Unfractionated Heparin Administered Every 8 h Outperforms 12 Hourly Administration for Venous Thromboembolism Prophylaxis in Reconstructive Head and Neck Tumor Patients: A 12 Year Retrospective Cohort Study.

BACKGROUND: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), poses a significant risk of morbidity and mortality in surgical patients, especially those undergoing head and neck cancer surgery with microvascular free flap reconstruction. These patients are at a heightened risk of VTE due to numerous patient and surgical risk factors. VTE chemoprophylaxis guidelines in these patients are limited due to a distinct paucity of research. This study aims to contribute to this scarcity of information, providing guidance for surgeons. METHODS: This retrospective cohort study evaluated the efficacy and safety of subcutaneous unfractionated heparin administered every 8 h versus every 12 h for postoperative VTE prophylaxis in patients undergoing head and neck resections with immediate free flap reconstruction. Data was collected from hospital medical records between January 2010 to December 2021. Patient demographics, operative details, and outcomes, including incidence of VTE and bleeding complications, were analyzed. RESULTS: Among 622 patients, those receiving heparin every 8 h (n = 393) demonstrated a significantly lower rate of VTE (0.8%) compared to 12-hourly group (n = 229; 3.9%) (p = 0.006). Additionally, there were no significant differences in the rates of postoperative hematoma between the two groups (9.4% versus 7.9% respectively, p = 0.510). CONCLUSION: Our study suggests that an increased daily dose of unfractionated heparin every 8 h for VTE chemoprophylaxis is superior to a 12-hourly regimen with comparable bleeding profiles. Further multicentre, prospective studies are needed to validate these results and compare the efficacy and safety of unfractionated heparin with other agents such as low-molecular-weight heparin in this patient group.

Magnetic Resonance Imaging-Related Anatomic and Functional Parameters for the Diagnosis and Prognosis of Chiari Malformation Type I: A Systematic Review and Meta-analysis.

OBJECTIVE: Imaging parameters of Chiari malformation type I (CMI) development are not well established. This study aimed to collect evidence of general or specific imaging measurements in patients with CMI, analyze indicators that may assist in determining the severity of CMI, and guide its diagnosis and treatment. METHODS: A comprehensive search was conducted across various databases including the Cochrane Library, PubMed, MEDLINE, Scopus, and Embase, covering the period from January 2002 to October 2023, following predefined inclusion criteria. Meta-analyses were performed using RevMan (ver. 5.4). We performed a quantitative summary and systematic analysis of the included studies. This study was registered in the PROSPERO (International Prospective Register of Systematic Reviews) prior to initiation (CRD42023415454). RESULTS: Thirty-three studies met our inclusion criteria. The findings indicated that out of the 14 parameters examined, 6 (clivus length, basal angle, Boogard's angle, supraocciput lengths, posterior cranial fossa [PCF] height, and volume) exhibited significant differences between the CMI group and the control group. Furthermore, apart from certain anatomical parameters that hold prognostic value for CMI, functional parameters like tonsillar movement, obex displacement, and cerebrospinal fluid dynamics serve as valuable indicators for guiding the clinical management of the disease. CONCLUSION: We collated and established a set of linear, angular, and area measurements deemed essential for diagnosing CMI. However, more indicators can only be analyzed descriptively for various reasons, particularly in prognostic prediction. We posit that the systematic assessment of patients' PCF morphology, volume, and other parameters at a 3-dimensional level holds promising clinical application prospects.

Viscoelastic properties of the equine hoof wall.

