[Modification of allergic dermatitis on the associations between early-life exposure to size-specific particulate matter and childhood allergic rhinitis].

To evaluate the modification of allergic dermatitis on the association between PM exposure and allergic rhinitis in preschool children. This cross-sectional study was based on a questionnaire conducted between June 2019 and June 2020 to caregivers of children aged 3 to 6 years in the kindergartens of 7 Chinese cities to collect information on allergic rhinitis and allergic dermatitis. A mature machine learning-based space-time extremely randomized trees model was applied to estimate early-life, prenatal, and first-year exposure of PM1, PM2.5 and PM10 at 1 km×1 km resolution. A combination of multilevel logistic regression and restricted cubic spline functions was used to quantitatively assess whether allergic dermatitis modifies the associations between size-specific PM exposure and the risk of childhood allergic rhinitis. The results showed that out of 28 408 children, 14 803 (52.1%) were boys and 13 605 (47.9%) were girls; the age of children ranged from 3.1 to 6.8 years, with a mean age of (4.9±0.9) years, of which 3 586 (12.6%) were diagnosed with allergic rhinitis. Among all children, 17 832 (62.8%) were breastfed for more than 6 months and 769 (2.7%) had parental history of atopy. A total of 21 548 children (75.9%) had a mother with an educational level of university or above and 7 338 (29.6%) had passive household cigarette smoke exposure. The adjusted ORs for childhood allergic rhinitis among the children with allergic dermatitis as per interquartile range (IQR) increase in early-life PM1(9.8 µg/m3), PM2.5 (14.9 µg/m3) and PM10 (37.7 µg/m3) were significantly higher than the corresponding ORs among the children without allergic dermatitis [OR: 1.45, 95%CI (1.26, 1.66) vs. 1.33, 95%CI (1.20, 1.47), for PM1; OR: 1.38, 95%CI (1.23, 1.56) vs. 1.32, 95%CI (1.21, 1.45), for PM2.5; OR: 1.56, 95%CI (1.31, 1.86) vs. 1.46, 95%CI (1.28, 1.67), for PM10]. The interactions between allergic dermatitis and size-specific PM exposure on childhood allergic rhinitis were statistically significant (Z value=19.4, all P for interaction<0.001). The similar patterns were observed for both prenatal and first-year size-specific PM exposure and the results of the dose-response relationship were consistent with those of the logistic regression. In conclusion, allergic dermatitis, as an important part of the allergic disease progression, may modify the association between ambient PM exposure and the risk of childhood allergic rhinitis. Children with allergic dermatitis should pay more attention to minimize outdoor air pollutants exposure to prevent the further progression of allergic diseases.

New insights into early recovery after robotic surgery for endometrial cancer.

OBJECTIVE: To assess early recovery of physical health after robotic minimally invasive surgery (RMIS) for early-stage endometrial cancer using the European Organisation of Research and Treatment of Cancer Computer Adaptive Test Core questionnaire (EORTC CAT Core). The EORTC CAT Core provides individualised measurements while maintaining comparability. A hypothesis of individual complete recovery to baseline within three post-surgical weeks was evaluated. METHODS: Ninety-four women who underwent RMIS for early-stage endometrial cancer were included consecutively. The EORTC CAT Core was distributed before surgery and prospectively every week during the first post-operative month. Repeated measures models were fitted for each of the four domains (physical functioning, role function, fatigue, and pain) and tested for impact of age, ASA score, minor/major surgery, and the individual baseline scores (poorest, intermediate, best). RESULTS: Women with the lowest physical functioning, lowest role function, highest fatigue level, and highest pain level at baseline all recovered within three weeks. Women with the highest physical functioning, highest role function, lowest level of fatigue, and lowest level of pain at baseline did not reach their individual baselines within the first post-operative month but had the most favourable domain-scores three weeks post-operatively. CONCLUSION: The individual woman's physical health baseline score is predictive for her postoperative recovery following RMIS for early-stage endometrial cancer. Women with the best physical health had the best postoperative functions and lowest level of symptoms; however their recovery to baseline was prolonged. Computer adaptive testing may be a valuable tool for individualised pre-operative information and supportive care during surveillance.

Risk profiles of personality traits for suicidality among mood disorder patients and community controls.

