Switching from premixed insulin to glargine-based insulin regimen improves glycaemic control in patients with type 1 or type 2 diabetes: a retrospective primary care-based analysis

Background: Insulin glargine (glargine) and premixed insulins (premix) are alternative insulin treatments. This analysis evaluated glycaemic control in 528 patients with type 1 (n = 183) or type 2 (n = 345) diabetes, after switching from premix to a glargine-based regimen, using unselected general practice (GP) data. Methods: Data for this retrospective observational analysis were extracted from a UK GP database (The Health Improvement Network). Patients were required to have at least 12 months of available data, before and after, switching from premix to a glargine-based regimen. The principal analysis was the change in HbA1c after 12 months of treatment with glargine; secondary analyses included change in weight, bolus usage and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable assessment of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. Results: Both cohorts showed significant reduction in mean HbA1c 12 months after the switch: by -0.67% (p < 0.001) in the type 1 cohort and by -0.53% (p < 0.001) in the type 2 cohort (adjusted data). The size of HbA1c improvement was positively correlated with baseline HbA1c; patients with a baseline HbA1c ≥ 10% had the greatest mean reduction in HbA1c, by -1.7% (p < 0.001) and -1.2% (p < 0.001), respectively. The proportion of patients receiving co-bolus prescriptions increased in the type 1 (mean 24.6% to 95.1%, p < 0.001) and type 2 (mean 16.2% to 73.9%, p < 0.001) cohorts. There was no significant change in weight in either cohort. Total mean insulin use increased in type 2 diabetes patients (from 0.67 ± 1.35 U/Kg to 0.88 ± 1.33 U/Kg, p < 0.001) with a slight decrease in type 1 diabetes patients (from 1.04 ± 2.51 U/Kg to 0.98 ± 2.58 U/Kg, p < 0.001). Conclusion: In everyday practice, patients with type 1 or type 2 diabetes inadequately controlled by premix insulins experienced significant improvement in glycaemic control over 12 months after switching to a glargine-based insulin regimen. These findings support the use of a basal-bolus glargine-based regimen in patients poorly controlled on premix.Peter Sharplin, Jason Gordon, John R Peters, Anthony P Tetlow, Andrea J Longman and Philip McEwa

Metataxonomic and histopathological study of rabbit epizootic enteropathy in Mexico.

Epizootic rabbit enteropathy (ERE) affects young rabbits and represents 32% of the enteropathies in rabbit production farms in Mexico. The etiology of this syndrome has not been clarified yet. A metataxonomic and histopathology study of ERE was carried out to compare the gastrointestinal microbiota and histopathological lesions of healthy and positive-ERE rabbits. The metataxonomic study was done using an Illumina MiSeq (MiSeq® system, Illumina, San Diego California, USA) massive segmentation platform, and a Divisive Amplicon Denoising Algorithm 2 (DADA2 algorithm) was used to obtain Shannon and Simpson diversity indices as well as the relative abundance of the identified communities. For the histopathological study, paraffin sections of the cecum, ileo-cecal valve, and colon were stained with eosin and hematoxylin. AxioVision 4.9 software (Carl Zeiss MicroImaging GmbH, Jena, Germany) was used to measure the crypt depths. Statistical analysis was done using PERMANOVA analysis for the metataxonomic study and ANOVA for the histopathology study. Histopathologic analysis showed smaller sizes of crypts in the colon of ERE rabbits. Differences were observed in the diversity and abundance of the gastrointestinal microbiota between the analyzed groups. The genus Clostridium and the species Cloacibacillus porcorum and Akkermansia muciniphila were associated with ERE. The results obtained from this study can provide information for future clarification of the etiology and proposals of effective treatments

The endolysosomal adaptor PLEKHM1 is a direct target for both mTOR and MAPK pathways

The lysosome is a cellular signalling hub at the point of convergence of endocytic and autophagic pathways, where the contents are degraded and recycled. Pleckstrin homology domain-containing family member 1 (PLEKHM1) acts as an adaptor to facilitate the fusion of endocytic and autophagic vesicles with the lysosome. However, it is unclear how PLEKHM1 function at the lysosome is controlled. Herein, we show that PLEKHM1 co-precipitates with, and is directly phosphorylated by, mTOR. Using a phospho-specific antibody against Ser432/S435 of PLEKHM1, we show that the same motif is a direct target for ERK2-mediated phosphorylation in a growth factor-dependent manner. This dual regulation of PLEKHM1 at a highly conserved region points to a convergence of both growth factor- and amino acid-sensing pathways, placing PLEKHM1 at a critical juncture of cellular metabolism

Zinc is essential for high-affinity DNA binding and recombinase activity of φC31 integrase

