Neuroprotective role of Carvacrol via Nrf2/HO-1/NLRP3 axis in Rotenone-induced PD mice model.

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder whose cause is unclear. Neuroinflammation is recognized as one of the major pathogenic mechanisms involved in the development and progression of PD. NLRP3 inflammasome is the most widely studied inflammatory mediator in various diseases including PD. Several phytoconstituents have shown neuroprotective role in PD. Carvacrol is a phenolic monoterpene commonly found in the essential oils derived from plants belonging to Lamiaceae family. It is well known for its anti-inflammatory and antioxidant properties and has been widely explored in several diseases. In this study, we explored the role of Carvacrol in suppressing neuroinflammation by regulating NLRP3 inflammasome through Nrf2/HO-1 axis and subsequently, inflammatory cytokines like IL-1ß, IL-18 in Rotenone induced PD mice model. Three doses (25 mg/kg, 50 mg/kg, 100 mg/kg p.o.) of Carvacrol were administered to, respectively, three groups (LD, MD, HD), one hour after administration of Rotenone (1.5 mg/kg, i.p.), every day, for 21 days. Treatment with Carvacrol ameliorated the motor impairment caused by Rotenone. It alleviated neurotoxicity and reduced inflammatory cytokines. Further, Carvacrol also alleviated oxidative stress and increased antioxidant enzymes. From these results, we show that Carvacrol exerts neuroprotective effects in PD via anti-inflammatory and antioxidant mechanisms and could be a potential therapeutic option in PD.

Addressing Irreversibility and Structural Distortion in WS2 Inorganic Fullerene-Like Nanoparticles: Effects of Voltage Cutoff Experiments in Beyond Li+-Ion Storage Applications.

Large interlayer spacing beneficially allows Na+- and K+-ion storage in transition-metal dichalcogenide (TMD)-based electrodes, but side reactions and volume change, which pulverize the TMD crystalline structure, are persistent challenges for the utilization of these materials in next-generation devices. This study first determines whether irreversibility due to structural distortion, which results in poor cycling stability, is also apparent in the case of inorganic fullerene-like (IF) tungsten disulfide (WS2) nanocages (WS2IF). To address these problems, this study proposes upper and lower voltage cutoff experiments to limit specific reactions in Na+/WS2IF and K+/WS2IF half-cells. Three-dimensional (3D) differential capacity curves and derived surface plots highlight the continuation of reversible reactions when a high upper cutoff technique is applied, thereby indirectly suggesting restricted structural dissolution. This resulted in improved capacity retention with stable performance and a higher Coulombic efficiency, laying the ground for the use of TMD-based materials beyond Li+-ion storage devices.

A Young Female With Takayasu Arteritis Involving the Coronary Arteries.

A rare form of large vessel vasculitis, Takayasu arteritis (TA) typically affects the aorta and its primary branches and rarely involves the coronary arteries. We present a case study of a female patient who had refractory hypertension and coronary artery disease for which she underwent percutaneous transluminal angioplasty. Subsequently, she was diagnosed with Takayasu arteritis. We wish to underscore the significance of timely identification and intervention as pivotal factors in improving patient outcomes and optimizing the effectiveness of therapeutic strategies in managing TA.

Exosome-mediated delivery and regulation in neurological disease progression.

Exosomes (EXOs), membranous structures originating from diverse biological sources, have recently seized the attention of researchers due to their theranostic potential for neurological diseases. Released actively by various cells, including stem cells, adipose tissue, and immune cells, EXOs wield substantial regulatory influence over the intricate landscape of neurological complications, exhibiting both positive and negative modulatory effects. In AD, EXOs play a pivotal role in disseminating and breaking down amyloid-ß protein. Moreover, EXOs derived from mesenchymal stem cells showcase a remarkable capacity to mitigate pro-inflammatory phenotypes by regulating miRNAs in neurodegenerative diseases. These vesicles possess the unique ability to traverse the blood-brain barrier, governing the aggregation of mutant huntingtin protein. Understanding the exosomal functions within the CNS holds significant promise for enhancing treatment efficacy in neurological diseases. This review intricately examines the regulatory mechanisms involving EXOs in neurological disease development, highlighting therapeutic prospects and exploring their utility in exosome-based nanomedicine for various neurological complications. Additionally, the review highlights the challenges associated with drug delivery to the brain, emphasizing the complexities inherent in this critical aspect of neurotherapeutics.

