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Trabecular bone is a spongy bone tissue that serves as a scaffolding-like support inside many skeletal elements. Previous research found allometric variation in some aspects of trabecular bone architecture (TBA) and bone microstructure, whereas others scale isometrically. However, most of these studies examined very wide size and phylogenetic ranges or focused exclusively on primates or lab mice. We examined the impact of body size on TBA across a smaller size range in the mammalian clade Xenarthra (sloths, armadillos, and anteaters). We µCT-scanned the last six presacral vertebrae of 23 xenarthran specimens (body mass 120 g-35 kg). We collected ten gross-morphology measurements and seven TBA metrics and analyzed them using phylogenetic and nonphylogenetic methods. Most metrics had similar allometries to previous work. However, because ecology and phylogeny align closely in Xenarthra, the phylogenetic methods likely removed some covariance due to ecology; clarifying the impact of ecology on TBA in xenarthrans requires further work. Regressions for Folivora had high P -values and low R -squared values, indicating that the extant sloth sample either is too limited to determine patterns or that the unique way sloths load their vertebral columns causes unusually high TBA variation. The southern three-banded armadillo sits far below the regression lines, which may be related to its ability to roll into a ball. Body size, phylogeny, and ecology impact xenarthran TBA, but parsing these effects is highly complex., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Teeth lie at the interface between an animal and its environment and, with some exceptions, act as a major component of resource procurement through food acquisition and processing. Therefore, the shape of a tooth is closely tied to the type of food being eaten. This tight relationship is of use to biologists describing the natural history of species and given the high instance of tooth preservation in the fossil record, is especially useful for paleontologists. However, correlating gross tooth morphology to diet is only part of the story, and much more can be learned through the study of dental biomechanics. We can explore the mechanics of how teeth work, how different shapes evolved, and the underlying forces that constrain tooth shape. This review aims to provide an overview of the research on dental biomechanics, in both mammalian and non-mammalian teeth, and to synthesize two main approaches to dental biomechanics to develop an integrative framework for classifying and evaluating dental functional morphology. This framework relates food material properties to the dynamics of food processing, in particular how teeth transfer energy to food items, and how these mechanical considerations may have shaped the evolution of tooth morphology. We also review advances in technology and new techniques that have allowed more in-depth studies of tooth form and function., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.)

Native insects can form novel associations with introduced invasive plants and use them as a food source. The recent introduction into eastern North America of a nonnative European vine, Vincetoxicum rossicum (Kleopow) Barbar., allows us to examine the initial response of a native chrysomelid beetle, Chrysochus auratus F., that feeds on native plants in the same family as V. rossicum (Apocynaceae). We tested C. auratus on V. rossicum and closely related or co-occurring native plants (Apocynum spp., Asclepias spp., and Solidago canadensis L.) using all life stages of the beetle in lab, garden, and field experiments. Experiments measured feeding (presence or absence and amount), survival, oviposition, and whether previous exposure to V. rossicum in the lab or field affected adult beetle feeding. Beetles fed significantly less on V. rossicum than on native Apocynum hosts. Adult beetles engaged in exploratory feeding on leaves of V. rossicum and survived up to 10 d. Females oviposited on V. rossicum, eggs hatched, and larvae fed initially on the roots; however, no larvae survived beyond second instar. Beetles collected from Apocynum cannabinum L. field sites intermixed with V. rossicum were less likely to feed on this novel nonnative host than those collected from colonies further from and less likely to be exposed to V. rossicum (>5 km). Our experimental work indicates that V. rossicum may act as an oviposition sink for C. auratus and that this native beetle has not adapted to survive on this recently introduced novel host plant., (© The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Context: Animal models and human studies suggest that osteocytes regulate the skeleton's response to mechanical unloading in part by an increase in sclerostin. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading., Objective: We determined changes in serum sclerostin and bone turnover markers in healthy adult men undergoing controlled bed rest., Design, Setting, and Participants: Seven healthy adult men (31 ± 3 yr old) underwent 90 d of 6° head down tilt bed rest at the University of Texas Medical Branch Institute for Translational Sciences-Clinical Research Center., Outcomes: Serum sclerostin, PTH, vitamin D, bone resorption and formation markers, urinary calcium and phosphorus excretion, and 24-h pooled urinary markers of bone resorption were evaluated before bed rest [baseline (BL)] and at bed rest d 28 (BR-28), d 60 (BR-60), and d 90 (BR-90). Bone mineral density was measured at BL, BR-60, and 5 d after the end of the study (BR+5). Data are reported as mean ± SD., Results: Consistent with prior reports, bone mineral density declined significantly (1-2% per month) at weight-bearing skeletal sites. Serum sclerostin was elevated above BL at BR-28 (+29 ± 20%; P = 0.003) and BR-60 (+42 ± 31%; P < 0.001), with a lesser increase at BR-90 (+22 ± 21%; P = 0.07). Serum PTH levels were reduced at BR-28 (-17 ± 16%; P = 0.02) and BR-60 (-24 ± 14%; P = 0.03) and remained lower than BL at BR-90 (-21 ± 21%; P = 0.14), but did not reach statistical significance. Serum bone turnover markers were unchanged; however, urinary bone resorption markers and calcium were significantly elevated at all time points after bed rest (P < 0.01)., Conclusions: In healthy men subjected to controlled bed rest for 90 d, serum sclerostin increased, with a peak at 60, whereas serum PTH declined, and urinary calcium and bone resorption markers increased.

