Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

A Topical Formulation of Melatoninergic Compounds Exerts Strong Hypotensive and Neuroprotective Effects in a Rat Model of Hypertensive Glaucoma

Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health.     

Genetically Modified Feeds in Poultry Diet: Safety,Performance, and Product Quality

Concerns have been expressed regarding the safety of using biotechnology derived feeds in diets of livestock animals and in regard to human consumption of products from species fed transgenic crops. As a consequence, a large number of poultry nutrition studies have been conducted to evaluate the wholesomeness of transgenic crops by examining performances of animals during growth or egg laying. Studies also evaluated whether foreign DNA and proteins could be detected in meat, egg, and tissue samples from broiler chickens and laying hens fed diets containing transgenic feeds. In all studies, the conclusions were in agreement that the transgenic crops provided comparable performance, carcass and egg yields, and meat and egg composition, when compared with conventional grains. Moreover, it was demonstrated that transgenic proteins and DNA present in livestock feeds are not detectable in food products derived from these animals, using the most sensitive detection methods available, confirming that they are rapidly degraded by normal digestive processes. The lack of significant differences were a result of the similarity in nutrient composition of the genetically modified feeds and lack of differences in intake and digestibility, while there were no evidences that the differences reported for performance response variables and carcass measurements between treatment groups were attributable to the presence of the transgenic gene and protein in the biotechnology derived plants. Results demonstrated that genetically modified feeds are substantially equivalent and they result as safe as existing conventional feeds.     

Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability.     

A Critical Review of Biological Processes and Technologies for Landfill Leachate Treatment

The most common method to deal with the huge production of municipal wastes is still the disposal in landfills which, however, generates a leachate with high contents of organic and nitrogen pollutants. Requirements must be fixed by law to control leachate release from such landfills, and effective treatment processes and technologies must be applied to reduce its impact on the environment. Biological processes for leachate treatment are discussed in this review, in the former part of which attention is paid to leachate formation and its qualitative and quantitative features, while the latter deals with the state‐of‐the‐art of the most effective biotechnological treatments presently employed. Processes, alternative methods, and technological improvements are compared, with special focus on novel technologies to remove nitrogen pollutants from leachate, highlighting advantages and drawbacks of each treatment.     

Identification of rockfall source areas using the seed cell concept and bivariate susceptibility modelling

The objective of this research was to prepare a rockfall susceptibility map. Explorations were conducted in the Dubra?ina River basin (Croatia). The input data included a geological map, an orthophoto and a 1-m digital terrain model (DTM). After a talus inventory was prepared, the seed cell concept was applied to define the rockfall source areas. The contributing factors (predictors) of rockfalls were evaluated by the chi-squared test. The analysis confirmed the following predictors: CORINE land cover, lithology, slope, aspect, distance from a spring, distance from a road, distance from a fault, distance from a stream, and distance from the rock-soil geological boundary. A matrix pairwise comparison of the predictor ratings was used to define the most significant contributing factors. The predictors that affected the susceptibility map in the share of 86.3% were the slope (61.6%), lithology (13.4%), CORINE land cover (6.2%), and distance from the rock-soil geological boundary (5.1%). Two susceptibility maps were prepared: one using all nine contributing factors and another using the four most significant factors. The analysis showed that both maps were good, with the same areas under the receiver operating characteristic (ROC) curves. The map prepared with only four contributing factors can be considered a better map due to its more precise spatial definition of critical areas. It can be concluded that geological map, 1-m DTM and orthophoto provide enough data to prepare reliable rockfall susceptibility map. The application of the bivariate statistical zonation method called the “frequency ratio method” was proven to be successful. This research demonstrates that the application of the seed cell concept can be useful to speed up the process of rockfall source area detections in large research regions.

     

A simple and effective design strategy to increase power conversion efficiency of linear charge pumps

This paper introduces a simple design strategy to increase the power efficiency of linear charge pumps. The technique exploits a voltage amplitude of the clock signal lower than the supply voltage to reduce the power conversion losses. The nominal output voltage is maintained unaltered by increasing the number of stages.