Analyzing genetic diversity in luffa and developing a Fusarium wilt-susceptible linked SNP marker through a single plant genome-wide association (sp-GWAS) study.

BACKGROUND: Luffa (Luffa spp.) is an economically important crop of the Cucurbitaceae family, commonly known as sponge gourd or vegetable gourd. It is an annual cross-pollinated crop primarily found in the subtropical and tropical regions of Asia, Australia, Africa, and the Americas. Luffa serves not only as a vegetable but also exhibits medicinal properties, including anti-inflammatory, antidiabetic, and anticancer effects. Moreover, the fiber derived from luffa finds extensive applications in various fields such as biotechnology and construction. However, luffa Fusarium wilt poses a severe threat to its production, and existing control methods have proven ineffective in terms of cost-effectiveness and environmental considerations. Therefore, there is an urgent need to develop luffa varieties resistant to Fusarium wilt. Single-plant GWAS (sp-GWAS) has been demonstrated as a promising tool for the rapid and efficient identification of quantitative trait loci (QTLs) associated with target traits, as well as closely linked molecular markers. RESULTS: In this study, a collection of 97 individuals from 73 luffa accessions including two major luffa species underwent single-plant GWAS to investigate luffa Fusarium wilt resistance. Utilizing the double digest restriction site associated DNA (ddRAD) method, a total of 8,919 high-quality single nucleotide polymorphisms (SNPs) were identified. The analysis revealed the potential for Fusarium wilt resistance in accessions from both luffa species. There are 6 QTLs identified from 3 traits, including the area under the disease progress curve (AUDPC), a putative disease-resistant QTL, was identified on the second chromosome of luffa. Within the region of linkage disequilibrium, a candidate gene homologous to LOC111009722, which encodes peroxidase 40 and is associated with disease resistance in Cucumis melo, was identified. Furthermore, to validate the applicability of the marker associated with resistance from sp-GWAS, an additional set of 21 individual luffa plants were tested, exhibiting 93.75% accuracy in detecting susceptible of luffa species L. aegyptiaca Mill. CONCLUSION: In summary, these findings give a hint of genome position that may contribute to luffa wild resistance to Fusarium and can be utilized in the future luffa wilt resistant breeding programs aimed at developing wilt-resistant varieties by using the susceptible-linked SNP marker.

Randomized Controlled Study of Tenofovir versus Lamivudine Followed by Tenofovir in Severe Exacerbation of Hepatitis B.

Spontaneous severe acute exacerbation (SAE) is not uncommon in the natural history of chronic hepatitis B (CHB). Lamivudine (LAM) has the advantages of low price, quick onset, good efficacy, and no drug resistance within 24 weeks. This study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and LAM for 24 weeks followed by TDF in the treatment of CHB with severe acute exacerbation. Consecutive patients of CHB with SAE were randomized to receive either TDF (19 patients) or LAM for 24 weeks, followed by TDF (18 patients). The primary endpoint was overall mortality or receipt of liver transplantation by week 24. This study was approved by the Institutional Review Board (IRB) of the Kaohsiung Veterans General Hospital (VGHKS12-CT5-10). The baseline characteristics were comparable between the two groups. By week 24, seven (37%) and five (28%) patients in the TDF and LAM-TDF groups died or received liver transplantation (P = 0.487). Multivariate analysis showed that albumin level, prothrombin time (PT), and hepatic encephalopathy were independent factors associated with mortality or liver transplantation by week 24. Early reductions in HBV DNA of more than or equal to 2 log at 1 and 2 weeks were similar between the two groups. The biochemical and virological responses at 12, 24, and 48 weeks were also similar between the two groups. TDF and LAM for 24 weeks followed by TDF achieved a similar clinical outcome in CHB patients with SAE. (This study has been registered at ClinicalTrials.gov under identifier NCT01848743).

Heart-targeting exosomes from human cardiosphere-derived cells improve the therapeutic effect on cardiac hypertrophy.

