Effect of pancreatic and/or renal transplantation on diabetic autonomic neuropathy

Thirty-nine Type 1 (insulin-dependent) diabetic patients were studied prospectively after simultaneous pancreas and kidney (n=26) and kidney grafting alone (n=13) by measuring heart rate variation during various manoeuvers and answering a standardized questionnaire every 6 to 12 months post-transplant. While age, duration of diabetes, and serum creatinine (168.1±35.4 vs 132.7±17.7 mgrmol/l) were comparable, haemoglobin A1 levels were significantly lower (6.6±0.2 vs 8.5±0.3%; p<0.01) and the mean observation time longer (35±2 vs 25±3 months; p<0.05) in the pancreas recipients when compared with kidney transplanted patients. Heart rate variation during deep breathing, lying/standing and Valsalva manoeuver were very similar in both groups initially and did not improve during follow-up. However, there was a significant reduction in heart rate in the pancreas recipient group. Autonomic symptoms of the gastrointestinal and thermoregulatory system improved more in the pancreas grafted subjects, while hypoglycaemia unawareness deteriorated in the kidney recipients. This study suggests that long-term normoglycaemia by successful pancreatic grafting is able to halt the progression of autonomic dysfunction

Electron Cryotomography of Bacterial Secretion Systems

In biology, function arises from form. For bacterial secretion systems, which often span two membranes, avidly bind to the cell wall, and contain hundreds of individual proteins, studying form is a daunting task, made possible by electron cryotomography (ECT). ECT is the highest-resolution imaging technique currently available to visualize unique objects inside cells, providing a three-dimensional view of the shapes and locations of large macromolecular complexes in their native environment. Over the past 15 years, ECT has contributed to the study of bacterial secretion systems in two main ways: by revealing intact forms for the first time and by mapping components into these forms. Here we highlight some of these contributions, revealing structural convergence in type II secretion systems, structural divergence in type III secretion systems, unexpected structures in type IV secretion systems, and unexpected mechanisms in types V and VI secretion systems. Together, they offer a glimpse into a world of fantastic forms—nanoscale rotors, needles, pumps, and dart guns—much of which remains to be explored

Bisphenol A: Quantification in Complex Matrices and Removal by Anaerobic Sludges

The endocrine disruptor bisphenol A (BPA) is one of the most commonly found micropollutants in the environment. However, the biodegradation of BPA under anaerobic (methanogenic) conditions is still an understudied process in wastewater treatment systems. The current study thus addresses the need for a simple and user-friendly analytical method for the rapid and accurate quantification of BPA in complex matrices such as digested and co-digester sludges. We established a microwave-assisted extraction method, followed by derivatization and gas chromatography–mass spectrometry to quantify BPA by comparing it with a deuterated internal standard. The BPA removal capabilities of three digester sludges and three co-digester sludges were examined under mesophilic methanogenic conditions in biogas plants. The endogenous BPA concentration (dry weight) ranged from 1596 to 10,973 µg kg −1 in digested sewage sludges, and from below the limit of quantification to 9069 µg kg −1 in co-digester sludges. When BPA was added to the sludges, the removal capabilities ranged from not significant to 50% after 21 days of incubation. Biogas production was unaffected by the addition of BPA (228 µg kg −1 ) to the aqueous sludge. The study demonstrated that BPA could be removed under anaerobic conditions in accustomed inoculates. The findings have far-reaching implications for understanding BPA persistence and detoxification under anaerobic conditions

Potential overtreatment in elderly patients with diabetes mellitus : Results from a cross-sectional study in German general practice

Background: It is important for general practitioners (GPs) to protect elderly patients with diagnosis of diabetes type 2 (DM2) from overtreatment. Objective: To analyse the metabolic control and treatment of elderly patients with DM2 in general practices. Methods: This cross-sectional study involved 46 general practices in a federal state of Germany. Inclusion criteria for patients were diagnosis of DM2, age of 70 years or above, no palliative care and at least one practice contact within the last six months. A study nurse randomly selected 10 eligible patients and extracted data on haemoglobin A1c (HbA1c), diabetes treatment, secondary prevention and GP’s characteristics. Risk of overtreatment was defined as having a HbA1c <47.5 mmol/mol (6.5%) and receiving glucose-lowering drugs, and overtreatment as being at risk of overtreatment and being aged 80 years or above or living in a nursing home. Results: Among 460 participants, 36.0% received oral-antidiabetic drugs, 16.7% insulin, 16.2% both and 31.1% received diet/exercise. Overtreatment occurred in 12% of elderly patients with DM2, risk of overtreatment in 24%. Overtreatment was significantly associated with urban residency (OR 2.17). Female elderly patients with DM2 were significantly less often at risk of overtreatment (OR 0.59). Cluster effects were evident between general practices’ treatment and monitoring of elderly patients with DM2 in quantitative data. Conclusion: Overtreatment is a relevant problem in elderly patients with DM2 for which GPs should regularly check and start deprescribing. Cluster effects suggest heterogeneity between general practices in diabetes management and monitoring

Biochemical and Structural Characterization of Selective Allosteric Inhibitors of the Plasmodium falciparum Drug Target, Prolyl-tRNA-synthetase

Plasmodium falciparum (<i>Pf</i>) prolyl-tRNA synthetase (ProRS) is one of the few chemical-genetically validated drug targets for malaria, yet highly selective inhibitors have not been described. In this paper, approximately 40,000 compounds were screened to identify compounds that selectively inhibit <i>Pf</i>ProRS enzyme activity versus Homo sapiens (<i>Hs</i>) ProRS. X-ray crystallography structures were solved for apo, as well as substrate- and inhibitor-bound forms of <i>Pf</i>ProRS. We identified two new inhibitors of <i>Pf</i>ProRS that bind outside the active site. These two allosteric inhibitors showed >100 times specificity for <i>Pf</i>ProRS compared to <i>Hs</i>ProRS, demonstrating this class of compounds could overcome the toxicity related to <i>Hs</i>ProRS inhibition by halofuginone and its analogues. Initial medicinal chemistry was performed on one of the two compounds, guided by the cocrystallography of the compound with <i>Pf</i>ProRS, and the results can instruct future medicinal chemistry work to optimize these promising new leads for drug development against malaria

Complete genome sequence of a new clostridium sp. isolated from anaerobic digestion and biomethanation

Here, we present the genome sequence and annotation of the bacterial strain HV4-5-A1G, a potentially new Clostridium species. Based on its genomic data, this strain may act as a keystone microorganism in the hydrolysis of complex polymers, as well as in the different acidogenesis and acetogenesis steps during anaerobic digestion. © 2020 Hahnke et al

Draft Genome Sequence of a New Oscillospiraceae Bacterium Isolated from Anaerobic Digestion of Biomass

Here, we present the genome sequence and annotation of the novel bacterial strain HV4-5-C5C, which may represent a new genus within the family Oscillospiraceae (order Eubacteriales). This strain is a potential keystone species in the hydrolysis of complex polymers during anaerobic digestion of biomass. © 2020 Pascual et al

Complete Genome Sequence of a New Ruminococcaceae Bacterium Isolated from Anaerobic Biomass Hydrolysis

A new Ruminococcaceae bacterium, strain HV4-5-B5C, participating in the anaerobic digestion of grass, was isolated from a mesophilic two-stage laboratoryscale leach bed biogas system. The draft annotated genome sequence presented in this study and 16S rRNA gene sequence analysis indicated the affiliation of HV4-5- B5C with the family Ruminococcaceae outside recently described genera. © 2018 Hahnke et al