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Eye tracking assessments that include pupil metrics can supplement current clinical assessments of vision and autonomic dysfunction in concussed adolescents.This study aimed to explore the utility of a 220-second eye tracking assessment in distinguishing eye position, saccadic movement, and pupillary dynamics among uninjured adolescents, those with acute post-concussion symptoms (≤28 days since concussion), or those with persistent post-concussion symptoms (28 days since concussion).Two hundred fifty-six eye tracking metrics across a prospective observational cohort of 180 uninjured adolescents recruited from a private suburban high school and 224 concussed adolescents, with acute or persistent symptoms, recruited from a tertiary care subspecialty concussion care program, 13 to 17 years old, from August 2017 to June 2021 were compared. Kruskal-Wallis tests were used, and Bonferroni corrections were applied to account for multiple comparisons and constructed receiver operating characteristic curves. Principal components analysis and regression models were applied to determine whether eye tracking metrics can augment clinical and demographic information in differentiating uninjured controls from concussed adolescents.Two metrics of eye position were worse in those with concussion than uninjured adolescents, and only one metric was significantly different between acute cases and persistent cases. Concussed adolescents had larger left and right mean, median, minimum, and maximum pupil size than uninjured controls. Concussed adolescents had greater differences in mean, median, and variance of left and right pupil size. Twelve metrics distinguished female concussed participants from uninjured; only four were associated with concussion status in males. A logistic regression model including clinical and demographics data and transformed eye tracking metrics performed better in predicting concussion status than clinical and demographics data alone.Objective eye tracking technology is capable of quickly identifying vision and pupillary disturbances after concussion, augmenting traditional clinical concussion assessments. These metrics may add to existing clinical practice for monitoring recovery in a heterogeneous adolescent concussion population.

RATIONALE: Recreational and medical use of stimulants is increasing, and their use may increase susceptibility to aging and promote neurobehavioral impairments. The long-term consequences of these psychostimulants and how they interact with age have not been fully studied. OBJECTIVES: Our study investigated whether chronic exposure to the prototypical psychostimulant, methamphetamine (METH), at doses designed to emulate human therapeutic dosing, would confer a pro-oxidizing redox shift promoting long-lasting neurobehavioral impairments. METHODS: Groups of 4-month-old male and female C57BL/6J mice were administered non-contingent intraperitoneal injections of either saline or METH (1.4 mg/kg) twice a day for 4 weeks. Mice were randomly assigned to one experimental group: (i) short-term cognitive assessments (at 5 months), (ii) long-term cognitive assessments (at 9.5 months), and (ii) longitudinal motor assessments (at 5, 7 and 9 months). Brain regions were assessed for oxidative stress and markers of neurotoxicity after behavior testing. RESULTS: Chronic METH exposure induced short-term effects on associative memory, gait speed, dopamine (DA) signaling, astrogliosis in females and spatial learning and memory, balance, DA signaling, and excitotoxicity in males. There were no long-term effects of chronic METH on cognition, however, it decreased markers of excitotoxicity in the striatum and exacerbated age-associated motor impairments in males. CONCLUSION: In conclusion, cognitive and motor function were differentially and sex-dependently affected by METH exposure, and oxidative stress did not seem to play a role in the observed behavioral outcomes. Future studies are necessary to continue exploring the long-term neurobehavioral consequences of drug use in both sexes and the relationship between aging and drugs.

OBJECTIVE: National data suggest drivers who are younger, older, and have lower socioeconomic status (SES) have heightened crash-related injury rates. Ensuring vulnerable drivers are in the safest vehicles they can afford is a promising approach to reducing crash injuries in these groups. However, we do not know the extent to which these drivers are disproportionately driving less safe vehicles. Our objective was to obtain population-based estimates of the prevalence of important vehicle safety criteria among a statewide population of drivers. METHODS: We analyzed data from the NJ Safety and Health Outcomes warehouse, which includes all licensing and crash data from 2010–2017. We borrowed the quasi-induced exposure method’s fundamental assumption—that non-responsible drivers in clean (i.e., only one responsible driver) multi-vehicle crashes are reasonably representative of drivers on the road—to estimate statewide prevalence of drivers’ vehicle characteristics across four driver age groups (17–20; 21–24; 25–64, and ≥65) and quintiles of census tract median household income (n=983,372). We used NHTSA’s Product Information Catalog and Vehicle Listing platform (vPIC) to decode the VIN of each crash-involved vehicle to obtain model year, presence of electronic stability control (ESC), vehicle type, engine horsepower, and presence of front, side, and curtain air bags. RESULTS: The youngest and oldest drivers were more likely than middle-aged drivers to drive vehicles that were older, did not have ESC, and were not equipped with side airbags. Additionally, across all age groups drivers of higher SES were in newer and safer vehicles compared with those of lower SES. For example, young drivers living in lowest-income census tracts drove vehicles that were on average almost twice as old as young drivers living in highest-income tracts (median [IQR]: 11 years [6–14] vs. 6 years [3–11]). CONCLUSIONS: Vehicle safety is an important component of seminal road safety philosophies that aim to reduce crash fatalities. However, driver groups that are overrepresented in fatal crashes--young drivers, older drivers, and those of lower SES—are also driving the less safe vehicles. Ensuring drivers are in the safest car they can afford should be further explored as an approach to reduce crash-related injuries among vulnerable populations.

Introduction Driving is important for well-being among older adults, but age-related conditions are associated with driving reduction or cessation and increased crash risk for older drivers. Our objectives were to describe population-based rates of older drivers’ licensing and per-driver rates of crashes and moving violations. Methods: We examined individual-level statewide driver licensing, crash, and traffic citation data among all New Jersey drivers aged ≥ 65 and a 35- to 54-year-old comparison group during 2010–2014. Rate ratios (RR) of crashes and moving violations were estimated using Poisson regression. Results: Overall, 86% of males and 71% of females aged ≥ 65 held a valid driver’s license. Older drivers had 27% lower per-driver crash rates than middle-aged drivers (RR: 0.73, 95% CI: 0.73, 0.74)—with appreciable differences by sex—but 40% higher fatal crash rates (RR: 1.40 [1.24, 1.58]). Moving violation rates among older drivers were 72% lower than middle-aged drivers (RR: 0.28 [0.28, 0.28]). Conclusion: The majority of older adults are licensed, with substantial variation by age and sex. Older drivers have higher rates of fatal crashes but lower rates of moving violations compared with middle-aged drivers. Practical applications: Future research is needed to understand the extent to which older adults drive and to identify opportunities to further reduce risk of crashes and resultant injuries among older adults.

