Development of a universal cutting guide for raising deep circumflex iliac artery flaps.

PURPOSE: The deep circumflex iliac crest flap (DCIA) is used for the reconstruction of the jaw. For fitting of the transplant by computer-aided planning (CAD), a computerized tomography (CT) of the jaw and the pelvis is necessary. Ready-made cutting guides save a pelvic CT and healthcare resources while maintaining the advantages of the CAD planning. METHODS: A total of 2000 CTs of the pelvis were divided into groups of 500 by sex and age (≤ 45 and > 45 years). Three-dimensional (3D) pelvis models were aligned and averaged. Cutting guides were designed on the averaged pelvis for each group and an overall averaged pelvis. The cutting guides and 50 randomly selected iliac crests (10 from each group and 10 from the whole collective) were 3D printed. The appropriate cutting guide was mounted to the iliac crest and a cone beam CT was performed. The thickness of the space between the iliac crest and the cutting guide was evaluated. RESULTS: Overall the mean thickness of the space was 2.137 mm and the mean volume of the space was 4513 mm3. The measured values were significantly different between the different groups. The overall averaged group had not the greatest volume, maximum thickness and mean thickness of the space. CONCLUSION: Ready-made cutting guides for the DCIA flap fit to the iliac crest and make quick and accurate flap raising possible while radiation dose and resources can be saved. The cutting guides fit sufficient to the iliac crest and should keep the advantages of a standard CAD planning.

3D DAS VSP for Coal Seam Exploration: A Case Study from Queensland, Australia.

Seismic methods are extensively used in coal mining for expanding resource discoveries and definition as well as for mine monitoring. However, the use of borehole seismic methods is relatively uncommon due to the high cost of borehole seismic acquisition using conventional downhole tools. The introduction of distributed acoustic sensing (DAS), which uses optical fibres to record seismic data, has dramatically increased the cost-effectiveness of borehole seismic methods. Fibre-optic cables are inexpensive and, once deployed in a borehole, can be abandoned or used later for further monitoring of the subsurface. The case study presented here concerns the use of DAS to record a 3D VSP (vertical seismic profiling) for coal seam exploration in Queensland, Australia. This study trialled effective strategies for deploying cables into boreholes and demonstrated how this technology could be incorporated into the standard coal exploration process. The final processing results produced a high-resolution 3D seismic cube where the coal seams below the basalt cover are clearly identifiable around the boreholes. Permanent installation of the fibre-optic cables into a set of boreholes provides immediate benefits of 3D seismic imaging and can create additional value in utilising these sensors for further discrete or continuous subsurface measurements, including stability monitoring of underground workings and detection of methane accumulations.

VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway.

Neuroinflammation, characterized by microglial activation and the subsequent secretion of inflammatory cytokines, plays a pivotal role in neurodegenerative diseases and brain injuries, often leading to neuronal damage and death. Alleviating neuroinflammation has thus emerged as a promising strategy to protect neurons and ameliorate neurodegenerative disorders. While peroxisome proliferator-activated receptor gamma (PPARγ) agonists have demonstrated potential therapeutic actions on neuroinflammation, their prolonged use, such as with rosiglitazone, can lead to cardiac risks and lipid differentiation disorders. In this study, we investigated the effects of a newly synthesized PPARγ agonist, VSP-2, on secretion of inflammatory cytokines in BV2 cells. Treatment with VSP-2 significantly reduced the mRNA and protein levels of proinflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α). Furthermore, VSP-2 attenuated the phosphorylation of nuclear factor kappa B (NF-κB) (65 kD) and IκBα, as well as the nuclear translocation of NF-κB (65 kD). Additionally, the use of PPARγ small interfering RNA was able to attenuate the effects of VSP-2 on proinflammatory cytokines and the NF-κB pathway. In conclusion, our findings suggest that VSP-2 effectively suppressed the expressions of IL-1ß, IL-6, and TNF-α via the PPARγ/NF-κB signaling pathway. Given its potential therapeutic benefits, VSP-2 may emerge as a promising candidate for the treatment of neurodegenerative diseases or brain injuries associated with neuroinflammation.

Successful repair of recurrent ventricular septal perforation after myocardial infarction using double patch technique via right ventriculotomy: a case report.

