Association between acetaminophen use and vitiligo in US women and men.

BACKGROUND/OBJECTIVES: Exposure to chemical phenols, which can act as tyrosine analogues and result in anti-melanocyte autoimmunity, has been associated with vitiligo. Acetaminophen (N-acetyl-p-aminophenol) is an over-the-counter analgesic of phenolic origin. The risk of vitiligo with systemic exposure to acetaminophen has not yet been evaluated. METHODS: We examined the risk of vitiligo with regular use acetaminophen in women, the Nurses' Health Study (NHS) and in men, the Health Professionals Follow-up Study (HPFS). Regular acetaminophen use was asked biennially from 1990 in NHS and from 1986 in HPFS, and the year of clinician-diagnosed vitiligo was asked retrospectively in 2012 in the cohorts. RESULTS: In NHS, a total of 161 vitiligo cases were identified during a follow-up of 571,724 person-years; in HPFS, a total of 183 vitiligo cases were identified during a follow-up of 680,313 person-years. Regular use of acetaminophen was associated with an increased vitiligo risk in NHS but not HPFS. The multivariable relative risk (RR) was 1.52 (95% confidence interval [CI] 1.03-2.25) in NHS and 1.09 (95% CI 0.76-1.55) in HPFS. The higher risk of vitiligo was similar by duration of acetaminophen use in women; the multivariable RRs were 1.47 (95% CI 0.98-2.21) for acetaminophen use under 5 years, and 1.78 (95% CI 1.11-2.84) for acetaminophen use over 5 years. CONCLUSIONS: Acetaminophen may be associated with a higher risk of vitiligo in women.

Tocotrienols: Exciting Biological and Pharmacological Properties of Tocotrienols and other Naturally Occurring Compounds, Part I.

Inflammation has been implicated in cardiovascular disease and tocotrienols are potent hypocholesterolemic agents that reduce ß-hydroxy-ß-methyl-glutaryl coenzyme A reductase activity, which is degraded via the ubiquitin-proteasome pathway. Impact of various tocotrienols (α-, γ-, or δ-tocotrienol) treatments inhibit the chymotrypsin-like activity of 20S rabbit muscle proteasome (>50%) in RAW 264.7 cells and BALB/c mice. Moreover, the effect of various tocotrienols (α-, γ-, or δ-tocotrienol), α-tocopherol, quercetin, riboflavin, (-) Corey lactone, amiloride, dexamethasone supplemented diets fed to chickens (4-weeks) resulted in reduction of total cholesterol, LDL-cholesterol, and triglycerides. This trend was also observed in macrophages from RAW 264.7 cells, in LPS-induced thioglycolate-elicited peritoneal macrophages derived from C57BL/6, BALB/c, LMP7/MECL-1-/-, and PPAR-α-/- knockout mice from young (4-week-old) and senescent (42-week-old) mice, resulting in significant inhibition of TNF-α and nitric oxide levels (30% to 70%), blocked degradation of P-IκB protein, and decreased activation of NF-κB, followed gene suppression of mRNA levels of TNF-α, IL-1ß, IL-6, and iNOS. In human study, normal or hypercholesterolemic subjects administered two capsules/d of NS-7 or NS-6 (4-weeks) showed decrease in serum CRP, NO, γ-GT, total cholesterol, LDL-cholesterol, and triglycerides levels in normal as compared to hypercholesterolemic subjects (12% to 39%). In second study, hypercholesterolemic subjects were given increasing doses of δ-tocotrienol (125 mg, 250 mg, 500 mg, and 750 mg/day) plus AHA Step-1 diet (4-weeks). The most effective dose of tocotrienols (250 mg/day) may be used to lower serum NO (40%), CRP (40%), MDA (34%), γ-GT (22 %), and inflammatory cytokines IL-1α, IL-12, IFN-γ by 15% to 17%, and increase TAS levels by 22%.

