Ultrasound guidance has improved the accuracy and safety of peripheral nerve blocks, yet intraneural and even intrafascicular needle placement remains possible. The true incidence of fascicular injury after direct nerve transfixion is uncertain due to limited histological data. This study aimed to determine the frequency of fascicular damage after needle transfixion of the sciatic nerve using a human anatomical model. A sciatic nerve segment was harvested from a fresh-frozen male cadaver without neurological disease. One hundred full-thickness transfixions were performed using a 22-gauge sharp needle, simulating accidental intraneural penetration. Each transfixion was replicated using a standardized technique. The nerve was fixed in formalin, sectioned every 5 mm, embedded in paraffin, and stained with hematoxylin and eosin for histological evaluation. The presence of fascicular injury or displacement was assessed microscopically. Descriptive statistics were used to summarize findings, and proportions with 95

BACKGROUND:The increasing availability of body donations and the expansion of reference centers provide forensic clinical anatomy with the opportunity to experimentally reproduce, in ex vivo settings, the effects of specific interactions on the human body, such as needle-tissue interaction in medical procedures. OBJECTIVES:The primary objective of this study was to develop a reproducible, standardized benchtop methodology that enables the identification of the trajectory traveled by the needle when piercing soft tissue, causing detectable iatrogenic tissue damage. MATERIAL AND METHODS:Skeletal muscle tissue samples were harvested from a fresh-frozen 78-year-old male body housed at our Reference Center, Center for Body Donation. Needle transfixions were then tested using a novel technique designed for this purpose (PassTrue® methodology): full-thickness tissue transfixion by a needle, insertion into the needle of a coaxial thread, grasping the thread with forceps, and needle withdrawal, so that the in-place thread indicates the route of transfixion. This procedure was tested against the control procedure without a thread. RESULTS:Microscopic analysis revealed a pattern consistent with the needle's course during transfixion in all cases with the PassTrue® technique (10/10), but not in controls (0/10). CONCLUSION:Our novel methodology improves the efficiency of assessing needle-tissue interactions, enabling identification of the needle's trajectory within biological tissues.

OBJECTIVES:To compare injectate spread between superficial parasternal intercostal plane (SPIP) and deep parasternal intercostal plane (DPIP) blocks, and to evaluate anatomical factors relevant to procedural safety. We hypothesized that DPIP blocks provide greater cranio-caudal distribution than SPIP blocks. DESIGN:An anatomical cadaveric study. SETTING:Secondary-level academic anatomy facility in northern Italy, within a body donation program. PARTICIPANTS:Five fresh-frozen human cadavers (10 hemithoraces). INTERVENTIONS:Ultrasound-guided SPIP and DPIP blocks were performed bilaterally at the third intercostal level using a 22-gauge, 50 mm needle. Each injection delivered 20 mL of diluted black tissue-marking dye (1:5 ratio with saline). MEASUREMENTS AND MAIN RESULTS:Gross dissection assessed the cranio-caudal spread of dye by the number of intercostal spaces. Histology measured the distance between the internal thoracic artery and the fourth rib. DPIP blocks spread across more intercostal spaces than SPIP blocks (median 4, IQR 4-5 vs median 2, IQR 2-2; p < 0.001). Histological analysis showed the internal thoracic artery was a median 1.9 mm (IQR 1.7-2.2) from the fourth rib, separated only by soft tissue. CONCLUSIONS:DPIP blocks produce a wider craniocaudal spread than SPIP blocks, which may enhance clinical efficacy. However, their close proximity to the internal thoracic artery and pleura underscores safety considerations.

