Emergency Department Pediatric Readiness: A Trauma Center Quality Improvement Initiative.

BACKGROUND: Most pediatric patients present to general emergency departments, yet maintaining pediatric equipment, skilled staff, and resources remains a challenge for many hospitals. Pediatric readiness assessment is now a requirement for trauma center verification. OBJECTIVE: This study aims to assess the impact of a quality improvement initiative to improve emergency department pediatric readiness. METHODS: A pre- and poststudy design was used to evaluate a quality improvement initiative to improve the National Pediatric Readiness assessment survey results conducted at a Southwestern United States adult Level I trauma center from September 2022 to April 2023. The multicomponent initiative included implementing a pediatric emergency care coordinator, pediatric-specific policies and procedures, identifying pediatric-specific quality and performance indicators, and educating pediatric-specific staff. Study inclusion criteria were all patients younger than 18 years who presented to the emergency department. The primary outcome measure was the improvement in the weighted Pediatric Readiness Score. Secondary outcomes were throughput, nursing documentation of vital signs, and pain scores. RESULTS: A total of N = 2,356 patients met inclusion, of which n = 1,158 (49.2%) were in the preintervention group and n = 1,198 (50.8%) postintervention group. The weighted Pediatric Readiness Score improved by 45.4%. Transfers to a pediatric hospital increased from 4.1% to 8.6% (p = .016). Blood pressure documentation improved slightly from 88.3% to 88.6%. Pain score documentation decreased from 83.9% to 63.1% (p = .008). Pain medication and administration improved from 19.8% to 26.7% (p = .046). CONCLUSION: We found that participation in the quality improvement initiative was associated with emergency department pediatric readiness improvements.

Influence of Oxygen Uptake on Pitch Carbon Fiber.

Carbon fiber precursor materials, such as polyacrylonitrile, pitch, and cellulose/rayon, require thermal stabilization to maintain structural integrity during conversion into carbon fiber. Thermal stabilization mitigates undesirable decomposition and liquification of the fibers during the carbonization process. Generally, the thermal stabilization of mesophase pitch consists of the attachment of oxygen-containing functional groups onto the polymeric structure. In this study, the oxidation of mesophase pitch precursor fibers at various weight percentage increases (1, 3.5, 5, 7.5 wt%) and temperatures (260, 280, 290 °C) using in situ differential scanning calorimetry and thermogravimetric analysis is investigated. The results are analyzed to determine the effect of temperature and weight percentage increase on the stabilization process of the fibers, and the fibers are subsequently carbonized and tested for tensile mechanical performance. The findings provide insight into the relationship between stabilization conditions, fiber microstructure, and mechanical properties of the resulting carbon fibers.

Cranial transposition and revascularization of autologous omentum: a novel surgical technique for resection of recurrent glioblastoma multiforme.

Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system. The study aims to assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM. Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study. Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients.

Consumption of whole purple and regular wheat modestly improves metabolic markers in adults with elevated high-sensitivity C-reactive protein: a randomised, single-blind parallel-arm study.

Whole-grain wheat, in particular coloured varieties, may have health benefits in adults with chronic metabolic disease risk factors. Twenty-nine overweight and obese adults with chronic inflammation (high-sensitivity C-reactive protein) > 1·0 mg/l) replaced four daily servings of refined grain food products with bran-enriched purple or regular whole-wheat convenience bars (approximately 41-45 g fibre, daily) for 8 weeks in a randomised, single-blind parallel-arm study where body weight was maintained. Anthropometrics, blood markers of inflammation, oxidative stress, and lipaemia and metabolites of anthocyanins and phenolic acids were compared at days 1, 29 and 57 using repeated-measures ANOVA within groups and ANCOVA between groups at day 57, with day 1 as a covariate. A significant reduction in IL-6 and increase in adiponectin were observed within the purple wheat (PW) group. TNF-α was lowered in both groups and ferulic acid concentration increased in the regular wheat (RW) group. Comparing between wheats, only plasma TNF-α and glucose differed significantly (P < 0·05), that is, TNF-α and glucose decreased with RW and PW, respectively. Consumption of PW or RW products showed potential to improve plasma markers of inflammation and oxidative stress in participants with evidence of chronic inflammation, with modest differences observed based on type of wheat.