Cognitive Functional Therapy compared with usual physiotherapy care in people with persistent low back pain: a mixed methods feasibility randomised controlled trial in the United Kingdom National Health Service.

OBJECTIVES: To determine the feasibility of completing a definitive randomised controlled trial (RCT), evaluating the clinical and cost-effectiveness of Cognitive Functional Therapy (CFT) in comparison to usual physiotherapy care (UPC), for people with persistent low back pain (LBP). DESIGN AND SETTING: A two-arm parallel feasibility RCT completed in a United Kingdom (UK) Secondary Care National Health Service (NHS) physiotherapy service. PARTICIPANTS: Sixty adult participants who reported LBP lasting for more than three months, that was not attributable to a serious (e.g. cancer) or specific (e.g. radiculopathy) underlying cause, were invited to participate. Participants were allocated at random to receive CFT or UPC. INTERVENTIONS: Cognitive Functional Therapy and Usual Physiotherapy Care for persistent LBP. MAIN OUTCOME MEASURES: The primary outcome was the feasibility of completing a definitive RCT, defined by recruitment of at least 5 participants per month, delivery of CFT per protocol and securing relevant and acceptable outcome measures. Data concerning study processes, resources, management and participant reported outcome measures were collected at baseline, 3, 6 and 12-month follow-up. RESULTS: Sixty participants (n = 30 CFT and n = 30 UPC) were recruited with 80% (n = 48), 72% (n = 43) and 53% (n = 32) retained at 3, 6 and 12-month follow-up respectively. NHS physiotherapists were trained to competence and delivered CFT with fidelity. CFT was tolerated by participants with no adverse events. Relevant and clinically important outcome data were collected at all time points (0.4%, 3%, 1% and 0.8% of data was missing from the returned outcome measure booklets at baseline and 3, 6 and 12-month follow-up respectively). The Roland-Morris disability questionnaire was considered the most suitable primary outcome measure with a proposed sample size of 540 participants for a definitive cluster RCT. CONCLUSION: It is feasible to conduct a randomised study of CFT in comparison to UPC for NHS patients. A future study should incorporate an internal pilot to address aspects of feasibility further, including participant retention strategies. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN12965286 CONTRIBUTION OF THE PAPER.

Analytical investigations of propagation of ultra-broad nonparaxial pulses in a birefringent optical waveguide by three computational ideas.

This paper mainly concentrates on obtaining solutions and other exact traveling wave solutions using the generalized G-expansion method. Some new exact solutions of the coupled nonlinear Schrödinger system using the mentioned method are extracted. This method is based on the general properties of the nonlinear model of expansion method with the support of the complete discrimination system for polynomial method and computer algebraic system (AS) such as Maple or Mathematica. The nonparaxial solitons with the propagation of ultra-broad nonparaxial pulses in a birefringent optical waveguide is studied. To attain this, an illustrative case of the coupled nonlinear Helmholtz (CNLH) system is given to illustrate the possibility and unwavering quality of the strategy utilized in this research. These solutions can be significant in the use of understanding the behavior of wave guides when studying Kerr medium, optical computing and optical beams in Kerr like nonlinear media. Physical meanings of solutions are simulated by various Figures in 2D and 3D along with density graphs. The constraint conditions of the existence of solutions are also reported in detail. Finally, the modulation instability analysis of the CNLH equation is presented in detail.

Cancer associated fibroblasts modulate the cytotoxicity of anti-cancer drugs in breast cancer: An in vitro study.

