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Background: For reasons poorly understood, strokes frequently occur in patients with atrial fibrillation (AF) despite oral anticoagulation. Better data are needed to inform randomised trials (RCTs) of new strategies to prevent recurrence in these patients. We investigate the relative contribution of competing stroke mechanisms in patients with AF who have stroke despite anticoagulation (OAC+) compared with those who are anticoagulant naïve (OAC−) at the time of their event. Patients and methods: We performed a cross-sectional study leveraging data from a prospective stroke registry (2015–2022). Eligible patients had ischemic stroke and AF. Stroke classification was performed by a single stroke-specialist blinded to OAC status using TOAST criteria. The presence of atherosclerotic plaque was determined using duplex ultrasonography, computerised tomography (CT) or magnetic resonance (MR) angiography. Imaging was reviewed by a single reader. Logistic regression was used to identify independent predictors of stroke despite anticoagulation. Results: Of 596 patients included, 198 (33.2%) were in the OAC+ group. A competing cause for stroke was more frequent in patients with OAC+ versus OAC− (69/198 (34.8%)) versus 77/398 (19.3%), p Discussion and conclusion: Patients with AF-associated stroke despite OAC are much more likely than patients who are OAC-naïve to have competing stroke mechanisms. Rigorous investigation for alternative stroke causes in stroke despite OAC has a high diagnostic yield. These data should be used to guide patient selection for future RCTs in this population.

Osteoarthritis (OA) is the most common joint disorder and currently affects > 500 million patients worldwide, with ~60% of them also suffering from obesity. There is no drug approved for human use that changes the course of OA progression. OA is one of the most common comorbidities of obesity, and obesity-related OA (ObOA) is a serious health concern because it shows heightened severity of tissue damage and also predominantly affects the working population. Unresolved inflammation is a major driver of ObOA, thus, resolving disease-associated inflammation is a viable strategy to treat ObOA. Resolvins are highly potent molecules that play a role in the resolution of inflammation and promote tissue healing. However, small molecules (like Resolvin D1; RvD1) have to be administered frequently or prior to injury because they lose theirin vivoactivity rapidly either by lymphatic clearance, or oxidation-mediated deactivation. In this study, we have encapsulated RvD1 in liposomes and established its efficacy in the mouse model of ObOA at much lower dosages than freely administered RvD1. Liposomal RvD1 (lipo-RvD1) acted as a source of the RvD1 molecules for ~11 daysin vitroin synovial fluid derived from patients. When administered prophylactically or therapeutically, lipo-RvD1 suppressed cartilage damage in male C57BL/6 mice compared to untreated and free RvD1 treatments. This efficacy was achieved by increasing the proportion of the proresolution M2 macrophages over proinflammatory M1 macrophages in the synovial membrane. These results show the potential of lipo-RvD1 as an anti-OA agent.Graphical abstract:Mechanism of working of lipo-RvD1 in ObOA joint.

Lung cancer has the highest mortality rate as compared to other cancers. The anti-proliferative and antioxidant potential of epigallocatechin gallate (EGCG) and Theaflavin -3,3’-digallate (TF3) can play a major role in treatment if delivered efficiently. To improve the chemical stability and medicinal potential of EGCG and TF3 in the respiratory tract, a spanlastic is developed which is composed of Tween-80, Span-60, and cholesterol which encapsulate EGCG and TF3 inside its vesicular structure and deliver it specifically to the target cancer cells. The cholesterol layer will produce efficient penetration while tween-80 and span-60 will help in easily deformability and lowers the interfacial tension hence, produces a small Z-average diameter which facilitates efficient penetration between layers of cells. The nano-vesicular structure ensures the APIs stability at alkaline pH (7.6) and also increases cellular antioxidant activity and Ferric reducing antioxidant powers values of APIs. Better encapsulation efficiency and safe consideration by MTT assay are major advantages of Spanlastic. The lung cancer cell loses the ability of apoptosis, which can revived with the help of a nano-vesicular system of EGCG and TF3 and in addition, there will be activation of several other properties such as cell arrest, activation of miR-210, suppression of cyclin D1, inhibition of MAPK, ERK, and JAK-STAT at their maximum potential. Furthermore, a special type of spacer and pMDI canister are developed in order to maximize the drug stability and efficiency of its delivery.