Sirex noctilio F. is an exotic woodwasp now found in eastern North America where it shares natural enemies with native woodwasps of Pinus spp. To study the extent to which native hymenopteran parasitoids and parasitic nematodes could affect woodwasp populations, 60 Pinus trees with symptoms of S. noctilio attack were felled in 2007 and 2008 in Ontario, Canada. Each tree bole was cut into 1-m sections that were placed in individual rearing tubes; emergence was monitored from May to November of the year of felling. Female S. noctilio were dissected to assess parasitism by the nematode Deladenus siricidicola Bedding. Two species of Siricidae emerged from these trees; S. noctilio, which accounted for most of the specimens collected, and S. nigricornis F. Of the three species of parasitoid that emerged, Ibalia leucospoides (Hochenwarth) was the most abundant, accounting for an overall hypothetical Siricidae parasitism rate of almost 20%. This parasitoid emerged over a similar time period as S. noctilio-between early July and early September. Except in trees >15 m in height, parasitism by I. leucospoides generally appeared uniform throughout the bole. Parasitism rates did not vary between the 2 yr, but did between sites in 1 yr. Parasitic nematodes were found in the haemocoel of about one third of S. noctilio females dissected but were never found sterilizing the eggs; none were found in S. noctilio emerging from P. resinosa. These findings suggest that I. leucospoides is currently the primary invertebrate natural enemy of S. noctilio in Ontario.

Normal aging is associated with cognitive decline. Functions such as attention, information processing, and working memory are compromised. It has been hypothesized that not only regional changes, but also alterations in the integration of regional brain activity (functional brain connectivity) underlie the observed age-related deficits. Here, we examined the functional properties of brain networks based on spontaneous fluctuations within brain systems using functional magnetic resonance imaging. We hypothesized that functional connectivity of intrinsic brain activity in the "default-mode" network (DMN) is affected by normal aging and that this relates to cognitive function. Ten younger and 22 older subjects were scanned at "rest," that is, lying awake with eyes closed. Our results show decreased activity in older versus younger subjects in 2 resting-state networks (RSNs) resembling the previously described DMN, containing the superior and middle frontal gyrus, posterior cingulate, middle temporal gyrus, and the superior parietal region. These results remain significant after correction for RSN-specific gray matter volume. The relevance of these findings is illustrated by the correlation between reduced activity of one of these RSNs and less effective executive functioning/processing speed in the older group.

The authors compared how four indexes-the Healthy Eating Index-2005, Alternate Healthy Eating Index, Mediterranean Diet Score, and Recommended Food Score-are associated with colorectal cancer in the National Institutes of Health-AARP Diet and Health Study (n = 492,382). To calculate each score, they merged data from a 124-item food frequency questionnaire completed at study entry (1995-1996) with the MyPyramid Equivalents Database (version 1.0). Other variables included energy, nutrients, multivitamins, and alcohol. Models were stratified by sex and adjusted for age, ethnicity, education, body mass index, smoking, physical activity, and menopausal hormone therapy (in women). During 5 years of follow-up, 3,110 incident colorectal cancer cases were ascertained. Although the indexes differ in design, a similarly decreased risk of colorectal cancer was observed across all indexes for men when comparing the highest scores with the lowest: Healthy Eating Index-2005 (relative risk (RR) = 0.72, 95% confidence interval (CI): 0.62, 0.83); Alternate Healthy Eating Index (RR = 0.70, 95% CI: 0.61, 0.81); Mediterranean Diet Score (RR = 0.72, 95% CI: 0.63, 0.83); and Recommended Food Score (RR = 0.75, 95% CI: 0.65, 0.87). For women, a significantly decreased risk was found with the Healthy Eating Index-2005, although Alternate Healthy Eating Index results were similar. Index-based dietary patterns that are consistent with given dietary guidelines are associated with reduced risk.

