The Opioid Analgesic Reduction Study (OARS) Pilot: A Double-Blind Randomized Multicenter Trial.

BACKGROUND: With addiction rates and opioid deaths increasing, health care providers are obligated to help stem the opioid crisis. As limited studies examine the comparative effectiveness of fixed-dose combination nonopioid analgesia to opioid-containing analgesia, a comparative effectiveness study was planned and refined by conducting a pilot study. METHODS: The Opioid Analgesic Reduction Study (OARS) pilot, a stratified, randomized, multisite, double-blind clinical trial, was designed to test technology and procedures to be used in the full OARS trial. Participants engaged in the full protocol, enabling the collection of OARS outcome data. Eligible participants reporting to 1 of 5 sites for partial or full bony impacted mandibular third molar extraction were stratified by biologic sex and randomized to 1 of 2 treatment groups, OPIOID or NONOPIOID. OPIOID participants were provided 20 doses of hydrocodone 5 mg/acetaminophen 300 mg. NONOPIOID participants were provided 20 doses of ibuprofen 400 mg/acetaminophen 500 mg. OARS outcomes data, including pain experience, adverse effects, sleep quality, pain interference, overall satisfaction, and remaining opioid tablets available for diversion, were collected via surveys, electronic medication bottles, eDiary, and activity/sleep monitor. RESULTS: Fifty-three participants were randomized with 50 completing the OARS pilot protocol. Across all outcome pain domains, in all but 1 time period, NONOPIOID was better in managing pain than OPIOID (P < 0.05 level). Other outcomes suggest less pain interference, less adverse events, better sleep quality, better overall satisfaction, and fewer opioid-containing tablets available for diversion. DISCUSSION: Results suggest patients requiring impacted mandibular third molar extraction would benefit from fixed-dose combination nonopioid analgesia. KNOWLEDGE TRANSFER STATEMENT: Study results suggest fixed-dose nonopioid combination ibuprofen 400 mg/acetaminophen 500 mg is superior to opioid-containing analgesic (hydrocodone 5 mg/acetaminophen 500 mg). This knowledge should inform surgeons and patients in the selection of postsurgical analgesia.

Impact of DHCWs' Safety Perception on Vaccine Acceptance and Adoption of Risk Mitigation Strategies.

OBJECTIVES: To estimate the association between safety perception on vaccine acceptance and adoptions of risk mitigation strategies among dental health care workers (DHCWs). METHODS: A survey was emailed to DHCWs in the New Jersey area from December 2020 to January 2021. Perceived safety from regular SARS-CoV-2 testing of self, coworkers, and patients and its association with vaccine hesitancy and risk mitigation were ascertained. Risk Mitigation Strategy (RiMS) scores were computed from groupings of office measures: 1) physical distancing (reduced occupancy, traffic flow, donning of masks, minimal room crowding), 2) personal protective equipment (fitted for N95; donning N95 masks; use of face shields; coverings for head, body, and feet), and 3) environmental disinfection (suction, air filtration, ultraviolet, surface wiping). RESULTS: SARS-CoV-2 testing of dental professionals, coworkers, and patients were perceived to provide safety at 49%, 55%, and 68%, respectively. While dentists were least likely to feel safe with regular self-testing for SARS-CoV-2 (P < 0.001) as compared with hygienists and assistants, they were more willing than hygienists (P = 0.004; odds ratio, 1.79 [95% CI, 1.21 to 2.66]) and assistants (P < 0.001; odds ratio, 3.32 [95% CI, 1.93 to 5.71]) to receive the vaccine. RiMS scores ranged from 0 to 19 for 467 participants (mean [SD], 10.9 [2.9]). RiMS scores did not significantly differ among groups of DHCWs; however, mean RiMS scores were higher among those who received or planned to receive the COVID-19 vaccine than those with who did not (P = 0.004). DHCWs who felt safer with regular testing had greater RiMS scores than those who did not (11.0 vs. 10.3, P = 0.01). CONCLUSIONS: Understanding DHCWs' perception of risk and safety is crucial, as it likely influences attitudes toward testing and implementation of office risk mitigation policies. Clinical studies that correlate risk perception and RiMS with SARS-CoV-2 testing are needed to demonstrate the effectiveness of RiMS in dental care settings. KNOWLEDGE TRANSFER STATEMENT: Educators, clinicians, and policy makers can use the results of this study when improving attitudes toward testing and implementation of risk mitigation policies within dental offices, for current and future pandemics.

