A randomized, double-blind, controlled study evaluating the effects of two facial serums on skin aging.

BACKGROUND: Skin aging is a natural process that occurs because of oxidative stress. Facial skin aging is often concerning for individuals due to the exposure of the face. OBJECTIVES: To assess and compare the effects of two anti-aging facial serums on the following characteristics associated with facial skin aging: fine lines/wrinkles, age spots, firmness, elasticity, texture, radiance, tone, lifting, clarity, and complexion. METHODS: A 24-week, double-blind controlled study was conducted on 130 participants who were randomized into two groups: facial serum with Liposomal Blend and facial serum without Liposomal Blend. Clinical evaluations (Visual Analog Scale) and instrumental evaluations (Cutometer, SIAscope, and Clarity Pro image analysis) were performed at weeks 0 (baseline), 2, 4, 8, 12, and 24 to assess for changes in skin aging characteristics. RESULTS: A total of 123 participants completed the study; participants that used the facial serum with Liposomal Blend had significantly greater improvements in skin aging characteristics compared to those that used the facial serum without Liposomal Blend. This study shows that Liposomal Blend is a vehicle with the ability to enhance the anti-aging properties of the ingredients within the facial serum by facilitating its delivery into the underlying layers of the skin. Higher concentration of ingredients at the site of action could potentially lead to greater damage repair and improvements in signs of facial skin aging. CONCLUSION: By using Liposomal Blend, practitioners and pharmacists could potentially improve the delivery of the ingredients within their formulations into the skin, which may lead to increased treatment efficacy.

A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases.

Newborn screening (NBS) dramatically improves outcomes in severe childhood disorders by treatment before symptom onset. In many genetic diseases, however, outcomes remain poor because NBS has lagged behind drug development. Rapid whole-genome sequencing (rWGS) is attractive for comprehensive NBS because it concomitantly examines almost all genetic diseases and is gaining acceptance for genetic disease diagnosis in ill newborns. We describe prototypic methods for scalable, parentally consented, feedback-informed NBS and diagnosis of genetic diseases by rWGS and virtual, acute management guidance (NBS-rWGS). Using established criteria and the Delphi method, we reviewed 457 genetic diseases for NBS-rWGS, retaining 388 (85%) with effective treatments. Simulated NBS-rWGS in 454,707 UK Biobank subjects with 29,865 pathogenic or likely pathogenic variants associated with 388 disorders had a true negative rate (specificity) of 99.7% following root cause analysis. In 2,208 critically ill children with suspected genetic disorders and 2,168 of their parents, simulated NBS-rWGS for 388 disorders identified 104 (87%) of 119 diagnoses previously made by rWGS and 15 findings not previously reported (NBS-rWGS negative predictive value 99.6%, true positive rate [sensitivity] 88.8%). Retrospective NBS-rWGS diagnosed 15 children with disorders that had been undetected by conventional NBS. In 43 of the 104 children, had NBS-rWGS-based interventions been started on day of life 5, the Delphi consensus was that symptoms could have been avoided completely in seven critically ill children, mostly in 21, and partially in 13. We invite groups worldwide to refine these NBS-rWGS conditions and join us to prospectively examine clinical utility and cost effectiveness.

Standardized Training for Physicians Practicing Pediatric Cardiac Critical Care.

OBJECTIVES: In the vast majority of Children's Hospitals, the critically ill patient can be found in one of three locations: the PICU, the neonatal ICU, and the cardiac ICU. Training, certification, and maintenance of certification for neonatology and critical care medicine are over seen by the Accreditation Council for Graduate Medical Education and American Board of Pediatrics. There is no standardization of training or oversight of certification and maintenance of certification for pediatric cardiac critical care. DATA SOURCES: The curricula from the twenty 4th year pediatric cardiac critical care training programs were collated, along with the learning objectives from the Pediatric Cardiac Intensive Care Society published "Curriculum for Pediatric Cardiac Critical Care Medicine." STUDY SELECTION: This initiative is endorsed by the Pediatric Cardiac Intensive Care Society as a first step toward Accreditation Council for Graduate Medical Education oversight of training and American Board of Pediatrics oversight of maintenance of certification. DATA EXTRACTION: A taskforce was established of cardiac intensivists, including the directors of all 4th year pediatric cardiac critical care training programs. DATA SYNTHESIS: Using modified Delphi methodology, learning objectives, rotational requirements, and institutional requirements for providing training were developed. CONCLUSIONS: In the current era of increasing specialized care in pediatric cardiac critical care, standardized training for pediatric cardiac critical care is paramount to optimizing outcomes.

