"This changes things": Children, targeting, and the making of precision.

Avoidance of civilian casualties increasingly affects the political calculus of legitimacy in armed conflict. "Collateral damage" is a problem that can be managed through the material production of precision, but it is also the case that precision is a problem managed through the cultural production of collateral damage. Bearing decisively on popular perceptions of ethical conduct in recourse to political violence, childhood is an important site of meaning-making in this process. In pop culture, news dispatches, and social media, children, as quintessential innocents, figure prominently where the dire human consequences of imprecision are depicted. Children thus affect the practical "precision" of even the most advanced weapons, perhaps precluding a strike for their presence, potentially coloring it with their corpses. But who count as children, how, when, where, and why are not at all settled questions. Drawing insights from what the 2015 film, Eye in the Sky, reveals about a key social technology of governance we have already internalized, I explore how childhood is itself a terrain of engagement in the (un)making of precision.

Force distribution of a cylindrical grip differs between dominant and nondominant hand in healthy subjects.

INTRODUCTION: Grip strength and load distribution of the hand are important parameters for evaluating hand function. The purpose of this study was to analyze and compare grip force and load distribution of dominant and nondominant hands in right-handed healthy subjects. METHODS: Gripping measurements were performed on 40 healthy right-handed subjects using a cylindrical gripping device. Two different cylinders with circumferences of 150 mm (small cylinder) and 200 mm (large cylinder), respectively, were used for the measurements. Subjects were assigned to either the small or the large cylinder with respect to their hand size. Maximum and mean force applied during three intervals of gripping as well as the percent contribution of each digit, thenar, and hypothenar in relation to the total load applied were acquired. Values of dominant and nondominant hands were compared. RESULTS: Percent contribution of mean grip strength differed for the thumb (p = 0.007), ring finger (p < 0.001), little finger (p = 0.047), and palm (p < 0.001). Comparing the dominant and nondominant side, the dominant hand showed a lower contribution of the thumb, ring finger, and little finger, but a higher contribution of the palm. When analyzing maximum grip, percent contribution of the small fingers was equal between dominant and nondominant side (p = 0.1). Differences between dominant and nondominant thumb, ring finger, and palm persisted (p = 0.007, p = 0.001, p = 0.005, respectively). No differences could be shown for the index finger, middle finger, thenar, and hypothenar when analyzing both mean and maximum force. DISCUSSION AND CONCLUSION: Percent contribution of the thumb and the fingers to total grip strength differed between dominant and nondominant hands with a change in distribution when assessing maximum grip force. In right-handed subjects, thumb and ring finger have important roles during gripping.

Mesenchymal stem cells and myoblast differentiation under HGF and IGF-1 stimulation for 3D skeletal muscle tissue engineering.

BACKGROUND: Volumetric muscle loss caused by trauma or after tumour surgery exceeds the natural regeneration capacity of skeletal muscle. Hence, the future goal of tissue engineering (TE) is the replacement and repair of lost muscle tissue by newly generating skeletal muscle combining different cell sources, such as myoblasts and mesenchymal stem cells (MSCs), within a three-dimensional matrix. Latest research showed that seeding skeletal muscle cells on aligned constructs enhance the formation of myotubes as well as cell alignment and may provide a further step towards the clinical application of engineered skeletal muscle. In this study the myogenic differentiation potential of MSCs upon co-cultivation with myoblasts and under stimulation with hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) was evaluated. We further analysed the behaviour of MSC-myoblast co-cultures in different 3D matrices. RESULTS: Primary rat myoblasts and rat MSCs were mono- and co-cultivated for 2, 7 or 14 days. The effect of different concentrations of HGF and IGF-1 alone, as well as in combination, on myogenic differentiation was analysed using microscopy, multicolour flow cytometry and real-time PCR. Furthermore, the influence of different three-dimensional culture models, such as fibrin, fibrin-collagen-I gels and parallel aligned electrospun poly-ε-caprolacton collagen-I nanofibers, on myogenic differentiation was analysed. MSCs could be successfully differentiated into the myogenic lineage both in mono- and in co-cultures independent of HGF and IGF-1 stimulation by expressing desmin, myocyte enhancer factor 2, myosin heavy chain 2 and alpha-sarcomeric actinin. An increased expression of different myogenic key markers could be observed under HGF and IGF-1 stimulation. Even though, stimulation with HGF/IGF-1 does not seem essential for sufficient myogenic differentiation. Three-dimensional cultivation in fibrin-collagen-I gels induced higher levels of myogenic differentiation compared with two-dimensional experiments. Cultivation on poly-ε-caprolacton-collagen-I nanofibers induced parallel alignment of cells and positive expression of desmin. CONCLUSIONS: In this study, we were able to myogenically differentiate MSC upon mono- and co-cultivation with myoblasts. The addition of HGF/IGF-1 might not be essential for achieving successful myogenic differentiation. Furthermore, with the development of a biocompatible nanofiber scaffold we established the basis for further experiments aiming at the generation of functional muscle tissue.

