Is heritability of alopecia areata sex-specific? A nationwide population-based cohort study.

Previous studies have demonstrated the heritability of alopecia areata (AA). However, whether the heritability of AA is sex-specific has not been examined. A nationwide population-based retrospective cohort study was performed using the Taiwan Maternal and Child Health Database from 2004 to 2017. We examined the heritability of AA in offspring of parents with and without AA, and determined whether the transmission of AA from parents to the next generation may occur in opposite directions depending on sex. We found that the risk ratio (RR) for heritability of AA between parents with and without AA was approximately two-fold. In addition, for fathers with AA, the risk of AA in offspring tended to be higher in girls than in boys (RR: 2.97; 95% confidence interval: 0.94, 9.31). Therefore, the present study confirms the heritability of AA, and further studies examining the sex-specific heritability of AA with a larger sample are warranted.

Association between psoriasis, psoriatic arthritis and gout: a nationwide population-based study.

BACKGROUND: Psoriasis is a common skin disease that has been recently found to be associated with various systemic inflammatory disorders. However, the association between psoriasis and gout has not been well defined. OBJECTIVE: We investigated whether there is an association between psoriasis, psoriatic arthritis and gout in a large population of patients in Taiwan. METHODS: A nationwide population-based cross-sectional study was performed using the Taiwanese National Health Insurance Research Database (NHIRD). A total of 114 623 patients with gout and 114 623 patients without gout (1 : 1 propensity score-matched according to age, sex, income category and urbanization level) were identified. The prevalence of psoriasis, psoriatic arthritis and other comorbid diseases in these two groups of patients was compared. Adjusted odds ratios (OR) were calculated using conditional logistic regression. RESULTS: There was an increased prevalence of psoriasis in patients with gout compared with patients without gout (1.6% vs. 1.1%, P < 0.0001). Subgroup analysis showed an increased prevalence of psoriatic arthritis (0.3% vs. 0.1%, P < 0.0001) in patients with gout compared with patients without gout. In addition, multiple conditional logistic regression analysis showed that gout was significantly associated with psoriasis (adjusted OR 1.30, 95% CI 1.20-1.42) and psoriatic arthritis (adjusted OR 2.50, 95% CI 1.95-3.22). After stratification by age and sex, it was found that the strength of the association between gout and psoriasis was similar among males and females but varied according to age group, with patients aged 41-50 years having the strongest association. CONCLUSION: Gout is significantly associated with psoriasis and psoriatic arthritis in the Taiwanese population, and the strength of the association varies with the patient's age. Further studies are warranted to elucidate the molecular mechanisms underlying this association.

Increased incidence of ischaemic heart disease and cerebrovascular disease in psoriasis patients with depression: a nationwide retrospective cohort study.

BACKGROUND: Psoriasis is known to confer a higher risk of cardiovascular and cerebrovascular diseases. However, very few studies have investigated whether the development of depression in psoriasis patients may further increase this vascular risk. OBJECTIVE: We investigated the risk of ischaemic heart disease and cerebrovascular disease in Taiwanese psoriasis patients with and without depression. METHODS: A nationwide population-based retrospective cohort study was performed using the National Health Insurance Research Database. We included 604 psoriasis patients with depression, who were matched to 2416 psoriasis patients without depression (1 : 4 ratio). Relative risks (RR) with 95% confidence intervals (CI) were determined using the Cox proportional hazards regression model, with adjustment for demographic characteristics and comorbidities. RESULTS: Compared with psoriasis patients without depression, psoriasis patients with depression had greater risk of developing incident ischaemic heart disease (19.5% vs. 8.3%, adjusted RR 1.98, 95% CI 1.57-2.49), cerebrovascular disease (15.6% vs. 5.9%, adjusted RR 2.29, 95% CI 1.76-2.98), and either ischaemic heart disease or cerebrovascular disease (28.3% vs. 12.5%, adjusted RR 1.94, 95% CI 1.60-2.35). Subgroup analysis showed that in psoriasis patients with depression, a higher risk of incident ischaemic heart disease or cerebrovascular disease was present in age groups 30-100 years, in both males and females, and in both lower and higher income categories. CONCLUSION: Depression is an independent risk factor for incident ischaemic heart disease and cerebrovascular disease in patients with psoriasis. Therefore, clinicians need to be vigilant for the increased vascular risk in psoriasis patients with depression.

