Constitutive melanin density is associated with prevalent and short-term, but not long-term, incident fracture risk in older Caucasian adults.

Higher cutaneous melanin reduces vitamin D3 production. This may increase fracture risk. We found that cutaneous melanin density was associated with prevalent and short-term, but not long-term, incident fracture risk in older Caucasian adults. Melanin density either acts as a surrogate marker or its relationship with fracture changes with time. INTRODUCTION: Higher cutaneous melanin reduces vitamin D3 production. This may impact lifetime vitamin D status and increase fracture risk. This study aimed to describe the relationship between spectrophotometrically determined constitutive melanin density, prevalent and incident fractures in a cohort of exclusively older Caucasian adults. METHODS: 1072 community-dwelling adults aged 50-80 years had constitutive melanin density quantified using spectrophotometry. Participants were followed up at 2.5 (n = 879), 5 (n = 767), and 10 (n = 571) years after the baseline assessment. Prevalence and number of symptomatic fractures were assessed by questionnaire. RESULTS: Higher melanin density was independently associated with greater prevalence of any fracture (RR 1.08, p = 0.03), vertebral fracture (RR 1.41, p = 0.04) and major fracture (RR 1.12, p = 0.04) and the number of fractures (RR 1.09, p = 0.04) and vertebral fractures (RR 1.47, p = 0.04) in cross-sectional analysis. At the 2.5-year follow-up, higher melanin density was associated with incident fractures (RR 1.42, p = 0.01) and major fractures (RR 1.81, p = 0.01) and the number of incident fractures (RR 1.39, p = 0.02) and major fractures (RR 2.14, p = 0.01). The relationship between melanin density and incident fracture attenuated as the duration of follow-up increased and was not significant at the 5- or 10-year follow-up. CONCLUSIONS: Constitutive melanin density was associated with prevalent and short-term, but not long-term, incident fracture risk in older Caucasian adults. This suggests melanin density either acts as a surrogate marker for an unmeasured fracture risk factor or the relationship between melanin density and fracture changes with time.

Skin Photosensitivity is Associated with 25-Hydroxyvitamin D and BMD but not Fractures Independent of Melanin Density in Older Caucasian Adults.

Whether skin photosensitivity modulates sun exposure behaviours, consequent vitamin D status and skeletal health outcomes independently of constitutive pigmentation have not been systematically investigated. 1072 community-dwelling adults aged 50-80 years had skin photosensitivity quantified by questionnaire and melanin density by spectrophotometry. Bone mineral density (BMD), falls risk and 25-hydroxyvitamin D (25OHD) were measured using DXA, short form physiological profile assessment and radioimmunoassay, respectively. Sun exposure and symptomatic fractures were assessed by questionnaire. Participants were followed up at 2.5 (n = 879), 5 (n = 767) and 10 (n = 571) years. Higher resistance to sunburn and greater ability to tan were associated with reduced sun protection behaviours (RR 0.87, p < 0.001 & RR 0.88, p < 0.001), higher lifetime discretionary sun exposure in summer (RR 1.05, p = 0.001 & RR 1.07, p = 0.001) and winter (RR 1.07, p = 0.001 & RR 1.08, p = 0.02) and fewer lifetime sunburns (RR 0.86, p < 0.001 & RR 0.91, p = 0.001). Higher resistance to sunburn was associated with lower total body (ß = - 0.006, p = 0.047) and femoral neck (ß = - 0.006, p = 0.038) BMD, but paradoxically, fewer prevalent fractures (RR 0.94, p = 0.042). Greater ability to tan was associated with higher 25OHD (ß = 1.43, p = 0.04), lumbar spine (ß = 0.014, p = 0.046) and total body (ß = 0.013, p = 0.006) BMD, but not fracture or falls risk. These associations were independent of constitutive melanin density. Cutaneous photosensitivity was associated with sun exposure behaviours, cutaneous sequelae and, consequently, 25OHD and BMD in older Caucasian adults independent of constitutive melanin density. There was no consistent association with fracture outcomes, suggesting environmental factors are at least as important.

