Tell Us! A survey of public opinion on how to deal with COVID-19 risks and subsequent harm.

SETTING: The COVID-19 pandemic has impacted all of us in many areas of life due to mitigation measures, delays in medical care, or the disease itself. When it concerns issues as complex and universal as COVID-19, the public should also have a say in how to deal with managing its impact. DESIGN: In a widely distributed online questionnaire, members of the Austrian public were invited to contribute experiences, ideas and opinions on the level of risk they were willing to accept regarding COVID-19. The huge variety of responses were categorised by social scientists into groups used in a workshop to draw up recommendations for responding to future challenges to the healthcare system from an interdisciplinary point of view. RESULTS: The results of the survey indicated that while members of the public are primarily afraid of illnesses caused by COVID-19, they also fear the psychological burden and effects at the societal level. CONCLUSION: Our study has shown that there is a significant public desire to have a say in issues which directly impact citizens.

CONTEXTE: La pandémie de COVID-19 a eu un impact sur chacun d'entre nous dans de nombreux domaines de la vie en raison des mesures d'atténuation, des retards dans les soins médicaux ou de la maladie elle-même. Lorsqu'il s'agit de questions aussi complexes et universelles que la COVID-19, le public devrait également avoir son mot à dire sur la façon de gérer son impact. MÉTHODE: Dans un questionnaire en ligne largement diffusé, les membres du public autrichien ont été invités à faire part de leurs expériences, idées et opinions sur le niveau de risque qu'ils étaient prêts à accepter concernant le COVID-19. La grande variété des réponses a été classée par des spécialistes en sciences sociales dans des groupes utilisés lors d'un atelier pour élaborer des recommandations visant à répondre aux futurs défis du système de santé d'un point de vue interdisciplinaire. RÉSULTATS: Les résultats de l'enquête ont indiqué que si les membres du public craignent avant tout les maladies causées par le COVID-19, ils craignent également le fardeau psychologique et les effets au niveau de la société. CONCLUSION: Notre étude a montré qu'il existe un désir significatif du public d'avoir son mot à dire sur les questions qui ont un impact direct sur les citoyens.

Exploring the link between molecular cloud ices and chondritic organic matter in laboratory.

Carbonaceous meteorites are fragments of asteroids rich in organic material. In the forming solar nebula, parent bodies may have accreted organic materials resulting from the evolution of icy grains observed in dense molecular clouds. The major issues of this scenario are the secondary processes having occurred on asteroids, which may have modified the accreted matter. Here, we explore the evolution of organic analogs of protostellar/protoplanetary disk material once accreted and submitted to aqueous alteration at 150 °C. The evolution of molecular compounds during up to 100 days is monitored by high resolution mass spectrometry. We report significant evolution of the molecular families, with the decreases of H/C and N/C ratios. We find that the post-aqueous products share compositional similarities with the soluble organic matter of the Murchison meteorite. These results give a comprehensive scenario of the possible link between carbonaceous meteorites and ices of dense molecular clouds.

Three-Dimensional Imaging of Biological Tissue by Cryo X-Ray Ptychography.

High-throughput three-dimensional cryogenic imaging of thick biological specimens is valuable for identifying biologically- or pathologically-relevant features of interest, especially for subsequent correlative studies. Unfortunately, high-resolution imaging techniques at cryogenic conditions often require sample reduction through sequential physical milling or sectioning for sufficient penetration to generate each image of the 3-D stack. This study represents the first demonstration of using ptychographic hard X-ray tomography at cryogenic temperatures for imaging thick biological tissue in a chemically-fixed, frozen-hydrated state without heavy metal staining and organic solvents. Applied to mammalian brain, this label-free cryogenic imaging method allows visualization of myelinated axons and sub-cellular features such as age-related pigmented cellular inclusions at a spatial resolution of ~100 nanometers and thicknesses approaching 100 microns. Because our approach does not require dehydration, staining or reduction of the sample, we introduce the possibility for subsequent analysis of the same tissue using orthogonal approaches that are expected to yield direct complementary insight to the biological features of interest.

Reducing necrotizing enterocolitis in very low birth weight infants using quality-improvement methods.