Role of lactoferrin and lactoferrin-derived peptides in oral and maxillofacial diseases.

The oral cavity harbors different taxonomic groups, the evolutionary coexistence of which develops the oral ecosystem. These resident microorganisms can alter the balance between the physiologic and pathologic conditions that affect the host, both locally and systemically. This highly sophisticated nature of the oral cavity poses a significant therapeutic challenge. Numerous human and animal studies have been conducted to potentiate the efficacy and competence of current treatments of pathologic conditions as well as to develop novel therapeutic modalities. One of these studies is the use of the potent antimicrobial agent lactoferrin (LF), which was originally derived from the host immune system. LF is an 80-kDa glycoprotein that has a free iron sequestration mechanism with evident antimicrobial, anti-tumor, and immunomodulatory properties. A wide range of active peptides have been isolated from the N-terminal region of LF, which possess antimicrobial activities. In this review, we discuss the role of LF and LF-derived peptides under a heterogeneous group of oral and maxillofacial conditions, including bacterial, fungal, viral infections; head and neck cancers; xerostomia; and implantology-bone-related manifestations.

Survival time with pacemaker implantation for dogs diagnosed with persistent atrial standstill.

OBJECTIVES: To evaluate survival time in dogs with persistent atrial standstill after pacemaker implantation and to compare the survival times for cardiac-related vs. non-cardiac deaths. Secondary objectives were to evaluate the effects of breed and the presence of congestive heart failure (CHF) at the time of diagnosis on survival time. ANIMALS: Twenty dogs with persistent atrial standstill and pacemaker implantation. METHODS: Medical records were searched to identify dogs diagnosed with persistent atrial standstill based on electrocardiogram that underwent pacemaker implantation. Survival after pacemaker implantation was analyzed using the Kaplan-Meier method. RESULTS: The median survival time after pacemaker implantation for all-cause mortality was 866 days. There was no significant difference (p=0.573) in median survival time for cardiac (506 days) vs. non-cardiac deaths (400 days). The presence of CHF at the time of diagnosis did not affect the survival time (P=0.854). No difference in median survival time was noted between breeds (P=0.126). CONCLUSIONS: Dogs with persistent atrial standstill have a median survival time of 866 days with pacemaker implantation, though a wide range of survival times was observed. There was no difference in the median survival time for dogs with cardiac-related deaths and those without. Patient breed and the presence of CHF before pacemaker implantation did not affect median survival time.

Long-term systemic lupus erythematosus disease control after allogeneic bone marrow transplantation.

Systemic lupus erythematosus (SLE), a disorder of the immune system, is potentially curable by allogeneic bone marrow transplantation (alloBMT). Until recently, alloBMT was limited by donor availability and toxicity. Reduced intensity conditioning (RIC) combined with post-transplantation cyclophosphamide (PTCy) has improved the availability and safety of alloBMT permitting its exploration in severe-refractory autoimmune illnesses. We report the six-year follow-up of a young female whose refractory SLE-associated nephrosis resolved after RIC alloBMT with PTCy.

Defining oliguria during cardiopulmonary bypass and its relationship with cardiac surgery-associated acute kidney injury.

