Biomarkers of abnormally invasive placenta.

INTRODUCTION: Abnormally invasive placenta (AIP, aka placenta accreta spectrum; PAS) is an increasingly common pregnancy pathology, which, despite significant morbidity risk to the mother, is often undiagnosed prior to delivery. We tested several potential biomarkers in plasma from PAS mothers to determine whether any were sufficiently robust for a formal, diagnostic accuracy study. METHODS: We examined hyperglycosylated hCG (h-hCG), decorin and IL-8, based on biological plausibility and literature indications that they might be altered in PAS. These analytes were assayed by ELISA in maternal plasma from five groups, comprising (1) normal term controls, (2) placenta previa controls, and cases of (3) placenta increta/percreta without placenta previa, (4) placenta previa increta/percreta and (5) placenta previa accreta. RESULTS: There were no differences in h-hCG, ß-hCG or the h-hCG/ß-hCG ratio between the groups. Mean decorin levels were increased in previa controls (Group 2) compared to the other groups, but there was substantial overlap between the individual values. While an initial multiplex assay showed a greater value for IL-8 in the placenta previa increta/percreta group (Group 4) compared to placenta previa controls (Group 2), the subsequent validation ELISA for IL-8 showed no differences between the groups. DISCUSSION: We conclude that the absence of differences and the extent of overlap between cases and controls does not justify further assessment of these biomarkers.

Human interaction in the NICU and its association with outcomes on the Brief Infant-Toddler Social and Emotional Assessment (BITSEA).

BACKGROUND: Extremely preterm infants represent one of the highest risk categories for impairments in social competence. Few studies have explored the impact of the neonatal intensive care unit (NICU) environment on social development. However, none have specifically analyzed the effects of the care structure the infant receives during hospitalization on later social competence indicators. OBJECTIVE: To identify associations between the care structures received by extremely preterm infants in the NICU and scores on the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) post-discharge. PARTICIPANTS: 50 extremely preterm infants (mean gestational age: 25 weeks during hospitalization; mean chronological age during follow-up assessment: 2 years, 4 months). METHODS: A secondary analysis of BITSEA data was performed exploring its relation to care structure data we extracted from electronic medical records (i.e., how much time infants were engaged in human interaction during their first thirty days of hospitalization and what types of interaction they were exposed to). RESULTS: Extremely preterm infants spend a considerable amount of time alone during hospitalization (80%) with nursing care comprising the majority of human interaction. Infants who experienced greater human interaction scored significantly higher on the Social Competence (p = 0.01) and lower on the Dysregulation (p = 0.03) BITSEA subscales. CONCLUSION: Human interaction and isolation in the NICU is associated with social competence and dysregulation outcomes in extremely preterm infants. Further research is needed to understand how various NICU care structures including centralized nursing teams, parental skin-to-skin care, and early therapy may synergistically play a positive role in developing social competence.

Lyme disease surveillance in the United States: Looking for ways to cut the Gordian knot.

Current surveillance methods have been useful to document geographic expansion of Lyme disease in the United States and to monitor the increasing incidence of this major public health problem. Nevertheless, these approaches are resource-intensive, generate results that are difficult to compare across jurisdictions, and measure less than the total burden of disease. By adopting more efficient methods, resources could be diverted instead to education of at-risk populations and new approaches to prevention. In this special issue of Zoonoses and Public Health, seven articles are presented that either evaluate traditional Lyme disease surveillance methods or explore alternatives that have the potential to be less costly, more reliable, and sustainable. Twenty-five years have passed since Lyme disease became a notifiable condition - it is time to reevaluate the purpose and goals of national surveillance.

Exploring an alternative approach to Lyme disease surveillance in Maryland.

