Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Regulatory mechanisms of stem cell differentiation: Biotechnological applications for neurogenesis.

The world population's life expectancy is growing, and neurodegenerative disorders common in old age require more efficient therapies. In this context, neural stem cells (NSCs) are imperative for the development and maintenance of the functioning of the nervous system and have broad therapeutic applicability for neurodegenerative diseases. Therefore, knowing all the mechanisms that govern the self-renewal, differentiation, and cell signaling of NSC is necessary. This review will address some of these aspects, including the role of growth and transcription factors, epigenetic modulators, microRNAs, and extracellular matrix components. Furthermore, differentiation and transdifferentiation processes will be addressed as therapeutic strategies showing their significance for stem cell-based therapy.

Strategic use of organoids and organs-on-chip as biomimetic tools.

Organoid development and organ-on-a-chip are technologies based on differentiating stem cells, forming 3D multicellular structures resembling organs and tissues in vivo. Hence, both can be strategically used for disease modeling, drug screening, and host-pathogen studies. In this context, this review highlights the significant advancements in the area, providing technical approaches to organoids and organ-on-a-chip that best imitate in vivo physiology.

Tripled yield in direct-drive laser fusion through statistical modelling.

Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.

Determinants of exposure to endocrine disruptors following hurricane Harvey.

Hurricane Harvey was a category four storm that induced catastrophic flooding in the Houston metropolitan area. Following the hurricane there was increased concern regarding chemical exposures due to damage caused by flood waters and emergency excess emissions from industrial facilities. This study utilized personal passive samplers in the form of silicone wristbands in Houston, TX to both assess chemical exposure to endocrine disrupting chemicals (EDCs) immediately after the hurricane and determine participant characteristics associated with higher concentrations of exposure. Participants from the Houston-3H cohort (n = 172) wore a wristband for seven days and completed a questionnaire to determine various flood-related and demographic variables. Bivariate and multivariate analysis indicated that living in an area with a high Area Deprivation Index (ADI) (indicative of low socioeconomic status), identifying as Black/African American or Latino, and living in the Houston neighborhoods of Baytown and East Houston were associated with increased exposure to EDCs. These results provide evidence of racial/ethnic and socioeconomic injustices in exposure to EDCs in the Houston Metropolitan Area. Since the multiple regression models conducted did not fully explain exposure (0.047 < R2 < 0.34), more research is needed on the direct sources of EDCs within this area to create effective exposure mitigation strategies.

Magnetic Control of Soft Chiral Phonons in PbTe.

PbTe crystals have a soft transverse optical phonon mode in the terahertz frequency range, which is known to efficiently decay into heat-carrying acoustic phonons, resulting in anomalously low thermal conductivity. Here, we studied this phonon via polarization-dependent terahertz spectroscopy. We observed softening of this mode with decreasing temperature, indicative of incipient ferroelectricity, which we explain through a model including strong anharmonicity with a quartic displacement term. In magnetic fields up to 25 T, the phonon mode splits into two modes with opposite handedness, exhibiting circular dichroism. Their frequencies display Zeeman splitting together with an overall diamagnetic shift with increasing magnetic field. Using a group-theoretical approach, we demonstrate that these observations are the result of magnetic field-induced morphic changes in the crystal symmetries through the Lorentz force exerted on the lattice ions. Thus, our Letter reveals a novel process of controlling phonon properties in a soft ionic lattice by a strong magnetic field.

Increased cholinergic activity under conditions of low estrogen leads to adverse cardiac remodeling.

