Septic arthritis in an in vivo murine model induced by Staphylococcus aureus : a comparison between actions of the haemolysin toxin and the effects of the host immune response.

AIMS: Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal's immune response to infection. METHODS: Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 107 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling. RESULTS: Chondrocyte death was greater with 8325-4 (96.2% (SD 5.5%); p < 0.001) than DU1090 (28.9% (SD 16.0%); p = 0.009) and both were higher than controls (3.8% (SD 1.2%)). Histology revealed cartilage/bone damage with 8325-4 or DU1090 compared to controls (p = 0.010). Both infected groups lost weight (p = 0.006 for both) and experienced limb swelling (p = 0.043 and p = 0.018, respectively). Joints inoculated with bacteria showed significant alterations in gait cycle with a decreased stance phase, increased swing phase, and a corresponding decrease in swing speed. CONCLUSION: Murine joints inoculated with Hla-producing 8325-4 experienced significantly more chondrocyte death than those with DU1090, which lack the toxin. This was despite similar immune responses, indicating that Hla was the major cause of chondrocyte death. Hla-deficient DU1090 also elevated chondrocyte death compared to controls, suggesting a smaller additional deleterious role of the immune system on cartilage.Cite this article: Bone Joint Res 2022;11(9):669-678.

A systematic review of factors affecting medication adherence among patients with osteoporosis.

The aim of this review was to identify factors that influence patients' adherence to anti-osteoporotic therapy. Factors identified that were associated with poorer medication adherence included polypharmacy, older age, and misconceptions about osteoporosis. Physicians need to be aware of these factors so as to optimize therapeutic outcomes for patients. INTRODUCTION: To identify factors that influence patients' adherence to anti-osteoporotic therapy. METHODS: A systematic review of literature was performed for articles published up till January 2018 using PubMed®, PsychINFO®, Embase®, and CINAHL®. Peer-reviewed articles which examined factors associated with anti-osteoporotic medication adherence were included. Classes of anti-osteoporotic therapy included bisphosphonates, parathyroid hormone-related analogue, denosumab, selective estrogen receptor modulators, estrogen/progestin therapy, calcitonin, and strontium ranelate. Meta-analyses, case reports/series, and other systematic reviews were excluded. Identified factors were classified using the World Health Organization's five dimensions of medication adherence (condition, patient, therapy, health-system, and socio-economic domains). RESULTS: Of 2404 articles reviewed, 124 relevant articles were identified. The prevalence of medication adherence ranged from 12.9 to 95.4%. Twenty-four factors with 139 sub-factors were identified. Bisphosphonates were the most well-studied class of medication (n = 59, 48%). Condition-related factors that were associated with poorer medication adherence included polypharmacy, and history of falls was associated with higher medication adherence. Patient-related factors which were associated with poorer medication adherence included older age and misconceptions about osteoporosis while therapy-related factors included higher dosing frequency and medication side effects. Health system-based factors associated with poorer medication adherence included care under different medical specialties and lack of patient education. Socio-economic-related factors associated with poorer medication adherence included current smoker and lack of medical insurance coverage. CONCLUSION: This review identified factors associated with poor medication adherence among osteoporotic patients. To optimize therapeutic outcomes for patients, clinicians need to be aware of the complexity of factors affecting medication adherence.

Return to sport following tibial plateau fractures: A systematic review.

