Validated image ordering guidelines for odontogenic infections.

Overuse of computed tomography (CT) is a prevalent problem across multiple disciplines in healthcare and is common in the workup of odontogenic infections. To address this problem, an imaging pathway was created through collaboration of the oral maxillofacial surgery and emergency medicine departments to reduce unnecessary CT orders. A prospective study was implemented to assess the success of the imaging pathway to guide in the selection of the most appropriate radiological imaging modality when managing an odontogenic infection. Subjects included were adults, presenting through the emergency department for confirmed odontogenic infection. The primary outcome was the rate of unnecessary CT scans performed after the introduction of the pathway. Statistics were performed via the t-test, χ2 test, and multiple regression analysis; P < 0.05 was considered significant. Between February 1 and December 15, 2019, 100 patients met the inclusion criteria and were enrolled. The rate of unnecessary CT scans was 25.6%, compared to 56.6% prior to the introduction of the imaging pathway. The pathway did not misclassify any patient to not receive a CT when it was medically necessary. Use of the imaging pathway has the potential to reduce unnecessary CT imaging for odontogenic infections, without negatively affecting patient outcomes.

Quantifying greenhouse gas emissions from municipal solid waste dumpsites in Cameroon.

Open dumpsites that receive municipal solid waste are potentially significant sources of greenhouse gas (GHG) emissions into the atmosphere. There is little data available on emissions from these sources, especially in the unique climate and management of central Africa. This research aimed at quantifying CH4, N2O and CO2 emissions from two open dumpsites in Cameroon, located in Mussaka-Buea, regional headquarters of the South West Region and in Mbellewa-Bamenda, regional headquarters of the North West Region. Emissions were measured during the wet season (May 2015 and August 2016) at the Mussaka and Mbellewa dumpsites respectively. Dumpsite surfaces were partitioned into several zones for emission measurements, based on the current activity and the age of the waste. Static flux chambers were used to quantify gas emission rates thrice a day (mornings, afternoons and evenings). Average emissions were 96.80 ±â€¯144 mg CH4 m-2 min-1, 0.20 ±â€¯0.43 mg N2O m-2 min-1 and 224.78 ±â€¯312 mg CO2 m-2 min-1 in the Mussaka dumpsite, and 213.44 ±â€¯419 mg CH4 m-2 min-1, 0.15 ±â€¯0.15 mg N2O m-2 min-1 and 1103.82 ±â€¯1194 mg CO2 m-2 min-1 at the Mbellewa dumpsite. Emissions as high as 1784 mg CH4 m-2 min-1, 2.3 mg N2O m-2 min-1 and 5448 mg CO2 m-2 min-1 were measured from both dumpsites. Huge variations observed in emissions between the different zones on the waste surface were likely a result of the heterogeneous nature of the waste, different stages in waste decomposition and different environmental conditions within the waste. Management activities that disturb waste, such as spreading and compressing potentially increase gas emissions, while covering waste with a layer of soil potentially mitigate gas emissions. Recommendations were for dumpsites to be upgraded to sanitary landfills, and biogas production from such landfills should be exploited to reduce CH4 emissions.

Reduced growth in wild juvenile sockeye salmon Oncorhynchus nerka infected with sea lice.

Daily growth rings were examined in the otoliths of wild juvenile sockeye salmon Oncorhynchus nerka to determine whether infection by ectoparasitic sea lice Caligus clemensi and Lepeophtheirus salmonis was associated with reduced host body growth, an important determinant of survival. Over 98% of the sea lice proved to be C. clemensi and the fish that were highly infected grew more slowly than uninfected individuals. Larger fish also grew faster than smaller fish. Finally, there was evidence of an interaction between body size and infection status, indicating the potential for parasite-mediated growth divergence.

Virgin coconut oil supplementation attenuates acute chemotherapy hepatotoxicity induced by anticancer drug methotrexate via inhibition of oxidative stress in rats.