Objectives The objectives are to (1) describe disability outcomes at 24 months after injury and (2) identify factors contributing to disability outcomes at 24 months after injury, for Māori and non-Māori who have been hospitalised for injury. Study design This is a prospective cohort study. Methods Prospective Outcomes of Injury Study participants were injured New Zealanders aged 18–64 years and recruited from New Zealand's no-fault injury insurer, the Accident Compensation Corporation's entitlement claims register. Data about a number of pre-injury, injury-related and early post-injury characteristics were collected from interviews held at 3 and 24 months after injury. Disability was measured using the World Health Organization Disability Assessment Schedule (WHODAS). Modified Poisson regression modelling was used to estimate relative risks (RRs) of disability for Māori and non-Māori who were hospitalised for injury. Results Analyses were restricted to 375 Māori and 1824 non-Māori participants for whom complete data were available. Of these, 105 (28%) Māori and 446 (24%) non-Māori were hospitalised for their injury. Of these hospitalised groups, 26% of Māori and 10% of non-Māori were experiencing disability (WHODAS ≥10) at 24 months after injury. Māori who were hospitalised for injury and who were not working for pay before their injury (RR = 2.7; 95% confidence interval [CI] 1.4–4.9), who were experiencing disability before their injury (RR = 3.1; 95% CI 1.6–5.8) or who reported trouble accessing healthcare services for their injury (RR = 2.6; 95% CI 1.3–5.2) were independently at increased risk of disability 24 months after injury. Non-Māori who were hospitalised for injury and who had inadequate household income before injury (RR = 2.4; 95% CI 1.4–4.1), less than the secondary school qualifications (RR = 2.0; 95% CI 1.1–3.8), were not working for pay before injury (RR = 2.8; 95% CI 1.5–5.1), were experiencing disability before their injury (RR = 3.0; 95% CI 1.7–5.2), had ≥2 chronic conditions (RR = 3.5; 95% CI 2.0–6.4) or had body mass index ≥30 kg/m2/undisclosed (RR = 2.4; 95% CI 1.3–4.4) were at increased risk of disability 24 months after injury. Conclusions Variables predicting disability 24 months after injury for Māori, also predict disability 24 months after injury for non-Māori, with one notable exception—trouble accessing healthcare services. Our findings show that having access to healthcare services for injury plays an important role after injury and must be focussed on to ensure that the burden of poor injury-related outcomes and injury-related inequities are reduced and ultimately eliminated.

Importance Concussion diagnosis remains clinical, without objective diagnostic tests available for adolescents. Known deficits in visual accommodation and autonomic function after concussion make the pupillary light reflex (PLR) a promising target as an objective physiological biomarker for concussion. Objective To determine the potential utility of PLR metrics as physiological biomarkers for concussion. Design, Setting, and Participants Prospective cohort of adolescent athletes between ages 12 and 18 years recruited between August 1, 2017, and December 31, 2018. The study took place at a specialty concussion program and private suburban high school and included healthy control individuals (n = 134) and athletes with a diagnosis of sport-related concussion (SRC) (n = 98). Analysis was completed June 30, 2020. Exposures Sports-related concussion and pupillometry assessments. Main Outcomes and Measures Pupillary light reflex metrics (maximum and minimum pupillary diameter, peak and average constriction/dilation velocity, percentage constriction, and time to 75% pupillary redilation [T75]). Results Pupillary light reflex metrics of 134 healthy control individuals and 98 athletes with concussion were obtained a median of 12.0 days following injury (interquartile range [IQR], 5.0-18.0 days). Eight of 9 metrics were significantly greater among athletes with concussion after Bonferroni correction (maximum pupil diameter: 4.83 mm vs 4.01 mm; difference, 0.82; 99.44% CI, 0.53-1.11; minimum pupil diameter: 2.96 mm vs 2.63 mm; difference, 0.33; 99.4% CI, 0.18-0.48; percentage constriction: 38.23% vs 33.66%; difference, 4.57; 99.4% CI, 2.60-6.55; average constriction velocity: 3.08 mm/s vs 2.50 mm/s; difference, 0.58; 99.4% CI, 0.36-0.81; peak constriction velocity: 4.88 mm/s vs 3.91 mm/s; difference, 0.97; 99.4% CI, 0.63-1.31; average dilation velocity, 1.32 mm/s vs 1.22 mm/s; difference, 0.10; 99.4% CI, 0.00-0.20; peak dilation velocity: 1.83 mm/s vs 1.64 mm/s; difference, 0.19; 99.4% CI, 0.07-0.32; and T75: 1.81 seconds vs 1.51 seconds; difference, 0.30; 0.10-0.51). In exploratory analyses, sex-based differences were observed, with girls with concussion exhibiting longer T75 (1.96 seconds vs 1.63 seconds; difference, 0.33; 99.4% CI, 0.02-0.65). Among healthy control individuals, diminished PLR metrics (eg, smaller maximum pupil size 3.81 mm vs 4.22 mm; difference, −0.41; 99.4% CI, −0.77 to 0.05) were observed after exercise. Conclusions and Relevance These findings suggest that enhancement of PLR metrics characterize acute adolescent concussion, while exercise produced smaller pupil sizes and overall slowing of PLR metrics, presumably associated with fatigue. Quantifiable measures of the PLR may serve in the future as objective physiologic biomarkers for concussion in the adolescent athlete.

Objective To comprehensively characterize the clinical presentation and course of care for concussion among 5- to 11-year-old children, identifying preinjury and injury factors potentially influencing clinical outcomes. Study design A single-institution retrospective cohort study using electronic health record data from children ages 5- to 11 years with a concussion from July 1, 2014, through June 30, 2015. Electronic health record data were abstracted for a 20% random sample of 292 patients. Results Three-fourths of patients (74.3%) presenting for concussion care had a standardized visiovestibular assessment performed. Almost all of those who eventually sought specialty care (92.9%) also had such an assessment, and only 42.9% patients initially seen in the emergency department or urgent care were examined in this manner. Of those assessed, 62.7% (n = 136) demonstrated deficits, with children ages 9-11 years more frequently exhibiting deficits than their younger counterparts (67.9% vs 53.2%; P = .03). Almost all patients (95.9%) reported at least 1 somatic symptom (eg, headache, dizziness), and one-half to two-thirds reported problems with sleep (54.1%) and visiovestibular symptoms (66.1%). Only 11.6% of children were referred for rehabilitation therapies and less than one-half of concussed patients (43.8%) were provided with a letter recommending school accommodations. Conclusions Somatic symptoms, sleep problems, and visiovestibular deficits are common in elementary school-aged children with concussion, but specific visiovestibular clinical assessments are often not performed, particularly in the emergency department setting. Recommendations for school accommodations are often not provided at the time of concussion diagnosis. Incorporating a standardized visiovestibular assessment into practice could facilitate early targeted school accommodations and thereby improve return to learning for elementary school-aged children with concussion.