[Surgical treatment of burns : Special aspects of pediatric burns]. / Chirurgische Behandlung von Verbrennungen : Besonderheiten bei Kindern.

BACKGROUND: Treatment of pediatric burn patients is very important because of the sheer frequency of burn wounds and the possible long-term ramifications. Extensive burns need special care and are treated in specialized burn centers. OBJECTIVES: The goal of this work is to present current standards in burn therapy and important innovations in the treatment of burns in children so that the common and small area burn wounds and scalds in pediatric patients in day-to-day dermatological practice can be adequately treated. MATERIALS AND METHODS: Analysis of current literature, discussion of reviews, incorporation of current guidelines. RESULTS: Burns in pediatric patients are common. Improvement of survival can be achieved by treatment in burn centers. The assessment of burn depth and area is an important factor for proper treatment. We give an overview for outpatient treatment of partial thickness burns. New methods may result in better long-term outcome. CONCLUSIONS: Adequate treatment of burn injuries considering current literature and guidelines improves patient outcome. Rational implementation of new methods is recommended.

A model for the coupling of the Greater Bairam and local environmental factors in promoting Rift-Valley Fever epizootics in Egypt.

OBJECTIVES: Rift-Valley Fever (RVF) is a zoonotic mosquito-borne disease in Africa and the Arabian Peninsula. Drivers for this disease vary by region and are not well understood for North African countries such as Egypt. A deeper understanding of RVF risk factors would inform disease management policies. STUDY DESIGN: The present study employs mathematical and computational modeling techniques to ascertain the extent to which the severity of RVF epizootics in Egypt differs depending on the interaction between imported ruminant and environmentally-constrained mosquito populations. METHODS: An ordinary differential system of equations, a numerical model, and an individual-based model (IBM) were constructed to represent RVF disease dynamics between localized mosquitoes and ruminants being imported into Egypt for the Greater Bairam. Four cases, corresponding to the Greater Bairam's occurrence during distinct quarters of the solar year, were set up in both models to assess whether the different season-associated mosquito populations present during the Greater Bairam resulted in RVF epizootics of variable magnitudes. RESULTS: The numerical model and the IBM produced nearly identical results: ruminant and mosquito population plots for both models were similar in shape and magnitude for all four cases. In both models, all four cases differed in the severity of their corresponding simulated RVF epizootics. The four cases, ranked by the severity of the simulated RVF epizootics in descending order, correspond with the occurrence of the Greater Bairam on the following months: July, October, April, and January. The numerical model was assessed for sensitivity with respect to parameter values and exhibited a high degree of robustness. CONCLUSIONS: Limiting the importation of infected ruminants beginning one month prior to the Greater Bairam festival (on years in which the festival falls between the months of July and October: 2014-2022) might be a feasible way of mitigating future RVF epizootics in Egypt.

A hundred patients with vertical rectus abdominis myocutaneous (VRAM) flap for pelvic reconstruction after total pelvic exenteration.

