Corporate Bankruptcies in Czech Republic, Slovakia, Croatia and Serbia

The corporate bankruptcies legal frameworks and their economic implications are compared for two pairs of post-communist countries (Czech Republic and Slovakia and Croatia and Serbia) originating from common federative republics. Their process of gradual divergence from the common legal and economic framework is shown. All four countries are identified as creditor friendly (Czech Republic, Croatia, Serbia) or neutral countries (Slovakia). The possibilities of further development of bankruptcy proceeding in these countries are outlined

Phenolics in aerial parts of Persian clover Trifolium resupinatum

The nutritional quality of Persian clover (Trifolium resupinatum), an important pasture crop, depends not only on a high protein content but also on the occurrence of animal health and welfare promoting phytochemicals. Nine phenolic constituents present in the aerial parts of this species were isolated and their structures confirmed by NMR and ESI-MS analyses. The compounds included two chlorogenic acids, four quercetin and two kaempferol glycosides, as well as the isoflavone formononetin-7-glucoside. The concentration of isoflavone was low, not exceeding 1.2 mg/g of dry matter. The concentration of flavonols ranged between 5.9 and 11.8 mg/g, depending on the sampling dates, with the highest concentration occurring in the first cut. A similar trend in the concentration was found for chlorogenic acids, which ranged from 2 mg/g in summer to 7.3 mg/g in spring

Cost-effectiveness of Store-and-Forward Teledermatology:A Systematic Review

Importance Teledermatology is a topical clinical approach being tested in Australia and elsewhere. With most dermatologists residing in metropolitan areas, teledermatology provides an apparent low-cost and convenient means of access for individuals living outside these areas. It is important that any proposed new addition to a health care system is assessed on the grounds of economic cost and effectiveness. Objective To summarize and evaluate the current economic evidence comparing store-and-forward teledermatology (S&FTD) with conventional face-to-face care. Evidence Review Search terms with appropriate amendments were used to identify S&FTD articles that included economic analysis. Six databases were searched, and title, abstract and full-text reviews were conducted by 2 researchers. References of all unique returned articles were searched by hand. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to evaluate quality of the included articles. Findings Eleven articles were selected for inclusion, including 1 cost analysis, 4 cost-minimization analyses, 4 cost-effectiveness analyses, and 2 cost-utility analyses. CHEERS scores ranged from 7 to 21 out of a possible 24 points, with a median score of 17. Conclusions and Relevance Current evidence is sparse but suggests that S&FTD can be cost-effective. It appears to be cost-effective when used as a triage mechanism to reduce face-to-face appointment requirements. The cost-effectiveness of S&FTD increases when patients are required to travel farther distances to access dermatology services. Further economic research is required for the emerging S&FTD, which uses dermoscopes in combination with smartphone applications, as well as regarding the possibility and consequences of patients self-capturing and transmitting images

miR824/AGAMOUS-LIKE16 Module Integrates Recurring Environmental Heat Stress Changes to Fine-Tune Poststress Development

Plant development is continually fine-tuned based on environmental factors. How environmental perturbations are integrated into the developmental programs and how poststress adaptation is regulated remains an important topic to dissect. Vegetative to reproductive phase change is a very important developmental transition that is complexly regulated based on endogenous and exogenous cues. Proper timing of flowering is vital for reproductive success. It has been shown previously that AGAMOUS LIKE 16 (AGL16), a MADS-box transcription factor negatively regulates flowering time transition through FLOWERING LOCUS T (FT), a central downstream floral integrator. AGL16 itself is negatively regulated by the microRNA miR824. Here we present a comprehensive molecular analysis of miR824/AGL16 module changes in response to mild and recurring heat stress. We show that miR824 accumulates gradually in response to heat due to the combination of transient transcriptional induction and posttranscriptional stability. miR824 induction requires heat shock cis-elements and activity of the HSFA1 family and HSFA2 transcription factors. Parallel to miR824 induction, its target AGL16 is decreased, implying direct causality. AGL16 posttranscriptional repression during heat stress, however, is more complex, comprising of a miRNA-independent, and a miR824-dependent pathway. We also show that AGL16 expression is leaf vein-specific and overlaps with miR824 (and FT) expression. AGL16 downregulation in response to heat leads to a mild derepression of FT. Finally, we present evidence showing that heat stress regulation of miR824/AGL16 is conserved within Brassicaceae. In conclusion, due to the enhanced post-transcriptional stability of miR824, stable repression of AGL16 is achieved following heat stress. This may serve to fine-tune FT levels and alter flowering time transition. Stress-induced miR824, therefore, can act as a "posttranscriptional memory factor" to extend the acute impact of environmental fluctuations in the poststress period

