Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns [PAMPs] and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use.
Adaptive Immunity ; Adjuvants, Immunologic ; Allergy and Immunology ; Aluminum Hydroxide ; Aluminum* ; Antigen Presentation ; Antigen-Presenting Cells ; Bias (Epidemiology) ; Chitosan ; Colloids ; Dendritic Cells ; Emulsions ; Immunity, Innate ; Ligands ; Nanoparticles ; Polymers ; Receptors, Pattern Recognition ; Salts* ; Systems Biology ; Toll-Like Receptors ; Vaccines

Myasthenia gravis (MG) is a neuromuscular autoimmune disorder which clinically presents as muscular weakness and fatigue due to autoantibody formation against acetylcholine receptors (AChR), leading to their subsequent destruction. Due to the neuromuscular implications of MG, certain considerations must be taken into account when providing anesthesia to MG patients. In the following case report, we have outlined procedural considerations for the anesthetic management of a patient with MG undergoing deep sedation for an elective oral surgery in an outpatient setting, as well as a discussion of relevant literature.
Anesthesia ; Deep Sedation ; Fatigue ; Humans ; Muscle Weakness ; Myasthenia Gravis ; Outpatients ; Receptors, Cholinergic ; Surgery, Oral

The aim of the study was to examine lipid profiles, arterial stiffness (AS), carotid intima-media thickness (cIMT), in 55 women with RA without overt cardiovascular disease (capital ES, CyrillicVD) treated with rituximab (RTX).The following parameters were recorded before and 24 weeks after RTX therapy (2 infusions of 500 or 1,000 mg RTX intravenously, fortnightly): plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, DAS 28-ESR, serum C-reactive protein (CRP), RF IgM, AS (SI - stiffness index, RI - reflection index) by digital volume pulse contour analysis (Micro Medical, UK), and common cIMT by high-resolution B-mode carotid ultrasound. Based on the European League Against Rheumatism (EULAR) criteria, patients were divided into two groups: 1) moderate/good response to RTX therapy after 24 weeks (41 patients, 75%), 2) no response to RTX therapy (14 patients, 25%). Effective RTX therapy resulted in 9% increase in TC, 23% increase in HDL-C and 14% decrease in atherogenic index, 57% decrease in SI and 24% decrease in RI. We observed a 9% decrease of cIMTmax at 24 weeks. The improvement of cardiovascular parameters was accompanied by statistically significant decreases of CRP, ESR, RF IgM and DAS 28 in group 1 (P < 0.05). There were not significant changes in lipid profile, AS parameters, and cIMT in group 2. Two infusions of RTX in case of moderate/good EULAR effect of therapy exerted favorable effects on lipid profile, AS and cIMT in women with RA without overt CVD.
Antirheumatic Agents/*therapeutic use ; Arthritis, Rheumatoid/complications/*drug therapy/physiopathology ; Biomarkers/blood ; C-Reactive Protein/analysis ; Cardiovascular Diseases/complications ; Carotid Intima-Media Thickness ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Female ; Humans ; Lipids/*blood ; Middle Aged ; Rituximab/*therapeutic use ; Treatment Outcome ; Triglycerides/blood ; Vascular Stiffness

The aim of the study was to examine lipid profiles, arterial stiffness (AS), carotid intima-media thickness (cIMT), in 55 women with RA without overt cardiovascular disease (capital ES, CyrillicVD) treated with rituximab (RTX).The following parameters were recorded before and 24 weeks after RTX therapy (2 infusions of 500 or 1,000 mg RTX intravenously, fortnightly): plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, DAS 28-ESR, serum C-reactive protein (CRP), RF IgM, AS (SI - stiffness index, RI - reflection index) by digital volume pulse contour analysis (Micro Medical, UK), and common cIMT by high-resolution B-mode carotid ultrasound. Based on the European League Against Rheumatism (EULAR) criteria, patients were divided into two groups: 1) moderate/good response to RTX therapy after 24 weeks (41 patients, 75%), 2) no response to RTX therapy (14 patients, 25%). Effective RTX therapy resulted in 9% increase in TC, 23% increase in HDL-C and 14% decrease in atherogenic index, 57% decrease in SI and 24% decrease in RI. We observed a 9% decrease of cIMTmax at 24 weeks. The improvement of cardiovascular parameters was accompanied by statistically significant decreases of CRP, ESR, RF IgM and DAS 28 in group 1 (P < 0.05). There were not significant changes in lipid profile, AS parameters, and cIMT in group 2. Two infusions of RTX in case of moderate/good EULAR effect of therapy exerted favorable effects on lipid profile, AS and cIMT in women with RA without overt CVD.
Antirheumatic Agents/*therapeutic use ; Arthritis, Rheumatoid/complications/*drug therapy/physiopathology ; Biomarkers/blood ; C-Reactive Protein/analysis ; Cardiovascular Diseases/complications ; Carotid Intima-Media Thickness ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Female ; Humans ; Lipids/*blood ; Middle Aged ; Rituximab/*therapeutic use ; Treatment Outcome ; Triglycerides/blood ; Vascular Stiffness