Diagnostic Tools for Coronavirus Disease (COVID-19): Comparing CT and RT-PCR Viral Nucleic Acid Testing.

OBJECTIVE. Multiple studies suggest CT should be a primary diagnostic tool for coronavirus disease (COVID-19) because they reported sensitivities with CT far superior to that of reverse transcriptase polymerase chain reaction (RT-PCR) testing. This review aimed to assess these reports and found chest CT to have a clinical utility that is limited, particularly for patients who show no symptoms and patients who are screened early in disease progression. CONCLUSION. CT has limited sensitivity for COVID-19 and a lower specificity than RT-PCR testing, and it carries a risk of exposing providers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chest CT should be considered a supplemental diagnostic tool, particularly for patients who show symptoms.

Glycaemic response of proso millet-based (Panicum miliaceum) products.

The glycaemic response of millet foods and the effect of processing are not known. Therefore, decorticated proso millet was used to produce four types of common food products (biscuits, couscous, porridge and an extruded snack). Postprandial blood glucose response of these products (all containing 50 g of total starch) was compared to the same foods produced with refined corn, in a crossover human study with 12 healthy male participants (age 26.3 ± 3.8 yr; BMI 23.3 ± 2.8 kg/m2). Capillary blood samples were collected and glycaemic response was determined; differences were assessed using repeat measures ANOVA. Overall, the mean (±SEM) incremental area under the blood glucose response curve (mmol min/l) of the proso millet products was different from the corn products, but individual products (couscous = 66.7 ± 11.6, biscuit = 82.6 ± 13.7, extrudate = 198.7 ± 20.9, porridge = 40.1 ± 5.8) were not significantly lower (couscous = 43.5 ± 5.8, biscuit = 102.0 ± 10.3, extrudate = 198.7 ± 20.9, porridge = 52.2 ± 8.1) (p > .05). Glycaemic response of the products was not dependent on the grain type, but rather product matrix.

Eight-day consumption of inulin added to a yogurt breakfast lowers postprandial appetite ratings but not energy intakes in young healthy females: a randomised controlled trial.

Increasing feelings of satiety may reduce appetite and energy intake. The role of inulin consumption in impacting satiety is unclear. A randomised double-blind controlled crossover trial aimed to determine the effects of inulin+yogurt on satiety after 1 and 8-d consumption. The preload breakfast included 100 g vanilla yogurt with (yogurt-inulin (YI)) and without (yogurt-control (YC)) 6 g inulin. A total of nineteen healthy females (22·8 (sd 2·7) years) with non-restrained eating behaviour and taking hormonal contraceptives participated in the study. Day 1 and 8 visual analogue scale (VAS) ratings of Hunger, Fullness, Desire to Eat and Prospective Food Consumption (PFC) were collected at fasting and every 30 min for 180 min. Energy intake was calculated from a weighed ad libitum lunch and remainder of day food records. Total AUC was calculated for each VAS. Day 1 (VAS only) and 8 (VAS and energy intakes) data were compared between YI and YC using ANCOVA, and ANOVA was used to compare energy intakes on Day 1. There were no significant differences between Day 1 YI and YC AUC appetite ratings or energy intakes. However, 8-d consumption of YI v. YC was associated with lower Desire to Eat and PFC ratings but similar lunch and total day energy intakes. Therefore, the addition of 6 g inulin to a commercially available yogurt affected feelings of appetite, but not energy intake, after repeated consumption. These results suggest that inulin may be a suitable ingredient to increase dietary fibre consumption, with potential to impact appetite.

Postprandial appetite ratings are reproducible and moderately related to total day energy intakes, but not ad libitum lunch energy intakes, in healthy young women.

