Cemented total knee arthroplasty provides greater knee range of motion at 2 years than cementless technique.

Introduction: Optimal fixation method between cemented, cementless, and hybrid techniques for total knee arthroplasty (TKA) is still debated. The purpose of this study is to evaluate the clinical outcomes of patients undergoing cemented versus cementless TKA.

Methods: We reviewed 168 patients who underwent a primary TKA at a single academic institution between January 2015 and June 2017.

Selective inhibitors of SARM1 targeting an allosteric cysteine in the autoregulatory ARM domain.

The nicotinamide adenine dinucleotide hydrolase (NADase) sterile alpha toll/interleukin receptor motif containing-1 (SARM1) acts as a central executioner of programmed axon death and is a possible therapeutic target for neurodegenerative disorders. While orthosteric inhibitors of SARM1 have been described, this multidomain enzyme is also subject to intricate forms of autoregulation, suggesting the potential for allosteric modes of inhibition. Previous studies have identified multiple cysteine residues that support SARM1 activation and catalysis, but which of these cysteines, if any, might be selectively targetable by electrophilic small molecules remains unknown.

Mutant LRRK2 in lymphocytes regulates neurodegeneration via IL-6 in an inflammatory model of Parkinson's disease.

Mutations in a number of genes contribute to development of Parkinson's disease (PD), including several within the LRRK2 gene. However, little is known about the signals that underlie LRRK2-mediated neuronal loss. One clue resides in the finding that the neurodegenerative cascades emanate from signals arising from the peripheral immune system.

Eptacog Alfa (Activated) Is Physically and Chemically Stable over 24 Hours when Administered as Bolus Injections in an Automated Infusion Pump.

 Eptacog alfa (activated) is a recombinant activated factor VII (rFVIIa) used for the treatment and prevention of bleeding episodes in patients with congenital hemophilia with inhibitors. Frequent dosing requirements make the use of an automated bolus infusion pump a promising alternative to manual administration.  The objective of this in vitro study was to evaluate the physical and chemical stability of room temperature-stable rFVIIa at 25°C over 24 hours in an automated bolus infusion pump.

Cardiovascular disease and associated comorbid conditions as determinants of adverse perinatal outcomes in pregnancy - an analysis of the results of the register of pregnant BEREG.

Aim: the Aim of the BEREG Registry was to analyze the prevalence and structure of cardiovascular diseases, associated comorbid conditions and assess their effects on pregnancy and perinatal outcomes in real clinical practice.

Materials And Methods: In Tula city regional perinatal center the observation study named "Assessment of the clinical condition of the pregnant women with cardiovascular disease during gestation, at child delivery, at the early postpartum period and at twelve months after childbirth and assesment of perinatal outcomes, condition of the fetus and the newborn and the quality of treatment of these patients groups.  All eligibly pregnant women hospitalized in 2014 to "Tula regional perinatal center" have been recruited in the Registry.

Mutant LRRK2 mediates peripheral and central immune responses leading to neurodegeneration in vivo.

Missense mutations in the leucine rich repeat kinase 2 (LRRK2) gene result in late-onset Parkinson's disease. The incomplete penetrance of LRRK2 mutations in humans and LRRK2 murine models of Parkinson's disease suggests that the disease may result from a complex interplay of genetic predispositions and persistent exogenous insults. Since neuroinflammation is commonly associated with the pathogenesis of Parkinson's disease, we examine a potential role of mutant LRRK2 in regulation of the immune response and inflammatory signalling in vivo.

MPTP Mouse Model of Preclinical and Clinical Parkinson's Disease as an Instrument for Translational Medicine.

Parkinson's disease (PD) is characterized by the appearance of motor symptoms many years after the onset of neurodegeneration, which explains low efficiency of therapy. Therefore, one of the priorities in neurology is to develop an early diagnosis and preventive treatment of PD, based on knowledge of molecular mechanisms of neurodegeneration and neuroplasticity in the nigrostriatal system. However, due to inability to diagnose PD at preclinical stage, research and development must be performed in animal models by comparing the nigrostriatal system in the models of asymptomatic and early symptomatic stages of PD.

Cooperative synthesis of dopamine by non-dopaminergic neurons as a compensatory mechanism in the striatum of mice with MPTP-induced Parkinsonism.

Since the late 80s it has been repeatedly shown that besides dopaminergic neurons, the brain contains so-called monoenzymatic neurons possessing one of the enzymes of dopamine (DA) synthesis, tyrosine hydroxylase (TH) or aromatic l-amino acid decarboxylase (AADC). However, the data on the existence of monoenzymatic neurons in the striatum remain controversial, and little is known about their functional significance. The aim of this study was to test our hypothesis that monoenzymatic TH-containing neurons produce DA in cooperation with the neurons containing AADC, which might help to compensate DA deficiency under the failure of the nigrostriatal dopaminergic system.

Reversible Pharmacological Induction of Motor Symptoms in MPTP-Treated Mice at the Presymptomatic Stage of Parkinsonism: Potential Use for Early Diagnosis of Parkinson's Disease.

