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Biomedical subjects

R Wagner

Publications and source records attributed to R Wagner.

At least 55 records · Page 3Linked to original sources
PubMed2001

[Performance of Slovak hospitals as related to Porter's generic strategies].

Porter's generic strategies characterize organizations in terms of their competitiveness, and are related to the performance of the organization. The aim of this study was to analyze the Porter's generic strategies and their effect on performance in the context of the Slovak hospital industry. Acute care hospitals with more than 30 beds were included into the study. National institutes providing specialized service were excluded from the study. Strategy and performance were evaluated on the basis of self-reported questionnaires, completed by chief administrators of hospitals (total 76 completed questionnaires were obtained, out of 81 distributed, i.e. 94% response rate). The cluster analysis was used for the identification of strategic orientation. Performance differences across strategic groups were tested using multivariate analysis of covariance (MANCOVA). The hierarchical cluster analysis uncovered a four-group taxonomy of hospitals: the group "Focused Cost Leadership" included 33% of hospitals, the group "Stuck-in-the middle" 49%, the group "Wait and See" 13% and the group "Cost leadership" 5%. Significant differences in performance were related to the Porter's pure, or hybrid strategies, respectively. In terms of industry evolution, the Slovak hospital industry could be characterized as fragmented, having a large number of small and medium size mainly state owned hospitals, with absence of market leaders, and with high exit barriers (mainly social and political) that hold back consolidation. (Tab. 1, Ref. 35.).

Economic Competition↗
PubMed2001

Change climate in the University Hospital Bratislava.

Organizational change can generate skepticism and resistance in employees, making it sometimes difficult or impossible to implement organizational improvements. To enable the University Hospital Bratislava to manage these realities in a most effective way, the assessment of attitudes to change was conducted among 304 full-time hospital employees in the summer of 1999. The assessment was based on the Change Climate Survey allowing for investigation of attitudes in four main areas: orientation towards change in general, understanding and acceptance of change, management of change, and change outcomes. In spite of some limitations due to the fact that the survey did not use a true random sample, in general, the results seem to be able to illustrate the University Hospital employees' attitudes to change. The findings indicate that, in general, the attitudes of the hospital employees towards change are rather positive. However, the mixed feelings prevail among the employees from the point of understanding and acceptance of the current changes. Similarly, the mixed feelings persist among the employees with respect to the way the change is managed, though with slightly positive attitudes towards the level of communication. From the practical point of view, the results imply that emphasizing the involvement of organization members in learning about their organization and how to change it might prove to be more effective in managing change in the University Hospital Bratislava, than the traditional approaches to planned change, where consultants carry out most of the change activities, with the agreement and collaboration of management. (Tab. 8, Ref. 28.)

Adolescent↗
PubMed2001

Motivational climate and attitudes to change: a hospital study.

Change can be highly motivating when it is perceived as results-oriented, well planned and well communicated. However, there appears to be a lack of evidence on the actual existence of such relationships between motivational climate and attitudes to change in management literature, especially under the specific conditions of health care organisations in Slovakia. Using a sample of 243 employees of the University Hospital Bratislava, the present study has investigated the validity of the assumption that: (i) low motivational climate will represent an inhibitor to change, and vice versa, (ii) the more attention is being paid by the organisation's management to implementation of change, resulting in the staff having positive attitudes to change, the higher the motivational climate within the organisation will be. The findings indicate that motivational climate of the hospital can be heavily influenced by the manner in which the change is being managed. Moreover, not only how change is being managed, but also how it is understood and accepted by the employees, as well as which outcomes the change results in, have significant effects on the perceived motivational climate. The results also show that to maintain the high motivational climate, thus stimulating desired behaviours in the staff, the hospital managers should keep, among other things, (i) encouraging the workers to make a creative contribution, (ii) informing them about the reasons why changes are being made, (iii) showing them how their work objectives relate to where the hospital is heading and that the cost of the current changes will not outweight the benefits, and (v) ensuring that adequate training is available to equip people for changes and giving them the support they need to cope with change. Last, but not least, the present study helps to demonstrate the importance of attitudes as a force that is powerful in determining work output. (Tab. 3, Ref. 37.)

Attitude of Health Personnel↗
PubMed2001

[The piggyback technique in venous outflow tract reconstruction in liver transplantation].

