Changes in Spina Bifida Lesion Level after Folic Acid Fortification in the US.

OBJECTIVE: To assess whether the severity of cases of spina bifida changed after the institution of mandatory folic acid fortification in the US. STUDY DESIGN: Six active population-based birth defects programs provided data on cases of spina bifida for 1992-1996 (prefortification period) and 1999-2016 (postfortification period). The programs contributed varying years of data. Case information included both a medical record verbatim text description of the spina bifida diagnosis and spina bifida codes (International Classification of Diseases, Clinical Modification, or a modified birth defects surveillance coding system). Comparing the prefortification and postfortification periods, aORs for case severity (upper-level lesions [cervical, thoracic] vs lower-level lesions [lumbar, sacral]) and prevalence ratios (PRs) were estimated. RESULTS: A total of 2593 cases of spina bifida (out of 7 816 062 live births) met the inclusion criteria, including 573 cases from the prefortification period and 2020 cases from the postfortification period. Case severity decreased by 70% (aOR, 0.30; 95% CI, 0.26-0.35) between the fortification periods. The decrease was most pronounced for non-Hispanic White mothers. Overall spina bifida prevalence declined by 23% (PR, 0.77; 95% CI, 0.71-0.85), with similar reductions seen across the early, mid, and recent postfortification periods. A statistically significant decrease in upper-level lesions occurred in the postfortification period compared with the prefortification period (PR, 0.28; 95% CI, 0.22-0.34), whereas the prevalence of lower-level lesions remained relatively similar (PR, 0.94; 95% CI, 0.84-1.05). CONCLUSIONS: The severity of spina bifida cases decreased after mandatory folic acid fortification in the US. Further examination is warranted to better understand the potential effect of folic acid on spina bifida severity.

LOCALIZATION OF MACULAR CRYSTALS ASSOCIATED WITH CHRONIC RETINAL DETACHMENT TO THE POSTERIOR HYALOID USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To present a case of crystalline retinopathy associated with chronic retinal detachment and localize the macular crystals using spectral domain optical coherence tomography. METHODS: Case Report. RESULTS: A 37-year-old man with previously treated chronic retinal detachment presented with normal vision and crystalline maculopathy. Spectral domain optical coherence tomography localized the macular crystals to the posterior hyaloid membrane and on the internal limiting membrane, but not within the retina. CONCLUSION: The macular crystals in crystalline retinopathy associated with chronic retinal detachment most likely originate in the subretinal space beneath the detached retina, migrate through the retinal break into the vitreous cavity, and lodge on the surface of the internal limiting membrane. When the posterior hyaloid membrane separates, the crystals, which are attached to the posterior hyaloid membrane, elevate from the retina.

Ecology of an ocelot population at the northern edge of the species' distribution in northern Sonora, Mexico.

We used data from eight years of camera trapping at Rancho El Aribabi, a cattle ranch and conservation property in northern Sonora, Mexico, to examine the ecology of the northern-most known breeding population of ocelots (Leopardus pardalis). Ocelots were found mostly in two discrete and disjunct areas: a riverine riparian canyon at just less than 1,000 masl elevation and along arroyos in an oak-mesquite savanna in the Sierra Azul at 1,266-1,406 masl. An ocelot was also detected at a site between those two areas, in an area of a Sonoran desertscrub-foothills thornscrub ecotone at 1,300 masl. At least 18 ocelots, both males and females, were detected during the 2007-2011 and 2014-2018 sampling periods. A female with a kitten was documented in 2011. No individual ocelots were photographed in both areas, which are separated by a minimum of 11.29 km, and no individuals were photographed in both time periods. In a binary logistic regression, key environmental variables predicting ocelot presence were, in order of importance, distance to a paved road, distance to human habitation, proximity to water, and an anthropogenic influences index that was dominated by cattle. Another analysis corroborated the finding regarding ocelot presence and cattle. Contrary to previous studies, ocelot presence was not tied to vegetation cover close to the ground. We present information about the types of habitats and sites ocelots used, short-term movements, daily and seasonal activity patterns, and behavior, including occurrence of different individuals at or near the same site over short periods of time. We discuss ocelot home range, density, and movements, but small sample sizes and study design problems limit the value of estimates derived from our work. Rancho El Aribabi is a private, conservation ranch for which the owners have made voluntary conservation commitments that provide habitat and protection for ocelots and other animals and plants. This northern-most known breeding population is a likely source of ocelots that are periodically detected in southeastern Arizona. Our results should help facilitate conservation of the ocelot in other semi-arid areas of northwestern Mexico and adjacent USA.