Cholinesterase inhibitors are used in postmenopausal women for the treatment of neurodegenerative diseases. Despite their widespread use in the clinical practice, little is known about the impact of augmented cholinergic signaling on cardiac function under reduced estrogen conditions. To address this gap, we subjected a genetically engineered murine model of systemic vesicular acetylcholine transporter overexpression (Chat-ChR2) to ovariectomy and evaluated cardiac parameters. Left-ventricular function was similar between Chat-ChR2 and wild-type (WT) mice. Following ovariectomy, WT mice showed signs of cardiac hypertrophy. Conversely, ovariectomized (OVX) Chat-ChR2 mice evolved to cardiac dilation and failure. Transcript levels for cardiac stress markers atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were similarly upregulated in WT/OVX and Chat-ChR2/OVX mice. 17ß-Estradiol (E2) treatment normalized cardiac parameters in Chat-ChR2/OVX to the Chat-ChR2/SHAM levels, providing a link between E2 status and the aggravated cardiac response in this model. To investigate the cellular basis underlying the cardiac alterations, ventricular myocytes were isolated and their cellular area and contractility were assessed. Myocytes from WT/OVX mice were wider than WT/SHAM, an indicative of concentric hypertrophy, but their fractional shortening was similar. Conversely, Chat-ChR2/OVX myocytes were elongated and presented contractile dysfunction. E2 treatment again prevented the structural and functional changes in Chat-ChR2/OVX myocytes. We conclude that hypercholinergic mice under reduced estrogen conditions do not develop concentric hypertrophy, a critical compensatory adaptation, evolving toward cardiac dilation and failure. This study emphasizes the importance of understanding the consequences of cholinesterase inhibition, used clinically to treat dementia, for cardiac function in postmenopausal women.

Experimentally Inferred Fusion Yield Dependencies of OMEGA Inertial Confinement Fusion Implosions.

Statistical modeling of experimental and simulation databases has enabled the development of an accurate predictive capability for deuterium-tritium layered cryogenic implosions at the OMEGA laser [V. Gopalaswamy et al.,Nature 565, 581 (2019)10.1038/s41586-019-0877-0]. In this letter, a physics-based statistical mapping framework is described and used to uncover the dependencies of the fusion yield. This model is used to identify and quantify the degradation mechanisms of the fusion yield in direct-drive implosions on OMEGA. The yield is found to be reduced by the ratio of laser beam to target radius, the asymmetry in inferred ion temperatures from the ℓ=1 mode, the time span over which tritium fuel has decayed, and parameters related to the implosion hydrodynamic stability. When adjusted for tritium decay and ℓ=1 mode, the highest yield in OMEGA cryogenic implosions is predicted to exceed 2×10^{14} fusion reactions.

Childhood food insecurity and incident diabetes: A longitudinal cohort study of 34 042 children in Ontario, Canada.

AIM: To examine the association between childhood food insecurity and incident diabetes. METHODS: Using health administrative databases linked to the Canadian Community Health Survey, we conducted a population-based cohort study of children aged <18 years from Ontario, Canada. Children without diabetes who had a household response to the Canadian Community Health Survey Household Food Security Survey Module were followed for a median of 9.5 years for incident diabetes. Multivariable Cox proportional hazards models were used to examine the association between childhood food insecurity and incident diabetes, adjusted sequentially for important clinical and socio-economic risk factors. RESULTS: We included 34 042 children, of whom 5.3% lived in food-insecure households. There were 184 new cases of diabetes, diagnosed at a median age of 16 and 18.5 years in food-secure and food-insecure children, respectively. In unadjusted analysis, childhood food insecurity was associated with an increased risk of incident diabetes (hazard ratio 1.69, 95% CI 1.01 to 2.81). When adjusted for clinical and socio-economic confounders, the relationship was no longer statistically significant (hazard ratio 1.55, 95% CI 0.91 to 2.66, adjusted for clinical confounders; hazard ratio 1.30, 95% CI 0.72 to 2.37, adjusted for clinical/socio-economic confounders). Our results remained robust in sensitivity analyses. CONCLUSIONS: Although food-insecure children are a medically and socially vulnerable population, they do not appear to be at increased risk of incident diabetes over a median of 9.5 years.

Skin-Related complications of Klippel-Trenaunay Syndrome: a retrospective review of 410 patients.

