Prenatal infection with Mycoplasma pulmonis in rats exaggerates the angiotensin II pressor response in adult offspring.

Exposure to different stressors in utero is linked to adult diseases such as obesity and hypertension. In this study, the impact of prenatal infection (PNI) on adult body weight and cardiovascular function was evaluated using a naturally occurring rodent pathogen, Mycoplasma pulmonis (MP). Pregnant Sprague-Dawley rats were infected with MP on gestationalday 14 and gave birth naturally. Adult PNI offspring weighed more than controls, but resting mean arterial pressure (MAP) was unchanged. Subcutaneous injection of angiotensin II (10 µg/kg) elicited a rise in MAP that was greater in both male and female PNI offspring compared with controls (P < 0.03). The accompanying reflex bradycardia was similar to the controls, suggesting that PNI induced baroreflex dysfunction. Subcutaneous nicotine administration, a potent cardiorespiratory stimulus, also elicited a transient rise in MAP that was generally greater in the PNI group, but the change in MAP from baseline was only significant in the PNI females compared with controls (P < 0.03). Elevated body weight and cardiovascular reactivity in the PNI offspring was associated with an increase in the ratio of hypothalamic corticotrophin-releasing hormone receptors type 1 to type 2 gene expression in both sexes compared with controls. These findings support previous studies demonstrating that PNI induces alterations in cardiovascular function and body weight. Yet, unlike previous studies utilizing other models of PNI (e.g., endotoxin), MP PNI did not induce resting hypertension. Thus, our study provides a foundation for future studies evaluating the cardiovascular risks of offspring exposed to microbial challenges in utero.

Brachionus leydigii (Monogononta: Ploima) reported from the western basin of Lake Erie.

Several species of non-indigenous planktonic invertebrates have historically been introduced to the Laurentian Great Lakes. Previous introductions of non-indigenous planktonic invertebrates to the Great Lakes have been crustacean zooplankton, specifically Cladocera and Copepoda. This report documents the first known occurrence of Brachionus leydigii var. tridentatus (Zernov, 1901) in Lake Erie and possibly the first detection of a non-indigenous rotifer species in the Laurentian Great Lakes. The specimen was collected from a U.S. EPA monitoring station in the western basin of Lake Erie on April 4, 2016.

DOCA/salt hypertension alters Period1 and orexin-related gene expression in the medulla and hypothalamus of male rats: Diurnal influences.

In peripheral tissues, aldosterone alters expression of multiple genes, including the clock gene Period 1 (Per1), 11 beta-hydroxysteroid dehydrogenase-2 (11-HSD2), and α-ENAC, the epithelial sodium channel subunit. We evaluated the impact of chronic aldosterone exposure (DOCA) and salt intake on nocturnal changes in gene expression in the male Sprague Dawley rat brain. Additionally, genes associated with the orexin (ORX) system were also evaluated based on the role of this neuropeptide in arousal, feeding and hypertension and an interconnection with Per1 expression. DOCA/salt treatment increased saline intake primarily at night, elevated arterial pressure and lowered heart rate. In the medulla oblongata, DOCA/salt upregulated Per1, 11-HSD2, and α-ENAC expression independent of time of day, but did not change ORX receptor type 1 (ORX-R1) or type 2 (ORX-R2) expression. ORX-R1, and ORX-R2 expression in the medulla did however correlate with Per1 expression following DOCA/salt treatment but not in controls. In the hypothalamus, DOCA/salt treatment upregulated Per1, ORX-A, and ORX-R2 expression, in general, and Per1 and ORX-A expression at night. ORX-A, ORX-R1 and ORX-R2 expression in the hypothalamus correlated with Per1 expression following DOCA/salt but not in controls. These findings demonstrate for the first time that DOCA/salt hypertension modulates ORX gene expression in the brain and suggest that changes in expression in the ORX system may occur directly or indirectly via aldosterone-induced changes in Per1 expression. Our findings also build on emerging evidence that monitoring gene expression during both the day and night is critical to understanding the role of specific genes in hypertension.

Undergraduates achieve learning gains in plant genetics through peer teaching of secondary students.