OBJECTIVE: To examine the associations between personality traits and suicidal ideation (SI) and attempt (SA) in mood disorder patients and community controls. METHOD: We recruited 365 bipolar, 296 major depressive disorder patients, and 315 community controls to assess their lifetime suicidality. Participants filled out self-reported personality questionnaires to collect data of personality traits, including novelty seeking (NS), harm avoidance (HA), extraversion (E), and neuroticism (N). We used logistic regression models adjusted for diagnoses to analyze combinational effects of personality traits on the risk of suicide. Additionally, radar charts display personality profiles for suicidal behaviours by groups. RESULTS: All personality traits were associated with the risk of suicidality with various effect size, except for E that showed protective effect. High N or HA had prominent and independent risk effects on SI and SA. Combinations of high N and low E, or high HA and NS were the risk personality profiles for suicidality. Higher N scores further distinguished SA from SI in mood disorder patients. CONCLUSION: Introvert personality traits showed independent risk effects on suicidality regardless of diagnosis status. Among high-risk individuals with suicidal thoughts, higher neuroticism tendency is further associated with increased risk of suicide attempt.

Comparative effect of antipsychotics on risk of self-harm among patients with schizophrenia.

OBJECTIVE: To investigate the association of different antipsychotic treatments with hospitalization due to self-harm among patients with schizophrenia. METHOD: This retrospective cohort study was based on Taiwan's universal health insurance database. Patients aged 15-45 years with a newly diagnosed schizophrenic disorder in 2001-2012 were included. The study outcome was the first hospitalization due to self-harm or undetermined injury after the diagnosis of schizophrenic disorders. The exposure status of antipsychotics was modeled as a time-dependent variable. The analyses were stratified by antipsychotic dosage based on defined daily dose (DDD). RESULTS: Among 70 380 patients with a follow-up of 500 355 person-years, 2272 self-harm hospitalization episodes were identified. Compared with none or former use, current use of several second-generation antipsychotics with a dose of one DDD or above, including amisulpride, aripiprazole, clozapine, risperidone, and sulpiride, was associated with decreased risk of self-harm hospitalization, with clozapine showing the strongest effect (adjusted rate ratio = 0.26, 95% confidence interval 0.15-0.47). CONCLUSION: The protective effect on self-harm may vary across different antipsychotics. Further studies are needed to replicate the findings.

[A therapeutic effect analysis of femur first principle and combined anteversion technique during total hip arthroplasty].

Objective: To investigate the situation of hip dislocation with the application of "femur first" principle and "combined anteversion technique" during total hip arthroplasty. Methods: A retrospective analysis has been done on the clinical data about 104 patients(133 hips)who were diagnosed as hip disease and were treated with total hip arthroplasty by the doctors from the Department of Joint Orthorpaedics of Shandong Provincial Hospital Affiliated to Shandong University from June 2014 to June 2016, and all the prostheses applied in the operation were cementless ones.Among them, 65 patients were males, 39 females and their age was 46.6 years (ranging from 23 to 76 years) .And 29 of them underwent bilateral hip operations and 75 unilateral ones.Seventy-six cases of aseptic necrosis of the femoral head in the terminal stage, 28 cases of hip dysplasia and osteoarthritis.Surgical approach: of all the operations, 103 hips were operated on with hardinge approach, 30 with posterolateral approach.During the operation, first of all, the femoral medullary cavity was broached and then the anteversion of intramedullary broacher was measured.After that, the anteversion of the acetabular cup was calculated as 37° minus the anteversion of the broacher, and the acetabular cup was implanted at that angle.The patients' prosthesis combined anteversion, range of motion of the hip joint, operation time, hemorrhage amount, and complications had been kept record.One, three, and six months respectively after the operation, all the patients received outpatient review, and took anteroposterior and lateral position X-ray examination.Harris hip score had been applied to evaluate their hip function before the operation and six months after the operation. Results: All the patients had been operated on smoothly, with the operation time of(57.6±14.5)minutes(36-115 minutes)and hemorrhage amount of (336.5±50.8)ml(180-620 ml). The operation finding showed that the combined anteversion by employing"femur first"principle and combined anteversion techniqueis was (36.6±6.8)°. Also, range of motion of the patients' hip conforms to the D'Lima criterion and no patients had experienced dislocation and some other serious complications.The follow-up ended at August 2017, which lasted for 12.2 months(6-18 months), and 88 cases(119 hips) were interviewed. The Harris hip score for the affected sides of the hip joints 6 months after the surgery was 94.6(86-100). Compared with the score of 29.8(12-43) before surgery, the t-test had proven its statistical significance(t=12.82, P=0.003). Conclusion: Based upon the "femoral first" principle and "combined anteversion technique" during total hip arthroplasty, these operations has been carried out well enough to meet the patients' needs of performing normal daily activities.

