Psychological distress in cervical cancer screening: results from a German online survey.

PURPOSE: The PODCAD study aimed at assessing the degree of psychological stress that women experience due to notification of an abnormal Papanicolaou (Pap) smear finding or a positive human papillomavirus (HPV) test result. METHODS: We designed a survey to address the question of psychological burden due to abnormal Pap smear results and/or positive HPV tests. In this online campaign approach, we aimed to reach > 2000 women all over Germany irrespective of kind and number of abnormal screening findings. We asked for different kinds of anxiety, distress and uncertainty regarding both, Pap and HPV status. RESULTS: A total of 3753 women completed the survey at least partially, and almost 2300 fully completed the survey. Of these, more than 50% were affected already since more than 1 year, and almost half of them had experienced at least three Pap smears in follow-up examinations. Almost 70% of the women were afraid of developing cancer. Intriguingly, almost half of the women with abnormal findings were not aware of their stage of the Pap smear. Furthermore, almost 30% of the women displayed signs of a post-traumatic stress disorder. CONCLUSION: Abnormal results in cervical cancer screening have an impact on patients' psychology, irrespective of the knowledge and severity of the findings. Better information concerning risks and benefits of cervical cancer screening and about the meaning of the outcome of its procedures are required to decrease this anxiety.

[Feline leukemia virus infection: importance and current situation in Switzerland]. / Die feline Leukämievirus-Infektion: Bedeutung und aktuelle Situation in der Schweiz.

INTRODUCTION: Feline leukemia virus (FeLV) leads to fatal disease in cats with progressive infection. The aim of this study was to determine the importance of FeLV infection in Switzerland and make a comparison with previous studies. Of 881 blood samples taken from cats living in Switzerland (minimum of 20 samples per Canton), 47 samples were provirus-positive (5.3%; 95% confidence interval (CI) 3.9-7.0%) and 18 samples were antigen-positive (2%; 95% CI 1.2-3.2%). Together with data previously collected in similar studies, these findings demonstrated a decrease in prevalence between 1997 and 2003 followed by a relative constant low prevalence thereafter. Young cats (=2 years) were more frequently infected than older cats, but FeLV-positive cats were up to 15 (antigen-positive) and 19 (provirus-positive) years old. Sexually intact cats were more frequently viremic than neutered cats; purebred cats were somewhat less frequently FeLV-positive than non-purebred cats. In a second study, in which 300 saliva samples were analyzed, samples from 5 cats were FeLV-RNA positive (1.7%; 95% CI, 0.5-3.8%), although one young feral cat had been falsely assumed to be FeLV-negative based on a point-of-care test. Of the 300 cats, only 50% were FeLV tested or vaccinated, although 90% of the cats were at risk of exposure to FeLV. Testing and vaccination of all cats with exposure risk may help further decrease the prevalence of FeLV infection. Moreover, characteristics of FeLV tests should be considered, such as the risk of false negative results in the early phase of infection when performing antigen testing.

INTRODUCTION: Le virus leucémogène félin (FeLV) conduit la plupart du temps à une maladie mortelle chez le chat avec une infection progressive. Le but du présent travail est de mettre en évidence l'importance de l'infection à FeLV en Suisse sur la base de recherches actuelles et de la comparer avec les résultats de recherches antérieures. Afin de répondre à la question de savoir combien de chats présentés à la consultation étaient porteurs du FeLV (positifs au provirus) respectivement excréteurs de FeLV (positifs à l'antigène), on a analysé 881 échantillons sanguins provenant de toute la Suisse (au minimum 20 par canton) : 47 échantillons étaient positifs au provirus (5.3%; 95% intervalle de confiance (CI) 3.9­7.0%) et 18 positifs à l'antigène (2%; 95% CI 1.2­3.2%). Une comparaison avec des recherches semblables faites antérieurement montre que la prévalence du FeLV a diminué entre 1997 et 2003 mais qu'elle stagne depuis lors. Actuellement ce sont plutôt les jeunes chats (=2 ans) qui sont touchés plutôt que les vieux; des chats ont toutefois été trouvés positifs jusqu'à l'âge de 15 ans (positifs à l'antigène) respectivement de 19 ans (positifs au provirus). Les chats non castrés étaient plus souvent virémiques que les castrés et les chats de races étaient aussi, mais un peu moins fréquemment FeLV-positifs. Dans une autre étude suisse, dans laquelle 300 échantillons de salive de chats ont été testés quant à la présence d'ARN-FeLV, 5 chats étaient excréteurs (1.7%; 95% CI 0.5­3.8%). Un jeune chat trouvé, qui avait été testé négatif au test rapide, a été trouvé infecté par le FeLV au moyen de la mise en évidence d'ARN. Sur ces 300 chats, seuls environ 50% avaient été testés quant au FeLV respectivement vaccinés, bien qu'environ 90% aient présenté un risque d'exposition au FeLV. Pour diminuer encore la prévalence du FeLV, il conviendrait de tester et de vacciner tous les chats avec un risque d'exposition au virus. Dans ce contexte, il faut tenir compte des différentes caractéristiques des tests comme la non reconnaissance de la phase d'infection très précoce au moyen du test FeLV rapide.

CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (Pcorrected<0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, ß=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.

Expression and characterization of a recombinant i-type lysozyme from the harlequin ladybird beetle Harmonia axyridis.

Lysozymes are enzymes that destroy bacterial cell walls by hydrolysing the polysaccharide component of peptidoglycan. In insects, there are two classes of lysozymes, the c-type with muramidase activity and the i-type whose prototypical members from annelids and molluscs possess both muramidase and isopeptidase activities. Many insect genes encoding c-type and i-type lysozymes have been identified during genome and transcriptome analyses, but only c-type lysozymes have been functionally characterized at the protein level. Here we produced one of five i-type lysozymes represented in the immunity-related transcriptome of the invasive harlequin ladybird beetle Harmonia axyridis as recombinant protein. This was the only one containing the serine and histidine residues that are thought to be required for isopeptidase activity. This i-type lysozyme was recombinantly expressed in the yeast Pichia pastoris, but the purified protein was inactive in both muramidase and isopeptidase assays. Transcription and immunofluorescence analysis revealed that this i-type lysozyme is produced in the fat body but is not inducible by immune challenge. These data suggest that i-type lysozymes in insects may have acquired novel and as yet undetermined functions in the course of evolution.

Detection of 'Candidatus Neoehrlichia mikurensis' and other Anaplasmataceae and Rickettsiaceae in Canidae in Switzerland and Mediterranean countries.

INTRODUCTION: 'Candidatus Neoehrlichia mikurensis' is an emerging tick-borne zoonotic agent that primarily affects immunocompromised human patients. Dogs and foxes are frequently exposed to ticks, and both species are in close proximity to humans. This is the first study to systematically investigate the occurrence of 'Candidatus Neoehrlichia mikurensis' in Canidae in Europa. We analyzed 1'739 blood samples from dogs in Switzerland, Italy, Spain and Portugal and 162 blood samples from free-ranging red foxes (Vulpes vulpes) in Switzerland. All samples were tested using a previously described multiplex real-time PCR for the Anaplasmataceae family, the 'Candidatus Neoehrlichia' genus and the 'Candidatus Neoehrlichia mikurensis' species. All Anaplasmataceae positive samples were subsequently tested using specific real-time PCRs for Anaplasma phagocytophilum, Anaplasma platys, Ehrlichia canis and Rickettsia helvetica. Among the tested animals, one dog from Zurich tested positive for 'Candidatus Neoehrlichia mikurensis'. The 12-year old West Highland white terrier had been splenectomized 3 months prior to the blood collection and presented with polyuria/polydipsia. Fanconi syndrome was diagnosed based on glucosuria with normoglycemia and hyperaminoaciduria. A. platys and E. canis were detected in 14/249 dogs from Sicily and Portugal; two of the dogs were coinfected with both agents. Four Swiss foxes tested positive for A. phagocytophilium. R. helvetica was detected for the first time in a red fox. In conclusion, 'Candidatus Neoehrlichia mikurensis' infection should be considered in sick dogs, particularly when immunocompromised. The pathogen seems not to be widespread in Canidae in the investigated countries. Conversely, other Anaplasmataceae were more readily detected in dogs and foxes.

