The prevention and bioactivity effects associated with the so-called “Mediterranean diet” make olive oil the most consumed edible fat in the food intake of the Mediterranean basin.The road to quality demands that legislation should be followed. Hence, official European Union classifications such as protected designation of origin (PDO), protected geographical indication (PGI), etc. guarantee the quality and the origin of the labeled foodstuff.The profiling of volatile components and the aroma of olive oil are key factors in the quality dimension and are affected by various factors and conditions such as cultivar; atmospheric, pedologic, and fostering conditions; the ripening degree; olive and oil storage; and the technology of oil extraction from drupes, as well as the quality of the pre-extraction procedures.In extra virgin olive oil production, as in all kinds of production, the maintenance of high quality standards is assured by the olive fruits’ and the final products’ quality. Modern milling technologies can aid in the direction of quality and safety, and thus can be employed in the production of extra virgin olive oil (EVOO), which can be directly consumed without any further manipulation. The overall quality of EVOO should be determined by quality characteristics including sensory analysis, stability, and nutritional value and safety , along with authenticity.Food authenticity issues are very important for the food industry due to legislation aspects, economics, quality specifications and conformance, safety concerns, and religious matters. Authentic EVOO should comply with the producer’s declaration regarding the quality of olive fruits, natural components, the absence of extraneous substances, production technology, the geographical and botanical origin, the production year, and the genetic identity. Hence, olive oil authenticity can be implemented by the validation of the application of accurate specifications for olive fruits and the selection of trustworthy suppliers with a quality assurance system in place. Adulteration is usually carried out for economical purposes such as the increase of the bulk volume, the increase in the yield of a process, or the advancing of the quality of a product of inferior quality by mixing. Authenticity methodologies will avoid adulteration but will also aid the control of accidental contaminations, e.g., in factories, where several oils are produced or used at the same time, or cross-contaminations.In this Special Issue, both issues of olive fruits and EVOO have been investigated.Virgin olive oil production parameters, composition, and quality were determined after storage for seven days at room temperature (RT), refrigerated, and frozen storage prior to oil production derived from post-harvest olive fruits (Istarska bjelica (IB) and Rosinjola (RO)). It was found that lower temperatures delayed the post-harvest maturation of IB fruits. Storage at RT maintained the highest oil yield and extractability index. Storage at RT increased the content of waxes, while the lower temperatures partially suppressed this phenomenon. Refrigerated storage preserved the concentration of the most phenolic compounds. Refrigeration seems to be the most suitable option for prolonged fruit storage .p < 0.001) between the Italian and foreign EVOO VIS-NIR matrices. They also employed an artificial neural network (ANN) model with an external test.Another study helped to prevent EVOO from fraud and adulteration and evaluated olive oil geographical origin by an open source visible and near infra-red (VIS-NIR) spectrophotometer . They anThe next paper deals with the adulteration and authentication of extra virgin olive oil (EVOO) using vibrational spectroscopy signatures combined with pattern recognition analysis . Oils weThe next work (H2020 OLEUM project)  represenThe following two studies come from Greece. The first one deals with the comparison and discrimination of two major monocultivar extra virgin olive oils from the two dominant olive cultivars in the southern region of Peloponnese, cv. Koroneiki and cv. Mastoides . The fatThe second study evaluated the extent to which Messinian olive oils comply with the “Kalamata Protected Designation of Origin (PDO)” regulation . QualityOlea europaea L.) varieties were subjected to gas chromatography ion trap mass spectrometry (GC-IT-MS) and ultra-performance liquid chromatography with diode array detection (UPLC-DAD). Quantitative descriptive sensory analysis was also performed.The inter-varietal diversity of typical volatile and phenolic profiles of Croatian EVOO was investigated  to strenNakazawaeamolendini-olei, Nakazawaea wickerhamii, Yamadazyma terventina), and this was dependent on the strain inoculated. They also reported that the extraction plant might be colonized by some yeast species and this might affect the chemical and sensory characteristics of the EVOO.The last paper in this Special Issue deals with the quality of olive oil produced by different extractive processes carried out in a Tuscany oil mill at different harvesting periods in the same crop season, as affected by the presence of yeasts . Yeast cThe results of this Special Issue demonstrate the necessity for more stringent controls to increase quality and avoid fraud and adulteration of EVOO. In this direction, authentication methods are employed. It is quite important to safeguard quality and safety with various and promising tools that labs are equipped with, and sensory methodologies should be more critically combined with physico-chemical methods in order not only to comply with existing regulations, but also to provide consumers with a final product with added value. Companies should stop sacrificing value in the name of cost. Transparency procedures are essential in this direction.


Exosomes are lipid membrane bilayer-encapsulated vesicles secreted by cells into the extracellular space. They carry abundant inclusions  that play pivotal roles in intercellular communication. Tumor stem cells are capable of self-renewal and are crucial for survival, proliferation, drug resistance, metastasis, and recurrence of tumors. The miRNAs (microRNAs) in exosomes have various functions, such as participating in inflammatory response, cell migration, proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition. Tumor stem cells secrete exosomes that act as important messengers involved in various tumor processes and several studies provide increasing evidence supporting the importance of these exosomes in tumor recurrence and metastasis. This review primarily focuses on the production and secretion of exosomes from tumors and tumor stem cells and their effects on cancer progression. Cancer stem cancer derived exosome play an important massager in the tumor microenvironment. It also emphasizes on the study of tumor stem cell exosomes in the light of cancer metastasis and recurrence aiming to provide valuable insights and novel perspectives, which could be beneficial for developing effective diagnostic and treatment strategies. In vivo, exosomes exist in body fluids such as blood, urine, cerebrospinal fluid, pleural fluid, abdominal fluid, saliva, amniotic fluid, breast milk, and semen, and can also be isolated from cell supernatants derived from in vitro cell cultures. Exosomes were previously regarded as worthless waste, and recent studies have shown that they play a pivotal role in cell interaction (In vitro studies have shown that exosomes secreted by tumors can induce high cell proliferation (Exosomes are extracellular vesicles (EVs) with a double-layer membrane structure without replication ability that all cells can secrete and release externally . In vivoeraction , 3. Exoseraction –7. The ceraction , 9. Exoseraction –12. In peraction –15. In peraction , 16, 17.eraction –21. In vferation –24, invaferation , 26, acqferation , angiogeferation –31, and feration –34. In aferation –37. TumoExosomes were first discovered in 1983 in vesicles secreted by immature red blood cells of sheep , 39. LatExosomes are nanometer-sized  membranous EVs formed by endocytosis . They haExosomes originate from cells budding inward, forming an early membrane-endosome structure. Early endosomes mature into late endosomes and then accumulate in the lumen to form multivesicular bodies (MVBs), which can also be called multivesicular endosomes (MVEs), which contain many intraluminal vesicles (ILVs). After cells form MVEs, they may be degraded by fusion with auto-phagosomes or lysosomes, or they may be fused with the plasma membrane to release the substances in them. These ILVs are the final exosome formed . ExosomeThe composition of exosomes differs depending on the cell source, indicating that tumor-derived exosomes may have specific markers . Comparevia delivery of functional proteins, RNAs and lipids  some genes of adult stem cells are mutated, their genome stability is reduced, and their cancer-causing mutation induction and self-renewal ability are excessively enhanced, so that they evolve into CSCs –66; (2) in vivo limiting-dilution tumorigenicity assays in immunocompromised mice  have lost the characteristics of stem cells and can regain their stem phenotype through dedifferentiation or reprogramming. CSCs and non-CSCs are in a dynamic balance between differentiation and dedifferentiation. This information exchange between cells and the extracellular matrix maintains the stemness of CSCs and promotes tumor survival and development. The interaction between CSCs and their microenvironment is conducive to the maintenance of homeostasis. Exosomes, as information transmitters between cells in the microenvironment of CSCs, play an irreplaceable messenger role.in vivo have shown that EMT is associated with tumor metastasis in vivo , key signaling pathways , and cytokines in the TME. Extracellular signal by exosome mediated stimulation promotes the overexpression of EMT transcription factors, which trigger the EMT by suppressing epithelial phenotypes, enhancing mesenchymal properties, and inducing the degradation of the basement membrane and extracellular matrix . The pheExcept for partial activation, the EMT of tumor cells is usually reversibly activated, and cancer cells can be restored to the epithelial state through the MET during tumor progression. During cancer invasion, tumor cells undergo a dynamic transition between epithelial mesenchymalization and mesenchymal epithelialization . Tumor sThe differences between CSCs and non-CSCs can be attributed to the biological process of EMT . EMT actThe EMT process contributes to the progression of many cancer types , 137. CaThe biological behavior of cancer cell invasion and metastasis is the same as that of other biological phenotypes, which are triggered by gene function. The propensity for metastasis is related to the expression patterns of specific genes in human breast cancer. Most cells in the primary tumor show this characteristic gene expression profile . In otheIn recent years there has been an increasing number of studies on the biological function of exosomes. Exosomes originate from various types of cellular secretion and are present in almost all body fluids. As a vehicle for intercellular communication, they can play an essential role in the physiological and pathological course of disease. As exosomes can be encapsulated in various contents, including lipids, proteins and RNA, they can signal and drive metastasis to specific recipient cells or tissues and organs. These exosomes, which are released into the tumor microenvironment, are received by the recipient cells, thereby inducing intracellular signaling and altered recipient cell physiology. Exosomes can occur organ-specific and direct organogenic metastasis of different metastatic tumors before tumor cells, especially tumor stem cells, reach the target organ. Exosomes are particularly important for supporting the formation of distal organogenic pre-metastatic niches. Cancer is the most common type of human tumor. The malignant epithelial cells in the tumor need to undergo EMT to acquire the ability to invade and metastasize. By blocking the expression of key regulatory factors, EMT plays an important role in the genesis of tumor EMT, MET, CSCs, and tumor metastasis to promote tumor proliferation, invasion, adhesion, angiogenesis, and acquired drug resistance, thereby affecting the process of tumor development. Metastatic dormancy is a challenge in tumor research; for instance, in breast cancer, metastases are found decades after the removal of the primary tumor, due to the long incubation period and multiple micro-metastases occurring.Exosomes secreted by tumor stem cells are regulated through the tumor stem cell-tumor microenvironment-target tissue interface, potentially serving as metastasis markers and promising as entry points for blocking tumor metastasis.The study of tumor stem cell exosomes facilitates the in-depth understanding of the mechanism of metastasis, which will hopefully lead to new treatment avenues. CSC exosomes, which are important in the promotion of CSCs and tumor foci, the effect of primary tumors and EMT, and the recurrence of metastases and cancer, have important research value for exploring cancer progression and tumor treatment. The personalized and pinpoint treatment of anti-tumors further raises the requirement to diagnose the mechanisms of tumor metastasis and recurrence. The close relationship between exosomes and metastasis is predicted to be a diagnostic marker for tumor recurrence; targeting the signal transduction of exosomes for interventional blockade will likely be useful for clinical application of therapeutic new therapies; the targeting ability of exosomes can also be utilized to target the contents of exosomes as drug carriers for research, which is expected to target drug delivery for effective treatment of recurrent tumors. The in-depth study of the effect of tumor stem cell exosomes on the regulation of tumor metastasis and recurrence in the process of cancer has far-reaching significance for the precise diagnosis of anti-tumor phased treatment, prognosis judgment, and other fields.KL conceptualized and wrote the article. XG, BK, DW, and YW revised the article. YW revised and finalized the article. All authors contributed to the article and approved the submitted version.Project supported by Jilin Province Science and Technology Support Program [Grant number 20200404121YY]; Education Department of Jilin Province [Grant number JJKH20201122KJ]; Guangzhou Science and Technology Planning Project, China (201904010443).