Boundary mode lubrication of articular cartilage with a biomimetic diblock copolymer.

We report the design of a diblock copolymer with architecture and function inspired by the lubricating glycoprotein lubricin. This diblock copolymer, synthesized by sequential reversible addition-fragmentation chain-transfer polymerization, consists of a cationic cartilage-binding domain and a brush-lubricating domain. It reduces the coefficient of friction of articular cartilage under boundary mode conditions (0.088 ± 0.039) to a level equivalent to that provided by lubricin (0.093 ± 0.011). Additionally, both the EC50 (0.404 mg/mL) and cartilage-binding time constant (7.19 min) of the polymer are comparable to purified human and recombinant lubricin. Like lubricin, the tribological properties of this polymer are dependent on molecular architecture. When the same monomer composition was evaluated either as an AB diblock copolymer or as a random copolymer, the diblock effectively lubricated cartilage under boundary mode conditions whereas the random copolymer did not. Additionally, the individual polymer blocks did not lubricate independently, and lubrication could be competitively inhibited with an excess of binding domain. This diblock copolymer is an example of a synthetic polymer with lubrication properties equal to lubricin under boundary mode conditions, suggesting its potential utility as a therapy for joint pathologies like osteoarthritis.

Nanocochleates containing N-Octylglicoside extracted Vibrio cholerae antigens elicited high vibriocidal antibodies titers after intragastric immunization in a mice model.

Biological detergents are used in research laboratories, to extract or solubilize proteins from cell membranes. In order to evaluate the ability to extract antigens from the bacterial cell surface of the wild Vibrio cholerae strain C7258 and study their immunogenic potential by forming proteoliposomes and cochleate and preserving their immunogenicity, the non-ionic detergent, n-Octylglucoside (n-OG), and the Zwitterionic detergent (3-cholamidopropyl dimethylammonio 1-propanesulfonate; CHAPS) were tested in concentrations between 5 and 15%. The anionic detergent sodium deoxycholate (DOC) was used as a reference. Electrophoretic, immunochemical and electron microscopy techniques have characterized the extracts and their chromatographic fractions. With CHAPS and n-OG detergents in concentrations between 5 and 15%, a higher yield was obtained in the extraction of proteins and lipopolysaccharides (LPS) and other components from the bacterial surface compared to 10% DOC. When using 10% DOC, 15% CHAPS and n-OG between 5 and 15%, stable proteoliposomes were formed, of average size between 82 and 93 nm in diameter, with known proportions of proteins, LPS and other components. In some of the concentrations, liposomes were formed with almost pure proteins. Some cholera outer membrane proteins like the 17 kDa protein, which corresponds to the mannose-sensitive hemagglutinin (MSHA), which mediates the adhesion to the brush border of the small intestine and the outer membrane protein U (OMPU) were identified with monoclonal antibodies (mAbs) and purified. The fundamental components of liposomes, proteins and LPS, retained their molecular weights, when compared with known standards and by processing programs of electrophoretic profiles and their antigenicity, without alterations due to the extraction procedure, as could be verified by immune identification techniques with monoclonal antibodies in the case of LPS, significant antigens in this pathogen. The main purpose of the present work was to show that a new anticholera vaccine formulation based on cochleates, containing selected protein and LPS fraction extracted by detergents, is able to elicit protective high titers of bactericidal antibodies after intragastric immunization in the mice model. The objective was achieved.

Integrable Floquet Hamiltonian for a Periodically Tilted 1D Gas.

An integrable model subjected to a periodic driving gives rise generally to a nonintegrable Floquet Hamiltonian. Here we show that the Floquet Hamiltonian of the integrable Lieb-Liniger model in the presence of a linear potential with a periodic time-dependent strength is instead integrable and its quasienergies can be determined using the Bethe ansatz approach. We discuss various aspects of the dynamics of the system at stroboscopic times and we also propose a possible experimental realization of the periodically driven tilting in terms of a shaken rotated ring potential.

Dynamics of Synovial Fluid Aggregation under Shear.