Nowadays, the piggyback technique of venous outflow tract reconstruction has been adopted by an increasing number of transplant teams. From January 1996 to August 2000, we used it in 73 of 84 liver transplantations (86.9%) in our institution. We observed one postoperative complication (1.4%) in direct relation to this technique. The main advantages of the piggyback are 1. maintaining of the haemodynamic stability during the anhepatic phase, 2. avoiding of the veno-venous bypass, 3. diminution of blood loss, 4. easier solution of the graft size mismatch problem, 5. shorter manipulation time and 6. easier retransplantation. Disadvantages of the piggyback technique include 1. more technically demanding recipient's hepatectomy, 2. the potential for venous outflow tract obstruction and 3. possible thrombosis in a blind caval pouch. According to our results and experience in the literature, we consider the piggyback technique as a method of choice for venous outflow tract reconstruction in liver transplantation. It can be used in the majority of patients after gaining some experience.

Anastomosis, Surgical↗
PubMed2000

A truncated plasminogen activator inhibitor-1 protein induces and inhibits angiostatin (kringles 1-3), a plasminogen cleavage product.

Plasminogen activator inhibitor-1 (PAI-1) is a serpin protease inhibitor that binds plasminogen activators (uPA and tPA) at a reactive center loop located at the carboxyl-terminal amino acid residues 320-351. The loop is stretched across the top of the active PAI-1 protein maintaining the molecule in a rigid conformation. In the latent PAI-1 conformation, the reactive center loop is inserted into one of the beta sheets, thus making the reactive center loop unavailable for interaction with the plasminogen activators. We truncated porcine PAI-1 at the amino and carboxyl termini to eliminate the reactive center loop, part of a heparin binding site, and a vitronectin binding site. The region we maintained corresponds to amino acids 80-265 of mature human PAI-1 containing binding sites for vitronectin, heparin (partial), uPA, tPA, fibrin, thrombin, and the helix F region. The interaction of "inactive" PAI-1, rPAI-1(23), with plasminogen and uPA induces the formation of a proteolytic protein with angiostatin properties. Increasing amounts of rPAI-1(23) inhibit the proteolytic angiostatin fragment. Endothelial cells exposed to exogenous rPAI-1(23) exhibit reduced proliferation, reduced tube formation, and 47% apoptotic cells within 48 h. Transfected endothelial cells secreting rPAI-1(23) have a 30% reduction in proliferation, vastly reduced tube formation, and a 50% reduction in cell migration in the presence of VEGF. These two studies show that rPAI-1(23) interactions with uPA and plasminogen can inhibit plasmin by two mechanisms. In one mechanism, rPAI-1(23) cleaves plasmin to form a proteolytic angiostatin-like protein. In a second mechanism, rPAI-1(23) can bind uPA and/or plasminogen to reduce the number of uPA and plasminogen interactions, hence reducing the amount of plasmin that is produced.

Angiostatins↗
PubMed2000

Rapid whole blood analysis of virus-specific CD4 and CD8 T cell responses in persistent HIV infection.

OBJECTIVES: Upon HIV infection, strong antiviral cytotoxic and helper T cell responses are generated. They are considered to be an important component in the control of HIV viral load. A simple and rapid whole blood assay was established to quantify and simultaneously characterize HIV-reactive CD4 and CD8 cells. The assay was applied to evaluate the effect of antiretroviral therapy on HIV-specific T cell responses. METHODS: Whole blood of 33 HIV-infected individuals was specifically stimulated by HIV-1 Pr55gag, and activation-induced intracellular cytokine expression in CD4 and CD8 T cells was analysed by flow cytometry. RESULTS: HIV-1-specific CD8 and CD4 T cells can be quantified simultaneously. As specific antigen, HIV-1 Pr55gag virus-like particles were superior to soluble protein, especially for the activation of CD8 T cells. In untreated individuals, a high frequency of HIV-specific T cells was observed. The frequency of CD8 T cells was consistently higher than the respective CD4 T cell response, thus demonstrating a dominance in CD8 T cell expansion in persistent HIV infection. Patients on antiretroviral therapy showed a significant reduction in HIV-specific CD4 and, even more strikingly, CD8 T cells. CONCLUSION: The whole blood assay provides a rapid estimate of the total antiviral T cell resources, and is highly suited for a clinical setting. It may thus have widespread applications for the evaluation of vaccination strategies and immunotherapy. Because antiretroviral therapy significantly reduces both HIV-specific cytotoxic and helper T cell responses, future therapeutic strategies should aim at improving cellular antiviral immunity.