BACKGROUND: While urine flow rate ≤0.5 ml kg-1 h-1 is believed to define oliguria during cardiopulmonary bypass (CPB), it is unclear whether this definition identifies risk for acute kidney injury (AKI) . The purpose of this retrospective study was to evaluate if urine flow rate during CPB is associated with AKI. METHODS: Urine flow rate was calculated in 503 patients during CPB. AKI in the first 48 h after surgery was defined by the Kidney Disease: Improving Global Outcomes classification. Adjusted risk factors associated with AKI and urine flow rate were assessed. RESULTS: Patients with AKI [n=149 (29.5%)] had lower urine flow rate than those without AKI (P<0.001). The relationship between urine flow and AKI risk was non-linear, with an inflection point at 1.5 ml kg-1 h-1 Among patients with urine flow <1.5 ml kg-1 h-1, every 0.5 ml kg-1 h-1 higher urine flow reduced the adjusted risk of AKI by 26% (95% CI 13-37; P<0.001). Urine flow rate during CPB was independently associated with the risk for AKI. Age up to 80 years and preoperative diuretic use were inversely associated with urine flow rate; mean arterial pressure on CPB (when <87 mmHg) and CPB flow were positively associated with urine flow rate. CONCLUSIONS: Urine flow rate during CPB <1.5 ml kg-1 h-1 identifies patients at risk for cardiac surgery-associated AKI. Careful monitoring of urine flow rate and optimizing mean arterial pressure and CPB flow might be a means to ensure renal perfusion during CPB. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00769691 and NCT00981474.

Surface display of Aggregatibacter actinomycetemcomitans autotransporter Aae and dispersin B hybrid act as antibiofilm agents.

Among the various proteins expressed by the periodontopathogen Aggregatibacter actinomycetemcomitans, two proteins play important roles for survival in the oral cavity. The autotransporter Aae facilitates the attachment of the pathogen to oral epithelial cells, which act as a reservoir, while the biofilm-degrading glycoside hydrolase dispersin B facilitates the movement of daughter cells from the mature biofilm to a new site. The objective of this study was to use the potential of these two proteins to control biofilms. To this end, we generated a hybrid construct between the Aae C-terminal translocating domain and dispersin B, and mobilized it into Escherichia coli Rosetta (DE3) pLysS cells. Immunofluorescence analysis of the modified E. coli cells confirmed the presence of dispersin B on the surface. Further, the membrane localization of the displayed dispersin B was confirmed with Western blot analysis. The integrity of the E. coli cells displaying the dispersin B was confirmed through FACS analysis. The hydrolytic activity of the surface-displayed dispersin B was confirmed by using 4-methylumbelliferyl-ß-d-glucopyranoside as the substrate. The detachment ability of the dispersin B surface-displaying E. coli cells was shown using Staphylococcus epidermidis and Actinobacillus pleuropneumoniae biofilms in a microtiter assay. We concluded that the Aae ß-domain is sufficient to translocate foreign enzymes in the native folded form and that the method of Aae-mediated translocation of surface displayed enzymes might be useful for control of biofilms.

Human lactoferrin protects against Streptococcus mutans-induced caries in mice.

OBJECTIVES: The objective of this study is to evaluate the importance of human lactoferrin (hLF) in an experimental caries induced by Streptococcus mutans in a lactoferrin-knockout (LFKO(-/-)) mouse model compared with C576J/BL wild-type (WT) mice. MATERIALS AND METHODS: The WT and LFKO(-/-) mice were infected with S. mutans (1 × 10(8) cells) and/or sham infection. Furthermore, the effect of hLF administration was evaluated in LFKO(-/-) mice infected with S. mutans. Mice were assessed for colonization, salivary pH, and caries development. RESULTS: The results showed that the lactoferrin-knockout infected (LFKO(-/-) I) mice had significantly higher colonization with S. mutans (P = 0.02), lower salivary pH (P = 0.01), and more carious lesions (P = 0.01) when compared to wild-type infected (WTI) mice. In addition, the administration of hLF did not show any evidence of S. mutans colonization as well as carious lesions (P = 0.001) in LFKO(-/-) I mice when compared to untreated LFKO(-/-) I mice. CONCLUSION: These results show that endogenous LF protects against S. mutans-induced caries and that exogenous hLF can exert a protective effect against caries development.

Lactoferrin: A Roadmap to the Borderland between Caries and Periodontal Disease.