Most insects' assemblages differ with forest type and show vertical stratification. We tested for differences in richness, abundance and composition of hymenopteran families and mymarid genera between sugar maple (Acer saccharum) and white pine (Pinus strobus) stands and between canopy and understory in northeastern temperate forests in Canada. We used flight interception traps (modified malaise traps) suspended in the canopy and the understory in a split-split block design, with forest type as the main factor, forest stratum as the first split factor, and collection bottle location as the second split factor. Hymenopteran families and mymarid genera differed in their diversity depending on forest type and stratum. Both family and genera richness were higher in maple than in pine forests, whereas family richness was higher in the canopy and top bottles and generic richness was higher in the understory and bottom bottles. Multivariate analysis separated samples by forest type, vegetation stratum, and bottle location. Family composition showed 77% similarity between forest types and 73% between the canopy and understory. At the lower taxa level, mymarid genera showed only 47% similarity between forest types and 40% between forest strata, indicating vertical stratification and relatively high beta-diversity. Our study suggests that hymenopteran diversity and composition is strongly dependent on forest type and structure, making flying members of this order particularly vulnerable to forest management practices. It also shows that insect assemblage composition (especially at low-taxon levels), rather than relative abundance and richness, is the community attribute most sensitive to forest type and vertical stratification.

Variable retention harvesting (VRH), in which trees are removed at variable intensity and spatial configuration across the landscape, retains greater forest structural heterogeneity than traditional clear-cut harvesting and is being recommended as an alternative for sustainable management of the boreal forest. Little is known about its effects on forest fauna; thus, we studied the influence of one type of VRH (harvesting with advanced regeneration [HARP]) on the Syrphidae (Diptera) community in northern Ontario forests of peatland black spruce (Picea mariana). We examined the effects of varying structural retention (from unharvested through partial retention to clear-cut) on syrphid species richness and abundance, and abundance of functional assemblages. Greater species richness and population abundances were found generally in harvested than in unharvested forests. Overall species richness and the abundance of four species (Platycheirus rosarum, Toxomerus marginatus, Xylota annulifera, and X. tuberculata) and larval predators were all higher in both clear-cut sites and those with structural retention than in unharvested sites. Similarly, overall species richness and the abundance of nine species were higher in clear-cut than in unharvested sites. Species responses are discussed in an ecological context. Differences among the levels of forest retention harvesting were relatively minor compared with those of the clear-cut and unharvested area, suggesting that local habitat characteristics may play a more important role in determining the syrphid community than the landscape configuration. However, a landscape level effect was evident, suggesting that syrphids may be useful in reflecting changes in stand structure at the landscape scale.

The aryl hydrocarbon receptor (AhR) was originally characterized because of its high affinity binding of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin. However, studies using AhR-null mice have demonstrated the importance of this protein in normal physiology and development. Here we demonstrate that AhR-null embryos develop cardiac enlargement, and that this phenotype is dependent, at least in part, on the maternal genotype. Neonates born to AhR-null females had increased heart weights regardless of the neonatal genotype, an outcome also observed in gestational diabetes. The cardiac hypertrophy markers, beta-myosin heavy chain and atrial natriuretic factor, and the cardiac proliferative index were increased in AhR-null embryos, indicating that the cardiac enlargement is associated with myocyte hypertrophy and hyperplasia, which begin prior to birth. Importantly, two- to three-month-old pregnant and seven-month-old nonpregnant females, but not nonpregnant three-month-old AhR-null females had significantly decreased fasting plasma insulin levels and a reduced ability to respond to exogenous insulin compared to controls. Despite these alterations in insulin regulation and responsiveness, pregnant AhR females did not have abnormal glucose tolerance tests and did not develop hyperglycemia, classic characteristics of gestational diabetes. However, twenty-three percent of seven-month-old AhR-null females did have altered glucose tolerance tests, but did not show hyperglycemia or increased hemoglobin A1C concentration under normal feeding conditions. While the ultimate cause of the neonatal phenotype remains unclear, these studies establish that the AhR is required for normal insulin regulation in pregnant and older mice and for cardiac development in embryonic mice.

Arabidopsis functional genomics resources now make the isolation of knockout mutants in any gene of choice both realistic and increasingly straightforward. Coupled with the completion of the genome sequence, this reverse genetics approach provides a platform facilitating dramatic progress in our understanding of fundamental aspects of plant metabolism. Recent experience shows that knockouts of genes encoding enzymes of primary metabolism can produce mutants with clear and sometimes unexpected phenotypes. They can provide new information about old pathways. Specific functions for individual members of multigene families can be revealed. Knockouts of enzymes of undefined function can lead to the discovery of those functions, and the analysis of enzymes which have previously never been studied at the biochemical level offers the potential to reveal new pathways of plant metabolism. Furthermore, the mutants isolated provide the starting point for genetic modification experiments to determine exactly how metabolism fuels growth and development, so providing a rational basis for the future modification of plant productivity.

