Evaluation of classic and novel ultrasound signs of placenta accreta spectrum.

OBJECTIVES: Improvement in the antenatal diagnosis of placenta accreta spectrum (PAS) would allow preparation for delivery in a referral center, leading to decreased maternal morbidity and mortality. Our objectives were to assess the performance of classic ultrasound signs and to determine the value of novel ultrasound signs in the detection of PAS. METHODS: This was a retrospective cohort study of women with second-trimester placenta previa who underwent third-trimester transvaginal ultrasound and all women with PAS in seven medical centers. A retrospective image review for signs of PAS was conducted by three maternal-fetal medicine physicians. Classic signs of PAS were defined as placental lacunae, bladder-wall interruption, myometrial thinning and subplacental hypervascularity. Novel signs were defined as small placental lacunae, irregular placenta-myometrium interface (PMI), vascular PMI, non-tapered placental edge and placental bulge towards the bladder. PAS was diagnosed based on difficulty in removing the placenta or pathological examination of the placenta. Multivariate regression analysis was performed and receiver-operating-characteristics (ROC) curves were generated to assess the performance of combined novel signs, combined classic signs and a model combining classic and novel signs. RESULTS: A total of 385 cases with placenta previa were included, of which 55 had PAS (28 had placenta accreta, 11 had placenta increta and 16 had placenta percreta). The areas under the ROC curves for classic markers, novel markers and a model combining classic and novel markers for the detection of PAS were 0.81 (95% CI, 0.75-0.88), 0.84 (95% CI, 0.77-0.90) and 0.88 (95% CI, 0.82-0.94), respectively. A model combining classic and novel signs performed better than did the classic or novel markers individually (P = 0.03). An increasing number of signs was associated with a greater likelihood of PAS. With the presence of 0, 1, 2 and ≥ 3 classic ultrasound signs, PAS was present in 5%, 24%, 57% and 94% of cases, respectively. CONCLUSIONS: We have confirmed the value of classic ultrasound signs of PAS. The use of novel ultrasound signs in combination with classic signs improved the detection of PAS. These findings have clinical implications for the detection of PAS and may help guide the obstetric management of patients diagnosed with these placental disorders. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Age-related changes in the propensity of dogs to bite.

This retrospective cohort study was aimed at describing the effects of age at acquisition, age, and duration of ownership of dogs on the risk of (1) bites during play and (2) non-play bites to humans. Data were collected on 110 dogs that had bitten during play with a person, 161 dogs that had bitten outside of play and 951 non-biting dogs from veterinary clients in Kingston (KGN), Jamaica and San Francisco (SF), USA. Modified Poisson regression was employed to model the relationships of both types of bites to each variable separately. Effects of the variables on dog bite risk (1) during and (2) outside of play with the dog, differed from each other and by type of bite. Effects varied with the dog's age and age-related associations were strongest in dogs younger than 1 year old. Ages at acquisition of dogs at highest risk for bites during play were substantially lower than those at risk for non-play bites. Ages and durations of ownership of dogs at highest risk for bites during play were also lower than those of dogs at highest risk for non-play bites. The propensity of a dog to bite changes as it ages and relationships between dog bites occurring during and outside of play and the dog's age at acquisition, current age, and duration of ownership, differ from each other.

Companion cats and the social support systems of men with AIDS.

60 male pet owners with AIDS were given a formal questionnaire including items related to demographic, lifestyle, and pet ownership, as well as the Comfort from Companion Animals Scale, the Revised UCLA Loneliness Scale, and the General Health Questionnaire (GHQ-28). The men lived in the San Francisco area and received assistance from Pets Are Wonderful Support (PAWS), a community organization, in caring for their companion dogs or cats. Participants were a convenience sample of pet owners who volunteered from among 500 PAWS clients and who do not necessarily represent a random sample of men with AIDS who keep companion animals. For these men, their comfort from companion animals was significantly associated with having cats but not dogs, closeness with friends, dissatisfaction with their practical support system, and listing pets as a source of support. Loneliness was negatively associated with having a large practical support network, scoring as healthy on the General Health Questionnaire, and living alone. For these male pet owners with AIDS, pet cats appeared to complement their supportive relationships with friends and family that were protective against loneliness.