The introduction of artificial intelligence (AI) in healthcare has created novel challenges for the field of medical malpractice. As healthcare professionals increasingly rely on AI in their decision-making processes, traditional medicolegal assessments may struggle to adapt. It is essential to examine AI's role in clinical care - both its current applications and future advancements - to clarify accountability for diagnostic and therapeutic errors. Clinical decision support systems (CDSSs), in particular, unlike other traditional medical technologies, work as co-decision makers alongside physicians. They function through the elaboration of patient information, medical knowledge, learnt patterns, etc., to generate a decision output (e.g., the suggested diagnosis), which should then be evaluated by the physician. In light of the AI Act, CDSSs cannot function fully autonomously, but instead physicians are to be assigned an oversight role. It is questionable, however, whether it would always be appropriate to assign full responsibility, and consequently liability, to the physician. This would be especially true if oversight is limited to reviewing outputs generated by the CDSS in a manner that leaves no real control in the hands of the physician. Future research should aim to define clear liability allocation frameworks and design workflows that ensure effective oversight, thereby preventing unfair liability burdens.

The concept of "gender" refers to the socially constructed characteristics that define feminine or masculine behavior, which are constantly changing and can influence access to healthcare and patterns of help-seeking. These factors significantly impact forensic toxicology, a key area within the medicolegal landscape, forcing the adoption of a gender-sensitive approach to better understand the differing impacts of substances on men and women. Research indicates significant disparities in drug use between genders; men are more likely to abuse alcohol and illicit drugs, while women tend to use prescription medications. Although men typically show higher rates of driving under influence (DUI) related to alcohol, significant alcohol-related DUI cases also exist among women. In postmortem toxicology, gender affects drug pharmacokinetics and pharmacodynamics, with a pressing need for more research focused on women's specific toxic and fatal ranges. The rise of new psychoactive substances (NPS) presents additional challenges; while most users are male, the gender gap appears to be narrowing. Further investigation into the gender differences in drug usage and effects, particularly regarding NPS, is essential for improving justice system responses and healthcare delivery. A gender-based approach in forensic toxicology is vital for addressing these issues effectively.

Multidirectional instability (MDI) of the shoulder joint involves the looseness of the joint capsule in multiple directions, resulting in difficulties in keeping the head of the humerus centered within the glenoid fossa. There is still considerable debate about the optimal treatment approach, ranging from conservative management to surgical intervention and it is even more challenging for complex or bilateral cases. An 18-year-old male with a rare congenital bilateral multidirectional glenohumeral hyperlaxity and instability is reported. After excluding other medical conditions, the patient was diagnosed with benign joint hypermobility syndrome. Despite undergoing four months of conservative treatment with physical therapy, there was no significant improvement, leading to the decision for bilateral surgical intervention. The procedure combined an autograft Posterior Bone Block procedure with the Arthroscopic Subscapularis Augmentation (ASA) Technique to enhance anterior stability. The latter involved a tenodesis of the superior third part of the subscapularis tendon. The fixating hole was drilled at the top position of the glenoid edge, and the insertion on the subscapularis tendon was positioned inferiorly to the superior border of the tendon. After surgery, an accelerated post-operative rehabilitation protocol for each shoulder was implemented. At the one-year follow-up after the second surgery, the patient demonstrated substantial improvements in shoulder stability and functional outcomes. The Constant Shoulder Score (CSS) improved from 53 to 77 for both shoulders, indicating a 45.3% improvement and progression from “Moderate” to “Good” function. Similarly, the American Shoulder and Elbow Surgeons (ASES) Orthopaedic Scores improved from 58.33 to 88.32 for the right shoulder (51.4% improvement) and from 61.65 to 94.99 for the left shoulder (54.1% improvement), reflecting a transition from “Fair” to “Good” and “Excellent” function, respectively. Importantly, no short- or medium-term adverse events were reported, and the patient achieved a full return to normal activities. The combination of autograft Posterior Bone Block and ASA techniques has proven to be a successful option in this case for restoring function and stability, even in rare and complex cases of congenital bilateral multidirectional glenohumeral hyperlaxity and instability. Nonetheless, in these complex cases, critical surgical, anatomical, and forensic issues should be carefully considered.

In the original publication [...].

