Explore the vast range of titles available.

PurposeNavigation is emerging as a useful adjunct in percutaneous, minimally invasive spinal surgery (MIS). The aim of this study was to compare C-Arm navigated, O-Arm navigated and conventional 2D-fluoroscopy assisted MIS thoracic and lumbosacral spine fixation techniques in terms of operating time, radiation exposure and accuracy of pedicle screw (PS) placement.MethodsRetrospective observational study of 152 consecutive adults who underwent MIS fixations for spinal instability: 96 2D-fluoroscopy assisted, 39 3D-C-Arm navigated and 27 using O-Arm navigated.ResultsO-Arm navigation significantly reduced PS misplacement (1.23%, p) compared to 3D-C-Arm navigation (7.29%, p = 0.0082) and 2D-fluoro guided placement (5.16%, p = 0379). 3D-C-Arm navigation was associated with lower procedural radiation exposure of the patient (0.4 mSv) than O-Arm navigation (3.24 mSv) or 2D-fluoro guidance (1.5 mSv). Operative time was comparable between three modalities.ConclusionsO-Arm navigation provides greater accuracy of percutaneous instrumentation placement with an acceptable procedural radiation dose delivered to the patients and comparable operative times.Graphical abstractThese slides can be retrieved under Electronic Supplementary material.

Spiking neural networks exploit spatiotemporal processing, spiking sparsity, and high interneuron bandwidth to maximize the energy efficiency of neuromorphic computing. While conventional silicon-based technology can be used in this context, the resulting neuron-synapse circuits require multiple transistors and complicated layouts that limit integration density. Here, we demonstrate unprecedented electrostatic control of dual-gated Gaussian heterojunction transistors for simplified spiking neuron implementation. These devices employ wafer-scale mixed-dimensional van der Waals heterojunctions consisting of chemical vapor deposited monolayer molybdenum disulfide and solution-processed semiconducting single-walled carbon nanotubes to emulate the spike-generating ion channels in biological neurons. Circuits based on these dual-gated Gaussian devices enable a variety of biological spiking responses including phasic spiking, delayed spiking, and tonic bursting. In addition to neuromorphic computing, the tunable Gaussian response has significant implications for a range of other applications including telecommunications, computer vision, and natural language processing. Designing high performance, scalable, and energy efficient spiking neural networks remains a challenge. Here, the authors utilize mixed-dimensional dual-gated Gaussian heterojunction transistors from single-walled carbon nanotubes and monolayer MoS2 to realize simplified spiking neuron circuits.

The objective of this study was to evaluate annual heart transplant volumes and 3-year post-transplant outcomes since establishment of United Network for Organ Sharing (UNOS) database stratified by race. The UNOS thoracic transplant database was evaluated for adult patients since 1987. The available database was then stratified by Race: Black, White and Other and era of transplant: group 1(1987-1991), group 2(1992-1996), group 3(1997-2001), group 4(2002-2006), group 5(2007-2011), group 6(2012-2016) and group 7(2017 and later). Demographic and clinical factors were evaluated. A total of 105,266 adults have been listed since 1987 and 67,824 have been transplanted. Of the transplanted patients 11,235 were Black, 48,786 White and 6803 were of Other race. The proportion of Black patients listed increased from 7% in 1987 to 13.4% in 1999 and 25% in 2019 and those transplanted increased from 5% in 1987 to 13.4% in 2001 and 26% in 2019. The survival of Black patients gradually improved. Historically, fewer Black patients received cardiac transplantation however, their access gradually improved over the years and account for over 25% of cardiac transplantations performed in recent years. The historically poor survival of Black patients has recently improved and became comparable to the rest.

