Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination.

Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of systems vaccinology provides detailed information on host responses to vaccination and has been successfully applied to study the molecular mechanisms of several vaccines. Long noncoding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from this analysis can be accessed easily. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of these lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children following immunization with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination.

CCR6 expression reduces mouse survival upon malarial challenge with Plasmodium berghei NK65 strain.

BACKGROUND: It has been demonstrated that proteins expressed by liver-stage Plasmodium parasites can inhibit the translocation of transcription factors to the nucleus of different cells. This process would hinder the expression of immune genes, such as the CCL20 chemokine. OBJECTIVE: Since CCR6 is the only cognate receptor for CCL20, we investigated the importance of this chemokine-receptor axis against rodent malaria. METHODS: CCR6-deficient (KO) and wild-type (WT) C57BL/6 mice were challenged with Plasmodium berghei (Pb) NK65 sporozoites or infected red blood cells (iRBCs). Liver parasitic cDNA, parasitemia and serum cytokine concentrations were respectively evaluated through reverse transcription-polymerase chain reaction (RT-PCR), staining thin-blood smears with Giemsa solution, and enzyme-linked immunosorbent assay (ELISA). FINDINGS: Although the sporozoite challenges yielded similar liver parasitic cDNA and parasitemia, KO mice presented a prolonged survival than WT mice. After iRBC challenges, KO mice kept displaying higher survival rates as well as a decreased IL-12 p70 concentration in the serum than WT mice. CONCLUSION: Our data suggest that malaria triggered by PbNK65 liver- or blood-stage forms elicit a pro-inflammatory environment that culminates with a decreased survival of infected C57BL/6 mice.

Alternative Formulation of Antenna Arrays for DF Systems Considering Active-Element Patterns and Scattering Matrices.

Direction finding (DF) systems are used to determine the direction-of-arrival (DoA) of electromagnetic waves, thus allowing for the tracking of RF sources. In this paper, we present an alternative formulation of antenna arrays for modeling DF systems. To improve the accuracy of the data provided by the DF systems, the effects of mutual coupling in the array, polarization of the received waves, and impedance mismatches in the RF front-end receiver are all taken into account in the steering vectors of the DoA algorithms. A closed-form expression, which uses scattering parameter data and active-element patterns, is derived to compute the receiver output voltages. Special attention is given to the analysis of wave polarization relative to the DF system orientation. Applying the formulation introduced here, a complete characterization of the received waves is accomplished without the need for system calibration techniques. The validation of the proposed model is carried out by measurements of a 2.2 GHz DF system running a MUSIC algorithm. Tests are performed with a linear array of printed monopoles and with a planar microstrip antenna array having polarization diversity. The experimental results show DoA estimation errors below 6° and correct classification of the polarization of incoming waves, confirming the good performance of the developed formulation.

Gestational trophoblastic neoplasia lethality among Brazilian women: A retrospective national cohort study.

OBJECTIVE: To investigate GTN lethality among Brazilian women comparing cases of death by GTN with those who survived, thereby identifying factors associated with GTN lethality. METHODS: We retrospectively reviewed medical records of women with GTN treated at ten Brazilian GTN Reference Centers, from January 1960 to December 2017. We evaluated factors associated with death from GTN and used Cox proportional hazards regression models to identify independent variables with significant influence on the risk of death. RESULTS: From 2186 patients with GTN included in this study, 2092 (95.7%) survived and 89 (4%) died due to GTN. When analyzing the relative risk (RR), adjusted for WHO/FIGO score, patients with low risk disease had a significantly higher risk of death if they had choriocarcinoma (RR: 12.40), metastatic disease (RR: 12.57), chemoresistance (RR: 3.18) or initial treatment outside the Reference Center (RR: 12.22). In relation to patients with high-risk GTN, these factors were significantly associated with death due to GTN: the time between the end of antecedent pregnancy and the initiation of chemotherapy (RR: 4.10), metastatic disease (RR: 14.66), especially in brain (RR: 8.73) and liver (RR: 5.76); absence of chemotherapy or initial treatment with single agent chemotherapy (RR: 10.58 and RR: 1.81, respectively), chemoresistance (RR: 3.20) and the initial treatment outside the Reference Center (RR: 28.30). CONCLUSION: The risk of mortality from low and high-risk GTN can be reduced by referral of these patients to a Reference Center or, if not possible, to involve clinicians in a Reference Center with consultation regarding management.

