Structural parameters defining distribution of collagen fiber directions in human carotid arteries.

Collagen fiber arrangement is decisive for constitutive description of anisotropic mechanical response of arterial wall. In this study, their orientation in human common carotid artery was investigated using polarized light microscopy and an automated algorithm giving more than 4·106 fiber angles per slice. In total 113 slices acquired from 18 arteries taken from 14 cadavers were used for fiber orientation in the circumferential-axial plane. All histograms were approximated with unimodal von Mises distribution to evaluate dominant direction of fibers and their concentration parameter. 10 specimens were analyzed also in circumferential-radial and axial-radial planes (2-4 slices per specimen in each plane); the portion of radially oriented fibers was found insignificant. In the circumferential-axial plane, most specimens showed a pronounced unimodal distribution with angle to circumferential direction µ = 0.7° ± 9.4° and concentration parameter b = 3.4 ± 1.9. Suitability of the unimodal fit was confirmed by high values of coefficient of determination (mean R2 = 0.97, median R2 = 0.99). Differences between media and adventitia layers were not found statistically significant. The results are directly applicable as structural parameters in the GOH constitutive model of arterial wall if the postulated two fiber families are unified into one with circumferential orientation.

Biomechanical performance of dental implants inserted in different mandible locations and at different angles: A finite element study.

STATEMENT OF PROBLEM: Accurate implant placement is essential for the success of dental implants. This placement influences osseointegration and occlusal forces. The freehand technique, despite its cost-effectiveness and time efficiency, may result in significant angular deviations compared with guided implantation, but the effect of angular deviations on the stress-strain state of peri-implant bone is unclear. PURPOSE: The purpose of this finite element analysis (FEA) study was to examine the effects of angular deviations on stress-strain states in peri-implant bone. MATERIAL AND METHODS: Computational modeling was used to investigate 4 different configurations of dental implant positions, each with 3 angles of insertion. The model was developed using computed tomography images, and typical mastication forces were considered. Strains were analyzed using the mechanostat hypothesis. RESULTS: The location of the implant had a significant impact on bone strain intensity. An angular deviation of ±5 degrees from the planned inclination did not significantly affect cancellous bone strains, which primarily support the implant. However, it had a substantial effect on strains in the cortical bone near the implant. Such deviations also significantly influenced implant stresses, especially when the support from the cortical bone was uneven or poorly localized. CONCLUSIONS: In extreme situations, angular deviations can lead to overstraining the cortical bone, risking implant failure from unfavorable interaction with the implant. Accurate implant placement is essential to mitigate these risks.

Donor nerve selection in free gracilis muscle transfer for facial reanimation. A systematic review and meta-analysis of clinical outcomes.

BACKGROUND: One of the critical factors in facial reanimation is selecting the donor nerve. The most favored neurotizers are the contralateral facial nerve with a cross-face nerve graft (CFNG) and motor nerve to the masseter (MNM). A relatively new dual innervation (DI) method has shown successful results. This study aimed to compare the clinical outcomes of different neurotization strategies for free gracilis muscle transfer (FGMT). METHODS: The Scopus and WoS databases were queried with 21 keywords. Three-stage article selection was performed for the systematic review. Articles presenting quantitative data for commissure excursion and facial symmetry were included in meta-analysis, using random-effects model. ROBINS-I tool and Newcastle-Ottawa scale were used to assess bias and study quality. RESULTS: One hundred forty-seven articles containing FGMT were systematically reviewed. Most studies indicated CFNG as the first choice. MNM was primarily indicated in bilateral palsy and in elderly. Clinical outcomes of DI studies were promising. 13 studies including 435 observations (179 CFNG, 182 MNM, 74 DI) were eligible for meta-analysis. The mean change in commissure excursion was 7.15 mm (95% CI: 4.57-9.72) for CFNG, 8.46 mm (95% CI: 6.86-10.06) for MNM, and 5.18 mm (95% CI: 4.01-6.34) for DI. In pairwise comparisons, a significant difference was found between MNM and DI (p = 0.0011), despite the superior outcomes described in DI studies. No statistically significant difference was found in resting and smile symmetry (p = 0.625, p = 0.780). CONCLUSIONS: CFNG is the most preferred neurotizer, and MNM is a reliable second option. Outcomes of DI studies are promising, but more comparison studies are needed to draw conclusions. Our meta-analysis was limited by incompatibility of the assessment scales. Consensus on a standardized assessment system would add value to future studies.