Dental professionals' knowledge, attitudes, and practice behaviors related to human papillomavirus vaccination.

OBJECTIVES: In Arizona, human papillomavirus (HPV)-related cancers are declining, with the exception of oropharyngeal cancer (OPC). HPV-related OPC is largely caused by persistent infection with oncogenic HPV strains, many of which the 9-valent HPV vaccine offers protection. Little is known about dental professionals' willingness to promote the HPV vaccine to prevent OPC. The current study assessed Arizona dental professionals' knowledge, attitudes, willingness, and current practice behaviors related to HPV vaccine promotion. Responses between dentists and hygienists were also compared. METHODS: A convenience sample of 711 dentists and hygienists attending a regional conference were recruited and asked to complete a 34-item survey assessing knowledge and attitudes about HPV, the HPV vaccine, HPV-related OPC, and their willingness to promote and administer the HPV vaccine. Fisher's exact tests and Mann-Whitney U tests were used for data analysis. RESULTS: Most respondents answered HPV knowledge questions correctly but did not know HPV-related OPC has a more favorable prognosis than other head and neck cancers. Dentists were more confident discussing and recommending the HPV vaccine. Both dentists and hygienists were willing to refer patients to their non-dental primary care providers for vaccination; however, they were less confident in administering the vaccine if it fell within their scope of practice. They reported willingness to receive training to recommend the vaccine. CONCLUSIONS: Given the willingness of respondents to receive training related to HPV vaccine communication, future research should develop and test talking points and communication training to aid dentists and hygienists in their promotion of the HPV vaccine.

MACULAR BURN DURING AN ATTEMPTED YAG LASER CAPSULOTOMY BY INADVERTENT USE OF SELECTIVE LASER TRABECULOPLASTY MODE OF A DUAL-MODE LASER.

PURPOSE: To present a case of a patient who suffered a macular burn after an attempted YAG laser capsulotomy because of the inadvertent use of the selective laser trabeculoplasty mode of a dual-mode laser. METHOD: Case report. RESULTS: A 62-year-old man with slight opacification of the posterior capsule noted sudden central vision loss immediately after an attempted YAG laser capsulotomy. The selective laser trabeculoplasty mode of a dual-mode laser had inadvertently been used. Color photographs, fluorescein angiography, and spectral domain optical coherence tomography revealed a laser burn in the macula. The patient's central vision was impaired. CONCLUSION: Inadvertent selection of the selective laser trabeculoplasty mode when attempting to perform a YAG laser capsulotomy with a dual-mode laser may cause a macular burn with impairment of central vision. We encourage all users of dual-mode lasers to actively choose and verify the appropriate settings to minimize the risk of inadvertent retinal damage.

Prevalence of selected birth defects by maternal nativity status, United States, 1999-2007.

OBJECTIVES: We investigated differences in prevalence of major birth defects by maternal nativity within racial/ethnic groups for 27 major birth defects. METHODS: Data from 11 population-based birth defects surveillance systems in the United States including almost 13 million live births (approximately a third of U.S. births) during 1999-2007 were pooled. We calculated prevalence estimates for each birth defect for five racial/ethnic groups. Using Poisson regression, crude and adjusted prevalence ratios (aPRs) were also calculated using births to US-born mothers as the referent group in each racial/ethnic group. RESULTS: Approximately 20% of case mothers and 26% of all mothers were foreign-born. Elevated aPRs for infants with foreign-born mothers were found for spina bifida and trisomy 13, 18, and 21, while lower prevalence patterns were found for pyloric stenosis, gastroschisis, and hypospadias. CONCLUSIONS: This study demonstrates that birth defects prevalence varies by nativity within race/ethnic groups, with elevated prevalence ratios for some specific conditions and lower prevalence for others. More detailed analyses focusing on a broader range of maternal behaviors and characteristics are required to fully understand the implications of our findings.

