The clinical-grade 42-kilodalton fragment of merozoite surface protein 1 of Plasmodium falciparum strain FVO expressed in Escherichia coli protects Aotus nancymai against challenge with homologous erythrocytic-stage parasites

A 42-kDa fragment from the C terminus of major merozoite surface protein 1 (MSP1) is among the leading malaria vaccine candidates that target infection by asexual erythrocytic-stage malaria parasites. The MSP1(42) gene fragment from the Vietnam-Oak Knoll (FVO) strain of Plasmodium falciparum was expressed as a soluble protein in Escherichia coli and purified according to good manufacturing practices. This clinical-grade recombinant protein retained some important elements of correct structure, as it was reactive with several functional, conformation-dependent monoclonal antibodies raised against P. falciparum malaria parasites, it induced antibodies (Abs) that were reactive to parasites in immunofluorescent Ab tests, and it induced strong growth and invasion inhibitory antisera in New Zealand White rabbits. The antigen quality was further evaluated by vaccinating Aotus nancymai monkeys and challenging them with homologous P. falciparum FVO erythrocytic-stage malaria parasites. The trial included two control groups, one vaccinated with the sexual-stage-specific antigen of Plasmodium vivax, Pvs25, as a negative control, and the other vaccinated with baculovirus-expressed MSP1(42) (FVO) as a positive control. Enzyme-linked immunosorbent assay (ELISA) Ab titers induced by E. coli MSP1(42) were significantly higher than those induced by the baculovirus-expressed antigen. None of the six monkeys that were vaccinated with the E. coli MSP1(42) antigen required treatment for uncontrolled parasitemia, but two required treatment for anemia. Protective immunity in these monkeys correlated with the ELISA Ab titer against the p19 fragment and the epidermal growth factor (EGF)-like domain 2 fragment of MSP1(42), but not the MSP1(42) protein itself or the EGF-like domain 1 fragment. Soluble MSP1(42) (FVO) expressed in E. coli offers excellent promise as a component of a vaccine against erythrocytic-stage falciparum malaria.     

Differences in host susceptibility to disease progression in the human challenge model of Haemophilus ducreyi infection

With human volunteers inoculated at two sites with Haemophilus ducreyi, outcomes for a subject were not independent. In a reinfection trial, 2 of 11 previous pustule formers and 6 of 10 previous resolvers resolved all sites of infection. There was no correlation between serum bactericidal or phagocytic activity and outcome in the trial. These data indicate that different hosts are differentially susceptible to disease progression versus resolution in the model.     

Adoptive transfer of mast cells does not enhance the impaired survival of Kit(W)/Kit(W-v) mice in a model of low dose intraperitoneal infection with bioluminescent Salmonella typhimurium

Mast cells are important effector cells in IgE-associated immune responses, but also can contribute to host defense in certain examples of bacterial infection. We found that genetically mast cell-deficient WBB6F1-Kit(W)/Kit(W-v) mice exhibited more bacterial CFUs per spleen by 6 days after intraperitoneal injection of bioluminescent Salmonella typhimurium, and died more rapidly after infection, than did the congenic WBB6F1-Kit(+/+) wild type mice. Adoptive transfer of bone marrow-derived cultured mast cells of Kit(+/+) origin to the peritoneal cavity of Kit(W)/Kit(W-v) mice resulted in engraftment of mast cells in the peritoneal cavity and mesentery of the recipient mice, and the development of large numbers of mast cells in the spleen. However, such mast cell-engrafted Kit(W)/Kit(W-v) mice appeared sicker after intraperitoneal injection with S. typhimurium than did mast cell-deficient Kit(W)/Kit(W-v) mice, and exhibited numbers of CFUs of bacteria per spleen, and a survival curve, that were not significantly different than those of Kit(W)/Kit(W-v) mice. These results, when taken together with prior studies investigating the roles of mast cells in innate immunity, strongly suggest that whether mast cells can be shown to have a significant role in enhancing survival during bacterial infections may depend critically on the details of the particular experimental systems examined.     

Energy Balance,Eating Disorder Risk,and Pathogenic Behaviors Among Athletic Trainers

ContextResearch exists on energy balances (EBs) and eating disorder (ED) risks in physically active populations and occupations by settings, but the EB and ED risk in athletic trainers (ATs) have not been investigated.ObjectiveTo assess ATs'' energy needs, including the macronutrient profile, and examine ED risk and pathogenic behavioral differences between sexes (men, women) and job statuses (part time or full time) and among settings (college or university, high school, nontraditional).DesignCross-sectional study.SettingFree living in job settings.Patients or Other ParticipantsAthletic trainers (n = 46; male part-time graduate assistant ATs = 12, male full-time ATs = 11, female part-time graduate assistant ATs = 11, female full-time ATs = 12) in the southeastern United States.Main Outcome Measure(s)Anthropometric measures (sex, age, height, weight, body composition), demographic characteristics (job status [full- or part-time AT], job setting [college/university, high school, nontraditional], years of AT experience, exercise background, alcohol use), resting metabolic rate, energy intake (EI), total daily energy expenditure (TDEE), EB, exercise energy expenditure, macronutrients (carbohydrates, protein, fats), the Eating Disorder Inventory-3, and the Eating Disorder Inventory-3 Symptom Checklist.ResultsThe majority of participants (84.8%, n = 39) had an ED risk, with 26.1% (n = 12) engaging in at least 1 pathogenic behavior, 50% (n = 23) in 2 pathogenic behaviors, and 10.8% (n = 5) in >2 pathogenic behaviors. Also, 82.6% of ATs (n = 38) presented in negative EB (EI < TDEE). Differences were found in resting metabolic rate for sex and job status (F_1,45 = 16.48, P = .001), EI (F_1,45 = 12.01, P = .001), TDEE (F_1,45 = 40.36, P < .001), and exercise energy expenditure (F_1,38 = 5.353, P = .026). No differences were present in EB for sex and job status (F_1,45 = 1.751, P = .193); χ² analysis revealed no significant relationship between ATs'' sex and EB (= 0.0, P = 1.00) and job status and EB ( = 2.42, P = .120). No significant relationship existed between Daily Reference Intakes recommendations for all macronutrients and sex or job status.ConclusionsThese athletic trainers experienced negative EB, similar to other professionals in high-demand occupations. Regardless of sex or job status, ATs had a high ED risk and participated in unhealthy pathogenic behaviors. The physical and mental concerns associated with these findings indicate a need for interventions targeted at ATs'' health behaviors.     

