Fracture trauma in a medieval British farming village

Farming is among the three most hazardous occupations in modern society and perhaps also held a similar position during the medieval period. The goal of this study was to determine if there is a significant difference in frequencies and patterns of longbone fracture trauma observed between rural and urban activity bases that distinguish farming as a particularly dangerous occupation during the medieval period. The longbones of 170 individuals excavated from Raunds, a rural medieval British site (10th–12th centuries AD) were examined for fractures and compared to data collected from four contemporary British medieval sites, one rural and three urban. The fracture frequency for the Raunds individuals (19.4%) was significantly different from the urban sites (4.7–5.5%). Female fractures were characterized by injury to the forearm, while the males were predisposed to diverse fracture locations. Clinical research provided a source of documented farm-related trauma from North America and Europe where the crops and animals raised, the manual chores performed, and the equipment used in traditional or small-scale farms have changed little in form or function since the medieval period. Nonmechanized causes of injury contribute to approximately 40% of all modern farm-related injuries and are attributed to falls from lofts and ladders, animal assaults and bites, and falls from moving vehicles. These hazardous situations were also present in the medieval period and may explain some of the fracture trauma from the rural sites. A high fracture frequency for both medieval males and females is significantly associated with farming subsistence when compared to craft-orientated urban dwellers. Am J Phys Anthropol 109:229–243, 1999. © 1999 Wiley-Liss, Inc.     

Are Seafood PCB Data Sufficient to Assess Health Risk for High Seafood Consumption Groups?

Some populations in Washington's Puget Sound area consume much more seafood than the general population. Mean consumption rates are 61?g/person/day for the Tulalip and Squaxin Island Tribes and 117.2?g/person/day for Asian and Pacific Islanders (API). There is concern about possible health risks from seafood PCB exposure for these groups, but exposure evaluation is difficult due to inadequacies of environmental data. Available seafood PCB data were matched to results from recent seafood consumption surveys. To rate quality of matches and identify data gaps, a ranking system based on species specificity, data quality, and location compatibility was developed. Sensitivity of total PCB and congenerspecific PCB testing (for use in TCDD toxic equivalency approaches) necessary for cancer risk assessment was explored and included in the ranking scheme. For the Squaxin Tribe, appropriate total PCB data for risk assessment were available for 58% of seafood consumed, which is dominated by local salmon. For API, appropriate total PCB data were identified for only 4% of seafood consumed, which is dominated by commercial shellfish. Insufficient sensitivity of commercial seafood PCB analysis and overall lack of sufficiently sensitive PCB congener analysis are major gaps in ability to characterize PCB exposure and risk for these groups.     

Lymphocyte apoptosis in murine Pneumocystis pneumonia

Background

Apoptosis of lymphocytes is important in the termination of an immune response to infection but has also been shown to have detrimental effects in animal models of systemic infection and sepsis. We sought to characterize lymphocyte apoptosis in an animal model of pneumonia due to Pneumocystis murina, an infection localized to the lungs.

Methods

Control mice and mice depleted of CD4+ lymphocytes were inoculated with Pneumocystis. Apoptosis of lung and spleen lymphocytes was assayed by flow cytometry and PCR assay of apoptotic proteins.

Results

In control mice, apoptosis of lung lymphocytes was maximal just after the infection was cleared from lung tissue and then declined. However, in CD4-depleted mice, apoptosis was also upregulated in recruited lymphocytes in spite of progressive infection. In splenic lymphocytes, apoptosis was observed early at 1 week after inoculation and then declined. Apoptosis of lung lymphocytes in control mice was associated with a decrease in mRNA for Bcl-2 and an increase in mRNA for Bim. In CD4-depleted mice, lavaged CD8+ cells did change intracellular Bcl-2 but showed increased mRNA for Bim.

Conclusion

Apoptosis of both pulmonary and extrapulmonary lymphocytes is part of the normal host response to Pneumocystis but is also triggered in CD4-deficient animals with progressive infection. In normal mice apoptosis of pulmonary lymphocytes may serve to terminate the immune response in lung tissue. Apoptosis of lung lymphocytes takes place via both the intrinsic and extrinsic apoptotic pathways and is associated with changes in both pro- and anti-apoptotic proteins.     

Antifungal activity of nontraditional antifungal agents

Invasive fungal infections are becoming increasingly important in the management of critically ill and immunocompromised patients. As organ and stem cell transplantation becomes more prominent and immune therapies are employed for diseases such as rheumatoid arthritis and plaque psoriasis, the population of patients at risk continues to grow. Many invasive fungal infections are associated with extremely high mortality rates. Antifungal options are limited and novel therapies are intriguing as we attempt to improve patient outcomes and preserve the antifungal armamentarium. Many other classes of pharmaceuticals typically seen as non-antifungal do in fact have significant antifungal activity. Prominent among these are calcineurin inhibitors, antiarrhythmics, antidepressants, antibacterials, and others. Some have activity alone and some augment the activity of conventional antifungals. Unfortunately, clinical data are lacking for most of these agents and their role in therapy remains undefined. This review focuses on several representative non-antifungal agents with antifungal activity.     