Substantial decrease in SARS-CoV-2 RNA after fixation of cadavers intended for anatomical dissection.

With the onset of the COVID-19 pandemic, a problem arose with classic body donation programmes for obtaining cadavers for anatomical dissections, science and research. The question has emerged whether bodies of individuals who died of COVID-19 or were infected by SARS-CoV-2 could be admitted to Departments of Anatomy. To determine the risk of SARS-CoV-2 transmission to employees or students, the presence and stability of SARS-CoV-2 RNA in cadavers after fixation agents' application and subsequent post-fixation baths over time were examined. The presence of viral RNA in swabs from selected tissues was assessed by the standardized routine RNA isolation protocol and subsequent real-time PCR analysis. To support the results obtained from the tissue swabs, samples of RNA were exposed in vitro to short and long-term exposure to the components of the injection and fixation solutions used for the bodies' conservation. Substantial removal of SARS-CoV-2 RNA was observed in post-mortem tissue following perfusion with 3.5% phenol, 2.2% formaldehyde, 11.8% glycerol and 55% ethanol, and subsequent post-fixation in an ethanol bath. In vitro experiments showed significant effects of formaldehyde on SARS-CoV-2 RNA, while phenol and ethanol showed only negligible effects. We conclude that cadavers subjected to fixation protocols as described here should not pose a considerable risk of SARS-CoV-2 infection while being handled by students and staff and are, therefore, suitable for routine anatomical dissections and teaching.

Impact of analgesic regimen on patient outcome following subarachnoid hemorrhage: positive adjuvant effects of metamizole.

INTRODUCTION: Various analgesics are used to control intense headaches in patients following subarachnoid hemorrhage. In addition to pain control, it has been shown that some analgesics can affect various pathophysiological cascades. Therefore, we devised a study to assess whether the use of metamizole has a significant impact on the development of ischemic complications, hydrocephalus, and the overall outcome in patients following aneurysmal subarachnoid hemorrhage in the context of the other non-opioids and opioids effects. METHODS: In our retrospective, single-center cohort study, we enrolled 192 patients diagnosed with subarachnoid hemorrhage. We recorded their initial clinical status, comorbidities, and the daily dosage of analgesics over 14 days of hospitalization after the onset of subarachnoid hemorrhage. Using univariate and subsequent multivariate logistic regression analysis, we assessed the influence of various factors, including analgesics, on the development of delayed cerebral ischemia and hydrocephalus, as well as on 2-week and 6-month outcomes. RESULTS: Although the administration of non-opioids, in general, had no effect on the development of delayed cerebral ischemia or hydrocephalus, the use of metamizole as the main analgesic was associated with a significantly lower chance of poor outcome at both 2-weeks and 6-months, as well as the development of delayed cerebral ischemia. As opioids were indicated primarily for analgosedation in mechanically ventilated patients with poor clinical status, their usage was associated with a significantly higher chance of poor outcome, delayed cerebral ischemia, and hydrocephalus. CONCLUSION: Our results suggest that the prescription of metamizole may be associated with better outcomes and a lower chance of delayed cerebral ischemia development in patients after subarachnoid hemorrhage. Considering the retrospective nature of our study and the limited worldwide availability of metamizole due to its prohibition in some countries, our results do not demonstrate a clear benefit but rather justify the need for subsequent prospective studies.

Use of free radial forearm and pronator quadratus muscle flap: Anatomical study and clinical application.

