A General Synthesis of Dihydronaphthyridinones with Aryl-Substituted Quaternary Benzylic Centers.

A variety of 7,8-dihydro-1,6-naphthyridin-5(6H)-ones and 3,4-dihydro-2,7-naphthyridin-1(2H)-ones with quaternary centers and aryl substitutions at the benzylic carbon were synthesized with a new 3-step, 2-pot method. The first step is an SNAr using widely available 2- and 4-chloronicotinate esters and tertiary benzylic nitriles. The last two steps are a one-pot selective nitrile reduction in the presence of various heterocycles followed by a lactam ring closure of the free amine on the ester.

Birth and newborn care policies and practices limit breastfeeding at maternity facilities in Vietnam.

The prevalence of early and exclusive breastfeeding in Vietnam remains sub-optimal. The objective of this study was to determine factors associated with early initiation of breastfeeding (EIBF) and exclusive breastfeeding for the first 3 days after birth (EBF3D). We conducted a population-based, cross-sectional survey of 726 mothers with children aged 0-11 months in two provinces and one municipality from May to July 2020. Multinomial logistic regression was used to examine factors associated with EIBF and EBF3D. The prevalence of EIBF was 39.7% and EBF3D 18.0%. The EIBF prevalence is positively associated with immediate and uninterrupted skin-to-skin contact (SSC) for 10-29 min (aOR: 2.55; 95% CI: 1.49, 4.37), 30-59 min (aOR: 4.15; 95% CI: 2.08, 8.27), 60-80 min (aOR: 4.35; 95% CI: 1.50, 12.6), or ≥90 min (aOR: 5.87; 95% CI: 3.14, 10.98). EIBF was negatively associated with cesarean birth (aOR: 0.24; 95% CI: 0.11, 0.51), bringing infant formula to the birth facility (aOR: 0.49; 95% CI: 0.30, 0.78), purchased it after arrival (aOR: 0.37; 95% CI: 0.24, 0.60), or did both (aOR: 0.43; 95% CI: 0.21, 0.89). EBF3D was negatively associated with cesarean section birth (aOR: 0.15; 95% CI: 0.06, 0.39), vaginal birth with episiotomy (aOR: 0.40; 95% CI: 0.18, 0.88), bringing formula to the maternity facility (aOR: 0.03; 95% CI: 0.01, 0.07), purchased it after arrival (aOR: 0.02; 95% CI: 0.01, 0.06) or did both (aOR: 0.04; 95% CI: 0.02, 0.10). Receiving counseling from any source was not significantly associated with early breastfeeding practices. Policy and health service delivery interventions should be directed at eliminating infant formula from birthing environments, reducing unnecessary cesarean sections and episiotomies, providing immediate and uninterrupted SSC for all births, and improving breastfeeding counseling and support.

Thymic stromal lymphopoietin controls hair growth.

Skin tissue regeneration after injury involves the production and integration of signals by stem cells residing in hair follicles (HFSCs). Much remains unknown about how specific wound-derived factors modulate stem cell contribution to hair growth. We demonstrate that thymic stromal lymphopoietin (TSLP) is produced in response to skin injury and during the anagen phase of the hair cycle. Intradermal injection of TSLP promoted wound-induced hair growth (WIHG), whereas neutralizing TSLP receptor (TSLPR) inhibited WIHG. Using flow cytometry and fluorescent immunostaining, we found that TSLP promoted proliferation of transit-amplifying cells. Lgr5CreER-mediated deletion of Tslpr in HFSCs inhibited both wound-induced and exogenous TSLP-induced hair growth. Our data highlight a novel function for TSLP in regulation of hair follicle activity during homeostasis and wound healing.

Quality of Early Essential Newborn Care in hospitals in Gaza: a pre-intervention and post-intervention study.

