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Background: The second most prevalent cause of disability and death worldwide, stroke is silently taking on the characteristics of an epidemic. Almost 85% of the all strokes are ischemic strokes. Objective: To assess the stress hyperglycemia as a prognostic factor in acute ischemic stroke at a tertiary care hospital. Design of the Study: It was a case control study. Place and Duration of Study: This study was conducted at the Department of medicine & Allied Services Hospital Lahore from March 2022 August 2022. Patients and Methods: Total 100 patients with Computerized Tomography (CT) Brain evidence of acute ischemic stroke who met the inclusion criteria were included in the study. At admission, a thorough history was taken and clinical examination was performed. The National Institutes of Health Stroke Scale (NIHSS scale) was used to measure the patient’s neurological state. Fasting Blood sugar (FBS) and Glycosylated Hemoglobin (HBA1c) were performed. Patients' functional recovery was measured by comparing their NIHSS scores on the day of admission and after 7 days in the hospital. Results of the Study: Most of the patients enrolled in our study had age of 61 to 70 years. In study sample 56% of patients were male and 44% were female. Out of 100 patients 56 had stress hyperglycemia and 44 were without stress hyperglycemia. Functional recovery was greater in patients with normoglycemia than in patients with stress hyperglycemia (based on differences in NIHSS score on day one and day seven). The mortality was observed to be 9.2% in patients who had stress hyperglycemia. The mean NIHSS scores was 3.45±1.64 in patients with stress hyperglycemia and 4.50 ± 1.05 was in participants with normoglycemia. Practical Implication: The present study was carried out to know whether stress hyperglycemia can be a prognostic marker in patients of acute ischemic stroke. Conclusion: When compared to patients with stress hyperglycemia, functional recovery was better in patients with normoglycemia. This study demonstrates that patients with normoglycemia had greater functional recovery as compared to patients with stress hyperglycemia, as measured by the difference between the NIHSS scores. As a result, patients with normoglycemia had better outcomes than those with stress hyperglycemia. Keywords: Stress hyperglycemia, Normoglycemia, Acute Ischemic Stroke, Prognostic Factor, NIHSS

This review is about 1,2,4-triazoles include their synthesis; their physio-chemical properties, SAR, reactions, derivatives. Finally, their biological activities with a demonstrated showing different requirements to achieve different activity

Objective: To compare the dynamic hip screw versus proximal femoral nail devices in the management of intertrochanteric fractures Design of the Study: It was a cross-sectional survey. Place and Duration of Study: This study was carried at the Department of Orthopaedic and Spine Surgery, Sahara Medical College (Sughra Shafi Medical Complex), Narowal from April 2022 to September 2022. Patients and Methods: In this study, 70 patients of both sexes, ranging in age from 40 to 70, had intertrochanteric fracture surgery. Two treatment groups were created by randomly dividing these patients; Group-A (n=35) patients got proximal femoral nailing while Group-B (n=35) patients underwent fracture fixation with DHS. The outcome variables that were used to compare the two groups were the frequency of infection (diagnosed clinically upon appearance of any two of the following signs within 4 weeks after surgery: redness around the wound, serosangious discharge, and fever >100oF). Every participant's signed informed permission was obtained. Results of the Study: The age of the patients ranged from 40 years to 70 years with a mean of 54.96±8.34 years. There were 28 (40%) male and 42 (60%) female patients. 46 (65.7%) patients had Type-I and 24 (34.3%) patients had Type-II fracture according to Evan’s Classification. The frequency of infection was significantly higher in the DHS group (31.4% vs. 0.0%; p=0.000) as compared to PFN group. Conclusion: In patients with intertrochanteric fractures, proximal femoral nail was found to be superior to DHS in terms of a significantly reduced risk of infection, regardless of the patient's age or gender. This supports the preferred use of proximal femoral nail in future practise, provided the necessary hardware and surgical skills are available. Keywords: Dynamic Hip Screw, Proximal Femoral Nail, Intertrochanteric Fractures, Infection, Evan’s Classification