Contamination of groundwater sources due to the presence of chromium ions, a heavy metal, and the detrimental impact of it on the health of consumers have become a serious global concern. The present study was designed to understand the effects of three process variables, namely feed chromium concentration, feed pH and pressure, on chromium removal and permeate flux, by employing response surface methodology and central composite design techniques. Spiral-wound reverse-osmosis membrane was used for the removal of chromium from the groundwater samples in this study. Membrane performance, in terms of high permeate quality and flux, was evaluated by optimization of various operating conditions. The obtained experimental results were then matched with the predicted values obtained from the models. The models indicated that the highest chromium removal of 98.38% and permeate flux of 48.73 L/m2 h could be achieved at the optimum feed pH of 3.00, pressure of 4 kg/cm2 and feed chromium concentration of 0.431 ppm. Experimental validation confirmed that the model had higher predictive capabilities. The changes in pressure and the chromium concentration significantly affected the chromium removal and permeate flux, the former being positively correlated and the latter being negative to both the responses. Therefore, small-scale RO membranes can be used to treat aqueous solution with chromium contamination.

Water pollution and scarcity of pure drinking water is a current challenging problem. In this situation, quality monitoring of water is of vital importance in order to avoid any health issues caused due to intake of contaminated water. Hence, in this paper, a non-destructive technique using multiple ring CSRR based microwave sensor has been proposed for accurate estimation of relative permittivity of unknown water of varying TDS values. Further, a closed form numerical expression using the curve fitting technique has been developed in order to accurately estimate the quality of any unknown water sample. Less than 1% of error has been achieved in the prediction of relative permittivity and hence, TDS of unknown water sample. The proposed planar microwave sensor will be of great importance towards the real-time water quality monitoring systems development.

BackgroundDhat syndrome, a clinical condition related to semen loss in urine often found among males in India, has rarely been described as a separate clinical condition in females. Women with the syndrome complain of passing vaginal discharge and can be excessively concerned and preoccupied with it, often attributing various physical symptoms to the loss of vaginal fluids.AimsThis study aimed to assess the sociodemographic and clinical profiles of female patients with Dhat syndrome and their perceived stress, disability and sexual functioning.MethodsSociodemographic details of 70 females with non-pathological vaginal discharge were evaluated with a semistructured sociodemographic assessment. The phenomenology of the vaginal discharge was assessed with the Scale for Assessment of Female Dhat Syndrome Questionnaire. Anxiety and depressive symptoms were measured with the Hospital Anxiety and Depression Scale. Perceived stress in the past month and disability caused by the illness were assessed with the Perceived Stress Scale and the World Health Organization Disability Assessment Scale. In addition, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Level 2 Somatic Symptoms Scale was administered to rate the severity of somatic symptoms, and sexual functioning was evaluated using the Female Sexual Function Index (FSFI) scale for women who had had sexual intercourse in the past month.ResultsThe mean age of onset vaginal discharge was 23.0 (6.6) years. Biological factors, such as urinary tract infection, were the commonly attributed cause of the loss of vaginal fluids. Psychiatric comorbidity and perceived moderate stress in the past month were found in 38.6% and 68.6% of female patients with Dhat syndrome, respectively. Disability scores tended to be low. Among the females having had sexual intercourse in the past month, 48.3% had FSFI scores indicative of a female sexual disorder.ConclusionsThe clinical presentation of women with non-pathological vaginal discharge is similar to that of males with Dhat syndrome. It requires comprehensive assessment and management that targets the biological, social and psychological factors and cultural issues.

