Non-competitive resource exploitation within mosquito shapes within-host malaria infectivity and virulence.

Malaria is a fatal human parasitic disease transmitted by a mosquito vector. Although the evolution of within-host malaria virulence has been the focus of many theoretical and empirical studies, the vector's contribution to this process is not well understood. Here, we explore how within-vector resource exploitation would impact the evolution of within-host Plasmodium virulence. By combining within-vector dynamics and malaria epidemiology, we develop a mathematical model, which predicts that non-competitive parasitic resource exploitation within-vector restricts within-host parasite virulence. To validate our model, we experimentally manipulate mosquito lipid trafficking and gauge within-vector parasite development and within-host infectivity and virulence. We find that mosquito-derived lipids determine within-host parasite virulence by shaping development (quantity) and metabolic activity (quality) of transmissible sporozoites. Our findings uncover the potential impact of within-vector environment and vector control strategies on the evolution of malaria virulence.

Long-term blood glucose monitoring with implanted telemetry device in conscious and stress-free cynomolgus monkeys.

AIMS: Continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. Nonhuman primate (NHP) is an excellent model for metabolic research, because NHPs can naturally develop Type 2 diabetes mellitus (T2DM) similarly to humans. This study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) during circadian, meal, stress and drug exposure. MATERIALS AND METHODS: Blood glucose, body temperature and physical activities were continuously and simultaneously recorded by implanted HD-XG telemetry device for up to 10 weeks. RESULTS AND DISCUSSION: Blood glucose circadian changes in normoglycemic monkeys significantly differed from that in diabetic animals. Postprandial glucose increase was more obvious after afternoon feeding. Moving a monkey from its housing cage to monkey chair increased blood glucose by 30% in both normoglycemic and diabetic monkeys. Such increase in blood glucose declined to the pre-procedure level in 30 min in normoglycemic animals and >2 h in diabetic monkeys. Oral gavage procedure alone caused hyperglycemia in both normoglycemic and diabetic monkeys. Intravenous injection with the stress hormones, angiotensin II (2 µg/kg) or norepinephrine (0.4 µg/kg), also increased blood glucose level by 30%. The glucose levels measured by the telemetry system correlated significantly well with glucometer readings during glucose tolerance tests (ivGTT or oGTT), insulin tolerance test (ITT), graded glucose infusion (GGI) and clamp. CONCLUSION: Our data demonstrate that the real-time telemetry method is reliable for monitoring blood glucose remotely and continuously in conscious, stress-free, and moving-free NHPs with the advantages highly valuable to diabetes research and drug discovery.

Wet corn gluten feed and alfalfa hay levels in dry-rolled corn finishing diets: effects on finishing performance and feedlot nitrogen mass balance.

One-hundred ninety-two crossbred steers (initial BW = 351 +/- 11 kg) were used to determine the effects of removing alfalfa hay (AH) from dry-rolled corn-based diets containing wet corn gluten feed (WCGF) on animal performance and nutrient (N and OM) mass balance in open feedlot pens. Steers were stratified by weight and assigned randomly to 24 pens (2 x 3 factorial) and fed for 132 d from June to October 2002. Experimental diets contained either 0 or 35% WCGF and 0, 3.75, or 7.5% AH, and were formulated to be isonitrogenous. For efficiency of gain, an interaction occurred (P = 0.09) between AH and WCGF. Feed efficiencies of cattle fed 35% WCGF were improved 4.4% (P = 0.10) compared with efficiencies of cattle fed no WCGF at 0% AH; there was a marked improvement in ADG for cattle fed WCGF compared with no WCGF in diets with 0% AH. Within 35% WCGF diets, efficiency decreased as AH inclusion increased (P = 0.06). Efficiency was equal across AH levels when 0% WCGF was fed; however, ADG was decreased when AH was removed. Interactions between AH and WCGF were not detected for other performance or carcass criteria; therefore, main effects of AH and WCGF are discussed. Daily intake, ADG, and HCW increased linearly (P < 0.05) as dietary AH level increased. Feeding 35% WCGF also resulted in greater DMI (P < 0.01) and a tendency for greater ADG and HCW (P < or = 0.10) compared with steers fed no WCGF. Interactions between AH and WCGF were not observed for feedlot N mass balance. As level of AH increased across diets, N intake, N retention, and N excretion increased (P < 0.05). Steers fed 35% WCGF consumed and excreted more N (P < 0.01) than those fed no WCGF. More manure DM (P = 0.11), OM, and N (P < 0.01) were removed from pens housing steers fed 35% WCGF as well as greater OM and N recovery in finished compost. More N (kilogram/steer) was also lost to volatilization as a result of greater N excretion when WCGF was fed. Expressed as a percentage of N excretion, loss of N from pens housing steers fed 0 and 35% WCGF was not different, averaging nearly 80%. These data suggest that AH has less value when dry-rolled corn-based diets contain 35% WCGF and can be decreased from conventional levels. Furthermore, loss of N from open feedlot pens is high during the summer months, and feeding WCGF may not reduce N losses during these times of year.

