Циклодиализ в лечении глаукомы. История и современность

Cyclodialysis was proposed in 1905 by Leopold Heine and actively criticized by his contemporaries, but later received a worldwide recognition in the field of open-angle and aphakic glaucoma surgery. A number of modifications has been proposed, including the combination with other hypotensive surgeries as well as the implantation of various drainage systems, fabrics and materials into the cyclodialys cleft. The effect of this surgical procedure can be attributed to the increase in uveoscleral outflow and the reduction of intraocular fluid production. Currently, cyclodialysis gave way to laser trabeculoplasty and trabeculectomy. However, cyclodialysis modifications are still used in surgical treatment of refractory glaucoma in combination with other surgeries, including cataract extraction.Циклодиализ, предложенный в 1905 г. Леопольдом Гейне и активно критикуемый его современниками, впоследствии получил мировое признание, главным образом, в хирургии открытоугольной и афакичной глаукомы. Было предложено много модификаций, в том числе сочетание циклодиализа с другими гипотензивными операциями, а также имплантации различных тканей и материалов в циклодиализную щель. Эффект вмешательства объясняется увеличением увеосклерального оттока и снижением продукции внутриглазной жидкости. В настоящее время циклодиализ уступил место лазерной трабекулопластике и трабекулэктомии. Тем не менее модификации циклодиализа применяются в хирургии рефрактерных форм глаукомы и в комбинации с другими вмешательствами, включая экстракцию катаракты

Long-term dementia prevalence in Parkinson Disease: Glass half-full?

Introduction: Dementia occurs in up to 80% of Parkinson’s disease (PD) patients long-term, but studies reporting such high rates were published years ago and had relatively small sample sizes and other limitations. Objective: To determine long-term, cumulative dementia prevalence rates in PD using data from two large, ongoing, prospective observational studies. Design: Analyses of data from the Parkinson’s Progression Markers Initiative (PPMI) and a longstanding PD research clinical core at the University of Pennsylvania (Penn). Setting: PPMI is a multi-site international study, and Penn is a single site study at a tertiary movement disorders center. Participants: PPMI enrolls de novo, untreated PD participants at baseline, and Penn enrolls a convenience cohort from a large clinical center. Methods: For PPMI a cognitive battery and MDS-UPDRS Part I are administered annually, and the site investigator assigns a cognitive diagnosis annually. At Penn a comprehensive cognitive battery is administered either annually or biennially, and a cognitive diagnosis is made by expert consensus. Main Outcomes: Kaplan-Meier (KM) survival curves were fit for time from PD diagnosis to stable dementia diagnosis for each cohort, using assigned cognitive diagnosis of dementia as the primary endpoint (for both PPMI and Penn), and MoCA score <21 and MDS-UPDRS Part I cognition score ≥3 as secondary endpoints (for PPMI). In addition, cumulative dementia prevalence by PD disease duration was tabulated for each study and endpoint. Results: For the PPMI cohort, 417 PD participants were seen at baseline; estimated cumulative probability of dementia at year 10 disease duration were: 7% (site investigator diagnosis), 9% (MoCA) or 7.4% (MDS-UPDRS Part I cognition). For the Penn cohort, 389 PD participants were followed over time, with 184 participants (47% of cohort) eventually diagnosed with dementia. The KM curve for the Penn cohort had median time to dementia diagnosis =15 years (95% CI: 13-15) disease duration; the estimated cumulative probability of dementia was 27% at year 10, 50% at year 15, and 74% at year 20. Conclusions and Relevance: Results from two large, prospective studies suggest that dementia in Parkinson disease occurs less frequently, or later in the disease course, than often-cited previous research studies have reported

Prevalence and Subtypes of Mild Cognitive Impairment in Parkinson's Disease.

The current study examined the prevalence and subtypes of Mild Cognitive Impairment (MCI) in an Australian sample of people with Parkinson's Disease (PD). Seventy participants with PD completed neuropsychological assessments of their cognitive performance, using MDS Task Force Level II diagnostic criteria for PD-MCI. A cut-off score of less than one standard deviation (SD) below normative data determined impaired performance on a neuropsychological test. Of 70 participants, 45 (64%) met Level II diagnostic criteria for PD-MCI. Among those with PD-MCI, 42 (93%) were identified as having multiple domain impairment (28 as amnestic multiple domain and 14 as nonamnestic multiple domain). Single domain impairment was less frequent (2 amnestic/1 nonamnestic). Significant differences were found between the PD-MCI and Normal Cognition groups, across all cognitive domains. Multiple domain cognitive impairment was more frequent than single domain impairment in an Australian sample of people with PD. However, PD-MCI is heterogeneous and current prevalence and subtyping statistics may be an artifact of variable application methods of the criteria (e.g., cut off scores and number of tests). Future longitudinal studies refining the criteria will assist with subtyping the progression of PD-MCI, while identifying individuals who may benefit from pharmacological and nonpharmacological interventions