BACKGROUND: Tumour microenvironment (TME) contributes to resistance to anti-cancer drugs through multiple mechanisms including secretion of pro-survival factors by cancer associated fibroblasts (CAFs). In this study, we determined the chemotherapy resistance producing potential of CAFs in molecular subtypes of breast cancer. METHODS: The CAFs were isolated from fresh lumpectomy/mastectomy specimens of different molecular subtypes of breast cancer. The CAFs were cultured and secretome was collected from each breast cancer subtype. Breast cancer cell lines MCF-7, SK-BR3, MDA-MB-231, and MDA-MB-468 were treated with different doses of tamoxifen, trastuzumab, cisplatin, and doxorubicin alone respectively and in combination with secretome of CAFs from respective subtypes. MTT assay was done to check cell death after drug treatment. Liquid chromatography-mass spectrometry (LCMS) analysis of CAF secretome was also done. RESULTS: MTT assay showed that anti-cancer drugs alone had growth inhibitory effect on the cancer cells however, presence of CAF secretome reduced the anti-cancer effect of the drugs. Resistant to drugs in the presence of secretome, was determined by increased cell viability i.e., MCF-7, 51.02% to 63.02%; SK-BR-3, 34.22% to 44.88%; MDA-MB-231, 52.59% to 78.63%; and MDA-MB-468, 48.92% to 55.08%. LCMS analysis of the secretome showed the differential abundance of CAFs secreted proteins across breast cancer subtypes. CONCLUSIONS: The treatment of breast cancer cell lines with anti-cancer drugs in combination with secretome isolated from molecular subtype specific CAFs, reduced the cytotoxic effect of the drugs. In addition, LCMS data also highlighted different composition of secreted proteins from different breast cancer associated fibroblasts. Thus, TME has heterogenous population of CAFs across the breast cancer subtypes and in vitro experiments highlight their contribution to chemotherapy resistance which needs further validation.

Studies on photocatalytic mineralization of organic pesticides by bimetallic Cu-Zn nanoparticles derived from Zingiber officinale Roscoe (ginger) using green chemistry approach.

Compared to monometallic nanoparticles, bimetallic nanoparticle synthesis and characterization have attracted more attention due to their superior environmental protection properties. In this study, we discuss the preparation and characterization of Cu-Zn bimetallic nanoparticles using Zinger extract, as well as their potential role in photocatalytic degradation of carbendazim, chlorpyrifos, monocrotophos, and cypermethrin. Surface properties were assessed with SEM and TEM, while UV-VIS, XRD, FTIR, and fluorescence spectroscopy were used to characterize the materials. It was observed that higher pH conditions were more conducive to the development of stable Cu-Zn BMNPs with diameters ranging from 60 to 100 nm. UV-VIS spectroscopy showed that the Cu-Zn bimetallic nanoparticles photodegraded 53-95% of the pesticides, monocrotophos, chlorpyrifos, and carbendazim during the 24-72-h incubation period. A number of pesticides may be photocatalytically degraded by primary reactive radicals produced by nanoparticles. We propose that the use of bimetallic nanoparticles could be one alternative strategy for pesticide mineralization.

Discovery of thiazolidinedione-based pancreatic lipase inhibitors as anti-obesity agents: synthesis, in silico studies and pharmacological investigations.

A series of new 2,5-disubstituted arylidene derivatives of thiazolidinedione (16a-e, 17a-d, 18a-c) designed using molecular hybridization approach were synthesized, structurally characterized, and explored for their anti-obesity potential via inhibition of Pancreatic Lipase (PL). Compound 18a presented the most potent PL inhibitory activity with IC50 = 2.71 ± 0.31 µM, as compared to the standard drug, Orlistat (IC50 = 0.99 µM). Kinetic study revealed reversible competitive mode of enzyme inhibition by compound 18a with an inhibitory constant value of 1.19 µM. The most promising compound 18a revealed satisfactory binding mode within the active site of the target protein (human PL, PDB ID: 1LPB). Also, MM/PBSA binding free energy and molecular dynamics (MD) simulation analysis were performed for the most promising compound 18a, which showed potent inhibition according to the results of in vitro studies. Furthermore, a stable conformation of the 1LPB-ligand suggested the stability of this compound in the dynamic environment. The ADME and toxicity analysis of the compounds were examined using web-based online platforms. Results of in vivo studies confirmed the anti-obesity efficacy of compound 18a, wherein oral treatment with compound 18a (30 mg/kg) resulted in a significant reduction in the body weight, BMI, Lee index, feed intake (in Kcal), body fat depots and serum triglycerides. Compound 18a significantly decreased the levels of serum total cholesterol (TC) to 128.6 ± 0.59 mg/dl and serum total triglycerides (TG) to 95.73 ± 0.67 mg/dl as compared to the HFD control group. The present study identified disubstituted TZD derivatives as a new promising class of anti-obesity agents.Communicated by Ramaswamy H. Sarma.

