Tissue engineered periosteum: Fabrication of a gelatin basedtrilayer composite scaffold with biomimetic properties for enhanced bone healing.

The periosteum, a vascularized tissue membrane, is essential in bone regeneration following fractures and bone loss due to some other reasons, yet there exist several research gaps concerning its regeneration. These gaps encompass reduced cellular proliferation and bioactivity, potential toxicity, heightened stiffness of scaffold materials, unfavorable porosity, expensive materials and procedures, and suboptimal survivability or inappropriate degradation rates of the implanted materials. This research used an interdisciplinary approach by forming a new material fabricated through electrospinning for the proposed application as a layer-by-layer tissue-engineered periosteum (TEP). TEP comprises poly(ε-caprolactone) (PCL), PCL/gelatin/magnesium-doped zinc oxide (vascular layer), and gelatin/bioactive glass/COD liver oil (osteoconductive layer). These materials were selected for their diverse properties, when integrated into the scaffold formation, successfully mimic the characteristics of native periosteum. Scanning electron microscopy (SEM) was employed to confirm the trilayer structure of the scaffold and determine the average fiber diameter. In-vitro degradation and swelling studies demonstrated a uniform degradation rate that matches the typical recovery time of periosteum. The scaffold exhibited excellent mechanical properties comparable to natural periosteum. Furthermore, the sustained release kinetics of COD liver oil were observed in the trilayer scaffold. Cell culture results indicated that the three-dimensional topography of the scaffold promoted cell growth, proliferation, and attachment, confirming its non-toxicity, biocompatibility, and bioactivity. This study suggests that the fabricated scaffold holds promise as a potential artificial periosteum for treating periostitis and bone fractures.

Visualization of atrophy of medial temporal lobes and the septal nuclei in patients with transient ischaemic attack and controls.

Introduction: Transient ischaemic attack (TIA) is associated with increased risk of cognitive decline and dementia as early as one-year post-event. Regional brain atrophy measurements may predict future cognitive decline. Aims: 1) To determine whether Medial Temporal Atrophy (MTA) scores and interseptal distance (ISD) measurements are greater in patients with TIA compared to controls; and 2) To determine whether MTA and ISD predicts cognitive change one year after TIA. Methods: Baseline demographic, vascular risk factors, structural imaging and cognitive tests scores were compared between 103 Patients with TIA and 103 age-and-sex-matched controls from the Predementia Neuroimaging of Transient Ischaemic Attack (PREVENT) Study. MTA was assessed using the Schelten's Scale, and ISD was calculated as the distance between the septal nucleus of each hemisphere. Multiple linear regression models were used to evaluate how MTA and ISD related to cognitive change after adjusting for covariates. Results: Patients with TIA had larger ISD measurements (1.4 mm [SD=1.2] vs. 0.9 mm [SD=1.0]); p < 0.001) and higher right/left MTA scores (both p < 0.05) compared to controls. At baseline, controls performed significantly better on the RAVLT (total recall), BVMT (total and delayed recall) and the Trail Making Task (A and B) compared to patients with TIA. However, at one-year follow-up there was no evidence of decline in the patients with TIA compared with controls. Higher MTA and ISD scores were not associated with cognitive decline. Conclusions: Patients with TIA had higher MTA scores and ISD measurements than controls, but neither were predictors of cognitive decline at one year. Future studies with longer follow-up periods will be required to determine whether higher MTA scores and ISD predict risk of cognitive decline in patients with TIA.

Innovative way to break the stone: Master lithoclast for bilateral simultaneous Percutaneous Nephrolithotomy.

The objective of our study was to evaluate the efficacy of Master Lithoclast, also known as trilogy lithoclast, in simultaneous bilateral Percutaneous Nephrolithotomy (PCNL). The study was a prospective case series, involving 40 patients undergoing bilateral simultaneous PCNL, with 20 (50%) males and 20 (50%) females. The mean age of subjects was 32.9±7.9 years. In Guy's stone scoring 7(17.5%) patients classified in Group I, 28 (70%) in group II and the remaining 5(12.5%) patients were placed in group III. Total operative time observed was 74.8±17.9 minutes. Complete stone clearance was observed in 30 (75%) patients. In conclusion, study data confirmed that Master Lithoclast provides faster stone clearance and is unaffected by the composition of stones, ease of usability, and improved tissue safety with reduced chances of fragments blocking are key factors.