Exosomes of human cardiosphere-derived cells (CDCs) are very promising for treating cardiovascular disorders. However, the current challenge is inconvenient delivery methods of exosomes for clinical application. The present study aims to explore the potential to enhance the therapeutic effect of exosome (EXO) from human CDCs to myocardial hypertrophy. A heart homing peptide (HHP) was displayed on the surface of exosomes derived from CDCs that were forced to express the HHP fused on the N-terminus of the lysosomal-associated membrane protein 2b (LAMP2b). The cardiomyocyte-targeting capability of exosomes were analyzed and their therapeutic effects were evaluated in a mouse model of myocardial hypertrophy induced by transverse aorta constriction (TAC). The molecular mechanisms of the therapeutic effects were dissected in angiotensin II-induced neonatal rat cardiomyocyte (NRCMs) hypertrophy model using a combination of biochemistry, immunohistochemistry and molecular biology techniques. We found that HHP-exosomes (HHP-EXO) accumulated more in mouse hearts after intravenous delivery and in cultured NRCMs than control exosomes (CON-EXO). Cardiac function of TAC mice was significantly improved with intravenous HHP-EXO administration. Left ventricular hypertrophy was reduced more by HHP-EXO than CON-EXO via inhibition of ß-MHC, BNP, GP130, p-STAT3, p-ERK1/2, and p-AKT. Similar results were obtained in angiotensin II-induced hypertrophy of NRCMs, in which the beneficial effects of HHP-EXO were abolished by miRNA-148a inhibition. Our results indicate that HHP-EXO preferentially target the heart and improve the therapeutic effect of CDCs-exosomes on cardiac hypertrophy. The beneficial therapeutic effect is most likely attributed to miRNA-148a-mediated suppression of GP130, which in turn inhibits STAT3/ERK1/2/AKT signaling pathway, leading to improved cardiac function and remodeling.

Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE-/- Mice.

Oxidative stress has a considerable influence on endothelial cell dysfunction and atherosclerosis. Acacetin, an anti-inflammatory and antiarrhythmic, is frequently used in the treatment of myocarditis, albeit its role in managing atherosclerosis is currently unclear. Thus, we evaluated the regulatory effects of acacetin in maintaining endothelial cell function and further investigated whether the flavonoid could attenuate atherosclerosis in apolipoprotein E deficiency (apoE-/- ) mice. Different concentrations of acacetin were tested on EA.hy926 cells, either induced or non-induced by human oxidized low-density lipoprotein (oxLDL), to clarify its influence on cell viability, cellular reactive oxidative stress (ROS) level, apoptotic ratios and other regulatory effects. In vivo, apoE-/- mice were fed either a Western diet or a chow diet. Acacetin pro-drug (15 mg/kg) was injected subcutaneously two times a day for 12 weeks. The effects of acacetin on the atherosclerotic process, plasma inflammatory factors and lipid metabolism were also investigated. Acacetin significantly increased EA.hy926 cell viability by reducing the ratios of apoptotic and necrotic cells at 3 µmol/L. Moreover, 3 µmol/L acacetin clearly decreased ROS levels and enhanced reductase protein expression through MsrA and Nrf2 pathway through phosphorylation of Nrf2 and degradation of Keap1. In vivo, acacetin treatment remarkably attenuated atherosclerosis by increasing reductase levels in circulation and aortic roots, decreasing plasma inflammatory factor levels as well as accelerating lipid metabolism in Western diet-fed apoE-/- mice. Our findings demonstrate the anti-oxidative and anti-atherosclerotic effects of acacetin, in turn suggesting its potential therapeutic value in atherosclerotic-related cardiovascular diseases (CVD).

Pearl Necklacelike Strategy Enables Quantification of Global 5-Hydroxymethylcytosine and 5-Formylcytosine by Inductively Coupled Plasma-Atomic Emission Spectrometry.

5-Hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) are key intermediates of active DNA demethylation, for which the global detection methods are still restricted by high cost and long operation time. Here, we demonstrate a pearl necklacelike strategy to accurately quantify global 5hmC and 5fC in genomic DNA. In this method, the metal-organic framework (MOF), [Cu3(BTC)2] (denoted as HKUST-1, H3BTC = 1,3,5-benzenetricarboxylic acid), with a diameter of ∼30 nm that contains ∼15 000 copper ions (Cu2+) as the "super label" was in situ grown in the carboxylated 5hmC and 5fC loci of genomic DNA via the coordination between Cu2+ and the carboxyl group. After the acid digestion of MOF, the concentration of Cu2+, which has a quantitative relationship with the 5hmC/5fC content, was measured by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The metal element enrichment during MOF growth has amplified the signal by 4 orders of magnitude, realizing sensitive and accurate quantification of global 5hmC and 5fC in different tissues with a detection limit of 0.031% and 0.019‰ in DNA, respectively. The bisulfite- and mass spectrometry-free strategy is easily performed in almost all research and medical laboratories and would provide potential capability to quantify other candidate modifications in nucleotides.