INTRODUCTION: 'Candidatus Neoehrlichia mikurensis' est un agent de zoonose transmis par les tiques qui gagne en importance et concerne principalement les patients immunosupprimés. Les chiens comme les renards sont souvent concernés par des morsures de tiques et vivent en contact étroit avec les êtres humains. Dans le présent travail, nous étudions pour la première fois systématiquement la présence de 'Candidatus Neoehrlichia mikurensis' chez les canidés en Europe. Les échantillons sanguins analysés provenaient de 1'739 chiens de Suisse, d'Italie, d'Espagne et du Portugal ainsi que de 162 renards (Vulpes vulpes) de Suisse. Tous les échantillons ont été examinés avec un test de PCR multiplex en temps réel déjà publié quant à la présence d'agents de la famille des Anaplasmataceae, du genre 'Candidatus Neoehrlichia' et de l'espèce 'Candidatus Neoehrlichia mikurensis'. Les échantillons positifs aux Anaplasmataceae ont ensuite été testés avec un test PCR en temps réel spécifique quant à Anaplasma phagocytophilum, Anaplasma platys, Ehrlichia canis und Rickettsia helvetica. Parmi les échantillons examinés se trouvait celui d'un chien de Zürich qui était infecté par 'Candidatus Neoehrlichia mikurensis'. Ce West Highland White Terrier de 12 ans avait été présenté pour polyurie/polydipsie; il avait été splénectomisé trois mois avant la prise de l'échantillon. Au vu d'une glycosurie et d'une hyperaminoacidurie accompagnées d'une glycémie normale, on a posé le diagnostic de syndrome de Fanconi. A. platys et E. canis ont été mis en évidence chez 14/249 chiens provenant de Sicile et du Portugal; deux chiens étaient infectés par les deux agents pathogènes. Quatre renards suisses étaient positifs à A. phagocytophilium et R. helvetica a été trouvé pour la première fois chez un renard. En résumé, on peut dire qu'une infection à 'Candidatus Neoehrlichia mikurensis' chez un chien malade doit être prise en considération comme diagnostic différentiel, particulièrement chez les anomaux immunosupprimés. Toutefois cet agent n'est pas très répandu chez les canidés des pays examinés, contrairement aux autres Anaplasmataceae spp. qui ont été trouvées plus souvent chez les chiens et les renards.

[Subcutaneous cervical and left thoracic emphysema in a 49-year-old woman on ventilation]. / Zervikales und linksthorakales Weichteilemphysem bei einer 49-jährigen beatmeten Patientin.

We report the case of a 49-year-old woman who was admitted with community-acquired pneumonia. The medical state worsened despite administration of antibiotics. She was intubated and ventilated because of respiratory distress. Several hours after intubation, she developed massive subcutaneous emphysema. The bronchoscopy showed tracheal transmural rupture 3 cm long on the posterior wall of the trachea. The high-risk surgery and massive doses of catecholamine favoured conservative treatment with bilateral endobronchial intubation and veno-venous extracorporeal membrane oxygenation. The patient made a full recovery.

Antiviral therapy in cats progressively infected with feline leukaemia virus: lessons from a series of 18 consecutive cases from Australia.