Coordination among Bond Formation/Cleavage in a Bifunctional-Catalyzed Fast Amide Hydrolysis: Evidence for an Optimized Intramolecular N-Protonation Event.

A density functional theory (DFT) computational analysis, using the ωB97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration. This mechanism is supported by molecular dynamic simulations which confirm a persistent key intramolecular hydrogen bonding. These theoretical conclusions, although not easily verified by experiment, are consistent with a bell-shaped pH/rate profile but are at odds with hydrolysis mechanisms in the classic literature.

Suction versus slow-pull for endoscopic ultrasound-guided fine-needle aspiration of pancreatic tumors: a prospective randomized trial.

BACKGROUND: Suction (S) is commonly used to improve cell acquisition during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Slow-pull (SP) sampling is another technique that might procure good quality specimens with less bloodiness. We aimed to determine if SP improves the diagnostic yield of EUS-FNA of pancreatic masses. METHODS: Patients with pancreatic solid masses were randomized to four needle passes with both techniques in an alternate fashion. Sensitivity, specificity, positive, and negative predictive values were calculated. Cellularity and bloodiness of cytological samples were assessed and compared according to the technique. RESULTS: Sensitivity, specificity, and accuracy of suction vs. SP were 95.2% vs. 92.3%; 100% vs. 100; 95.7% vs. 93%, respectively. As to the association of methods, they were 95.6, 100 and 96%, respectively. Positive predictive values for S and SP were 100%. There was no difference in diagnostic yield between S and SP (p = 0.344). Cellularity of samples obtained with SP and Suction were equivalent in both smear evaluation (p = 0.119) and cell-block (0.980). Bloodiness of SP and suction techniques were similar as well. CONCLUSIONS: S and SP techniques provide equivalent sensitivity, specificity, and accuracy. Association of methods seems to improve diagnostic yield. Suction does not increase the bloodiness of samples compared to slow-pull.

Inhibitory and Cooperative Effects Regulated by pH in Host-Guest Complexation between Cationic Pillar[5]arene and Reactive 2-Carboxyphthalanilic Acid.

The study of host-guest complexation between reactive 2-carboxyphthalanilic acid (CPA) and two cationic pillararenes has been carried out. Host-guest complexation with significant kinetic effects was observed only with the smaller cavity size pillararene (P5A). Kinetics in the pH range 1.50-6.40, ESI-MS, 1H NMR titration, and ROESY experiments were performed to characterize the complexes. High binding stoichiometry (H:G2) was observed for all CPA protonation states. The system is pH-dependent, and inversion of cooperativity (negative to positive) occurs by increasing the dianionic CPA2- concentration (allosteric behavior). Toward physiological pH, association constant K1:1 does not change (104 M-1), and K1:2 increased from 102 to 104 M-1, as well as the inhibitory effect increased up to 222-fold. NMR results elucidated the structure of the complex and allowed us to create a map of H-H interactions that describes well the diversity and number of interactions in the complex.

Immune Cell Dynamics in Rhesus Macaques Infected with a Brazilian Strain of Zika Virus.

Zika virus (ZIKV) is a mosquito-borne and sexually transmitted flavivirus that is associated with fetal CNS-damaging malformations during pregnancy in humans. This study documents the viral kinetics and immune responses in rhesus macaques infected with a clinical ZIKV Brazilian isolate. We evaluated the viral kinetics and immune responses induced after an i.v. infection with a Brazilian ZIKV clinical isolate (HS-2015-BA-01) in rhesus macaques for up to 142 d. ZIKV-specific Ab-secreting cells, germinal center reactions, and monocyte, dendritic cell, NK, and T cell frequencies were monitored. ZIKV loads were readily detected in plasma (until day 5 or 7), semen and urine (until days 7 and 14), and saliva (until day 42), but the viremia was rapidly controlled. No detectable clinical manifestations were observed. However, lymph node hyperplasia was clearly visible postviremia but was associated with low frequencies of ZIKV-specific Ab-secreting cells in lymph nodes and bone marrow, correlating with low Ab titers. CD14+/CD16- monocytes and myeloid CD11chi dendritic cells decreased in blood, whereas NK and T cell numbers were only marginally altered during the course of the study. ZIKV infection caused a significant lymphoid tissue activation but limited induction of ZIKV-specific B cells, suggesting that these parameters need to be considered for ZIKV vaccine design.