Highly Sensitive Fluorescence Detection of Global 5-Hydroxymethylcytosine from Nanogram Input with Strongly Emitting Copper Nanotags.

Quantitative analysis of 5-hydroxymethylcytosine (5hmC) has remarkable clinical significance to early cancer diagnosis; however, it is limited by the requirement in current assays for large amounts of starting material and expensive instruments requring expertise. Herein, we present a highly sensitive fluorescence method, termed hmC-TACN, for global 5hmC quantification from several nanogram inputs based on terminal deoxynucleotide transferase (TdT)-assisted formation of fluorescent copper (Cu) nanotags. In this method, 5hmC is labeled with click tags by T4 phage ß-glucosyltransferase (ß-GT) and cross-linked with a random DNA primer via click chemistry. TdT initiates the template-free extension along the primer at the modified 5hmC site and then generates a long polythymine (T) tail, which can template the production of strongly emitting Cu nanoparticles (CuNPs). Consequently, an intensely fluorescent tag containing numerous CuNPs can be labeled onto the 5hmC site, providing the sensitive quantification of 5hmC with a limit of detection (LOD) as low as 0.021% of total nucleotides (S/N = 3). With only a 5 ng input (∼1000 cells) of genomic DNA, global 5hmC levels were accurately determined in mouse tissues, human cell lines (including normal and cancer cells of breast, lung, and liver), and urines of a bladder cancer patient and healthy control. Moreover, as few as 100 cells can also be distinguished between normal and cancer cells. The hmC-TACN method has great promise of being cost effective and easily mastered, with low-input clinical utility, and even for the microzone analysis of tumor models.

Association between the pattern of mobile phone use and sleep quality in Northeast China college students.

OBJECTIVES: Currently, mobile penetration is high amongst college students. The aims of this study were to investigate the characteristics of mobile phone use and to explore the influence of mobile phone use characteristics on sleep quality amongst college students. METHODS: From December 2016 to January 2017, we collected mobile phone use characteristics and sleep quality data using the Pittsburgh Sleep Quality Index (PSQI) and standardised questionnaires that were answered by 4500 medical university students in Liaoning Province (actual response rate of 94%, n = 4234 college students). This study used the SPSS 21.0 software to establish the database and perform the statistical analysis. RESULTS: One hundred percent of the college students had mobile phones and used mobile phones for entertainment (91%), work (51%), obtaining information (61%), and other purposes (23%). Additionally, there was a statistically significant difference in the PSQI score between students who held the phone at a distance of more than 10 cm from their eyes and those who held it a distance of less than 10 cm (P = 0.002). Multiple logistic regression analysis showed that the risk of poor sleep quality was 1.21-1.53 times higher for those who spent more than 5 h a day using their phones and 1.41-1.59 times higher for those who used their phones for more than half an hour before going to bed when the lights were off. CONCLUSIONS: Daily cumulative mobile phone use and use with the lights off before sleep are associated with poorer sleep quality.

Doxorubicin cardiomyopathy is ameliorated by acacetin via Sirt1-mediated activation of AMPK/Nrf2 signal molecules.

Doxorubicin cardiotoxicity is frequently reported in patients undergoing chemotherapy. The present study investigates whether cardiomyopathy induced by doxorubicin can be improved by the natural flavone acacetin in a mouse model and uncovers the potential molecular mechanism using cultured rat cardiomyoblasts. It was found that the cardiac dysfunction and myocardial fibrosis induced by doxorubicin were significantly improved by acacetin in mice with impaired Nrf2/HO-1 and Sirt1/pAMPK molecules, which is reversed by acacetin treatment. Doxorubicin decreased cell viability and increased ROS production in rat cardiomyoblasts; these effects are significantly countered by acacetin (0.3-3 µM) in a concentration-dependent manner via activating Sirt1/pAMPK signals and enhancing antioxidation (Nrf2/HO-1 and SOD1/SOD2) and anti-apoptosis. These protective effects were abolished in cells with silencing Sirt1. The results demonstrate for the first time that doxorubicin cardiotoxicity is antagonized by acacetin via Sirt1-mediated activation of AMPK/Nrf2 signal molecules, indicating that acacetin may be a drug candidate used clinically for protecting against doxorubicin cardiomyopathy.