OBJECTIVE: Owing to a rise in necrotizing enterocolitis (NEC, stage ⩾ 2) among very low birth weight (VLBW, birth weight <1500 g) infants from 4% in 2005 to 2006 to 10% in 2007 to 2008, we developed and implemented quality improvement (QI) initiatives. The objective was to evaluate the impact of QI initiatives on NEC incidence in VLBW infants. STUDY DESIGN: In September 2009, we developed an NEC QI multidisciplinary team that conducted literature reviews and reviewed practices from other institutions to develop a feeding protocol, which was implemented in December 2009. The team tracked intervention compliance and occurrence of NEC stage ⩾ 2. In May 2010, we reviewed our nasogastric tube practice and relevant literature to develop a second intervention that reduced nasogastric tube indwelling time. The infants were divided into three groups: baseline (January 2008 to Novovember 2009, n219), QI phase 1 (December 2009 to May 2010, n62) and QI phase 2 (June 2010 to November 2011, n170). RESULT: The NEC incidence did not decrease after implementation of the feeding protocol in QI phase 1 (19.4%) but did decline significantly after changing nasogastric tube management in QI phase 2 (2.9%). Multivariable logistic regression analysis demonstrated a significant relationship between QI phase and the incidence of NEC. CONCLUSION: QI initiatives were effective in decreasing NEC incidence in our high human milk-feeding NICU. Nasogastric tube bacterial contamination may have contributed to our peak in NEC incidence.

Coagulation status in patients with coronary artery disease taking 100 mg aspirin and healthy volunteers using PFA-100® and ROTEM®.

Previous investigation revealed that age is a major risk factor for thomboembolic events. Earlier studies with thrombelastography have demonstrated procoagulant activity in elderly patients with coronary artery disease. The aim of the present study was to investigate age-related differences in the coagulation status of patients with documented coronary artery disease, healthy elderly and healthy young volunteers with the rotation thrombelastography (ROTEM®) and PFA-100®. Measured with ROTEM®, mean clot formation time (CFT (EXTEM)) in healthy young volunteers (120.8 ± 73.5 s) was significantly longer than in healthy elderly (78.3 ± 36.7 s, p < 0.05) and in patients with coronary artery disease (74.3 ± 59.1 s, p < 0.05). No difference was found between healthy elderly and patients with coronary artery disease. The lowest value for mean maximum clot formation (MCF (EXTEM)) was seen in healthy young volunteers (57.0 ± 6.1 mm) which was significantly different to healthy elderly (61.9 ± 4.8 mm, p < 0.05) and patients with coronary artery disease (65.3 ± 8.4 mm, p < 0.05). No difference could be found between healthy elderly and patients with coronary artery disease, although a trend to higher mean MCF (EXTEM) and lower mean CFT (EXTEM)in patients with coronary artery disease was found. Measured with the collagen/epinephrine cartridge of the PFA-100®, healthy young volunteers (166.4 ± 59.5 s) had numerical but insignificantly longer mean closure times compared to healthy elderly (138.5 ± 53.3 s). These findings point to agerelated differences in thrombelastographic parameters. The ROTEM® analysis indicates an increased coagulability in patients with coronary artery disease and healthy elderly compared to healthy young volunteers.

The PFA-100R cannot detect blood group-dependent inhibition of platelet function by eptifibatide or abciximab at therapeutic plasma concentrations.

Previous investigations revealed that AB0 blood groups are associated with divergent concentrations of several coagulation factors. Concentrations of von Willebrand factor (vWF) and factor VIII are lower in individuals with blood group 0 compared to subjects with blood group A, B or AB, which might in turn result in a reduced inhibition of platelet aggregation in individuals with blood group 0. The aim of the present in vitro investigation was to elucidate the impact of AB0 blood group-dependent vWF concentrations on eptifibatide and abciximab mediated inhibition of GPIIb/IIIa function. Platelet function was measured with the platelet function analyzer PFA-100(R) at baseline and at increasing concentrations of eptifibatide and abciximab. It was stratified for blood group 0 vs A. If measured with the collagen/ADP cartridge, blood group 0 was associated with a prolonged mean baseline closure time in comparison with blood group A (94.3 +/- 14.6 s vs. 74.6 +/- 9.9 s, p = 0.007) which was paralleled by reduced concentrations of vWF and factor VIII. In contrast, no statistically significant differences in closure times (167.4 +/- 83.9 s vs. 140.1 +/- 99.0 s, p = 0.562) could be found in the presence of eptifibatide (0.1 microg/ml). Higher concentrations of abciximab (1 microg/ml) than those of eptifibatide were needed to increase the closure times in both cartridges of the PFA-100, but at this concentration of abciximab differences in closure times could not be detected most probably due to higher variability at these drug concentrations. The PFA-100(R) is not suitable for monitoring abciximab or eptifibatide within the therapeutic concentration range because the highest concentrations where the PFA-100(R) had measurable closure times of below 300 s is much too low to lead to the necessary platelet inhibition and, consequently, does not resemble the in vivo situation.