Sarcoidosis.

Much has been learned over the last decade about the genetic predisposition to different patterns of sarcoidosis and its pathogenesis. These major advances have been possible through the very rapid evolution of newer molecular technology. The last two years have also seen the publication of an international statement on sarcoidosis that defines very clearly the presentation, clinical features, diagnosis and treatment of sarcoidosis and also clearly identifies areas where we need to know more. This review aims to highlight key issues that have emerged over the last five years. Specific focus is given to genetic predisposition and trigger factors-molecular epidemiology. The more novel approaches that have been taken to attempt to treat this disease more effectively are also addressed.

Linkage studies suggest a possible locus for developmental dyslexia on chromosome 1p.

Eight extended dyslexic families with at least four affected individuals were genotyped with twelve genetic markers spanning the Rh (rhesus factor) locus. Eleven of these markers were located on the short arm and the other was on the long arm of chromosome 1. Five theoretically derived phenotypes were used in the linkage analyses: 1) phonemic awareness; 2) phonological decoding; 3) rapid automatized naming; 4) single word reading; and 5) vocabulary. In addition, a lifetime diagnosis of dyslexia was used as a phenotype. Both parametric and non-parametric genetic analyses were completed. The results supported the importance of a putative locus on 1p. In addition, two-locus analyses assuming the interaction between a 1p locus and a 6p locus, previously shown to be of interest for dyslexia, were conducted. As a result, the nonparametric linkage (NPL) scores for rapid automatized naming and phonological decoding were significantly increased. In particular, the NPL scores for rapid automatized naming exceeded 5.0 for certain markers. These results provide strong evidence for separate but jointly acting contributions of the 1p and 6p loci to the reading impairments associated with rapid naming and suggestive evidence for a similar mechanism involving phonological decoding.

The MAP kinase inhibitors, PD098059, UO126 and SB203580, inhibit IL-1beta-dependent PGE(2) release via mechanistically distinct processes.

1. In common with human bronchial epithelial cells, pulmonary A549 cells release prostaglandin (PG) E(2) in response to pro-inflammatory cytokines. We have therefore used these cells to examine the effect of the selective mitogen activated protein (MAP) kinase inhibitors; PD098059, a mitogen activated and extracellular regulated kinase kinase (MEK) 1 inhibitor, UO126, a dual MEK1 & MEK2 inhibitor, and SB203580, a p38 MAP kinase inhibitor in the IL-1beta-dependent release of PGE(2). 2. Following IL-1beta treatment the extracellular regulated kinases (ERKs) and the p38 MAP kinases were rapidly phosphorylated. 3. PD09059, UO126 and SB203580 prevented IL-1beta-induced PGE(2) release at doses that correlated closely with published IC(50) values. Small or partial effects at the relevant doses were observed on induction of cyclo-oxygenase (COX) activity or COX-2 protein suggesting that the primary effects were at the level of arachidonate availability. 4. Neither PD098059 nor SB203580 showed any effect on IL-1beta-induced arachidonate release. We therefore speculate that the MEK1/ERK and p38 kinase cascades play a role in the functional coupling of arachidonate release to COX-2. 5. In contrast, UO126 was highly effective at inhibiting IL-1beta-dependent arachidonate release, implicating MEK2 in the activation of the PLA(2) that is involved in IL-1beta-dependent PGE(2) release. 6. We conclude that the MEK1, MEK2 and p38 MAP kinase inhibitors, PD098059, UO126 and SB203580, are highly potent in respect of inflammatory PG release. Finally, we conclude that these inhibitors act via mechanistically distinct processes, which may have anti-inflammatory benefits.

Event-related potentials correlate with task-dependent glucose metabolism.

