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Background Endoscopic transnasal transclival intradural surgery is limited by a high postoperative cerebrospinal fluid leak rate. The aim of this study was to investigate the role of three-dimensional printing to create a personalized, rigid scaffold for clival reconstruction. Methods Two different types of clivectomy were performed in 5 specimens with the aid of neuronavigation, and 11 clival reconstructions were simulated. They were repaired with polylactide, three-dimensional–printed scaffolds that were manually designed in a computer-aided environment based either on the real or on the predicted defect. Scaffolds were printed with a fused filament fabrication technique and different offsets. They were positioned and fixed either following the gasket seal technique or with screws. Postdissection radiological evaluation of scaffold position was performed in all cases. In 3 specimens, the cerebrospinal fluid leak pressure point was measured immediately after reconstruction. Results The production process took approximately 30 hours. The designed scaffolds were satisfactory when no offset was added. Wings were added during the design to allow for screw positioning, but broke in 30% of cases. Radiological assessment documented maximal accuracy of scaffold positioning when the scaffold was created on the real defect; accuracy was satisfactory when the predicted clivectomy was performed under neuronavigation guidance. The cerebrospinal fluid leak pressure point was significantly higher when the scaffold was fixed with screws compared with the gasket technique. Conclusions In this preclinical setting, additive manufacturing allows the creation of customized scaffolds that are effective in reconstructing even large and geometrically complex clival defects.

Non-alcoholic fatty liver disease is a chronic metabolic disorder representing the most common cause of chronic liver disease in western civilization and one of the main causes of cirrhosis with a significant impact on all-cause mortality in the most advanced phases. It is characterized by hepatic fat accumulation in the absence of significant ethanol consumption, virus infection or other specific causes of liver disease. Accumulation of fat in liver tissue occurs as a consequence of the imbalance between overconsumption of high-fat diet and increased de novo lipogenesis and decreased lipid disposal. Novel dietary and pharmacological therapies for the prevention of fatty liver disease and the progression to cirrhosis are an actual field of study but still poorly understood. In this perspective, the current review aims to summarise and clarify the transcription factor NFκB effects, which may exert among non-alcoholic fatty liver diseases and their progression. Through extensive previous research, it has become clear that several signaling pathways are involved: metabolic dysregulation (such as free fatty acids increase, adipokine alteration, insulin resistance), oxidative stress and inflammation contribute together in a “vicious circle” to the pathogenesis of non-alcoholic fatty liver diseases. Within this, NFκB signaling is a primary factor in inflammatory reactions and diseases, with important molecular connections between metabolic, oxidative, immune and inflammation systems.

Physiology of orofacial pain pathways embraces primary afferent neurons, pathologic changes in the trigeminal ganglion, brainstem nociceptive neurons, and higher brain function regulating orofacial nociception. The goal of this study was to investigate the nitroxidergic system alteration at brainstem level (spinal trigeminal nucleus), and the role of peripheral P2 purinergic receptors in an experimental mouse model of pediatric inflammatory orofacial pain, to increase knowledge and supply information concerning orofacial pain in children and adolescents, like pediatric dentists and pathologists, as well as oro-maxillo-facial surgeons, may be asked to participate in the treatment of these patients. The experimental animals were treated subcutaneously in the perioral region with pyridoxalphosphate-6-azophenyl-2 ′ ,4 ′ -disulphonic acid (PPADS), a P2 receptor antagonist, 30 minutes before formalin injection. The pain-related behavior and the nitroxidergic system alterations in the spinal trigeminal nucleus using immunohistochemistry and western blotting analysis have been evaluated. The local administration of PPADS decreased the face-rubbing activity and the expression of both neuronal and inducible nitric oxide (NO) synthase isoforms in the spinal trigeminal nucleus. These results underline a relationship between orofacial inflammatory pain and nitroxidergic system in the spinal trigeminal nucleus and suggest a role of peripheral P2 receptors in trigeminal pain transmission influencing NO production at central level. In this way, orofacial pain physiology should be elucidated and applied to clinical practice in the future.