Systemic GFP silencing is associated with high transgene expression in Nicotiana benthamiana.

Gene silencing in plants using topical dsRNA is a new approach that has the potential to be a sustainable component of the agricultural production systems of the future. However, more research is needed to enable this technology as an economical and efficacious supplement to current crop protection practices. Systemic gene silencing is one key enabling aspect. The objective of this research was to better understand topically-induced, systemic transgene silencing in Nicotiana benthamiana. A previous report details sequencing of the integration site of the Green Fluorescent Protein (GFP) transgene in the well-known N. benthamiana GFP16C event. This investigation revealed an inadvertent co-integration of part of a bacterial transposase in this line. To determine the effect of this transgene configuration on systemic silencing, new GFP transgenic lines with or without the transposase sequences were produced. GFP expression levels in the 19 single-copy events and three hemizygous GFP16C lines produced for this study ranged from 50-72% of the homozygous GFP16C line. GFP expression was equivalent to GFP16C in a two-copy event. Local GFP silencing was observed in all transgenic and GFP16C hemizygous lines after topical application of carbon dot-based formulations containing a GFP targeting dsRNA. The GFP16C-like systemic silencing phenotype was only observed in the two-copy line. The partial transposase had no impact on transgene expression level, local GFP silencing, small RNA abundance and distribution, or systemic GFP silencing in the transgenic lines. We conclude that high transgene expression level is a key enabler of topically-induced, systemic transgene silencing in N. benthamiana.

Zeaxanthin-based dietary supplement and topical serum improve hydration and reduce wrinkle count in female subjects.

BACKGROUND: Dietary modification, through supplementation and elimination diets, has become an area of interest to help slow skin aging, reduce symptom severity or prevent reoccurrence of certain dermatologic conditions [Clinical Dermatology vol. 31 (2013) 677-700]. Free radical components (reactive oxygen species or ROS) or lipid peroxide (LPO) is involved in the pathogenesis and progression of accelerated skin aging when prolonged oxidative stress occurs. The use of antioxidant-related therapies such as nutraceuticals is of particular interest in restoring skin homeostasis. Antioxidant carotenoid zeaxanthin is concentrated in the eye and skin tissue and believed to decrease the formation of ROS associated with UV light exposure. With zeaxanthin, phytoceramides, and botanical extracts an oral and topical test product (with zeaxanthin, algae extracts, peptides, hyaluronate) have been developed to improve the appearance and condition of skin when used as directed. METHODS: Subjects were divided into three groups: two tests (skin formula 1 - oral product alone (ZO-1), skin formula 2- oral product with topical product (ZO-2 + ZT)), and one placebo control. The study consisted of a washout visit, baseline (randomization), week two (2), week four (4), week six (6), week eight (8), and week twelve (12). Key parameters measured were as follows: fine lines, deep lines, total wrinkles, wrinkle severity, radiance/skin color (L, a*, b*), discolorations, and skin pigment homogeneity. RESULTS: Thirty-one subjects completed the twelve-week study; no adverse events were recorded during the study. Statistically significant improvements from baseline mean hydration score were observed in active groups at weeks 2, 6, and 8. A statistically significant difference was observed between mean differences from baseline scores for total wrinkle count at week 4 for the combination active groups compared to placebo. A statistically significant difference from baseline scores for fine lines count was also observed at the week 4 visit compared to placebo for both active groups. Statistically significant differences from baseline scores for average wrinkles severity were seen for week 12 visit for both active groups compared to placebo. CONCLUSION: We have shown that the combination of zeaxanthin-based dietary supplement plus a topical formulation produces superior hydration to that of placebo. Additionally, we have shown that the combination of oral and topical combination vs. oral alone has superior abilities to improve parameters associated with facial lines and wrinkles compared to placebo, although the dietary supplement alone proved most effective in reducing wrinkle count and severity.

Human papillomavirus and diseases of the upper airway: head and neck cancer and respiratory papillomatosis.