Diode-pumped orthogonally polarized self-mode-locked Nd:YLF lasers subject to gain competition and thermal lensing effect.

The stable condition for π-polarization emission in an a-cut Nd:YLF laser is numerical analyzed to find the critical pump power for generating the orthogonally polarized emission. With the numerical analysis, an orthogonally polarized SML lasers at wavelength of 1047 nm and 1053 nm is experimentally achieved in a simple concave-plano cavity without any additional optical element. It is experimentally observed that the polarization switching and coexistence was successfully demonstrated by introducing gain competition and anisotropic thermal lens effect. In the orthogonal polarization mode-locked operation, the pulse durations are found to be 19.1 and 18.8 ps for π- and σ-polarization with pulse repetition rates of 3.85 and 3.89 GHz, respectively.

Comparative risk of self-harm hospitalization amongst depressive disorder patients using different antidepressants: a population-based cohort study in Taiwan.

BACKGROUND: The aim of the study was to evaluate the comparative risk of self-harm associated with the use of different antidepressants. METHOD: A cohort study was conducted using data from Taiwan's National Health Insurance Research Database from 2001 to 2012. A total of 751 606 new antidepressant users with depressive disorders were included. The study outcome was hospitalization due to self-harm (International Classification of Diseases, Ninth Revision, Clinical Modification codes: E950-E958 and E980-E988). Cox proportional hazards models with stratification of the propensity score deciles were used to estimate the hazard ratios of self-harm hospitalization during the first year following the initiation of antidepressant treatment. RESULTS: There were 1038 hospitalization episodes due to self-harm that occurred during the follow-up of 149 796 person-years, with an overall incidence rate of 6.9 [95% confidence interval (CI) 6.5-7.4] per 1000. Compared with fluoxetine, the risk of self-harm hospitalization was higher for maprotiline [adjusted hazard ratio (aHR) = 3.00, 95% CI 1.40-6.45], milnacipran (aHR = 2.34, 95% CI 1.24-4.43) and mirtazapine (aHR = 1.40, 95% CI 1.06-1.86), lower for bupropion (aHR = 0.51, 95% CI 0.30-0.86), and similar level of risk was found for other selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine, paroxetine and sertraline). CONCLUSIONS: The risk of self-harm may vary across different antidepressant drugs. It would be of importance to conduct further research to investigate the influence of antidepressant use on self-harm behaviors.

Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity.

BACKGROUND/OBJECTIVES: Cannabinoid receptor 1 (CB1) is the best-characterized cannabinoid receptor, and CB1 antagonists are used in clinical trials to treat obesity. Because of the wide range of CB1 functions, the side effects of CB1 antagonists pose serious concerns. G-protein-coupled receptor 55 (GPR55) is an atypical cannabinoid receptor, and its pharmacology and functions are distinct from CB1. GPR55 regulates neuropathic pain, gut, bone, immune functions and motor coordination. GPR55 is expressed in various brain regions and peripheral tissues. However, the roles of GPR55 in energy and glucose homeostasis are unknown. Here we have investigated the roles of GPR55 in energy balance and insulin sensitivity using GPR55-null mice (GPR55(-/-)). METHODS: Body composition of the mice was measured by EchoMRI. Food intake, feeding behavior, energy expenditure and physical activity of GPR55(-/-) mice were determined by indirect calorimetry. Muscle function was assessed by forced treadmill running test. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Adipose inflammation was assessed by flow cytometry analysis of adipose tissue macrophages. The expression of inflammatory markers in adipose tissues and orexigenic/anorexigenic peptides in the hypothalamus was also analyzed by real-time PCR. RESULTS: GPR55(-/-) mice had normal total energy intake and feeding pattern (i.e., no changes in meal size, meal number or feeding frequency). Intriguingly, whereas adult GPR55(-/-) mice only showed a modest increase in overall body weight, they exhibited significantly increased fat mass and insulin resistance. The spontaneous locomotor activity of GPR55(-/-) mice was dramatically decreased, whereas resting metabolic rate and non-shivering thermogenesis were unchanged. Moreover, GPR55(-/-) mice exhibited significantly decreased voluntary physical activity, showing reduced running distance on the running wheels, whereas muscle function appeared to be normal. CONCLUSIONS: GPR55 has an important role in energy homeostasis. GPR55 ablation increases adiposity and insulin resistance by selectively decreasing physical activity, but not by altering feeding behavior as CB1.