BACKGROUND: It is doubtful that any of the treatments proposed for feline leukaemia virus (FeLV) infection are effective, despite the entity being described 60 years ago. METHODS: Eighteen pet cats with progressive FeLV infections were recruited in Australia. One or more antiviral drugs were trialled in 16 cats, while two FeLV-infected cats were not handleable and served as untreated controls. Six cats were administered RetroMAD1™ only (0.5 mg/kg orally twice daily), a commercially available recombinant chimeric protein with proposed antiretroviral activity. Three cats were administered the integrase inhibitor raltegravir only (10-15 mg/kg orally twice daily), a drug used as a component of highly effective antiretroviral therapy for human immunodeficiency virus (HIV-1) infection. Three cats were administered RetroMAD1™ and raltegravir concurrently, and four cats were administered raltegravir and the reverse transcriptase inhibitor zidovudine (AZT, 5 mg/kg orally twice daily) concurrently. FeLV RNA and p27 antigen loads were measured at two timepoints (T1-2 months and T3-5 months) during therapy and compared to baseline (pretreatment) levels, to assess the response to therapy using linear modelling. The median survival time (MST) of the cats from commencement of FeLV treatment to death was also determined and compared between treatments. RESULTS: The MST for the 16 FeLV-positive cats which received antiviral therapy was 634 days, while the MST from FeLV diagnosis to death for the two untreated control cats was 780 days. In cats treated with RetroMAD1™, FeLV viral load decreased from T0 to T1-2 months (median viral load reduced from 1339 × 106 to 705 × 106 copies/mL plasma; P = 0.012), but MST was reduced compared to cats not given RetroMAD1™ (426 days vs 1006 days; P = 0.049). Cats treated with raltegravir and AZT had no significant changes in FeLV viral load over time, but p27 antigen load was decreased from T0 to T3-5 months in cats treated with raltegravir (median p27 antigen level reduced from 50.2% to 42.7%; P = 0.005). All other results were not significantly affected by the treatment provided. Importantly, statistically significant and substantial associations were found between age at FeLV diagnosis and survival time (P = 0.046, R2 = 18.6) and between FeLV viral load at T0 and survival time (P = 0.004, R2 = 44.4). Younger cats, and cats with higher levels of pretreatment FeLV RNA, had reduced survival times. Cats treated with RetroMAD1™ were typically younger (median age 2.0 vs 8.0 years), likely explaining the observed reduction in MST. A significant association was found between FeLV viral load and p27 antigen load at T0 (P = 0.015, R2 = 32.9). CONCLUSIONS: Results from this small case series do not provide convincing support for the use of RetroMAD1™, raltegravir or AZT, alone or in combination, for the treatment of cats progressively infected with FeLV. The changes observed were biologically insignificant. Age and FeLV viral load at diagnosis are useful prognostic markers, and p27 antigen concentration can be used to predict viral load. Larger field trials should be performed examining antiretroviral therapy in FeLV-positive cats with progressive infections, preferably using three or more drugs from at least two classes, as is standard with human antiretroviral therapy. Future studies would be easier in countries with a higher prevalence of FeLV infections than Australia.

An armed oncolytic measles vaccine virus eliminates human hepatoma cells independently of apoptosis.

Due to late diagnosis and a pronounced chemoresistance, most patients with hepatocellular carcinoma (HCC) have an overall poor prognosis. Measles vaccine viruses (MeV) have been shown to possess anti-tumor properties and their efficacy has been enhanced by arming with suicide genes. To test armed MeV for the treatment of HCC, we equipped it with the suicide gene Super-cytosine deaminase (SCD) and tested the efficacy in cell culture and in a mouse xenograft model of human HCC. Prodrug conversion was investigated in cell culture and quantified by high-performance liquid chromatography. We observed a strong oncolytic activity of MeV-SCD against human HCC in vitro and in vivo. The prodrug was efficiently converted in infected cells leading to a significant enhancement of the cytotoxic effect. Treatment of HCC xenografts with MeV caused long-term virus replication in tumor tissue. We show that the suicide gene therapy induces an apoptosis-like cell death but is not dependent on intact apoptosis pathways. These results demonstrate that MeV-based suicide gene therapy is a promising novel therapy regimen for HCC overcoming resistance towards conventional therapy. The independence from apoptosis raises hopes for the treatment of patients whose tumor cells exert defects in this cell death mechanism.

Smoking is associated with impaired long-term glucose metabolism in patients with type 1 diabetes mellitus.

