Human glioblastoma is the most aggressive type of primary malignant brain tumors. Standard treatment includes surgical resection followed by radiation and chemotherapy but it only provides short-term benefits and the prognosis of these brain tumors is still very poor. Glioblastomas contain a population of glioma stem cells (GSCs), with self-renewal ability, which are partly responsible for the tumor resistance to therapy and for the tumor recurrence after treatment. The human adult subventricular zone contains astrocyte-like neural stem cells (NSCs) that are probably reminiscent of the radial glia present in embryonic brain development. There are numerous molecules involved in the biology of subventricular zone NSCs that are also instrumental in glioblastoma development. These include cytoskeletal proteins, telomerase, tumor suppressor proteins, transcription factors, and growth factors. Interestingly, genes encoding these molecules are frequently mutated in glioblastoma cells. Indeed, it has been recently shown that NSCs in the subventricular zone are a potential cell of origin that contains the driver mutations of human glioblastoma. In this review we will describe common features between GSCs and subventricular zone NSCs, and we will discuss the relevance of this important finding in terms of possible future therapeutic strategies. Glioblastoma (GBM) is the most malignant primary brain tumor in humans. The World Health Organization classified this tumor as Grade IV glioblastoma, and consists of poorly differentiated cells with vascular proliferation and pseudopalisading necrosis. Glioblastomas are characterized by rapid cell infiltration and invasion, frequent relapses and poor prognosis, and survival rates . Like otGlioblastomas (GBMs) contain a small subpopulation of cancer cells with stem cell characteristics including self-renewal ability, proliferation, multilineage potency, and migration capacity, that are referred to as glioma stem cells (GSCs) –7. CompeIn this review, we will focus on the existing link between NSCs in the SVZ and the initiation and development of the GBM, and we will discuss possible therapeutic interventions in the SVZ.The adult SVZ lining the lateral ventricles contains NSCs that share features of astrocytes and of immature progenitors , 12. To The organization of the adult human SVZ differs from the classical SVZ described above for other mammalian species. During development radial glia in the human SVZ generate neurons and macroglia that populate the developing brain. The main difference relies on the existence of an outer SVZ, which also contains radial glia from which neurogenesis takes place that leads to extensive cortical expansion. This accounts for the larger and more complex cortical characteristics of the human brain. Following corticogenesis, the neurogenic niche of the SVZ and outer SVZ remains proliferative in neonates, generating new neurons that populate the prefrontal cortex and, to a lesser extent, the olfactory bulb. After approximately 2 years, SVZ neurogenesis ceases and the SVZ acquires an organization that differs from the classical SVZ cytoarchitecture described for rodents . A detaiHuman GBMs consist of a heterogeneous cell population, both neoplastic and non-neoplastic, that are organized as a cellular and functional hierarchy based on a subpopulation of glioma cells with stem cell properties, the GSCs . GSCs haGlioma stem cells (GSCs) of GBMs maintain localization within a vascular niche , 38 Fig and dispImmune cells are also important constituents of the GBM niche . MicroglAstrocytes and extracellular matrix proteins of the GBM microenvironment also contribute to the support of proliferation and migration of the GSCs , 57 and,Despite all the similarities between tumor and SVZ stem cell niches, there is a niche constituent that is specific to the SVZ, the CSF. The CSF is a source of soluble factors with a role in mediating NSC quiescence through molecules involved in G-protein-coupled receptor signaling .de novo in elderly patients without clinical or histological evidence of a less malignant precursor lesion. Secondary GBMs progress from low-grade gliomas such as diffuse astrocytomas or anaplastic astrocytomas and are prevalent in younger patients. Histologically, primary and secondary GBMs are indistinguishable, but they carry specific genetic alterations in cancer-driving genes (IDH1 (isocitrate dehydrogenase 1) mutations  gene are often identified in GBMs (The vast majority of GBMs (80% of cases) are considered primary GBMs; they develop rapidly ng genes . Typicalutations , which aary GBMs . Howeversubtypes . Mutatio in GBMs  and corrIDH-1, all the above mentioned genes also control these functions in NSCs from the SVZ. Next, we will describe in more detail the effect of genes that control quiescence, proliferation, differentiation, or migration of SVZ NSCs that are frequently mutated in GBMs , telomerase RNA (TERC) and specialized proteins  . The enzactivity , 71. Moral times .ATRX) gene is a suppressor of these alternative mechanisms. Therefore, mutations in ATXR are also frequently identified in GBMs  induces the formation of GBM-like tumors in the adult SVZ  promotes proliferation of NSCs of the rodent SVZ by EGFR activation –88. Spect of GBM . What reSimilarly to EGF, platelet-derived growth factor (PDGF) also activates proliferation of NSCs in the SVZ and creates areas of hyperplasia with features of early glioma formation . But conPDGF expression in GBM correlates well with other mentioned bad prognosis factors such as PTEN deletion and IDH1 mutation  are extremely difficult to treat since they are constituted by a heterogeneous group of cells with genetic and epigenetic variations, which interact with their microenvironment , through different communication routes , in order to support GBM progression. In addition, most chemical treatments have to deal with difficulties derived of the drug penetration through the blood-brain-barrier or of the severe side-effects.Current treatment options for GBM include maximal surgical resection, followed by radiation and temozolomide treatment . Post-suTumor microenvironment is considered one of the main targets for new therapies since the dialogue established between the tumor cells and the tumor niche is essential for the tumor to progress. For instance, vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis in GBM. A monoclonal antibody that inhibits VEGF signaling pathway, bevacizumab, has been used to decrease tumor angiogenesis in GBM, but it has considerable side effects . Tumor-aAnother important issue to consider in terms of possible therapies is the heterogeneity of the GBM populations, with fast-dividing- and quiescent GSCs combined within the tumoral tissue . ConventIn the context of this review, we will discuss possible therapeutic options targeting GSCs, and more specifically, targeting their putative cells of origin, NSCs of the SVZ with driver mutations. Therapies aimed to develop treatments directed not only to GBM cells and their microenvironment, but also to the SVZ, must be taken into account in order to achieve better prognosis for GBM patients.in vivo (Glioma stem cells (GSCs) in the human SVZ are specifically resistant to radiation in vivo . Factorsin vivo  and reduin vivo . The relChen et al. showed that increasing the mean radiation dose in the SVZ after gross total resection to 40 Gy or greater, significantly improved the survival of GBM patients .TERT promoter in the tumor-free SVZ (Angelica sinensis (in vitro and in vivo in mice injected subcutaneously with the drug (As mentioned before, patients with GBM present mutations in the free SVZ . As a cofree SVZ , 127. Spfree SVZ . Interessinensis . Butylidthe drug . In ordethe drug . The autAs demonstrated by Lee et al. , astrocyHowever, the application of CRISPR/Cas9 technology to GBM is challenging since in this cancer type there are numerous cell clones, often with multiple mutations in different pathways per clone, making unclear which are the driver mutations to target. Further experiments and clinical trials will reveal the feasibility of this technology in GBM.Due to the close contact of SVZ NSCs with the lateral ventricle, a possible way to target the SVZ would be the administration of drugs, vectors or cells in the lateral ventricles. This might be an adequate approach not only to directly target the population of NSCs in the SVZ, circumventing limitations imposed by the blood brain barrier, but also to target factors in the SVZ microenvironment that might be contributing to the GBM development.Some authors have used viral vectors encoding anti-tumor proteins infused in the lateral ventricles. For instance, Meijer et al.  showed tTherefore, the ICV method of delivery bypasses blood brain barrier limitation, has been shown to be effective for the delivery of molecules, viruses and cells, and due to the proximity of the SVZ, where glioma-initiating cells may be formed, emerges as a promising approach for GBM therapy that warrants further research.Shared similarities between NSCs of the SVZ and GSCs have led to the hypothesis that GBMs may arise from NSCs residing in the lining of the lateral ventricles that undergo malignant transformation.Recent findings have corroborated this hypothesis showing that astrocyte-like NSCs of the adult human SVZ acquire driver mutations which enable them to escape from niche control leading to uncontrolled proliferation and tumorigenesis.TERT promoter or in cancer-driving genes, such as PTEN, TP53, and EGFR.Mutations identified in the tumor of GBM patients and also in tumor-free SVZ tissue include low-level driver mutations in The knowledge of the cell of origin that contain the driver mutations of GBM will allow a better understanding of the nature of the GSCs in order to overcome their resistance to chemo- and radiotherapy or to avoid their progression, and it may help in the development of novel treatment interventions for this incurable disease.EM and AP revised the literature, designed the review and the illustrations, and wrote the manuscript.The authors declare that the submitted work has not been carried out in the presence of any personal, professional or financial relationships that could potentially be construed as a conflict of interest.