Cognitive processing is associated with brain electrical activity that is reflected in event-related potentials (ERP). ERP during a target detection task, and regional cerebral glucose metabolism (CMRglc) measured simultaneously, may be influenced by the same neurophysiologic processes. We tested the hypothesis that ERP factors could be directly correlated with CMRglc to derive functional brain maps of brain activity at 120, 160, 200, 280, and 400 ms following stimulus presentation in a target detection task. We controlled for the potential confounding effects of age, sex, and task accuracy, and correlate target-related and nontarget-related ERP separately. Increases and decreases in CMRglc at each time point were identified with statistical parametric mapping (P < 0.001, uncorrected). The 120- and 160-ms maps were the same for target and nontarget processing, while maps for 280 and 400 ms clearly distinguished between targets and nontargets. Extrinsic (early) cognitive processes that depend mainly on stimulus characteristics show less variation based on stimulus meaning (i.e., letter vs shape; target vs nontarget) than later (intrinsic) cognitive processes. These early effects are lateralized to the left hemisphere, for negative ERP factors, and positive ERP-PET correlations are more likely than negative ERP-PET correlations. Thus, brain areas related to task processing impact both ERP and CMRglc measures, suggesting a shared neurophysiologic mechanism for negative ERP factors and increased CMRglc. Direct statistical analysis of these two measures using statistical parametric mapping provides high spatial and temporal resolution in multisubject experiments, while requiring only a single (18)FDG PET scan per subject.

The role of police dogs as companions and working partners.

Written responses to a questionnaire by 255 officers who used canines in police work were assessed. Almost all officers frequently played with, talked to, petted, and brushed their dogs and believed the dogs benefitted their health and well-being. Officers whose dogs slept indoors, often in the same bedroom, generally said they loved their dogs and they described their dogs as calm rather than active, as indicated by a multiple correspondence analysis. These 96 officers more than the 154 officers whose dogs slept outdoors or in kennels also planned to remain in canine work. Although departments often assumed responsibility for purchasing the dogs, the more experienced officers usually were involved in the final selection of dogs (logistic regression: p < .0001). Compared with 94 officers not involved in selecting their dogs, 106 officers with a specific role in selecting their dogs planned to stay in canine work, as shown by a multiple correspondence analysis. They believed the dogs had saved their lives (p < .01). Over-all, officers reported spending 4.1 hr. on-duty and 2.9 hr. off-duty per week training their dogs, and also played with them for 6.5 hr. per week, assuring a regular pattern of exercise for the officers. Virtually all officers valued canine service and believed the dogs enhanced the department's effectiveness. This study showed that both close companionship with the dog and involvement in selecting the dog were associated both with satisfaction with the dog and with working as a canine officer.

Seismic properties of Asian elephant (Elephas maximus) vocalizations and locomotion.

Seismic and acoustic data were recorded simultaneously from Asian elephants (Elephas maximus) during periods of vocalizations and locomotion. Acoustic and seismic signals from rumbles were highly correlated at near and far distances and were in phase near the elephant and were out of phase at an increased distance from the elephant. Data analyses indicated that elephant generated signals associated with rumbles and "foot stomps" propagated at different velocities in the two media, the acoustic signals traveling at 309 m/s and the seismic signals at 248-264 m/s. Both types of signals had predominant frequencies in the range of 20 Hz. Seismic signal amplitudes considerably above background noise were recorded at 40 m from the generating elephants for both the rumble and the stomp. Seismic propagation models suggest that seismic waveforms from vocalizations are potentially detectable by instruments at distances of up to 16 km, and up to 32 km for locomotion generated signals. Thus, if detectable by elephants, these seismic signals could be useful for long distance communication.

Animals in elementary school education in California.

