Lactoferrin for the treatment of age-associated inflammation - A pilot study.

BACKGROUND: Chronic inflammation (CI) is a common trait of aging associated with adverse outcomes including mortality. We hypothesized that recombinant human Lactoferrin (rhLf) would reduce chronic inflammation of aging. METHODS: Thirty-six community dwelling older adults were randomly assigned to rhLf or placebo treatment in 1:1 ratio for 3 months. IL-6, sTNFR1, Comprehensive Metabolic Panel (CMP), and Complete Blood Count (CBC) were measured at baseline, 1 month, 3 months, and 6 months. Physical and cognitive measures were completed at same timepoints, including 4-m walking speed (m/s), grip strength (kg), 6-min walking distance (m), home activity measured by accelerometer, trail making test - Part A (s) and - Part B (s), and Digit symbol substitution test (number correctly coded). Primary outcomes were differences in IL-6 and sTNFR1 concentrations evaluated by generalized linear model with log-link and gamma family distribution, controlling for baseline cytokine concentrations. RESULTS: rhLF was well-tolerated. There were a significant number of abdominal complaints and increased drop-out rate in placebo group. Participants in rhLf arm had non-significant lower mean percent increase in IL6 at 3 months (rhLf mean IL-6 6% lower than control, P = 0.843), and sTNFaR1 (rhLf mean 2% lower than control, P = 0.36). No significant changes were observed for the cognitive or physical measures. CONCLUSION: Treatment with rhLf did not significantly alter serum IL6 or sTNFR1 concentrations of older adults. This study may have been underpowered to detect difference, but provided evidence that a larger sample-size could more definitively determine the effect of rhLF on age-associated CI.

Intracerebral hemorrhage after external ventricular drain placement: an evaluation of risk factors for post-procedural hemorrhagic complications.

BACKGROUND: The objective of this study was to evaluate and identify the risk factors for developing a new or enlarged intracranial hemorrhage (ICH) after the placement of an external ventricular drain. METHODS: A single center, nested case-control study of individuals who received an external ventricular drain from June 1, 2011 to June 30, 2014 was conducted at a large academic medical center. A bivariate analysis was conducted to compare those individuals who experienced a post-procedural intracranial hemorrhage to those who did not experience a new bleed. The variables identified as having a p-value less than 0.15 in the bivariate analysis were then evaluated using a multivariate logistic regression model. RESULTS: Twenty-seven of the eighty-one study participants experienced a new or enlarged intracranial hemorrhage after the placement of an external ventricular drain. Of these twenty-seven patients, 6 individuals received an antiplatelet within ninety-six hours of external ventricular drain placement (p = 0.024). The multivariate logistic regression model identified antiplatelet use within 96 h of external ventricular drain insertion as an independent risk factor for post-EVD ICH (OR 13.1; 95% CI 1.95-88.6; p = 0.008). CONCLUSION: Compared to those study participants who did not receive an antiplatelet within 96 h of external ventricular drain placement, those participants who did receive an antiplatelet were 13.1 times more likely to exhibit a new or enlarged intracranial hemorrhage.

Management of apixaban-associated subdural hematoma: a case report on the use of factor eight inhibitor bypassing activity.

OBJECTIVE: We report a case of a patient receiving apixaban who developed a spontaneous subdural hematoma and declining mental status that improved after administration of a single dose of factor eight inhibitor bypassing activity. DESIGN: Case report. SETTING: Comprehensive Stroke Center, Neurocritical Care Unit. PATIENT: A 76-year-old man presented to an outside facility with a chief complaint of headache and pain behind his right eye. A CT scan of his head revealed a subdural hematoma. The patient was transferred to our facility with worsening clinical status. INTERVENTIONS: After a confirmatory cranial CT scan revealed a worsening subdural hematoma with midline shift, a single dose of factor VIII inhibitor bypassing activity (25 U/kg) was administered. MEASUREMENTS AND MAIN RESULTS: Coagulation tests following the administration of factor VIII inhibitor bypassing activity and a follow-up CT scan confirmed hemostasis. The patient was discharged home with no focal deficits. CONCLUSIONS: Factor VIII inhibitor bypassing activity may be a viable, nonspecific reversal agent for life-threatening bleeding associated with apixaban.