Analysis of metabolic profiles of generalized aggressive periodontitis.

BACKGROUND AND OBJECTIVE: The specific pathogenesis of generalized aggressive periodontitis (GAgP) has not yet been clarified, and few studies have focused on the association between GAgP and metabolomics. To elucidate the roles of metabolic profiles in the status of GAgP, this study aimed to identify the differential metabolic profiles between patients with GAgP and healthy controls using an untargeted metabolomic profiling method. MATERIAL AND METHODS: Serum and gingival crevicular fluid samples were collected from healthy controls (n = 20) and patients with GAgP (n = 20) in this cross-sectional study. The relative levels of biomarkers in the samples were measured by gas chromatography-mass spectrometry. Principal components analysis and orthogonal partial least-squares discriminant analysis were used for statistical analysis. Metabolites were analysed qualitatively using the FiehnLib and NIST databases. Full-mouth probing depth and clinical attachment loss were recorded as indexes of periodontal disease. RESULTS: A total of 349 metabolites were qualitatively detected in the gingival crevicular fluid samples, and 200 metabolites were detected in the serum samples. Compared with healthy controls, patients with GAgP showed significant increases in serum urea and allo-inositol levels. In contrast, glutathione, 2,5-dihydroxybenzaldehyde, adipic acid and 2-deoxyguanosine levels were decreased in patients with GAgP. In the gingival crevicular fluid samples, noradrenaline, uridine, α-tocopherol, dehydroascorbic acid, xanthine, galactose, glucose-1-phosphate and ribulose-5-phosphate levels were increased in patients with GAgP, while thymidine, glutathione and ribose-5-phosphate levels were decreased. CONCLUSION: The metabolomics analysis by gas chromatography-mass spectrometry is an effective and minimally non-invasive way to differentiate the metabolites characteristic of patients with GAgP. Both serum and gingival crevicular fluid metabolomics are significantly different between patients with GAgP and healthy controls. These metabolic profiles have great potential in detecting GAgP and helping to understand its underlying mechanisms.

Factors affecting the use of anti-amoebiasis protective measures among Taiwan immigrants returning to amoebiasis-endemic regions.

OBJECTIVE: To investigate the predictors of use of anti-amoebiasis protective measures (AAPMs) among Taiwan immigrants returning to their country of origin, using the Health Belief Model (HBM) to guide the investigation. DESIGN: Cross-sectional study. METHODS: Between March and May 2011, all permanent immigrants originating from amoebiasis-endemic countries who received services at the immigrant service centres in Taipei or Tainan and who reported that they had returned to their country of origin within the past five years were enrolled in the study. A structured questionnaire containing questions on sociodemographic characteristics and items related to the constructs of the HBM was used as the data collection instrument. RESULTS: Complete information was collected from 384 immigrants, with a response rate of 80% (384/480). The mean age of the subjects was 38.4 years (standard deviation 10.6 years). The majority (70%) of participants did not receive travel information through a pretravel consultation, and more than 17% reported that they did not use measures to prevent amoebiasis. Multiple regression analyses revealed that Chinese proficiency, pretravel consultation and lower barriers to using protective measures were significantly associated with the use of AAPMs during return trips to country of origin (R(2) = 0.45; F = 77.5; P < 0.001). CONCLUSION: The HBM significantly predicted the use of AAPMs in this study. A high proportion of immigrants did not use appropriate AAPMs when they returned to their country of origin. Educational approaches should be targeted at immigrants originating from amoebiasis-endemic regions who return to their country of origin.

Mutations in NR5A1 and PIN1 associated with idiopathic hypogonadotropic hypogonadism.

We tested the hypothesis that mutations in NR5A1 and PIN1 cause disorders in gonadotropin-gonadal system development and function, throught direct DNA sequencing of the coding sequence and splice-sites of NR5A1 and PIN1 in 50 subjects with sporadic idiopathic hypogonadotropic hypogonadism. These patients were recruited from the Pediatrics section of Tongji Hospital, Tongji Medical College, in Wuhan, China. None of the affected subjects had clinical signs of adrenal insufficiency. The NR5A1 and PIN1 mutations were found in 7 of the 50 cases. These 7 individuals presented severely low serum concentrations of testosterone or of estradiol and gonadotropin. Adrenal insufficiency was not diagnosed in any of these patients. Consequently, NR5A1 and PIN1 mutations should be considered in idiopathic hypogonadotropic hypogonadism patients with normal karyotypes and without adrenal insufficiency.