Background Few previous studies have directly compared crash rates of older and younger novice drivers. To inform discussion about whether Graduated Driver Licensing (GDL) policies that are applied in the US for younger novice drivers should be applied to older novice drivers, we conducted a longitudinal study to examine overall, nighttime, and multiple passenger crash rates over the initial four years of licensure differ for novice drivers licensed at different ages. Methods Using data from the New Jersey Traffic Safety Outcomes (NJ-TSO) data warehouse, we selected all NJ drivers who obtained their initial intermediate driver’s license from 2006 through 2014 and had at least one month of follow-up from the date of licensure to study end or death (n = 1,034,835). Novice drivers were grouped based on age at licensure: age 17; 18–20; 21–24; and 25 or older. We estimated monthly rates for overall crashes (per 10,000 licensed drivers) as well as: late night crashes (11:01 p.m.–4:59 a.m.); early night crashes (9:00 p.m.–11:00 p.m.); and multiple passenger crashes (two or more passengers). Average monthly rates were calculated for specific relevant time periods and Poisson regression models were used to compare rates: (1) between novice driver groups with the same time since licensure; (2) over the first 48 months of licensure within each novice driver group; and (3) between same-aged 21-year-old drivers with varying lengths of licensure. Results Although initial (three months post-licensure) overall crash rates of novice NJ drivers age 21 and older were higher than rates of same-aged experienced drivers, they were substantially lower than initial rates for 17- to 20-year-old novice drivers, who are licensed under GDL policies. Moreover, older novice drivers experience much less steep crash reductions over the first year of licensure than younger novice drivers. Nighttime crash rates among the 21- to 24-year old and aged 25 and older novice driver groups were stable over the first year of licensure. For novice drivers under age 21, early night crash rates declined rapidly over the course of licensure, while changes in late night crashes were much smaller. First-year multiple passenger crash rates were highest for drivers licensed at age 18–20, and novice driver groups experienced varying amounts of reduction in multiple passenger crashes over time. Conclusions Study findings support NJ’s current GDL policies for 17- to 20-year-old novice drivers and the potential for added benefits from beginning the nighttime restriction at 9:00 p.m. Conversely, there was a lack of compelling evidence for additional policies for drivers licensed at age 21–24 and no evidence to indicate a need for additional GDL policies for NJ novices aged 25 years and older.

Primary care providers are increasingly providing youth concussion care but report insufficient time and training, limiting adoption of best practices. We implemented a primary care–based intervention including an electronic health record–based clinical decision support tool (“SmartSet”) and in-person training. We evaluated consequent improvement in 2 key concussion management practices: (1) performance of a vestibular oculomotor examination and (2) discussion of return-to-learn/return-to-play (RTL/RTP) guidelines. Data were included from 7284 primary care patients aged 0 to 17 years with initial concussion visits between July 2010 and June 2014. We compared proportions of visits pre- and post-intervention in which the examination was performed or RTL/RTP guidelines provided. Examinations and RTL/RTP were documented for 1.8% and 19.0% of visits pre-intervention, respectively, compared with 71.1% and 72.9% post-intervention. A total of 95% of post-intervention examinations were documented within the SmartSet. An electronic clinical decision support tool, plus in-person training, may be key to changing primary care provider behavior around concussion care.

Introduction: An increasing number of middle-aged men are being screened for low testosterone levels and the number of prescriptions for various forms of testosterone replacement therapy (TRT) has increased dramatically over the last 10 years. However, the safety of TRT has come into question with some studies suggesting increased morbidity and mortality. Objective: Because the benefits of estrogen replacement in postmenopausal women and ovariectomized rodents are lost if there is an extended delay between estrogen loss and replacement, we hypothesized that TRT may also be sensitive to delayed replacement. Methods: We compared the effects of testosterone replacement after short-term (2 weeks) and long-term testosterone deprivation (LTTD; 10 weeks) in middle-aged male rats on cerebral ischemia, oxidative stress, and cognitive function. We hypothesized that LTTD would increase oxidative stress levels and abrogate the beneficial effects of TRT. Results: Hypogonadism itself and TRT after short-term castration did not affect stroke outcome compared to intact rats. However, after long-term hypogonadism in middle-aged male Fischer 344 rats, TRT exacerbated the detrimental behavioral effects of experimental focal cerebral ischemia, whereas this detrimental effect was prevented by administration of the free-radical scavenger tempol, suggesting that TRT exacerbates oxidative stress. In contrast, TRT improved cognitive performance in non-stroked rats regardless of the length of hypogonadism. In the Morris water maze, peripheral oxidative stress was highly associated with decreased cognitive ability. Conclusions: Taken together, these data suggest that TRT after long-term hypogonadism can exacerbate functional recovery after focal cerebral ischemia, but in the absence of injury can enhance cognition. Both of these effects are modulated by oxidative stress levels.

OBJECTIVES:To compare monthly rates of specific types of crashes, violations, and license suspensions over the first years of licensure for drivers with and without attention-deficit/hyperactivity disorder (ADHD).METHODS:We identified patients of New Jersey primary care locations of the Children’s Hospital of Philadelphia who were born in 1987–1997, were New Jersey residents, had their last primary care visit at age ≥12 years, and acquired a driver’s license (N = 14 936). Electronic health records were linked to New Jersey’s licensing, crash, and violation databases. ADHD diagnosis was based on International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes. We calculated monthly per-driver rates of crashes (at fault, alcohol related, nighttime, and with peers), violations, and suspensions. Adjusted rate ratios were estimated by using repeated-measures Poisson regression.RESULTS:Crash rates were higher for drivers with ADHD regardless of licensing age and, in particular, during the first month of licensure (adjusted rate ratio: 1.62 [95% confidence interval: 1.18−2.23]). They also experienced higher rates of specific crash types: their 4-year rate of alcohol-related crashes was 2.1 times that of drivers without ADHD. Finally, drivers with ADHD had higher rates of moving violations (for speeding, seat belt nonuse, and electronic equipment use) and suspensions. In the first year of driving, the rate of alcohol and/or drug violations was 3.6 times higher for adolescents with ADHD.CONCLUSIONS:Adolescents with ADHD are at particularly high crash risk in their initial months of licensure, and engagement in preventable risky driving behaviors may contribute to this elevated risk. Comprehensive preventive approaches that extend beyond current recommendations are critically needed.

Ethanol withdrawal (EW) is referred to the abrupt termination of long-term heavy drinking, and provokes oxidative brain damage. Here, we investigated whether the cerebellum and hippocampus of female rats are less affected by prooxidant EW than male rats due to the antioxidant effect of 17β-estradiol (E2). Female and male rats received a four-week ethanol diet and three-week withdrawal per cycle for two cycles. Some female rats were ovariectomized with E2 or antioxidant (Vitamin E+Co-Q10) treatment. Measurements were cerebellum (Rotarod) and hippocampus (water-maze)-related behaviors, oxidative markers (O2(-), malondialdehyde, protein carbonyls), mitochondrial membrane swelling, and a key mitochondrial enzyme, cytochrome c oxidase (CcO). Separately, HT22 (hippocampal) cells were subjected to ethanol-exposure and withdrawal for two cycles to assess the effect of a CcO inhibitor on E2's protection for mitochondrial respiration and cell viability. Ethanol-withdrawn female rats showed a smaller increase in oxidative markers in cerebellum and hippocampus than male rats, and E2 treatment decreased the oxidative markers. Compared to male counterparts, ethanol-withdrawn female rats showed better Rotarod but poorer water-maze performance, accompanied by more severe mitochondrial membrane swelling and CcO suppression in hippocampus. E2 or antioxidant treatment improved Rotarod but not water-maze performance. In the presence of a CcO inhibitor, E2 treatment failed to protect mitochondrial respiration and cell viability from EW. These data suggest that antioxidant E2 contributes to smaller oxidative stress in ethanol-withdrawn female than male rats. They also suggest that EW-induced severe mitochondrial damage in hippocampus may blunt E2's antioxidant protection for hippocampus-related behavior.