Perineural dexamethasone is widely used as an adjuvant to local anesthetics in regional anesthesia to prolong analgesia. However, concerns persist regarding its potential neurotoxic effects, particularly when administered perineurally. This systematic review aims to synthesize preclinical evidence evaluating the neurotoxicity or neuroprotective properties of perineural dexamethasone. A systematic search of PubMed, CENTRAL, Scopus, and Embase was conducted through May 22, 2025. Eligible studies included in vivo or in vitro preclinical models assessing the neurotoxic or neuroprotective effects of perineural dexamethasone compared to control conditions. Risk of bias was assessed using the SYRCLE tool for in vivo studies and a narrative evaluation for in vitro studies. A total of 14 studies (11 in vivo, 3 in vitro) met inclusion criteria. In vitro studies showed that dexamethasone alone was not neurotoxic at clinically relevant doses but could enhance cytotoxicity when combined with local anesthetics at higher concentrations. In vivo models generally demonstrated no significant long-term nerve inflammation, degeneration or demyelination, with some early protective effects observed in perineural dexamethasone groups. However, all in vivo studies were rated at high risk of bias. In nerve injury models, dexamethasone reduced apoptotic and inflammatory markers when administered immediately post-injury, with limited effect when delayed. Preclinical evidence supports the general safety of low-dose, preservative-free perineural dexamethasone. Nonetheless, high-dose use, additives, and application in patients with neuropathies may pose risks. Given the high risk of bias in existing studies and minimal added benefit over systemic administration, clinical caution is advised.

Mechanical asphyxiation has been a common method used to commit homicide, including femicide, throughout history. A recent report by the United Nations has shed light on the issue of misidentification and concealment of gender-related killings, which makes it difficult to effectively fight against it. Forensic pathologists are frequently asked to examine cases involving suspected asphyxia to determine whether other persons have been involved. Therefore, medicolegal experts must look for signs of occlusion of the oral/nasal orifices, compression of the neck, or specific signs such as the "facie sympathique". There are situations where the physical signs are not distinctive enough to diagnose asphyxia, especially in cases where the individual has limited ability to resist external compression. In such cases, judicial autopsies should include an anatomical dissection of the neck structures through a layer-by-layer progression. It is important to search for the Amussat's sign, e.g., as part of a Forensic Clinical Anatomy approach. Additionally, individual anatomical variations, age or artefactual modifications, must be considered for the correct interpretation of findings. Microscopic examinations could aid in the diagnosis by providing additional findings, and several attempts have been made to identify unique markers of asphyxia through various laboratory techniques such as biochemistry, radiology and miRNA studies. However, no single finding or method has been identified as definitive. In the future, biomedical-legal sciences will have to rely on scientific research and the retrospective case series to provide a scientific framework on which to base their hypothesis, giving weight to evidence in the trial.

Forensic toxicology faces several challenges in research and daily practice, including new drugs and futuristic technologies requiring innovative testing methods and continuous education and training of professionals. One of the most pressing issues in recent years is the emergence of novel psychoactive substances, often created by modifying the chemical structure of existing drugs to produce compounds with similar effects that are not yet regulated and lack standardized references. To overcome this challenge, forensic toxicologists have employed a range of analytical methods, including qualitative and quantitative analysis using highly sensitive technologies such as liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS), which are the most reliable and accurate methods for detecting drugs in biological samples. Liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS) is becoming the gold standard for detecting controlled substances, their derivatives and metabolites. Despite advancements in testing methods, challenges persist in forensic toxicology. As such, the field must invest in research and development to improve testing methods, utilize cutting-edge technologies, increase funding for training programs, and promote multidisciplinary interactions.