Rainbow pattern in Kaposi's sarcoma under polarized dermoscopy: a dermoscopic pathological study.

BACKGROUND: We found previously that the features of Kaposi's sarcoma (KS) under polarized dermoscopy are characterized by a bluish-reddish coloration, a scaly surface, small brown globules and, most distinctively, the multicoloured 'rainbow pattern'. OBJECTIVES: To evaluate the significance of the rainbow pattern on dermoscopy as a diagnostic feature in KS, and to demonstrate that it is associated with the unique vascular structure of the tumour. METHODS: More than 100 lesions from seven patients with histologically proven KS were examined with polarized light dermoscopy. Sixty-three patients with various other cutaneous vascular and nonvascular tumours were also examined. KS lesions exhibiting the rainbow pattern and KS lesions lacking the rainbow pattern on dermoscopy were excised, and dermoscopic features were compared with histopathological structures. The dermoscopic patterns of other vascular tumours were also compared with histological features. In addition, the changes in dermoscopic features and histological structures were assessed before and after surgical therapy in one patient with KS. RESULTS: On the basis of evaluations with polarized dermoscopy, the rainbow pattern was found to be a highly specific dermoscopic feature for KS. Histology of KS lesions showing the rainbow pattern under polarized light dermoscopy demonstrated a vascular lumen-rich pattern of closely arranged 'back-to-back' vascular structures, whereas histology of KS lesions without the rainbow pattern showed a vascular lumen-poor pattern with vascular lumina separated further apart by intervening stromal and cellular tissue. Other vascular tumours did not exhibit the rainbow pattern and were characterized histologically by variably sized vascular structures separated by substantial amounts of stromal and cellular tissue. In one patient with KS, disappearance of the rainbow pattern was associated with obliteration of the vascular structure following surgical ablation therapy. CONCLUSIONS: The rainbow pattern in KS is associated with the vascular lumen-rich histological subtype, is not manifest in the vascular lumen-poor subtype and disappears following total tumour removal. Therefore, the underlying structural arrangement of the vessels in KS may determine whether or not the rainbow pattern can be seen on polarized dermoscopy.

Dermoscopy of Kaposi's sarcoma: areas exhibiting the multicoloured 'rainbow pattern'.

BACKGROUND: Kaposi's sarcoma is a vascular tumour characterized by a proliferation of spindle cells and endothelial cells to form closely arranged slit-like vascular spaces. Currently, the definitive diagnosis of Kaposi's sarcoma relies on histology. The dermoscopic features of Kaposi's sarcoma are not clearly defined in the scientific literature. OBJECTIVES: We seek to evaluate the dermoscopic features of Kaposi's sarcoma and compare them with other vascular tumours. METHODS: One hundred forty-one lesions from seven patients with histologically proven Kaposi's sarcoma were evaluated using polarized light dermoscopy for the presence of various dermoscopic features. Twenty patients with other vascular tumours were also examined. RESULTS: Dermoscopic examination revealed bluish-reddish coloration (84% of lesions), multicoloured areas showing various colours of the rainbow spectrum (36%), scaly surface (29%), and small brown globules (15%). The 'rainbow pattern' was found in six out of seven patients with Kaposi's sarcoma and was not observed in other vascular tumours. In addition, there was an absence of dermoscopic features specific for other vascular and non-vascular skin tumours, such as well-defined lacunae or structured vascular pattern, in most of the Kaposi's sarcoma lesions. CONCLUSIONS: The most frequent dermoscopic patterns in Kaposi's sarcoma were found to be bluish-reddish coloration, the 'rainbow pattern', and scaly surface. The rainbow pattern is a dermoscopic feature which has not been previously described. We propose that dermoscopy, as an adjunct to clinical examination, may enhance accuracy in the preoperative diagnosis of Kaposi's sarcoma.

[Clinical and genetic manifestations of immunodeficiency, centromeric instability, and facial anomalies syndrome: a case report and literature review].