PURPOSE: We analysed the outcomes of a series of 100 consecutive patients with anorectal cancer with neoadjuvant radiochemotherapy and abdominoperineal exstirpation or total pelvic exenteration, who received a transpelvic vertical rectus abdominis myocutaneous (VRAM) flap for pelvic, vaginal and/or perineal reconstruction and compare a cohort to patients without VRAM flaps. METHODS: Within a 10-year period (2003-2013) in our institution 924 patients with rectal cancer stage y0 to y IV were surgically treated. Data of those 100 consecutive patients who received a transpelvic VRAM flap were collected and compared to patients without flaps. RESULTS: In 100 consecutive patients with transpelvic VRAM flaps, major donor site complications occurred in 6 %, VRAM-specific perineal wound complications were observed in 11 % of the patients and overall 30-day mortality was 2 %. CONCLUSIONS: The VRAM flap is a reliable and safe method for pelvic reconstruction in patients with advanced disease requiring pelvic exenteration and irradiation, with a relatively low rate of donor and recipient site complications. In this first study, to compare a large number of patients with VRAM flap reconstruction to patients without pelvic VRAM flap reconstruction, a clear advantage of simultaneous pelvic reconstruction is demonstrated.

Participatory Risk Mapping of Malaria Vector Exposure in Northern South America using Environmental and Population Data.

Malaria elimination remains a major public health challenge in many tropical regions, including large areas of northern South America. In this study, we present a new high spatial resolution (90 × 90 m) risk map for Colombia and surrounding areas based on environmental and human population data. The map was created through a participatory multi-criteria decision analysis in which expert opinion was solicited to determine key environmental and population risk factors, different fuzzy functions to standardize risk factor inputs, and variable factor weights to combine risk factors in a geographic information system. The new risk map was compared to a map of malaria cases in which cases were aggregated to the municipio (municipality) level. The relationship between mean municipio risk scores and total cases by muncípio showed a weak correlation. However, the relationship between pixel-level risk scores and vector occurrence points for two dominant vector species, Anopheles albimanus and An. darlingi, was significantly different (p < 0.05) from a random point distribution, as was a pooled point distribution for these two vector species and An. nuneztovari. Thus, we conclude that the new risk map derived based on expert opinion provides an accurate spatial representation of risk of potential vector exposure rather than malaria transmission as shown by the pattern of malaria cases, and therefore it may be used to inform public health authorities as to where vector control measures should be prioritized to limit human-vector contact in future malaria outbreaks.

[Extended skin and soft tissue defects after vascular wounds: plastic surgical concepts]. / Ausgedehnte Gewebedefekte bei vaskulären Wunden--Möglichkeiten der plastischen Chirurgie.

INTRODUCTION: Skin and soft-tissue defects at the ischaemic lower extremity represent a challenging condition. Major amputations can be prevented by optimised surgical therapy. The aim of any intervention is the revascularisation and defect reconstruction of the extremity. METHODS: This article aims to provide a structured overview on up-to-date therapeutic strategies and differentiated indications for certain surgical flaps in combination with bypass surgery for the treatment of chronic "vascular" wounds. RESULTS: Optimised conservative wound therapy, skin grafts, pedicled or microsurgical free flaps in combination with vascular bypasses can be applied to salvage ischaemic extremities. These operations require an interdisciplinary cooperation between vascular surgeons and plastic surgeons. DISCUSSION: These procedures should accordingly only be performed in specialised high-volume centres with significant vascular surgical and microsurgical expertise.

[Registry Research Funding of the German Society of Plastic, Reconstructive and Aesthetic Surgery (DGPRÄC) and Research Funding Report 2021/2022]. / Register Forschungsförderung der Deutschen Gesellschaft für Plastische, Rekonstruktive und Ästhetische Chirurgie (DGPRÄC) und Forschungsförderungs-Bericht 2021/2022.