Adult↗
PubMed2000

Rev-independent expression of synthetic gag-pol genes of human immunodeficiency virus type 1 and simian immunodeficiency virus: implications for the safety of lentiviral vectors.

The safety of lentiviral vectors for clinical applications is still a major concern. The gag-pol expression plasmids and the lentiviral vectors used in previous studies contain homologous regions, which constitute a risk for recombination events. Synthetic gag-pol genes of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) were therefore constructed, in which the codon usage was optimized for expression in human cells without altering the amino acid sequences. The synthetic gag-pol genes allowed efficient expression of these genes in the absence of Rev and the 5' untranslated leader region. Both the HIV-1 and the SIV synthetic gag-pol expression plasmids could mediate transduction of an SIV vector into nondividing human cells with titers of about 10(6) transducing units/ml. Similar titers were obtained with a four-plasmid vector-packaging system based on HIV-1. Using a biological assay, homologous recombination events between the synthetic gag-pol expression plasmids and an SIV vector were undetectable and in comparison with a previously used gag-pol expression plasmid at least approximately 100-fold less frequent. By eliminating regions of homology and sequences involved in packaging, synthetic gag-pol genes should improve the safety profile of lentiviral vectors.

5' Untranslated Regions↗
PubMed2000

Concentration dependence of the spectroscopic and photochemical properties of atomic and molecular oxygen in argon matrices.

Vacuum ultraviolet (VUV) excitation (200-100 nm) and visible emission (300-650 nm) spectra of O2 imbedded in Ar matrices at different concentrations are presented. At 0.1 and 0.2% concentrations a linear increase in the intensities of the excitation and emission spectra is observed. At these concentrations, photolysis of O2 is found to be negligible. At higher concentrations (0.5, 1 and 2%) the normalized intensities of the excitation and emission spectra of O2 decrease. With increasing concentration of O2 the permanent photolysis of O2 increases, which does not correlate, based on the excitation spectra of O in Ar, to the production of isolated O atoms. It has been shown that this anomalous behavior should be due to the formation of van der Waals dimers and oligomers at higher concentrations of O2 that upon photolysis produce ozone.

Argon↗
PubMed2000

Field efficacy of moxidectin in dogs and rabbits naturally infested with Sarcoptes spp., Demodex spp. and Psoroptes spp. mites.

The efficacy of moxidectin 1% injectable for cattle was evaluated in dogs and rabbits with naturally acquired sarcoptic, demodectic or psoroptic mites. Twenty-two dogs with generalised demodicosis were orally treated with 0.4mg/kg moxidectin daily. Forty-one dogs suffering from sarcoptic mange were treated with 0.2-0.25mg/kg moxidectin either orally or subcutaneously every week for three to six times. Seven rabbits were treated orally with 0.2mg/kg moxidectin twice 10 days apart. Of the 22 dogs with demodicosis, 14% were stopped treatment because of side effects, 14% were lost and of the remaining 72% all were cured (mean therapy duration 2.4 months). Thirty-seven of the sarcoptic mange-infected dogs finished treatment and were cured. In 17% of dogs, side effects were noted. All seven rabbits treated for psoroptic mange were cured and did not show any side effect. Our results indicate that moxidectin is effective and a good alternative for the treatment of demodicosis and scabies in dogs and psoroptic mange in rabbits. Side effects seem to occur more frequently if applied subcutaneously, therefore the oral route should be preferred.

Animals↗
PubMed2000

A Ca(2+)- and voltage-modulated flagellar ion channel is a component of the mechanoshock response in the unicellular green alga Spermatozopsis similis.