BACKGROUND: Little is known about skin-related complications in Klippel-Trenaunay syndrome (KTS), a complex vascular anomaly defined by capillary malformation (CM), venous malformation (VM) ± lymphatic malformation (LM) and limb overgrowth. Reported skin-related complications of KTS include ulceration, vascular ectasias (blebs), bleeding and infection. OBJECTIVE: To determine the spectrum, prevalence and predictors of skin-related complications in KTS. METHODS: A retrospective review of 410 patients fulfilling KTS criteria was performed to assess for the presence of skin-related complications. RESULTS: Skin-related complications were present in 45% of patients. Most prevalent were CM-related complications including blebs, bleeding, thickening (25%), cellulitis (22%) and ulceration (21%). Features positively associated with skin-related complications were presence of LM (OR 17.17; P < 0.001), VM on the buttocks/perineum/genitalia (OR 1.92; P = 0.009), CM on the feet (OR 1.77; P = 0.039) and male sex (OR 1.63; P = 0.034). Features negatively associated with skin-related complications were CM on the trunk (OR 0.59; P = 0.029) and tissue hypertrophy of the hands (OR 0.27; P = 0.025). CONCLUSION: Skin-related complications affect nearly half of patients with KTS. Those with lymphatic involvement or malformation presence in the undergarment area or feet are most at risk.

The association between sleep and cognitive abnormalities in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is associated with attentional and processing abnormalities. Such abnormalities are also seen in healthy subjects with sleep disruption. We hypothesised cognitive abnormalities in BD patients would be worse in those with objectively verified sleep abnormalities. METHODS: Forty-six BD patients and 42 controls had comprehensive sleep/circadian rhythm assessment over 21 days alongside mood questionnaires. Cognitive function was assessed with a range of tasks including Psychomotor Vigilance Test (PVT), Attention Network Task (ANT) and Digit Symbol Substitution Test (DSST). BD participants with normal and abnormal sleep were compared with age- and sex-matched controls. RESULTS: BD patients had longer response times and made more lapses (responses >500 ms) than controls on the PVT (both p < 0.001). However, patients with normal sleep patterns did not differ from controls while those with sleep abnormalities did (p < 0.001). An identical pattern of effects were seen with the ANT response times, with the abnormality in bipolar abnormal sleepers related to the executive attentional network. Similarly, patients made fewer correct responses on the DSST compared with the controls (p < 0.001). Bipolar normal sleepers did not differ while those with abnormal sleep did (p < 0.001). All these differences were seen in bipolar abnormal sleepers who were euthymic (p < 0.01) and across the main abnormal sleep phenotypes. CONCLUSIONS: We confirm impairment in attention and processing speed in BD. Rather than sleep abnormalities exacerbating such dysfunction, the impairments were confined to bipolar abnormal sleepers, consistent with sleep disturbance being the main driver of cognitive dysfunction.

Age at migration and the risk of psychotic disorders: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the existing evidence on the association between age at migration and the risk of psychotic disorders. METHODS: Observational studies were eligible for inclusion if they presented data on the association between age at migration and the risk of psychotic disorders among first-generation migrant groups. We used two random effects meta-analyses to pool effect estimates for each stratum of age at migration relative to (i) a native-born reference category and (ii) the youngest age stratum (0 to 2 years). RESULTS: Ten studies met inclusion criteria, and five were included in the meta-analysis. The risk of psychotic disorder among people who migrate prior to age 18 is nearly twice as high as the native-born population, with no evidence of effect modification by age strata. People who migrate during early adulthood (19 to 29 years) have a similar risk of psychotic disorder as the native-born population (IRR = 0.93, 95% CI = 0.60, 1.44) and a lower risk relative to those who migrate during infancy (0 to 2 years) (IRR = 0.58, 95% CI = 0.33, 1.04). CONCLUSIONS: Migrant status is one of few well-established risk factors for psychotic disorder, yet we have limited understanding of the underlying etiology. The findings of this review advance our understanding of this association and identify high-risk groups to target for intervention.