The synovial fluid (SF) that lubricates articular joints exhibits complex rheological and tribological properties due to the interactions and behaviors of its various molecular components. Under shear, SF films abruptly thicken by more than 300% and large, dense aggregates form within the fluid. In this study, we used the Surface Force Apparatus to elucidate which SF components are involved in this shear-induced transformation by (i) determining which (if any) of all major SF components replicate the behavior of SF under shear and (ii) observing the effect of removing implicated components from SF by enzymatic digestion. While most previous studies of SF have focused on the tribological roles of lubricin or hyaluronic acid, our results indicate that albumin is a key contributor to the formation of aggregates in SF under shear. Our results also suggest that SF aggregation is associated with efficient surface protection against wear. As our findings are based on experiments involving rigid, nonporous surfaces, they may be used to investigate shear-mediated aggregation mechanisms occurring during the lubrication of artificial joints, ultimately advancing our current vision of implant design.

Fibronectin mediates enhanced wear protection of lubricin during shear.

Fibronectin (FN) is a glycoprotein found in the superficial zone of cartilage; however, its role in the lubrication and the wear protection of articular joints is unknown. In this work, we have investigated the molecular interactions between FN and various components of the synovial fluid such as lubricin (LUB), hyaluronan (HA), and serum albumin (SA), which are all believed to contribute to joint lubrication. Using a Surface Forces Apparatus, we have measured the normal (adhesion/repulsion) and lateral (friction) forces across layers of individual synovial fluid components physisorbed onto FN-coated mica substrates. Our chief findings are (i) FN strongly tethers LUB and HA to mica, as indicated by high and reversible long-range repulsive normal interactions between surfaces, and (ii) FN and LUB synergistically enhance wear protection of surfaces during shear, as suggested by the structural robustness of FN+LUB layers under pressures up to about 4 MPa. These findings provide new insights into the role of FN in the lubricating properties of synovial fluid components sheared between ideal substrates and represent a significant step forward in our understanding of cartilage damage involved in diseases such as osteoarthritis.

Transcriptional regulation of esophageal, intestinal, and branchial solute transporters by salinity, growth hormone, and cortisol in Atlantic salmon.

In marine habitats, Atlantic salmon (Salmo salar) imbibe seawater (SW) to replace body water that is passively lost to the ambient environment. By desalinating consumed SW, the esophagus enables solute-linked water absorption across the intestinal epithelium. The processes underlying esophageal desalination in salmon and their hormonal regulation during smoltification and following SW exposure are unresolved. To address this, we considered whether two Na+ /H+ exchangers (Nhe2 and -3) expressed in the esophagus contribute to the uptake of Na+ from lumenal SW. There were no seasonal changes in esophageal nhe2 or -3 expression during smoltification; however, nhe3 increased following 48 h of SW exposure in May. Esophageal nhe2, -3, and growth hormone receptor b1 were elevated in smolts acclimated to SW for 2.5 weeks. Treatment with cortisol stimulated branchial Na+ /K+ -ATPase (Nka) activity, and Na+ /K+ /2Cl- cotransporter 1 (nkcc1), cystic fibrosis transmembrane regulator 1 (cftr1), and nka-α1b expression. Esophageal nhe2, but not nhe3 expression, was stimulated by cortisol. In anterior intestine, cortisol stimulated nkcc2, cftr2, and nka-α1b. Our findings indicate that salinity stimulates esophageal nhe2 and -3, and that cortisol coordinates the expression of esophageal, intestinal, and branchial solute transporters to support the SW adaptability of Atlantic salmon.

Diversity and composition of dengue virus type 2 in Venezuela.

Dengue is a mosquito-borne disease caused by four closely related dengue virus (genus Flavivirus)serotypes (DENV-1­4). The clinical outcomes vary from mild febrile illness to life-threatening haemorrhagic manifestations. DENVs are endemic in the tropics and subtropics globally and currently no specific treatment or vaccines are available. In Venezuela, the American-Asian genotype of DENV-2 is the most prevalent and has been associated with severe disease outcomes.We aimed to follow-up the molecular epidemiology of DENV-2 in Venezuela to investigate if the evolution of the virus has remained the same throughout time or if the same dynamics documented in Brazil (hyperendemic co-circulation) also occurred. The results show that whereas the epidemiology of DENV in several endemic areas is characterized by serotype replacements through time, in Venezuela the American-Asian genotype DENV-2 has evolved into several genetic lineages and has remained in hyperendemic co-circulation with the other serotypes.

