Constructing Ebola transmission chains from West Africa and estimating model parameters using internet sources.

During the recent Ebola crisis in West Africa, individual person-level details of disease onset, transmissions, and outcomes such as survival or death were reported in online news media. We set out to document disease transmission chains for Ebola, with the goal of generating a timely account that could be used for surveillance, mathematical modeling, and public health decision-making. By accessing public web pages only, such as locally produced newspapers and blogs, we created a transmission chain involving two Ebola clusters in West Africa that compared favorably with other published transmission chains, and derived parameters for a mathematical model of Ebola disease transmission that were not statistically different from those derived from published sources. We present a protocol for responsibly gleaning epidemiological facts, transmission model parameters, and useful details from affected communities using mostly indigenously produced sources. After comparing our transmission parameters to published parameters, we discuss additional benefits of our method, such as gaining practical information about the affected community, its infrastructure, politics, and culture. We also briefly compare our method to similar efforts that used mostly non-indigenous online sources to generate epidemiological information.

A circuit perspective on narcolepsy.

The sleep disorder narcolepsy is associated with symptoms related to either boundary state control that include excessive daytime sleepiness and sleep fragmentation, or rapid eye movement (REM) sleep features including cataplexy, sleep paralysis, hallucinations, and sleep-onset REM sleep events (SOREMs). Although the loss of Hypocretin/Orexin (Hcrt/Ox) peptides or their receptors have been associated with the disease, here we propose a circuit perspective of the pathophysiological mechanisms of these narcolepsy symptoms that encompasses brain regions, neuronal circuits, cell types, and transmitters beyond the Hcrt/Ox system. We further discuss future experimental strategies to investigate brain-wide mechanisms of narcolepsy that will be essential for a better understanding and treatment of the disease.

Validation of an electronic tool for flagging surgical site infections based on clinical practice patterns for triaging surveillance: Operational successes and barriers.

BACKGROUND: Surveillance is an effective strategy for reducing surgical site infections (SSIs); however, current identification methods are resource-intensive. Therefore, we sought to validate an electronic SSI triaging tool for detection of probable infections and identify operational barriers and challenges. METHODS: A retrospective cohort study was conducted among all Veterans Affairs Surgical Quality Improvement Program (VASQIP)-reviewed surgeries at 2 Veterans Affairs medical centers from October 1, 2011-September 30, 2014. During the postoperative period, clinical and administrative variables associated with SSI (relevant microbiology order, antibiotic order, radiology order, and administrative codes) were extracted from the electronic medical record and used to score the probability (high, intermediate, and low) that an SSI occurred. VASQIP manual chart review was used as the gold standard of comparison. RESULTS: VASQIP manual review identified 118 SSIs out of 3,700 surgeries (3.2%). There were 2,041, 1,428, and 231 surgeries that met criteria for low, intermediate, and high probability for SSI. The tool's area under the curve was 0.86 (95% confidence interval, 0.82-0.89). The sensitivity among low-probability surgeries was 92.4%, and the specificity among high-probability surgeries was 95.1%. CONCLUSIONS: The electronic SSI tool has the potential to be used for triaging VASQIP surveillance toward the high-probability surgeries and to avoid manual review of surgeries with low probability of SSI.

A pleiotropic element in the medium-chain acyl coenzyme A dehydrogenase gene promoter mediates transcriptional regulation by multiple nuclear receptor transcription factors and defines novel receptor-DNA binding motifs.

We previously identified a complex regulatory element in the medium-chain acyl coenzyme A dehydrogenase gene promoter that confers transcriptional regulation by the retinoid receptors RAR and RXR and the orphan nuclear receptor HNF-4. In this study we demonstrate a trans-repressing regulatory function for the orphan receptor COUP-TF at this same nuclear receptor response element (NRRE-1). The transcriptional regulatory properties and receptor binding sequences of each nuclear receptor response element within NRRE-1 are also characterized. NRRE-1 consists of four potential nuclear hormone receptor hexamer binding sites, arranged as [<--1-(n)s-2-->-3-->(n)4<--4], three of which are used in alternative pairwise binding by COUP-TF and HNF-4 homodimers and by RAR-RXR heterodimers, as demonstrated by mobility shift assays and methylation interference analysis. Binding and transactivation studies with mutant NRRE-1 elements confirmed the existence of distinct retinoid, COUP-TF, and HNF-4 response elements that define novel receptor binding motifs: COUP-TF homodimers bound sites 1 and 3 (two hexamer repeat sequences arranged as an everted imperfect repeat separated by 14 bp or ER14), RAR-RXR heterodimers bound sites 1 and 2 (ER8), and HNF-4 homodimers bound sites 2 and 3 (imperfect DR0). Mixing cotransfection experiments demonstrated that the nuclear receptor dimers compete at NRRE-1 to modulate constitutive and ligand-mediated transcriptional activity. These data suggest a mechanism for the transcriptional modulation of genes encoding enzymes involved in cellular metabolism.