The equine hoof wall has outstanding impact resistance, which enables high-velocity gallop over hard terrain with minimum damage. To better understand its viscoelastic behavior, complex moduli were determined using two complementary techniques: conventional (∼5 mm length scale) and nano (∼1 µm length scale) dynamic mechanical analysis (DMA). The evolution of their magnitudes was measured for two hydration conditions: fully hydrated and ambient. The storage modulus of the ambient hoof wall was approximately 400 MPa in macro-scale experiments, decreasing to ∼250 MPa with hydration. In contrast, the loss tangent decreased for both hydrated (∼0.1-0.07) and ambient (∼0.04-0.01) conditions, over the frequency range of 1-10 Hz. Nano-DMA indentation tests conducted up to 200 Hz showed little frequency dependence beyond 10 Hz. The loss tangent of tubular regions showed more hydration sensitivity than in intertubular regions, but no significant difference in storage modulus was observed. Loss tangent and effective stiffness were higher in indentations for both hydration levels. This behavior is attributed to the hoof wall's hierarchical structure, which has porosity, functionally graded aspects, and material interfaces that are not captured at the scale of indentation. The hoof wall's viscoelasticity characterized in this work has implications for the design of bioinspired impact-resistant materials and structures. STATEMENT OF SIGNIFICANCE: The outer wall of horse hooves evolved to withstand heavy impacts during gallop. While previous studies have measured the properties of the hoof wall in slowly changing conditions, we wanted to quantify its behavior using experiments that replicate the quickly changing forces of impact. Since the hoof wall's structure is complex and contributes to its overall performance, smaller scale experiments were also performed. The behavior of the hoof wall was within the range of other biological materials and polymers. When hydrated, it becomes softer and can dissipate more energy. This work improves our understanding of the hoof's function and allows for more accurate simulations that can account for different impact speeds.

A systematic review: Sinomenine.

Sinomenine (SIN), an alkaloid derived from the traditional Chinese medicine, Caulis Sinomenii, has been used as an anti-inflammatory drug in China for over 30 years. With the continuous increase in research on the pharmacological mechanism of SIN, it has been found that, in addition to the typical rheumatoid arthritis (RA) treatment, SIN can be used as a potentially effective therapeutic drug for anti-tumour, anti-renal, and anti-nervous system diseases. By reviewing a large amount of literature and conducting a summary analysis of the literature pertaining to the pharmacological mechanism of SIN, we completed a review that focused on SIN, found that the current research is insufficient, and offered an outlook for future SIN development. We hope that this review will increase the public understanding of the pharmacological mechanisms of SIN, discover SIN research trial shortcomings, and promote the effective treatment of immune diseases, inflammation, and other related diseases.

Rate of Benign and Malignant Secondary Tumors Associated With Nevus Sebaceous: A Systematic Review and Meta-Analysis.

BACKGROUND: Nevus sebaceous (NS) is a rare congenital skin lesion affecting approximately 0.3% of all newborns. Although benign, NS lesions can harbor malignant secondary tumors. The published rate of development of these malignant tumors varies. This meta-analysis aimed to identify the rate of malignant and benign secondary neoplasms occurring in NS. METHODS: A literature search was conducted using PubMed, Embase, and Web of Science from inception to April 2023. Eligible studies reported incidence or risk of secondary neoplasms in patients with NS. Two independent reviewers screened studies, extracted data, and assessed the quality of included studies. The primary outcome was the pooled incidence of secondary neoplasms. Studies with sample sizes greater than 50 patients were eligible for meta-analysis using the random-effects model. RESULTS: Twenty-eight studies were identified, 22 of which were eligible for meta-analysis. The overall rate of secondary neoplasms was 12.8% (95% confidence interval [Cl], 9.2%-17.6%). The rates of development of malignant and benign tumors were 2.4% (95% CI, 1.4%-4.1%) and 10.3% (95% CI, 7.5%-13.9%), respectively. The rate of development of basal cell carcinoma was 1.7% (95% CI, 0.9%-3.2%), whereas the rate of the development of syringocystadenoma papilliferum was 3.6% (95% CI, 2.5%-5.3%) and that if trichoblastoma was 2.6% (95% CI, 1.7%-3.8%). CONCLUSIONS: Although the rate of development of malignant tumors within a primary NS lesion is low, it is not negligible. Prophylactic early excision remains a viable approach to prevent secondary malignant neoplasms, address cosmetic and functional complications, and preempt the need for complex reconstruction in the future. We propose that resection of NS lesions in childhood remains a reasonable first-line option in the appropriate patient keeping in mind that it may leave an undesirable scar.