AIM: To systemically review all studies reporting return to sport following tibial plateau fracture, in order to provide information on return rates and times to sport, and to assess variations in sporting outcome for different treatment methods. METHODS: A systematic search of CINAHAL, Cochrane, EMBASE, Google Scholar, MEDLINE, PEDro, Scopus, SPORTDiscus and Web of Science was performed in January 2017 using the keywords "tibial", "plateau", "fractures", "knee", "athletes", "sports", "non-operative", "conservative", "operative", "return to sport". All studies which recorded return rates and times to sport following tibial plateau fractures were included. RESULTS: Twenty-seven studies were included: 1 was a randomised controlled trial, 7 were prospective cohort studies, 16 were retrospective cohort studies, 3 were case series. One study reported on the outcome of conservative management (n = 3); 27 reported on the outcome of surgical management (n = 917). Nine studies reported on Open Reduction Internal Fixation (ORIF) (n = 193), 11 on Arthroscopic-Assisted Reduction Internal Fixation (ARIF) (n = 253) and 7 on Frame-Assisted Fixation (FRAME) (n = 262). All studies recorded "return to sport" rates. Only one study recorded a "return to sport" time. The return rate to sport for the total cohort was 70%. For the conservatively-managed fractures, the return rate was 100%. For the surgically-managed fractures, the return rate was 70%. For fractures managed with ORIF, the return rate was 60%. For fractures managed with ARIF, the return rate was 83%. For fractures managed with FRAME was 52%. The return rate for ARIF was found to be significantly greater than that for ORIF (OR 3.22, 95%CI: 2.09-4.97, P < 0.001) and for FRAME (OR 4.33, 95%CI: 2.89-6.50, P < 0.001). No difference was found between the return rates for ORIF and FRAME (OR 1.35, 95%CI: 0.92-1.96, P = 0.122). The recorded return time was 6.9 mo (median), from a study reporting on ORIF. CONCLUSION: Return rates to sport for tibial plateau fractures remain limited compared to other fractures. ARIF provides the best return rates. There is limited data regarding return times to sport. Further research is required to determine return times to sport, and to improve return rates to sport, through treatment and rehabilitation optimisation.

Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001).

PURPOSE: Vatalanib (PTK 787/ZK22584) is an oral poly-tyrosine kinase inhibitor with strong affinity for platelet-derived growth factor and vascular endothelial growth factor (VEGF) receptors. We conducted an open-label, phase II multicenter therapeutic trial investigating the efficacy and tolerability of vatalanib in patients with metastatic or advanced pancreatic cancer who failed first-line gemcitabine-based therapy. METHODS: Vatalanib treatment consisted of a twice daily oral dosing using a "ramp-up schedule," beginning with 250 mg bid during week 1,500 mg bid during week 2, and 750 mg bid on week three and thereafter. The primary objective of this study was to evaluate the 6-month survival rate. RESULTS: Sixty-seven patients were enrolled. The median age was 64, and 66% (N = 43) had only one prior regimen. Common grade 3/4 adverse events included hypertension (20%; N = 13), fatigue (17%; N = 11), abdominal pain (17%; N = 11), and elevated alkaline phosphatase (15%; N = 10). Among the 65 evaluable patients, the 6-month survival rate was 29% (95% CI 18-41%) and the median progression-free survival was 2 months. Fifteen patients survived 6 months or more. Two patients had objective partial responses, and 28% of patients had stable disease. Changes in biomarkers including soluble VEGF and vascular endothelial growth factor receptor did not correlate with response to drug. CONCLUSION: Vatalanib was well tolerated as a second-line therapy and resulted in favorable 6-month survival rate in patients with metastatic pancreatic cancer, compared with historic controls.

Post-traumatic stress disorder, child abuse history, birthweight and gestational age: a prospective cohort study.

OBJECTIVE: To determine the extent to which prenatal post-traumatic stress disorder (PTSD) is associated with lower birthweight and shorter gestation, and to explore the effects of childhood maltreatment as the antecedent trauma exposure. DESIGN: Prospective three-cohort study. SETTING: Ann Arbor and Detroit, Michigan, United States. SAMPLE: In all, 839 diverse nulliparas in PTSD-positive (n = 255), trauma-exposed, resilient (n = 307) and non-exposed to trauma (n = 277) cohorts. METHODS: Standardised telephone interview before 28 weeks of gestation to ascertain trauma history, PTSD, depression, substance use, mental health treatment history and sociodemographics, with chart abstraction to obtain chronic condition history, antepartum complications and prenatal care data, as well as outcomes. MAIN OUTCOME MEASURES: Infant birthweight and gestational age per delivery record. RESULTS: Infants born to women with PTSD during pregnancy had a mean birthweight 283 g less than infants of trauma-exposed, resilient women and 221 g less than infants of non-exposed women (F(3,835) = 5.4, P = 0.001). PTSD was also associated with shorter gestation in multivariate models that took childhood abuse history into account. Stratified models indicated that PTSD subsequent to child abuse trauma exposure was most strongly associated with adverse outcomes. PTSD was a stronger predictor than African American race of shorter gestation and a nearly equal predictor of birthweight. Prenatal care was not associated with better outcomes among women abused in childhood. CONCLUSIONS: Abuse-related PTSD may be an additional or alternative explanation for adverse perinatal outcomes associated with low socio-economic status and African American race in the USA. Biological and interventions research is warranted along with replication studies in other nations.