BACKGROUND: The emerging health benefit of virgin coconut oil (VCO) has been associated with its potent natural antioxidants; however, the antioxidant and hepatoprotective effect of VCO against methotrexate-induced liver damage and oxidative stress remains unexplored. The study explored the antioxidant and hepatoprotective effects of VCO against oxidative stress and liver damage induced by anticancer drug methotrexate (MTX) in rats. METHODS: Liver damage was induced in Wistar rats pretreated with dietary supplementation of VCO (5% and 15%) by intraperitoneal administration of MTX (20mg/kg bw) on day 10 only. After 12days of treatment, assays for serum liver biomarkers (aminotransferases), alkaline phosphatase, albumin and total protein as well as hepatic content of malondialdehyde, reduced glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were carried out. Liver was used to examine histopathological changes. RESULTS: MTX administration induced significant increase in serum liver enzymes along with marked decrease in albumin and total protein compared to control group. Hepatic activities of antioxidant enzymes were significantly decreased, while malondialdehyde increased significantly. Treatment with VCO supplemented diet prior to MTX administration attenuated MTX-induced liver injury and oxidative stress evidenced by significant improvements in serum liver markers, hepatic antioxidant enzymes and malondialdehyde comparable to control group. Histopathological alterations were prevented and correlated well with the biochemical indices. CONCLUSION: The study suggests antioxidant and hepatoprotective effects of VCO supplementation against hepatotoxicity and oxidative damage via improving antioxidant defense system in rats. Our findings may have beneficial application in the management of hepatotoxicity associated with MTX cancer chemotherapy.

Prevalence and Antimicrobial Resistance of Enterobacteriaceae in Shell Eggs from Small-Scale Poultry Farms and Farmers' Markets.

Public health concerns over the emergence of antimicrobial resistant bacteria have increased recently. The purpose of this study was to investigate the prevalence of antimicrobial resistant Enterobacteriaceae in shell eggs purchased from small poultry farms and farmers' markets. A total of 504 eggs were pooled to make 252 composite samples, consisting of 2 eggs per composite. The microbial quality of shell eggs was determined by standard quantitative, biochemical, and PCR techniques. Susceptibility to 13 antimicrobial agents was determined by the Kirby-Bauer disk diffusion technique, and results were interpreted based on Clinical and Laboratory Standards Institute values. Shell eggs and egg contents were positive for Escherichia coli (11.9 and 5.2%, respectively), Enterobacter (9.1 and 7.9%), and Serratia (11.5 and 4.8%). Salmonella was isolated from 3.6% of egg shells but not from egg contents. Mean (±SD) Enterobacteriaceae levels (4.4 ± 2.0 log CFU per eggshell) on shell eggs from poultry farms was significantly higher (P ≤ 0.05) than that on shell eggs from farmers' markets (2.1 ± 1.3 log CFU per eggshell). Of the 134 isolates recovered, resistance among isolates from farm and market shell eggs to erythromycin was most common (48.5 and 32.8%, respectively) followed by ampicillin (44.8 and 17.2%), and tetracycline (29.9 and 17.2%). The multiple antibiotic resistance index value for E. coli and Pantoea was 0.62, and that for Salmonella and Klebsiella terrigena was 0.08, indicating that Enterobacteriaceae in shell eggs can be resistant to multiple antimicrobial agents. These data reveal that shell eggs from small poultry farms and farmers' markets can harbor antimicrobial resistant pathogenic and commensal bacteria. Thus, failure to properly handle shell eggs poses a potential health hazard to consumers.

Frequency, risk factors and feto-maternal outcomes of abruptio placentae in Northern Tanzania: a registry-based retrospective cohort study.