Lactoferrin is one of a number of multifunctional proteins that are present in or on all mucosal surfaces throughout the body. Levels of lactoferrin are consistently elevated in inflammatory diseases such as arthritis, inflammatory bowel diseases, corneal disease, and periodontitis. Single-nucleotide polymorphisms (SNPs) in lactoferrin have been shown to be present in individuals susceptible to Escherichia coli-induced travelers' diarrhea and in tear fluid derived from virally associated corneal disease. Here, we review data showing a lactoferrin SNP in amino acid position 29 in the antimicrobial region of lactoferrin that acts against caries associated bacteria. This SNP was initially discovered in African American subjects with localized aggressive periodontitis (LAP) who had proximal bone loss but minimal proximal caries. Results were confirmed in a genetic association study of children from Brazil with this same SNP who showed a reduced level of caries. In vitro data indicate that lactoferrin from whole saliva derived from subjects with this SNP, recombinant human lactoferrin containing this SNP, or an 11-mer peptide designed for this SNP kills mutans streptococci associated with caries by >1 log. In contrast, the SNP has minimal effect on Gram-negative species associated with periodontitis. Moreover, periodontally healthy subjects homozygous for this lysine (K) SNP have lactoferrin in their saliva that kills mutans streptococci and have reduced proximal decay. The review summarizes data supporting the ecologic plaque hypothesis and suggests that a genetic variant in lactoferrin with K in position 29 when found in saliva and crevice fluid can influence community biofilm composition. We propose that, for caries, this SNP is ethnicity independent and protective by directly killing caries-provoking bacteria (reducing proximal decay). However, the clinical effect of this SNP in LAP is ethnicity dependent, destructive (increases LAP incidence), and complex with mechanisms still to be determined.

Oral lactoferrin protects against experimental candidiasis in mice.

AIMS: To determine the role of human lactoferrin (hLF) in protecting the oral cavities of mice against Candida albicans infection in lactoferrin knockout (LFKO(-/-)) mice was compared to wild-type (WT) mice. We also aim to determine the protective role of hLF in LFKO(-/-) mice. METHODS AND RESULTS: Antibiotic-treated immunosuppressed mice were inoculated with C. albicans (or sham infection) by oral swab and evaluated for the severity of infection after 7 days of infection. To determine the protective role of hLF, we added 0·3% solution of hLF to the drinking water given to some of the mice. CFU count, scoring of lesions and microscopic observations were carried out to determine the severity of infection. LFKO(-/-) I mice showed a 2 log (P = 0·001) higher CFUs of C. albicans in the oral cavity compared to the WT mice infected with C. albicans (WTI). LFKO(-/-) I mice given hLF had a 3 log (P = 0·001) reduction in CFUs in the oral cavity compared to untreated LFKO(-/-) I mice. The severity of infection, observed by light microscopy, revealed that the tongue of the LFKO(-/-) I mice showed more white patches compared to WTI and LFKO(-/-) I + hLF mice. Scanning electron microscopic observations revealed that more filiform papillae were destroyed in LFKO(-/-) I mice when compared to WTI or LFKO(-/-) I + hLF mice. CONCLUSIONS: Human LF is important in protecting mice from oral C. albicans infection. Administered hLF may be used to prevent C. albicans infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Human LF, a multifunctional iron-binding glycoprotein can be used as a therapeutic active ingredient in oral healthcare products against C. albicans.

Renal biopsy in the management of lupus nephritis during pregnancy.

The differential diagnosis of proteinuria and hematuria in pregnancy is broad and includes active lupus nephritis. Identification of the correct diagnosis often has a profound therapeutic impact on not only the mother but also the fetus. To date, relatively few reports exist on the role of renal biopsy during pregnancy among women with systemic lupus erythematosus (SLE). We present a case series of 11 pregnant women with SLE who underwent a renal biopsy to evaluate a presumptive flare of lupus nephritis. The electronic medical record was retrospectively analyzed for pre-biopsy serum creatinine, proteinuria, hematuria, antinuclear antibodies (ANA), and antibodies to double-stranded DNA (anti-dsDNA); histologic findings on renal biopsy; and the clinical course of each mother and fetus. From 2001 to 2012, 11 pregnant women with SLE flares during pregnancy underwent a renal biopsy at an academic tertiary medical center. At the time of biopsy, median gestational age was 16 weeks (range 9 to 27), median serum creatinine was 0.6 mg/dl (interquartile range 0.5 to 0.9), six (55%) had hematuria, and all had proteinuria >500 mg/24 hours. Proliferative lupus nephritis was found in 10 (91%) of 11 biopsies (five with ISN/RPS Class III; five with ISN/RPS Class IV). All but one individual underwent a change in management guided by information gleaned from renal biopsy. No apparent biopsy-related complications occurred to mother or fetus. Three women elected to terminate their pregnancy; although many factors were involved, the findings on renal biopsy informed the decision-making process. Among the remaining cases, there were three pre-term deliveries, one fetus with complete heart block, one in utero demise, and one maternal death. Renal biopsy is helpful at informing the management of patients with lupus nephritis during pregnancy.