Experience with minimally invasive esophagectomy.

BACKGROUND: Minimally invasive esophagectomy (MIE) is an evolving surgical alternative to traditional open esophagectomy. Despite considerable technical challenges, it was hypothesized that MIE could be performed effectively by surgeons experienced in open esophageal resection and advanced laparoscopic surgery. The authors report their experience with 25 patients who underwent MIE for esophageal disease. METHODS: A multidisciplinary esophageal cancer team evaluated all the patients enrolled in this institutional review board-approved retrospective review study. Over an 18-month period, 25 consecutive patients (22 men and 3 women; mean age, 62 years; range, 48-77 years) with resectable esophageal cancer underwent MIE. Six patients were treated with neoadjuvant chemoradiotherapy. The preoperative diagnoses were adenocarcinoma (64%, n = 16), high-grade dysplasia (20%, n = 5), and squamous cell cancer (16%, n = 4). The outcomes evaluated included operative course, hospital and intensive care unit lengths of stay, pathologic stage, morbidity, and mortality. RESULTS: Two patients required conversion to open esophagectomy. Operative mortality was 4% (n = 1). The mean operative time was 350 min (range, 300-480), and the average blood loss was 200 ml. The patients remained ventilated for a median of 12 h, and the median intensive care unit utilization was 1 day. The median hospital length of stay was 9 days (range, 6-33 days). Major complications occurred in 32% of the patients. The anastomotic leak rate was 12%. Minor pulmonary complications occurred in 32% and atrial fibrillation in 16% of the patients. An anastomotic stricture developed in 24% of all the patients. One patient showed a positive proximal margin in the final pathology results. CONCLUSIONS: Minimally invasive esophagectomy is a technically challenging procedure that can be performed safely at the Virginia Piper Cancer Institute. Optimal results require appropriate patient selection and a multidisciplinary team experienced in the management of esophageal cancer.

Ampicillin/penicillin-binding protein interactions as a model drug-target system to optimize affinity pull-down and mass spectrometric strategies for target and pathway identification.

The identification and validation of the targets of active compounds identified in cell-based assays is an important step in preclinical drug development. New analytical approaches that combine drug affinity pull-down assays with mass spectrometry (MS) could lead to the identification of new targets and druggable pathways. In this work, we investigate a drug-target system consisting of ampicillin- and penicillin-binding proteins (PBPs) to evaluate and compare different amino-reactive resins for the immobilization of the affinity compound and mass spectrometric methods to identify proteins from drug affinity pull-down assays. First, ampicillin was immobilized onto various amino-reactive resins, which were compared in the ampicillin-PBP model with respect to their nonspecific binding of proteins from an Escherichia coli membrane extract. Dynal M-270 magnetic beads were chosen to further study the system as a model for capturing and identifying the targets of ampicillin, PBPs that were specifically and covalently bound to the immobilized ampicillin. The PBPs were identified, after in situ digestion of proteins bound to ampicillin directly on the beads, by using either one-dimensional (1-D) or two-dimensional (2-D) liquid chromatography (LC) separation techniques followed by tandem mass spectrometry (MS/MS) analysis. Alternatively, an elution with N-lauroylsarcosine (sarcosyl) from the ampicillin beads followed by in situ digestion and 2-D LC-MS/MS analysis identified proteins potentially interacting noncovalently with the PBPs or the ampicillin. The in situ approach required only little time, resources, and sample for the analysis. The combination of drug affinity pull-down assays with in situ digestion and 2-D LC-MS/MS analysis is a useful tool in obtaining complex information about a primary drug target as well as its protein interactors.

Transducible heat shock protein 20 (HSP20) phosphopeptide alters cytoskeletal dynamics.