BACKGROUND: Post-myocardial infarction (MI) ventricular septal perforation (VSP) is a rare but life-threatening complication. Surgical repair is challenging and carries significant risks, particularly in the context of recurrent VSPs. This case study presents a patient with recurrent VSP after initial surgical repair following myocardial infarction. CASE PRESENTATION: A 65-year-old male were re-administered to our hospital due to recurrent VSP. He was during follow up after undergone emergency VSP closure surgery 2 months earlier, utilizing the bovine double patch technique via left ventriculostomy. The initial VSP was located in the apical part of the interventricular septum, while the recurrent VSP appeared in the upper middle portion of the interventricular septum (Fig. 1). As the previous patch remained intact, the second surgery employed the bovine double patch technique via right ventriculostomy. The patient's condition remained stable without the development of heart failure symptoms. CONCLUSION: Repairing recurrent VSPs remains a challenge, necessitating the mastery of appropriate approaches to achieve optimal outcomes. Further research and guidelines are required to refine management strategies for recurrent VSPs.

Patient-Specific 3D-Printed Osteotomy Guides and Titanium Plates for Distal Femoral Deformities in Dogs with Lateral Patellar Luxation.

The aim of this study was to describe the diagnosis and treatment of grade IV lateral patellar luxation (LPL) in two adult large breed dogs with complex femoral deformities using patient-specific three-dimensionally (3D) printed osteotomy guides and implants. Computed tomography (CT) scans were obtained for virtual surgical planning (VSP) using computer-aided design (CAD) software, which allowed for 3D reconstruction and manipulation of the femoral deformities, providing a preoperative view of the correction. Of the two patients, one was affected bilaterally and the other unilaterally, but both dogs were from the same litter. Therefore, the healthy femur of the unilaterally affected patient was used as the physiological reference for the virtual surgical correction. Three distal femoral trapezoid osteotomies (DF-TO) followed by reduction and internal fixation with plates were performed using patient-specific 3D-printed osteotomy guides and implants. This type of osteotomy permitted correction of procurvatum in all the femurs to increase knee extension, raise the dog's lumbar spine and correct the kyphosis. Preoperative, expected and postoperative femoral angles were compared to evaluate the efficacy of virtual surgical planning and the outcome of surgical correction. Radiographic follow-up, passive range of motion and functional recovery were recorded. There were no major complications requiring revision surgery. Significant clinical improvement was observed in both patients. This study suggests that the treatment used represents a viable surgical alternative to restore limb alignment in patients with complex femoral deformities.

Raloxifene-driven benzothiophene derivatives: Discovery, structural refinement, and biological evaluation as potent PPARγ modulators based on drug repurposing.

By virtue of the drug repurposing strategy, the anti-osteoporosis drug raloxifene was identified as a novel PPARγ ligand through structure-based virtual high throughput screening (SB-VHTS) of FDA-approved drugs and TR-FRET competitive binding assay. Subsequent structural refinement of raloxifene led to the synthesis of a benzothiophene derivative, YGL-12. This compound exhibited potent PPARγ modulation with partial agonism, uniquely promoting adiponectin expression and inhibiting PPARγ Ser273 phosphorylation by CDK5 without inducing the expression of adipongenesis associated genes, including PPARγ, aP2, CD36, FASN and C/EBPα. This specific activity profile resulted in effective hypoglycemic properties, avoiding major TZD-related adverse effects like weight gain and hepatomegaly, which were demonstrated in db/db mice. Molecular docking studies showed that YGL-12 established additional hydrogen bonds with Ile281 and enhanced hydrogen-bond interaction with Ser289 as well as PPARγ Ser273 phosphorylation-related residues Ser342 and Glu343. These findings suggested YGL-12 as a promising T2DM therapeutic candidate, thereby providing a molecular framework for the development of novel PPARγ modulators with an enhanced therapeutic index.

Comparison of Five Different Treatment Approaches of Mandibular Keratocystic Odontogenic Keratocyst (OKC): A Retrospective Recurrence Analysis of Clinical and Radiographic Parameters.