Concordance between health administrative data and survey-derived diagnoses for mood and anxiety disorders.

OBJECTIVE: To assess whether estimates of survey structured interview diagnoses of mood and anxiety disorders were concordant with diagnoses of these disorders obtained from health administrative data. METHODS: All Ontario respondents to the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH) were linked to health administrative databases at ICES (formerly known as the Institute for Clinical Evaluative Sciences). Survey structured interview diagnoses were compared with health administrative data diagnoses obtained using a standardized algorithm. We used modified Poisson regression analyses to assess whether socio-demographic factors were associated with concordance between the two measures. RESULTS: Of the 4157 Ontarians included in our sample, 20.4% had either a structured interview diagnosis (13.9%) or health administrative diagnosis (10.4%) of a mood or anxiety disorder. There was high discordance between measures, with only 19.4% agreement. Migrant status, age, employment, and income were associated with discordance between measures. CONCLUSIONS: Our findings indicate that previous estimates of the 12-month prevalence of mood and anxiety disorders in Ontario may be underestimating the true prevalence, and that population-based surveys and health administrative data may be capturing different groups of people. Understanding the limitations of data commonly used in epidemiologic studies is a key foundation for improving population-based estimates of mental disorders.

What is the impact of psychiatric decision units on mental health crisis care pathways? Protocol for an interrupted time series analysis with a synthetic control study.

BACKGROUND: The UK mental health system is stretched to breaking point. Individuals presenting with mental health problems wait longer at the ED than those presenting with physical concerns and finding a bed when needed is difficult - 91% of psychiatric wards are operating at above the recommended occupancy rate. To address the pressure, a new type of facility - psychiatric decision units (also known as mental health decision units) - have been introduced in some areas. These are short-stay facilities, available upon referral, targeted to help individuals who may be able to avoid an inpatient admission or lengthy ED visit. To advance knowledge about the effectiveness of this service for this purpose, we will examine the effect of the service on the mental health crisis care pathway over a 4-year time period; the 2 years proceeding and following the introduction of the service. We use aggregate service level data of key indicators of the performance of this pathway. METHODS: Data from four mental health Trusts in England will be analysed using an interrupted time series (ITS) design with the primary outcomes of the rate of (i) ED psychiatric presentations and (ii) voluntary admissions to mental health wards. This will be supplemented with a synthetic control study with the same primary outcomes, in which a comparable control group is generated for each outcome using a donor pool of suitable National Health Service Trusts in England. The methods are well suited to an evaluation of an intervention at a service delivery level targeting population-level health outcome and the randomisation or 'trialability' of the intervention is limited. The synthetic control study controls for national trends over time, increasing our confidence in the results. The study has been designed and will be carried out with the involvement of service users and carers. DISCUSSION: This will be the first formal evaluation of psychiatric decision units in England. The analysis will provide estimates of the effect of the decision units on a number of important service use indicators, providing much-needed information for those designing service pathways. TRIAL REGISTRATION: primary registry: isrctn.com Identifying number: ISRCTN77588384 Link: Date of registration in primary registry: 27/02/2020. PRIMARY SPONSOR: St George's, University of London, Cramner Road, Tooting, SW17 ORE. Primary contact: Joe Montebello.

Analysis of milk leukocyte differential measures for use in management practices for decreased mastitis incidence.

