Evidence-based clinical use of insulin premixtures

Brazil is expected to have 19.6 million patients with diabetes by the year 2030. A key concept in the treatment of type 2 diabetes mellitus (T2DM) is establishing individualized glycemic goals based on each patient’s clinical characteristics, which impact the choice of antihyperglycemic therapy. Targets for glycemic control, including fasting blood glucose, postprandial blood glucose, and glycated hemoglobin (A1C), are often not reached solely with antihyperglycemic therapy, and insulin therapy is often required. Basal insulin is considered an initial strategy; however, premixed insulins are convenient and are equally or more effective, especially for patients who require both basal and prandial control but desire a more simplified strategy involving fewer daily injections than a basal-bolus regimen. Most physicians are reluctant to transition patients to insulin treatment due to inappropriate assumptions and insufficient information. We conducted a nonsystematic review in PubMed and identified the most relevant and recently published articles that compared the use of premixed insulin versus basal insulin analogues used alone or in combination with rapid-acting insulin analogues before meals in patients with T2DM. These studies suggest that premixed insulin analogues are equally or more effective in reducing A1C compared to basal insulin analogues alone in spite of the small increase in the risk of nonsevere hypoglycemic events and nonclinically significant weight gain. Premixed insulin analogues can be used in insulin-naïve patients, in patients already on basal insulin therapy, and those using basal-bolus therapy who are noncompliant with blood glucose self-monitoring and titration of multiple insulin doses. We additionally provide practical aspects related to titration for the specific premixed insulin analogue formulations commercially available in Brazil.

Neonatally induced mild diabetes: influence on development, behavior and reproductive function of female Wistar rats

Abstract Background Neonatal STZ treatment induces a state of mild hyperglycemia in adult rats that disrupts metabolism and maternal/fetal interactions. The aim of this study was investigate the effect of neonatal STZ treatment on the physical development, behavior, and reproductive function of female Wistar rats from infancy to adulthood. Methods At birth, litters were assigned either to a Control (subcutaneous (s.c.) citrate buffer, n = 10) or STZ group, (streptozotocin (STZ) - 100 mg/kg-sc, n = 6). Blood glucose levels were measured on postnatal days (PND) 35, 84 and 120. In Experiment 1 body weight, length and the appearance of developmental milestones such as eye and vaginal opening were monitored. To assess the relative contribution of the initial and long term effects of STZ treatment this group was subdivided based on blood glucose levels recorded on PND 120: STZ hyperglycemic (between 120 and 300 mg/dl) and STZ normoglycemic (under 120 mg/dl). Behavioral activity was assessed in an open field on PND 21 and 75. In Experiment 2 estrous cyclicity, sexual behavior and circulating gonadotropin, ovarian steroid, and insulin levels were compared between control and STZ-hyperglycemic rats. In all measures the litter was the experimental unit. Parametric data were analyzed using one-way or, where appropriate, two-way ANOVA and significant effects were investigated using Tukey’s post hoc test. Fisher’s exact test was employed when data did not satisfy the assumption of normality e.g. presence of urine and fecal boli on the open field between groups. Statistical significance was set at p < 0.05 for all data. Results As expected neonatal STZ treatment caused hyperglycemia and hypoinsulinemia in adulthood. STZ-treated pups also showed a temporary reduction in growth rate that probably reflected the early loss of circulating insulin. Hyperglycemic rats also exhibited a reduction in locomotor and exploratory behavior in the open field. Mild hyperglycemia did not impair gonadotropin levels or estrous cylicity but ovarian steroid concentrations were altered. Conclusions In female Wistar rats, neonatal STZ treatment impairs growth in infancy and results in mild hyperglycemia/hypoinsulinemia in adulthood that is associated with changes in the response to a novel environment and altered ovarian steroid hormone levels.

Increased SGLT1 expression in salivary gland ductal cells correlates with hyposalivation in diabetic and hypertensive rats

Abstract Background: Oral health complications in diabetes and hypertension include decreased salivary secretion. The sodium-glucose cotransporter 1 (SGLT1) protein, which transports 1 glucose/2 Na+/264 H2O molecules, is described in salivary glands. We hypothesized that changes in SGLT1 expression in the luminal membrane of ductal cell may be related to an altered salivary flow. Findings: By immunohistochemistry, we investigated SGLT1 expression in ductal cells of parotid and submandibular glands from Wistar Kyoto rats (WKY), diabetic WKY (WKY-D), spontaneously hypertensive rats (SHR) and diabetic SHR (SHR-D), as well as in parotid glands from WKY subjected to sympathetic stimulation, with or without previous propranolol blockade. Diabetes and hypertension decreased the salivary secretion and increased SGLT1 expression in the luminal membrane of ductal cells, and their association exacerbated the regulations observed. After 30 min of sympathetic stimulation, SGLT1 increased in the luminal membrane of ductal cells, and that was blocked by previous injection of propranolol. Conclusions: SGLT1 expression increases in the luminal membrane of salivary gland ductal cells and the salivary flow decreases in diabetic and hypertensive rats, which may be related to sympathetic activity. This study highlights the water transporter role of SGLT1 in salivary glands, which, by increasing ductal water reabsorption, may explain the hyposalivation of diabetic and hypertensive subjects.