Pathweb - Virtual Pathology Museum

Museo de patología virtual que contiene imágenes e información (etiología, epidemiología, descripción, referencias...) de enfermedades y órganos.

Effects of supplementation of whole corn germ on reproductive performance, calf performance, and leptin concentration in primiparous and mature beef cows.

A 2-yr study using primiparous and multiparous, spring-calving, crossbred beef cows was conducted to evaluate the effects of supplemental whole corn germ on reproductive performance, calf performance, and serum leptin concentrations. Each year, cows were blocked by age and BCS and assigned randomly to one of three treatments: PRE (n = 115) cows received 1.14 kg/d (DM basis) of whole corn germ for approximately 45 d before calving; POST (n = 109) cows were fed 1.14 kg/d of whole corn germ for approximately 45 d after calving; and control cows (n = 118) were fed similar energy and protein from dry-rolled corn (1.82 kg of DM/d) for 45 d before and after calving. Additionally, PRE cows were grouped with controls after calving, and POST cows were grouped with control cows before calving, so that corn germ-supplemented cows received the control supplement in the alternate feeding period. Cow BW (538 +/- 13 kg) and BCS (5.4 +/- 0.13) did not differ among treatments at any time during the experiment. Calf birth weight (39 +/- 2 kg), weaning weight (225 +/- 7 kg), and age-adjusted weaning weight (234 +/- 8 kg) did not differ because of dam supplementation regimen. Treatment did not affect the proportion of cows exhibiting ovarian luteal activity before the start of the breeding season (67%) or pregnancy rate (91%). The interval from exposure to bulls until subsequent calving did not differ (P = 0.16) among PRE (298 +/- 2.3 d), POST (303 +/- 2.6 d), and control (304 +/- 2.3 d) cows. Leptin concentrations did not differ among treatments and were 2.15 +/- 0.75, 1.88 +/- 0.76, and 1.91 +/- 0.75 ng/mL for control, POST, and PRE cows, respectively. Age and week relative to calving influenced leptin concentration. Primiparous cows had similar leptin concentrations to 3-yr-old and mature cows for wk -7 and -6 relative to calving, but lower (P < 0.10) concentrations than mature cows for wk -5, and lower (P < 0.05) concentrations than either 3-yr-old or mature cows for wk -4 to +7 relative to calving. Serum leptin was correlated with BCS (P < 0.0001; r = 0.35) at initiation of the feeding period and was correlated with BCS (P = 0.02; r = 0.12) and weight (P < 0.01; r = 0.14) at the completion of the supplement period, but it was not correlated with initial BW or interim BCS. Calving interval was not correlated (P > 0.12) with weekly measures of serum leptin concentration. Supplementing beef cows with whole corn germ had no effect on cow performance, calf performance, or serum leptin concentrations of cows.

Issues in complementary therapies: how we got to where we are.

Consumer interest in and use of complementary/alternative therapies has increased exponentially in the past decades. Although many of the over 1800 therapies have not been used in the delivery of nursing care, a number of these therapies have a long tradition of use in nursing. Additionally, nurses have conducted research on selected complementary therapies. Nursing is in an excellent position to be a leader in integrating these therapies into the Western biomedical health model and in continuing the research that will provide a better scientific base for the use of complementary therapies.