Объемные показатели офтальмогемодинамики при миопии и сопутствующей глаукоме с «нормализованным» давлением

PURPOSE: To study volumetric measurements of ocular hemodynamics in patients with myopia and primary open-angle glaucoma with statistically normal IOP on hypotensive medication. METHODS: The study included 326 eyes (206 patients) with myopia and glaucoma with IOP 25 мм в сравнении с аналогичным показателем у пациентов с ПЗ

Reducing AD-Like Pathology in 3xTg-AD Mouse Model by DNA Epitope Vaccine — A Novel Immunotherapeutic Strategy

BACKGROUND: The development of a safe and effective AD vaccine requires a delicate balance between providing an adequate anti-Abeta antibody response sufficient to provide therapeutic benefit, while eliminating an adverse T cell-mediated proinflammatory autoimmune response. To achieve this goal we have designed a prototype chemokine-based DNA epitope vaccine expressing a fusion protein that consists of 3 copies of the self-B cell epitope of Abeta(42) (Abeta(1-11)) , a non-self T helper cell epitope (PADRE), and macrophage-derived chemokine (MDC/CCL22) as a molecular adjuvant to promote a strong anti-inflammatory Th2 phenotype. METHODS AND FINDINGS: We generated pMDC-3Abeta(1-11)-PADRE construct and immunized 3xTg-AD mouse model starting at age of 3-4 months old. We demonstrated that prophylactic immunizations with the DNA epitope vaccine generated a robust Th2 immune response that induced high titers of anti-Abeta antibody, which in turn inhibited accumulation of Abeta pathology in the brains of older mice. Importantly, vaccination reduced glial activation and prevented the development of behavioral deficits in aged animals without increasing the incidence of microhemorrhages. CONCLUSIONS: Data from this transitional pre-clinical study suggest that our DNA epitope vaccine could be used as a safe and effective strategy for AD therapy. Future safety and immunology studies in large animals with the goal to achieve effective humoral immunity without adverse effects should help to translate this study to human clinical trials

Immunomodulation Targeting Abnormal Protein Conformation Reduces Pathology in a Mouse Model of Alzheimer's Disease

Many neurodegenerative diseases are characterized by the conformational change of normal self-proteins into amyloidogenic, pathological conformers, which share structural properties such as high β-sheet content and resistance to degradation. The most common is Alzheimer's disease (AD) where the normal soluble amyloid β (sAβ) peptide is converted into highly toxic oligomeric Aβ and fibrillar Aβ that deposits as neuritic plaques and congophilic angiopathy. Currently, there is no highly effective treatment for AD, but immunotherapy is emerging as a potential disease modifying intervention. A major problem with most active and passive immunization approaches for AD is that both the normal sAβ and pathogenic forms are equally targeted with the potential of autoimmune inflammation. In order to avoid this pitfall, we have developed a novel immunomodulatory method that specifically targets the pathological conformations, by immunizing with polymerized British amyloidosis (pABri) related peptide which has no sequence homology to Aβ or other human proteins. We show that the pABri peptide through conformational mimicry induces a humoral immune response not only to the toxic Aβ in APP/PS1 AD transgenic mice but also to paired helical filaments as shown on AD human tissue samples. Treated APP/PS1 mice had a cognitive benefit compared to controls (p<0.0001), associated with a reduction in the amyloid burden (p = 0.0001) and Aβ40/42 levels, as well as reduced Aβ oligomer levels. This type of immunomodulation has the potential to be a universal β-sheet disrupter, which could be useful for the prevention or treatment of a wide range of neurodegenerative diseases

TKira—A hybrid N-body code

Accurately modeling the evolution of a star cluster in a strong tidal field poses unique computational challenges. We present a hybrid code that combines the strengths of two different approaches to computing gravitational forces. The internal, collisional, dynamics of the cluster is followed with a direct N-body integrator, Kira, while the galactic tidal field is modeled with a cosmological code, GADGET, that uses a Barnes-Hut tree to evaluate gravitational forces in O(N log N) time. The quadrupole moment at the center of mass of the cluster is used to compute the external potential and provides a mechanism for mass loss. This forms a robust, bidirectional interaction. The advantages of combining two highly-developed and well-established software packages at such high level are obvious and many; not the least of the these is the ability to include other physical processes, e.g., stellar evolution. One problem to which we applied this technique is the evolution of a dense star cluster near the Galactic Center. We are also using this code to explore the effects of the strong time variation in the tidal field of merging galaxies on the evolution of young star clusters forming during the merger