The hematoxylin and eosin (H&E) stain is the standard used for microscopic examination of tissues that have been fixed, processed, embedded, and sectioned. It can be performed manually or by ...automation. For economic reasons, the manual technique is generally the method of choice for facilities with a low sample volume. This protocol describes manual H&E staining of fixed, processed, paraffin-embedded, and sectioned mouse tissues. In H&E-stained tissues, the nucleic acids stain dark blue and the proteins stain red to pink or orange. For accurate phenotyping and delineation of tissue detail, the protocol must be adhered to rigorously. This includes frequent reagent changes as well as the use of "in-date" reagents. Appropriate color in a good H&E stain allows for identification of many tissue subtleties that are necessary for accurate diagnosis.
The database iPfam, available at http://ipfam.org, catalogues Pfam domain interactions based on known 3D structures that are found in the Protein Data Bank, providing interaction data at the ...molecular level. Previously, the iPfam domain-domain interaction data was integrated within the Pfam database and website, but it has now been migrated to a separate database. This allows for independent development, improving data access and giving clearer separation between the protein family and interactions datasets. In addition to domain-domain interactions, iPfam has been expanded to include interaction data for domain bound small molecule ligands. Functional annotations are provided from source databases, supplemented by the incorporation of Wikipedia articles where available. iPfam (version 1.0) contains >9500 domain-domain and 15 500 domain-ligand interactions. The new website provides access to this data in a variety of ways, including interactive visualizations of the interaction data.
Objective
To analyze the clinical findings, response to therapy, outcome, and incidence of primary central nervous system vasculitis (PCNSV) in a large cohort from a single center
Methods
We ...retrospectively studied 101 patients with PCNSV, selected by predetermined diagnostic criteria, who were seen during a 21‐year period. This was a collaborative study by five departments at a large multispecialty clinic. Clinical findings and outcomes were compared among patients categorized by method of diagnosis, response to therapy, survival, and degree of disability. An annual incidence rate was calculated
Results
Seventy patients were diagnosed by angiography and 31 by central nervous system biopsy. Three histological patterns were observed during biopsy. Although most patients responded to therapy, an increased mortality rate was observed. Relapses occurred in one fourth of patients. Mortality rate and disability at last follow‐up were greater in those who presented with a focal neurological deficit, cognitive impairment, cerebral infarctions, and angiographic large‐vessel involvement but were lower in those with prominent gadolinium‐enhanced lesions when evaluated by magnetic resonance imaging. The annual incidence rate of PCNSV was 2.4 cases per 1,000,000 person‐years
Interpretation
PCNSV is a rare disease that may result in serious neurological outcomes or death. Angiography and brain biopsy may complement each other when determining the diagnosis. Early recognition and treatment may reduce poor outcomes. PCNSV is a variable syndrome that appears to consist of several subsets of heterogeneous diseases. Ann Neurol 2007
HMMER web server: 2015 update Finn, Robert D; Clements, Jody; Arndt, William ...
Nucleic acids research,
07/2015, Volume:
43, Issue:
W1
Journal Article
Peer reviewed
Open access
The HMMER website, available at http://www.ebi.ac.uk/Tools/hmmer/, provides access to the protein homology search algorithms found in the HMMER software suite. Since the first release of the website ...in 2011, the search repertoire has been expanded to include the iterative search algorithm, jackhmmer. The continued growth of the target sequence databases means that traditional tabular representations of significant sequence hits can be overwhelming to the user. Consequently, additional ways of presenting homology search results have been developed, allowing them to be summarised according to taxonomic distribution or domain architecture. The taxonomy and domain architecture representations can be used in combination to filter the results according to the needs of a user. Searches can also be restricted prior to submission using a new taxonomic filter, which not only ensures that the results are specific to the requested taxonomic group, but also improves search performance. The repertoire of profile hidden Markov model libraries, which are used for annotation of query sequences with protein families and domains, has been expanded to include the libraries from CATH-Gene3D, PIRSF, Superfamily and TIGRFAMs. Finally, we discuss the relocation of the HMMER webserver to the European Bioinformatics Institute and the potential impact that this will have.
Objective
To describe the treatment and outcomes of patients with primary central nervous system (CNS) vasculitis.
Methods
We retrospectively studied a cohort of 163 consecutive patients with primary ...CNS vasculitis who were seen at the Mayo Clinic over a 29‐year period. We analyzed treatments, treatment responses, and factors predictive of outcomes.
