Autophagy is an important intracellular degradative process that delivers cytoplasmic proteins to lysosome for degradation. Dysfunction of autophagy is implicated in several human diseases, such as neurodegenerative diseases, infectious diseases, and cancers. Autophagy-related proteins are constitutively expressed in the eye. Increasing studies have revealed that abnormal autophagy is an important pathological feature of several ocular diseases. Pharmacological manipulation of autophagy may provide an alternative therapeutic target for some ocular diseases. In this manuscript, we reviewed the relevant progress about the role of autophagy in the pathogenesis of ocular diseases.

/pdf/repertoires-of-autophagy-in-the-pathogenesis-of-ocular-2lklvj9lx2.pdf

Repertoires of Autophagy in the Pathogenesis of Ocular Diseases

There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.

/pdf/genome-wide-association-study-of-14-000-cases-of-seven-5ay7q0q3vy.pdf

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classifi cation criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classifi cation criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated infl ammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/ or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classifi cation as ‘defi nite RA’ is based on the confi rmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classifi cation system redefi nes the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defi ning the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.

/pdf/2010-rheumatoid-arthritis-classification-criteria-an-h6w7bcnbf6.pdf

2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classification as ‘definite RA’ is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.

https://ard.bmj.com/content/annrheumdis/69/9/1580.full.pdf

2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

Objective. The development and validation of Modified Disease Activity Scores (DAS) that include different 28-joint counts.

Methods. These scores were developed by canonical discriminant analyses and validated for criterion, correlational, and construct validity. The influence of disease duration on the composition of the DAS was also investigated.

Results. No influence of disease duration was found. The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists).

Conclusion. The Modified DAS are as valid as disease activity scores that include more comprehensive joint counts.

/pdf/modified-disease-activity-scores-that-include-twenty-eight-1x0unex9gh.pdf

Modified disease activity scores that include twenty-eight-joint counts : development and validation in a prospective longitudinal study of patients with rheumatoid arthritis

The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780310302

The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

https://www.archives-pmr.org/article/0003-9993(91)90072-Q/pdf

Corticosteroid injections in adhesive capsulitis: investigation of their value and site.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780300421

Survival in rheumatoid arthritis.

Sulfasalazine in the rheumatic disease.

To determine the prevalence and clinical significance of leukocytosis in rheumatoid arthritis (RA), records of 98 consecutive outpatients with this disease were reviewed. Leukocytosis, defined as 2 or more white blood cell counts (WBC) greater than 10,000/mm, was found in 27%. Among patients currently receiving steroid therapy (mean dose prednisone 7 mg daily), the prevalence was 40%; in all others, the prevalence was 7.5%. The WBC elevation was primarily caused by an increase in neutrophils. Patients with leukocytosis tended to have more active arthritis, but there were no differences in extra-articular manifestations or drug therapy except for the use of corticosteroids.A review of the literature confirms the contributions of both disease activity and steroid therapy to WBC elevation. There is little published information on the effect of chronic, low dose corticosteroids on WBC counts, but our study suggests that this is an important factor in leukocytosis in RA.Newly detected leukocytosis in RA should alert the physician to the possibility of occult infection. In the absence of suggestive signs and symptoms, an infectious cause is seldom found, but, despite the few infections found in this series, continuing vigilance is recommended.

Leukocytosis in rheumatoid arthritis.

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