Isospora belli infection after isolated intestinal transplant.

Isospora belli is a protozoan that only affects humans, after ingestion of Isospora's oocysts. Immunocompetent patients usually do not develop the infection. Immunocompromised hosts may have profuse diarrhea with other gastrointestinal symptoms. Treatment is based on trimethoprim-sulfamethoxazole. In 2006 we performed an isolated intestinal transplantation in a patient with ultra-short bowel syndrome. Neither rejection nor clinical problems occurred after transplant, but signs of intestinal inflammation were seen in every protocol biopsy starting at the first month post transplant. Almost 3 months after the procedure, the patient was re-admitted with diarrhea. I. belli infection was diagnosed by detection of the oocysts in stool samples. Antibiotic treatment with trimethoprim-sulfamethoxazole was initiated with excellent outcome and without relapses. To the best of our knowledge, this is the first case of isosporosis in a small bowel recipient.

Circadian variation of platelet function measured with the PFA-100.

The circadian rhythm plays an important role in the physiology and pathophysiology of the human being. Previous investigations revealed a circadian rhythm also in platelet function but these investigations have been limited to optical aggregometry with platelet-rich plasma and low shear stress. The aim of the present study was to further elucidate the impact of the circadian rhythm on platelet function using whole blood at high shear rates. Platelet function determined with the platelet function analyzer PFA-100 and concentration of fibrinogen and factor VIII activity were measured in healthy volunteers during day and night time, and even at shorter intervals (8:00, 12:00, 16:00, 20:00, 22:00, 0:00, 2:00, 4:00, 6:00 h). The mean peak closure time of the collagen/epinephrine cartridge of the PFA-100 was maximal at 2:00 h (192.0 +/- 57.4 s) and declined to the trough value at 8:00 h (140.1 +/- 33.4 s) (p = 0.004). This was paralleled by data from the collagen/ADP cartridge (22:00 h: 99.1 +/- 38.5 s/2:00 h: 81.3 +/- 16.7 s; p = 0.049). Concentration of fibrinogen and factor VIII activity were lowest during night time (22:00-4:00 h). These findings demonstrate a circadian rhythm in platelet function as measured with the PFA-100. The PFA-100 seems to be an appropriate tool to describe circadian alterations and is easier to use than optical aggregometry in analogous studies.

Impact of ABO blood groups on tirofiban mediated inhibition of platelet function.

Previous investigations revealed that ABO blood groups are associated with divergent concentrations of several coagulation factors. Concentrations of von Willebrand factor (vWF) and factor VIII are lower in individuals with blood group O as compared to subjects with blood group A, B or AB which might result in a reduced inhibition of platelet aggregation. The aim of the present in-vitro-investigation was to elucidate the impact of ABO blood group dependent vWF concentrations on tirofiban mediated inhibition of GPIIb/IIIa function. Platelet function was measured with the platelet function analyzer PFA-100 at baseline and at increasing concentrations of tirofiban and stratified for blood group O vs. A. If measured with the collagen/epinephrine cartridge, blood group O was associated with a prolonged mean baseline closure time in comparison with blood group A (175.8 +/- 64.9 s vs. 121.4 +/- 33.4 s, p = 0.037) which was paralleled by reduced concentrations of vWF and factor VIII. In contrast, no differences in closure time (227.6 +/- 76.1 s vs. 223.9 +/- 81.9 s, p = 0.96) could be found in the presence of tirofiban (0.1 microg/ml). Thus, tirofiban mediated GP IIb/IIIa receptor antagonism as determined with the PFA-100 seems to be independent on plasma concentration of vWF.

Storage of single donor platelet concentrates: paired comparison of storage as single or double concentrates.

