Improvement in the Appearance of Wrinkles with Topical Transforming Growth Factor β1 and l-Ascorbic Acid

BACKGROUND AND OBJECTIVE: Facial rhytides are a common cosmetic concern. Surgical treatment effects dramatic improvement; however, the associated risk and cost may be prohibitive. Recent focus is on developing topical products containing biologically active ingredients for at-home therapy. Our study examines the effects of a topical cream containing transforming growth factor-beta(1) (TGF-beta(1)), l-ascorbic acid, and Cimicifuga racemosa extract (CRS) (Topix Pharmaceuticals, North Amityville, NY, USA). MATERIALS AND METHODS: In the first arm of the study, 12 subjects were randomized to apply CRS to the left or right side of their face and a cream containing l-ascorbic acid and C. racemosa in silicone base (vitamin C [Vit C]) to the contralateral side twice daily for 3 months. In the second arm of the study, 20 subjects were randomized to apply CRS to the left or right side of their face and Tissue Nutrient Solution Recovery Complex (TNS) (SkinMedica, Carlsbad, CA, USA), a product containing a variety of growth factors including VEGF, PDGF-A, G-CSF, HGF, IL-6, IL-8, and TGF-beta(1) (Nouricel-MD) without l-ascorbic acid, C. racemosa extract, or silicone base, to the contralateral side of their face twice daily for 3 months. Digital photographs were scored by study-blinded physicians, and self-assessments were completed by all subjects at baseline and at the conclusion of the protocol. RESULTS: CRS and TNS were well tolerated, and all subjects completed the 3-month protocol for the CRS versus Vit C arm of the study. Physicians rated success in facial wrinkling scores on the CRS-treated side of the face for 27 of 31 subjects. Responders showed, on average, 21.7% improvement in physician-rated wrinkle scores. The mean improvement in the group of 31 patients as a whole was 12%. Eighteen of 31 subjects reported a noticeable improvement on their CRS-treated side. Both CRS and TNS demonstrate significant success between baseline and 3-month scores, and both growth factor products are superior to Vit C. Patients preferred CRS over TNS. CONCLUSION: CRS is effective in minimizing the appearance of facial rhytides. The success of the CRS product is largely attributable to the incorporation of TGF-beta(1).     

Viral Persistence in Neurons Alters Synaptic Plasticity and Cognitive Functions without Destruction of Brain Cells

Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection bothin vitroandin vivoselectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury.     

Disclosure,Apology, and Offer Programs: Stakeholders’ Views of Barriers to and Strategies for Broad Implementation

Context: The Disclosure, Apology, and Offer (DA&O) model, a response to patient injuries caused by medical care, is an innovative approach receiving national attention for its early success as an alternative to the existing inherently adversarial, inefficient, and inequitable medical liability system. Examples of DA&O programs, however, are few. Methods: Through key informant interviews, we investigated the potential for more widespread implementation of this model by provider organizations and liability insurers, defining barriers to implementation and strategies for overcoming them. Our study focused on Massachusetts, but we also explored themes that are broadly generalizable to other states. Findings: We found strong support for the DA&O model among key stakeholders, who cited its benefits for both the liability system and patient safety. The respondents did not perceive any insurmountable barriers to broad implementation, and they identified strategies that could be pursued relatively quickly. Such solutions would permit a range of organizations to implement the model without legislative hurdles. Conclusions: Although more data are needed about the outcomes of DA&O programs, the model holds considerable promise for transforming the current approach to medical liability and patient safety.     

