Severely Photosensitive Psoriasis: A Phenotypically Defined Patient Subset

A subset of patients with chronic plaque psoriasis exhibits severely photosensitive psoriasis (PP) with a pronounced seasonal pattern, but the pathomechanism is not understood. We performed two related studies; first, a detailed clinical characterization of PP, and second, a controlled investigation exploring the underlying pathomechanisms through the assessment of disease onset after photoprovocation. Patients with PP (n=20) showed striking female predominance (19F:1M), very low mean age of psoriasis onset (11 years, range 2–24), family history of psoriasis (13/20), a strong HLA–Cw*0602 association (16/17), and a rapid abnormal clinical response to broadband UVA, comprising erythema±scaling plaques (17/20). Subsequently, patients with PP (n=10), non-PP (n=9), and healthy volunteers (n=11) were challenged with low-dose broadband UVA on 3 consecutive days, and serial biopsies were taken after 6hours to 7 days and from unchallenged skin. Histological changes consistent with early psoriasis occurred in 4 of 10 PP patients, but in neither of the control groups, with significant dermal infiltration by neutrophils, CD4+, CD8+, and CD45RO+ cells at 24h, accompanied by acanthosis. Thus, a phenotypically distinct subset of psoriasis has been characterized. In contrast with earlier assumptions, UV can provoke psoriasiform features rapidly de novo; a role for memory effector T cells is supported in the early phase

Effects of Harmful Algal Blooms on Fish and Shellfish Species: A Case Study of New Zealand in a Changing Environment

Harmful algal blooms (HABs) have wide-ranging environmental impacts, including on aquatic species of social and commercial importance. In New Zealand (NZ), strategic growth of the aquaculture industry could be adversely affected by the occurrence of HABs. This review examines HAB species which are known to bloom both globally and in NZ and their effects on commercially important shellfish and fish species. Blooms of Karenia spp. have frequently been associated with mortalities of both fish and shellfish in NZ and the sub-lethal effects of other genera, notably Alexandrium spp., on shellfish (which includes paralysis, a lack of byssus production, and reduced growth) are also of concern. Climate change and anthropogenic impacts may alter HAB population structure and dynamics, as well as the physiological responses of fish and shellfish, potentially further compromising aquatic species. Those HAB species which have been detected in NZ and have the potential to bloom and harm marine life in the future are also discussed. The use of environmental DNA (eDNA) and relevant bioassays are practical tools which enable early detection of novel, problem HAB species and rapid toxin/HAB screening, and new data from HAB monitoring of aquaculture production sites using eDNA are presented. As aquaculture grows to supply a sizable proportion of the world’s protein, the effects of HABs in reducing productivity is of increasing significance. Research into the multiple stressor effects of climate change and HABs on cultured species and using local, recent, HAB strains is needed to accurately assess effects and inform stock management strategies

Comparative study of healthy older and younger adults shows they have the same skin concentration of vitamin D3 precursor, 7-dehydrocholesterol, and similar response to UVR

Vitamin D3 synthesis in human skin is initiated by solar ultraviolet radiation (UVR) exposure of precursor 7-dehydrocholesterol (7DHC), but influence of age on the early stage of vitamin D3 metabolism is uncertain. We performed a prospective standardised study in healthy ambulant adults aged ≥65 and ≤40 years examining (1) if baseline skin 7DHC concentration differs between younger and older adults and (2) the impact of older age on serum vitamin D3 response to solar simulated UVR. Eleven younger (18–40 years) and 10 older (65–89 years) adults, phototype I–III, received low-dose UVR (95% UVA, 5% UVB, 1.3 SED) to ~35% of the body surface area. Biopsies were taken for 7DHC assay from unexposed skin, skin immediately and 24 h post-UVR, and blood sampled at baseline, 24 h and 7 d post-UVR for vitamin D3 assay. Samples were analysed by HPLC-MS/MS. Baseline skin 7DHC (mean ± SD) was 0.22 ± 0.07 and 0.25 ± 0.08 µg/mg in younger versus older adults (no significant difference). Baseline serum vitamin D3 concentration was 1.5 ± 1.5 and 1.5 ± 1.7 nmol/L in younger versus older adults, respectively, and showed a significant increase in both groups post-UVR (no significant differences between age groups). Thus, skin 7DHC concentration was not a limiting factor for vitamin D3 production in older relative to younger adults. This information assists public health guidance on sun exposure/vitamin D nutrition, with particular relevance to the growing populations of healthy ambulant adults ≥65 years