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This report describes a novel surgical technique for trans-articular external skeletal fixation (TA-ESF) of the hip to stabilize a rare, highly comminuted juxta-articular fracture of the proximal femoral segment involving the metaphysis and diaphysis in a cat. A 2-year-old, castrated male, Korean shorthair cat was admitted for a left femoral fracture caused by gunshot injury. Radiographs and computed tomography (CT) scans revealed a highly comminuted proximal femoral diaphyseal fracture that involved the femoral neck and the greater trochanter. The left femoral head was intact on CT. Under fluoroscopic guidance, an intramedullary Steinmann pin was placed to align the femur, and five positive-profile, end-threaded pins were placed in the left hemipelvis and distal femur. A triangulated frame of connecting bars was constructed using Steinmann pins and epoxy resin for TA-ESF. This secured the pins placed in the pelvis and femur as well as the intramedullary pin, providing proximal femoral stabilization by trans-articular fixation of the hip. The cat began placing weight on the left pelvic limb 4 days postoperatively, and progressively obtained near-normal limb function by day 112. The TA-ESF was partially dismantled to a linear tie-in construct on day 64 and was completely removed on day 161. Final radiographs on day 161 revealed lack of bone healing in the proximal segment, especially femoral head and neck, despite functional recovery of the injured leg. At one year postoperatively, the cat had normal limb function without any noticeable complications. On follow-up 29 months after surgery, the owner reported that the cat had normal limb function without any noticeable complications. Despite insufficient bone healing in the cat, TA-ESF of the hip allowed for satisfactory functional recovery of this challenging juxta-articular fracture of the proximal femur, which was not amenable to stabilization with a traditional non-load-sharing fixation system. Surgical stabilization of highly comminuted fractures of the proximal or distal juxta-articular bones has rarely been reported in veterinary literature. These comminuted juxta-articular fractures are difficult to stabilize since the presence of a short proximal or distal segment limits the types of fixation that can be used . A circuThis report describes a novel surgical technique for the successful management and functional recovery of a highly comminuted juxta-articular fracture of the proximal femur caused by a gunshot injury using trans-articular ESF (TA-ESF) of the hip in a cat. These results were obtained despite a lack of bone healing.A 2-year-old castrated, male, Korean shorthair cat weighing 4.4 kg was admitted with a highly comminuted proximal femoral fracture caused by a gunshot injury sustained 3 days earlier. On presentation, the cat could not bear weight on the left pelvic limb. Additionally, there was a small skin puncture wound, suspected to be the bullet trajectory, over the left hemipelvis. The cat showed signs of pain during palpation of the left pelvis and pelvic limb, but did not show any neurological deficits. Abnormalities on a complete blood count and biochemistry panel included a decreased packed cell volume of 24.7%  and an elevated creatine kinase level of 675 U/L .A proximal segmental fracture of the left femur and multiple radiopaque objects of various sizes were identified on both plain radiographs and computed tomography scans . A commiThe comminuted proximal femoral fracture was stabilized with a closed approach. Written informed consent for the surgical procedure and complications was obtained from the owner. The major bullet fragments embedded in the abdominal wall were removed. However, the other small intraabdominal bullet fragments were not removed due to the costs involved and since they did not pose any immediate clinical problems.Under general anesthesia, the cat was placed in the right lateral recumbent position, and the left pelvic limb was prepared using a routine hanging limb preparation. Under fluoroscopic guidance, the femoral condyles were secured with a pair of AO forceps and indirect reduction was achieved by applying traction to the distal femur. A small skin incision was made medial to the greater trochanter, and a 2.4-mm Steinmann pin was inserted into the medullary canal of the femur in a normograde fashion . The intTo construct the TA-ESF of the hip, two 2.5 mm and one 1.8 mm positive-profile end-threaded pins were placed in the ilium and ischium, respectively. Then, one 2.0 mm and one 1.8 mm positive-profile end-threaded pins were also placed perpendicular to the distal femur . The thrDuring this process, the limb was temporarily supported by an assistant to maintain appropriate rotation and angulation of the femur based on palpation of the condyles and the comminuted greater trochanter. This also allowed for fluoroscopic identification of the femoral head, femoral diaphysis, and linea aspera. Additionally, the coxofemoral joint was flexed and maintained at a normal weight-bearing angle while the epoxy resin polymerized. After polymerization, the left coxofemoral joint was fixed at ~90°. The fixator was lightly bandaged, and the cat was then re-positioned in left lateral recumbency to remove the bullet from the right abdominal wall.The cat recovered from anesthesia and surgery without complications and was administered a constant-rate infusion of fentanyl for 24 h , followed by meloxicam for 4 days (0.1 mg/kg PO for 24 h) for analgesia. Postoperative radiographs were taken to verify appropriate placement of the pins and alignment of the femur . CraniocThe day after surgery, the cat would not place weight on the left pelvic limb, which was very painful, and could not tolerate palpation of the left femur . On postThe cat was re-evaluated on postoperative days 18, 32, 46, 64, 80, 112, and 161. During these evaluations, the fixator was monitored for complications. Pain and limb function were subjectively assessed using an ordinal scoring system . Serial The cat's condition progressively improved over the next couple of weeks, and it did not appear to be in pain when examined on postoperative day 80. The examination on day 112 showed nearly normal gait . The ranTelephone follow-up was conducted for 29 months postoperatively. The owner reported that the cat represented normal gait without any noticeable pain and lameness .ESF, as chosen in this cat, is the preferred mode of trans-articular fixation in small animals for supporting tendon , 5 and lThe TA-ESF frame in the present study was creatively developed based on the anatomical features of the pelvis–distal femoral interconnection and physical distribution of the load. For stabilizing the comminuted proximal juxta-articular femur, the pelvis was utilized as the proximal segment instead of the comminuted proximal segment of the femur. The fixation pins in the pelvis were placed in the sacropelvic area of the ilium and the ischiatic tuberosity based on a previous study , consideA previous case report revealed a similar TA-ESF frame of the hip in a cat . HoweverFemoral malalignment and deformities were the major concerns for this patient. To align the fractured femur and avoid postoperative deformities, the anatomical landmarks, including the greater trochanter, femoral condyle, and linea aspera, were consistently assessed by palpation and fluoroscopic guidance. The greater trochanter, though highly comminuted, could be easily palpated since its fragments were not scattered and remained closely enough to maintain a near-normal shape. Thus, it could be used as a landmark to evaluate the rotational alignment of the femur with the condyles and the linea aspera. Using these landmarks, intramedullary pinning was performed to restore the length and axial alignment of the femur, thus, helping the cat gain functional recovery of the injured gait. However, due to the limitations of the closed approach in this kind of comminuted fracture for bridging and biological osteosynthesis, each bone fragment could not be opposed accurately, and this might lead to delayed bone healing and the residual rotational malalignment of femoral head. Additionally, since the femoral neck had a highly comminuted fracture, the anteversion and inclination angle of the femoral neck could not be accurately assessed perioperatively. Therefore, the appropriate angles were estimated intraoperatively under fluoroscopic guidance by comparing the locations of the center of the femoral head, greater trochanter, and ideal axis of the shaft to avoid increasing these angles markedly. If an abnormal anteversion and inclination angle occurred despite these preventive efforts, a salvage procedure was planned, involving femoral head and neck osteotomy.Another major concern was postoperative degenerative changes of the femoral head, possibly due to immobilization of the hip joint and ischemic osteonecrosis secondary to reduced blood supply. Joint immobilization is the most significant cause of degenerative joint disease associated with trans-articular ESF , 15, 20,Damaged blood supply to the proximal femur was considered to be the main cause of degenerative changes in the femoral head of this cat. Arterial branches that supply blood to the femoral head propagate from extra osseous vessels, such as the lateral and medial circumflex femoral arteries and the caudal and cranial gluteal and iliolumbar arteries, which are supplied from the surrounding soft tissue to the femoral head through the femoral neck and trochanteric fossa , 23. ComAt the last follow-up, lack of bone healing was identified in the proximal diaphyseal segments of the radiograph, despite functional recovery of the injured leg. This is thought to be due to the characteristics of a comminuted fracture and impaired blood supply caused by high energy-induced trauma, such as gunshot injury. Further, the sustained instability of the proximal segment caused by the inability to place implants in the comminuted proximal segment was also considered to have contributed to delayed bone healing. To increase the stability of the proximal segment, the preferred surgeries for biologic osteosynthesis of comminuted fractures, such as minimally invasive plate osteosynthesis or an interlocking nail, were considered. However, these conventional methods were unsuitable for this cat since the proximal segment was comminuted and not durable enough to place the implants. And, the femoral head and neck osteotomy with repair of diaphyseal fracture were also considered as a salvage procedure, however, since the femoral head was intact, it was decided to withhold and considered as a later option. Due to the limitations of conventional surgery, a TA-ESF of the hip was used for bridging osteosynthesis and a triangular configuration was developed to reduce the load and increase the stability of the TA-ESF. Nevertheless, since a secure connection between TA-ESF and the proximal segment was not possible due to the comminuted and longitudinally fractured proximal diaphyseal fragment, it might have led to constant instability of the proximal segment inducing deficient bone healing.Performed surgery and contributed to the conception and design There are some limitations to the present case report. Although, this cat had several problems requiring long-term follow-up, this was not possible. In the radiograph at the last follow-up visit, lack of fracture healing, degenerative change of the affected femoral head and thinning and sclerotic changes of the femoral neck were identified. These abnormalities should have been consistently monitored because they might progress to malunion of the fractured femur, especially non-union of the femoral neck and degenerative joint disease of the hip joint. Moreover, the intramedullary pin, which was left due to insufficient remodeling of the femoral diaphysis, was to be removed as soon as complete union was confirmed. For this reason, constant long-term follow-up was strongly recommended to the owner. However, the owner did not presented after ESF removal, since the cat could walk normally, without any signs and the owner had financial and long-distance restrictions. Additionally, partial failure of this TA-ESF of the hip due to several weak points, including fracture of some fixation pins and instability of the proximal segment, were seen in this case. Although, these problems did not affect functional recovery in this cat, further, investigation on the number and location of taxation pins and frame of connecting bars with more cases is necessary to improve the stability and configuration of this TA-EFS of the hip.In summary, despite the lack of fracture healing, TA-ESF provided a satisfactory clinical outcome, including successful biological osteosynthesis and functional recovery of a comminuted fracture of the proximal femur caused by gunshot injury in this cat. The ESF configuration was determined based on the principle of physical force distribution, and the tied-in configuration enhanced its stability. Further, the use of epoxy made it possible to construct this complicated configuration easily without the limitations of angles, planes, or the position of fixation pins. This configuration is a feasible surgical option for such highly comminuted juxta-articular fractures of the proximal femur, in which the implant cannot be secured to the proximal segment.The original contributions presented in the study are included in the article/Ethical review and approval were not required for the animal study because this is a case report which has been written using clinical data. Written informed consent was obtained from the owners for the participation of their animal in this study.H-JH performed surgery and contributed to the conception and design of the work, analyses of the data, and writing the manuscript. KL contributed to providing the concept of the most stable frame for TA-ESF based on physics theory and preparing the relevant part of manuscript, while H-YY supervised aftercare, and critically revised the manuscript. All authors contributed substantially to the study design, preparation, and final approval of 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.