This study tests the hypothesis that undergraduates who peer teach genetics will have greater understanding of genetic and molecular biology concepts as a result of their teaching experiences. Undergraduates enrolled in a non-majors biology course participated in a service-learning program in which they led middle school (MS) or high school (HS) students through a case study curriculum to discover the cause of a green tomato variant. The curriculum explored plant reproduction and genetic principles, highlighting variation in heirloom tomato fruits to reinforce the concept of the genetic basis of phenotypic variation. HS students were taught additional activities related to mole-cular biology techniques not included in the MS curriculum. We measured undergraduates' learning outcomes using pre/postteaching content assessments and the course final exam. Undergraduates showed significant gains in understanding of topics related to the curriculum they taught, compared with other course content, on both types of assessments. Undergraduates who taught HS students scored higher on questions specific to the HS curriculum compared with undergraduates who taught MS students, despite identical lecture content, on both types of assessments. These results indicate the positive effect of service-learning peer-teaching experiences on undergraduates' content knowledge, even for non-science major students.

Ultrasound-guided tandem placement for low-dose-rate brachytherapy in advanced cervical cancer minimizes risk of intraoperative uterine perforation.

OBJECTIVES: Tandem placement as part of low-dose-rate (LDR) brachytherapy boost for cervical cancer may be complicated by uterine perforation. The objective of this study was to describe a 10-year experience of using intraoperative ultrasound guidance in an attempt to minimize the risk of uterine perforation. METHODS: Operative and inpatient records were reviewed to identify cases in which intraoperative ultrasound guidance was employed in order to assist tandem placement, and to determine whether clinical or radiographic findings subsequently suggested uterine perforation. Demographic factors were collected in order to determine the baseline risk of perforation within this population. RESULTS: Between 1998 and 2008, 71 patients underwent 110 ultrasound-guided placements of tandem applicators. The median age was 48 (range, 26-88) years, and 20% were older than 60 years. Disease stage was FIGO IB1 (n = 10), IB2 (n = 13), IIA (n = 4), IIB (n = 19), IIIA (n = 2), IIIB (n = 16), IVA (n = 5) and IVB (n = 2). The median gravidity was 3 (range 1-10) and median parity was 3 (range 0-10). Seven patients had a preimplant history of pelvic infection, four had a history of intrauterine contraceptive device use, and 10 had a prior history of Cesarean section delivery. Only one patient experienced infection that may have been attributable to tandem placement-associated uterine perforation. At median survivor follow-up of 34 months, 19 patients had died. The estimated 3-year disease-free and overall survival rates for the entire population were 60% and 66%, respectively. CONCLUSIONS: Within the present population, intraoperative ultrasound guidance of tandem placement was associated with no confirmed cases of uterine perforation.

High-dose fractionated radiotherapy to 80 Gy for stage I-II medically inoperable non-small-cell lung cancer.

INTRODUCTION: Management of medically inoperable non-small-cell lung cancer (NSCLC) has been historically challenging, with poor rates of local control and disease-specific survival. Nearly all published series of standard fractionation radiotherapy have utilised doses <70 Gy. The present investigation describes disease control and survival outcomes for a large series of patients prescribed high-dose radiotherapy for early-stage NSCLC. METHODS: Retrospective analysis of disease control and survival outcomes for stages I-II NSCLC patients prescribed ≥70 Gy at 1.8-2.5 Gy per fraction. RESULTS: Between May 1997 and August 2008, 100 primary lung tumours in 98 patients (two metachronous) were eligible for analysis. The median age was 71 years (range 49-93), and 92 patients were considered medically inoperable. Nearly all cases were clinical stage cT1N0 (51 patients) or cT2N0 (35). The median radiotherapy dose prescribed was 80.5 Gy (range 70-90). At a median follow-up of 18 months, 72 patients died (44 of/with disease) and 50 experienced recurrence. The estimated 3-year in-field control, progression-free survival, disease-specific, and overall survival rates were 50, 29, 30 and 24%, respectively. Univariate analyses demonstrated an inverse association between local control and tumour size. Medical inoperability was associated with decreased disease-specific and overall survivals. Patient age and biologically equivalent dose were also associated with overall survival. CONCLUSIONS: Disease control and survival of fractionated radiotherapy for early-stage NSCLC remain suboptimal. Medical inoperability is associated with worse overall survival; however, local control remains a predominant pattern of failure despite 80 Gy in standard fractionation, particularly in patients with larger tumour size.

Attention in HIV-infected children: results from the Hemophilia Growth and Development Study.