Partial resection of bilateral ulnar remnants for treatment of carpus valgus in a 3-week-old Hanoverian foal.

A 3-week old Hanoverian foal was presented with bilateral moderate to severe carpal valgus. The deviations were 10 and 14 degrees, respectively for the left and right carpi and orthogonal radiographs of both front limbs highlighted bilateral persistent ulnar remnants. A partial resection of the ulnar remnants and periosteal transection on the disto-lateral aspect of the radius were performed bilaterally under general anesthesia. The valgus deviations began to improve within the first month and the limbs were almost straight (2 degrees for the left and right carpi) 5 1/2 months after surgery. This is the first report of successful surgical correction of bilateral carpal valgus secondary to persistent ulnar remnants in a large breed foal. The combination of partial ulnar remnant resection and radial disto-lateral periosteal transection, detailed in this report, should be considered for treatment of foals with this condition.

Résection ulnaire bilatérale partielle comme traitement d'un valgus des carpes chez un poulain Hanovrien de 3 semaines d'âge. Un poulain Hanovrien de 3 semaines d'âge a été présenté avec un valgus bilatéral des carpes. Les déviations étaient de 10 et 14 degrés, pour les carpes gauche et droit respectivement. Des projections radiographiques orthogonales des deux membres antérieurs ont mis en évidence un ulna persistant bilatéralement. Une résection partielle des ulnas persistants et une section périostée de l'aspect disto-latéral de chaque radius a été effectuée sous anesthésie générale. Une amélioration des déviations a d'abord été observé durant le premier mois et les deux membres antérieurs étaient quasi droits (2 degrés pour chacun des carpes) 5 1/2 mois après la chirurgie. Ceci est le premier rapport de cas à décrire la correction chirurgicale d'un valgus bilatéral des carpes secondaire à la présence d'ulnas persistants, chez un poulain de grande taille. La combinaison de la résection ulnaire partielle et de la section périostée disto-latérale du radius présentée ici devraient être considérée comme traitement des poulains présentant cette condition.(Traduit par Dre Julia Dubuc).

Immune Priming and Long-term Persistence of Memory B Cells After Inactivated Poliovirus Vaccine in Macaque Models: Support for at least 2 Doses.

Background: As a risk-mitigation strategy to minimize paralytic polio following withdrawal of Sabin type 2 from the oral poliovirus vaccine in April 2016, a single full dose or 2 fractional doses of inactivated poliovirus vaccine (IPV) are recommended. However, limited knowledge exists on long-term persistence of immune memory following 1- or 2-dose IPV schedules. Methods: We examined induction and maintenance of immune memory following single- vs 2-dose IPV schedules, either full-dose intramuscular or fractional-dose intradermal, in rhesus macaques. Humoral responses, bone marrow-homing antibody-secreting plasma cells, and blood-circulating/lymph node-homing memory B cells were examined longitudinally. Results: A single dose of IPV, either full or fractional, induced binding antibodies and memory B cells in all vaccinated macaques, despite failing to induce neutralizing antibodies (NT Abs) in many of them. However, these memory B cells declined rapidly, reaching below detection in the systemic circulation by 5 months; although a low frequency of memory B cells was detectable in draining lymph nodes of some, but not all, animals. By contrast, a 2-dose vaccination schedule, either full or fractional, efficiently induced NT Abs in all animals along with bone marrow-homing plasma cells and memory B cells. These memory B cells persisted in the systemic circulation for up to 16 months, the maximum duration tested after the second dose of vaccination. Conclusions: Two doses of IPV, regardless of whether fractional or full, are more effective than a single dose for inducing long-lasting memory B cells.

Adjuvanting a Simian Immunodeficiency Virus Vaccine with Toll-Like Receptor Ligands Encapsulated in Nanoparticles Induces Persistent Antibody Responses and Enhanced Protection in TRIM5α Restrictive Macaques.