Reproducibility and validity testing of appetite ratings and energy intakes are needed in experimental and natural settings. Eighteen healthy young women ate a standardized breakfast for 8 days. Days 1 and 8, they rated their appetite (Hunger, Fullness, Desire to Eat, Prospective Food Consumption (PFC)) over a 3.5 h period using visual analogue scales, consumed an ad libitum lunch, left the research center and recorded food intake for the remainder of the day. Days 2-7, participants rated their at-home Hunger at 0 and 30 min post-breakfast and recorded food intake for the day. Total area under the curve (AUC) over the 180 min period before lunch, and energy intakes were calculated. Reproducibility of satiety measures between days was evaluated using coefficients of repeatability (CR), coefficients of variation (CV) and intra-class coefficients (ri). Correlation analysis was used to examine validity between satiety measures. AUCs for Hunger, Desire to Eat and PFC (ri = 0.73-0.78), ad libitum energy intakes (ri = 0.81) and total day energy intakes (ri​ = 0.48) were reproducible; fasted ratings were not. Average AUCs for Hunger, Desire to Eat and PFC, Desire to Eat at nadir and PFC at fasting, nadir and 180 min were correlated to total day energy intakes (r = 0.50-0.77, P < 0.05), but no ratings were correlated to lunch consumption. At-home Hunger ratings were weakly reproducible but not correlated to reported total energy intakes. Satiety ratings did not concur with next meal intake but PFC ratings may be useful predictors of intake. Overall, this study adds to the limited satiety research on women and challenges the accepted measures of satiety in an experimental setting.

Regulation of L-type calcium channel by phospholemman in cardiac myocytes.

We evaluated whether phospholemman (PLM) regulates L-type Ca(2+) current (ICa) in mouse ventricular myocytes. Expression of α1-subunit of L-type Ca(2+) channels between wild-type (WT) and PLM knockout (KO) hearts was similar. Compared to WT myocytes, peak ICa (at -10 mV) from KO myocytes was ~41% larger, the inactivation time constant (τ(inact)) of ICa was ~39% longer, but deactivation time constant (τ(deact)) was similar. In the presence of isoproterenol (1 µM), peak ICa was ~48% larger and τ(inact) was ~144% higher in KO myocytes. With Ba(2+) as the permeant ion, PLM enhanced voltage-dependent inactivation but had no effect on τ(deact). To dissect the molecular determinants by which PLM regulated ICa, we expressed PLM mutants by adenovirus-mediated gene transfer in cultured KO myocytes. After 24h in culture, KO myocytes expressing green fluorescent protein (GFP) had significantly larger peak ICa and longer τ(inact) than KO myocytes expressing WT PLM; thereby independently confirming the observations in freshly isolated myocytes. Compared to KO myocytes expressing GFP, KO myocytes expressing the cytoplasmic domain truncation mutant (TM43), the non-phosphorylatable S68A mutant, the phosphomimetic S68E mutant, and the signature PFXYD to alanine (ALL5) mutant all resulted in lower peak ICa. Expressing PLM mutants did not alter expression of α1-subunit of L-type Ca(2+) channels in cultured KO myocytes. Our results suggested that both the extracellular PFXYD motif and the transmembrane domain of PLM but not the cytoplasmic tail were necessary for regulation of peak ICa amplitude. We conclude that PLM limits Ca(2+) influx in cardiac myocytes by reducing maximal ICa and accelerating voltage-dependent inactivation.

Pupillary light reflex measured with quantitative pupillometry has low sensitivity and high specificity for predicting neuroworsening after traumatic brain injury.

