Folic acid conjugated PAMAM-modified mesoporous silica-coated superparamagnetic iron oxide nanoparticles for potential cancer therapy.

In this study, novel folate-receptor-targeted polyamidoamine (PAMAM) dendrimer functional mesoporous silica-coated magnetic nanoparticles were prepared for drug delivery agents for photodynamic therapy applications. The surface of the magnetic nanoparticles was coated with mesoporous silica (M-MSN). The M-MSN nanoparticles were functionalized with siloxane-cored PAMAM dendrons (generation 1 to 3). The surface of the M-MSN-PAMAM nanocarriers was targeted with folic acid. Indocyanine green (ICG) a near-infrared dye was loaded in the M-MSN-PAMAM nanocarriers and the photodynamic therapy efficiency of the drug-loaded nanocarriers was evaluated on MCF-7 cells. MCF-7 cells were subjected to tissue culture E-Plate that was used to generate dynamic real-time data by measuring electrical impedance across interdigitated microelectrodes on the bottom of the plate. Light source (LEDs) was designed as a system that fit 96 well-plate and cells were irradiated at 785 nm for 20 min. Also, these results were confirmed by WST-1 assay in dark and light conditions for MCF-7 cells. The results showed that in vitro application of ICG loaded M-MSN-PAMAM-FA causes apoptosis in the MCF-7 cell line.

MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.

OBJECTIVE: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). DESIGN PATIENTS: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). INTERVENTIONS: 1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. BASELINE POPULATION: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

How to design nutritional intervention trials to slow cognitive decline in apparently healthy populations and apply for efficacy claims: a statement from the International Academy on Nutrition and Aging Task Force.

Interventions are crucial as they offer simple and inexpensive public health solutions that will be useful over the long term use. A Task Force on designing trials of nutritional interventions to slow cognitive decline in older adults was held in Toulouse in September 2012. The aim of the Task Force was to bring together leading experts from academia, the food industry and regulatory agencies to determine the best trial designs that would enable us to reach our goal of maintaining or improving cognitive function in apparently healthy aging people. An associated challenge for this Task Force was to determine the type of trials required by the Public Food Agencies for assessing the impact of nutritional compounds in comparison to well established requirements for drug trials. Although the required quality of the study design, rationale and statistical analysis remains the same, the studies designed to show reduction of cognitive decline require a long duration and the objectives of this task force was to determine best design for these trials. Two specific needs were identified to support trials of nutritional interventions: 1- Risk- reduction strategies are needed to tackle the growing burden of cognitive decline that may lead to dementia, 2- Innovative study designs are needed to improve the quality of these studies.

Effect of 12 months treatment with chondroitin sulfate on cartilage volume in knee osteoarthritis patients: a randomized, double-blind, placebo-controlled pilot study using MRI.

This pilot study aimed to evaluate the correlation between clinical symptoms and cartilage volume through MRI in patients with knee osteoarthritis after 48 weeks of treatment with Structum®. Multicenter, double-blind, placebo-controlled, parallel-group study. Symptomatic knee osteoarthritis patients aged 50-75 years received either Structum® (500 mg twice daily; N = 22) or placebo (N = 21) during 48 weeks. Inclusion criteria were global pain in the target knee ≥30 mm (VAS 0-100) and radiological Kellgren-Lawrence grade 2 or 3. Clinical assessments included Lequesne index and VAS for pain on motion, at baseline, 24 and 48 weeks, and MRI at baseline and at 24 and 48 weeks. Global and compartments cartilage volume, joint cartilage abnormalities, meniscal lesions, ligaments abnormalities, synovitis, synovial effusion, osteophytes, subchondral cysts, popliteal cysts and subchondral oedema were quantified. The quantitative and qualitative reproducibility of MRI was tested by the Spearman correlation coefficient and kappa coefficients, respectively. Treatments were compared by an analysis of covariance with baseline value as covariate. Groups were comparable at baseline for demographics, disease characteristics, and cartilage volumes. A significant inter-readers correlation was seen for the assessment of cartilage volumes, number of cysts, and osteophytes (correlation coefficients from 0.951 to 0.980 within investigator and from 0.714 to 0.957). After 48 weeks, symptoms improved in both groups. The total cartilage volume increased in the Structum® group (+180 mm(3) + SD) which opposed to a loss in the placebo (-46 mm(3) + SD; NS). No statistically significant differences between groups were observed for the other MRI parameters. No correlations were evidenced between key MRI parameters changes and symptoms. The difference in the evolution of cartilage volume between the two groups could reflect a structure modifying effect of Structum®. This pilot study confirms the usefulness of quantitative and qualitative MRI as a sensitive tool to assess a structure modifying drugs in knee osteoarthritis.