Appropriate duration of post-surgical intravenous antibiotic therapy for pyogenic spondylodiscitis.

BACKGROUND: Most guidelines recommend 6 to 12 weeks of parenteral antibiotic treatment for pyogenic spondylodiscitis. When surgical debridement is adequately performed, further intravenous antibiotic treatment duration can be reduced than that of conservative treatment alone theoretically. However, the appropriate duration of post-surgical parenteral antibiotic treatment is still unknown. This study aimed to identify the risk factors of recurrence and evaluate the appropriate duration after surgical intervention. METHODS: This 3-year retrospective review included 102 consecutive patients who were diagnosed with pyogenic spondylodiscitis and underwent surgical intervention. Recurrence was defined as recurrent signs and symptoms and the need for another unplanned parenteral antibiotic treatment or operation within one year. This study included two major portions. First, independent risk factors for recurrence were identified by multivariable analysis, using the database of demographic information, pre-operative clinical signs and symptoms, underlying illness, radiographic findings, laboratory tests, intraoperative culture results, and treatment. Patients with any one of the risk factors were considered high-risk; those with no risk factors were considered low-risk. Recurrence rates after short-term (≤3 weeks) and long-term (> 3 weeks) parenteral antibiotic treatment were compared between the groups. RESULTS: Positive blood culture and paraspinal abscesses were identified as independent risk factors of recurrence. Accordingly, 59 (57.8%) patients were classified as low-risk and 43 (42.2%) as high-risk. Among the high-risk patients, a significantly higher recurrence rate occurred with short-term than with long-term antibiotic therapy (56.2% vs. 22.2%, p = 0.027). For the low-risk patients, there was no significant difference between short-term and long-term antibiotic therapy (16.0% vs. 20.6%, p = 0.461). CONCLUSIONS: The appropriate duration of parenteral antibiotic treatment in patients with pyogenic spondylodiscitis after surgical intervention could be guided by the risk factors. The duration of postoperative intravenous antibiotic therapy could be reduced to 3 weeks for patients without positive blood culture or abscess formation.

Prevention of acute exacerbation of chronic hepatitis B infection in cancer patients receiving chemotherapy in a hepatitis B virus endemic area.

UNLABELLED: Reactivation of hepatitis B viral (HBV) infection in cancer patients undergoing chemotherapy may cause interruption of chemotherapy and lead to liver failure and death. In our institute, a computerized order entry-based alert system was introduced in September 2011 to remind healthcare providers of HBV testing when prescribing chemotherapy. Since August 2012, an order entry-based therapeutic control system has been applied to ensure HBV prophylaxis during chemotherapy. This retrospective cohort study included cancer patients receiving chemotherapy in the Kaohsiung Veterans General Hospital from November 2009 to June 2013. The prechemotherapy HBV screening rate, HBV prophylactic rate, and severe HBV acute exacerbation rate were compared between stages with different order systems. Newly diagnosed cancer patients (n = 2512) were included. The HBV testing rate in the screening reminder stage was higher than that in the educational stage (93.5% versus 40.2%, P < 0.001), whereas the adequate HBV prophylactic rates in the two order entry-based stages were comparable (41.1% versus 39.2%). Patients in the order entry-based therapeutic control stage had a higher HBV screening rate (99.3% versus 40.2%, P < 0.001) and a higher HBV prophylactic rate (95.8% versus 39.2%, P < 0.001) than those in the educational stage. Additionally, the severe HBV acute exacerbation rate in the therapeutic control stage was lower than those in the educational and screening reminder stages (0% versus 1.2% and 1.2%, respectively; both P < 0.01). CONCLUSION: A computerized order entry-based therapeutic control system can provide excellent prechemotherapy HBV screening for cancer patients undergoing chemotherapy and can effectively prevent severe acute exacerbation of HBV infection in hospitals among HBV endemic areas.