Objective: To analyze the clinical and genetic features of immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome with a case report and literature review. Methods: The clinical data and genetic test of a girl diagnosed with ICF syndrome in the Department of Nephrology and Immunology in Qingdao Women and Children's Hospital in December 2016 were extracted and analyzed. "ICF syndrome" "immunodeficiency, centromeric instability and facial anomalies syndrome" "ICF syndrome and DNMT3B" were used as key words to search Chinese databases and Pubmed for literature until March 2018, and the literature was reviewed. Results: A female patient aged 22 months old with ocular hypertelorism and low-set ears was admitted due to recurrent infection over one year. Laboratory tests showed humoral immune deficiency with IgG<1.34 g/L, IgA<0.060 g/L, and IgM<0.179 g/L, but normal cellular immunity (total T lymphocyte 0.503, hepler T lymphocyte 0.328, cytotoxic T lymphocyte 0.166, natural killer cell 0.184, total B lymphocyte 0.276). Whole-exome sequencing revealed a de novo heterozygous splice site mutation c.922-2A>G in intron 8, and a de novo heterozygous missense mutation c.2477G>A in exon 23 of DNMT3B gene. Chromosome karyotype analysis showed 46, XX, with 64 out of 100 karyotypes showing centromere instability in chromosome 1. Five papers were found which were all in English, with total of 29 patients. Forty-three mutations were reported, including 34 missense, 2 deletion, 1 insertion, 6 splice site mutations. Eleven patients had complex heterozygosis mutations. All patients had centromere instability, humoral immune deficiency and facial dysplasia which were mainly ocular hypertelorism and low-set ears. Most patients had language and motor development delay, and a few were combined with mental retardation. Conclusions: ICF syndrome is a rare autosomal recessive primary immunodeficiency with classic clinical triad manifestations. De novo mutation of DNMT3B gene is one of etiologies according to genetic test.

Regulation of CBP-mediated transcription by neuronal calcium signaling.

The transcription factor CREB is involved in mediating many of the long-term effects of activity-dependent plasticity at glutamatergic synapses. Here, we show that activation of NMDA receptors and voltage-sensitive calcium channels leads to CREB-mediated transcription in cortical neurons via a mechanism regulated by CREB-binding protein (CBP). Recruitment of CBP to the promoter is not sufficient for transactivation, but calcium influx can induce CBP-mediated transcription via two distinct transactivation domains. CBP-mediated transcription is stimulus strength-dependent and can be induced by activation of CaM kinase II, CaM kinase IV, and protein kinase A, but not by activation of the Ras-MAP kinase pathway. These observations indicate that CBP can function as a calcium-sensitive transcriptional coactivator that may act as a regulatory switch for glutamate-induced CREB-mediated transcription.

Identification of a signaling pathway involved in calcium regulation of BDNF expression.

A signaling pathway by which calcium influx regulates the expression of the major activity-dependent transcript of BDNF in cortical neurons has been elucidated. Deletion and mutational analysis of the promoter upstream of exon III reveals that transactivation of the BDNF gene involves two elements 5' to the mRNA start site. The first element, located between 72 and 47 bp upstream of the mRNA start site, is a novel calcium response element and is required for calcium-dependent BDNF expression in both embryonic and postnatal cortical neurons. The second element, located between 40 and 30 bp upstream of the mRNA start site, matches the consensus sequence of a cAMP response element (CRE) and is required for transactivation of the promoter in postnatal but not embryonic neurons. The CRE-dependent component of the response appears to be mediated by CREB since it is part of the complex that binds to this CRE, and since dominant negative mutants of CREB attenuate transactivation of the promoter. A constitutively active mutant of CaM kinase IV, but not of CaM kinase II, leads to activation of the promoter in the absence of extracellular stimuli, and partially occludes calcium-dependent transactivation. The effects of CaM kinase IV on the promoter require an intact CRE. These mechanisms, which implicate CaM kinase IV and CREB in the control of BDNF expression, are likely to be centrally involved in activity-dependent plasticity during development.

Cutaneous metastases from different internal malignancies: a clinical and prognostic appraisal.