BACKGROUND: Research is an integral part of academic medicine. In plastic surgery, it sets the course for innovations in the specialty. The purpose of this study is to present the research performance of plastic surgeons in Germany for the period 2021/2022 and to compare it with previous periods. MATERIALS AND METHODS: The directors of plastic surgical academic institutions reported all requested/approved and rejected research applications to public, non-public and industrial funding organizations. Data was gathered within an established online database. In addition, the DFG´s public database GEPRIS was screened for plastic surgical research grants. Data was also collected regarding research infrastructure and organization at the participating centers. RESULTS: 105 applications were reported to 54 different funding agencies from 20 plastic surgery centers. 37 funding applications were submitted to the major public funding agencies DFG, BMBF, BMWi, BMG, BMVg, G-BA and EU. Of these, 59,5% (22/37) were DFG, 13,5% (5/37) each BMBF and EU, 5,4% (2/37) BMWi, and 2,7% (1/37) each BMG, BMVg, and G-BA applications. The average funding volume of these proposals was 401,515 euros. Approved DFG proposals were most frequently assigned to the review board 205-27 Orthopedics, Trauma Surgery, Reconstructive Surgery (n=10/16, 62,5%). Over time, the research registry shows an increase in the number of proposals in general and those granted. 70,0% (14/20) of participating sites had their own experimental research laboratory, while only 40,0% (8/20) had their own clinical trial center. CONCLUSION: The 2021/2022 Research Funding Report once again highlights the impressive research accomplishments of the plastic surgery community.

Attraction of Stomoxys sp. to various fruits and flowers in Mali.

The attraction of three Stomoxys species to 26 fruits and 26 flowers of different plant species was investigated in two different sites in Mali during 2008. Stomoxys niger bilineatus Grunberg (Diptera: Muscidae) was attracted to a wider spectrum of species, significantly attracted by four fruits and eight flowers compared with control traps, whereas S. sitiens Rondani (Diptera: Muscidae) was attracted to six fruits and seven flowers of different plants, and S. calcitrans L. (Diptera: Muscidae) was only attracted to one fruit and three flowers. Cold anthrone assays showed a significantly higher prevalence of sugar feeding amongst all three species at the lagoon site than at the site near Mopti. The rhythm of activity study shows temporally separated blood- and sugar-feeding periods for S. niger bilineatus and S. sitiens, but not for S. calcitrans. A comparison between blood and sugar feeding throughout the day shows that sugar feeding activity is as frequent as blood feeding activity. Because not much is known about the preferred sugar sources for Stomoxys species in their natural habitats, the present study provides valuable information regarding the attraction capability of several plants with possible future implication for Stomoxys control strategies.

Axially vascularized bone substitutes: a systematic review of literature and presentation of a novel model.

INTRODUCTION: The creation of axially vascularized bone substitutes (AVBS) has been successfully demonstrated in several animal models. One prototypical indication is bone replacement in patients with previously irradiated defect sites, such as in the mandibular region. The downside of current clinical practice, when free fibular or scapular grafts are used, is the creation of significant donor site morbidity. METHODS: Based on our previous experiments, we extended the creation of an arterio-venous loop to generate vascularized bone substitutes to a new defect model in the goat mandibula. In this report, we review the literature regarding different models for axially vascularized bone substitutes and present a novel model demonstrating the feasibility of combining this model with synthetic porous scaffold materials and biological tissue adhesives to grow cells and tissue. RESULTS: We were able to show the principal possibility to generate axially vascularized bony substitutes in vivo in goat mandibular defects harnessing the regenerative capacity of the living organism and completely avoiding donor site morbidity. CONCLUSION: From our findings, we conclude that this novel model may well offer new perspectives for orthopedic and traumatic bone defects that might benefit from the reduction of donor site morbidity.

Leaving the perfusion zones? Individualized flap design in 100 free DIEP and ms-TRAM flaps for autologous breast reconstruction using indocyanine green angiography.