Management of the use of public health pesticides in the face of the increasing burden of vector-borne diseases in the Eastern Mediterranean region.

The Eastern Mediterranean Region of the World Health Organization is facing an increasing burden of vector-borne diseases. Progress in controlling these diseases is compromised by the limited number of vector control interventions, most of which rely on the use of pesticides. Seventeen countries of the Region participated in a global survey that aimed to map and document registration and management practices for public health pesticides. This paper aims to draw the attention of policy- and decision-makers to the challenges the Region is facing in managing public health pesticides properly to control disease vectors and, based on the outcome of the survey, recommends a set of actions to guide national policy and to strengthen national capacity for the sound management and judicious use of public health pesticides.

Management of the use of public health pesticides in the face of the increasing burden of vector-borne diseases in the Eastern Mediterranean Region

The Eastern Mediterranean Region of the World Health Organization is facing an increasing burden of vector-borne diseases. Progress in controlling these diseases is compromised by the limited number of vector control interventions, most of which rely on the use of pesticides. Seventeen countries of the Region participated in a global survey that aimed to map and document registration and management practices for public health pesticides. This paper aims to draw the attention of policy- and decision-makers to the challenges the Region is facing in managing public health pesticides properly to control disease vectors and, based on the outcome of the survey, recommends a set of actions to guide national policy and to strengthen national capacity for the sound management and judicious use of public health pesticides

Implementation of integrated vector management for disease vector control in the Eastern Mediterranean: where are we and where are we going?

Integrated vector management (IVM) is an acknowledged strategy of choice for the prevention and control of vector-borne diseases. The paper describes and documents the progress countries of the World Health Organization (WHO) Eastern Mediterranean Region have made in endorsing and translating the strategy into action at the national level. These include increased political commitment; strengthened intersectoral coordination and partnership; strengthened capacity in entomology and vector control; and scaling up of vector control interventions through universal access. These efforts, however, are compromised by inappropriate institutional arrangements in some countries; weak national capacities to address management of pesticides; , development and spread of vector resistance to insecticides, including to pyrethroids; and the expansion of emerging and re-emerging vector-borne diseases. With WHO leadership and support from partners, countries continue to address these challenges head-on.

Comparative efficacy and safety of two different molecular weight (MW) hyaluronans F60027 and Hylan G-F20 in symptomatic osteoarthritis of the knee (KOA). Results of a non inferiority, prospective, randomized, controlled trial.

OBJECTIVES: To compare the efficacy and safety of a 'medium' molecular weight (MW) hyaluronan product (F60027, Structovial) with a 'high' MW (Hylan G-F20, Synvisc). METHODS: Prospective, randomised, multicentre, double-blind, active controlled, parallel-group study with a non-inferiority design. Patients with symptomatic KOA, global pain ≥ 40 mm (VAS, 0-100), Lequesne index (LFI, 0-24) score >7 and radiological Kellgren-Lawrence grade 2/3 were centrally randomised to receive F60027 or Hylan G-F20, administered via three weekly injections, with regular follow-up evaluations up to week 24 (W24). The primary outcome was LFI score change over 24 weeks. Secondary outcomes comprised pain VAS, quality of life, patient's and physician's global assessments, rescue medication consumption and OMERACT-OARSI responders rate. RESULTS: 276 patients were analysed in the full analysis dataset (FAS), 236 in the Per Protocol dataset (PP). In the main efficacy analysis (PP), the difference of the LFI score change over 24 weeks between F60027 (-4.67 (0.27)) and Hylan G-F20 (-4.54 (0.28)) was 0.132 [95%CI: -0.598, 0.861] which met the predefined non-inferiority margin. Analyses of secondary efficacy criteria showed clinically relevant improvements of all outcomes at W24 for each treatment on both PP/FAS populations. Changes of LFI score between baseline and W24 were -5.73 in the F60027 and -5.57 in the Hylan G-F20 group (PP dataset). Few local reactions were reported: 3.6% of patients in each group. CONCLUSIONS: F60027 and Hylan G-F20 were equally effective in reducing functional impairment and relieving pain in KOA patients, and well-tolerated.