BACKGROUND AND AIMS: Smoking is known to negatively influence glucose metabolism both in healthy subjects and in patients with diabetes. The aim of this study was to compare glycemic control in patients with type 1 diabetes mellitus who were smokers with those who did not smoke during a prospective long-term follow-up. METHODS AND RESULTS: In a single center, 763 patients with type 1 diabetes mellitus were included, 160 (21.0%) of them were smokers. Patients were treated with intensive insulin therapy according to existing guidelines. Glucose control was monitored quarterly, diabetes related complications and cardiovascular risk factors were assessed at least once a year. Glucose control in smokers was significantly worse than in non-smokers at baseline and during follow-up (mean HbA1c during 5047 patient-years of follow-up 7.9 ± 1.3% in smokers and 7.3 ± 1.1% in non-smokers, p < 0.001) despite a higher insulin dosage in smokers (0.71 ± 0.30 U/kg vs. 0.65 ± 0.31 U/kg in non-smokers, p = 0.046). HDL cholesterol was lower in smokers at baseline (1.53 ± 0.45 vs. 1.68 ± 0.51 in non-smokers, p = 0.048). Diabetes related complications tended to occur with a higher frequency in smokers, with a significant difference in macroalbuminuria (9.8% vs. 4.8% in non-smokers, p = 0.047). CONCLUSION: Smoking is associated with worse glucose control in patients with type 1 diabetes mellitus despite the same treatment strategies as in non-smokers. Hyperglycemia, therefore, may contribute to an earlier incidence of diabetes related complications in these patients, in addition to direct toxic effects of smoking.

Body iron stores and risk of type 2 diabetes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study.

AIMS/HYPOTHESIS: The aim of this study was to prospectively examine the association between body iron stores and risk of type 2 diabetes. METHODS: We designed a case-cohort study among 27,548 individuals within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. During 7 years of follow-up, 849 incident cases of type 2 diabetes were identified. Of these, 607 remained for analyses after exclusion of participants with missing data or abnormal glucose levels at baseline. A sub-cohort of 2,500 individuals was randomly selected from the full cohort, comprising 1,969 individuals after applying the same exclusion criteria. RESULTS: After adjustment for age, sex, BMI, waist circumference, sports activity, bicycling, education, occupational activity, smoking habit, alcohol consumption and circulating levels of γ-glutamyltransferase, alanine aminotransferase, fetuin-A, high-sensitivity C-reactive protein, adiponectin, HDL-cholesterol and triacylglycerol, higher serum ferritin concentrations were associated with a higher risk of type 2 diabetes (RR in the highest vs lowest quintile, 1.73; 95% CI 1.15, 2.61; p(trend) = 0.002). No significant association was observed for soluble transferrin receptor (RR 1.33; 95% CI 0.85, 2.09; p(trend) = 0.50). The soluble transferrin receptor-to-ferritin ratio was significantly inversely related to risk (RR 0.61; 95% CI 0.41, 0.91; p(trend) = 0.02). CONCLUSIONS/INTERPRETATION: High ferritin levels are associated with higher risk of type 2 diabetes independently of established diabetes risk factors and a range of diabetes biomarkers whereas soluble transferrin receptor concentrations are not related to risk. These results support the hypothesis that higher iron stores below the level of haemochromatosis are associated with risk of type 2 diabetes.

Exercise-induced albuminuria is associated with perivascular renal sinus fat in individuals at increased risk of type 2 diabetes.

AIMS/HYPOTHESIS: Microalbuminuria represents an established surrogate marker of early diabetic nephropathy and glomerular microangiopathy. Increasing evidence is emerging of a role of perivascular adipose tissue (PVAT) as an important link between obesity, insulin resistance and both macro- and microangiopathy. It is not known whether perivascular renal sinus fat (RSF) has an impact on microalbuminuria in the prediabetic stage. We investigated whether RSF quantified by MRI is associated with microalbuminuria before or after exercise. METHODS: Non-diabetic individuals at increased risk of type 2 diabetes were recruited into the Tübingen Lifestyle Intervention Program (TULIP); 146 participants took part in the analysis. RSF was measured in axial MRI sections at the level of the renal artery. Urine was collected before and after exercise stress testing. RESULTS: Participants (age 47 ± 12 years; mean ± SD) reached a mean exercise load of 176 ± 49 W, with a mean arterial peak pressure (MAPP) of 112 ± 14 mmHg. After adjusting for sex, age, visceral adipose tissue (VAT) and MAPP during exercise, RSF was significantly associated with postexercise albumin/creatinine ratio (ACR; p = 0.006). No association between RSF and baseline BP could be observed after adjusting for confounders (p = 0.26), and there was no association between RSF and baseline ACR either (p = 0.2). CONCLUSIONS: RSF is associated with exercise-induced albuminuria independently of sex, age, VAT and MAPP in a non-diabetic cohort at diabetic risk. We conclude that PVAT in the renal sinus may play a role in the pathogenesis of microalbuminuria.