In flagellate green algae, behavioral responses to photo- and mechanoshock are induced by different external stimuli within 10-15 ms. In the accompanying changes in flagella beat, Ca(2+) has important regulatory roles. Although the axonemal Ca(2+) responsive elements are well characterized, analyses of flagellar channels involved in Ca(2+) signalling as well as other ion channels at the single-channel level were not yet conducted in green algae. To gain a further understanding of these important signaling elements in movement responses, intact flagella of Spermatozopsis similis were isolated and characterized and the solubilized flagellar membrane proteins were reconstituted into liposomes. We observed three types of channel activity, two of which were weakly anion and cation-selective and in the high-conductance regime typical for porin-like solute channels. The dominating channel activity was a voltage dependent, rectifying, low conductance (Lambda=80 pS in 50 mM KCl) cation-selective channel modulated by, and highly permeable to, Ca(2+) ions (SFC1: Spermatozopsis flagellar cation channel 1). Depolarizations necessary to activate SFC1 probably only occur in vivo during avoidance reactions of this alga. Ca(2+)-activation of SFC1 points to a direct link to Ca(2+)-mediated signaling pathway(s) in the flagella. Both the response to mechanoshock and SFC1 activity were inhibited by Gd(3+) and Ba(2+), thus supporting our assumption that SFC1 represents a major flagellar ion channel involved in this green algal avoidance reaction.

Algal Proteins↗
PubMed2000

The bacterial DNA-binding protein H-NS represses ribosomal RNA transcription by trapping RNA polymerase in the initiation complex.

The interaction of the bacterial regulatory protein H-NS with RNA polymerase and the ribosomal RNA P1 promoter was analyzed to better understand the mechanism of H-NS-dependent transcriptional repression. We could show that initial binding of RNA polymerase to the promoter was not inhibited by the simultaneous interaction of H-NS, although H-NS binding sites extend into the core promoter region. Binding of sigma(70)-saturated RNA polymerase and H-NS to the promoter DNA occurs cooperatively and results in a stable complex of slower gel electrophoretic mobility as compared to complexes formed with the single proteins. The presence of the upstream curved H-NS binding site contributes strongly to the cooperative RNA polymerase-promoter interaction. By KMnO(4) modification of single-stranded template nucleotides we could show that open complex formation at the rrnB P1 promoter was not inhibited by H-NS binding. An increased KMnO(4) reactivity of several positions within the open complex rather supports the view that open complex formation is stimulated in presence of H-NS. Moreover, subtle changes in the modification pattern indicate that the open complex formed in the presence of H-NS are structurally distinct from the H-NS-free complex. In vitro transcriptional analysis of the abortive and productive yields revealed that the formation of transcription products longer than three nucleotides is dramatically reduced in the presence of H-NS, while the amount of shorter abortive products remained unaffected. Together the results demonstrate that H-NS inhibits transcription at the rrnB P1 promoter not by interfering with initial RNA polymerase binding but by blocking chain elongation steps subsequent to the first (two) phosphodiester bond formations. The mechanism of H-NS dependent repression at rRNA promoters can thus be explained as a trap which inhibits substrate NTP incorporation beyond template position +3 into the initial transcribing complex.

Allosteric Site↗
PubMed2000

Solute pores, ion channels, and metabolite transporters in the outer and inner envelope membranes of higher plant plastids.

All plant cells contain plastids. Various reactions are located exclusively within these unique organelles, requiring the controlled exchange of a wide range of solutes, ions, and metabolites. In recent years, several proteins involved in import and/or export of these compounds have been characterized using biochemical and electrophysiological approaches, and in addition have been identified at the molecular level. Several solute channels have been identified in the outer envelope membrane. These porin-like proteins in the outer envelope membrane were formerly thought to be quite unspecific, but have now been shown to exhibit significant substrate specificity and to be highly regulated. Therefore, the inter-envelope membrane space is not as freely accessible as previously thought. Transport proteins in the inner envelope membrane have been characterized in more detail. It has been proved unequivocally that a family of proteins (including triose phosphate-/phosphoenolpyruvate-, and glucose 6-phosphate-specific transporters) permit the exchange of inorganic phosphate and phosphorylated intermediates. A new type of plastidic 2-oxoglutarate/malate transporter has been identified and represents the first carrier with 12 putative transmembrane domains, to be located in the inner envelope membrane. The plastidic ATP/ADP transporter also contains 12 putative transmembrane domains and possesses striking structural similarity to ATP/ADP transporters found in intracellular, human pathogenic bacteria.

Adenosine Diphosphate↗
PubMed2000

[Dobutamine-induced changes in the myocardial blood flow in patients with coronary heart diseases. A quantitative analysis using [15O] H2O positron emission tomography].