The purpose of this project was to provide preliminary, descriptive data concerning the uses of nonhuman animals in northern California elementary school classrooms. The project comprised a mail survey that was sent to all elementary school teachers in Stanislaus County, California, followed by a workshop with survey respondents. Information gathered included that about animals and the use of animals, the learning objectives for the animal-related instructional activities, and the kinds of resources that would help teachers to improve or expand their existing animal-related activities or to create new ones. Most of the teachers were keeping either live animals or a variety of nonliving specimens in the classroom. They reported that animals and information about animals are popular and effective foci of instruction throughout the primary grades. The majority of respondents stated that live animals, in addition to providing formal lessons in science and cross-curricular instruction, are important for teaching children humane values. They also reported the many drawbacks of maintaining live classroom animals, such as the responsibility and cost of ongoing care, potential health and safety issues for the children, and concerns about the welfare of the animals. Because animals used in precollege education are not subject to legal regulations in the United States, some degree of oversight by the school or school district may help to avert potential problems.

Effect of inhaled endotoxin on induced sputum in normal, atopic, and atopic asthmatic subjects.

BACKGROUND: Inhalation of lipopolysaccharide (LPS) causes an inflammatory response in the lungs. To explore this response, inflammatory indices were measured in induced sputum from atopic asthmatic patients and compared with atopic and non-atopic subjects after inhalation of LPS. METHODS: The effects of inhaled LPS (60 micrograms) or placebo (0.9% saline) were examined in a randomised, double blind, crossover trial in 11 non-atopic normal subjects, seven atopic, non-asthmatic individuals, and eight atopic, asthmatic patients. Sputum was induced by inhalation of 3.5% saline before the test inhalation and again at six hours and 24 hours. Spirometry (forced expiratory volume in one second (FEV1), forced vital capacity (FVC)), heart rate, blood pressure, and temperature were recorded before challenge and at intervals until eight hours, and at 24 hours after challenge. RESULTS: There was no change in cardiovascular parameters or spirometry with either exposure in any group. In the asthmatic patients only, inhalation of LPS caused a rise in temperature, with a peak of 0.6 degree C at seven hours, which was significantly higher than following placebo inhalation (p < 0.05). In normal subjects, LPS caused a significant rise in absolute neutrophil counts at 24 hours compared with placebo (median 1.1 x 10(6) cells/ml after LPS; median 0.2 x 10(6) cells/ml after placebo, p < 0.01), but no change in differential counts. In asthmatic patients, LPS caused a significant rise in differential neutrophil counts at six hours compared with placebo (median 88% after LPS; median 56% after placebo, p < 0.05), but no change in absolute cell counts at any time point. There was no change in neutrophil counts in the atopic subjects. There was a significant rise in sputum interleukin 8 (IL-8) concentrations in normal subjects at six hours compared with placebo (mean placebo 1.1 ng/ml; LPS 3.0 ng/ml, p < 0.05) and in asthmatics at 24 hours (mean placebo 2.0 ng/ml, LPS 6.9 ng/ml, p < 0.05). There were no changes in sputum concentrations of tumour necrosis factor alpha or granulocyte macrophage colony stimulating factor at any time. CONCLUSIONS: Inhalation of LPS causes a neutrophilic inflammation with increases in IL-8 in both normal and asthmatic subjects.

Activation and localization of transcription factor, nuclear factor-kappaB, in asthma.

Asthma is associated with increased expression of inflammatory proteins including cytokines, enzymes, and adhesion molecules. Induction of many of the genes for these proteins is regulated by the transcription factor, nuclear factor-kappaB (NF-kappaB). We therefore examined whether airway cells from patients with asthma show increased activation of NF-kappaB. Nuclear proteins were extracted from cells of induced sputum and from bronchial biopsies of normal subjects and patients with asthma. NF-kappaB-binding to its consensus DNA binding site, as investigated with 32P-labeled oligonucleotides and electrophoretic-mobility-shift assay, showed a 2.5-fold increase (p < 0.003) in NF-kappaB-DNA binding in induced sputum of asthma patients. Nuclear staining, representing activated NF-kappaB, was observed in macrophages of induced sputum. Immunohistochemical examination of bronchial biopsy specimens with an antibody to p65, a constituent of NF-kappaB, showed more airway epithelial cells with nuclear staining in asthma patients (45.1 +/- 7.2% versus 20.7 +/- 3.9%; n = 9; p < 0.01), and a 2.5-fold greater number of cells with cytoplasmic staining in the mucosal region (p < 0.05). Pooled nuclear extracts of bronchial biopsy specimens from asthma patients showed a 44% greater level of NF-kappaB-DNA binding. Activation of NF-kappaB may be the basis for increased expression of many inflammatory genes and for the perpetuation of chronic airway inflammation in asthma.