Transverse demagnetization dynamics of a unitary Fermi gas.

Understanding the quantum dynamics of strongly interacting fermions is a problem relevant to diverse forms of matter, including high-temperature superconductors, neutron stars, and quark-gluon plasma. An appealing benchmark is offered by cold atomic gases in the unitary limit of strong interactions. Here, we study the dynamics of a transversely magnetized unitary Fermi gas in an inhomogeneous magnetic field. We observe the demagnetization of the gas, caused by diffusive spin transport. At low temperatures, the diffusion constant saturates to the conjectured quantum-mechanical lower bound ≃ h/m, where m is the particle mass. The development of pair correlations, indicating the transformation of the initially noninteracting gas toward a unitary spin mixture, is observed by measuring Tan's contact parameter.

Hemodynamic and biochemical alterations in dogs with lymphoma after induction of chemotherapy.

BACKGROUND: Doxorubicin is a common antineoplastic agent with dose-dependent cardiotoxic adverse effects, and pre-existing myocardial dysfunction is a contraindication to its use. OBJECTIVES: To systematically define the hemodynamic and biochemical alterations in dogs undergoing chemotherapy for newly diagnosed lymphoma and assess the reversibility of these alterations with fluid administration. ANIMALS: Twenty-one client-owned dogs with newly diagnosed lymphoma were evaluated 1 week after induction of chemotherapy. Underlying degenerative valve disease was exclusionary. Eighteen healthy age- and weight-matched dogs were used as controls. METHODS: Physical examination, blood pressure by Doppler, echocardiography, and biochemical evaluation (routine serum biochemistry, plasma renin activity and aldosterone concentrations, plasma and urine osmolalities, and urine electrolyte concentrations) were measured in dogs with lymphoma and compared to controls. Dogs with lymphoma received crystalloids IV at 6 mL/kg/h for 24 hours. All variables were reassessed at 4 and 24 hours. Deuterium oxide dilution and bromide dilution were used to determine total body water and extracellular water space, respectively. RESULTS: Baseline echocardiograms showed significantly smaller chamber dimensions in dogs with lymphoma compared to controls. These changes were reversed by fluid administration. Systolic blood pressure and urine sodium concentration were significantly increased, and bromide dilution space, PCV, urine specific gravity, and urine potassium concentration were significantly decreased compared to controls. CONCLUSION AND CLINICAL IMPORTANCE: Echocardiographic and biochemical abnormalities in dogs with lymphoma appear consistent with volume depletion, and may be the result of systemic hypertension and subsequent pressure natriuresis.

Influence of beta blockers on survival in dogs with severe subaortic stenosis.

BACKGROUND: Subaortic stenosis (SAS) is one of the most common congenital cardiac defects in dogs. Severe SAS frequently is treated with a beta adrenergic receptor blocker (beta blocker), but this approach largely is empirical. OBJECTIVE: To determine the influence of beta blocker treatment on survival time in dogs with severe SAS. METHODS: Retrospective review of medical records of dogs diagnosed with severe, uncomplicated SAS (pressure gradient [PG] ≥80 mmHg) between 1999 and 2011. RESULTS: Fifty dogs met the inclusion criteria. Twenty-seven dogs were treated with a beta blocker and 23 received no treatment. Median age at diagnosis was significantly greater in the untreated group (1.2 versus 0.6 years, respectively; P = .03). Median PG at diagnosis did not differ between the treated and untreated groups (127 versus 121 mmHg, respectively; P = .2). Cox proportional hazards regression was used to identify the influence of PG at diagnosis, age at diagnosis, and beta blocker treatment on survival. In the all-cause multivariate mortality analysis, only age at diagnosis (P = .02) and PG at diagnosis (P = .03) affected survival time. In the cardiac mortality analysis, only PG influenced survival time (P = .03). Treatment with a beta blocker did not influence survival time in either the all-cause (P = .93) or cardiac-cause (P = .97) mortality analyses. CONCLUSIONS: Beta blocker treatment did not influence survival in dogs with severe SAS in our study, and a higher PG at diagnosis was associated with increased risk of death.