Infections caused by bacteria have a significant impact on public health. Chemical synthesis of new derivatives of cephalexin inked to amino acid (tryptophan or histidine) through an amide bond at the acyl side chain is achieved. This is a new approach of incorporating, tryptophan and histidine into the the primary amino group of cephalexin, in order to provide a bulky group very close to the β-lactam ring. This chemical addition act as isosteric group to the alkoximino that protect beta lactam ring from bacterial beta lactamase enzyme. The new derivatives may show resistance to β-lactamases, improve activity and pharmacokinetic properties and may give new life for old drugs that are susceptible to hydrolysis by most β-lactamases. The chemical structures of these derivatives were confirmed by: FTIR, 1H-NMR spectroscopy, elemental micro analysis and some physical properties. Molecular docking on serine beta lactamase and prediction of ADME parameters were recorded using GOLD suite and Swiss ADME software respectively. Docking scores of the new derivatives of Cephalexin on β-lactamases were higher than those of Cephalexin, which may indicate better activity

Summary Background Exposure and Response Prevention (ERP) is a form of behavioural therapy for tics; however, its effectiveness remains uncertain. We aimed to evaluate the effectiveness of internet-delivered, therapist-supported, and parent-assisted ERP for treatment of tics in children and young people with Tourette syndrome or chronic tic disorder. Methods This multicentre, parallel group, single-blind, randomised controlled trial was conducted across two study sites in England. Participants were recruited via 16 patient identification centres, two study sites in England (Nottingham and London), or online self-referral. Eligible participants were aged 9–17 years, had Tourette syndrome or chronic tic disorder, had not received behavioural therapy for tics in the past 12 months or were about to start, and had a Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTSS) of more than 15 or more than 10 if they had only motor or vocal tics. Patients were excluded if they had started or stopped medication for tics within the past 2 months; had current alcohol or substance dependence, psychosis, suicidality, anorexia nervosa, or suspected moderate to severe intellectual disability; or presented an immediate risk to self or others; or the parent or carer was unable to speak, read, or write in English. Eligible patients were randomly assigned (1:1) by masked outcome assessors to receive 10 weeks of online, remotely delivered, therapist-supported ERP or psychoeducation (active control). Outcome assessors, statisticians, health economists, the trial manager, and the chief investigator were masked to group allocation. Patients were not directly informed of their allocation, but this could be established from the content once treatment commenced and the patients were not, therefore, considered masked to treatment. The primary outcome was YGTSS-TTSS 3 months after randomisation, and analysis was done in all randomised patients for whom data were available for each timepoint and outcome. Safety analysis was by intention to treat. Longer term follow-up is ongoing. This trial is registered with ISRCTN (ISRCTN70758207) and ClinicalTrials.gov ( NCT03483493 ). Findings Between May 8, 2018, and Sept 30, 2019, we assessed 445 candidates for inclusion in the study. 221 potential participants were excluded (90 did not meet inclusion criteria, 84 declined to participate, and 47 unable to contact family). 224 participants were enrolled and randomly assigned to ERP (n=112) or psychoeducation (n=112). The enrolled patients were mostly male (n=177; 79%) and of White ethnicity (n=195; 87%). 11 patients were lost to follow-up 3 months after randomisation in the ERP group, compared with 12 patients in the psychoeducation group. Mean YGTSS-TTSS at 3 months after randomisation was 23·9 (SD 8·2) in the ERP group and 26·8 (7·3) in the psychoeducation group. The mean total decrease in YGTSS-TTSS at 3 months was 4·5 (16%, SD 1·1) in the ERP group versus 1·6 (6%, 1·0) in the psychoeducation group. The estimated mean difference in YGTSS-TTSS change between the groups adjusted for baseline and site was –2·29 points (95% CI –3·86 to –0·71) in favour of ERP, with an effect size of –0·31 (95% CI –0·52 to –0·10). Two serious adverse events occurred (one collapse and one tic attack), both in the psychoeducation group, neither of which were related to study treatment. Interpretation ERP is an effective behavioural therapy for tics. Remotely delivered, online ERP with minimal therapist contact time represents an efficient public mental health approach to improve access to behavioural therapy for tics in children and adolescents. Funding National Institute for Health Research and Health and Technology Assessment.

