Behavioural and Emotional Problems in Children and Educational Outcomes: A Dynamic Panel Data Analysis

This study investigates the effects of behavioural and emotional problems in children on their educational outcomes using data from the Longitudinal Survey of Australian Children (LSAC). We contribute to the extant literature using a dynamic specification to test the hypothesis of knowledge accumulation. Further, we apply the system generalised method of moments (GMM) estimator to minimise biases due to unobserved factors. We find that mental disorders in children has a negative effect on the National Assessment Program—Literacy and Numeracy (NAPLAN) test scores. Among all mental disorders, having emotional problems is found to be the most influential with one standard deviation (SD) increase in emotional problems being associated with 0.05 SD reduction in NAPLAN reading, writing and spelling; 0.04 SD reduction in matrix reasoning and grammar; and 0.03 SD reduction in NAPLAN numeracy.     

Patellar Rebar Augmentation in Revision Total Knee Arthroplasty

BackgroundIn revision total knee arthroplasty, osteolysis, mechanical abrasion, and infection may leave patellar bone stock severely attenuated with cavitary and/or segmental rim deficiencies that compromise fixation of patellar implant pegs. The purpose of this study was to retrospectively review the use of cortical “rebar” screws to augment cement fixation in revision patelloplasty.MethodsFrom 2006 to 2018, dorsal patellar rebar technique was used for patellar reconstruction in 128 of 1037 revision total knee arthroplasty cases (12.3%). Follow-up was achieved with serial radiographs and prospective comparison of Knee Society Scores (KSSs) for clinical outcome. Complications and implant failures requiring reoperation or modified rehabilitation were also assessed.ResultsOf the 128 patellar revisions performed using the rebar technique, 69 patients were women and 59 patients were men. The average age of the group was 69.5 years (range, 32-83 years). The mean follow-up of the cohort was 37 months (range, 13-109 months). The most common causes for revision were kinematic conflict, periprosthetic joint infection, and aseptic loosening. The median number of rebar screws used was 5 (range, 1-13). Preoperative KSSs for the study cohort averaged 50 (range, 0-90) At latest follow-up, mean KSS was 85 (range, 54-100). There were 4 patellar-related complications (3.1%) with no implant failures at study conclusion. Retrieval analysis revealed rigid fixation of the reconstructed patellar component in all cases.ConclusionsPatellar rebar screw augmentation is a useful technique when there are significant cavitary deficiencies and limited segmental rim deficiencies. This technique allows the surgeon to extend indications for patellar revision arthroplasty.     

Effect of alprazolam on anxiety and cardiomyopathy induced by doxorubicin in mice

Anxiety following heart failure (HF) and/or myocardial infarction (MI) can impede recovery and constitute a major risk factor for further cardiac events. The present study was aimed to evaluate anxiety following doxorubicin (DOX)-induced cardiomyopathy, a rodent model for HF, in mice. Furthermore, the study investigated the effect of alprazolam on anxiety and cardiomyopathy in this model. The study was carried out in Swiss albino mice. DOX was used at a dose of 10 mg/kg i.v. Alprazolam was administered at doses of 0.5, 1 and 2 mg/kg po for 7 days' pre- and 7 days' post-DOX. Anxiety was measured on day 8 and on day 14 using elevated plus maze and Vogel's conflict test. On 14th day, serum lactate dehydrogenase (LDH) was estimated. The mice were then killed and hearts were dissected out for estimation of thiobarbituric acid reactive substance and Transmission Electron Microscopy (TEM) studies. Our results showed that DOX administration induced cardiomyopathy in mice. This was evidenced by an increased serum LDH and tissue malondialdehyde (MDA) and was confirmed by TEM studies. Alprazolam treatment for 14 days dose dependently reversed DOX-induced increase in LDH and MDA as well as the morphological alterations induced by DOX in TEM studies. Furthermore, alprazolam also reversed the anxiety-like effects induced by DOX in both the tests for anxiety. Thus, alprazolam appears to be a good candidate for alleviating anxiety in patients following MI or HF.     