Human papillomavirus (HPV) infection is causally associated with benign and malignant diseases of the upper airway, including respiratory papillomatosis and oropharyngeal cancer. Low-risk HPV types 6 and 11 are the predominant cause of papillomatosis, whereas only HPV16 definitively satisfies both molecular and epidemiological causal criteria as a carcinogenic or high-risk type in the upper airway. HPV16 E6/E7 mRNA expression and integration are observed predominantly among oropharyngeal cancers, and experimental models have shown E6/E7 expression to be necessary for the initiation and maintenance of the malignant phenotype of these cancers. From an epidemiological perspective, a strong and consistent association between markers of HPV16 exposure and oropharyngeal cancer has been demonstrated in numerous case-control studies. HPV-positive oropharyngeal cancers have also been shown to be distinct from HPV-negative head and neck squamous cell cancers with regard to risk-factor profiles, molecular genetic alterations, population-level incidence trends over time, and prognosis. Tumor HPV status (as determined by certain HPV16 in situ hybridization assays or certain p16 immunohistochemistry assays) is the strongest determinant of survival for patients with local-regionally advanced oropharyngeal cancer: patients with HPV-positive cancer have at least a 50% improvement in overall survival at 5 years, which is equivalent to an approximate 30% difference in absolute survival. Thus, HPV status determination is now part of the routine diagnostic evaluation for prognostication. Preliminary evidence indicates that a small proportion of head and neck cancers may be caused by additional HPV types (e.g., 18, 31, 33, 35) and that HPV-caused cancers may rarely arise from non-oropharyngeal sites (e.g., the oral cavity, nasopharynx, and larynx). Whether or not HPV vaccination has the potential to prevent oral HPV infections that lead to cancer or papillomatosis in the upper airway is currently unknown, as is the potential for secondary prevention with HPV detection. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012.

The formation of Anthocyanic Vacuolar Inclusions in Arabidopsis thaliana and implications for the sequestration of anthocyanin pigments.

Anthocyanins are flavonoid pigments that accumulate in the large central vacuole of most plants. Inside the vacuole, anthocyanins can be found uniformly distributed or as part of sub-vacuolar pigment bodies, the Anthocyanic Vacuolar Inclusions (AVIs). Using Arabidopsis seedlings grown under anthocyanin-inductive conditions as a model to understand how AVIs are formed, we show here that the accumulation of AVIs strongly correlates with the formation of cyanidin 3-glucoside (C3G) and derivatives. Arabidopsis mutants that fail to glycosylate anthocyanidins at the 5-O position (5gt mutant) accumulate AVIs in almost every epidermal cell of the cotyledons, as compared to wild-type seedlings, where only a small fraction of the cells show AVIs. A similar phenomenon is observed when seedlings are treated with vanadate. Highlighting a role for autophagy in the formation of the AVIs, we show that various mutants that interfere with the autophagic process (atg mutants) display lower numbers of AVIs, in addition to a reduced accumulation of anthocyanins. Interestingly, vanadate increases the numbers of AVIs in the atg mutants, suggesting that several pathways might participate in AVI formation. Taken together, our results suggest novel mechanisms for the formation of sub-vacuolar compartments capable of accumulating anthocyanin pigments.

Correlates of depression at baseline among African Americans enrolled in cardiac rehabilitation.

PURPOSE: To compare baseline psychosocial characteristics of African Americans entering phase 2 cardiac rehabilitation who have depression symptoms at or above threshold (Center for Epidemiological Studies Depression Scale [CES-D] score >or=16) with those who do not (CES-D score <16). METHODS: A nonrandom sample of 112 men and women (n = 78 without depression, n = 34 with depression) was recruited through local phase 2 cardiac rehabilitation programs. Data were obtained by a structured interview and brief physical examination using several reliable and valid instruments. Chi-square tests, Kruskal-Wallis 2-sample tests, Spearman rank correlation coefficients, and logistic regression models were used for analyses. RESULTS: We found that 30% of the participants were above the depression symptom threshold. Demographic characteristics were not significantly different between individuals at or above threshold and those below threshold. However, depressed individuals above threshold were more likely to be dissatisfied with their neighborhoods (P = .01) and had lower optimism scores (P < .0001), higher stress scores (P < .0001), lower adaptive coping scores (P = .05), and higher problematic coping scores (P < .01) than their counterparts who were below threshold. In the logistic regression model, the odds of being above the depression symptom threshold increased with stress (P < .001) and decreased with optimism (P = .03); none of the other psychosocial characteristics had an independent effect on depression symptoms. CONCLUSIONS: At baseline, African Americans starting phase 2 cardiac rehabilitation with depression symptoms at or above threshold had more stress and fewer stress resilience factors. Assessing depression and stress resilience factors is important and may lead to more active participation in cardiac rehabilitation once enrolled, as well as optimal cardiovascular health outcomes.