The clivus was defined as “no man’s land” in the early 1990s, but since then, multiple approaches have been described to access it. This study is aimed at quantitatively comparing endoscopic transnasal and microsurgical transcranial approaches to the clivus in a preclinical setting, using a recently developed research method. Multiple approaches were performed in 5 head and neck specimens that underwent high-resolution computed tomography (CT): endoscopic transnasal (transclival, with hypophysiopexy and with far-medial extension), microsurgical anterolateral (supraorbital, mini-pterional, pterional, pterional transzygomatic, fronto-temporal-orbito-zygomatic), lateral (subtemporal and subtemporal transzygomatic), and posterolateral (retrosigmoid, far-lateral, retrolabyrinthine, translabyrinthine, and transcochlear). An optic neuronavigation system and dedicated software were used to quantify the working volume of each approach and calculate the exposure of different clival regions. Mixed linear models with random intersections were used for statistical analyses. Endoscopic transnasal approaches showed higher working volume and larger exposure compared with microsurgical transcranial approaches. Increased exposure of the upper clivus was achieved by the transnasal endoscopic transclival approach with intradural hypophysiopexy. Anterolateral microsurgical transcranial approaches provided a direct route to the anterior surface of the posterior clinoid process. The transnasal endoscopic approach with far-medial extension ensured a statistically larger exposure of jugular tubercles as compared with other approaches. Presigmoid approaches provided a relatively limited exposure of the ipsilateral clivus, which increased in proportion to their invasiveness. This is the first anatomical study that quantitatively compares in a holistic way exposure and working volumes offered by the most used modern approaches to the clivus.

Nowadays, it is known that the sex differences regard many organs, e.g., liver, vessels, pancreas, lungs, bronchi and also the brain. Sex differences are not just a matter of ethical and moral principles, as they are central to explain many still unknown diseases and their understanding is a prerequisite to develop an effective therapy for each individual. This review reports on those sex differences that are not only macroscopic and morphological, but also involve molecular and functional dimorphism in the brain. It will recapitulate the main structural differences between male and female brain including the neurotransmission systems; in particular, the main objective is to identify a correlation, already known or to be investigated in the future, between the differences that characterize male and female brains from a morphological and biochemical point of view and neurological syndromes. This correlation could provide a starting point for future scientific research aimed to investigate and define a personalized therapy.

In Italy, recent legislation (Law No. 10/2020) has tuned regulations concerning the donation of one's postmortem body and tissues for study, training, and scientific research purposes. This study discusses several specific issues to optimise the applicability and effectiveness of such an important, novel regulatory setting. Some of these unsolved issues may involve the grantees of teaching and training activities, the role of academic anatomical institutes, the role of family members in the donation process, the universal time limit indicated for any donation, the handling of corpses, and the limited body donation and its subordination to the donation of organs and tissues. Critical issues arise concerning the learners, the type of training and teaching activities that can be planned, the position of academic anatomy institutes, the role of family members in the donation process, the time frame of the donation process, the eligibility of partial donation, or the simultaneous donation of organs and tissues to patients awaiting transplantation. In particular, a universal time limit for donations (i.e., one year) makes it impossible to plan the long-term use of specific body parts, which could be effectively preserved for the advanced teaching and training of medical students and surgeons. The abovementioned conditions lead to the limited use of corpses, thus resulting in the inefficiency of the whole system of body donation. Overall, the donors' scope for the donation of their body could be best honoured by a more flexible and tuneable approach that can be used on a case-by-case basis. Furthermore, it is deemed necessary to closely monitor the events scheduled for corpses in public nonacademic institutions or private enterprises. This paper presents useful insights from Italian anatomists with the hope of providing inspiration for drafting the regulations. In conclusion, this paper focuses on the critical issues derived from the recently introduced Italian law on the donation and use of the body after death and provides suggestions to lawmakers for future implementations.

A rare branching pattern of the aortic arch in a female cadaver is reported. An aberrant right subclavian artery originated from the distal part of the aortic arch and following a retroesophageal course was recognized. Next to it, from the left to the right, the left subclavian artery and a short bicarotid trunk originating the left and the right common carotid artery were recognized. An unusual origin of the vertebral arteries was also identified. The left vertebral artery originated directly from the aortic arch, whereas the right vertebral artery originated directly from the right common carotid artery. Retroesophageal right subclavian artery associated with a bicarotid trunk and ectopic origin of vertebral arteries represents an exceptional and noteworthy case.