People of South Asia (Indian Subcontinent) faced a threatening situation after their defeat at the hands of British in 1857 in social, religious and economical fields. Especially, Muslims received irreparable setback, as they were held accountable for the war. The post 1857 period post many challenges which were multifarious in nature including the loss of political power, the ruin of their economic basis and a threat to annihilation of Islamic culture both material and non-material. The Muslims scholars and Ulama felt the intensity of these challenges deeply. They purified the minds of Muslims with their written Islamic Literature and influence their mind-set and thoughts. Especially, the Urdu translations of Holy Quran and Tafaseer along with the Islamic Books contributed a lot in the fields of theology, History, Education, Politics, Culture, Economics, Islamic Jurisprudence and Quranic exegesis along with authentic Muslim traditions. This paved the way of freedom for the Muslim of subcontinent. In the proposed paper, an effort will be made to discuss the social and economical influences of Tafaseer during 1857 to 1947 on the Muslims of Subcontinent.

In this research work, aluminum substituted Ni-Co ferrite nanoparticles have been produced by a simple and cost-effective method, i.e., sol–gel auto-combustion. Synthesized nanoparticles were annealed in a muffle furnace at 600°C for 3 h before characterization. The x-ray diffraction patterns revealed that the ferrite nanoparticles grew preferentially along the (311) plane and exhibit face centered cubic structure. The crystallite size of nanoparticles (14 to 17 nm) was estimated by Scherrer’s relation. The effect of aluminum substitution on structural parameters of ferrite nanoparticles, such as lattice constant and stacking faults, have been studied. Structural analysis revealed that the lattice constant of the nanoparticles decreases as a function of aluminum content. The Fourier transform infrared spectroscopy confirmed the spinal ferrite crystal structure of synthesized aluminum substituted Ni-Co ferrite nanoparticles. The surface morphology observed through scanning electron microscopy depicts the growth and distribution of nanograins with uniform size with in the samples. Dielectric properties investigated through impedance analyzer spectroscopy revealed that aluminum substituted Ni-Co ferrite nanoparticles demonstrated the high conductivity along with potential dielectric properties. These aluminum substituted Ni-Co ferrite nanoparticles would have possible applications in high storage memory and microwave devices.

Copper-substituted manganese (Mn1-xCuxFe2O4) spinel ferrite nanoparticles have been synthesized by adopting sol–gel self-combustion chemical route where 0.0 ≤ × ≤ 0.5. All samples were sintered at temperature of 600 °C for three hours to achieve stable crystalline structure of ferrites. XRD analysis revealed that ferrite nanoparticles exhibit face-centered cubic (FCC) structure. The Mn1-xCuxFe2O4 spinel ferrite nanoparticles have been grown with preferred orientation along (311) plane. The crystallite size was estimated through Scherrer’s equation and observed to be 17–18 nm. The impedance spectroscopy was employed to investigate the electrical and dielectric characteristics of synthesized samples. The tangent loss was observed to decrease with copper (Cu2+) concentration. The effect of tangent loss, dielectric constant, imaginary dielectric constant, real impedance, imaginary impedance loss, modulus, real and imaginary modulus have been studied in the applied electric field frequency ranging from 20 Hz to 20 MHz for all the samples. The real part of impedance was observed to decrease as a function of Cu2+ concentration and frequency, suggesting the decrement in conductivity of the samples. The prepared Mn1-xCuxFe2O4 spinel ferrite nanoparticles would have potential viability in microwave applications.

New 2-methyl benzimidazole derivatives were prepared and evaluated as possible inhibitor agents for cyclooxygenase-2 (COX-2). The synthesized derivatives structures have been recognized according to their spectral FT-IR, 1H-NMR data and physical properties. The newly synthesized compounds were inspected in vivo for their anti-inflammation efficiency using egg-white stimulated edema of paw method regarding the effect of propylene glycol 50%v/v as a control group. Ibuprofen (10mg/kg i.p.) was chosen as a reference ligand. New compounds exhibit a significant in vivo anti-inflammatory efficacy approached with ibuprofen as a reference drug. Selective evaluation of cyclooxygenase-2 by stimulating molecular cohesion through (GOLD suite v.5.6.2). All the investigated compounds via molecular docking showed significant more activities comparable with diclofenac and ibuprofen as referenced drugs. ADME studies were performed to estimate site of absorption, bioavailability, topological polar surface area and drug-likeness and it appeared that all synthesized compounds absorbed from GIT.

