Evaluation of the residual efficacy and physical durability of five long-lasting insecticidal nets (LLINs) in Senegal.

BACKGROUND: The preventive and curative strategies of malaria are based on promoting the use of long-lasting insecticidal nets (LLINs) and treating confirmed cases with artemisinin-based combination therapy. These strategies have led to a sharp decline in the burden of malaria, which remains a significant public health problem in sub-Saharan countries. The objective of this study was to determine and compare the residual efficacy of LLINs recommended by the World Health Organization. METHODS: The study was conducted in six villages in two sites in Senegal located in the Sahelo-Sudanian area of the Thiès region, 70 km from Dakar and in Mbagame, a semi-urban zone in the Senegal River Valley. A census was conducted of all sleeping places in each household to be covered by LLINs. Five brands of LLIN were distributed, and every six months, retention rates, net use, maintenance, physical integrity, insecticide chemical content, and biological efficacy were examined for each type of LLIN. RESULTS: A total of 3012 LLINs were distributed in 1249 households in both sites, with an average coverage rate of 94% (95% CI 92.68-95.3). After 36 months, the average retention rate was 12.5% and this rate was respectively 20.5%, 15.1%, 10%, 7%, and 3% for Olyset Net®, Dawa Plus® 2.0, PermaNet® 2.0, NetProtect® and Life Net®, respectively. The proportion of LLINs with holes and the average number of holes per mosquito net increased significantly during each follow-up, with a large predominance of size 1 (small) holes for all types of LLINs distributed. During the three-year follow-up, bioassay mortality rates of a susceptible strain of insectary reared Anopheles coluzzii decreased in the following net types: in Dawa Plus® 2.0 (100% to 51.7%), PermaNet® 2.0 (96.6% to 83%), and Olyset Net® (96.6% to 33.3%). Mortality rates remained at 100% in Life Net® over the same time period. After 36 months, the average insecticide content per brand of LLIN decreased by 40.9% for Dawa Plus® 2.0, 31% for PermaNet® 2.0, 39.6% for NetProtect® and 51.9% for Olyset Net® and 40.1% for Life Net. CONCLUSIONS: Although some net types retained sufficient insecticidal activity, based on all durability parameters measured, none of the net types survived longer than 2 years.

Host-Guest Interactions between Candesartan and Its Prodrug Candesartan Cilexetil in Complex with 2-Hydroxypropyl-ß-cyclodextrin: On the Biological Potency for Angiotensin II Antagonism.

Renin-angiotensin aldosterone system inhibitors are for a long time extensively used for the treatment of cardiovascular and renal diseases. AT1 receptor blockers (ARBs or sartans) act as antihypertensive drugs by blocking the octapeptide hormone Angiotensin II to stimulate AT1 receptors. The antihypertensive drug candesartan (CAN) is the active metabolite of candesartan cilexetil (Atacand, CC). Complexes of candesartan and candesartan cilexetil with 2-hydroxylpropyl-ß-cyclodextrin (2-HP-ß-CD) were characterized using high-resolution electrospray ionization mass spectrometry and solid state 13C cross-polarization/magic angle spinning nuclear magnetic resonance (CP/MAS NMR) spectroscopy. The 13C CP/MAS results showed broad peaks especially in the aromatic region, thus confirming the strong interactions between cyclodextrin and drugs. This experimental evidence was in accordance with molecular dynamics simulations and quantum mechanical calculations. The synthesized and characterized complexes were evaluated biologically in vitro. It was shown that as a result of CAN's complexation, CAN exerts higher antagonistic activity than CC. Therefore, a formulation of CC with 2-HP-ß-CD is not indicated, while the formulation with CAN is promising and needs further investigation. This intriguing result is justified by the binding free energy calculations, which predicted efficient CC binding to 2-HP-ß-CD, and thus, the molecule's availability for release and action on the target is diminished. In contrast, CAN binding was not favored, and this may allow easy release for the drug to exert its bioactivity.