Perceived corporate social responsibility and pro-environmental behaviour: Insights from business schools of Peshawar, Pakistan.

Corporate Social Responsibility (CSR) and environmental sustainability have become urgent concerns for contemporary businesses. This study focuses on the interplay between corporate social responsibility perceptions and pro-environmental behaviour (PEB) in response to experts' call for research on the micro-foundations of corporate social responsibility. In addition, it reveals the mechanism underpinning how perceived CSR shapes pro-environmental behaviour in an understudied developing context. Empirically, a qualitative multiple-case research design is utilised by selecting three business schools from Peshawar, Pakistan. Fourteen semi-structured interviews were conducted with senior management and faculty to collect data. Besides primary data, a qualitative documentary review is used to enhance the research. Data analysis is done through the thematic network technique. Plantation, cleanliness, waste reduction, and energy conservation are the environmental aspects of CSR as regarded by employees. In addition, perceived CSR shapes pro-environmental behaviour via environmental knowledge and awareness, eco-civic sense, environmental values, personality traits, religious perspective, and perceived organisational support for the environment. This study provides original additions to the CSR literature by suggesting eco-civic sensibility and religious perspective as new CSR drivers for pro-environmental conduct. Incorporating stakeholder salience into the context of the present study also advances CSR research. The findings are also valuable for management to make the CSR agenda of business schools more strategic, comprehensive, and centred on the priorities of salient stakeholders.

An image dataset of fruitfly species (Bactrocera Zonata and Bactrocera Dorsalis) and automated species classification through object detection.

This data article describes the image dataset collection and annotation of the two most common fruitfly species Bactrocera Zonata and Bactrocera Dorsalis. The dataset is released as a collection of more than 2000 images captured through two sources: images of specially reared fruitfly species in laboratory captured by (48-megapixels) smartphone camera, and images of fruitflies captured by (8-megapixels) Raspberry Pi camera through insect traps installed in fruit orchards. Each image sample is associated with a ground truth label that mentions the fruit fly species. The dataset has been classified and annotated using the object detection method into two fruitfly species with an average 85% accuracy. The results of classification and annotation have been validated by expert entomologists by manually examining test samples in a laboratory setting. This dataset is best suited for developing smart monitoring systems to provide advisory services to farmers through mobile applications that provides real-time information about fruitfly species for effective control and management.

Application of In silico Methods in the Design of Drugs for Neurodegenerative Diseases.

Neurodegenerative diseases are complex disorders that cause neuron loss, brain aging and ultimately lead to death. These diseases are difficult to treat because of the complex nature of the nervous system, and the available medicines are unable to heal them effectively. This fact implies the need for novel therapeutics to be designed that are ready to stop or a minimum of retard the neurodegeneration process. These days, Computer-Assisted Drug Design (CADD) approaches are a passage to extend the drug development efficiency and to reduce time and cost because traditional drug discovery is both time-consuming as well as costly. Computational or in silico methods came up with powerful tools in drug design against neurodegenerative diseases. This review presents the approaches and theoretical basis of CADD. Also, the successful applications of various in silico studies, including homology modeling, molecular docking, Quantitative Structure-Activity Relationship (QSAR), Molecular Dynamic (MD), De novo drug design, Pharmacophore-based drug design, Virtual Screening (VS), LIGPLOT Analysis, In silico ADMET and drug safety prediction, for treating neurodegenerative diseases have also been included in this review. Major emphasis is given to Alzheimer's disease and Parkinson's disease because these two are the most familiar neurodegenerative diseases.

Nutraceuticals for Sleep Disorders.