Recombinant streptokinase suppositories in the treatment of acute haemorrhoidal disease. Multicentre randomized double-blind placebo-controlled trial (THERESA-2).

AIM: A four-arm multicentre randomized double-blind placebo-controlled trial was undertaken to assess the effect and safety of suppositories containing recombinant streptokinase (rSK) at two dose levels (100,000 IU and 200,000 IU) with sodium salicylate (SS) compared with placebo and SS for the treatment of acute haemorrhoidal disease. METHOD: Patients with acute symptoms of haemorrhoids were randomized to four treatment groups: (I) placebo, (II) SS, (III) SS + rSK 100,000 IU and (IV) SS + rSK 200,000 IU per suppository. Inpatient treatment was by four suppositories given every 6 h to discharge at 24 h. Evaluations were made at the time of discharge (24 h) and at 3, 5 and 20 days later. The main end-point was the degree of relief of pain, oedema and reduction in the size of the lesion by 90% on day 5. Adverse events and the occurrence of anti-SK antibodies were also determined. RESULTS: Eighty patients were included. Respective response rates in the four groups were 16%, 30%, 25% and 52%. In the last group there was a significant difference (36.8%) compared with control (95% CI 7.0-58.4%). The time to response was significantly shorter (median 5 days) in the 200,000 IU rSK group with respect to the others. There were no adverse events attributable to the treatment. No increase in anti-SK antibodies was detected 20 days after treatment. CONCLUSION: Suppositories with 200,000 IU rSK showed a significant improvement in symptoms of acute haemorrhoids, with an adequate safety profile.

Wild Zebrafish Sentinels: Biological Monitoring of Site Differences Using Behavior and Morphology.

Environmental change poses a devastating risk to human and environmental health. Rapid assessment of water conditions is necessary for monitoring, evaluating, and addressing this global health danger. Sentinels or biological monitors can be deployed in the field using minimal resources to detect water quality changes in real time, quickly and cheaply. Zebrafish (Danio rerio) are ideal sentinels for detecting environmental changes due to their biomedical tool kit, widespread geographic distribution, and well-characterized phenotypic responses to environmental disturbances. Here, we demonstrate the utility of zebrafish sentinels by characterizing phenotypic differences in wild zebrafish between two field sites in India. Site 1 was a rural environment with flowing water, low-hypoxic conditions, minimal human-made debris, and high iron and lead concentrations. Site 2 was an urban environment with still water, hypoxic conditions, plastic pollution, and high arsenic, iron, and chromium concentrations. We found that zebrafish from Site 2 were smaller, more cohesive, and less active than Site 1 fish. We also found sexually dimorphic body shapes within the Site 2, but not the Site 1, population. Advancing zebrafish sentinel research and development will enable rapid detection, evaluation, and response to emerging global health threats.

An Evidence-Based Review of Overuse Wrist Injuries in Athletes.

Overuse wrist injuries are a common problem in athletes and can be related to tendinopathies or osteoarticular pathology. Fortunately, athletes rarely miss time from their sport due to these conditions because many can be treated nonoperatively. For refractory cases, there often is a curative surgical procedure that can be done during the off-season.

Interaction with Cartilage Increases the Viscosity of Hyaluronic Acid Solutions.

Injection of hyaluronic acid (HA) viscosupplements is a prevalent treatment for patients suffering from mild to moderate osteoarthritis. The efficacy of these supplements is attributed to increased synovial fluid viscosity, which leads to improved lubrication and reduced pain. Therefore, viscosity is a key parameter to consider in the development of HA supplements. HA localizes near the cartilage surface, resulting in a viscosity gradient with heightened viscosity near the surface. Traditional rheological measurements confine HA between metal fixtures and therefore do not capture the effect of HA localization that occurs on cartilage. In these experiments, we investigate the effect of modifying rheometer fixtures with cartilage surface coatings on the effective viscosity of HA solutions. Our results demonstrate up to a 20-fold increase in effective viscosity when HA was confined between cartilage surfaces compared to steel surfaces. For low-molecular-weight HA, the effective viscosity was dependent on the gap height between the rheometer plates, which is consistent with the formation of a viscous boundary film. Together, these results indicate that this method for assessing HA viscosity may be more relevant to lubrication than traditional methods and may provide a more accurate method for predicting the viscosity of HA viscosupplements in vivo where HA is able to interact with the cartilage surface.