The aim of this study was to compare fear of childbirth, state and trait anxiety, and childbirth self-efficacy among primiparous and multiparous women in Ahvaz, southwest of Iran.This cross-sectional study was conducted with 200 pregnant women (100 primiparous and 100 multiparous women) who had been admitted to the maternity ward of hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. The instruments used for data collection in this study included a demographic questionnaire, Delivery Fear Scale (DFS), Spielberger's State-Trait Anxiety Inventory (STAI), and Childbirth Self-Efficacy Inventory (CBSEI). The data were analyzed by chi-square test and independent t-test. Also, the univariate general linear model was used by adjusting for the socio-demographic and obstetric characteristics that were considered as possible confounding variables.The mean score of DFS in primiparous women was significantly higher than that of multiparous women. The mean of the overall score of childbirth self-efficacy of primiparous women was significantly lower than that of multiparous women. The mean score of the outcome expectancies and self-efficacy expectancies was significantly lower in primiparous women compared with multiparous women. There was no statistically significant difference between the two groups in terms of the mean score of STAI. After adjusting for possible confounding variables, the differences between the two groups in terms of fear of childbirth scores, overall childbirth self-efficacy score and self-efficacy expectancies remained significant.Given the high fear of childbirth and low childbirth self-efficacy in primiparous women compared to the multiparous women, appropriate interventions should be adopted by health care providers in order to reduce fear and improve childbirth self-efficacy in primiparous women. Giving birth to a baby is a process accompanied with both joy and pain. In recent decades, labor pains and fears of childbirth have attracted the attention of many researchers who have described childbirth as a very painful phenomenon .According to previous studies, fear of childbirth (FOC) affects about 7.6–8.8% of pregnancies , 3 and iUntil 1990, FOC was studied based on tools used for measuring anxiety such as Manifest Anxiety Scale (MAS) that has three subscales including worry–oversensitivity, fear–concentration, and physiological anxiety. However, psychological domains were later identified for FOC which made anxiety identification instruments less suitable for accurate measurement of this specific fear . Fear ofIn order to reduce the FOC in women, it is necessary to identify the factors contributing to it. Childbirth self-efficacy may be one of the factors that can play an important role against fear of childbirth. High self-efficacy can reduce this fear and therefore indirectly reduce labor length and the likelihood of the need for epidural analgesia, thus causing better parental outcome . In factAlthough medical advances in the present century have improved the health of women during pregnancy and childbirth, these advances may have led to the medicalization of almost all deliveries. Thus, the concept of childbirth as a normal psychological phenomenon of life that only occasionally requires intervention has lost its currency . AccordiPrimiparous and multiparous women have been suggested to be different in terms of their childbirth expectations . There mi) The level of fear of childbirth variesbetween primiparous and multiparous women.ii) The level of childbirth anxiety variesbetween primiparous and multiparous women.iii) The level of childbirth self-efficacyvaries between primiparous and multiparous women.Two hundred pregnant women including 100 primiparous and 100 multiparous women participated in this cross-sectional study. Inclusion criteria were: having a plan for normal delivery according to self-report, being at a gestational age of 36 weeks and more based on the history of obstetrics  and expecting the birth of a healthy and live baby based on obstetrical history and physical examination.Exclusion criteria were: parity more than 4, experiencing any pregnancy complications requiring medical intervention, receiving anesthesia, having pregnancy risk factors  and having an abnormal fetus according to self-report and medical documents.Convenience sampling was used to select the participants from women referring to one of the university hospitals affiliated to Ahvaz Jundishapur University of Medical Sciences , who were admitted for normal delivery and hospitalized in the maternity ward with the diagnosis of labor pains. Pregnant women with spontaneous onset of labor pain during an early stage of active labor  were recruited. After being examined in terms of eligibility criteria, the participants were briefed on the study objectives and methods. In case they were willing to participate in the study and they met the eligibility criteria, written informed consent was obtained from them, and the study questionnaires were completed through interviews with them conducted by the first author. The participants were divided into two groups according to whether or not they had a history of childbirth (primiparous or multiparous). Sampling was continued until the number of samples in both groups was completed.The instruments used to collect the data in this study included a socio-demographic and obstetrics characteristics questionnaire, delivery fear scale (DFS), Spielberger's state and trait anxiety inventory (STAI), and the short form of childbirth self-efficacy inventory (CBSEI).This questionnaire was completed using obstetrical medical records and interviews. The questionnaire included questions about a woman's age, her BMI in the first trimester of pregnancy, the woman's and her husband's occupation, her education, economic status, history of infertility, history of abortion, difficult delivery in this pregnancy (dystocia), attendance to childbirth preparation classes, attendance of doula at birth, and having wanted or unwanted pregnancy.The DFS was designed by Wijma et al. (2002) to assess fear of childbirth during labor . DFS is The STAI was developed in 1970 . This quThe childbirth self-efficacy inventory was developed by Lowe (1993) . This 62Based on the results of the study of Alehagen et al.,  and consP < 0.2). Parity was entered as independent variable. Age, BMI, economic status, education, intention of pregnancy, and history of abortion were entered as confounder variables, whereas fear of childbirth, total childbirth self-efficacy and its domains (outcome expectancies and self-efficacy expectancies), state anxiety and trait anxiety were entered as dependent variables. Significance level was set at α = 0.05.Data collected by questionnaires were entered into IBM SPSS Statistics ver. 24 . The normal distribution of numeric data was assessed and confirmed based on skewness (within ± 1.5) and kurtosis (within ± 2.0). To describe of the socio-demographic and obstetrics characteristics, frequency (percentage) was used for qualitative variables and mean (standard deviation) for quantitative variables. To compare numeric normal and categorical variables between the two groups of primiparous and multiparous women, chi-square and independent t tests were used, respectively. Mean (standard deviation) was used to describe the scores of the Delivery Fear Scale (DFS), State and trait anxiety (STAI), Childbirth Self-Efficacy Inventory (CBSEI) and their subscales. To compare these numeric normal variables between the two groups, independent t-test was used, and the univariate general linear model was used by adjusting for the socio-demographic and obstetrics characteristics that were considered as possible confounding variables (The maternal characteristics stratified by parity are shown in Table The comparison of the scores of primiparous and multiparous women obtained from delivery fear scale, total childbirth self-efficacy and its subscales, and state and trait anxiety inventory is displayed in Table The comparison of the above scales is displayed in Table The hypotheses of the present study were that the levels of fear, anxiety and self-efficacy of childbirth vary between primiparous and multiparous women. According to the results of the present study, the mean score of fear of childbirth in primiparous women was significantly higher than that in multiparous women. In terms of mean total self-efficacy, outcome expectancies, and self-efficacy expectancies, primiparous women had significantly lower scores compared with multiparous women. There was no significant difference between the two groups in terms of the mean score of state and trait anxiety. After adjustment for age, BMI, economic status, mother's education level, intention of pregnancy, and history of abortion, there was a statistically significant difference between the two groups in terms of the mean score of fear of childbirth, total self-efficacy score, and self-efficacy expectancies score.In the present study, the mean score of fear of childbirth was higher in primiparous women compared with multiparous women. Consistent with the results of the present study, in some previous studies, fear of childbirth has been found to be more severe in primiparous women than in multiparous women , 5. Of cIn the present study, the mean score of childbirth self-efficacy in primiparous women was significantly lower than that of multiparous women. There are a number of studies that are in line with the results of our study in terms of childbirth self-efficacy scores after adjusting for possible confounding variables. Lowe et al., for example, found no significant difference between the two groups in terms of outcome expectancies score. However, in terms of self-efficacy expectancies and total self-efficacy, multiparous women scored significantly higher than primiparous women . MoreoveAccording to the theory of self-efficacy, an individual may believe that certain behaviors can facilitate their adaptation to an unfavorable situation, but they may doubt their ability to perform those behaviors . Since bIn the present study, there was no difference between primiparous and multiparous women in terms of state and trait anxiety, which is consistent with the results of numerous other studies –19. HoweGiven that the fear of childbirth can affect the choice of delivery method, measuring the level of fear and anxiety and determining the level of self-confidence and self-efficacy of women in pregnancy can help members of the health care team to identify those women who request cesarean section out of fear or anxiety . During The findings of this study can provide important insights into women's experiences of childbirth and the emotional aspects of childbirth. Therefore, knowing these experiences can be used to evaluate and improve reproductive health policies and services. For example, this could be achieved by the implementation of some appropriate interventions for each woman such as execution of birth plan according to women's preferences, which seems to have been neglected in most settings.Despite using standard and valid tools in this study, which is one of its strengths, there are a number of limitations to take into account. First of all, the cross-sectional design of the study and the convenience sampling method may have affected the results obtained. Failure to study the factors affecting the fear and anxiety of pregnant women such as socio-economic status, psychological status, marital satisfaction, social support, etc. can be regarded as another limitation. Also, using non-specific tool to measure anxiety was another limitation. Therefore, longitudinal studies investigating participants from the very beginning of pregnancy in terms of the factors affecting the mode of delivery are recommended.Given the high fear of childbirth and low childbirth self-efficacy in primiparous women compared to the multiparous women, appropriate interventions such as implementation of birth plan according to women's preferences should be taken into account by health care providers in order to decrease this fear and improve childbirth self-efficacy in these women.


