Development of a RP-HPLC method for evaluation of in vitro permeability of voriconazole in the presence of enhancers through rat skin

AbstractAn isocratic RP-HPLC–UV method for the analysis of voriconazole in skin diffusate samples has been developed and validated. Experimental design was employed to optimize the method. The method was validated as per ICH guidelines. Linearity was observed over the concentration range of 2–100μgmL−1 (r2=0.999). Limits of detection and quantification were 0.6 and 2μgmL−1, respectively. Intra-day and inter-day precision (% RSD) was within the ICH limits (⩽2%). The method was successfully used to analyze skin diffusate samples, and the effectiveness of different permeation enhancers was compared with respect to flux and permeability coefficient

Light traps fail to estimate reliable malaria mosquito biting rates on Bioko Island, Equatorial Guinea

BACKGROUND: The human biting rate (HBR), an important parameter for assessing malaria transmission and evaluating vector control interventions, is commonly estimated by human landing collections (HLC). Although intense efforts have been made to find alternative non-exposure mosquito collection methods, HLC remains the standard for providing reliable and consistent HBRs. The aim of this study was to assess the relationship between human landing and light trap collections (LTC), in an attempt to estimate operationally feasible conversion factors between the two. The study was conducted as part of the operational research component of the Bioko Island Malaria Control Project (BIMCP), Equatorial Guinea. METHODS: Malaria mosquitoes were collected indoors and outdoors by HLCs and LTCs in three villages on Bioko Island, Equatorial Guinea during five bimonthly collections in 2009. Indoor light traps were suspended adjacent to occupied long-lasting, insecticide-treated bed nets. Outdoor light traps were placed close to the outer wall under the roof of the collection house. Collected specimens were subjected to DNA extraction and diagnostic PCR to identify species within the Anopheles gambiae complex. Data were analysed by simple regression of log-transformed values and by Bayesian regression analysis. RESULTS: There was a poor correlation between the two collection methods. Results varied by location, venue, month, house, but also by the statistical method used. The more robust Bayesian analyses indicated non-linear relationships and relative sampling efficiencies being density dependent for the indoor collections, implying that straight-forward and simple conversion factors could not be calculated for any of the locations. Outdoor LTC:HLC relationships were weak, but could be estimated at 0.10 and 0.07 for each of two locations. CONCLUSIONS: Light trap collections in combination with bed nets are not recommended as a reliable method to assess human biting rates on Bioko Island. Different statistical analyses methods give variable and inconsistent results. Substantial variation in collection methods prevents the determination of reliable and operationally feasible conversion factors for both indoor and outdoor data. Until improved mosquito collection methods are developed that can provide reliable and unbiased HBR estimates, HLCs should continue to serve as the reference method for HBR estimation

Trends in matriculation from neurological surgery training programs into academic versus private practice

OBJECTIVE: A career in academic neurosurgery is an arduous endeavor. Specific factors influencing physician practice preferences remain unclear. This study analyzes data from the American Association of Neurological Surgeons membership identifying the impact of several demographic and educational characteristics influencing neurosurgical career choices centered on academia, private practice, or a combination in the United States. METHODS: A list of all current neurosurgeons was obtained from the American Association of Neurological Surgeons membership, and information on physician characteristics was collected via internet searches and institutional databases. The practice type of all neurosurgeons considered in this study were categorized as follows: private practice, academic, or a combination of private practice and academic, termed privademic. These data were subsequently correlated to race, gender, current age, training at a top 40 National Institutes of Health-funded medical school or residency program, and current practice. RESULTS: The median age of private practice and academic neurosurgeons was 58.18 and 53.61 years, respectively (P \u3c 0.001). Age was significantly associated with practicing in an academic setting (odds ratio 0.96), with younger neurosurgeons pursuing careers in academia. Data indicated a positive and statistically significant contribution of female gender (P \u3c 0.001) and training at a top-40 National Institutes of Health-funded institution to practicing in an academic setting (P \u3c 0.01). CONCLUSIONS: Neurosurgery as a field has grown significantly over the past century. The authors recommend that future efforts seek to diversify the neurosurgical workforce by considering practice setting, demographic characteristics, and educational background

Increasing outdoor host-seeking in Anopheles gambiae over 6 years of vector control on Bioko Island.

BACKGROUND: Vector control through indoor residual spraying (IRS) has been employed on Bioko Island, Equatorial Guinea, under the Bioko Island Malaria Control Project (BIMCP) since 2004. This study analyses the change in mosquito abundance, species composition and outdoor host-seeking proportions from 2009 to 2014, after 11 years of vector control on Bioko Island. METHODS: All-night indoor and outdoor human landing catches were performed monthly in the Bioko Island villages of Mongola, Arena Blanca, Biabia and Balboa from 2009 to 2014. Collected mosquitoes were morphologically identified and a subset of Anopheles gambiae sensu lato (s.l.) were later identified molecularly to their sibling species. Mosquito collection rates, species composition and indoor/outdoor host-seeking sites were analysed using generalized linear mixed models to assess changes in mosquito abundance and behaviour. RESULTS: The overall mosquito collection rate declined in each of the four Bioko Island villages. Anopheles coluzzii and Anopheles melas comprised the An. gambiae s.l. mosquito vector population, with a range of species proportions across the four villages. The proportion of outdoor host-seeking An. gambiae s.l. mosquitoes increased significantly in all four villages with an average increase of 58.8 % [57.9, 59.64 %] in 2009 to 70.0 % [67.8, 72.0 %] in 2014. Outdoor host-seeking rates did not increase in the month after an IRS spray round compared to the month before, suggesting that insecticide repellency has little impact on host-seeking behaviour. CONCLUSION: While vector control on Bioko Island has succeeded in substantial reduction in overall vector biting rates, populations of An. coluzzii and An. melas persist. Host-seeking behaviour has changed in these An. gambiae s.l. populations, with a shift towards outdoor host-seeking. During this study period, the proportion of host-seeking An. gambiae s.l. caught outdoors observed on Bioko Island increased to high levels, exceeding 80 % in some locations. It is possible that there may be a genetic basis underlying this large shift in host-seeking behaviour, in which case outdoor feeding could pose a serious threat to current vector control programmes. Currently, the BIMCP is preparing for this potential challenge by testing source reduction as a complementary control effort that also targets outdoor transmission