Constitutive melanin density is associated with higher 25-hydroxyvitamin D and potentially total body BMD in older Caucasian adults via increased sun tolerance and exposure.

Greater skin pigmentation reduces dose equivalent cutaneous vitamin D3 production, potentially impacting lifetime vitamin D status and fracture risk. We show that melanin density was positively associated with 25-hydroxyvitamin D and total body bone mineral density. These relationships were partially explained by greater sun exposure due to more permissive skin phenotype. INTRODUCTION: Higher cutaneous melanin reduces vitamin D3 production. This may impact lifetime vitamin D status and increase fracture risk. This study aimed to describe the relationship between spectrophotometrically determined constitutive melanin density, osteoporotic risk factors and potential intermediaries in a cohort of exclusively older Caucasian adults. METHODS: One thousand seventy-two community-dwelling adults aged 50-80 years had constitutive melanin density quantified using spectrophotometry. Sun exposure, skin phenotype, non-melanoma skin cancer (NMSC) prevalence and smoking status were assessed by questionnaire. Bone mineral density (BMD), falls risk, physical activity and 25-hydroxyvitamin D were measured using DXA, the short form Physiological Profile Assessment, pedometer and radioimmunoassay, respectively. RESULTS: Higher melanin density was independently associated with greater ability to tan (RR = 1.27, p < 0.001), less propensity to sunburn (RR = 0.92, p < 0.001), fewer lifetime sunburns (RR = 0.94, p = 0.01), current smoking (RR = 1.41, p < 0.001), female sex (RR = 1.24, p < 0.001) and less photodamage (RR = 0.98, p = 0.01). The associations between melanin density and sun exposure (RR = 1.05-1.11, p < 0.001-0.01), sun protection behaviours (RR = 0.89, p < 0.001) and NMSC prevalence (RR = 0.75, p = 0.001) were no longer significant after taking into account skin phenotype and sun exposure, respectively. 25-Hydroxyvitamin D was strongly associated with higher melanin density (ß = 1.71-2.05, p = 0.001). The association between melanin density and total body BMD (ß = 0.007, p = 0.04) became non-significant after adjustment for 25-hydroxyvitamin D. There was no association between melanin density and physical activity, falls risk or BMD at other sites. CONCLUSIONS: Our data support a model of higher constitutive melanin density underpinning a less photosensitive skin phenotype, permitting greater sun exposure with fewer sequelae and yielding higher 25-hydroxyvitamin D and, potentially, total body BMD.

Independent evolution of sexual dimorphism and female-limited mimicry in swallowtail butterflies (Papilio dardanus and Papilio phorcas).

Several species of swallowtail butterflies (genus Papilio) are Batesian mimics that express multiple mimetic female forms, while the males are monomorphic and nonmimetic. The evolution of such sex-limited mimicry may involve sexual dimorphism arising first and mimicry subsequently. Such a stepwise scenario through a nonmimetic, sexually dimorphic stage has been proposed for two closely related sexually dimorphic species: Papilio phorcas, a nonmimetic species with two female forms, and Papilio dardanus, a female-limited polymorphic mimetic species. Their close relationship indicates that female-limited polymorphism could be a shared derived character of the two species. Here, we present a phylogenomic analysis of the dardanus group using 3964 nuclear loci and whole mitochondrial genomes, showing that they are not sister species and thus that the sexually dimorphic state has arisen independently in the two species. Nonhomology of the female polymorphism in both species is supported by population genetic analysis of engrailed, the presumed mimicry switch locus in P. dardanus. McDonald-Kreitman tests performed on SNPs in engrailed showed the signature of balancing selection in a polymorphic population of P. dardanus, but not in monomorphic populations, nor in the nonmimetic P. phorcas. Hence, the wing polymorphism does not balance polymorphisms in engrailed in P. phorcas. Equally, unlike in P. dardanus, none of the SNPs in P. phorcas engrailed were associated with either female morph. We conclude that sexual dimorphism due to female polymorphism evolved independently in both species from monomorphic, nonmimetic states. While sexual selection may drive male-female dimorphism in nonmimetic species, in mimetic Papilios, natural selection for protection from predators in females is an alternative route to sexual dimorphism.