Protective effects of human lactoferrin during Aggregatibacter actinomycetemcomitans-induced bacteremia in lactoferrin-deficient mice.

Aggregatibacter actinomycetemcomitans, a periodontopathogen, has been associated with several systemic diseases. Herein, we report the protective effect of human lactoferrin (hLF) during A. actinomycetemcomitans bacteremia in lactoferrin knockout (LFKO(-/-)) mice. The prophylactic, concurrent, and therapeutic intravenous (i.v.) administrations of hLF significantly cleared the bacteria from blood and organs. Nevertheless, all modes of hLF administration significantly decreased the concentrations of serum proinflammatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-10, and IL-12p70. Additionally, hLF administration significantly decreased hepatic and splenic proinflammatory cytokine expression levels compared to those in the non-hLF-treated group. Furthermore, administration of hLF decreased the serum C-reactive protein level, inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO) gene expression levels in liver and spleen. hLF treatment has also resulted in a 6-fold decrease in spleen weight with the migration of typical inflammatory cells in infected mice as a result of decreased inflammatory response. These results reveal that hLF protects against A. actinomycetemcomitans bacteremia, as indicated by rapid bacterial clearance and decreased host proinflammatory mediators.

An overview of children's oral health-related quality of life assessment: from scale development to measuring outcomes.

The objectives of this paper are to present an overview of children's oral health-related quality of life and include specific applications for using quality of life assessment in dental research. The process of developing pediatric oral health- related quality of life measures, in particular the Child Oral Health Impact Profile, is outlined. Examples of children's oral health-related quality of life measurement in caries research are also provided. Quality of life outcomes are presented and discussed in the context of caries research. Lastly, the relevance of measuring clinically meaningful difference in the context of measuring outcomes research is highlighted with recommendations for future research.

Lactoferrin knockout mice demonstrates greater susceptibility to Aggregatibacter actinomycetemcomitans-induced periodontal disease.

BACKGROUND: Among the innate defense mechanisms in the oral cavity, lactoferrin (LF) is a vital antimicrobial that can modify the host response against periodontopathogens. Aggregatibacter actinomycetemcomitans is the main periodontopathogen of localized aggressive periodontitis. The aim of this study is to evaluate the role of LF during A. actinomycetemcomitans-induced periodontitis. METHODS: Differences in the expression levels of cytokines, chemokines, chemokine receptors, and bone loss markers between wild-type (WT) and LF knockout mice (LFKO(-/-)) were evaluated by real time-PCR. Serum IgG and LF levels were quantified by ELISA. Alveolar bone loss among the groups was estimated by measuring the distance from cemento-enamel junction (CEJ) to the alveolar bone crest (ABC) at 20 molar sites. RESULTS: Oral infection with A. actinomycetemcomitans increased LF levels in periodontal tissue (P = 0.01) and saliva (P = 0.0004) of wild-type infected (WTI) mice compared to wild-type control mice. Pro-inflammatory cytokines such as interferon-γ, tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-12 were increased in the infected LF knockout (LFKO(-/-)I) mice compared to the WTI mice, whereas the anti-inflammatory cytokines IL-4 and IL-10 were decreased. Chemokines and chemokine receptors showed different expression patterns between WTI and LFKO(-/-)I mice. The LFKO(-/-)I mice developed increased bone loss (P = 0.002), in conjunction with increased expression of receptor activator of nuclear factor-κB ligand and decrease in osteoprotegerin, compared to WTI mice. CONCLUSIONS: These results demonstrate that the infected LFKO(-/-) mice were more susceptible to A. actinomycetemcomitans-induced alveolar bone loss, with different patterns of immune responses compared to those of WTI mice.

