Oral Prophylaxis

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The prevalence of peripheral neuropathy severe enough to cause a loss of protective sensation in a population-based sample of people with known and newly detected diabetes in Barbados: a cross-sectional study.

AIMS: To determine the prevalence and potential risk factors for diabetic peripheral neuropathy with a loss of protective sensation in Barbados. METHODS: A representative population sample aged > 25 years with previously diagnosed diabetes or a fasting blood glucose ≥ 7 mmol/l or HbA1c ≥ 48 mmol/mol (6.5%) was tested by 10 g monofilament at four plantar sites per foot and a 28 Hz tuning fork and neurothesiometer at the hallux. Data were adjusted to the age structure of people with diabetes in Barbados. Multivariable logistic regression assessed associations with peripheral neuropathy with a loss of protective sensation. RESULTS: Of 236 participants [74% response rate, 33% men, 91% black, median age 58.6 years, mean BMI 30.1 kg/m2 , mean HbA1c 54 mmol/mol (7.1%)], 51% had previously diagnosed diabetes. Foot examination demonstrated that 25.8% (95% CI 20.2 to 31.5) had at least one insensate site with monofilament testing, 14.8% (95% CI 10.2 to 19.4) had an abnormal tuning fork test and 10.9% (95% CI 6.9 to 14.9) had a vibration perception threshold > 25 V. Peripheral neuropathy with a loss of protective sensation prevalence was 28.5% (95% CI 22.7 to 34.4) as indicated by monofilament with ≥ 1 insensate site and/or vibration perception threshold > 25 V. With previously diagnosed diabetes the prevalence was 36.4% (95% CI 27.7 to 45.2) with 98.4% of cases identified by monofilament testing. Increasing age, previously diagnosed diabetes, male sex and abdominal obesity were independently associated with peripheral neuropathy with a loss of protective sensation. CONCLUSIONS: Over a third of people with previously diagnosed diabetes had evidence of peripheral neuropathy with a loss of protective sensation. Monofilament testing alone may be adequate to rule out peripheral neuropathy with a loss of protective sensation. Monofilament and neurothesiometer stimuli are reproducible but dependent on participant response

Automated ligand fitting by core-fragment fitting and extension into density

An automated ligand-fitting procedure has been developed and tested on 9327 ligands and (F o − F c)exp(iϕc) difference density from macromolecular structures in the Protein Data Bank

HLA class I and II genotype of the NCI-60 cell lines

Sixty cancer cell lines have been extensively characterized and used by the National Cancer Institute's Developmental Therapeutics Program (NCI-60) since the early 90's as screening tools for anti-cancer drug development. An extensive database has been accumulated that could be used to select individual cells lines for specific experimental designs based on their global genetic and biological profile. However, information on the human leukocyte antigen (HLA) genotype of these cell lines is scant and mostly antiquated since it was derived from serological typing. We, therefore, re-typed the NCI-60 panel of cell lines by high-resolution sequence-based typing. This information may be used to: 1) identify and verify the identity of the same cell lines at various institutions; 2) check for possible contaminant cell lines in culture; 3) adopt individual cell lines for experiments in which knowledge of HLA molecule expression is relevant. Since genome-based typing does not guarantee actual surface protein expression, further characterization of relevant cell lines should be entertained to verify surface expression in experiments requiring correct antigen presentation

Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases

Key physiological functions of the liver, including glucose and lipid metabolism, become disturbed in the setting of non-alcoholic fatty liver disease (NAFLD) and may be associated with a systemic inflammatory 'milieu' initiated in part by liver-secreted cytokines and molecules. Consequently, the pathophysiological effects of NAFLD extend beyond the liver with a large body of clinical evidence demonstrating NAFLD to be independently associated with both prevalent and incident cardiovascular disease (CVD), chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). The magnitude of risk of developing these extrahepatic diseases parallels the underlying severity of NAFLD, such that patients with non-alcoholic steatohepatitis (NASH) appear to be at greater risk of incident CVD, CKD and T2DM than those with simple steatosis. Other modifiers of risk may include genetic variants (eg, patatin-like phospholipase domain-containing 3 and trans-membrane 6 superfamily member 2 polymorphisms), visceral adipose tissue accumulation, dietary intake and the gut microbiome. Emerging data also suggest that NAFLD may be a risk factor for colonic neoplasia and reduced bone mineral density, especially among men. Importantly, improvement/resolution of NAFLD is associated with a reduced incidence of T2DM and improved kidney function, adding weight to causality and suggesting liver focused treatments may reduce risk of extrahepatic complications. Awareness of these associations is important for the clinicians such that CVD risk factor management, screening for T2DM and CKD are part of the routine management of patients with NAFLD

Impacts and effects of ocean warming on intertidal rocky habitats.

• Intertidal rocky habitats comprise over 50% of the shorelines of the world, supporting a diversity of marine life and providing extensive ecosystem services worth in the region of US$ 5-10 trillion per year. • They are valuable indicators of the impacts of climate change on the wider marine environment and ecosystems. • Changes in species distributions, abundance and phenology have already been observed around the world in response to recent rapid climate change. • Species-level responses will have considerable ramifications for the structure of communities and trophic interactions, leading to eventual changes in ecosystem functioning (e.g. less primary producing canopy-forming algae in the North-east Atlantic). • Whilst progress is made on the mitigation1 required to achieve goals of a lower-carbon world, much can be done to enhance resilience to climate change. Managing the multitude of other interactive impacts on the marine environment, over which society has greater potential control (e.g. overfishing, invasive non-native species, coastal development, and pollution), will enable adaptation1 in the short and medium term of the next 5-50 years