One-pot DTECT enables rapid and efficient capture of genetic signatures for precision genome editing and clinical diagnostics.

The detection of genomic sequences and their alterations is crucial for basic research and clinical diagnostics. However, current methodologies are costly and time-consuming and require outsourcing sample preparation, processing, and analysis to genomic companies. Here, we establish One-pot DTECT, a platform that expedites the detection of genetic signatures, only requiring a short incubation of a PCR product in an optimized one-pot mixture. One-pot DTECT enables qualitative, quantitative, and visual detection of biologically relevant variants, such as cancer mutations, and nucleotide changes introduced by prime editing and base editing into cancer cells and human primary T cells. Notably, One-pot DTECT achieves quantification accuracy for targeted genetic signatures comparable with Sanger and next-generation sequencing. Furthermore, its effectiveness as a diagnostic platform is demonstrated by successfully detecting sickle cell variants in blood and saliva samples. Altogether, One-pot DTECT offers an efficient, versatile, adaptable, and cost-effective alternative to traditional methods for detecting genomic signatures.

An Assessment of Sikh Turban's Head Protection in Bicycle Incident Scenarios.

Due to religious tenets, Sikh population wear turbans and are exempted from wearing helmets in several countries. However, the extent of protection provided by turbans against head injuries during head impacts remains untested. One aim of this study was to provide the first-series data of turbans' protective performance under impact conditions that are representative of real-world bicycle incidents and compare it with the performance of bicycle helmets. Another aim was to suggest potential ways for improving turban's protective performance. We tested five different turbans, distinguished by two wrapping styles and two fabric materials with a size variation in one of the styles. A Hybrid III headform fitted with the turban was dropped onto a 45 degrees anvil at 6.3 m/s and head accelerations were measured. We found large difference in the performance of different turbans, with up to 59% difference in peak translational acceleration, 85% in peak rotational acceleration, and 45% in peak rotational velocity between the best and worst performing turbans. For the same turban, impact on the left and right sides of the head produced very different head kinematics, showing the effects of turban layering. Compared to unprotected head impacts, turbans considerably reduce head injury metrics. However, turbans produced higher values of peak linear and rotational accelerations in front and left impacts than bicycle helmets, except from one turban which produced lower peak head kinematics values in left impacts. In addition, turbans produced peak rotational velocities comparable with bicycle helmets, except from one turban which produced higher values. The impact locations tested here were covered with thick layers of turbans and they were impacted against flat anvils. Turbans may not provide much protection if impacts occur at regions covered with limited amount of fabric or if the impact is against non-flat anvils, which remain untested. Our analysis shows that turbans can be easily compressed and bottom out creating spikes in the headform's translational acceleration. In addition, the high friction between the turban and anvil surface leads to higher tangential force generating more rotational motion. Hence, in addition to improving the coverage of the head, particularly in the crown and rear locations, we propose two directions for turban improvement: (i) adding deformable materials within the turban layers to increase the impact duration and reduce the risk of bottoming out; (ii) reducing the friction between turban layers to reduce the transmission of rotational motion to the head. Overall, the study assessed Turbans' protection in cyclist head collisions, with a vision that the results of this study can guide further necessary improvements for advanced head protection for the Sikh community.

Association of transcatheter left atrial appendage occlusion with acute changes in left atrial pressure: An invasive hemodynamic study.

