Does soil track-in contribute to house dust concentrations of perfluoroalkyl acids (PFAAs) in areas affected by soil or water contamination?

The Minnesota Department of Health measured levels of perfluoroalkyl acids (PFAAs) in house dust at homes in communities impacted by PFAA-contaminated soil and drinking water to determine whether PFAAs in soil outside the home are associated with concentrations in dust. House dust samples from both interior living spaces and entryways to the yard were collected and analyzed separately based on the presumption that PFAAs in entryway dust may better reflect "track-in" of PFAAs into the home from contaminated soil or lawns irrigated with contaminated water. PFAA detections and concentrations in living rooms were significantly higher compared to entryways; and concentrations in both sampling locations were higher than corresponding soil concentrations, suggesting that interior sources were the main contributors to PFAAs in house dust. PFAA dust concentrations in entryways were significantly associated with living room dust levels for all analytes except PFBA. Relationships between entryway dust and soil were only seen for one PFAA (PFOA). However, median concentrations of PFOA in entryway and living room dust were 35 and 70 times higher (respectively) than in soil, which highlights the lack of importance of PFAA soil track-in as a contributor to dust concentration in this setting. Due to the small sample size, larger scale studies are needed to further assess the potential for migration of PFAA contaminated soil to indoor dust.

Occurrence of perfluoroalkyl substances (PFAS) in garden produce at homes with a history of PFAS-contaminated drinking water.

The decades-long disposal of manufacturing waste containing perfluoroalkyl substances (PFAS) in landfills resulted in contamination of groundwater serving as the drinking water supply for the eastern Twin Cities metropolitan region. While measures were taken to reduce the levels of PFAS in the drinking water, questions remained about possible non-drinking water pathways of exposure in these communities. The Minnesota Department of Health (MDH) investigated whether PFAS in water used for yard and garden irrigation results in elevated concentrations of PFAS in soil and home-grown produce. In 2010, samples of outdoor tap water, garden soil, and garden produce were collected at homes impacted by the contamination and analyzed for several PFAS. Perfluorobutanoic acid (PFBA) was the primary PFAS present in water, followed by perfluoropentanoic acid (PFPeA). Although PFBA, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were present in 100% of soil samples at higher concentrations compared to other PFAS, only PFBA was readily translocated to plants. Significant determinants of PFBA concentration in produce were the amount of PFBA applied to the garden via watering and the type of produce tested. Results from this real-world study are consistent with experimental findings that short-chain PFAS have the highest potential to translocate to and bioaccumulate in edible plants. These findings are globally relevant, as short-chain PFAS serve as commercial substitutes for longer-chain compounds and are increasingly detected in water due to their relatively high solubility and mobility.

Susceptibility-weighted imaging helps to discriminate pediatric multiple sclerosis from acute disseminated encephalomyelitis.

BACKGROUND: Susceptibility-weighted imaging is a relatively new magnetic resonance imaging sequence that can identify lesions of multiple sclerosis in adults. This study was designed to determine if susceptibility-weighted imaging is a useful discriminator between children who develop multiple sclerosis and children with monophasic acute disseminated encephalomyelitis. METHODS: Eighteen children who presented with acute central nervous system demyelination and had a brain magnetic resonance imaging study including susceptibility-weighted imaging within 6 months of the first clinical attack were studied. Final diagnosis was based on international consensus definitions. Brain lesions detected on the fluid-attenuated inversion recovery sequence were assessed for abnormal signal on susceptibility-weighted imaging. The burden of susceptibility abnormalities was then analyzed for differences between the multiple sclerosis and acute disseminated encephalomyelitis groups. RESULTS: Eight patients had a final diagnosis of acute disseminated encephalomyelitis and ten had multiple sclerosis. Twenty-two percent of fluid-attenuated inversion recovery lesions were identified on susceptibility-weighted imaging. The percentage of fluid-attenuated inversion recovery lesions identified on susceptibility-weighted imaging differed between the multiple sclerosis and acute disseminated encephalomyelitis groups (P = 0.04). The median percentage (minimum-maximum) of lesions identified on susceptibility-weighted imaging in the multiple sclerosis group was 0.22 (0-0.68) and in the acute disseminated encephalomyelitis group was 0.0 (0-0.17). CONCLUSION: Susceptibility-weighted imaging may be a useful technique in differentiating acute disseminated encephalomyelitis from multiple sclerosis at initial presentation.

Successful Use of Temocillin as Salvage Therapy for Cervical Osteomyelitis Secondary to Multidrug-Resistant Burkholderia cepacia.

Infection with multidrug resistant Burkholderia cepacia presents a therapeutic challenge in patients with cystic fibrosis. In this study, we present a case of progressive cervical osteomyelitis secondary to B cepacia that failed surgical drainage and extended therapy with meropenem, piperacillin-tazobactam, doxycycline, and aminoglycosides. Temocillin (Negaban) was successfully used to clear the infection.