Isolated itching of external auditory canal: clinicopathological study with immunohistochemical determination of antimicrobial peptides.

OBJECTIVE: This study aimed to demonstrate the histological and immunohistological features of skin biopsy specimens from patients complaining of isolated itching of the external auditory canal. MATERIALS AND METHODS: A prospective, case-control study was performed of 24 patients undergoing evaluation for contact dermatitis of the external auditory canal, and 24 controls. Skin biopsies were examined histologically by a single, blinded dermatopathologist, using light microscopy, to determine histopathological characteristics. The immunohistological presence of the antimicrobial peptides human ß-defensin-3 and LL-37 cathelicidin was also assessed. Findings for patients and controls were compared. RESULTS: There was a statistically significant difference in the degree of inflammation, comparing patients and controls (p < 0.05). There was no significant difference in the presence of spongiotic changes, comparing patients and controls (p > 0.05). Furthermore, the patients' skin biopsies did not show pronounced expression of human ß-defensin-3 or LL-37 cathelicidin. CONCLUSION: Histological and immunohistological examination of skin biopsies from cases of isolated itching of the external auditory canal did not support a diagnosis of dermatitis.

Implementation of integrated vector management for disease vector control in the Eastern Mediterranean: where are we and where are we going?

Integrated vector management [IVM] is an acknowledged strategy of choice for the prevention and control of vector-borne diseases. The paper describes and documents the progress countries of the World Health Organization [WHO] Eastern Mediterranean Region have made in endorsing and translating the strategy into action at the national level. These include increased political commitment; strengthened intersectoral coordination and partnership; strengthened capacity in entomology and vector control; and scaling up of vector control interventions through universal access. These efforts, however, are compromised by inappropriate institutional arrangements in some countries; weak national capacities to address management of pesticides; development and spread of vector resistance to insecticides, including to pyrethroids; and the expansion of emerging and re-emerging vector-borne diseases. With WHO leadership and support from partners, countries continue to address these challenges head-on

Efficacy of novaluron against Culex quinquefasciatus in small- and medium-scale trials, India.

Novaluron 10% emulsifiable concentrate (EC), an insect growth regulator (IGR), was tested against Culex quinquefasciatus immatures at 1, 5, and 10 mg active ingredient (AI)/m2 applied to cesspits, drains, and abandoned wells. The IGR produced 80-100% inhibition of adult emergence (IE) for > 1 week (10-14 days) in cesspits, 1-2 weeks in street drains, and 5-10 weeks in abandoned wells at the 3 application rates. The efficacy increased with the increasing dose in street drains and abandoned wells. The residual activity of the IGR was longer in abandoned wells compared to drains and cesspits. Based on the small-scale trial, doses of 1, 5, and 10 mg AI/m2 were used in the medium-scale trial for cesspits, abandoned wells, and street drains, respectively. The efficacy observed in medium-scale trial was similar to that in the small-scale trial. The results indicate that novaluron 10% EC can be used for larval control against Cx. quinquefisciatus at the application rate of 1 mg AI/m2 at 10-day intervals in cesspits, at 5 mg AI/m2 at 2-month intervals in abandoned wells, and at 10 mg AI/m2 applied at fortnightly intervals to drains. Even at the lowest rate of 1 mg AI/m2, the IGR prevented adult emergence for at least a week in cesspits and street drains and for a month in abandoned wells. Novaluron 10% EC could be one of the options for larval control operations in integrated vector management.