Results
A favorable response was observed in 85% of patients treated with prednisone alone and in 80% of patients treated with prednisone and cyclophosphamide. Relapses were observed in 27% of patients, and 25% of patients had discontinued therapy by the time of the last followup visit. Treatment with prednisone alone was associated with more frequent relapses (odds ratio OR 2.90), while large vessel involvement (OR 6.14) and cerebral infarcts at the time of diagnosis (OR 3.32) were associated with a poor response to treatment. Prominent gadolinium‐enhanced cerebral lesions or meninges were linked with continued treatment at the last followup encounter (OR 2.28). Higher disability scores at the last followup visit were associated with increasing age at the time of diagnosis (OR 1.44) and cerebral infarctions (OR 3.74), while lower disability scores were associated with gadolinium‐enhanced cerebral lesions or meninges (OR 0.35) and cerebral amyloid angiopathy (OR 0.24). Increased mortality was associated with increasing age at diagnosis (hazard ratio HR 1.39), diagnosis by angiography (HR 3.28), cerebral infarction (HR 4.44), and large vessel involvement (HR 4.98), while reduced mortality was associated with gadolinium‐enhanced cerebral lesions or meninges (HR 0.20).
Conclusion
The majority of patients with primary CNS vasculitis responded to treatment. Recognition of findings at diagnosis that predict the course or outcome may aid in decision‐making regarding therapy.
Objective
To provide evidence‐based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA).
Methods
A core group led the ...development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946–2014), PubMed (1966–2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework.
Results
In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS.
Conclusion
These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.
In Western tradition, St. George is known as the dragon slayer. In the Middle East, he is called Khidr (“Green One”), and in addition to being a dragon slayer, he is also somehow the ...prophet Elijah. In this book, Robert D. Miller II untangles these complicated connections and reveals how, especially in his Middle Eastern guise, St. George is a reincarnation of the Canaanite storm god Baal, another “Green One” who in Ugaritic texts slays dragons.
Combining art history, theology, and archeology, this multidisciplinary study demystifies the identity of St. George in his various incarnations, laying bare the processes by which these identifications merged and diverged. Miller traces the origins of this figure in Arabic and Latin texts and explores the possibility that Middle Eastern shrines to St. George lie on top of ancient shrines of the Canaanite storm god Baal. Miller examines these holy places, particularly in modern Israel and around Mount Hermon on the Syrian-Lebanese-Israeli border, and makes the convincing case that direct continuity exists from the Baal of antiquity to the St. George/Khidr of Christian lore.
Convincingly argued and thoroughly researched, this study makes a unique contribution to such diverse areas as ancient Near Eastern studies, Roman history and religion, Christian hagiography and iconography, Quranic studies, and Arab folk religion.
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are believed to partially share genetic factors and biological influences. As the number of children with these ...diagnoses rises, so does the number of younger siblings at presumed risk for ADHD and ASD; reliable recurrence risk estimates within and across diagnoses may aid screening and early detection efforts and enhance understanding of potential shared causes.
To examine within-diagnosis sibling recurrence risk and sibling cross-aggregation of ADHD and ASD among later-born siblings of children with either disorder.
Using data extracted from medical records of 2 large health care systems in the United States, estimates of recurrence risk and cross-aggregation in later-born siblings of children with ADHD or ASD were compared with later-born siblings of children without these diagnoses. One data set included children seen between January 1, 1995, and December 31, 2013; the other included children born between January 1, 1998, and May 17, 2010. Participants included 15 175 later-born siblings of children with ADHD, ASD, and no known diagnosis. The study was conducted from October 2, 2017, to August 14, 2018.
Diagnoses of ASD or ADHD in the later-born sibling, ascertained from medical records, were the primary outcomes of interest; moderators included sex, gestational age, and maternal age.
A total of 15 175 later-born siblings were classified by familial risk status based on the older child's diagnostic status: ADHD risk (n = 730; male 51.92%), ASD risk (n = 158; male 48.10%), and no known risk (n = 14 287; male 50.73%). Compared with later-born siblings of children without ADHD or ASD, later-born siblings of children with ASD were more likely to be diagnosed with ASD (odds ratio OR, 30.38; 95% CI, 17.73-52.06) or ADHD in the absence of ASD (OR, 3.70; 95% CI, 1.67-8.21). Compared with later-born siblings of children without a diagnosis, later-born siblings of children with ADHD were more likely to be diagnosed with ADHD (OR, 13.05; 95% CI, 9.86-17.27) or ASD in the absence of ADHD (OR, 4.35; 95% CI, 2.43-7.79).
Later-born siblings of children with ASD or ADHD appear to be at elevated risk for the same disorder, but also of being diagnosed with the other disorder. These findings provide further support for shared familial mechanisms underlying ASD and ADHD, which may be useful for genetic and prospective developmental studies. Later-born siblings of children with ADHD or ASD should be monitored for both conditions.
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