BACKGROUND: In 2017, the Ministry of Health in Gaza introduced Early Essential Newborn Care (EENC) as its primary maternal and neonatal care strategy. EENC comprises a package of simple evidence-based interventions that are delivered during labour and delivery, and in the early post-partum period, to prevent or treat the most important causes of morbidity and mortality in newborn babies. Four public maternity hospitals in Gaza, responsible for approximately 75% of all deliveries, began implementation of EENC in June, 2017. Clinical coaching was delivered by national facilitators over 2 days, and targeted all clinical staff in maternity and neonatal units. Subsequently, EENC quality improvement teams were formed to address contextual factors that influence practice. This study aimed to determine whether introduction of EENC resulted in changes in clinical practices for vaginal births. METHODS: A pre-intervention and post-intervention design was used to review key clinical practices before and after EENC introduction in the four hospitals. Trained data collection staff visited each hospital for 1 day in each of the months of March and June, 2017 (before EENC implementation), January and April, 2018 (in the early stages of EENC implementation), September, 2018, and June, 2019 (after full EENC implementation). Standard WHO data collection methods and tools were used to gather practice data using exit interviews and chart reviews of 10-15 randomly selected post-partum mothers who had delivered vaginally in the previous 2-24 h and had not experienced a newborn death or stillbirth. Delivery observations were conducted for five to ten randomly selected vaginal deliveries using a standard clinical skills observation checklist, beginning at the second stage of labour. The Ministry of Health in Gaza approved EENC assessments for programme use, and informed verbal consent was obtained before maternal interviews. No personal identifiers were used in assessments. FINDINGS: 259 maternal post-partum interviews and 139 observations of birth practices were done across the four maternity hospitals, representing 8·8% (259 of 2940) and 4·7% (139) of expected vaginal births during the observation periods, respectively. Comparing practices at baseline, early implementation, and after full implementation, significant trend improvements were noted for proportion of babies receiving thorough drying (0% [0 of 12], 49% [32 of 66], 72% [43 of 60], respectively, p<0·0004), immediate skin-to-skin contact (SSC) for less than 1 min (0% [0 of 14], 33% [43 of 127], 66% [72 of 110], p<0·0001), uninterrupted SSC for at least 60 min (0% [0 of 14], 21% [27 of 129], 48% [53 of 111], p<0·0001), uninterrupted SSC for at least 90 min (0% [0 of 14], 10% [13 of 129], 36% [39 of 110], p<0·0001), early breastfeeding (15-90 min after birth) (0% [0 of 15], 39% [50 of 130], 61% [65 of 107], p<0·0001), breastfeeding before separation (0% [0 of 15], 28% [36 of 131], 52% [56 of 108], p<0·0001), and exclusive breastfeeding before discharge (33% [5 of 15], 68% [89 of 131], 81% [87 of 107], p=0·0010). Average clinical practice scores rose from five of 42 (12%) to 16 of 42 (38%) and 24 of 42 (57%). Practice improvements were supported by updated clinical guidelines, hospital policies, and routines, by reorganisation of work, and by the provision of simple supplies, including gowns for mothers and caps for newborn babies. INTERPRETATION: The EENC clinical coaching approach coupled with regular self-assessments and action by hospital teams has significantly improved care practices during delivery and in the early post-partum period. It is possible that periodic cross-sectional practice reviews were not representative of routine practices, which may have varied with time of day, case load, and case complexity. Limitations were mitigated by assessing a systematic random sample of post-partum women delivering throughout the previous 24 h, and by measuring practices in two different time periods in each phase of implementation. Post-partum interviews were used to limit the Hawthorne effect. No other maternal or newborn initiatives were introduced during the study period, and no additional staff training was available, therefore the EENC approach was the primary influence on health worker practices. FUNDING: Support for this work was provided by WHO, occupied Palestinian territory.

Factors Associated with the Use of Pasteurized Donor Milk for Healthy Newborns: Experience from the First Human Milk Bank in Vietnam.