Activation of cyclic nucleotide dependent signaling pathways leads to relaxation of smooth muscle, alterations in the cytoskeleton of cultured cells, and increases in the phosphorylation of HSP20. To determine the effects of phosphorylated HSP20 on the actin cytoskeleton, phosphopeptide analogs of HSP20 were synthesized. These peptides contained 1) the amino acid sequence surrounding the phosphorylation site of HSP20, 2) a phosphoserine, and 3) a protein transduction domain. Treatment of Swiss 3T3 cells with phosphopeptide analogs of HSP20 led to loss of actin stress fibers and focal adhesion complexes as demonstrated by immunocytochemistry, interference reflection microscopy, and biochemical quantitation of globular-actin. Treatment with phosphopeptide analogs of HSP20 also led to dephosphorylation of the actin depolymerizing protein cofilin. Pull-down assays demonstrated that 14-3-3 proteins associated with phosphopeptide analogs of HSP20 (but not peptide analogs in which the serine was not phosphorylated). The binding of 14-3-3 protein to phosphopeptide analogs of HSP20 prevented the association of cofilin with 14-3-3. These data suggest that HSP20 may modulate actin cytoskeletal dynamics by competing with the actin depolymerizing protein cofilin for binding to the scaffolding protein 14-3-3. Interestingly, the entire protein was not needed for this effect, suggesting that the association is modulated by phosphopeptide motifs of HSP20. These data also suggest the possibility that cyclic nucleotide dependent relaxation of smooth muscle may be mediated by a thin filament (actin) regulatory process. Finally, these data suggest that protein transduction can be used as a tool to elucidate the specific function of peptide motifs of proteins.

Minimal toxicity of stabilized compacted DNA nanoparticles in the murine lung.

Nanoparticles containing DNA compacted with poly-l-lysine modified on an N-terminal cysteine with polyethylene glycol can effectively transfect cells of the airway epithelium when applied by the luminal route. To evaluate the toxicity of these nanoparticles, we administered 10 and 100 microg DNA compacted into nanoparticles suspended in normal saline by the intranasal route to mice and determined the pulmonary and systemic responses to this challenge, compared to administration of saline alone, and in some experiments, compared to administration of naked DNA, Escherichia coli genomic DNA, or lipofectin-complexed naked DNA. There was no systemic response to either dose of nanoparticles in serum chemistries, hematologic parameters, serum complement, IL-6, or MIP-2 levels or in the activity, growth, and grooming of the mice. Nanoparticles containing 10 microg DNA induced responses comparable to saline in all measures, including BAL cell counts and differentials and cytokine levels and histology. However, mice dosed with 100 microg DNA in nanoparticles had modest increases in BAL neutrophils 48 and 72 h after dosing, modest increases in BAL IL-6 and KC beginning 24 and 48 h, respectively, after dosing, and, on histology of the lung, a trace to 1+ mononuclear cell infiltrates about the pulmonary veins at 48 h, which were markedly reduced by 10 days and gone by 28 days after dosing. BAL neutrophil and cytokine responses were no greater than those entrained by naked DNA for up to 24 h. However, compared to administration of only 10 microg E. coli genomic DNA, the response to compacted DNA was much less. A low dose of lipofectin-complexed DNA (5 microg DNA) induced the same response as 20-fold higher doses of DNA nanoparticles. These data indicate that DNA nanoparticles have no measurable toxic effect at a dose of 10 microg and a very modest effect, which is not limiting, at a dose of 100 microg, which gives maximal gene expression. This favorable toxicity profile encourages development of stabilized compacted DNA for airway administration.

A new species and three new combinations in Cyphellophora, with a note on the taxonomic affinities of the genus, and its relation to Kumbhamaya and Pseudomicrodochium.

Cyphellophora guyanensis sp. nov., isolated from leaf litter in French Guyana, is described and illustrated. This fungus is characterized by ampulliform to flask-shaped phialides, with a conspicuous, funnel-shaped collarette, and nearly straight to falcate or slightly sigmoid, (2-)3-6 septate conidia. Cyphellophora guyanensis is compared to the other Cyphellophora species, and the latter genus is compared to Kumbhamaya and Pseudomicrodochium. Kumbhamaya indica, P. fusarioides, and P. suttonii are transferred to Cyphellophora. The phylogenetic relationships of Cyphellophora with other genera of ascomycetes and related mitosporic fungi were inferred from the analysis of the partial nuclear ribosomal DNA SSU sequences data. The analysis supports a placement of Cyphellophora in Chaetothyriales, and probably in the Herpotrichiellaceae

Expression screen by enzyme-linked immunofiltration assay designed for high-throughput purification of affinity-tagged proteins.