Attentional functioning was examined in three groups of 7- to 19-year-old male participants with hemophilia: (1) HIV seronegative controls (HIV-, N = 66), (2) HIV seropositive participants with CD4+ lymphocyte counts greater than or equal to 200 (HIV+ CD4+ > or = 200, N = 79), and (3) severely immune suppressed HIV seropositive participants (HIV+ CD4+ < 200, N = 28). Two measures sensitive to attention deficits were used: the Continuous Performance Test (CPT) and the Span of Apprehension (Span). On the CPT, there was a decrement in attention in both HIV+ groups, as indexed by an increase in false alarm rate from Block 1 to Block 3, that was not present in the HIV- group. The longer the HIV+ children were required to sustain attention to the CPT, the more they responded to the incorrect stimulus. This effect decreased as age increased. Span percent correct and latency to correct were associated with the presence of a premorbid history of intracerebral hemorrhage, but were not sensitive to HIV status or degree of immune suppression in the HIV+ children, suggesting morbidity related to hemophilia. The remaining CPT and Span variables--hit rate, sensitivity, latency, percent correct, and latency to correct--showed the expected associations with age, but none showed conclusive associations with HIV status or immune suppression in the HIV+ participants.

Declining immune function in children and adolescents with hemophilia and HIV infection: effects on neuropsychological performance. Hemophilia Growth and Development Study.

OBJECTIVE: To determine whether declines in immune functioning are associated with changes in neuropsychological performance in children and adolescents with hemophilia who are infected with the human immunodeficiency virus (HIV). METHODS: Participants were 333 males with hemophilia, ages 6-19 years at entry. A baseline and four annual neuropsychological evaluations were given. A longitudinal growth curves analysis of data was performed to detect changes associated with declining immune function. The cohort was stratified into four groups: (1) HIV- (n = 126); (2) HIV+, average of first two and last two CD4 counts > or = 200, (n = 106; High CD4 group); (3) HIV+, average first two counts > or = 200, average last two counts < 200 (n = 41; CD4 Drop group); and (4) HIV+, average first two and last two counts < 200 (n = 60; Low CD4 group). RESULTS: There were significant differences among the four groups over time in nonverbal intelligence, perceptual/performance skills, nonverbal memory, academic achievement, and language. The Low CD4 group consistently showed the greatest decrement in performance. On measures showing a practice effect for repeated measurements, the Low CD4 group participants' scores remained stable over time, suggesting opposing effects of practice and HIV-related declines. Lowered academic performance relative to IQ was found in all groups. CONCLUSIONS: Declines in neuropsychological functioning are directly related to declines in immune functioning in HIV+ children, adolescents, and young adults with hemophilia. Hemophilia itself may be a risk factor for academic underachievement.

Heparan preserves intestinal perfusion after hemorrhage and resuscitation.

BACKGROUND: Multiple system organ failure (MOF) remains a major source of morbidity and mortality in trauma patients. Despite restoration of central hemodynamics, intestinal hypoperfusion can persist. Mucosal ischemia and barrier breakdown are factors in the genesis of MOF. Heparan sulfate is a gycosaminoglycan similar to heparin, but with minimal anticoagulant properties. As an adjunct to resuscitation, it improves immunologic function and restores mucosal oxygenation and function. We hypothesized that resuscitation with heparan following hemorrhage wound prevents intestinal hypoperfusion. MATERIALS AND METHODS: In vivo videomicroscopy was used to study small intestine microcirculation in rats. Animals were hemorrhaged to 50% of baseline mean arterial pressure (MAP) and maintained there. Resuscitation was initiated when the return of 10% shed blood was required to keep MAP at 50%. Animals received either heparan (7 mg/kg/1 ml saline) or saline (1 ml) followed by the remaining shed blood and an equal volume of saline. MAP, cardiac output (CO), A1 arteriole diameters, and flow were determined. RESULTS: Resuscitation of the saline control group resulted in normal MAP with elevation of CO to 25-40% above baseline. The heparan group had return of MAP but only a moderate increase in CO (7-15%). Saline resuscitation led to progressive deterioration in A1 diameters and flow. The addition of heparan prevented delayed A1 constriction and significantly improved perfusion. CONCLUSIONS: Heparan prior to resuscitation improved intestinal perfusion, despite a relative reduction in CO. Improvement in nutrient blood flow may protect the mucosal barrier, reducing the incidence of MOF, and suggests that heparan may be useful in resuscitation of trauma patients.

Cognitive/neuropsychological studies of children with a schizophrenic disorder.

This article summarizes a series of cognitive/neuropsychological studies of children with schizophrenia. One set of studies, which surveyed a broad range of neuropsychological functions, revealed no evidence that children with schizophrenia are consistently impaired in sensory, perceptual, or language functions. Rather, the studies showed that children with schizophrenia performed poorly on tasks requiring sensory, perceptual, and language processing that made extensive demands on information-processing capacity. A second series of studies, which examined visual information processing by manipulating the processing demands of span of apprehension tasks, yielded similar findings. The key characteristic of tasks that elicit impaired performance in children with schizophrenia is that the task makes extensive demands on processing resources. This suggests that these children have limited information-processing capacity. Three hypotheses are proposed concerning the cognitive processes that are impaired in children with schizophrenia: (1) the cognitive processes that seem to be impaired in these children are part of a more general, hierarchically organized attention system; (2) the component processes of the system are subserved by different brain structures; and (3) the structures are part of a network that includes the frontal lobe and thalamus in interaction with the reticular activating system.