In Maryland, Lyme disease (LD) is a reportable disease and all laboratories and healthcare providers are required to report to the local health department. Given the volume of LD reports and effort required for investigation, surveillance for LD is burdensome and subject to underreporting. We explored the utility of International Classification of Diseases, 9th Revision, Clinical Modification (administrative) codes for use with LD surveillance. We aimed to collect the administrative codes for a 10% sample of 2009 LD reports (n = 474) from 292 facilities stratified by case classification (confirmed, probable, suspected and not a case). Sixty-three per cent (n = 184) of facilities responded to the survey, and 341 different administrative codes were obtained for 91% (n = 430) of sampled reports. The administrative code for Lyme disease (088.81) was the most commonly reported code (133/430 patients) among sampled reports; while it was used for 62 of 151 (41%) confirmed cases, it was also used for 48 of 192 (25%) not a case reports (sensitivity 41% and specificity 73%). A combination of nine codes was developed with sensitivity of 74% and specificity of 37% when compared to not a case reports. We conclude that the administrative code for LD alone has low ability to identify LD cases in Maryland. Grouping certain codes improved sensitivity, but our results indicate that administrative codes alone are not a viable surveillance alternative for a disease with complex manifestations such as LD.

Pet ownership increases human risk of encountering ticks.

We examined whether pet ownership increased the risk for tick encounters and tickborne disease among residents of three Lyme disease-endemic states as a nested cohort within a randomized controlled trial. Information about pet ownership, use of tick control for pets, property characteristics, tick encounters and human tickborne disease were captured through surveys, and associations were assessed using univariate and multivariable analyses. Pet-owning households had 1.83 times the risk (95% CI = 1.53, 2.20) of finding ticks crawling on and 1.49 times the risk (95% CI = 1.20, 1.84) of finding ticks attached to household members compared to households without pets. This large evaluation of pet ownership, human tick encounters and tickborne diseases shows that pet owners, whether of cats or dogs, are at increased risk of encountering ticks and suggests that pet owners are at an increased risk of developing tickborne disease. Pet owners should be made aware of this risk and be reminded to conduct daily tick checks of all household members, including the pets, and to consult their veterinarian regarding effective tick control products.

Characterizing Lyme Disease Surveillance in an Endemic State.

Lyme disease (LD) is the most common vector-borne disease in Maryland and the United States. Surveillance for LD is valuable for understanding the burden of the disease, particularly to assess whether the disease is spreading and to appreciate who is affected. However, not all cases of LD in Maryland are reported, and surveillance practices vary across each of Maryland's 24 local health departments (LHDs). To better understand this variability and to systematically characterize the surveillance process, we surveyed Maryland's LHDs regarding LD surveillance. The Maryland Local Health Department Lyme Disease Surveillance Survey has been administered annually since 2011. Questions asked each year included whether all LD reports are investigated or only a subset, and how many reports are not entered into the surveillance database. Since 2011, Maryland has lost surveillance personnel for LD. Each year from 2009 to 2012, a median 3598 (range 2462 to 5722) reports were not entered into the surveillance database and hence not investigated. These reports represent 43-55% of all reports received for the year. Over time, more LHDs chose to streamline their LD investigation approach by investigating only those reports that met the criteria for laboratory evidence of infection: in 2008, 5 (21%) LHDs investigated only a subset of LD reports; by 2013, this increased to 15 (63%). There is wide variability across LHDs in how LD investigations are conducted. Maryland LHDs have experienced a loss of LD surveillance personnel with a concomitant increase in the number of LHDs adopting a streamlined approach to investigating cases. These findings underscore the tremendous burden of LD on the public health agencies and highlight the need for alternative approaches that can both reduce burden and preserve surveillance data quality.

Assessing diagnostic coding practices among a sample of healthcare facilities in Lyme disease endemic areas: Maryland and New York - A Brief Report.

The value of using diagnostic codes in Lyme disease (LD) surveillance in highly endemic states has not been well studied. Surveys of healthcare facilities in Maryland (MD) and New York (NY) regarding coding practices were conducted to evaluate the feasibility of using diagnostic codes as a potential method for LD surveillance. Most respondents indicated that their practice utilized electronic medical records (53%) and processed medical/billing claims electronically (74%). Most facilities were able to search office visits associated with specific ICD-9-CM and CPT codes (74% and 73%, respectively); no discernible differences existed between the healthcare facilities in both states. These codes were most commonly assigned by the practitioner (82%), and approximately 70% of respondents indicated that these codes were later validated by administrative staff. These results provide evidence for the possibility of using diagnostic codes in LD surveillance. However, the utility of these codes as an alternative to traditional LD surveillance requires further evaluation.

Perceptions and Practices of Mass Bat Exposure Events in the Setting of Rabies Among U.S. Public Health Agencies.