A crucial event in the pathogenesis of Parkinson's disease is the death of dopaminergic neurons of the nigrostriatal system, which are responsible for the regulation of motor function. Motor symptoms first appear in patients 20-30 years after the onset of the neurodegeneration, when there has been a loss of an essential number of neurons and depletion of compensatory reserves of the brain, which explains the low efficiency of treatment. Therefore, the development of a technology for the diagnosing of Parkinson's disease at the preclinical stage is of a high priority in neurology.

Activity of Monoamine Oxidase in the Nigrostriatal System at Presymptomatic and Early Symptomatic Stages of Parkinsonism in Mice.

Activities of monoamine oxidases A and B were examined on the models of presymptomatic and early symptomatic stages of Parkinson's disease developed in mice treated with MPTP, a specific neurotoxin affecting dopaminergic neurons. Activity of monoamine oxidases A, the key enzyme of dopamine degradation, is increased in neuronal somas during the symptomatic stage, and it is augmented in the axons during both stages. Neuronal activity of monoamine oxidases A is higher during the symptomatic stage than that during the presymptomatic stage, which can explain depletion of intercellular dopamine and appearance of motor disturbances.

[The determination of amitriptyline and its metabolite, nortriptyline, in the biological objects of the corpse by the high-performance liquid chromatography technique].

Tricyclic antidepressants are among the preparations that most frequently cause intoxication in adults and children; moreover, poisoning with these substances not infrequently has a fatal outcome. Medications belonging to this group, such as amitriptyline, are extensively used to manage manifestations of depression, anxiety, migraine, neuropathic pain, and hyperactivity syndrome. Amitriptyline overdosage causes non-specific symptoms of intoxication, and its clinical picture does not allow to identify the nature of a psychotropic xenobiotic.

Tyrosine hydroxylase expression and activity in nigrostriatal dopaminergic neurons of MPTP-treated mice at the presymptomatic and symptomatic stages of parkinsonism.

Progressive degeneration of nigrostriatal dopaminergic (DA-ergic) neurons is a key component in the pathogenesis of Parkinson's disease, which develops for a long time at the preclinical stage with no motor dysfunctions due to the initiation of compensatory processes. The goal of this study was to evaluate the changes in surviving nigrostriatal DA-ergic neurons with focus on tyrosine hydroxylase (TH) in MPTP-treated mice at the presymptomatic and early symptomatic stages of parkinsonism. According to our data, a partial degeneration of DA-ergic neurons at the presymptomatic stage was accompanied by: (i) no change in TH mRNA content in the substantia nigra (SN) suggesting a compensatory increase of TH gene expression in individual neurons; (ii) a decrease of TH protein content in the nigrostriatal system and no change in individual neurons, suggesting a slowdown of TH translation.

Experimental modeling of preclinical and clinical stages of Parkinson's disease.

Degeneration of dopaminergic (DAergic) neurons of the nigrostriatal system is the key stage in the pathogenesis of Parkinson's disease. The first symptoms of this disease are observed after degeneration of 70-80% neurons, which occurs over 20-30 years. The clinical stage of Parkinson's disease begins after this period.

Modeling of presymptomatic and symptomatic stages of parkinsonism in mice.

A degradation of the nigrostriatal dopaminergic (DA-ergic) system is the key component of pathogenesis of Parkinson's disease (PD). Initial clinical symptoms appear 20-30 years after the onset of neurodegeneration, at a 70% DA depletion in the striatum and a 50% loss of nigral DA-ergic neurons. Low efficacy of the therapy might be improved if preclinical diagnostics and preventive therapy are developed.

[Rapid detection of caffeine in blood by freeze-out extraction].

A new method for the detection of caffeine in blood has been proposed based on the combination of extraction and freezing-out to eliminate the influence of sample matrix. Metrological characteristics of the method are presented. Selectivity of detection is achieved by optimal conditions of analysis by high performance liquid chromatography.

The discovery of tricyclic pyridone JAK2 inhibitors. Part 1: hit to lead.

This paper describes the discovery and design of a novel class of JAK2 inhibitors. Furthermore, we detail the optimization of a screening hit using ligand binding efficiency and log D. These efforts led to the identification of compound 41, which demonstrates in vivo activity in our study.

[Modeling of preclinical and early clinical stages of Parkinson's disease].

The first symptoms of Parkinson's disease manifest 20-30 years after the disease onset when the most dopaminergic neurons degenerated. Therefore, it is necessary to work out preclinical diagnostics and preventive treatment of this disease. Modeling of preclinical and early stages of Parkinson's disease was conducted in mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropiridine (MPTP).

[Experimental modeling of functional deficiency of the nigrostriatal dopaminergic system in mice].

The dopaminergic nigrostriatal system is a key component of regulation of the motor behaviour. Cell bodies of dopaminergic DA-ergic neurons are located in the compact zone of the substantia nigra, and their axons are projected along the nigrostriatal tract to the striatum. This study was aimed to develop an experimental model of the functional insufficiency of the DA-ergic neurons of the nigrostriatal system without any manifestation of movement disorders, i.

[Prevalence of myopia in Khakasia].

The paper presents the results of studying the prevalence of myopic refraction in adolescents in the Republic of Khakasia in relation to the state of their accommodation-convergence apparatus, constitution, ethnicity, and the type of a settlement. Myopia has been found to occur 3 times more frequently among the urban adolescents. The results have led to the conclusion that urban living conditions may be a determinant of enhanced refraction.