Presenilin-1 (PS1) is a core component of γ-secretase that is involved in neurodegeneration. We have previously shown that PS1 interacts with a mitogen-activated protein kinase [(MAPK) jun-NH2-terminal-kinase], and another MAPK (p38) is activated by ethanol withdrawal (EW), abrupt termination from chronic ethanol exposure. EW is excitotoxic in nature, induces glutamate upregulation, and provokes neuronal damage. Here, we explored a potential mechanistic pathway involving glutamate, p38 (p38α isozyme), and PS1 that may mediate EW-induced excitotoxic stress. We used the prefrontal cortex of male rats withdrawn from a chronic ethanol diet. Additionally, we used ethanol-withdrawn HT22 cells (mouse hippocampal) treated with the inhibitor of glutamate receptors [dizocilpine (MK-801)], p38α (SB203580; 4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine), or γ-secretase [N-[N- (3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT)] during EW. Separately, ethanol-free HT22 cells were exposed to glutamate with or without SB203580 or DAPT. Protein levels, mRNA levels, and cell viability were assessed using immunoblotting, qualitative polymerase chain reaction, and calcein assay, respectively. The prefrontal cortex of ethanol-withdrawn rats or HT22 cells showed an increase in PS1 and p38α, which was attenuated by MK-801 and SB203580, but mimicked by glutamate treatment to ethanol-free HT22 cells. DAPT attenuated the toxic effect of EW or glutamate on HT22 cells. These results suggest that PS1 expression is triggered by glutamate through p38α, contributing to the excitotoxic stimulus of EW.

Introduction Motor vehicle crashes are the leading cause of adolescent death. Inattention to the roadway contributes to crash risk. The objective of this study was to deploy an initial study of a web-based intervention (Let’s Choose Ourselves) designed to improve adolescent driver attention to the roadway. Methods We used a randomized controlled trial design in a sample of adolescent drivers to test if a web-based intervention decreased cell phone engagement in driving simulation at 3 months as compared with controls. As secondary hypotheses, we tested if the intervention increased the use of peer passengers to manage distractions and decreased eyes off the forward roadway in driving simulation and decreased self-reported risky driving behaviors. Adolescents, aged 16-17 years, licensed for ≤90 days were randomized to Let’s Choose Ourselves with distractions in the simulator protocol at baseline, Let’s Choose Ourselves with no distractions, an attention control intervention on healthy eating with distractions, or attention control with no distractions. We used Poisson regression modeling to test the primary and secondary hypotheses. Results The trial included 60 adolescents (66.7% female, 78.3% non-Hispanic white subjects, mean age 16.8 years, licensed 50.8 days). In Poisson regression, controlling for sex, we found no significant effects of Let’s Choose Ourselves on primary or secondary outcomes. However, there was a significant effect of visit on self-report outcomes, with self-reported distracted driving behaviors increasing over time. Discussion Although there were no significant effects of Let’s Choose Ourselves, self-reported risky driving behaviors increased over time. Further investigation of the relationship between driving experience and increasing inattention to the road in adolescents is warranted.

Abrupt cessation of chronic alcohol consumption triggers signaling cascades that harm vulnerable brain regions and produce neurobehavioral deficits. We have demonstrated that a program of intermittent, normobaric hypoxia training (IHT) in rats prevents brain damage and neurobehavioral impairment resulting from abrupt ethanol withdrawal (EW). Moreover, EW induced expression of stress-activated protein kinase p38 and presenilin 1 (PS1), the catalytic subunit of γ-secretase that produces the neurotoxic amyloid-β (Aβ) peptides Aβ40 and Aβ42. We tested the hypotheses that 1) IHT limits EW-induced activation of the p38-PS1 axis, thereby attenuating γ-secretase activation and Aβ accumulation, and 2) EW disables heat shock protein 25 (HSP25), a p38 substrate, molecular chaperone, and antioxidant, and provokes protein carbonylation in a manner suppressed by IHT. Adult male rats completed two cycles of a 4-wk ethanol diet (6.5% wt/vol) and a 3-wk EW or an isocaloric, dextrin-based control diet. A 20-day IHT program (5–8 daily cycles of 5–10 min of 9.5–10% fractional inspired O2 + 4 min of 21% fractional inspired O2) was administered during the first EW phase. After the second EW phase, the brain was excised and the prefrontal cortex extracted. PS1, phosphorylated p38 (p-p38), and HSP25 were analyzed by immunoblot, PS1 messenger RNA by quantitative polymerase chain reaction, protein carbonyl content by spectrometry, and Aβ40 and Aβ42 contents by enzyme-linked immunosorbent assay. IHT attenuated the EW-associated increases in PS1, p-p38, Aβ40, Aβ42, and protein carbonyl contents, but not that of PS1 messenger RNA, while preserving functionally competent HSP25 dimers in EW rats. Collectively, these findings suggest that IHT may attenuate EW-induced γ-secretase overactivation by suppressing activation of the p38-PS1 axis and by preventing oxidative protein damage.

Driving may increase mobility and independence for adolescents with autism without intellectual disability (autism spectrum disorder); however, little is known about rates of licensure. To compare the proportion of adolescents with and without autism spectrum disorder who acquire a learner’s permit and driver’s license, as well as the rate at which they progress through the licensing system, we conducted a retrospective cohort study of 52,172 New Jersey residents born in the years 1987–1995 who were patients of the Children’s Hospital of Philadelphia healthcare network ⩾12 years of age; 609 (1.2%) had an autism spectrum disorder diagnosis. Electronic health records were linked to New Jersey’s driver licensing database (2004–2012). Kaplan–Meier curves and log-binomial regression models were used to determine the age at and rate of licensure, and estimate adjusted risk ratios. One in three adolescents with autism spectrum disorder acquired a driver’s license versus 83.5% for other adolescents and at a median of 9.2 months later. The vast majority (89.7%) of those with autism spectrum disorder who acquired a permit and were fully eligible to get licensed acquired a license within 2 years. Results indicated that a substantial proportion of adolescents with autism spectrum disorder do get licensed and that license-related decisions are primarily made prior to acquisition of a permit instead of during the learning-to-drive process.