Sleep is considered as one of the most important aspects for maintaining a healthy life. For a person to function normally, at least 6-8 hours of sleep daily is necessary. Sleep not only affects our mood, but also regulates the efficiency of work done. Many complications arise due to inadequacy of sleep. The unhealthy food and lifestyle choices have made us more prone to sleep disorders. The medications used for the treatment of sleep disorders are mainly habit forming and have tendencies of withdrawal symptoms. This inadequacy in medication has lead to search for newer, better options. The field of nutraceuticals fits apt for treating such disorders. The quality of being non-toxic, non-habit forming, and being practically more efficient has had made it an excellent option. Nutraceuticals make use of food or part of food for the treatment or to prevent any disease. Remarkable positive effects of nutraceuticals like Caffeine, Chamomile, Kava kava, Cherries and Cherry juice, L tryptophan, Valerian, Vitamin D, Marijuana, melatonin, Lemon balm had been mentioned in the treatment of sleep disorders. The present review gives a general overview of nutraceuticals and discusses their use in sleep disorders.

White matter tract microstructure and cognitive performance after transient ischemic attack.

BACKGROUND AND PURPOSE: Patients with transient ischemic attack (TIA) show evidence of cognitive impairment but the reason is not clear. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. We report WM changes using DTI and the relationship with neuropsychological performance in a cohort of transient ischemic attack (TIA) and non-TIA subjects. METHODS: Ninety-five TIA subjects and 51 non-TIA subjects were assessed using DTI and neuropsychological batteries. Fractional anisotropy (FA) and mean diffusivity (MD) maps were generated and measurements were collected from WM tracts. Adjusted mixed effects regression modelled the relationship between groups and DTI metrics. RESULTS: Transient ischemic attack subjects had a mean age of 67.9 ± 9.4 years, and non-TIA subjects had a mean age 64.9 ± 9.9 years. The TIA group exhibited higher MD values in the fornix (0.36 units, P < 0.001) and lower FA in the superior longitudinal fasciculus (SLF) (-0.29 units, P = 0.001), genu (-0.22 units, P = 0.016), and uncinate fasciculus (UF) (-0.26 units, P = 0.004). Compared to non-TIA subjects, subjects with TIA scored lower on the Addenbrooke's Cognitive Assessment-Revised (median score 95 vs 91, P = 0.01) but showed no differences in scores on the Montreal Cognitive Assessment (median 27 vs 26) or the Mini-Mental State Examination (median 30). TIA subjects had lower scores in memory (median 44 vs 52, P < 0.01) and processing speed (median 45 vs 62, P < 0.01) but not executive function, when compared to non-TIA subjects. Lower FA and higher MD in the fornix, SLF, and UF were associated with poorer performance on tests of visual memory and executive function but not verbal memory. Lower FA in the UF and fornix were related to higher timed scores on the TMT-B (P < 0.01), and higher SLF MD was related to higher scores on TMT-B (P < 0.01), confirming worse executive performance in the TIA group. CONCLUSIONS: DTI scans may be useful for detecting microstructural disease in TIA subjects before cognitive symptoms develop. DTI parameters, white matter hyperintensities, and vascular risk factors underly some of the altered neuropsychological measures in TIA subjects.

Recanalization following Endovascular treatment and imaging of PErfusion, Regional inFarction and atrophy to Understand Stroke Evolution-NA1 (REPERFUSE-NA1).

RATIONALE: Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery. AIM: The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion. Specifically, REPERFUSE NA1 will determine if administration of the neuroprotectant NA1 prior to endovascular therapy can significantly reduce early (Day 2 subtract Day 1 diffusion-weighted imaging volume) and delayed secondary infarct (90-day whole brain atrophy plus FLAIR volume-Day 1 diffusion-weighted imaging volume) growth, as measured by magnetic resonance imaging. METHODS AND DESIGN: REPERFUSE-NA1 is a magnetic resonance imaging observational substudy of ESCAPE-NA1 (ClinicalTrialGov NCT02930018). A total of 150 acute stroke patients will be recruited (including 20% attrition) that have been randomized to either NA1 or placebo in the ESCAPE-NA1 trial. STUDY OUTCOMES: Primary-Early infarct growth measured using diffusion-weighted imaging will be at least 30% smaller in patients receiving NA1 compared to placebo. Secondary-Delayed secondary stroke injury at 90 days will be significantly reduced in patients receiving NA1 compared to placebo, as well as delayed secondary growth at 90 days. CONCLUSION: REPERFUSE-NA1 will demonstrate the effect of NA1 neuroprotection on reducing the early and delayed stroke injury after reperfusion treatment.