Is endoscopic treatment beneficial in patients with clinically suspicious of common bile duct stones but no obvious filling defects during the ERCP examination?

BACKGROUND: Sometimes, no definite filling defect could be found by cholangiogram (ERC) during the endoscopic retrograde cholangio-pancreatiographic (ERCP) exam; even prior images had evidence of common bile duct stones (CBDS). We aimed in estimating the positive rate of extraction of CBDS who had treated by endoscopic sphincterotomy/endoscopic papillary balloon dilation (EST/EPBD) with negative ERC finding. METHODS: One hundred forty-one patients with clinically suspicious of CBDS but negative ERC, who had received EST/EPBD treatments was enrolled. Potential factors for predicting CBDS, as well as the treatment-related complications were analyzed. RESULTS: Nearly half of the patients with negative ERC, had a positive stone extraction. Only patients with high probability of CBDS were significantly associated with positive stone extraction. Moreover, patients with intermediate probability of CBDS had higher rates of overall complications, including post-ERCP pancreatitis. In addition, no significant difference of post-ERCP pancreatitis was found between EST and EPBD groups in any one group of patients with the same probability of CBDS. CONCLUSIONS: Regarding patients with negative ERC, therapeutic ERCP is beneficial and safe for patients present with high probability of CBDS. Moreover, under the same probability of CBDS, there was no significance difference in post-ERCP pancreatitis between EST and EPBD.

Influence of various pilot hole profiles on pedicle screw fixation strength in minimally invasive and traditional spinal surgery: a comparative biomechanical study.

Despite advancements in pedicle screw design and surgical techniques, the standard steps for inserting pedicle screws still need to follow a set of fixed procedures. The first step, known as establishing a pilot hole, also referred to as a pre-drilled hole, is crucial for ensuring screw insertion accuracy. In different surgical approaches, such as minimally invasive or traditional surgery, the method of creating pilot holes varies, resulting in different pilot hole profiles, including variations in size and shape. The aim of this study is to evaluate the biomechanical properties of different pilot hole profiles corresponding to various surgical approaches. Commercially available synthetic L4 vertebrae with a density of 0.16 g/cc were utilized as substitutes for human bone. Four different pilot hole profiles were created using a 3.0 mm cylindrical bone biopsy needle, 3.6 mm cylindrical drill, 3.2-5.0 mm conical drill, and 3.2-5.0 mm conical curette for simulating various minimally invasive and traditional spinal surgeries. Two frequently employed screw shapes, namely, cylindrical and conical, were selected. Following specimen preparation, screw pullout tests were performed using a material test machine, and statistical analysis was applied to compare the mean maximal pullout strength of each configuration. Conical and cylindrical screws in these four pilot hole configurations showed similar trends, with the mean maximal pullout strength ranking from high to low as follows: 3.0 mm cylindrical biopsy needle, 3.6 mm cylindrical drill bit, 3.2-5.0 mm conical curette, and 3.2-5.0 mm conical drill bit. Conical screws generally exhibited a greater mean maximal pullout strength than cylindrical screws in three of the four different pilot hole configurations. In the groups with conical pilot holes, created with a 3.2-5.0 mm drill bit and 3.2-5.0 mm curette, both conical screws exhibited a greater mean maximal pullout strength than did cylindrical screws. The strength of this study lies in its comprehensive comparison of the impact of various pilot hole profiles commonly used in clinical procedures on screw fixation stability, a topic rarely reported in the literature. Our results demonstrated that pilot holes created for minimally invasive surgery using image-guided techniques exhibit superior pullout strength compared to those utilized in traditional surgery. Therefore, we recommend prioritizing minimally invasive surgery when screw implantation is anticipated to be difficult or there is a specific need for stronger screw fixation. When opting for traditional surgery, image-guided methods may help establish smaller pilot holes and increase screw fixation strength.

Forcefully engaging rods into tulips with gap discrepancy leading to pedicle screw loosening-a biomechanical analysis using long porcine spine segments.