Effect of dexamethasone on interleukin-1beta-(IL-1beta)-induced nuclear factor-kappaB (NF-kappaB) and kappaB-dependent transcription in epithelial cells.

The production of inflammatory mediators by epithelial cells in inflammatory lung diseases may represent an important target for the anti-inflammatory effects of glucocorticoids. Nuclear factor-kappaB (NF-kappaB) is a major activator of inflammatory genes and has been proposed as a target for inhibition by glucocorticoids. We have used human pulmonary type-II A549 and airway epithelial BEAS-2B cells to investigate the effect of glucocorticoids on NF-kappaB regulation and kappaB-dependent transcription. In A549 cells following interleukin-1beta (IL-1beta) treatment, there was no effect of dexamethasone on the disappearance of I kappaB alpha protein, its subsequent reappearance 90-min later or the rapid induction of I kappaB alpha mRNA and transcription rate. Expression of p65 and p50/p105 proteins were also unaffected by dexamethasone. In addition, the rapid IL-1beta-induction of NF-kappaB DNA binding and p65 nuclear localisation was unaffected by short (1-6 hours) dexamethasone pre-treatments. Similarly, BEAS-2B cells showed no effect of dexamethasone on IL-1beta-induced NF-kappaB (p50/p65). Stable transfection of a kappaB-dependent reporter in A549 cells resulted in an 8-9-fold activation by IL-1beta or phorbol ester, that was repressed 30-40% by dexamethasone. However, in these cells, IL-1beta induction of inducible nitric oxide synthase, granulocyte-macrophage colony stimulating factor and cyclooxygenase-2 mRNA showed 70-90% repression by dexamethsone. We, therefore, conclude that in these epithelial cells, the repressive effects of glucocorticoids are not mediated by up-regulation of I kappaB alpha, decreased p50/p65 gene expression or inhibition of NF-kappaB DNA binding. Furthermore, since the maximal repression of IL-1beta or phorbol-ester-induced kappaB-dependent transcription by dexamethasone was less than 40%, simple inhibition of kappaB-dependent transcription cannot by itself account for the full repressive effects of glucocorticoids observed in these cells.

A high-throughput hybridization method for titer determination of viruses and gene therapy vectors.

One of the challenges facing researchers working with viruses and gene therapy vectors is the need to rapidly assay for infectious virus. Current methods used to titer many viruses are cumbersome and are not amenable to handling large numbers of samples. Here we describe the development of an assay that can rapidly quantify infectious viruses and gene therapy vectors. The assay relies on biological amplification of viral sequences and hybridization of labeled probes to immobilized nucleic acid from infected cells. The amplification of the viral genome makes this a highly sensitive method. The assay is configured in a high-throughput format that has been used to detect recombinant adeno-associated virus (AAV), wild-type AAV and infectious adenovirus. The assay is quantitative, and can be used to titer virus preparations with or without a known standard.

Selective predictive value of rapid automatized naming in poor readers.

