Position effect on FGF13 associated with X-linked congenital generalized hypertrichosis.

X-linked congenital generalized hypertrichosis (Online Mendelian Inheritance in Man 307150) is an extremely rare condition of hair overgrowth on different body sites. We previously reported linkage in a large Mexican family with X-linked congenital generalized hypertrichosis cosegregating with deafness and with dental and palate anomalies to Xq24-27. Using SNP oligonucleotide microarray analysis and whole-genome sequencing, we identified a 389-kb interchromosomal insertion at an extragenic palindrome site at Xq27.1 that completely cosegregates with the disease. Among the genes surrounding the insertion, we found that Fibroblast Growth Factor 13 (FGF13) mRNA levels were significantly reduced in affected individuals, and immunofluorescence staining revealed a striking decrease in FGF13 localization throughout the outer root sheath of affected hair follicles. Taken together, our findings suggest a role for FGF13 in hair follicle growth and in the hair cycle.

Evaluation of internal consistency of the epidermolysis bullosa oropharyngeal severity score (EBOS).

OBJECTIVE: To evaluate the internal consistency of the epidermolysis bullosa oropharyngeal severity score (EBOS). MATERIALS AND METHODS: Data from 92 patients of varying EB types/sub-types already described in a previous multi-center study were re-analyzed via the coefficient Cronbach's α (CR-α). Additionally, the corrected item total correlation between each item and the items' overall score with Pearson's product-moment correlation (ρ) was calculated. RESULTS: The alpha coefficient for the mean total score of 17 items is 0.941. The inter-observer reliability for disease severity score was excellent for oral medicine specialist (α = 0.924) and dermatologist (α = 0.916) and the intra-observer reliability was good at Time 1 (α = 0.895) and Time 2 (α = 0.897). The analysis of CR-α per single item revealed that alpha was greater than 0.904 for disease activity and 0.743 for structural damage, after the elimination of four items for oral medicine specialist and greater than 0.898 for disease activity and 0.769 for structural damage after the elimination of five items for dermatologist. Similarly the analysis of the corrected items-EBOS correlation showed that the same items do not correlate very well (ρ < 0.4) with the overall EBOS. CONCLUSIONS: The EBOS turned out to have a strong and reliable internal consistency, as the majority of the EBOS' items were consistent with each other.

Case-control study of arsenic in drinking water and kidney cancer in uniquely exposed Northern Chile.

Millions of people worldwide are exposed to arsenic in drinking water. The International Agency for Research on Cancer has concluded that ingested arsenic causes lung, bladder, and skin cancer. However, a similar conclusion was not made for kidney cancer because of a lack of research with individual data on exposure and dose-response. With its unusual geology, high exposures, and good information on past arsenic water concentrations, northern Chile is one of the best places in the world to investigate the carcinogenicity of arsenic. We performed a case-control study in 2007-2010 of 122 kidney cancer cases and 640 population-based controls with individual data on exposure and potential confounders. Cases included 76 renal cell, 24 transitional cell renal pelvis and ureter, and 22 other kidney cancers. For renal pelvis and ureter cancers, the adjusted odds ratios by average arsenic intakes of <400, 400-1,000, and >1,000 µg/day (median water concentrations of 60, 300, and 860 µg/L) were 1.00, 5.71 (95% confidence interval: 1.65, 19.82), and 11.09 (95% confidence interval: 3.60, 34.16) (Ptrend < 0.001), respectively. Odds ratios were not elevated for renal cell cancer. With these new findings, including evidence of dose-response, we believe there is now sufficient evidence in humans that drinking-water arsenic causes renal pelvis and ureter cancer.

Epidermolysis Bullosa Oropharyngeal Severity (EBOS) score: a multicenter development and reliability assessment.