This research compares the performance efficiencies of Nanofiltration (NF), Reverse osmosis (RO), and Nanofiltration-Reverse Osmosis (NF-RO) hybrid membrane filtration systems, for treatment of brackish groundwater in Delhi-NCR region. Central composite design (CCD) of response surface methodology (RSM) were applied to formulate predictive models for the optimization and simulation of various responses, viz. Water flux, salt rejection, permeate recovery and specific energy consumption (SEC). Three different input factors (feed concentration, pH and pressure) were evaluated. Significance of RSM model was tested and validated with use of an analysis of variance (ANOVA). The models were also compared graphically for their prediction ability. The optimum conditions were determined by numerical optimization of the NF and RO membrane pilot plants. Finally, hybrid configurations of NF and RO were investigated utilising the optimum conditions to identify the technology suitable for the remediation of brackish groundwater. Despite, RO membrane eliminating over 99% of TDS from groundwater, the lower recovery rate renders it environmentally unfavourable. Result indicates that recovery of the hybrid system (40.35%) was greater than that of RO alone (18.796%) and SEC also decreases (5.090-3.8 kW H/m

ObjectivesTimely thrombolysis of ischaemic stroke improves functional recovery, yet its delivery nationally is challenging due to shortages in the stroke specialist workforce and large geographical areas. One solution is remote stroke specialist input to regional centres via telemedicine. This study evaluates the usage and key metrics of performance of the East of England Stroke Telemedicine Partnership—the largest telestroke service in the UK—in providing hyperacute stroke care.DesignProspective observational study.SettingThe East of England Stroke Telemedicine Partnership provides a horizontal ‘hubless’ model of out-of-hours hyperacute stroke care to a population of 6.2 million across a 7500 square mile semirural region.ParticipantsAll (2709) telestroke consultations between 1 January 2014 and 31 December 2019.Main outcome measuresThrombolysis decision, pre-thrombolysis and post-thrombolysis stroke severity (National Institutes of Health Stroke Scale, NIHSS), haemorrhagic complications, and hyperacute pathway timings.ResultsOver the period, 1149 (42.4%) individuals were thrombolysed. Thrombolysis rates increased from 147/379 (38.8%) in 2014 to 225/490 (45.9%) in 2019. Median (IQR) pre-thrombolysis NIHSS was 10 (6–17), reducing to 6 (2–14) 24-hour post-thrombolysis (pConclusionsThe results from this large hyperacute telestroke cohort indicate two important points for clinical practice. First, telemedicine via a hubless horizontal model provides a clinically effective and safe method for delivering hyperacute stroke thrombolysis. Second, improved door-to-needle times were offset by a concerning rise in prehospital timings. These findings indicate that although telemedicine may benefit in-hospital hyperacute stroke care, improvements across the whole stroke pathway are essential.

Dyes are a significant group of organic contaminants known to negatively affect both humans and aquatic environments. In the textile industry, interest in agricultural-based adsorbents has increased, particularly around adsorption. In this study, methylene blue was eliminated from an aqueous solution using a walnut (Juglans regia) shell. These materials are widely available and inexpensive, and its cost can be a major factor in wastewater treatment batch experiments. Response surface methodology (RSM) is based on a face-centred central composite design, used to identify the independent variable. With the use of RSM, the biomass of J. regia shells was assessed for its capacity to absorb dyes from aqueous solutions, including methylene blue. Maximum methylene blue dye removal percentages (97.70%) were obtained with a 30 mg/L concentration of methylene blue dye, 1.5 gm of biomass, an initial pH of 6, and a contact duration of 60 min at 25 °C. Additionally, particles were absorbed onto the J. regia shell’s surface throughout the biosorption process, according to scan electron microscopy. Functional groups were discovered in the Fourier Transform Infrared Spectroscopy spectra, which are crucial for binding during the biosorption of methylene blue. It has been demonstrated that J. regia shell biomass performs well as a biosorbent in the removal of methylene blue from wastewater effluents. It is also a promising, biodegradable, environmentally friendly, economical, and cost-effective biosorbent.