This study examines the impact of monsoon systems on the isotopic composition of rainfall in India’s core monsoon zone (CMZ). The CMZ is influenced by the monsoon trough and the low-pressure systems that cause considerable rain. However, there is a lack of systematic studies on how these monsoon systems affect the isotopic composition of precipitation in the CMZ. A six-year precipitation isotopic record shows that the low-pressure systems, through their origin, trajectory, and intensity, significantly impact the isotopic values of rainfall. These systems and convective activities typically produce depleted isotopic values. An examination of the monthly composited LPS (low-pressure system) intensity and its corresponding precipitation isotopic values revealed a noteworthy inverse relation. Additionally, terrestrial evaporation could significantly impact the isotopic values of precipitation. The isotopic variabilities in central and northeastern India showed an out-of-phase distribution, mimicking the dipolar nature of rainfall variability. This characteristic feature makes the CMZ ideal for proxy analysis to reconstruct past rainfall variability.

Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic β subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation. WFA increased expression of osteoblast-specific transcription factor and mineralizing genes, promoted osteoblast survival and suppressed inflammatory cytokines. In osteoclast, WFA treatment decreased osteoclast number directly by decreasing expression of tartarate-resistant acid phosphatase and receptor activator of nuclear factor kappa-B (RANK) and indirectly by decreasing osteoprotegrin/RANK ligand ratio. Our data show that in vitro treatment of WFA to calvarial osteoblast cells decreased expression of E3 ubiquitin ligase, Smad ubiquitin regulatory factor 2 (Smurf2), preventing degradation of Runt-related transcription factor 2 (RunX2) and relevant Smad proteins, which are phosphorylated by bone morphogenetic protein 2. Increased Smurf2 expression due to exogenous treatment of tumor necrosis factor α (TNF α ) to primary osteoblast cells was decreased by WFA treatment. This was corroborated by using small interfering RNA against Smurf2. Further, WFA also blocked nuclear factor kappa-B (NF-kB) signaling as assessed by tumor necrosis factor stimulated nuclear translocation of p65-subunit of NF-kB. Overall data show that in vitro proteasome inhibition by WFA simultaneously promoted osteoblastogenesis by stabilizing RunX2 and suppressed osteoclast differentiation, by inhibiting osteoclastogenesis. Oral administration of WFA to osteopenic ovariectomized mice increased osteoprogenitor cells in the bone marrow and increased expression of osteogenic genes. WFA supplementation improved trabecular micro-architecture of the long bones, increased biomechanical strength parameters of the vertebra and femur, decreased bone turnover markers (osteocalcin and TNF α ) and expression of skeletal osteoclastogenic genes. It also increased new bone formation and expression of osteogenic genes in the femur bone as compared with vehicle groups (Sham) and ovariectomy (OVx), Bortezomib (known PI), injectible parathyroid hormone and alendronate (FDA approved drugs). WFA promoted the process of cortical bone regeneration at drill-holes site in the femur mid-diaphysis region and cortical gap was bridged with woven bone within 11 days of both estrogen sufficient and deficient (ovariectomized, Ovx) mice. Together our data suggest that WFA stimulates bone formation by abrogating proteasomal machinery and provides knowledge base for its clinical evaluation as a bone anabolic agent.

Tumor necrosis factor α -related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent with cancer cell-selective cell death inducing effect. However, the major limitation in the usage of TRAIL as a chemotherapeutic agent is the development of TRAIL resistance in many cancer types including myeloid leukemia. In this study, we report for the first time that Medicarpin (Med), a naturally occurring phytoalexin sensitizes myeloid leukemia cells to TRAIL-induced apoptosis. Combination of Med and TRAIL induced significantly higher apoptosis compared with that of the individual treatments of either agent alone through activation of both the extrinsic and the intrinsic cell death pathways characterized by the activation of caspases 8, 9, 3, and 7. Med treatment downregulated antiapoptotic proteins (Survivin, Bcl2, Bcl-xL, XIAP, and c-FLIP), upregulated pro-apoptotic proteins (Bax, Cytochrome C, Smac/Diablo, Bid, truncated Bid (tBid), p-eIF2 α , Bip, and CHOP (CCAAT-enhancer binding protein homologous protein)), induced G2/M cell-cycle arrest, and increased the expression of the functional TRAIL receptor DR5 through activation of the ROS-JNK-CHOP pathway. Gain and loss of function studies clearly indicated that DR5 expression was critical for Med-induced TRAIL sensitization. The Med-induced TRAIL sensitization did not involve the NFkB signaling pathway or redistribution of DR5 in lipid rafts. The concomitant treatment with Med and TRAIL showed robust apoptotic effects in primary myeloid leukemia cells but had no toxic effects in primary human peripheral blood mononuclear cells (PBMCs). In conclusion, our results suggest that Med sensitizes myeloid leukemia cells to TRAIL-induced apoptosis through the upregulation of DR5 through activation of the ROS-JNK-CHOP pathway.