Influence of vitamin D supplementation by sunlight or oral D3 on exercise performance

Purpose: To determine the relationship between vitamin D status and exercise performance in a large, prospective cohort study of young men and women across seasons (Study-1). Then, in a randomized, placebo-controlled trial, to investigate the effects on exercise performance of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol·L-1) by a unique comparison of safe, simulated-sunlight and oral vitamin D3 supplementation in wintertime (Study-2).  Methods: In Study-1, we determined 25(OH)D relationship with exercise performance in 967 military recruits. In Study-2, 137 men received either placebo, simulated-sunlight (1.3x standard erythemal dose in T-shirt and shorts, three-times-per-week for 4-weeks and then once-per-week for 8-weeks) or oral vitamin D3 (1,000 IU[BULLET OPERATOR]day-1 for 4-weeks and then 400 IU[BULLET OPERATOR]day-1 for 8-weeks). We measured serum 25(OH)D by LC-MS/MS and endurance, strength and power by 1.5-mile run, maximum-dynamic-lift and vertical jump, respectively.  Results: In Study-1, only 9% of men and 36% of women were vitamin D sufficient during wintertime. After controlling for body composition, smoking and season, 25(OH)D was positively associated with endurance performance (P ≤ 0.01, [INCREMENT]R2 = 0.03–0.06, small f2 effect sizes): 1.5-mile run time was ~half-a-second faster for every 1 nmol·L-1 increase in 25(OH)D. No significant effects on strength or power emerged (P > 0.05). In Study-2, safe simulated-sunlight and oral vitamin D3 supplementation were similarly effective in achieving vitamin D sufficiency in almost all (97%); however, this did not improve exercise performance (P > 0.05).  Conclusion: Vitamin D status was associated with endurance performance but not strength or power in a prospective cohort study. Achieving vitamin D sufficiency via safe, simulated summer sunlight or oral vitamin D3 supplementation did not improve exercise performance in a randomized-controlled trial

The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases.

yesSunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids and their subsequent metabolism by cyclooxygenases (COX) and lipoxygenases (LOX) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and for 72h examined (i) expression of pro- and anti-inflammatory eicosanoids using LC/ESI-MS/MS and (ii) immunohistochemical expression of COX-2, 12-LOX, 15-LOX and leucocyte markers, while (iii) quantifying clinical erythema. We show that vasodilatory prostaglandins (PG)E2, PGF2¿ and PGE3 accompany the erythema in the first 24-48h, associated with increased COX-2 expression at 24h. Novel, potent leukocyte chemoattractants 11-, 12- and 8-monohydroxy-eicosatetraenoic acid (-HETE) are elevated from 4-72h, in association with peak dermal neutrophil influx at 24h, and increased dermal CD3+ lymphocytes and 12- and 15-LOX expression from 24-72h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72h. Sunburn is characterized by overlapping phases of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution.The Wellcome Trus

Environmental Effects of Stratospheric Ozone Depletion, UV Radiation, and interactions with Climate Change: 2022 Assessment Report