The best and the brightest: exploiting tryptophan-sensitized Tb(3+) luminescence to engineer lanthanide-binding tags.

Consider the lanthanide metals, comprising lanthanum through lutetium. Lanthanides form stable cations with a +3 charge, and these ions exhibit a variety of useful physical properties (long-lifetime luminescence, paramagnetism, anomalous X-ray scattering) that are amenable to studies of biomolecules. The absence of lanthanide ions in living systems means that background signals are generally a nonissue; however, to exploit the advantageous properties it is necessary to engineer a robust lanthanide-binding sequence that can be appended to any macromolecules of interest. To this end, the luminescence produced by tryptophan-sensitized Tb(3+) has been used as a selection marker for peptide sequences that avidly chelate these ions. A combinatorial split-and-pool library that uses two orthogonal linkers-one that is cleaved for selection and one that is cleaved for sequencing and characterization-has been used to develop lanthanide-binding tags (LBTs): peptides of 15-20 amino acids with low-nM affinity for Tb(3+). Further validating the success of this screen, knowledge about LBTs has enabled the introduction of a lanthanide-binding loop in place of one of the four native calcium-binding loops within the protein calcineurin B.

Intrinsic site-selectivity of ubiquitin dimer formation.

The post-translational modification of proteins with ubiquitin can take on many forms, including the decoration of substrates with polymeric ubiquitin chains. These chains are linked through one of the seven lysine residues in ubiquitin, with the potential to form a panoply of linkage combinations as the chain length increases. The ensuing structural diversity of modifications serves a variety of signaling functions. Still, some linkages are present at a much higher level than others in cellulo. Although ubiquitination is an enzyme-catalyzed process, the large disparity of abundancies led us to the hypothesis that some linkages might be intrinsically faster to form than others, perhaps directing the course of enzyme evolution. Herein, we assess the kinetics of ubiquitin dimer formation in an enzyme-free system by measuring the rate constants for thiol-disulfide interchange between appropriate ubiquitin variants. Remarkably, we find that the kinetically expedient linkages correlate with those that are most abundant in cellulo. As the abundant linkages also appear to function more broadly in cellulo, this correlation suggests that the more accessible chains were selected for global roles.

Thromboelastographic changes in patients experiencing an acute ischemic stroke and receiving alteplase.

BACKGROUND: Thromboelastography is a method of measuring whole-blood coagulation changes and has been used to guide therapy and monitor changes in a variety of disease states. However, few studies have investigated the thromboelastographic changes experienced in a patient who has received alteplase for an acute ischemic stroke. This pilot study sought to describe the effect of alteplase on the thromboelastogram tracings of patients experiencing an acute ischemic stroke. METHODS: This was an institutional review board-approved prospective cohort study. Patients who presented to the emergency department with symptoms of acute ischemic stroke and received intravenous alteplase were evaluated for inclusion. Blood samples were obtained before alteplase administration and at 30, 60, 90, 120, and 150 minutes after alteplase administration. In addition, baseline variables collected included patient age, sex, prothrombin time, partial thromboplastin time, and the use of pretreatment anticoagulants or antiplatelet agents. Patients were also followed throughout their hospital stay for development of intracranial hemorrhage. RESULTS: A total of 7 patients were included in the analysis. At baseline, thromboelastogram parameters of all patients were within the normal range. The maximum inhibition of fibrin buildup was seen at 30 minutes after the start of alteplase infusion, and the lowest clot strength was observed at 60 minutes after initiation of alteplase. Most patients return to near baseline parameters within 150 minutes of alteplase initiation; however, 2 patients did not return to their baseline values within the 150-minute time frame. CONCLUSIONS: Our study suggests that thromboelastogram (TEG) is a useful tool for determining changes in the coagulation system of patients whom have received recombinant tissue plasminogen activator (rt-PA). Further study is needed to determine if TEG can be used to predict those patients who may be at higher risk of adverse events because of rt-PA.