An evaluation of the most prominent bioinformatics tools showed that their ability to predict the pathogenicity was highly variable indicating that special efforts should be directed at developing new bioinformatics tools dedicated to the mitochondrial genome. In addition, massive parallel sequencing raised several issues related to the interpretation of very low mtDNA mutational loads, discovery of variants of unknown significance, and mutations unrelated to patient phenotype or the co-occurrence of mtDNA variants. This review provides an overview of the current strategies and bioinformatics tools for accurate annotation, prioritization and reporting of mtDNA variations from NGS data, in order to carry out accurate genetic counseling in individuals with primary mitochondrial diseases.The development of next generation sequencing (NGS) has greatly enhanced the diagnosis of mitochondrial disorders, with a systematic analysis of the whole mitochondrial DNA (mtDNA) sequence and better detection sensitivity. However, the exponential growth of sequencing data renders complex the interpretation of the identified variants, thereby posing new challenges for the molecular diagnosis of mitochondrial diseases. Indeed, mtDNA sequencing by NGS requires specific bioinformatics tools and the adaptation of those developed for nuclear DNA, for the detection and quantification of mtDNA variants from sequence alignment to the calling steps, in order to manage the specific features of the mitochondrial genome including heteroplasmy, i.e., coexistence of mutant and wildtype mtDNA copies. The prioritization of mtDNA variants remains difficult, relying on a limited number of specific resources: population and clinical databases, and  Query dedicated mtDNA databases which are regularly updated .Consider the variant's frequency both within the general population and specific haplogroup.Detection and interpretation of low heteroplasmy levels should be carefully evaluated.Integrate additional information that might modulate the clinical penetrance .Evaluate inter-species and primates amino-acid or nucleotide conservation.in silico prediction tools dedicated to mtDNA .Favor The prevalence of mitochondrial diseases primarily affecting oxidative phosphorylation (OXPHOS) is estimated at about 1 in 4,300 , molecular diagnosis of mitochondrial disorders was based on a combination of several techniques, including targeted Sanger sequencing for the detection of mutations, long-range polymerase chain reaction (PCR) and Southern blotting, for the detection of mtDNA rearrangements and depletions, whereas fluorescent PCR restriction fragment length polymorphism (RFLP) and pyrosequencing were used for the quantification of mtDNA variants and rearrangements  and 224 variants considered to be polymorphisms (P) according to Mitomap, were assessed with a set of 19 different prediction tools gathered in MitImpact2  and functional in vivo and in vitro evaluation show better performances, but their use is still limited, because functional studies are time-consuming and tissues such as fibroblasts, cybrids, or muscle samples, are not always available for assessing the consequences of the variants on mitochondrial physiology. Given the increasing number of variants of unknown significance identified by NGS, it would be interesting to regularly re-evaluate these pathogenicity scores based on new information.Thus, many bioinformatics tools are useful for predicting the functional impact of mtDNA variants, nevertheless results should still be considered with caution, due to the high rate of false negative and false positive predictions as demonstrated in Figure The development of NGS techniques and dedicated bioinformatics pipelines  is then helpful for the clinicians for the interpretation of low-level of the m.3243A>G mutation identified in peripheral tissues. Coupling the mtDNA copy number with mutant load quantification is another argument to assess the clinical variability  and m.14582A> G ; m.14258G> A, m.10680G> A in the MT-ND4L gene and m.12033A> G in the MT-ND4 gene (Caporali et al., Even with well-characterized mitochondrial phenotypes such as LHON or MELAS, shown to be associated with confirmed mtDNA variants, such as the m.11778G>A or m.3243A>G, respectively, mitochondrial whole genome screening may provide additional information with the co-occurrences of mtDNA variants that may modulate the phenotype (El Meziane et al., YARS2, a gene coding for mitochondrial tyrosyl-tRNA synthetase was associated with a mitochondrial protein translation defect, worsening mitochondrial respiratory chain deficiency in patients carrying the m.11778G>A LHON mutation (Jiang et al., YARS2 appeared as a nuclear modifier, capable of triggering optic atrophy in individuals carrying the m.11778G>A mutation, and would explain the incomplete penetrance of LHON, in addition to other parameters or environmental factors (Dimitriadis et al., As mitochondria are driven by two genomes, several studies have demonstrated that nuclear variants may modulate the phenotypic expression of mtDNA pathogenic variants (Davidson et al., The integration of additional information in mitochondrial databases or in the filtering and prioritization process of bioinformatics pipelines, such as haplogroups, co-occurrences of mtDNA or nuclear variants shown to modulate the phenotype should be very helpful to assess the pathogenicity of a given variant for a better interpretation and as a possible explanation for incomplete penetrance or phenotypic variability. Special efforts should be directed at developing bioinformatics tools dedicated to the mitochondrial genome such as MseqDR.Due to NGS technologies the amount of mtDNA is now constantly increasing and special efforts from the mitochondrial and scientific community have to be made to collect and organize the large quantity of generated information. In addition, the complexity of mtDNA interpretation is increasing in an exponential manner, requiring better and specific prediction tools to assess mtDNA variant pathogenicity or to assess the co-occurrence of variants.CB and VP decided on the content and structure of the first version of the manuscript. CB, DG, VD-D, EC, PA-B, and MC collected the information. VP and CB drafted the first and final version of the manuscript while DG, GL, DB, and PR revised the 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.


