Mikrozephaliesyndrome und geistige Behinderung

Clarification of the cause of mental retardation, which has a prevalence of 2–3%, is a common reason for genetic consultation. On the basis of the cardinal sign of microcephaly, which also has a prevalence of 2–3%, an overview on different conditions with developmental delay/mental retardation is given according to the mode of inheritance. The current version of the Winter–Baraitser Dysmorphology Database lists 558 conditions with the combination of microcephaly and developmental delay/mental retardation. This makes clear that the following overview gives only a limited look at the comprehensive field of clinical genetics/dysmorphology.     

The effect of different substrates and humic acid on power generation in microbial fuel cell operation

Electricity production from acetate, glucose and xylose with humic acid as mediator was investigated in two chambers microbial fuel cells (MFCs). Acetate produced the highest voltage (570 mV with 1000 Omega) and maximum power density (P(maxd)=123 mW/m(2)) due to a simpler metabolism than with glucose and xylose. Glucose and xylose resulted in P(maxd) of 28 mW/m(2) and 32 mW/m(2) at lower voltage of 380 mV and 414 mV, respectively. P(maxd) increased by 84% and 30%, for glucose and xylose respectively, when humic acid (2g/l) was present in the medium. No significant effect was found with acetate since the internal resistance possessed a limiting effect. The increase of P(maxd) due to humic acid presence was attributed to its ability to act as mediator. Even though pH decreased to 5 with glucose and xylose, due to production of acetate and propionate, the voltage remained on the same level of 250-350 mV.     

Bioethanol,biohydrogen and biogas production from wheat straw in a biorefinery concept

The production of bioethanol, biohydrogen and biogas from wheat straw was investigated within a biorefinery framework. Initially, wheat straw was hydrothermally liberated to a cellulose rich fiber fraction and a hemicellulose rich liquid fraction (hydrolysate). Enzymatic hydrolysis and subsequent fermentation of cellulose yielded 0.41 g-ethanol/g-glucose, while dark fermentation of hydrolysate produced 178.0 ml-H₂/g-sugars. The effluents from both bioethanol and biohydrogen processes were further used to produce methane with the yields of 0.324 and 0.381 m³/kg volatile solids (VS)_added, respectively. Additionally, evaluation of six different wheat straw-to-biofuel production scenaria showed that either use of wheat straw for biogas production or multi-fuel production were the energetically most efficient processes compared to production of mono-fuel such as bioethanol when fermenting C6 sugars alone. Thus, multiple biofuels production from wheat straw can increase the efficiency for material and energy and can presumably be more economical process for biomass utilization.     

Solubilized phenyl-pyrazole ureas as potent, selective 5-HT2A inverse-agonists and their application as antiplatelet agents

Potent 5-HT_2A inverse-agonists containing phenyl-pyrazole ureas with an amino side chain were identified. Optimization of this series resulted in selective compounds that proved effective in modulating 5HT-induced amplification of ADP-stimulated human platelet aggregation.     

Acidocalcisomen,Mitosomen und Apicoplasten. Neu entdeckte Zellorganellen

Three new, membrane‐bounded organelles were detected in the last decade. Acidocalcisomes which occur in pro‐ and eukaryotes are acidic and store calcium, and further also phosphate, oxygen, magnesium, zink, sodium, potassium, and iron. Furthermore, they are engaged in osmoregulation, pH‐ and Ca²⁺‐homeostasis. Mitosomes are strongly reduced mitochondria of different parasitic protists, which were previously grouped as primarily mitochondria‐free organisms. Apicoplasts are the strongly reduced plastids of the parasitic apicomplexans (formerly sporozoa). They are a target for the development of new drugs, e.g. against the cause of malaria, Plasmodium.     

First-in-Man Open Clinical Trial of a Combined rdESAT-6 and rCFP-10 Tuberculosis Specific Skin Test Reagent

Background

Tuberculin is still the only available skin test reagent for the diagnosis of mycobacterial infection. The product has a remarkable sensitivity, but poor specificity. Previous studies, including two human phase I clinical trials, have indicated that rdESAT-6 has a potential as an improved skin test reagent. Animal studies have shown that the sensitivity may be increased by inclusion of the genetically related CFP-10 antigen in the preparation without loosing specificity.