Decoding Novel Mechanisms and Emerging Therapeutic Strategies in Breast Cancer Resistance.

Breast cancer (BC), an intricate and highly heterogeneous disorder, has presently afflicted 2.09 million females globally. Chemoresistance remains a paramount challenge in the treatment of BC. Owing to its assorted nature, the chemoresistant mechanisms of BC still need intensive research. Accumulating evidence suggests that abnormalities related to the biogenesis of cancer stem cells (CSCs) and microRNAs (miRNAs) are associated with BC progression and chemoresistance. The presently available interventions are inadequate to target chemoresistance, therefore more efficient alternatives are urgently needed to improvise existing therapeutic regimens. A myriad of strategies is being explored, such as immunotherapy, gene therapy, and combination treatment to surmount chemoresistance. Additionally, nanoparticles as chemotherapeutic carriers put forward the options to encapsulate numerous drugs, alone as well as in combination for cancer theranostics. This review summarizes the chemoresistance mechanisms of miRNAs and CSCs as well as the most recently documented therapeutic approaches for the treatment of chemoresistance in BC. By unraveling the underpinning mechanism of BC chemoresistance, researchers could possibly develop more efficient treatment strategies towards BC.

Association of perceived stress with healthy and unhealthy food consumption among teenagers.

OBJECTIVE: To evaluate unhealthy and healthy food consumption and their association with perceived stress in teenagers. METHODS: The cross-sectional study was conducted from February to April 2017 at five educational institutions in Faisalabad, Pakistan, and comprised individuals of either gender aged 13-19 years. Dietary habits were recorded on a proforma and perceived stress scores were calculated using Cohen's perceived stress scale. Multiple regression analysis was used to predict perceived stress scores. RESULTS: Of the226 subjects, 96(42.5%) were males and 130(57.5%) were females. The frequency of consumption per week of sweet snacks, fried foods, soft drinks, sports drinks, energy drinks and vegetables was significantly more in males compared to the females (p<0.05 each). The consumption of such unhealthy food had significant positive relationship with perceived stress scores, while consumption of healthy food, like fresh fruits and vegetables, had a significant negative relationship with it in males only (p<0.05 each). Perceived stress score was primarily predicted by higher consumption of sports drinks (p<0.05) and lower consumption of fresh fruits (p<0.05). CONCLUSIONS: Increased consumption of unhealthy food items and low intake of healthy food could lead to stress in young individuals, especially in males.

Non-enzymatic glucose sensor with electrodeposited silver/carbon nanotubes composite electrode.

Diabetes mellitus is a debilitating disease that affects each and every organ of human body. Hence it is important to continuously monitor the glucose level throughout the day and night. Glucose sensors are in great demand due to a rapid increase in diabetic community. A strategy has been implemented here to fabricate silver nanoparticles (AgNPs) with the support of functionalized carbon nanotubes (f-CNTs). Silver/carbon nanotubes (Ag/CNTs) nanocomposite electrode have been prepared by electrochemical process on Fluorine doped tin oxide (FTO) glass, by varying silver (Ag) concentrations for non-enzymatic glucose sensor. The variable Ag concentration in the morphology of Ag/CNTs nanocomposite has influenced the electrical conductivity, oxidation and reduction potential and electrochemical activity of glucose. Highest current density and good electrocatalytic activity for electrodes are obtained at 70 mM concentration of silver in Ag/CNTs composite. The present study indicates that the Ag/CNTs electrode is a possible substitute of the expensive glassy carbon electrode for enzyme-free glucose sensors.

Synthesis, evaluation and docking of novel pyrazolo pyrimidines as potent p38α MAP kinase inhibitors with improved anti-inflammatory, ulcerogenic and TNF-α inhibitory properties.