Association of blood mercury levels with nonmelanoma skin cancer in the U.S.A. using National Health and Nutrition Examination Survey data (2003-2016).

BACKGROUND: Some studies have reported increased incidence or mortality of lung and brain cancers associated with occupations involving potential mercury exposure. Epidemiological evidence related to skin cancer is also limited. OBJECTIVES: To investigate the association between blood mercury (Hg) levels and nonmelanoma skin cancer (NMSC). METHODS: We used National Health and Nutrition Examination Survey data from 2003 to 2016. The exposures were blood total (tHg), inorganic (iHg) and methylmercury (MeHg). The outcome was a self-reported diagnosis of NMSC. We included participants aged ≥ 20 years who had information on blood mercury and sociodemographic factors. We conducted a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of NMSC associated with quartiles of blood Hg, after adjusting for the sociodemographic factors and survey year. RESULTS: The number of participants was 29 413; mean age was 49 years and 52% were female. Compared with those with a tHg ≤ 0·47 µg L-1 (Q1), those with a tHg > 1·74 µg L-1 (Q4) had nearly double the odds of NMSC (OR 1·79, 95% CI 1·19-2·71; Ptrend = 0·004). Similarly, those in the highest quartile of MeHg (> 1·44 µg L-1 ) had 1·7 times greater odds of NMSC (OR 1·74, 95% CI 1·13-2·70; Ptrend = 0·01) than those in the lowest quartile (≤ 0·21 µg L-1 ). iHg levels were nonsignificantly positively associated with NMSC (Ptrend = 0·08). CONCLUSIONS: We found that higher blood tHg and MeHg levels were associated with a higher prevalence of NMSC. Linked Comment: Taylor. Br J Dermatol 2020; 183:413-414.

Diagnosis validation and clinical characterization of atopic dermatitis in Nurses' Health Study 2.

BACKGROUND: Epidemiologic studies of atopic dermatitis (AD) are often limited by case definitions that have not been validated. OBJECTIVE: In this study, we assessed the accuracy of self-report of AD in a large cohort of US female nurses, the Nurses' Health Study 2 (NHS2). We also provide clinical characteristics of AD in the cohort. METHODS: We sent an electronic questionnaire to NHS2 participants who previously reported ever having a diagnosis of AD. This questionnaire was designed to confirm cases of AD using previously validated algorithms with >85% specificity. We assessed the association of AD with asthma, comparing the results when different definitions of AD were applied. We also inquired about various aspects of participants' AD. RESULTS: Responses were received from 2509 of 5126 (49%) nurses who were sent the questionnaire, with an average age of 62. Most participants (1996/2509, 80%) reiterated their previously reported clinician diagnosis of AD. Application of the two diagnostic algorithms yielded confirmation of 1538 and 1293 prevalent cases, respectively. The association of AD with asthma was stronger when more stringent AD case definitions were applied. Participants generally reported mild disease (92% with ≤10% maximal body surface area involved) and a high proportion (57%) reported adult-onset disease. CONCLUSIONS: Self-report of AD diagnosis has good reliability, and future analyses will be strengthened by our ability to conduct sensitivity analyses with refined confirmed AD subgroups.

ASSESSMENT OF RADIATION DOSE AND EXCESSIVE LIFE-TIME CANCER RISK FROM THE BUNAIR GRANITE, NORTHERN PAKISTAN.

Natural radioactivity was measured in Bunair Granite using high purity germanium gamma-ray spectrometer and compared to world's granites and building materials to access its suitability for the construction purpose. Average gamma-activities of 226Ra, 232Th and 40K were found to be 52.41, 58.41 and 1130.12 Bq kg-1, respectively. The Indoor and outdoor radiation indices including excessive life-time cancer risk (ELCR) were calculated. The average indoor ELCR was estimated as 3.49 × 10-3. The average outdoor ELCR was assessed as 0.46 × 10-3. As a basic building material Bunair Granite should be on low propriety. For flooring, facing the buildings and as Table tops, in kitchens and other utilities it is safe.