BACKGROUND: Abruptio placentae remains a major cause of maternal and perinatal morbidity and mortality in developing countries. Little is known about the burden of abruptio placentae in Tanzania. This study aimed to determine frequency, risk factors for abruptio placentae and subsequent feto-maternal outcomes in women with abruptio placentae. METHODS: We designed a retrospective cohort study using maternally-linked data from Kilimanjaro Christian Medical Centre (KCMC) medical birth registry. Data on all women who delivered live infants and stillbirths at 28 or more weeks of gestation at KCMC hospital from July 2000 to December 2010 (n = 39,993) were analysed. Multivariate logistic models were used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for risk factors, and feto-maternal outcomes associated with abruptio placentae. RESULTS: The frequency of abruptio placentae was 0.3% (112/39,993). Risk factors for abruptio placentae were chronic hypertension (OR 4.1; 95% CI 1.3-12.8), preeclampsia/eclampsia (OR 2.1; 95% CI 1.1-4.1), previous caesarean delivery (OR 1.3; 95% CI 1.2-4.2), previous abruptio placentae (OR 2.3; 95% CI 1.8-3.4), fewer antenatal care visits (OR 1.3; 95% 1.1-2.4) and high parity (OR 1.4; 95% CI 1.2-8.6). Maternal complications associated with abruptio placentae were antepartum haemorrhage (OR 11.5; 95% CI 6.3-21.2), postpartum haemorrhage (OR 17.9; 95% 8.8-36.4),), caesarean delivery (OR 5.6; 95% CI 3.6-8.8), need for blood transfusions (OR 9.6; 95% CI 6.5-14.1), altered liver function (OR 5.3; 95% CI 1.3-21.6) and maternal death (OR 1.6; 95% CI 1.5-1.8). In addition, women with abruptio placentae had prolonged duration of hospital stay (more than 4 days) and were more likely to have been referred during labour. Adverse fetal outcomes associated with abruptio placentae include low birth weight (OR 5.9; 95% CI 3.9-8.7), perinatal death (OR 17.6; 95% CI 11.3-27.3) and low Apgar score (below 7) at 1 and 5 min. CONCLUSIONS: Frequency of abruptio placentae is comparable with local and international studies. Chronic hypertension, preeclampsia, prior caesarean section delivery, prior abruptio placentae, poor attendance to antenatal care and high parity were independently associated with abruptio placentae. Abruptio placentae was associated with adverse maternal and foetal outcomes. Clinicians should identify risk factors for abruptio placentae during prenatal care when managing pregnant women to prevent adverse maternal and foetal outcomes.

Asthma Control in Cities of Developing Countries: Results of a Five-City Survey

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Prevalence and antimicrobial resistance of Cronobacter sakazakii isolated from domestic kitchens in middle Tennessee, United States.

Cronobacter sakazakii is an emerging opportunistic pathogen that has been implicated in cases of severe meningitis, sepsis, and necrotizing enterocolitis in premature and full-term infants. In this study, the prevalence of C. sakazakii was estimated in selected domestic kitchens in middle Tennessee. Antimicrobial resistance patterns of these C. sakazakii isolates were examined for points of public health significance. A total of 234 contact sites in 78 domestic kitchens were tested for C. sakazakii. Consumers' used dishcloths and cleaning sponges were also tested. Antimicrobial susceptibility of the identified C. sakazakii isolates was determined for 10 antimicrobial drugs by means of the disk diffusion method. C. sakazakii was recovered from 26.9% of domestic kitchens visited. Multidrug resistance was observed; the highest resistance was to penicillin (76.1% of isolates) followed by tetracycline (66.6%), ciprofloxacin (57.1%), and nalidixic acid (47.6%). None of the C. sakazakii isolates were resistant to gentamicin. These results suggest that antibiotic-resistant C. sakazakii could be present at various sites in domestic kitchens.

African American and non-Hispanic white children's health: integrating alternative explanations.

