Exposure to dipeptidyl-peptidase-4 inhibitors and COVID-19 among people with type 2 diabetes: A case-control study

Because other coronaviruses enter the cells by binding to dipeptidyl-peptidase-4 (DPP-4), it has been speculated that DPP-4 inhibitors (DPP-4is) may exert an activity against severe acute respiratory syndrome coronavirus 2. In the absence of clinical trial results, we analysed epidemiological data to support or discard such a hypothesis. We retrieved information on exposure to DPP-4is among patients with type 2 diabetes (T2D) hospitalized for COVID-19 at an outbreak hospital in Italy. As a reference, we retrieved information on exposure to DPP-4is among matched patients with T2D in the same region. Of 403 hospitalized COVID-19 patients, 85 had T2D. The rate of exposure to DPP-4is was similar between T2D patients with COVID-19 (10.6%) and 14 857 matched patients in the region (8.8%), or 793 matched patients in the local outpatient clinic (15.4%), 8284 matched patients hospitalized for other reasons (8.5%), and when comparing 71 patients hospitalized for COVID-19 pneumonia (11.3%) with 351 matched patients with pneumonia of another aetiology (10.3%). T2D patients with COVID-19 who were on DPP-4is had a similar disease outcome as those who were not. In summary, we found no evidence that DPP-4is might affect hospitalization for COVID-19.     

Effect of cardiac resynchronization therapy on cardiotrophin-1 circulating levels in patients with heart failure

Cardiotrophin-1 (CT-1) is a member of the interleukin (IL-6) family of cytokines. Plasma CT-1 levels correlate with the left ventricle mass index in patients with dilatated cardiomyopathy and congestive heart failure (CHF). The aim of this paper was to evaluate CT-1 plasma levels, before and after cardiac resynchronization therapy CRT, and to characterizeits prognostic role in patients with CHF. Fifty-two consecutive patients (M/F = 39/13; 56 ± 11 years old) underwent clinical and echocardiographic evaluation, and blood sample collection at baseline. The same evaluation was repeated 6.4 ± 0.79 months after CRT. Patients with a decreased LV end-systolic volume by at least 15% (reverse remodeling) were considered echo responders to CRT. Twenty-nine patients (56%) were responders to CRT. After CRT, only 15 patients (29%) showed increased CT-1 after CRT. They were all non responders to CRT. A multivariate, logistic modelshowed CT-1 as an independent predictor of CRT echo response (p = 0.005; OR 0.97). During follow-up (18 ± 7 months), 21 cardiac events in 18 patients occurred. A Cox multivariable model showed plasma BNP pre-CRT (p = 0.02; CI 1.2–5.6; OR 3.1) and CT1 post-CRT (p = 0.01; CI 1.4–4.3; OR 2.7) as independent predictors of cardiac events. Analysis of CT-1 plasma levels deserves future consideration for larger, longitudinal studies in patients with CHF.     

Is there a clinical role for oxidative stress biomarkers in atherosclerotic diseases?

Growing evidences suggest that reactive oxidant species (ROS) are involved in the pathogenesis and progression of the atherosclerotic diseases. Markers assessing the oxidation of LDL and formation of eicosanoids, such as isoprostanes, were among the first that were analyzed. More recently, new biomarkers, such as endogenous secretory receptor for AGEs have been suggested to play an oxidative role in specific atherosclerotic settings, such as diabetes. Unfortunately, clinical trials included cross-sectional as well as retrospective and prospective studies which provide inconclusive results. Thus, clear evidence that oxidative biomarkers can improve risk stratification in addition to the common used atherosclerotic risk factors is still lacking. The analysis of oxidative stress focused on enzymatic systems generating ROS. The most studied enzymes were NADPH oxidase and myeloperoxidase (MPO). Experimental and clinical studies suggest that both enzymes may be implicated in promoting atherosclerotic disease. Novel laboratory methodologies have been, therefore, developed to study NADPH oxidase and MPO in patients with stable atherosclerosis as well in patients with acute coronary syndrome and cerebrovascular accident. This review will report on the more relevant studies in which the clinical application of the oxidative biomarkers was evaluated.     