Inner-city older blacks have high levels of functional disability.

OBJECTIVES: To describe the frequency and severity of functional problems in two groups of noninstitutionalized inner-city blacks aged 70 years and older contrasted with results from appropriate groups of white and black older adults and with the goals of the Healthy People 2000 program. DESIGN: Cross-sectional descriptive study. SETTING: Community-based samples. PARTICIPANTS: A population-based sample of 416 older adults living in a 3.5-square mile catchment area in north St. Louis (NSL), Missouri, and a sample of 197 older residents living in public housing in East St. Louis (ESL), Illinois. MEASUREMENTS: Health status, preventive health activities, health services utilization, and risks for progressive frailty were assessed by self report and observation using well validated, standardized instruments. Whenever possible, comparison data were derived from national datasets, original samples used to validate the measures, and other useful comparison groups. RESULTS: The NSL sample had somewhat better health status and risk for progressive disability than the ESL sample. However, compared with national or regional reference groups using age-gender adjustments, both study groups demonstrated increased levels of dependence in intermediate activities of daily living, restricted activity days, inability to walk one-half mile without assistance, reported poor vision, living alone, and limited income compared with both older whites and blacks, and increased levels of worsening health, inability to perform heavy work around the house, never walking a mile or more, and currently unmarried versus whites with variable decrements versus blacks. Contrasted with other comparison groups, the two samples had increased body fat; consistent decrements in gait speed, timed chair stands, timed one-leg balance, and frequency of preventive exercise; and lower levels of dental care; results relative to physician visits and hospital days were mixed. They also had high levels of measured visual and hearing impairments, unmet needs for home delivered meals, and problems with false teeth. Deficiencies compared with the goals of Healthy People 2000 were large. CONCLUSIONS: The special attributes of inner-city blacks, including poverty and access to and acceptance of remedial programs, will have to be considered if the goals of Healthy People 2000 are to be met in this important and growing segment of older Americans. 44:0000-0000, 1996.

Nutritional risk in inner-city-dwelling older black Americans.

OBJECTIVE: To define the degree of nutritional risk in older inner-city black Americans and to identify important underlying factors associated with high nutritional risk. DESIGN: Cross-sectional descriptive study. SETTING AND PARTICIPANTS: A population-based sample of 400 noninstitutionalized persons older than 69 years of age in north St. Louis (NSL), Missouri, and a community-based sample of 115 residents aged 50 years and older living in public housing in East St. Louis (ESL), Illinois. Both study areas have high levels of poverty. MEASUREMENTS: Nutritional risk was measured using the Nutrition Screening Initiative Checklist. Demographic information, economic status, self-rated health, Geriatric Depression Scale score, and body mass index were assessed using established standardized instruments. MAIN RESULTS: Forty-eight percent of NSL and 66% of ESL subjects scored high on the Checklist. Compared with a mostly white (96%) comparison group from New England, both samples demonstrated particularly high prevalence for limited intake of fruits, vegetables, and milk; tooth and mouth problems; lack of money for food; eating alone; polypharmacy; and inability to shop, cook or feed on their own. High levels of depressive symptoms, fair or poor self-rated health, perceived inadequacy of income, and low income levels were associated with high risk, but even those subjects with no or few such predisposing factors were still high on the Checklist score compared with the New England sample. CONCLUSIONS: If confirmed, these results indicate that inner-city-dwelling older black Americans are at high nutritional risk. Attempts to reduce their nutritional risk should focus on improving nutritional content of their diet, oral health, polypharmacy, depressive symptoms, and poor general health; offering group meals; and providing assistance with shopping and cooking.

Home bowel preparation for elective colonic procedures in children: cost savings with quality assurance and improvement.