Congenital megaprepuce (CMP) is a type of buried penis characterized by extensive redundancy and ballooning of the inner prepuce as a result of preputial stenosis and phimosis. The malformation typically presents with difficulty voiding, often requiring manual expression of stagnant urine. Multiple techniques have been reported for the treatment of CMP with varying levels of positive outcomes. The authors provide a review of published literature, in addition to describing the procedure and results of our surgical technique in three children aged eleven months, two years, and twelve years. The literature review was conducted using PubMed with keywords “congenital megaprepuce,” “megaprepuce,” “buried penis,” “CMP,” and “correction.” Results were then differentiated based on presence or absence of true congenital megaprepuce and the surgical correction thereof. Regarding our cases, all patients completed the procedure with excellent cosmesis and without complication. Our technique is shown to provide consistent, excellent esthetic outcome across a wide range of ages and may be replicated by others. Congenital megaprepuce is a subtype of buried penis. Maizels et al. defined buried penis as a penis of normal size hidden by preputial skin . We condThe condition can present as early as birth but commonly is diagnosed later in infancy, most often due to parental concern regarding the need for manual urine expression and abnormal appearance , 10, 11.Various methods have been used for the correction of CMP including the ventral v-plasty, Cuckow's technique, preputial unfurling, and a multitude of other methods; however, there is no “gold-standard” or consensus of the most efficacious technique , 10, 11.Three cases of CMP, aged eleven months, two years, and twelve years, were surgically treated in 2017-2018 at our institution via excision of excess preputial skin, penile reconstruction, and scrotoplasty.The eleven-month-old had a history of preterm birth at 24 weeks. He underwent unsuccessful circumcision at an outside facility and was sent to us for difficulty with micturition with ballooning and manual expression, in addition to requirement of circumcision revision. Upon examination, he was noted to have a phimotic ring and right-sided cryptorchidism.The two-year-old presented to the Urology clinic with difficulty of micturition and ballooning, sometimes requiring parental manual expression of foul urine. Upon examination, he was noted to have severe phimosis and buried penis with a large amount of trapped urine Figures .The twelve-year-old presented to the Urology clinic primarily for circumcision. He also described the need for postvoiding manual expression of urine.Radical degloving of the penis: a circumferential incision 10 mm from the coronal sulcus was made. The penile shaft skin then incised ventrally and longitudinally down to the penoscrotal junction in order to radically deglove the penis to Buck's fascia until reaching the penile base deep in the scrotum.Radical excision of the dysplastic and thick dartos muscle down to the base of the penis .Excision of the redundant inner prepuce and preparing the penile shaft Byer skin flaps, which were rotated ventrally in order to have sufficient penile shaft skin coverage.Recreation of the penopubic and penoscrotal angles by using two PDS anchoring stitches dorsally and ventrally, retrospectively, between the dermis and Buck's fascia at the dorsal and ventral base of the penis. The scrotum was reapproximated in two layers at the midline using 4.0 Monocryl sutures and the ventral penile skin was similarly reapproximated at the ventral midline and circumferentially as shown in Figures All surgeries were performed under general anesthesia. Using a hemostat, the glans of the penis was exposed by ventrally or dorsally opening the phimotic ring. A 5.0 PDS stitch was placed in the glans for intraoperative control of the penile shaft, as shown in All patients completed the procedure with excellent cosmesis. No immediate postoperative complications such as infection, bleeding, or urinary retention were observed.The two-year-old boy showed excellent cosmesis and parental satisfaction at eleven-month follow-up visit .Unfortunately, the twelve-year-old and eleven-month-old failed to appear for follow-up and cannot be reached for short-term results.Discussion regarding the condition of congenital megaprepuce can be especially confusing given the ill-defined nomenclature surrounding the disease. The first case of congenital megaprepuce was described in 1994 . VariousOur method of correction provided similar levels of cosmetic repair in patients of very different ages and is thus applicable across a wide spectrum of patients. The technique reaffirms some of the most important aspects of repair including removal of the stenotic ring, excision of redundant inner preputial skin, and anchoring of the skin to Buck's fascia to recreate the penopubic and penoscrotal angles. However, we believe that the most important step in correcting CMP is excising the dysplastic dartos muscle which helps achieve excellent penile skin reconstruction, penoscrotal angle, penopubic angle, and penile shaft skin approximation, based on our limited case series. Leaving the dartos muscle results in downward retraction of the penile skin with thick and poor cosmesis of the penile skin reapproximation. This critical step is described in the majority of papers reviewed.Although the ventral v-plasty technique described by Alexander et al. has shown good results, we believe a dorsal skin flap provides excellent cosmetic repair , 11. ThiOne of the most important aspects of CMP is early recognition and proper age of surgical correction. Murakami et al. reported a common misbelief among parents that the patients would eventually grow out of the appearance of their penis . Liu et Given the rarity of this disease, it is difficult to have a sample size large enough for strong recommendations on technique. In addition to having a larger sample size to draw conclusions from, longer follow-up is needed to confirm parental and patient satisfaction, lack of recurrent buried penis, and general results of cosmesis and repair. In our humble series, the lack of follow-up with the twelve-year-old is especially disappointing, as he is one of the oldest presenting patients we found during our review of the literature.


Since the first in-man liver transplantation was performed by Starzl et al.  in the eIn the last decade, dynamic (hypo- or normothermic) machine perfusion protocols were introduced to preserve donor livers as opposed to static cold storage which, until then, was the standard ,8,9. In Potential alternatives for liver transplantation may include allogenic hepatocyte transplantation, in which the transplanted cells engraft the recipient’s liver and restore liver function . So far,Next to functional cells, the actual organ scaffold is of key importance for the maintenance and potential engineering of functional liver tissue. If cells lack this spatiotemporal control of physical and biochemical cues, they cannot properly function and likely dedifferentiate . A suppoThe diverse contributions in this Special Issue on Bioengineering Liver Transplantation provides an overview of the novel and exciting opportunities in the field of liver regenerative medicine, biomaterials, and stem cell research that can be applied in future transplantations and personalized treatments of end-stage liver disease.