BACKGROUND: There is still no consensus regarding the ideal zoning in abdominal-based autologous breast reconstruction using free DIEP or ms-TRAM flaps. In particular, the perfusion pattern of the flap according to the number of perforators used and their location remains controversial. In this study, the perfusion of free DIEP and ms-TRAM flaps is assessed intraoperatively and analyzed with regard to different perfusion patterns. METHODS: A retrospective analysis of 100 free flaps for breast reconstruction was performed. Following complete flap harvest, we used indocyanine green angiography for perfusion analysis. By applying two different contour levels, DIEP flaps with lateral or medial perforators and ms-TRAM flaps were assessed for their respective perfusion patterns. RESULTS: No statistically significant differences were found in the size of the perfusion area between the different flap types when applying the contour level of 20% (p >0.05). For the contour level of 30%, however, statistically significant differences were found between DIEP flaps with medially or laterally located perforators (p = 0.038). Laterally or medially located perforators in DIEP flaps showed no significant differences in their ability to cross the midline (contour level 20%, p = 0.068; contour level 30%, p = 0.058). CONCLUSION: Considering the variability of the perfusion of the abdominal wall and the high sensitivity of indocyanine green angiography for their detection, the abdominal zonings play a minor role. By using intraoperative indocyanine green angiography, a precise and patient-specific free flap surgery for autologous breast reconstruction is possible independent of perforator location.

The effect of hypergravity, hyperbaric pressure, and hypoxia on osteogenic differentiation of adipose stem cells.

Human adipose stem cells (ASCs) hold great potential for regenerative medicine approaches, including osteogenic regeneration of bone defects, that fail to heal autonomously. Osteogenic differentiation of stem cells is dependent on the stimulation of biophysical factors. In the present study, the effects of hypergravity, hypoxia, and hyperbaric treatment were investigated on adipose stem cell (ASC) metabolic activity, quantified by PrestoBlue conversion, and cell numbers, evaluated by crystal violet staining. Osteogenic differentiation was assessed by alkaline phosphatase (ALP) activity and cresolphthalein staining of calcium deposition. Differentiation was performed for 12 days, which was accompanied by periodical stimulation. Increasing gravity forces up to 50x g did not affect ASC viability, but it enhanced osteogenic markers with a strongest effect between 20 and 30x g. Hyperbaric stimulation at 3 bar decreased ASC cell numbers but increased ALP activity and calcium deposition. Hypoxia at 8 % atmospheric oxygen did not affect ASC proliferation, while cell numbers were reduced at 3 % oxygen. Furthermore, hypoxic conditions produced opposing results on osteogenic markers, as ALP activity increased whereas cresolphthalein staining decreased upon stimulation. These data demonstrated that intermittent short duration of basal physical or chemical impulses interfere with the osteogenic differentiation of ASCs. Our findings could be of specific relevance in ASC based therapies for regenerative medicine and bone tissue engineering approaches.

The impact of VEGF and bFGF on vascular stereomorphology in the context of angiogenic neo-arborisation after vascular induction.

The aim of this in vivo study was to gather quantitative information on the three-dimensional morphology of a new vascular network under the influence of angioactive growth factors. For this purpose, the arteriovenous loop model was used in 10 Lewis rats to generate a bioartificial vascular assembly by means of vascular induction. In this model, an isolated organoid is created in the medial thigh of the animal by methods of tissue engineering. A fibrin gel containing vascular endothelial growth factor (VEGF(165)) and basic fibroblastic growth factor (bFGF) was used as a matrix in the effect group (GF+). Fibrin matrices devoid of growth factors were used as controls (GF-). A microvascular replica of the organoid was created by means of corrosion casting and the network was investigated on stereo-paired images obtained by scanning electron microscopy. Vectors of intercapillary and interbranching distances as well as the diameter of the pores in the intussusceptive events diameter and the ratio of sprouting versus intussusceptive angiogenic events were compared in the two groups. The results were highly significant. In the GF+ group there were more profound three-dimensional morphological traits of angiogenesis, whereas advanced neovascularisation in the phase of remodelling was demonstrated by a higher incidence of intussusception, compared to control. These results illustrate the importance of morphological studies with focus on the generation of three-dimensional vascular networks.

De novo generation of an axially vascularized processed bovine cancellous-bone substitute in the sheep arteriovenous-loop model.