[Primary hyperaldosteronism in cats]. / Primärer Hyperaldosteronismus bei Katzen.

Primary hyperaldosteronism is a clinical syndrome characterized by an elevated aldosterone secretion by the adrenals. The present case series describes 7 cats with primary hyperaldosteronism, which were presented between 2002 and 2011. Common clinical symptoms were weakness, anorexia, cervical ventroflexion and blindness. All cats showed hypokalemia. In 6 cats, blood pressure was determined: 5 cats showed hypertension, of which 4 animals exhibited retinal detachment and blindness. In the ultrasonographic examination, unilateral adrenomegaly was present in 6 cats whereas one animal showed normal adrenals. In 4 cats, the serum aldosterone concentration was above the reference range. Five cats underwent unilateral adrenalectomy, which was accomplished uneventfully and returned the electrolytes back to normal. Histopathological examination of the adrenals revealed 2 carcinomas and 4 adenomas; one cat with ultrasonographic normal adrenals exhibited bilateral nodular hyperplasia.

Resistance mechanisms in BRAFV600E paediatric high-grade glioma and current therapeutic approaches.

Paediatric high-grade gliomas (pHGG) are aggressive central nervous system tumours with a poor prognosis. BRAFV600E mutant pHGGs can be treated with targeted BRAF inhibitors, which have shown both preclinical activity and potent clinical efficacy. Unfortunately, the development of drug resistance results in disease relapse or progression and is the primary cause of treatment failure. While there is a lot of data to explain mechanisms of resistance in other BRAFV600E tumours, comparatively little is known about the mechanisms of BRAF inhibitor resistance in BRAFV600E pHGG. Recent literature has identified aberrations in members of the RAS/RAF/ERK pathway, the PI3K/AKT/MTOR pathway and the cell cycle as major contributors to the resistance profile. A range of novel therapies have been suggested to overcome BRAF inhibitor drug resistance in BRAFV600E pHGG. This review will discuss the current literature available for BRAF inhibitor resistant BRAFV600E pHGGs and provide an overview of the currently available and proposed therapies.

Feline leukemia virus outbreak in the critically endangered Iberian lynx (Lynx pardinus): high-throughput sequencing of envelope variable region A and experimental transmission.

The Iberian lynx is the most endangered felid species. During winter/spring 2006/7, a feline leukemia virus (FeLV) outbreak of unexpected virulence killed about 2/3 of the infected Iberian lynxes. All FeLV-positive animals were co-infected with feline hemoplasmas. To further characterize the Iberian lynx FeLV strain and evaluate its potential virulence, the FeLV envelope gene variable region A (VRA) mutant spectrum was analyzed using the Roche 454 sequencing technology, and an in vivo transmission study of lynx blood to specified-pathogen-free cats was performed. VRA mutations indicated weak apolipoprotein B mRNA editing enzyme and catalytic polypeptide-like cytidine deaminase (APOBEC) restriction of FeLV replication, and variants characteristic of aggressive FeLV strains, such as FeLV-C or FeLV-A/61C, were not detected. Cats exposed to FeLV/Candidatus Mycoplasma haemominutum-positive lynx blood did not show a particularly severe outcome of infection. The results underscore the special susceptibility of Iberian lynxes to infectious diseases.

Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection.

Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50-70% of all infected children seem to acquire HIV-1 shortly before or during delivery. Epidemiological evidence indicates that mucosal exposure is an important aspect of intrapartum HIV transmission. A simian immunodeficiency virus (SIV) macaque model has been developed that mimics the mucosal exposure that can occur during intrapartum HIV-1 transmission. To develop immunoprophylaxis against intrapartum HIV-1 transmission, we used SHIV-vpu+ (refs. 5,6), a chimeric simian-human virus that encodes the env gene of HIV-IIIB. Several combinations of human monoclonal antibodies against HIV-1 have been identified that neutralize SHIV-vpu+ completely in vitro through synergistic interaction. Here, we treated four pregnant macaques with a triple combination of the human IgG1 monoclonal antibodies F105, 2G12 and 2F5. All four macaques were protected against intravenous SHIV-vpu+ challenge after delivery. The infants received monoclonal antibodies after birth and were challenged orally with SHIV-vpu+ shortly thereafter. We found no evidence of infection in any infant during 6 months of follow-up. This demonstrates that IgG1 monoclonal antibodies protect against mucosal lentivirus challenge in neonates. We conclude that epitopes recognized by the three monoclonal antibodies are important determinants for achieving substantial protection, thus providing a rational basis for AIDS vaccine development.

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

Investigations into the antiadhesive activity of herbal extracts against Campylobacter jejuni.

Campylobacter jejuni is one of the most common bacterial causes of diarrhoea in the industrialized world, being associated with the occurrence of Guillain-Barré Syndrome, and inducing diseases partially through intestinal adherence. With increasing reports of C. jejuni drug resistance against standard antibiotics, investigations into antiadhesive agents for the prevention of bacterial infection are highly significant. Given the consumer-driven development towards holistic and integrative healthcare, research into additional anti-Campylobacter effects of herbal medicines that are already used for their beneficial effects on bowel and digestive functions is important. Twenty-one herbal extracts were screened for antiadhesive activity against C. jejuni using modifications of previously published antiadhesion assays. Antiadhesion effects with IC(50) values <3 mg/mL were obtained for seven ethanol plant extracts, with Zingiber officinale (ginger), Capsicum annum (cayenne) and Glycyrrhiza glabra (licorice) displaying the highest antiadhesion activity against C. jejuni (IC(50) : <0.1 mg/mL, 0.29 mg/mL and 0.65 mg/mL, respectively). Differences in antiadhesion activity were found for two different Echinacea species, with E. purpurea displaying significantly higher and dose dependent antiadhesion activity than E. angustifolia. No significant antiadhesion activity (IC(50) values >35 mg/mL) was found for Agrimonia eupatoria (agrimony), Andrographis paniculata (andrographis), Matricaria recutita (chamomile), Foeniculum vulgare (fennel), Filipendula ulmaria (meadowsweet) and Artemisia absinthium (wormwood) extracts. This study provides evidence for additional beneficial effects of marketed herbal medicines in gastrointestinal disorders.

[Valvular heart disease: anesthesia in non-cardiac surgery]. / Herzklappenerkrankungen : Anästhesie bei nichtkardiochirurgischen Eingriffen.

The probability of treating patients with valvular heart disease during non-cardiac surgery increases with the age of the patient. The prevalence of valvular heart disease is approximately 2.5% and increases further in the patient group aged over 75 years old. Patients with valvular heart disease undergoing non-cardiac surgery have an increased perioperative cardiovascular risk depending on the severity of the disease. Knowledge of the hemodynamic alterations and compensation mechanisms which accompany diseases of the valve apparatus is essential for a suitable treatment of patients with such pre-existing diseases. The most common valvular heart diseases lead to volume (mitral valve insufficiency) or pressure load (aortic stenosis) of the left ventricle and in the case of mitral stenosis to a pressure load on the left atrium. Depending on the underlying disease and the type of surgery planned a corresponding choice of anesthesia procedure and medication must be made. In the present review article the pathophysiology of the relevant valvular heart diseases and the implications for perioperative anesthesia management will be presented. An individually tailored extended perioperative monitoring allows hemodynamic alterations to be rapidly recognized and adequately treated.

[FeLV infection in the cat: clinically relevant aspects]. / Die FeLV-Infektion der Katze: Praxis-relevante Aspekte.

The feline leukemia virus (FeLV) is a retrovirus of the domestic cat that was described almost 50 years ago. The FeLV-infection may lead to fatal diseases in domestic and small wild cats. The use of efficacious diagnostics assays and vaccines led to a reduction of the FeLV prevalence; however, FeLV still poses a problem for the cat presented with the infection. This article aims to describe recent developments in diagnostics and findings in the infection pathogenesis that are clinically relevant.