A Case of Pediatric Melanoma: Treatment Considerations in Advanced Disease.

We document a 3-year-old healthy African American girl who developed malignant melanoma on her lower extremity. The clinical appearance offered little indication of the lesion’s severity (T4), and only the history of de novo presentation and disproportionate growth raised clinical suspicion. This case report highlights the subtle clinical findings of this condition and presents controversies related to surgical management of pediatric melanoma

ATM activation accompanies histone H2AX phosphorylation in A549 cells upon exposure to tobacco smoke

<p>Abstract</p> <p>Background</p> <p>In response to DNA damage or structural alterations of chromatin, histone H2AX may be phosphorylated on <it>Ser</it>139 by phosphoinositide 3-kinase related protein kinases (PIKKs) such as <it>ataxia telangiectasia </it>mutated (ATM), ATM-and Rad-3 related (ATR) kinase, or by DNA dependent protein kinase (DNA-PKcs). When DNA damage primarily involves formation of DNA double-strand breaks (DSBs), H2AX is preferentially phosphorylated by ATM rather than by the other PIKKs. We have recently reported that brief exposure of human pulmonary adenocarcinoma A549 cells or normal human bronchial epithelial cells (NHBE) to cigarette smoke (CS) induced phosphorylation of H2AX.</p> <p>Results</p> <p>We report here that H2AX phosphorylation in A549 cells induced by CS was accompanied by activation of ATM, as revealed by ATM phosphorylation on <it>Ser</it>1981 (ATM-S1981^P) detected immunocytochemically and by Western blotting. No cell cycle-phase specific differences in kinetics of ATM activation and H2AX phosphorylation were observed. When cells were exposed to CS from cigarettes with different tobacco and filter combinations, the expression levels of ATM-S1981^Pcorrelated well with the increase in expression of phosphorylated H2AX (γH2AX) (R = 0.89). In addition, we note that while CS-induced γH2AX expression was localized within discrete foci, the activated ATM was distributed throughout the nucleoplasm.</p> <p>Conclusion</p> <p>These data implicate ATM as the PIKK that phosphorylates H2AX in response to DNA damage caused by CS. Based on current understanding of ATM activation, expression and localization, these data would suggest that, in addition to inducing potentially carcinogenic DSB lesions, CS may also trigger other types of DNA lesions and cause chromatin alterations. As checkpoint kinase (Chk) 1, Chk2 and the p53 tumor suppressor gene are known to be phosphorylated by ATM, the present data indicate that exposure to CS may lead to their phosphorylation, with the downstream consequences related to the halt in cell cycle progression and increased propensity to undergo apoptosis. Defining the nature and temporal sequence of molecular events that are disrupted by CS through activation and eventual dysregulation of normal defense mechanisms such as ATM and its downstream effectors may allow a more precise understanding of how CS promotes cancer development.</p

Clinical Factors Associated with the Non-Operative Airway Management of Patients with Robin Sequence.

BACKGROUND: The indications for surgical airway management in patients with Robin sequence (RS) and severe airway obstruction have not been well defined. While certain patients with RS clearly require surgical airway intervention and other patients just as clearly can be managed with conservative measures alone, a significant proportion of patients with RS present with a more confusing and ambiguous clinical course. The purpose of this study was to describe the clinical features and objective findings of patients with RS whose airways were successfully managed without surgical intervention. METHODS: The authors retrospectively reviewed the medical charts of infants with RS evaluated for potential surgical airway management between 1994 and 2014. Patients who were successfully managed without surgical intervention were included. Patient demographics, nutritional and respiratory status, laboratory values, and polysomnography (PSG) findings were recorded. RESULTS: Thirty-two infants met the inclusion criteria. The average hospital stay was 16.8 days (range, 5-70 days). Oxygen desaturation ( CONCLUSIONS: Nonsurgical airway management was successful in patients who demonstrated consistent weight gain and mild to moderate obstruction on PSG, with a mean AHI of/hour