BACKGROUND: Pasteurized donor milk (PDM) is typically prescribed to preterm or low birthweight newborns when their mother's own milk is unavailable. In surplus, PDM is prescribed to meet the nutritional needs of healthy newborns in the first few days of life. However, its overuse can undermine efforts to promote and support breastfeeding, waste resources, and reduce the availability of PDM for at-risk newborns. We conducted this study to examine factors associated with the prescription and prolonged use (>48 h) of privately purchased PDM to healthy newborns. METHODS: Prospective observational study of 2440 mothers of healthy, term, and normal birthweight newborns born at Da Nang Hospital for Women and Children between April and August 2019. In addition to the descriptive analysis, we performed multiple logistic regressions to examine factors associated with the prescription of PDM (n = 2440) and prolonged PDM use among those who used PDM (n = 566). RESULTS: Twenty-three percent (566/2440) of healthy, term, and birthweight ≥2500 g newborns received PDM and were included in the study. The prevalence of PDM use was higher for cesarean births (OR: 2.05; 95% CI: 1.66, 2.55) and among male newborns (OR: 1.33; 95% CI: 1.09, 1.62), but lower for farmers or workers (vs. other jobs; OR: 0.71; 95% CI: 0.54, 0.93), family income <10 million VND (vs. ≥10 million VND; OR: 0.67; 95% CI: 0.55, 0.82), and duration of skin-to-skin ≥90 min (vs. <90 min; OR: 0.54; 95% CI: 0.39, 0.76). Prolonged PDM use (12.4% of 566 newborns who used PDM) was associated with the mother having a higher socioeconomic status job (professional, small trader or homemaker; OR: 4.00; 95% CI: 1.39, 12.5), being a first-time mother (OR: 3.39; 95% CI: 1.92, 6.01) or having a cesarean birth (OR: 2.09; 95% CI: 1.02, 4.28). CONCLUSIONS: The prescription and prolonged use of privately purchased PDM was associated with non-medical factors unrelated to the ability to breastfeed effectively. The findings suggest the need for improved breastfeeding communication, counseling and support skills for health staff, development, and application of strict criteria on PDM use for healthy newborns and better routine monitoring of PDM use over time.

Early Essential Newborn Care can still be used with mothers who have COVID-19 if effective infection control measures are applied.

We describe the first infant born to a woman with COVID-19 in Vietnam, by Caesarean section at 36 weeks and 5 days of gestation. The mother and baby remained together during their hospital stay and prolonged skin-to-skin contact and early and exclusive breastfeeding were achieved. This was in line with the World Health Organization's Early Essential Newborn Care (EENC) recommendations, the national Vietnamese standard of care since 2014. The baby remained virus-free throughout the 34-day postpartum follow-up. CONCLUSION: The EENC approach can still be used with mothers who have COVID-19 if effective infection control measures are applied.

A case for updating the WHO Safe Childbirth Checklist to improve newborn care: Experience from seven Asia and Pacific countries.

The WHO Safe Childbirth Checklist (the SCC) is a clinical tool developed to help health workers follow evidence-based maternal and perinatal care practices at childbirth. Newborn delivery care practices at facilities in seven countries in East Asia and the Pacific were compared to practices checked by the SCC. The analysis found that the SCC does not incorporate several key evidence-based practices around birth demonstrated to prevent newborn morbidity or mortality, or harmful practices associated with increased risks. A revision of the standard SCC is needed to maximise its potential to improve newborn outcomes. This can be initiated under the coordinating umbrella of WHO, but must ensure that the realities of labour and childbirth practices in low- and middle-income countries are considered and addressed.

Perception of artificial conspecifics by bearded dragons (Pogona vitticeps).

Artificial animals are increasingly used as conspecific stimuli in animal behavior research. However, researchers often have an incomplete understanding of how the species under study perceives conspecifics, and, hence, which features are needed for a stimulus to be perceived appropriately. To investigate the features that bearded dragons (Pogona vitticeps) attend to, we measured their lateralized eye use when assessing a successive range of stimuli. These ranged through several stages of realism in artificial conspecifics, to see how features such as color, the presence of eyes, body shape and motion influence behavior. We found differences in lateralized eye use depending on the sex of the observing bearded dragon and the artificial conspecific, as well as the artificial conspecific's behavior. Therefore, this approach can inform the design of robotic animals that elicit biologically-meaningful responses in live animals.

Design and Synthesis of Clinical Candidate PF-06751979: A Potent, Brain Penetrant, ß-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor Lacking Hypopigmentation.

A major challenge in the development of ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer's disease is the alignment of potency, drug-like properties, and selectivity over related aspartyl proteases such as Cathepsin D (CatD) and BACE2. The potential liabilities of inhibiting BACE2 chronically have only recently begun to emerge as BACE2 impacts the processing of the premelanosome protein (PMEL17) and disrupts melanosome morphology resulting in a depigmentation phenotype. Herein, we describe the identification of clinical candidate PF-06751979 (64), which displays excellent brain penetration, potent in vivo efficacy, and broad selectivity over related aspartyl proteases including BACE2. Chronic dosing of 64 for up to 9 months in dog did not reveal any observation of hair coat color (pigmentation) changes and suggests a key differentiator over current BACE1 inhibitors that are nonselective against BACE2 in later stage clinical development.