The authors present an anatomical study and clinical experience with radial forearm flap (RFF) and pronator quadratus muscle (PQM) application in the reconstruction of various body areas. The aim was to describe the anatomical placement and proportions of the PQM, the anatomical location of the major arterial branch of the radial artery supplying the PQM, and the application of this knowledge in clinical practice. The anatomical study was based upon an analysis of 13 fresh adult cadaver upper extremities, of which nine were female and four male; both arms from the same donors were used in four cases. The study of the PQM was performed using a dye-containing intraarterial injection, standard macro- and micro-preparation techniques, and chemical digestion. The data on the PQM size in males and females, thickness of the radial artery branch (the principal artery nourishing the muscle), and its position were analysed. The radial artery branch nourishing the PQM was identified in all cadaveric specimens of the anatomical study. In addition, 12 patients underwent reconstructions of soft and bony tissue defects using a RFF + PQM (pedicled or free flap). The radial artery branch perfusing the PQM was identified in all cases. The flap was used for the management of defects of the head (seven cases), arm (three cases) and lower leg (two cases). The harvest site healed well in all cases and, with the exception of one case in which a partial necrosis of the flap was observed, all flaps remained viable, which demonstrated the safety of the method.

Current issues of body donation for teaching and research purposes and their use in the Czech Republic.

Since time immemorial, bodies of deceased have been an integral part of teaching anatomy, and therefore the study of medicine. Without them, the teaching of anatomy, clinical anatomy and many research projects could not be realized. Nowadays, the European countries allow to use exclusively bodies of the deceased donors. Recently, we have registered a growing trend in the needs of the bodies not only for the purposes of medical education, but also for those of clinical anatomy. The question also arose of the suitability of using COVID-19 positive donors or the legislative possibility of obtaining bodies in the absence of donors in the donor program. Our communication addresses current issues of body donation for teaching and research purposes and their use in the Czech Republic.

The Use of Confocal Laser Endomicroscopy in Diagnosing Barrett's Esophagus and Esophageal Adenocarcinoma.

Confocal laser endomicroscopy (CLE) is a diagnostic technique that enables real-time microscopic imaging during microscopic examination and evaluation of epithelial structures with 1000-fold magnification. CLE can be used in the diagnosis of various pathologies, in pneumology, and in urology, and it is very widely utilized in gastroenterology, most importantly in the diagnosis of Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), biliary strictures, and cystic pancreatic lesions. A literature search was made in MEDLINE/PubMed and Google Scholar databases while focusing on diagnostics using CLE of BE and EAC. We then examined randomized and observational studies, systematic reviews, and meta-analyses relating to the utilization of CLE in BE and EAC diagnostics. Here, we discuss whether CLE can be a suitable diagnostic method for surveillance of BE. Even though many studies have proven that CLE increases diagnostic accuracy in detecting neoplastic transformation of BE, CLE is still not used as a standard diagnostic tool in BE surveillance due to a deficiency of scientific evidence. More studies and data are needed if CLE is to find a place as a new technique in BE surveillance.

The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments.

The response of the blood-brain barrier (BBB) following a stroke, including subarachnoid hemorrhage (SAH), has been studied extensively. The main components of this reaction are endothelial cells, pericytes, and astrocytes that affect microglia, neurons, and vascular smooth muscle cells. SAH induces alterations in individual BBB cells, leading to brain homeostasis disruption. Recent experiments have uncovered many pathophysiological cascades affecting the BBB following SAH. Targeting some of these pathways is important for restoring brain function following SAH. BBB injury occurs immediately after SAH and has long-lasting consequences, but most changes in the pathophysiological cascades occur in the first few days following SAH. These changes determine the development of early brain injury as well as delayed cerebral ischemia. SAH-induced neuroprotection also plays an important role and weakens the negative impact of SAH. Supporting some of these beneficial cascades while attenuating the major pathophysiological pathways might be decisive in inhibiting the negative impact of bleeding in the subarachnoid space. In this review, we attempt a comprehensive overview of the current knowledge on the molecular and cellular changes in the BBB following SAH and their possible modulation by various drugs and substances.

