Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.     

Ukrainian health care system and its chances for successful transition from Soviet legacies

Background

Ukraine, one of the largest states formed on the rubble of the Soviet Union, is widely perceived as a country that has lost its opportunities. Being devastated by corruption, it shows incapable to modernize and enter the economic path of sustainable growth. Similarly in the health care system no deeper reform efforts have been taken in the entire post-soviet period, leaving the system in bonds of ineffective solutions taken out of the Soviet era.

Main body

The recent geopolitical and economic crisis seem to favor the introduction of radical solutions that might lead to a rapid change in the organizational paradigm of the economic system, as well as in health care in Ukraine. In this paper we aim to highlight the key features of the ongoing health reform in Ukraine, identify basic challenges for it, and assess rationality and feasibility of the reform. We found that the projected scope and schedule of changes in the Ukrainian health system give promising prognosis regarding its final effect.

Conclusions

The final success of health reform in Ukraine is dependent on a number of factors, including the financial foundation arising of economic stability of the country, balance assurance between public and private spending for health and ability to eliminate the long-lasting practices, particularly when they are connected with activities of lobbying groups occupying particular positions in the health system. A consequence of actions taken by the political decision-makers in the longer perspective are also to highly determine the reform’s chances for success.

     

Assessment of Technological Capabilities for Forming Al-C-B System Coatings on Steel Surfaces by Electrospark Alloying Method

In this paper, the possibility of applying the electrospark alloying (ESA) method to obtain boron-containing coatings characterised by increased hardness and wear resistance is considered. A new method for producing such coatings is proposed. The method consists in applying grease containing aluminium powder and amorphous boron to the surface to be treated and subsequently processing the obtained surface using the ESA method by a graphite electrode. The microstructural analysis of the Al-C-B coatings on steel C40 showed that the surface layer consists of several zones, the number and parameters of which are determined by the energy conditions of the ESA process. Durametric studies showed that with an increase in the discharge energy influence, the microhardness values of both the upper strengthened layer and the diffusion zone increased to W_p = 0.13 J, Hµ = 6487 MPa, and W_p = 4.9 J, Hµ = 12350 MPa, respectively. The results of X-ray diffraction analysis indicate that at the discharge energies of 0.13 and 0.55 J, the phase composition of the coating is represented by solid solutions of body-centred cubic lattice (BCC) and face-centred cubic lattice (FCC). The coatings obtained at W_p = 4.9 J were characterised by the presence of intermetallics Fe₄Al₁₃ and borocementite Fe₃ (CB) in addition to the solid solutions. The X-ray spectral analysis of the obtained coatings indicated that during the electrospark alloying process, the surface layers were saturated with aluminium, boron, and carbon. With increasing discharge energy, the diffusion zone increases; during the ESA process with the use of the discharge energy of 0.13 J for steel C40, the diffusion zone is 10–15 μm. When replacing a substrate made of steel C40 with the same one material but of steel C22, an increase in the thickness of the surface layer accompanied by a slight decrease in microhardness is observed as a result of processing with the use of the ESA method. There were simulated phase portraits of the Al-C-B coatings. It is shown that near the stationary points in the phase portraits, one can see either a slowing down of the evolution or a spiral twisting of the diffusion-process particle.     

The Association between Long-Term Care Setting and Potentially Preventable Hospitalizations among Older Dual Eligibles

ObjectiveTo compare the probability of experiencing a potentially preventable hospitalization (PPH) between older dual eligible Medicaid home and community-based service (HCBS) users and nursing home residents.ConclusionsHCBS users’ increased probability for potentially and non-PPHs suggests a need for more proactive integration of medical and long-term care.     

Acoustical enrichment during early postnatal development changes response properties of inferior colliculus neurons in rats

The structure and function of the auditory system may be influenced by acoustic stimulation, especially during the early postnatal period. This study explores the effects of an acoustically enriched environment applied during the third and fourth week of life on the responsiveness of inferior colliculus neurons in rats. The enrichment comprised a spectrally and temporally modulated complex sound reinforced with several target acoustic stimuli, one of which triggered a reward release. The exposure permanently influenced neuronal representation of the sound frequency and intensity, resulting in lower excitatory thresholds at neuronal characteristic frequency, an increased frequency selectivity, larger response magnitudes, steeper rate–intensity functions and an increased spontaneous activity. The effect was general and non‐specific, spanning the entire hearing range – no changes specific to the frequency band of the target stimuli were found. The alterations depended on the activity of animals during the enrichment – a higher activity of rats in the stimulus–reward paradigm led to more profound changes compared with the treatment when the stimulus–reward paradigm was not used. Furthermore, the exposure in early life led to permanent changes in response parameters, whereas the application of the same environment in adulthood influenced only a subset of the examined parameters and had only a temporary effect. These findings indicate that a rich and stimulating acoustic environment during early development, particularly when reinforced by positive feedback, may permanently affect signal processing in the subcortical auditory nuclei, including the excitatory thresholds of neurons and their frequency and intensity resolution.     