A Prospective Observational Study of Physical Activity Levels and Physical Fitness of People at High Risk for Lung Cancer.

Introduction: Physical activity (PA) is a potentially modifiable risk factor for lung cancer, with previous research revealing that people who engage in more PA have lower risk of developing lung cancer. PA levels of lung cancer screening participants have not previously been explored. Methods: Participants at a single Australian International Lung Screen Trial site were eligible for assessment of self-reported PA levels (International Physical Activity Questionnaire and Physical Activity Scale for the Elderly) and physical assessments (6-min walk distance, hand grip muscle strength, daily step count, and body composition) at a single time point during lung cancer screening. Statistics were predominantly descriptive, with parametric data presented as mean and SD and nonparametric data presented as median and interquartile range (IQR). Results: A total of 178 participants were enrolled in this study, with a median age of 61 years. Of the participants, 61% were men and 51% were people who currently smoke. The median total International Physical Activity Questionnaire score was 1756 MET/min/wk (IQR 689, 4049). Mean total Physical Activity Scale for the Elderly score was 160 (SD 72), higher than described in healthy sedentary adults. The median daily step count was 7237 steps (IQR 5353, 10,038) and mean 6-minute walk distance was 545 m (SD 92). Median grip strengths were within predicted normal range, with an elevated median percentage body fat and low skeletal muscle mass found on body composition. Conclusion: Almost a quarter of International Lung Screen Trial participants assessed reported low levels of PA and have a potentially modifiable risk factor to improve health outcomes. Larger studies are needed to characterize the burden of inactivity among high-risk lung cancer screening populations.

Validation of the psychosocial consequences of screening in lung cancer questionnaire in the international lung screen trial Australian cohort.

BACKGROUND: Evaluation of psychosocial consequences of lung cancer screening with LDCT in high-risk populations has generally been performed using generic psychometric instruments. Such generic instruments have low coverage and low power to detect screening impacts. This study aims to validate an established lung cancer screening-specific questionnaire, Consequences Of Screening Lung Cancer (COS-LC), in Australian-English and describe early results from the baseline LDCT round of the International Lung Screen Trial (ILST). METHODS: The Danish-version COS-LC was translated to Australian-English using the double panel method and field tested in Australian-ILST participants to examine content validity. A random sample of 200 participants were used to assess construct validity using Rasch item response theory models. Reliability was assessed using classical test theory. The COS-LC was administered to ILST participants at prespecified timepoints including at enrolment, dependent of screening results. RESULTS: Minor linguistic alterations were made after initial translation of COS-LC to English. The COS-LC demonstrated good content validity and adequate construct validity using psychometric analysis. The four core scales fit the Rasch model, with only minor issues in five non-core scales which resolved with modification. 1129 Australian-ILST participants were included in the analysis, with minimal psychosocial impact observed shortly after baseline LDCT results. CONCLUSION: COS-LC is the first lung cancer screening-specific questionnaire to be validated in Australia and has demonstrated excellent psychometric properties. Early results did not demonstrate significant psychosocial impacts of screening. Longer-term follow-up is awaited and will be particularly pertinent given the announcement of an Australian National Lung Cancer Screening Program. TRIAL REGISTRATION: NCT02871856.

Progress in the generation of spinal cord organoids over the past decade and future perspectives.

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo. As emerging bioengineering methods have led to the optimization of cell culture protocols, spinal cord organoids technology has made remarkable advancements in the past decade. Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes. Moreover, fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment. These qualities make spinal cord organoids valuable tools for disease modeling, drug screening, and tissue regeneration. By utilizing this emergent technology, researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases. However, at present, spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine. Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

Correlation between reference point indentation and mechanical properties of 3D-printed polymers.