Current guidelines in the setting of exposures to potentially rabid bats established by the Advisory Committee on Immunization Practices (ACIP) address post-exposure prophylaxis (PEP) administration in situations where a person may not be aware that a bite or direct contact has occurred and the bat is not available for diagnostic testing. These include instances when a bat is discovered in a room where a person awakens from sleep, is a child without an adult witness, has a mental disability or is intoxicated. The current ACIP guidelines, however, do not address PEP in the setting of multiple persons exposed to a bat or a bat colony, otherwise known as mass bat exposure (MBE) events. Due to a dearth of recommendations for response to these events, the reported reactions by public health agencies have varied widely. To address this perceived limitation, a survey of 45 state public health agencies was conducted to characterize prior experiences with MBE and practices to mitigate the public health risks. In general, most states (69% of the respondents) felt current ACIP guidelines were unclear in MBE scenarios. Thirty-three of the 45 states reported prior experience with MBE, receiving an average of 16.9 MBE calls per year and an investment of 106.7 person-hours annually on MBE investigations. PEP criteria, investigation methods and the experts recruited in MBE investigations varied between states. These dissimilarities could reflect differences in experience, scenario and resources. The lack of consistency in state responses to potential mass exposures to a highly fatal disease along with the large contingent of states dissatisfied with current ACIP guidance warrants the development of national guidelines in MBE settings.

Increased CSF concentrations of myelin basic protein after TBI in infants and children: absence of significant effect of therapeutic hypothermia.

BACKGROUND: The objectives of this study were to determine effects of severe traumatic brain injury (TBI) on cerebrospinal fluid (CSF) concentrations of myelin basic protein (MBP) and to assess relationships between clinical variables and CSF MBP concentrations. METHODS: We measured serial CSF MBP concentrations in children enrolled in a randomized controlled trial evaluating therapeutic hypothermia (TH) after severe pediatric TBI. Control CSF was obtained from children evaluated, but found not to be having CNS infection. Generalized estimating equation models and Wilcoxon Rank-Sum test were used for comparisons of MBP concentrations. RESULTS: There were 27 TBI cases and 57 controls. Overall mean (± SEM) TBI case MBP concentrations for 5 days after injury were markedly greater than controls (50.49 ± 6.97 vs. 0.11 ± 0.01 ng/ml, p < 0.01). Mean MBP concentrations were lower in TBI patients <1 year versus >1 year (9.18 ± 1.67 vs. 60.22 ± 8.26 ng/ml, p = 0.03), as well as in cases with abusive head trauma (AHT) versus non-abusive TBI (14.46 ± 3.15 vs. 61.17 ± 8.65 ng/ml, p = 0.03). TH did not affect MBP concentrations. CONCLUSIONS: Mean CSF MBP increases markedly after severe pediatric TBI, but is not affected by TH. Infancy and AHT are associated with low MBP concentrations, suggesting that age-dependent myelination influences MBP concentrations after injury. Given the magnitude of MBP increases, axonal injury likely represents an important therapeutic target in pediatric TBI.

Design and evaluation of consensus PCR assays for henipaviruses.

Henipaviruses were first discovered in the 1990s, and their potential threat to public health is of increasing concern with increasing knowledge. Old-world fruit bats are the reservoir hosts for these viruses, and spill-over events cause lethal infections in a wide range of mammalian species, including humans. In anticipation of these spill-over events, and to investigate further the geographical range of these genetically diverse viruses, assays for detection of known and potentially novel strains of henipaviruses are required. The development of multiple consensus PCR assays for the detection of henipaviruses, including both SYBR Green and TaqMan real-time PCRs and a conventional heminested PCR is described. The assays are highly sensitive and have defined specificity. In addition to being useful tools for detection of known and novel henipaviruses, evaluation of assay efficiency and sensitivity across both biological and synthetic templates has provided valuable insight into consensus PCR design and use.

A large outbreak of scombroid fish poisoning associated with eating escolar fish (Lepidocybium flavobrunneum).