Carbon nanotubes (CNT) are promising electroconductive nano-scale materials for neuroregeneration. Herein, we report on a new electroconductive composite scaffold made of the polymer 1% oxidized polyvinyl alcohol (OxPVA) combined with functionalized water soluble multiwalled CNT (OxPVA + MWCNT-S) (diazotization reaction). Preliminarily, MWCNT-S were characterized to evaluate the reaction outcome, the degree of functionalization and the dispersibility in water. Thereafter, OxPVA + MWCNT-S nanocomposite membranes were fabricated and analyzed for physicochemical properties (Raman spectroscopy, thermal decomposition, calorimetric properties, electroconductivity), macroscopic appearance and ultrastructure, mechanical behavior, in vitro cytotoxicity and in vivo biocompatibility. In parallel, OxPVA + MWCNT-S membranes with a linear pattern were also developed and analyzed for interaction with SH-SY5Y cells. Compared to OxPVA, the presence of MWCNT-S (only 0.016 wt%) significantly increased polymer conductivity and imparted a certain porosity without altering mechanical behaviour, as corroborated by uniaxial tensile tests. Neither cytotoxicity nor local signs of inflammation were detected in vitro and after subcutaneous implantation (14 and 42 days), proving composite material biocompatibility. OxPVA + MWCNT-S nanocomposite revealed as promising for future electroconductive conduits free from toxic effects amenable to CNT agglomeration within the polymer. Ideally, nerve lesions with wide gaps, may be effectively supported by those “active” devices, overcoming limitations of the available ones. Despite preliminary data, the presence of a linear pattern confirmed to have a beneficial effect over the scaffold/cells interaction.

Carbon nanotubes (CNT) are promising electroconductive nano-scale materials for neuroregeneration. Herein, we report on a new electroconductive composite scaffold made of the polymer 1% oxidized polyvinyl alcohol (OxPVA) combined with functionalized water soluble multiwalled CNT (OxPVA + MWCNT-S) (diazotization reaction). Preliminarily, MWCNT-S were characterized to evaluate the reaction outcome, the degree of functionalization and the dispersibility in water. Thereafter, OxPVA + MWCNT-S nanocomposite membranes were fabricated and analyzed for physicochemical properties (Raman spectroscopy, thermal decomposition, calorimetric properties, electroconductivity), macroscopic appearance and ultrastructure, mechanical behavior, in vitro cytotoxicity and in vivo biocompatibility. In parallel, OxPVA + MWCNT-S membranes with a linear pattern were also developed and analyzed for interaction with SH-SY5Y cells. Compared to OxPVA, the presence of MWCNT-S (only 0.016 wt%) significantly increased polymer conductivity and imparted a certain porosity without altering mechanical behaviour, as corroborated by uniaxial tensile tests. Neither cytotoxicity nor local signs of inflammation were detected in vitro and after subcutaneous implantation (14 and 42 days), proving composite material biocompatibility. OxPVA + MWCNT-S nanocomposite revealed as promising for future electroconductive conduits free from toxic effects amenable to CNT agglomeration within the polymer. Ideally, nerve lesions with wide gaps, may be effectively supported by those "active" devices, overcoming limitations of the available ones. Despite preliminary data, the presence of a linear pattern confirmed to have a beneficial effect over the scaffold/ cells interaction.

Background: Nowadays, a challenging task concerns the biomechanical study of the human lower urinary tract (LUT) due to the variety of its tissues and the low availability of samples. Methods: This work attempted to further extend the knowledge through a comprehensive mechanical characterization of the male LUT by considering numerous tissues harvested from the same cadaver, including some never studied before. Samples of the bladder, urethra, prostate, Buck’s fascia and tunica albuginea related to corpora cavernosa were considered and distinguished according to testing direction, specimen conformation and anatomical region. Uniaxial tensile and indentation tests were performed and ad hoc protocols were developed. Results: The tissues showed a non-linear and viscoelastic response but different mechanical properties due to their specific functionality and microstructural configuration. Tunica albuginea longitudinally displayed the highest stiffness (12.77 MPa), while the prostate transversally had the lowest one (0.66 MPa). The minimum stress relaxation degree (65.74%) was reached by the tunica albuginea and the maximum (88.55%) by the bladder. The prostate elastic modulus was shown to vary according to the presence of pathological changes at the microstructure. Conclusions: This is the first experimental work that considers the mechanical evaluation of the LUT tissues in relation to the same subject, setting the basis for future developments by expanding the sample population and for the development of effective in silico models to improve the solutions for most LUT pathologies.