BACKGROUND/AIMS: The aim of this study was to generate an axially vascularized bone substitute. The arteriovenous (AV)-loop approach in a large-animal model was applied in order to induce axial vascularization in a clinically approved processed bovine cancellous bone (PBCB) matrix of significant volume with primary mechanical stability and to assess the course of increasing axial vascularization. METHODS: PBCB constructs were implanted into 13 merino sheep together with a microsurgically created AV loop in an isolation chamber. The vascularization process was monitored by sequential magnetic resonance imaging (MRI) scans. Explants were subjected to micro-computed tomography (micro-CT) analysis, histomorphometry and immunohistochemistry for CD31 and CD45. RESULTS: Increasing axial vascularization in PBCB constructs was quantified by histomorphometry and visualized by micro-CT scans. Intravital sequential MRI scans demonstrated a significant progressive increase in perfused volume within the matrices. Immunohistochemistry confirmed endothelial lining of newly formed vessels. CONCLUSION: This study demonstrates successful axial vascularization of a clinically approved, mechanically stable bone substitute with a significant volume by a microsurgical AV loop in a large-animal model. Thus microsurgical transplantation of a tissue-engineered, axially vascularized and mechanically stable bone substitute with clinically relevant dimensions may become clinically feasible in the future.

Generation of two iPSC clones (MHHi021-A and MHHi021-B) from a patient with hypertrophic cardiomyopathy with p.Arg723Gly mutation in the MYH7 gene.

Hypertrophic cardiomyopathy (HCM) is the most common form of genetic heart disease and is characterized by abnormal thickening of the left ventricular wall and interventricular septum. Here we describe the generation of two induced pluripotent stem cell (iPSC) clones from a HCM patient, heterozygous for the p.Arg723Gly (c.2169C > G) mutation in the MYH7 gene. The generated iPSC clones may provide a useful resource for disease modelling to study the mechanisms underlying HCM pathogenesis in iPSC derived progenies, in particular cardiomyocytes.

[Registry Research Funding of the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC) and Research Funding Report 2019/2020]. / Register Forschungsförderung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC) und Forschungsförderungsbericht 2019/2020.

BACKGROUND: Since 2015/16 the DGPRÄC collects, evaluates and publishes the research activities of academic sections, departments and clinics for plastic surgery at university hospitals in Germany, in order to raise the awareness of plastic surgical research performance. MATERIALS AND METHODS: The directors of plastic surgical academic institutions were contacted via the DGPRÄC and asked to report any requested/approved and rejected research applications to public, non-public and industrial funding organizations. Data was collected in our previously established online database: https://docs.google.com/forms/d/e/1FAIpQLSe6F5xmTyw-k7VKJx_2jkPA4LBXsA0sgBGMrC3rx_4bHj6uzQ/viewform?usp=sf_link. In addition, applications were identified via the DFG's public database GEPRIS. RESULTS: A total of 41 funding applications to the public funding institutes DFG, BMBF, BMWi, BMG and EU were identified. 75.6 % (31/41) of the applications had already been approved at the time of data collection, of which 77.4 % (24/31) were DFG, 9.7 % (3/31) were BMWi, 6.5 % (2/31) were EU and 3.2 % (1/31) were BMBF or BMG applications. The average funding amounted to 358 301 Euro. In 50.0 % (12/24) of the cases, the approved DFG proposals were assigned to the subject review board 205-27 Orthopedics, Trauma Surgery, Reconstructive Surgery. CONCLUSION: The continuous publication of plastic surgical research funding reports submitted by the convention of university plastic surgeons of the DGPRÄC portraits the excellent, collaborative research activity in the field of plastic surgery.

Foetal hepatocyte transplantation in a vascularized AV-Loop transplantation model in the rat.