Osteoarthritis is one of the most common chronic health problems in the world that causes disability and chronic pain with reduced mobility and is a progressive degenerative disease in weight-bearing joints such as the knee. The pathology of the joint resulting from OA includes loss of cartilage volume and cartilage lesions leading to inflammation of the articular joint structures; its incidence and progression are associated with a variety of risk factors. Most of the current treatments focus on symptom management such as physical and occupational therapies, pharmacological intervention for pain management, and surgical intervention with limited success and do not address nor halt the progression of the disease. In this review, we will describe the current treatment options for OA and the exciting new translational medical research currently underway utilising mesenchymal stem cells for OA therapy. Osteoarthritis is the pathology of articular joints most commonly associated with defects in cartilage such as osteochondral defects and is one of the most common chronic disabling diseases affecting people worldwide. It can cause severe limitation of daily activities that can seriously affect the quality of life. Approximately, 9.6% of men and 18% of women who are over 60 years old have symptomatic osteoarthritis worldwide . The musOA is usually associated with synovial joints (diarthroses), also known as the freely moveable joints . The norArticular cartilage is a special type of connective tissue which is nonneural, nonlymphatic, nonvascular, and therefore restricted in self-repair. Articular cartilage is a metabolically active tissue, and its architecture and biochemical composition are regulated, developed, and repaired by chondrocytes. Chondrocytes are the only cell type in the articular cartilage . NutritiOA is also associated with the physiological imbalance of degradation and synthesis by chondrocytes resulting in alterations in the composition of the cartilage matrix . In the As mentioned above, the degeneration of the articular cartilage remains the most significant structural change seen in OA, resulting in severe pain and reduced mobility , 22. Thewww.arthitis.org) recommends that OA patients undertake self-education in managing the condition and encourages losing weight for overweight and obese patients. This entails diet and exercise to reduce and manage healthy weight; however, due to pain and physical limitation resulting from OA, exercise is hard to implement and sustain. Joint targeted physical therapy has shown to improve the pain and function; however, there is no long-term improvement. An assistive device is designed to provide mechanical support to the joint structure in the patients with OA causing instabilities in the joint and also to distribute the load bearing for relief in pain and improve function, but these only have limited success.The Arthritis Foundation  used to be the first-line pharmacologic management to treat mild to moderate OA pain. However, it became an inconclusive recommendation due to lack of compelling evidence . FurtherNonsteroidal anti-inflammatory drugs (NSAIDs) are a big family of drugs including oral NSAIDs such as ibuprofen, aspirin, naproxen, COX-2 inhibitors, and topical NSAIDs such as diclofenac formed as cream, patches, gels, or solution. Issues with oral NSAIDs include adverse gastrointestinal (GI) effects and need to be taken in conjunction with the GI protectant . FurtherOpioids can be used for pain relief when patients cannot use NSAIDs and acetaminophen due to their associated side effects. However, they have limited long-term efficacy  and are Surgical interventions are recommended when the progression of OA has resulted in severe damage to the joint, severity in pain, and function deterioration that cannot be managed with any other options. The initial surgical option to restore the structural stability such as joint debridement by arthrotomy or arthroscopy to remove loose cartilage, fragments of meniscus, shaving of the cartilage, and removing osteophytes has shown to result in limited pain and function relief . ArthrosJoint replacement is considered the final option provided to OA patients when the condition progresses to the most severe. Surgical procedures for the replacement of the hip and the knees are extremely painful and require a long period of time for rehabilitation. Furthermore, total knee replacement has shown adverse outcomes such as pulmonary embolism, infections, and surgery-related deaths in some cases .In more recent times, many regenerative techniques have been used such as autologous chondrocyte transplantation (ACT) for focal damage of cartilage, microfracture, and mosaicplasty. The ACT technique in addressing confined cartilage damage involves the transplantation of chondrocytes that are harvested from non-weight-bearing cartilage from the patient  but doesThe above demonstrates that the current treatment for OA is only focused on symptom management and none of these options addresses or halts the progression of the disease or offers long-term benefits. Hence, there is an unmet medical demand for the treatment for OA suffers that can halt the progression of the disease and to provide long-term relief from the symptoms of OA. Cellular therapy has provided a real promise to combat this debilitating degenerative condition and can provide disease-modifying long-term benefit. Tremendous efforts have been made in the preclinical studies and now in the clinical trials evaluating the regenerative potential of the adult stem cells, especially mesenchymal stem cells (MSCs), to repair the structural damages of the joint space, cartilage degeneration, and inflammation.st century and provides an exciting promise to chronic degenerative conditions. Currently, there are over 500 clinical trials registered on ClinicalTrials.gov, exploring the safety and efficacy of adult stem cells, e.g., pluripotent stem cells, umbilical cord-derived stem cells, placental stem cells, and mesenchymal stem cells, to treat OA. Of these, mesenchymal stem cells have been a leading choice for many medical researchers around the world with over 352 registered clinical trials [Modern medicine is exploring the regenerative potential of cellular therapy to address the currently unmet medical needs of various degenerative conditions such as OA. Cellular therapy has been extensively invested in exploring a new paradigm for the treatment of many degenerative conditions including degenerative disc disease (DDD) and osteoarthritis of the joints, among many other conditions. For this reason, this review will focus on the therapeutic properties of MSCs to treat OA. The disease-modifying potential of cellular therapy such as the use of adult stem cells for regeneration of the damaged tissues has been hailed as a breakthrough in the 21l trials . In the in vitro due to their plastic adherence property and have a fibroblast-like morphology under the microscope [In vivo, the main role of MSCs is believed to be for self-repair and for maintaining tissue homeostasis [In 1974, Friedenstein and colleagues first described stromal precursors derived from the bone marrow that were able to form plastic-adherent fibroblast colonies in the monolayer culture and their differentiation characteristics . The tercroscope . Multipocroscope . In vivoeostasis . The reseostasis .in vitro [Originally, MSCs were isolated from bone marrow, but more recently they have been successfully isolated from various other tissues such as adipose tissue , brain, in vitro .in vitro with standard differentiation conditions [Since human MSCs are heterogeneous and can be obtained from many sources, different methods of isolation and expansion, and different approaches to characterize the cells have been described in the literature, this has caused the difficulty of comparing study outcomes. The Mesenchymal Stem Cell Committee of the International Society for Cellular Therapy (ISCT) has provided three minimal criteria to define MSCs for laboratory-based investigation and preclinical studies in 2006. First, MSCs must be plastic-adherent in the tissue culture flasks. Second, more than 95% of the MSC population must express CD105, CD73, and CD90 and lack expression (less than 2% population) of CD45, CD34, CD14 or CD11b, CD79a or CD19, and HLA class II. Third, MSCs must be able to differentiate into osteoblasts, adipocytes, and chondroblasts nditions .Drosophila wingless (Wnts), among other growth factors and cytokines [The “stemness” of MSCs is maintained by the leukemia inhibitory factor (LIF), fibroblast growth factors (FGFs), and mammalian homologues of ytokines . The intytokines , 52. Theytokines  and decrytokines . The lonytokines . Furtherytokines , 57.γ); the biomarkers for chondrogenic differentiation are aggrecan collagen type II and Sox9; and alkaline phosphatase, bone sialoprotein, osteocalcin, osterix, and runx2 are biomarkers for osteogenic differentiation [The differentiation process of MSCs is tightly controlled and involves the activities of various transcription factors, cytokines, growth factors, and extracellular matrix molecules . The difntiation –62.MSCs have shown disease-modifying effects in bone and cartilage defects, as discussed previously. Because of the multipotent properties of MSCs, they have also generated significant clinical interest in cardiovascular, neural, and orthopedic therapeutic applications. Moreover, the anti-inflammatory and antifibrotic properties of MSCs make them the ideal candidate for regenerative medicine. These cells are able to suppress the growth of activated T-cells and help regulate the production of regulatory T-cells (Treg) , 63. TheMSC-based treatment of OA has a lower risk to the patient and a variety of sources such as adipose tissue, bone marrow, and synovium . These aA proof-of-concept clinical trial conducted in Korea showed promising safety and efficacy results of adipose-derived MSCs to treat OA. Patients showed reduced pain, improved function of the joint and in the high-dose patient cohort, and regeneration of hyaline-like cartilage suggesting the disease-modifying effects of MSCs when injected into the affected joint . AnotherAdipose-derived MSCs to treat patients with joint disease also act as a precursor to treat degenerative OA. Osteochondritis dissecans is a joint disorder pertaining to articular cartilage and chondral defects resulting in damage to the articular cartilage and underlying bone. Adipose-derived MSCs have been reported to have disease-modifying effects in a clinical case series published recently . This stThese evidence-based clinical outcomes strengthen the model for treatment of OA with MSCs Figures  and 5. Tγ), and T helper cell 2 to increase IL-4 production and help reduce production of IFN-γ from natural killer (NK) cells [The choice between autologous and allogeneic MSC treatment is another aspect that will need further supportive data. Due to the immune-privileged aspect of MSCs , allogenK) cells –78. WhenK) cells –78. In aK) cells . In a caK) cells . Given tWith the approval of Prochymal, an adult stem cell therapy to treat graft versus host disease (GVHD) in children, in Canada and New Zealand, it heralds a new era for cellular therapy to address the unmet medical conditions of previously untreatable diseases. The translational medical research currently underway targeting MSCs for OA therapy in the clinical trial database is promising; however, they need careful evaluation of the outcome data. The results require focus primarily on the safety and then on the efficacy. Furthermore, the various stages of clinical trials currently registered need their outcome data published for the wider scientific community to consider and to evaluate the robustness of the therapy. The large number of MSCs trials indicates the promise of these cells; however, there is considerable paucity of the published clinical trial data and therefore it is early to envisage the extent of their therapeutic application.