Current treatments for osteoarthritis (OA) offer symptomatic relief but do not prevent or halt the disease progression. Chronic low-grade inflammation is considered a significant driver of OA. Specialized proresolution mediators are powerful agents of resolution but have a short in vivo half-life. In this study, we have engineered a Resolvin D1 (RvD1)-loaded nanoliposomal formulation (Lipo-RvD1) that targets and resolves the OA-associated inflammation. This formulation creates a depot of the RvD1 molecules that allows the controlled release of the molecule for up to 11 days in vitro. In surgically induced mice model of OA, only controlled-release formulation of Lipo-RvD1 was able to treat the progressing cartilage damage when administered a month after the surgery, while the free drug was unable to prevent cartilage damage. We found that Lipo-RvD1 functions by damping the proinflammatory activity of synovial macrophages and recruiting a higher number of M2 macrophages at the site of inflammation. Our Lipo-RvD1 formulation was able to target and suppress the formation of the osteophytes and showed analgesic effect, thus emphasizing its ability to treat clinical symptoms of OA. Such controlled-release formulation of RvD1 could represent a patient-compliant treatment for OA.

Most of the dyes are toxic and non-biodegradable in textile industry wastewaters. Therefore, removal of textile dye using agriculture waste becomes crucial for the environment. This can be accomplished by the biosorption process which is the passive uptake of pollutants by agricultural waste. In this study, Response Surface Methodology (RSM), Artificial Neural Network (ANN) and Adaptive Neuro-Fuzzy Inference System (ANFIS) were used to obtain optimum conditions for Methylene Blue (MB) removal using sugarcane bagasse and peanut hulls as low-cost agricultural waste. The experimental design was carried out to study the effect of temperature, pH, biosorbent amount and dye concentration. The maximum MB dye removal considering the effect of total dissolved solids from aqueous solutions of 74.49% and 67.99% by sugarcane bagasse and peanut hulls, respectively. The models specify that they could predict biosorption with high accuracy having R2-value above 0.9. Statistical studies for RSM, ANFIS and ANN models were compared. Further, the models were optimized for maximum dye removal was at 1.21 g of biosorbent, pH 5.24, 31.24 mg/L MB concentration, 22.29°C of dye solution using sugarcane bagasse and at 1.37 g of biosorbent, pH 5.77, 36.7 mg/L MB concentration, 26.8°C of dye solution using peanut hulls. Additionally, Fourier Transform Infra-Red (FTIR) spectral analysis was also carried out to confirm the biosorption.

Trauma to the knee joint is associated with significant cartilage degeneration and erosion of subchondral bone, which eventually leads to osteoarthritis (OA), resulting in substantial morbidity and healthcare burden. With no disease-modifying drugs in clinics, the current standard of care focuses on symptomatic relief and viscosupplementation. Modulation of autophagy and targeting senescence pathways are emerging as potential treatment strategies. Rapamycin has shown promise in OA disease amelioration by autophagy upregulation, yet its clinical use is hindered by difficulties in achieving therapeutic concentrations, necessitating multiple weekly injections. Here, we have synthesized rapamycin - loaded poly (lactic-co-glycolic acid) microparticles (RMPs) that induced autophagy, prevented senescence and sustained sulphated glycosaminoglycans(sGAG) production in primary human articular chondrocytes from OA patients. RMPs were potent, nontoxic, and exhibited high retention time (up to 35 days) in mice joints. Intra-articular delivery of RMPs effectively mitigated cartilage damage and inflammation in surgery-induced OA when administered as a prophylactic or therapeutic regimen. Together, our studies demonstrate the feasibility of using RMPs as a potential clinically translatable therapy to prevent and treat post-traumatic osteoarthritis.Graphical Abstract