Background Chitosan is a dietary fibre which acts by reducing fat absorption and thus used as a means for controlling weight. Weight loss clinical trial outcomes, however, have contradictory results regarding its efficacy. The primary objective of the present study was to evaluate the efficacy and safety of a chitosan from fungal origin in treatment of excess weight in the absence of dietary restrictions. Methods A phase IV, randomised, multicentre, single-blind, placebo-controlled, clinical study was conducted by administering chitosan capsules (500 mg, five/day) and indistinguishable placebo capsules as daily supplements to 96 overweight and obese subjects for 90 days. The study participants were divided in 2:1 ratio to receive either chitosan ( n  = 64) or placebo ( n  = 32). Efficacy was assessed by measuring body weight, body composition parameters, anthropometric measurements, HbA1C level and lipid profile at day 45 and day 90. Also, short form-36 quality of life (QoL) questionnaire was assessed to evaluate improvement in life-style and dietary habits were recorded for calorie intake. Safety was assessed by evaluating safety parameters and monitoring adverse events. Results The mean changes in body weight were -1.78 ± 1.37 kg and -3.10 ± 1.95 kg at day 45 and day 90 respectively in chitosan group which were significantly different ( p  < 0.0001) as compared to placebo. BMI was decreased by10.91 fold compared to placebo after 90 day administration. In concert with this, there was also reduction in body composition and anthropometric parameters together with improvement in QoL score. Chitosan was also able to reduce HbA1C levels (below 6 %) in subjects who had initial higher values. The mean caloric intake shows that there was no change in dietary habits of subjects in both groups. Lipid levels were unaffected and all adverse events were mild in nature and unrelated to study treatment. Conclusion Chitosan from fungal origin was able to reduce the mean body weight up to 3 kg during the 90 day study period. Together with this, there was also improvement in body composition, anthropometric parameters and HbA1C, reflecting overall benefits for the overweight individuals. Additionally, there was also improvement in QoL score. It was safe and well tolerated by all subjects. Trial registration CTRI/2014/08/004901.

Objective/Purpose. Chronic contiguous osteomyelitis (CCO) is a well-recognized clinical condition. Causative factors include direct trauma, prior surgery, or underlying comorbidities like diabetes and vascular insufficiency. Staphylococci especially S. aureus, Streptococci especially beta-hemolytic Streptococci, Gram-negative bacilli, and anaerobes are the most common pathogens isolated. Corynebacterium striatum (C. striatum) is a ubiquitous Gram-positive rod that colonizes the skin and mucous membranes of normal hosts and hospitalized patients. The pathogenic potential of C. striatum has only been reported in immunocompromised hosts and in patients with retained foreign bodies and prosthetic devices. However, it is not a known causative agent of chronic contiguous osteomyelitis. Design/Method. We recognized seven cases of CCO whereby amidst polymicrobial growth, C. striatum appeared to be a true pathogen and required targeted treatment along with surgical intervention. Main Outcome Measures. A pre-post analysis was used to assess the outcome. Results. All patients were cured after successful completion of an antibiotic course with a resolution of infection. Cure was defined as granulation of the infected wound and resolution of clinical symptoms at outpatient follow-up between 6 and 8 weeks. Conclusion. This series emphasizes that C. striatum is often a true pathogen in the setting of CCO. When isolated in polymicrobial infections, a targeted antibiotic therapy towards this pathogen along with other causative pathogens accompanied by surgical intervention is typically required for a successful cure of CCO.