The acetylation of histone proteins in the core of DNA regulates gene expression, including those affecting mitochondria. Both histone acetylation and mitochondrial deficit have been implicated in neuronal damage associated with drinking problems. Many alcoholics will repeat unsuccessful attempts at abstaining, developing a pattern of repeated drinking and withdrawal. We investigated whether aberrant histone acetylation contributes to mitochondrial and cellular damage induced by repeated ethanol withdrawal (EW). We also investigated whether this effect of histone acetylation involves let-7f, a small noncoding RNA (microRNA). Male rats received two cycles of an ethanol/control diet (7.5%, 4 weeks) and withdrawal. Their prefrontal cortex was collected to measure the mitochondrial respiration and histone acetylation using extracellular flux (XF) real-time respirometry and gold immunostaining, respectively. Separately, HT22 (mouse hippocampal) cells received two cycles of ethanol exposure (100 mM, 20 hours) and withdrawal. Trichostatin A (TSA) as a histone acetylation promoter and let-7f antagomir were applied during withdrawal. The mitochondrial respiration, let-7f level, and cell viability were assessed using XF respirometry, quantitative polymerase chain reaction, TaqMan let-7f primers, and a calcein-acetoxymethyl assay, respectively. Repeated ethanol withdrawn rats showed a more than 2-fold increase in histone acetylation, accompanied by mitochondrial respiratory suppression. EW-induced mitochondrial respiratory suppression was exacerbated by TSA treatment in a manner that was attenuated by let-7f antagomir cotreatment. TSA treatment did not alter the increasing effect of EW on the let-7f level but dramatically exacerbated the cell death induced by EW. These data suggest that the multiple episodes of withdrawal from chronic ethanol impede mitochondrial and cellular integrity through upregulating histone acetylation, independent of or additively with let-7f.

Objective To quantify the risk of repeat concussions for children and identify demographic and clinical aspects of the index concussion associated with repeat injury. Study design For this retrospective cohort study, we queried the Children's Hospital of Philadelphia healthcare network's unified electronic health record to identify all 5- to 15-year-old patients who had their first clinical visit for an index concussion at a Children's Hospital of Philadelphia location from July 2012 through June 2013. A 25% random sample (n = 536) were selected. Clinical data were abstracted for their index concussion and all concussion-related visits for 2 years following the index concussion. Results Overall, 16.2% (n = 87) of patients experienced at least 1 repeat concussion within 2 years of their index concussion. The risk of repeat concussion increased with patient age (9.5% for ages 5-8 years; 10.7% for ages 9-11 years; and 19.8% for ages 12-15 years). After we adjusted for other factors, risk was particularly heightened among patients whose index concussion had a longer clinical course (>30 vs 0-7 days, adjusted risk ratio 1.65 [1.01-2.69]) and greater symptom burden (>11 vs 0-2 symptoms, adjusted risk ratio 2.12 [1.12-3.72]). Conclusions We estimate that 1 in 6 youth diagnosed with a concussion are diagnosed with a subsequent concussion within 2 years and that several clinical characteristics of the index concussion increase this risk. Identifying factors associated with a repeat injury is essential to inform the clinical management of concussion and direct injury prevention efforts.

p38 is a mitogen-activated protein kinase and mediates cell growth, cell differentiation, and synaptic plasticity. The aim of this study is to determine the extent to which p38 plays a role in maintaining mitochondrial respiration in male and female mice under a normal condition. To achieve this aim, we have generated transgenic mice that lack p38 in cerebellar Purkinje neurons by crossing Pcp2 (Purkinje cell protein 2)-Cre mice with p38(loxP/loxP) mice. Mitochondria from cerebellum were then isolated from the transgenic and wild-type mice to measure mitochondrial respiration using XF24 respirometer. The mRNA and protein expression of cytochrome c oxidase (COX) in cerebellum were also measured using RT-PCR and immunoblot methods. Separately, HT22 cells were used to determine the involvement of 17β-estradiol (E2) and COX in mitochondrial respiration. The genetic knockout of p38 in Purkinje neurons suppressed the mitochondrial respiration only in male mice and increased COX expression only in female mice. The inhibition of COX by sodium azide (SA) sharply suppressed mitochondrial respiration of HT22 cells in a manner that was protected by E2. These data suggest that p38 is required for the mitochondrial respiration of male mice. When p38 is below a normal level, females may maintain mitochondrial respiration through COX up-regulation.

Objectives To assess the distribution of injury mechanisms and activities among children with concussions in a large pediatric healthcare system. Study design All patients, age 0-17 years, who had at least 1 clinical encounter with an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis of concussion in the Children's Hospital of Philadelphia's electronic health record system from July 1, 2012 to June 30, 2014, were selected (N = 8233) and their initial concussion-related visit identified. Approximately, 20% of the patients (n = 1625) were randomly selected for manual record review to examine injury mechanisms and activities. Results Overall, 70% of concussions were sports related; however, this proportion varied by age. Only 18% of concussions sustained by children aged 0-4 were sports related, compared with greater proportions for older children (67% for age 5-11, 77% for age 12-14, and 73% for age 15-17). When the concussion was not sports related, the primary mechanisms of injury were struck by an object (30%) and falls (30%). Conclusions Sports-related injuries in children older than 6 years of age contributed to the majority of concussions in this cohort; however, it is important to note that approximately one-third of concussions were from non–sports-related activities. Although there is increased participation in community and organized sports activities among children, a focus on prevention efforts in other activities where concussions occur is needed.

We explored if an alternative CRS design that utilized a mechanical adjunct to amplify the force applied to the adult seat belt (intervention CRS) results in more accurate and secure attachment between the CRS and the vehicle compared to similar CRS models that use LATCH or the existing adult seat belt. We conducted three separate studies to address this question and additionally explored: (1) the contribution of prior CRS installation experience (Study 1), (2) the value-added of CRS labeling (Study 2), and (3) paper-based vs. video instructions (Study 3).In Studies 1 and 2 we assessed a forward facing combination CRS design (intervention CRS) compared to a commercially available LATCH equipped model (control CRS) and in Study 3 we conducted a similar study using a convertible model of both the intervention and control CRS. Participants installed both CRS in a contemporary minivan and could choose which type of attachment to use for the control CRS (LATCH or seat belt); order of installation was counter-balanced. Evaluators systematically examined installations for accuracy and security.Study 1: A greater proportion of participants in both the experienced and inexperienced groups was able to securely install the intervention CRS compared to the control CRS: (45% vs. 16%, p =.0001 for experienced) and (37% vs. 6%, p =.003 for inexperienced). No differences between the CRS were observed for accuracy of installation in either user group. Study 2: A greater proportion of participants were able to securely install the enhanced intervention CRS compared to the control CRS: (62% vs. 9%, p =.001). The intervention CRS demonstrated reduced installation accuracy: (30% vs. 61%, p =.001). Study 3: A greater proportion of participants was able to securely install the intervention CRS compared to the control CRS: 79% vs. 66% p =.03, but this effect was smaller than in the previous studies. Participants were less likely to achieve an accurate installation with the intervention CRS compared to the control CRS: 54% vs. 79%, p =.004. Common accuracy errors in each study included twisting or misrouting the seatbelt when installing the intervention CRS.Our results suggest that novel CRS designs that utilize mechanical advantage to facilitate attachment of the CRS to the vehicle result in a tighter installation compared to LATCH equipped models, but an increase in accuracy errors occurred.