Currently, spinel ferrites are of great interest due to their large range of practical high frequency applications. Nickel spinel ferrites with formula NiAlxFe2-xO4 (where x = 0.0, 0.05, 0.10, 0.15, 0.20, 0.25) were prepared by a wet chemical sol-gel auto-combustion method. All the samples were annealed at 600 °C for 3 h and pellets were made to investigate the dielectric properties. The spinel structure of the nickel-based ferrites was confirmed by using X-rays diffraction analysis. The crystallite size was estimated using Scherrer’s formula and observed to be in the range from 11 to 17 nm. The addition of Al3+ varies the lattice constant from 8.26 to 8.35 A. The study of dielectric properties of interest (complex dielectric constant, dielectric tangent loss, impedance, A.C. conductivity, and electric modulus) as a function of the Al doping concentration was carried out in the frequency range from 1 MHz to 3 GHz using an impedance analyser. On the basis of these investigations, it was found that both the real and imaginary parts of the dielectric constant decreased with increasing applied frequency. Cole–Cole plots of electric modulus revealed evidence of contribution from grains and grain boundaries in the conduction mechanism. The observations revealed that with increasing aluminium doping, the dielectric properties of these ferrite materials are 6.

A series of lanthanum (La)-doped nickel (Ni) ferrites NiLaxFe2-xO4 with doping concentrations (x = 0.0, 0.01, 0.02, 0.03, 0.04, and 0.05) is synthesized via a sol–gel auto-combustion method. Structural properties are determined with the help of X-ray diffraction (XRD). The effect of La doping on dielectric properties of Ni ferrites is discussed. XRD analysis confirms the existence of pure FCC spinel phase, and no impurity phase was detected. The lattice constant decreases initially due to strain produced by La3+ ions replacement. At higher doping concentrations, the lattice constant increases due to the large ionic radius of La3+ as compared to Fe3+. Tangent loss (tanδ), dielectric constant, and dielectric loss values are determined in the 1 MHz to 3 GHz frequency range, and explained by the Maxwell–Wagner model. A persistent behavior of dielectric loss and dielectric constant was found in the mid microwave frequency region. The most stable behavior of the dielectric constant (e′) and dielectric loss (e″) in the high-frequency region is found with (x = 0.04). Ac conductivity is also discussed in the 1 MHz to 3 GHz region, and is found to be impacted by grain and grain boundary resistive behavior at low and high frequencies. Cole–Cole plots of different samples, corresponding to different doping concentrations, are used to describe the conduction phenomena. The stable response of dielectric constant (e′) and dielectric loss (e″) in the mid microwave frequency region makes NiLaxFe2-xO4 nanoparticles a potential candidate for microwave devices.

To understand how children and young people with tic disorders were affected by COVID-19, we compared pre and during pandemic scores on the Yale Global Tic Severity Scale (YGTSS). Participants were young people (N = 112; male:78%; 9–17 years) randomised to the control arm of the “ORBIT-Trial” (ISRCTN70758207, ClinicalTrials.gov-NCT03483493). For this analysis, the control arm was split into two groups: one group was followed up to 12-months’ post-randomisation before the pandemic started (pre-COVID group, n = 44); the other group was impacted by the pandemic at the 12-month follow-up (during-COVID group, n = 47). Mixed effects linear regression modelling was conducted to explore differences in YGTSS at 6- and 12-months post-randomisation. There were no significant differences in tic symptom or severity between participants who were assessed before and during COVID-19. This finding was not influenced by age, gender, symptoms of anxiety or autism spectrum disorder. Thus, the COVID-19 pandemic did not significantly impact existing tic symptoms.

A new series of sulfamethoxazole derivatives bearing some biologically active heterocycles such as pyrazole (2), 3,4-dihydropyrimidin (3-7, 11, 12), pyrrole (9) and 1,3-dihydropyrimidin (10) rings were successfully synthesized. Identification of designed compounds was done by physicochemical properties and spectral measurements (