BACKGROUND AND OBJECTIVE: Although dobutamine is currently widely used for stress testing, only little is known about the effects of dobutamine on myocardial blood flow. The purpose of the present study was therefore to analyze quantitatively the regional changes in myocardial blood flow during rest and stress. PATIENTS AND METHODS: In order to assess these effects 17 patients (12 men, five women, mean age 57 +/- 8 years) with symptomatic single vessel coronary artery disease (> 70% stenosis) scheduled for coronary angioplasty underwent dobutamine stress testing with a maximum dose of 40 micrograms/kg/min. Myocardial blood flow was measured using 15O H2O position emission tomography at rest and during maximum stress in ischemic and non-ischemic myocardial regions. RESULTS: Dobutamine stress (median dose 30 micrograms/kg/min) increased the rate pressure product significantly (from rest 8697 [95% confidence interval 7959-9435] to stress 16,512 [15,208-17,815] mmHg/min (p < 0.001). Myocardial blood flow during rest was similar in non-ischaemic and ischaemic regions (0.91 [0.93; 0.83-1.28] vs. 1.10 [1.23; 0.91-1.28] ml/min/g, n.s.). During dobutamine stress myocardial blood flow increased in non-ischaemic regions to 2.17 (2.15; 1.77-2.57) ml/min/g, while myocardial blood flow did not increase in ischaemic regions (1.06 [0.97; 0.83-1.28], p < 0.001). Accordingly, dobutamine coronary reserve was 2.42 (2.55; 2.10-2.74) for non-ischaemic regions and 0.98 (1.05; 0.84-1.13) for ischemic regions (p < 0.001). Rate pressure product and myocardial blood flow were significantly correlated (r = 0.79, p < 0.001). CONCLUSION: A dobutamine-induced increase in rate pressure product was proportional to an increase in myocardial blood flow in non-ischaemic regions. In contrast, myocardial blood flow did not increase in myocardial regions supplied by a severely stenosed coronary artery.

Blood Flow Velocity↗
PubMed2000

Identification of the pore-forming region of the outer chloroplast envelope protein OEP16.

The chloroplast outer envelope protein OEP16 forms a cation-selective high conductance channel with permeability to amines and amino acids. The region of OEP16 directly involved in channel formation has been identified by electrophysiological analysis of a selection of reconstituted OEP16 mutants. Because analysis of these mutants depended on the use of recombinant protein, we evaluated the electrophysiological properties of OEP16 isolated directly from pea chloroplasts and of the recombinant protein produced in Escherichia coli. The results show that the basic properties like conductance, selectivity, and open probability of the channel formed by native pea OEP16 are comparable with the channel activity formed by the recombinant source of the protein. Following electrophysiological analysis of OEP16 mutants we found that point mutations and insertion of additional amino acid residues in the region of the putative helix 1 (Glu(73) to Val(91)) did not change the properties of the OEP16 channel. The only exception was a Cys(71)-->Ser mutation, which led to a loss of the CuCl(2) sensitivity of the channel. Analysis of N- and C-terminal deletion mutants of OEP16 and mutants containing defined shuffled domains indicated that the minimal continuous region of OEP16, which is able to form a channel in liposomes, lies in the first half of the protein between amino acid residues 21 and 93.

Amines↗
PubMed2000

Proline residues in the HIV-1 NH2-terminal capsid domain: structure determinants for proper core assembly and subsequent steps of early replication.