Increased SGLT1 expression in salivary gland ductal cells correlates with hyposalivation in diabetic and hypertensive rats

Background Oral health complications in diabetes and hypertension include decreased salivary secretion. The sodium-glucose cotransporter 1 (SGLT1) protein, which transports 1 glucose/2 Na+/264 H2O molecules, is described in salivary glands. We hypothesized that changes in SGLT1 expression in the luminal membrane of ductal cell may be related to an altered salivary flow. Findings By immunohistochemistry, we investigated SGLT1 expression in ductal cells of parotid and submandibular glands from Wistar Kyoto rats (WKY), diabetic WKY (WKY-D), spontaneously hypertensive rats (SHR) and diabetic SHR (SHR-D), as well as in parotid glands from WKY subjected to sympathetic stimulation, with or without previous propranolol blockade. Diabetes and hypertension decreased the salivary secretion and increased SGLT1 expression in the luminal membrane of ductal cells, and their association exacerbated the regulations observed. After 30 min of sympathetic stimulation, SGLT1 increased in the luminal membrane of ductal cells, and that was blocked by previous injection of propranolol. Conclusions SGLT1 expression increases in the luminal membrane of salivary gland ductal cells and the salivary flow decreases in diabetic and hypertensive rats, which may be related to sympathetic activity. This study highlights the water transporter role of SGLT1 in salivary glands, which, by increasing ductal water reabsorption, may explain the hyposalivation of diabetic and hypertensive subjects

The impact of frozen sections on final surgical margins in squamous cell carcinoma of the oral cavity and lips: a retrospective analysis over an 11 years period

Taking intraoperative frozen sections (FS) is a widely used procedure in oncologic surgery. However so far no evidence of an association of FS analysis and premalignant changes in the surgical margin exists. Therefore, the aim of this study was to evaluate the impact of FS on different categories of the final margins of squamous cell carcinoma (SCC) of the oral cavity and lips.

First report of a multidrug-resistant Klebsiella pneumoniae of sequence type 11 causing sepsis in a free-ranging beaver (Castor fiber).

Klebsiella pneumoniae of sequence type (ST) 11 is a hyper-epidemic nosocomial clone spreading worldwide among humans and also emerging in pets. In this report, we describe a clinical case of fatal sepsis due to this multidrug-resistant (MDR) pathogen in a Eurasian beaver. The isolate showed resistance to six different classes of antimicrobials including third generation cephalosporins and fluoroquinolones. This is the first report describing the detection of a MDR K. pneumoniae ST11 in a free-ranging animal. Our finding highlights the potential for environmental dissemination of hyper-epidemic clones of K. pneumoniae and possible spread in wildlife and cause epizootics.

Seagrass biofilm communities at a naturally CO2-rich vent at Papua New Guinea

Seagrass meadows are a crucial component of tropical marine reef ecosystems. The seagrass plants are colonized by a multitude of epiphytic organisms that contribute to determining the ecological role of seagrasses. To better understand how environmental changes like ocean acidification might affect epiphytic assemblages, the microbial community composition of the epiphytic biofilm of Enhalus acroides was investigated at a natural CO2 vent in Papua New Guinea using molecular fingerprinting and next generation sequencing of 16S and 18S rRNA genes. Both bacterial and eukaryotic epiphytes formed distinct communities at the CO2-impacted site compared to the control site. This site-related CO2 effect was also visible in the succession pattern of microbial epiphytes. We further found an increased abundance of bacterial types associated with coral diseases at the CO2-impacted site (Fusobacteria, Thalassomonas) whereas eukaryotes such as certain crustose coralline algae commonly related to healthy reefs were less diverse. These trends in the epiphytic community of E. acroides suggest a potential role of seagrasses as vectors of coral pathogens and may support previous predictions of a decrease in reef health and prevalence of diseases under future ocean acidification scenarios.