Methodology

In this study a Lactococcus fermented, recombinant skin test reagent consisting of a 1∶1 wt/wt of rdESAT-6 and CFP-10 was manufactured according to GMP standards and tested for the first time in 42 healthy adult volunteers. The two doses of 0.01 µg or 0.1 µg were injected intradermally by the Mantoux technique with 6 or 12 weeks interval. No serious adverse events and only mild adverse reactions were reported. The reagent elicited a positive skin test reaction after the first injection in one participant, who most likely was latently infected with M. tuberculosis as indicated by an appreciable IFN γ response just below the Quantiferon® cut-off level at the screening visit. None of the remaining participants in the four groups had any skin test reactions and sensitisation by the reagent could therefore be excluded.

Conclusion

The investigational skin test reagent rdESAT-6 and CFP-10 appeared safe and non-sensitising in this first-in-man clinical trial in human volunteers and can now be tested in larger clinical trials involving individuals with latent M. tuberculosis infection or active TB disease.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00793702","term_id":"NCT00793702"}}NCT00793702     

Infections in temporal proximity to HPV vaccination and adverse effects following vaccination in Denmark: A nationwide register-based cohort study and case-crossover analysis

BackgroundPublic trust in the human papilloma virus (HPV) vaccination programme has been challenged by reports of potential severe adverse effects. The reported adverse symptoms were heterogeneous and overlapping with those characterised as chronic fatigue syndrome (CFS) and have been described as CFS-like symptoms. Evidence suggests that CFS is often precipitated by an infection. The aim of the study was to examine if an infection in temporal proximity to HPV vaccination is a risk factor for suspected adverse effects following HPV vaccination.Methods and findingsThe study was a nationwide register-based cohort study and case-crossover analysis. The study population consisted of all HPV vaccinated females living in Denmark, born between 1974 and 2006, and vaccinated between January 1, 2006 and December 31, 2017. The exposure was any infection in the period ± 1 month around time of first HPV vaccination and was defined as (1) hospital-treated infection; (2) redemption of anti-infective medication; or (3) having a rapid streptococcal test done at the general practitioner. The outcome was referral to a specialised hospital setting (5 national HPV centres opened June 1, 2015) due to suspected adverse effects following HPV vaccination. Multivariable logistic regression was used to estimate the association between infection and later HPV centre referral. The participants were 600,400 HPV-vaccinated females aged 11 to 44 years. Of these, 48,361 (9.7%) females had a hospital-treated infection, redeemed anti-infective medication, or had a rapid streptococcal test ± 1 month around time of first HPV vaccination. A total of 1,755 (0.3%) females were referred to an HPV centre. Having a hospital-treated infection in temporal proximity to vaccination was associated with significantly elevated risk of later referral to an HPV centre (odds ratio (OR) 2.75, 95% confidence interval (CI) 1.72 to 4.40; P < 0.001). Increased risk was also observed among females who redeemed anti-infective medication (OR 1.56, 95% CI 1.33 to 1.83; P < 0.001) or had a rapid streptococcal test (OR 1.45, 95% CI 1.10 to 1.93; P = 0.010). Results from a case-crossover analysis, which was performed to adjust for potential unmeasured confounding, supported the findings. A key limitation of the study is that the HPV centres did not open until June 1, 2015, which may have led to an underestimation of the risk of suspected adverse effects, but stratified analyses by year of vaccination yielded similar results.ConclusionsTreated infection in temporal proximity to HPV vaccination is associated with increased risk for later referral with suspected adverse vaccine effects. Thus, the infection could potentially be a trigger of the CFS-like symptoms in a subset of the referred females. To our knowledge, the study is the first to investigate the role of infection in the development of suspected adverse effects after HPV vaccination and replication of these findings are needed in other studies.

Lene Wulff Krogsgaard and co-workers study temporal associations between infections and HPV vaccination.     

Absence of Mycobacterium bovis in feral swine (Sus scrofa) from the southern Texas border region

Free-ranging wildlife, such as feral swine (Sus scrofa), harbor a variety of diseases that are transmissible to livestock and could negatively impact agricultural production. Information is needed regarding the exposure and infection rates of Mycobacterium bovis and many other diseases and parasites in feral swine occurring in the Texas border region. Our main objective was to determine exposure rates and possible infection rates of M. bovis in feral swine by opportunistically sampling animals from the Texas border region. From June to September 2010, we obtained samples from 396 feral swine and tested 98 samples for M. bovis by histopathology and mycobacteriologic culture. We found no evidence of M. bovis infection. We believe that it is important to periodically and strategically sample feral swine for M. bovis in high-risk areas of the United States because they are capable of becoming reservoirs of the disease.