BACKGROUND: Triage and neurological assessment of the 1.7 million traumatic brain injuries occurring annually is often done by nurse practitioners and physician assistants in the emergency department. Subjective assessments, such as the neurological examination that includes evaluation of the pupillary light reflex (PLR), can contain bias. Quantitative pupillometry (QP) standardizes and objectifies the PLR examination. Additional data are needed to determine whether QP can predict neurological changes in a traumatic brain injury (TBI) patient. PURPOSE: This study examines the effectiveness of QP in predicting neurological decline within 24 hours of admission following acute TBI. METHODOLOGY: This prospective, observational, clinical trial used pragmatic sampling to assess PLR in TBI patients using QP within 24 hours of ED admission. Chi-square analysis was used to determine change in patient status, through Glasgow Coma Scale (GCS), at baseline and within 24 hours of admission, to the QP. RESULTS: There were 95 participants included in the analysis; of whom 35 experienced neuroworsening, defined by change in GCS of >2 within the first 24 hours of admission. There was a significant association between an abnormal Neurological Pupil index (NPi), defined as NPi of <3, and neuroworsening (p < .0001). The sensitivity (51.43%) and specificity (91.67%) of abnormal NPi in predicting neuroworsening were varied. CONCLUSION: There is a strong association between abnormal NPi and neuroworsening in the sample of TBI patients with high specificity and moderate sensitivity. IMPLICATIONS: NPi may be an early indicator of neurological changes within 24 hours of ED admission in patients with TBI.

A Primer to Cost-Effectiveness Analysis in Breast Cancer Imaging: A Review of the Literature.

Currently, there is a multitude of methods for evaluating the costs and benefits of programs, tools, etc. While cost-benefit analysis (CBA) is commonly used, cost-effectiveness analysis (CEA) is a more appropriate method of evaluation in clinical contexts, such as radiology practices, as CEAs use units such as life years gained as opposed to money (as is the case for CBAs). This review examines CEAs performed within the past 15 years to highlight their applications and key findings in the context of medical imaging. In total, 20 articles published between 2006 and 2022 were identified using a PubMed search for keywords including "cost-effectiveness analysis," "breast cancer," and "medical imaging," with studies lacking a substantial discussion of CEA or a related topic being excluded. CEAs have traditionally been criticized for lack of a standard methodology, despite their utility in the detection and treatment of various pathologies. Although mammography and magnetic resonance imaging (MRI) are the preferred and cost-effective imaging modalities for breast cancer, other imaging modalities, such as contrast-enhanced mammography and digital breast tomosynthesis, may be more cost-effective in the appropriate clinical context. Different combinations of mammography and MRI screenings for certain breast cancers may also prove to be more cost-effective compared to current mammography/MRI screening schedules. While CEA has shown potential utility in estimating the costs (per unit of health gained) of different imaging tools, CEA risks ignoring important outcomes not included in the analysis and cannot address if the benefits of the imaging tool exceed its costs, as a CBA would, suggesting the need for combining several economic evaluations for a more complete understanding.

Regulation of in vivo cardiac contractility by phospholemman: role of Na+/Ca2+ exchange.

Phospholemman (PLM), when phosphorylated at serine 68, relieves its inhibition on Na(+)-K(+)-ATPase but inhibits Na(+)/Ca(2+) exchanger 1 (NCX1) in cardiac myocytes. Under stress when catecholamine levels are high, enhanced Na(+)-K(+)-ATPase activity by phosphorylated PLM attenuates intracellular Na(+) concentration ([Na(+)](i)) overload. To evaluate the effects of PLM on NCX1 on in vivo cardiac contractility, we injected recombinant adeno-associated virus (serotype 9) expressing either the phosphomimetic PLM S68E mutant or green fluorescent protein (GFP) directly into left ventricles (LVs) of PLM-knockout (KO) mice. Five weeks after virus injection, ∼40% of isolated LV myocytes exhibited GFP fluorescence. Expression of S68E mutant was confirmed with PLM antibody. There were no differences in protein levels of α(1)- and α(2)-subunits of Na(+)-K(+)-ATPase, NCX1, and sarco(endo)plasmic reticulum Ca(2+)-ATPase between KO-GFP and KO-S68E LV homogenates. Compared with KO-GFP myocytes, Na(+)/Ca(2+) exchange current was suppressed, but resting [Na(+)](i), Na(+)-K(+)-ATPase current, and action potential amplitudes were similar in KO-S68E myocytes. Resting membrane potential was slightly lower and action potential duration at 90% repolarization (APD(90)) was shortened in KO-S68E myocytes. Isoproterenol (Iso; 1 µM) increased APD(90) in both groups of myocytes. After Iso, [Na(+)](i) increased monotonically in paced (2 Hz) KO-GFP but reached a plateau in KO-S68E myocytes. Both systolic and diastolic [Ca(2+)](i) were higher in Iso-stimulated KO-S68E myocytes paced at 2 Hz. Echocardiography demonstrated similar resting heart rate, ejection fraction, and LV mass between KO-GFP and KO-S68E mice. In vivo closed-chest catheterization demonstrated enhanced contractility in KO-S68E compared with KO-GFP hearts stimulated with Iso. We conclude that under catecholamine stress when [Na(+)](i) is high, PLM minimizes [Na(+)](i) overload by relieving its inhibition of Na(+)-K(+)-ATPase and preserves inotropy by simultaneously inhibiting Na(+)/Ca(2+) exchanger.