High-throughput purification of affinity-tagged fusion proteins is currently one of the fastest developing areas of molecular proteomics. A prerequisite for success in protein purification is sufficient soluble protein expression of the target protein in a heterologous host. Hence, a fast and quantitative evaluation of the soluble-protein levels in an expression system is one of the key steps in the entire process. Here we describe a high-throughput expression screen for affinity-tagged fusion proteins based on an enzyme linked immunofiltration assay (ELIFA). An aliquot of a crude Escherichia coli extract containing the analyte, an affinity-tagged protein, is adsorbed onto the membrane. Subsequent binding of specific antibodies followed by binding of a secondary antibody horseradish peroxidase (HRP) complex then allows quantitative evaluation of the analyte using tetramethylbenzidine as the substrate for HRP. The method is accurate and quantitative, as shown by comparison with results from western blotting and an enzymatic glutathione S-transferase (GST) assay. Furthermore, it is a far more rapid assay and less cumbersome than western blotting, lending itself more readily to high-throughput analysis. It can be used at the expression level (cell lysates) or during the subsequent purification steps to monitor yield of specific protein.

The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: implications for chronic studies.

A study was undertaken to determine the effects of incremental levels of dietary restriction (DR) in rats. Survival, growth, reproductive, and dietary intake (DI) variables were monitored in a chronic study in which male Sprague Dawley (SD) rats (NCTR colony) were fed their ration ad libitum (AL), or DR. The main objectives were to determine if low levels of DR could be used to increase the survival rate of SD rats in the chronic bioassay, and to identify the survival characteristics of a long-lived SD rat strain (NCTR colony). The average life span of AL rats was 115 months. At 104 weeks on study (110 weeks of age), the survival rate for the AL and 10%, 25%, and 40% DR groups was 63.4, 87.5, 87.5, and 97.5%, respectively. The largest increase in survival (24.1%) occurred between AL and 10% DR, indicating that very low levels of DR have a significant effect on survival. Whole-body, liver, prostate, and epididymis weights and body length were decreased by DR, whereas brain weight, testicular weight, and skull length were not altered by DR. Rats from the NCTR colony were found to be ideal for chronic studies because they are much longer-lived than other SD stocks. Although the 104-week survival rate for these SD, non-obese AL rats exceeds the FDA's "Redbook" survival guideline (> 50%) for chronic bioassays, the use of DR is advocated because it reduces individual variability in body weight.

Posttraumatic stress disorder and pregnancy complications.

OBJECTIVE: To assess the associations between specific pregnancy complications and posttraumatic stress disorder based on neurobiologic and behavioral characteristics, using Michigan Medicaid claims data from 1994-1996. METHODS: Two thousand, two hundred nineteen female recipients of Michigan Medicaid who were of childbearing age had posttraumatic stress disorder on the basis of International Classification of Diseases, 9th Revision (ICD-9) codes. Twenty percent (n = 455) of those recipients and 30% of randomly selected comparison women with no mental health diagnostic codes (n = 638; P <.001) had ICD-9 diagnostic codes for pregnancy complications. We used multiple logistic regression to investigate associations between specific pregnancy complications and posttraumatic stress disorder, controlling for demographic and psychosocial variables. Obstetric complications were hypothesized based on high-risk behaviors and neurobiologic alterations in stress axis function in posttraumatic stress disorder. RESULTS: After controlling for demographic and psychosocial factors, women with posttraumatic stress disorder had higher odds ratios (ORs) for ectopic pregnancy (OR 1.7, 95% confidence interval [CI] 1.1, 2.8), spontaneous abortion (OR 1.9, 95% CI 1.3, 2.9), hyperemesis (OR 3.9, 95% CI 2.0, 7.4), preterm contractions (OR 1.4, 95% CI 1.1, 1.9), and excessive fetal growth (OR 1.5, 95% CI 1.0, 2.2). Hypothesized labor differences were not confirmed and no differences were found for complications not thought to be related to traumatic stress. CONCLUSIONS: Pregnant women with posttraumatic stress disorder might be at higher risk for certain conditions, and assessment and treatment for undiagnosed posttraumatic stress might be warranted for women with those obstetric complications. Prospective studies are needed to confirm present findings and to determine potential biologic mechanisms. Treatment of traumatic stress symptoms might improve pregnancy morbidity and maternal mental health.