The mechanism through which the large serine recombinases bind DNA is poorly understood. Alignments of ϕC31 integrase (Int) and its relatives indicate the presence of a conserved motif containing four cysteines resembling a zinc finger. Inductively coupled plasma–mass spectrometry (ICP–MS) confirmed that an Int monomer contains one atom of zinc. Pre-incubation of Int with ethylenediaminetetraacetic acid (EDTA) was detrimental for both recombination activity and DNA binding affinities but full activity could be restored by adding back Zn2+. Mutations in the cysteines and other highly conserved residues yielded proteins that were hypersensitive to proteases, suggesting that without zinc the domain is unfolded. Substitutions in the highly charged region between the conserved cysteines led to lowered DNA binding affinities while circular dichroism revealed that these variant Ints were not greatly affected in overall folding. Int was protected from inhibition by EDTA when DNA containing an attachment site was present suggesting that the zinc finger and the DNA are in close proximity. A truncated mutant of Int, hInt V371SUGA, lacking the putative zinc finger could bind DNA with low affinity. The data are consistent with there being at least two DNA binding motifs in Int one of which is the zinc finger-like motif

Effect of feeding insoluble fiber on the microbiota and metabolites of the caecum and feces of rabbits recovering from epizootic rabbit enteropathy relative to non-infected rabbits.

This study aimed to investigate the effect of feeding insoluble fiber on the microbiota and metabolites of the caecum and feces of rabbits recovering from epizootic rabbit enteropathy relative to non-infected rabbits. Rabbits that had either recovered from epizootic rabbit enteropathy or ones that had never had epizootic rabbit enteropathy were fed on a diet of 32% or 36% neutral detergent fiber until they were 70 days of age. At this point, the short-chain fatty acid and ammonia levels were measured in caecotroph and fecal samples and compared using 2 × 2 ANOVA. The microbial composition of the samples was also analyzed using next-generation sequencing and compared by PERMANOVA. Caecotrophic samples from previously affected rabbits on lower fiber diets had higher short-chain fatty acid contents and higher species diversity index values for some indices (p [less than] 0.05), although the fecal samples showed lower species diversity levels (p [less than] 0.05). In addition, the PERMANOVA analyses demonstrated that differences were detected in the microbial composition of both fecal and caecotrophic samples, depending on the disease status at the outset of the experiment (p [less than] 0.05). The results of this work show that, although there is some potential in the use of high-fiber diets for the treatment of rabbits that have had epizootic rabbit enteropathy, they are not able to produce the same digestive tract properties as those seen in rabbits that have never had the condition. This is true even after the rabbits have recovered from epizootic rabbit enteropathy

Sustainable forest operations (SFO) : a new paradigm in a changing world and climate

The effective implementation of sustainable forest management depends largely on carrying out forest operations in a sustainable manner. Climate change, as well as the increasing demand for forest products, requires a re-thinking of forest operations in terms of sustainability. In this context, it is important to understand the major driving factors for the future development of forest operations that promote economic, environmental and social well-being. The main objective of this paper is to identify important issues concerning forest operations and to propose a new paradigm towards sustainability in a changing climate, work and environmental conditions. Previously developed concepts of forest operations are reviewed, and a newly developed concept – Sustainable Forest Operations (SFO), is presented. Five key performance areas to ensure the sustainability of forest operations include: (i) environment; (ii) ergonomics; (iii) economics; (iv) quality optimization of products and production; and (v) people and society. Practical field examples are presented to demonstrate how these five interconnected principles are relevant to achieving sustainability, namely profit and wood quality maximization, ecological benefits, climate change mitigation, carbon sequestration, and forest workers' health and safety. The new concept of SFO provides integrated perspectives and approaches to effectively address ongoing and foreseeable challenges the global forest communities face, while balancing forest operations performance across economic, environmental and social sustainability. In this new concept, we emphasize the role of wood as a renewable and environmentally friendly material, and forest workers' safety and utilization efficiency and waste management as additional key elements of sustainability.http://www.elsevier.com/locate/scitotenv2019-09-01hj2018Plant Production and Soil Scienc

Characterisation of the effect of day length, and associated differences in dietary intake, on the gut microbiota of Soay sheep.

Differences in the rumen bacterial community have been previously reported for Soay sheep housed under different day length conditions. This study extends this previous investigation to other organs of the digestive tract, as well as the analysis of ciliated protozoa and anaerobic fungi. The detectable concentrations of ciliated protozoa and anaerobic fungi decreased with increased day length in both the rumen and large colon, unlike those of bacteria where no effect was observed. Conversely, bacterial community composition was affected by day length in both the rumen and large colon, but the community composition of the detectable ciliated protozoa and anaerobic fungi was not affected. Day length associated differences in the bacterial community composition extended to all of the organs examined, with the exception of the duodenum and the jejunum. It is proposed that differences in rumen fill and ruminal ‘by-pass’ nutrients together with endocrinological changes cause the observed effects of day length on the different gut microbial communities