Prolonged myelination in human neocortical evolution

Nerve myelination facilitates saltatory action potential conduction and exhibits spatiotemporal variation during development associated with the acquisition of behavioral and cognitive maturity. Although human cognitive development is unique, it is not known whether the ontogenetic progression of myelination in the human neocortex is evolutionarily exceptional. In this study, we quantified myelinated axon fiber length density and the expression of myelin-related proteins throughout postnatal life in the somatosensory (areas 3b/3a/1/2), motor (area 4), frontopolar (prefrontal area 10), and visual (areas 17/18) neocortex of chimpanzees (N = 20) and humans (N = 33). Our examination revealed that neocortical myelination is developmentally protracted in humans compared with chimpanzees. In chimpanzees, the density of myelinated axons increased steadily until adult-like levels were achieved at approximately the time of sexual maturity. In contrast, humans displayed slower myelination during childhood, characterized by a delayed period of maturation that extended beyond late adolescence. This comparative research contributes evidence crucial to understanding the evolution of human cognition and behavior, which arises from the unfolding of nervous system development within the context of an enriched cultural environment. Perturbations of normal developmental processes and the decreased expression of myelin-related molecules have been related to psychiatric disorders such as schizophrenia. Thus, these species differences suggest that the human-specific shift in the timing of cortical maturation during adolescence may have implications for vulnerability to certain psychiatric disorders.     

The sense of mastery as a mediator and moderator in the association between economic hardship and health in late life

OBJECTIVES: This study examines the ways in which the sense of mastery modifies the association between economic hardship experienced at different life stages and late-life depression, anxiety, and physical symptoms. METHODS: Using data from a sample of 1,167 older adults, ordinary least squares regression techniques were used to estimate the main and mastery-contingent effects of economic hardship. RESULTS: Results underscore the dual role of the sense of mastery in the stress process. First, mastery mediates the effects of both earlier- and later-life economic hardships on elders' current physical and mental health. Second, mastery moderates the health impact of economic hardship, although those patterns depend on the period of economic hardship and health outcome. DISCUSSION: Integrating the stress process model and a life course perspective, the authors argue that to fully understand protective capacity of psychosocial resources, stressors encountered at different life stages should be taken into account.     

Catalase inhibition by amino triazole induces oxidative stress in goldfish brain

The effects of in vivo inhibition of catalase by 3-amino 1,2,4-triazole (AMT) on the levels of damage products resulting from reactive oxygen species attack on proteins and lipids as well as on the activities of five antioxidant and associated enzymes were studied in the brain of goldfish, Carassius auratus. Intraperitoneal injection of AMT at a concentration of 0.1 mg/g wet weight caused a gradual decrease in brain catalase activity over 72 h, whereas higher AMT concentrations (0.5 or 1.0 mg/g) reduced catalase activity by about two-thirds within 5-10 h. AMT effects on antioxidant enzyme activities and oxidative stress markers were studied in detail using fish treated with 0.5 mg/g AMT for 24 or 168 h. The levels of thiobarbituric acid-reactive substances (a lipid damage product) increased 6.5-fold by 24 h after AMT injection but fell again after 168 h. The content of carbonylproteins (CP) also rose within 24 h (by approximately 2-fold) and remained 1.5-fold higher compared with respective sham-injected fish after 168 h. CP levels correlated inversely with catalase activity (R(2) = 0.83) suggesting that catalase may protect proteins in vivo against oxidative modification. The activities of both glutathione peroxidase and glutathione-S-transferase increased by approximately 50% and 80%, respectively, in brain of AMT-treated fish and this might represent a compensatory response to lowered catalase activity. Possible functions of catalase in the maintenance of prooxidant/antioxidant balance in goldfish brain are discussed.