Scaphoid Fractures in Athletes.

Scaphoid fractures are common injuries in athletes. Most can be treated with cast immobilization, with an expected rate of union of 90% to 95%. Cast treatment, however, has the disadvantages of longer immobilization time, joint stiffness, reduced grip strength, and longer time to return to manual work or athletics. Closed reduction and percutaneous screw fixation generally are preferred in athletes to allow a quicker return to sport; if closed reduction cannot be obtained, open reduction and internal fixation may be required.

Collective Behavior in Wild Zebrafish.

Anthropogenic change is expected to alter environments at alarming rates. To predict the impact of modified environments on social behavior, we must study the relationship between environmental features and collective behavior in a genetically tractable model, zebrafish (Danio rerio). Here, we conducted a field study to examine the relationship between salient environmental features and collective behavior in four populations of zebrafish. We found zebrafish in flowing water formed volatile groups, whereas those in still water had more consistent membership and leadership. Groups in fast-flowing water were large (up to 2000 fish) and tightly knit with short nearest neighbor distances, whereas group sizes were smaller (11 fish/group) with more space between individual fish in still and slow-flowing water. These observations point to a possible profound role of water flow in influencing collective behavior in wild zebrafish.

Extraskeletal Myxoid Chondrosarcoma of the Midfoot Presenting as Charcot Arthropathy: A Case Report.

CASE: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue malignancy that very seldomly presents in the foot or ankle and as a result is not commonly in the differential of patients presenting with foot pain. We cite a case of EMC presenting in the atypical location of the midfoot. Because of its location and similarities, this tumor was initially misdiagnosed and mistreated by multiple medical providers as midfoot Charcot arthropathy. CONCLUSIONS: Neoplastic etiologies, including EMC, should remain in the differential for atypical, refractory foot pain that presents in a manner similar to Charcot foot.

Metabolic syndrome and hip fracture: Epidemiology and perioperative outcomes.

INTRODUCTION: Hip fractures and metabolic syndrome (MetS) are becoming major global healthcare burdens as populations age. This study sought to determine the impact of MetS in hip fracture patients on perioperative outcomes following operative fixation or arthroplasty. METHODS: Data from the 2004-2014 Nationwide Inpatient Sample was used to select 3,348,207 discharges with hip fracture. MetS patients were identified by having at least 3 of 4 component comorbidities: hypertension, dyslipidemia, obesity, and diabetes. Logistic regression was used to estimate odds ratios for the association between MetS and perioperative outcomes adjusted for age, gender, race, payer status, and comorbidities. RESULTS: Overall, 32% of hip fracture patients were treated with open reduction internal fixation (ORIF), 28% hemiarthroplasty (HA), 18% closed reduction with internal fixation (CRPP), and 3% primary total hip arthroplasty (THA). The remaining 19% of cases were either treated via unspecified procedure of hip repair (9%), managed non-operatively (2%), underwent multiple procedures during the hospital stay (6%), or the surgical procedure data was missing (2%) and were excluded from procedural analyses. The prevalence of MetS was 7.9% and increased among minorities, patients treated at urban hospitals, with comorbidities (heart failure, kidney disease, peripheral vascular disease), and with Medicare coverage. MetS was associated with increased odds of any adverse event (p < 0.0001), specifically: acute renal failure, myocardial infarction, acute posthemorrhagic anemia. MetS was also associated with increased LOS (p < 0.0001) and increased total charges (p < 0.0001). However, MetS was associated with reduced odds of postoperative pneumonia, deep vein thrombosis and pulmonary embolism, surgical site infection, septicemia, and in-hospital mortality (p < 0.0001). The above associations were maintained for MetS patients stratified according to their treatment groups: HA, CRPP, and ORIF. CONCLUSIONS: MetS is associated with increased odds of complications in hip fracture patients but decreased odds of in-hospital mortality. This may be related to patients' nutritional status and catabolic states in the perioperative period.