Effect of acute exercise on endothelial progenitor cells in patients with peripheral arterial disease

To determine whether exercise increases endothelial progenitor cells (EPCs) in patients with peripheral vascular disease, we developed a multi-parameter flow cytometry assay to rigorously assess EPCs and mature endothelial cells (ECs) in control subjects and patients with peripheral artery disease (PAD) subjected to graded exercise. Blood was collected from young healthy subjects (n = 9, mean age 33 years), older healthy subjects (n = 13, mean age 66 years), and older subjects with PAD (n = 15, mean age 69 years) before and 10 minutes after exercise. White blood cells were isolated and stained with a five-color antibody panel: FITC-anti-CD31, PE-anti-CD146, PE-anti-CD133, PerCP-Cy5.5-anti-CD3,-CD19,-CD33, PE-Cy7-anti-CD34, and APC-anti-VEGF-R2. Viability was assessed by propidium iodide exclusion. Viable, low, side scatter singlets that were CD3-, 19-, and 33-negative were counted. While baseline levels of EPCs and ECs were similar among all subjects, young healthy subjects demonstrated significantly greater (p < 0.05) levels of progenitor cells (PCs) than older healthy and PAD subjects. Levels of EPCs and ECs tended to increase in all subjects after exercise; however, increases in PCs were only observed in young healthy and PAD subjects. Further, trends in the magnitude of change of subsets with exercise were most similar between young and PAD subjects. Our findings suggest that aging may reduce baseline circulating levels of PCs, but not EPCs or ECs, and that exercise-induced mobilization of subsets may differ depending on age and presence of PAD.     

Flow cytometric measurement of circulating endothelial cells: the effect of age and peripheral arterial disease on baseline levels of mature and progenitor populations

BACKGROUND: Age and cardiovascular disease status appear to alter numbers and function of circulating endothelial progenitor cells (EPCs). Despite no universal phenotypic definition, numerous studies have implicated progenitors with apparent endothelial potential in local responses to vascular injury and with cardiovascular disease in general. To further define the role of this lineage in peripheral artery disease (PAD), we developed a multiparameter flow cytometry assay to analyze multiple phenotypic definitions of progenitor cells (PCs), EPCs, and mature endothelial cells (ECs) and evaluate effects of age and PAD on baseline levels of each subset. METHODS: Blood was collected from young healthy subjects (N = 9, mean age 33 +/- 8 years), older healthy subjects (N = 13, mean age 66 +/- 8 years), and older subjects with PAD (N = 15, mean age 69 +/- 8 years). After ammonium chloride lysis, cells were stained and analyzed on a Becton-Dickinson LSR II with a 5-color antibody panel: FITC-anti-CD31, PE-anti-CD146, PE-anti-CD133, PerCP-Cy5.5-anti-CD3,-CD19,-CD33 (lineage panel), PE-Cy7-anti-CD34, and APC-anti-VEGF-R2. Viability was assessed by propidium iodide exclusion, and only viable, low to medium side scatter lineage-negative singlets were analyzed. In some studies, cells were sorted for morphological studies. Subsets were defined as indicated later. RESULTS: Our results, using a comprehensive flow cytometric panel, indicate that CD133+, CD34+, and CD133+/CD34+ PCs are elevated in younger healthy individuals compared to older individuals, both healthy and with PAD. However, the number of EPCs and mature ECs did not significantly differ among the three groups. Assessment of endothelial colony forming units and dual acLDL-lectin staining supported the flow cytometric findings. CONCLUSIONS: We describe a comprehensive flow cytometric method to detect circulating mature and progenitor endothelial populations confirmed by conventional morphological and functional assays. Our findings suggest that aging may influence circulating levels of PCs, but not EPCs or ECs; PAD had no effect on baseline levels of any populations investigated. This study provides the basis for evaluating the potential effects of acute stress and therapeutic intervention on circulating progenitor and endothelial populations as a biomarker for cardiovascular status.     

Randomised controlled trial of a lay-led self-management programme for Bangladeshi patients with chronic disease

