Influence of ultraviolet A1 exposures on mood states: a randomized controlled study.

We investigated the effects of daily ultraviolet A1 (UV-A1, 340-400 nm) exposures on mood states (#R19055, approval on 21 October 2020). Based on our earlier findings of the influence of diurnal preference on mood, we investigated further whether diurnal preference plays a role in the influence of UV-A1 on mood states. Forty-one healthy participants aged 19-55 years were randomized to receive either UV-A1 (n = 21) or control (n = 20) exposures (violet light, 390-440 nm). The irradiations were administered on three consecutive mornings on the skin of the buttocks and middle back. Diurnal preference was assessed with the modified 6-item Morningness-Eveningness Questionnaire (mMEQ). Changes in mood were assessed with Total Mood Disturbance (TMD) score of the 40-item Profile of Mood States (POMS) before the first irradiation, immediately after each irradiation and one week after the last irradiation. Mood improved among those subjected to UV-A1 exposures compared with the controls (p = 0.031). Individuals with more pronounced morningness had mood improvement (p = 0.011), whereas those with more pronounced eveningness did not (p = 0.41). At follow-up of one week after the last irradiation the mood improvement had disappeared.

Narrow-band UVB radiation triggers diverse changes in the gene expression and induces the accumulation of M1 macrophages in human skin.

BACKGROUND: The underlying molecular mechanisms that determine the biological effects of UVB radiation exposure on human skin are still only partially comprehended. OBJECTIVES: Our goal is to examine the human skin transcriptome and related molecular mechanisms following a single exposure to UVB in the morning versus evening. METHODS: We exposed 20 volunteer females to four-fold standard erythema doses (SED4) of narrow-band UVB (309-313 nm) in the morning or evening and studied skin transcriptome 24 h after the exposure. We performed enrichment analyses of gene pathways, predicted changes in skin cell composition using cellular deconvolution, and correlated cell proportions with gene expression. RESULTS: In the skin transcriptome, UVB exposure yielded 1384 differentially expressed genes (DEGs) in the morning and 1295 DEGs in the evening, of which the most statistically significant DEGs enhanced proteasome and spliceosome pathways. Unexposed control samples showed difference by 321 DEGs in the morning vs evening, which was related to differences in genes associated with the circadian rhythm. After the UVB exposure, the fraction of proinflammatory M1 macrophages was significantly increased at both timepoints, and this increase was positively correlated with pathways on Myc targets and mTORC1 signaling. In the evening, the skin clinical erythema was more severe and had stronger positive correlation with the number of M1 macrophages than in the morning after UVB exposure. The fractions of myeloid and plasmacytoid dendritic cells and CD8 T cells were significantly decreased in the morning but not in the evening. CONCLUSIONS: NB-UVB-exposure causes changes in skin transcriptome, inhibiting cell division, and promoting proteasome activity and repair responses, both in the morning and in the evening. Inflammatory M1 macrophages may drive the UV-induced skin responses by exacerbating inflammation and erythema. These findings highlight how the same UVB exposure influences skin responses differently in morning versus evening and presents a possible explanation to the differences in gene expression in the skin after UVB irradiation at these two timepoints.

Melatonin immunoreactivity of epidermal skin is higher in the evening than morning but does not account for erythema sensitivity.

The skin is a site of melatonin synthesis, and melatonin has a role in protecting against ultraviolet radiation-induced damage. Ultraviolet B (UVB) induced erythema seems to vary between morning and evening. We investigated whether epidermal melatonin immunoreactivities in the morning differed from those in the evening, and whether UVB-induced erythema was associated with these melatonin immunoreactivities in healthy volunteers. Erythema sensitivity of the skin was determined in the morning and in the evening by scoring the Minimal Erythema Dose and quantifying the erythema index (EI). We took biopsies from the non-UVB-exposed skin of healthy volunteers (n = 39) in the morning and in the evening to study melatonin immunoreactivity with immunohistochemistry (IHC). In the IHC staining, there was more melatonin immunoreactivity in the evening than in the morning (p < .001). Erythema was more pronounced in the evening than in the morning irradiated skin (p < .001). The graded amount of melatonin immunoreactivity in the samples was not associated with the EI. We discovered melatonin immunoreactivity of the non-irradiated skin to vary diurnally. However, endogenous skin melatonin does not seem to be the reason why NB-UVB induces more erythema in the evening than in the morning.

Premalignant lesions, basal cell carcinoma and melanoma in patients with cutaneous squamous cell carcinoma.