Our previous work has shown that antigens adjuvanted with ligands specific for Toll-like receptor 4 (TLR4) and TLR7/8 encapsulated in poly(lactic-co-glycolic) acid (PLGA)-based nanoparticles (NPs) induce robust and durable immune responses in mice and macaques. We investigated the efficacy of these NP adjuvants in inducing protective immunity against simian immunodeficiency virus (SIV). Rhesus macaques (RMs) were immunized with NPs containing TLR4 and TLR7/8 agonists mixed with soluble recombinant SIVmac239-derived envelope (Env) gp140 and Gag p55 (protein) or with virus-like particles (VLPs) containing SIVmac239 Env and Gag. NP-adjuvanted vaccines induced robust innate responses, antigen-specific antibody responses of a greater magnitude and persistence, and enhanced plasmablast responses compared to those achieved with alum-adjuvanted vaccines. NP-adjuvanted vaccines induced antigen-specific, long-lived plasma cells (LLPCs), which persisted in the bone marrow for several months after vaccination. NP-adjuvanted vaccines induced immune responses that were associated with enhanced protection against repeated low-dose, intravaginal challenges with heterologous SIVsmE660 in animals that carried TRIM5α restrictive alleles. The protection induced by immunization with protein-NP correlated with the prechallenge titers of Env-specific IgG antibodies in serum and vaginal secretions. However, no such correlate was apparent for immunization with VLP-NP or alum as the adjuvant. Transcriptional profiling of peripheral blood mononuclear cells isolated within the first few hours to days after primary vaccination revealed that NP-adjuvanted vaccines induced a molecular signature similar to that induced by the live attenuated yellow fever viral vaccine. This systems approach identified early blood transcriptional signatures that correlate with Env-specific antibody responses in vaginal secretions and protection against infection. These results demonstrate the adjuvanticity of the NP adjuvant in inducing persistent and protective antibody responses against SIV in RMs with implications for the design of vaccines against human immunodeficiency virus (HIV). IMPORTANCE: The results of the RV144 HIV vaccine trial, which demonstrated a rapid waning of protective immunity with time, have underscored the need to develop strategies to enhance the durability of protective immune responses. Our recent work in mice has highlighted the capacity of nanoparticle-encapsulated TLR ligands (NP) to induce potent and durable antibody responses that last a lifetime in mice. In the present study, we evaluated the ability of these NP adjuvants to promote robust and durable protective immune responses against SIV in nonhuman primates. Our results demonstrate that immunization of rhesus macaques with NP adjuvants mixed with soluble SIV Env or a virus-like particle form of Env (VLP) induces potent and durable Env-specific antibody responses in the serum and in vaginal secretions. These responses were superior to those induced by alum adjuvant, and they resulted in enhanced protection against a low-dose intravaginal challenge with a heterologous strain of SIV in animals with TRIM5a restrictive alleles. These results highlight the potential for such NP TLR L adjuvants in promoting robust and durable antibody responses against HIV in the next generation of HIV immunogens currently being developed.

Is chemotherapy always necessary for patients with nonmetastatic gestational trophoblastic neoplasia with histopathological diagnosis of choriocarcinoma?

OBJECTIVE: To evaluate expectant management versus immediate chemotherapy following pathological diagnosis of gestational choriocarcinoma (GCC) in patients with nonmetastatic disease. METHODS: Multicenter retrospective cohort that included patients with histological diagnosis of GCC with nonmetastatic disease followed at one of thirteen Brazilian referral centers for gestational trophoblastic disease from January 2000 to December 2016. RESULTS: Among 3191 patients with gestational trophoblastic neoplasia, 199 patients with nonmetastatic GCC were identified. Chemotherapy was initiated immediately in 152 (76.4%) patients per FIGO 2000 guideline, while 47 (23.6%) were managed expectantly. Both groups presented with similar characteristics and outcomes. All patients (n=12) who had normal human chorionic gonadotropin (hCG) in the first 2-3weeks of expectant management achieved complete sustained remission with no chemotherapy. Only 44.7% (21 patients) of patients who were expectantly managed needed to receive chemotherapy due to plateauing or rising hCG level in the first 2-3weeks of follow up. The outcome of patients receiving chemotherapy after initial expectant management was similar to those who received chemotherapy immediately after the diagnosis in terms of need for multi-agent chemotherapy or number of cycles of chemotherapy. There was no case of relapse or death in either group. Logistic regression analysis showed that age≥40years and hCG≥92,428IU/L at GCC diagnosis were risk factors for needing chemotherapy after initial expectant management of nonmetastatic GCC. CONCLUSION: In order to avoid exposing patients unnecessarily to chemotherapy, close surveillance of women with pathological diagnosis of nonmetastatic GCC seems to be a safe practice, particularly for those who have a normal hCG at the time of diagnosis. If confirmed by other studies, the FIGO guidelines may need to be revised.