Study of selected birth defects among American Indian/Alaska Native population: A multi-state population-based retrospective study, 1999-2007.

BACKGROUND: Higher prevalence of selected birth defects has been reported among American Indian/Alaska Native (AI/AN) newborns. We examine whether known risk factors for birth defects explain the higher prevalence observed for selected birth defects among this population. METHODS: Data from 12 population-based birth defects surveillance systems, covering a birth population of 11 million from 1999 to 2007, were used to examine prevalence of birth defects that have previously been reported to have elevated prevalence among AI/ANs. Prevalence ratios (PRs) were calculated for non-Hispanic AI/ANs and any AI/ANs (regardless of Hispanic ethnicity), adjusting for maternal age, education, diabetes, and smoking, as well as type of case-finding ascertainment surveillance system. RESULTS: After adjustment, the birth prevalence of two of seven birth defects remained significantly elevated among AI/ANs compared to non-Hispanic whites (NHWs): anotia/microtia was almost threefold higher, and cleft lip +/- cleft palate was almost 70% higher compared to NHWs. Excluding AI/AN subjects who were also Hispanic had only a negligible impact on adjusted PRs. CONCLUSIONS: Additional covariates accounted for some of the elevated birth defect prevalences among AI/ANs compared to NHWs. Exclusion of Hispanic ethnicity from the AI/AN category had little impact on birth defects prevalences in AI/ANs. NHWs serve as a viable comparison group for analysis. Birth defects among AI/ANs require additional scrutiny to identify modifiable risk and protective factors.

Birth Weight and Risk of Childhood Acute Lymphoblastic Leukemia in Arizona, Illinois, and Kentucky.

OBJECTIVE: To confirm the previously reported increased risk of leukemia among macrosomic children (those with birth weight >4 kg). METHODS: Birth certificates of Arizona, Illinois, and Kentucky children diagnosed as having acute lymphoblastic leukemia (ALL) before age 5 years were matched with birth certificates from leukemia-free children of the same sex, race, and ethnicity who were born in the same county on or about the same day. Odds ratios (ORs) for ALL among children of low (<2.5 kg) or high (>4 kg) birth weight were calculated by conditional logistic regression. RESULTS: Children with high birth weight had an elevated risk of ALL in the first 5 years of life (OR 1.28, 95% confidence interval [CI] 1.01-1.61). The excess risk was confined to non-Hispanic whites (OR 1.77, 95% CI 1.27-2.48), both boys (OR 1.57, 95% CI 1.01-2.45) and girls (OR 2.10, 95% CI 1.26-3.52). CONCLUSIONS: This study confirms the association between high birth weight and ALL previously reported by other studies in children of European ancestry. The literature on maternal risk factors for both macrosomia and ALL is reviewed, with maternal overnutrition emerging as a plausible risk factor for both outcomes.

Postfolate spina bifida lesion level change.

BACKGROUND: Spina bifida accounts for a large proportion of birth defects in the United States. Studies have evaluated the decrease in prevalence at birth after folate fortification of food grains, but little is known about neurologic functional changes related to fortification. This study assesses the functional level of lesions in the prefortification and postfortification eras. METHODS: Data were collected through retrospective review of medical records from a regional multispecialty clinic in Arizona. This study included individuals born between 1981-1995 (prefortification) and 1999-2013 (postfortification). Patients were included if they had a primary diagnosis of spina bifida with or without hydrocephalus. RESULTS: There was a significant difference in functional lesion level with an 85% reduction in thoracic level lesions in the postfortification era (p < .005). There were no differences in gender or ethnicity across eras; however, Hispanic ethnicity had a higher number of cases overall (51.7%). The most common lesion level in both eras was mid-lumbar, accounting for 35.7 and 34.4% of cases in the prefolate and postfolate eras, respectively. CONCLUSIONS: This study demonstrates a significant difference in the distribution of lesion level of spina bifida patients born in the postfortification era, based on neurologic function. Further research with a larger sample size is needed to determine if this observation holds true nationally.

