Lead and Lead Poisoning from Antiquity to Modern Times

Author Institution: Department of Physiology, Ohio State UniversityLead, because of its low melting point, was one of the first metals used by man. It was probably isolated soon after the ancients discovered the use of fire. Archeological discoveries indicate the presence of lead objects and pigments during the early Bronze Age. In ancient Egyptian and Greco-Roman times metallic lead was produced as a by-product of silver mining. Extensive evidence of ancient mining and smelting exists in both the Orient and Mediterranean regions. Although generally thought of as a disease of the Industrial Revolution, lead poisoning has been documented for 6,000 years. As early as the 4th century BCE, Hippocrates accurately described the symptoms of lead poisoning. However, it was not until the 19th and 20th centuries that lead as an occupational health factor became a public issue. During Greco-Roman and Medieval times sapa, a sweet lead acetate syrup, was added to both wines and food. This resulted in widespread lead intoxication among the affluent and has been suggested as a probable reason for the fall of the Roman Empire. Fortified wines from Spain and Portugal, rum from the Colonies, and cider precipitated epidemics of lead poisoning. Since 1970 the National Institutes of Occupational Safety and Health have monitored environmental lead and significantly reduced lead exposure in air, water, and food

Variation in dengue virus plaque reduction neutralization testing: systematic review and pooled analysis.

BackgroundThe plaque reduction neutralization test (PRNT) remains the gold standard for the detection of serologic immune responses to dengue virus (DENV). While the basic concept of the PRNT remains constant, this test has evolved in multiple laboratories, introducing variation in materials and methods. Despite the importance of laboratory-to-laboratory comparability in DENV vaccine development, the effects of differing PRNT techniques on assay results, particularly the use of different dengue strains within a serotype, have not been fully characterized.MethodsWe conducted a systematic review and pooled analysis of published literature reporting individual-level PRNT titers to identify factors associated with heterogeneity in PRNT results and compared variation between strains within DENV serotypes and between articles using hierarchical models.ResultsThe literature search and selection criteria identified 8 vaccine trials and 25 natural exposure studies reporting 4,411 titers from 605 individuals using 4 different neutralization percentages, 3 cell lines, 12 virus concentrations and 51 strains. Of 1,057 titers from primary DENV exposure, titers to the exposure serotype were consistently higher than titers to non-exposure serotypes. In contrast, titers from secondary DENV exposures (n = 628) demonstrated high titers to exposure and non-exposure serotypes. Additionally, PRNT titers from different strains within a serotype varied substantially. A pooled analysis of 1,689 titers demonstrated strain choice accounted for 8.04% (90% credible interval [CrI]: 3.05%, 15.7%) of between-titer variation after adjusting for secondary exposure, time since DENV exposure, vaccination and neutralization percentage. Differences between articles (a proxy for inter-laboratory differences) accounted for 50.7% (90% CrI: 30.8%, 71.6%) of between-titer variance.ConclusionsAs promising vaccine candidates arise, the lack of standardized assays among diagnostic and research laboratories make unbiased inferences about vaccine-induced protection difficult. Clearly defined, widely accessible reference reagents, proficiency testing or algorithms to adjust for protocol differences would be a useful first step in improving dengue PRNT comparability and quality assurance

Statistical mechanics and thermodynamics of viral evolution

This paper analyzes a simplified model of viral infection and evolution using the 'grand canonical ensemble' and formalisms from statistical mechanics and thermodynamics to enumerate all possible viruses and to derive thermodynamic variables for the system. We model the infection process as a series of energy barriers determined by the genetic states of the virus and host as a function of immune response and system temperature. We find a phase transition between a positive temperature regime of normal replication and a negative temperature 'disordered' phase of the virus. These phases define different regimes in which different genetic strategies are favored. Perhaps most importantly, it demonstrates that the system has a real thermodynamic temperature. For normal replication, this temperature is linearly related to effective temperature. The strength of immune response rescales temperature but does not change the observed linear relationship. For all temperatures and immunities studied, we find a universal curve relating the order parameter to viral evolvability. Real viruses have finite length RNA segments that encode for proteins which determine their fitness; hence the methods put forth here could be refined to apply to real biological systems, perhaps providing insight into immune escape, the emergence of novel pathogens and other results of viral evolution.Comment: 39 pages (55 pages including supplement), 9 figures, 11 supplemental figure