Modern cell separators allow the collection of two plateletpheresis concentrates (PCs) at one session. This study evaluates the quality of PCs stored as double concentrates in standard storage containers of two manufacturers. We collected 20 PCs that contained 4.5 x 10(11) platelets in 375 ml plasma (10 using the COBE Spectra and 10 using the Fresenius AS.TEC 204 with 500 ml bags) that were split into one unit of 3.0 x 10(11) platelets in 250 ml (3.0-PC) and one of 1.5 x 10(11) platelets in 125 ml (1.5-PC). Storage of one 3.0-PC per bag of a two-bag system corresponded to storage conditions for double PCs and storage of one 1.5-PC per bag to storage conditions of single PCs. Cell counts, blood gas analysis, glucose and lactate levels, platelet aggregation, and activation and plasma levels of beta- thromboglobulin (beta-TG) and complement factor 3a (C3a) were measured before storage and again on days 3 and 5. COBE 3.0-PCs demonstrated less pH rise, lactate production, CD 62P expression and beta-TG plasma levels, and better aggregability after storage than COBE 1.5-PCs. Fresenius 1.5-PCs had similar platelet quality to COBE 3.0-PCs. Fresenius 3.0-PCs showed a fall of pH (day 5: 6.22 +/- 0.56), the highest amount of anaerobic glycolysis compared to all other storage conditions investigated, high CD 62P- expression and beta-TG plasma levels, and impaired aggregability on days 3 and 5. The highest C3a levels were found in COBE 1.5-PCs. 3.0 x 10(11) platelets in 250 ml plasma should be stored either in one bag of the COBE system or in two 500 ml bags of the Fresenius system. The COBE two-bag system allows the storage of two PCs without loss of platelet quality. Two PCs should not be stored in the Fresenius C4L 500 ml storage containers.

Platelet activation through triathlon competition in ultra-endurance trained athletes: impact of thrombin and plasmin generation and catecholamine release.

The aims of this study were to evaluate whether platelets are activated during strenuous exercise in healthy athletes. Also, to determine the impact of plasmin and thrombin activity and catecholamine release. Previous studies have shown activation of the hemostatic system after competitive exercise, but platelet activation was thought to be absent in trained athletes. The impact of thrombin and other potent platelet activators is still a matter for debate. We examined 30 healthy triathletes during a triathlon competition. Flow cytometric detection of CD62p (P-selectin) was used to measure in vivo activation of platelets. Platelet-leukocyte aggregates were also determined. Thrombin concentration was assessed by the thrombin-antithrombin III complex (TAT) and the fibrinolytic state was characterised by the plasmin-alpha2-antiplasmin complex (PAP). Catecholamines were measured by means of high-pressure liquid chromatography. CD62p rose from baseline (2.3%) to 3.4% and was still elevated after 2 hours (3.1%, p = 0.0133). Platelet-leukocyte aggregates were elevated 30 min after exercise (4.3 % vs 3.6%) and decreased significantly after 60 min (2.9 %, p = 0.008). TAT increased from 3.9 microg/l to 8.3 microg/l after competition and to 5.4 microg/l 2 hours later (p < 0.001). PAP increased 10-fold from 350 microg/l to 3,267 microg/l after the triathlon and was still elevated after 2 hours (1,074 microg/l, p<0.001). No linear correlation was found between the hemostatic markers, catecholamines and platelet activation. Platelets, coagulation and fibrinolysis are activated by competitive exercise in athletes, whereby fibrinolytic changes are pronounced. Mechanisms of platelet activation during exercise include phenomena other than plasmatic hemostatic factors and catecholamines.

Differential antiplatelet effects of various glycoprotein IIb-IIIa antagonists.

The blockade of platelet glycoprotein IIb-IIIa (GPIIb-IIIa) was recently introduced as a new antiplatelet strategy. At present, various GPIIb-IIIa inhibitors are available to treat patients with acute coronary syndrome or when undergoing percutaneous coronary interventions. The current study systematically evaluates the antiplatelet effects of GPIIb-IIIa inhibitors in clinical use. Using conformation-dependent monoclonal antibodies [ligand-induced binding sites (LIBS-1), PMI-1] and flow cytometry, we showed that the GPIIb-IIIa antagonists abciximab, integrelin, lamifiban, and tirofiban, but not EMD 122347 or YM 337, induced LIBS activity of platelet GPIIb-IIIa. The LIBS activity of GPIIb-IIIa antagonists correlates with a proaggregatory response of fixed platelets pretreated with GPIIb-IIIa antagonists (intrinsic activity). All tested GPIIb-IIIa antagonists completely inhibit concentration-dependent ADP (20 micromol/l)-induced aggregation. In contrast, substantial TRAP (25 micromol/l)-induced platelet aggregation still occurs even at high inhibitor concentrations of the tested GPIIb-IIIa antagonists. In addition, we show that GPIIb-IIIa antagonists are poor inhibitors of platelet release reaction (ATP and P-selectin secretion) especially when strong agonists such as TRAP are used to activate platelets. Inhibition of platelet procoagulant activity (thrombin generation) by GPIIb-IIIa antagonists is dependent on the type and concentration of antagonists and on the strength of stimulus (thrombin, tissue factor) used to induce platelet-dependent thrombin generation. The present data show that significant pharmacological differences exist between GPIIb-IIIa antagonists that may have consequences for antithrombotic strategies and for future drug development.