The odontogenic keratocyst (OKC) is a benign but locally aggressive growing lesion that infiltrates the bone and surrounding tissue. It is characterized by high rates of recurrence along with rapid growth. Different forms of partly successful treatment therapies are reported. The retrospective study at hand examined 114 patients with OKC treated over a period of 20 years. Data extracted includes gender, age, location, previous treatment for the lesion, surgery, outcome, recurrence rate and follow-up. 63.1% of the patients underwent cystectomy, 22.5% by cystectomy and carnoy solution, 7.2% by cystectomy, and curettage, 4.5% by cystostomy and 2.7% by partial resection. In this study, no significant differences could be observed regarding the surgical method. Most recurrences occurred with 91.9% in the mandible with an average size of 5.5 cm2 and increased in women. Within a mean follow-up time of 3.6 years the recurrence rate was 36.9%, on average after 36 months. Recurrences were most frequently diagnosed at the age of 31-50 (43.9%). Despite numerous studies, there is still no unanimous opinion on an effective therapy for OKC. However, precise resection of OKC can be facilitated by preoperative 3D-imaging and virtual planning.

In-house virtual surgical planning and guided mandibular reconstruction is less precise, but more economical and time-efficient than commercial procedures.

BACKGROUND: To compare an in-house and a commercially available surgical planning solution for mandibular reconstruction in terms of postoperative reconstruction accuracy and economic benefit. METHODS: Twenty-nine consecutive patients with advanced oral squamous cell carcinoma (OSCC) requiring segmental mandibular reconstruction were enrolled. Fifteen patients underwent in-house surgical planning and 14 patients underwent a commercially available planning solution. A morphometric comparison of preoperative and postoperative computed tomography (CT) data sets and a cost-benefit comparison were performed. RESULTS: Volumes of planned and reconstructed bone segments differed significantly for both in-house planning (p = 0.0431) and commercial planning (p < 0.0001). Significant differences in osteotomy angles were demonstrated for in-house planning (p = 0.0391). Commercial planning was superior to in-house planning for total mandibular deviation (p = 0.0217), intersegmental space volumes (p = 0.0035), and lengths (p = 0.0007). No significant difference was found between the two planning solutions in terms of intersegmental ossification and the incidence of wound healing disorders. In-house planning took less time than commercial planning (p < 0.0001). Component manufacturing costs (p < 0.0001) and total cumulative costs (p < 0.0001) were significantly lower for in-house planning. CONCLUSIONS: In-house surgical planning is less accurate but has a cost advantage and could be performed in less time.

The accuracy of virtual surgical planning assisted management for L-shaped reduction malarplasty: A retrospective study.

This study aims to evaluate the accuracy of L-shaped reduction malarplasty with bone setback or resection on the zygoma and the mortice and tenon joint structure on the zygomatic arch under the guidance of virtual surgical planning (VSP). Adult patients with zygomatic protrusion or hypertrophy were enrolled and divided. L-shaped reduction malarplasty with or without bone resection and with the mortice and tenon joint structure on the zygomatic arch was conducted either by digital procedures comprising VSP and three-dimensional (3D) printing titanium templates (Group I) or by conventional methods (Group II). Positions of representative landmarks and superimposition models were analyzed by 3D cephalometry. Satisfaction rate and incidences of clinical complications were compared as well. Satisfactory reduction of zygomatic protrusion or hypertrophy was recognized among all 78 patients. Improved symmetry and great surgical accuracy were observed according to the cephalometry analyses. The bone segment movement of virtual plans and actual results in Group I were measured and showed no obvious difference for the inward movement (5.42 ± 0.98 mm vs. 5.33± 0.93 mm, P = 0.6906) and the sagittal overlap (4.77 ± 1.32 mm vs. 4.87± 1.21 mm, P = 0.7386) at the zygoma roots, along with the step length at the long-arm of the L-shaped osteotomy line (2.43 ± 1.11 mm vs. 2.39± 0.89 mm, P = 0.8665). The high resemblance between virtual plans and actual results was depicted via superimposition models. Meanwhile, a higher satisfaction rate (28 in 36, 78% vs. 20 in 42, 48%) and a lower incidence rate of complications (11 in 36, 31% vs. 21 in 42, 50%) were found in Group I. Within the limitations of the study it seems that the application of VSP in reduction malarplasty could significantly contribute to better surgical accuracy and reduced difficulties in the operation, which would be beneficial to patients with zygoma hypertrophy or prominence.