In August 2003, an outbreak of scombroid fish poisoning occurred at a retreat centre in California, USA. In a retrospective cohort study, 42 (75%) of the 56 dinner attendees who ate escolar fish (Lepidocybium flavobrunneum) met the case definition. Individuals who ate at least 2 oz of fish were 1.5 times more likely to develop symptoms than those who ate less (relative risk 1.5, 95% confidence interval 0.9-2.6), and to develop more symptoms (median 7 vs. 3 symptoms, P = 0.03). Patients who took medicine had a longer duration of symptoms than those who did not (median 4 vs. 1.5 h, P = 0.05), and experienced a greater number of symptoms (median 8 vs. 3 symptoms, P = 0.0002). Samples of fish contained markedly elevated histamine levels (from 2000 to 3800 ppm). This is one of the largest reported outbreaks of scombroid fish poisoning in the United States and was associated with a rare vehicle for scombroid fish poisoning, escolar.

Non-tuberculous mycobacteria: patterns of isolation. A multi-country retrospective survey.

OBJECTIVE: To collect data on non-tuberculous mycobacteria (NTM) isolated from clinical laboratories in different countries to establish: 1) whether the isolation of NTM was increasing, 2) which species were increasing, and 3) whether there was any pattern of geographical distribution. DESIGN: In 1996, the Working Group of the Bacteriology and Immunology Section of the International Union Against Tuberculosis and Lung Disease contacted 50 laboratories in different countries for the necessary information. RESULTS: The number of patients reported with NTM was 36099 from 14 countries. Mycobacterium avium complex, M. gordonae, M. xenopi, M. kansasii and M. fortuitum were the five species most frequently isolated. There was a significant upward trend for M. avium complex and M. xenopi. Pigmented mycobacteria predominated in Belgium, the Czech Republic and the Mediterranean coast of Spain. Non-chromogenic mycobacteria were found to be predominant in the area of the Atlantic coast of Brazil and in Turkey, the United Kingdom, Finland and Denmark. CONCLUSIONS: There was an increase in the number of NTM isolated from clinical samples of patients. Isolation of the most frequent species is constantly changing in most of the geographical areas, and newer species are emerging due to better diagnostic techniques to detect and identify NTM.

Flake-Austin modification of the STA-Peg arthroereisis: a retrospective study.

The Smith subtalar arthroereisis implant (STA-peg) is used to correct severe collapsing pes valgoplanus in children. Flake and Austin modified the placement of this implant to block the leading wall of the lateral talus. Twenty-one patients with a total of 40 STA-peg procedures were evaluated subjectively and objectively. The average age at the time of surgery was 9.7 years (4 to 16 years). The follow-up period averaged 36 months (12 to 90 months). The subjective, objective, and radiographic results were positive and the complication rate was low. A significant advantage of the Flake-Austin modification of the STA-peg placement in transverse planar dominant foot types is also noted.

The cause of infant and toddler subdural hemorrhage: a prospective study.

OBJECTIVE: To determine the frequency of child abuse and unintentional injury as a cause of infant and toddler subdural hemorrhage (SDH). METHODS: A prospective case series of a level I regional trauma center, regional children's hospital, and county medical examiner's office assessed consecutive children who were

In vitro and In vivo inhibition of LPS-stimulated tumor necrosis factor-alpha secretion by the gallotannin beta-D-pentagalloylglucose.

The naturally occurring gallotannin beta-D-pentagalloylglucose (beta-PGG) decreases tumor necrosis factor-alpha (TNF-alpha) output from human peripheral blood mononucleocytes exposed to lipopolysaccharide (LPS) by as much as 90% (vs control) at approximately 5 microM concentration. A qualitatively similar but less pronounced effect ( approximately 50% decrease) was observed in the serum of rats dosed with both LPS and beta-PGG. These results may have relevance to therapies that target disease states characterized by an overproduction of TNF-alpha.

Accusations that hospital staff have abused pediatric patients.