Reference point indentation (RPI) is a novel experimental technique designed to evaluate bone quality. This study utilizes two RPI instruments, BioDent and Osteoprobe, to investigate the mechanical responses of several 3D-printed polymers. We correlated the mechanical properties from a tensile test with the RPI parameters obtained from the BioDent and OsteoProbe. In addition, we tested the same polymers five years later (Age 5). The results show that for Age 0 polymers, the elastic modulus is highly correlated with average unloading slope (r = 0.87), first unloading slope (r = 0.85), bone material strength index (BMSi) (r = 0.85), average loading slope (r = 0.82), first indentation distance (r = 0.79), and total indentation distance (r = 0.76). The ultimate stress correlates significantly with first unloading slope (r = 0.85), average unloading slope (r = 0.83), BMSi (r = 0.81), first indentation distance (r = 0.73), average loading slope (r = 0.71), and total indentation distance (r = 0.70). The elongation has no significant correlation with the RPI parameters except with the average creep indentation distance (r = 0.60). For Age 5 polymers, correlations between mechanical properties and RPI parameters are low. This study illustrates the potential of RPI to assess the mechanical properties of polymers nondestructively with simple sample requirements. Furthermore, for the first time, 3D-printed polymers and aged polymers are investigated with RPI.

Comparison of different protocols for demineralization of cortical bone.

Bone is a biological composite material consisting of two main components: collagen and mineral. Collagen is the most abundant protein in vertebrates, which makes it of high clinical and scientific interest. In this paper, we compare the composition and structure of cortical bone demineralized using several protocols: ethylene-diamine-tetraacetic acid (EDTA), formic acid (CH2O2), hydrochloric acid (HCl), and HCl/EDTA mixture. The efficiencies of these four agents were investigated by assessing the remaining mineral quantities and collagen integrity with various experimental techniques. Raman spectroscopy results show that the bone demineralized by the CH2O2 agent has highest collagen quality parameter. The HCl/EDTA mixture removes the most mineral, but it affects the collagen secondary structure as amide II bands are shifted as observed by Fourier transform infrared spectroscopy. Thermogravimetric analysis reveals that HCl and EDTA are most effective in removing the mineral with bulk measurements. In summary, we conclude that HCl best demineralizes bone, leaving the well-preserved collagen structure in the shortest time. These findings guide on the best demineralization protocol to obtain high-quality collagen from bone for clinical and scientific applications.

Interfacial bonding between mineral platelets in bone and its effect on mechanical properties of bone.

Bone is a composite material consisting principally of apatite mineral, collagen fibrils, non-collagenous proteins, and other organic species. Recent electron microscopy studies have shown that the mineral in bone occurs as stacks of thin polycrystalline sheets ("mineral lamellae," MLs) which surround and lie between the collagen fibrils. We focus on the effect of the interface between these mineral lamellae on the mechanical properties of bone. Previous studies on bone treated with sodium hypochlorite (NaClO) to remove all organic material showed a greatly weakened mineral framework. Here, we treated femoral cortical bone with ethylenediamine (EDA), which only removes collagen, to study the effect of its removal on bone properties. We tested the degree of completion of the treatment by Raman spectroscopy and thermogravimetric analysis. When only collagen is removed, a continuous mineral structure remains and is less weakened than by NaClO treatment. Transmission electron microscopy study of finely ground particles of the EDA treated bone shows that stacks of MLs remain joined, whereas in NaClO treated bone, only isolated crystals are present. Thus, we infer that the MLs in bone are held together in stacks by an organic glue, which is destroyed by NaClO, but which survives the EDA treatment. We show that this glue may contribute to the stiffness, strength, and energy absorption of bone. Further studies are needed to discover the chemical nature of this glue. This study provides a starting point for such investigations.