The first step for a harmonious bio-psycho-social framework in approaching autism spectrum disorders (ASD) is overcoming the conflict between the biological and the psychosocial perspective. Biological research can provide clues for a correct approach to clinical practice, assuming that it would lead to the conceptualization of a pathogenetic paradigm able to account for epidemiologic and clinical findings. The upward trajectory in ASD prevalence and the systemic involvement of other organs besides the brain suggest that the epigenetic paradigm is the most plausible one. The embryo-fetal period is the crucial window of opportunity for keeping neurodevelopment on the right tracks, suggesting that women’s health in pregnancy should be a priority. Maladaptive molecular pathways beginning in utero, in particular, a vicious circle between the immune response, oxidative stress/mitochondrial dysfunction, and dysbiosis-impact neurodevelopment and brain functioning across the lifespan and are the basis for progressive multisystemic disorders that account for the substantial health loss and the increased mortality in ASD. Therefore, the biological complexity of ASD and its implications for health requires the enhancement of clinical skills on these topics, to achieve an effective multi-disciplinary healthcare model. Well-balanced training courses could be a promising starting point to make a change. Autism is an early onset, and in most cases lifelong, neurodevelopmental condition, currently diagnosed on the basis of the clinical assessment of behavioral features . The widThe consistent upward trajectory in autism prevalence since the 1990s  is causeThe frequent medical comorbidities  go hand-With this review we wish to draw the attention of clinicians to the multidimensional, personalized, and integrated health care model required to meet the complex health needs of this broad, and increasing, psycho-neurobiological condition and to the need to pay particular attention to the period that precedes the clinical diagnosis, including the embryo-fetal window, since the crucial events for neurodevelopment occur before the clinic onset of ASD. To that end, we are going to pinpoint a number of key issues, integrating our previous review  with infWe will first address the recent increase in prevalence of ASD that should be understood within the broader model of an ongoing epidemiological transition, affecting also non-communicable diseases other than neurodevelopmental disorders. The awareness of the underlying reasons for the recent increase in prevalence of ASD may help to design and analyze cost-effective models in healthcare and to suggest effective strategies to make a change.Then, we will summarize the main biological evidence underlying the complexity of the pathogenetic model of ASD, detailing the broad array of metabolic, immunologic, and microbiological imbalances affecting ASD people, from pregnancy throughout their entire lifespan. We will point out how biological characteristics should be harmonically integrated in the bio-psycho-social framework ,16, overFirst 1000 Days [Finally, we will point out the urgency to provide early and integrated support to children at high-risk of neurodevelopmental disorders, so as not to lose the opportunity of exploiting early-life neuroplasticity, in particular, in the time window that precedes the diagnosis (000 Days ). The laIn the following paragraphs, some biological issues, not limited to ASD research, are discussed, with the purpose of highlighting the connections between some topics rather than describing them in detail. These will constitute the premises for understanding the shortcomings of current clinical practice and propose coherent strategies to ameliorate both research and clinical intervention.The great clinical heterogeneity of ASD persons may imply a great heterogeneity in the pathogenesis of ASD. Besides a ~10% incidence of monogenic syndromic mutations , more thBy examining the functions of proteins encoded by ASD susceptibility genes, three main functional categories emerge ,21. TheySeveral ASD syndromic mutations involve pathways that anchor synaptic machinery, regulate synaptic vesicle release, control subcellular signaling pathways, and orchestrate neuronal migration and connections . The finThe incomplete concordance between homozygous twins mentioned above , especiaEpigenetic mechanisms are also the most plausible explanation for the increase in prevalence of ASD in the past decades ,14 sinceDOHaD Theory) which suggests an epigenetic/embryo-fetal origin of diseases [First 1000 Days, from conception to age 2 [The supposed reasons for the steep increase in prevalence of neurodevelopmental disorders as a whole are the same for the increased prevalence of numerous inflammatory, metabolic, degenerative, and neoplastic diseases , as put diseases ,38. Accodiseases ,37. Duridiseases . Heindeldiseases  and recediseases  have supdiseases , has beediseases . The Firto age 2 , are conto age 2  during tto age 2 . Placentto age 2 ,47. Wortto age 2 . Abruzzoto age 2 . Embertito age 2 .The three most common approaches to DNA methylation pattern profiling are global, epigenome-wide (EWAS), and candidate-gene DNA methylation analyses . Dall’AgMaternal immune response is one of the effector arms of epigenetic dysregulation . NotablyThe immune system deeply affects brain development, both in physiological and in abnormal trajectories ,56,57. AA broad variety of maternal immune mechanisms are involved in MIA, both in specific and in natural immunity. As for the former, maternal autoantibodies targeted against the Folate Receptor α (FRα) provide one of the clearest examples to understand the relevance of biological issues in research and clinical practice in ASD. Folate is one of the vitamins of the B-complex. It plays a pivotal role in neurodevelopment during the ontogenesis and in the first years of life . The conA pivotal role in MIA is played by IL-6, a major pro-inflammatory cytokine . As a coGarbett KA et al. (2012) explored the mechanisms by which maternal infection increases the risk for schizophrenia and autism in the offspring by administering three MIA-inducing treatments  and interleukin IL-6) to mouse dams and examining the immediate effects on the fetal brain transcriptome . All thrAmong infectious agents, major concerns relate to the current SARS-CoV-2 pandemic. In fact, while the transplacental transmission of this virus is unlikely to occur , maternaDiscussion of the immune response in pregnancy includes the maternal microbiota, a complex system that is constantly evolving during pregnancy and adapting to the energetic fetal needs ,93. The The topics and links which have been described in this paragraph show a cross-section of the many possible paths that neurodevelopment can take and how this complex process cannot be considered an automatic execution of instructions written in DNA.Numerous risk and protective factors have been linked to the onset of ASD in the offspring, highlighting the need of paying particular attention to maternal diet, nutraceutical supplementation, prevention and treatment of metabolic abnormalities, protection from toxicant exposure, and numerous other factors linked with an increased risk for ASD . HoweverThe link between immune response and neurodevelopment begins in the womb and continues throughout life. Interest for neuroinflammation in ASD began with the demonstration of cerebral inflammation in autoptic brains of autistic people . NumerouThe immunologic imbalance in ASD concerns both innate immunity and the specific response of T lymphocytes, with a shift toward a Th1-type pattern and prevalence of pro-inflammatory cytokines, increase of B-lymphocytes, NK cells, and dendritic cells; and different expression of surface markers . AbruzzoAs a whole, findings about immune abnormalities in ASD support evidence of an early and ongoing dysfunction in the peripheral immune system and the brain . FurtherResearch on neuroinflammation in ASD benefits from the growing body of knowledge concerning the microbiota-gut-brain (MGB) axis, that is the complex multidirectional interactions between central nervous system, gut, gut microbiome, mucosal immune system, enteric nervous system (ENS), autonomic nervous system  .A pivotal role in the MGB axis is played by central processes receiving input from the vagus nerve with vagal afferent information relayed to the hypothalamus via the nucleus tractus solitarius and area postrema in the caudal brainstem .First 1000 Days  should be considered crucial risk/health factors for neurodevelopment [Accumulating evidence reveals the multifaceted features of the disturbances of the MGB-axis in the pathophysiology of brain disorders and its potential mechanisms . Accordielopment ,109,110.The ANS has a pivotal role in the regulation of body’s physiology, beginning before birth, and contributing to fetal development by allowing the organism to efficiently cope with endogenous and exogenous stressors . In partIn the past decade, several studies focused on ANS activity in ASD , and itWithin the gut-brain axis, the microbiota behaves like the conductor of the immune-neuroendocrine communication orchestra ,122,123.Numerous studies demonstrate a correlation between the state of unbalanced microbial communities—named “dysbiosis”—and a wide range of diseases ,132, incConverging evidence suggests that the gut-brain axis and the numerous mechanisms involved in its function play important roles in the pathogenesis and symptoms in ASD. Deciphering the relationships in this complex system and translating them into clinical practice is a great and difficult challenge that we must face. There is no doubt that this is a crucial issue for the health of autistic people. In fact, the microbiota imbalance affects several pathophysiological processes.Vitamin deficiencies are among the most frequent metabolic abnormalities related to gut microbial imbalance and are frequent in ASD. B-vitamin deficiencies are of utmost interest for their key role in numerous physiological processes involved in brain energetic metabolism and cell respiration, such as the metabolism of glucose, fatty acids, and amino acids, homocysteine metabolism, metabolism of tryptophan in the kynurenine pathway, synthesis and metabolism of various neurotransmitters and neurohormones . B-vitamIn the postmortem frontal cortex, Zhang