The aim of this study was to assess the usefulness of measures derived from milk leukocyte differential (MLD) in practices that improve fresh cow mastitis monitoring and decrease mastitis incidence. Quarter milk samples were collected from Holstein and Jersey cows on d 4 and 11 postcalving. Samples were analyzed using MLD, whereby cell counts and quarter infection diagnosis were obtained. Measures derived from MLD included cell scores (total leukocyte, neutrophil, macrophage, and lymphocyte scores), cell proportions (neutrophil, macrophage, and lymphocyte percentages), cell thresholds (total leukocyte, neutrophil, macrophage, and lymphocyte thresholds), and MLD diagnosis at different threshold settings (A, B, and C). Microbiological culturing of milk samples was used to determine infection status to compare the MLD diagnosis and serve as an indicator of infection. Measures derived from the microbiological analysis included occurrence of major pathogens, minor pathogens, and infection. Data analysis was based on a linear mixed model, which was used on all measures for the estimation of the fixed effects of breed, lactation number, day of sample collection, time of sampling, and quarter location, and the random effects of animal and week of sampling. All the fixed effects studied were significant for one or more of the analyzed measures. The results of this study showed that MLD-derived measures justify further study on their use for management practices for mastitis screening and prevention in early lactation.

Use of aspirin, other nonsteroidal anti-inflammatory drugs and acetaminophen and risk of endometrial cancer: the Epidemiology of Endometrial Cancer Consortium.

BACKGROUND: Regular use of aspirin has been associated with a reduced risk of cancer at several sites but the data for endometrial cancer are conflicting. Evidence regarding use of other analgesics is limited. PATIENTS AND METHODS: We pooled individual-level data from seven cohort and five case-control studies participating in the Epidemiology of Endometrial Cancer Consortium including 7120 women with endometrial cancer and 16 069 controls. For overall analyses, study-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using logistic regression and combined using random-effects meta-analysis; for stratified analyses, we used mixed-effects logistic regression with study as a random effect. RESULTS: At least weekly use of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an approximately 15% reduced risk of endometrial cancer among both overweight and obese women (OR = 0.86 [95% CI 0.76-0.98] and 0.86 [95% CI 0.76-0.97], respectively, for aspirin; 0.87 [95% CI 0.76-1.00] and 0.84 [0.74-0.96], respectively, for non-aspirin NSAIDs). There was no association among women of normal weight (body mass index < 25 kg/m2, Pheterogeneity = 0.04 for aspirin, Pheterogeneity = 0.003 for NSAIDs). Among overweight and obese women, the inverse association with aspirin was stronger for use 2-6 times/week (OR = 0.81, 95% CI 0.68-0.96) than for daily use (0.91, 0.80-1.03), possibly because a high proportion of daily users use low-dose formulations. There was no clear association with use of acetaminophen. CONCLUSION: Our pooled analysis provides further evidence that use of standard-dose aspirin or other NSAIDs may reduce risk of endometrial cancer among overweight and obese women.

How well do the FRAX (Australia) and Garvan calculators predict incident fractures? Data from the Geelong Osteoporosis Study.

This study reports that both FRAX and Garvan calculators underestimated fractures in Australian men and women, particularly in those with osteopenia or osteoporosis. Major osteoporotic fractures were poorly predicted, while both calculators performed acceptably well for hip fractures. INTRODUCTION: This study assessed the ability of the FRAX (Australia) and Garvan calculators to predict fractures in Australian women and men. METHODS: Women (n = 809) and men (n = 821) aged 50-90 years, enrolled in the Geelong Osteoporosis Study, were included. Fracture risk was estimated using FRAX and Garvan calculators with and without femoral neck bone mineral density (BMD) (FRAXBMD, FRAXnoBMD, GarvanBMD, GarvannoBMD). Incident major osteoporotic (MOF), fragility, and hip fractures over the following 10 years were verified radiologically. Differences between observed and predicted numbers of fractures were assessed using a chi-squared test. Diagnostics indexes were calculated. RESULTS: In women, 115 MOF, 184 fragility, and 42 hip fractures occurred. For men, there were 73, 109, and 17 fractures, respectively. FRAX underestimated MOFs, regardless of sex or inclusion of BMD. FRAX accurately predicted hip fractures, except in women with BMD (20 predicted, p = 0.004). Garvan underestimated fragility fractures except in men using BMD (88 predicted, p = 0.109). Garvan accurately predicted hip fractures except for women without BMD (12 predicted, p < 0.001). Fractures were underestimated primarily in the osteopenia and osteoporosis groups; MOFs in the normal BMD group were only underestimated by FRAXBMD and fragility fractures by GarvannoBMD, both in men. AUROCs were not different between scores with and without BMD, except for fragility fractures predicted by Garvan in women (0.696, 95% CI 0.652-0.739 and 0.668, 0.623-0.712, respectively, p = 0.008) and men, which almost reached significance (0.683, 0.631-0.734, and 0.667, 0.615-0.719, respectively, p = 0.051). Analyses of sensitivity and specificity showed overall that MOFs and fragility fractures were poorly predicted by both FRAX and Garvan, while hip fractures were acceptably predicted. CONCLUSIONS: Overall, the FRAX and Garvan calculators underestimated MOF and fragility fractures, particularly in individuals with osteopenia or osteoporosis. Hip fractures were predicted better by both calculators. AUROC analyses suggest that GarvanBMD performed better than GarvannoBMD for prediction of fragility fractures.