Atopic dermatitis and risk of hypertension, type 2 diabetes, myocardial infarction and stroke in a cross-sectional analysis from the Canadian Partnership for Tomorrow Project.

BACKGROUND: Atopic dermatitis (AD) has been associated with cardiovascular risk factors and diseases, but epidemiological studies to date have found conflicting results. OBJECTIVES: To determine the associations of AD with hypertension, type 2 diabetes (T2D), myocardial infarction (MI) and stroke. METHODS: We conducted a cross-sectional analysis of baseline data from the Canadian Partnership for Tomorrow Project, which includes Canadian residents aged 30-74 years living in British Columbia, Alberta, Ontario, Quebec and the Atlantic Provinces. We excluded participants with incomplete data on AD, hypertension, T2D, MI or stroke, who had type 1 or gestational diabetes or who developed any of the outcomes at an age prior to a diagnosis of AD. This left 259 119 participants in our analysis. We used logistic regression to calculate age- and sex-, and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between AD and subsequent hypertension, T2D, MI and stroke. RESULTS: AD was reported by 21 379 (8·4%) participants. In total, 52 787 cases of hypertension, 12 739 cases of T2D, 4390 cases of MI and 2235 cases of stroke were reported by participants at enrolment. In the multivariable-adjusted model, AD was associated with decreased odds of hypertension (OR 0·87, 95% CI 0·83-0·90), T2D (OR 0·78, 95% CI 0·71-0·84), MI (OR 0·87, 95% CI 0·75-1·00) and stroke (OR 0·79, 95% CI 0·66-0·95). CONCLUSIONS: We did not find evidence of a positive association between AD and subsequent hypertension, T2D, MI or stroke; AD was inversely associated with these outcomes in our study. Given our findings and the conflicting literature, AD is likely not a major risk factor for cardiovascular disease.

Incident alopecia areata and vitiligo in adult women with atopic dermatitis: Nurses' Health Study 2.

We aimed to determine the risk of alopecia areata (AA) and vitiligo associated with atopic dermatitis (AD) in a large cohort of US women, the Nurses' Health Study 2. We used logistic regression to calculate age- and multivariate-adjusted odds ratios to determine the risk of incident AA and vitiligo associated with AD diagnosed in or before 2009. A total of 87 406 and 87 447 participants were included in the AA and vitiligo analyses, respectively. A history of AD in 2009 was reported in 11% of participants. There were 147 incident cases of AA and 98 incident cases of vitiligo over 2 years of follow-up. AD was associated with increased risk of developing AA (OR 1.80, 95% CI 1.18-2.76) and vitiligo (OR 2.14, 95% CI 1.29-3.54) in multivariate models. In this study of US women, AD was associated with increased risk of incident vitiligo and AA in adulthood.

Atopic dermatitis is not independently associated with nonfatal myocardial infarction or stroke among US women.

We aimed to determine the association between atopic dermatitis (AD) and cardiovascular events in the Nurses' Health Study 2, a cohort of US women. We used logistic regression models to calculate age- and multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between history of AD and nonfatal MI and nonfatal stroke. Of the 78 702 participants in our analysis, 7916 (10%) had a history of AD. There were 392 and 391 cases of nonfatal MI and stroke, respectively. AD was not associated with MI in age- or multivariate-adjusted analyses. AD was significantly associated with stroke in the age-adjusted analysis (OR 1.38, 95% CI 1.03-1.85). This was no longer significant in multivariate models that adjusted for hypertension, hypercholesterolemia and diabetes (OR 1.31, 95% CI 0.98-1.76) and atopic comorbidities (OR 1.17, 95% CI 0.86-1.58). AD was not independently associated with nonfatal MI or stroke in this study.

Prevalence of psoriasis phenotypes among men and women in the USA.