Interaction of the hepatitis B core antigen and the innate immune system.

Previous studies demonstrated that the primary APCs for the hepatitis B core Ag (HBcAg) were B cells and not dendritic cells (DC). We now report that splenic B1a and B1b cells more efficiently present soluble HBcAg to naive CD4(+) T cells than splenic B2 cells. This was demonstrated by direct HBcAg-biotin-binding studies and by HBcAg-specific T cell activation in vitro in cultures of naive HBcAg-specific T cells and resting B cell subpopulations. The inability of DC to function as APCs for exogenous HBcAg relates to lack of uptake of HBcAg, not to processing or presentation, because HBcAg/anti-HBc immune complexes can be efficiently presented by DC. Furthermore, HBcAg-specific CD4(+) and CD8(+) T cell priming with DNA encoding HBcAg does not require B cell APCs. TLR activation, another innate immune response, was also examined. Full-length (HBcAg(183)), truncated (HBcAg(149)), and the nonparticulate HBeAg were screened for TLR stimulation via NF-kappaB activation in HEK293 cells expressing human TLRs. None of the HBc/HBeAgs activated human TLRs. Therefore, the HBc/HBeAg proteins are not ligands for human TLRs. However, the ssRNA contained within HBcAg(183) does function as a TLR-7 ligand, as demonstrated at the T and B cell levels in TLR-7 knockout mice. Bacterial, yeast, and mammalian ssRNA encapsidated within HBcAg(183) all function as TLR-7 ligands. These studies indicate that innate immune mechanisms bridge to and enhance the adaptive immune response to HBcAg and have important implications for the use of hepadnavirus core proteins as vaccine carrier platforms.

The benefit of intravenous thrombolysis prior to mechanical thrombectomy within the therapeutic window for acute ischemic stroke.

The increase in risk for acute ischemic stroke (AIS) with age is well established. If not treated properly and promptly, AIS can result in permanent neurological damage and even death. This literature review assesses the clinical outcomes of AIS patients treated with both intravenous thrombolysis (IVT) prior to mechanical thrombectomy (MT) compared to those treated solely with mechanical thrombectomy. Randomized controlled trials (RCTs) and meta-analyses published from 2015 to 2020 and available on PubMed were selected for review, and their quantitative and qualitative findings were extrapolated and summarized. Post-hoc analyses from ASTER and ETIS trials were reviewed as well as the impact of combined therapy and monotherapy on large vessel occlusions (LVO). Clinical outcomes in all examined trials demonstrated significant successful reperfusion as well as a higher rate of functional independence at 90 days for IVT prior to MT. Concerns of thrombus fragility, safety and cost effectiveness of dual therapy are also addressed. Based on these findings, we recommend the use of IVT as a pretreatment procedure to MT for AIS when eligible for IVT. Recent articles further strengthen this recommendation and provide new insights that IVT prior to MT is especially beneficial for patients presenting with multiple LVOs localized to the anterior intracranial circulation. Additional multi-center RCTs are necessary for further analysis of statistical outcomes demonstrating mixed effects.