Changes in Adhesion and the Expression of Adhesion Molecules in PBMCs after Aneurysmal Subarachnoid Hemorrhage: Relation to Cerebral Vasospasm.

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurovascular disease produced by extravasation of blood to the subarachnoid space after rupture of the cerebral vessels. After bleeding, the immune response is activated. The role of peripheral blood mononuclear cells (PBMCs) in this response is a current subject of research. We have analysed the changes in PBMCs of patients with aSAH and their interaction with the endothelium, focusing on their adhesion and the expression of adhesion molecules. Using an in vitro adhesion assay, we observed that the adhesion of PBMCs of patients with aSAH is increased. Flow cytometry analysis shows that monocytes increased significantly in patients, especially in those who developed vasospasm (VSP). In aSAH patients, the expression of CD162, CD49d, CD62L and CD11a in T lymphocytes and of CD62L in monocytes increased. However, the expression of CD162, CD43, and CD11a decreased in monocytes. Furthermore, monocytes from patients who developed arteriographic VSP had lower expression of CD62L. In conclusion, our results confirm that after aSAH, monocyte count and adhesion of PBMCs increase, especially in patients with VSP, and that the expression of several adhesion molecules is altered. These observations can help predict VSP and to improve the treatment of this pathology.

Clinical and molecular heterogeneity of VPS13D-related neurodevelopmental and movement disorders.

BACKGROUND: The VPS13 family of proteins has been implicated in lipid transport and trafficking between endoplasmic reticulum and organelles, to maintain homeostasis of subcellular membranes. Recently, pathogenic variants in each human VPS13S gene, have been linked to distinct human neurodevelopmental or neurodegenerative disorders. Within the VPS13 family of genes, VPS13D is known to be implicated in mitochondria homeostasis and function. METHODS: We investigated a Pakistani sibship affected with neurodevelopmental impairment and severe hyperkinetic (choreoathetoid) movements. Whole exome sequencing (WES) and Sanger sequencing were performed to identify potential candidate variants segregating in the family. We described clinical phenotypes and natural history of the disease during a 3-year clinical follow-up and summarized literature data related to previously identified patients with VPS13D-related neurological disorders. RESULTS: We identified by WES an homozygous non-synonymous variant in VPS13D (c.5723 T > C; p.Ile1908Thr) as the potential underlying cause of the disease in our family. Two young siblings developed an early-onset neurological impairment characterized by global developmental delay, with impaired speech and motor milestones, associated to hyperkinetic movement disorders as well as progressive and non-progressive neurological abnormalities. CONCLUSION: In this study we delineated the heterogeneity of VPS13D-related clinical phenotypes and described a novel VPS13D homozygous variant associated with severe neurological impairment. Further studies will be pivotal to understand the exact VPS13D function and its impact on mitochondria homeostasis, brain development and regulation of movements, to further clarify genotype-phenotype correlations and provide crucial prognostic information and potential therapeutic implications.

The use of ethyl cellulose film lifts to collect particle traces from exposed adhesive on the edges of duct tape.

Environmentally acquired particles (EAP), trapped along the edges of duct tape in the exposed adhesive, are a possible source of information regarding prior exposures of the tape and a possible means to associate duct tape rolls to segments of duct tape that are collected as traces during the investigation of criminal activity. The recovery and separation of EAP is complicated by (1) the need to separate the particles from the adhesive, and (2) the presence of adhesive filler and pigment particles that are part of adhesive formulations. Approaches such as cutting the tape edge, followed by solvent extraction, or swabbing of the duct tape edges using solvents, result in thousands of adhesive filler/pigment particles, overwhelming much smaller numbers of EAP. A recovery method has been developed employing a 10% solution of ethylcellulose (EC) in ethanol. Duct tape segments are pressed onto a glass plate and a bead of the viscous EC solution is pipetted along the edge. After drying, the EC forms a robust film that is peeled away from the tape edge, lifting the EAP along with only very small amounts of adhesive. The film lift (containing EC, duct tape adhesive and EAP) can be examined directly by steromicroscopy and particles of interest can be removed by softening the film using locally applied ethanol. Particles can be examined in situ by transmitted light microscopy using glycerol as a mounting medium to match the EC film. Batch recovery of particles from the film can be achieved by dissolution of the film lift in xylene and washing to remove adhesive residues. Xylene is then removed by washing with ethanol, leaving an ethanol suspension of EAP along with the duct tape filler/pigment particles. Larger particles can be separated by sieving and smaller particles can be recovered by filtration. This method was found to efficiently collect EAP found trapped along the edges of duct tape in the exposed adhesive, as well as for the preparation of these particles for microscopical and instrumental analysis. Limitations, not fully evaluated, include the loss or alteration of some particle types by dissolution, agitation and filtration steps. Further development of this method is expected to provide a means to recover trace particles from the edges of other types of tape and from related adhesive products such as stamps and labels.