Harnessing parallelism in multicore clusters with the All-Pairs,Wavefront, and Makeflow abstractions

Both distributed systems and multicore systems are difficult programming environments. Although the expert programmer may be able to carefully tune these systems to achieve high performance, the non-expert may struggle. We argue that high level abstractions are an effective way of making parallel computing accessible to the non-expert. An abstraction is a regularly structured framework into which a user may plug in simple sequential programs to create very large parallel programs. By virtue of a regular structure and declarative specification, abstractions may be materialized on distributed, multicore, and distributed multicore systems with robust performance across a wide range of problem sizes. In previous work, we presented the All-Pairs abstraction for computing on distributed systems of single CPUs. In this paper, we extend All-Pairs to multicore systems, and introduce the Wavefront and Makeflow abstractions, which represent a number of problems in economics and bioinformatics. We demonstrate good scaling of both abstractions up to 32 cores on one machine and hundreds of cores in a distributed system.     

Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1

Successful intracellular pathogens must evade or neutralize the innate immune defenses of their host cells and render the cellular environment permissive for replication. For example, to replicate efficiently in CD4(+) T lymphocytes, human immunodeficiency virus type 1 (HIV-1) encodes a protein called viral infectivity factor (Vif) that promotes pathogenesis by triggering the degradation of the retrovirus restriction factor APOBEC3G. Other APOBEC3 proteins have been implicated in HIV-1 restriction, but the relevant repertoire remains ambiguous. Here we present the first comprehensive analysis of the complete, seven-member human and rhesus APOBEC3 families in HIV-1 restriction. In addition to APOBEC3G, we find that three other human APOBEC3 proteins, APOBEC3D, APOBEC3F, and APOBEC3H, are all potent HIV-1 restriction factors. These four proteins are expressed in CD4(+) T lymphocytes, are packaged into and restrict Vif-deficient HIV-1 when stably expressed in T cells, mutate proviral DNA, and are counteracted by HIV-1 Vif. Furthermore, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H of the rhesus macaque also are packaged into and restrict Vif-deficient HIV-1 when stably expressed in T cells, and they are all neutralized by the simian immunodeficiency virus Vif protein. On the other hand, neither human nor rhesus APOBEC3A, APOBEC3B, nor APOBEC3C had a significant impact on HIV-1 replication. These data strongly implicate a combination of four APOBEC3 proteins--APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H--in HIV-1 restriction.     

Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model

Background

Different patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns.As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals.

Results

In comparison to HIV-WT, the HIV-M184 variants were less efficiently transmitted to CCR5⁺ Jurkat T cells by both LCs and DCs. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. Replication experiments in CCR5⁺ Jurkat T cells revealed no apparent differences in replication capacity between the mutant viruses and HIV-WT. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs.

Conclusions

Our data demonstrate that drug resistant M184-variants display a reduced replication capacity in LCs and DCs which directly impairs their transmission efficacy. As such, diminished transmission efficacy may contribute to the lower prevalence of drug resistant variants in therapy naive individuals.

     

The geographic distribution of obesity in the US and the potential regional differences in misreporting of obesity

Objective: State‐level estimates of obesity based on self‐reported height and weight suggest a geographic pattern of greater obesity in the Southeastern US; however, the reliability of the ranking among these estimates assumes errors in self‐reporting of height and weight are unrelated to geographic region. Design and Methods: Regional and state‐level prevalence of obesity (body mass index ≥ 30 kg m^?2) for non‐Hispanic black and white participants aged 45 and over were estimated from multiple sources: ( 1 ) self‐reported from the behavioral risk factor surveillance system (BRFSS 2003‐2006) (n = 677,425), ( 2 ) self‐reported and direct measures from the National Health and Nutrition Examination Study (NHANES 2003‐2008) (n = 6,615 and 6,138, respectively), and ( 3 ) direct measures from the REasons for Geographic and Racial Differences in Stroke (REGARDS 2003‐2007) study (n = 30,239). Results: Data from BRFSS suggest that the highest prevalence of obesity is in the East South Central Census division; however, direct measures suggest higher prevalence in the West North Central and East North Central Census divisions. The regions relative ranking of obesity prevalence differs substantially between self‐reported and directly measured height and weight. Conclusions: Geographic patterns in the prevalence of obesity based on self‐reported height and weight may be misleading, and have implications for current policy proposals.     

Impaired calcium mobilisation in the 7315a prolactin-secreting pituitary tumour

The 7315a tumour secretes prolactin, but is refractory to enhancement of prolactin release by thyrotrophin-releasing hormone (TRH). In order to investigate further this refractoriness of the 7315a tumour cell, we compared cells from the tumour and from the normal pituitary with regard to TRH-enhanced fractional 45Ca2+ efflux and inositol phosphate production. TRH caused a large efflux of calcium from normal pituitary cells, but only mildly enhanced calcium efflux from the tumour cells. In contrast, TRH enhanced total inositol phosphate generation in both groups of cells to a similar degree. We therefore conclude that prolactin release from 7315a tumour cells is refractory to TRH due, at least in part, to impaired mobilisation of intracellular calcium by inositol phosphates.