BACKGROUND: Epidermolysis bullosa (EB) is a genetic mucocutaneous disorder characterized by blister formation upon mild trauma. All 4 EB types may show oropharyngeal lesions involving either hard or soft tissues. Currently, there are very few data on EB scoring that include the oropharyngeal cavity. OBJECTIVES: We sought to develop an oropharyngeal severity score that was objective, valid, reliable, reproducible, easy to perform, and appropriate for all EB types. METHODS: In this study, oral medicine specialists developed a new score, the EB Oropharyngeal Severity (EBOS) score. This measured oropharyngeal disease activity (erythema, atrophy, blisters, erosion/ulceration) and structural damage (microstomia, ankyloglossia, scarring phenotype beyond microstomia and ankyloglossia, enamel hypoplasia). It was tested on 92 patients with different types/subtypes of EB, and interobserver and intraobserver reliability were assessed. RESULTS: The EBOS mean total score was 12.9 ± 10.9 (range: 0-34). Both interobserver and intraobserver reliability for total score on all patients with EB were considered excellent (intraclass correlation coefficient 0.94; 95% confidence interval 0.90-0.96 and intraclass correlation coefficient 0.90; 95% confidence interval 0.84-0.94, respectively). Even analyzing each single parameter of the disease activity and structural damage, a substantial to excellent correlation was found in the interobserver (except for 4 sites) and intraobserver reliability. A significant correlation was found between EB types/subtypes and the EBOS median score (P < .001), but not between age and the EBOS mean total score in each group. LIMITATIONS: The sample size was small and the number of EB subtypes was limited. CONCLUSIONS: The EBOS score seems to represent an instrument capable of truly quantifying the oropharyngeal severity in different types/subtypes of EB, demonstrating excellent interobserver and intraobserver reliability.

Patterns of oral mucosa lesions in patients with epidermolysis bullosa: comparison and agreement between oral medicine and dermatology.

BACKGROUND: The oral mucosa in patients with epidermolysis bullosa (EB) can be affected with different lesions and degrees of severity. However, patterns of oral lesions in distinct types of EB are still unclear. OBJECTIVES: The purpose of this study was to determine the frequency and distribution of four types of lesions (erythema, erosion, atrophy, and blister) for each oral site and to calculate the interobserver reliability for each type of lesion in each site. METHODS: Ninety-two patients with different EB types were assessed independently by an oral medicine specialist and a dermatologist. The degree of agreement was calculated by the intraclass correlation coefficient (ICC). RESULTS: The most affected oral site was the tongue, with the most frequent lesion being erythema and atrophy [54(58.7%) patients] for the oral medicine specialist and erosion [54(58.7%) patients] for the dermatologist. Patients with recessive dystrophic EB-severe generalized (RDEB-sev gen) showed the highest mean of sites involved by each lesion for both oral medicine and dermatology. The interobserver reliability on the total of lesions was excellent on only 3 sites: lower lip (ICC: 0.89; 95%CI:0.83-0.92), hard palate (ICC:0.85; 95%CI:0.72-0.91), and tongue (ICC:0.89; 95%CI:0.84-0.92), whereas the interobserver reliability calculated for each single oral lesion showed a lower agreement. CONCLUSION: Total distribution of sites involved by four types of lesions was higher in RDEB-sev gen than in the rest of EB types, with a predominance of erythema followed by erosion. The agreement on the type of lesion was found to be poor-moderate for many oral sites.

Impact of a Digital Atopic Dermatitis Educational Intervention on Hispanic Patients and Family Members.

With the increasing incidence of atopic dermatitis (AD) in the U.S., the highest prevalence of AD being found in Hispanic countries, and the rising Hispanic-American population, educational resources on eczema focused on Spanish-speaking populations are needed more than ever. As such, the primary goal of this project was to assess the beneficial impact of an educational intervention conducted through a virtual platform for Hispanic individuals living with atopic dermatitis. Utilizing WhatsApp, the study enrolled 55 participants diagnosed with AD and/or parents of children diagnosed with AD. Participants were enrolled in a seven-day educational module with daily topics on AD health knowledge. A health knowledge survey was administered before the educational program, upon completion of the program, and one month after completion. The program found a 14% increase in AD health knowledge upon completion of the program (p < 0.001). Most importantly, there was no significant difference found between the health knowledge survey submitted at program completion and one month after completion, signaling that health knowledge taught through the course was successfully retained by participants (p = 0.29). Qualitative themes involving atopic disease were additionally explored through group discussions, including mental health and peer stigma. This study is the first of its kind in dermatology utilizing the WhatsApp format. The success of retained health knowledge regarding AD demonstrates that future virtual endeavors can be effective and accessible methods of patient education overall for populations that might not have ease of access to major medical centers.

Effect of Warning Labels on Consumer Motivation and Intention to Avoid Consuming Processed Foods.