Improving immediate newborn care practices in Philippine hospitals: impact of a national quality of care initiative 2008-2015.

OBJECTIVE: To determine whether intrapartum and newborn care practices improved in 11 large hospitals between 2008 and 2015. DESIGN: Secondary data analysis of observational assessments conducted in 11 hospitals in 2008 and 2015. SETTING: Eleven large government hospitals from five regions in the Philippines. PARTICIPANTS: One hundred and seven randomly sampled postpartum mother-baby pairs in 2008 and 106 randomly sampled postpartum mothers prior to discharge from hospitals after delivery. INTERVENTIONS: A national initiative to improve quality of newborn care starting in 2009 through development of a standard package of intrapartum and newborn care services, practice-based training, formation of multidisciplinary hospital working groups, and regular assessments and meetings in hospitals to identify actions to improve practices, policies and environments. Quality improvement was supported by policy development, health financing packages, health facility standards, capacity building and health communication. MAIN OUTCOME MEASURES: Sixteen intrapartum and newborn care practices. RESULTS: Between 2008 and 2015, initiation of drying within 5 s of birth, delayed cord clamping, dry cord care, uninterrupted skin-to-skin contact, timing and duration of the initial breastfeed, and bathing deferred until 6 h after birth all vastly improved (P<0.001). The proportion of newborns receiving hygienic cord handling and the hepatitis B birth dose decreased by 11-12%. Except for reduced induction of labor, inappropriate maternal care practices persisted. CONCLUSIONS: Newborn care practices have vastly improved through an approach focused on improving hospital policies, environments and health worker practices. Maternal care practices remain outdated largely due to the ineffective didactic training approaches adopted for maternal care.

Early Essential Newborn Care Is Associated With Reduced Adverse Neonatal Outcomes in a Tertiary Hospital in Da Nang, Viet Nam: A Pre- Post- Intervention Study.

BACKGROUND: To accelerate reductions in neonatal mortality, Viet Nam rolled out early essential newborn care (EENC) using clinical coaching, quality improvement assessments in hospitals, and updated protocols. Da Nang Hospital for Women and Children, a tertiary referral hospital in central Viet Nam, compared outcomes pre- and post-EENC introduction. METHODS: Records of live births and NICU admissions were reviewed pre- (November 2013-October 2014) and post- (November 2014-October 2015) EENC implementation. Delivery room practices, NICU admissions and adverse outcomes on NICU admission were compared using descriptive statistics. FINDINGS: A total of 13,201 live births were delivered pre- and 14,180 live births post-EENC introduction. Post-EENC, delivery practice scores, rates of early and prolonged skin-to-skin contact and early breastfeeding rose significantly. There was a significant reduction in risk of NICU admissions (relative risk [RR] 0.68; 95% confidence interval [CI] 0.64-0.71; p < 0.0001), hypothermia on NICU admission (RR 0.72; 95% CI 0.65-0.81, p < 0.0001) and sepsis (RR 0.28; 95% CI 0.23-0.35, p < 0.0001). Exclusive breastfeeding rates in NICU increased from 49% to 88% (p < 0.0001) and of kangaroo mother care (KMC) from 52% to 67% (p < 0.0001). Reduced formula use resulted in decreased monthly costs. INTERPRETATION: EENC introduction, including staff coaching, quality improvement assessments and changes in hospital protocols and environments, were associated with improved clinical practices, reduced NICU admissions, admissions with hypothermia and sepsis and increased rates of exclusive breastfeeding and KMC in the NICU. FUNDING: Data collection was funded by the World Health Organization Western Pacific Regional Office and Newborns Vietnam. OUTSTANDING QUESTIONS: •What is the impact of the package of early essential newborn care interventions on newborn mortality?•What are the total direct and indirect cost savings of early essential newborn care implementation?•What is the cost effectiveness of kangaroo mother care for preterm and low birth weight babies?•What strategies can help reduce unnecessary cesarean sections in hospitals?

