Studies indicate that West African and Congo basin isolates of monkeypox virus (MPXV) are genetically distinct. Here, we show Congo basin MPXV-ZAI-V79 is more virulent for cynomolgus monkeys as compared to presumed West African MPXV-COP-58. This finding may explain the lack of case-fatalities in the U.S. 2003 monkeypox outbreak, which was caused by a West African virus. Virulence differences between West African and Congo basin MPXV are further supported by epidemiological analyses that observed a similar prevalence of antibodies in non-vaccinated humans in both regions, while >90% of reported cases occurred in the Congo basin, and no fatal cases were observed outside of this region. To determine the basis for this difference in virulence, we sequenced the genomes of one human West African isolate, and two presumed West African isolates and compared the sequences to Congo basin MPXV-ZAI-96-I-16. The analysis identified D10L, D14L, B10R, B14R, and B19R as possible virulence genes, with D14L (ortholog of vaccinia complement protein) as a leading candidate.

NCT01140009 and NCT01368796.

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change ≥1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and β2-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and controls throughout the period of quiescent follow-up. Results were validated using ELISA where possible, and initial cross-validation estimated a sensitivity of 80% and specificity of 90% for classification of BCAR based on a four-protein ELISA classifier. This study provides evidence that protein concentrations in plasma may provide a relevant measure for the occurrence of BCAR and offers a potential tool for immunologic monitoring.

Glomerulonephritis (GN) is the leading cause of chronic kidney disease among recipients of renal transplants. Because modern immunosuppressive regimens have reduced the incidence of rejection-related graft loss, the probability and clinical significance of posttransplantation GN (PTGN) requires reevaluation. In this Canadian epidemiologic study, we monitored 2026 sequential renal transplant recipients whose original renal disease resulted from biopsy-proven GN (36%), from presumed GN (7.8%), or from disorders other than GN (56%) for 15 yr without loss to follow-up. Kaplan-Meier estimates of PTGN in the whole population were 5.5% at 5 yr, 10.1% at 10 yr, and 15.7% at 15 yr. PTGN was diagnosed in 24.3% of patients whose original renal disease resulted from biopsy-proven GN, compared with 11.8% of those with presumed GN and 10.5% of those with disorders other than GN. Biopsy-proven GN in the native kidney, male gender, younger age, and nonwhite ethnicity predicted PTGN. Current immunosuppressive regimens did not associate with a reduced frequency of PTGN. Patients who developed PTGN had significantly reduced graft survival (10.2 versus 69.7%; P < 0.0001). In summary, in the Canadian population, PTGN is a common and serious complication that causes accelerated graft failure, despite the use of modern immunosuppressive regimens.

Emergence agitation is a frequent complication that can have serious consequences during recovery from general anesthesia. However, agitation has been poorly investigated in patients after craniotomy. In this prospective cohort study, adult patients were enrolled after elective craniotomy for brain tumor. The sedation-agitation scale was evaluated during the first 12 hours after surgery. Agitation developed in 35 of 123 patients (29%). Of the agitated patients, 28 (80%) were graded as very and dangerously agitated. By multivariate stepwise logistic regression analysis, independent predictors for agitation included male sex, history of long-term use of anti-depressant drugs or benzodiazepines, frontal approach of the operation, method and duration of anesthesia and presence of endotracheal intubation. Total intravenous anesthesia and balanced anesthesia with short duration were protective factors. Emergence agitation was associated with self-extubation (8.6% vs 0%, P = 0.005). Sedatives were administered more in agitated patients than non-agitated patients (85.7% vs 6.8%, P<0.001). In conclusion, emergence agitation was a frequent complication in patients after elective craniotomy for brain tumors. The clarification of risk factors could help to identify the high-risk patients, and then to facilitate the prevention and treatment of agitation. For patients undergoing craniotomy, greater attention should be paid to those receiving a frontal approach for craniotomy and those anesthetized under balanced anesthesia with long duration. More researches are warranted to elucidate whether total intravenous anesthesia could reduce the incidence of agitation after craniotomy.Trial RegistrationClinicalTrials.gov NCT00590499.

Vaccination campaigns for pandemic H1N1 vaccine should use messages that emphasize the risk of illness among younger people and the opportunity to protect loved ones by getting the vaccine and should address concerns about the safety and effectiveness of the vaccine.

Parasitoids are ubiquitous in natural ecosystems. Parasitic strategies are highly diverse among parasitoid species, yet their underlying genetic bases are poorly understood. Here, we focus on the divergent adaptation of a specialist and a generalist drosophilid parasitoids. We find that a novel protein (Lar) enables active immune suppression by lysing the host lymph glands, eventually leading to successful parasitism by the generalist. Meanwhile, another novel protein (Warm) contributes to a passive strategy by attaching the laid eggs to the gut and other organs of the host, leading to incomplete encapsulation and helping the specialist escape the host immune response. We find that these diverse parasitic strategies both originated from lateral gene transfer, followed with duplication and specialization, and that they might contribute to the shift in host ranges between parasitoids. Our results increase our understanding of how novel gene functions originate and how they contribute to host adaptation.

Addition of the RTN to the HD care team facilitated transition to independent modalities of RRT in suboptimal HD starts. This standardized approach to the care of such patients should be considered in HD units where suboptimal HD starts are common.