Association of sleep bruxism with ceramic restoration failure: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Ceramic restorations are popular because of their excellent optical properties. However, failures are still a major concern, and dentists are confronted with the following question: is sleep bruxism (SB) associated with an increased frequency of ceramic restoration failures? PURPOSE: The purpose of this systematic review and meta-analysis was to assess whether the presence of SB is associated with increased ceramic restoration failure. MATERIAL AND METHODS: Observational studies and clinical trials that evaluated the short- and long-term survival rate of ceramic restorations in SB participants were selected. Sleep bruxism diagnostic criteria must have included at least 1 of the following: questionnaire, clinical evaluation, or polysomnography. Seven databases, in addition to 3 nonpeer-reviewed literature databases, were searched. The risk of bias was assessed by using the meta-analysis of statistics assessment and review instrument (MAStARI) checklist. RESULTS: Eight studies were included for qualitative synthesis, but only 5 for the meta-analysis. Three studies were categorized as moderate risk and 5 as high risk of bias. Clinical and methodological heterogeneity across studies were considered high. Increased hazard ratio (HR=7.74; 95% confidence interval [CI]=2.50 to 23.95) and odds ratio (OR=2.52; 95% CI=1.24 to 5.12) were observed considering only anterior ceramic veneers. Nevertheless, limited data from the meta-analysis and from the restricted number of included studies suggested that differences in the overall odds of failure concerning SB and other types of ceramic restorations did not favor or disfavor any association (OR=1.10; 95% CI=0.43 to 2.8). The overall quality of evidence was considered very low according to the GRADE criteria. CONCLUSIONS: Within the limitations of this systematic review, the overall result from the meta-analysis did not favor any association between SB and increased odds of failure for ceramic restorations.

Systems Vaccinology Applied to DNA Vaccines: Perspective and Challenges.

DNA vaccination represents a new milestone in our technological efforts to avoid infectious diseases. Although this method of vaccination has had success in providing protection in animals, these vaccines suffer from low immunogenicity in humans. Questions remain over the molecular mechanism of DNA vaccination, the best ways in which to safely increase vaccine reactogenecity, and what biomarkers can be used as correlates of protection. Systems vaccinology, which utilizes modern experimental and computational approaches to provide an integrated view of the vaccination process, offers the potential to answer these questions. In this review we discuss the current tools utilized in systems vaccinology, the ways in which they have and can be applied to DNA vaccinology, and challenges faced in the field.

Chemical composition, antioxidant and antibacterial activities of essential oils from leaves and flowers of Eugenia klotzschiana Berg (Myrtaceae).

Many essential oils (EOs) of different plant species possess interesting antimicrobial effects on buccal bacteria and antioxidant properties. Eugenia klotzschiana Berg (pêra-do-cerrado, in Portuguese) is a species of Myrtaceae with restricted distribution in the Cerrado. The essential oils were extracted through the hydrodistillation technique using a modified Clevenger apparatus (2 hours) and chemically characterized by GC-MS. The major compounds were α-copaene (10.6 %) found in oil from leaves in natura, ß-bisabolene (17.4 %) in the essential oil from dry leaves and α-(E)-bergamotene (29.9 %) in oil from flowers. The antioxidant activity of essential oils showed similarities in both methods under analysis (DPPH and ABTS˙+) and the results suggested moderate to high antioxidant activity. The antibacterial activity was evaluated by determining minimum inhibitory concentrations (MICs), using the microdilution method. MIC values below 400 µg/mL were obtained against Streptococcus salivarius (200 µg/mL), S. mutans (50 µg/mL), S. mitis (200 µg/mL) and Prevotella nigrescens (50 µg/mL). This is the first report of the chemical composition and antibacterial and antioxidant activities of the essential oils of E. klotzschiana. These results suggest that E. klotzschiana, a Brazilian plant, provide initial evidence of a new and alternative source of substances with medicinal interest.

Association between signs and symptoms of bruxism and presence of tori: a systematic review.