Efficacy of two formulations of the bioinsecticide spinosad against Culex quinquefasciatus in India.

Spinosad 12% suspension concentrate (SC) and 0.5% granular (G) formulations were tested against Culex quinquefasciatus immatures at 3 dosages--50, 100, and 150 mg active ingredient (AI)/m2--in cesspits, street drains, and disused wells in comparison with temephos 1% G at 1 part per million. The 2 formulations reduced the density of pupae of Cx. quinquefasciatus by 80-100% for 7-14 days in cesspits, 7-18 days in drains, and 33-69 days in disused wells at the 3 dosages tested. The 12% SC and 0.5% G formulations were equally effective in suppressing the larval and pupal populations of Cx. quinquefasciatus in all the habitats treated. At 100 mg AI/m2 in drains and cesspits, the efficacy of spinosad 0.5% G was greater than that of temephos (1% G) and that of spinosad 12% SC was comparable to that of temephos (1% G) applied to the 2 habitats. In disused wells, both the formulations lasted longer than temephos. Based on the small-scale trial, the rate of 150 mg AI/m2 of spinosad was selected for field application to cesspits and drains and 50 mg AI/m2 for application to disused wells. The efficacy observed in medium-scale trials was in agreement with that of small-scale trials. The trial showed that the 2 formulations of spinosad can be used for larval control of Cx. quinquefasciatus, at 50 mg AI/m2, applied at weekly intervals to cesspits and street drains and at monthly intervals to disused wells. At the higher dose of 150 mg AI/m2, the 2 formulations were effective in suppressing the pupal population for 2 wk in cesspits and street drains and for 2 months in disused wells.

Field evaluation of an insect growth regulator, pyriproxyfen 0.5% GR against Culex quinquefasciatus, the vector of Bancroftian filariasis in Pondicherry, India.

Pyriproxyfen, 0.5% granular formulation (GR), an insect growth regulator (IGR) was tested against Culex quinquefasciatus larvae and pupae in disused wells, cesspits and drains at the dosages of 0.1, 0.25, and 0.5kg(ai)/ha to determine the most appropriate field dosage. The IGR was found to be effective against C. quinquefasciatus larvae and pupae in all the larval habitats tested. In drains with slow moving water, application of pyriproxyfen 0.5% GR at 0.5kg(ai)/ha resulted in >80% emergence inhibition (EI) of adults for 4 weeks. At 0.1 and 0.25kg(ai)/ha, the EI was always less than 80%. In stagnant drains, the IGR yielded >80% EI for 1-week period at 0.1kg(ai)/ha. At 0.25 and 0.5kg(ai)/ha, the efficacy was 5-10 times higher. In cesspits, the EI was >80% for 6 weeks when pyriproxyfen 0.5% GR was applied at 0.1kg(ai)/ha, for 11 weeks at 0.25kg(ai)/ha and 9 weeks at 0.5kg(ai)/ha. In disused wells treated at the dosage 0.1kg(ai)/ha, there was >80% EI for 15 weeks and at 0.25 and 0.5kg(ai)/ha, the effective duration was about 1.6-1.8 times longer (24-28 weeks). Considering the quantum of IGR required and the cost and also for safety reasons, the low dosage 0.1kg(ai)/ha is recommended as the field dosage to be applied at weekly interval in stagnant drains, 6 weeks interval in cesspits and 15 weeks interval in disused wells. Since pyriproxyfen 0.5% GR has a relatively longer residual effect than the other IGRs the operational cost could be minimized. Pyriproxyfen 0.5% GR could be one of the choices in the chemical control strategy in Integrated Vector Control Programmes.

Exploiting the potential of vector control for disease prevention.