Lapidus arthrodesis in combination with arthrodesis of the first metatarsophalangeal joint-biomechanical cadaver study comparing two methods of fixation.

AIMS: To assess the results of a biomechanical test of cadaveric specimens, comparing 2 methods of fixation of modified Lapidus arthrodesis in combination with arthrodesis of the first metatarsophalangeal joint. METHODS: A total of 12 cadaveric specimens were used in the test. Arthrodesis of the first MTP joint was in all patients fixed with a Variable Angle LCP 1st MTP Fusion Plate 2.4/2.7. Two methods of fixation of the Lapidus arthrodesis were compared, i.e. fixation with two screws in the PS (plate-screw) version versus fixation with X-Locking Plate 2.4/2.7 in the PP (plate-plate) version. Measurements were obtained with the use of a testing machine ZWICK Z 020-TND with an optical device Mercury RT for measuring deformities. Each specimen was subjected to 3 loading options, a. displacement 5 mm, the support is placed under the proximal phalanx, b. displacement 5 mm, the support is placed under the first metatarsal head and c. load to failure, the support is placed under the first metatarsal head. RESULTS: In all specimens the PS construct showed a statistically considerably higher stiffness than the PP construct. In all specimens treated with the PP construct the load to failure was lower than in the PS construct. For loading mode a., at a significance level of 0.05 (P<0.05), the P-value was 0.036, for mode b. the P-value was 0.007 and for loading mode c. the P-value was 0.006. In addition, age-related decrease in stiffness of the specimen was proved at a significance level of 5% (P=0.004). CONCLUSION: In all the three loading modes, the PS (plate-screw) construct showed a statistically higher stiffness than the PP (plate-plate) construct.

Toll-Like Receptor 9-Mediated Neuronal Innate Immune Reaction Is Associated with Initiating a Pro-Regenerative State in Neurons of the Dorsal Root Ganglia Non-Associated with Sciatic Nerve Lesion.

One of the changes brought about by Wallerian degeneration distal to nerve injury is disintegration of axonal mitochondria and consequent leakage of mitochondrial DNA (mtDNA)-the natural ligand for the toll-like receptor 9 (TLR9). RT-PCR and immunohistochemical or Western blot analyses were used to detect TLR9 mRNA and protein respectively in the lumbar (L4-L5) and cervical (C7-C8) dorsal root ganglia (DRG) ipsilateral and contralateral to a sterile unilateral sciatic nerve compression or transection. The unilateral sciatic nerve lesions led to bilateral increases in levels of both TLR9 mRNA and protein not only in the lumbar but also in the remote cervical DRG compared with naive or sham-operated controls. This upregulation of TLR9 was linked to activation of the Nuclear Factor kappa B (NFκB) and nuclear translocation of the Signal Transducer and Activator of Transcription 3 (STAT3), implying innate neuronal immune reaction and a pro-regenerative state in uninjured primary sensory neurons of the cervical DRG. The relationship of TLR9 to the induction of a pro-regenerative state in the cervical DRG neurons was confirmed by the shorter lengths of regenerated axons distal to ulnar nerve crush following a previous sciatic nerve lesion and intrathecal chloroquine injection compared with control rats. The results suggest that a systemic innate immune reaction not only triggers the regenerative state of axotomized DRG neurons but also induces a pro-regenerative state further along the neural axis after unilateral nerve injury.

On the limits of finite element models created from (micro)CT datasets and used in studies of bone-implant-related biomechanical problems.