Infants born with critical CHD in Arizona and capacities of birth centres for screening and management.

OBJECTIVES: The aims of this study were to identify locations of births in Arizona with critical CHD, as well as to assess the current use of pulse-oximetry screening and capacities of birth centres to manage a positive screen. Study design Infants (n=487) with a potentially critical CHD were identified from the Arizona Department of Health Services from 2012 and 2013; charts were retrospectively reviewed. Diagnosis was confirmed using echocardiographies. ArcGIS was used to generate maps to visualise the location of treating facility and mother's residence. Birth centres were surveyed to assess screening practices and capacities to manage critical CHD in 2015. RESULTS: Of the 272 patients identified with critical CHD, 52% had been diagnosed prenatally. Patients travelled an average distance of 55.1 miles to their treating facility. Mortality was not related to prenatal diagnosis (p=0.30), living at a high elevation (p=0.82), or to distance travelled to the treating facility (p=0.68). Of 50 birth centres, 33 responded to the survey and all centres practiced critical CHD screening. A total of 25 centres could perform paediatric echocardiographies; 64% of these centres could digitally transmit echocardiograms. In all, 24 birth centres maintained access to prostaglandins. CONCLUSIONS: Pulse-oximetry screening in newborns is currently implemented in the majority of Arizona hospitals. Although most centres could perform initial management steps following a positive screen, access to paediatric cardiology services was limited. Patients with critical CHD sometimes travelled a great distance to treating facilities. Digital transmission of echocardiograms or tele-echocardiography would reduce the distance travelled for the management of a positive screen, decrease the financial burden of transportation, and expedite care for critically ill neonates.

Using state and provincial surveillance programs to reduce risk of recurrence of neural tube defects in the United States and Canada: A missed opportunity?

BACKGROUND: Once a woman has had a fetus or infant affected with a neural tube defect (NTD), the risk of recurrence is approximately 3%. This risk can be significantly reduced by folic acid supplement consumption during the periconceptional period; however, this requires women at risk to be adequately informed about the appropriate dosage and timing of supplement intake before planning another pregnancy. As birth defects surveillance programs are tasked with identifying and documenting NTD-affected pregnancies and births, they are in a unique position to support recurrence prevention activities. METHODS: In 2015, we surveyed state and provincial birth defects surveillance programs to assess their NTD recurrence prevention activities. The online survey was sent to programs in 52 United States (U.S.) jurisdictions and all 13 provinces and territories in Canada. Findings were compared with a similar survey conducted in 2005 among U.S. programs. RESULTS: In 2015, of the 44 U.S. and Canadian surveillance programs that responded, only 9 programs (7 U.S. and 2 Canadian) reported currently having activities specifically directed toward preventing NTD recurrence. Compared with a 2005 survey of U.S. programs, the number of U.S. programs working on NTD recurrence prevention decreased by almost 50% (from 13 to 7 programs). CONCLUSION: The number of birth defects surveillance programs with NTD recurrence prevention activities has decreased over the past decade due to a range of barriers, most notably a lack of resources. However, while some recurrence prevention activities require part-time staff, other activities could be accomplished using minimal resources. Birth Defects Research (Part A) 106:875-880, 2016.© 2016 Wiley Periodicals, Inc.

Survival of children with trisomy 13 and trisomy 18: A multi-state population-based study.