L'opera, basata sul Prometheus di M. Schünke, E. Schulte e U. Schumacher con illustrazioni di M. Voll e K. Wesker, include tre volumi: I, Basi Anatomiche per la Semeiotica; II, Basi Anatomiche per la Fisiopatologia; III: Basi Anatomiche per le Neuroscienze. Il trattato è impostato in maniera moderna, rendendo complementari la trattazione regionalistica e quella sistematica, prevedendone e consentendone il pieno utilizzo virtualmente in tutte le sedi accademiche, a prescindere dal numero di crediti e dall’organizzazione del corso. Ne risulta uno strumento didattico che consentirà non solo la personalizzazione dello studio, ma anche il successivo approfondimento dei contenuti per tutta la vita professionale del medico.

BACKGROUND The spheno-orbital region (SOR) is a complex anatomic area that can be accessed with different surgical approaches. OBJECTIVE To quantitatively compare, in a preclinical setting, microsurgical transcranial approaches (MTAs), endoscopic endonasal transpterygoid approach (EEA), and endoscopic transorbital approaches (ETOAs) to the SOR. METHODS These approaches were performed in 5 specimens: EEA, ETOAs (superior eyelid and inferolateral), anterolateral MTAs (supraorbital, minipterional, pterional, pterional-transzygomatic, and frontotemporal-orbitozygomatic), and lateral MTAs (subtemporal and subtemporal transzygomatic). All specimens underwent high-resolution computed tomography; an optic neuronavigation system with dedicated software was used to quantify working volume and exposed area for each approach. Mixed linear models with random intercepts were used for statistical analyses. RESULTS Anterolateral MTAs offer a direct route to the greater wings (GWs) and lesser wings (LWs); only they guarantee exposure of the anterior clinoid. Lateral MTAs provide access to a large area corresponding to the GW, up to the superior orbital fissure (SOF) anteriorly and the foramen rotundum medially. ETOAs also access the GW, close to the lateral portion of SOF, but with a different angle of view as compared to lateral MTAs. Access to deep and medial structures, such as the lamina papyracea and the medial SOF, is offered only by EEA, which exposes the LW and GW only to a limited extent. CONCLUSION This is the first study that offers a quantitative comparison of the most used approaches to SOR. A detailed knowledge of their advantages and limitations is paramount to choose the ideal one, or their combination, in the clinical setting.

Background A landmark for the identification of the lingual artery (LA) through a transoral perspective can provide surgeons with an easy method to prevent and manage intraoperative bleeding during transoral approach to the base of tongue (BOT). Methods Thirteen tongue and five head and neck specimens were dissected to identify and assess the reliability of the lingual point (LP) as a new landmark for the LA at BOT. The pathway of 42 LAs was radiologically evaluated; axial depth and vertical offset were measured for each LA. Results Dissection study: a description of LP is provided; the LA was easily identified in all specimens (36/36 sides) using LP as a landmark. Radiologic study: the mean depth of the LA was 4.2 mm, the mean vertical offset was 1.3 mm. Conclusions LP is a simple and reliable landmark for identification of the LA, potentially helping surgeons to prevent and manage intraoperative bleeding.

Obesity is a risk factor for vascular dysfunction and insulin resistance. The study aim was to demonstrate that adipocyte-specific HO-1 (heme oxygenase-1) gene therapy is a therapeutic approach for preventing the development of obesity-induced metabolic disease in an obese-mice model. Specific expression of HO-1 in adipose tissue was achieved by using a lentiviral vector expressing HO-1 under the control of the adiponectin vector (Lnv-adipo-HO-1). Mice fed a high-fat diet (HFD) developed adipocyte hypertrophy, fibrosis, decreased mitochondrial respiration, increased levels of inflammatory adipokines, insulin resistance, vascular dysfunction, and impaired heart mitochondrial signaling. These detrimental effects were prevented by the selective expression of HO-1 in adipocytes. Lnv-adipo-HO-1-transfected mice on a HFD display increased cellular respiration, increased oxygen consumption, increased mitochondrial function, and decreased adipocyte size. Moreover, RNA arrays confirmed that targeting adipocytes with HO-1 overrides the genetic susceptibility of adiposopathy and correlated with restoration of the expression of anti-inflammatory, thermogenic, and mitochondrial genes. Our data demonstrate that HO-1 gene therapy improved adipose tissue function and had positive impact on distal organs, suggesting that specific targeting of HO-1 gene therapy is an attractive therapeutic approach for improving insulin sensitivity, metabolic activity, and vascular function in obesity.