The Montreal Protocol on Substances that Deplete the Ozone Layer was established 35 years ago following the 1985 Vienna Convention for protection of the environment and human health against excessive amounts of harmful ultraviolet-B (UV-B, 280-315 nm) radiation reaching the Earth’s surface due to a reduced UV-B-absorbing ozone layer. The Montreal Protocol, ratified globally by all 198 Parties (countries), controls ca 100 ozone-depleting substances (ODS). These substances have been used in many applications, such as in refrigerants, air conditioners, aerosol propellants, fumigants against pests, fire extinguishers, and foam materials. The Montreal Protocol has phased out nearly 99% of ODS, including ODS with high global warming potentials such as chlorofluorocarbons (CFC), thus serving a dual purpose. However, some of the replacements for ODS also have high global warming potentials, for example, the hydrofluorocarbons (HFCs). Several of these replacements have been added to the substances controlled by the Montreal Protocol. The HFCs are now being phased down under the Kigali Amendment. As of December 2022, 145 countries have signed the Kigali Amendment, exemplifying key additional outcomes of the Montreal Protocol, namely, that of also curbing climate warming and stimulating innovations to increase energy efficiency of cooling equipment used industrially as well as domestically. As the concentrations of ODS decline in the upper atmosphere, the stratospheric ozone layer is projected to recover to pre-1980 levels by the middle of the 21st century, assuming full compliance with the control measures of the Montreal Protocol. However, in the coming decades, the ozone layer will be increasingly influenced by emissions of greenhouse gases and ensuing global warming. These trends are highly likely to modify the amount of UV radiation reaching the Earth\u27s surface with implications for the effects on ecosystems and human health. Against this background, four Panels of experts were established in 1988 to support and advise the Parties to the Montreal Protocol with up-to-date information to facilitate decisions for protecting the stratospheric ozone layer. In 1990 the four Panels were consolidated into three, the Scientific Assessment Panel, the Environmental Effects Assessment Panel, and the Technology and Economic Assessment Panel. Every four years, each of the Panels provides their Quadrennial Assessments as well as a Synthesis Report that summarises the key findings of all the Panels. In the in-between years leading up to the quadrennial, the Panels continue to inform the Parties to the Montreal Protocol of new scientific information

Ozone depletion, ultraviolet radiation, climate change and prospects for a sustainable future

Changes in stratospheric ozone and climate over the past 40-plus years have altered the solar ultraviolet (UV) radiation conditions at the Earth's surface. Ozone depletion has also contributed to climate change across the Southern Hemisphere. These changes are interacting in complex ways to affect human health, food and water security, and ecosystem services. Many adverse effects of high UV exposure have been avoided thanks to the Montreal Protocol with its Amendments and Adjustments, which have effectively controlled the production and use of ozone-depleting substances. This international treaty has also played an important role in mitigating climate change. Climate change is modifying UV exposure and affecting how people and ecosystems respond to UV; these effects will become more pronounced in the future. The interactions between stratospheric ozone, climate and UV radiation will therefore shift over time; however, the Montreal Protocol will continue to have far-reaching benefits for human well-being and environmental sustainability.Peer reviewe

A High-Throughput Screen for Tuberculosis Progression

One-third of the world population is infected with Mycobacterium tuberculosis and multi-drug resistant strains are rapidly evolving. The noticeable absence of a whole organism high-throughput screening system for studying the progression of tuberculosis is fast becoming the bottleneck in tuberculosis research. We successfully developed such a system using the zebrafish Mycobacterium marinum infection model, which is a well-characterized model for tuberculosis progression with biomedical significance, mimicking hallmarks of human tuberculosis pathology. Importantly, we demonstrate the suitability of our system to directly study M. tuberculosis, showing for the first time that the human pathogen can propagate in this vertebrate model, resulting in similar early disease symptoms to those observed upon M. marinum infection. Our system is capable of screening for disease progression via robotic yolk injection of early embryos and visual flow screening of late-stage larvae. We also show that this system can reliably recapitulate the standard caudal vein injection method with a throughput level of 2,000 embryos per hour. We additionally demonstrate the possibility of studying signal transduction leading to disease progression using reverse genetics at high-throughput levels. Importantly, we use reference compounds to validate our system in the testing of molecules that prevent tuberculosis progression, making it highly suited for investigating novel anti-tuberculosis compounds in vivo