Comparing the new Ifakara Ambient Chamber Test with WHO cone and tunnel tests for bioefficacy and non-inferiority testing of insecticide-treated nets.

BACKGROUND: Insecticide-treated net (ITN) durability, measured through physical integrity and bioefficacy, must be accurately assessed in order to plan the timely replacement of worn out nets and guide procurement of longer-lasting, cost-effective nets. World Health Organization (WHO) guidance advises that new intervention class ITNs be assessed 3 years after distribution, in experimental huts. In order to obtain information on whole-net efficacy cost-effectively and with adequate replication, a new bioassay, the Ifakara Ambient Chamber Test (I-ACT), a semi-field whole net assay baited with human host, was compared to established WHO durability testing methods. METHODS: Two experiments were conducted using pyrethroid-susceptible female adult Anopheles gambiae sensu stricto comparing bioefficacy of Olyset®, PermaNet® 2.0 and NetProtect® evaluated by I-ACT and WHO cone and tunnel tests. In total, 432 nets (144/brand) were evaluated using I-ACT and cone test. Olyset® nets (132/144) that did not meet the WHO cone test threshold criteria (≥ 80% mortality or ≥ 95% knockdown) were evaluated using tunnel tests with threshold criteria of ≥ 80% mortality or ≥ 90% feeding inhibition for WHO tunnel and I-ACT. Pass rate of nets tested by WHO combined standard WHO bioassays (cone/tunnel tests) was compared to pass in I-ACT only by net brand and time after distribution. RESULTS: Overall, more nets passed WHO threshold criteria when tested with I-ACT than with standard WHO bioassays 92% vs 69%, (OR: 4.1, 95% CI 3.5-4.7, p < 0.0001). The proportion of Olyset® nets that passed differed if WHO 2005 or WHO 2013 LN testing guidelines were followed: 77% vs 71%, respectively. Based on I-ACT results, PermaNet® 2.0 and NetProtect® demonstrated superior mortality and non-inferior feeding inhibition to Olyset® over 3 years of field use in Tanzania. CONCLUSION: Ifakara Ambient Chamber Test may have use for durability studies and non-inferiority testing of new ITN products. It measures composite bioefficacy and physical integrity with both mortality and feeding inhibition endpoints, using fewer mosquitoes than standard WHO bioassays (cone and tunnel tests). The I-ACT is a high-throughput assay to evaluate ITN products that work through either contact toxicity or feeding inhibition. I-ACT allows mosquitoes to interact with a host sleeping underneath a net as encountered in the field, without risk to human participants.

Intracellular rebinding of transition-state analogues provides extended in vivo inhibition lifetimes on human purine nucleoside phosphorylase.

Purine nucleoside phosphorylase (PNP) is part of the human purine salvage pathway. Its deficiency triggers apoptosis of activated T-cells, making it a target for T-cell proliferative disorders. Transition-state analogues of PNP bind with picomolar (pm) dissociation constants. Tight-binding PNP inhibitors show exceptionally long lifetimes on the target enzyme. We solve the mechanism of the target residence time by comparing functional off-rates in vitro and in vivo We report in vitro PNP-inhibitor dissociation rates (t½) from 3 to 31 min for seven Immucillins with dissociation constants of 115 to 6 pm Treatment of human erythrocytes with DADMe-Immucillin-H (DADMe-ImmH, 22 pm) causes complete inhibition of PNP. Loss of [14C]DADMe-ImmH from erythrocytes during multiple washes is slow and biphasic, resulting from inhibitor release and rebinding to PNP catalytic sites. The slow phase gave a t½ of 84 h. Loss of [14C]DADMe-ImmH from erythrocytes in the presence of excess unlabeled DADMe-ImmH increased to a t½ of 1.6 h by preventing rebinding. Thus, in human erythrocytes, rebinding of DADMe-ImmH is 50-fold more likely than diffusional loss of the inhibitor from the erythrocyte. Humans treated with a single oral dose of DADMe-ImmH in phase 1 clinical trials exhibit regain of PNP activity with a t½ of 59 days, corresponding to the erythropoiesis rate in humans. Thus, the PNP catalytic site recapture of DADMe-ImmH is highly favored in vivo We conclude that transition-state analogues with picomolar dissociation constants exhibit long lifetimes on their targets in vivo because the probability of the target enzyme recapturing inhibitor molecules is greater than diffusional loss to the extracellular space.

