles and 2 original research papers contributed by the leading scientists in the field.Savistski and co-workers summarize the recent developments in thermal proteome profiling (TPP) . This teProtein-protein and drug-protein interactions have been studied by a variety of techniques including affinity chromatography, peptide arrays, activity and affinity-based probes, drug Western and photoaffinity labeling . In the In the third review, Kim and co-workers provide a targeted review on the use of the tetrazine ligation reactions in chemical proteomics. Since Sharpless introduced the idea of bioorthogonal “click chemistry” in 2001 , there hIn addition to these three review articles, Thomas et al. examines the influence of specificity of bivalent kinase probes that contain either a SH2 or SH3 binder plus an ATP mimic. In this excellent example of the design, synthesis and application of dual functional chemical proteomics probes, the authors confirmed the affinity and selectivity of their bivalent inhibitors against Abl along with other off targets. They found bivalent inhibitor A-2 has improved affinity as well as selectivity over the original ATP competitive inhibitor, KAM. These results provide interesting molecular design strategy applicable to many other bivalent inhibitors/probes that could find utility in chemical proteomics. Finally, Karuso and Kwon presented their findings on the unbiased, genome wide identification of a human protein target for the new antibiotic Daptomycin (DAP). They used a phage display cDNA expression platform  to screen selected human cancer cDNA libraries for human binding partners for DAP . Using tCollectively, the papers of this special issue devoted to chemical proteomics nicely highlights and exemplifies the applications of this emerging research field that promises to overcome the hurdle to identify protein targets of biologically active small molecules with unknown modes of action. Chemical proteomics is also applicable to the functional study of proteomes, understanding modes of action and for the development of novel drugs modulating novel targets. We hope you will enjoy this special issue and trust that these articles will stimulate further developments in the field.


Primary breast cancer fairly infrequently occurs in ectopic breast tissue, and primary ectopic breast cancer of the vulva is particularly rare. Only 26 cases have been published in the English-language literature, and there has been no report of primary breast carcinoma of the vulva in Japan. We report a rare case of primary ectopic breast cancer of the vulva that was treated with local excision of the vulva and sentinel lymph node biopsy (SLNB). The patient was a 72-year-old woman who had noticed a right vulvar tumor 10 years earlier. The tumor was excised by the Department of Plastic Surgery of our hospital. The histology of the vulvar tumor revealed an invasive ductal carcinoma of the breast, and immunohistochemical staining of the vulvar specimen showed the tumor cells to be 100% estrogen-receptor-positive and 100% progesterone-receptor-positive. All margins of resection were positive for neoplastic involvement. An additional local excision of the vulva and right inguinal SLNB were performed in our department. The intraoperative frozen section was negative for metastasis, and lymph node dissection was not performed. The final pathology was negative for residual disease, and a partially normal ductal component was present. Adjuvant hormonal therapy with an aromatase inhibitor was indicated post-operatively. The patient was asymptomatic and free of detectable disease at a 6-month follow-up. Due to the rarity of this diagnosis, there are no established guidelines for treatment. Although cases in which SLNB was performed are rare, we consider SLNB to be an effective alternative to inguinal node dissection for ectopic primary breast cancer of the vulva. Ectopic mammary tissue may occur anywhere along the milk line, which extends bilaterally from the axilla to the groin. The frequency of ectopic breast tissue in females is 1 to 6%, and it is relatively common in the axilla or on the thorax but rare in the vulva [The patient was a 72-year-old woman (gravida 0 and para 0), with no history of malignancy or breast disease and no family history of carcinoma. She had been aware of a left third finger tumor for 20 years and a right vulvar tumor for 10 years. These tumors were excised at the Department of Plastic Surgery of our hospital. The histology of the finger tumor revealed a schwannoma, and the vulvar tumor revealed an invasive ductal carcinoma of the breast  lymph node localization in the SLNB. 99mTc-phytic acid was injected into the subcutaneous tissue near the previous right surgical site on the day before surgery. Lymphoscintigraphy showed hot areas at the right inguinal lymph node and right obturator lymph node  a morphology consistent with breast carcinoma; (2) positive estrogen and/or progesterone-receptor expression on immunohistochemical staining; (3) immunostaining positive for additional common breast cancer-associated markers including carcinoembryonic antigen, CK7, and mammoglobin; and (4) presence of a non-neoplastic breast tissue or carcinoma in situ component . The GCDSentinel node mapping in vulva cancer is a more contemporary topic in the literature . An obseWe suppose that pelvic node resection following inguinal lymph node resection is necessary if the sentinel node is found to be positive for ectopic breast cancer of the vulva because, in our case, lymphoscintigraphy showed a hot area in a right obturator lymph node. In a randomized, controlled trial that followed 114 patients with vulvar cancer with groin node metastasis allocated to postoperative pelvic and groin radiation or to ipsilateral pelvic node resection after radical vulvectomy and inguinal lymphadenectomy, long-term follow-up confirmed a significant recurrence-free and cancer-related death benefit of radiation compared with pelvic node resection [Due to the rarity of this diagnosis, there are no established guidelines for postoperative treatment. Virtually all of the literature consists of individual case reports, and most authors recommend appropriate treatment for primary orthotopic breast cancer of a similar stage. Therefore, treatment should consist of an individualized combination of surgery, chemotherapy, trastuzumab therapy, radiotherapy, and hormonal therapy .Ectopic primary breast cancer of the vulva is an extremely rare condition, and diagnosis is made based on the pathology as well as exclusion of orthotopic breast cancer. Due to the rarity of this diagnosis, there are no established guidelines for the treatment of the patient. The appropriate treatment for a primary orthotopic breast cancer of a similar stage is recommended. Our patient was treated with local excision of the vulva and SLNB and adjuvant hormonal therapy with an aromatase inhibitor. We consider SLNB to be an effective alternative to inguinal node dissection for ectopic primary breast cancer of the vulva.