Airway inflammation is a key feature of upper and lower respiratory allergic diseases, such as allergic rhinitis and asthma. Characteristically, histological alterations such as goblet cell hyperplasia, mucus hypersecretion, loss of epithelial barrier function, airway infiltration and structural changes such as basal membrane thickening and airway smooth muscle hyperplasia. These inflammatory signs are often obvious already early in life and may be accompanied by structural changes (remodeling) occurring in early lifetime. This review focusses on the main mechanisms underlying the development of airway inflammation and remodeling and discusses the question which factors contribute to the persistence of airway inflammation in chronic allergic airway disease.  This initial step, together with the release of Th2 cytokines (interleukin (IL) 4, 5, 6, 13), leads, on the one hand, to the activation of eosinophils and mast cells from the bone marrow, and, on the other, to their infiltration into the pulmonary tissue and to the activation of IgE-producing plasma cells from B-cells. After re-exposure to the same allergen, the classic IgE-mediated immediate-type reaction occurs, which is characterized by bronchial obstruction, hypersecretion, and hyperpermeability/edema . It was This paper focuses on the mechanisms of (i) the development of airway inflammation, (ii) structural remodeling, and (iii) the chronification/persistence of airway inflammation. In general, three components contribute to the development of allergic airway inflammation : genetic predisposition, allergic sensitization, environmental factors (aggravating or protective factors). Currently, seven genome-wide studies (GWAS) on the association of genes/gene polymorphisms with the development or presence of asthma, in which also asthma during childhood and adolescence was investigated, are available . These sThe impact of genetic factors on the development of allergic airway inflammation becomes even more complex when gene expression is considered. Experimental data observed in a murine model of bronchial asthma showed that in presensitized mice, acute or chronic allergic airway exposure led to the up- or down-regulation of very different genes . In thisIn the development of allergic airway inflammation, several types of cells play an important role . The first contact is mediated by the airway epithelium (AE), which has much more than a mere barrier function - it is actively involved in the process. By means of protease-activated receptors and Toll-like receptors, the AE is able to recognize allergens and allergen fragments directly. As a reaction to this, the AE itself produces proinflammatory mediators . These mediators activate dendritic cells (DCs), the professional APCs directly below the epithelium, and guide them into a proallergic direction. The type of immune reaction after presentation by the DCs is mainly determined by the type of Th-cells that are predominantly activated . The major role played by regulatory T-cells (Treg) in the suppression of allergic inflammation has been confirmed in experimental murine models and in studies on patients with early sensitization or manifestation of bronchial asthma , 20. ThuTraditionally, the structural changes in the airways were interpreted to be a kind of scarring due to the alternation between inflammation and recovery. In the meantime, there has been increasing evidence for the fact that the constantly-present airway inflammation, which is, e.g., regularly triggered by infectious exacerbations, very soon leads to changes of the airway structure (remodeling). According to this theory, airway inflammation and remodeling occur simultaneously and together participate in the pathogenesis of asthma development, already at early stages. This hypothesis is supported by various clinical trials in which pulmonary biopsies were taken very early in life (in some cases as early as the 1st year of life) in order to correlate the histological changes with the presence of current or later signs suggestive of bronchial asthma. In detail, these studies show: Signs of airway remodeling, like a thickening of the basement membrane or hyperplasia of the airway smooth muscle, are already present in infants who are later diagnosed as having bronchial asthma , 19. The occurrence of remodeling is also predictive of a later development of clinical bronchial asthma . In school-aged children, pronounced remodeling is particularly observed in cases of therapy-resistant, severe, or poorly-controlled asthma . Remodeling is observed independently of eosinophilic airway inflammation or increased Th2 activity . In conclusion, airway remodeling plays a crucial role in allergic airway inflammation, even if it occurs as early as preschool age. Furthermore, airway remodeling might also be partially responsible for the development of severe forms of asthma. One important question is which mechanisms lead to the chronification of airway inflammation as the pathological basis of persistent asthma. We know that most small children who, particularly in winter, have a tendency to develop episodes of obstructive bronchitis after viral infections, no longer show these symptoms after they have reached school age. On the other hand, predominantly children with early atopy  develop lasting symptoms of persistent bronchial asthma . HoweverEvidence from large clinical studies and birth cohorts demonstrating the high impact of early viral infections, particularly those caused by human rhinoviruses (HRV) and respiratory synsytial viruses (RSV), has become so strong that a dual mechanism of asthma development – allergic plus virus-triggered persistent airway inflammation – can be assumed. This is mainly based on the following observations: Lower airway infections in fall and winter are the main reason for obstructive bronchitis . Large-scale birth cohort studies have demonstrated that early viral infections of the lower airways are an important risk factor for the later development of bronchial asthma . Furthermore, prospective studies, in particular large-scale birth cohorts, have shown that these lower-airway viral infections lead to persistent asthma predominantly in those children with a history of allergic sensitization/atopy . In addition, recent prospective studies have shown that a loss of symptom control due to viral infections mainly occurs in allergic children and adolescents with asthma  and thatFinally, it has been demonstrated that in allergic patients, molecules of the allergic cascade  are directly triggered and up-regulated by viral infections of the lower airways . In conclusion, these results clearly illustrate that: allergic sensitization and viral infections are two independent risk factors for the development of bronchial asthma; their interaction significantly increases the risk; and from a pathophysiological point of view, they are both involved in the development of chronic airway inflammation and airway remodeling. Thus, a model as shown in For pediatric allergists, the main task will be an early prevention of asthma and allergy . With reprevention of early viral infections of the lower airways, prevention of early allergic sensitization. Currently, several clinical studies investigating an active vaccination against RSV are about to start. For HRV, the situation is significantly more difficult because there are numerous serotypes for which no common vaccination has been found. Nevertheless, a successful, active vaccination against RSV and HRV would significantly reduce the risk of developing persistent bronchial asthma! In addition, all measures against early allergic sensitization are certainly helpful in reducing the risk of developing persistent asthma. In this context, first clinical trials from the last years could demonstrate that unspecific immunomodulation, either by probiotics or by bacterial lysates , 18, can