Intravascular Food Reward

Consumption of calorie-containing sugars elicits appetitive behavioral responses and dopamine release in the ventral striatum, even in the absence of sweet-taste transduction machinery. However, it is unclear if such reward-related postingestive effects reflect preabsorptive or postabsorptive events. In support of the importance of postabsorptive glucose detection, we found that, in rat behavioral tests, high concentration glucose solutions administered in the jugular vein were sufficient to condition a side-bias. Additionally, a lower concentration glucose solution conditioned robust behavioral responses when administered in the hepatic-portal, but not the jugular vein. Furthermore, enteric administration of glucose at a concentration that is sufficient to elicit behavioral conditioning resulted in a glycemic profile similar to that observed after administration of the low concentration glucose solution in the hepatic-portal, but not jugular vein. Finally using fast-scan cyclic voltammetry we found that, in accordance with behavioral findings, a low concentration glucose solution caused an increase in spontaneous dopamine release events in the nucleus accumbens shell when administered in the hepatic-portal, but not the jugular vein. These findings demonstrate that the postabsorptive effects of glucose are sufficient for the postingestive behavioral and dopaminergic reward-related responses that result from sugar consumption. Furthermore, glycemia levels in the hepatic-portal venous system contribute more significantly for this effect than systemic glycemia, arguing for the participation of an intra-abdominal visceral sensor for glucose

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Delayed versus Delayed-Immediate Autologous Breast Reconstruction: A Blinded Evaluation of Aesthetic Outcomes

Background The technique of delayed-immediate breast reconstruction includes immediate insertion of a tissue expander, post-mastectomy radiation, followed by reconstruction. The aesthetic benefits of delayed-immediate reconstruction compared to delayed reconstruction are postulated but remain unproven. The purpose of this study was to compare aesthetic outcomes in patients following delayed and delayed-immediate autologous breast reconstruction. Methods A retrospective analysis was performed of all patients who underwent delayed or delayed-immediate autologous breast reconstruction by the senior author from 2005 to 2011. Postoperative photographs were used to evaluate aesthetic outcomes: skin quality, scar formation, superior pole contour, inferior pole contour, and overall aesthetic outcome. Ten non-biased reviewers assessed outcomes using a 5-point Likert scale. Fisher's Exact and Wilcoxon-Mann-Whitney tests were used for comparative analysis. Results Patient age and body mass index were similar between delayed (n=20) and delayed-immediate (n=20) cohorts (P>0.05). Skin and scar quality was rated significantly higher in the delayed-immediate cohort (3.74 vs. 3.05, P<0.001 and 3.41 vs. 2.79, P<0.001; respectively). Assessment of contour-related parameters, superior pole and inferior pole, found significantly improved outcomes in the delayed-immediate cohort (3.67 vs. 2.96, P<0.001 and 3.84 vs. 3.06, P<0.001; respectively). Delayed-immediate breast reconstruction had a significantly higher overall score compared to delayed breast reconstructions (3.84 vs. 2.94, P<0.001). Smoking and the time interval from radiation to reconstruction were found to affect aesthetic outcomes (P<0.05). Conclusions Preservation of native mastectomy skin may allow for improved skin/scar quality, breast contour, and overall aesthetic outcomes following a delayed-immediate reconstructive algorithm as compared to delayed breast reconstruction

Through Knee Amputation: Technique Modifications and Surgical Outcomes

Background Knee disarticulations (KD) are most commonly employed following trauma or tumor resection but represent less than 2% of all lower extremity amputations performed in the United States annually. KDs provide enhanced proprioception, a long lever arm, preservation of adductor muscle insertion, decreased metabolic cost of ambulation, and an end weight-bearing stump. The role for KDs in the setting of arterial insufficiency or overwhelming infection is less clear. The purpose of this study is to describe technique modifications and report surgical outcomes following KDs at a high-volume Limb Salvage Center. Methods A retrospective study of medical records for all patients who underwent a through-knee amputation performed by the senior author (C.E.A.) between 2004 and 2012 was completed. Medical records were reviewed to collect demographic, operative, and postoperative information for each of the patients identified. Results Between 2004 and 2012, 46 through-knee amputations for 41 patients were performed. The mean patient age was 68 and indications for surgery included infection (56%), arterial thrombosis (35%), and trauma (9%). Postoperative complications included superficial cellulitis (13%), soft tissue infection (4%), and flap ischemia (4%) necessitating one case of surgical debridement (4%) and four trans-femoral amputations (9%). 9 (22%) patients went on to ambulate. Postoperative ambulation was greatest in the traumatic cohort and for patients less than 50 years of age, P<0.05. Alternatively, diabetes mellitus and infection reduced the likelihood of postoperative ambulation, P<0.01. Conclusions Knee disarticulations are a safe and effective alternative to other lower extremity amputations when clinically feasible. For patient unlikely to ambulate, a through-knee amputation maximizes ease of transfers, promotes mobility by providing a counterbalance, and eliminates the potential for knee flexion contracture with subsequent skin breakdown