Paired comparison of apheresis platelet function after storage in two containers.

Platelet quality after storage strongly depends on the pre-storage quality as well as on the storage conditions determined by the storage container. In this paired study, we evaluated two different containers (MedSep CLX and Delmed DPL-110). The Fresenius AS104 cell separator was used to prepare 17 platelet concentrates that were split and distributed into the containers to be compared. Cell counts, blood gas analysis, morphological scores, glucose and lactate levels, platelet activation, and platelet aggregation were measured before splitting at the day of preparation and after storage at day 3 and day 5. At day 3, there was no significant difference between the two bags apart from increased lactate and decreased pCO(2) concentrations in the CLX bags. At day 5 there were significantly higher lactate concentrations, pO(2) levels, and aggregation after stimulation in the CLX group, while the glucose and pCO(2) concentrations were significantly lower in these platelet concentrates as compared to the DPL-110 group. However, these parameters did not influence the functional parameters tested. While the platelet quality decreased during storage in all bags, the functional changes were nearly identical in both bags tested. We conclude that both bags are equivalent for 5-day storage of platelet concentrates.

Effect of gamma radiation on the in vitro aggregability of WBC-reduced apheresis platelets.

BACKGROUND: The effect of gamma radiation on single-donor apheresis platelet concentrates (SDPs) has been elucidated only incompletely. The only existing report on the function of SDPs stored in the irradiated state found a deterioration in the in vitro aggregability at the end of shelf life in SDPs divided before irradiation with 1500 cGy. STUDY DESIGN AND METHODS: The in vitro properties of platelets were examined in four series of irradiated and control platelets, each obtained from the same 15 donors. Irradiation with 3000 cGy was performed on Days 0, 3, and 5. Cellular content, aggregability by ADP alone or ADP and epinephrine, spontaneous and induced CD62 expression, beta-thromboglobulin release, glucose consumption, lactate production, and pH were measured immediately after preparation and on Days 3 and 5 after donation. RESULTS: Comparable in vitro properties were measured in irradiated and control platelets, whether irradiation was performed on Day 3 or Day 5. However, in platelets irradiated on Day 0, we found a significantly better in vitro aggregability by 20 microM: ADP immediately after irradiation and by 10 microM: ADP and 2 microM: epinephrine at the end of shelf life than was found in the other groups (Day 5 results: Day 0 irradiation: 75 +/- 32%; Day 3 irradiation: 45 +/- 45%; Day 5 irradiation: 47 +/- 41%; control: 40 +/- 24%; p<0.05). CONCLUSION: Gamma radiation had no adverse effect on platelet quality in extremely WBC-reduced SDPs. On the contrary, a slight, but significantly better in vitro aggregability was found in SDPs irradiated before storage than in platelets irradiated later during storage and in unirradiated platelets. This increased in vitro aggregability persisted until the end of shelf life.

Changes in surface expression of platelet membrane glycoproteins and progression of heart transplant vasculopathy.

BACKGROUND: Transplant vasculopathy is the main limiting factor of the long-term success of heart transplantation. We sought to establish the role of platelets in the development and progression of transplant vasculopathy. METHODS AND RESULTS: Platelet analysis and intracoronary ultrasound examination were performed in 78 heart transplant recipients. Quantitative intracoronary ultrasound was used to define the severity of disease at baseline (48.8+/-4.5 months after transplantation) and at 1-year follow-up. Platelet activation was assessed with the use of immunological surface markers of activation (ligand-induced binding site 1 [LIBS-1], P-selectin, GPIIb-IIIa) and flow cytometry. We found that LIBS-1 immunoreactivity was significantly increased in patients with diffuse disease when compared with focal transplant disease (median [quartile], 27[14, 64] versus 18[7.9, 47], P=0.04). In a logistic regression model, we found that LIBS-1 was an independent predictor for the presence and progression of diffuse transplant vasculopathy (P=0.04). Patients with enhanced LIBS-1 levels (>75% quartile) had a 3.3-fold increased relative risk (95% CI 1.8 and 18.9, P=0.002) for the presence of diffuse transplant vasculopathy. When a cutoff value of 16.5 for the level of LIBS-1 was used, patients had a 4.8-fold increased relative risk (95% CI 1.9 and 12.5, P<0.01) for the progression of transplant vasculopathy. CONCLUSIONS: Enhanced platelet activation is strongly associated with the development and progression of transplant vasculopathy. Understanding the underlying pathophysiological mechanisms might contribute to the development of treatment strategies to prevent transplant vasculopathy.