Based on the requirements of underwater acoustic stealth, the classification and research background of acoustic coatings are introduced herein. The research significance of acoustic coatings is expounded from the perspective of both the military and civilian use. A brief overview of the conventional design process of acoustic coatings is presented, which describes the substrates used in different countries. Aimed at the local design of acoustic coatings, research progress on passive and semi-active/active sound absorption structure is summarized. Focused on the passive acoustic coatings; acoustic cavity design and optimization, acoustic performance of acoustic coatings with rigid inclusions or scatterers, and acoustic coatings with a hybrid structure are discussed. Moreover, an overview of the overall design of acoustic coatings based on the sound field characteristics of the submarine is also presented. Finally, the shortcomings of the research are discussed, breakthroughs in acoustic coating design research are forecast, and the key technical issues to be solved are highlighted. As acoustic stealth equipment widely used in submarines, the acoustic coating can absorb the sound waves emitted by the active sonar. It can also suppress the vibration of the hull and isolate the noise inside the boat. Therefore, the acoustic coating becomes the only key component on the submarine that can effectively counter active enemy sonar and passive sonar detection. Based on the sound field characteristics of the submarine, namely, radiation noise characteristics, self-noise characteristics, and target strength characteristics , acoustiIn practice, properties of acoustic materials can change under hydrostatic pressure conditions , which affects the sound absorption performance of the materials. With the development of low-frequency sonar, high-efficiency sound absorption of underwater acoustic stealth materials with finite thickness under low frequency  and wide frequency conditions has become a hot topic in current research . In the In the civilian field, acoustic coating generally refers to various functional materials used underwater. In civil water-sound systems, involving seabed resource exploration , seabed To acquire a better understanding of the design of acoustic coatings, in this study a brief overview of the conventional design process for acoustic coatings is provided first, and then the local structure design of acoustic coatings was introduced . An overview of the overall performance of acoustic coatings was also outlined. Finally, the shortcomings of the research were discussed, followed by the development of a new prospect.The design process of the acoustic coating was developed around the performance requirements presented in Local design of acoustic coatings mainly refers to designing of local acoustic structure. Acoustic coatings are usually laid on the hull piece by piece; therefore, design of a single-piece acoustic coating (or unit structure) can also be defined as local design. Local design consists of passive and semi-active/active acoustic coatings’ design . Passive sound absorption design involves optimization of acoustic cavities, acoustic performance of acoustic coatings with rigid inclusions or scatterers, and hybrid structure acoustic coatings. In contrast, semi-active or active sound absorption is achieved by semi-active or active control of sound waves.The origin of the world’s first passive acoustic structure dates back to the end of World War II when the concept of German “Alberich”-type acoustic coating was introduced. The historical synthetic rubber coatings installed on German submarines were designed with lattices of resonant cavities, which had sound-absorbing properties . With thThe study of oblique incidence provides a more practical and comprehensive significance for characterizing the acoustic performance of the Alberich-type acoustic coating; therefore, sound absorption performance of the steel-backed acoustic coating was studied when the acoustic wave was obliquely incident. By using numerical calculation methods, the sound absorption coefficient of the Alberich-type acoustic coating was calculated, and the mechanism of sound absorption was studied in terms of the structural displacement vector and deformation, as presented in Most of the current researches focus on acoustic coatings laid on the surface of rigid steel plates; however, different acoustic coatings laid on the surface of water-immersed steel sheets have rarely been investigated. Therefore, differential evolution algorithms combined with FEM were used for optimizing two types of Alberich acoustic coatings. The two resonance modes of acoustic coatings were different; therefore, we could obtain good absorption properties through acoustic coupling between two acoustic coatings and the cooperation with the damping rubber , as showAcoustic and physical characteristics of acoustic coatings can be modified by adding various components. By redesigning materials and structures of the Alberich-type acoustic coating, the tapered bore structure led to the enhancement in its low-frequency performance in the use of underwater testing and calibration cells .In the aspect of the establishment and calculation of an analysis model for acoustic coatings, an analytical model was established based on the homogenization theory, which has higher computational efficiency. The results shown in Most literatures have studied the optimization of structure and material on single-layer acoustic coatings; however, acoustic coatings with a multilayer structure have not been extensively studied. A program based on finite element simulation was developed in ANSYS. Through the comparison between a cone frustum hole and a cylindrical hole, the frustum hole  theory of sound waves under normal incidence. A coupled model of acoustic performance calculation based on the compression deformation of the cavity was obtained, and the influence of the internal pressure of the cavity was considered. With increasing hydrostatic pressure, the peak frequency was toward the high frequency and became wider, absorption effect became more significant for overall degradation, and internal air pressure reduced the cavity deformation and improved the low-frequency sound absorption effect .For the problem of the sound insulation effect associated with sound insulation decoupling material under hydrostatic pressure, the influence of hydrostatic pressure on the insulation performance of acoustic coating was analyzed, as shown in Structural design of the acoustic cavity better solves the problem of low-frequency sound absorption, but it also needs to consider its pressure resistance performance. A United States Patent discloses a composite material comprising a spherical shell inclusion for a subsea platform, which exhibited a strong static stiffness . This prIn 2000, Liu et al. proposed the concept of locally resonant sonic metamaterials. A lead ball coated with a layer of soft silicone rubber was embedded in the hard epoxy resin matrix to form a three-dimensional lattice structure. The acoustic band gap was generated by resonance, thereby achieving the purpose of absorbing sound waves and dissipating energy . CompariFor a more realistic understanding, the influence of frequency-dependent material parameters on the performance of local resonance acoustic metamaterials (LRAMs), a generalized Maxwell model was used to simulate the behavior of multi-polymer materials. Studies have shown that the parameters of the rubber coating material vary with the frequency and influence the wave attenuation effect in the frequency range around the band gap . The acoCurrent research focuses on symmetric resonant cavities, such as spherical resonators or coaxial cylindrical resonant cavities. However, characteristics of non-symmetric resonators, such as non-concentric resonators or non-coaxial resonators, have been less studied. Thus, FEM was used to study the absorption characteristics of a viscoelastic plate periodically embedded in an infinitely long non-coaxial cylindrical local scatterer, as shown in To overcome the shortcomings of the narrow range of the effective sound-absorption frequency of local resonance phononic crystals, a novel multilayer local resonance acoustic metamaterial was proposed, in which a multilayer local resonance scatterer was embedded into the matrix structure, as shown in Since the existing technology cannot realize effective absorption of subwavelength structure, an underwater element structure was proposed to achieve low-frequency broadband sound absorption below 1000 Hz, which was based on the structural combination design of common viscoelastic damping materials and metal materials, as shown in An acoustic coating with a hybrid structure takes sound absorption and pressure resistance performance into account, which incorporates other rigid materials while retaining the acoustic cavity. Sound absorption performance of a composite structure combining rubber material containing a cylindrical cavity and porous metal material was studied. The results revealed that the addition of porous metal material could improve the low-frequency sound absorption capability . For acoPassive sound absorption technology relies on