Evaluation of wet corn gluten feed in diets for lactating dairy cows.

Two experiments were conducted to evaluate responses of primiparous and multiparous Holstein cows to diets containing wet corn gluten feed (WCGF). In both experiments, WCGF replaced a mix of alfalfa hay, corn silage, and corn grain. In experiment 1, 32 primiparous Holstein cows (four pens with eight cows/pen) were used in two 2 x 2 Latin squares with 28-d periods. Cows were housed in free stalls and fed diets containing 0 or 20% WCGF dry matter (DM) basis. Cows fed WCGF consumed more DM and produced more energy-corrected milk (ECM) than controls. Production efficiency (ECM/DM intake) was not affected, but yield of milk components was improved by WCGF. In experiment 2, 24 multiparous Holstein cows were used in six 4 x 4 Latin squares with 28-d periods to determine the optimal dietary inclusion rate for WCGF. Cows were housed in a tie-stall barn and fed a total mixed ration twice daily. Treatments were 0, 20, 27.5, and 35% WCGF (DM basis). Cows fed WCGF produced more ECM than controls, but ECM did not differ among cows fed WCGF diets. Cows fed 20 and 27.5% WCGF consumed more DM as a percentage of body weight than those fed either 0 or 35% WCGF. Cows fed WCGF produced ECM more efficiently than controls. Percent milk fat was lower, but fat yield was not different when WCGF was added to diets. Milk protein and lactose yields were higher when WCGF was fed. Plasma glucose, alpha-amino N, and triglyceride concentrations were similar among diets in both experiments, but plasma urea N was higher for cows fed WCGF in experiment 2.

Development of health care delivery systems that are sensitive to the needs of stroke survivors and their caregivers.

The life-altering event of a stroke has long-term effects not only on stroke survivors but also on their caregivers, health care professionals, and health care delivery systems. The nurse administrator is faced with an obvious challenge to organize nursing systems to meet the multiple needs of the stroke survivor. The article presents data on the perceived needs of stroke survivors and their caregivers that provide direction and assistance to nursing administrators in organizing nursing services to address these perceived needs.

A case for multisite studies in critical care.

Studies in critical care settings are essential to improve critical care practice. Critical care research conducted at a single site may be limited with respect to sample size leading to large type II error, diminished statistical power, decreased generalizability, and inconclusive results. Multiple-site studies are more likely to change nursing practice in critical care. They allow for larger sample size, broader sampling, faster accrual rates, and meaningful subgroup analyses. Successful multisite research requires more thorough planning, and deliberate steps are required to ensure its feasibility and acceptability. Multisite research protocols can be challenging regarding communication, reliability, and data integrity. However, defining and addressing these challenges and selecting subjects and settings appropriately can lead to results that are more generalizable and relevant to practice.

Interleukin-1 family expression in human breast cancer: interleukin-1 receptor antagonist.

We hypothesize that interleukin-1 alpha, beta, and receptor antagonist (IL-1 alpha, IL-1 beta, and IL-1 ra, respectively) are present and tumor cell associated in human breast cancer (HBC). We believe the levels of these cytokines in breast tumor homogenates relate to other known prognosticators of patient survival (i.e., estrogen receptor [ER] status). Our results demonstrated that, immunohistochemically, tumor cells express IL-1 alpha, IL-1 beta, and IL-1 ra in most specimens tested. In breast tissue homogenates, IL-1 alpha levels correlated inversely with ER levels (p < 0.06), whereas IL-1 ra levels correlated directly with both ER levels (p < 0.009) and IL-1 beta levels (p < 0.06). When analyzing cytokine levels for the ER (-) versus ER (+) patient groups, we found that in many instances these groups showed a different cytokine profile. These studies suggest that the IL-1 family of cytokines may be important in regulating protumorigenic activities within the HBC tumor microenvironment.

Mutagen exposures and chromosome 3 aberrations in acute myelocytic leukemia.