Emerging evidence suggests that red blood cells (RBCs) are involved in many functions essential for life. Nuclear factor-kB (NF-kB), nitric oxide synthases (inducible nitric oxide synthase -iNOS-, endothelial nitric oxide synthase -eNOS-) and interleukin-1β (-IL-1β-) are all proteins that have been identified in RBCs. In nucleated cells, such as white blood cells (WBCs), these proteins have well investigated roles, linked to stress and inflammation. It is not the same in erythrocytes, for this reason, we considered obese patients for studying the morphology of RBCs. We studied a possible correlation between their morphological changes and several protein expressions. Moreover, we compared the results about the aforementioned proteins and antioxidant markers with those obtained in WBCs from healthy and obese patients before and after omega-3 polyunsaturated fatty acid supplementation. This latter scientific point is important in order to determine whether there are differences in the expression of nucleated and anucleated cells. The morphology of RBCs changed in obese patients, but it is significantly restored after six weeks of supplementation. The expression of antioxidant enzymes changed in RBCs and WBCs in obesity but all proteins restore their positivity after supplementation. We found that: the presence of NF-kB, antioxidant enzymes and eNOS in healthy RBCs could indicate a role of these proteins as regulators of cellular metabolism; obese WBCs showed a higher NF-kB, iNOS and IL-1β positivity, whereas eNOS presence did not significantly change in these cells. We tried to explain the different positivity of NF-kB, proposing a dual role for this protein, as prolifespan and as proinflammatory processes, depending on examined cells. In conclusion, we have considered the literature that focuses on the omega-6/omega-3 ratio. The ratio changed from the past, especially in people whose diet is strongly westernized worsening the state of health of the patient and leading to an higher incidence of obesity. Our study hypothesizes that the supplementation could help to restore the correct ratio.

Infrahyoid muscles are usually supplied by muscular arteries, originating from the superior and inferior thyroid artery and the internal thoracic artery. In this work, we reported a unilateral anatomical variation of the branching pattern of the lingual artery, which was observed during dissection studies at the University of Brescia. We found an accessory branch arising from the root of the lingual artery that run down medially and supplied the infrahyoid muscles. A similar case has not yet been reported in literature. Considering the current use of the infrahyoid muscles as pedicled myocutaneous flap for reconstructing surgical defects in the head and neck, this vascular variation appears interesting to be reported for appropriate clinical and surgical consideration.

Objective To quantitatively compare different microsurgical and endoscopic approaches to the middle cranial fossa in a preclinical setting with a novel, computer-based research method. Methods Different approaches were performed bilaterally in 5 head and neck specimens that underwent high-resolution computed tomography scans: 5 transcranial anterolateral (supraorbital, mini-pterional, pterional, pterional-transzygomatic, fronto-temporal-orbito-zygomatic) without and with anterior clinoidectomy; 2 transcranial lateral (subtemporal and subtemporal-transzygomatic); 2 endoscopic transnasal (transpterygoid, transpterygoid to infratemporal fossa); 2 endoscopic transorbital (superior eyelid and inferolateral), and endoscopic transmaxillary. A dedicated navigation system was used to quantify surgical working volumes and exposure of different areas of the middle cranial fossa (ApproachViewer, part of GTx-Eyes II, University Health Network, Toronto, Canada). Statistical analysis was performed using a mixed linear model with bootstrap resampling. Results Endoscopic transnasal and fronto-temporal-orbito-zygomatic approaches with anterior clinoidectomy showed the largest surgical volumes. Endoscopic approaches allowed a wider exposure of medial anatomical surfaces (e.g., the petrous apex) compared with transcranial ones. Transcranial approaches with larger craniotomies allowed the widest exposure of superomedial anatomical structures (e.g., roof of cavernous sinus). The resection of the zygomatic arch allowed exposure of more medial surfaces with an inferior to superior trajectory. Conclusions This study implemented a novel neuronavigation-based research method to quantitatively compare different approaches to the middle cranial fossa; its results might guide, after consideration of clinical implications, the choice of the neurosurgical approach to different areas of this complex skull base region.