Multimodal characterization of the bone-implant interface using Raman spectroscopy and nanoindentation.

Titanium implants are widely used in dental and orthopedic surgeries. Osseointegration phenomena lead to direct contact between bone tissue and the implant surface. The quality of the bone-implant interface (BII), resulting from the properties of newly formed bone, determines the implant stability. This study investigates the BII properties using a dedicated in vivo implant model consisting of a coin-shaped Ti-6Al-4V implant inserted in a rabbit femur for 10 weeks. A gap created below the implant was filled with newly formed bone tissue after healing. The properties of mature and newly formed bone tissues were compared using: i) Raman spectroscopy to assess the nanoscale compositional bone properties and ii) nanoindentation to quantify microscale elastic properties in site-matched regions. The mineral-to-matrix ratio, crystallinity (mineral size and lattice order), and the collagen cross-link ratio were significantly lower in newly formed bone tissue (e.g., a mineral-to-matrix ratio of 9.3 ± 0.5 for proline 853 cm-1) compared to mature bone (15.6 ± 1). Nanoindentation measurements gave Young's modulus of 12.8 ± 1.8 GPa for newly formed bone and 15.7 ± 2.3 GPa for mature bone. This multimodal and multiscale approach leads to a better understanding of osseointegration phenomena.

Merging versatile polymer chemistry with multifunctional nanoparticles: an overview of crosslinkable aromatic polyester matrix nanocomposites.

The current trend in the global advanced material market is expeditiously shifting towards more lightweight, multifunctional configurations, considering very recent developments in electrical aircraft, biomedical devices, and autonomous automobiles. Hence, the development of novel polymer nanocomposite materials is critical to advancing the current state-of-the-art of structural material technologies to address the pressing performance demands. Aiming at expanding the existing material design space, we have investigated crosslinkable aromatic polyester matrix nanocomposites. Aromatic polyesters, in the thermosetting form, are a prospective high-performance/high-temperature polymer technology, which is on a par with conventional epoxy-derivative resins and high-performance engineering thermoplastics in the range of their potential applications. The aromatic matrix-based thermosetting nanocomposites manifest greatly enhanced physical properties enabled by a chemistry-favored robust interfacial covalent coupling mechanism developed during the in situ polymerization reaction with various nanofiller particle configurations. Here, we provide a summary review of our recent efforts in developing this novel polymer nanocomposite material system. We highlight the chemical strategy, fabrication approach, and processing techniques developed to obtain various nanocomposite representations for structural, electrical, optical, biomedical, and tribological applications. The unique characteristic features emerging in the nanocomposite morphologies, along with their physicochemical effects on the multifunctional macroscale properties, are demonstrated. This unique matrix configuration introduces superior performance elements to polymer nanocomposite applications towards designing advanced composite materials.

Tunable and passively Q-switched laser operation of Nd,Lu:CaF2 disordered crystal.

We report the first demonstration, to the best of our knowledge, of tunable and Q-switched lasers based on diode-pumped Nd,Lu:CaF2 disordered crystal. A continuous tuning range of approximately 32 nm (1047-1079 nm) was obtained for tunable operations. A passively Q-switched laser was successfully achieved using a Cr4+:YAG as a saturable absorber. The shortest pulse width of 275 ns was obtained with a repetition rate of 1.85 kHz and corresponding peak power and single pulse energy of 189 W and 51.9 µJ, respectively.

Deproteinization of Cortical Bone: Effects of Different Treatments.

