Sun Protective Clothing and Sun Avoidance: The Most Critical Components of Photoprotection in Patients With Melanoma.

BACKGROUND: Ultraviolet radiation is the main modifiable risk factor for melanoma which can be reduced by avoiding excess sun exposure. OBJECTIVE: We sought to explore (1) sun protective practices, (2) effectiveness of these sun protective practices, and (3) vitamin D supplementation in patients with melanoma. METHODS: Using the National Health Interview Survey, the authors conducted a cross-sectional analysis to investigate sun protective behaviors and sunburns among adults with melanoma compared with those without skin cancer. We calculated adjusted odds ratio (aOR), 95% confidence interval (95% CI), and p-values using logistic regression. RESULTS: Patients with melanoma reported increased use of sun avoidance, shade, sunscreen, long sleeves, and hats, but had similar sunburn rates compared with those without skin cancer. Only sun avoidance and long sleeves were associated with decreased odds of sunburn. Patients with melanoma also reported decreased vitamin D supplementation. CONCLUSION: Although it is reassuring that patients with melanoma practice sun protective behaviors, this does not always translate into reduced sunburns. Physicians should emphasize the importance of photoprotection, especially sun avoidance and sun protective clothing, to reduce future melanoma risk.

Novel Multitarget Directed Triazinoindole Derivatives as Anti-Alzheimer Agents.

The multifaceted nature of Alzheimer's disease (AD) demands treatment with multitarget-directed ligands (MTDLs) to confront the key pathological aberrations. A novel series of triazinoindole derivatives were designed and synthesized. In vitro studies revealed that all the compounds showed moderate to good anticholinesterase activity; the most active compound 23e showed an IC50 value of 0.56 ± 0.02 µM for AChE and an IC50 value of 1.17 ± 0.09 µM for BuChE. These derivatives are also endowed with potent antioxidant activity. To understand the plausible binding mode of the compound 23e, molecular docking studies and molecular dynamics simulation studies were performed, and the results indicated significant interactions of 23e within the active sites of AChE as well as BuChE. Compound 23e successfully diminished H2O2-induced oxidative stress in SH-SY5Y cells and displayed excellent neuroprotective activity against H2O2 as well as Aß-induced toxicity in SH-SY5Y cells in a concentration dependent manner. Furthermore, it did not show any significant toxicity in neuronal SH-SY5Y cells in the cytotoxicity assay. Compound 23e did not show any acute toxicity in rats at doses up to 2000 mg/kg, and it significantly reversed scopolamine-induced memory deficit in mice model. Additionally, compound 23e showed notable in silico ADMET properties. Taken collectively, these findings project compound 23e as a potential balanced MTDL in the evolution process of novel anti-AD drugs.

Fractional CO2 Laser Treatment Outcomes for Pediatric Hypertrophic Burn Scars.

Carbon dioxide ablative fractional laser (CO2-AFL) therapy has not been widely adopted in pediatric burn care given limited outcomes literature and no established guidelines on laser treatment protocols. We present our experience to further elucidate the clinical role of CO2-AFL therapy for pediatric hypertrophic burn scars. We conducted a prospective cohort study of pediatric burn patients undergoing CO2-AFL treatment of hypertrophic, symptomatic burn scars at a tertiary care regional burn center during a 2-year period. Scars were assessed before each treatment using the Patient and Observer Scar Assessment Scale (POSAS), a validated, subjective, comprehensive scar assessment tool. We treated 49 pediatric patients for a total of 180 laser sessions. Burn severity was full thickness (63.6%) or deep partial thickness (47.7%). Observer-rated POSAS scores revealed statistically significant improvements in pigment, thickness, relief, pliability, and surface area after one treatment with continued improvement until the last laser session. Patient-rated POSAS revealed statistically significant improvements in color, stiffness, thickness, and irregularity after laser treatments. Total POSAS improved from 89.6 ± 17.5 to 76.6 ± 16.8 (P < .0001) after one treatment with further improvement to 69.2 ± 14.9 (P < .0001) at the final laser session. We found convincing evidence that CO2-AFL therapy improves hypertrophic burn scars on both patient- and observer-rated scales confirming statistical and clinical significance to both providers and families. These findings demonstrate that CO2-AFL can improve hypertrophic burn scars in pediatric patients providing a lower risk alternative to invasive therapies and a more immediate, efficacious alternative to more conservative scar treatments.