Thirteen patients with acute myelocytic leukemia (AML) and with clonal aberrations involving chromosome 3 were studied. Three patients had monosomy 3, four had trisomy 3, and six had structural aberrations of chromosome 3. In the majority of cases chromosome 3 aberrations were parts of complex karyotypes, but in two patients, the abnormalities appeared as single aberrations, one as an interstitial deletion del(3)(p13p21) and the other as monosomy 3. All breakpoints of chromosome 3 were found in the fragile site regions 3p14.2, 3q21 and 3q26-27. All patients with monosomy 3 or structural aberrations of chromosome 3 and one of the four patients with trisomy 3 had been exposed to mutagens, such as occupational exposures to organic solvents and/or petroleum products or treatments with irradiation or antineoplastic agents. The association among mutagen exposure, structural chromosome 3 aberrations and fragile sites in AML may indicate that targeting of the mutagens to these sites is of importance for the etiology of the disease. Leukemia (2000) 14, 112-118.

Expression of vascular endothelial growth factor receptors in human prostate cancer.

OBJECTIVES: We recently reported the expression and cytokine regulation of vascular endothelial growth factor (VEGF) in human prostate cancer (PCa). VEGF exerts its angiogenic and pro-tumorigenic properties by way of two high affinity receptors, fms-like tyrosine kinase 1 (FLT-1) and fetal liver kinase 1 (FLK-1). We hypothesized that these receptors are expressed and control VEGF functions in the PCa microenvironment. Herein, we evaluate the expression of these receptors in ex vivo PCa tissue, benign prostatic hypertrophy (BPH) tissue, and cultured PCa cell lines. METHODS: Ex vivo PCa specimens were obtained from patients undergoing radical retropubic prostatectomy. Specimens were selected to contain both PCa and BPH tissue (n = 15). Immunohistochemical analysis using antihuman FLT-1 and FLK-1 was performed and specimens were analyzed to characterize the expression and distribution of both receptors. Immunocytochemical analysis for FLT-1 and FLK-1 was also performed on cultured PCa cell lines (DU-145 and LNCaP). RESULTS: PCa cells expressed the VEGF receptor FLT-1 in 100% of specimens evaluated. Expression of FLK-1 was variable and related to tumor grade; high-grade tumors displayed little or no FLK-1 expression. Vascular endothelial cells (VECs) within areas of PCa consistently expressed both FLT-1 and FLK-1 receptors. FLT-1 and FLK-1 were both expressed in BPH tissue. FLT-1 was expressed in the glandular epithelial cells in BPH, but in most cases FLK-1 was localized specifically to the basal cell layer of hypertrophic glands. FLT-1, but not FLK-1, was expressed by the DU-145 and LNCaP cell lines. CONCLUSIONS: Although they are differentially expressed, both FLT-1 and FLK-1 are present in PCa and BPH. Expression of receptors on VECs of tumor vessels supports the well-established role of VEGF in paracrine stimulation of VECs in the tumor microenvironment. The expression of FLT-1 and FLK-1 on tumor cells themselves suggests a potential autocrine function for VEGF (such as regulating tumor cell proliferation). These findings imply that a novel dual role may exist for VEGF, such that it is involved in tumor cell activation (autocrine), in addition to paracrine actions whereby it regulates endothelial cell functions and subsequent neovascular development.

Cytokines in human breast cancer: IL-1alpha and IL-1beta expression.

We hypothesize that interleukin 1alpha (IL-1alpha) and interleukin 1beta (IL-1beta) are present and tumor cell associated in human breast cancer (HBC) specimens. To test our hypothesis: a) immunologic analysis was performed on HBC histologic sections for IL-1alpha (n=49) and IL-1beta (n=42) distribution; and b) homogenates of HBC tumors were analyzed for levels of IL-1alpha (n=82), IL-1beta (n=101) and interleukin 8 (IL-8) (n=103) expression. Immunohistochemical analysis demonstrated the presence of IL-1alpha and IL-1beta in tumor cells in patients with invasive cancer and ductal carcinoma in situ. Quantitative analysis confirmed the presence and positive correlation of IL-1alpha and IL-1beta to IL-8, a known angiogenic factor, in cancer specimens. These studies demonstrate that tumor-associated IL-1alpha+, IL-1beta are present in the tumor microenvironment and may play a pivotal role in regulating breast tumor growth and metastasis.