Phospholemman and beta-adrenergic stimulation in the heart.

Phosphorylation at serine 68 of phospholemman (PLM) in response to beta-adrenergic stimulation results in simultaneous inhibition of cardiac Na(+)/Ca(2+) exchanger NCX1 and relief of inhibition of Na(+)-K(+)-ATPase. The role of PLM in mediating beta-adrenergic effects on in vivo cardiac function was investigated with congenic PLM-knockout (KO) mice. Echocardiography showed similar ejection fraction between wild-type (WT) and PLM-KO hearts. Cardiac catheterization demonstrated higher baseline contractility (+dP/dt) but similar relaxation (-dP/dt) in PLM-KO mice. In response to isoproterenol (Iso), maximal +dP/dt was similar but maximal -dP/dt was reduced in PLM-KO mice. Dose-response curves to Iso (0.5-25 ng) for WT and PLM-KO hearts were superimposable. Maximal +dP/dt was reached 1-2 min after Iso addition and declined with time in WT but not PLM-KO hearts. In isolated myocytes paced at 2 Hz. contraction and intracellular Ca(2+) concentration ([Ca(2+)](i)) transient amplitudes and [Na(+)](i) reached maximum 2-4 min after Iso addition, followed by decline in WT but not PLM-KO myocytes. Reducing pacing frequency to 0.5 Hz resulted in much smaller increases in [Na(+)](i) and no decline in contraction and [Ca(2+)](i) transient amplitudes with time in Iso-stimulated WT and PLM-KO myocytes. Although baseline Na(+)-K(+)-ATPase current was 41% higher in PLM-KO myocytes because of increased alpha(1)- but not alpha(2)-subunit activity, resting [Na(+)](i) was similar between quiescent WT and PLM-KO myocytes. Iso increased alpha(1)-subunit current (I(alpha1)) by 73% in WT but had no effect in PLM-KO myocytes. Iso did not affect alpha(2)-subunit current (I(alpha2)) in WT and PLM-KO myocytes. In both WT and NCX1-KO hearts, PLM coimmunoprecipitated with Na(+)-K(+)-ATPase alpha(1)- and alpha(2)-subunits, indicating that association of PLM with Na(+)-K(+)-ATPase did not require NCX1. We conclude that under stressful conditions in which [Na(+)](i) was high, beta-adrenergic agonist-mediated phosphorylation of PLM resulted in time-dependent reduction in inotropy due to relief of inhibition of Na(+)-K(+)-ATPase.

A mechanism to explain the selection of the hepatitis e antigen-negative mutant during chronic hepatitis B virus infection.

Hepatitis B virus (HBV) expresses two structural forms of the nucleoprotein, the intracellular nucleocapsid (hepatitis core antigen [HBcAg]) and the secreted nonparticulate form (hepatitis e antigen [HBeAg]). The aim of this study was to evaluate the ability of HBcAg- and HBeAg-specific genetic immunogens to induce HBc/HBeAg-specific CD4(+)/CD8(+) T-cell immune responses and the potential to induce liver injury in HBV-transgenic (Tg) mice. Both the HBcAg- and HBeAg-specific plasmids primed comparable immune responses. Both CD4(+) and CD8(+) T cells were important for priming/effector functions of HBc/HBeAg-specific cytotoxic T-lymphocyte (CTL) responses. However, a unique two-step immunization protocol was necessary to elicit maximal CTL priming. Genetic vaccination did not prime CTLs in HBe- or HBc/HBeAg-dbl-Tg mice but elicited a weak CTL response in HBcAg-Tg mice. When HBc/HBeAg-specific CTLs were adoptively transferred into HBc-, HBe-, and HBc/HBeAg-dbl-Tg mice, the durations of the liver injury and inflammation were significantly greater in HBeAg-Tg recipient mice than in HBcAg-Tg mice. Importantly, liver injury in HBc/HBeAg-dbl-Tg mice was similar to the injury observed in HBeAg-Tg mice. Loss of HBeAg synthesis commonly occurs during chronic HBV infection; however, the mechanism of selection of HBeAg-negative variants is unknown. The finding that hepatocytes expressing wild-type HBV (containing both HBcAg and HBeAg) are more susceptible to CTL-mediated clearance than hepatocytes expressing only HBcAg suggest that the HBeAg-negative variant may have a selective advantage over wild-type HBV within the livers of patients with chronic infection during an immune response and may represent a CTL escape mutant.