The incidence of keratinocyte carcinomas is increasing worldwide and currently there is no standardised strategy for the follow-up of patients with multiple tumours. The objective of this study was to assess the prevalence of premalignant lesions, i.e., actinic keratosis and Bowen's disease, as well as basal cell carcinoma (BCC) and cutaneous melanoma (CM) among patients with cutaneous squamous cell carcinoma (cSCC). Pathology database search was performed to identify all cSCC patients diagnosed in the Pirkanmaa region of Finland in 2006-2015. Details of the patients and tumours were obtained through medical record review. The cohort consisted of 774 patients with 1131 cSCC tumours. Overall 559 patients (72%) had premalignant lesions. A total of 316 patients (41%) had BCC and 52% of these (n = 164) had more than one BCC tumour. 50 patients (6%) had CM. Overall 180 cSCC patients (23%) had no premalignant changes, BCC or CM. The median age of these patients was 6 years less than that of the patients with premalignant lesions (p < 0.001) or BCC (p < 0.001). The invasion depth of the tumours was deeper in the patients with only cSCC (median 3 mm, interquartile range 2-6) than in those with premalignant lesions or BCC (median 2 mm, interquartile range 1-3), p < 0.001. CSCC patients have a high risk of developing multiple skin cancers and need long-term follow-up.

Recurrent and Metastatic Cutaneous Squamous Cell Carcinomas in a Cohort of 774 Patients in Finland.

Recognising patients with high risk cutaneous squamous cell carcinomas is essential in planning effective monitoring. The aim of this study was to determine the rate of local recurrences and metastases of cutaneous squamous cell carcinomas in a previously defined patient cohort in Finland. Pathology database search was performed to identify cutaneous squamous cell carcinoma patients and their medical records were reviewed. The cohort consisted of 774 patients with 1,131 cutaneous squamous cell carcinoma tumours. Overall, 4.2% (48/1,131) of the tumours were metastatic and 2.2% (25/1,131) had a local recurrence. Three of the metastatic tumours and 8 of the recurrent tumours had an invasion depth of ≤ 2 mm. The majority of metastases (28/48; 58%) were found within 3 months of the diagnosis of cutaneous squamous cell carcinoma. In conclusion, our study demonstrated recurrences and metastases even in the case of thin cutaneous squamous cell carcinomas and in high-risk cases close monitoring should be organised during the first years after diagnosis.

Narrow-band ultraviolet B (NB UV-B) exposures improve mood in healthy individuals differently depending on chronotype.

The evening chronotype is associated with psychological symptoms such as depressed mood, while skin exposure to ultraviolet radiation (UVR) may affect mood and behavior through neural and humoral routes. This pilot study aimed to investigate the impact of whole-body narrow-band (NB) UV-B exposure on current mood state and circulating 25-hydroxyvitamin D3 (25(OH)D3), interleukin-6 (IL-6), cortisol and ß-endorphin (ß-END) levels in healthy participants. Here, eleven healthy women received full-body NB UV-B exposures on four afternoons, and the chronotype was assessed with a shortened version of Horne and Östberg's Morningness-Eveningness Questionnaire (MEQ). Perceived mood was evaluated using the Visual Analogue Scale (VAS), and serum 25(OH)D3, IL-6, cortisol and ß-END concentrations were monitored daily. Decreasing VAS values showed mood to improve significantly over the five days after the four suberythematous NB UV-B exposures (p = .038), and the more the circadian preference was inclined toward eveningness, the greater the improvement in the mood dimension of wellbeing (p = .021). Baseline mood state was correlated with baseline 25(OH)D3 (r = -0.54, 95% CI: -0.86 to -0.09) and with baseline cortisol (r = -0.57, 95% CI: -0.87 to -0.04). During the NB UV-B exposures, 25(OH)D3 increased significantly, as expected, and IL-6 declined significantly by -0.35 (95% CI: -0.69 to -0.07) pg/mL from the initial values of 1.12 ± 0.66 pg/mL (p = .025). In conclusion, in our pilot study, NB UV-B exposure improved mood, especially among those with evening preference for their daily activities, as well as circulating 25(OH)D3 levels, whereas circulating IL-6 levels decreased. Abbreviations: UVR: Ultraviolet radiation; NB UV-B: narrow-band UV-B; VAS: Visual Analogue Scales; ß-END: ß-endorphin; IL-6: Interleukin-6.

Narrowband ultraviolet B phototherapy improves quality of life of psoriasis and atopic dermatitis patients up to 3 months: Results from an observational multicenter study.