et al. (2016) demonstrated concentrations of vitamin B12 more than three-fold lower in both autistic and schizophrenic subjects than in age-matched controls . SimultaAbnormalities in tryptophan pathways are also a relevant metabolic issue, which is reported in ASD and might be linked with dysbiosis. Tryptophan is an essential aromatic amino acid and is one of the pivotal metabolites in microbiota–host crosstalk in health and disease. Levels of this amino acid depend on diet intake and on the composition of gut microbiota. Microbial balance controls the three major tryptophan metabolism pathways leading to serotonin, kynurenine, and indole derivatives . NumerouIncreased levels of homocysteine in ASD have been reported by several studies ,158,159.Research in this field should be encouraged in order to ascertain the risk of neurodegeneration and engage appropriate prevention strategies toward adulthood. Furthermore, evidence suggests that future therapies might involve modifying neuroglial responses in the brain .Among the products of the gut microbiota and in relation to neuroinflammation, SCFA are worth mentioning, as these participate in manifold processes of utmost interest for neurodevelopment, from the increase of gut permeability to epigenetic modifications in the brain . In partMitochondrial abnormalities and oxidative stress in ASD are treated last because it allows us to link mitochondrial dysfunctions to numerous abnormalities that we have considered in the course of the article.Mitochondria are cell organelles with matrilinear transmission and their own DNA. They are essential for a wide range of functions, such as the production of adenosine triphosphate (ATP) by oxidative phosphorylation, redox metabolism, lipid homeostasis, steroid synthesis, calcium buffering, regulation of apoptosis and metabolic pathways of the urea cycle, porphyrin and amino acid production ,171. MitMitochondria are key targets of many environmental contaminants and toxicants ,177. ThiBoth increased oxidative stress and imbalance in cell membrane fatty acids composition, a result of free radical attack to polyunsaturated fatty acids, resulting in dysfunctional cell membranes, have been shown in ASD children , where sFollowing the hypothesis that oxidative stress represents a hallmark of metabolic abnormalities in several brain disorders and given that it influences a wide array of molecular pathways, the possible impact of this imbalance was studied in relation to the impairment of chloride homeostasis occurring in the GABAergic system in CNS . This stThe broad array of fuzzy interactions described above shows that biological complexity underlying behavioral characteristics of ASD is very different from a traditional linear model of “a symptom, a biomarker”. Metabolomics gives the chance to get away from the “juniper bush” of ASD . It alloIn conclusion, a wide array of interconnected metabolic, immunologic, microbiologic abnormalities is found in ASD people. From the earliest stage of life and across life span, the interconnections between these three systems are always active and are crucial to restore the homeostatic balance for health. In the case adverse events persist for a long time or when they exceed the possibility to restore the balance, a vicious circle is established between inflammation, mitochondrial dysfunction/oxidative stress, and dysbiosis. These three mechanisms, as a whole, form a “Bad Trio”, with progressive imbalances and dysfunctions not limited to the nervous system and a major impact on fetal development . SubsequAutistic people show several comorbidities besides neuropsychiatric conditions. A high prevalence of obesity and obesity-related disorders  have been reported in children , which mEpilepsy is another frequent comorbidity in ASD ,215,216.Hopefully, a better understanding of the gut-brain axis and of systemic neuroinflammation will provide insights into the onset and progression of frequent neuropsychiatric disorders in ASD  and intoThe paradigm shift from genetics to epigenetics highlights the priority of primary prevention during pregnancy . Fetal nNumerous studies have assessed the characteristics and the frequency of potential environmental factors in pregnancy which increase the risk of ASD in the offspring ,63,83. TMany risks and protective factors have been linked to the onset of ASD in the offspring, providing suggestions for clinical practice. Numerous studies focusing on the risk of ASD in the offspring demonstrate the relevance of carefully designed maternal diet, including nutraceutical supplementation ,225, theMaternal fetal stress is another important risk factor, with numerous and complex effects on neurodevelopment , but verThe second issue proposed in this study concerns the application of the systemic perspective in clinical practice. A large population-based study by Hirvikoski et al. (2016)  confirmeAdopting a systemic perspective in place of the behavioral-centered approach, health needs of autistic people appear much more complex and require a wide array of professional expertise for assessment and treatment, in the medical as well as in the educational field. Medical semeiotics is different in individuals with ASD compared to general population. Differences in somatosensory integration may influence pain threshold and therefore change perceptions and awareness of somatic disturbs. Moreover, impaired communication skills often make it difficult to inform caregivers and doctors about pain and organic ailment . As a coIf the observation of behavioral abnormalities in ASD lacks the biological dimension, there would be high risk of ascribing by default any disruptive and challenging behavior to autism, with consequent risk of incorrect use of psychotropic drugs. The high rate of psychotropic polypharmacy in ASD should be a matter of reflection . Since cp < 0.001), with relative risk 4.40 [The multidimensional perspective is critical in early observation by pediatricians. The frequency of persistent crying  was sigisk 4.40 . The autisk 4.40 . Furtherisk 4.40 . Thus, eisk 4.40 , the actisk 4.40 ,245, andisk 4.40 ,247 makeisk 4.40 . ResearcThe issue of early interventions is in many ways interlaced with the heterogeneous developmental pathways of ASD children. In this regard, promising insights are expected from metabolomics. The study of the “bloomers” trajectory  and insIn the gut-brain axis framework, diet is crucial. Frequent eating disorders  and the A very rich literature supports the notion that oxidative stress occurs in ASD as well as in several, if not all, brain diseases and disorders . SourcesThis review examines the contribution that biologic research could provide to the updating of the healthcare system, in order to meet needs of autistic people of today and tomorrow, from the womb to adulthood.First 1000 Days.A recent systematic review and meta-analysis examined age at ASD diagnosis: the subgroup analysis for studies that only included children younger than 10 years found a mean age at diagnosis of 43 months with a range of 31–75 months , which mHere, we have presented the reasons why the highest level of well-being throughout life in ASD may be warranted by an integrated model that includes expert and comprehensive medical interventions besides psycho-educational-social support.The undeniable biological dimension in ASD is evidenced by a broad array of biochemical, immunological, and microbiological imbalances, and data about mortality and morbidity ,237,238.Knowledge and awareness of the biological bases of ASD increase day by day. A striking number of publications have demonstrated abnormalities in peripheral biomarkers in numerous psychiatric conditions and brain disorders besides ASD ,268,269.The bio-psycho-social model’s sense, in the words of its founder Engel, is that “all three levels, biological, psychological, and social, must be taken into account in every health care task” ,16. ThisWithin the interconnected bio-psycho-social framework, one of the most intriguing challenges in ASD deserves a mention: the enhancement of “thinking different” and the awareness that psycho-neurodiversity and disease are not the same . EstabliEngel’s paradigm is still valid  and new The transfer of the theoretical construct of the bio-psycho-social paradigm into concrete and effective clinical practice requires a rethinking of current training courses for doctors, psychologists, educators, and therapists. Otherwise, the multidimensional construct is likely to be a rhetorical slogan and just an illusion with no positive effects for people lives. Current professional training courses are strongly unbalanced and deal almost exclusively with psychosocial matters, leading researchers and clinicians to fix their gaze on what they are accustomed to seeing. As a consequence, change seems unlikely, both in research and in clinical practice. Therefore, a cultural shift and the rethinking of training models is likely to be the starting point to look at and answer the unmet needs in ASD. People in the autism spectrum are presenting us with a unique challenge involving every aspect of human action, from the scientific area, to social, economic, and ethical fields. The wide variability in presentation and the extremely diversified needs of ASD people require personalized answers, within the harmonious framework of bio-psycho-social wellbeing.The topics we have gathered in this study suggest that the answers we get from research largely depend on which questions we ask and what tools we rely on. There are still unexplored fields in healthcare that should be urgently addressed, e.g., the reasons of health loss and of different life expectancy for people in the spectrum disorders compared to the general population.The current hardships reported by autistic people and their families and the expected worsening of their difficulties and social burden in the next years due to the increased prevalence of ASD underscore the need for timely and concrete solutions. Current knowledge allows us to improve ASD people’s care right now and to imagine different life trajectories and outcomes for them in the future.Autistic people and their families cannot achieve these results by themselves. They need to be supported by a multidimensional approach based on an open, dynamic, multi- and inter-disciplinary collaboration, both in research and in clinical practice.