Dolichoectatic Carotid Arterial Compression of the Optic Nerve: The Unusual Suspect in the Setting of a Coexisting Incidental Pituitary Adenoma.

BACKGROUND: Anatomic compression of the optic nerve secondary to a dolichoectatic cerebrovascular compression is a rare clinical entity. Because of the limited number of published cases and variable clinical presentation, the natural history remains ambiguous and no consensus exists regarding management. In addition, there is an ongoing debate regarding whether a dolichoectatic cerebral blood vessel can actually cause optic neuropathy, or it merely represents an incidental finding. As a result, it is thought that a diagnosis of compressive optic neuropathy from an adjacent dolichoectatic internal carotid artery (ICA) should be considered only after other possible etiologies are excluded. Although this might seem straightforward, the clinical scenario becomes complex if the patient is also found to have additional incidental pituitary lesions. Such coexistence has not been reported previously in the literature. CASE DESCRIPTION: A 52-year-old left-handed man presented to us with intermittent headache and painless progressive visual deterioration in the right eye for 1 month. Screening magnetic resonance imaging (MRI) scan revealed a 9-mm eccentrically placed pituitary adenoma with right optic nerve compression because of dolichoectatic ICA. He underwent microvascular decompression of the right optic nerve. On follow-up, significant vision improvement was noticed and MRI scan revealed no change in the size of the pituitary adenoma. CONCLUSIONS: The compression of the optic nerve by dolichoectatic ICA is commonly thought to be a diagnosis of exclusion. However, the presence of a coexisting pathology should not prompt the exclusion in every case and a case-based approach is highly recommended to correctly manage this rare clinical condition.

Surgical Management of Symptomatic Boxing-Induced Spinal Cerebrospinal Fluid Leak After Failed Epidural Blood Patch.

BACKGROUND: Spontaneous spinal cerebrospinal fluid (CSF) leak is an increasingly recognized condition responsible for spontaneous intracranial hypotension. A host of connective tissue disorders and mechanical factors may precipitate the condition. Conservative treatment has limited efficacy, and many patients with persistent symptoms ultimately require epidural blood patch (EBP). However, about 23%-44% of patients experience recurrence of symptoms after EBP. Unidentified or multiple sites of CSF leaks are thought to be responsible for the failure of EBP. Using our previously published technique, we treated a patient who developed a large spontaneous CSF leak in her cervicothoracic spine after a boxing class, offering further evidence of the utility of the technique for select patients. CASE DESCRIPTION: A 28-year-old woman was referred to our center with recurrent, severe headaches and associated nausea and vomiting. She underwent EBP 3 times with no resolution of her symptoms. A right-side partial C7-T1 hemilaminotomy was performed to identify a large meningocele filled with CSF. After dissection, dural sealant was applied using an angled needle with a syringe to buttress the meningocele to allow for normalization of the hydrostatic pressure. At 5-month follow-up, her symptoms have resolved with no headaches and paresthesias in upper limbs. CONCLUSIONS: Commonplace events, such as a boxing/sparring class, may precipitate a spontaneous spinal CSF leak. Our minimally invasive surgical approach can be safely used in patients with spontaneous intracranial hypotension with recurrent symptoms, no identified leak site, and prior failed attempts of EBP.

Extracellular potassium dependence of the Na+-K+-ATPase in cardiac myocytes: isoform specificity and effect of phospholemman.