OBJECTIVE: This systematic review aims to answer the question: "Is there an association between any specific signs and symptoms of bruxism and the presence of tori?" MATERIAL AND METHODS: Observational studies, which evaluated the association between signs and symptoms of bruxism and tori, were selected. Signs and symptoms of bruxism (such as teeth grinding, jaw clenching, abnormal tooth wear, facial muscle hypertrophy, pain, or fatigue) had to be determined by questionnaire or anamnesis and tori within clinical assessment. Search-strategies were developed for five databases, in addition to three gray literature's databases. The risk of bias was evaluated using the "Meta-Analysis of Statistics Assessment and Review Instrument". A summary of overall strength of evidence was estimated using GRADE's Summary of findings table. RESULTS: Among 575 studies, five were included. Two studies were categorized as moderate risk of bias and three as high risk of bias. Self-report of teeth grinding and/or clenching presented contradictory results. Presence of abnormal tooth wear increased the odds of having tori, mainly for torus mandibularis. The overall quality of evidence ranged from low to very low. CONCLUSION: Based on available evidence, the presence of abnormal tooth wear might be associated with tori, mainly torus mandibularis. There is no sufficient evidence to credit or discredit the association of tori and other signs and/or symptoms of bruxism. CLINICAL RELEVANCE: Bruxism diagnosis is a challenge. The association between signs and symptoms of bruxism and tori could help clinicians on the recognition of patients susceptible to bruxism. This knowledge might also aid to the understanding of tori's development and stimulate new relevant research.

Frequency of Undetected Glove Perforation and Associated Risk Factors in Equine Surgery.

OBJECTIVE: To estimate the frequency of undetected perforations in surgical gloves during equine surgery and to identify risk factors associated with occurrence. STUDY DESIGN: Observational cohort study. SAMPLE POPULATION: Surgical gloves-292 pairs. METHODS: Water leak tests were performed on gloves after equine surgery to detect perforations. Fifty pairs of unused gloves were also tested. Potential risk factors were recorded. Logistic regression was used to explore associations between putative risk factors and perforation. RESULTS: No perforations were detected in the unused gloves. Of 292 pairs of used gloves tested, 80 (27%) had at least one glove perforation per pair. The frequency of perforations was not different between surgery diplomates and residents (P=.69). The length and type of surgery were significantly associated with the likelihood of undetected glove perforation with surgeries longer than 60 minutes approximately 2.5 times more likely to result in glove perforation (P=.005). Surgery classified as soft tissue, orthopedic or exploratory celiotomy was 3 times more likely to result in glove perforation than minimally invasive surgery. The perforations occurred significantly more frequently in the nondominant hand (19%) than the dominant hand (11%) (P=.009). CONCLUSION: There is a high occurrence of undetected glove perforation in equine surgery. Precautions can be suggested based on this study although further investigation is required to assess whether glove perforations are associated with surgical site infections.

Comparison of an alcohol-based hand rub and water-based chlorhexidine gluconate scrub technique for hand antisepsis prior to elective surgery in horses.

This prospective clinical study evaluates the effectiveness of an alcohol-based hand rub (Avagard™) for pre-surgical hand antisepsis in an equine hospital and compares it with traditional scrubbing technique using 4% chlorhexidine gluconate sponges and water. Prior to elective surgery, 3 board-certified surgeons were randomly assigned to hand antisepsis with either technique. Culture samples of each hand were taken at 4 times: before and after neutral soap hand wash, after scrub or rubbing technique, and after surgery. There was no significant difference in mean bacterial colony forming units between scrub and rub techniques over the 3 time periods (P = 0.6), controlling for initial counts. One horse from the scrub group had a skin incision infection following stifle arthroscopy; this was resolved with medical treatment. The alcohol-based hand rub is equivalent in efficacy for pre-surgical hand antisepsis to traditional water-based scrubs in an equine hospital setting.