BACKGROUND: Cutaneous metastases are perceived as a sign of advanced disease and are regarded as a grave prognostic indicator. In addition, few reports have focused on the cutaneous metastasis profiles of Asian patients. OBJECTIVES: We seek to analyse the clinical and prognostic characteristics of cutaneous tumour metastases in a Taiwanese medical centre. METHODS: Clinical records from Kaohsiung Medical University Hospital over the last 20 years (1986-2006) were reviewed, and cases of biopsy-proven cutaneous metastases from internal malignancies identified. Survival rates were evaluated using the Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used for univariate analysis to determine the risk of mortality among different groups. RESULTS: A total of 141 cases of cutaneous metastases were identified. The clinical profiles were similar to those from western countries, although the frequencies of primary tumours were different. The duration of survival was usually short following diagnosis of cutaneous metastases, but prognosis is significantly better in breast cancer patients with metastases. Moreover, the survival was even longer for breast cancer patients when the metastasis was confined to the skin. CONCLUSIONS: The risk of skin metastases depends largely on the characteristics of tumour cells, which is similar among different ethnic groups. In terms of prognosis, a subset of breast cancer patients has superior prognosis, even among breast cancer patients with stage IV disease. Physicians should consider this finding in clinical situations to avoid possible misinformation about the prognosis of the disease.

Pigmented eccrine poromas: expression of melanocyte-stimulating cytokines by tumour cells does not always result in melanocyte colonization.

BACKGROUND: Although eccrine poroma (EP) occurs preferentially in palmoplantar areas, pigmented variants of EP have not been documented on the palms and soles. OBJECTIVES: We seek to confirm the notion regarding lack of pigmented EP on palmoplantar areas and determine whether the absence of pigmentation in palmoplantar EPs is due to lack of expression of melanocyte-stimulating cytokines by tumour cells. METHODS: We searched the PubMed and Web of Science databases (1966-2006) for reports of pigmented EPs. In addition, a total of 17 EPs were collected from our pathology department. The presence of melanin was examined with haematoxylin-eosin sections, and melanocyte colonization was shown by immunohistochemical stains for tyrosinase. In addition, immunohistochemical staining with antibodies to melanocyte-stimulating cytokines, including endothelin-1, stem cell factor, and nerve growth factor, was done on these tumours. RESULTS: A review of the literature revealed 15 pigmented EP reports, none of which were located in palmoplantar areas. Among 17 EPs collected from our pathology department, 7 occurred in palmoplantar areas and 10 in non-palmoplantar areas. Three of the palmoplantar EPs and three of the non-palmoplantar EPs showed positive staining with melanocyte-stimulating cytokines. However, none of the palmoplantar EPs contained melanocytes or melanin pigment, wheras the three non-palmoplantar EPs that stained positively with melanocyte-stimulating cytokines were colonized with melanocytes and showed pigmentation clinically. CONCLUSIONS: The expression of melanocyte-stimulating factors by tumour cells is associated with melanocyte colonization in non-palmoplantar EPs but not palmoplantar EPs. Therefore, the presence of melanocyte-stimulating cytokines per se is not sufficient by itself to induce melanocyte colonization. Certain characteristics of palmoplantar skin, such as the dermal components of these anatomical sites, may play a role in inhibiting melanocyte colonization of EPs.

Workplace smoking related absenteeism and productivity costs in Taiwan.

OBJECTIVE: To estimate productivity losses and financial costs to employers caused by cigarette smoking in the Taiwan workplace. METHODS: The human capital approach was used to calculate lost productivity. Assuming the value of lost productivity was equal to the wage/salary rate and basing the calculations on smoking rate in the workforce, average days of absenteeism, average wage/salary rate, and increased risk and absenteeism among smokers obtained from earlier research, costs due to smoker absenteeism were estimated. Financial losses caused by passive smoking, smoking breaks, and occupational injuries were calculated. RESULTS: Using a conservative estimate of excess absenteeism from work, male smokers took off an average of 4.36 sick days and male non-smokers took off an average of 3.30 sick days. Female smokers took off an average of 4.96 sick days and non-smoking females took off an average of 3.75 sick days. Excess absenteeism caused by employee smoking was estimated to cost USD 178 million per annum for males and USD 6 million for females at a total cost of USD 184 million per annum. The time men and women spent taking smoking breaks amounted to nine days per year and six days per year, respectively, resulting in reduced output productivity losses of USD 733 million. Increased sick leave costs due to passive smoking were approximately USD 81 million. Potential costs incurred from occupational injuries among smoking employees were estimated to be USD 34 million. CONCLUSIONS: Financial costs caused by increased absenteeism and reduced productivity from employees who smoke are significant in Taiwan. Based on conservative estimates, total costs attributed to smoking in the workforce were approximately USD 1032 million.