Clinician-specific episiotomy rates: impact on perineal outcomes.

Recent, large, randomized, controlled trials of the effects of episiotomy on perineal damage have confirmed that episiotomy is associated with an increased risk of damage to the perineum. Yet episiotomy remains the most common surgical procedure women undergo. This article examines if clinician experience, rather than scientific evidence, forms the basis for continuing this practice. Perineal outcome data are analyzed for 865 low-risk women who were attended at birth by the staff nurse-midwives or faculty obstetricians at a university-based, tertiary-care hospital. Data were collected under routine, nonexperimental conditions such that the circumstances of the labor and the clinician's preferences were allowed to determine management decisions regarding the use of episiotomy or other techniques of perineal management. Multivariate findings indicate that in the absence of episiotomy, rates of perineal integrity were highest among clinicians who usually had the lowest rate of episiotomy use. When an episiotomy was done, rates of third- and fourth-degree extensions were highest among clinicians who used episiotomy most frequently. This finding challenges the idea that clinicians who were very experienced with the use of episiotomy would avoid complications such as extensions. Future research should explore the use of nonsurgical techniques such as those employed by midwives to promote perineal integrity. Then interdisciplinary research and evidence-based education regarding these techniques can occur to improve perineal outcomes for all women.

Physical activity and postpartum well-being.

OBJECTIVE: To describe reported patterns of postpartum physical activity and to identify benefits or risks associated with postpartum physical activity at 6 weeks postpartum. DESIGN: Secondary analysis of longitudinal data collected prenatally and postpartum in a study of obstetric outcomes at a midwestern tertiary-care center and its ambulatory satellite and hospital clinics. PARTICIPANTS: One thousand three women completed a questionnaire at the 6-week postpartum clinic visit. Mean age was 29.7 years, and mean education level was 15.3 years. VARIABLES OF INTEREST: Participation in vigorous exercise, change in postpartum activity level, postpartum weight retention, infant feeding method, maternal postpartum adaptation, and participation in activities for fun. RESULTS: Nearly 35% reported doing vigorous exercise with a modal frequency of three times per week. More active women had retained significantly less weight (8.6 lb [3.9 kg]) than their less active counterparts (11.3 lb [5.1 kg]). Vigorous exercisers demonstrated a consistent pattern of better scores on measures of postpartum adaptation and were more likely than nonexercisers to participate in fun activities, such as socializing, hobbies, and entertainment. Breastfeeding was not adversely affected by vigorous exercise. CONCLUSIONS: These exploratory results indicate that physical and psychologic benefits may accrue to postpartum women who are able to exercise vigorously and avoid decreasing their usual level of activity. A prospective randomized test of this relationship is warranted. Although positive outcomes of physical activity have been demonstrated in the population at large, exercise has rarely been an element in postpartum care plans. Nurses who care for women after childbirth should assess women's exercise goals and support them in their desired activities.

Adaptive role of caloric intake on the degenerative disease processes.