Impact of the use and efficacy of long lasting insecticidal net on malaria infection during the first trimester of pregnancy - a pre-conceptional cohort study in southern Benin.

BACKGROUND: Malaria in pregnancy is prevalent in Sub-Saharan Africa. The first trimester of pregnancy is a critical period and the best preventive measure is Long Lasting Insecticidal Nets (LLIN). Unfortunately, few studies have been conducted which focuses on the usage and efficacy of LLIN on malaria prevention during the first trimester. METHODS: We assessed the use and effectiveness of LLIN in early pregnancy in Benin and its impact on malaria infection risk. We followed-up a cohort of 240 pregnant women from pre-conception to the end of the first trimester of pregnancy in Southern Benin. Parasitological, maternal and LLIN data were actively collected before, at the beginning and end of the first trimester of pregnancy. A Cox regression model was used to determine the relationship between the time to onset of the first malaria infection and the use, physical integrity, and bio-efficacy of the LLIN, adjusted for relevant covariables. RESULTS: The good use, good physical integrity and biological efficacy of LLIN were associated with a decreased risk of occurrence of the first malaria infection in early pregnancy (HRa = 0.38; (0.18-0.80); p < 0.001; HRa = 0.59; (0.29-1.19); p < 0.07; HRa = 0.97; (0.94-1.00); p < 0.04 respectively), after adjustment for other covariates. Primi/secundigravidity and malaria infection before pregnancy were associated with a risk of earlier onset of malaria infection. CONCLUSION: The classically used LLIN's indicators of possession and use may not be sufficient to characterize the true protection of pregnant women in the first trimester of pregnancy. Indicators of physical integrity and bio-efficacy should be integrated with those indicators in evaluation studies.

Feasibility of cord blood bank in high altitude Abha: preclinical impacts.

We explored the possibility of the cryo-storage of cord blood hematopoietic stem cells (CBHPSC) with respect to the quantity, quality and biologic efficacy of high altitude (HA) region Abha against sea level (SL) region. The results of the post-processed total nucleated cell count was 8.03 ± 0.31 × 107 and 8.44 ± 0.23 × 107 cells in the HA and SL regions respectively. The mean post processing viability of the nucleated cells was about 87.03 ± 1.39 (HA) and 88.33 ± 1.55% (SL) while post thaw cells were 85.61 ± 1.44 (HA) and 86.58 ± 1.61% (SL) after transient cryo-storage. The proliferation of CBHSCs after thawing were comparable between the HA and SL regions. The results of the colony forming unit (CFU) assays of CFU-E, CFU-GEMM, CFU-GM and BFU-E were comparable between HA and SL in both fresh and post thaw, while a declining trend with viability was significant. The differentiation capability of post thaw samples into adipocytes and osteocytes were comparable between HA and SL regions. Overall from the results, it can be evidenced that HA cord blood collection, processing or storage does not hinder the quality or biological efficacy of the CBHPSC.

Biological efficacy and toxic effect of emergency water disinfection process based on advanced oxidation technology.