Importance Attention-deficit/hyperactivity disorder (ADHD) often persists into adolescence, when motor vehicle crash risk peaks. We know little about when adolescents with ADHD get licensed and, once they do, the extent to which they have increased crash risk compared with adolescents without ADHD. Objectives To examine the association between ADHD and both driver licensing and crash involvement and whether it varies by sex, licensing age, and/or being prescribed ADHD medication at licensure. Design, Setting, and Participants This retrospective cohort study was conducted at 6 primary care practices of the Children’s Hospital of Philadelphia, a large pediatric health care network in southeastern Pennsylvania and southern New Jersey. Using electronic health records, we defined a cohort of 2479 adolescents and young adults with ADHD and 15 865 without ADHD who were (1) born from 1987 to 1997; (2) residents of New Jersey and patients at 1 of 6 New Jersey primary care practices at age 12 years or older; and (3) age-eligible to obtain a driver’s license from 2004 through 2014. Electronic health records data were then linked with New Jersey’s statewide driver licensing and crash databases for 2004 through 2014. Main Outcomes and Measures Acquisition of a driver’s license and first involvement as a driver in a police-reported crash. Survival analysis was used to estimate adjusted hazard ratios for licensing and crash outcomes through age 25 years. Results The median age of individuals at the end of the study was 22.2 years (interquartile range, 19.7-24.8). Compared with individuals without ADHD, the licensing probability of individuals with ADHD 6 months after eligibility was 35% lower (for males: adjusted hazard ratio, 0.65; 95% CI, 0.61-0.70; females: adjusted hazard ratio, 0.64; 95% CI, 0.58-0.70). Among individuals with a driver’s license, 764 of 1785 with ADHD (42.8%) and 4715 of 13 221 without ADHD (35.7%) crashed during the study period. The adjusted risk for first crash among licensed drivers with ADHD was 1.36 times higher than for those without ADHD (95% CI, 1.25-1.48) and did not vary by sex, licensing age, or over time. Only 129 individuals with ADHD (12.1%) were prescribed medication in the 30 days before licensure. Conclusions and Relevance Adolescents with ADHD get licensed less often and at an older age. Once licensed, this cohort has a greater risk of crashing. Additional research is needed to understand the specific mechanisms by which ADHD influences crash risk.

In 1993 Sin Nombre virus was recognized as the cause of hantavirus pulmonary syndrome (HPS) and the deer mouse (Peromyscus maniculatus) was identified as the reservoir host. Surveillance by the Centers for Disease Control and Prevention and state health departments includes investigation to determine the likely site(s) and activities that led to infection, an environmental assessment of the home and workplace, and possibly rodent trappings at these sites. As of December 31, 1998, there were 200 confirmed cases from 30 states (43% case-fatality ratio). The national HPS case registry was examined to determine the incubation period of HPS. Review of 11 case-patients with well-defined and isolated exposure to rodents suggests that the incubation period of HPS is 9 to 33 days, with a median of 14-17 days. Case investigations allow a better understanding of the incubation time of HPS and may define high-risk behaviors that can be targeted for intervention.

OBJECTIVES: To describe the disposition of young children diagnosed with physical abuse in the emergency department (ED) setting and identify factors associated with the decision to discharge young abused children. STUDY DESIGN: We performed a retrospective cross-sectional study of children less than 2 years of age diagnosed with physical abuse in the 2006-2012 Nationwide Emergency Department Sample. National estimates were calculated accounting for the complex survey design. We developed a multivariable logistic regression model to evaluate the relationship between payer type and discharge from the ED compared with admission with adjustment for patient and hospital factors. RESULTS: Of the 37 655 ED encounters with a diagnosis of physical abuse among children less than 2 years of age, 51.8% resulted in discharge, 41.2% in admission, 4.3% in transfer, 0.3% in death in the ED, and 2.5% in other. After adjustment for age, sex, injury type, and hospital characteristics (trauma designation, volume of young children, and hospital region), there were differences in discharge decisions by payer and injury severity. The adjusted percentage discharged of publicly insured children with minor/moderate injury severity was 56.2% (95% CI 51.6, 60.7). The adjusted percentages discharged were higher for both privately insured children at 69.9% (95% CI 64.4, 75.5) and self-pay children at 72.9% (95% CI 67.4, 78.4). The adjusted percentages discharged among severely injured children did not differ significantly by payer. CONCLUSIONS: The majority of ED visits for young children diagnosed with abuse resulted in discharge. The notable differences in disposition by payer warrant further investigation.Copyright © 2016 Elsevier Inc. All rights reserved. Language: en

The objective of this survey was to investigate the prevalence of Hepatozoon infection in dogs in the rural and urban areas of Uberlândia, Brazil by PCR and molecular characterization. DNA was obtained from blood samples collected from 346 local dogs from both genders and various ages. Seventeen PCR products from positive blood samples of urban dogs and 13 from the rural dogs were sequenced. Partial sequences of the 18S rRNA gene indicated that all 30 dogs were infected with Hepatozoon canis similar in sequence to H. canis from southern Europe. Four local dog sequences were submitted to GenBank (accessions JN835188; KF692038; KF692039; KF692040). This study indicates that H. canis is the cause of canine hepatozoonosis in Uberlândia and that infection is similarly widespread in rural and urban dogs.

Cancer incidence and mortality were ascertained in a cohort of 1910 male participants of the Albany Cardiovascular Health Center (CVHC). The New York State Cancer Registry, vital records files, CVHC follow-up records, New York State Retirement System files, and New York State Department of Motor Vehicles driver's license files were used. Serum cholesterol measurements as well as values for other exposure variables were obtained from records of medical examinations which began in 1953-1954. The study cohort was divided into two groups, based on initial serum cholesterol measurement (less than or equal to 190 mg/100 ml and less than or equal to 190 mg/100 ml). For total cancers, both incidence and mortality were similar in these groups. For digestive cancer, both incidence and mortality were slightly lower in the less than or equal to 190 mg/100 ml group. The deficit was not statistically significant. For respiratory cancer, relative risk and rate ratio estimates were in the range of 1.4-1.7 for incidence and mortality. The excess risk in the less than or equal to 190 mg/100 ml group was of borderline statistical significance. The association was concentrated in the lowest cholesterol quintile rather than suggesting a strong dose-response relationship. The estimates were not found to be confounded by cigarette smoking, body mass index, education or age. A reduction in the crude rate ratio estimate from 1.5 to 1.2 was observed when early cases were excluded, suggesting that part of the observed excess may be due to preclinical cancer.