The relationship between cumulative lifetime ultraviolet radiation exposure, bone mineral density, falls risk and fractures in older adults.

Data linking cumulative lifetime vitamin D status with skeletal outcomes are lacking. We show that increasing cumulative sun exposure was associated with higher bone mineral density in younger males and protective against fractures in females independent of current vitamin D. This supports the concept that cumulative sun exposure is an important contributor to skeletal health. INTRODUCTION: While low 25-hydroxyvitamin D levels are associated with increased fracture risk, this reflects only recent sun exposure. The Beagley-Gibson (BG) method utilises microtopographical skin changes to quantify cumulative lifetime ultraviolet radiation (sun) exposure. This study aimed to describe the relationship between BG grade, BMD, falls risk and fractures in older adults. METHODS: Eight hundred thirty-five community-dwelling adults aged 53-83 years had silicone casts from the dorsum of both hands graded by the BG method. BMD was measured using DXA and falls risk using the short form of the Physiological Profile Assessment. Vertebral deformities and symptomatic fractures were assessed by DXA and questionnaire, respectively. RESULTS: The relationship between BG grade, spine BMD and vertebral fracture varied depending upon sex. In females, increasing grade was associated with lower vertebral fracture prevalence (OR = 0.44/grade, p = 0.018) and fewer fractures (OR = 0.82/grade, p = 0.021), particularly major fractures (OR = 0.75/grade, p = 0.03). In males, increasing grade was associated with more DXA-detected vertebral deformities (RR = 1.28/grade, p = 0.001), but not symptomatic fractures. These relationships were independent of BMD, falls risk, smoking and current 25-hydroxyvitamin D. BG grade was not associated with falls risk. For BMD, there were interactions between BG grade and both age and sex and a positive trend with hip BMD in younger males. CONCLUSIONS: BG grade demonstrated beneficial associations with fracture outcomes in females and BMD in younger males independent of current 25-hydroxyvitamin D. These data support the concept that cumulative ultraviolet radiation exposure is an important determinant of skeletal health. The association with vertebral deformities in males may reflect outdoor physical trauma in younger life.

Systematic review of the diagnosis of scabies in therapeutic trials.

Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a significant disease burden worldwide, yet there are no agreed diagnostic guidelines. We aimed to determine whether a consistent approach to diagnosing scabies has been used for published scabies therapeutic trials. The data sources used were the MEDLINE, Embase and Cochrane databases, from 1946 to 29 August 2013. Eligible studies were trials of therapeutic interventions against scabies in human subjects, published in English, enrolling patients with scabies, and using various therapeutic interventions. Language was a limitation of this study as some relevant trials published in languages other than English may have been excluded. Each study was reviewed by two independent authors, who assessed the clinical examination and testing approaches used for scabies diagnosis in the included studies. We found that of 71 included trials, 40 (56%) specified which clinical findings were used for diagnosis, which were predominantly rash, rash distribution, pruritus and mite burrows. Parasitological testing was used in 63% of trials (n = 45) and was used more frequently in clinic-based than in field studies. Nearly one-quarter of trials (24%, n = 17) did not define the diagnostic method used. Overall, the diagnostic approaches were poorly described, prohibiting accurate comparison of existing studies. This review further supports the need for consensus diagnostic guidelines for scabies.

Predictors of Beagley-Gibson skin cast grade in older adults.