Robotics has already been applied to several surgical fields, but only transoral robotic surgery has a recognized role in skull base surgery. Different preclinical prototypes have been described for endoscopic transnasal skull base surgery (ESBS), but only recently a dedicated, hybrid robotic system has become available for clinical practice. This chapter reviews the use of holders in neurosurgery and skull base surgery, provides an overview of limitations of previous robotic systems that were designed for other surgical applications, describes the different preclinical robotic prototypes that have been developed for ESBS, and reports the initial preclinical and clinical experience with a novel, dedicated, hybrid robotic solution for endoscopic skull base surgery (EndoscopeRobot®, Medineering, Munich, Germany). The era of robotics in skull base surgery is at its dawn, but advantages of the hybrid solution are already evident, though further studies are needed to gain additional data.

Aim. Nonalcoholic steatohepatitis (NASH) is the consequence of insulin resistance, fatty acid accumulation, oxidative stress, and lipotoxicity. We hypothesize that an increase in the inflammatory adipokine NOV decreases antioxidant Heme Oxygenase 1 (HO-1) levels in adipose and hepatic tissue, resulting in the development of NASH in obese mice. Methods. Mice were fed a high fat diet (HFD) and obese animals were administered an HO-1 inducer with or without an inhibitor of HO activity to examine levels of adipose-derived NOV and possible links between increased synthesis of inflammatory adipokines and hepatic pathology. Results. NASH mice displayed decreased HO-1 levels and HO activity, increased levels of hepatic heme, NOV, MMP2, hepcidin, and increased NAS scores and hepatic fibrosis. Increased HO-1 levels are associated with a decrease in NOV, improved hepatic NAS score, ameliorated fibrosis, and increases in mitochondrial integrity and insulin receptor phosphorylation. Adipose tissue function is disrupted in obesity as evidenced by an increase in proinflammatory molecules such as NOV and a decrease in adiponectin. Importantly, increased HO-1 levels are associated with a decrease of NOV, increased adiponectin levels, and increased levels of thermogenic and mitochondrial signaling associated genes in adipose tissue. Conclusions. These results suggest that the metabolic abnormalities in NASH are driven by decreased levels of hepatic HO-1 that is associated with an increase in the adipose-derived proinflammatory adipokine NOV in our obese mouse model of NASH. Concurrently, induction of HO-1 provides protection against insulin resistance as seen by increased insulin receptor phosphorylation. Pharmacological increases in HO-1 associated with decreases in NOV may offer a potential therapeutic approach in preventing fibrosis, mitochondrial dysfunction, and the development of NASH.

Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used either alone or in combination with different approaches when dealing with the pathologies of the skull base. The objective of the current study is to evaluate the surgical anatomy of transorbital endoscopic approaches by cadaver dissections as well as providing objective clinical data on their actual employment and morbidity through a systematic review of the current literature. Four cadaveric specimens were dissected, and step-by-step dissection of each endoscopic transorbital approach was performed to identify the main anatomic landmarks and corridors. A systematic review with pooled analysis of the current literature from January 2000 to April 2020 was performed and the related studies were analyzed. Main anatomical landmarks are presented based on the anatomical study and systematic review of the literature. With emphasis on the specific transorbital approach used, indications, surgical technique, and complications are reviewed through the systematic review of 42 studies (19 in vivo and 23 anatomical dissections) including 193 patients. In conclusion, transorbital endoscopic approaches are promising and appear as feasible techniques for the surgical treatment of skull base lesions. Surgical anatomy of transorbital endoscopic approaches can be mastered through knowledge of a number of anatomical landmarks. Based on data available in the literature, transorbital endoscopic approaches represent an important complementary that should be included in the armamentarium of a skull base team.