A picture is worth a thousand words: Children's representations of family as indicators of early attachment

To ascertain whether attachment representations at age 7 are related to early attachment behaviour, family drawings of 123 7-year-olds of known infant attachment status (25 avoidant, 80 secure, 18 resistant) were scored in four ways. Three of these were based in previous attachment research and one was based on a clinical method. The attachment-based coding schemes included specific markers for each attachment pattern (Kaplan & Main, 1985), global ratings (Fury, Carlson, & Sroufe, 1997) and efforts to classify each drawing as belonging to one of the three primary infant attachment groups (secure, avoidant, resistant). In the clinical scheme, children who had been resistant infants were distinguished from the others by use of overlapping and encapsulated figures. For the attachment based schemes, although individual markers were not successful in discriminating attachment groups, the more global approaches (aggregation of markers, global rating scales and judgments of attachment classification) succeeded in this task. In regression analyses controlling for concurrent child and parent measures, infant attachment did not make a significant contribution to predicting insecurity markers in drawings, although child current emotional functioning did. These findings linking attachment relationships with later representations of family relationships were in accord with the conception that avoidant attachment strategies de-emphasize intimate relationships, while resistant attachment strategies are preoccupied with close relationships. These links are most evident in global interpretive strategies rather than those that rely on specific markers.     

How does the pitch and pattern of a signal affect auditory arousal thresholds?

How arousal thresholds vary with different sounds is a critical issue for emergency awakenings, especially as sleepers are dying in fires despite having a working smoke alarm. Previous research shows that the current high-pitched (3000+ Hz) smoke alarm signal is significantly less effective than an alternative signal, the 520 Hz square wave, in all populations tested. However, as the number of sounds tested has been small further research is needed. Here we measured auditory arousal thresholds (AATs) across signals with a range of characteristics to determine the most effective waking signal. Thirty-nine young adults participated over three nights. In Part A, nine signals were presented in stage 4 sleep with ascending decibel levels. Signals were short beeps in the low- to mid-frequency range with different spectral complexities: square waves, pure tones, whoops and white noise. Part B manipulated temporal patterns, inserting silences of 0, 10 and 21 s after each 12 s of beeps. It was found that the low-frequency (400 and 520 Hz) square waves yielded significantly lower AATs than the alternatives. A trend was found across the three temporal manipulations, with a 10 s intervening silence showing some advantage. These findings support earlier research indicating that the best sound for awakening from deep sleep is a low-frequency square wave. It is argued that the signal with the lowest response threshold when awake may be the same as the most arousing signal when asleep, especially where the sleeper processes the signal as meaningful.     

Induction of Abnormal Ventilatory Responses to CO2 and Evaluation of Agents Given to Prevent or Reverse These Responses

Induction of Abnormal Ventilatory Responses to CO2 and Evaluationof Agents Given to Prevent or Reverse These Responses. SCHAPER,M., AND ALARIE, Y. (1988). Fundam. Appl Toxicol 10, 506–516.This study demonstrates how a previously described animal modelcan be utilized to evaluate the effects of multiple aerosols.For the exposures presented in this report, unanesthetized butmildly restrained guinea pigs were used. Airflow (V), tidalvolume (V_T), and respiratory frequency (f) were continuouslymeasured in all animals and their flow-volume (V–V_T) loopswere also obtained. The animals were first exposed to room airand then challenged with a 10% CO2 (in 19% O₂, 71% N₂) mixture.The normal ventilatory response to 10% CO₂ consists of increasesin V, VT, and f. This response is very stable for long periodsof time and is highly reproducible. It is possible, however,to alter the normal CO₂ response by adding an aerosol to theCO₂ mixture. Two types of acute responses can be induced, TypeI and Type II. In this study, histamine and carbamylcholineaerosols were used to induce the Type I response while propranololaerosols were used to induce the Type II response. Serotoninaerosols were used to induce both types of effects. We reportthat the bronchodilator, isoproterenol, reversed the Type Ipulmonary effects where the level of reversal was deoendentupon isoproterenol concentration. The rapid, shallow breathing,characteristic of the Type II response, was not reversed byisoproterenol but could be prevented by blocking the vagus nervewith cocaine. Since no invasive techniques are required andthe same animals can be used repeatedly, combinations of aerosolscan be tested in order to delineate how Type I or Type II abnormalventilatory responses to CO₂ are induced by a wide variety ofairborne chemicals.