Trisomy 13 (T13) and trisomy 18 (T18) are among the most prevalent autosomal trisomies. Both are associated with a very high risk of mortality. Numerous instances, however, of long-term survival of children with T13 or T18 have prompted some clinicians to pursue aggressive treatment instead of the traditional approach of palliative care. The purpose of this study is to assess current mortality data for these conditions. This multi-state, population-based study examined data obtained from birth defect surveillance programs in nine states on live-born infants delivered during 1999-2007 with T13 or T18. Information on children's vital status and selected maternal and infant risk factors were obtained using matched birth and death certificates and other data sources. The Kaplan-Meier method and Cox proportional hazards models were used to estimate age-specific survival probabilities and predictors of survival up to age five. There were 693 children with T13 and 1,113 children with T18 identified from the participating states. Among children with T13, 5-year survival was 9.7%; among children with T18, it was 12.3%. For both trisomies, gestational age was the strongest predictor of mortality. Females and children of non-Hispanic black mothers had the lowest mortality. Omphalocele and congenital heart defects were associated with an increased risk of death for children with T18 but not T13. This study found survival among children with T13 and T18 to be somewhat higher than those previously reported in the literature, consistent with recent studies reporting improved survival following more aggressive medical intervention for these children. © 2015 Wiley Periodicals, Inc.

Updated estimates of neural tube defects prevented by mandatory folic Acid fortification - United States, 1995-2011.

In 1992, the U.S. Public Health Service recommended that all women capable of becoming pregnant consume 400 µg of folic acid daily to prevent neural tube defects (NTDs). NTDs are major birth defects of the brain and spine that occur early in pregnancy as a result of improper closure of the embryonic neural tube, which can lead to death or varying degrees of disability. The two most common NTDs are anencephaly and spina bifida. Beginning in 1998, the United States mandated fortification of enriched cereal grain products with 140 µg of folic acid per 100 g. Immediately after mandatory fortification, the birth prevalence of NTD cases declined. Fortification was estimated to avert approximately 1,000 NTD-affected pregnancies annually. To provide updated estimates of the birth prevalence of NTDs in the period after introduction of mandatory folic acid fortification (i.e., the post-fortification period), data from 19 population-based birth defects surveillance programs in the United States, covering the years 1999-2011, were examined. After the initial decrease, NTD birth prevalence during the post-fortification period has remained relatively stable. The number of births occurring annually without NTDs that would otherwise have been affected is approximately 1,326 (95% confidence interval = 1,122-1,531). Mandatory folic acid fortification remains an effective public health intervention. There remain opportunities for prevention among women with lower folic acid intakes, especially among Hispanic women, to further reduce the prevalence of NTDs in the United States.

The association between race/ethnicity and major birth defects in the United States, 1999-2007.

OBJECTIVES: We investigated the relationship between race/ethnicity and 27 major birth defects. METHODS: We pooled data from 12 population-based birth defects surveillance systems in the United States that included 13.5 million live births (1 of 3 of US births) from 1999 to 2007. Using Poisson regression, we calculated prevalence estimates for each birth defect and 13 racial/ethnic groupings, along with crude and adjusted prevalence ratios (aPRs). Non-Hispanic Whites served as the referent group. RESULTS: American Indians/Alaska Natives had a significantly higher and 50% or greater prevalence for 7 conditions (aPR = 3.97; 95% confidence interval [CI] = 2.89, 5.44 for anotia or microtia); aPRs of 1.5 to 2.1 for cleft lip, trisomy 18, and encephalocele, and lower, upper, and any limb deficiency). Cubans and Asians, especially Chinese and Asian Indians, had either significantly lower or similar prevalences of these defects compared with non-Hispanic Whites, with the exception of anotia or microtia among Chinese (aPR = 2.08; 95% CI = 1.30, 3.33) and Filipinos (aPR = 1.90; 95% CI = 1.10, 3.30) and tetralogy of Fallot among Vietnamese (aPR = 1.60; 95% CI = 1.11, 2.32). CONCLUSIONS: This is the largest population-based study to our knowledge to systematically examine the prevalence of a range of major birth defects across many racial/ethnic groups, including Asian and Hispanic subgroups. The relatively high prevalence of birth defects in American Indians/Alaska Natives warrants further attention.

Cancer risk in children and adolescents with birth defects: a population-based cohort study.