Effects of stimulus emotionality and sentence generation on memory for words in adults with unilateral brain damage

Does sentence generation and/or stimulus emotionality enhance verbal memory in patients with neurological impairment? This question was addressed by testing 40 patients with unilateral stroke (20 with left-brain and 20 with right-brain damage) and 20 healthy control participants for recall and recognition of 48 target words. During encoding, emotional and nonemotional words were either presented in sentences (read condition) or used to form sentences (generate condition). Both word emotionality and generative processing improved memory performance in all groups. The authors suggest that a similar influence (i.e., cognitive activation) underlies both of these memory-enhancing effects, although the putative origins of the 2 effects are quite different. Neuropsychological underpinnings and clinical implications of these phenomena are discussed.     

Improved Maternal and Infant Outcomes with Serial,Self-Reported Early Prenatal Substance Use Screening

Maternal and Child Health Journal - Most screening tools identifying women with substance use are not validated, used once in pregnancy, and are not reflective of continued substance use. We...     

Long-Term Functional Outcomes and Quality of Life at Minimum 10-Year Follow-Up After Fixed-Bearing Unicompartmental Knee Arthroplasty and Total Knee Arthroplasty for Isolated Medial Compartment Osteoarthritis

BackgroundThe aim of this study is to compare the long-term functional outcome and quality of life between total knee arthroplasty (TKA) and fixed-bearing unicompartmental knee arthroplasty (UKA) for the treatment of isolated medial compartment osteoarthritis.MethodsBetween 2000 and 2008, a total of 218 patients underwent primary UKA at our tertiary hospital. A TKA group was matched through 1:1 propensity score matching and adjusted for age, gender, body mass index, preoperative knee flexion, and function scores. All patients had medial compartment osteoarthritis. The patients were assessed with the range of motion, Knee Society Knee Score and Knee Society Function Score, Oxford Knee Score, Short Form-36 physical component score (PCS) and mental component score preoperatively, at 6 months, 2 years, and 10 years. Patients’ satisfaction, expectation fulfillment, and minimal clinically important difference were analyzed.ResultsThere were no differences in baseline characteristics between groups after propensity score matching (P > .05). UKA had greater knee flexion at all time points. Although the Knee Society Function Score was superior in UKA by 5.5, 3, and 4.3 points at 6 months, 2 years, and 10 years, respectively (P < .001), these differences did not exceed the minimal clinically important difference (Knee Society Knee Score 6.1). There were no significant differences in the Oxford Knee Score and Short Form-36 physical component score/mental component score. At 10 years, similar proportions of UKA and TKA were satisfied (90.8% vs 89.9%, P = .44) and had expectation fulfillment (89.4% vs 88.5%, P = .46). Between 2 and 10 years, all function scores deteriorated significantly for both groups (P < .01).ConclusionUKA and TKA are excellent treatment modalities for isolated medial compartment osteoarthritis, with similar functional outcomes, quality of life, and satisfaction at 10 years.     

Authors’ reply to Grundtvig Gram et al.

European Journal of Epidemiology -     

Long-term neurologic and neurosensory sequelae in adult survivors of a childhood brain tumor: childhood cancer survivor study.

PURPOSE: To describe the neurologic and neurosensory deficits in children with brain tumors (BTs), compare incidence of these deficits with that of a sibling control group, and evaluate the factors associated with the development of these deficits. PATIENTS AND METHODS: Detailed questionnaires were completed on 1,607 patients diagnosed between 1970 and 1986 with a primary CNS tumor. Neurosensory and neurologic dysfunctions were assessed and results compared with those of a sibling control group. Medical records on all patients were abstracted, including radiotherapy dose and volume. RESULTS: Seventeen percent of patients developed neurosensory impairment. Relative to the sibling comparison group, patients surviving BTs were at elevated risk for hearing impairments (relative risk [RR], 17.3; P = <.0001), legal blindness in one or both eyes (RR, 14.8; P = <.0001), cataracts (RR, 11.9; P = <.0001), and double vision (RR, 8.8; P = <.0001). Radiation exposure greater than 50 Gy to the posterior fossa was associated with a higher likelihood of developing any hearing impairment. Coordination and motor control problems were reported in 49% and 26%, respectively, of survivors. Children receiving at least 50 Gy to the frontal brain regions had a moderately elevated risk for motor problems (RR, 2.0; P <.05). Seizure disorders were reported in 25% of patients, including 6.5% who had a late first occurrence. Radiation dose of 30 Gy or more to any cortical segment of the brain was associated with a two-fold elevated risk for a late seizure disorder. CONCLUSION: Children surviving BTs are at significant risk for both early and late neurologic or neurosensory sequelae. These sequelae need to be prospectively monitored.