An innovative and removable water treatment system consisted of strong electric field discharge and hydrodynamic cavitation based on advanced oxidation technologies was developed for reactive free radicals producing and waterborne pathogens eliminating in the present study. The biological efficacy and toxic effects of this advanced oxidation system were evaluated during water disinfection treatments. Bench tests were carried out with synthetic microbial-contaminated water, as well as source water in rainy season from a reservoir of Dalian city (Liaoning Province, China). Results showed that high inactivation efficiency of Escherichia coli (>5 log) could be obtained for synthetic contaminated water at a low concentration (0.5-0.7 mg L(-1)) of total oxidants in 3-10 s. The numbers of wild total bacteria (108 × 10(3) CFU mL(-1)) and total coliforms (260 × 10(2) MPN 100 mL(-1)) in source water greatly reduced to 50 and 0 CFU mL(-1) respectively after treated by the advanced oxidation system, which meet the microbiological standards of drinking water, and especially that the inactivation efficiency of total coliforms could reach 100%. Meanwhile, source water qualities were greatly improved during the disinfection processes. The values of UV254 in particular were significantly reduced (60-80%) by reactive free radicals. Moreover, the concentrations of possible disinfection by-products (formaldehyde and bromide) in treated water were lower than detection limits, indicating that there was no harmful effect on water after the treatments. These investigations are helpful for the ecotoxicological studies of advanced oxidation system in the treatments of chemical polluted water or waste water. The findings of this work suggest that the developed water treatment system is ideal in the acute phases of emergencies, which also could offer additional advantages over a wide range of applications in water pollution control.

Relative biological efficacy of methionine hydroxy analogue-free acid compared to dl-methionine in the broiler chickens.

BACKGROUND: In the broiler's diets based on corn-soya bean meal, methionine (Met) and cystine (Cys), known as sulphur amino acids (SAAs), are the first limiting indispensable amino acids because of their limited presence, which are supplemented with different synthetic sources. Evaluation of the biological effectiveness of these sources can be important in their correct replacement, especially in the starter and growth diets. OBJECTIVES: The current study was done to assess the relative biological efficacy (RBE) of liquid Met hydroxy analogue-free acid (MHA-FA) in comparison with dl-Met (dl-Met) based on broiler performance traits at different levels of digestible SAA in the 1-11 (starter) and 11-25 (grower) days of age periods. METHODS: Two experiments were developed with treatments consisting of a basal diet without Met addition that met the nutrient and energy requirements of broilers with the exception of SAAs (Met + Cys) and five increasing Met doses for both sources (dl-Met and/or MHA-FA), resulting in digestible SAA concentrations from 0.62% to 1.02% of diet in the starter period (Trial 1) and 0.59% to 0.94% of diet in the grower period (Trial 2). The multi-linear regression model and slope ratio method were employed to calculate the RBE of MHA-FA compared with dl-Met for measured variables. RESULTS: In both experiments, the results obtained during the starter and grower periods with the different Met supplementations show significant growth responses to digestible SAAs levels. By increasing dietary dl-Met and/or MHA-FA levels, the growth performance traits and immune responses were improved (quadratic; p < 0.05). The RBE of MHA-FA compared to dl-Met on an equimolar basis was estimated 66%-89% (59%-79% on a weight-to-weight basis). CONCLUSIONS: It is concluded that the RBE of MHA-FA in comparison with dl-Met depends on broiler chicken age and what attribute is being evaluated.

Design of novel isoxazole derivatives as tubulin inhibitors using computer-aided techniques: QSAR modeling, in silico ADMETox, molecular docking, molecular dynamics, biological efficacy, and retrosynthesis.

In the current work, computational methods were used to investigate new isoxazole derivatives that could be used as tubulin inhibitors. The study aims to develop a reliable quantitative structure-activity relationship (QSAR) model, following the criteria set by Golbraikh, Tropsha, and Roy. As a result, seven candidate compounds were developed, all having higher activity than the well-established anticancer agent Cisplatin (Cisp). According to the ADMETox in silico test, the candidates Pr4, Pr5, and P6 can be toxic. As a result, we have chosen to focus our study on compounds Pr1, Pr2, and Pr3. Molecular docking analysis revealed that drug candidate Pr2 exhibits the highest stability within the oxidized quinone reductase 2 (PDB ID: 4zvm), target receptor (ΔG(Pr2) = ΔG(Pr3) = -10.4 < ΔG(Pr1) = -10.0 < ΔG(Cisp) = -7.3 kcal/mol). This finding aligns with the activity predictions made by the QSAR model. Furthermore, molecular dynamics simulations of the Pr2-4zvm complex over 100 ns confirm the ligand's robust stability within the receptor's active site, supporting the results obtained from molecular docking and the QSAR model predictions. The CaverDock software was utilized to identify the tunnels likely to be followed by ligands moving from the active site to the receptor surface. This analysis also helped in determining the biological efficacy of the target compounds. The results indicated that the Pr2 compound is more effective than the others. Finally, the computer-assisted retrosynthesis process of two high confidence sequences was used to synthesize drug candidates.Communicated by Ramaswamy H. Sarma.