Computer assisted skull base surgery: a contemporary review.

Skull base surgery has evolved significantly since Harvey Cushing's first descriptions in the early 1900s. Computer aided surgery (CAS) applications continue to expand; they include virtual surgical planning, augmented and virtual reality, 3D printing of models/cutting guides/implants, surgical navigation, and intraoperative imaging. The authors will review the current skull base CAS literature and propose a computer aided surgical workflow categorizing these applications into 3 phases: 1) Virtual planning, 2) Surgical execution, 3) Intraoperative verification.

Redefining precision and efficiency in orthognathic surgery through virtual surgical planning and 3D printing: a narrative review.

Orthognathic surgery, essential for addressing jaw and facial skeletal irregularities, has historically relied on traditional surgical planning (TSP) involving a series of time-consuming steps including two-dimensional radiographs. The advent of virtual surgical planning (VSP) and 3D printing technologies has revolutionized this field, bringing unprecedented precision and customization to surgical processes. VSP facilitates 3D visualization of the surgical site, allowing for real-time adjustments and improving preoperative stress for patients by reducing planning time. 3D printing dovetails with VSP, offering the creation of anatomical models and surgical guides, enhancing the predictability of surgical outcomes despite higher initial setup and material costs. The integration of VSP and 3D printing promises innovative and effective solutions in orthognathic surgery, surpassing the limitations of traditional methods. Patient-reported outcomes show a positive post-surgery impact on the quality of life, underlining the significant role of these technologies in enhancing self-esteem and reducing anxiety. Economic analyses depict a promising long-term fiscal advantage with these modern technologies, notwithstanding the higher initial costs. The review emphasizes the need for large-scale randomized controlled trials to address existing research gaps and calls for a deeper exploration into the long-term impacts and ethical considerations of these technologies. In conclusion, while standing on the cusp of a technological renaissance in orthognathic surgery, it is incumbent upon the medical fraternity to foster a collaborative approach, balancing innovation with scrutiny to enhance patient care. The narrative review encourages the leveraging of VSP and 3D printing technologies for more efficient and patient-centric orthognathic surgery, urging the community to navigate uncharted territories in pursuit of precision and efficiency in the surgical landscape.

Side-to-Side Flipping Wedge Osteotomy: Virtual Surgical Planning Suggested an Innovative One-Stage Procedure for Aligning Both Knees in "Windswept Deformity".

(1) Background: The adoption of Virtual Surgical Planning (VSP) and 3D technologies is rapidly growing within the field of orthopedic surgery, opening the door to highly innovative and individually tailored surgical techniques. We present an innovative correction approach successfully used in a child affected by "windswept deformity" of the knees. (2) Methods: We report a case involving a child diagnosed with "windswept deformity" of the knees. This condition was successfully addressed through a one-stage bilateral osteotomy of the distal femur. Notably, the wedge removed from the valgus side was flipped and employed on the varus side to achieve the correction of both knees simultaneously. The surgical technique was entirely conceptualized, simulated, and planned in a virtual environment. Customized cutting guides and bony models were produced at an in-hospital 3D printing point of care and used during the operation. (3) Results: The surgery was carried out according to the VSP, resulting in favorable outcomes. We achieved good corrections of the angular deformity with an absolute difference from the planned correction of 2° on the right side and 1° on the left side. Moreover, this precision not only improved surgical outcomes but also reduced the procedure's duration and overall cost, highlighting the efficiency of our approach. (4) Conclusions: The integration of VSP and 3D printing into the surgical treatment of rare limb anomalies not only deepens our understanding of these deformities but also opens the door to the development of innovative, personalized, and adaptable approaches for addressing these unique conditions.