Expression of a Constitutively Active Human Insulin Receptor in Hippocampal Neurons Does Not Alter VGCC Currents.

Memory and cognitive decline are the product of numerous physiological changes within the aging brain. Multiple theories have focused on the oxidative, calcium, cholinergic, vascular, and inflammation hypotheses of brain aging, with recent evidence suggesting that reductions in insulin signaling may also contribute. Specifically, a reduction in insulin receptor density and mRNA levels has been implicated, however, overcoming these changes remains a challenge. While increasing insulin receptor occupation has been successful in offsetting cognitive decline, alternative molecular approaches should be considered as they could bypass the need for brain insulin delivery. Moreover, this approach may be favorable to test the impact of continued insulin receptor signaling on neuronal function. Here we used hippocampal cultures infected with lentivirus with or without IRß, a constitutively active, truncated form of the human insulin receptor, to characterize the impact continued insulin receptor signaling on voltage-gated calcium channels. Infected cultures were harvested between DIV 13 and 17 (48 h after infection) for Western blot analysis on pAKT and AKT. These results were complemented with whole-cell patch-clamp recordings of individual pyramidal neurons starting 96 h post-infection. Results indicate that while a significant increase in neuronal pAKT/AKT ratio was seen at the time point tested, effects on voltage-gated calcium channels were not detected. These results suggest that there is a significant difference between constitutively active insulin receptors and the actions of insulin on an intact receptor, highlighting potential alternate mechanisms of neuronal insulin resistance and mode of activation.

Exposure to solar ultraviolet radiation limits diet-induced weight gain, increases liver triglycerides and prevents the early signs of cardiovascular disease in mice.

BACKGROUND AND AIMS: Sunlight exposure is associated with a number of health benefits including protecting us from autoimmunity, cardiovascular disease, obesity and diabetes. Animal studies have confirmed that ultraviolet (UV)-B radiation, independently of vitamin D, can limit diet-induced obesity, metabolic syndrome and atherosclerosis. The aim of this study is to investigate whether exposure to the UV radiation contained in sunlight impacts on these disease parameters. METHODS AND RESULTS: We have trialled an intervention with solar UV in obese and atherosclerosis-prone mice. We have discovered that solar-simulated UV can significantly limit diet-induced obesity and reduce atheroma development in mice fed a diet high in sugar and fat. The optimal regime for this benefit was exposure once a week to solar UV equivalent to approximately 30 min of summer sun. Exposure to this optimal dose of solar UV also led to a significant increase in liver triglycerides which may protect the liver from damage. CONCLUSION: Our results show that the UV contained in sunlight has the potential to prevent and treat chronic disease at sites distant from irradiated skin. A major health challenge going forward will be to harness the power of the sun safely, without risking an increase in skin cancers.