3D-QSAR methods were used to design eight new compounds and anti-tubulin agents.3D-QSAR models were validated by Golbraikh­Tropsha and Roy methods.The toxicity and pharmacokinetics of the proposed compounds were identified by the Lipinski rule of five, Veber rules, and ADMETox.Pr2 and Pr3 had a reasonable affinity to the receptor protein (ID PDB: 4zvm) based on molecular docking, reactivity indices, and molecular dynamics simulation.Metadynamics was used to study ligand transport in the receptor (ID PDB:3zvm).

Thirty-minute test to detect insecticide resistance under field conditions: the case of the Asian citrus psyllid.

BACKGROUND: Diaphorina citri Kuwayama is one of the most destructive citrus pests worldwide. It is controlled mainly through applications of conventional insecticides. Methodologies used to estimate resistance to insecticides do not correlate with field efficacy, and do not provide timely and reliable information to make decisions at a site where spraying is needed. The use of diagnostic doses with 30-min exposure is proposed for estimating the resistance of D. citri to imidacloprid, spinosad, malathion and chlorpyrifos at the orchard level. RESULTS: Under laboratory conditions, we estimated the lowest doses that caused 100% mortality within 30 min of exposure (diagnostic dose) in a susceptible D. citri colony. The diagnostic doses for imidacloprid, spinosad, malathion and chlorpyrifos were 7.4, 4.2, 1.0 and 5.5 mg a.i. L-1 , respectively. Under field conditions, we applied the diagnostic doses to D. citri feeding on Citrus aurantifolia Swingle at five localities in Michoacan state, Mexico (Nueva Italia, Santo Domingo, El Varal, Gambara and El Ceñidor). Additionally, the field efficacy of these insecticides against these populations was evaluated. A significant correlation between field efficacy and mortality was observed with the diagnostic doses for imidacloprid, malathion and chlorpyrifos (R2 ≥ 0.93). The correlation for spinosad could not be estimated because the mortality caused by the diagnostic dose and its field efficacy at all study sites was consistently >98%. CONCLUSIONS: Field efficacy and resistance were estimated based on the field diagnostic doses with 30-min exposure for all tested insecticides. Consequently, growers and pest management technicians can estimate the performance of the evaluated insecticides at the orchard level and before insecticide application. © 2023 Society of Chemical Industry.

Antifungal Activity of Industrial Bacillus Strains against Mycogone perniciosa, the Causative Agent of Wet Bubble Disease in White Button Mushrooms.

White button mushrooms yield instability in artificial cultivation, often caused by crop diseases. The main disease is wet bubble disease. The appearance of its causative agent, M. perniciosa, may lead to total yield loss. The microbiocontrol of M. perniciosa is focused on casing soil antagonist use. Since no industrial producer strains of polyfunctional biologics have been used in previous studies, our research goal was to characterize the effect of B. subtilis B-10 and M-22 on a mycopathogen and reveal its control possibilities. The reason for B. subtilis B-10 and M-22 use in mycopathogen control has been revealed by interactions between producer strains and the studying of M. perniciosa. The suppression of M. perniciosa development by producer strains was established, indicating a prolonged B-10 and M-22 effect on the mycopathogen. High biological efficacy in both strains at the early stages of mycopathogen development upon introducing them into the wells and spraying was shown: B-10-50.9-99.6% and M-22-57.5-99.2%, respectively (p ≤ 0.05). Significant differences between producer strains were not revealed, although during the first day of exposure to developed M. perniciosa colonies, M-22 showed greater activity. The high efficiency of preventive treatment when producer strains completely suppressed mycoparasite development permits us to recommend them both for introducing when preparing casing for M. perniciosa control.