OBJECTIVES: Three questions were examined: does a structural equation model (SEM) of the links among family resources (socioeconomic status, SES), sociocultural (perception of quality of care), structural (health insurance coverage and health care utilization), parental psychological resources (parental depression and perception of quality of parenting), and child health apply similarly across blacks and whites? Do the items used to indicate the factors exhibit differences across groups? Is race/ethnicity associated with differences in structural paths? DESIGN: Data on 18,092 black and white children (ages 0-11) from the 2002 National Survey of American Families data set was used. A two-stage, eight-step multigroup SEM was used to examine the associations among family resources, sociocultural, structural, parental psychological resources and child health status. RESULTS: First, the patterning of the structural model applied similarly to black and whites. Second, there were some differences in factor loadings across groups. Third, although sociocultural, structural, and parental psychological resources mediated the link between SES and health status, the effects of SES on these mediators differed between blacks and whites; but there was no difference between groups in the effects of SES on health status. Fourth, perception of quality of care and health care use mediated the effects of health insurance on health and the effects of parental depression and quality of parenting on health status, respectively. Fifth, health care use mediated the effects of perception of quality of care on health status. Finally, health insurance was linked with a greater increase in health care use among blacks than whites; and perception of quality of care was strongly associated with better health for blacks than for whites. CONCLUSIONS: When sociocultural, structural, and parental psychological constructs are adjusted for, there are no significant differences in SES effects on health status between groups. Perception of quality of care is an important determinant of health care utilization, given health insurance coverage and SES. Finally, parental depression and behaviors also determine perception of care and health care utilization decisions.

Children's health status: examining the associations among income poverty, material hardship, and parental factors.

BACKGROUND: We examined a model of multiple mediating pathways of income poverty, material hardship, parenting factors, and child health status to understand how material hardship and parental factors mediate the effects of poverty on child health. We hypothesized that: (a) poverty will be directly associated with material hardship, parental depression, and health status, and indirectly with parenting behaviors through its effects on parental depression and material hardship; (b) material hardship will be associated with parental depression, parenting behaviors, and health status; and (c) parental depression will be correlated with parenting behaviors, and that both parental depression and parenting behaviors will predict child health. METHODS AND RESULTS: We used data from the 2002 National Survey of American Families for a sample of 9,645 6-to-11 year-olds to examine a 4-step structural equation model. The baseline model included covariates and income poverty. In the hardship model, food insufficiency and medical need were added to the baseline model. The parental model included parental depression and parenting behavior and baseline model. In the full model, all the constructs were included. First, income poverty had a direct effect on health status, and an indirect effect through its association with material hardship, parental depressive affect, and parenting behaviors. Medical need and food insufficiency had negative effects on child health, and indirect effects on health through their association with parental depression and parenting behaviors. Finally, parental depression and parenting behaviors were associated with child health, and part of the effect of parental depression on health was explained by its association with parenting behaviors. CONCLUSIONS: Poverty has an independent effect on health, however, its effects are partially explained by material hardship, parental depression and parental behaviors. To improve children's health would require a multi-pronged approach involving income transfers, health insurance coverage, food and nutrition assistance, and parenting interventions.

Poverty and child outcomes: a focus on Jamaican youth.

Compared with children from more affluent families, poor children face a higher risk of developmental delays and fare worse on various measures of developmental outcomes. This paper examines the relationship between poverty and child outcomes in the Jamaican context. Specifically, the paper focuses on the detrimental consequences for poor Jamaican children. The literature is reviewed on the effects of economic disadvantage on children and the short- and long-term implications for individuals and society is discussed. In addition, the modus operandi and implications for human development utilizing a theoretical model that hypothesizes the associations among economic deprivation and various aspects of child well-being is examined. Suggestions to policy makers for addressing the issues related to economically deprived families and children are offered.

Calcium-sensing receptor-mediated activation of phospholipase C-gamma1 is downstream of phospholipase C-beta and protein kinase C in MC3T3-E1 osteoblasts.