This study considers the differential predictive value of rapid naming tests for various aspects of later reading, where the differential is between nondisabled and poor readers. Two large-N longitudinal samples of students who have been evaluated from third through eighth grades are studied: (a) a randomly accessed, normally distributed group including students with varying degrees of reading ability (N = 154), and (b) a group of poor readers whose single-word reading in third grade is at or below the population 10th percentile (N = 64). Outcomes in fifth and eighth grade were measured in both groups. Single-word reading in both grades was strongly predicted from third-grade rapid naming only within the poor readers, even when IQ, socioeconomic status, and third-grade single-word reading were statistically controlled. Although rapid naming had predictive value within the large, normally distributed group, its predictive power was entirely absent in the average-reading nondisabled students who were between the 10th and 90th percentiles (n = 122). The fact that rapid naming has predictive power only for poor readers but not for average readers is interpreted as suggesting that impaired readers are qualitatively different from the normal-reading population and are not simply the "tail" of a normal distribution of reading ability. It also seems that it is the automaticity of retrieval, not the knowledge of names itself (as in confrontational naming tasks), that gives the predictive power in rapid naming. These data are considered in light of the one- and two-factor theories of the underlying processes involved in reading disability or dyslexia.

Superinduction of COX-2 mRNA by cycloheximide and interleukin-1beta involves increased transcription and correlates with increased NF-kappaB and JNK activation.

Many primary response genes, including cyclooxygenase-2 (COX-2), exhibit mRNA superinduction following agonist stimulation in the presence of translational blockers such as cycloheximide. This is widely assumed to result from mRNA stabilisation. However, superinduction of IL-1beta-induced COX-2 mRNA levels by cycloheximide in pulmonary type II A549 cells occurred by increased transcription and not by mRNA stabilisation. Furthermore, equivalent effects were observed on NF-kappaB binding to COX-2 promoter kappaB sites and activation of the Jun N-terminal kinases (JNK), p54 and p46. These signalling pathways play important roles in COX-2 induction and may therefore account for the observed increases in COX-2 transcription. These data are consistent with negative feed-back involving down-regulation of NF-kappaB by de novo IkappaB alpha synthesis and suggest that JNK activation may also be down-regulated by a cycloheximide sensitive process.

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report.

The purpose of this study was to evaluate the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin in patients with endometrial cancer known to be resistant to standard therapy. Subjects were taken from three groups: (1) recurrent or persistent disease following surgery and/or radiation, (2) advanced disease at diagnosis, and (3) high-risk histology. The combination of carboplatin (pharmacologically dosed at an area under the concentration-time curve of 5) and paclitaxel (135 to 175 mg/m2 over 3 hours) was given intravenously every 4 weeks for eight courses. Data about response, overall and progression-free survival, and toxicity were collected. Response and toxicity were evaluated by physical examinations, x-ray films, and blood tests. Twenty patients have participated to date, including eight considered evaluable for response. Due to limited follow-up, survival and progression-free intervals are not yet assessable. Of patients with measurable disease, five of eight (63%) have had significant reduction in the size of evaluable tumor masses, constituting a partial response. Although two patients had clinical and radiographic complete responses, occult disease was found at surgery. There were no complete responders. Fifteen patients had grade 3 or 4 hematologic toxicity, but none had neutropenic fever or hospitalization for sepsis. One patient was taken off study for grade 3 neuropathy. There was one possible treatment-related death. In this preliminary report, this combination is active against tumors of the endometrium, with acceptable levels of toxicity. Further follow-up will be required to determine the duration of response and whether progression-free and overall survival are influenced by treatment with these drugs.

Correlation among three psychological scales used in research of caregivers for patients with Alzheimer's disease.

This study was conducted to assess whether three scales commonly used in psychological research of Alzheimer's disease caregivers-Caregiver Burden Interview, Life Satisfaction Index-Z, and Geriatric Depression Scale-measure similar or different aspects of mental health. Responses from 244 nonprofessional caregivers were used to estimate factor structure, intercorrelation, and independent variables associated with the three scales. Self-rated health was the only variable significantly associated with scores on all three scales. Financial concern and number of weekly telephone calls were associated with total scores on the Satisfaction and Depression scales. Factor models of five, three, and six factors were fitted for the Burden, Satisfaction, and Depression scales, respectively. Correlations of factor scores and canonical variables among the scales did not yield strong associations between subsets of items. Although a few common aspects of caregiving influence scores of all three techniques, the facets of caregivers' psychology assessed by the three scales appear to be different.