Recent Advancements in the Discovery of MDM2/MDM2-p53 Interaction Inhibitors for the Treatment of Cancer.

Discovery of MDM2 and MDM2-p53 interaction inhibitors changed the direction of anticancer research as it is involved in about 50% of cancer cases globally. Not only the inhibition of MDM2 but also its interaction with p53 proved to be an effective strategy in anticancer drug design and development. Various molecules of natural as well as synthetic origin have been reported to possess excellent MDM2 inhibitory potential. The present review discusses the pathophysiology of the MDM2-p53 interaction loop and MDM2/MDM2-p53 interaction inhibitors from literature covering recent patents. Focus has also been put on characteristic features of the active site of the target and its desired interactions with the currently FDA-approved inhibitor. The designing approach of previously reported MDM2/MDM2-p53 interaction inhibitors, their SAR studies, in silico studies, and the biological efficacy of various inhibitors from natural as well as synthetic origins are also elaborated. An attempt is made to cover recently patented MDM2/MDM2- p53 interaction inhibitors.

Pneumatic spray delivery-based solid set canopy delivery system for oblique banded leaf roller and codling moth control in a high-density modern apple orchard.

BACKGROUND: Pneumatic spray delivery (PSD)-based solid set canopy delivery systems (SSCDS) have demonstrated comparable spray deposition and reduced off-target drift compared with axial-fan airblast sprayers in high-density apple orchards. An important next step is to quantify whether PSD-based SSCDS can provide effective pest management. This study evaluated the biological efficacy of this fixed spray system variant and compared it with that of an axial-fan airblast sprayer. Partial field trials were conducted in a commercial apple orchard (cv. Jazz) trained in tall spindle architecture. Insecticides were applied at a rate of 935 L ha-1 (100 gallons per acre) for both application systems. Twenty-four hours after spraying, leaves and fruits were collected to prepare the laboratory bioassays enabling evaluation of efficacy against obliquebanded leafroller (OBLR) and codling moth (CM). RESULTS: OBLR mortality for SSCDS, airblast sprayer and untreated control treatments after 24 h of larval exposure was 91%, 98% and 4%, respectively and increased to 98%, 100% and 19% after 48 h. First-instar CM leaf bioassay mortality was 100% for SSCDS and airblast sprayer treatment, and 13% for the untreated control at 24 h post exposure. Larval CM mortality on fruit was 100% for SSCDS and airblast sprayer treatments, and 33% on the untreated control. CONCLUSIONS: Insecticides applied using SSCDS and an airblast sprayer had comparable larval mortality in all three assays, significantly higher than the untreated controls. These results suggest that PSD-based SSCDS may provide a viable alternative to axial-fan airblast sprayers in high-density apple orchards. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Development of a rapid methodology for biological efficacy assessment in banana plantations: application to reduced dosages of contact fungicide for Black Leaf Streak Disease (BLSD) control.

BACKGROUND: Black sigatoka is the main disease of banana crop production and is controlled by using either systemic or contact fungicides through spray applications. Biological efficacy is typically assessed on a whole cropping cycle with a natural infestation and periodic spray applications. Developing a faster methodology for assessment of the biological efficacy of a contact fungicide offers promising perspectives for testing current and new fungicides or application techniques. RESULTS: The methodology is based on the time of occurrence of the first BLSD symptoms. An artificial infestation protocol was optimized by multiplying the infestation spots and by covering the infested plants. Biological efficacy tests were based on a single spray application after infestation combining three mancozeb dose reductions and two nozzle types. Results demonstrated that a 50% reduction in the mancozeb rated dosage gave significant efficacy independently of the nozzle type, with a reduction of the number of lesions of up to 55% compared with control plants. CONCLUSIONS: The described method provides rapid and significant infestation. Further comparison of spray settings and fungicide doses was possible. This methodology will be tested at the plantation scale over a longer period covering the whole crop cycle. © 2018 Society of Chemical Industry.