We investigated whether protein kinase P38 plays a role in the brain-aging changes associated with repeated ethanol withdrawal (EW). Ovariectomized young, middle-age and older rats, with or without 17β-estradiol (E2) implantation, received a 90-day ethanol with repeated withdrawal. They were tested for active pP38 expression in cerebellar Purkinje neurons and whole-cerebellar lysates using immunohistochemistry and enzyme-linked immunosorbent assay, respectively. They were also tested for the Rotarod task to determine the behavioral manifestation of cerebellar neuronal stress and for reactive oxygen species (ROS) and mitochondrial protein carbonyls to determine oxidative mechanisms. Middle-age EW rats showed higher levels of pP38-positive Purkinje neurons/cerebellar lysates, which coincided with increased mitochondrial protein oxidation than other diet/age groups. Exacerbated motor deficit due to age–EW combination also began at the middle-age. In comparison, ROS contents peaked in older EW rats. E2 treatment mitigated each of the EW effects to a different extent. Collectively, pP38 may mediate the brain-aging changes associated with pro-oxidant EW at vulnerable ages and in vulnerable neurons in a manner protected by estrogen.

Syndromic surveillance monitors trends in nonspecific health indicator data to detect disease outbreaks in a timely manner; however, only a limited percentage of persons with mild illness might exhibit behaviors that could be detected by syndromic surveillance.The objectives of this study were to 1) examine the demographic characteristics of New Yorkers with recent flu-like or diarrheal illness, 2) describe behaviors associated with having flu-like illness, and 3) estimate the citywide burden for selected illnesses by calculating the syndromic multiplier (i.e., the number of citywide illnesses represented by each visit to an emergency department [ED]).A cross-sectional telephone survey of 2,433 adult residents of New York City (NYC) was conducted during March 19-March 31, 2003, and October 27-November 23, 2003. Respondents were asked about flu-like illness, behaviors related to flu-like illness, and diarrheal illness during the 30 days before the interview. Estimated numbers of citywide illnesses were compared with ED visits for flu-like and diarrheal illnesses that were recorded by the NYC syndromic surveillance system for the same periods.Every ED visit for flu-like illness represented approximately 60 illnesses among city residents; every visit for diarrheal illness represented approximately 251 illnesses. Among adults who reported a recent flu-like illness, 53.2% purchased over-the-counter (OTC) medications; 32.6% reported missing school or work; 29.1% visited a physician; 21.4% called a physician for advice; 8.8% visited an ED; and 3.8% called a nurse or health hotline for advice. Of those who reported multiple behaviors, respondents most commonly reported purchasing OTC medications as their first response to a flu-like illness.Population-based survey data can be used in conjunction with syndromic surveillance data to better understand the relation between nonspecific health indicators and the burden of certain illnesses in the community, and to assess the representativeness of different syndromic data sources.

The objective was to assess the single- and multiple-dose pharmacokinetics of levodopa and 3-O-methyldopa following administration of a new dual-release and conventional slow-release formulation of levodopa/benserazide in the dose ratio of 4:1. In an open-label, two-way cross-over study, 20 healthy volunteers were randomized to receive first either Madopar® DR or Madopar® HBS for 8 days. Then they crossed over to the other formulation. A first dose of 200 mg levodopa and 50 mg benserazide (‘250’ mg) was given on day 1, ‘125’ mg t.i.d. on the subsequent 6 days (days 2–7), followed by ‘250’ mg on day 8. The two treatment periods of 8 days were separated by a wash-out period of at least 7 days. Blood samples were taken at specific times over a 12-hour period (day 1) or a 36-hour period (day 8). Plasma concentrations of levodopa and 3-O-methyldopa were measured by high-performance liquid chromatography for pharmacokinetic evaluation. The pharmacokinetics of levodopa after a single-dose administration (day 1) of Madopar DR and Madopar HBS were significantly different as reflected by the respective mean values of maximum plasma concentration (Cmax 1.99 vs. 0.82 mg·l–1), time to reach maximum concentration (tmax 0.7 vs. 2.6 h) and area under the plasma concentration-time curve (AUC0–∞ 4.52 vs. 3.18 mg·h·l–1). The respective values after multiple doses (day 8) were: Cmax 1.98 vs. 0.93 mg·l–1, tmax 0.7 vs. 2.3 h and AUC0–∞ 4.84 vs. 3.96 mg·h·l–1. The relative bioavailability (Madopar DR vs. Madopar HBS) was 1.73 on day 1 and 1.32 on day 8. Bioequivalence could not be demonstrated for log-transformed data of AUC and Cmax within a predefined range of 80–125 and 70–143%, respectively. In conclusion, the observed differences in Cmax, tmax and AUC are consistent with a faster rate and higher extent of levodopa absorption after administration of Madopar DR. Statistical evaluation of these kinetic data showed that Madopar DR is not bioequivalent to Madopar HBS.

Childhood obesity has been connected to hyperlipidemia, diabetes, hypertension, and atherosclerosis (Klish, 1998). Both genetic and environmental influences play a role in the development of obesity. Prevention of obesity in childhood is the best chance of instituting lifestyle change for the reduction of cardiovascular morbidity and mortality. Children at high risk for obesity-related cardiovascular disease (CVD) should receive family-based individualized treatment. Nurse practitioners practicing in the primary care setting are in an ideal position to address children and families with regard to lifestyle modification of diet and exercise.

Background This study examined the relationship between antecedent syphilis infection and cancer incidence in an attempt to identify specific cancer patterns. Methods The study cohort consisted of 16,420 people diagnosed with syphilis between 1972 and 1987 and who were residents of New York State, exclusive of New York City, at time of diagnosis. Incident cancers among cohort members were identified through linkage with files maintained by the New York State Cancer Registry. Results A total of 350 cancer cases were diagnosed among cohort members. For males and females combined, incidence was significantly elevated for cancers of the oral cavity standardized incidence ratio (SIR = 169, 95% confidence interval [CI]: 109-249), and specifically for cancer of the tongue (SIR = 251, 95% CI: 108-494). Significantly elevated incidence was observed among males for Kaposi's sarcoma (SIR = 2000, 95% CI: 1290-2950). Conclusion While no conclusions may be reached concerning causality, the data do argue for increased cancer surveillance among people with syphilis. Moreover, findings are discussed in light of historical considerations.

BACKGROUND AND OBJECTIVES Few studies have examined the patterns of death among persons with a history of syphilis infection. GOALS OF THIS STUDY This analysis examines the cause-specific mortality patterns among a cohort of persons diagnosed with syphilis. STUDY DESIGN Individuals diagnosed with serologically confirmed syphilis in New York State (excluding New York City) between 1972 and 1987 were matched to the New York State mortality files to identify the deaths among members of the cohort. RESULTS The overall observed mortality between 1973 and 1987 was generally comparable to the expected number among both men (SMR = 0.94; 95% CI = 0.87-1.02) and women (SMR = 0.88; 0.78-0.99). An excess of deaths due to all causes was observed among men between the ages of 25 and 54 (SMR = 1.74; 1.53-1.97), with the largest excess observed in the 25- to 34-year-old age group (SMR = 2.32; 1.87-2.85). Among men, excesses were noted for deaths due to AIDS-related causes. Among both genders, excess deaths were observed for possible alcohol-related causes. CONCLUSION The unique mortality patterns of this cohort suggest the need for increased identification of and interventions directed toward high-risk behavior of individuals diagnosed with syphilis.