Rp1 is a complex rust resistance locus of maize. The HRp1-D haplotype is composed of Rp1-D and eight paralogues, seven of which also code for predicted nucleotide binding site-leucine rich repeat (NBS-LRR) proteins similar to the Rp1-D gene. The paralogues are polymorphic (DNA identities 91-97%), especially in the C-terminal LRR domain. The remaining family member encodes a truncated protein that has no LRR domain. Seven of the nine family members, including the truncated gene, are transcribed. Sequence comparisons between paralogues provide evidence for past recombination events between paralogues and diversifying selection, particularly in the C-terminal half of the LRR domain. Variants selected for complete or partial loss of Rp1-D resistance can be explained by unequal crossing over that occurred mostly within coding regions. The Rp1-D gene is altered or lost in all variants, the recombination breakpoints occur throughout the genes, and most recombinant events (9/14 examined) involved the same untranscribed paralogue with the Rp1-D gene. One recombinant with a complete LRR from Rp1-D, but the amino-terminal portion from another homologue, conferred the Rp1-D specificity but with a reduced level of resistance.

Few target epitopes have been described for human CD8 T lymphocytes in antigens of Mycobacterium tuberculosis. By use of a reverse immunogenetics approach, 23 motif-bearing peptides of the Ag85 complex were tested for binding to HLA-B*35, one of the common B-types in West Africa. Three 9-mer peptides bound with high affinity to HLA-B*3501 and displayed low dissociation rates of peptide-major histocompatibility complexes (MHCs). IC(50) and half-life values of peptide-MHC class I complexes were in the same range as reported earlier for other immunogenic peptides. Immune responses against peptide Ag85C (aa 204-212) WPTLIGLAM were characterized in detail. Peptide-stimulated effector cells were able to kill macrophages infected with M. tuberculosis or bacille Calmette-Guérin. Peptide-specific CD8 T cells could be visualized by using HLA-B*3501 tetramers and were shown to produce interferon-gamma and tumor necrosis factor-alpha. Together with other published epitopes, these peptides can be used to study more closely the role of CD8 T cells in mycobacterial infection and tuberculosis.

Postmenopausal women and women who use injectable, progestin-based contraceptives are at increased risk of human immunodeficiency virus (HIV) infection, suggesting that progesterone and estrogen affect HIV-1 vaginal transmission. To evaluate the individual roles of these sex hormones in vaginal transmission, ovariectomized female macaques were treated with either progesterone or estrogen followed by intravaginal inoculation with SIVmac. All 6 untreated control macaques and 5 (83%) of 6 progesterone-treated animals became infected following intravaginal SIV inoculation. Conversely, none of 6 estrogen-treated macaques was infected. Vaginal subepithelial inoculation of estrogen-treated animals resulted in infection, which shows that the block occurred at the vaginal epithelium and/or lumen. These data suggest that estrogen-deficient women are at increased risk of HIV infection, because their vaginal microenvironments are rendered more susceptible. Moreover, topical vaginal estrogen therapy may be an effective means of reducing HIV vaginal transmission in these high-risk groups.

Motivational interviewing offers health care professionals a potentially effective strategy for increasing a patient's readiness to change health behaviors. Recently, elements of motivational interviewing and the stages of change model have been simplified and adapted for use with patients in brief clinical encounters. This paper describes in detail a brief motivational intervention model to improve and renew dietary adherence with adolescents in the Dietary Intervention Study in Children (DISC). DISC is a randomized, multi-center clinical trial assessing the efficacy and safety of lowering dietary fat to decrease low-density lipoprotein cholesterol in high-risk children. In the first 3 years of follow-up covering ages 8-13, intervention participants (n = 334) were exposed to a family-based group intervention approach to change dietary choices. To address adherence and retention obstacles as participants moved into adolescence (age 13-17), an individual-level motivational intervention was implemented. The DISC motivational intervention integrates several intervention models: stages of change, motivational interviewing, brief negotiation and behavioral self-management. A preliminary test of the intervention model suggests that it was acceptable to the participants, popular with interventionists and appeared to be an age-appropriate shift from a family-based intervention model.

Extended exposure to weightlessness results in bone loss. However, little information exists as to the precise nature or time course of this bone loss. Bone resorption results in the release of collagen breakdown products, including N-telopeptide and the pyridinium (PYD) cross-links, pyridinoline and deoxypyridinoline. Urinary pyridinoline and deoxypyridinoline are known to increase during bed rest. We assessed excretion of PYD cross-links and N-telopeptide before, during, and after long (28-day, 59-day, and 84-day) Skylab missions, as well as during short (14-day) and long (119-day) bed-rest studies. During space flight, the urinary cross-link excretion level was twice those observed before flight. Urinary excretion levels of the collagen breakdown products were also 40-50% higher, during short and long bed rest, than before. These results clearly show that the changes in bone metabolism associated with space flight involve increased resorption. The rate of response (i.e. within days to weeks) suggests that alterations in bone metabolism are an early effect of weightlessness. These studies are important for a better understanding of bone metabolism in space crews and in those who are bedridden.