Emergency Laparotomy in the Critically Ill: Futility at the Bedside.

BACKGROUND: Critically ill patients are often evaluated for an intra-abdominal catastrophe. In the absence of a preoperative diagnosis, abdominal exploration may be offered despite desperate circumstances. We hypothesize that (1) abdominal exploration for such patients is associated with a high mortality and (2) commonly obtained physiologic measures at laparotomy anticipate mortality. METHODS: All acute care surgery (ACS) patients undergoing emergency laparotomy at a quaternary referral center during a 3-year period were reviewed. Inclusion was defined by emergency laparotomy in the operating room (OR) in a patient with an American Society of Anesthesiologists (ASA) score ≥4 or bedside laparotomy in the ICU (BSL). Mortality was the primary endpoint and was stratified by demographics, admitting service, surgical findings, and physiology. Comparisons between OR and BSL were by Fisher's exact and Mann-Whitney tests. RESULTS: 144 patients underwent emergency laparotomy (45 BSL vs. 99 OR). Overall mortality was 55.6% (77.8% BSL vs. 45.5% OR; p < 0.001). Mortality by admitting service was cardiac 71.4% (n=42), medical 70% (n=30), ACS 42% (n=50), and other 36.4% (n=22) services. Preoperative lactate levels were higher in nonsurvivors (2.7 vs. 8.5 mmol/L, p < 0.001), as was vasopressor use (62.5% vs. 97.5%, p < 0.001), acute kidney injury (51.6% vs. 72.5%, p < 0.01), leukocytosis (53.1% vs. 71.3%, p < 0.04), and anemia (45.3% vs. 71.3%, p < 0.01). The presence of any identifiable abdominal pathology established a 90% mortality rate. CONCLUSIONS: The need for BSL portends an extremely high mortality rate and is likely useful in preintervention counselling. Emergency OR laparotomy leads to mortality in nearly half of such patients and is anticipatable based on concurrent abnormal physiology.

Ganglioside-linked terminal sialic acid moieties on murine macrophages function as attachment receptors for murine noroviruses.

Noroviruses are the major cause of nonbacterial gastroenteritis in humans. However, little is known regarding the norovirus life cycle, including cell binding and entry. In contrast to human noroviruses, the recently discovered murine norovirus 1 (MNV-1) readily infects murine macrophages and dendritic cells in culture. Many viruses, including the related feline calicivirus, use terminal sialic acids (SA) as receptors for infection. Therefore, we tested whether SA moieties play a role during MNV-1 infection of murine macrophages. Competition with SA-binding lectins and neuraminidase treatment led to a reduction in MNV-1 binding and infection in cultured and primary murine macrophages, suggesting a role for SA during the initial steps of the MNV-1 life cycle. Because SA moieties can be attached to glycolipids (i.e., gangliosides), we next determined whether MNV-1 uses gangliosides during infection. The gangliosides GD1a, GM1, and asialo-GM1 (GA1) are natural components of murine macrophages. MNV-1 bound to ganglioside GD1a, which is characterized by an SA on the terminal galactose, but not to GM1 or asialo-GM1 in an enzyme-linked immunosorbent assay. The depletion of gangliosides using an inhibitor of glycosylceramide synthase (d-threo-P4) led to a reduction of MNV-1 binding and infection in cultured and primary murine macrophages. This defect was specifically rescued by the addition of GD1a. A similar phenotype was observed for MNV field strains WU11 (GV/WU11/2005/USA) and S99 (GV/Berlin/2006/DE). In conclusion, our data indicate that MNV can use terminal SA on gangliosides as attachment receptors during binding to murine macrophages.