Human salivary cystatin SA exhibits antimicrobial effect against Aggregatibacter actinomycetemcomitans.

BACKGROUND AND OBJECTIVE: Healthy subjects who do not have Aggregatibacter actinomycetemcomitans in their oral cavity may possess factors in saliva that might demonstrate antibacterial activity against the bacterium. The aim of this study was to identify and purify proteins from saliva of healthy subjects that might demonstrate antibacterial activity against A. actinomycetemcomitans and test the same against the bacteria. MATERIAL AND METHODS: Saliva from 10 healthy volunteers was tested individually for its anti-A. actinomycetemcomitans activity. Among the 10 subjects, eight demonstrated anti-A. actinomycetemcomitans activity. Saliva was collected from one healthy volunteer who demonstrated the highest antimicrobial activity against A. actinomycetemcomitans. After clarifying the saliva, it was subjected to an affinity chromatography column with A. actinomycetemcomitans. The proteins bound to A. actinomycetemcomitans were eluted from the column and identified using mass spectrometry (MALDI-TOF/TOF MS). Among other proteins that bound to A. actinomycetemcomitans, which included lactoferrin, immunoglobulin A and kallikrein, cystatin SA was observed in significantly higher concentrations, and this was purified from the eluate. The purified cystatin SA was tested at different concentrations for its ability to kill A. actinomycetemcomitans in a 2 h cell killing assay. The bacteria were also treated with a proteinase inhibitor, leupeptin, to clarify whether the antimicrobial effect of cystatin SA was related to its protease inhibitory function. Cystatin SA was also tested for its ability to prevent binding of A. actinomycetemcomitans to buccal epithelial cells (BECs) in an A. actinomycetemcomitans-BEC binding assay. RESULTS: Cystatin SA (0.1 mg/mL) demonstrated a statistically significant antimicrobial activity against A. actinomycetemcomitans. The effect of cystatin SA decreased with lower concentrations, with 0.01 mg/mL showing no effect. The addition of monoclonal cystatin SA antibodies to the purified sample completely negated the antimicrobial effect. Treatment of A. actinomycetemcomitans with leupeptin resulted in no antimicrobial effect, suggesting that the antimicrobial activity of cystatin SA is independent of its protease inhibitory function. A. actinomycetemcomitans pretreated with cystatin SA showed reduced binding to BECs, suggesting a potential role for cystatin SA in decreasing the colonization of A. actinomycetemcomitans. CONCLUSION: The present study shows that cystatin SA demonstrates antimicrobial activity against the periodontopathogen A. actinomycetemcomitans, and future studies determining the mechanism of action are necessary. The study also shows the ability of cystatin SA to reduce significantly the binding of A. actinomycetemcomitans to BECs.

Predictors of kidney biopsy complication among patients with systemic lupus erythematosus.

Kidney biopsy is essential for the diagnosis and management of lupus nephritis. The risk of bleeding complication, however, is not defined in the systemic lupus erythematosus population. A retrospective cohort study was conducted to determine predictors of major and minor complications among patients with systemic lupus erythematosus undergoing percutaneous ultrasound-guided kidney biopsy. Major complications included bleeding necessitating intervention, hypotension requiring vasopressors or higher level of care or death. Minor complications included moderate or large (≥ 4 cm in largest diameter) perinephric hematoma, gross hematuria or voiding difficulties. All patients were observed for at least 23 h post-procedure. The overall incidence of bleeding was 10.5% (2.7% major, 7.8% minor). Adjusted logistic regression showed that for every 10,000 cells/mm(3) decrease in platelet count, risk for major and any complication increased by 27% (odds ratio 1.27; 95% confidence intervals 1.06-1.51; p = 0.01) and 8% (odds ratio 1.08; 95% confidence intervals 1.02-1.15; p = 0.01), respectively. Patients with a platelet count <150,000 cells/mm(3) were 30 times more likely to experience a major complication (p = 0.002). Other candidate predictors, including steroid exposure, kidney function, hematocrit and histopathology, were not significant. Kidney biopsies are well tolerated in patients with systemic lupus erythematosus. However, patients with pre-biopsy platelet counts <150,000 cells/mm(3) are at markedly increased risk for a major bleeding complication.