BACKGROUND: The hemodynamic effects of transcatheter left atrial appendage occlusion (LAAO) remain unclear. OBJECTIVE: We sought to assess the effect of LAAO on invasive hemodynamics and their correlation with clinical outcomes. METHODS: We recorded mean left atrial pressure (mLAP) before and after device deployment. We assessed the prevalence and predictors of mLAP increase after deployment, the association between significant mLAP increase after deployment and 45-day peridevice leak (PDL), and the association between mLAP increase and heart failure (HF) hospitalization. A significant mLAP increase was defined as one equal to or greater than the mean percentage increase in mLAP after deployment (≥28%). RESULTS: We included 302 patients (36.4% female; mean age, 75.8 ± 9.5 years). After deployment, mLAP increased in 48% of patients, 38% of whom experienced significant mLAP increase. Independent predictors of mLAP increase were baseline mLAP ≤14 mm Hg, nonparoxysmal atrial fibrillation, and age per 5 years (odds ratios: 3.66 [95% CI, 2.21-6.05], 1.81 [95% CI, 1.08-3.02], and 0.85 [95% CI, 0.73-0.99], respectively). Significant mLAP increase was an independent predictor of 45-day PDL (odds ratio, 2.55; 95% CI, 1.04-6.26). There was no association between mLAP increase and HF hospitalization. CONCLUSION: After deployment, mLAP acutely rises in 48% of patients, although this is not associated with increased HF hospitalizations. PDL is more likely to develop at 45 days in patients with significant increase in mLAP after deployment, although most leaks were small (<5 mm). These findings suggest that mLAP increase after deployment is not associated with major safety concerns. Additional studies are warranted to explore the long-term hemodynamic effects of LAAO.

Tracking an untracked space debris after an inelastic collision using physics informed neural network.

With the sustained rise in satellite deployment in Low Earth Orbits, the collision risk from untracked space debris is also increasing. Often small-sized space debris (below 10 cm) are hard to track using the existing state-of-the-art methods. However, knowing such space debris' trajectory is crucial to avoid future collisions. We present a Physics Informed Neural Network (PINN)-based approach for estimation of the trajectory of space debris after a collision event between active satellite and space debris. In this work, we have simulated 8565 inelastic collision events between active satellites and space debris. To obtain the states of the active satellite, we use the TLE data of 1647 Starlink and 66 LEMUR satellites obtained from space-track.org. The velocity of space debris is initialized using our proposed velocity sampling method, and the coefficient of restitution is sampled from our proposed Gaussian mixture-based probability density function. Using the velocities of the colliding objects before the collision, we calculate the post-collision velocities and record the observations. The state (position and velocity), coefficient of restitution, and mass estimation of un-tracked space debris after an inelastic collision event along with the tracked active satellite can be posed as an optimization problem by observing the deviation of the active satellite from the trajectory. We have applied the classical optimization method, the Lagrange multiplier approach, for solving the above optimization problem and observed that its state estimation is not satisfactory as the system is under-determined. Subsequently, we have designed Deep Neural network-based methods and Physics Informed Neural Network (PINN) based methods for solving the above optimization problem. We have compared the performance of the models using root mean square error (RMSE) and interquartile range of the predictions. It has been observed that the PINN-based methods provide a better estimation performance for position, velocity, mass and coefficient of restitution of the space debris compared to other methods.

Quality by design fostered fabrication of cabazitaxel loaded pH-responsive Improved nanotherapeutics against prostate cancer.

Cabazitaxel has been approved for the treatment of prostate cancer since 2010. However, its poor solubility and permeability pitfalls prevent its accumulation at the target site and promote severe adverse effects. About 90% of prostate cancer (PCa) patients suffer from bone metastasis. This advent reports the development of CBZ-loaded pH-responsive polydopamine nanoparticles (CBZ NP) against metastatic PCa cells. Quality by design (QbD) and multivariate analysis tools were employed for the optimization of CBZ NP. Amorphisation of CBZ along with metastatic microenvironment responsive release was observed thereby imparting spatial release and circumventing solubility pitfalls. CBZ NP retained its cytotoxic potential, with a significant increase in quantitative cellular uptake. Apoptotic markers observed from nuclear staining with elevated reactive oxygen species (ROS) and mitochondrial damage revealed by JC-1 staining demonstrated the efficacy of CBZ NP against PC-3 cells with good serum stability and diminished hemolysis. Cell cycle analysis revealed substantial S and G2/M phase arrest with enhancement in apoptosis was observed. Western blot studies revealed an elevation in caspase-1 and suppression in Bcl-2 indicating enhanced apoptosis compared to the control group. Substantial reduction in the diameter of 3D-Tumoroid and enhanced cell proliferation inhibition indicated the efficacy of CBZ NP in PCa. Thus, we conclude that CBZ NP could be a promising Nanotherapeutic approach for PCa.