Incomplete inhibition of platelet aggregation and glycoprotein IIb-IIIa receptor blockade by abciximab: importance of internal pool of glycoprotein IIb-IIIa receptors.

Resting platelets contain a substantial internal pool of GPIIb-IIIa complexes that is exposed on the surface of activated platelets. Whether the exposure of internal GPIIb-IIIa complexes on the activated platelet surface affects therapy with GPIIb-IIIa antagonists is poorly understood. We addressed this issue in thirteen patients who underwent elective coronary stenting and received abciximab. Platelet aggregation, surface expression of GPIIb-IIIa and P-selectin, receptor blockade of GPIIb-IIIa, and platelet release in response to ADP and thrombin-receptor activating peptide (TRAP) were determined ex vivo by Lumi-aggregometry and flow cytometry before, during and after abciximab administration. We found that inhibition of aggregation and GPIIb-IIIa blockade of ADP-stimulated platelets was almost complete during abciximab administration. In contrast, when TRAP was used to stimulate platelets ex vivo aggregation was only partially inhibited, most likely due to release of internal pool of unblocked GPIIb-IIIa complexes. Using electron microscopy we found that 7E3-occupied GPIIb-IIIa complexes are internalized into the surface connected system (SCS) and the alpha-granules of washed platelets which was associated with a reduced degranulation of the alpha-granula membrane protein P-selectin. We conclude, that despite internalization of abciximab into the internal pool of GPIIb-IIIa, upon strong platelet activation with thrombin a significant amount of unblocked internal GPIIb-IIIa can be exposed on the platelet surface and mediate platelet aggregation. Incomplete blockade of the internal GPIIb-IIIa pool may limit clinical efficacy of abciximab.

Activation of blood platelets in response to maximal isometric exercise of the dominant arm.

Isometric exercise is a popular form of physical activity for many people. Only few studies exist on the effects of this type of exercise on the hemostatic system. Eleven male healthy subjects (21-42 years) of varying fitness levels were investigated before, immediately after and 10 min after strenuous isometric exercise of the dominant arm. Blood samples were drawn by repetitive puncture from both the exercising and the contralateral arm. The following variables were studied: Prothrombin time and partial thromboplastin time as group tests for the plasmatic coagulation system; platelet count as well as p-selectin expression for the platelet system; tissue plasminogen activator (t-PA) activity and antigen for the fibrinolytic system. The partial thromboplastin time was shortened immediately after maximal isometric exercise of the dominant arm, the prothrombin time remained unchanged. No change was found in the platelet count, but a marked p-selectin expression was observed immediately after maximal isometric exercise of the dominant arm (p < 0.05) and even in the resting contralateral arm. Values returned to baseline after 10 min. There was a slight increase of t-PA antigen concentration and white blood cell count at maximal isometric contraction which did not occur in the resting arm, although changes over the 3 time points were significant in both arms. Maximal isometric exercise leads to platelet activation in both arms, a slight aPTT decrease and t-PA antigen increase in local blood stream. As compensatory fibrinolytic changes do not occur, it is an open question whether isometric exercise increases the potential risk of thromboembolism.

CpG DNA overcomes hyporesponsiveness to hepatitis B vaccine in orangutans.

Oligonucleotides containing immunostimulatory CpG motifs (CpG ODN) have been shown to be potent Th1-type adjuvants for augmenting antigen-specific responses in mice against hepatitis B surface antigen (HBsAg). The hepatitis B virus (HBV) infects only humans and great apes and appears to exist among wild chimpanzees and orangutans. An outbreak of HBV among orangutans being rehabilitated for re-introduction to the jungle caused the death of several animals. A prophylactic vaccination program revealed that orangutans are quite hypo-responsive to a current commercial vaccine compared to results obtained previously in humans and chimpanzees. Addition of CpG ODN to hepatitis B vaccine greatly increased the seroconversion rate and the titers of antibody against HBsAg (anti-HBs). This is the first demonstration of CpG DNA in a great ape and the results have important implications for the vaccination of humans against HBV and other diseases.