Recent reports on ischemic mitral valve (MV) regurgitation surgical strategies have suggested better hemodynamic performance with MV replacement (MVR) than MV repair (MVr) with no survival difference at 2 years. We evaluated the difference between MVR and MVr outcomes in patients with ischemic MR, including hemodynamic MV performance at 1 and 2 years postoperatively. A single center cardiac surgery database was queried for patients (aged >/ = 18 years) requiring mitral valve surgery with concomitant CABG or PCI between January 2010 and June 2018. Patients were separated into two groups: mitral valve repair using ring annuloplasty (MVr) and mitral valve replacement (MVR). A total of 111 patients (median age 66 years, 76% male) underwent an operation for ischemic mitral regurgitation during the study period. (44%) had MVr and 62 (56%) had MVR. Both groups had > 80% concomitant CABG. The MVr group had lower EF (40% vs. 55%, p < 0.01), shorter cardiopulmonary bypass time (117 vs. 164 minutes, p < .01) and shorter aortic cross-clamp time (80 vs. 116 minutes, p < .01). The in-hospital mortality (6% vs. 10%, p = 1.00) and 1-year mortality (14% vs. 18%, p = 0.17) were similar between the groups. Pre-operative left ventricular internal diameter at end-diastole was greater in the MVr group (5.6cm vs. 4.6cm, p < .01). At 1-year, more patients in the MVR group had no or trace regurgitation (29% vs. 61%, p = 0.01), however, the number of patients with moderate or greater mitral regurgitation was similar (6% vs. 12%, p = 0.69). At 2-years, the MVr and MVR groups had no difference in moderate or severe mitral regurgitation (7% vs. 13%, p = 0.68). Our findings demonstrate similar early mortality and mid-term mitral valve performance, suggesting that MV repair could be a good surgical option in patients with ischemic MR requiring surgical revascularization.

Background Chlorogenic acid, a phenolic derivative, shows excellent pharmacological properties. However, poor lipidic solubility, permeability, and oral bioavailability restrict its clinical use. Therefore, two different phospholipids—Phospholipon® 90H and LIPOID® S100 nanophytovesicles (NPVs)—were optimized, formulated and compared with central composite design for improved biopharmaceutical properties, antioxidant, anticancer and wound-healing activities. Results Higher entrapment (> 95%) and partition coefficient values were obtained with optimized CGA 90H NPVs and S100 NPVs. Particle size and zeta potential values confirmed small particle size(≅ 450 nm) with optimum stability. Non-covalent interactions between CGA and both phospholipids were confirmed with Fourier transform infrared spectrophotometry, differential scanning calorimetry and proton nuclear magnetic resonance. NPVs significantly enhanced the lipidic solubility (> 25 times) supported by high-performance thin-layer chromatography. A sustained dissolution and diffusion release were obtained with NPVs as compared to pure CGA. Likewise, ≅ twofold increase in permeability was obtained, supported by confocal microscopy. Enhanced oral bioavailability of CGA with improved C max , T max , AUC, half-life values was obtained with NPVs along with IVIV correlation. Enhanced DPPH radical scavenging and Fe 2+ chelation ability were obtained with CGA 90H NPVs > CGA S100 NPVs, with lower IC 50 values in HeLa and HL-60 cell lines (< 0.75 times) as compared to CGA in MTT(3-(4,5-dimethylthiazol-2-yl)- 2,5- diphenyltetrazolium bromide) assay. Higher wound contraction percentages were observed at day 3 with CGA S100 NPVs (71.56%) > CGA 90H NPVs (34.0%) in wound-healing studies. Conclusions The formulated NPVs exhibited efficiency of Phospholipon®90 H in enhancing oral bioavailability and LIPOID® S100 in increasing transdermal permeability, thus proving as promising carriers for enhancing biopharmaceutical and pharmacological properties of chlorogenic acid.