Twenty-seven transfusion dependent patients with end-stage renal disease on long-term dialysis had blood cell counts, serum chemistries, blood pressure, and whole blood viscosity measured, as well as having transfusion requirements assessed. Three months after the institution of recombinant human erythropoietin (rHU-EPO) (75 u per kg per wk), there was an 88 percent fall in transfusion requirement. After four months, the hematocrit increased from 24 +/- 3.8 to 25.6 +/- 4.2 percent, mean corpuscular volume from 93 +/- 4.9 to 97 +/- 6.6 fl, 2-3-diphosphoglycerate (2,3-DPG) from 13.2 +/- 3.2 to 15.6 +/- 4.3 microM per g of Hb. Whole blood viscosity fell from 14.1 +/- 2.1 to 12.7 +/- 2.3 seconds, and ferritin levels fell from 3282 +/- 3889 to 2131 +/- 2441 ng per ml. In eight patients in whom the dose of rHU-EPO was further increased by up to 50 units per kg three times weekly for three months, the hematocrit rose further to 29.3 +/- 3.0 percent and the rise in hematocrit was accompanied by a further increase in 2,3-DPG to 17.9 +/- 2.8 microM per g of Hb (p0.03). There were no major side effects or vascular complications.

Thirty frequently transfused patients on long term hemodialysis were studied and a similar number of age and sex-matched patients who were infrequently transfused were used as a control group to ascertain the influence of a previous myocardial infarction (MI) on transfusion requirements. The frequency of previous MI on electrocardiogram (ECG) in the transfused and control groups was similar (40 percent and 37 percent, respectively). In frequently transfused dialysis patients with MI, the hemoglobin level (transfusion trigger) at which these patients were transfused was higher than that of frequently transfused patients without MI (8.3 +/- 1.5 g per dl vs. 6.9 +/- 1 g per dl, p less than 0.01) which indicated that patients without MI tolerated a greater degree of anemia than those with MI. The 2,3-diphosphoglycerate (2,3-DPG) levels were significantly elevated in all transfused patients when compared to matched controls. However, levels of 2,3-DPG were significantly higher in MI patients receiving frequent transfusions than in other transfused patients, suggesting oxygen demands may not have been fully met despite the frequent transfusions. The results suggest levels of 2,3-DPG deserve further study in relation to the adequacy of tissue oxygenation in anemic dialysis patients.

The health impacts of exposure to summertime heat are a significant problem in New York City (NYC) and for many cities and are expected to increase with a warming climate. Most studies on heat-related mortality have examined risk factors at the municipal or regional scale and may have missed the intra-urban variation of vulnerability that might inform prevention strategies. We evaluated whether place-based characteristics (socioeconomic/demographic and health factors, as well as the built and biophysical environment) may be associated with greater risk of heat-related mortality for seniors during heat events in NYC. As a measure of relative vulnerability to heat, we used the natural cause mortality rate ratio among those aged 65 and over (MRR65+), comparing extremely hot days (maximum heat index 100°F+) to all warm season days, across 1997–2006 for NYC’s 59 Community Districts and 42 United Hospital Fund neighborhoods. Significant positive associations were found between the MRR65+ and neighborhood-level characteristics: poverty, poor housing conditions, lower rates of access to air-conditioning, impervious land cover, surface temperatures aggregated to the area-level, and seniors’ hypertension. Percent Black/African American and household poverty were strong negative predictors of seniors’ air conditioning access in multivariate regression analysis.

It is reported about 70 patients with bronchogenic cancer during the period of 1967 to 1978, which were treated by a wedge-lobe-resection of cardiorespiratory reasons. The results of this operation method don't stand behind those of lobe- respectively pneumonectomy. The reasons are the comparatively lower operation stress and the smaller loss of lung parenchyma. In critical use the economic method of treatment presents a true alternative treatment on patients with increased risk, though it should not remove the classic resection methods.

A case report involving a pleuropulmonary mixed bacterial infection in association with Aspergillus niger is described. The patient responded to a combination of antibiotics, aerosolized and intravenously administered amphotericin B, and surgery. Aspergillus niger appeared to be a secondary invader and caused lung damage by the production of oxalic acid.

Factitious hyperinsulinism was suspected in a patient with an 11-year history of insulin-dependent, ketosis-prone diabetes mellitus who began to experience repetitive episodes of "spontaneous" hypoglycemia. Insulin mediation of the hypoglycemia was confirmed by documenting that urinary insulin and total extractable insulin in plasma increased during periods of hypoglycemia. Failure to detect significant amounts of human C-peptide by radioimmunoassay during periods of hypoglycemia or in response to stimulation with glucagon, leucine, or tolbutamide indicated that the insulin was not endogenous. The diagnosis of factitious hyperinsulinism was ultimately proved by the finding of radioactivity in the patient's urine after 131-I Hippuran was added to a vial of insulin found in the patient's room.

A population-based case-control study was conducted with 338 patients less than 15 years of age who were diagnosed with a primary tumor of the central nervous system from January 1968 through December 1977 in 53 contiguous New York counties. The study also included 676 controls who were selected from the birth certificate files of the New York State Department of Health. Parental occupational exposures at the time of each child's birth and at the time of tumor diagnosis were derived from maternal interviews. The current data set failed to show any consistent association between childhood central nervous system tumor risk and paternal occupational exposures to hydrocarbons or to electromagnetic fields, or employment in the aerospace industry or pulp and paper manufacturing. Findings for occupational exposures to ionizing radiation were also inconsistent. A positive association was observed between central nervous system tumor risk and paternal exposures to ionizing radiation based on industrial codes. Odds ratios ranged from 1.71 to 2.15. This association was not observed when paternal occupational titles were used to define exposure (range of odds ratios, 1.01-1.10). Maternal exposures to ionizing radiation were not related to risk regardless of the classification scheme used.

We conducted a population-based case-control study with 338 patients, less than 15 years of age, diagnosed with a primary tumor of the central nervous system from January 1968 through December 1977 in 53 New York State counties. The study also included 676 controls selected from the birth certificate files of the New York State Department of Health. We collected information on neurofibromatosis and congenital anomalies in study subjects, their siblings and parents by telephone interview with the mother of each case and control. We obtained supplemental information on neurofibromatosis in the patients and their families from hospital medical records. This study confirmed the strong association of neurofibromatosis with risk of CNS tumors. Thirteen cases and no controls had neurofibromatosis. Two fathers and 3 mothers of cases had neurofibromatosis. Five cases had siblings with neurofibromatosis. None of the first-degree relatives of controls had neurofibromatosis. We observed a relative risk of 4.49 for history of seizures. Seizures are often among the presenting symptoms for CNS tumors. We observed no difference between cases and controls in the occurrence of congenital anomalies. There was a nonsignificant excess of congenital anomalies among siblings of cases compared with controls. This decreased to 1.13 when adjusted for number of siblings.