BACKGROUND The complexity of the frontal sinus drainage pathway (FSDP) can be challenging even for expert surgeons. Several classifications have been proposed to simplify the understanding of FSDP, whose anatomical variability can be simplified based on the knowledge of its developmental mechanisms. METHODS Cone-beam computed tomography studies performed at the Unit of Radiology of the University of Brescia between March and November 2012 were retrospectively analyzed. FSDP was classified as medial or lateral to the vertical portion of the uncinate process and the following anatomical variants were studied: agger nasi cell, Kuhn's cells, suprabullar cell, supraorbital ethmoid cell, suprabullar frontal cell, and frontal septal cell. The developmental model of the FSDP proposed by Terracol and Ardouin was analyzed and expected associations between the position of the drainage pathway and anatomical variants were formulated. Statistical associations between anatomical variants and the position of FSDP were calculated and compared with expected associations to validate the developmental model. RESULTS The anatomical variants of FSDP statistically validated the developmental model of Terracol and Ardouin. CONCLUSION Knowledge of the possible developmental patterns of FSDP helps the surgeon in the understanding of the complexity of the frontoethmoidal region.

The aim of this study was to investigate the in vitro effect of Silicon, in the soluble form of sodium orthosilicate, combined and not with the concentrated growth factors (CGF), a platelet-rich preparation, on three different human cell lines of fibroblasts (NHDF), endothelial cells (HUVEC), and osteoblasts (HOBs). Each cell type was treated with sodium orthosilicate at the final concentration of 0.5 mM and 1 mM, CGF, and sodium orthosilicate combined with CGF, for 72 h. At the end of the experimental period, the in vitro effect on cell growth, proliferation, and metabolic activity was evaluated by performing a simple cell count, using an automated cell counter and by evaluating the expression of the intracellular proliferation marker Ki-67, using Fluorescence-activated cell sorting (FACS) analysis. Moreover, the expression of other cell markers and active molecules, such as Collagen type I, Osteopontin, Vascular Endothelial Growth Factor, and endothelial Nitric Oxide Synthase, was evaluated, through immunohistochemistry. Results obtained showed that the combined use of CGF and sodium orthosilicate stimulates cell growth, proliferation, and metabolic activity, suggesting that this treatment could be effective in tissue regeneration.

Background Endoscopic medial maxillectomies (EMMs) are used to optimize exposure of the maxillary sinus and retromaxillary areas. Although in type D EMM (Sturmann-Canfield procedure) the anterior superior alveolar nerve (ASAN) is always at risk of injury, only 29% of patients complained of alveolar process and dental anesthesia. The purpose of this anatomical study is to assess the neural anastomotic network of the ASAN (ASAN-NAN) and describe different extensions of type D EMMs in a preclinical setting. Methods The ASAN and its medial anastomotic branches (MABs) and lateral anastomotic branches (LABs) were evaluated by cone-beam computerized tomography (CBCT). Five different extensions of type D (D1 to D5) EMMs were identified and nerves at risk of injury in each type were assessed by CBCT. Moreover, quantification of surgical corridors was performed on cadaver heads with a neuronavigation system. Results Fifty-seven CBCT scans were analyzed. The ASAN would be spared in 16.3% of cases with a type D1 EMM, while it would be injured in the majority of type D2 to D5 resections. At least 1 nerve of the ASAN-NAN was spared in 96.6%, 93%, 74.6%, 0%, and 65.8% of type D1 to D5 EMMs, respectively. Two cadaver heads were dissected and the incremental volume and number of maxillary subsites exposed was assessed in type D1 to D5 EMMs. Conclusion ASAN function impairment is probably compensated by LABs and MABs. If this hypothesis will be validated in a prospective study on patients, preoperative CBCT evaluation could predict neurological morbidity after type D EMM, and allow tailoring the procedure to minimize impairment of the ASAN-NAN.

To describe the anatomical variability of the ethmoidal arteries (EAs). To evaluate the reliability of cone beam computed tomography (CBCT) in preoperative assessment of EAs. Fourteen cadaver heads underwent CBCT and endoscopic dissection. The following anatomical features were evaluated for anterior (AEA), middle (MEA), and posterior (PEA) EAs: presence, cranio-caudal position, antero-posterior position, and dehiscence of the bony canal. Accuracy of radiological assessment was calculated. AEA, MEA, and PEA were identified in 100, 28.6, and 100% of sides. They were caudal to the skull base in 60.7, 25, and 17.9%, respectively. CBCT showed a high accuracy in identifying these features. The antero-posterior position of EAs, which was highly variable, was correctly assessed by CBCT. A dehiscent bony canal of AEA, MEA, and PEA was found in 46.4, 12.5, and 28.6% of sides, respectively. Accuracy of CBCT in picking up this feature was poor but negative predictive value was high. CBCT was adequate in identifying and localizing EAs. In addition, it can be used to exclude the presence of MEA and dehiscence of ethmoidal canals, whereas the accuracy in detecting these anatomic variants was low.