Comparison of two methods for RNA extraction from the nucleus pulposus of intervertebral discs.

RNA extraction from the nucleus pulposus of intervertebral discs has been extensively used in orthopedic studies. We compared two methods for extracting RNA from the nucleus pulposus: liquid nitrogen grinding and enzyme digestion. The RNA was detected by agarose gel electrophoresis, and the purity was evaluated by absorbance ratio using a spectrophotometer. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression was assayed by reverse transcription-polymerase chain reaction (RT-PCR). Thirty human lumbar intervertebral discs were used in this study. The liquid nitrogen-grinding method was used for RNA extraction from 15 samples, and the mean RNA concentration was 491.04 ± 44.16 ng/mL. The enzyme digestion method was used on 15 samples, and the mean RNA concentration was 898.42 ± 38.64 ng/mL. The statistical analysis revealed that there was a significant difference in concentration between the different methods. Apparent 28S, 18S, and 5S bands were detectable in RNA extracted using the enzyme digestion method, whereas no 28S or 18S bands were detected in RNA extracted using the liquid nitrogen-grinding method. The GAPDH band was visible, and no non-specific band was detected in the RT-PCR assay by the enzyme digestion method. Therefore, the enzyme digestion method is an efficient and easy method for RNA extraction from the nucleus pulposus of intervertebral discs for further intervertebral disc degeneration-related studies.

The association of peer pressure and peer affiliation with the health risk behaviors of secondary school students in Hong Kong.

OBJECTIVE: The aim of this study was to explore the relationship between peer pressure and the health risk behaviors of secondary school students. STUDY DESIGN: Cross-sectional study using a self-completed questionnaire. METHODS: Secondary school students in Year 3 were the target population of this study. Information was solicited from students on their perceptions of peer pressure using a questionnaire employing the Peer Pressure Inventory and their involvement in risk behaviors using a modified global school-based student health survey. RESULTS: A total of 840 secondary students from Hong Kong completed the questionnaires. The prevalence of secondary students who had ever smoked was 6.4%, consumed alcohol 39.2%, ever used drugs 0.5%, were sexually active 3.9%, and involved in bullying 20.5%. A higher proportion of secondary students involved in risk behaviors were affiliated with peers who were involved in the same activities: smoking (48.9%), drinking alcohol (86.5%), using drugs (18.2%), engaged in sexual activity (34.5%), and bullying (82.6%). The perception of peer conformity and peer involvement was found to be significantly correlated with the students' health risk behaviors, particularly with regard to smoking, drinking alcohol, and bullying. A logistic regression analysis showed that having friends who are involved in the same risk behaviors is the single most important factor associated with the participation of secondary students in those specific risk behaviors. CONCLUSIONS: The results of this study provided a better understanding of the association between peer pressure and the adoption of health behaviors. The development of effective peer-led prevention programs to reduce the uptake of health risk behaviors should therefore be promoted to prevent adolescents from developing serious health problems.

Hypersingular meshless method using double-layer potentials for three-dimensional exterior acoustic problems.

Three-dimensional exterior acoustic problems with irregular domains are solved using a hypersingular meshless method. In particular, the method of fundamental solutions (MFS) is used to formulate and analyze such acoustic problems. It is well known that source points for MFS cannot be located on the real boundary due to the singularity of the kernel functions. Thus, the diagonal terms of the influence matrices are unobtainable when source points are located on the boundary. An efficient approach is proposed to overcome such difficulties, when the MFS is used for three-dimensional exterior acoustic problems. This work is an extension of previous research on two-dimensional problems. The solution of the problem is expressed in terms of a double-layer potential representation on the physical boundary. Three examples are presented in which the proposed method is compared to the MFS and boundary element method. Good numerical performance is demonstrated by the proposed hypersingular meshless method.