Background Process evaluations are an important component in the interpretation and understanding of outcomes in trials. The Online Remote Behavioural Intervention for Tics (ORBIT) study is a randomized controlled trial evaluating the effectiveness of an Internet-delivered behavioural intervention (called BIP TIC) compared to an Internet-delivered education programme aimed at children and young people with tics. A process evaluation will be undertaken alongside the main trial to determine precisely how the behavioural intervention works and ascertain whether, and if so, how, the intervention could be successfully implemented in standard clinical practice. This protocol paper describes the rationale, aims, and methodology of the ORBIT trial process evaluation. Methods The process evaluation will have a mixed-methods design following the UK Medical Research Council 2015 guidelines, comprising both quantitative and qualitative data collection. This will include analysing data usage of participants in the intervention arm; purposively sampled, semi-structured interviews of parents and children, therapists and supervisors, and referring clinicians of the ORBIT trial, as well as analysis of qualitative comments put into the online therapy platform by participants at the end of treatment. Qualitative data will be analysed thematically. Quantitative and qualitative data will be integrated in a triangulation approach, to provide an understanding of how the intervention works, and what resources are needed for effective implementation, uptake and use in routine clinical care. Discussion This process evaluation will explore the experiences of participants, therapists and supervisors and referring clinicians of a complex online intervention. By contextualising trial efficacy results, this will help understand how and if the intervention worked and what may be required to sustain the implementation of the treatment long term. The findings will also aid in our understanding of factors that can affect the success of complex interventions. This will enable future researchers developing online behavioural interventions for children and young people with mental health and neurological disorders to gain invaluable information from this process evaluation. Trial registration International Standard Randomised Controlled Trials Number, ISRCTN70758207. Registered on 20 March 2018. ClinicalTrials.gov, NCT03483493. Registered on 30 March 2018.

Nickel-substituted manganese spinel ferrite NixMn1−xFe2O4 (x = 0.1, 0.2, 0.3, 0.4 and 0.5) nanoparticles have been prepared by sol–gel auto-combustion method. X-ray diffraction analysis reveals that prepared nanomaterials are spinel ferrite due to existence of secondary phase. The synthesis parameters such as molarity of reactants, magnetic stirring speed, temperature, amount of citric acid and annealing in ambient atmosphere have been optimized to control the crystallite size from 14 to 16 nm. The nickel substitution significantly affects the structural parameters such as lattice strain, micro-train, stacking fault and dislocation density. Dielectric properties were analyzed through impedance analyzer (LCR meter) for frequencies ranging from 1 kHz to 20 MHz and results depicted that synthesized nanoparticles respond to the electromagnetic radiations in terms of variation in tangent loss and dielectric constant as a function of Ni2+ content. This behavior is related to the microstructural differences among conducting grains and resistive grain boundaries that contribute to the dielectric relaxation in these nanoparticles. The structural, dielectric and impedance analysis suggested that these nickels incorporated manganese spinel ferrite nanoparticles would have potential applications in high-frequency applications.

New two derivatives of 2- methyl benzoimidazole were designed, synthesized and evaluated as a potential cyclooxygenase-2 [COX-2] inhibitors. The synthesized compounds have been recognized according to their spectral FT-IR, 1H-NMR data and physical pro- perties. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using egg-white stimulated paw edema method with respect to the effect of propylene glycol 50%v/v [control group] and the ibuprofen [10mg/kg i.p.] was selected as a reference ligand. New compounds showed a significantly higher in vivo anti-inflammatory activity compared with ibuprofen as a reference drug. COX-2 selectivity evaluation through molecular docking via GOLD suite [v. 5.6.2.]. The new compounds via molecular docking showed significant higher activities when compared with ibuprofen as referenced drugs because of having hydrogen bonding interaction toward the key amino acids within COX-2 structure and all these results were compatible with the study of in vivo acute anti-inflammatory activities for tested compounds. ADME studies were performed to predict absorption, bioavailability, topological polar surface area, and drug-likeness. The results of ADME studies showed that all synthesized compounds absorbed from the gastrointestinal tract.