BACKGROUND CONTEXT: Long-segment pedicle screw instrumentation is widely used to treat complex spinal disorders. Rods are routinely precontoured to maximize assistance on the correcting side of the deformity, but there often exists a residual gap discrepancy between the precontoured rods and screw tulips. No previous research has investigated the diminished pullout strength of the most proximal or distal pedicle screw resulting from a mismatched rod in long-segment pedicle screw instrumentation. PURPOSE: The present study aimed to investigate the decreased pullout force of pedicle screws affected by the gap discrepancy when forcefully engaging a mismatched rod into a tulip in a normal-density porcine spine. STUDY DESIGN: The pedicle screw fixation strength under axial pullout force was compared among three different gap discrepancies between rods and tulips using long porcine spine segments. METHODS: Twelve porcine lumbar vertebrae (L3-L6) were implanted with pedicle screws and rods. Screws on one side had no gap between the tulip and rod (0-mm group), while the most proximal screw on the other side had an intentional gap of 3 mm (3-mm group) or 6 mm (6-mm group). Three hours after forcefully engaging the rod into the tulips at room temperature, the set screws in all specimens were loosened, and each specimen was dissected into individual vertebrae for subsequent pullout testing. RESULTS: The control group exhibited significantly greater pullout strength (1987.68 ± 126.80 N) than the groups from different rod-tulip configurations (p<.05), with significantly greater strength in the 3-mm group (945.62 ± 97.43 N) than the 6-mm group (655.30 ± 194.49 N) (p<.05). Only 47.6% and 33.0% of the pullout strength was retained in the 3-mm and 6-mm groups, respectively, compared to the control group. CONCLUSIONS: Gap discrepancies between rods and tulips can significantly reduce pedicle screw pullout strength, with a correlation between decreased strength and increased gaps. Surgeons should avoid forcefully engaging mismatched rods and consider well-fitted contoured rods in spinal surgery to minimize the risk of screw loosening. CLINICAL SIGNIFICANCE: The gap discrepancy between rod and tulip significantly affected pullout strength, with greater gaps leading to reduced strength. Forcefully engaging mismatched rods into tulips in degenerative spinal surgery should be avoided to minimize the risk of early screw pullout.

Biomechanical evaluation of position and bicortical fixation of anterior lateral vertebral screws in a porcine model.

Although an anterior approach with anterior lateral screw fixation has been developed for stabilizing the thoracolumbar spine clinically, screw loosening still occurs. In this novel in vitro study, we attempted to elucidate the optimal screw position in the lateral lumbar vertebra and the effect of bicortical fixation. A total of 72 fresh-frozen lumbar vertebrae from L1-6 were harvested from 12 mature pigs and randomly assigned to two modalities: bicortical fixation (n = 36) and unicortical fixation (n = 36). Six groups of screw positions in the lateral vertebral body in each modality were designated as central-anterior, central-middle, central-posterior, lower-anterior, lower-middle, and lower- posterior; 6 specimens were used in each group. The correlations between screw fixation modalities, screw positions and axial pullout strength were analyzed. An appropriate screw trajectory and insertional depth were confirmed using axial and sagittal X-ray imaging prior to pullout testing. In both bicortical and unicortical fixation modalities, the screw pullout force was significantly higher in the posterior or middle position than in the anterior position (p < 0.05), and there was no significant differences between the central and lower positions. The maximal pullout forces from the same screw positions in unicortical fixation modalities were all significantly lower, decreases that ranged from 32.7 to 74%, than those in bicortical fixation modalities. Our study using porcine vertebrae showed that screws in the middle or posterior position of the lateral vertebral body had a higher pullout performance than those in the anterior position. Posteriorly positioned lateral vertebral screws with unicortical fixation provided better stability than anteriorly positioned screws with bicortical fixation.

Finite element analysis of optimized novel additively manufactured non-articulating prostheses for cervical total disc replacement.