Bone is a biological composite material having collagen and mineral as its main constituents. In order to better understand the arrangement of the mineral phase in bone, porcine cortical bone was deproteinized using different chemical treatments. This study aims to determine the best method to remove the protein constituent while preserving the mineral component. Chemicals used were H2O2, NaOCl, NaOH, and KOH, and the efficacy of deproteinization treatments was determined by thermogravimetric analysis and Raman spectroscopy. The structure of the residual mineral parts was examined using scanning electron microscopy. X-ray diffraction was used to confirm that the mineral component was not altered by the chemical treatments. NaOCl was found to be the most effective method for deproteinization and the mineral phase was self-standing, supporting the hypothesis that bone is an interpenetrating composite. Thermogravimetric analyses and Raman spectroscopy results showed the preservation of mineral crystallinity and presence of residual organic material after all chemical treatments. A defatting step, which has not previously been used in conjunction with deproteinization to isolate the mineral phase, was also used. Finally, Raman spectroscopy demonstrated that the inclusion of a defatting procedure resulted in the removal of some but not all residual protein in the bone.

Avalanche criticality during compression of porcine cortical bone of different ages.

Crack events developed during uniaxial compression of cortical bones cut from femurs of developing pigs of several ages (4, 12, and 20 weeks) generate avalanches. These avalanches have been investigated by acoustic emission analysis techniques. The avalanche energies are power-law distributed over more than four decades. Such behavior indicates the absence of characteristic scales and suggests avalanche criticality. The statistical distributions of energies and waiting times depend on the pig age and indicate that bones become stronger, but less ductile, with increasing age. Crack propagation is equally age-dependent. Older pigs show, on average, larger cracks with a time distribution similar to those of aftershocks in earthquakes, while younger pigs show only statistically independent failure events.

Administration of amyloid-ß42 oligomer-specific monoclonal antibody improved memory performance in SAMP8 mice.

Amyloid-ß peptide (Aß) is recognized by many as the leading cause of Alzheimer's disease (AD), and Aß oligomers play a major role in the early-onset form of AD. Recently, the application of passive immunization targeting Aß has been investigated as a potential method of AD immunotherapy. We used a strain of monoclonal antibody against Aß42 oligomers, designated A8, as an Aß inhibitor to suppress Aß aggregation and Aß-derived cell toxicity in vitro, and as a passive immunotherapy approach to treat SAMP8 (senescence accelerated mouse sub-line P8) mice, an animal model of AD, in vivo. First, our results showed that pre-incubation of A8 with Aß oligomers inhibited both the maturation of Aß fiber and Aß oligomer toxicity on SH-SY5Y cells. Second, learning and memory was improved through intraperitoneal administration of A8 in SAMP8 mice. Third, Aß pathology was ameliorated with decreased Aß oligomers and phospho-tau levels in SAMP8 mice. Our data suggest that our monoclonal antibody A8 may be a candidate as a potential immunotherapeutic agent in AD.

[Isolation and identification of a human single chain Fv antibody against amyloid-beta 1-42 soluble oligomers from a human phage display library].

To get specific scFv (Single-chain fragment variable) antibody against soluble Abeta1-42(Amyloid-beta) oligomers, we constructed a human single-chain Fv (scFv) antibody library by phage display technology. Using RT-PCR, we amplified the variable heavy (VH) and variable light (VL) genes from peripheral blood lymphocytes (PBL). Then we obtained the scFv fragments through SOE-PCR, and the scFv fragments were cloned into the vector pCANTAB5E and electroporated into competent Escherichia coli TG1 cells. Consequently, a scFv phage display library containing 2.5 x 10(9) clones was constructed. The recombinant phagemids were rescued by reinfection of helper phage M13K07. Recombinant phages specific for Abeta1-42 oligomers were enriched after four rounds of biopanning and the antigen-positive clones were selected from the enriched clones by phage ELISA. Positive clone B19 was used to infect E. coli HB2151 to express soluble scFv antibody. SDS-PAGE and Western blotting analysis showed that the soluble scFv B19 antibody was expressed successfully and could bind specifically to Abeta1-42 trimer and protofiber. The specific scFv against Abeta1-42 oligomers can be used in the therapeutic research on Alzheimer's disease.