This study was designed to validate the utility of a commercial portable clinical blood analyzer (PCBA) in ground-based studies and on the space shuttle. Ionized calcium, pH, electrolytes, glucose, and hematocrit were determined. Results agreed well with those from traditional laboratory methods, and the PCBA demonstrated good between-day precision for all analytes. In-flight analysis of control samples revealed differences in one analyte (sodium). There were few changes in crew members' results during flight, and these were expected. Potassium increased in flight compared with before flight, and potassium, pH, and hematocrit decreased after flight. Ionized calcium was decreased in flight and on landing day. Changes during flight were likely related to sample collection technique. Postflight changes likely reflected the fluid redistribution that occurs after exposure to weightlessness. These data confirm that the PCBA is a reliable instrument for most analytes, and can provide important medical data in remote locations, such as orbiting spacecraft.

A randomized trial was conducted to compare amphotericin B bladder irrigation (AmBBI) with oral fluconazole in terms of efficacy and safety in the treatment of candidal funguria. Fifty-three patients with two consecutive positive funal cultures of urine were randomized to undergo AmBBI (50 mg/L over 24 hours or 50 mg/L for 7 days) or to receive fluconazole (200 mg/d for 7 days). Urinary catheters were changed upon entry into the study and following therapy. Blood and urine specimens were obtained throughout the study. Candida albicans was the species isolated most frequently from urine cultures. Eradication rates for funguria at 24 hours and 5-9 days after therapy were 82.4% and 75%, respectively, with the 7-day AmBBI regimen; and 83.3% and 76.9%, respectively, with fluconazole. There were no differences in the posttherapy eradication rates between the regimens at 24 hours (P = .597) and at 5-9 days (P = .66). Candida glabrata was the predominant organism recovered from patients in the fluconazole group 5-9 days after the completion of therapy. Adverse events were limited to bladder fullness in a patient who underwent AmBBI and hypoglycemia in a patient who received concomitant therapy with fluconazole and glyburide. AmBBI (once or for 7 days) and fluconazole appear to be equally efficacious in the treatment of candidal funguria.

A prototypic hammerhead ribozyme has three helices that surround an asymmetrical central core loop. We have mutagenized a hammerhead type ribozyme. In agreement with previous studies, progressive removal of stem-loop II from a three stemmed ribozyme showed that this region is not absolutely critical for catalysis. However, complete elimination of stem II and its loop did reduce, but did not eliminate, function. In a stem-loop II-deleted ribozyme, activity was best preserved when a purine, preferably a G, was present at position 10.1. This G contributed to catalysis irregardless of its role as either one part of a canonical pair with a C residue at 11.1 or a lone nucleotide with C (11.1) deleted. Computational methods using lattices generated 87 million three-dimensional chain forms for a stem-loop II-deleted RNA complex that preserved one potential G.C base pair at positions 10.1 and 11.1. This exhaustive set of chain forms included one major class of structures with G(10.1) being spatially proximal to the GUCX cleavage site of the substrate strand. Strong correlations were observed between colinear arrangement of stems I and III, constraints of base-pairing in the central core loop, and one particular placement of G(10.1) relative to the cleavage site. Our calculations of a stem-loop II-deleted ribozyme indicate that without needing to invoke any other constraints, the inherent asymmetry in the lengths of the two loop strands (3 nt in one and 7 nt in the other) that compose the core and flank G10.1-C11.1 stipulated strongly this particular G placement. This suggests that the hammerhead ribozyme maintains an asymmetry in its internal loop for a necessary structure/function reason.

Gonotrophic-age structure of a population of Aedes provocans (Walker) and nectar sources used by adults were studied for 2 yr at a field site near Belleville, Ontario, Canada. Females emerged during a short period, and aging of the population was highly synchronous. Complete parity of the population was achieved within about 17 d in 1978 and 27 d in 1979. Some females completed as many as four gonotrophic cycles. This synchronous pattern of population aging is compared with patterns in other species of snow-melt Aedes, which typically age much more gradually. The pattern of synchronous aging permitted estimation of daily mortality rates from an index of population size derived from human-bait catches; peaks in the biting index were related to each gonotrophic cycle in the population. Nectar sources for adults were ranked according to abundance and the extent to which they were used by Ae. provocans, permitting a coarse, semiquantitative estimate of preferences. Ae. provocans obtained nectar from the extrafloral nectaries of one species and the floral nectaries of 19 species of angiosperms. Shrubs and trees, especially of the Rosaceae (primarily species of Prunus), were particularly important as nectar sources and bloomed concurrently with the appearance of nulliparous females. Sharp declines in the population of Ae. provocans were associated with the cessation of blooming of these plant species. It is hypothesized that the highly synchronous pattern of gonotrophic aging in Ae. provocans was attributable, in part, to the ready availability of nectar sources and bloodmeal hosts near breeding sites.