Diffusion Model for DAS-VSP Data Denoising.

Distributed acoustic sensing (DAS) has emerged as a transformational technology for seismic data acquisition. However, noise remains a major impediment, necessitating advanced denoising techniques. This study pioneers the application of diffusion models, a type of generative model, for DAS vertical seismic profile (VSP) data denoising. The diffusion network is trained on a new generated synthetic dataset that accommodates variations in the acquisition parameters. The trained model is applied to suppress noise in synthetic and field DAS-VSP data. The results demonstrate the model's effectiveness in removing various noise types with minimal signal leakage, outperforming conventional methods. This research signifies diffusion models' potential for DAS processing.

Cohen Syndrome: Novel VPS13B Genetic Variants in a Male Portuguese Patient with Pigmentary Retinopathy.

The purpose of this clinical report was to describe a case of Cohen syndrome with its classical ophthalmological manifestations and novel VPS13B genetic variants. A 39-year-old Caucasian male patient with severe rod-cone retinal dystrophy and no history of parental consanguinity was referred to our ophthalmology department. Ophthalmologic history included high bilateral myopia and a 3-year prior bilateral cataract surgery. Systemic history included facial dysmorphism, intellectual disability, transient neutropenia, microcephaly, truncal obesity, and joint hyperextensibility. The patient presented classic fundoscopic features of pigmentary retinopathy in both eyes (OU). Optical coherence tomography (OCT) revealed bilateral central and diffuse retinal pigment epithelium (RPE) and outer retinal atrophy without concomitant macular edema, while fluorescein angiography (FA) demonstrated diffuse RPE atrophy with prominent choroidal vessels. The full-field ERG (ffERG) showed no dark-adapted or light-adapted responses and the P50 wave was not identified in the pattern ERG (pERG). The genetic study revealed two novel heterozygous variants in the VPS13B gene: (1) c.5138T>C p.(Leu1713Pro) and (2) c.10179del p.(Asn3393Lysfs*37), thus confirming the diagnosis of Cohen syndrome. This case report introduces these two novel genetic variants to the literature, in a patient with classic phenotypic characteristics of Cohen syndrome, a rare genetic disease which has been increasingly reported since its first description in 1973.

Surgical accuracy of CAD/CAM splints using virtual surgical planning in orthognathic surgery: policy implications for healthcare in Australia.

BACKGROUND: This study examines post-surgical outcomes of maxillary position using virtual surgical planning (VSP) with computer designed and manufactured surgical splints, without the use of costly patient specific implants (PSI), in the treatment of routine nonsyndromic orthognathic patients. The cost of these personalized medical devices and their impact in the setting of cranio-maxillofacial surgery is currently under review by The Department of Health and Aged Care in Australia. METHODS: This is a single-centre retrospective analysis of 49 patients who underwent bimaxillary orthognathic surgery by a single surgeon at Epworth Richmond Hospital (Victoria, Australia) over a period spanning 2016 to 2020. Patients were included in the study provided their surgery was facilitated using VSP with manufacture of computer designed occlusal splints. RESULTS: Use of computer designed and manufactured splints were highly reliable in reproducing the virtual surgical plan, when using palatal plane, upper incisor angulation, and anterior upper facial height. CONCLUSION: Use of computer designed and manufactured splints provide a method of leveraging the accuracy of VSP methods, without the additional costs associated with PSI. These findings may assist in appropriate resource allocation and case stratification in patients undergoing orthognathic surgery.

Clinical application of 3-dimensional tissue volume assessment using CloudCompare.

Adjunctive procedures, including autologous fat grafting and surgical debulking, may be required to optimise facial contours following maxillomandibular reconstruction. A standardised method for the quantitative analysis of volumetric change and the impact of restoration of facial symmetry on health-related quality of life remains unclear. We use two case studies to illustrate the value of a combination of objective 3-dimenmsional (3D) measurements, clinical assessments, and patient-reported outcomes, using the FACE-Q questionnaire to elucidate the benefits of adjunctive procedures.