Chemical modifications of insulin: Finding a compromise between stability and pharmaceutical performance.

Insulin, a key peptide hormone that conjointly with its receptor regulates blood glucose levels, is used as the major means to treat diabetes. This therapeutic hormone may undergo different chemical modifications during industrial processes, pharmaceutical formulation, and through its endogenous storage in the pancreatic ß-cells. Insulin is highly sensitive to the environmental stresses and easily undergoes structural changes, being also able to unfold and aggregate. Even small changes altering the structural integrity of insulin may have important impact on the biological efficacy in relation to the physiological and pharmacological activities of this hormone. The chemical modifications of insulin may occur either randomly or based on the well-planned strategies to enhance its pharmaceutical properties. A plethora of studies have attempted to answer the fundamental questions of how chemical modifications and which environmental conditions may have either destructive effects or improve structural stability and pharmaceutical performance of insulin. The aim of this review is to highlight the impact of different modifications on structure, stability, biological activity, and pharmaceutical properties of insulin.

Dosimetry and Radiobiology of Alpha-Particle Emitting Radionuclides.

BACKGROUND: Radiopharmaceutical therapy is a cancer treatment modality by which radiation is delivered directly to targeted tumor cells or to their microenvironment. This makes it possible to deliver highly potent alpha-particle radiation. The short-range and highly potent nature of alpha-particles require a dosimetry methodology that considers microscale distributions of the alpha-emitting agent. The high energy deposition density along an alpha-particle track causes a spectrum of DNA lesions. The majority of these are irreparable DNA double-stranded breaks. Accordingly the biologic effects of alpha- particles are largely impervious to the adaptive and resistance mechanism that renders other therapeutics ineffectual. OBJECTIVES: In this review, the radiobiology and dosimetry of alpha-particle emitting radionuclides as related to their use in radiopharmaceutical therapy, are presented. CONCLUSION: Alpha-particle emitter radiopharmaceutical therapy is distinguished from other treatment modalities. Its safe clinical use requires an understanding of its unique dosimetry and radiobiology.

Preparation and characterization of indole-3-butyric acid nanospheres for improving its stability and utilization.

Indole-3-butyric acid (IBA) is an efficient plant growth regulator for promoting germination and the formation of rooting of various plants. Since it is unstable and presents the low utilization ratio, there is a compelling need to design an environmentally friendly formulation for IBA, which can reduce the loss of degradation and improve its utilization. Nano-sized controlled-release formulations can provide better durability and penetrate through the plant epidermis to efficiently deliver the agrochemicals to the target tissues. In this work, a kind of novel nano controlled-release formulation was prepared by conjugating the IBA and 3-glycidoxypropyltrimethoxysilane (GPTMS) through a covalent cross-linking reaction, and subsequently hydrolyzation and polycondensation with tetraethoxysilane. The resulting nanospheres were characterized by Fourier transform infrared spectroscopy, ultraviolet spectrophotometry, scanning electron microscope, and thermal gravity analysis. The results showed that the obtained nanospheres had a remarkable loading efficiency of IBA (about 43% w/w). The formation of covalent between IBA and GPTMS enabled the nanospheres with a good chemical stability that could protect against photo-degradation effectively. The released rate of the IBA from nanospheres was related to the temperature, pH value. With increased temperature as well as acidity and alkality, the release of the IBA was sped up. The IBA could also be released effectively from IBA-silica nanospheres by esterase, and the sustainable release characteristics of IBA-silica nanospheres were in conformity with the Ritger and Peppas equation. The IBA-silica nanospheres displayed excellent dual stimuli-responsive properties under esterase and weak acid conditions, and could obviously promote the growth of root and bud of pea. Thus, the IBA silica nanospheres prepared by covalent cross-linking reaction have a good potential application as a controlled-release formulation and environmentally-friendly plant growth regulator.