A series of nine new N-substituted-4-((1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)amino)benzamides (6a-i) derivatives was synthesized. All the compounds were screened in-vitro for BSA anti-denaturation property, antioxidant assay and p38α MAP kinase inhibition. The in vitro anti-inflammatory assay results revealed that the compounds (6f-i) showed better activity than the compounds 6a-e. Compound 6f bearing the 4-chlorophenyl group showed in vitro anti-inflammatory activity (82.35 ±â€¯4.04) comparable to standard drug diclofenac sodium (84.13 ±â€¯1.63) and better p38α MAP kinase inhibitory activity (IC50 = 0.032 ±â€¯1.63 µM) than the prototypic inhibitor SB203580 (IC50 = 0.041 ±â€¯1.75 µM). The selected active compounds (6f-i) were further studied in animal models for anti-inflammatory activity, ulcerogenic liability, lipid peroxidation and TNF-α inhibition potential. Compound 6f showed promising anti-inflammatory potential with a percentage inhibition of 83.73% when compared to the standard, diclofenac sodium (78.05%). Compound 6f was also found to show reduced ulcerogenic liability and lipid peroxidation in comparison to the standard. This compound also potently inhibited the lipopolysaccharide (LPS)-induced TNF-α production in mice model (ID50 = 8.23 mg/kg) in comparison to SB 203580 (ID50 = 26.38 mg/kg). The molecular docking of compounds 6a-i against p38α MAP kinase receptor was also performed to understand ligand receptor interaction. Amongst all synthesized molecules compound 6f displayed highest docking score of -9.824. It showed hydrogen bonding interactions with Asn115 and pi-cation interaction with Lys53.

Longitudinal Brain Atrophy Rates in Transient Ischemic Attack and Minor Ischemic Stroke Patients and Cognitive Profiles.

Introduction: Patients with transient ischemic attack (TIA) and minor stroke demonstrate cognitive impairment, and a four-fold risk of late-life dementia. Aim: To study the extent to which the rates of brain volume loss in TIA patients differ from healthy controls and how they are correlated with cognitive impairment. Methods: TIA or minor stroke patients were tested with a neuropsychological battery and underwent T1 weighted volumetric magnetic resonance imaging scans at fixed intervals over a 3 years period. Linear mixed effects regression models were used to compare brain atrophy rates between groups, and to determine the relationship between atrophy rates and cognitive function in TIA and minor stroke patients. Results: Whole brain atrophy rates were calculated for the TIA and minor stroke patients; n = 38 between 24 h and 18 months, and n = 68 participants between 18 and 36 months, and were compared to healthy controls. TIA and minor stroke patients demonstrated a significantly higher whole brain atrophy rate than healthy controls over a 3 years interval (p = 0.043). Diabetes (p = 0.012) independently predicted higher atrophy rate across groups. There was a relationship between higher rates of brain atrophy and processing speed (composite P = 0.047 and digit symbol coding P = 0.02), but there was no relationship with brain atrophy rates and memory or executive composite scores or individual cognitive tests for language (Boston naming, memory recall, verbal fluency or Trails A or B score). Conclusion: TIA and minor stroke patients experience a significantly higher rate of whole brain atrophy. In this cohort of TIA and minor stroke patients changes in brain volume over time precede cognitive decline.

Development of spatial orientation skills: an fMRI study.

The ability to orient and navigate in spatial surroundings is a cognitive process that undergoes a prolonged maturation with progression of skills, strategies and proficiency over much of childhood. In the present study, we used functional Magnetic Resonance Imaging (fMRI) to investigate the neurological mechanisms underlying the ability to orient in a virtual interior environment in children aged 10 to 12 years of age, a developmental stage in which children start using effective spatial orientation strategies in large-scale surroundings. We found that, in comparison to young adults, children were not as proficient at the spatial orientation task, and revealed increased neural activity in areas of the brain associated with visuospatial processing and navigation (left cuneus and mid occipital area, left inferior parietal region and precuneus, right inferior parietal cortex, right precentral gyrus, cerebellar vermis and bilateral medial cerebellar lobes). When functional connectivity analyses of resting state fMRI data were performed, using seed areas that were associated with performance, increased connectivity was seen in the adults from the right hippocampal/parahippocampal gyrus to the contralateral caudate, the insular cortex, and the posterior supramarginal gyrus; children had increased connectivity from the right paracentral lobule to the right superior frontal gyrus as compared to adults. These findings support the hypothesis that, as children are maturing in their navigation abilities, they are refining and increasing the proficiency of visuospatial skills with a complimentary increase in connectivity of longer-range distributed networks allowing for flexible use of efficient and effective spatial orientation strategies.