BackgroundA growing number of studies investigated the factors that contribute to driving under the influence (DUI) of alcohol in relation to gender. However, a gendered approach of the scientific evidence is missing in the literature. To fill this gap, a gender-driven systematic review on real case studies of the last two decades was performed. In addition to the gender of the drivers involved, major independent variables such as the period of recruitment, the type of drivers recruited, and the geographical area where the study was conducted, were examined. Afterwards, a meta-analysis was performed comparing alcohol-positive rates (APR) between male and female drivers in three subgroups of drivers: those involved in road traffic accidents, those randomly tested on the road, and volunteers.MethodsThree databases were searched for eligible studies in October 2023. Real-case studies reporting APR in man and women convicted for DUI of alcohol worldwide were included. Univariate analysis by ANOVA with post-hoc tests identified the independent variables with a significant impact on the dependent variable APR, according to a relationship subsequently investigated by standard multiple linear regression. The meta-analysis of random effects estimates was performed to investigate the change in overall effect size (measured by Cohen's d standardized mean difference test) and 95% confidence interval (CI).ResultsAmong papers addressing driver gender, univariate analysis of independent variables revealed a higher Alcohol Positive Rate (APR) in men, particularly in drivers involved in crashes, with a noticeable decrease over time. Analyzing the gender of drivers involved in crashes, the meta-analysis showed that men had a significantly higher APR (30.7%; 95%CI 26.8-35.0) compared to women (13.2%; 95%CI 10.7-16.1). However, in drivers randomly tested, there was no significant difference in APR between genders (2.1% for men and 1.4% for women), while in volunteers, there was a statistically significant difference in APR with 3.4% (95%CI 1.5-7.6) for men and 1.1% (95%CI 0.5-2.7) for women.ConclusionDespite a progressive decrease in the epidemiological prevalence of alcohol-related DUI over time, this phenomenon remains at worryingly high levels among drivers involved in road traffic accidents in both genders, with a higher prevalence in men. It's important for policymakers, professionals, and scientists to consider gender when planning research, analysis, interventions, and policies related to psychoactive substances, such as alcohol or other licit drugs. Forensic sciences can play a vital role in this regard, enabling a thorough analysis of gender gaps in different populations.

Plantar adipose tissue is a connective tissue whose structural configuration changes according to the foot region (rare or forefoot) and is related to its mechanical role, providing a damping system able to adsorb foot impact and bear the body weight. Considering this, the present work aims at fully describing the plantar adipose tissue’s behaviour and developing a proper constitutive formulation. Unconfined compression tests and indentation tests have been performed on samples harvested from human donors and cadavers. Experimental results provided the initial/final elastic modulus for each specimen and assessed the non-linear and time-dependent behaviour of the tissue. The different foot regions were investigated, and the main differences were observed when comparing the elastic moduli, especially the final elastic ones. It resulted in a higher level for the medial region (89 ± 77 MPa) compared to the others (from 51 ± 29 MPa for the heel pad to 11 ± 7 for the metatarsal). Finally, results have been used to define a visco-hyperelastic constitutive model, whose hyperelastic component, which describes tissue non-linear behaviour, was described using an Ogden formulation. The identified and validated tissue constitutive parameters could serve, in the early future, for the computational model of the healthy foot.

Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it is still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms. Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia/respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in the dorsal medulla and in the substantia nigra of five COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2 and characterize the role of brainstem inflammation in COVID-19, its potential implications for neurodegeneration, especially in Parkinson's disease, require further investigations.