Nutritional warnings (NWs) as a front-of-package label were implemented as a public policy aiding consumers with recognizing processed foods with high levels of critical nutrients (sodium, saturated fats, carbohydrates, and calories). However, in spite of this tool being well positioned in consumer decision making, there is little extant knowledge about the relationship between the message sent by NW, nutritional knowledge, consumer motivation, and the intention to avoid consuming processed foods. To understand these dimensions' relations, a theoretical model was created and subsequently tested through structural equations. We applied a survey to 807 home food purchasing decision makers. The results show that the direct effect of NW messages raises the intention to avoid processed foods, while eating motivation is negative in its direct effect on the same avoidance intention. However, the message sent by NWs had a mediating effect between the intentions to avoid processed food and eating motivation but showed no such effect on nutritional knowledge. This suggests that the message sent by NWs was able to turn negative eating motivation into positive eating motivation to avoid processed foods. In conclusion, NWs help mitigate eating motivations, as well as boost the intention to avoid processed foods.

[Mutation in the ED1, Ala349Thr in a patient with X-linked hypohidrotic ectodermal dysplasia]. / Mutación en el gen EDA1, Ala349Thr en paciente con displasia ectodérmica hipohidrótica ligada a X.

Hypohidrotic ectodermal dysplasia (HED) is a very rare disease characterized by the absence of eccrine glands, dry skin, scanty hair, and dental abnormalities. It is caused by mutations within the ED1 gene, which encodes a protein, ectodysplasin-A (EDA). Clinical characteristic are frontal bossing, saddle nose, pointed chin, a prominent supraorbital ridge with periorbital hyperpigmenta-tion, and anodontia. Those affected show great intolerance to heat. We report the first Mexican 2-year-old boy with an Ala349Thr missense mutation from Tamaulipas, México.

The effect of COVID-19 on the economy: Evidence from an early adopter of localized lockdowns.

BACKGROUND: Governments worldwide have implemented large-scale non-pharmaceutical interventions, such as social distancing or school closures, to prevent and control the growth of the COVID-19 pandemic. These strategies, implemented with varying stringency, have imposed substantial social and economic costs to society. As some countries begin to reopen and ease mobility restrictions, lockdowns in smaller geographic areas are increasingly considered an attractive policy intervention to mitigate societal costs while controlling epidemic growth. Nevertheless, there is a lack of empirical evidence to support these decisions. METHODS: Drawing from a rich data set of localized lockdowns in Chile, we used econometric methods to measure the reduction in local economic activity from lockdowns when applied to smaller or larger geographical areas. We measured economic activity by tax collection at the municipality-level. RESULTS: Our results show that lockdowns were associated with a 10%-15% drop in local economic activity, which is twice the reduction in local economic activity suffered by municipalities that were not under lockdown. A three-to-four-month lockdown had a similar effect on economic activity than a year of the 2009 great recession. We found costs are proportional to the population under lockdown, without differences when lockdowns were measured at the municipality or city-wide levels. CONCLUSIONS: Our findings suggest that localized lockdowns have a large effect on local economic activity, but these effects are proportional to the population under lockdown. Our results suggest that epidemiological criteria should guide decisions about the optimal size of lockdown areas since the proportional impact of lockdowns on the economy seems to be unchanged by scale.

Arborizing vessels in a targetoid hemosiderotic hemangioma: mistaken dermoscopic diagnosis of basal cell carcinoma.

Targetoid hemosiderotic hemangioma (THH) or hobnail hemangioma (HH) is a benign vascular lesion that presents with the classical clinical presentation of a ring-shaped tumor having a targetoid appearance, with a central purple-brown papule surrounded by a thin pale area and an ecchymotic ring on the outside. Dermoscopic features and patterns of HH have been documented and have proven to be sufficient to establish a clinical diagnosis in many cases. We present a facial lesion in which both the clinical presentation and dermoscopy were atypical. The presence of arborizing vessels in the dermoscopic pattern, never before described for this lesion, led us to the diagnosis of basocellular carcinoma (BCC). We also report the changes in this pattern experienced over 12 months of progression and their correlation with the histopathologic findings.

Pain in Patients with Dystrophic Epidermolysis Bullosa: Association with Anxiety and Depression.