OBJECTIVE: Birth defects are an increasing health priority worldwide, and the subject of a major 2010 World Health Assembly Resolution. Excess cancer risk may be an added burden in this vulnerable group of children, but studies to date have provided inconsistent findings. This study assessed the risk for cancer in children and young adolescents with major birth defects. METHODS AND FINDINGS: This retrospective, statewide, population-based, cohort study was conducted in three US states (Utah, Arizona, Iowa). A cohort of 44,151 children and young adolescents (0 through 14 years of age) with selected major, non-chromosomal birth defects or chromosomal anomalies was compared to a reference cohort of 147,940 children without birth defects randomly sampled from each state's births and frequency matched by year of birth. The primary outcome was rate of cancer prior to age 15 years, by type of cancer and type of birth defect. The incidence of cancer was increased 2.9-fold (95% CI, 2.3 to 3.7) in children with birth defects (123 cases of cancer) compared to the reference cohort; the incidence rates were 33.8 and 11.7 per 100,000 person-years, respectively. However, the excess risk varied markedly by type of birth defect. Increased risks were seen in children with microcephaly, cleft palate, and selected eye, cardiac, and renal defects. Cancer risk was not increased with many common birth defects, including hypospadias, cleft lip with or without cleft palate, or hydrocephalus. CONCLUSION: Children with some structural, non-chromosomal birth defects, but not others, have a moderately increased risk for childhood cancer. Information on such selective risk can promote more effective clinical evaluation, counseling, and research.

External cavity laser biosensor.

Utilizing a tunable photonic crystal resonant reflector as a mirror of an external cavity laser cavity, we demonstrate a new type of label-free optical biosensor that achieves a high quality factor through the process of stimulated emission, while at the same time providing high sensitivity and large dynamic range. The photonic crystal is fabricated inexpensively from plastic materials, and its resonant wavelength is tuned by adsorption of biomolecules on its surface. Gain for the lasing process is provided by a semiconductor optical amplifier, resulting in a simple detection instrument that operates by normally incident noncontact illumination of the photonic crystal and direct back-reflection into the amplifier. We demonstrate single-mode, biomolecule-induced tuning of the continuous-wave laser wavelength. Because the approach incorporates external optical gain that is separate from the transducer, the device represents a significant advance over previous passive optical resonator biosensors and laser-based biosensors.

A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products.

High-throughput screening is the dominant method used to identify lead compounds in drug discovery. As such, the makeup of screening libraries largely dictates the biological targets that can be modulated and the therapeutics that can be developed. Unfortunately, most compound-screening collections consist principally of planar molecules with little structural or stereochemical complexity, compounds that do not offer the arrangement of chemical functionality necessary for the modulation of many drug targets. Here we describe a novel, general and facile strategy for the creation of diverse compounds with high structural and stereochemical complexity using readily available natural products as synthetic starting points. We show through the evaluation of chemical properties (which include fraction of sp(3) carbons, ClogP and the number of stereogenic centres) that these compounds are significantly more complex and diverse than those in standard screening collections, and we give guidelines for the application of this strategy to any suitable natural product.

Process for determining the cancer burden of the Hopi Tribe.

The Hopi Tribe is located in the northeastern part of Arizona on more than one million acres of federally reserved land. Tribally based community research, conducted in collaboration with University of Arizona researchers, has been successfully implemented on Hopi beginning with a cross-sectional community survey in 1993 and continuing with a second survey in 2006. Both surveys identified a strong community interest in cancer. This article reports on the process involved in a third study, in which official Hopi enrollment data were matched with Arizona Cancer Registry data. The process involved bringing in a new partner and obtaining tribal, state, and university approvals, as well as a signed data exchange agreement between the state and the Hopi Tribe. Technical implementation of the data match required computer programming and epidemiologic expertise, as well as an understanding of the community and the culture. Close collaboration among Hopi residents and university epidemiologists was critical.

Penetrating knife injury to the frontal lobe--a case report.

Penetrating injuries of the craniofacial region are increasing and have the potential to cause severe vascular and neurological deficit. We present our management of a case with a knife stab injury to the infra-orbital region, traversing the orbit and penetrating into the anterior cranial fossa, the tip lying in close proximity to the anterior cerebral circulation.