Spiropiperidine Sultam and Lactam Templates: Diastereoselective Overman Rearrangement and Metathesis followed by NH Arylation.

We report the diastereoselective synthesis of novel spiropiperidine templates for use in SAR studies of ß-secretase (BACE) inhibitors and also as versatile ligands for other receptor types. The overall synthetic approach stems from chiral starting material benzyl (S)-2-methyl-4-oxopiperidine-1-carboxylate and employs an Overman rearrangement to control the stereochemistry at the quaternary center. This process is followed by a Grubbs metathesis to close a five-membered "top" ring to form an α,ß-unsaturated lactam or an α,ß-unsaturated sultam. We also demonstrate that this chemistry can accommodate additional substituents on the lactam/sultam ring and allows late stage sequential functionalization of the amine and amide nitrogens to rapidly produce diverse analogues.

Using robots to understand animal cognition.

In recent years, robotic animals and humans have been used to answer a variety of questions related to behavior. In the case of animal behavior, these efforts have largely been in the field of behavioral ecology. They have proved to be a useful tool for this enterprise as they allow the presentation of naturalistic social stimuli whilst providing the experimenter with full control of the stimulus. In interactive experiments, the behavior of robots can be controlled in a manner that is impossible with real animals, making them ideal instruments for the study of social stimuli in animals. This paper provides an overview of the current state of the field and considers the impact that the use of robots could have on fundamental questions related to comparative psychology: namely, perception, spatial cognition, social cognition, and early cognitive development. We make the case that the use of robots to investigate these key areas could have an important impact on the field of animal cognition.

Utilizing structures of CYP2D6 and BACE1 complexes to reduce risk of drug-drug interactions with a novel series of centrally efficacious BACE1 inhibitors.

In recent years, the first generation of ß-secretase (BACE1) inhibitors advanced into clinical development for the treatment of Alzheimer's disease (AD). However, the alignment of drug-like properties and selectivity remains a major challenge. Herein, we describe the discovery of a novel class of potent, low clearance, CNS penetrant BACE1 inhibitors represented by thioamidine 5. Further profiling suggested that a high fraction of the metabolism (>95%) was due to CYP2D6, increasing the potential risk for victim-based drug-drug interactions (DDI) and variable exposure in the clinic due to the polymorphic nature of this enzyme. To guide future design, we solved crystal structures of CYP2D6 complexes with substrate 5 and its corresponding metabolic product pyrazole 6, which provided insight into the binding mode and movements between substrate/inhibitor complexes. Guided by the BACE1 and CYP2D6 crystal structures, we designed and synthesized analogues with reduced risk for DDI, central efficacy, and improved hERG therapeutic margins.

2-Aryl-3-methyloctahydrophenanthrene-2,3,7-triols as potent dissociated glucocorticoid receptor agonists.

A significant improvement in agonist activity of the previously described 2-aryloctahydrophenanthrene-2,3,7-triol series of dissociated glucocorticoid receptor agonists (DAGRs) was achieved by modifying the substitution at C3 from (S)-3-hydroxy to (R)-3-hydroxy-3-methyl. The IC50 of the prototype 13 in the efficacy assay measuring repression of IL-1 induced MMP-13 expression was 3.5 nM, exhibiting 87% of the maximal effect of dexamethasone (DEX). It displayed a dissociated profile by exhibiting 42% of the maximal effect of DEX in a mouse mammary tumor virus (MMTV) luciferase reporter transactivation assay. Compound 13 and analogues containing heterocyclic replacements for the C2 phenyl and modified B rings showed high repression of TNFα production in human whole blood, with IC50 values (43-167 nM) approaching the level of DEX (21 nM). On the basis of X-ray structures and force field calculations, the overall potency of this series was attributed to a favorable conformation of the C2α phenyl, induced by the neighboring C3α methyl.

Discovery of a series of efficient, centrally efficacious BACE1 inhibitors through structure-based drug design.