BACKGROUND AND PURPOSE: The Beagley-Gibson (BG) grading system utilizes microtopographical skin changes to generate an individualized, objective estimate of cumulative, lifetime ultraviolet radiation (UVR) exposure. However, predictors of BG grade are ill-defined, particularly in older populations. The aim of this cross-sectional study was to describe the factors associated with skin damage as measured by the BG method in 835 community-dwelling older adults. METHODS: Study participants aged 53-83 years had silicone casts taken from the dorsum of both hands and graded by the BG method. Lifetime sun exposure, skin phenotypic traits and smoking status were assessed by questionnaire. 25-hydroxyvitamin D and melanin density were measured using radioimmunoassay and spectrophotometry, respectively. Ordered logistic regression was used to compute a single odds ratio (OR) by taking BG grade as the outcome variable. RESULTS: Higher 25-hydroxyvitamin D was associated with increasing BG grade (OR = 1.39, P = 0.02) in adjusted analysis. Age (OR = 1.14, P < 0.001), occupational sun exposure (OR = 1.62, P < 0.001), ability to tan (OR = 1.40, P < 0.001), melanin density (OR=0.79, P = 0.001), lifetime leisure time sun exposure (OR = 1.21, P = 0.004), current smoking (OR = 1.82, P = 0.007), propensity to sunburn (OR = 1.18, P = 0.016), and waist-hip ratio (OR = 1.10, P = 0.02) were independent predictors of BG grade. Hair colour, number of sunburns, body mass index and gender were not independent predictors of BG grade. CONCLUSIONS: Beagley-Gibson skin cast grade is a biologically relevant marker of UVR exposure in older adults influenced by both intrinsic and extrinsic factors.

Mitogenomics of 'Old World Acraea' butterflies reveals a highly divergent 'Bematistes'.

Afrotropical Acraeini butterflies provide a fascinating potential model system to contrast with the Neotropical Heliconiini, yet their phylogeny remains largely unexplored by molecular methods and their generic level nomenclature is still contentious. To test the potential of mitogenomes in a simultaneous analysis of the radiation, we sequenced the full mitochondrial genomes of 19 African species. Analyses show the potential of mitogenomic phylogeny reconstruction in this group. Inferred relationships are largely congruent with a previous multilocus study. We confirm a monophyletic Telchinia to include the Asiatic Pareba with a complicated paraphylum, traditional (sub)genus Acraea, toward the base. The results suggest that several proposed subgenera and some species groups within Telchinia are not monophyletic, while two other (sub)genera could possibly be combined. Telchinia was recovered without strong support as sister to the potentially interesting system of distasteful model butterflies known as Bematistes, a name that is suppressed in some treatments. Surprisingly, we find that this taxon has remarkably divergent mitogenomes and unexpected synapomorphic tRNA rearrangements. These gene order changes, combined with evidence for deviating dN/dS ratios and evidence for episodal diversifying selection, suggest that the ancestral Bematistes mitogenome has had a turbulent past. Our study adds genetic support for treating this clade as a distinct genus, while the alternative option, adopted by some authors, of Acraea being equivalent to Acraeini merely promotes redundancy. We pave the way for more detailed mitogenomic and multi-locus molecular analyses which can determine how many genera are needed (possibly at least six) to divide Acraeini into monophyletic groups that also facilitate communication about their biology.

The diversification of Heliconius butterflies: what have we learned in 150 years?

Research into Heliconius butterflies has made a significant contribution to evolutionary biology. Here, we review our understanding of the diversification of these butterflies, covering recent advances and a vast foundation of earlier work. Whereas no single group of organisms can be sufficient for understanding life's diversity, after years of intensive study, research into Heliconius has addressed a wide variety of evolutionary questions. We first discuss evidence for widespread gene flow between Heliconius species and what this reveals about the nature of species. We then address the evolution and diversity of warning patterns, both as the target of selection and with respect to their underlying genetic basis. The identification of major genes involved in mimetic shifts, and homology at these loci between distantly related taxa, has revealed a surprising predictability in the genetic basis of evolution. In the final sections, we consider the evolution of warning patterns, and Heliconius diversity more generally, within a broader context of ecological and sexual selection. We consider how different traits and modes of selection can interact and influence the evolution of reproductive isolation.