Respiratory Activity of Isolated Chondrocytes with a Miniaturized Oxygen Electrade System

Author Institution: Department of Physiology, Ohio State University ; Department of Surgery, Ohio State UniversityA technique for the isolation of chondrocytes from the articular cartilage of rabbits was modified and improved to yield 5 to 20 x 106 viable cells per preparation. A YSI Model 5331 O2 sensor was modified so that it could rapidly respond in as little as 1 ml of medium. Mean oxygen uptake of cell samples showed that chondrocytes obtained from mature rabbits (1.33 /J! O2/107 cells/hr) had a higher oxidative activity than chondrocytes from immature rabbits (0.8 (A O2/107 cells/hr). Elevation of the incubation temperature from 25 °C to 35 °C increased the chondrocyte oxygen uptake approximately 20% but incubation at 37 °C tended to decrease oxygen uptake. It is evident that articular chondrocyte cells have a real, but fairly low, temperature sensitive oxidative metabolism

Controlled Phenylhydrazine-Induced Reticulocytosis in the Rat

Author Institution: Department of Physiology, Ohio State University, College of Medicine, Columbus, Ohio 43210The pattern of development of phenylhydrazine-induced rat reticulocytosis was studied over a period of nine days. Intraperitoneal injections of phenylhydrazine (4 mg/100 gm) every other day caused a fall in hematocrit which leveled off at 60% of normal by the fifth day. Increased erythropoiesis was indicated by a three-fold increase in the number of circulating reituclocytes after the first three injections. The immediate response was the release of stored mature reticulocytes from the bone marrow. As the anemia progressed, more and more young reticulocytes appeared until 70 to 85% of the red cells in the peripheral circulation were reticulocytes and 20% of these were juvenile forms

Bacterial infections in neonates following mupirocin-based MRSA decolonization: A multicenter cohort study

OBJECTIVETo characterize the risk of infection after MRSA decolonization with intranasal mupirocin.DESIGNMulticenter, retrospective cohort study.SETTINGTertiary care neonatal intensive care units (NICUs) from 3 urban hospitals in the United States ranging in size from 45 to 100 beds.METHODSMRSA-colonized neonates were identified from NICU admissions occurring from January 2007 to December 2014, during which a targeted decolonization strategy was used for MRSA control. In 2 time-to-event analyses, MRSA-colonized neonates were observed from the date of the first MRSA-positive surveillance screen until (1) the first occurrence of novel gram-positive cocci in sterile culture or discharge or (2) the first occurrence of novel gram-negative bacilli in sterile culture or discharge. Mupirocin exposure was treated as time varying.RESULTSA total of 522 MRSA-colonized neonates were identified from 16,144 neonates admitted to site NICUs. Of the MRSA-colonized neonates, 384 (74%) received mupirocin. Average time from positive culture to mupirocin treatment was 3.5 days (standard deviation, 7.2 days). The adjusted hazard of gram-positive cocci infection was 64% lower among mupirocin-exposed versus mupirocin-unexposed neonates (hazard ratio, 0.36; 95% confidence interval [CI], 0.17–0.76), whereas the adjusted hazard ratio of gram-negative bacilli infection comparing mupirocin-exposed and -unexposed neonates was 1.05 (95% CI, 0.42–2.62).CONCLUSIONSIn this multicentered cohort of MRSA-colonized neonates, mupirocin-based decolonization treatment appeared to decrease the risk of infection with select gram-positive organisms as intended, and the treatment was not significantly associated with risk of subsequent infections with organisms not covered by mupirocin’s spectrum of activity.Infect Control Hosp Epidemiol2017;38:930–936</jats:sec

Seven challenges for model-driven data collection in experimental and observational studies.

Infectious disease models are both concise statements of hypotheses and powerful techniques for creating tools from hypotheses and theories. As such, they have tremendous potential for guiding data collection in experimental and observational studies, leading to more efficient testing of hypotheses and more robust study designs. In numerous instances, infectious disease models have played a key role in informing data collection, including the Garki project studying malaria, the response to the 2009 pandemic of H1N1 influenza in the United Kingdom and studies of T-cell immunodynamics in mammals. However, such synergies remain the exception rather than the rule; and a close marriage of dynamic modeling and empirical data collection is far from the norm in infectious disease research. Overcoming the challenges to using models to inform data collection has the potential to accelerate innovation and to improve practice in how we deal with infectious disease threats