Recent analyses suggest that the p24 capsid (p24(CA)) domain of the HIV-1 group-specific antigen (Gag) may be divided into two structurally and functionally distinct moieties: (i) an amino-terminal portion, previously shown to bind the cellular chaperone cyclophilin A, and (ii) a carboxy-terminal domain, known to contribute to the interaction of the Gag and Gag-Pol precursors during the early assembly process. In order to gain deeper insight into the role of the amino-terminal domain of the p24(CA) protein during viral replication, eight highly conserved proline residues known to promote turns and to terminate alpha-helices within the p24 tertiary structure were replaced by a leucine residue (P-position-L). Following transfection of the proviral constructs in COS7 cells, the majority of the mutants resembled wild-type viruses with respect to the assembly and release of virions. However, although the released particles contained wild-type levels of genomic viral RNA, the mature products of the Gag and Gag-Pol polyproteins as well as the Env glycoproteins-all of them, except mutant P225L-were either noninfectious or severely affected in their replicative capacity. Entry assays monitoring the process of viral DNA synthesis led to the classification of selected provirus mutants into four different phenotypes: (i) mutant P225L was infectious and allowed complete reverse transcription including formation of 2-LTR circles; (ii) mutants P149L, P170L, and P217L failed to form 2-LTR circles; (iii) mutant P222L displayed a severe defect in binding and incorporating cyclophilin A into virions, was delayed with respect to DNA polymerization, and failed to form a 2-LTR replication intermediate; and (iv) mutant P133L was unable even to synthesize a first-strand cDNA product. All replication-defective mutants were characterized by severe alterations in the stability of virion cores, which were in two cases reflected by visible changes in the core morphology. These results suggest that proline residues in the NH(2)-terminal capsid domain represent critical structure determinants for proper formation of functional virion cores and subsequent stages of early replication.

Amino Acid Substitution↗
PubMed2000

A prospective study on the incidence and clinical relevance of heparin-induced antibodies in patients after vascular surgery.

The heparin-platelet factor 4-antibody assay, polyanion-platelet factor 4-antibody assay and heparin-induced platelet activation test are used for laboratory diagnosis of the immune form of heparin-induced thrombocytopenia. Fifty consecutive patients receiving heparin treatment for more than 5 days after vascular surgery were prospectively screened for heparin-induced thrombocytopenia antibodies, thrombocytopenia (daily platelet counts), deep-vein thrombosis (color-coded duplex sonography), and arterial reocclusion (clinical assessment). None of the patients developed thrombocytopenia or thrombosis in association with formation of heparin-induced thrombocytopenia antibodies. Despite the absence of clinical evidence of heparin-induced thrombocytopenia, many patients formed heparin-induced thrombocytopenia antibodies: 34% of the patients were positive in the heparin-platelet factor 4-antibody assay, 28% in the polyanion-platelet factor 4-antibody assay, 14% in the heparin-induced platelet activation test, and 54% with any of these tests. Patients predominantly developed IgM (24%) and IgA antibodies (16%), whereas IgG antibodies were found in 12% of patients. Whereas the majority of patients with positive ELISA assays had IgM and IgA antibodies, patients with a positive functional assay (heparin-induced platelet activation test) predominantly had IgG antibodies. We conclude that a high percentage of patients develop heparin-induced antibodies after vascular surgery without any clinical symptoms of heparin-induced thrombocytopenia. None of the assays therefore is predictive of the clinical manifestation of heparin-induced thrombocytopenia in asymptomatic patients. Therefore, the diagnostic specificity of both antigen and activation assays for heparin-induced thrombocytopenia appears to be relatively low in the vascular surgery patient population.

Aged↗
PubMed2000

Priming of strong, broad, and long-lived HIV type 1 p55gag-specific CD8+ cytotoxic T cells after administration of a virus-like particle vaccine in rhesus macaques.

Despite advances in the clinical management of HIV infection, using combinations of antiretroviral pharmaceuticals, a safe and efficacious vaccine is needed to limit the AIDS pandemic. It is now thought that an effective HIV-1 vaccine should prime both cross-neutralizing antibodies and long-lasting cytotoxic CD8+ T lymphocytes (CTLs) recognizing multiple codominant HIV-1 epitopes. To that end, many novel vaccine strategies have been tested. However, only a few of these strategies, beside those relying on live-attenuated viruses, are able to prime strong CTL responses in nonhuman primates and humans. In this study, three rhesus macaques were immunized with HIV-1 p55gag virus-like particles (VLPs) in the absence of adjuvant to assess the potential of such a vaccine to prime CTL responses. After intramuscular injection of p55gag VLP, all three animals mounted CTL responses against HIV-1 p55gag. Notably, these CTLs primed by vaccination recognized naturally processed peptides and were long lived (>8.5 months) both in the peripheral blood and draining lymph node. Furthermore, these CTLs were directed against multiple HIV-1 p55gag epitopes. This indicated that immunization with p55gag VLP primes strong MHC class I-restricted, CD8+ cell-mediated immune responses and suggested that HIV-1 p55gag VLPs should be a reasonable vaccine candidate, when combined with strategies priming cross-neutralizing antibodies.

AIDS Vaccines↗