Antipsychotic exposure prior to acute myocardial infarction in patients with serious mental illness.

OBJECTIVE: To investigate the association between acute myocardial infarction (AMI) and recent exposure to antipsychotic agents in people with serious mental illness (SMI), and modifying influences. METHOD: A case-crossover design was applied using the Taiwan National Health Insurance Research Database (NHIRD) to compare the exposure frequency of antipsychotic agents within individuals of schizophrenia or bipolar disorder between 60-day case and control periods prior to their first AMI episode during 1996-2007. RESULTS: A sample of 834 patients with incident AMI was analysed. AMI was significantly associated with more recent antipsychotic exposure in schizophrenia after adjustment (OR 1.87, 95% confidence interval 1.15-3.03) bipolar disorder (OR 1.06, 0.51-2.21). This association in schizophrenia was significantly stronger in men and in patients without previous diagnoses of cardiovascular risk factors. CONCLUSION: These findings are consistent with a short-term risk effect of antipsychotic exposure on risk of AMI and identify potentially vulnerable groups. Further research is required to clarify underlying biological mechanisms.

The ultraviolet A-activated photosensitizer 2-(4-aminophenyl)-7-methoxybenzothiazole suppresses proliferation and induces apoptosis of keloid fibroblasts: a potential adjunctive therapy for keloids.

BACKGROUND: Photodynamic therapy (PDT), a therapeutic approach employing a photosensitizer and a specific wavelength of light, is an emerging option for treating neoplastic and nonneoplastic diseases. Keloids are fibroproliferative dermal lesions characterized by the proliferation of fibroblasts. Recently, PDT has been demonstrated as a potential treatment for keloids. AIM: To investigate the effects of our newly synthesized photosensitizer 2-(4-aminophenyl)-7-methoxybenzothiazole (6d) plus ultraviolet (UV)A irradiation (6d-UVA) on proliferation and apoptosis in keloid fibroblasts (KFs). METHODS: Fibroblasts cultured from normal skin and keloids were treated with 6d-UVA. Relevant assays including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 5-bromo-2'-deoxyuridine incorporation assay, immunofluorescence assay and flow cytometry analysis were performed. RESULTS: The combination of 6d (2.0 or 5.0 µmol/L) and UVA 0.5 J/cm(2) significantly decreased the viability and proliferation of KFs but not normal fibroblasts (NFs). Cell cycle analyses showed significant G0/G1 arrest and increased sub-G1 distribution in NFs induced by UVA-activated 6d at 5.0 µmol/L (hereafter referred to as 6d-UVA). This treatment also significantly induced generation of intracellular reactive oxygen species (ROS), loss of mitochondrial membrane potential (ΔΨm), and increased expression of active caspase-3. Pretreatment with N-acetyl-L-cysteine (aROS scavenger) reversed the increased active caspase-3 expression induced by 6d-UVA, indicating the involvement of ROS in 6d-UVA-induced apoptosis. CONCLUSIONS: This study indicates that 6d-UVA treatment exerts antiproliferative and pro-apoptotic effects in KFs. We propose that 6d-UVA could be a potentially usefull ancillary method for keloid treatment.

Comparison of amoxicillin + clavulanate with or without intranasal fluticasone for the treatment of uncomplicated acute rhinosinusitis in children.

AIM: Intranasal corticosteroids (INS) have been proven effective in controlling postnasal drip, decreasing inflammatory response, reducing nasal swelling, and increasing aeration of the sinuses such that INS are recommended as treatment of sinusitis. METHODS: Fifty children with acute rhinosinusitis, 50 children with acute rhiniosinusitis and allergic rhinitis (AR), and 20 rhiniosinusitis children as control were selected for investigation. Each group had a single-blind treatment of three types: with coamoxiclav only, with coamoxiclav plus INS, and with matched placebo (without antibiotics and INS) for two weeks. Nasal symptoms were then evaluated. The outcome was measured by using major symptom score (MSS) after treatment for 14 days. RESULTS: Therapeutic effectiveness was 92% in rhinosinusitis patients treated with co-amoxiclav and 84% in those treated with co-amoxiclav plus INS. Among patients with sinusitis combined with AR, therapeutic efficacy was 88% for those treated with co-amoxiclav and 96% for those treated with co-amoxiclav plus INS. Only 30% of the symptoms were reduced in the placebo group. CONCLUSION: There are no statistical differences in the acute sinusitis group treated with co-amoxiclav with or without INS. In the sinusitis with AR group, the efficacy of co-amoxiclav with INS is higher than in children treated with co-amoxiclav alone.