BACKGROUND: Reducing the impact of chronic disease in minority ethnic groups is an important public health challenge. Lay-led education may overcome cultural and language barriers that limit the effectiveness of professionally-led programmes. We report the first randomised trial of a lay-led self-management programme - the Chronic Disease Self-Management Programme (CDSMP) (Expert Patient Programme) - in a south Asian group. AIM: To determine the effectiveness of a culturally-adapted lay-led self-management programme for Bangladeshi adults with chronic disease. DESIGN OF STUDY: Randomised controlled trial. SETTING: Tower Hamlets, east London. METHOD: We recruited Bangladeshi adults with diabetes, cardiovascular disease, respiratory disease or arthritis from general practices and randomised them to the CDSMP or waiting-list control. Self-efficacy (primary outcome), self-management behaviour, communication with clinician, depression scores, and healthcare use were assessed by blinded interviewer-administered questionnaires in Sylheti before randomisation and 4 months later. RESULTS: Of the 1363 people invited, 476 (34%) agreed to take part and 92% (439/476) of participants were followed up. The programme improved self-efficacy (difference: 0.67, 95% confidence interval [CI] = 0.08 to 1.25) and self-management behaviour (0.53; 95% CI = 0.01 to 1.06). In the 51% (121/238) of intervention participants attending three or more of the 6-weekly education sessions the programme led to greater improvements in self-efficacy (1.47; 95% CI = 0.50 to 1.82) and self-management behaviour (1.16; 95% CI = 0.50 to 1.82), and reduced HADS depression scores (0.64; 95% CI = 0.07 to 1.22). Communication and healthcare use were not significantly different between groups. The programme cost pound123 (181) per participant. CONCLUSION: A culturally-adapted CDSMP improves self-efficacy and self-care behaviour in Bangladeshi patients with chronic disease. Effects on health status were marginal. Benefits were limited by moderate uptake and attendance.     

A chemotherapeutic approach targeting the acidic tumor microenvironment: combination of a proton pump inhibitor and paclitaxel for statistically optimized nanotherapeutics

Paclitaxel (PTX) is a major chemotherapeutic drug that is effective against a wide variety of cancers, particularly breast, ovarian and lung cancer. For a weakly basic chemotherapeutic drug such as PTX, the development of the acidic tumor microenvironment (Warburg effect) has a remarkable impact on therapeutic resistance. The present approach takes advantage of the acidic tumor microenvironment by incorporating lansoprazole (LAN), a proton pump inhibitor (PPI), with PTX as a potent therapeutic combination that is capable of reversing PTX resistance. To deliver optimal amounts of the drugs to neoplastic cells, a nano drug delivery system was selected. To design the nanoformulation process in a limited framework, typical formulation parameters were optimized and validated by the application of response surface methodology (RSM) using Box–Behnken design (BBD). On the basis of critical quality aspects, the experimental design helped to determine the optimal particle size (243.7 nm), zeta potential (−9.14 mV) and encapsulation efficiencies (88.91% and 80.35% for PTX and LAN respectively). The optimized formulation (PTX–LAN–PLGA-NPs) exhibited sustained in vitro release profiles over 384 hours for both the encapsulated drugs. The Korsmeyer–Peppas model was found to be the best fitted model for the release kinetics, where the release mechanism follows Fickian diffusion. In in vitro anti-tumor efficacy experiments using Michigan Cancer Foundation-7 (MCF-7) breast cancer cells, the PTX–LAN–PLGA-NPs exhibited a steep decrease in cell viability compared to the pure drugs. Taken together, the results strongly support that incorporation of PTX and LAN in nanoparticles (NPs) is a promising approach for cancer chemotherapy.

Development of statistically optimized, paclitaxel–lansoprazole, dual drug loaded PLGA nanoparticles as a promising tumor acidic microenvironment targeted chemotherapeutic approach.     

Effect of physiochemical variables on phase solubility and dissolution behavior of indomethacin solid dispersion system

To study the influence of temperature and pH on solubility and dissolution behavior of indomethacin solid dispersions were prepared using several classes of hydrophilic carriers. Investigations on dissolution of indomethacin in binary system are reported earlier. However the phase solubility and dissolution behavior at different pH and temperature left void. The present investigation includes: phase solubility study at various pH; preparation of solid dispersion by solvent evaporation, melting and kneading method; characterization of various blends by dissolution study, and solid state studies to ensure interaction of drug with carrier. The binding between drug and carriers (PVP K30, βCD and PEG) was explained by thermodynamic parameters as calculated from phase solubility study. Indomethacin in association with PVP K30 showed very high apparent binding constant (Ka) and Gibb’s free energy change (?G) in comparison to other blends. The ternary system (drug:βCD:PVP K30, 1:5:1) showed better dissolution of about 80.97 and 99 % at pH 7.2 after 5 and 30 min respectively. At higher proportion of carrier (1:9) in binary solid dispersion of drug and PVP K30, drug dissolution was 96.23 and 97.85 % after 5 and 30 min respectively. This raised solubility of indomethacin would be helpful in designing a dosage form.