Expression of interleukin-8 receptors on tumor cells and vascular endothelial cells in human breast cancer tissue.

UNLABELLED: Recently, we demonstrated the presence of Interleukin-8 (IL-8) in human breast cancer (HBC) tissue. We hypothesize that the IL-8 receptors are present and play a role in tumor cell and vascular endothelial cell (VEC) activation (e.g. proliferation and angiogenesis). MATERIALS AND METHODS: Immunohistochemical analysis for IL-8 receptors (IL-8RA and IL-8RB) was performed on 43 malignant and 8 benign breast tissue samples. RESULTS: Tumor cells expressed IL-8RA and IL-8RB in all of the malignant specimens. Only 50% of the benign ductal epithelial cell (DEC) samples expressed these receptors. The majority of small vessel endothelial cells (SVEC) expressed IL-8RA and IL-8RB, while large vessel endothelial cells (LVEC) showed primarily IL-8RB expression. CONCLUSIONS: Our results demonstrate that tumor and VEC express the IL-8 receptors and likely play a role in regulating tumor and VEC activation which controls proliferation, angiogenesis and metastasis in HBC.

Understanding and preventing adverse drug events.

Adverse drug events affect approximately 10% of patients in hospitals and result in increased rates of morbidity and mortality. These adverse events extend hospital stays an estimated 1.7 to 2.2 days and increase costs by approximately $3,200 for patients who are affected. Nurses play a key role in reducing risks of adverse drug events. Through purposeful, planned actions, nurses can help to curtail unexpected costs and can further promote safe patient care. Specific problem areas of the drug delivery system resulting in high numbers of significant (lethal or severe) drug events can be targeted for precautionary actions. An interdisciplinary "safety net" can be developed and maintained to reduce these events. Guidelines are recommended for system-wide approaches to prevention and continuous quality improvement activities.

Coexpression of interleukin-8 receptors in head and neck squamous cell carcinoma.

BACKGROUND: Interleukin 8 (IL-8) is an important cytokine involved in tumor growth and angiogenesis in a variety of malignancies. We hypothesize that IL-8 plays an important role in the cellular proliferation and angiogenesis seen in head and neck squamous cell carcinoma (HNSCC) and set out to identify its receptors, IL-8RA and IL-8RB. METHODS: Immunohistochemical analysis was performed on specimens from 38 HNSCC patients with stage I to IV disease and control tissues. RESULTS: All of cancer specimens demonstrated positive staining for IL-8RA. The IL-8RA staining of microvessel endothelial cells was seen in 51%. The IL-8RB pattern was similar to the IL-8RA pattern in that 97% of cancer sections demonstrated positive cancer cell staining, and 74% of the specimens demonstrated positive staining for microvessel endothelial cells. CONCLUSION: Our studies demonstrate that IL-8 receptors are expressed by cancer cells and microvessel endothelial cells in HNSCC, suggesting that IL-8 may act in an autocrine/paracrine fashion to stimulate cellular proliferation and angiogenesis.

Comparison of preoperative characteristics of men and women undergoing coronary artery bypass grafting (the Post Coronary Artery Bypass Graft [CABG] Biobehavioral Study).

A cohort of 759 coronary artery bypass grafting (CABG) patients (269 women and 490 men) was enrolled in the prospective POST CABG Biobehavioral Study at 5 clinical centers in the United States and Canada. Sociodemographic and medical data were obtained by interview and from medical charts. Health-related quality of life and psychosocial data were ascertained preoperatively by interview and questionnaire for those patients whose condition allowed preoperative assessment and was compared among patients from hospitals enrolling both male and female patients (143 women and 267 men). Women enrolled in the Biobehavioral Study were older than men (65.4 +/- 9.0 vs 61.8 +/- 9.7 years, p < 0.001) and more likely to have a preoperative medical condition which precluded biobehavioral evaluation (47% vs 34%, p < 0.001). Women were less likely to be high school graduates (59% vs 74%, p < 0.001), were less likely to be earning > or = $25,000 per year (39% vs 69%, p < 0.001), and were married less often at the time of surgery (59% vs 85%, p < 0.001). Fewer women than men were able to perform basic self-care activities (p < 0.001) and social activities (p < 0.001). Women were also less able to perform the more demanding activities required for independent living, recreation, and maintaining a household (p < 0.001). Women were also more anxious (p = 0.01) and reported more depressive symptoms (p < 0.001) than men. These data suggest that plans for perioperative and convalescent care for women undergoing CABG should take into account their less favorable medical and psychosocial status relative to men.