Background: Additional extrinsic muscles of the tongue are reported in literature and one of them is the myloglossus muscle (MGM). Since MGM is nowadays considered as anatomical variant, the aim of this study is to clarify some open questions by evaluating and describing the myloglossal anatomy (including both MGM and its ligamentous counterpart) during human cadaver dissections. Materials and methods: Twenty-one regions (including masticator space, sublingual space and adjacent areas) were dissected and the presence and appearance of myloglossus were considered, together with its proximal and distal insertions, vascularisation and innervation. Results: The myloglossus was present in 61.9% of cases with muscular, ligamentous or mixed appearance and either bony or muscular insertion. Facial artery provided myloglossal vascularisation in the 84.62% and lingual artery in the 15.38%; innervation was granted by the trigeminal system (buccal nerve and mylohyoid nerve), sometimes (46.15%) with hypoglossal component. Conclusions: These data suggest us to not consider myloglossus as a rare anatomical variant.

Background Achieving an effective endoscopic skull base reconstruction in case of large dural defects requires specific training and can be extremely challenging. The aim of this study was to describe the development and validation of a preclinical model for cerebrospinal fluid (CSF) leak repair, which can be used for training and to test the mechanical efficacy of endoscopic skull base reconstruction. Methods Eleven fresh-frozen cadaver heads were dissected. A catheter was inserted in the subdural space via a cervical access, which was sealed with mastic; a vertical graduated tube connected to the catheter measured intracranial pressure (ICP), while stained water was injected intracranially. After endoscopic skull base reconstruction was performed, an expert surgeon assessed its efficacy. ICP was then gradually increased until a leak was evident and CSF leak pressure value was recorded. The correlation between subjective and quantitative evaluations was investigated through Pearson and Spearman correlation tests. Results The model was successfully tested in 11 specimens. A single, large dural defect was created in each model (transplanum-transtuberculum = 4; transplanum-transtuberculum-transsellar = 3; transclival = 3; transcribriform-transplanum = 1). Skull base reconstruction always comprised a rigid buttress with temporal fascia and/or fat. The CSF leak pressure ranged from 4 to 110 cmH2 O. The correlation between expert subjective and quantitative assessment of skull base reconstruction mechanical efficacy was high (r = 0.7; rs = 0.7; p = 0.010 and p = 0.006, respectively). Conclusion This preclinical model is simple, easily reproducible, and effective in simulating an intraoperative leak and objectively measures the CSF leak pressure point of a skull base reconstruction.

Background The armamentarium for anterior skull base (ASB) reconstruction includes a variegate spectrum of grafts, endonasal pedicled flaps, regional pedicled flaps, and free flaps, which are selected to face specific scenarios. The use of a vascularized flap in case of large ABS defects ensures an adequate blood supply. The aim of this study was to evaluate the possible role of temporoparietal fascia flap (TPFF) in ASB reconstruction. Methods Eight fresh-frozen head specimens were dissected to evaluate the adequacy of TPFF and pericranial flap (PF) for the reconstruction of ASB defects. The percentage of coverage of the ASB was calculated for TPFF and PF. An anatomic-radiologic analysis was performed to provide useful practical information for flap harvesting and positioning. Results The TPFF was easily transposed to the ABS defect through an epidural corridor; the edges of the TPFF were successfully placed in the intradural space, in the epidural space, or on the extracranial surface of the ABS defect. The PF was particularly adequate for median defects, and the TPFF was shown to be useful also in cases with paramedian-supraorbital extension. The median percentage of coverage of the ASB was significantly higher for TPFF (85.1%) than PF (65.7%) (P = 0.018). Conclusions The supraorbital epidural corridor is a possible novel pathway for transposition of the TPFF for ASB reconstruction. Side-door TPFF was shown to be an ideal choice for large ASB defect with lateral supraorbital extension and could be useful in the scenario of salvage reconstruction for recurrent ABS cerebrospinal fluid leak.