Diffusion-Weighted MRI Stroke Volume Following Recanalization Treatment is Threshold-Dependent.

PURPOSE: Infarct lesion segmentation has been problematic as there are a wide range of relative and absolute diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) thresholds that have been used for this purpose. We examined differences of stroke lesion volume and evolution evaluated by magnetic resonance imaging (MRI) during the immediate post-treatment phase (<5 h) and at 24 h. METHODS: In this study 33 acute ischemic stroke patients were imaged with MRI <5 h and 24 h post-reperfusion treatment. Lesion volumes were segmented on ADC maps and average DWI using literature cited absolute ADC and relative DWI thresholds. The segmented lesion volumes within both time points were compared and the absolute change in lesion volume (infarct growth) between the two time points was calculated and compared using Bland-Altman analysis. RESULTS: Lesion volumes differed significantly when different relative DWI or absolute ADC thresholds were used (p < 0.05), which held true for baseline as well as follow-up lesions. The median absolute changes in lesion volume from baseline to follow-up for ADC thresholds of 550 × 10-6 mm2/s, 600 × 10-6 mm2/s, 630 × 10-6 mm2/s and 650 × 10-6 mm2/s were 3.5 ml, 4.2 ml, 4.5 ml, and 6.5 ml, respectively (p < 0.05). Likewise, the median absolute changes in lesion volume from baseline to follow-up for DWI thresholds, k = 0.85, 1.28, 1.64, 1.96, and 2.7 were 10.1 ml, 7.3 ml, 5.7 ml, 5.4 ml and 4.2 ml, respectively (p < 0.05). CONCLUSION: Absolute lesion volumes and changes in lesion volumes (infarct growth) measured after recanalization treatment were dependent on absolute ADC and relative DWI thresholds, which may have clinical significance. Standardization of techniques for measuring DWI lesion volumes requires immediate attention.

Therapeutic advancement of benzothiazole derivatives in the last decennial period.

Benzothiazole, a fused heterocyclic moiety, has attracted synthetic and medicinal chemists for good reasons. It is a valuable scaffold that possesses diverse biological activities, such as anticancer, anti-inflammatory, antimicrobial, antiviral, antimalarial, and anticonvulsant effects. This review mainly focusses on the recent research work on the different biological activities of benzothiazole-based compounds.

Diffusion-weighted imaging lesion growth occurs despite recanalization in acute ischemic stroke: Implications for future treatment trials.

BACKGROUND: A proportion of patients presenting with acute small ischemic strokes have poor functional outcomes, even following rapid recanalization treatment. AIMS: Infarct growth may occur even after successful recanalization and could represent an appropriate endpoint for future stroke therapy trials. METHODS: Magnetic resonance diffusion-weighted imaging lesion volumes were obtained at 5 h (initial posttreatment) and 24 h (follow-up) after acute stroke treatment for n = 33 in ischemic stroke patients. Sample sizes per arm (90% power, 30% effect size) for diffusion-weighted imaging lesion growth between initial and 24 h, early change in the National Institutes of Health Stroke Scale between pre- and 24 h, National Institutes of Health Stroke Scale at 24 h, and diffusion-weighted imaging lesion volume at 24 h were estimated to power a placebo-controlled stroke therapy trial. RESULTS: For patients with poor recanalization (modified thrombolysis in cerebral infarction <2 a; modified arterial occlusion lesion = 0-2) (n = 11), the median diffusion-weighted imaging lesion growth was 8.1 (interquartile range: 4.5, 22.4) ml and with good recanalization (modified thrombolysis in cerebral infarction =2 b or 3; modified arterial occlusion lesion = 3) (n = 22), the median diffusion-weighted imaging lesion growth was 10.0 (interquartile range: 6.0, 28.2) ml ( P = 0.749). When considering a 30% effect size, the sample size required per arm to achieve significance in an acute stroke study would be: (1) N = 49 for the diffusion-weighted imaging lesion growth between initial posttreatment and follow-up time points, (2) N = 65 for the change in the National Institutes of Health Stroke Scale between admission and 24 h, (3) N = 259 for the National Institutes of Health Stroke Scale at 24 h, and (4) N = 256 for diffusion-weighted imaging volume at 24 h. CONCLUSION: Despite best efforts to recanalize the ischemic brain, early diffusion-weighted imaging lesion growth still occurs. Treatment trials in stroke should consider early diffusion-weighted imaging lesion growth as a surrogate outcome measure to significantly reduce sample sizes.