Geochemistry of sediment cores from METEOR cruise M76/1b

Marine sediments are the main sink in the oceanic phosphorus (P) cycle. The activity of benthic microorganisms is decisive for regeneration, reflux, or burial of inorganic phosphate (Pi), which has a strong impact on marine productivity. Recent formation of phosphorites on the continental shelf and a succession of different sedimentary environments make the Benguela upwelling system a prime region for studying the role of microbes in P biogeochemistry. The oxygen isotope signature of pore water phosphate (d18OP) carries characteristic information of microbial P cycling: Intracellular turnover of phosphorylated biomolecules results in isotopic equilibrium with ambient water, while enzymatic regeneration of Pi from organic matter produces distinct offsets from equilibrium. The balance of these two processes is the major control for d18OP. Our study assesses the importance of microbial P cycling relative to regeneration of Pi from organic matter from a transect across the Namibian continental shelf and slope by combining pore water chemistry (sulfate, sulfide, ferrous iron, Pi), steady-state turnover rate modeling, and oxygen isotope geochemistry of Pi. We found d18OP values in a range from 12.8 per mill to 26.6 per mill, both in equilibrium as well as pronounced disequilibrium with water. Our data show a trend towards regeneration signatures (disequilibrium) under low mineralization activity and low Pi concentrations, and microbial turnover signatures (equilibrium) under high mineralization activity and high Pi concentrations. These findings are opposite to observations from water column studies where regeneration signatures were found to coincide with high mineralization activity and high Pi concentrations. It appears that preferential Pi regeneration in marine sediments does not necessarily coincide with a disequilibrium d18OP signature. We propose that microbial Pi uptake strategies, which are controlled by Pi availability, are decisive for the alteration of the isotope signature. This hypothesis is supported by the observation of efficient microbial Pi turnover (equilibrium signatures) in the phosphogenic sediments of the Benguela upwelling system.

Robust fabrication of electrospun-like polymer mats to direct cell bahaviour

Currently, cell culture systems that include nanoscale topography are widely used in order to provide cells additional cues closer to the in vivo environment, seeking to mimic the natural extracellular matrix. Electrospinning is one of the most common techniques to produce nano fiber mats. However, since many sensitive parameters play an important role in the process, a lack of reproducibility is a major drawback. Here we present a simple and robust methodology to prepare reproducible electrospun-like samples. It consists of a polydimethylsiloxane mold reproducing the fiber pattern to solvent-cast a polymer solution and obtain the final sample. To validate this methodology, poly(L-lactic) acid (PLLA) samples were obtained and, after characterisation, bioactivity and ability to direct cell response were assessed. C2C12 myoblasts developed focal adhesions on the electrospun-like fibers and, when cultured under myogenic differentiation conditions, similar differentiation levels to electrospun PLLA fibers were obtained.

Gender-sensitive reporting in medical research

Sex and gender differences influence the health and wellbeing of men and women. Although studies have drawn attention to observed differences between women and men across diseases, remarkably little research has been pursued to systematically investigate these underlying sex differences. Women continue to be underrepresented in clinical trials, and even in studies in which both men and women participate, systematic analysis of data to identify potential sex-based differences is lacking. Standards for reporting of clinical trials have been established to ensure provision of complete, transparent and critical information. An important step in addressing the gender imbalance would be inclusion of a gender perspective in the next Consolidated Standards of Reporting Trials (CONSORT) guideline revision. Uniform Requirements for Manuscripts Submitted to Biomedical Journals, as a set of well-recognized and widely used guidelines for authors and biomedical journals, should similarly emphasize the ethical obligation of authors to present data analyzed by gender as a matter of routine. Journal editors are also promoters of ethical research and adequate standards of reporting, and requirements for inclusion of gender analyses should be integrated into editorial policies as a matter of urgency.

Direct electrospinning of 3D auricle-shaped scaffolds for tissue engineering applications.

Thirty-two poly(ε)caprolactone (PCL) scaffolds have been produced by electrospinning directly into an auricle-shaped mould and seeded with articular chondrocytes harvested from bovine ankle joints. After seeding, the auricle shaped constructs were cultured in vitro and analysed at days 1, 7, 14 and 21 for regional differences in total DNA, glycosaminoglycan (GAG) and collagen (COL) content as well as the expression of aggrecan (AGG), collagen type I and type II (COL1/2) and matrix metalloproteinase 3 and 13 (MMP3/13). Stress-relaxation indentation testing was performed to investigate regional mechanical properties of the electrospun constructs. Electrospinning into a conductive mould yielded stable 3D constructs both initially and for the whole in vitro culture period, with an equilibrium modulus in the MPa range. Rapid cell proliferation and COL accumulation was observed until week 3. Quantitative real time PCR analysis showed an initial increase in AGG, no change in COL2, a persistent increase in COL1, and only a slight decrease initially for MMP3. Electrospinning of fibrous scaffolds directly into an auricle-shape represents a promising option for auricular tissue engineering, as it can reduce the steps needed to achieve an implantable structure.