Soluble epoxide hydrolase inhibition improves myocardial perfusion and function in experimental heart failure

The study addressed the hypothesis that soluble epoxide hydrolase (sEH) inhibition, which increases cardiovascular protective epoxyeicosatrienoic acids (EETs), exerts beneficial effects in an established chronic heart failure (CHF) model. In CHF rats, left ventricular (LV) function, perfusion and remodeling were assessed using MRI and invasive hemodynamics after 42-day (starting 8 days after coronary ligation) and delayed 3-day (starting 47 days after coronary ligation) treatments with the sEH inhibitor AUDA (twice 0.25 mg/day). Delayed 3-day and 42-day AUDA increased plasma EETs demonstrating the effective inhibition of sEH. Delayed 3-day and 42-day AUDA enhanced cardiac output without change in arterial pressure, thus reducing total peripheral resistance. Both treatment periods increased the slope of the LV end-systolic pressure-volume relation, but only 42-day AUDA decreased LV end-diastolic pressure, relaxation constant Tau and the slope of the LV end-diastolic pressure-volume relation, associated with a reduced LV diastolic volume and collagen density. Delayed 3-day and, to a larger extent, 42-day AUDA increased LV perfusion associated with a decreased LV hypoxia-inducible factor-1alpha. Both treatment periods decreased reactive oxygen species level and increased reduced-oxidized glutathione ratio. Finally, MSPPOH, an inhibitor of the EET-synthesizing enzyme cytochrome epoxygenases, abolished the beneficial effects of 3-day AUDA on LV function and perfusion. Augmentation of EET availability by pharmacological inhibition of sEH increases LV diastolic and systolic functions in established CHF. This notably results from short-term processes, i.e. increased LV perfusion, reduced LV oxidative stress and peripheral vasodilatation, but also from long-term effects, i.e. reduced LV remodeling.     

Long-term perspective on wildfires in the western USA

Understanding the causes and consequences of wildfires in forests of the western United States requires integrated information about fire, climate changes, and human activity on multiple temporal scales. We use sedimentary charcoal accumulation rates to construct long-term variations in fire during the past 3,000 y in the American West and compare this record to independent fire-history data from historical records and fire scars. There has been a slight decline in burning over the past 3,000 y, with the lowest levels attained during the 20th century and during the Little Ice Age (LIA, ca. 1400–1700 CE [Common Era]). Prominent peaks in forest fires occurred during the Medieval Climate Anomaly (ca. 950–1250 CE) and during the 1800s. Analysis of climate reconstructions beginning from 500 CE and population data show that temperature and drought predict changes in biomass burning up to the late 1800s CE. Since the late 1800s , human activities and the ecological effects of recent high fire activity caused a large, abrupt decline in burning similar to the LIA fire decline. Consequently, there is now a forest “fire deficit” in the western United States attributable to the combined effects of human activities, ecological, and climate changes. Large fires in the late 20th and 21st century fires have begun to address the fire deficit, but it is continuing to grow.Forest fires in the western United States have been increasing in size (1) and possibly severity (2) for several decades. The increase in fire has prompted multiple investigations into both the causes (3, 4) and consequences of this shift for communities, ecosystems, and climate (5). Climate changes and human activities have both contributed to the observed changes in fire, but understanding the nature and magnitude of these impacts has been challenging first because there is substantial ecological heterogeneity and variability in terms of vegetation, soils, hydrology, topography, and other factors that affect fire regimes across the western United States, and second because most fire-history data come from recent decades and centuries when climate and human activities have both undergone rapid and unique transformations. As a result, studies tend to focus either on local ecological and anthropogenic factors that drive fire at fine scales (6, 7), or on climatic influences at broad scales (3, 4). Furthermore, the limited temporal scope of many fire-history studies does not provide adequate context for examining the joint impacts of climate and human activities on broad-scale, long-term fire regime changes. In addition, projections of future climate change and its ecosystem impacts place the expected changes well outside the range of variations in the past few centuries. Thus, coupling multi-decadal-to millennial-scale data on fire, climate changes, and human activities can reveal linkages among these components that are often missed in studies restricted to finer scales or fewer factors.Here we use sedimentary charcoal accumulation rates to construct variations in levels of burning for the past 3,000 y in the western United States (i.e., the West) and compare this record to independent fire-history data from historical records and fire scars. The long charcoal records enable identification of baseline shifts in fire regimes that cannot be detected with shorter records and allow us to view the nature and extent of human impacts on fire in a long-term context; this approach helps to distill the dominant patterns in fire activity across the West, but it does not reveal the important differences in fire controls and effects among vegetation types, ecoregions, or elevation gradients that exist at finer spatial scales (e.g., ref. 8).Our focus here is specifically on multi-decadal-to-centennial-scale variations in fire over the past few millennia and on the West as a whole. Climatic variations on this time scale are characterized by extended periods of persistent anomalies, such as the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA) (9, 10), which feature broad-scale (i.e., across the whole of the western United States) anomalies of both surface climates and atmospheric circulation (10). We use temperature (10), drought (9), and population (11) data to compare with the fire-history reconstructions. We also construct a simple statistical model for predicting biomass burning from the temperature and drought data. Our analysis builds on the rich historical narratives of fire in the western United States (12) as well as on many more detailed but shorter broad-scale studies (4, 13, 14). The results illustrate the importance of climate in explaining the variations in fire over time, and show the development of a 20th century “fire deficit” related to the combined effects of fire exclusion, land-use change, and ongoing climate change.     