Tailoring encodable lanthanide-binding tags as MRI contrast agents.

Lanthanide-binding tags (LBTs), peptide-based coexpression tags with high affinity for lanthanide ions, have previously been applied as luminescent probes to provide phasing for structure determination in X-ray crystallography and to provide restraints for structural refinement and distance information in NMR. The native affinity of LBTs for Gd(3+) indicates their potential as the basis for engineering of peptide-based MRI agents. However, the lanthanide coordination state that enhances luminescence and affords tightest binding would not be ideal for applications of LBTs as contrast agents, due to the exclusion of water from the inner coordination sphere. Herein, we use structurally defined LBTs as the starting point for re-engineering the first coordination shell of the lanthanide ion to provide for high contrast through direct coordination of water to Gd(3+) (resulting in the single LBT peptide, m-sLBT). The effectiveness of LBTs as MRI contrast agents was examined in vitro through measurement of binding affinity and proton relaxivity. For imaging applications that require targeted observation, fusion to specific protein partners is desirable. However, a fusion protein comprising a concatenated double LBT (dLBT) as an N-terminal tag for the model protein ubiquitin had reduced relaxivity compared with the free dLBT peptide. This limitation was overcome by the use of a construct based on the m-sLBT sequence (q-dLBT-ubiquitin). The structural basis for the enhanced contrast was examined by comparison of the X-ray crystal structure of xq-dLBT-ubiquitin (wherein two tryptophan residues are replaced with serine), to that of dLBT-ubiquitin. The structure shows that the backbone conformational dynamics of the MRI variant may allow enhanced water exchange. This engineered LBT represents a first step in expanding the current base of specificity-targeted agents available.

Marathon of eponyms: 26 Zinsser-Engman-Cole syndrome (Dyskeratosis congenita).

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognised relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarises data about Zinsser-Engman-Cole syndrome.

Marathon of eponyms: 24 Xmas (Christmas) disease.

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognised relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarises data about Christmas disease.

Marathon of eponyms: 25 Yersiniosis.

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognised relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarises data about Yersiniosis.

Marathon of eponyms: 23 Wegener granulomatosis.

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology and oral, oral and maxillofacial radiology and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognized relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarizes data about Wegener granulomatosis.

Marathon of eponyms: 22 Virchow node.

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognized relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarizes data about Virchow node.

Marathon of eponyms: 21 Urbach-Wiethe disease (Lipoid proteinosis).

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognized relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarizes data about Urbach-Wiethe disease.

Marathon of eponyms: 20 Treacher Collins syndrome.

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognized relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarizes data about Treacher Collins syndrome.

Marathon of eponyms: 19 Sjögren syndrome.

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognized relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarizes data about Sjögren syndrome.

Marathon of eponyms: 18 Robin sequence.

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognized relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarizes data about Robin sequence.

Marathon of eponyms: 17 Quincke oedema (Angioedema).

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognized relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarizes data about Quincke's oedema.

Marathon of eponyms: 16 Paget disease of bone.

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognised relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarises data about Paget disease of bone.

Marathon of eponyms: 15 Osler-Rendu-Weber disease (Hereditary haemorrhagic telangiectasia).

The use of eponyms has long been contentious, but many remain in common use, as discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms in diseases of the head and neck is found mainly in specialties dealing with medically compromised individuals (paediatric dentistry, special care dentistry, oral and maxillofacial medicine, oral and maxillofacial pathology, oral and maxillofacial radiology and oral and maxillofacial surgery) and particularly by hospital-centred practitioners. This series has selected some of the more recognised relevant eponymous conditions and presents them alphabetically. The information is based largely on data available from MEDLINE and a number of internet websites as noted below: the authors would welcome any corrections. This document summarises data about Osler-Rendu-Weber disease.