OBJECTIVE: We investigate the presence and the quality of pain in patients with dystrophic epidermolysis bullosa (DEB), and its correlation with the level of anxiety and depression. METHODS: We collected data from 27 DEB patients and 26 healthy individuals. DEB patients and controls completed 1 scale for the quality of pain, and 1 scale for anxiety and depression. Pain was assessed with the short form of the McGill Pain Questionnaire, whereas anxiety and depression were assessed with the Hamilton rating scale for anxiety and depression. RESULTS: DEB patients and healthy control individuals were homogeneous for age and gender (p>0.05). A statistically significant difference in the two groups was seen for sensory pain rating scale (p<0.001), affective pain rating scale (p=0.029), total pain rating scale (p<0.001), visual analogue scale (p=0.012) and present pain intensity (p=0.001), but not for anxiety (p=0.169) and depression (p=0.530). The characteristics of pain that showed a significant difference between DEB patients and healthy controls were shooting, splitting, tender and throbbing (p<0.05). In DEB patients pain was not correlated with anxiety or depression (p>0.05), whereas a slight correlation between pain and anxiety was found in healthy controls (p<0.05). No difference was found between quality of pain and anxiety-depression in DEB patients (p>0.05), but was between the DEB dominant and the recessive form of DEB (p=0.025). CONCLUSION: The perception of pain in DEB patients appears greater than in healthy individuals, with splitting and tender characteristics being the most significant ones, but was not associated with anxious and/or depressive symptoms.

Role of dystrophic epidermolysis bullosa in anxiety, depression and self-esteem: A controlled cross-sectional study.

The psychological aspect in patients with dystrophic epidermolysis bullosa (DEB) is poorly documented. We sought to determine the role of DEB in anxiety, depression and self-esteem. We conducted a cross-sectional study, collecting data from 27 DEB patients and 26 healthy individuals. DEB patients and healthy controls completed three different psychometric scales for anxiety and depression and one scale for self-esteem. DEB patients and healthy controls were homogeneous for age and sex (P > 0.05), but not for employment, marital status and economic level (P < 0.05). Median values of all psychometric battery scales were not statistically significant between DEB patients and healthy controls, except for Goldberg scale for anxiety (P = 0.003) and depression (P = 0.037) and slightly significant for Zung Scale for anxiety (P = 0.048) with no difference between DEB patients with dominant versus recessive form in all scales (P > 0.05). Among DEB patients, only employment showed a significant difference in all scales (P < 0.05) but Hamilton for depression, whereas self-esteem seemed to be affected by marriage (P = 0.04) and education (P = 0.016). DEB patients apparently are not more anxious and/or depressed and do not have less self-esteem than healthy individuals.

Respiratory disease and particulate air pollution in Santiago Chile: contribution of erosion particles from fine sediments.

Air pollution in Santiago is a serious problem every winter, causing thousands of cases of breathing problems within the population. With more than 6 million people and almost two million vehicles, this large city receives rainfall only during winters. Depending on the frequency of storms, statistics show that every time it rains, air quality improves for a couple of days, followed by extreme levels of air pollution. Current regulations focus mostly on PM10 and PM2.5, due to its strong influence on respiratory diseases. Though more than 50% of the ambient PM10s in Santiago is represented by soil particles, most of the efforts have been focused on the remaining 50%, i.e. particulate material originating from fossil and wood fuel combustion, among others. This document emphasizes the need for the creation of erosion/sediment control regulations in Chile, to decrease respiratory diseases on Chilean polluted cities.

Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

BACKGROUND: From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer. METHODS: We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls. RESULTS: ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and >800 µg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96-3.71], and 5.24 (3.05-9.00; P(trend) < 0.001) for lung cancer, and 1.00, 2.94 (1.29-6.70), and 8.11 (4.31-15.25; P(trend) < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 µg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed. CONCLUSION: Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. IMPACT: Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease.

Argyria mimicking a blue nevis: dermoscopy features.

Argyria is a rare disease caused by prolonged skin contact with silver. Localized cases have been described regarding the use of topical medications, and trauma with objects containing this metal such as acupuncture needles and jewelry. Clinically, a macule or a patch, round or oval, appears in the infected area, with a characteristic bluey-gray color. To our knowledge this is the first time that this clinical condition has been described through the use of dermoscopy.

Basal cell carcinoma appearing in a facial nevus sebaceous of Jadassohn: dermoscopic features.

The nevus sebaceous of Jadassohn usually affects the face or scalp. It tends to evolve in three stages, and the final stage is characterized by the appearance of tumours. We present the case of a facial nevus sebaceous of Jadasshon in which a basal cell carcinoma developed. We also explore the diagnosis of this disease, which was established through dermoscopy, and propose using this technique in the clinical follow-up of this type of hamartoma, thereby allowing the early detection of cancer development.