Prevalence of white matter lesions and stroke in children with migraine.

OBJECTIVES: To determine the prevalence of white matter lesions (WMLs) and infarcts in children with migraine and whether pediatric migraine could be a risk factor for silent ischemic lesions or stroke. METHODS: Prospectively collected data from 1,008 pediatric patients with headache were reviewed. The MRI data were collected and retrospectively reviewed. RESULTS: Of the 926 patients diagnosed with migraine, 375 patients had MRIs and 115 had abnormalities, of which 39 had WMLs. Among them, 24 (6% of migraine) patients had incidental white matter findings without known neurovascular disease, risk factors, or etiologies for WMLs. The prevalence of WMLs is more common in migraine with aura (10%) than without aura (4%) (p = 0.038), but it is not statistically significant compared with controls (4%) (p = 0.119). Deep WMLs are more prevalent than periventricular lesions; these are detected mainly in the frontal and parietal lobes. No lesions appeared to be infarct-like lesions. There was no association between the total lesion load and chronicity or the frequency of migraine. WMLs are nonprogressive. Pediatric migraineurs with aura do not develop stroke, based on the available follow-up data. CONCLUSION: WMLs in pediatric patients with migraine and aura are no more prevalent than in controls. They appear to be benign and are not associated with stroke.

Inhibition of the late sodium current slows t-tubule disruption during the progression of hypertensive heart disease in the rat.

The treatment of heart failure (HF) is challenging and morbidity and mortality are high. The goal of this study was to determine if inhibition of the late Na(+) current with ranolazine during early hypertensive heart disease might slow or stop disease progression. Spontaneously hypertensive rats (aged 7 mo) were subjected to echocardiographic study and then fed either control chow (CON) or chow containing 0.5% ranolazine (RAN) for 3 mo. Animals were then restudied, and each heart was removed for measurements of t-tubule organization and Ca(2+) transients using confocal microscopy of the intact heart. RAN halted left ventricular hypertrophy as determined from both echocardiographic and cell dimension (length but not width) measurements. RAN reduced the number of myocytes with t-tubule disruption and the proportion of myocytes with defects in intracellular Ca(2+) cycling. RAN also prevented the slowing of the rate of restitution of Ca(2+) release and the increased vulnerability to rate-induced Ca(2+) alternans. Differences between CON- and RAN-treated animals were not a result of different expression levels of voltage-dependent Ca(2+) channel 1.2, sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a, ryanodine receptor type 2, Na(+)/Ca(2+) exchanger-1, or voltage-gated Na(+) channel 1.5. Furthermore, myocytes with defective Ca(2+) transients in CON rats showed improved Ca(2+) cycling immediately upon acute exposure to RAN. Increased late Na(+) current likely plays a role in the progression of cardiac hypertrophy, a key pathological step in the development of HF. Early, chronic inhibition of this current slows both hypertrophy and development of ultrastructural and physiological defects associated with the progression to HF.

Yield of catheter angiography in patients with intracerebral hemorrhage with and without intraventricular extension.

BACKGROUND AND AIM: The role of imaging for the detection of vascular lesions in patients with intracerebral hemorrhage (ICH) is poorly defined. A study was undertaken to compare the yield of digital subtraction angiography (DSA) in patients with ICH with intraventricular hemorrhage (IVH) and those without IVH. METHODS: The DSA database at our institution was reviewed for patients who underwent DSA for acute spontaneous ICH over a period of 68 months. Patients with known vascular malformation or brain neoplasm, prior surgery, ischemic infarction, subarachnoid hemorrhage or isolated IVH were excluded. Patients were grouped into those with associated IVH (group A) and those without (group B). Baseline demographic and clinical data, non-contrast head CT (NCCT) probability for a vascular lesion and angiographic results were compared. RESULTS: 293 patients met the inclusion and exclusion criteria (141 women, 152 men, mean age 57, range 18-88), 139 in group A and 154 in group B. Age and sex distributions were similar (p>0.05). Group A patients were more likely to be hypertensive or coagulopathic (p=0.001). Group B had more patients with high probability NCCT scans (p<0.001). Underlying vascular lesions were found in 21 patients (15.1%) in group A and 34 (22.1%) in group B (p>0.05). CONCLUSION: The presence of IVH in patients with acute spontaneous ICH is not associated with an increased risk of an underlying vascular lesion and should not be used to select patients for neurovascular evaluation.

Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats.