Elevated extracellular calcium (Ca(e)) stimulates both chemotaxis and mitogenesis of MC3T3-E1 osteoblasts via a calcium-sensing receptor (CasR). Ca(e)-mediated chemotaxis of these bone-forming cells is dependent on phospholipase C (PLC) and blocked by the Gi-protein inhibitor pertussis toxin. In this study, we examine the signaling mechanisms by which the CasR stimulates PLC activity in MC3T3-E1 osteoblasts. We found that elevated Ca(e) stimulated PLC-gamma1 tyrosine phosphorylation in a time-dependent and Ca(e)-concentration-dependent manner. The maximal increase in PLC-gamma1 tyrosine phosphorylation was observed 3-5 min after increasing Ca(e) by 3.2 mmol/L from 1.8 mmol/L. Elevated Ca(e) also promoted a rapid increase in both inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], a second messenger formed by PLC-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate, and cytosolic free calcium ([Ca+2]i). The kinetics of the CasR-mediated increases in Ins(1,4,5)P3 and [Ca+2]i and the sensitivity of the Ca(e)-stimulated elevation in [Ca+2]i to U73122 (a PLC inhibitor) together suggest that the osteoblast CasR is coupled via Gq to PLC-beta. U73122 blocked the Ca(e)-promoted, but not PDGF-promoted, PLC-gamma1 tyrosine phosphorylation, suggesting that the activation of PLC-beta is upstream of PLC-gamma1 activation. Inhibition of protein kinase C (PKC) disrupted Ca(e)-stimulated tyrosine phosphorylation of PLC-gamma1. In addition, exposure to pertussis toxin or exogenous activation of protein kinase A (PKA) inhibited PLC-gamma1 tyrosine phosphorylation in response to Ca(e). The results indicate that: (a) the osteoblast CasR activates PLC-gamma1 downstream of PLC-beta in a PKC-dependent manner; (b) PKA is a negative regulator of Ca(e)-promoted PLC-gamma1 phosphorylation; and (c) Gq and Gi are both involved in the CasR-mediated phosphorylation of PLC-gamma1.

Teaching patient empathy: the ED visit program.

OBJECTIVE: Residency programs only are not challenged with developing competent emergency clinicians, but should strive to develop caring, empathetic, and community-minded physicians. An exercise was designed to help residents experience emergency department (ED) visits from the patient's perspective. METHODS: This study occurred in emergency medicine residency program at an urban teaching institution with an annual ED census of 94,000. On the first day of residency orientation, each resident was given a clinical scenario and registered through triage into the ED. Nurses were blinded to the study. The study concluded when the examining physician entered the exam room. Residents were then presented with a simulated bill based on their scenario. Residents completed a survey initially and at six months. Survey ratings were measured using a 100-mm visual analog scale (VAS) (0 = not at all; 100 = a great deal). RESULTS: Twenty-five residents participated over two years. Sixty-four percent had never been an ED patient before. Median length of stay was 139 minutes. This exercise was found to improve resident empathy for patients on initial survey, 66 mm (range 16-71), and at follow-up, 66 mm (range 23-91). Residents found the exercise useful both initially, 50 mm (range 4-86), and at follow-up, 49 mm (range 15-81). Ninety-two percent of the residents thought the goals of the exercise had been met. Residents also stated the study changed their approach to patient care (45 mm, range 4-76) and made them a better physician (49 mm, range 5-80). CONCLUSIONS: The ED visit study enhanced patient empathy within residents and was useful in improving patient care attitude.

Cognitive strategies for reporting portion sizes using dietary recall procedures.