BACKGROUND/PURPOSE: Narrowband UVB phototherapy is a common treatment modality in psoriasis and atopic dermatitis, but evidence of its actual effect in clinical setting is sparse. Our aim was to assess the effectiveness and costs of narrowband UVB phototherapy in psoriasis and atopic dermatitis in clinical setting. METHODS: We observed 207 psoriasis patients and 144 atopic dermatitis patients in eight centers. SAPASI, PO-SCORAD, and VAS measures were used at baseline, at the end, and 3 months after the narrowband UVB phototherapy course. Quality of life was measured using Dermatology Life Quality Index (DLQI), and costs were assessed using a questionnaire. RESULTS: In both psoriasis and atopic dermatitis, the DLQI and Self-Administrated PASI (SAPASI)/Patient-Oriented SCORAD (PO-SCORAD) improved significantly and the results remained improved for at least 3 months in both groups. Alleviation of pruritus correlated with better quality of life in both patient groups. We reported slight redness and burning side effects which were due to lack of MED testing. Self-administered tools proved to be useful in evaluating pruritus and severity of the disease in psoriasis and atopic dermatitis. Mean patient costs were 310 € and 21 hours of time, and mean costs for the healthcare provider were 810 €. CONCLUSION: In psoriasis, narrowband UVB is a very efficient treatment in clinical setting, whereas in atopic dermatitis, more studies are needed to determine the best dosage.

Characteristics and Trends of Cutaneous Squamous Cell Carcinoma in a Patient Cohort in Finland 2006-2015.

The incidence of cutaneous squamous cell carcinoma is increasing worldwide. In most epidemiological studies, only the first case of cutaneous squamous cell carcinoma is registered, underestimating the burden of the disease. To determine the frequency and detailed characteristics of cutaneous squamous cell carcinoma in a Finnish patient cohort, we performed a retrospective 10-year study taking into account multiple tumours in one patient. On the pathology database search and medical record review we identified 774 patients with a total of 1,131 cutaneous squamous cell carcinomas. The crude incidence increased from 18.6/100,000 persons in 2006 to 28.1 in 2015. The location of tumours differed between men and women: the greatest difference concerned cutaneous squamous cell carcinoma of the ear, with 93% of cases occurring in men. One fourth (24%) of patients had more than one tumour. A small shift from poorly to well-differentiated tumours was seen. In conclusion, the incidence of cutaneous squamous cell carcinoma increased, with many patients presenting with multiple tumours.

Tanning dependence and seasonal affective disorder are frequent among sunbathers but are not associated.

Ultraviolet radiation (UVR) is a known risk factor for skin cancers. Those who are tanning dependent seek out UVR exposure. Many tanners have expressed symptoms of seasonal affective disorder (SAD), but conclusive evidence of a connection with tanning dependence is lacking. We evaluated the frequency of tanning dependence or abuse and symptoms of SAD among Finnish sunbathers and analysed whether phenomena are associated which could indicate a common biological mechanism. Sunbathing related tanning dependence/abuse among Finnish sunbathers were assessed using the Structured Interview for Tanning Abuse and Dependence measure (SITAD), and symptoms of SAD were assessed with the Seasonal Pattern Assessment Questionnaire (SPAQ). Of 229 sunbathers, 8% (n = 18) were classified as tanning-dependent, and 26% (n = 59) were classified as tanning abusers. Additionally, 16% (n = 37) met the criteria for SAD, and 26% (n = 60) met the criteria for subsyndromal seasonal affective disorder (S-SAD), but there was no significant association between tanning dependence or abuse and SAD or S-SAD. Sunbathing dependence or abuse and SAD/S-SAD were frequent among sunbathers, and they may promote sun-seeking risk behaviour. However, within this sample, tanning dependence and SAD/S-SAD were not associated.

Ultraviolet B radiation modifies circadian time in epidermal skin and in subcutaneous adipose tissue.

BACKGROUND: Recent findings suggest that circadian time regulates cellular functions in the skin and may affect protection against ultraviolet radiation (UVR). It is not known, however, whether UVR through skin directly affects the expression of circadian genes. We investigated the effect of ultraviolet B (UVB) exposure on cryptochrome circadian clock 1 (CRY1), cryptochrome circadian clock 2 (CRY2), and circadian associated repressor of transcription (CIART) genes. METHODS: Healthy volunteers (n = 12) were exposed to narrow-band UVB radiation of four standard erythemal dose (SED). Epidermal/dermal and subcutaneous adipose tissue samples were obtained by punch biopsies from irradiated and non-irradiated skin 10 cm away from the irradiated site 24 hours after UVB exposure. Gene expression of CRY1, CRY2, and CIART was measured using RT-PCR (TaqMan). RESULTS: Ultraviolet B radiation affected mRNA expression in the epidermal/dermal skin and in the subcutaneous adipose tissue. It down-regulated expression of CRY2 gene in the epidermal/dermal skin, whereas it up-regulated expression of CRY1 and CIART genes in the subcutaneous adipose tissue. CONCLUSION: We showed for the first time that UVB radiation affects expression of circadian genes in the subcutaneous adipose tissue. Further studies are warranted to understand the mechanisms in detail.