OBJECTIVE: Study objectives were to describe a hospital Child Protection Team's (CPT) efforts to develop and implement a protocol for systematic evaluation and management of accusations that hospital staff have abused pediatric patients, and to learn how to avoid problematic patient encounters and cope with existing accusations. METHOD: This study reports on a retrospective series of cases from one pediatric hospital between 1982 and 1996. It includes a survey of national children's hospitals' experience from 1990 through 1995. RESULTS: After initial complaints to our hospital's CPT, it became apparent that procedures were inadequate to protect the safety of patients and rights of the accused. A protocol for reporting, evaluation, and management of accusations was developed and implemented by the CPT. Thirty-four accusations of abuse of children by staff were reviewed. Seventeen of the physical abuse cases included bruising, fractures, rough handling, and verbal abuse. Eighteen sexual abuse complaints included touching and sexual statements. Complaints were substantiated in 23% of the accusations, and a third of the identified staff members were fired or resigned. Child victims had a high frequency of chronic illness. They and their families frequently had histories of prior abuse, mental illness, and social disarray. These factors made children more likely to become victims of real abuse and to misinterpret standard hospital procedures as abusive. All service areas of the hospital and types of hospital staff were accused of patient abuse. CONCLUSIONS: Few children's hospitals have formal protocols for internal management of or training programs to avoid complaints. Institutions and their staff who care for children should anticipate abuse complaints, train them in risk reduction methods, and develop accusation management plans.

An outbreak of primary pneumonic tularemia on Martha's Vineyard.

BACKGROUND: In the summer of 2000, an outbreak of primary pneumonic tularemia occurred on Martha's Vineyard, Massachusetts. The only previously reported outbreak of pneumonic tularemia in the United States also occurred on the island in 1978. METHODS: We conducted a case-control study of adults with pneumonic tularemia and investigated the environment to identify risk factors for primary pneumonic tularemia. Patients with confirmed cases were residents of or visitors to Martha's Vineyard who had symptoms suggestive of primary pneumonic tularemia, were ill between May 15 and October 31, 2000, and had a positive laboratory test for tularemia. Controls were adults who had spent at least 15 days on Martha's Vineyard between May 15 and September 28, 2000. RESULTS: We identified 15 patients with tularemia; 11 of these cases were primary pneumonic tularemia. Francisella tularensis type A was isolated from blood and lung tissue of the one man who died. Patients were more likely than controls to have used a lawn mower or brush cutter in the two weeks before the illness or before an interview, for controls (odds ratio, 9.2; 95 percent confidence interval, 1.6 to 68.0) and during the summer (odds ratio, undefined; 95 percent confidence interval, 1.8 to infinity). Lawn mowing and brush cutting remained significant risk factors after adjustment for other potentially confounding variables. Only one patient reported being exposed to a rabbit while cutting brush. Of 40 trapped animals, 1 striped skunk (Mephitis mephitis) and 1 Norway rat (Rattus norvegicus) were seropositive for antibodies against F. tularensis. CONCLUSIONS: Study of this outbreak of primary pneumonic tularemia implicates lawn mowing and brush cutting as risk factors for this infection.

Alkynyliodonium salts in organic synthesis. Dihydrofuran formation via a formal stevens shift of a carbon substituent within a disubstituted-carbon oxonium ylide.

The addition of p-toluenesulfinate to the silyl, 1-furanyl, and 1-pyranyl ethers of 1-hydroxybut-3-ynyl(phenyl)iodonium triflate triggers a sequence of reactions that ultimately delivers 2-substituted 3-p-toluenesulfonyldihydrofuran products in variable yields. A putative 1,2-group shift within an unsaturated oxonium ylide (Stevens rearrangement) accounts for the oxygen-to-carbon transfer of the ether substituent. Deuterium labeling studies clarify the mechanistic course of this shift by providing evidence consistent with intramolecular substituent transfer and by identifying the primary source of the proton that intercepts the ylide in the major yield-limiting process.

Ellagitannin chemistry. Evolution of a three-component coupling strategy for the synthesis of the dimeric ellagitannin coriariin A and a dimeric gallotannin analogue.

The total synthesis of the dimeric ellagitannin coriariin A is reported. The key reaction to access the dimeric framework was realized early in the synthesis pathway via a bis acylation reaction of a dehydrodigalloyl diacid with 2 equiv of a glucopyranose trichloroacetimidate. The glucose rings were subsequently functionalized, culminating in a double oxidative cyclization to form stereoselectively both (S)-HHDP ester units. This bis acylation strategy was also employed to prepare a gallotannin analogue of coriariin A whose earlier synthesis by orthoquinone dimerization was plagued by yield-limiting side reactions.