Fighting melanoma with smartphones: a snapshot of where we are a decade after app stores opened their doors

Background: Smartphone applications (“apps”) exist for primary and secondary prevention of melanoma. Our aim was to review currently available apps for community, patient and generalist clinician users. Design: Prospective study, April 2017 – May 2017. Main outcomes: Appropriate apps available to Android and Apple smartphones were assessed in regards to app specific information (target user, cost, store rating, last update), functions offered and clinician, professional or scientific input and or peer review. Comparison was made with a similar 2014 review of the app market. Results: 43 apps meeting inclusion criteria were found. Compared to 2014, 24 of 43 (55.8%) were new, and apps performing automated image analysis declined from 46.1% to 23.3% market share. 23 of 43 (53.4%) were free to download, 48.8% (n = 20) required payments of some form. The most common functionality was monitoring/tracking with 24 of 43 (55.8%) apps performing this. 15 of 43 apps (34.9%) reported clinician, professional or scientific input; in 2014 it was only 4 of 39 (10.3%). 2 of 43 apps (5%) mentioned peer-reviewed evidence along with professional input. Not all apps had ratings. On Android 20 of 22 apps had ratings; average app rating was 3.5, range 1.6 to 4.6. On Apple, 13 of 13 had ratings; average rating was 3.5; range 1– 5. Conclusions: Since 2014 there have been an expanding and changing landscape of apps targeting melanoma diagnosis. There remains a lack of evidence backing their efficacy. This is concerning given their public availability and the gravity of their subject matter

Thymus transplantation for complete DiGeorge syndrome: European experience

Background: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Methods: Twelve patients with cDGS were transplanted with allogeneic cultured thymus. Objective: To confirm and extend the results previously obtained in a single centre. Results: Two patients died of pre-existing viral infections without developing thymopoeisis and one late death occurred from autoimmune thrombocytopaenia. One infant suffered septic shock shortly after transplant resulting in graft loss and the need for a second transplant. Evidence of thymopoeisis developed from 5-6 months after transplantation in ten patients. The median (range) of circulating naïve CD4 counts (x10663 /L) were 44(11-440) and 200(5-310) at twelve and twenty-four months post-transplant and T-cell receptor excision circles were 2238 (320-8807) and 4184 (1582 -24596) per106 65 T-cells. Counts did not usually reach normal levels for age but patients were able to clear pre-existing and later acquired infections. At a median of 49 months (22-80), eight have ceased prophylactic antimicrobials and five immunoglobulin replacement. Histological confirmation of thymopoeisis was seen in seven of eleven patients undergoing biopsy of transplanted tissue including five showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator (AIRE) expression was also demonstrated. Autoimmune complications were seen in 7/12 patients. In two, early transient autoimmune haemolysis settled after treatment and did not recur. The other five suffered ongoing autoimmune problems including: thyroiditis (3); haemolysis (1), thrombocytopaenia (4) and neutropenia (1). Conclusions: This study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors

Instability of the mitochondrial alanyl-tRNA synthetase underlies fatal infantile-onset cardiomyopathy