3,5-Disubstituted-thiazolidine-2,4-dione hybrids as antidiabetic agents: Design, synthesis, in-vitro and In vivo evaluation.

Diabetes is one of the fastest-growing metabolic disorders, nearly doubling the number of patients each year. There are different treatment approaches available for the management of diabetes, which lacks due to their side effects. The inhibition of enzymes involved in the metabolism of complex polysaccharides to monosaccharides has proven beneficial in patients with type 2 diabetes mellitus. Two enzymes, α-amylase and α-glucosidase, have emerged as potential drug targets and are widely explored for drug development against type 2 diabetes mellitus. In this context, thiazolidine-2,4-diones (TZDs) have emerged as potential drug candidates for developing newer molecules against α-amylase and α-glucosidase. Nineteen TZD-hybrids were synthesized and evaluated in vitro α-amylase and α-glucosidase inhibitory activity. The compounds 7i, 7k, and 7p have emerged as the best dual inhibitors with IC50 of 10.33 ± 0.11-20.94 ± 0.76 µM and 10.19 ± 0.25-24.07 ± 1.56 µM against α-glucosidase and α-amylase, respectively. The derivatives had good anti-oxidant activity, displaying IC50 = 14.95 ± 0.65-23.27 ± 0.99 µM. The compounds 7k and 7p showed the best inhibition of reactive oxygen species in the PNAC-1 cells. The molecules exhibit good binding within the active site of α-amylase (PDB id: 1B2Y) and α-glucosidase (PDB id: 3W37), displaying binding energies of -7.5 to -10.7 kcal/mol and -7.4 to -10.3 kcal/mol, respectively. Further, the compounds were nontoxic (LD50 = 500-1311 mg/kg) and possessed good GI absorption. The compounds 7i, 7k, and 7p were evaluated in vivo antidiabetic activity in an STZ-induced diabetic model in Wistar rats. The compound 7p emerged as the best compound in the in vivo studies; however, the activity was lesser than that of the standard drug pioglitazone.

Development and effect of a coordinated Community Health Worker (CHW) Intervention (C-CHW-I) model for the stroke survivors in Kerala, South India.

INTRODUCTION: Structured models for secondary prevention of stroke in community settings are scarce. We aimed to develop and evaluate a model for improving medication adherence and enhanced risk factor monitoring. METHODS: We developed a multimodal C-CHW-I model for stroke survivors. Following training, all patients received a minimum of three CHW home visits, and once in 3-month telephone-call and health education for six months by CHWs. Seven blocks from 16 blocks of the study area were randomised to additionally receive an SMS alert for six months to reinforce CHW involvement. The primary outcomes were medication adherence and risk factor monitoring, and the secondary outcome was risk factor control. RESULTS: The mean age of the study population was 64+12 years, 765(85%) had ischaemic stroke. In the overall study cohort receiving the CHW intervention, mean medication adherence significantly improved from 3.56(0.88) at baseline to 3.78(0.61) at 6 months; p<0.001. Overall risk factor monitoring improved from 42.7% to 49.7%, and mean (standard deviation) systolic blood pressure (SBP) significantly reduced from 138(21) mmHg to 132(15) mmHg at 6-months; p<0.001. In patients additionally receiving SMS-based intervention, a statistically significant improvement in medication adherence was seen at 3 months (3.76+0.64 versus 3.61+0.81; p=0.008) however no difference persisted at 6 months. The proportion of smokers and alcohol users reduced in both groups with a trend to greater reduction in the intervention group (smokers:5.9% versus 2.8% (p=0.446) and alcohol users: 1.6% versus 1.4%(p=0.474)). At six months, the SBP did not differ (SBP (132.1(16.2) in the SMS group versus 133.2(15.8) mmHg in the control group, p=0.409). CONCLUSION: Our model improved medication adherence and risk factor monitoring of stroke survivors in community settings, and this can reduce stroke burden in the community.

A Lateral Expandable Cage with Independently Adjustable Anterior and Posterior Heights Can Improve the Pressure Distribution at the Cage-Endplate Interface: A Biomechanics Study.