Outdoor host seeking behaviour of Anopheles gambiae mosquitoes following initiation of malaria vector control on Bioko Island, Equatorial Guinea

<p>Abstract</p> <p>Background</p> <p>Indoor-based anti-vector interventions remain the preferred means of reducing risk of malaria transmission in malaria endemic areas around the world. Despite demonstrated success in reducing human-mosquito interactions, these methods are effective solely against endophilic vectors. It may be that outdoor locations serve as an important venue of host seeking by <it>Anopheles gambiae </it>sensu lato (s.l.) mosquitoes where indoor vector suppression measures are employed. This paper describes the host seeking activity of anopheline mosquito vectors in the Punta Europa region of Bioko Island, Equatorial Guinea. In this area, <it>An. gambiae </it>sensu stricto (s.s.) is the primary malaria vector. The goal of the paper is to evaluate the importance of <it>An gambiae </it>s.l. outdoor host seeking behaviour and discuss its implications for anti-vector interventions.</p> <p>Methods</p> <p>The venue and temporal characteristics of host seeking by anopheline vectors in a hyperendemic setting was evaluated using human landing collections conducted inside and outside homes in three villages during both the wet and dry seasons in 2007 and 2008. Additionally, five bi-monthly human landing collections were conducted throughout 2009. Collections were segregated hourly to provide a time distribution of host-seeking behaviour.</p> <p>Results</p> <p>Surprisingly high levels of outdoor biting by <it>An. gambiae </it>senso stricto and <it>An. melas </it>vectors were observed throughout the night, including during the early evening and morning hours when human hosts are often outdoors. As reported previously, <it>An. gambiae </it>s.s. is the primary malaria vector in the Punta Europa region, where it seeks hosts outdoors at least as much as it does indoors. Further, approximately 40% of <it>An. gambiae </it>s.l. are feeding at times when people are often outdoors, where they are not protected by IRS or LLINs. Repeated sampling over two consecutive dry-wet season cycles indicates that this result is independent of seasonality.</p> <p>Conclusions</p> <p><it>An. gambiae </it>s.l. mosquitoes currently seek hosts in outdoor venues as much as indoors in the Punta Europa region of Bioko Island. This contrasts with an earlier pre-intervention observation of exclusive endophagy of <it>An. gambiae </it>in this region. In light of this finding, it is proposed that the long term indoor application of insecticides may have resulted in an adaptive shift toward outdoor host seeking in <it>An. gambiae </it>s.s. on Bioko Island.</p

Quality by Design (QbD) approach to develop HPLC method for eberconazole nitrate: Application oxidative and photolytic degradation kinetics

Stability of eberconazole nitrate (EBZ) was investigated using a stability indicating HPLC method. Quality by Design (QbD) approach was used to facilitate method development. EBZ was exposed to different stress conditions, including hydrolytic (acid, base, neutral), oxidative, thermal and photolytic. Relevant degradation was found to take place in all the conditions. The degradation of EBZ followed (pseudo) first-order kinetics under experimental conditions. The kinetic parameters (rate constant, t1/2, and t90) of the degradation of EBZ were calculated

Light traps fail to estimate reliable malaria mosquito biting rates on Bioko Island, Equatorial Guinea

Abstract Background The human biting rate (HBR), an important parameter for assessing malaria transmission and evaluating vector control interventions, is commonly estimated by human landing collections (HLC). Although intense efforts have been made to find alternative non-exposure mosquito collection methods, HLC remains the standard for providing reliable and consistent HBRs. The aim of this study was to assess the relationship between human landing and light trap collections (LTC), in an attempt to estimate operationally feasible conversion factors between the two. The study was conducted as part of the operational research component of the Bioko Island Malaria Control Project (BIMCP), Equatorial Guinea. Methods Malaria mosquitoes were collected indoors and outdoors by HLCs and LTCs in three villages on Bioko Island, Equatorial Guinea during five bimonthly collections in 2009. Indoor light traps were suspended adjacent to occupied long-lasting, insecticide-treated bed nets. Outdoor light traps were placed close to the outer wall under the roof of the collection house. Collected specimens were subjected to DNA extraction and diagnostic PCR to identify species within the Anopheles gambiae complex. Data were analysed by simple regression of log-transformed values and by Bayesian regression analysis. Results There was a poor correlation between the two collection methods. Results varied by location, venue, month, house, but also by the statistical method used. The more robust Bayesian analyses indicated non-linear relationships and relative sampling efficiencies being density dependent for the indoor collections, implying that straight-forward and simple conversion factors could not be calculated for any of the locations. Outdoor LTC:HLC relationships were weak, but could be estimated at 0.10 and 0.07 for each of two locations. Conclusions Light trap collections in combination with bed nets are not recommended as a reliable method to assess human biting rates on Bioko Island. Different statistical analyses methods give variable and inconsistent results. Substantial variation in collection methods prevents the determination of reliable and operationally feasible conversion factors for both indoor and outdoor data. Until improved mosquito collection methods are developed that can provide reliable and unbiased HBR estimates, HLCs should continue to serve as the reference method for HBR estimation.</p