The effect of vernal solar UV radiation on serum 25-hydroxyvitamin D concentration depends on the baseline level: observations from a high latitude in Finland.

Humans obtain vitamin D from conversion of 7-dehydrocholesterol in the skin by ultraviolet B (UVB) radiation or from dietary sources. As the radiation level is insufficient in winter, vitamin D deficiency is common at higher latitudes. We assessed whether vernal solar UVB radiation at latitudes 61°N and 67°N in Finland has an impact on serum 25-hydroxyvitamin D [S-25(OH)D] concentrations. Twenty-seven healthy volunteers participated in outdoor activities in snow-covered terrain for 4-10 days in March or April, with their face and hands sun-exposed. The personal UVB doses and S-25(OH)D levels were monitored. A mean UVB dose of 11.8 standard erythema doses (SED) was received during an average of 12.3 outdoor hours. The mean S-25(OH)D concentration in subjects with a baseline concentration below 90.0 nmol/L (n=13) increased significantly, by 6.0 nmol/L from an initial mean of 62.4 nmol/L (p<0.001), whereas in those with a basal concentration above 90.0 nmol/L (n=12) it decreased significantly, by 6.7 nmol/L from a mean of 116.9 nmol/L (p<0.01). To conclude, only 7% of total body surface area was exposed to vernal sunlight and this was capable of increasing S-25(OH)D levels in subjects with a baseline level below 90 nmol/L but not in those with higher levels.

Narrow-band ultraviolet B radiation induces the expression of ß-endorphin in human skin in vivo.

BACKGROUND: Ultraviolet radiation (UVR) from the sun and solaria has addictive properties that may develop into dependence. In mice, UVR addiction was connected to ß-endorphin (ß-END) formed in the skin after UVR exposure. In humans, the formation of ß-END in skin keratinocytes has not been confirmed in vivo. OBJECTIVE: To determine with immunohistochemistry if sub-erythematous narrow-band UV-B (NB-UV-B) exposures stimulate p53 mediated expression of pro-opiomelanocortin (POMC), ß-END and α-melanocyte stimulating hormone (α-MSH) in human skin keratinocytes in vivo. METHODS: Within 12 healthy volunteers, 7 received a single 1 standard erythema dose (SED) of NB-UV-B on their whole body, and 5 volunteers received a cumulative dose of 3 SED delivered on two subsequent days i.e., 1+2 SED. Skin biopsies were taken immediately before the first exposure and at 24h from the last UV-B exposure to assess p53, ß-END, POMC, and α-MSH expression. RESULTS: Nuclear p53 expression increased in all samples taken at 24h after NB-UV-B exposure. UV-B irradiation also increased epidermal ß-END expression in 11 out of 12 samples taken at 24h after UV-B exposure. The brownish staining was localized in the cytoplasm of keratinocytes and around the nuclei, being more pronounced in the basal cell layers. POMC and α-MSH staining showed no obvious meaningful increase since only one section of each showed any change compared with basal levels. CONCLUSIONS: Our study is the first to show that UV-B exposures increase ß-END expression in epidermal keratinocytes of human skin in vivo, which could be the link to proposed UVR addiction.

Photodynamic Therapy for Actinic Keratoses: A Randomized Prospective Non-sponsored Cost-effectiveness Study of Daylight-mediated Treatment Compared with Light-emitting Diode Treatment.

Daylight-mediated photodynamic therapy (DL-PDT) is considered as effective as conventional PDT using artificial light (light-emitting diode (LED)-PDT) for treatment of actinic keratoses (AK). This randomized prospective non-sponsored study assessed the cost-effectiveness of DL-PDT compared with LED-PDT. Seventy patients with 210 AKs were randomized to DL-PDT or LED-PDT groups. Effectiveness was assessed at 6 months. The costs included societal costs and private costs, including the time patients spent in treatment. Results are presented as incremental cost-effectiveness ratio (ICER). The total costs per patient were significantly lower for DL-PDT (€132) compared with LED-PDT (€170), giving a cost saving of €38 (p = 0.022). The estimated probabilities for patients' complete response were 0.429 for DL-PDT and 0.686 for LED-PDT; a difference in probability of being healed of 0.257. ICER showed a monetary gain of €147 per unit of effectiveness lost. DL-PDT is less costly and less effective than LED-PDT. In terms of cost-effectiveness analysis, DL-PDT provides lower value for money compared with LED-PDT.