Parkinson's Disease in Central Asian and Transcaucasian Countries: A Review of Epidemiology, Genetics, Clinical Characteristics, and Access to Care

Our understanding of Parkinson’s disease (PD) has significantly accelerated over the last few years, but predominant advances have been made in developed, Western countries. Little is known about PD in the Central Asian (CA) and Transcaucasian (TC) countries. Here, we review the clinical characteristics, treatments used, epidemiology, and genetics of PD in CA and TC countries via a methodological search in MEDLINE, EMBASE, Scopus, Web of Science, and Google Scholar databases. For the acquisition of PD care-related data, the search was extended to the local web resources. Our findings showed that PD prevalence in the region is averaging 62 per 100,000 population. The mean age of onset is 56.4 ± 2.8 in females and 63.3 ± 3.5 in males. Large-scale national studies on PD prevalence from the region are currently lacking. A limited number of genetic studies with small cohorts and inconclusive results were identified. The G2019S LRRK2 mutation, the commonest mutation in PD worldwide, was found in 5.7% of patients with idiopathic PD and 17.6% of familial cases in 153 Uzbek patients. Our review highlighted systematic deficiencies in PD health care in the region including lacks of neurologists specializing in PD, delays in PD diagnosis, absence of specialized PD nurses and PD rehab services, limited access to PD medications and surgery, and the unavailability of PD infusion therapies. Overall, this article demonstrated the paucity of data on this common neurological disorder in CA and TC countries and identified a number of healthcare areas that require an urgent consideration. We conclude that well-designed large-scale epidemiological, genetic, and clinical studies are desperately needed in this region. Healthcare professionals, local and national institutions, and stakeholders must come together to address deficiencies in PD healthcare systems in CA and TC countries

Features of cardiovascular remodeling, the level of neurohumoral factors depending on the degree of chronic heart failure and kidney dysfunction

Aim. To study the relationship between the level of the N-terminal prohormone of brain natriuretic peptide (NTproBNP) and aldosterone in serum, cardiovascular remodeling parameters with the degree of chronic heart failure (CHF) and kidney dysfunction (KD).Material and methods. Fifty two patients with coronary artery disease with CHF of I (19 patients), II (21) and III (12) functional classes (FC) were examined. All patients underwent echocardiography with assessment of systolic function and structural-geometric parameters of the left ventricle (LV), blood flow study at the level of the common carotid artery (CCA) with the determination of the thickness of the intim-media complex, velocity parameters of blood flow, resistance (RI) and pulsation (PI) indexes, estimated glomerular filtration rate (eGFR) by CKD-ЕРI method, the level of NTproBNP and aldosterone in serum. The patients were divided depending on the eGFR elvel: 30< eGFR ≤60 ml/min/1,73 m2 — 14 patients, eGFR >60 ml/min/1,73 m2 — 38 patients.Results. Patients with II FC CHF had the medium-high NTproBNP and aldosterone values. Subjects with FC III CHF had high levels of NTproBNP and aldosterone. A correlation relationship was found between the NTproBNP, aldosterone and ejection fraction (EF) levels (r=-0,70 and r=-0,72, respectively), between the NTproBNP, aldosterone and enddiastolic LV velocity (r=0,78 and r=0,70, respectively). There was a significant thickening of the carotid intima-media complex and a decrease in the blood flow velocity and an increase in vascular resistance with increasing CHF. We also noted a significant difference in the maximum end-diastolic velocity in patients with eGFR ≤60 ml/min/1,73 m2 compared with this indicator in patients with eGFR >60 ml/min/1,73 m2.Conclusion. In patients with CHF, a significant increase in NTproBNP and aldosterone levels is associated with FC of CHF, LV systolic dysfunction and KD. The interrelation of cardiovascular remodeling indicators with the degree of CHF and KD was revealed

Biochemical and immunological characterization of an ETEC CFA/I adhesin cholera toxin B subunit chimera.

Surface-expressed colonization factors and their subunits are promising candidates for inclusion into a multivalent vaccine targeting enterotoxigenic Escherichia coli (ETEC), a leading cause of acute bacterial diarrhea in developing regions. However, soluble antigens are often poorly immunogenic in the absence of an adjuvant. We show here that the serum immune response to CfaE, the adhesin of the ETEC colonization factor CFA/I, can be enhanced in BALB/c mice by immunization with a chimeric antigen containing CfaE and pentameric cholera toxin B subunit (CTB) of cholera toxin from Vibrio cholerae. We constructed this antigen by replacing the coding sequence for the A1 domain of the cholera toxin A subunit (CTA) with the sequence of donor strand complemented CfaE (dscCfaE) within the cholera toxin operon, resulting in a dscCfaE-CTA2 fusion. After expression, via non-covalent interactions between CTA2 and CTB, the fusion and CTB polypeptides assemble into a complex containing a single dscCfaE-CTA2 protein bound to pentameric CTB (dscCfaE-CTA2/CTB). This holotoxin-like chimera retained the GM1 ganglioside binding activity of CTB, as well as the ability of CfaE to mediate the agglutination of bovine red blood cells when adsorbed to polystyrene beads. When administered intranasally to mice, the presence of CTB in the chimera significantly increased the serum immune response to CfaE compared to dscCfaE alone, stimulating a response similar to that obtained with a matched admixture of dscCfaE and CTB. However, by the orogastric route, immunization with the chimera elicited a superior functional immune response compared to an equivalent admixture of dscCfaE and CTB, supporting further investigation of the chimera as an ETEC vaccine candidate

Structure of the archaeal pab87 peptidase reveals a novel self-compartmentalizing protease family.

Self-compartmentalizing proteases orchestrate protein turnover through an original architecture characterized by a central catalytic chamber. Here we report the first structure of an archaeal member of a new self-compartmentalizing protease family forming a cubic-shaped octamer with D(4) symmetry and referred to as CubicO. We solved the structure of the Pyrococcus abyssi Pab87 protein at 2.2 A resolution using the anomalous signal of the high-phasing-power lanthanide derivative Lu-HPDO3A. A 20 A wide channel runs through this supramolecular assembly of 0.4 MDa, giving access to a 60 A wide central chamber holding the eight active sites. Surprisingly, activity assays revealed that Pab87 degrades specifically d-amino acid containing peptides, which have never been observed in archaea. Genomic context of the Pab87 gene showed that it is surrounded by genes involved in the amino acid/peptide transport or metabolism. We propose that CubicO proteases are involved in the processing of d-peptides from environmental origins