There is a spelling mistake of an author's name, and they want to change to Samir Pancholy from Sameer Pancholy.

BACKGROUND/AIMS: Several prognostic markers for heart failure (HF) have been determined but the importance of liver function tests (LFTs) remains unknown. The aim of this study was to determine the prognostic significance, if any, of abnormal LFTs in acute decompensated HF. METHODS: All adult patients (> 18 years of age) who were admitted to a community hospital with a diagnosis of acute decompensated HF during the period January 2008 to December 2009 were identified. Exclusion criteria included acute coronary syndrome, active hepatobiliary disease, renal failure (serum creatinine > or = 2 mg/dL), and malignancy. The primary end point was readmission secondary to acute exacerbation of HF. The Cox proportional hazard model was used for statistical analyses. RESULTS: Univariate analysis showed that serum total bilirubin (TB, p < 0.01), serum B-type natriuretic peptide (p < 0.05), ejection fraction (EF, p < 0.05), and heart rate (p < 0.05) were significant predictors of hospital readmission secondary to acute decompensated HF. Multivariate analysis showed that high serum TB (> 1.3 mg/dL) on admission was an independent predictor (p < 0.05) of hospital readmission secondary to HF. The 'at-risk' group-patients with serum TB > 1.3 mg/dL and/or EF < 35% on admission-had a readmission rate that was 87% +/- 20% (p < 0.05) higher than those with neither criterion. CONCLUSIONS: In patients with acute decompensated HF, elevated serum TB on admission with or without low EF (< 35%) predicts a worse prognosis and early future readmission, secondary to HF.
Aged ; Aged, 80 and over ; Bilirubin/*blood ; Biological Markers/blood ; Female ; Heart Failure/*blood/diagnosis ; Humans ; Kaplan-Meier Estimate ; Liver Function Tests ; Male ; Patient Readmission/statistics & numerical data ; Prognosis ; Retrospective Studies

In this work, we used a preparation of diminazene, which belongs to the group of aromatic diamidines. This compound acts on the causative agents of blood protozoan diseases produced by both flagellated protozoa (Trypanosoma) and members of the class Piroplasmida (Babesia, Theileria, and Cytauxzoon) in various domestic and wild animals, and it is widely used in veterinary medicine. We examined the behavior of water-disperse diminazene (immobilized in Tween 80 micelles) at the cellular and organismal levels. We assessed the interaction of an aqueous and a water-disperse preparation with cells of the reticuloendothelial system. We compared the kinetic parameters of aqueous and water-disperse diminazene in sheep erythrocytes and plasma. The therapeutic properties of these two preparations were also compared. We found that the surface-active substances improved intracellular penetration of the active substance through interaction with the cell membrane. In sheep blood erythrocytes, micellar diminazene accumulated more than its aqueous analog. This form was also more effective therapeutically than the aqueous analog. Our findings demonstrate that use of micellar diminazene allows the injection dose to be reduced by 30%.
Animals ; Babesiosis/drug therapy/veterinary ; Diminazene/metabolism/*pharmacokinetics ; Dose-Response Relationship, Drug ; Female ; Macrophages, Peritoneal/cytology/metabolism ; Male ; Micelles ; Polysorbates ; Rats ; Sheep/*blood ; Sheep Diseases/drug therapy ; Trypanocidal Agents/*pharmacokinetics