The Second Victim Experience and Support Tool: Validation of an Organizational Resource for Assessing Second Victim Effects and the Quality of Support Resources.

OBJECTIVES: Medical errors and unanticipated negative patient outcomes can damage the well-being of health care providers. These affected individuals, referred to as "second victims," can experience various psychological and physical symptoms. Support resources provided by health care organizations to prevent and reduce second victim-related harm are often inadequate. In this study, we present the development and psychometric evaluation of the Second Victim Experience and Support Tool (SVEST), a survey instrument that can assist health care organizations to implement and track the performance of second victim support resources. METHODS: The SVEST (29 items representing 7 dimensions and 2 outcome variables) was completed by 303 health care providers involved in direct patient care. The survey collected responses on second victim-related psychological and physical symptoms and the quality of support resources. Desirability of possible support resources was also measured. The SVEST was assessed for content validity, internal consistency, and construct validity with confirmatory factor analysis. RESULTS: Confirmatory factor analysis results suggested good model fit for the survey. Cronbach α reliability scores for the survey dimensions ranged from 0.61 to 0.89. The most desired second victim support option was "A respected peer to discuss the details of what happened." CONCLUSIONS: The SVEST can be used by health care organizations to evaluate second victim experiences of their staff and the quality of existing support resources. It can also provide health care organization leaders with information on second victim-related support resources most preferred by their staff. The SVEST can be administered before and after implementing new second victim resources to measure perceptions of effectiveness.

Synergistic Interactions of a Synthetic Lubricin-Mimetic with Fibronectin for Enhanced Wear Protection.

Lubricin (LUB), a major mucinous glycoprotein of mammalian synovial fluids, is believed to provide excellent lubrication to cartilage surfaces. Consequently, when joint disease or replacement leads to increased friction and surface damage in the joint, robust synthetic LUB alternatives that could be used therapeutically to improve lubrication and surface protection are needed. Here, we report the characterization of a lubricating multiblock bottlebrush polymer whose architecture was inspired by LUB, and we investigate the role of fibronectin (FN), a glycoprotein found in the superficial zone of cartilage, in mediating the tribological properties of the polymer upon shear between mica surfaces. Our surface forces apparatus (SFA) normal force measurements indicate that the lubricin-mimetic (mimLUB) could be kept anchored between mica surfaces, even under high contact pressures, when an intermediate layer of FN was present. Additional SFA friction measurements show that FN would also extend the wearless friction regime of the polymer up to pressures of 3.4 MPa while ensuring stable friction coefficients (µ ≈ 0.28). These results demonstrate synergistic interactions between mimLUB and FN in assisting the lubrication and wear protection of ideal (mica) substrates upon shear. Collectively, these findings suggest that our proposed mimLUB might be a promising alternative to LUB, as similar mechanisms could potentially facilitate the interaction between the polymer and cartilage surfaces in articular joints and prosthetic implants in vivo.

Predictive value of wavelet correlation functions of signal-averaged electrocardiogram in patients after anterior versus inferior myocardial infarction.

OBJECTIVES: This study sought to evaluate the prognostic value of wavelet correlation functions of the signal-averaged electrocardiogram (ECG) for arrhythmic events in patients after myocardial infarction. BACKGROUND: Wavelet transform of the signal-averaged ECG has been shown to be a nonstationary analysis technique describing the time evolution of frequency spectra throughout the QRS complex. To quantify the wavelet transform, we introduced the new concept of the wavelet correlation function. METHODS: The relation among wavelet correlation functions, ventricular late potentials and the site of infarction was investigated in 769 men < 66 years old who survived the acute phase of myocardial infarction (351 [46%] anterior, 418 [54%] inferior infarctions). Signal-averaged ECG recordings were obtained 2 to 3 weeks after infarction. During 6 months of follow-up, 33 patients (4.3%) experienced a malignant arrhythmic event. Wavelet correlation functions of the signal-averaged ECG were evaluated in a time-frequency plane ranging from 25 ms before QRS onset to 25 ms after QRS offset in the frequency range between 40 and 100 Hz. RESULTS: Patients with an anterior infarction had lower mean wavelet correlation coefficients (p < 0.001) and a lower incidence of ventricular late potentials than patients with an inferior infarction (32.3% vs. 42.7%, p = 0.003). The combination of wavelet correlation functions and late potentials increased the total predictive accuracy from 52% to 72% for inferior and from 64% to 76% for anterior infarctions. CONCLUSIONS: Spectral changes in the signal-averaged QRS complex are more prominent in anterior than inferior infarctions. Combination of late potential analysis and wavelet correlation functions increases the prognostic value for serious arrhythmic events after myocardial infarction.