the structural design of acoustic coatings and material modification; however, its sound absorption mechanism is limited, and control of low frequency and wide frequency sound waves is not good. Therefore, a semi-active/active control method for sound waves was proposed.Piezoelectric composites have been widely used in semi-active acoustic coatings. Through internal loss, part of the acoustic energy can be directly converted into thermal energy; another part of the acoustic energy can be converted into electrical energy due to the piezoelectric effect and then converted into thermal energy by piezoelectric passive control. The effect of rubber damping materials in the piezoelectric parallel sound absorption layer was investigated, and a design for acoustic coating with a multilayer structure  ceramic) was proposed, which effectively improved the low-frequency sound absorption coefficient . CombineActive sound absorption controls the secondary sound source to generate sound waves that are opposite to the primary sound source through the principle of coherent cancellation, thus achieving the objective of active sound absorption . A low-fIn recent years, overall design on acoustic coatings based on the characteristics of the submarine sound field has progressively received more attention, with a focus on acoustic radiation of underwater cylindrical shells, including finite/infinite long cylindrical shells, elastic or viscoelastic single/double shells, stiffened cylindrical shells, etc. The finite element and boundary element model of the submarine section were built, and sound radiation calculations revealed that functionally graded materials exhibited better vibration and noise reduction performance . By matcOther studies were on the target strength characteristics of the submarine. A high-frequency analysis program based on Kirchhoff approximation was developed for the prediction of submarine target strength (TS) , as presOf note, material parameters and structural forms of acoustic coatings are the main factors affecting the acoustic stealth performance. Overall, material properties are affected by its structural form. From local structure to overall performance, design of acoustic coatings needs to grasp the key research content of each stage. Wang et al. classified the underwater sound absorption materials, introduced the corresponding sound absorption mechanism, and compared their advantages and disadvantages, as summarized in (1)Although the local-structure design based on traditional acoustic theory is clear, its preparation is difficult, or the parameters of the prepared materials are contradictory to the setting parameters, which make it hard to achieve the expected performance .(2)Some theoretical studies are limited in terms of preparation techniques, and they lack experimental verification. Examples are specified in (3)Few researches focus on other performance requirements for acoustic coatings during design, such as temperature performance , inspect(4)Researches on low-frequency sound absorption of acoustic coatings are few, especially the study of underwater acoustic materials below 1000 Hz.After a literature investigation, we find that current research still has some shortcomings:(1)Compared to passive control, the active control of sound waves is more adaptable and has broad application prospects. Accordingly, the design of active acoustic coatings will be a major direction for future development.(2)Overall modeling and prediction of acoustic coatings under the coupling state of the shell structure require further study. When acoustic coatings are fabricated on the shell, acoustic characteristics in the coupling state of the structure and fluid are different from that in the natural state .(3)Applications of other acoustic metamaterials in underwater environments are also worthy of further research, such as thin-film acoustic metamaterials ,56, Helm(4)Theoretical breakthroughs have been brought by the electricity–mechanics–acoustics analogy  and mutu(1)The realization of low-frequency sound absorption performance of acoustic coatings without increasing thickness and weight of materials.(2)The guarantee of strong sound absorption effect of acoustic coatings in low frequency and broadband range.(3)The maintenance of sound absorption performance of acoustic coatings under deep-sea hydrostatic pressure.However, it must be emphasized that there are still some key technical issues to be solved  as follo


This article evaluates the psychometric properties of a new measure for assessing Substance-Related and Addictive Disorders: the Addictive Behavior Questionnaire (ABQ). The ABQ is a self-report measure composed of two sections: the Severity Index (SI) and the Seven Domains Addiction Scale (7DAS). Materials and methods. A total sample of 698 subjects divided into two groups , participated in this study. We applied Exploratory Factor Analysis (EFA) to examine features of ABQ construct validity, we used Cronbach’s alpha coefficient to assess its internal reliability, and explored some aspects of its concurrent validity by examining its associations with other measures assessing addictive behaviors and psychopathology. Results and conclusions: results of EFA indicated that all the scales of the ABQ are unidimensional and showed good internal consistency. The correlations between the sections of the ABQ and the other measures used in the current study were significant and in the expected directions. These results suggest that the ABQ has good psychometric properties and allows researchers and clinicians to gather relevant information regarding behaviors, psychopathology and severity of symptoms, for the best clinical reasoning and for planning tailored treatment for each patient. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) , a sectiFrom a more phenomenological perspective, the domain of impulsivity, obsessiveness, and compulsivity may have a similar relevance with respect to tolerance and withdrawal for the understanding of addictive behaviors. In fact, many people displaying problematic substance use and/or excessive behaviors may be obsessed with thoughts, memories, and desires concerning their addictive behaviors (obsessiveness), and they might impulsively enact them for achieving pleasure (impulsivity) and/or they might feel forced to enact them to avoid unpleasant feelings (compulsivity). Paradoxically, addictive behaviors may provide some stability to the needs of many addicted individuals, as they allow these individuals to obtain an immediate gratification of dysregulated urges and impulses on one side, and to tolerate otherwise painful or unbearable affect states on the other side . AccordiThe developmental environment of an individual plays a critical role in the development of this vulnerability to addictive behaviors. In fact, a positive environment and supportive relationships in childhood and adolescence may represent a protective factor with respect to the onset of substance use or addictive-related disorders: as the studies on resilience indicate , relatioSuch condition of emotional, cognitive, and relational dysregulation might in turn induce the individual to the obsessive, impulsive and compulsive use of a substance or a behavior, which allows a defensive withdrawal into mental states that are dissociated  from the ordinary consciousness. The withdrawal into these states by means of substance and/or behaviors may temporarily allow the addicted individual to push away the dysregulated emotions and traumatized mental states from the awareness. However, the escape into the temporary retreat of substance use and/or excessive behaviors further weakens the capacity for self- regulation of affects and fuels instead the impulsive need to reenact the addictive behavior to achieve again the sensation of pleasure and the reduction in the intensity of negative affect states. This creates a vicious circle, in which the reinforcing memory of the pleasure for the behavior and the compulsive ritualization of the behavior aimed to reducing pain, feed the thoughts and the obsessive urge to repeat the behavior, despite the negative effects that such action may produce on the individual’s psychological and physical health. Some studies have partially confirmed these clinical speculations ,14,15,16According to this theoretical model of addiction, we consider addictive behaviors as disorders resulting from the interactions between impulsivity, compulsivity, obsessiveness, emotional dysregulation, traumatized mental states, dissociation, and insecure attachment styles. Therefore, these domains of psychological functioning may represent key features to make a careful assessment and an individualized treatment plan for people suffering from addictive behaviors.