1,2,4-Triazole-based benzothiazole/benzoxazole derivatives: Design, synthesis, p38α MAP kinase inhibition, anti-inflammatory activity and molecular docking studies.

Novel N-(benzothiazol/oxazol-2-yl)-2-[(5-(phenoxymethyl)-4-aryl-4H-1,2,4-triazol-3-yl)thio] acetamide derivatives (5a-n) were synthesized and investigated for in vitro anti-inflammatory activity and p38α MAP kinase inhibition. Compounds showing good in vitro activities (5a, 5b, 5d, 5e, 5i, 5k and 5l) were studied for their in vivo anti-inflammatory activity using carrageenan induced rat paw edema model. Compound 5b emerged as the most active compound with an edema inhibition of 84.43%. It also showed improved GI safety profile with lower ulcer severity index and lipid peroxidation potential. Also, p38α MAP kinase assay of 5b showed superior inhibitory potency (IC50:0.031 ±â€¯0.14 µM) than the standard SB 203580 (IC50:0.043 ±â€¯0.14 µM). To predict their binding mode compounds were also docked against p38α MAP kinase enzyme. Compound 5b and SB 203580 showed hinge region interaction with MET 109.

A longitudinal magnetic resonance imaging study of neurodegenerative and small vessel disease, and clinical cognitive trajectories in non demented patients with transient ischemic attack: the PREVENT study.

BACKGROUND: Late-life cognitive decline, caused by progressive neuronal loss leading to brain atrophy years before symptoms are detected, is expected to double in Canada over the next two decades. Cognitive impairment in late life is attributed to vascular and lifestyle related risk factors in mid-life in a substantial proportion of cases (50%), thereby providing an opportunity for effective prevention of cognitive decline if incipient disease is detected earlier. Patients presenting with transient ischemic attack (TIA) commonly display some degree of cognitive impairment and are at a 4-fold increased risk of dementia. In the Predementia Neuroimaging of Transient Ischemic Attack (PREVENT) study, we will address what disease processes (i.e., Alzheimer's vs. vascular disease) lead to neurodegeneration, brain atrophy, and cognitive decline, and whether imaging measurements of brain iron accumulation using quantitative susceptibility mapping predicts subsequent brain atrophy and cognitive decline. METHODS: A total of 440 subjects will be recruited for this study with 220 healthy subjects and 220 TIA patients. Early Alzheimer's pathology will be determined by cerebrospinal fluid samples (including tau, a marker of neuronal injury, and amyloid ß1-42) and by MR measurements of iron accumulation, a marker for Alzheimer's-related neurodegeneration. Small vessel disease will be identified by changes in white matter lesion volume. Predictors of advanced rates of cerebral and hippocampal atrophy at 1 and 3 years will include in vivo Alzheimer's disease pathology markers, and MRI measurements of brain iron accumulation and small vessel disease. Clinical and cognitive function will be assessed annually post-baseline for a period of 5-years using a clinical questionnaire and a battery of neuropsychological tests, respectively. DISCUSSION: The PREVENT study expects to demonstrate that TIA patients have increased early progressive rates of cerebral brain atrophy after TIA, before cognitive decline can be clinically detected. By developing and optimizing high-level machine learning models based on clinical data, image-based (quantitative susceptibility mapping, regional brain, and white matter lesion volumes) features, and cerebrospinal fluid biomarkers, PREVENT will provide a timely opportunity to identify individuals at greatest risk of late-life cognitive decline early in the course of disease, supporting future therapeutic strategies for the promotion of healthy aging.