Artificial neural network (ANN) and response surface methodology (RSM) were employed to develop models for process optimisation of pilot scale nanofiltration (NF) and reverse osmosis (RO) membrane filtration system for the treatment of brackish groundwater. The process variables for this study were feed concentration, temperature, pH and pressure. The performance of NF/RO was assessed in terms of permeate flux, water recovery, salt rejection and specific energy consumption, which were considered as responses. The experimental design was employed to develop both RSM and ANN models. RSM model was validated for the whole range of experimental levels, while the ANN model was considered for the whole range of experimental design. RSM and ANN models were statistically analysed using analysis of variance (ANOVA). Further, the models were graphically compared for its predictive capacity. Numerical optimisation of NF and RO pilot plant to determine the optimum conditions were verified. Finally, using the optimum conditions, three hybrid configurations of NF and RO were studied to determine the best mode for the treatment of brackish groundwater. It was found that parallel NF-RO had a recovery of 57.18% and rejection of 44.89%, for RO-concentrate-NF (RO-C-NF) recovery was 49.55% and rejection of 38.64% & for NF-concentrate-RO (NF-C-RO), the recovery of 39.53% and rejection of 49.66% was obtained. Results obtained also suggested that the mode of configurations and the feed concentration affect the performance of the hybrid system.

BACKGROUND AND PURPOSE Predicting the course of behavioural variant frontotemporal dementia (bvFTD) remains a major clinical challenge. This study aimed to identify factors that predict survival and clinical progression in bvFTD. METHODS Consecutive patients with clinically probable bvFTD were prospectively followed up over an 8-year period. Baseline neuropsychological variables, presence of a known pathogenic frontotemporal dementia gene mutation and a systematic visual magnetic resonance imaging assessment at baseline were examined as candidate predictors using multivariate modelling. RESULTS After screening 121 cases, the study cohort consisted of 75 patients with probable bvFTD, with a mean age of 60.8 ± 8.5 years, followed up for a mean duration of 7.2 ± 3.5 years from symptom onset. Median survival time from disease onset was 10.8 years and median survival, prior to transition to nursing home, was 8.9 years. A total of 25 of the 75 patients died during the study follow-up period. Survival without dependence was predicted by shorter disease duration at presentation (hazard ratio, 0.49, P = 0.001), greater atrophy in the anterior cingulate cortex (hazard ratio, 1.75, P = 0.047), older age (hazard ratio, 1.07, P = 0.026) and a higher burden of behavioural symptoms (hazard ratio, 1.04, P = 0.015). In terms of disease progression, presence of a known pathogenic frontotemporal dementia mutation (β = 0.46, P

Forward osmosis (FO) is an emerging low energy membrane-based technology and can be applied if the diluted draw solution (DS) is directly utilized without additional recovery/treatment. In this study, FO process was applied for the treatment of textile industry wastewater using fertilizer as DS. This paper focuses on modelling and optimisation of FO process using machine learning techniques like Response Surface Methodology (RSM), Artificial Neural Network (ANN) and Adaptive Neuro-Fuzzy Inference System (ANFIS). To model the FO process, central composite design was utilized to examine the effect of initial draw concentration, initial feed concentration, time, initial feed pH and temperature on the water flux and reverse salt flux. The optimum water flux (8.527 L.m−2.h−1 (LMH)) and reverse salt flux (7.246 g.m−2.h−1 (GMH)) was obtained using initial draw concentration of 1.625 M, initial feed concentration of 1090 mg/L, reaction time of 90 min, initial feed pH of 7.33 and temperature of 35 °C. Under these conditions, FO performance was carried out experimentally and validated with the models. The model developed for the FO process by ANN and RSM was considerably better than that of other models in terms of precision of predicting the water flux and the reverse salt flux, respectively. About six different chemical fertilizer solutions were screened and tested at optimum conditions to identify the best suitable fertilizer DS for FO process using textile wastewater. The results indicate that Diammonium Phosphate (DAP) along with Potassium Chloride (KCl) fertilizer as DS gave better performance with respect to water flux.