Ball-and-socket designs of cervical total disc replacement (TDR) have been popular in recent years despite the disadvantages of polyethylene wear, heterotrophic ossification, increased facet contact force, and implant subsidence. In this study, a non-articulating, additively manufactured hybrid TDR with an ultra-high molecular weight polyethylene core and polycarbonate urethane (PCU) fiber jacket, was designed to mimic the motion of normal discs. A finite element (FE) study was conducted to optimize the lattice structure and assess the biomechanical performance of this new generation TDR with an intact disc and a commercial ball-and-socket Baguera®C TDR (Spineart SA, Geneva, Switzerland) on an intact C5-6 cervical spinal model. The lattice structure of the PCU fiber was constructed using the Tesseract or the Cross structures from the IntraLattice model in the Rhino software (McNeel North America, Seattle, WA) to create the hybrid I and hybrid II groups, respectively. The circumferential area of the PCU fiber was divided into three regions (anterior, lateral and posterior), and the cellular structures were adjusted. Optimal cellular distributions and structures were A2L5P2 in the hybrid I and A2L7P3 in the hybrid II groups. All but one of the maximum von Mises stresses were within the yield strength of the PCU material. The range of motions, facet joint stress, C6 vertebral superior endplate stress and path of instantaneous center of rotation of the hybrid I and II groups were closer to those of the intact group than those of the Baguera®C group under 100 N follower load and pure moment of 1.5 Nm in four different planar motions. Restoration of normal cervical spinal kinematics and prevention of implant subsidence could be observed from the FE analysis results. Superior stress distribution in the PCU fiber and core in the hybrid II group revealed that the Cross lattice structure of a PCU fiber jacket could be a choice for a next-generation TDR. This promising outcome suggests the feasibility of implanting an additively manufactured multi-material artificial disc that allows for better physiological motion than the current ball-and-socket design.

Biomechanical evaluation of pedicle screw stability after 360-degree turnback from full insertion: effects of screw shape, pilot hole profile and bone density.

Intraoperative pedicle screw depth adjustment after initial insertion, including both forward and backward adjustments, is sometimes necessary to facilitate rod application and ensure that the screw is in the correct position, which is determined by intraoperative fluoroscopy. Adjusting the screw with forward turns has no negative influence on the screw fixation stability; however, screw turnback may weaken the fixation stability. The aim of this study is to evaluate the biomechanical properties of screw turnback and demonstrate the reduction in the fixation stability after the screw is turned 360° from its full insertion position. Commercially available synthetic closed-cell polyurethane foams with three different densities simulating various degrees of bone density were utilized as substitutes for human bone. Two different screw shapes (cylindrical and conical) together with two different pilot hole profiles (cylindrical and conical) were tested. Following specimen preparation, screw pullout tests were conducted using a material test machine. The mean maximal pullout strength between full insertion and 360-degree turnback from full insertion in each setting was statistically analyzed. The mean maximal pullout strength after 360-degree turnback from full insertion was generally lower than that at full insertion. The reduced mean maximal pullout strength after turnback increased with decreasing bone density. Conical screws had significantly lower pullout strength after 360-degree turnback than cylindrical screws. The mean maximal pullout strength was reduced by up to approximately 27% after 360-degree turnback when using a conical screw in a low bone density specimen. Additionally, specimens treated with a conical pilot hole presented a less reduction in pullout strength after screw turnback as compared to those with a cylindrical pilot hole. The strength of our study was that we systematically investigated the effects of various bone densities and screw shapes on screw stability after turnback, which has rarely been reported in the literature. Our study suggests that pedicle screw turnback after full insertion should be reduced in spinal surgeries, particularly procedures that use conical screws in osteoporotic bone. Pedicle screw secured with a conical pilot hole might be beneficial for screw adjustment.

The role of counter-torque holders in tightening of pedicle screw-rod constructs: a biomechanical study in a porcine model.