[Evaluation of Physical Integrity and Biological Efficacy of Two Types of LLINs Aged 5 to 36 Months Sampled in 11 Districts of Senegal]. / Évaluation de l'état physique et de l'efficacité biologique de deux types de moustiquaires imprégnées à longue durée d'action utilisés depuis 5 à 36 mois et collectés dans 11 districts du Sénégal.

The long-lasting insecticidal nets (LLINs) have been promulgated to compensate the low re-impregnation rate of conventional mosquito nets. Today, the cornerstone of the fight against malaria vectors is based on a large distribution of these LLINs for universal coverage. Despite this promotion, the question of their effective life in operational conditions remains unresolved. Between September and October 2013, a survey was conducted in 11 districts of Senegal where LLINs were sampled and routed to the laboratory for assessing their physical integrity and biological effectiveness. A total of 207 LLINs that were sampled in the 11 districts have been monitored during this study. Our results showed that Olyset® Net and PermaNet® 2.0 are the most represented brands in the districts. These two major brands have a good biological efficiency providing a high rate of knockdown despite their failing physical integrity.

Les moustiquaires imprégnées à longue durée d'action (MILDA) ont été promues pour pallier le faible taux de réimprégnation des moustiquaires conventionnelles. Aujourd'hui, la pierre angulaire de la lutte antivectorielle repose sur une forte distribution de ces MILDA pour une couverture universelle. En dépit de cette promotion, la question de leur durée de vie effective en conditions opérationnelles reste toujours posée. Entre septembre et octobre 2013, une enquête a été menée dans 11 districts du Sénégal. Des MILDA y ont été échantillonnées et acheminées au laboratoire pour évaluer leur intégrité physique et leur efficacité biologique. Au total, 207 MILDA ont été collectées dans les 11 districts suivis au cours de cette étude. Nos résultats ont montré que les deux marques majoritairement distribuées présentaient une bonne efficacité biologique, car induisant un taux élevé de knock-down malgré leur état détérioré.

Strontium-doped calcium polyphosphate/ultrahigh molecular weight polyethylene composites: A new class of artificial joint components with enhanced biological efficacy to aseptic loosening.

To enhance implant stability and prolong the service life of artificial joint component, a new approach was proposed to improve the wear resistance of artificial joint component and endow artificial joint component with the biological efficacy of resistance to aseptic loosening. Strontium calcium polyphosphate (SCPP) were interfused in ultrahigh molecular weight polyethylene (UHMWPE) by a combination of liquid nitrogen ball-milling and flat-panel curing process to prepare the SCPP/UHMWPE composites. The micro-structure, mechanical characterization, tribological characterization and bioactivities of various SCPP/UHMWPE composites were investigated. The results suggested that this method could statistically improve the wear resistance of UHMWPE resulting from a good SCPP particle dispersion. Moreover, it is also observed that the SCPP/UHMWPE composites-wear particles could promote the production of OPG by osteoblasts and decrease the production of RANKL by osteoblasts, and then increase the OPG/RANKL ratio. This indicated that the SCPP/UHMWPE composites had potential efficacy to prevent and treat aseptic loosening. Above all, the SCPP/UHMWPE composites with a suitable SCPP content would be the promising materials for fabricating artificial joint component with ability to resist aseptic loosening.

Nonparametric inference for assessing treatment efficacy in randomized clinical trials with a time-to-event outcome and all-or-none compliance.

To evaluate the biological efficacy of a treatment in a randomized clinical trial, one needs to compare patients in the treatment arm who actually received treatment with the subgroup of patients in the control arm who would have received treatment had they been randomized into the treatment arm. In practice, subgroup membership in the control arm is usually unobservable. This paper develops a nonparametric inference procedure to compare subgroup probabilities with right-censored time-to-event data and unobservable subgroup membership in the control arm. We also present a procedure to estimate the onset and duration of treatment effect. The performance of our method is evaluated by simulation. An illustration is given using a randomized clinical trial for melanoma.