Comparaison de l'alcool à friction et d'une technique de brossage au gluconate de chlorhexidine à base d'eau pour l'antisepsie des mains avant les chirurgies non urgentes chez les chevaux. Cette étude clinique prospective évalue l'efficacité d'un alcool à friction (AvagardMD) pour l'antisepsie des mains préalable à une chirurgie dans un hôpital équin et elle la compare à la technique de brossage traditionnelle au moyen d'éponges de gluconate de chlorhexidine 4 % et d'eau. Avant une chirurgie non urgente, trois chirurgiens agréés ont été assignés au hasard à l'antisepsie des mains avec l'une ou l'autre technique. Des échantillons de chaque main ont été prélevés quatre fois pour culture : avant et après le lavage des mains avec un savon neutre, après la technique de brossage et de friction et après la chirurgie. Il n'y avait aucune différence significative dans les moyennes des dénombrements bactériens d'unités formatrices de colonies entre les techniques de brossage et de friction pendant les trois périodes de temps (P = 0,6), en tenant compte des témoins pour les dénombrements initiaux. Un cheval du groupe de brossage a développé une infection au site de l'incision après une arthroscopie du grasset qui a été résolue par traitement médical. La friction des mains à l'alcool est équivalente, en matière d'efficacité pour l'antisepsie des mains avant la chirurgie, au brossage traditionnel à l'eau dans un milieu hospitalier équin.(Traduit par Isabelle Vallières).

Comparison Costs of ERCP and MRCP in Patients with Suspected Biliary Obstruction Based on a Randomized Trial.

BACKGROUND: The optimal management of patients with suspected biliary obstruction remains unclear, and includes the possible performance of magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP). OBJECTIVES: To complete a cost analysis based on a medical effectiveness randomized trial comparing an ERCP-first approach with an MRCP-first approach in patients with suspected bile duct obstruction. METHODS: The management strategies were based on a medical effectiveness trial of 257 patients over a 12-month follow-up period. Direct and indirect costs were included, adopting a societal perspective. The cost values are expressed in 2012 Canadian dollars. RESULTS: Total per-patient direct costs were Can$3547 for ERCP-first patients and Can$4013 for MRCP-first patients. Corresponding indirect costs were Can$732 and Can$694, respectively. Causes for differences in direct costs included a more frequent second procedure and a greater mean number of hospital days over the year in patients of the MRCP-first group. In contrast, it is the ERCP-first patients whose indirect costs were greater, principally due to more time away from activities of daily living. Choosing an ERCP-first strategy rather than an MRCP-first strategy saved on average Can$428 per patient over the 12-month follow-up duration; however, there existed a large amount of overlap when varying total cost estimates across a sensitivity analysis range based on observed resources utilization. CONCLUSIONS: This cost analysis suggests only a small difference in total costs, favoring the ERCP-first group, and is principally attributable to procedures and hospitalizations with little impact from indirect cost measurements.

Mutations in HBV DNA polymerase associated with nucleos(t)ide resistance are rare in treatment-naive patients.

BACKGROUND & AIMS: Prior studies have detected hepatitis B virus (HBV) DNA polymerase mutations in treatment-naive patients. However, most of these studies used either direct polymerase chain reaction sequencing, which detects these mutations with low levels of sensitivity, or patient cohorts that were not well-characterized. We investigated the prevalence of HBV mutations in DNA polymerase by using a line probe assay. METHODS: In a prospective, cross-sectional study, we enrolled 198 treatment-naive patients with chronic hepatitis B (52.5% male; mean age, 41 years) from February 2009 to May 2011 from 3 gastroenterology and liver clinics in Northern California. Exclusion criteria included infection with hepatitis C or D viruses or human immunodeficiency virus. All patients completed a questionnaire (to determine demographics, history of liver disease, prior treatments, family medical history, drug and alcohol use, and environmental risk factors for hepatitis) that was administered by a research coordinator; mutations in HBV DNA polymerase were detected by using the INNO-LiPA HBV DR v.3 assay. RESULTS: Most patients were Vietnamese (48.5%) or Chinese (36.4%) and were infected with HBV genotypes B (67.5%) or C (24.2%). Mutations in HBV DNA polymerase were found in 2 patients (1%), rtI233V (n = 1) and rtM250M/L (n = 1). CONCLUSIONS: In a multicenter prospective study of treatment-naive patients with chronic hepatitis B, we detected mutations in HBV DNA polymerase in only 1%. Because of the low prevalence of these mutations and the uncertain clinical significance of such quasispecies, routine HBV DNA polymerase mutation analysis cannot be recommended before initiation of antiviral therapy for treatment-naive patients with chronic hepatitis B. The analysis requires further molecular and clinical studies.