OBJECTIVE: Motor impairments related to hand function are common symptoms in patients with movement disorders, such as Parkinson’s disease (PD) and focal hand dystonia (FHD). However, hand dysfunction has not been quantitatively assessed as a clinical tool for screening patient groups from healthy controls (HCs). The aim of our study was 1) to quantitatively assess hand dysfunction in patients with PD and FHD and its usefulness as a screening tool 2) to grade disease severity in PD and FHD based on hand dysfunction. METHODS: The current case-control study included HCs (n = 50) and patients with known history of PD (n = 25) or FHD (n = 16). Hand function was assessed by a precision grip task while participants lifted objects of 1.3 N and 1.7 N under dry skin conditions, followed by very wet skin conditions (VWSCs). Receiver operating characteristic and summative scoring analyses were performed. RESULTS: In PD, the combination of loading phase duration and lifting phase duration at quantitative cutoffs of 0.36 and 0.74 seconds identified 21/25 patients as diseased and 49/50 subjects as HCs with 1.7 N under VWSCs. In PD, 5/21 was graded as “mild” and 16/21 as “moderate cases.” In FHD, slip force at a cutoff of 1.2 N identified 13/16 patients as diseased and 41/50 subjects as HC with 1.7 N under VWSCs, but disease severity could not be graded. CONCLUSION: Our results demonstrate the use of precision grip task as an important clinical tool in assessment of hand dysfunction in movement disorder patients. Use of quantitative cutoffs may improve diagnostic accuracy and serve as a valuable adjunct to existing clinical assessment methods.
Case-Control Studies ; Dystonia ; Hand Strength ; Hand ; Humans ; Lifting ; Mass Screening ; Movement Disorders ; Parkinson Disease ; ROC Curve ; Skin

Objective: The aim of this study was to introduce a gelatin/bovine serum albumin (BSA) tissue standard, which provides dissolution properties identical to those of biological tissues. Further, the study evaluated whether the utilization of endodontic activating devices led to enhanced phantom dissolution rates. Materials and Methods: Bovine pulp tissue was obtained to determine a benchmark of tissue dissolution. The surface area and mass of samples were held constant while the ratio of gelatin and BSA were varied, ranging from 7.5% to 10% gelatin and 5% BSA. Each sample was placed in an individual test tube that was filled with an appropriate sodium hypochlorite solution for 1, 3, and 5 minutes, and then removed from the solution, blotted dry, and weighed again. The remaining tissue was calculated as the percent of initial tissue to determine the tissue dissolution rate. A radiopaque agent (sodium diatrizoate) and a fluorescent dye (methylene blue) were added to the phantom to allow easy quantification of phantom dissolution in a canal block model when activated using ultrasonic (EndoUltra) or sonic (EndoActivator) energy. Results: The 9% gelatin + 5% BSA phantom showed statistically equivalent dissolution to bovine pulp tissue at all time intervals. Furthermore, the EndoUltra yielded significantly more phantom dissolution in the canal block than the EndoActivator or syringe irrigation. Conclusions Our phantom is comparable to biological tissue in terms of tissue dissolution and could be utilized for in vitro tests due to its injectability and detectability.

Objective: The aim of this study was to introduce a gelatin/bovine serum albumin (BSA) tissue standard, which provides dissolution properties identical to those of biological tissues. Further, the study evaluated whether the utilization of endodontic activating devices led to enhanced phantom dissolution rates. Materials and Methods: Bovine pulp tissue was obtained to determine a benchmark of tissue dissolution. The surface area and mass of samples were held constant while the ratio of gelatin and BSA were varied, ranging from 7.5% to 10% gelatin and 5% BSA. Each sample was placed in an individual test tube that was filled with an appropriate sodium hypochlorite solution for 1, 3, and 5 minutes, and then removed from the solution, blotted dry, and weighed again. The remaining tissue was calculated as the percent of initial tissue to determine the tissue dissolution rate. A radiopaque agent (sodium diatrizoate) and a fluorescent dye (methylene blue) were added to the phantom to allow easy quantification of phantom dissolution in a canal block model when activated using ultrasonic (EndoUltra) or sonic (EndoActivator) energy. Results: The 9% gelatin + 5% BSA phantom showed statistically equivalent dissolution to bovine pulp tissue at all time intervals. Furthermore, the EndoUltra yielded significantly more phantom dissolution in the canal block than the EndoActivator or syringe irrigation. Conclusions Our phantom is comparable to biological tissue in terms of tissue dissolution and could be utilized for in vitro tests due to its injectability and detectability.