Although vector control has proven highly effective in preventing disease transmission, it is not being used to its full potential, thereby depriving disadvantaged populations of the benefits of well tried and tested methods. Following the discovery of synthetic residual insecticides in the 1940s, large-scale programmes succeeded in bringing many of the important vector-borne diseases under control. By the late 1960s, most vector-borne diseases--with the exception of malaria in Africa--were no longer considered to be of primary public health importance. The result was that control programmes lapsed, resources dwindled, and specialists in vector control disappeared from public health units. Within two decades, many important vector-borne diseases had re-emerged or spread to new areas. The time has come to restore vector control to its key role in the prevention of disease transmission, albeit with an increased emphasis on multiple measures, whether pesticide-based or involving environmental modification, and with a strengthened managerial and operational capacity. Integrated vector management provides a sound conceptual framework for deployment of cost-effective and sustainable methods of vector control. This approach allows for full consideration of the complex determinants of disease transmission, including local disease ecology, the role of human activity in increasing risks of disease transmission, and the socioeconomic conditions of affected communities.

[A descriptive analysis of naratriptan use among migraineurs in ambulatory medicine]. / Analyse descriptive des modalités d'usage du naratriptan dans la prise en charge de la migraine en médecine de ville.

The objective of this study was to provide an epidemiological description of naratriptan use in ambulatory medicine. 1695 patients were recruited by 384 primary care physicians and 111 neurologists, and followed for 12 weeks. Physicians had to document the migraine history, and to report symptoms and health care in a structured case report form. Patients were to document each episode of migraine (EM) in a diary. At baseline, 45 p.cent of the patients reported their migraine treatment as unsatisfactory. Ninety-eight percent of included patients were migraineurs according to criteria of the International Headache Society (IHS), including migrainous disorders. Ninety-two percent of naratriptan prescriptions were established in the second intention in patients with migraine, according to the IHS classification, including migrainous disorders. A total of 79 p.cent of patients had complied with the good practices for all EMs. More appropriate health education strategies should target the small group of patients who over-use naratriptan, and patients with aura. However, this study shows that naratriptan tends to be correctly prescribed by physicians, and used by patients with acute migraine.

Insecticide-treated plastic tarpaulins for control of malaria vectors in refugee camps.

Spraying of canvas tents with residual pyrethroid insecticide is an established method of malaria vector control in tented refugee camps. In recent years, plastic sheeting (polythene tarpaulins) has replaced canvas as the utilitarian shelter material for displaced populations in complex emergencies. Advances in technology enable polythene sheeting to be impregnated with pyrethroid during manufacture. The efficacy of such material against mosquitoes when erected as shelters under typical refugee camp conditions is unknown. Tests were undertaken with free-flying mosquitoes on entomological study platforms in an Afghan refugee camp to compare the insecticidal efficacy of plastic tarpaulin sprayed with deltamethrin on its inner surface (target dose 30 mg/m2), tarpaulin impregnated with deltamethrin (initially > or = 30 mg/m2) during manufacture, and a tent made from the factory impregnated tarpaulin material. Preliminary tests done in the laboratory with Anopheles stephensi Liston (Diptera: Culicidae) showed that 1-min exposure to factory-impregnated tarpaulins would give 100% mortality even after outdoor weathering in a temperate climate for 12 weeks. Outdoor platform tests with the erected materials (baited with human subjects) produced mosquito mortality rates between 86-100% for sprayed or factory-impregnated tarpaulins and tents (average approximately 40 anophelines and approximately 200 culicines/per platform/night), whereas control mortality (with untreated tarpaulin) was no more than 5%. Fewer than 20% of mosquitoes blood-fed on human subjects under either insecticide-treated or non-treated shelters. The tarpaulin shelter was a poor barrier to host-seeking mosquitoes and treatment with insecticide did not reduce the proportion blood-feeding. Even so, the deployment of insecticide-impregnated tarpaulins in refugee camps, if used by the majority of refugees, has the potential to control malaria by killing high proportions of mosquitoes and so reducing the average life expectancy of vectors (greatly reducing vectorial capacity), rather than by directly protecting refugees from mosquito bites. Mass coverage with deltamethrin-sprayed or impregnated tarpaulins or tents has strong potential for preventing malaria in displaced populations affected by conflict.