Patient-specific approach is gaining a wide popularity in computational simulations of biomechanical systems. Simulations (most often based on the finite element method) are to date routinely created using data from imaging devices such as computed tomography which makes the models seemingly very complex and sophisticated. However, using a computed tomography in finite element calculations does not necessarily enhance the quality or even credibility of the models as these depend on the quality of the input images. Low-resolution (medical-)CT datasets do not always offer detailed representation of trabecular bone in FE models and thus might lead to incorrect calculation of mechanical response to external loading. The effect of image resolution on mechanical simulations of bone-implant interaction has not been thoroughly studied yet. In this study, the effect of image resolution on the modeling procedure and resulting mechanical strains in bone was analyzed on the example of cranial implant. For this purpose, several finite element models of bone interacting with fixation-screws were generated using seven computed tomography datasets of a bone specimen but with different image resolutions (ranging from micro-CT resolution of 25 µm to medical-CT resolution of 1250 µm). The comparative analysis revealed that FE models created from images of low resolution (obtained from medical computed tomography) can produce biased results. There are two main reasons: 1. Medical computed tomography images do not allow generating models with complex trabecular architecture which leads to substituting of the intertrabecular pores with a fictitious mass; 2. Image gray value distribution can be distorted resulting in incorrect mechanical properties of the bone and thus in unrealistic or even completely fictitious mechanical strains. The biased results of calculated mechanical strains can lead to incorrect conclusion, especially when bone-implant interaction is investigated. The image resolution was observed not to significantly affect stresses in the fixation screw itself; however, selection of bone material representation might result in significantly different stresses in the screw.

Non-steroidal anti-inflammatory drugs in the pathophysiology of vasospasms and delayed cerebral ischemia following subarachnoid hemorrhage: a critical review.

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition associated with the development of early brain injury (EBI) and delayed cerebral ischemia (DCI). Pharmacological treatment of vasospasm following aSAH currently mainly comprises nimodipine administration. In the past few years, many drugs that can potentially benefit cases of subarachnoid hemorrhage have become available. The objective of this review is to critically assess the effects of non-steroidal anti-inflammatory drugs (NSAIDs) following aSAH. A systematic literature review was conducted following PRISMA guidelines. The search was aimed at studies addressing aSAH and NSAIDs during the 2010 to 2019 period, and it yielded 13 articles. Following the application of search criteria, they were divided into two groups, one containing 6 clinical articles and the other containing 7 experimental articles on animal models of aSAH. Inflammatory cerebral changes after aneurysm rupture contribute to the development of EBI, DCI and cerebral vasospasm. It appears that NSAIDs (especially coxibs) are even more effective in reducing vasospasm than nimodipine. Other beneficial effects of NSAIDs include reduction in mortality, improved functional outcome and increased hypoaggregability. However, despite these positive effects, there is only one randomized, double-blind, placebo-controlled trial showing a tendency towards a better outcome with lower incidence of vasospasm or mortality in patients following aSAH.

Subarachnoid Hemorrhage Increases Level of Heme Oxygenase-1 and Biliverdin Reductase in the Choroid Plexus.

Subarachnoid hemorrhage is a specific, life-threatening form of hemorrhagic stroke linked to high morbidity and mortality. It has been found that the choroid plexus of the brain ventricles forming the blood-cerebrospinal fluid barrier plays an important role in subarachnoid hemorrhage pathophysiology. Heme oxygenase-1 and biliverdin reductase are two of the key enzymes of the hemoglobin degradation cascade. Therefore, the aim of present study was to investigate changes in protein levels of heme oxygenase-1 and biliverdin reductase in the rat choroid plexus after experimental subarachnoid hemorrhage induced by injection of non-heparinized autologous blood to the cisterna magna. Artificial cerebrospinal fluid of the same volume as autologous blood was injected to mimic increased intracranial pressure in control rats. Immunohistochemical and Western blot analyses were used to monitor changes in the of heme oxygenase-1 and biliverdin reductase levels in the rat choroid plexus after induction of subarachnoid hemorrhage or artificial cerebrospinal fluid application for 1, 3, and 7 days. We found increased levels of heme oxygenase-1 and biliverdin reductase protein in the choroid plexus over the entire period following subarachnoid hemorrhage induction. The level of heme oxygenase-1 was the highest early (1 and 3 days) after subarachnoid hemorrhage indicating its importance in hemoglobin degradation. Increased levels of heme oxygenase-1 were also observed in the choroid plexus epithelial cells at all time points after application of artificial cerebrospinal fluid. Biliverdin reductase protein was detected mainly in the choroid plexus epithelial cells, with levels gradually increasing during subarachnoid hemorrhage. Our results suggest that heme oxygenase-1 and biliverdin reductase are involved not only in hemoglobin degradation but probably also in protecting choroid plexus epithelial cells and the blood-cerebrospinal fluid barrier from the negative effects of subarachnoid hemorrhage.