Supergenes and their role in evolution.

Adaptation is commonly a multidimensional problem, with changes in multiple traits required to match a complex environment. This is epitomized by balanced polymorphisms in which multiple phenotypes co-exist and are maintained in a population by a balance of selective forces. Consideration of such polymorphisms led to the concept of the supergene, where alternative phenotypes in a balanced polymorphism segregate as if controlled by a single genetic locus, resulting from tight genetic linkage between multiple functional loci. Recently, the molecular basis for several supergenes has been resolved. Thus, major chromosomal inversions have been shown to be associated with polymorphisms in butterflies, ants and birds, offering a mechanism for localised reduction in recombination. In several examples of plant self-incompatibility, the functional role of multiple elements within the supergene architecture has been demonstrated, conclusively showing that balanced polymorphism can be maintained at multiple coadapted and tightly linked elements. Despite recent criticism, we argue that the supergene concept remains relevant and is more testable than ever with modern molecular methods.

Is Hypertension Diagnostic Testing and Diagnosis Associated With Psychological Distress?

BACKGROUND: Psychological impacts of hypertension diagnostic testing and new hypertension diagnoses are unclear. METHODS: BP-CHECK was a randomized diagnostic study conducted in 2017-2019 in an integrated healthcare system. Participants with no hypertension diagnosis or medications and elevated blood pressure (BP) were randomized to one of three diagnostic regimens: (i) Clinic, (ii) Home, or (iii) Kiosk. Participants completed questionnaires at baseline, after completion of the diagnostic regimens, and at 6 months. Outcomes included changes from baseline in health-related quality of life (HRQOL), BP-related worry, and thoughts about having a stroke or heart attack. RESULTS: Participants (n = 482) were mostly over age 50 (77.0%), and White race (80.3%). HRQOL did not significantly change from baseline to 3 weeks or 6 months. Among all participants, BP-related worry and concerns about having a heart attack or stroke increased significantly from baseline to 3 weeks, with heart attack and stroke concerns significantly higher in the Kiosk compared Clinic and Home groups. At 6 months, thoughts about having a heart attack or stroke returned to baseline overall and in the Kiosk group, however BP-related worry was significantly higher among those with, compared to those without, a new hypertension diagnosis. CONCLUSIONS: The hypertension diagnostic process did not lead to short-term or intermediate-term changes in self-reported HRQOL. However, BP-related worry increased short-term and persisted at 6 months among individuals with a new hypertension diagnosis. Results warrant validation in more representative populations and additional exploration of the impacts of this worry on psychological well-being and hypertension control. CLINICALTRIALS.GOV IDENTIFIER: NCT03130257.

Phenotypic variation in urban environments: mechanisms and implications.

In the past decade, numerous studies have explored how urbanisation affects the mean phenotypes of populations, but it remains unknown how urbanisation impacts phenotypic variation, a key target of selection that shapes, and is shaped by, eco-evolutionary processes. Our review suggests that urbanisation may often increase intraspecific phenotypic variation through several processes; a conclusion aligned with results from our illustrative analysis on tit morphology across 13 European city/forest population pairs. Urban-driven changes in phenotypic variation will have immense implications for urban populations and communities, particularly through urbanisation's effects on individual fitness, species interactions, and conservation. We call here for studies that incorporate phenotypic variation in urban eco-evolutionary research alongside advances in theory.

Insect hormones: alpha ecdysone and 20-hydroxyecdysone in bracken fern.

The two major molting hormones of insects, alpha ecdysone and 20-hydroxyecdysone, were isolated in crystalline form from dry pinnae of the bracken fern, Pteridium aquilinum (L.) Kuhn. Three unidentified substances with molting hormone activity were also detected. Bracken is the first plant found to contain both of the major insect ecdysones, and it is the first known plant source of alpha ecdysone.