Expression of the malate synthase (MS) gene is activated in cotyledons of cucumber seedlings during postgerminative growth and then repressed as the cotyledons become photosynthetic. MS gene expression is subsequently reactivated in the cotyledons as they senesce a few weeks later. In situ hybridization revealed that MS RNA is distributed throughout the organ during postgerminative growth and senescence, showing that the same cells express the gene at different stages of development. MS RNA also appears in senescing leaves and petals of cucumber plants. In addition, we found that MS RNA appears in mature expanded leaves and roots when they are removed from the plant and incubated in darkness for several days, thus providing a potential experimental system for the manipulation of MS gene expression. Leaves from transgenic Nicotiana plumbaginifolia containing the cucumber MS promoter fused to the [beta]-glucuronidase (GUS) reporter gene accumulated GUS activity when detached, demonstrating an activation of transcription from the MS promoter following leaf excision. These results are discussed in terms of the metabolic regulation of MS gene expression.

Reference strains of Escherichia coli (ampicillin-susceptible and -resistant ATCC strains, and known TEM-1 and TEM-2 beta-lactamase producers) were tested in vitro and in the in-vivo mouse thigh infection model against four beta-lactamase inhibitor compounds (BICs: amoxycillin/clavulanic acid, ampicillin/sulbactam, ticarcillin/clavulanic acid, and piperacillin/tazobactam), selected cephalosporins, and imipenem. The ATCC strains (ampicillin-susceptible and -resistant) were susceptible to the BICs in disc and MIC tests. Three or more logs of killing were observed at the NCCLS breakpoint concentrations. However, the TEM-1 and TEM-2 producers were resistant in disc tests to ampicillin/sulbactam and amoxycillin/clavulanic acid, and showed intermediate susceptibility to ticarcillin/clavulanic acid. MICs were at or near the breakpoint, but bactericidal activity was only noted at the probable breakpoint concentration of piperacillin/tazobactam. Cefoxitin, cefotaxime, cefpirome and imipenem, but not cephalothin, showed greater bactericidal activity and lower MICs for the TEM-producing strains than the BICs. The viable count of the TEM-1 producer was not reduced in the mouse thigh model by ampicillin/sulbactam or amoxycillin/clavulanic acid, but cefpirome and cefotaxime reduced the viable count by approximately three logs. There was a 50% mortality rate in mice receiving the two BICs. The ampicillin-susceptible ATCC strain of E. coli was killed to a similar degree by all agents tested. Overall, the BICs appeared inferior, in both in-vivo and in-vitro tests to selected cephalosporins and imipenem when tested against reference strains of E. coli producing TEM-1 or TEM-2 beta-lactamase. The large inoculum effect and poor bactericidal activity observed with the BICs suggest they could be less effective in certain clinical situations.

More than 20 million non-US residents visit the United States each year. Data on deaths in this country among these non-US residents were obtained from US vital records. These data showed that from 1979 through 1984, 17,988 deaths occurred. Cardiovascular disease (International Classification of Diseases [ICD-9] 390-459) was the leading cause of death among non-residents. Injuries (ICD-9 E800-E999) ranked second as a cause of death and accounted for 23% of the deaths (4078). More than half of these injury deaths occurred among people aged 15-34 years and 79% of the people who died from injuries were males. The most frequent causes of injury deaths were motor vehicle traffic crashes (37%), drownings (15%), and homicides (11%). Although general patterns of injury mortality among non-US residents and US residents were similar, there were differences in the proportion of deaths due to homicides, drownings, and falls. Prevention efforts targeted to the major causes of injury mortality in the US will affect both US and non-US residents.

During the first twelve months after ciprofloxacin was introduced for clinical use at our institution, 65 new patients were found to be either infected or colonized by methicillin-resistant Staphylococcus aureus (MRSA) which were also ciprofloxacin resistant (CR-MRSA). Only 18 of these patients (28%) had been previously exposed to this antibiotic. Nine (50%) of the 18 patients had received ciprofloxacin for treatment for a pathogen other than MRSA. Although the initial cases of colonization or infection with CR-MRSA can be directly related to ciprofloxacin use, many of the subsequent cases of colonization and infection were not the consequence of ciprofloxacin therapy but rather hospital transmission of existing CR-MRSA.