Bone marrow and adipose tissue human mesenchymal stem cells were seeded in highly performing 3D gelatin–chitosan hybrid hydrogels of varying chitosan content in the presence of human platelet lysate and evaluated for their proliferation and osteogenic differentiation. Both bone marrow and adipose tissue human mesenchymal stem cells in gelatin–chitosan hybrid hydrogel 1 (chitosan content 8.1%) or gelatin–chitosan hybrid hydrogel 2 (chitosan 14.9%) showed high levels of viability (80%–90%), and their proliferation and osteogenic differentiation was significantly higher with human platelet lysate compared to fetal bovine serum, particularly in gelatin–chitosan hybrid hydrogel 1. Mineralization was detected early, after 21 days of culture, when human platelet lysate was used in the presence of osteogenic stimuli. Proteomic characterization of human platelet lysate highlighted 59 proteins mainly involved in functions related to cell adhesion, cellular repairing mechanisms, and regulation of cell differentiation. In conclusion, the combination of our gelatin–chitosan hybrid hydrogels with hPL represents a promising strategy for bone regenerative medicine using human mesenchymal stem cells.

Understanding the association between fetal nervous system structure and functioning should be an important goal in neurodevelopmental sciences, especially when considering the emerging knowledge regarding the importance of prenatal onset. Intrauterine development of the human central nervous system consists of specific processes: neurogenesis, neuronal migration, synaptogenesis, and myelination. However, as extensively shown by the neurobehavioral studies in the last century, the development of the central nervous system involves both structure and functioning. It is now recognised that the developing motor and sensory systems are able to function long before they have completed their neural maturation and that the intrauterine experience contributes to neurobehavioral development. This review analyzes the recent literature, looking at the association between the human nervous system maturation and fetal behavior. This article will follow the development and skill acquisition of the anatomical nervous system across the three trimesters of the gestation period.

Background Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and is considered to be an inflammatory disorder characterized by fatty acid accumulation, oxidative stress, and lipotoxicity. We have previously reported that epoxyeicosatrienoic acid-agonist (EET-A) has multiple beneficial effects on cardiac, renal and adipose tissue function while exhibiting both anti-inflammatory and anti-oxidant activities. We hypothesized that EET-A intervention would play a central role in attenuation of obesity-induced steatosis and hepatic fibrosis that leads to NAFLD. Methods We studied the effect of EET-A on fatty liver using db/db mice as a model of obesity. Mice were fed a high fat diet (HFD) for 16 weeks and administered EET-A twice weekly for the final 8 weeks. Results db/db mice fed HFD significantly increased hepatic lipid accumulation as manifested by increases in NAS scores, hepatic fibrosis, insulin resistance, and inflammation, and decreases in mitochondrial mitofusin proteins (Mfn 1/2) and anti-obesity genes Fibroblast growth factor 21 (FGF21) and Cellular Repressor of E1A-Stimulated Genes 1 (CREG1). EET-A administration reversed the decrease in these genes and reduced liver fibrosis. Knockout of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in EET-A treated mice resulted in a reversal of the beneficial effects of EET-A administration. Conclusions EET-A intervention diminishes fatty acid accumulation, fibrosis, and NFALD associated with an increase in HO-1-PGC1α and increased insulin receptor phosphorylation. A pharmacological strategy involving EETs may offer a potential therapeutic approach in preventing fibrosis, mitochondrial dysfunction, and the development of NAFLD.

Background: The aims of this narrative review were to examine up-to-date literature in order to evaluate the effectiveness of arthrocentesis or injections with platelet-rich plasma in temporomandibular affections and to compare them to arthrocentesis alone or with hyaluronic acid (HA) or to hyaluronic acid injections. Methods: The search of international literature was made on the PMC, PubMed and Cochrane databases, including all full-length text of studies on humans focused on osteoarthritis and disc displacements and their treatment with platelet-rich plasma arthrocentesis or injections. All design studies were included in the review and they were examined for three different outcomes: pain, joint sound and mandibular motion. English papers were only selected. Results: Even though the low number of studies in this field, arthrocentesis with platelet-rich plasma and platelet-rich plasma injections in temporomandibular disorders’ management were found to be effective in reducing pain and joint sound as well as in improving mandibular motion in a maximum follow-up of 24 months. Conclusion: Comparison to arthrocentesis alone or to HA use in arthrocentesis or by injections provided encouraging results in terms of the effectiveness of platelet-rich plasma use.