OBJECTIVES: To examine recall strategies used by interview respondents when making judgments about portion size and to better understand how respondents use various portion-size aids. DESIGN: Study participants were separated into groups, each using a different set of portion-size estimation aids: (a) 2-dimensional paper aids presented in stacks, (b) 2-dimensional aids, cut out and presented on rings, (c) household-type aids, and (d) a combination of 2- and 3-dimensional aids, many of which are used in national government surveys. Respondents gave a "quick list" of foods consumed the previous day and practiced cognitive thinking skills. Then the interviewer selected at least 2 solid, 2 liquid, and 2 amorphous foods for probing. Respondents were asked to think aloud as they reported how much they ate of each food. Types and frequencies of cognitive strategies used for portion-size estimation were determined. SUBJECTS: Interviews of 1 to 1 1/2 hours were conducted with 76 adults aged 18 to 65 years. Participants were recruited to obtain a mix of races, ages, educational levels, and genders. RESULTS: The most frequently used strategy was visualization and comparison to aids. Others strategies were known amounts, estimations based on known amounts, visualization of volume or a container, and actions such as pouring or moving hands to the mouth. Respondents preferred aids that were similar in size and shape to actual portions consumed for liquid or amorphous food and preferred the ruler for solid foods. APPLICATIONS: To obtain the best data from dietary recalls, expect answers that are possible for respondents to give, supply respondents with aids that help them recall amounts consumed, and guide respondents to appropriate aids that help them formulate focused responses.

Effects of central infusion of ANG II and losartan on the cardiac baroreflex in rabbits.

The effect of chronic activation or inhibition of central ANG II receptors on cardiac baroreflex function in conscious normotensive rabbits was examined. Animals received a fourth ventricular (4V) infusion of ANG II (30 and 100 ng/h), losartan (3 and 30 microg/h), or Ringer solution (2 microl/h) for 2 wk. After 1 and 2 wk, ANG II (100 ng/h) decreased cardiac baroreflex gain by 20 and 37%, respectively (P = 0.015), whereas losartan (30 microg/h) increased baroreflex gain by 24 and 58%, respectively (P = 0.02). Within 1 wk of the end of the infusions, cardiac baroreflex gain had returned to control. Ringer solution or the lower doses of ANG II or losartan did not modify the cardiac baroreflex function. Blood pressure and heart rate were not altered by any treatment, nor was their variability affected. These data demonstrate a novel long-term modulation of cardiac baroreflexes by endogenous ANG II that is independent of blood pressure level.

Multiple roles for Src in a PDGF-stimulated cell.

The observation that platelet-derived growth factor (PDGF) increases the catalytic activity of Src family members (Src) suggests that they contribute to PDGF-dependent responses. The role of Src in PDGF-dependent cell cycle progression, phosphorylation of proteins, and chemotaxis has been tested by investigators using a variety of cell types and approaches, and it appears that the contribution of Src is highly variable. This idea is perhaps best illustrated by the finding that Src plays radically different roles downstream of the PDGF alpha- and beta-receptor subunits. Hence, Src is a versatile signal relay enzyme, whose contribution to a signaling cascade depends on variables such as the nature of the receptor via which the cell is activated, as well as the cell type itself.

Comparison of the baroreceptor-heart rate reflex effects of moxonidine, rilmenidine and clonidine in conscious rabbits.

In 10 conscious rabbits, the baroreceptor-heart rate (HR) reflex effects of centrally acting antihypertensive agents with high affinity for imidazoline receptors (IRs), moxonidine and rilmenidine, were compared with clonidine which acts predominantly via central alpha2-adrenoceptors. Dose regimens were chosen to give similar hypotension (-17+/-1 mm Hg) and bradycardia (-27+/-2 b/min) for all three agents given into the fourth ventricle. Baroreceptor-HR reflex curves were assessed by i.v. drug induced changes in blood pressure. With all treatments, the baroreflex curves with both vagal and sympathetic effectors intact were shifted to the left, corresponding to the hypotension, and the bradycardia plateau was reduced. Rilmenidine and moxonidine also reduced the upper plateau such that the curves were shifted parallel down the HR scale with no change in the HR range. By contrast, clonidine only decreased the lower plateau, and thus increased HR range (+19+/-6%). Moxonidine, but not rilmenidine, reduced the baroreflex gain by reducing the curvature. Clonidine also decreased curvature but this did not result in a reduction in gain as it was offset by the increase in HR range. The gain and range of the cardiac sympathetic component, as assessed after vagal blockade, was reduced by rilmenidine by 53 and 40% respectively, but was not affected by the other agents. The calculated vagal component of the curves showed that all agents produced a greater vagal bradycardia in response to a rise in pressure and that both rilmenidine and clonidine increased vagal HR range. The present study results show that many of the baroreflex effects of clonidine, such as facilitating cardiac vagal responses, are shared by the second generation agent rilmenidine, suggesting that they are primarily due to alpha2-adrenoceptor activation. In addition, the inhibition of the sympathetic component of the baroreflex, observed with rilmenidine, and not clonidine suggests that this effect may involve IRs. By contrast moxonidine, the most specific agent for I1 receptors, produces mainly a baroreflex independent inhibition of cardiac sympathetic activity with little effect on vagal activity.