(1)Categorical assessment of addictive behaviors. The ABQ evaluates the presence of substance-related disorder, gambling disorder, and problematic Internet use.(2)Dimensional assessment of addictive behaviors in relation to their severity level. The ABQ allows clinicians to have a specific dimensional picture of the severity of the addictive behaviors, to improve the professional reasoning and the decision making.(3)Assessment of psychopathological and behavioral variables. The ABQ measures seven domains related to addictive behaviors, according to the theoretical model behind the measures that conceives addictive behaviors as the results of an interaction between impulsivity, compulsivity, obsessiveness, emotional dysregulation, traumatized mental states, dissociation, and insecure attachment styles.(4)Good psychometric properties.In line with this new model of addiction, it was important to develop a measure for assessing addictions that can be used in professional practice with clinical populations and as a screening tool for nonclinical populations. Besides, in our context, there is a lack of self-report measures that assess addictive behaviors in a complex, multidimensional manner in both clinical and nonclinical populations. Thus, in the development of this new measure we paid attention to several criteria:In this paper, we present the Addictive Behavior Questionnaire (ABQ) and examine the main psychometric properties of the ABQ in an Italian sample.χ2 = 162.50, p < 0.001) gender  and years of education . The recruitment of patients was made possible thanks to the collaboration of various organizations  that work in the field of addictions. Each participant of the clinical group received a clinical diagnosis based on the DSM-5 that falls in the diagnostic class of “Substance-Related and Addictive Disorders”. In addition to ABQ, participants completed other questionnaires described in the measure section. The questionnaires were administered according to the laws of privacy and informed consent of the Italian law (Law Decree DL-196/2003) by the professionals of the services. The participants were also told that they could withdraw from the study at any time and that there would be no payment for participating in the study. Regarding ethical standards for research, the study followed procedures consistent with the latest version of the Declaration of Helsinki revised in Fortaleza [A total sample of 698 subjects , with a mean age of 36.44 years old (SD = 11.77) participated in this study. Participants were divided into two groups: a clinical sample composed of 515 subjects  and a control sample of 183 subjects  see . The cliDemographics questionnaire. A brief demographic survey was administered, assessing information concerning age, gender, area of residence, relationship status, education, employment status and ethnicity.Addictive Behavior Questionnaire (ABQ) . The ABQSouth Oaks Gambling Screen (SOGS) . The SOGBarratt Impulsiveness Scale (BIS-11) . The BarTwenty-Items Toronto Alexithymia Scale (TAS-20) ,24,25. TDissociative Experience Scale-II (DES-II) . DissociSomatoform Dissociation Questionnaire (SDQ-5) . The SDQPsychological Treatment Inventory—Attachment Styles Scale . The PsyInternet Addiction Test (IAT) . The IATYale-Brown Obsessive Compulsive Scale (Y-BOCS) ,35. The Alcohol Use Disorders Identification Test (AUDIT) . The AUDTraumatic Experiences Checklist (TEC) . The TECDescriptive statistics for clinical and control samples were calculated. Besides, Exploratory Factor Analysis (EFA) was applied. We first analyzed the Bartlett’s Test of Sphericity and the Kaiser-Meyer-Olkin’s (KMO) Measure of Sampling Adequacy to assess if the items were significantly correlated and shared sufficient variance to justify factor extraction. Maximum likelihood (ML) was selected as the method of factor extraction; eigenvalues greater than 1, the Kaiser criterion, and the scree test were checked for agreement. The reliability of the scale was calculated using the Cronbach’s alpha coefficient . FeatureMeans and SD of the two samples are shown in Cronbach’s alpha coefficients for the scales of the SI and for the scales of the Seven Domains Addictions Scale (7DAS) suggested good reliability see . ExaminaThe ABQ (SI and 7DAS) showed significant correlations with the majority of measures used to assess concurrent validity see .ANOVA results showed that the clinical group obtained significantly higher values for most variables analyzed than the nonclinical group, indicating a good discriminant validity of the ABQ see .The aim of this work was to illustrate the theoretical and clinical model behind the ABQ and to verify its psychometric properties . The importance of creating this new measure for assessing substance-related and addictive disorders lies in the fact that the ABQ is based on a novel and integrated model of addiction that can provide an empirically grounded framework for understanding, assessing, and treating the dysfunctional processes at the basis of addictive behaviors. In fact, we believe that the seven domains of addiction identified in the ABQ allow clinicians and researchers to identify the dysfunctional processes and dynamics that foster the development and maintenance of addiction. From a behavioral perspective, addictive behaviors are reinforced by both positive (the pleasure linked to the behaviors) and negative stimuli , which fosters impulsivity and compulsivity, as well as obsessiveness toward the behavior. However, from a developmental perspective, addictive behaviors may also emerge from a need to regulate painful internal states, and/or to dissociate traumatic memories and/or to deal with attachment insecurities and mistrust in close relationships ,42,43,44Finally, the ABQ showed good levels of discriminant validity, and this testifies to the ability of the ABQ scales to distinguish between clinical and normal population. An exception was observed in the SI scale assessing problematic Internet use. This likely results from the current lack of formal diagnosis of Internet addiction or Internet gaming disorder in current diagnostic manuals, which makes it difficult to recruit patients who are seeking treatment for such problems. In fact, very few participants in the clinical group presented concurrent problems with Internet use, and their excessive use of the Internet was mostly related with PG. However, the positive correlation of IAT scores with the scales of Impulse dyscontrol, Compulsive behavior and ritualization, and Obsessive thoughts of the 7DAS suggest that the ABQ may be used for screening problems linked to excessive Internet use, even though the SI scale concerning problematic Internet use may need further empirical examination. Further caution should be needed in the assessment of problematic Internet use, because the current trend in research is to identify specific domains of addiction to Internet applications, such as Internet gaming disorder, even though this trend is criticized among many scholars .As with all research, this study comes with several limitations. First, we did not differentiate participants in the clinical group based on their specific diagnosis. This allowed us to improve the statistical power of our study, but at the cost of obscuring potentially specific differences in symptoms and way of functioning within the clinical group. Second, even though the theoretical rationale behind the ABQ may be considered as comprehensive, and its scales demonstrated to be clinically meaningful, addictive disorders are biopsychosocial disorders and many factors may contribute to their development, including other factors that are not comprised in the ABQ. Finally, this study represents an initial validation of a promising measure, but further validation with clinical and nonclinical samples are needed to better understand the strengths and limitations of the ABQ with respect to other comprehensive measures of addictive behaviors.These limitations notwithstanding, our findings suggest that the ABQ is a comprehensive and easily administered and scored instrument for assessing addiction in adults, with good psychometric properties. Therefore, it can be used in both research and clinical practice for the assessment of addictive behaviors and for the development of individualized treatment plans directed to people who suffer from substance-related and addictive disorders.