BACKGROUND: We present the largest set of US prevalence data for psoriasis to date, obtained from three prospective cohort studies describing validated clinical phenotypes of psoriasis, including novel data about the prevalence of inverse (intertriginous) psoriasis in these groups. Nonplaque psoriasis phenotypes have been largely unmeasured in observational and interventional studies, and this has led to an under-recognition of this aspect of psoriatic disease. AIM: To describe the prevalence of nonplaque psoriasis phenotypes in a large prospective cohort. METHODS: We included 3179 women and 646 men in the analysis. Participants in the Nurses Health Study (NHS) and Health Professionals Follow-up Study (HPFS) with physician-diagnosed psoriasis completed a validated, self-administered questionnaire to assess plaque and nonplaque subsets of psoriasis. RESULTS: Psoriasis phenotypes were as follows: plaque 55%, scalp 52%, palmar-plantar 14%, nail 23% and inverse 21% in the NHS (n = 1604); plaque 60%, scalp 56%, palmar-plantar 16%, nail 27% and inverse 24% in the second NHS study (NHS II) (n = 1575); and plaque 55%, scalp 45%, palmar-plantar 12%, nail 27% and inverse 30% in the HPFS (n = 646). Scalp, nail, palmar-plantar and inverse disease represent highly prevalent phenotypes of psoriasis in the USA. CONCLUSION: Scalp, nail, palmar-plantar and inverse disease represent highly prevalent phenotypes of psoriasis.

Risk of depression in women with psoriasis: a cohort study.

BACKGROUND: Psoriasis is a common, chronic and inflammatory disease of the skin, which has been associated with depression in cross-sectional studies with limited adjustment for confounders. OBJECTIVES: In this prospective cohort study, we investigated the risk of incident depression among individuals with psoriasis and psoriatic arthritis (PsA). METHODS: We included 50 750 US female nurses from the Nurses' Health Study who were free of depression at baseline in 2000. Those participants who had ever self-reported clinician-diagnosed depression or regular use of antidepressants, or had a Mental Health Inventory score of ≤ 52 were excluded. In 2008, we retrospectively asked participants if they had ever received a physician's diagnosis of psoriasis or PsA. We defined depression as self-report of clinician-diagnosed depression or regular use of antidepressant medication. Time-dependent Cox proportional hazard models were used to estimate age and multivariate-adjusted relative risks (RRs) of clinical depression. RESULTS: After adjusting for covariates including body mass index, physical activity, smoking and the presence of major chronic conditions, the multivariate-adjusted RRs of clinical depression were 1·29 [95% confidence interval (CI) 1·10-1·52] for women with psoriasis and 1·52 (95% CI 1·06-2·19) for women with psoriasis and concomitant PsA, compared with women without psoriasis. CONCLUSIONS: We found an increased risk of depression in US women with psoriasis compared with those without psoriasis. This risk was higher in those who reported concomitant PsA. Future studies are needed to confirm these findings in other populations and to identify pathophysiological mechanisms linking psoriasis to depression.

Personal history of rosacea and risk of incident cancer among women in the US.

BACKGROUND: Rosacea is an inflammatory skin disease. We examined the association between personal history of rosacea and risk of incident cancers. METHODS: A total of 75 088 whites were included from the Nurses' Health Study II (1991-2011). Information on clinician-diagnosed rosacea and diagnosis year was collected in 2005. All cancers other than basal cell carcinoma (BCC) were confirmed. RESULTS: During 1 447 205 person-years, we identified 5194 cases with internal malignancies and 5788 with skin cancers. We did not observe significant associations between personal history of rosacea and internal malignancies, except for thyroid cancer (hazard ratio (HR)=1.59, 95% confidence interval (CI)=1.07-2.36). Among skin cancers, personal history of rosacea was associated with an elevated risk of BCC (HR=1.50, 95% CI=1.35-1.67). CONCLUSIONS: We suggest possible associations between personal history of rosacea and an increased risk of thyroid cancer and BCC. Further studies are warranted to replicate our findings and to explore the underlying mechanisms.