BACKGROUND/PURPOSE: The current health care environment pressures providers to lower cost and demands quality care that is measured by outcomes and patient satisfaction. Most insurers will not approve bed days for in-hospital preoperative bowel preparations for elective colorectal procedures. This policy does not take into account that infants and children are unable to tolerate large volumes of enteral preparation, which adversely affects outcome because of an inadequate preparation. This report describes a prospective evaluation of a standard home bowel preparation regimen utilizing local and regional home health care agency support. METHODS: For an elective colorectal procedure, pediatric patients underwent a home bowel preparation using GoLYTELY (100 mL/kg) via a nasogastric tube infused over 4 hours by a pediatric home health nurse trained in this technique. During the bowel preparation, the nurse educated the family members about the service and performed physiological monitoring to insure safety. At the completion of the preparation, any unusual events were transmitted to the staff surgeon for further instructions. Our initial 30 patients were treated by our hospital home health agency personnel to insure safety. Since then, 41 additional bowel preparations have been performed by statewide agencies. RESULTS: Seventy-one patients underwent complete home bowel preparation (45 boys; 26 girls). The age range was 3 months to 9 years (average, 5 months). There was one complication caused by incorrect mixing of GoLYTELY causing gastrointestinal cramping. All 71 home bowel preparations were recorded as good at the time of the colorectal procedure by the staff pediatric surgeon. The average cost for home bowel preparation was $300 in network, and $350 out of network. This compares with an inpatient hospital day cost of greater than $800 ($36,000 savings). CONCLUSIONS: This technique offers the pediatric surgeon an opportunity to maintain a high standard of quality care while using home health agency personnel to minimize cost. This program is safe, effective, and associated with a good outcome and a high degree of family satisfaction.

Adrenocortical postirradiation fibrosis.

At autopsy, the adrenal zona reticularis showed linear hyaline fibrosis in 19 cases of cancer, after averages of six months and 5,000 roentgens of irradiation to the abdominal, lumbar, or pelvic regions. The associated roentgen dose was significantly greater than when postirradiation adrenal fibrosis was absent. Primary radiation damage to the reticular vascular plexus is suspected.

Observations on acute salmonellosis in four Waikato dairy herds.

Acute epidemic salmonellosis was investigated in the winter of 1978 in 4 dairy herds in the Waikato district. The outbreaks involved pregnant or recently calved cows. Calves were affected on only one farm. Salmonella bovismorbificans was isolated from the faecal, uterine and environmental samples from the herd most severely affected. In this herd 20, (20%) of the cows died; 10 calves were either born dead or died soon after birth; and 10 cows were culled as unlikely to return to production. S. typhimurium was involved in the outbreaks in the other 3 herds and from one of these farms salmonellae were isolated from the faeces of the 2 farm dogs and from a 12-month-old infant with dysentery. Salmonellae were recovered from all of the clinically ill cows and from 36% of the asymptomatic animals. Salmonellae were widespread on the properties and were isolated from 81% of soil samples; 36% of drain swabs; and from all the pairs of rubber boots worn while collecting samples.

Effects of prolonged tremor due to penitrem A in mice.

Adult mice were given subcutaneous injections of purified penitrem A (10 mg/kg) dissolved in corn oil. The mycotoxin was prepared by ether extraction and absorption chromatography; identity was established by absorption and mass spectra. Tremors were sustained for 72 hr following a single dose; readministration every 3 days was used to provide continuous trembling for 18 days. No lesions specifically attributed to penitrem A could be detected by histological examination of brains even after 18 days of trembling. Pharmacological agents affecting central nervous system neurotransmitters had some capacity to modify the effects of penitrem A. The results of those studies were such that a definitive conclusion regarding mechanisms of action of the toxin could not be determined.

Human plasma platelet-activating factor acetylhydrolase. Association with lipoprotein particles and role in the degradation of platelet-activating factor.

Platelet-activating factor (PAF) is a bioactive phospholipid (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) synthesized by a variety of mammalian cell types. PAF induces hypotension, and activates neutrophils and platelets, among other actions. Removal of the acetyl moiety abolishes biological activity, so this reaction may regulate the concentration of PAF and its physiological effects. We have studied the significance of this reaction, which is catalyzed in vitro by an acetylhydrolase present in mammalian plasma, blood cells, and tissues. We have shown that the plasma PAF-acetylhydrolase is responsible for the degradation of PAF in whole human blood and that alternate pathways for PAF degradation in plasma or blood cells are negligible. Human plasma PAF-acetylhydrolase is associated with low and high density lipoproteins (LDL and HDL with apoE). We have confirmed that the activity is a stable component of these particles by density gradient ultracentrifugation, chromatography on heparin-agarose, and immunoprecipitation. The LDL-associated activity accounts for most or all of the PAF degradation that occurs in plasma ex vivo, while the HDL-associated activity contributes little to this process. However, the two activities likely are due to a single protein since the HDL- and LDL-associated PAF-acetylhydrolase activities can transfer from one lipoprotein to the other. These transfer processes are pH-dependent and specific, since they only occur from LDL to a well characterized subclass of HDL (apoE-containing HDL) and vice versa. We discuss the equilibrium between the two particles and the role that this process may have in vivo.