Rapid creation of Arabidopsis doubled haploid lines for quantitative trait locus mapping

Quantitative trait loci (QTL) mapping is a powerful tool for investigating the genetic basis of natural variation. QTL can be mapped using a number of different population designs, but recombinant inbred lines (RILs) are among the most effective. Unfortunately, homozygous RIL populations are time consuming to construct, typically requiring at least six generations of selfing starting from a heterozygous F(1). Haploid plants produced from an F(1) combine the two parental genomes and have only one allele at every locus. Converting these sterile haploids into fertile diploids (termed "doubled haploids," DHs) produces immortal homozygous lines in only two steps. Here we describe a unique technique for rapidly creating recombinant doubled haploid populations in Arabidopsis thaliana: centromere-mediated genome elimination. We generated a population of 238 doubled haploid lines that combine two parental genomes and genotyped them by reduced representation Illumina sequencing. The recombination rate and parental allele frequencies in our population are similar to those found in existing RIL sets. We phenotyped this population for traits related to flowering time and for petiole length and successfully mapped QTL controlling each trait. Our work demonstrates that doubled haploid populations offer a rapid, easy alternative to RILs for Arabidopsis genetic analysis.     

Establishment of the epithelial attachment and connective tissue adaptation to implants installed under the concept of "platform switching": a histologic study in minipigs

Aim: To validate the “platform switching” concept at oral implants with respect to the preservation of the alveolar crestal bone levels in an animal model. Material & methods: Five minipigs received three implants each with a 0.25 mm implant/abutment mismatch and were placed flush (T₀), 1 mm below (T₁) and 1 mm above (T₊₁) the alveolar bony crest, and as a control, one conventionally restored implant placed at the bone level. The implants were randomly inserted flapless into the mandible. Four months after implant insertion, the animals were sacrificed, and undecalcified block sections were obtained and used for histological analyses. Results: The mean values for peri‐implant bone resorption were 1.09±0.59 mm (Control), 0.51 (±0.27 mm, T₀), 0.50 (±0.46 mm, T₊₁) and 1.30 (±0.21 mm, T_?1), respectively. Statistically significant differences (P<0.05) were found among the test (T₀, T_?1) and the control sites. Control implants presented an average biologic width length of 3.20 mm (±0.33), with a connective tissue adaptation compartment of 1.29 mm (±0.53) and an epithelial attachment of 1.91 mm (±0.71). T₀, T₊₁ and T_?1 implants presented with a mean biologic width of 1.97mm (± 1.20), 2.70mm (± 1.36) and 2.84mm (± 0.90), respectively, with a connective tissue adaptation compartment of 1.21mm (± 0.97), 1.21mm (± 0.65) and 1.50mm (± 0.70) and an epithelial attachment of 0.84mm (± 0.93), 1.66mm (±0.88) and 1.35mm (± 0.44), respectively. Differences between the configurations were mainly associated with the length of the epithelial attachment. The epithelial attachment was significantly longer in the C sites than in T₀ (P=0.014). However, no other differences between configurations were detected. Conclusion: If the implants are positioned at the level of the alveolar bony crest, the platform‐switching concept may have a minor impact on the length of the epithelial attachment (0.84 vs. 1.91 mm), while the connective tissue adaptation compartment remains relatively unaffected. Moreover, platform switching resulted in less resorption of the alveolar crest (0.58 mm). To cite this article:
Farronato D, Santoro G, Canullo L, Botticelli D, Maiorana C, Lang NP. Establishment of the epithelial attachment and connective tissue adaptation to implants installed under the concept of “platform switching”: a histologic study in minipigs
Clin. Oral Impl. Res. 23 , 2012; 90–94.
doi: 10.1111/j.1600‐0501.2011.02196.x