Decreased expression of transforming growth factor beta receptors on head and neck squamous cell carcinoma tumor cells.

BACKGROUND: Transforming growth factor beta (TGF-beta) has antiproliferative effects on normal and neoplastic cells that express specific TGF-beta receptors. We hypothesize that diminished expression of TGF-beta and/or its receptors may contribute to the uncontrolled proliferation of head and neck squamous cell carcinoma (HNSCCA) cancer cells. METHODS: Using immunohistochemical techniques, we characterized the expression of TGF-beta isoforms and TGF-beta receptors, TGF-beta(RI) and TGF-beta(RII), in HNSCCA. Tumor production of TGF-beta was evaluated in culture supernatants from a cytokine-stimulated HNSCCA tumor line (HTB-43). RESULTS: All control specimens displayed strong cell-associated staining of TGF-beta as well as both receptors. Forty-seven of 47 cancer specimens exhibited positive staining for TGF-beta in the tumor matrix. Forty of the 47 cancer specimens demonstrated no expression of TGF-beta(RI), and 43 of the 47 expressed no TGF-beta(RII). Only interleukin 1 alpha (IL-1 alpha) and IL-1 beta induced significant TGF-beta expression from the HTB-43 cells. CONCLUSIONS: Decreased expression of TGF-beta receptors may play a significant role in the pathogenesis of HNSCCA by allowing uncontrolled cell proliferation.

Interleukin-1 receptor antagonist in head and neck squamous cell carcinoma.

BACKGROUND: We hypothesized that in head and neck squamous cell carcinoma, the overexpression of protumorigenic interleukin-1 (IL-1) activity within the tumor tissue is a result of decreased expression of the specific antagonist or inhibitor (ie, IL-1 receptor antagonist) by the tumor cells. Ultimately, this local overexpression of IL-1 activity increases tumor growth and metastasis. DESIGN: To test our hypotheses, immunologic analysis for IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist was performed on histologic sections and tumor homogenates of human head and neck squamous cell carcinomas. SETTING: University teaching hospital. PATIENTS OR OTHER PARTICIPANTS: Normal and tumor specimens were obtained from patients undergoing surgical resections of the head and neck for benign and malignant disease. RESULTS: Immunohistochemical analysis demonstrated the presence of IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist within tumor cells and inflammatory cells in the tumor stroma in 19 of 19 tumor specimens. Quantitatively, IL-1 alpha was present in 19 of 19 tumor specimens (1.97 +/- 0.46 ng/mg of total protein [mean +/- SD]) and 5 of 9 normal specimens (0.23 +/- 0.12 ng/mg of total protein). All specimens contained IL-1 beta in detectable quantities (1.60 +/- 0.29 ng/mg of total protein in tumor specimens and 0.189 +/- 0.04 ng/mg of total protein in normal specimens). All specimens contained IL-1 receptor antagonist (368.87 +/- 57.63 ng/mg of total protein in tumor specimens and 585.10 +/- 166.03 ng/mg of total protein in normal specimens). The mean total IL-1/IL-1 receptor antagonist ratio was 13.26 +/- 2.31 in patients with cancer compared with 0.997 +/- 0.26 in normal patients. CONCLUSIONS: The increased IL-1 index in the cancer state compared with the normal state reflects an imbalance of IL-1 and IL-1 receptor antagonist, which may contribute to unrestricted growth and metastasis of head and neck squamous cell carcinoma.