The identification of centrally efficacious ß-secretase (BACE1) inhibitors for the treatment of Alzheimer's disease (AD) has historically been thwarted by an inability to maintain alignment of potency, brain availability, and desired absorption, distribution, metabolism, and excretion (ADME) properties. In this paper, we describe a series of truncated, fused thioamidines that are efficiently selective in garnering BACE1 activity without simultaneously inhibiting the closely related cathepsin D or negatively impacting brain penetration and ADME alignment, as exemplified by 36. Upon oral administration, these inhibitors exhibit robust brain availability and are efficacious in lowering central Amyloid ß (Aß) levels in mouse and dog. In addition, chronic treatment in aged PS1/APP mice effects a decrease in the number and size of Aß-derived plaques. Most importantly, evaluation of 36 in a 2-week exploratory toxicology study revealed no accumulation of autofluorescent material in retinal pigment epithelium or histology findings in the eye, issues observed with earlier BACE1 inhibitors.

Stereoselective synthesis of spiropiperidines as BACE-1 aspartyl protease inhibitors via late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore.

A stereoselective synthesis of spiropiperidine compounds, exemplified by compound 1, was developed, which was based upon the late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore. Previously, compound 1 was prepared in low overall yield from piperidinone 2 via the Strecker reaction. A new route was developed, which employed the stereospecific Corey-Link reaction of an enantiomerically pure trichloromethylcarbinol to give a template compound amenable to late stage N-arylation.

Octahydrophenanthrene-2,7-diol analogues as dissociated glucocorticoid receptor agonists: discovery and lead exploration.

As exemplified by the lead compound 2, octahydrophenanthrene-2,7-diol analogues exhibit the profile of a pathway-selective or "dissociated" agonist of the glucocorticoid receptor (GR), retaining the potent activity that glucocorticoids have for transrepression (as measured by inhibition of IL-1 induced MMP-13 expression) but showing an attenuated capacity for transactivation (as measured in an MMTV luciferase reporter assay). With the guidance of a homology model of the GR ligand binding domain, structural modifications to 2 were carried out that were successful in replacing the allyl and propynyl side chains with groups likely to be more chemically stable and less likely to produce toxic metabolites. Key to success was the introduction of an additional hydroxyl group onto the tricyclic carbon framework of the series.

Robotic sound-source localisation architecture using cross-correlation and recurrent neural networks.

In this paper we present a sound-source model for localising and tracking an acoustic source of interest along the azimuth plane in acoustically cluttered environments, for a mobile service robot. The model we present is a hybrid architecture using cross-correlation and recurrent neural networks to develop a robotic model accurate and robust enough to perform within an acoustically cluttered environment. This model has been developed with considerations of both processing power and physical robot size, allowing for this model to be deployed on to a wide variety of robotic systems where power consumption and size is a limitation. The development of the system we present has its inspiration taken from the central auditory system (CAS) of the mammalian brain. In this paper we describe experimental results of the proposed model including the experimental methodology for testing sound-source localisation systems. The results of the system are shown in both restricted test environments and in real-world conditions. This paper shows how a hybrid architecture using band pass filtering, cross-correlation and recurrent neural networks can be used to develop a robust, accurate and fast sound-source localisation model for a mobile robot.

A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation.

BACKGROUND: Skin cancer and photoaging changes result from ultraviolet (UV)-induced oxidative stress. Topical antioxidants may protect skin from these effects. OBJECTIVE: We sought to determine whether a stable topical formulation of 15% L-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid (CEFer) could protect human skin in vivo from substantial amounts of solar-simulated UV radiation. METHODS: CEFer and its vehicle were applied to separate patches of normal-appearing human skin for 4 days. Each patch was irradiated with solar-simulated UV, 2 to 10 minimal erythema doses, at 2-minimal erythema dose intervals. One day later, skin was evaluated for erythema and sunburn cells, and immunohistochemically for thymine dimers and p53. UV-induced cytokine formation, including interleukin (IL)-1alpha, IL-6, IL-8, and IL-10, and tumor necrosis factor-alpha, were evaluated by real-time polymerase chain reaction. RESULTS: CEFer provided significant and meaningful photoprotection for skin by all methods of evaluation. LIMITATIONS: The number of patients evaluated was relatively small. CONCLUSION: CEFer provided substantial UV photoprotection for skin. It is particularly effective for reducing thymine dimer mutations known to be associated with skin cancer. Its mechanism of action is different from sunscreens and would be expected to supplement the sun protection provided by sunscreens.