ZnO and doped ZnO films with non-ferromagnetic metal have been widely used as biosensor elements. In these studies, the electrochemical measurements are explored, though the electrical impedance of the system. In this sense, the ferromagnetic properties of the material can be used for multifunctionalization of the sensor element using external magnetic fields during the measurements. Within this context, we investigate the room-temperature ferromagnetism in pure ZnO and Ag-doped ZnO films presenting zigzag-like columnar geometry. Specifically, we focus on the films’ structural and quasi-static magnetic properties and disclose that they evolve with the doping of low-Ag concentrations and the columnar geometry employed during the deposition. The magnetic characterization reveals ferromagnetic behavior at room temperature for all studied samples, including the pure ZnO one. By considering computational simulations, we address the origin of ferromagnetism in ZnO and Ag-doped ZnO and interpret our results in terms of the Zn vacancy dynamics, its substitution by an Ag atom in the site, and the influence of the columnar geometry on the magnetic properties of the films. Our findings bring to light an exciting way to induce/explore the room-temperature ferromagnetism of a non-ferromagnetic metal-doped semiconductor as a promising candidate for biosensor applications. ZnO and doped ZnO:NFM materials, with NFM being a non-ferromagnetic metal such as Cu or Ag, have received increasing attention in the last decade, not just for their interesting electric properties ,5,6,7,8,Remarkably, such materials may exhibit room-temperature ferromagnetism (RTFM) ,10,11,12Regarding technological applications, ZnO and doped ZnO films have received special attention associated with biosensors ,20,21,22Surprisingly rare studies consider the columnar structure’s influence on the magnetic response of ZnO and doped ZnO:NFM materials. In this sense, the employment of reactive magnetron sputtering associated with Glancing Angle Deposition (GLAD) emerges as an interesting experimental mechanism to produce a system with controllable columnar structure . The GLALooking in this direction, our group has recently shown the RTFM in ZnO:Ag-doped system with high Ag concentrations has been considered. In particular, we explored the magnetic properties of ZnO:Ag films in a wide range of temperatures and magnetic fields, revealing that structural columnar growth influences the RTFM verified in this set of samples . HoweverWithin this context, DFT calculations appear to be a powerful tool to study not just the electric and structural properties of ZnO and ZnO:NFM materials, but also the mechanisms responsible for the RTFM behavior ,32,33.From a general perspective, these studies explore the multifunctionality of ZnO and doped ZnO:NFM materials for future biosensor applications ,34,35,36The comprehension of the mechanism that leads to the RTFM can help us to produce systems with tunable electric and magnetic properties by modifying the columnar structure of the films.In this work, we explore the RTFM in undoped ZnO and doped ZnO:Ag films with a low concentration of Ag and zigzag-like columnar structure. For this purpose, we realize a systematic study of structural and quasi-static magnetic properties of the films with 0, 2, and 4 wt.% doping of Ag on ZnO films. The structural behavior shows a clear modification of the space group of the system as Ag concentration increases, although the zigzag-like structure remains unchanged. Furthermore, the magnetic characterization reveals ferromagnetic behavior at room temperature for all studied samples, for the system without Ag doping. By considering computational simulations, we investigate the origin of ferromagnetism in ZnO and Ag-doped ZnO and interpret our results in terms of the Zn vacancy dynamics and its substitution by an Ag atom in the site and columnar structure employed during the deposition. Our findings provide the exciting ability of ZnO films and their capacity to compose multifunctional systems.We investigated here a set of samples composed of pure ZnO and doped ZnO:Ag films doped with distinct Ag concentrations. Specifically, the doped ZnO:Ag films were prepared with the low-Ag concentrations of 2% and 4%, from now on known as ZnO:2Ag and ZnO:4Ag, respectively. The samples were produced onto glass substrate with dimensions of d 4 wt.% ,37. In pne rules ,39,40. Hprotocol . In partk points along with the hexagonal cell, and the reciprocal space was sampled considering the Monkhorst–Pack scheme with a We used the SIESTA software  to perfoint mesh . RegardiAg films . AlthougAg films ,47.Regarding SEM measurements, Ag films . This fed system . These rd system ,16. Howed system . With thd system  uncovereFrom a technological perspective, the present results allow us to produce ZnO and doped ZnO:Ag films in which we infer a ferromagnetic response on the studied system, in addition to the well-known electrical properties. Although the induced magnetic moment is small, our findings bring to light an exciting rote to infer a ferromagnetic response on the ZnO system that can be easily manipulated during electrochemical measurements, modifying the electrical impedance by employing an external magnetic field.From a theoretical perspective, the mechanisms responsible for the change in the magnetic properties are discussed in the following, in which we make use of DFT calculations to obtain the magnetic moment of Ag-doped supercell. Previous studies have demonstrated that Zn vacancies induce magnetic moment in ZnO ,48. Our x-axis indicates the distance between the dopant atoms. It is interesting to notice that two configurations are likely to retain their magnetic moment at room temperature, i.e., large Next, for each structure containing two Ag atoms, we calculated the energy difference between the ferromagnetic and antiferromagnetic configurations (i) reduced the concentration of Zn vacancies and/or (ii) interacted with nearby Ag atoms, possibly forming arrangements with low thermal stability. It is important to point out that the increase in Ag concentration to These simulation results allow us to interpret the fact that in the experiments, magnetization increases with the raise of Ag concentration at first and then decreases. Qualitatively, it is likely that for low Ag concentrations, the added silver atoms contributed to the magnetization. On the other hand, for higher concentrations, the added Ag atoms may have ( in Ref. , leads t in Ref. .As a final note, let us discuss how defects introduced by GLAD sputtering contribute to the improved RTFM in the investigated samples, specifically Zn vacancies. Towards this goal, we remark that the effect of increasing the concentration of Zn vacancies in a ZnO thin film has been investigated before . The autIn a general point of view, the presented results reveal an interesting rote to induce the RTFM in ZnO and doped ZnO systems. This characteristic is associated with the well-known capability of the ZnO to compose biosensors, gas sensors, humidity sensors, among others, and allow us to produce multifunctional systems that can be activated by external magnetic fields, for instance.In summary, here we have explored room-temperature ferromagnetism in pure ZnO and doped ZnO:Ag films produced by GLAD sputtering. Here we have shown the dependence of the structural and quasi-static magnetic properties of the films produced with zigzag-like columnar structure and low-Ag concentrations.The structural characterization has demonstrated a hexagonal structure with a remarkable modification in the preferential growth direction when low Ag concentrations have been inserted as the dopant. The cross-section SEM images have proved the zigzag-like structure induced during the deposition due to the GLAD sputtering technique. The magnetic characterization has revealed ferromagnetic behavior at room temperature for all samples of our set. By considering computational simulations, we have addressed the origin of ferromagnetism in ZnO and Ag-doped ZnO and interpreted our results in terms of the Zn vacancy dynamics and its substitution of an Ag atom in the site. In particular, the RTFM observed for our pure ZnO film, without the Ag dopant, results from the interplay of the Zn vacancy and the structural defects associated with the columnar growth in a zigzag-like structure. However, the modification in the saturation magnetization of the doped ZnO films is a consequence of the Zn vacancy dynamics and its substitution by an Ag atom in the site. Here we integrate the experimental and theoretical results and explain the mechanism responsible for the RTFM induction in ZnO films doped with low NFM materials. Our findings provide the exciting ability of ZnO films and their capacity to compose multifunctional systems. In particular, magnetic behavior can be associated with the well-known gas sensing ability to compose smart sensors activated by external magnetic fields in the future.