Opening the foramen transversarium of the cervical vertebrae is necessary for accessing the vertebral vessels. There are no specialist tools for cutting the anterior lamina of the transverse processes, and alternatives lead to questionable results. A novel tool, the transversoclasiotome, is described and tested. The literature and patent databases were systematically reviewed. A blueprint of the transversoclasiotome was created, and the prototype was tested through autopsy on ten fresh-frozen cadavers within our Body Donation Program. The transversoclasiotome consists of two delicate branches mounted as a scissor, one a cutting jaw and the other a knocker with a rounded tip, both angled 30° to the principal axis. The jaws shut, facing each other in parallel. The cutting jaw corresponds to a slit on the knocker profile without protruding beyond it even when entirely closed. It acts by cutting and wedging. The testing autopsies demonstrated its suitability for its purpose, with an adequate response to the pressure exerted on the bone lamina. The section cut cleanly, without sliding off while closing on the bone. The vertebral vessels were not injured either during instrument insertion or cutting. Their morphological features are described. The transversoclasiotome has been proven appropriate for sectioning the anterior lamina of transverse processes of the cervical vertebrae. It meets the needs of clinical anatomy in teaching and training clinicians or surgeons, forensic clinical anatomy during medico-legal investigation, and research.

Oxidized polyvinyl alcohol (OxPVA) is a new polymer for the fabrication of nerve conduits (NCs). Looking for OxPVA device optimization and coupling it with a natural sheath may boost bioactivity. Thus, OxPVA/chitosan sponges (ChS) as hybrid scaffolds were investigated to predict in the vivo behaviour of two-layered NCs. To encourage interaction with cells, ChS were functionalized with the self-assembling-peptide (SAP) EAK, without/with the laminin-derived sequences -IKVAV/-YIGSR. Thus, ChS and the hybrid scaffolds were characterized for mechanical properties, ultrastructure (Scanning Electron Microscopy, SEM), bioactivity, and biocompatibility. Regarding mechanical analysis, the peptide-free ChS showed the highest values of compressive modulus and maximum stress. However, among +EAK groups, ChS+EAK showed a significantly higher maximum stress than that found for ChS+EAK-IKVAV and ChS+EAK-YIGSR. Considering ultrastructure, microporous interconnections were tighter in both the OxPVA/ChS and +EAK groups than in the others; all the scaffolds induced SH-SY5Y cells' adhesion/proliferation, with significant differences from day 7 and a higher total cell number for OxPVA/ChS+EAK scaffolds, in accordance with SEM. The scaffolds elicited only a slight inflammation after 14 days of subcutaneous implantation in Balb/c mice, proving biocompatibility. ChS porosity, EAK 3D features and neuro-friendly attitude (shared with IKVAV/YIGSR motifs) may confer to OxPVA certain bioactivity, laying the basis for future appealing NCs.

Volumetric muscle loss (VML) is the traumatic/surgical loss of skeletal muscle, causing aesthetic damage and functional impairment. Suboptimal current surgical treatments are driving research towards the development of optimised regenerative therapies. The grafting of bioengineered scaffolds derived from decellularized skeletal muscle may be a valid option to promote structural and functional healing. In this work, a cellular human diaphragm was considered as a scaffold material for VML treatment. Decellularization occurred through four detergent-enzymatic protocols involving (1) sodium dodecyl sulfate (SDS), (2) SDS + TergitolTM, (3) sodium deoxycholate, and (4) TergitolTM. After decellularization, cells, DNA (≤50 ng/mg of tissue), and muscle fibres were efficiently removed, with the preservation of collagen/elastin and 60%–70% of the glycosaminoglycan component. The detergent-enzymatic treatments did not affect the expression of specific extracellular matrix markers (Collagen I and IV, Laminin), while causing the loss of HLA-DR expression to produce non-immunogenic grafts. Adipose-derived stem cells grown by indirect co-culture with decellularized samples maintained 80%–90% viability, demonstrating the biosafety of the scaffolds. Overall, the tested protocols were quite equivalent, with the patches treated by SDS + TergitolTM showing better collagen preservation. After subcutaneous implant in Balb/c mice, these acellular diaphragmatic grafts did not elicit a severe immune reaction, integrating with the host tissue.