This study explored the use of D-lactic acid as a marker for bacterial infections. D-Lactic was produced by frequently encountered human bacterial pathogens under anaerobic growth conditions; Bacteroides fragilis produced the largest amount. Orally administered D-lactic acid was absorbed from the intestines of rats and later found in measurable quantities in the blood and urine. Eunephric and anephric rats that received D-lactic acid intravenously showed similar quantities of this metabolite in the blood. These quantities are consistent with the distribution of D-lactic acid to total body water. Isolated liver and lung tissues from rats did not metabolize or produce D-lactic acid. Rats with experimentally induced, sublethal klebsiella peritonitis had D-lactic acidemia of 0.2 mM and 25.6 mM at 0 and 6 hr of infection, respectively. In a normal human, D-lactic acid was detected in the urine and blood after a subcutaneous injection of D-lactic acid, and pharmacokinetics of elimination similar to those of rats were found.

Ciprofloxacin exhibited good in-vitro activity for methicillin-resistant Staphylococcus aureus with a MIC90 of 0.5 mg/l. The postantibiotic effect was 2.16 h. When ciprofloxacin was evaluated in combination studies with an aminoglycoside, none of the strains met the criterion of synergy as defined by FIC or FBC interaction indices of less than or equal to 0.25. However, killing kinetic experiments indicated that the combination of ciprofloxacin was synergistic for two of 12 strains with gentamicin and three of 12 strains with amikacin. Although the inoculum size had no effect on the rate of killing by ciprofloxacin, an increase in turbidity was noted when a high inoculum was tested. This increase in turbidity was due to the swelling of the staphylococci to several times their normal size and the formation of clusters of multicellular, incompletely divided staphylococci. If a high inoculum is used for susceptibility testing, this increase in turbidity could be misinterpreted as bacterial growth and could result in a false report of an elevated MIC.

Rifampicin resistance developed easily in methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus during an overnight incubation in broth containing 0.1 mg/l of rifampicin. Incubation of methicillin-susceptible Staph. aureus and 0.1 mg/l of rifampicin with 1 mg/l of nafcillin reduced the emergence of rifampicin resistance with only 5 of 50 strains (10%) becoming rifampicin-resistant. However, incubation of the methicillin-susceptible or methicillin-resistant strains with 0.1 mg/l of rifampicin and 1 mg/l of vancomycin did not prevent the development of rifampicin resistance. Rifampicin resistance developed in 25 of 50 (50%) of methicillin-susceptible and 32 of 50 (64%) methicillin-resistant Staph. aureus strains tested. These data would suggest that differences exist in the abilities of nafcillin and vancomycin to suppress the development of rifampicin resistance in Staph. aureus (P less than 0.01). Caution should be exercised when the combination of vancomycin and rifampicin is used for infections caused by Staph. aureus and Staph. aureus isolates recovered during therapy should be monitored for the development of rifampicin resistance.

Between June 1, 1983 and August 30, 1984, an epidemic involving 313 cases of hepatitis A occurred in Muskingum County, Ohio. One hundred ninety-seven cases occurred in the city of Zanesville, with 34.7% of cases concentrated in two neighborhoods in the eastern part of the city. Case characteristics were similar to those reported in previous community-wide outbreaks, including a maximum attack rate among 5-9-year-olds and a very low attack rate in adults over 30 years. Case households were larger, and their members were less educated than the mean for households in the city. Forty-eight per cent of the cases reported exposures to other cases which temporally could have been the source of infection. A case-control study failed to show differences in several behavioral factors between case and control households, but did confirm that lower socioeconomic status was a risk factor for the disease. Broad use of immunoglobulin was effective in preventing clinical disease among family contacts, but did not stop the outbreak. This outbreak typifies a genre of hepatitis A epidemic transmitted from person to person in which exact routes of spread are poorly understood and control is difficult. Lower socioeconomic status may be a marker for some unidentified behaviors that promote hepatitis A transmission.

To evaluate the usefulness of plasmid pattern analysis as an epidemiologic tool and to determine the mechanism of resistance to silver sulfadiazine and mafenide acetate, silver sulfadiazine-resistant, mafenide acetate-resistant Enterobacter cloacae isolates from a 1976 outbreak of infections in a burn unit (group I) were analyzed retrospectively. These strains were compared with various E cloacae isolates (groups II-V), including E cloacae isolates from a more recent (1982) burn unit outbreak (group V). Agarose gel electrophoresis (AGE) of DNA isolated from "epidemic" strains of E cloacae revealed a uniform pattern of four plasmid DNA bands, ranging in molecular size from 66 to 2 megadaltons. No such plasmid pattern was seen in silver sulfadiazine-, mafenide acetate-susceptible isolates of E cloacae in groups II, III, and V. Analysis of non-E cloacae coisolates suggested that silver sulfadiazine resistance was associated with the 55-megadalton plasmid. Plasmid pattern analysis easily separated "epidemic" E cloacae isolated in 1976 from those isolated in 1982.