Ventilator-associated pneumonia in the pediatric intensive care unit: characterizing the problem and implementing a sustainable solution.

OBJECTIVES: To characterize ventilator-associated pneumonia (VAP) in our pediatric intensive care unit (PICU), implement an evidence-based pediatric VAP prevention bundle, and reduce VAP rates. STUDY DESIGN: The setting is a 25-bed PICU in a 475-bed free-standing pediatric academic medical center. VAP was diagnosed according to Centers for Disease Control and National Nosocomial Infections Surveillance System definitions. A pediatric VAP prevention bundle was established and implemented. Baseline VAP rates were compared with implementation and post-bundle-implementation periods. RESULTS: VAP is significantly associated with increased PICU length of stay, mechanical ventilator days, and mortality rates (length of stay VAP 19.5+/-15.0 vs non-VAP 7.5+/-9.2, P< .001; ventilator days VAP 16.3+/-14.7 vs non-VAP 5.3+/-8.4, P< .001; mortality VAP 19.1% vs non-VAP 7.2%, P= .01). The VAP rate was reduced from 5.6 (baseline) to 0.3 infections per 1000 ventilator days after bundle implementation; P< .0001. Subglottic/tracheal stenosis, trauma, and tracheostomy are significantly associated with VAP. CONCLUSIONS: PICU VAP is associated with increased morbidity and mortality rates. A multidisciplinary improvement team can implement a sustainable pediatric-specific VAP prevention bundle, resulting in VAP rate reduction.

Cryosurgery: an innovative technique for the treatment of plantar fasciitis.

A prospective study testing the efficacy of cryosurgery on painful plantar fasciitis of the heel was performed. Cryosurgery, a minimally invasive, percutaneous, office-based technique, was used to treat 59 consecutive patients (61 heels), who had failed prior conservative therapy and were considered surgical candidates. Patients were evaluated on an 11-point visual analog scale administered preoperatively and up to 1 year of follow-up. The mean pain rating (8.38) before cryosurgery (day 0) is statistically significant to the mean pain rating (1.26) at day 365 postoperatively. Pain decreased significantly after the procedure (analysis of variance, P < .0001). These results suggest cryosurgery is significantly effective in treating patients with recalcitrant plantar fasciitis. Cryosurgery offers a highly effective treatment modality after failed conservative treatment without resorting to open invasive outpatient surgery.

Rapid, specific, and sensitive detection of spoilage molds in orange juice using a real-time Taqman PCR assay.

The outgrowth of spoilage organisms, including molds and yeasts, results in significant financial loss to the food industry and wastes natural resources. The objective of this study was to develop a rapid, specific, and sensitive real-time PCR method for detecting spoilage molds during screening of raw materials and final product quality control analysis. The 18S rRNA gene was used to develop PCR primers and probe. With this set of primers and probe, less than 1,000 mold cells per milliliter of orange juice (10 cells per reaction) were detected with the real-time PCR system within 6 to 7 h. No cross-reactivity was found with other common foodborne bacteria, yeasts, or food ingredients. This technique is significantly faster than current detection and identification procedures, which take from days to weeks.

The effect of pesticide spraying on the rate and severity of ED asthma.

We report on the incidence of emergency department (ED) asthma presentations and admissions to the Lincoln Hospital, located in the South Bronx of New York City, during the 1999 eradication program of the mosquito vector for West Nile virus. Spraying of Malathion and Resmethrin occurred in the hospital's geographic area over 4 days in September 1999. During that time, 1318 pediatric and adult patients were seen in the ED for asthma-related symptoms. Of these, 222 (16.8%) were hospitalized. Emergency department visits, during days when spraying occurred, were compared with visits during days when no spraying occurred. Comparisons were made with previous years as a reference point. Findings showed that the spraying of insecticides did not increase the rate or severity of asthma presentations as measured by the Lincoln Hospital's ED asthma census or hospital admissions for asthma.