Carcinogenicity and aging are characterized by a set of complex endpoints, which appear as a series of molecular events. Many of these events can be modified by caloric intake. Since most of these processes determine an organism's ability to cope with various environmental stressors, it is not surprising that a relationship (in the presence of a constant nutrient density) exists between caloric intake and time-to-tumor and/or life span. Our studies have clearly shown that generally, the greater the caloric intake, the greater the body weight, the higher the incidence of spontaneous tumor occurrence, the greater the susceptibility to chemical carcinogens, and the shorter the life span. It is also recognized that variables other than body weight influence the life span and carcinogenesis. We have focused our attention on the questions of how and to what extent caloric intake modifies those homeostatic processes believed to be critical in determining the ability of an organism to cope with endogenous and exogenous stresses such as chemical, physical, and biological carcinogens. The response of an organism to its environment can be divided into four categories--physiological, metabolic, molecular, and cellular. We have found that, from a physiological perspective, decreasing caloric intake causes body temperature in rodents to be decreased by 0.5 to 1.8 degrees C and water consumption to be increased by 80%, as is running activity. However, metabolic output per gram of lean body mass is not altered. Reproductive capacity declines, whereas the ECG waveform is preserved as caloric intake decreases. Alterations in these and other physiological functions suggests that energy intake serves as a signal to up-regulate or down-regulate functions related to the flight-or-fight response observed in placental mammals. A number of key metabolic pathways are altered as a function of lowered caloric intake, even though the rate of food consumption per gram of lean body mass remains steady during body weight decreases caused by decreasing caloric intake. Pharmacological compartmentalization, however, is altered. As caloric intake declines, changes occur in the expression of a number of drug-metabolizing enzymes, with the most striking effect seen in sex-specific growth hormones and liver-dependent phase I and phase II enzymes. Additionally, oxidative stress (free-radical and mediated damage to macromolecules) appears to decrease as a function of reduced caloric intake. A number of molecular processes also change with changes in energy consumption. Our studies have shown that, regardless of the source and nature of DNA damage, DNA repair is better preserved and/or enhanced when caloric consumption decreases. In addition, the fidelity of DNA replication increases and oncogene expression is stabilized, P53 gene expression is increased, and apoptosis is elevated by up to 500% with decreased caloric intake. At the cellular level, cell proliferation is decreased in direct proportion to lower energy intake in some but not all tissues. Studies have also shown an enhancement in immune capacity, changes in IGF1, and accelerated rates of wound healing proportionate to declines in energy consumption. Our most recent findings, however, have shown that the benefits associated with decreases in caloric intake only occur in the presence of sufficient nutrient quality and density. In the absence of proper nutrition, however, sensitivity to carcinogens and toxic substances appears to be enhanced. These findings are supported by independent studies. These observations have led us to conclude that, in certain organisms, when caloric intake is decreased, there is an up-regulation of those processes that modulate the responses to a wide range of environmental stressors. This response allows for a better survival rate and a down-regulation of reproductive activity. It is our belief that, during periods of environmental stress, these systems may be essential to perpetu

Relationship strategies and interdisciplinary collaboration. Improving maternity care with survivors of childhood sexual abuse.

Women's health care providers are being challenged to screen for and respond to the effects of abuse and violence in their clinical practices. Many feel poorly equipped to do so. Addressing the impact of a history of childhood sexual abuse on the survivor client's experience of pregnancy, birth, breastfeeding, and postpartum adjustment is a particularly challenging task. Professionals from several disciplines experienced in working with trauma survivors responded to a case study. Valuable points common to all six case respondents focused on strategies to use to improve communication and relationships with survivor clients. These health care providers also advocate interdisciplinary collaboration.

Praxis as a conceptual framework for participatory research in nursing.

Nursing scholars have often called upon the concept of praxis to inspire and inform our work. This article derives from praxis a conceptual framework for participatory nursing research. A praxis model can not only guide research, but it can also provide congruent ways to assess the quality of the project and ensure that researchers are accountable to the needs of the groups they study. The intellectual history of the term provides grounding for activist, collaborative, constructive science. Along with Marx and Freire's definition-in-use, this article presents descriptions of components that are specific to the tasks of participatory research. A review of epistemic considerations makes the argument that it is possible to justify research based on a praxis-oriented framework.

Aortic stenosis in pregnancy: a case report.

This case report describes a pregnant patient with severe aortic stenosis. A multidisciplinary plan of care was developed for the antepartum, intrapartum, postpartum, and, ultimately, postoperative clinical course. Salient points reviewed include normal cardiovascular anatomy and physiology, hemodynamic and physiologic changes of pregnancy, bicuspid aortic valvular stenosis, and the patient's clinical data profile. Numerous psychosocial stresses and the need for specialized nursing added to the complexity of caring for this patient.