BACKGROUND CONTEXT: Pedicle screw-rod assembly procedures following pedicle screw insertion include contouring and placing rods into screw tulips, introducing set screws into the tulip along the screw thread, applying a counter-torque holder and tightening all the set screws clockwise. Even if an appropriate pedicle screw is implanted, screw dislodgement after tightening of the tulip and set screw is not uncommon. Pedicle wall violation resulting from excessive rotational force due to inadequate use of a counter-torque holder might be the reason. However, the strain change in the pedicle during tulip-set screw tightening and the role of counter-torque have never been investigated. PURPOSE: This study determined differences in the strain change in the outer and inner pedicle walls during tulip-set screw tightening; additionally, the influence of counter-torque on pedicle wall violation was elucidated. STUDY DESIGN: A controlled biomechanical study; the strain values of outer and inner pedicle walls in cadaveric porcine L4-L5 vertebrae during tulip-set screw tightening with or without a counter-torque holder were measured. METHODS: Twelve L4-L5 fresh-frozen porcine lumbar vertebrae were implanted with screw-rod constructs; the set screw was randomly locked into the tulip in the right L5, right L4, left L5 and left L4 testing groups. The maximal values from eight strain gauges (P-R-O: outer cortex of right pedicle in proximal vertebra; P-R-I: inner cortex of right pedicle in proximal vertebra; D-R-O: outer cortex of right pedicle in distal vertebra; D-R-I: inner cortex of right pedicle in distal vertebra; P-L-O: outer cortex of left pedicle in proximal vertebra; P-L-I: inner cortex of left pedicle in proximal vertebra; D-L-O: outer cortex of left pedicle in distal vertebra; D-L-I: outer cortex of left pedicle in proximal vertebra) for each specimen during tightening to 12 Nm were measured. RESULTS: The maximal strain values of the ipsilateral strain gauges in all testing groups were almost significantly higher when a counter-torque holder was not used than when one was used. The strain values in the adjacent pedicle of specimens without a counter-torque holder were significantly increased: P-R-O and P-R-I in the right L5 group; D-R-I in the right L4 group; P-L-I and P-L-O in the left L5 group; D-L-O and D-L-I in the left L4 group. CONCLUSIONS: The constraint effect of counter-torque during tulip-set screw tightening is necessary. Clockwise rotational force with a fragile lateral pedicle wall suggests that caution is required when using a counter-torque holder to tighten the right L5 and left L4 constructs. CLINICAL SIGNIFICANCE: A counter-torque holder is important during tulip-set screw tightening; improper use may lead to adjacent pedicle wall violation, sequentially resulting in pedicle screw loosening.

Enzastaurin cardiotoxicity: QT interval prolongation, negative inotropic responses and negative chronotropic action.

Several clinical trials observed that enzastaurin prolonged QT interval in cancer patients. However, the mechanism of enzastaurin-induced QT interval prolongation is unclear. Therefore, this study aimed to assess the effect and mechanism of enzastaurin on QT interval and cardiac function. The Langendorff and Ion-Optix MyoCam systems were used to assess the effects of enzastaurin on QT interval, cardiac systolic function and intracellular Ca2+ transient in guinea pig hearts and ventricular myocytes. The effects of enzastaurin on the rapid delayed rectifier (IKr), the slow delayed rectifier K+ current (IKs), transient outward potassium current (Ito), action potentials, Ryanodine Receptor 2 (RyR2) and the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) expression and activity in HEK 293 cell system and primary cardiomyocytes were investigated using whole-cell recording technique and western blotting. We found that enzastaurin significantly prolonged QT interval in guinea pig hearts and increased the action potential duration (APD) in guinea pig cardiomyocytes in a dose-dependent manner. Enzastaurin potently inhibited IKr by binding to the human Ether-à-go-go-Related gene (hERG) channel in both open and closed states, and hERG mutant channels, including S636A, S631A, and F656V attenuated the inhibitory effect of enzastaurin. Enzastaurin also moderately decreased IKs. Additionally, enzastaurin also induced negative chronotropic action. Moreover, enzastaurin impaired cardiac systolic function and reduced intracellular Ca2+ transient via inhibition of RyR2 phosphorylation. Taken together, we found that enzastaurin prolongs QT, reduces heart rate and impairs cardiac systolic function. Therefore, we recommend that electrocardiogram (ECG) and cardiac function should be continuously monitored when enzastaurin is administered to cancer patients.

Continuous-wave terahertz in-line digital holography.

A terahertz (THz) in-line digital holography project has been proposed based on a CO2 pumped 2.52 THz continuous-wave laser and a pyroelectric-array camera used as the detector. The THz Gabor in-line digital holograms have been obtained and then the high resolution reconstruction of THz in-line digital holography was realized. The resolution of an in-line digital holography system has been tested by the use of a series of objects. High-quality and high-resolution reconstructed images have been obtained, and the real lateral resolution is higher than 0.2 mm. It can be inferred from the results that the THz Gabor in-line digital holography system has the abilities of real-time and high-resolution imaging.