Aortic stiffness in type-1 diabetes mellitus; beware of hypertension

Cardiolog

Children's opinions about organ donation:a first step to assent?

Background: Parents have to decide about organ donation after the death of their child. Although most parents probably would like to respect their child's intentions, parents often are not aware of their child's wishes. This requires insight into children's opinions about donation. Methods: An internet survey that investigated whether Dutch children in the age range of 12 through 15 years had heard about organ donation, what their opinions were on donation and whether the topic had been discussed at home. Questionnaire response rate 38%. Results: Around 99% of 2016 responders had heard about organ donation and about the possibility of becoming a donor, 75% preferred to decide for themselves about donation, 43% had discussed organ donation more than once at home, 66% were willing to donate. The willingness to donate was positively associated with age and socio-economic status. Conclusion: This survey indicates that these children at 12 through 15 years of age are capable and willing to think about organ donation. Thought should be given about how to raise awareness and how to enable parents and children to develop some sort of health literacy concerning the concept of organ donation. Children and their parents should be given adequate opportunities to receive appropriate information, suited to their psychological and moral developmental status

On the Lagrangian Realization of Non-Critical W{\cal W}-Strings

A large class of non-critical string theories with extended worldsheet gauge symmetry are described by two coupled, gauged Wess-Zumino-Witten Models. We give a detailed analysis of the gauge invariant action and in particular the gauge fixing procedure and the resulting BRST symmetries. The results are applied to the example of ${\cal W}_3$ strings.Comment: 19 pages, LaTeX (REVTEX macro's

Selective expansion of viral variants following experimental transmission of a reconstituted feline immunodeficiency virus quasispecies

Following long-term infection with virus derived from the pathogenic GL8 molecular clone of feline immunodeficiency virus (FIV), a range of viral variants emerged with distinct modes of interaction with the viral receptors CD134 and CXCR4, and sensitivities to neutralizing antibodies. In order to assess whether this viral diversity would be maintained following subsequent transmission, a synthetic quasispecies was reconstituted comprising molecular clones bearing envs from six viral variants and its replicative capacity compared in vivo with a clonal preparation of the parent virus. Infection with either clonal (Group 1) or diverse (Group 2) challenge viruses, resulted in a reduction in CD4+ lymphocytes and an increase in CD8+ lymphocytes. Proviral loads were similar in both study groups, peaking by 10 weeks post-infection, a higher plateau (set-point) being achieved and maintained in study Group 1. Marked differences in the ability of individual viral variants to replicate were noted in Group 2; those most similar to GL8 achieved higher viral loads while variants such as the chimaeras bearing the B14 and B28 Envs grew less well. The defective replication of these variants was not due to suppression by the humoral immune response as virus neutralising antibodies were not elicited within the study period. Similarly, although potent cellular immune responses were detected against determinants in Env, no qualitative differences were revealed between animals infected with either the clonal or the diverse inocula. However, in vitro studies indicated that the reduced replicative capacity of variants B14 and B28 in vivo was associated with altered interactions between the viruses and the viral receptor and co-receptor. The data suggest that viral variants with GL8-like characteristics have an early, replicative advantage and should provide the focus for future vaccine development

Adaptability and learning Intraprofessional collaboration of residents during the COVID-19 pandemic

CONTEXT: The COVID-19 pandemic created a worldwide public health emergency, in which hospitals created new COVID departments and doctors from different disciplines had to work together. In the Netherlands, a large proportion of doctors in these departments were residents. With knowledge of the disease developing only gradually, the influx of COVID-19 patients called for adaptability, innovative work behavior, and intraprofessional collaboration (intraPC) between residents and between residents and medical specialists. RESEARCH GOAL: This study investigates how the delivery of COVID-19 care in hospital settings altered the way residents develop their sense of adaptability and intraPC during their training. METHODS: Sixteen semi-structured interviews were conducted with residents and medical specialists from various disciplines who worked at a COVID department or Intensive Care Unit (ICU) during the COVID pandemic in the Netherlands, focusing on adaptability and intraPC learning. Transcripts were analyzed using (thematic) template analysis. RESULTS: Four themes that influenced learning during COVID care were identified: collective uncertainty, social cohesion and a sense of safety, the need for adaptive performance and intraPC learning. During the first wave, collective uncertainty about the unknown disease and the continuation of the crisis urged residents to adapt in order to take care of patients with a disease that was as yet unknown. The combination of collective uncertainty, social cohesion and a sense of safety, and the presence of different disciplines in one department promoted residents’ intraPC learning. However, intraPC learning was not always the matter of course due to the scope of the crisis and the huge numbers of new patients. CONCLUSION: Collective uncertainty affected the residents’ adaptability. The combination of collective uncertainty, social cohesion, and the presence of different disciplines in one department promoted the residents’ intraPC learning. An important facilitating factor for both adaptability and intraPC learning is a high level of social cohesion and safety. The physical and psychological proximity of supervisors is an important factor contributing to a safe learning environment. This study provides implications for practice for learning during postgraduate training in non-crisis settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12909-022-03868-9

Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy

AbstractOBJECTIVESWe performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC).BACKGROUNDPatients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur.METHODSWe studied 22 patients with IDC and 22 control subjects using PET with nitrogen-13 ammonia to measure myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia. To investigate glucose metabolism, fluorine-18 deoxyglucose (18FDG) was used. For imaging of oxygen consumption, carbon-11 acetate clearance rate constants (kmono) were assessed at rest and during submaximal dobutamine infusion (20 μg/kg body weight per min).RESULTSGlobal MBF reserve (dipyridamole-induced) was impaired in patients with IDC versus control subjects (1.7 ± 0.21 vs. 2.7 ± 0.10, p < 0.05). In patients with IDC, MBF reserve correlated with left ventricular (LV) systolic wall stress (r = −0.61, p = 0.01). Furthermore, in 16 of 22 patients with IDC (derived by dipyridamole perfusion) mismatch (decreased flow/increased 18FDG uptake) was observed in 17 ± 8% of the myocardium. The extent of mismatch correlated with LV systolic wall stress (r = 0.64, p = 0.02). The MBF reserve was lower in the mismatch regions than in the normal regions (1.58 ± 0.13 vs. 1.90 ± 0.18, p < 0.05). During dobutamine infusion kmonowas higher in the mismatch regions than in the normal regions (0.104 ± 0.017 vs. 0.087 ± 0.016 min−1, p < 0.05). In the mismatch regions 18FDG uptake correlated negatively with rest kmono(r = −0.65, p < 0.05), suggesting a switch from aerobic to anaerobic metabolism.CONCLUSIONSPatients with IDC have a decreased MBF reserve. In addition, low MBF reserve was paralleled by high LV systolic wall stress. These global observations were associated with substantial myocardial mismatch areas showing the lowest MBF reserves. In geographically identical regions an abnormal oxygen consumption pattern was seen together with a switch from aerobic to anaerobic metabolism. These data support the notion that regional myocardial ischemia plays a role in IDC

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes

The impact and challenges of implementing CTCA according to the 2019 ESC guidelines on chronic coronary syndromes:a survey and projection of CTCA services in the Netherlands

BACKGROUND: The 2019 ESC-guidelines on chronic coronary syndromes (ESC-CCS) recommend computed tomographic coronary angiography (CTCA) or non-invasive functional imaging instead of exercise ECG as initial test to diagnose obstructive coronary artery disease. Since impact and challenges of these guidelines are unknown, we studied the current utilisation of CTCA-services, status of CTCA-protocols and modeled the expected impact of these guidelines in the Netherlands. METHODS AND RESULTS: A survey on current practice and CTCA utilisation was disseminated to every Dutch hospital organisation providing outpatient cardiology care and modeled the required CTCA capacity for implementation of the ESC guideline, based on these national figures and expert consensus. Survey response rate was 100% (68/68 hospital organisations). In 2019, 63 hospital organisations provided CTCA-services (93%), CTCA was performed on 99 CTCA-capable CT-scanners, and 37,283 CTCA-examinations were performed. Between the hospital organisations, we found substantial variation considering CTCA indications, CTCA equipment and acquisition and reporting standards. To fully implement the new ESC guideline, our model suggests that 70,000 additional CTCA-examinations would have to be performed in the Netherlands. CONCLUSIONS: Despite high national CTCA-services coverage in the Netherlands, a substantial increase in CTCA capacity is expected to be able to implement the 2019 ESC-CCS recommendations on the use of CTCA. Furthermore, the results of this survey highlight the importance to address variations in image acquisition and to standardise the interpretation and reporting of CTCA, as well as to establish interdisciplinary collaboration and organisational alignment

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

&lt;b&gt;BACKGROUND:&lt;/b&gt; In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.&lt;p&gt;&lt;/p&gt; &lt;b&gt;RESULTS:&lt;/b&gt; Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.&lt;p&gt;&lt;/p&gt; &lt;b&gt;CONCLUSIONS:&lt;/b&gt; The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.&lt;p&gt;&lt;/p&gt