OBJECTIVE: To investigate how the expansion trajectory of a lateral expandable cage affects pressure distribution at the cage-endplate interface under well-controlled biomechanical loading conditions. METHODS: Three unique vertical height expansion trajectories used by clinically relevant lateral expandable cages were evaluated: craniocaudal, fixed-arc, and independently adjustable anterior and posterior height expansion. Two biomechanical loading scenarios were performed. The first scenario used custom bone foam test blocks to assess resultant pressure distribution at varying test block lordotic angles and expansion heights. The second scenario simulated expansion using synthetic spine units and compared the pressure distribution following expansion. RESULTS: For an expandable cage with craniocaudal expansion, the pressure distribution at the cage-endplate interface was found to depend heavily on the lordotic angle of the test block (P < 0.001), but not expansion height (P = 0.634). The greatest maximum pressure occurred at higher test block lordotic angles. For an expandable cage with fixed-arc expansion, the pressure distribution shifted anteriorly throughout expansion. In the simulated expansion trials, an expandable cage with adjustable anterior and posterior height expansion was found to improve the pressure distribution at the cage-endplate interface, reducing the maximum pressure measurements by 22% and 14% in the craniocaudal and fixed-arc expansion, respectively. CONCLUSIONS: Of the cage designs evaluated in this study, an expandable cage with independently adjustable anterior and posterior heights lowered the maximum pressure measured at the cage-endplate interface and alleviated the potential of cage edge loading, both of which are important considerations that are fundamental for a successful fusion procedure and the mitigation of implant subsidence risk.

Impact of chronic obstructive pulmonary disease on right ventricular function and remodeling after aortic valve replacement.

BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and right ventricular (RV) dysfunction are common factors that have been associated with poor prognosis after aortic valve replacement (AVR). Since there is still uncertainty about the impact of COPD on RV function and dilatation in patients undergoing AVR, we sought to explore RV function and remodeling in the presence and absence of COPD as well as their prognostic implications. METHODS: Patients who received surgical or transcatheter AVR due to severe AS were screened for COPD. Demographic and clinical data were collected at baseline while echocardiographic measurements were performed at baseline and 1 year after AVR. The study end-point was all-cause mortality. RESULTS: In total 275 patients were included, with 90 (33%) patients having COPD. At 1-year follow-up, mild worsening of tricuspid annular planar systolic excursion and RV dilatation were observed in patients without COPD, while there were significant improvements in RV longitudinal strain, RV wall thickness but dilatation of RV outflow tract distal dimension in the COPD group compared to the baseline. On multivariable analysis, the presence of COPD provided significant incremental prognostic value over RV dysfunction and remodeling. CONCLUSIONS: At 1-year after AVR, RV function and dimensions mildly deteriorated in non-COPD group whereas COPD group received significant benefit of AVR in terms of RV function and hypertrophy. COPD was independently associated with >2-fold all-cause mortality and had incremental prognostic value over RV dysfunction and remodeling.

Musculoskeletal physiotherapists' discharge practices for people treated with low back pain: A United Kingdom survey.

BACKGROUND: Persistent low back pain (LBP) is the leading cause of disability, and a major burden on the healthcare system globally. Many people with LBP experience recurrent pain flares and receive repeated appointments and re-referrals to services such as physiotherapy. However, it is not clear what the criteria are for discharging people with LBP from physiotherapy services. This study aims to describe the current practices for discharging people from physiotherapy for LBP in the United Kingdom (UK). METHODS: A cross-sectional study using an anonymous online national (UK) survey was conducted among qualified physiotherapists who treat people with LBP in UK musculoskeletal out-patient services. RESULTS: A total of 104 surveys were completed. The majority of respondents reported using (i) a shared decision-making (77%) and (ii) person-physiotherapist goal attainment (74%) approach to discharging people with LBP. Sixty-three percent of respondents reported using a patient-initiated follow-up (PIFU) approach. Only 8% of respondents reported using a graded discharge approach with 'booster' appointments. A PIFU or graded discharge approach was considered most pertinent for people at higher risk of a pain flare (97%; 86%) and with low self-efficacy to self-manage their LBP. CONCLUSIONS: This UK survey established that discharge practices for people with LBP after physiotherapy vary. Whilst the majority of people are currently discharged with a PIFU appointment, a graded discharge approach may be more beneficial for people who are less likely to initiate a PIFU appointment. Further consideration on the development of such a pathway is now required.