Background Plasma cell leukemia (PCL) is diagnosed by the presence of an absolute plasma cell count of > 2 × 109/L or 20% plasma cells in the peripheral blood. Because the incidence of PCL is relatively low, our case report study presents a rare opportunity to describe the clinical and pathological characteristics of this leukemia, as well as different modalities of treatment and outcomes of primary PCL (pPCL). Case summary A 56-year-old male with a history of hypertension complained of pain in the left flank area which started four months prior to admission. On admission, his vital signs were stable, and physical examination was completely benign. Laboratory evaluation showed hemoglobin of 5.1 g/dL, white blood cell count of 6.6 cells per cubic millimeter with 16% atypical lymphocytes, and platelet count of 51000 per microliter. Peripheral smear showed more than 10%-15% of plasma cells (Figure 1), and flow cytometry of peripheral blood confirmed PCL with 24% plasma cells CD138+. Bone marrow biopsy demonstrated 80% plasma cells (38+, 138+, 117+, 10-, 19-, 20-, 56-) with 90% cellularity. The Oncology team was consulted, and VCD therapy was started. After completing therapy at 1, 4, 8, and 11 d, the patient was discharged home. The patient was being considered for a bone marrow transplant evaluation within two months of discharge. Conclusion PCL is a rare and aggressive form of leukemia with a poor prognosis. Multi-center studies and clinical trials should be conducted to develop accurate criteria for the initial diagnosis and prompt treatment of this disease.

Background: Breast Cancer (BC) is common, with 1 in 8 U.S. women (12.4%) developing invasive breast cancer in their lifetime. BC is associated with the most awareness campaigns with pink ribbon as its symbol. October was earmarked as the breast cancer awareness month (CAM) in 1985. Cervical (CC) and ovarian cancers (OC) are associated with a high mortality as well and have awareness months dedicated to them. The aim of these awareness drives is to change public attitude and help in early detection and ultimately prevention of various cancers. Internet search activity can be used as a method to gauge interest and awareness in the masses. We aimed to assess the popularity of BC compared to other gynecological cancers, including OC and CC. Methods: We compared the relative frequency of search terms “Breast Cancer,” “Ovarian Cancer,” and “Cervical Cancer” between January 1, 2004 and December 31, 2017 (n=168 months) using Google Trends, a public web facility of Google Inc. The software designates a reference value of 100 for the point of highest popularity and it provides relative monthly popularity scores for all the terms, which we termed as comparative interest scores (CIS). Within each cancer, average CIS was then compared for their respective awareness months (n=14 months; October for BC, September for OC, and January for CC) to the remaining months (n=154 months). Results: The mean CIS for BC was significantly higher during its CAM, 70.5 as compared to other months 35.9; pP=1.00. And for OC, CIS was significantly higher during its CAM (9.2) compared to other months (7.7); P=.0002. The peak of highest popularity for breast cancer was observed during October 2004 and all peaks corresponded to the CAM; other smaller peaks were seen during significant news events associated with BC, all of which surpassed OC and CC in those months. Overall BC CIS were significantly higher compared to CC (PPConclusions: We conclude that BC awareness campaigns have succeeded in increasing internet search activity during its CAM but ovarian and cervical cancer campaigns especially when compared to breast cancer have not been as successful. There is still a need to increase awareness among masses. Google trends data also tells us which states in US have more internet search activity compared to others which can be used to target the relatively unaware public.

Furan, oxazole-derived Schiff base, and different aldehydes are to be combined to study their potential activities including anti-inflammatory action through COX enzyme inhibition. Molecular docking studies determine the most detailed probable view of drug-receptor interaction and have created a new rational approach to drug design. It suggests that these twelve compounds have strong interaction with COX-1 and COX-2 enzymes, which are responsible for the activity. In this article, 12 oxazole derivatives were docked inside cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme’s crystal structures to calculate the binding potency of each derivative within the active site. Molecular modeling and In silico prediction of ADME properties approaches were conducted and the two most effective derivatives were chosen with docking binding range (-10.311 to -9.02) kcal/mol and (-9.642 to -9.18) respectively. The binding ability of indomethacin, aspirin, and mofezolac were selected as non-selective COX inhibitors. Whereas celecoxib, valdecoxib, rofecoxib, and parecoxib stand for selective COX inhibitors.