We have isolated and sequenced three cDNA clones for the nuclear-encoded precursor to the small subunit of the chloroplast enzyme, ribulose-1,5-bisphosphate carboxylase of wheat. The nucleotide sequences of these clones are different, indicating that they are probably derived from three different mRNAs. This finding is consistent with the proposal that this polypeptide is encoded by a multigene family in wheat, in support of similar data reported by Broglie et al. (Bio/Technology 1:55-61, 1983). We deduce that the mature small subunit polypeptide is comprised of 128 amino acids and that its precursor contains an N-terminal transit peptide sequence. The sequences of both the mature small subunit and its transit peptide differ at several positions from those determined by Broglie et al, (1983) from a different wheat cultivar. Different wheat cultivars might therefore contain different small subunit polypeptides. A comparison of nucleotide and amino acid sequences of the small subunit from wheat, pea, soybean and spinach shows that these sequences are not highly conserved, particularly between monocotyledon and dicotyledon species.

Patients with acquired immune deficiency syndrome (AIDS) are known to have identifiable host defense deficiencies, especially deficiencies in cell-mediated immunity. They are at increased risk for developing infections of the bloodstream caused by Cryptococcus neoformans and Salmonella species. However, bacteremias caused by other enteric gram-negative rods and Pseudomonas aeruginosa are found less frequently in patients with AIDS than in patients without AIDS (P less than 0.001 and P less than 0.01, respectively). The findings of specific organisms in blood is consistent with the known types of host defense deficiencies in these patients.

The characteristics of the normal adult thymus in both sexes were determined in 50 cases of accidental death by a simplified quantitative histologic technic. A table of normal values derived from these findings was used for making comparisons with thymus from autopsies of 50 additional patients suffering terminal illness. It was observed that thymic changes considered to be part of physiologic involution occurred earlier and were more advanced at a given age in males than in females. These changes included disappearance of septae, diminished demarcation between cortex and medulla, and a decreased number of Hassall's corpuscles with an increase in their size. Changes ascribed to disease included accelerated involution of the thymus accompanied by loss of septae, smaller lobules, increased adipose tissue and fusiform cells, a reduced number of lymphocytes and Hassall's corpuscles and a relative increase in the number of cystic corpuscles. No lymphoid follicles were observed. Changes were not identical in all disease conditions. In neoplasia, the limit between the cortex and medulla was preserved; in immune diseases, the epithelial nests of the medulla were increased.

The frequency with which resistant variants could be found in Pseudomonas aeruginosa ATCC 27853 during growth in media with and without antibiotics was determined for ticarcillin, piperacillin, cefotaxime, latamoxef, cefoperazone, ceftriaxone, ceftazidime, aztreonam and imipenem. The resistance frequency was highest for ceftriaxone, cefotaxime, cefoperazone and piperacillin (up to 2 X 10(-4)) and lowest for ticarcillin, latamoxef, ceftazidime, aztreonam and imipenem (less than 10(-8)). The resistant variants showed cross-resistance to all of the beta-lactam antibiotics tested with the exception of imipenem. The MIC profiles of all variants were similar regardless of which antibiotic the cultures had been exposed to previously. Although all resistant variants produced and excreted cephalosporinases, increased resistance was demonstrated to both cephalosporinase-susceptible and cephalosporinase-stable beta-lactam antibiotics.

With cefpirome (HR 810) the MICs for both methicillin-resistant Staphylococcus aureus (MRSA) and for Streptococcus faecalis were 8.0 mg/l. At 4 x MIC, cefpirome killed MRSA as rapidly as did vancomycin while for enterococci, cefpirome, vancomycin or ampicillin alone were not bactericidal. However, all agents were bactericidal when combined with 2 mg/l of gentamicin, although gentamicin combined with cefpirome showed a smaller decrease in cfu/ml than the combination with ampicillin or vancomycin. A mouse thigh infection model was developed in which the thigh muscle was infected with bacteria and either no therapy or concurrent antibiotic therapy was initiated. On the subsequent day, the entire thigh muscle was quantitatively cultured. In this model, the numbers of enterococci at the infection site at 24 h were reduced by 2.1 logs with no treatment, 2.6 with cefpirome (25 mg/kg/day), 2.8 with ampicillin (150 mg/kg/day), and 2.7 with vancomycin (25 mg/kg/day). For MRSA the reductions were 1.1 logs with no therapy, 2.8 with vancomycin, and 3.0 with cefpirome. The apparent enhanced in-vivo activity of cefpirome for MRSA argues for further evaluation of this antibiotic for treatment of MRSA and other Gram-positive cocci, including enterococci.