Role of central catecholaminergic pathways in the actions of endogenous ANG II on sympathetic reflexes.

In the present study, we examined the effect of blockade of the brain stem renin-angiotensin system on renal sympathetic baroreflexes and chemoreflexes in conscious rabbits and examined the role of central catecholaminergic pathways in these responses. Eleven rabbits underwent preliminary surgical instrumentation and pretreatment with central 6-hydroxydopamine (6-OHDA, 500 micrograms/kg) or ascorbic acid 6 wk before the commencement of the experiments. Baroreflex curves were determined under conditions of normoxia and hypoxia (10% O2 + 3% CO2) before and after central administration of either Ringer solution, the ANG II receptor antagonist losartan (10 micrograms), or the angiotensin-converting enzyme inhibitor enalaprilat (500 ng) on separate days. Losartan increased the upper plateau and the range of the mean arterial pressure (MAP)-renal sympathetic nerve activity (RSNA) curve (79 and 78%, respectively) in intact rabbits, whereas this effect was not observed in 6-OHDA-pretreated rabbits. Hypoxia elicited an increase in resting RSNA (111% in intact rabbits and 74% in 6-OHDA-injected rabbits) and elevated the upper plateau of the RSNA-MAP curve in both groups (89% in intact rabbits and 114% in 6-OHDA-injected rabbits). During hypoxia, losartan and enalaprilat increased the RSNA upper plateau in intact rabbits but had no effect in 6-OHDA-pretreated rabbits. No effects on the MAP-heart rate baroreflex curves were observed. Thus the effect of losartan to increase RSNA, particularly during hypoxia and baroreceptor unloading, being abolished by central noradrenergic depletion suggests that the endogenous ANG II which normally causes an inhibition of renal sympathetic motoneurons is dependent on the integrity of central catecholaminergic pathways.

Adeno-associated virus Rep proteins target DNA sequences to a unique locus in the human genome.

We have developed a system for site-specific DNA integration in human cells, mediated by the adeno-associated virus (AAV) Rep proteins. In its normal lysogenic cycle, AAV integrates at a site on human chromosome 19 termed AAVS1. We describe a rapid PCR assay for the detection of integration events at AAVS1 in whole populations of cells. Using this assay, we determined that the AAV Rep proteins, delivered in cis or trans, are required for integration at AAVS1. Only the large forms of the Rep protein, Rep78 and Rep68, promoted site-specific integration. The AAV inverted terminal repeats, present in cis, were not essential for integration at AAVS1, but in cells containing Rep, they increased the efficiency of integration. In the presence of the Rep proteins, the integration of a plasmid containing AAV inverted terminal repeats occurred at high frequency, such that clones containing the plasmid could be isolated without selection. In two of the five clones analyzed by fluorescence in situ hybridization, the plasmid DNA was integrated at AAVS1. In most of the clones, at least one copy of the entire plasmid was integrated in a tandem array. Detailed analysis of the integrated plasmid structure in one clone suggested a complex mechanism producing rearrangements of the flanking genomic DNA, similar to those observed with wild-type AAV.