Reactivity of monoclonal antibody E5 with endotoxin. I. Binding to lipid A and rough lipopolysaccharides.

The murine IgM monoclonal antibody (mAb) E5 was produced by a hybridoma derived from spleen cells of a mouse immunized with the J5 rough mutant of Escherichia coli O111:B4. In a multicenter randomized placebo-controlled clinical trial, E5 has been shown to reduce significantly the mortality and morbidity of patients with Gram-negative sepsis. The characteristics of E5 binding to endotoxin were studied in vitro. We report here the results of binding to an extensive panel of rough lipopolysaccharide (LPS) and lipid A preparations. Using standard immunologic techniques, including enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), as well as an antibody capture assay using immobilized antibody and a chromogenic Limulus amebocyte lysate (LAL) detection system, E5 was shown to bind to all rough LPS (chemotypes Ra through Re from Salmonella minnesota and E. coli J5) and lipid A preparations tested. E5 displayed a Kd for Ra LPS of approximately 6.5 nM. These results confirm and extend those reported previously and provide evidence that E5 binds specifically to lipid A and to the lipid A moiety of rough LPS.

Symptom development in childhood onset schizophrenia.

Symptom development from birth to 12 years of age was examined in 18 children who met DSM-III criteria for schizophrenia with onset before 10 years of age. Using a follow-back design, symptom development was rated at each of four age levels using a DSM-III Symptom Rating Scale and the Achenbach Child Behavior Checklist. Results revealed a gradual developmental unfolding of a broad spectrum of symptoms affecting social, cognitive, sensory and motor functioning and beginning many years before the appearance of schizophrenic symptoms--usually in early infancy. Prior to 6 years of age, severe language deficits and motor development problems were each found in 72% of the sample and symptoms of infantile autism were found in 39% of the sample. Onset of schizophrenia occurred at an earlier age for children with a history of autistic symptoms during infancy than for other children in the sample. Schizophrenia as defined by DSM-III was entirely absent before 6 years of age.

Emergency department screening for unsuspected carbon monoxide exposure.

Carbon monoxide (CO) is the leading toxic cause of death in the United States today. Unsuspected exposure to this gas will sometimes result in clinically significant, but undiagnosed, toxicity. A high incidence of such unsuspected exposures would make screening for these worthwhile among high-risk populations. We conducted a two-part study to determine the value of screening for unsuspected CO exposure in a population of patients presenting to an emergency department. The first part of our study involved the prospective screening of ED patients using CO breath analysis, regardless of their chief complaint. In the second part, COHGB levels of all patients who underwent arterial blood gas analysis during the study period were reviewed retrospectively. Of 1,038 patients screened by this combined approach, only 29 (2.8%) had abnormal CO breath readings and/or COHGB levels. Of a condensed subgroup of 152 patients defined retrospectively by chief complaint, eight (5.3%) had abnormal values. We conclude that routine screening of ED patients for unsuspected CO exposure is not practical. Although yield increases when patients are screened in a more selective manner on the basis of chief complaint, such an increase still does not appear to justify the screening process.

A longitudinal study of respiratory viruses and bacteria in the etiology of acute otitis media with effusion.

We analyzed data from a 14-year longitudinal study of respiratory infections in young children to determine the relative importance of viral respiratory infection and nasopharyngeal colonization with Streptococcus pneumoniae and Haemophilus influenzae as factors influencing the occurrence of acute otitis media with effusion. The incidence of this disorder was increased in children with viral respiratory infections (average relative risk, 3.2; P less than 0.0001). Infection with respiratory syncytial virus, influenza virus (type A or B), and adenovirus conferred a greater risk of otitis media than did infection with parainfluenza virus, enterovirus, or rhinovirus. Colonization of the nasopharynx with Str. pneumoniae or H. influenzae had a lesser effect on the incidence of the disease (average relative risk; 1.5; P less than 0.01). Infections with the viruses more closely associated with acute otitis media (respiratory syncytial virus, adenovirus, and influenza A or B) were correlated with an increased risk of recurrent disease. Prevention of selected otitis-associated viral infections should reduce the incidence of this disease.