Leptospirosis: I. Clinical investigation of the infection in dairy cattle in the Waikato district of New Zealand.

An investigation was made into the prevalence of leptospiral infection in cattle. An area 50 km radius was selected in a region where leptospirosis was reputedly common. Farmers volunteered 250 herds with 39 500 cows for testing and 7 500 animals were selected and sampled. Twenty-nine cows (0.4%) on 14 (5.6%) of the farms had leptospiruria at the first examination. Leptospirae were cultured from the urines of nine of these animals and all were Leptospira interrogans serovar hardjo. Serologically 12.5% of cows had titres of 1:200 or greater to hardjo and 3.5% titres of 1:200 or greater to pomona. In the Spring of 1977, there was evidence of clinical leptospirosis in calves associated with only one of the herds and no clinical leptospirosis in the 250 lactating herds, although leptospiral titres were found in 88% of them. This indicated that clinical disease was much less common than infection. We concluded that leptospirosis was of minor economic importance in dairy cattle, although it could be significant in individual herds, and a health hazard to farm workers.

Leptospirosis: II. Investigation of clinical disease in dairy cattle in the Waikato district of New Zealand.

Investigations were carried out in 1975, 1976 and 1977 in 16 dairy herds where leptospiral abortions were suspected and in five other herds where clinical disease was not present. Both Leptospira interrogans serovars pomona and hardjo were isolated from cattle in herds with leptospirosis, but only pomona was recovered from those that had aborted. There was no evidence that hardjo caused clinical disease in dairy cattle in the Waikato district. It was found that 73% of the cows that aborted and 19% of other animals in the same herds had microscopic agglutination test titres to pomona of 1:2,000 or greater. By contrast, only 2% of cattle in herds without clinical evidence of leptospirosis had such titres. One cow retained a titre of 1:2,000 or greater to pomona for 7 months; titres of this order had a shorter duration in other cows. Leptospiruria occurred in 50% of cows that had aborted and in 9% of in-contact cows in the same herds. Only 0.7% of cows had leptospiruria in the herds with no clinical disease. Ten of 35 cows shedding pomona still had leptospiruria one month later. It was concluded that clinical leptospirosis should be diagnosed by testing a sample of the herd, rather than just individual cows, because of the variability and persistence of leptospiruria and serological titres in cows with and without clinical signs. Although hardjo is common in cattle in the Waikato district, it was not found to cause abortion in cattle.

Lipoproteins alter the catalytic behavior of the platelet-activating factor acetylhydrolase in human plasma.

Platelet-activating factor (PAF) has been implicated as a mediator of inflammation, allergy, shock, and thrombosis. A specific degradative enzyme, PAF acetylhydrolase (EC 3.1.1.47), is found in plasma and could regulate the concentration of PAF in blood. In plasma, 70% of the PAF acetylhydrolase is found with low density lipoprotein (LDL), and the remainder is in high density lipoprotein (HDL). In previous studies we found that with subsaturating concentrations of PAF the activity in LDL seemed to be the relevant one; e.g., depletion of LDL slowed degradation of PAF, while removal of HDL accelerated the degradation slightly. We have pursued this observation by using plasma from humans with lipoprotein mutations. In abetalipoproteinemia, all of the PAF acetylhydrolase activity was in HDL, whereas in Tangier disease all of the activity was in LDL. In both conditions the total activity measured in an optimized assay was normal or increased. However, when we measured the t1/2 of PAF in plasma, we found that it was prolonged in subjects with abetalipoproteinemia compared to normal controls. Conversely, the t1/2 in Tangier plasma was shortened. We next demonstrated that the PAF acetylhydrolase in HDL was recognized by an antibody to the enzyme purified from LDL, establishing that the enzyme in the two particles is the same protein. Finally, we inactivated the PAF acetylhydrolase in isolated lipoprotein particles and then reconstituted them with enzyme from the opposite particle. The reconstituted particles were used to measure the t1/2 of PAF, and we again found that the LDL particle was more efficient. We conclude that the lipoprotein environment of the PAF acetylhydrolase markedly influences its catalytic behavior. This may be important in pathophysiology and will complicate attempts to assess the role of this enzyme in such circumstances.