The Chernevaya taiga of Western Siberia is a unique and complex ecosystem, distinguished by the unusually large sizes of herbaceous plants, the reasons for which are poorly understood. Here, we explored the fungal diversity of the Chernevaya taiga soils in the Tomsk regions of Western Siberia in comparison with other soil types. The soil biomes of Chernevaya taiga and the control regions were investigated using Illumina ITS rRNA sequencing, and taxonomic analysis revealed a predominance of fungal phyla in the different soils. These results demonstrate that the fungi of the Chernevaya taiga regions have a higher species diversity (Faith’s PD) vs. the control soils, and the diversity is due more to the sampling sites rather than to the seasons (Bray-Curtis distance). We studied most of the differentially abundant taxa among the soil types, and we annotated the taxa with their ecological guilds and trophic types. Some of the abundant fungal taxa in the summer- and fall-Chernevaya taiga samples belong to the phylum Glomeromycota—arbuscular mycorrhizal symbiotrophs, which are known to establish symbiotic relationships and enhance plant growth. Additionally, several OTUs were assigned to novel genera in the Glomeraceae and Claroideoglomeraceae families. Our findings add a potential explanation of the high productivity and plant gigantism in Chernevaya taiga and expand our knowledge of fungal biodiversity. Abies sibirica) and common aspen (Populus tremula); (ii) tall-growing shrubs such as Siberian mountain-ash (Sorbus sibirica), birds cherry (Padus avium), and goat willow  that can reach up to 18 m in height and 30 cm in diameter; (iii) dense layers of large perennial herbs of up to 4.5 m; (iv) several species representative of Tertiary nemoral relict flora; (v) an absence of moss cover on the soil surface [The forests of Chernevaya taiga represent unique boreal forest formations that are limited in their distribution by hyper-humid sectors of the Altai-Sayan mountain region. These ecosystems are characterized by several features: (i) the growth of two main dominant tree species—Siberian fir , and an unusually high decomposition rate of plant residues. Obviously, both the productivity of Chernevaya taiga soils and the rapid decomposition of leaf litter are a complex of related properties, the analysis of which in the framework of a metagenomic study is an important fundamental task . In addiThe role of fungi in the decomposition of plant litter and carbon cycling ,4, and iOne of the most striking examples is the arbuscular mycorrhizal (AM) fungi of the phylum Glomeromycota. Forming intraradical hyphae, the AM increases the uptake of nutrients and facilitates the transfer of phosphorus and nitrogen to the plant under limiting conditions ,9. This Along with the AM, it was shown  that borUntil recently, Chernevaya taiga soils were studied very superficially, the phenomenon of plant gigantism was described only morphologically, and just a few attempts were made to find the cause of this peculiarity, mostly in terms of environmental and climatic factors. At the same time, the identification of such features could have an impact on agricultural technology.One of the reasons could be geographical features, such as high humidity and peculiarities of snow cover, but the results of vegetation experiments show that when the soil is extracted and used for growing control plants in lab conditions, the effect of increased productivity is maintained; therefore, the microbial components of the soil, such as bacteria and fungi, could be the drivers of fertility.In this study we explored the composition and properties of the Chernevaya taiga fungal communities, and their roles in the unique features of this ecosystem.In May 2020, field expeditions were conducted to collect samples of model plant species and soil samples at key sites of the Chernevaya taiga of Salair, and in the grass pine forest on the ancient terraces of the Ob River  by cryo-microtome. The visualization of the AM fungal structures as bright-field images using wheat germ agglutinin (WGA) coupled to 3,3′-diaminobenzidine (DAB) was carried out according to .Analysis was performed using QIIME2  and addic. Core diversity metrics calculation. Alpha-diversity (diversity within an ecosystem) was calculated using Faith’s PD index, beta-diversity—using UniFrac metric. d. Taxonomy assignment according to UNITE database v. 8.2 . Pre-trae. Differential abundance was calculated using phyloseq  and Desehttps://doi.org/10.6084/m9.figshare.16565721.v3 (accessed on 12 September 2021).Association of the fungal taxa with ecological guilds was performed using the FUNGuild approach . All theIn order to study the relationships between Chernevaya taiga fungi and plant gigantism, we explored the diversity of the fungal communities, taxonomic composition and relative abundance between the Chernevaya taiga and control samples. A higher biodiversity usually corresponds to a higher soil quality and nutrient supply, and can serve as a soil health indicator . The taxWe performed the diversity analysis in order to study the fungal community structures and the impact of the soil type and season. First, we analyzed the alpha-diversity, which is a measure of the species richness of a particular sample, using the Faith’s phylogenetic diversity index (Faith’s PD). The results of the alpha-diversity analysis show that the Chernevaya taiga samples have significantly higher diversity, and that the time of the year does not have a significant impact see . At the The beta-diversity analysis was performed in order to compare the fungal communities from the different sampling sites. We used a weighted UniFrac distance metric  that shoMortierella species, which demonstrates the domination of a single genus across all of the fungal communities. It was followed by yeast Solicoccozyma (Tremellomycetes) and mushroom-forming Inocybe (Agaricomycetes) species, which is typical for boreal forests [We analyzed the fungal taxonomic composition of the soil samples in each season and sampling site. When the results were grouped at the class level, the most abundant class of fungi in the Chernevaya taiga samples belonged to the Mortierellomycetes, followed by the Agaricomycetes . After b forests .We observed a significant abundance of Agaricomycetes in the summer and fall seasons in the control samples. In the Chernevaya taiga soils, we also saw an increase in the number of Agaricomycetes in the fall , which reflects their seasonal dynamics. Although Agaricomycetes are symbiotrophs, their main role in the ecosystem is the lignification of woody debris . Thus, iAs a next step, we studied the global picture of the ecological properties of the communities using the FUNGuild approach . The ratMortierella species. The species of Mortierella live as saprotrophs in the soil, playing an important role in the decaying of leaf litter and other organic materials, and can likely impact the soil fertility, as shown previously [Mortierella as one of the major fertility drivers in the Chernevaya taiga soils.Given the prevalence of the saprotrophs and symbiotrophs in the Chernevaya taiga samples, we examined the species content in more detail. Based on the normalized read count, the vast majority (75.2%) of saprotrophs and symbiotrophs belong to different eviously ,28. ThisMortierella in the soil samples, we have analyzed the taxa that are differentially abundant among the soil types, in order to investigate the less-abundant fungi that, nevertheless, may play an important role in the soil fertility . Unlikely to establish symbiosis with plants, they nevertheless can grow on substrates containing chitin , cellulose  and keratin , and we may assume that they can also take part in leaf-litter decomposition.Rozellomycota, which are parasitic microorganisms, differ from classical fungi per se, and are represented in our data by three orders of Rozellomycotina The ecosystem and litter type, in general, may have a significant influence on composition of the fungal species in the soil . RozelloThe most differentially abundant taxa in the summer and fall samples (log2 fold change −4.11 between Chernevaya taiga and control soils) belong to the phylum Glomeromycota—arbuscular mycorrhizal symbiotrophs, which are known to establish symbiotic relationships and enhance plant growth .Aconitum septentrionale and Crepis sibirica were chosen as model herbs for this ecosystem. A. septentrionale, an herbaceous perennial plant, does not usually form an association with arbuscular mycorrhiza (to the best of our knowledge). We took three root samples from each set of samples that were collected in the summer of 2019 at locations T1 and T3, respectively. From these, we prepared slices for cryomicroscopic imaging (see Methods section for details). Only in the Chernevaya taiga samples did the roots of A. septentrionale demonstrate the presence of arbuscular mycorrhizal fungi , indicates the important role of nutrient intake from the litter. Plant litter decomposition is a key step in nutrient recycling  and leadBased on the results obtained in the current work, the fungi of the Chernevaya taiga regions have a higher species diversity, which is determined by the sampling sites rather than the seasons. This observation is consistent with the data that boreal-forest fungal communities are usually clustered by site, thereby maintaining the vertical pattern of fungi segregation in different horizons .Mortierella species may serve as very valuable decomposers, increasing the nutrient uptake efficiency, utilizing carbon sources (including polymers such as cellulose or chitin) and promoting plant growth.Our analysis of the taxonomic composition of the soil samples in different seasons and sampling sites revealed the Mortierellomycota, Basidiomycota and Ascomycota phyla as the most abundant taxa. It is assumed that Ascomycota members predominantly participate in the early stages of leaf-litter decomposition, then are displaced by the Basidiomycota phylum, especially basidiomycetous yeasts . In geneAmong the most differentially abundant taxa, we also found members of the phylum Glomeromycota—arbuscular mycorrhizal symbiotrophs. It was shown that they can increase nutrient and water availability, hormonal regulation, and the mycorrhiza-induced resistance of host plants ,9. ArbusThe novel Glomeromycota taxa that were found in our study confirmed the observed high diversity of the AM in herb-rich coniferous forests . As is oThus, speaking of the potential application of our results in agriculture, we can consider arbuscular mycorrhiza as an enhancer of nutrient availability for host plants. From this we can conclude that conventional farmer fertilization practices (FFP) based on nutrient addition can be optimized with respect to their effect on mycorrhizal fungi, thereby increasing the richness and diversity of fungal communities, and through them influencing soil productivity. These findings are consistent with those of Muneer et al. , who comOf course, properties of such complex ecosystems cannot be attributed to specific fungal components alone. Both fungi and bacteria play a role in the active degradation of plant biomass, by encoding a distinct pool of carbohydrate-active enzymes  and demonstrating the interplay in the maintenance of the ecosystem . Prelimi


The VIABAHN stent graft is often used for traumatic and iatrogenic vascular injuries. In this case, vascular injury at both edges of the VIABAHN stent graft was noted 4 months after endovascular repair for idiopathic superficial femoral artery (SFA) rupture. The longitudinal compression of the SFA with a decrease in hematoma size was assumed to exceed the flexibility of the stent graft. Thus, the use of stent grafts for vascular injuries with giant pseudoaneurysms may result in late vascular injuries at both edges of the stent graft. Therefore, cautious assessment of its indications and strict surveillance are required. Its use has been correlated to the risk of late graft occlusion. However, the occurrence of late vascular injury due to the use of a stent graft placed in an appropriate position has been deemed rare.The VIABAHN®  stent graft has been determined to be effective for the treatment of peripheral artery disease (PAD) in the superficial femoral artery (SFA). Moreover, it is often used for traumatic and iatrogenic arterial injuries due to its minimally invasive property and long-term outcomes.In this study, we report a case of a patient who presented with late vascular injuries at both edges of the stent graft (VIABAHN) after endovascular treatment for idiopathic SFA rupture with a giant pseudoaneurysm.A 61-year-old Asian woman was admitted to the emergency room at our institution due to exacerbating pain in the right thigh and swelling 2 days back. Two months prior to admission, the patient reportedly underwent patch-closure surgery for a ruptured sinus of Valsalva and re-surgery for re-rupture of the sinus of Valsalva after 1 month . The patient was taking warfarin after cardiac surgery.The patient’s level of consciousness was found to be normal, and she was not in a state of shock. Significant swelling and pain in the right thigh were observed. However, no signs of infection were noted, and there was no ischemia in the right lower extremity. Blood examination findings upon admission were as follows: white blood cell count, 7350/µL; C-reactive protein level, 