Cardiac Na(+)-K(+)-ATPase (NKA) regulates intracellular Na(+), which in turn affects intracellular Ca(2+) and contractility via the Na(+)/Ca(2+) exchanger. Extracellular K(+) concentration ([K(+)]) is a central regulator of NKA activity. Phospholemman (PLM) has recently been recognized as a critical regulator of NKA in the heart. PLM reduces the intracellular Na(+) affinity of NKA, an effect relieved by PLM phosphorylation. Here we tested whether the NKA alpha(1)- vs. alpha(2)- isoforms have different external K(+) sensitivity and whether PLM and PKA activation affects the NKA affinity for K(+) in mouse cardiac myocytes. We measured the external [K(+)] dependence of the pump current generated by the ouabain-resistant NKA isoform in myocytes from wild-type (WT) mice (i.e., current due to NKA-alpha(1)) and mice in which the NKA isoforms have swapped ouabain affinities (alpha(1) is ouabain sensitive and alpha(2) is ouabain resistant) to assess current due to NKA-alpha(2). We found that NKA-alpha(1) has a higher affinity for external K(+) than NKA-alpha(2) [half-maximal pump activation (K(0.5)) = 1.5 +/- 0.1 vs. 2.9 +/- 0.3 mM]. The apparent external K(+) affinity of NKA was significantly lower in myocytes from WT vs. PLM-knockout mice (K(0.5) = 2.0 +/- 0.2 vs. 1.05 +/- 0.08 mM). However, PKA activation by isoproterenol (1 microM) did not alter the K(0.5) of NKA for external K(+) in WT myocytes. We conclude that 1) NKA-alpha(1) has higher affinity for K(+) than NKA-alpha(2) in cardiac myocytes, 2) PLM decreases the apparent external K(+) affinity of NKA, and 3) phosphorylation of PLM at the cytosolic domain does not alter apparent extracellular K(+) affinity of NKA.

Phospholemman-mediated activation of Na/K-ATPase limits [Na]i and inotropic state during beta-adrenergic stimulation in mouse ventricular myocytes.

BACKGROUND: Cardiac Na/K-ATPase (NKA) regulates intracellular Na ([Na](i)), which in turn affects intracellular Ca and thus contractility via Na/Ca exchange. Recent evidence shows that phosphorylation of the NKA-associated small transmembrane protein phospholemman (PLM) mediates beta-adrenergic-induced NKA stimulation. METHODS AND RESULTS: Here, we tested whether PLM phosphorylation during beta-adrenergic activation limits the rise in [Na](i), Ca transient amplitude, and triggered arrhythmias in mouse ventricular myocytes. In myocytes from wild-type (WT) mice, [Na](i) increased on field stimulation at 2 Hz from 11.1+/-1.8 mmol/L to a plateau of 15.2+/-1.5 mmol/L. Isoproterenol induced a decrease in [Na](i) to 12.0+/-1.2 mmol/L. In PLM knockout (PLM-KO) mice in which beta-adrenergic stimulation does not activate NKA, [Na](i) also increased at 2 Hz (from 10.4+/-1.2 to 17.0+/-1.5 mmol/L) but was unaltered by isoproterenol. The PLM-mediated decrease in [Na](i) in WT mice could limit the isoproterenol-induced inotropic state. Indeed, the isoproterenol-induced increase in the amplitude of Ca transients was significantly smaller in the WT mice (5.2+/-0.4- versus 7.1+/-0.5-fold in PLM-KO mice). This also was the case for the sarcoplasmic reticulum Ca content, which increased by 1.27+/-0.09-fold in WT mice versus 1.53+/-0.09-fold in PLM-KO mice. The higher sarcoplasmic reticulum Ca content in PLM-KO versus WT mice was associated with an increased propensity for spontaneous Ca transients and contractions in PLM-KO mice. CONCLUSIONS: These data suggest that PLM phosphorylation and NKA stimulation are an integral part of the sympathetic fight-or-flight response, tempering the rise in [Na](i) and cellular Ca loading and perhaps limiting Ca overload-induced arrhythmias.