Cancer is a significant worldwide public health issue.The adverse effects of anticancer chemotherapies still compromise the quality of life of patients .To identify new potential targeted anticancer agents, a series of pyrazoline derivatives were synthesized and evaluated for anticancer effects on A549 (human lung adenocarcenoma cell line). The new derivatives were synthesized by incorporating pyrazoline pharmacophore into nabumetone moiety as a starting molecule and the chalcone derivatives as intermediate products. In silico evaluation methods were done before synthesis through .molecular docking via genetic optimization for ligand docking (GOLD) Suite software with EGFR tyrosine kinase and exhibited significant tyrosine kinase inhibition activities compared with erlotinb as a reference drug due to their hydrogen bonding interaction with key amino acids and these results are compatible with the experimental findings . The Compound structures were confirmed by 1H-NMR , some physicochemical properties and infrared spectroscopy . An in vitro assay demonstrated that the final compounds (P1,P2,P3 and P4) exerted potent to moderate cytotoxic activity in the micromolar range with an IC50 values (15.409µM, 7.24µM, 27.05µM, 22.45µM) respectively when compared with erlotinib (IC50 =25.23µM) while (P5&P6) show weak activity . Pharmacokinetic and physicochemical properties of the final compounds predicted by using ADME Evaluations . The results showed all the synthesized compounds have high oral bioavailability and good GI absorption.

Background: Behaviour therapy is an effective treatment in children and adolescents with tic disorders but is rarely available. Online delivery could widen access to therapy. We evaluated the efficacy of internet-delivered, therapist-supported and parent-assisted Exposure and Response Prevention (ERP) for tics. Methods: Multi-centre, parallel group, single-blind, randomised controlled trial. Eligible participants were aged 9-17 years with Tourette syndrome/chronic tic disorder, who had not received behaviour therapy for tics within 12 months, and had a Yale Global Tic Severity Scale (YGTSS) Total Tic Severity Score (TTSS) of >15, or >10 if motor or vocal tics only. Participants were recruited via 16 patient identification centres, two study sites, or online self-referral, and were randomised (1:1) by blinded outcome-assessors to receive either 10 weeks of ERP or psychoeducation (active control). The primary outcome was YGTSS-TTSS at 3 months’ post-randomisation, analysis was by intention-to-treat. The mean cost per patient for the intervention and health care costs were calculated. Registrations are ISRCTN (ISRCTN70758207) and ClinicalTrials.gov (NCT03483493). Findings: Between 8 th May 2018 and 30 th September 2019, 224 participants were enrolled; 112 to ERP and 112 to psychoeducation. The ERP intervention reduced YGTSS-TTSS by 2 . 29 points (95% CI: ‑3 . 86 to -0 . 71) compared to the psychoeducation group at 3 months, an effect that increased by 6 months post-randomisation (-2 . 64, 95% CI: -4 . 56 to -0 . 73). The average therapist time spent supporting the intervention was 2 . 5 hours. The additional cost per participant of the ERP intervention compared to psychoeducation was £159 (95% CI -£53 to £370). There were two unrelated serious adverse events, both in the psychoeducation group. Interpretation: Online-delivered, therapist-supported ERP therapy is clinically effective at reducing tics, with minimal therapist contact time. Online delivery could improve access to evidence-based treatment for tics in children and adolescents. Trial Registration: Registrations are ISRCTN (ISRCTN70758207) and ClinicalTrials.gov (NCT03483493). Funding: National Institute for Health Research, Health and Technology Assessment (HTA) Declaration of Interest: All authors have completed the ICMJE uniform disclosure from. Aside from receiving funding from NIHR to support their salaries CLH, LM, EBD, RJ, KK, BJB, CS, CM, ES, PA, TM, IS, JK, RH, MLN, AE, LRC, NK, SB, CG, EM declare no conflict of interests. CH declares he was Principal Investigator on a grant from the National Institute of Health Research (NIHR) Health Technology Assessment programme to conduct an Evidence Synthesis on the treatments for tics and Tourette syndrome in children and young people’ HTA Project:10/142/01. DM-C reports personal fees from Elsevier, personal fees from UpToDate Inc. outside the submitted work. Ethical Approval: Ethical and Health Research Authority (HRA) approval was received from North West Greater Manchester Research Ethics Committee on 23 March 2018 (ref.:18/NW/0079). The published trial protocol is available online15 and was approved by an independent trial steering committee (TSC) and data monitoring committee (DMC). Two substantial amendments were made and can be found in the appendix p1. The trial was prospectively registered with the ISRCTN (ISRCTN70758207) and ClinicalTrials.gov (NCT03483493).