5.23 mg/dL; and procalcitonin level, 0.21 ng/mL. As per her contrast-enhanced computed tomography (CT) scans, a giant pseudoaneurysm (with a diameter of 10 cm) was found in her right thigh with extravasation from the main trunk of the distal SFA. A shift and lumen narrowing of the SFA due to pseudoaneurysm displacement were observed. The three tibial vessels were clearly visible.The patient was then diagnosed with SFA rupture and immediately underwent surgery using the endovascular stent graft approach. A 7-Fr sheath was placed into the right SFA with a right common femoral artery antegrade puncture. A 0.018-in stiff wire was cannulated into the below-the-knee artery, and the VIABAHN  stent graft was placed, without predilatation, from the distal SFA  to the above-the-knee popliteal artery  superior to the patella  from the middle SFA to the below-the-knee popliteal artery, embolization of the behind-the-knee popliteal artery , embolization of the proximal edge of the stent graft , and ligation of the SFA at the peripheral area of the proximal graft anastomosis , and imaging results. Furthermore, the presence of true aneurysms was also dismissed, as per her CT findings. Therefore, the diagnosis was idiopathic SFA rupture, which is determined to be a rare condition. To the best of our knowledge, only seven other cases presenting with this condition have been reported worldwide. The cause of idiopathic SFA rupture remains to be unknown. In young patients, some investigators have reported connective tissue disorder or congenital arterial abnormalities, such as Ehlers–Danlos syndrome, as the possible causes of idiopathic SFA rupture. Meanwhile in elderly patients, atherosclerosis is considered to be its primary contributing factor. But in this case, systemic atherosclerosis might have caused both rupture of the sinus of Valsalva and SFA.Pseudoaneurysms are often caused by trauma and infections, or they may be iatrogenic. In this case, an endovascular approach was determined as the most suitable treatment because of the presentation, history of cardiac surgery, intake of warfarin, and presence of a giant pseudoaneurysm. We opted to not select open surgery considering the risks of general anesthesia complications, massive bleeding, and wound infections. Because the rupture hole and pseudoaneurysm were large, coil embolization and thrombin injection were deemed to be inappropriate. Percutaneous insertion of a stent graft was instead selected because there were healthy landing zones, both proximal and peripheral of the rupture site, greater than or equal to 2 cm, which did not come in contact with the joints.An appropriate treatment regimen is chosen based on the rupture site, cause of the rupture, presence of an infection, peripheral ischemia, age, and performance status. There are also reports examining late vascular injuries at stent graft edges after using the VIABAHN stent graft across the joints (non-stenting zone) or using an oversized VIABAHN. However, no study has assessed the occurrence of late arterial injuries in patients with PAD using a proper size VIABAHN stent graft for SFA with proper landing zones , avoiding the hip or knee joints (non-stenting zone), which is attributed to excellent flexibility and the graft material.Although there have been a number of reports on late vascular injury after bare stent insertion into SFAs avoiding knee joints, most cases are due to the fracture of the stent body, and not the edges, owing to physiological loading; thus, the deformity and torsion of the distal SFA could be due to muscle movement with knee joint motion.In this case, the cause of arterial injuries at the edges of the stent graft might have been the insertion of the stent graft into the SFA in the state of being extended and bended by the giant pseudoaneurysm due to idiopathic SFA rupture. CT scan at 19 days after endovascular treatment revealed a tendency for repositioning and longitudinal compression of SFA due to a decrease in hematoma size, and CT scan after 4 months revealed further repositioning and compression of the SFA and significant meandering of the stent graft ( Recently, endovascular repair using stent grafts across the knee joint was performed for popliteal artery aneurysms. However, the long-term outcomes of placement at the same site are yet to be clearly elucidated, and this treatment option was not selected in this case due to the risk of recurrence of vascular injury at the stent graft edges. Exclusion and bypass procedures from the SFA to the below-the-knee popliteal artery were selected. However, autovein was not used considering the risk of coronary artery bypass and good runoff below-the-knee artery.The surgical bypass procedure and stent graft reinsertion have been considered for new pseudoaneurysms.In this patient’s case, the rupture of an infectious aneurysm was not completely ruled out but was thought to be unlikely as there were no findings of an infection throughout the treatment process and also the hematoma quickly disappeared after the exclusion procedure alone, without drainage or long-term use of antibiotics.Thus, cautious follow-up, including assessments of graft occlusion, infection, anastomotic pseudoaneurysms, and blood vessel rupture at other sites, is necessary.As per the findings of this study, it was determined that endovascular treatment using stent grafts for arterial ruptures with giant pseudoaneurysms may result in new arterial injuries at the stent graft edges due to the repositioning and longitudinal compression of the artery associated with the decrease in hematoma size after treatment. Therefore, cautious assessment of indications and strict surveillance are a must.


Data accumulated over the past four decades have confirmed that adult hippocampal neurogenesis (HN) plays a key role in the wide spectrum of hippocampal pathology. Epilepsy is a disorder of the central nervous system characterized by spontaneous recurrent seizures. Although neurogenesis in persistent germinative zones is altered in the adult rodent models of epilepsy, the effects of seizure-induced neurogenesis in the epileptic brain, in terms of either a pathological or reparative role, are only beginning to be explored. In this review, we described the most recent advances in neurogenesis in epilepsy and outlooked future directions for neural stem cells (NSCs) and epilepsy-in-a-dish models. We proposed that it may help in refining the underlying molecular mechanisms of epilepsy and improving the therapies and precision medicine for patients with epilepsy. Despite being assumed to be non-existent for decades, the occurrence and regulation of hippocampal neurogenesis (HN) in adult mammals has been widely accepted . Since vAdult neurogenesis in the mammalian brain is a process by which functional neurons are generated from the division of neural stem cells (NSCs), which have a high capacity for long-term self-renewal while giving rise to the neurons and glia in the subventricular zone/olfactory bulb (SVZ/OB) system and hippocampal dentate gyrus (DG) from the embryo throughout the lifespan of animals . ConclusThe production of neurons decreases with age, possibly due to an alteration of the neurogenic niche in the SVZ, a developing environment, or the limited neurogenic capacity of NSCs in the brain . Over tiOver the years, multiple neurological diseases, such as epileptic seizures, ischemic stroke, Alzheimer's disease, and traumatic brain injury, have been demonstrated to be involved in the hippocampal neurogenic cascade in multiple ways . These cAdult hippocampal neurogenesis in animals or humans is a multi-step process that includes migration, activation, proliferation, differentiation of local NSCs, and neuronal differentiation; thus, each stage may be more vulnerable to the dysregulation brought about by the pathological environment and external stimuli . In the At present, among the common neurodegenerative diseases associated with AHN, one of the most studied is epilepsy and psychogenic non-epileptic seizures . AlthougWith the extensive research and understanding of stem cells, hyperactivation of NSCs has been studied in detail in recent years. Upon stimulation with inflammation and stress from convulsive seizures, quiescent NSCs  in the subgranular zone (SGZ) enter the cell cycle and become proliferative NSCs . Once acUnderstanding how physiological stimuli may affect neurogenesis through unique neural stem and progenitor cell populations may reveal mechanisms underlying phenotypic outcomes and provide novel therapeutic targets for disease . InteresNeurogenesis is a common physiological phenomenon that continues throughout life and represents the ability of brain cells to regenerate themselves. In most cases, adult neurogenesis in mammals is thought to be beneficial for maintaining physiological homeostasis in the brain and repairing neurological damage. For example, increasing adult HN is sufficient to reduce anxiety and depression-like behaviors in mice administered corticosterone . MoreoveRecent studies have also suggested the beneficial roles of activated microglia in neurogenesis in the adult brain for providing structural, metabolic, and trophic roles for new neurons, phagocytic removal of dead cells, and modulation of the adaptive immune system in the central nervous system , 41. In via the activation of toll-like receptor 9 (TLR9), a pattern recognition receptor of the innate immune system that recognizes microbial DNA and triggers inflammatory responses -6 and IL-1β are the cytokines released from astrocytes and are proposed to act as protectors in the promotion of neuronal differentiation , 52. A pout mice . These rout mice .The relief of AHN caused by epileptic seizures has become a hot topic of current research, and scholars have put forward many assumptions during this period. In recent years, miRNAs  have gained significant attention as accumulating evidence has shown that most miRNAs play a crucial role in regulating AHN, and are also deregulated in the cases of seizures or chronic epilepsy . Here, aThe list of miRNAs that regulate AHN continues to grow, and AHN-focused miRNA-based therapy may be a promising strategy for epilepsy, although the complexity by which miRNAs regulate biological processes makes it challenging. Interestingly, several attempts to identify miRNA-based anti-epileptic therapies have been performed, although they have not primarily focused on AHN –58. AccuMore compelling evidence for the role of miRNA-based regulation in epilepsy implications for therapy comes from several studies on developing possible targets for antagomir-134 anti-epileptogenic effects . As mentin vivo and human-induced pluripotent stem cells (iPSC)-NPS models in vitro is a hot topic for future research on epilepsy .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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


More precisely, the blockade of 5-HT6 receptors by SB-271046 was shown to reduce the pilocarpine-induced LTP impairments by regulating the KCNQ2-mediated M-currents in rats. As a seminal conclusion, it was shown that the 5-HT6 receptor blockade decreases the excitability of the hippocampal pyramidal neurons in pilocarpine-induced status epilepticus in rats by an improved regulation of inhibitory and excitatory neurotransmission balance, with a significant and potential impact for the further advances in the treatment of epilepsies.Still, Kohek et al. have written an original research paper in which the influence of different anxiety conditions in the temporal lobe epilepsy and immunohistological modifications on interconnected brain areas were investigated regarding different aspects of epileptogenesis. Neuronal loss and the expression of selective neuromodulators, such as neuropeptide Y, in rodent hippocampus and amygdala, were finely studied with relevant considerations about common and potential therapeutic targets to better management of both disorders.Also, using pilocarpine-induced status epilepticus, Pinna and Colasanti showed evidence about the reciprocal relationship between the particular vulnerability of parvalbumin interneurons to metabolic stress and the newly associated mitochondrial dysfunction in affective disorders. The role of those interneuron losses or dysfunction/downregulation on mood instability of excitability states in bipolar affective disorder was discussed. Finally, the potential pharmacological targeting of parvalbumin-labelled interneurons was suggested as a new strategic avenue in the management of psychiatric and neurological conditions, in which the cyclic neurometabolic and neuroexcitability abnormalities promoted by the losses or downregulation of those inhibitory cells have been determined.Parvalbumin inhibitory interneurons are strictly involved in different neural pathways activity, as well as in neurometabolic mechanisms underlying the onset and maintenance of different brain disorders, in which mood regulation is substantially required. In a systematic review and in a subsequent meta-analysis, Finally, considering the diversified contribution of articles published here, we expected to motivate researchers to explore new horizons focusing on new approaches aiming a better understanding of epilepsy in comorbidity with mood disorders expecting a safe and most effective treatment of these disorders, complying with the improvement of the overall quality of life of affected patients.