Defects in excitation-contraction coupling have been reported in failing hearts, but little is known about the relationship between these defects and the development of heart failure (HF). We compared the early changes in intracellular Ca(2+) cycling to those that underlie overt pump dysfunction and arrhythmogenesis found later in HF. Laser-scanning confocal microscopy was used to measure Ca(2+) transients in myocytes of intact hearts in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) at different ages. Early compensatory mechanisms include a positive inotropic effect in SHRs at 7.5-9 mo compared with 6 mo. Ca(2+) transient duration increased at 9 mo in SHRs, indicating changes in Ca(2+) reuptake during decompensation. Cell-to-cell variability in Ca(2+) transient duration increased at 7.5 mo, decreased at 9 mo, and increased again at 22 mo (overt HF), indicating extensive intercellular variability in Ca(2+) transient kinetics during disease progression. Vulnerability to intercellular concordant Ca(2+) alternans increased at 9-22 mo in SHRs and was mirrored by a slowing in Ca(2+) transient restitution, suggesting that repolarization alternans and the resulting repolarization gradients might promote reentrant arrhythmias early in disease development. Intercellular discordant and subcellular Ca(2+) alternans increased as early as 7.5 mo in SHRs and may also promote arrhythmias during the compensated phase. The incidence of spontaneous and triggered Ca(2+) waves was increased in SHRs at all ages, suggesting a higher likelihood of triggered arrhythmias in SHRs compared with WKY rats well before HF develops. Thus serious and progressive defects in Ca(2+) cycling develop in SHRs long before symptoms of HF occur. Defective Ca(2+) cycling develops early and affects a small number of myocytes, and this number grows with age and causes the transition from asymptomatic to overt HF. These defects may also underlie the progressive susceptibility to Ca(2+) alternans and Ca(2+) wave activity, thus increasing the propensity for arrhythmogenesis in HF.

Variability in timing of spontaneous calcium release in the intact rat heart is determined by the time course of sarcoplasmic reticulum calcium load.

BACKGROUND: Abnormalities in intracellular calcium (Ca) cycling during Ca overload can cause triggered activity because spontaneous calcium release (SCR) activates sufficient Ca-sensitive inward currents to induce delayed afterdepolarizations (DADs). However, little is known about the mechanisms relating SCR and triggered activity on the tissue scale. METHODS AND RESULTS: Laser scanning confocal microscopy was used to measure the spatiotemporal properties of SCR within large myocyte populations in intact rat heart. Computer simulations were used to predict how these properties of SCR determine DAD magnitude. We measured the average and standard deviation of the latency distribution of SCR within a large population of myocytes in intact tissue. We found that as external [Ca] is increased, and with faster pacing rates, the average and SD of the latency distribution decreases substantially. This result demonstrates that the timing of SCR occurs with less variability as the sarcoplasmic reticulum (SR) Ca load is increased, causing more sites to release Ca within each cell. We then applied a mathematical model of subcellular Ca cycling to show that a decrease in SCR variability leads to a higher DAD amplitude and is dictated by the rate of SR Ca refilling following an action potential. CONCLUSIONS: Our results demonstrate that the variability of the timing of SCR in a population of cells in tissue decreases with SR load and is dictated by the time course of the SR Ca content.

Multiple defects in intracellular calcium cycling in whole failing rat heart.

BACKGROUND: A number of defects in excitation-contraction coupling have been identified in failing mammalian hearts. The goal of this study was to measure the defects in intracellular Ca(2+) cycling in left ventricular epicardial myocytes of the whole heart in an animal model of congestive heart failure (CHF). METHODS AND RESULTS: Intracellular Ca(2+) transients were measured using confocal microscopy in whole rat hearts from age-matched Wistar-Kyoto control rats and spontaneously hypertensive rats at approximately 23 months of age. Basal Ca(2+) transients in myocytes in spontaneously hypertensive rats were smaller in amplitude and longer in duration than Wistar-Kyoto control rats. There was also greater variability in transient characteristics associated with duration between myocytes of CHF than Wistar-Kyoto controls. Approximately 21% of CHF myocytes demonstrated spontaneous Ca(2+) waves compared with very little of this activity in Wistar-Kyoto control rats. A separate population of spontaneously hypertensive rat myocytes showed Ca(2+) waves that were triggered during pacing and were absent at rest (triggered waves). Rapid pacing protocols caused Ca(2+) alternans to develop at slower heart rates in CHF. CONCLUSIONS: Epicardial cells demonstrate both serious defects and greater cell-to-cell variability in Ca(2+) cycling in CHF. The defects in Ca(2+) cycling include both spontaneous and triggered waves of Ca(2+) release, which promote triggered activity. The slowing of Ca(2+) repriming in the sarcoplasmic reticulum is probably responsible for the increased vulnerability to Ca(2+) alternans in CHF. Our results suggest that defective Ca(2+) cycling could contribute both to reduced cardiac output in CHF and to the establishment of repolarization gradients, thus creating the substrate for reentrant arrhythmias.