BACKGROUND The Online Remote Behavioral Intervention for Tics (ORBIT) study was a multicenter randomized controlled trial of a complex intervention that consisted of a web-based behavioral intervention for children and young people with tic disorders. In the first part of a two-stage process evaluation, we conducted a mixed methods study exploring the reach, dose, and fidelity of the intervention and contextual factors influencing engagement. OBJECTIVE This study aims to explore the fidelity of delivery and contextual factors underpinning the ORBIT trial. METHODS Baseline study data and intervention usage metrics from participants in the intervention arm were used as quantitative implementation data (N=112). The experiences of being in the intervention were explored through semistructured interviews with children (n=20) and parent participants (n=20), therapists (n=4), and referring clinicians (n=6). A principal component analysis was used to create a comprehensive, composite measure of children and young people’s engagement with the intervention. Engagement factor scores reflected relative uptake as assessed by a range of usage indices, including chapters accessed, number of pages visited, and number of log-ins. The engagement factor score was used as the dependent variable in a multiple linear regression analysis with various contextual variables as independent variables to assess if there were any significant predictors of engagement. RESULTS The intervention was implemented with high fidelity, and participants deemed the intervention acceptable and satisfactory. The engagement was high, with child participants completing an average of 7.5 of 10 (SD 2.7) chapters, and 88.4% (99/112) of participants completed the minimum of the first four chapters—the predefined threshold effective dose. Compared with the total population of children with tic disorders, participants in the sample tended to have more educated parents and lived in more economically advantaged areas; however, socioeconomic factors were not related to engagement factor scores. Factors associated with higher engagement factor scores included participants enrolled at the London site versus the Nottingham site (P=.01), self-referred versus clinic referred (P=.04), higher parental engagement as evidenced by the number of parental chapters completed (n=111; ρ=0.73; PPt110=10.18; Pt110=2.95; P=.004) were the only significant independent predictors of child engagement factor scores. CONCLUSIONS Overall, the intervention had high fidelity of delivery and was evaluated positively by participants, although reach may have been constrained by the nature of the randomized controlled trial. Parental engagement and therapist time for parents were strong predictors of intervention implementation, which has important implications for designing and implementing digital therapeutic interventions in child and adolescent mental health services. INTERNATIONAL REGISTERED REPORT RR2-10.1186/s13063-019-3974-3

Pancreatic cancer prognosis has remained poor and no significant improvement has been achieved over the past two decades. A number of genetic alterations are found in pancreatic cancer with a complex genome and proteome that needs further research investigation and discovery. There is an urgent need for innovative research findings that would increase the 5-year survival rate in patients with pancreatic ductal carcinoma, which in fact has seen only small increments over the past two decades. Targeting the tumor and modifying the stroma could help improve therapy responses. Genomic medicine is useful in a fraction of patients currently; however, the newer proteomic approaches are potentially more likely to help the majority of patients in the future. Future treatments of pancreatic cancer will likely be based on the development of novel therapies per genomic and proteomic identifications of cellular/immunological processes and molecular pathways as therapeutic targets. Herein, we systematically review the newer trends in pancreatic cancer treatment with emphasis on the genetic alterations and role of immune therapeutics and targeted therapies.

Aluminum substituted nickel copper Ni0.5Cu0.5AlxFe2 − xO4 (x = 0.0, 0.2, 0.4 and 0.6) spinel ferrite nanoparticles were prepared via sol–gel auto combustion method. All the samples were annealed at 600 °C for three hours in muffle furnace. The prepared samples were characterized using X-ray diffraction, scanning electron microscopy, Fourier transform infra-red spectroscopy and Impedance Spectroscopy to investigate their structure, morphology and electrical properties. The cubic structure (FCC) with preferred orientation along (311) plane was found with crystallite size of 17–21 nm. Few diffraction peaks corresponding to the secondary phase appear due to insufficient reaction between Al3+ and Fe3+ ions. Lattice constant, unit cell volume, dislocation density, stacking fault, lattice strain and micro-strain have been studied as a function of substitution effect. The appropriate substitution is evident from reduction in lattice strain and unit cell volume resulted from significant change in lattice parameters. The real and imaginary parts of dielectric constant, complex modulus, impedance and tangent loss of prepared nanoparticles have been investigated in the frequency range from 100 Hz to 20 MHz. The hopping of charge carriers at higher frequencies would result in improved conduction mechanism for these nanomaterials. Small crystallite size and low dielectric loss of aluminum substituted nickel copper spinel ferrite nanoparticles would make them potential candidate for high storage memory devices, cancer treatment and microwave applications, respectively.