Small-vessel occlusion versus large-artery atherosclerotic strokes in diabetics: Patient characteristics, outcomes, and predictors of stroke mechanism

Peer reviewe

Association of genetic variants in RAB23 and ANXA11 with uveitis in sarcoidosis

Purpose Uveitis occurs in a subset of patients with sarcoidosis. The purpose of this study was to determine whether genetic variants that have been associated previously with overall sarcoidosis are associated with increased risk of developing uveitis. Methods: Seventy-seven subjects were enrolled, including 45 patients diagnosed with sarcoidosis-related uveitis as cases and 32 patients with systemic sarcoidosis without ocular involvement as controls. Thirty-eight single nucleotide polymorphisms (SNPs) previously associated with sarcoidosis, sarcoidosis severity, or other organ-specific sarcoidosis involvement were identified. Allele frequencies in ocular sarcoidosis cases versus controls were compared using the chi-square test, and p values were corrected for multiple hypotheses testing using permutation. All analyses were conducted with PLINK. Results: SNPs rs1040461 and rs61860052, in ras-related protein RAS23 (RAB23) and annexin A11 (ANXA11) genes, respectively, were associated with sarcoidosis-associated uveitis. The T allele of rs1040461 and the A allele of rs61860052 were found to be more prevalent in ocular sarcoidosis cases. These associations remained after correction for the multiple hypotheses tested (p=0.01 and p=0.02). In a subanalysis of Caucasian Americans only, two additional variants within the major histocompatibility complex (MHC) genes on chromosome 6, in HLA-DRB5 and HLA-DRB1, were associated with uveitis as well (p=0.009 and p=0.04). Conclusions: Genetic variants in RAB23 and ANXA11 genes were associated with an increased risk of sarcoidosis-associated uveitis. These loci have previously been associated with overall sarcoidosis risk

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Mutations disrupting neuritogenesis genes confer risk for cerebral palsy

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance. We identified two novel monogenic etiologies, FBXO31 and RHOB, and showed that the RHOB mutation enhances active-state Rho effector binding while the FBXO31 mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in a Drosophila reverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy

MDR/XDR-TB management of patients and contacts: Challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities

Incidence of submacular haemorrhage (SMH) in Scotland : a Scottish Ophthalmic Surveillance Unit (SOSU) study

PURPOSE: Submacular haemorrhage (SMH) is a cause of severe visual loss in neovascular age-related macular degeneration (nAMD). The incidence is uncertain and furthermore there is no widely used classification system nor agreed best practice. The aim of this national surveillance study was to identify the incidence, presenting features and clinical course of new fovea-involving submacular haemorrhage associated with nAMD. METHODS: A questionnaire was sent monthly to every ophthalmic specialist in Scotland over a 12-month period asking them to report all newly presenting patients with acute SMH secondary to nAMD of at least two disc diameters (DDs) in greatest linear diameter. A follow-up questionnaire was sent 6 months after initial presentation. Cases related to other causes were excluded. RESULTS: Twenty-nine cases were reported giving an incidence of 5.4 per million per annum (range 2-15). The mean age was 83 years (range 66-96) and females accounted for 17/29 (59%). Fifteen of the 29 cases (52%) had a past history of AMD, of which 7 had nAMD. Nineteen of the 29 cases (66%) presented within 7 days of onset and the majority had SMH of < 11 DD (20/29, 69%). Treatment options comprised the following: observation (n = 6, 21%), anti-VEGF alone (n = 6, 21%) or vitrectomy with co-application of tissue plasminogen activator (TPA), anti-VEGF and gas (n = 17, 58%). The vitrectomy group experienced the greatest change in vision from logMAR 1.89-1.50 (p = 0.374). Four of 20 (20%) cases with 6 months follow-up suffered a re-bleed at a mean time of 96 days. CONCLUSIONS: The incidence, clinical features and course of a consecutive national cohort of patients with SMH secondary to nAMD are presented

GROMACS IFT input topologies and conformations used in the research article entitled: "Predictions of water/oil interfacial tension at elevated temperatures and pressures: A molecular dynamics simulation study with biomolecular force fields."

Sample configurations and topology files used as input in Gromacs for the calculation by means of molecular dynamics (MD) simulations of the interfacial tension (IFT) of mixtures of water with i) toluene (water/toluene), ii) n-dodecane (water/n-dodecane) and iii) a 50:50 % wt toluene:n-dodecane mixture (water/toluene/n-dodecane), at 1.83 MPa and temperatures ranging from 383.15 to 443.15 K

GROMACS IFT input topologies and conformations used in the research article entitled: "Predictions of water/oil interfacial tension at elevated temperatures and pressures: A molecular dynamics simulation study with biomolecular force fields."

Sample configurations and topology files used as input in Gromacs for the calculation by means of molecular dynamics (MD) simulations of the interfacial tension (IFT) of mixtures of water with i) toluene (water/toluene), ii) n-dodecane (water/n-dodecane) and iii) a 50:50 % wt toluene:n-dodecane mixture (water/toluene/n-dodecane), at 1.83 MPa and temperatures ranging from 383.15 to 443.15 K

Comparative antimicrobial susceptibility of biofilm versus planktonic forms of Salmonella enterica strains isolated from children with gastroenteritis

In the present study, 194 Salmonella enterica strains, isolated from infected children and belonging to various serotypes, were investigated for their ability to form biofilms and the biofilm forms of the isolated strains were compared to their corresponding planktonic forms with respect to the antimicrobial susceptibility. For the biofilm-forming strains, the minimum inhibitory concentration for bacterial regrowth (MICBR) from the biofilm of nine clinically applicable antimicrobial agents was determined, and the results were compared to the respective MIC values of the planktonic forms. One hundred and nine S. enterica strains out of 194 (56%) belonging to 13 serotypes were biofilm-forming. The biofilm forms showed increased antimicrobial resistance compared to the planktonic bacteria. The highest resistance rates of the biofilm bacteria were observed with respect to gentamicin (89.9%) and ampicillin (84.4%), and the lowest rates with respect to ciprofloxacin and moxifloxacin (2.8% for both). A remarkable shift of the MICBR50 and MICBR 90 toward resistance was observed in the biofilm forms as compared to the respective planktonic forms. The development of new consensus methods for the determination of the antimicrobial susceptibility of biofilm forms seems to be a major research challenge. Further studies are required in order to elucidate the biofilm antimicrobial resistance mechanisms of the bacterial biofilms and their contribution to therapeutic failure in infections with in vitro susceptible bacteria. © 2010 Springer-Verlag