Juvenile hormone: identification of an active compound from balsam fir.

A sesquiterpenoid ester with high juvenile hormone activity for Pyrrhocoris apterus (L.) was isolated from balsam fir, Abies balsamea (L.) Miller, and identified as the methyl ester of todomatuic acid.

Ecdysone analog: conversion to alpha ecdysone and 20-hydroxyecdysone by an insect.

The tritium-labeled synthetic ecdysone analog Delta(7)-5beta-cholestene-2beta,-3beta,14alpha-triol-6-one terminated diapause when injected into diapausing tobacco hornworm pupae and was converted into tritium-labeled alpha-ecdysone and tritium-labeled 20-hydroxyecdysone. About half of the crystalline alpha-ecdysone and 20-hydroxyecdysone isolated from the tobacco hornworms 7(1/2) to 8(1/2) days after injection was derived from endogenous steroid precursors and half from the transformation of the synthetic ecdysone analog.

26-hydroxyecdysone: new insect molting hormone from the egg of the tobacco hornworm.

Five kilograms of tobacco hornworm eggs (48 to 64 hours old) afforded 26.5 milligrams of a new crystalline insect molting hormone identified as 26-hydroxyecdysone. The three known insect ecdysones-alpha-ecdysone, 20-hydroxyecdysone, and 20,26-dihydroxyecdysone-were also present but in much smaller quantities. The new hormone is the predominant molting hormone in the hornworm during this stage of embryonic development. These results takent in context with the current knowledge of the chemistry and biochemistry of the molting hormones during postembryonic development in the hornworm indicate quantitative and qualitative differences in the biosynthetic-mnetabolic pathways as well as in the ecdysones in different developmental stages of this insect.

Ecdysones and analogs: effects on development and reproduction of insects.

Ingestion of certain synthetic ecdysone analogs inhibited larval growth and development in several species of insects, whereas 20-hydroxyecdysone was inactive or considerably less active. Natural 20-hydroxyecdysone and ponasterone A, and a synthetic ecdysone analog inhibited ovarian maturation and egg production in the adult housefly. These effects appeared to be related to hormonal activity.

Makisterone A:a 28-carbon hexahydroxy molting hormone from the embryo of the milkweed bug.

Makisterone A is the predominant ecdysone in the 96 +/- 4-hour-old embryo of the large milkweed bug and it is the first molting hormone with a C-24 alkyl substituent of the side chain to be isolated and identified from an insect. In addition, unknown compounds that may represent other C28 ecdysones were detected in very low concentrations. The milkweed bug could well possess a biosynthetic-metabolic pathway for C28 molting hormones instead of or in addition to known pathways for the C27 ecdysones.

DIP: The Database of Interacting Proteins: 2001 update.

The Database of Interacting Proteins (DIP; http://dip.doe-mbi.ucla. edu) is a database that documents experimentally determined protein-protein interactions. Since January 2000 the number of protein-protein interactions in DIP has nearly tripled to 3472 and the number of proteins to 2659. New interactive tools have been developed to aid in the visualization, navigation and study of networks of protein interactions.

Which thermometer? Factors influencing best choice for intermittent clinical temperature assessment.

The objectives of this study are (a) to review the current technologies, (b) to examine comparative costing data for six selected representative devices, and (c) to discuss the clinical factors related to selection of devices for intermittent temperature measurement. Financial estimates indicate that mercury-in-glass thermometers are the cheapest devices. Compact electronic and chemical (phase change) thermometers are cheaper alternatives than multi-patient contact thermometers requiring probe covers and infrared sensing models, which are commonly adopted in hospitals and clinical practice. However, time required to obtain readings will influence overall costs. Rigorous independent clinical research studies are now needed to establish which of these alternative technologies are 'fit for purpose'. As a minimum they should offer comparable clinical accuracy and reliability to mercury-in-glass and be suitable for most clinical measurement situations. Furthermore any additional costs should bring demonstrable benefits to the patient, user and healthcare system.