Recessively inherited variants in AARS2 (NM_020745.2) encoding mitochondrial alanyl-tRNA synthetase (mt-AlaRS) were first described in patients presenting with fatal infantile cardiomyopathy and multiple oxidative phosphorylation defects. To date, all described patients with AARS2-related fatal infantile cardiomyopathy are united by either a homozygous or compound heterozygous c.1774C>T (p.Arg592Trp) missense founder mutation that is absent in patients with other AARS2-related phenotypes. We describe the clinical, biochemical and molecular investigations of two unrelated boys presenting with fatal infantile cardiomyopathy, lactic acidosis and respiratory failure. Oxidative histochemistry showed cytochrome c oxidase-deficient fibres in skeletal and cardiac muscle. Biochemical studies showed markedly decreased activities of mitochondrial respiratory chain complexes I and IV with a mild decrease of complex III activity in skeletal and cardiac muscle. Using next-generation sequencing, we identified a c.1738C>T (p.Arg580Trp) AARS2 variant shared by both patients that was in trans with a loss-of-function heterozygous AARS2 variant; a c.1008dupT (p.Asp337*) nonsense variant or an intragenic deletion encompassing AARS2 exons 5-7. Interestingly, our patients did not harbour the p.Arg592Trp AARS2 founder mutation. In silico modelling of the p.Arg580Trp substitution suggested a deleterious impact on protein stability and folding. We confirmed markedly decreased mt-AlaRS protein levels in patient fibroblasts, skeletal and cardiac muscle, although mitochondrial protein synthesis defects were confined to skeletal and cardiac muscle. In vitro data showed that the p.Arg580Trp variant had a minimal effect on activation, aminoacylation or misaminoacylation activities relative to wild-type mt-AlaRS, demonstrating that instability of mt-AlaRS is the biological mechanism underlying the fatal cardiomyopathy phenotype in our patients.Peer reviewe

The ubiquity of frequency effects in first language acquisition

This review article presents evidence for the claim that frequency effects are pervasive in children's first language acquisition, and hence constitute a phenomenon that any successful account must explain. The article is organized around four key domains of research: children's acquisition of single words, inflectional morphology, simple syntactic constructions, and more advanced constructions. In presenting this evidence, we develop five theses. (i) There exist different types of frequency effect, from effects at the level of concrete lexical strings to effects at the level of abstract cues to thematic-role assignment, as well as effects of both token and type, and absolute and relative, frequency. High-frequency forms are (ii) early acquired and (iii) prevent errors in contexts where they are the target, but also (iv) cause errors in contexts in which a competing lower-frequency form is the target. (v) Frequency effects interact with other factors (e.g. serial position, utterance length), and the patterning of these interactions is generally informative with regard to the nature of the learning mechanism. We conclude by arguing that any successful account of language acquisition, from whatever theoretical standpoint, must be frequency sensitive to the extent that it can explain the effects documented in this review, and outline some types of account that do and do not meet this criterion

Modeling Parkinson's Disease Neuropathology and Symptoms by Intranigral Inoculation of Preformed Human α-Synuclein Oligomers.

The accumulation of aggregated α-synuclein (αSyn) is a hallmark of Parkinson's disease (PD). Current evidence indicates that small soluble αSyn oligomers (αSynOs) are the most toxic species among the forms of αSyn aggregates, and that size and topological structural properties are crucial factors for αSynOs-mediated toxicity, involving the interaction with either neurons or glial cells. We previously characterized a human αSynO (H-αSynO) with specific structural properties promoting toxicity against neuronal membranes. Here, we tested the neurotoxic potential of these H-αSynOs in vivo, in relation to the neuropathological and symptomatic features of PD. The H-αSynOs were unilaterally infused into the rat substantia nigra pars compacta (SNpc). Phosphorylated αSyn (p129-αSyn), reactive microglia, and cytokine levels were measured at progressive time points. Additionally, a phagocytosis assay in vitro was performed after microglia pre-exposure to αsynOs. Dopaminergic loss, motor, and cognitive performances were assessed. H-αSynOs triggered p129-αSyn deposition in SNpc neurons and microglia and spread to the striatum. Early and persistent neuroinflammatory responses were induced in the SNpc. In vitro, H-αSynOs inhibited the phagocytic function of microglia. H-αsynOs-infused rats displayed early mitochondrial loss and abnormalities in SNpc neurons, followed by a gradual nigrostriatal dopaminergic loss, associated with motor and cognitive impairment. The intracerebral inoculation of structurally characterized H-αSynOs provides a model of progressive PD neuropathology in rats, which will be helpful for testing neuroprotective therapies