Peripheral Deltorphin II Inhibits Nociceptors Following Nerve Injury.

Clinical and preclinical studies have revealed that local administration of opioid agonists into peripheral tissue attenuates inflammatory pain. However, few studies have examined whether peripherally restricted opioids are effective in reducing mechanical allodynia and hyperalgesia that usually follows nerve injury. The aim of the present study was to determine whether the mechanical responsiveness of C-fiber mechanical nociceptors innervating skin under neuropathic pain conditions is depressed by direct activation of delta opioid receptors (DORs) on their peripheral terminals. A murine model of peripheral neuropathic pain was induced with a spared nerve (tibial) injury, in which mice survived 7 or 28 days after surgery before electrophysiological testing began. Control groups comprised naïve and sham-operated animals. An ex vivo preparation of mouse plantar skin with attached tibial nerve was used to examine electrophysiologically the effects of the selective DOR agonist, deltorphin II, on the response properties of individual cutaneous C-fiber nociceptors. In contrast to naïve and sham-operated animals, deltorphin II induced an inhibition of the mechanical responsiveness of C-fiber mechanical nociceptors innervating skin under neuropathic conditions. The effects of deltorphin II were concentration-dependent and prevented by pretreatment with naltrindole indicating DOR-mediated inhibitory effects of deltorphin II. Our results provide the first direct evidence for expression of functional DORs on mechanical nociceptors innervating skin in an animal model of neuropathic pain.

Choroid plexus and the blood-cerebrospinal fluid barrier in disease.

The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research.

Subarachnoid Hemorrhage Induces Dynamic Immune Cell Reactions in the Choroid Plexus.

Subarachnoid hemorrhage (SAH) is a specific form of hemorrhagic stroke that frequently causes intracranial hypertension. The choroid plexus (CP) of the brain ventricles is responsible for producing cerebrospinal fluid and forms the blood - cerebrospinal fluid barrier. The aim of the current study was to determine whether SAH induces an immune cell reaction in the CP and whether the resulting increase in intracranial pressure (ICP) itself can lead to cellular changes in the CP. SAH was induced by injecting non-heparinized autologous blood to the cisterna magna. Artificial cerebrospinal fluid (ACSF) instead of blood was used to assess influence of increased ICP alone. SAH and ACSF animals were left to survive for 1, 3, and 7 days. SAH induced significantly increased numbers of M1 (ED1+, CCR7+) and M2 (ED2+, CD206+) macrophages as well as MHC-II+ antigen presenting cells (APC) compared to naïve and ACSF animals. Increased numbers of ED1+ macrophages and APC were found in the CP only 3 and 7 days after ACSF injection, while ED2+ macrophage number did not increase. CD3+ T cells were not found in any of the animals. Following SAH, proliferation activity in the CP gradually increased over time while ACSF application induced higher cellular proliferation only 1 and 3 days after injection. Our results show that SAH induces an immune reaction in the CP resulting in an increase in the number of several macrophage types in the epiplexus position. Moreover, we also found that increased ICP due to ACSF application induced both an immune reaction and increased proliferation of epiplexus cells in the CP. These findings indicate that increased ICP, and not just blood, contributes to cellular changes in the CP following SAH.