The use of foetal liver cells (FLC) in the context of hepatic tissue engineering might permit efficient in vitro expansion and cryopreservation in a cell bank. A prerequisite for successful application of bioartificial liver tissue is sufficient initial vascularization. In this study, we evaluated the transplantation of fibrin gel-immobilized FLC in a vascularized arterio-veno-venous (AV)-loop model. FLC were isolated from embryonic/foetal (ED 16) rat livers and were enriched by using magnetic cell sorting (MACS). After cryopreservation, FLC were labelled by pkh-26. Cells were transplanted in a fibrin matrix into a subcutaneous chamber containing a microsurgically created AV-loop in the femoral region of the recipient rat. The chambers were explanted after 14 days. Subcutaneous implants without an AV-loop and cell-free implants served as controls. Fluorescence microscopy of the constructs was used to identify pkh-26(+)- donor cells. Characterization was performed by RT-PCR and immunhistology (IH) for CK-18 and CD31. Transplantation of FLC using the AV-loop permitted a neo-tissue formation in the fibrin matrix. A high-density vascularization was observed in the AV-loop constructs as shown by CD31 IH. Viable foetal donor cells were detected which expressed CK-18. FLC can be successfully used for heterotopic transplantation. Fibrin matrix permits rapid blood vessel ingrowth from the AV-loop and supports engraftment of FLC. It is therefore an appropriate environment for hepatocyte transplantation in combination with microsurgical vascularization strategies. Transplantation of fibrin gel-immobilized FLC may be a promising approach for the development of highly vascularized in vivo tissue-engineering-based liver support systems.

Biological cost of tolerance to heavy metals in the mosquito Anopheles gambiae.

The global rate of heavy metal pollution is rapidly increasing in various habitats. Anopheles malaria vector species (Diptera: Culicidae) appear to tolerate many aquatic habitats with metal pollutants, despite their normal proclivity for 'clean' water (i.e. low levels of organic matter). Investigations were conducted to establish whether there are biological costs for tolerance to heavy metals in Anopheles gambiae Giles sensu stricto and to assess the potential impact of heavy metal pollution on mosquito ecology. Anopheles gambiae s.s. were selected for cadmium, copper or lead tolerance through chronic exposure of immature stages to solutions of the metals for three successive generations. Biological costs were assessed in the fourth generation by horizontal life table analysis. Tolerance in larvae to cadmium (as cadmium chloride, CdCl(2)), copper [as copper II nitrate hydrate, Cu(NO(3))(2) 2.5 H(2)O] and lead [as lead II nitrate, Pb(NO(3))(2)], monitored by changes in LC(50) concentrations of the metals, changed from 6.07 microg/L, 12.42 microg/L and 493.32 microg/L to 4.45 microg/L, 25.02 microg/L and 516.69 microg/L, respectively, after three generations of exposure. The metal-selected strains had a significantly lower magnitude of egg viability, larval and pupal survivorship, adult emergence, fecundity and net reproductive rate than the control strain. The population doubling times were significantly longer and the instantaneous birth rates lower in most metal-selected strains relative to the control strain. Our results suggest that although An. gambiae s.s. displays the potential to develop tolerance to heavy metals, particularly copper, this may occur at a significant biological cost, which can adversely affect its ecological fitness.

Evaluation of blood vessel ingrowth in fibrin gel subject to type and concentration of growth factors.

Our aim was to quantitatively assess the angiogenetic effects of VEGF and bFGF immobilized in a fibrin-based drug delivery system in a suitable subcutaneous rat model. After evaluation of a suitable implantation technique (6 rats), four teflon isolation chambers containing fibrin gel matrices were implanted subcutaneously in an upside-down fashion on the back of 30 Lewis rats. The matrices consisted of 500 microl fibrin gel with two different fibrinogen concentrations (10 mg/ml or 40 mg/ml fibrinogen) and 2 I.U./ml thrombin and contained VEGF and bFGF in five different concentrations (0 to 250 ng/ml each). At 3, 7 and 14 days after implantation, matrices were explanted and subjected to histological and morphometrical analysis. At 1 week, the volume of the fibrin clots was significantly smaller in the 100 and 250 ng/ml VEGF and bFGF groups in comparison to lower concentrated growth factors. At 1 and 2 weeks, the use of growth factors in low concentrations (25 ng/ml VEGF and bFGF) significantly increased the amount of fibrovascular tissue, average fraction of blood vessels and number of blood vessels at the matrix-host interface in comparison to growth factor-free controls. Higher concentrations were neither associated with further increase of tissue formation nor with increased sprouting of blood vessels in this model. This study demonstrates that fibrin gel-immobilized angioinductive growth factors efficiently stimulate generation of fibrovascular tissue and sprouting of blood vessels in a newly developed subcutaneous upside-down isolation chamber model with an optimum between 25 and 100 ng/ml.