[Juvenile production of the red sea urchin Strongylocentrotus franciscanus (Echinodermata: Echinoidea) in Baja California, Mexico]. / Producción de juveniles de erizo rojo Strongylocentrotus franciscanus (Echinodermata: Echinoidea) en Baja California, México.

The red sea urchin Strongylocentrotusfranciscanus (Agassiz 1863) is harvested commercially in Baja California, Mexico, since 1970; however, in the last ten years the capture per unit effort (CPUE) has decreased from 310 kg/fishing unit/day to 120 kg/fishing unit/day. For this reason, actions were taken to develop a culture technology allowing massive production of juveniles for re-stocking natural populations or for growing them commercially. We summarize some of the basic studies and main achievements in this effort. In Baja California, considerably faster larval development (approximately 21 days) has been attained than in the US northwest coast (62 days). Spawning of red sea urchins was routinely induced with KCI while egg fertilization was performed using a 100,000-sperm/ml solution. Six microalgae species were tested and Rhodomonas sp. produced the best larval development. The mean survival rate at the end of the larval period was 25%, but results varied widely with bactch. From the feed ratios tested, best results were obtained using 7000 cel/ml during the first week of larval development, followed by 10,000 cel/ml during the second and 15,000 cel/ml during the third week. KCl proved the most consistent metamorphic inducer, regularly yielding metamorphosis percentages higher than 90%. Metamorphosis was considered complete when the functional jaw that juveniles use for first benthic feeding appeared (as soon as 20 days after induction). With this method several thousands of red sea urchin juveniles were produced. They reached up to 1.5 mm in size during the first 50 days of culture after metamorphosis, showing the great potential for mass production of this species in the laboratory.

Noninvasive risk modeling after myocardial infarction.

The aim of this study was to extract and combine non-invasive risk parameters from the signal-averaged electrocardiogram (SAECG) and heart rate variability (HRV) based on 24-hour ambulatory electrocardiography to optimize the prognostic value for arrhythmic events after acute myocardial infarction. A prospective series of 553 men < 66 years of age enrolled in the Post-Infarction Late Potential study were analyzed. Within 2 to 4 weeks after acute myocardial infarction, all patients underwent SAECG and 24-hour ambulatory electrocardiography before hospital discharge. During 6 months of followup, 25 patients (4.5%) experienced arrhythmic events (sustained ventricular tachycardia, n = 11; ventricular fibrillation, n = 7; sudden cardiac death, n = 7). The predictive power of SAECG and HRV parameters was assessed using a Cox proportional-hazards model. In HRV analysis, the most significant differences between patients with and without arrhythmic events were observed for the beat-to-beat parameter root-meansquare of successive RR differences [RMSSD]): 25.7 +/- 16.9 ms in patients with arrhythmic events versus 34.1 +/- 18.6 ms in patients free of arrhythmic events (p = 0.004). Time domain analysis of the SAECG showed the QRS duration to be most significantly different in both patient groups: 106.4 +/- 18.7 ms (arrhythmic events) versus 95.3 +/- 18.7 ms (no arrhythmic events) (p = 0.001). Based on the Cox regression model, RMSSD and QRS duration were demonstrated to be independent significant risk factors (regression coefficient for QRS duration: cq = 0.014 +/- 0.006 ms(-1), p = 0.014; for RMSSD: cr = -0.041 +/- 0.016 ms(-1), p = 0.009). Based on the regression coefficients, an analytic risk model was developed describing the arrhythmic risk as a function of QRS duration, RMSSD, and time after infarction. We conclude that the combination of beat-to-beat changes of heart rate measured by RMSSD and QRS duration from the SAECG enhances noninvasive risk stratification after myocardial infarction.