In the present study, dielectric and microwave absorption behavior of flower-like Ni/SiC composites has been studied in the 2–18 GHz frequency range. Single-phase flower-like Ni particles were successfully synthesized via a facile hydrothermal method. The synthesized flower-like Ni particles were mixed with SiC using mortar pestle in varying SiC:Ni weight ratios viz. 4:1, 1:1, and 1:4. The phase and morphology of prepared materials were studied using X-ray diffraction and FE-SEM techniques, respectively. The dielectric results show improvement in the complex permittivity and complex permeability values for the prepared composites with the increase in the concentration of synthesized Ni particles in SiC. Improvement in the dielectric properties translates into better microwave absorption behavior for flower-like Ni/SiC composites as compared to pure SiC. The synthesized flower-like Ni/SiC composites exhibited a minimum reflection loss of −31.04 dB and −28.53 dB for samples with 1:1 and 1:4 compositions, respectively. The corresponding −10 dB absorption bandwidth is 3.44 GHz and 2.89 GHz, respectively. The reflection loss results suggest that flower-like Ni/SiC composites may be tuned for optimal operation in C, X and, Ku bands by varying the Ni concentration and the thickness of absorber. In addition, the radar cross section (RCS) studies were simulated using HFSS. The RCS study of perfect electric conductor (PEC) substrate coated with flower-like Ni/SiC composite coatings indicate the effectiveness of the developed composites in reducing the RCS by efficiently suppressing the strong microwave scatterings.

Introduction Loss of hemispheric asymmetry during cognitive tasks has been previously demonstrated in the literature. In the context of language, increased right hemisphere activation is observed with aging. Whether this relates to compensation to preserve cognitive function or dedifferentiation implying loss of hemispheric specificity without functional consequence, remains unclear. Methods With a multifaceted approach, integrating structural and functional imaging data during a word retrieval task, in a group of younger and older adults with equivalent cognitive performance, we aimed to establish whether interactions between hemispheres or reorganization of dominant hemisphere networks preserve function. We examined functional and structural connectivity on data from our previously published functional activation study. Functional connectivity was measured using psychophysiological interactions analysis from the left inferior frontal gyrus (LIFG) and the left insula (LINS), based on published literature, and the right inferior frontal gyrus (RIFG) based on our previous study. Results Although RIFG showed increased activation, its connectivity decreased with age. Meanwhile, LIFG and LINS connected more bilaterally in the older adults. White matter integrity, measured by fractional anisotropy (FA) from diffusion tensor imaging, decreased significantly in the older group. Importantly, LINS functional connectivity to LIFG correlated inversely with FA. Conclusions We demonstrate that left hemispheric language areas show higher functional connectivity in older adults with intact behavioral performance, and thus, may have a role in preserving function. The inverse correlation of functional and structural connectivity with age is in keeping with emerging literature and merits further investigation with tractography studies and in other cognitive domains.

To investigate whether primary lateral sclerosis (PLS) represents part of the amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD) spectrum of diseases. Comprehensive assessment was taken on 21 patients with PLS and results were compared to patients diagnosed with pure motor ALS (n = 27) and ALS–FTD (n = 12). Clinical features, Addenbrooke’s Cognitive Examination (ACE) scores, Motor Neuron Disease Behaviour (Mind-B) scores, motor disability on the ALS functional rating scale (ALSFRS) and survival times were documented. Motor cortex excitability was evaluated using transcranial magnetic stimulation (TMS). Global cognition was impaired in PLS (mean total ACE score 82.5 ± 13.6), similar to ALS–FTD (mean total ACE score 76.3 ± 7.7, p > 0.05) while behavioural impairments were not prominent. TMS revealed that resting motor threshold (RMT) was significantly higher in PLS (75.5 ± 6.2) compared ALS–FTD (50.1 ± 7.2, p