Mapping forested wetlands in the Great Zhan River Basin through integrating optical, radar, and topographical data classification techniques.

Knowledge of the spatial extent of forested wetlands is essential to many studies including wetland functioning assessment, greenhouse gas flux estimation, and wildlife suitable habitat identification. For discriminating forested wetlands from their adjacent land cover types, researchers have resorted to image analysis techniques applied to numerous remotely sensed data. While with some success, there is still no consensus on the optimal approaches for mapping forested wetlands. To address this problem, we examined two machine learning approaches, random forest (RF) and K-nearest neighbor (KNN) algorithms, and applied these two approaches to the framework of pixel-based and object-based classifications. The RF and KNN algorithms were constructed using predictors derived from Landsat 8 imagery, Radarsat-2 advanced synthetic aperture radar (SAR), and topographical indices. The results show that the objected-based classifications performed better than per-pixel classifications using the same algorithm (RF) in terms of overall accuracy and the difference of their kappa coefficients are statistically significant (p<0.01). There were noticeably omissions for forested and herbaceous wetlands based on the per-pixel classifications using the RF algorithm. As for the object-based image analysis, there were also statistically significant differences (p<0.01) of Kappa coefficient between results performed based on RF and KNN algorithms. The object-based classification using RF provided a more visually adequate distribution of interested land cover types, while the object classifications based on the KNN algorithm showed noticeably commissions for forested wetlands and omissions for agriculture land. This research proves that the object-based classification with RF using optical, radar, and topographical data improved the mapping accuracy of land covers and provided a feasible approach to discriminate the forested wetlands from the other land cover types in forestry area.

Attention deficit hyperactivity disorder and autism spectrum disorder in children born to mothers with thyroid dysfunction: a Danish nationwide cohort study.

OBJECTIVE: To examine the association between maternal hyper- and hypothyroidism and the risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in the child. DESIGN: A population-based cohort study. SETTING: Singletons liveborn in Denmark between 1991 and 2004. POPULATION: A total of 857 014 singletons alive and living in Denmark at the age of 3 years. METHODS: Information on the diagnosis and/or treatment of maternal thyroid disease and the neurodevelopmental disorders ADHD and ASD in the child was obtained from Danish nationwide registers. The Cox proportional hazards model was used to estimate the hazard ratio (HR) with 95% confidence interval (95% CI) for risk of ADHD and ASD in children born to mothers with thyroid dysfunction, adjusting for potential confounding factors. MAIN OUTCOME MEASURES: ADHD and ASD in the child. RESULTS: Altogether, 30,295 singletons (3.5%) were born to mothers with thyroid dysfunction. Maternal hyperthyroidism diagnosed and treated for the first time after the birth of the child increased the risk of ADHD in the child (adjusted HR 1.23; 95% CI 1.05-1.44), whereas hypothyroidism increased the risk of ASD (adjusted HR 1.34; 95% CI 1.14-1.59). No significant association was seen for maternal diagnosis and treatment prior to the birth of the child. CONCLUSIONS: Children born to mothers diagnosed and treated for the first time for thyroid dysfunction after their birth may have been exposed to abnormal levels of maternal thyroid hormone already present during the pregnancy, and this untreated condition could increase the risk of specific neurodevelopmental disorders in the child.

Tacrolimus abrogates TGF-ß1-induced type I collagen production in normal human fibroblasts through suppressing p38MAPK signalling pathway: implications on treatment of chronic atopic dermatitis lesions.

BACKGROUND: Atopic dermatitis (AD) is a commonly encountered inflammatory skin disease. Although acute lesions of acute AD are characterized by intense inflammation, the hallmarks of chronic AD lesions include lichenified fibrosis and thickening of the upper dermis. The increased expression of transforming growth factor beta 1 (TGF-ß1), a well-known fibrogenic cytokine, is observed in chronic AD lesions. Tacrolimus (FK506) ointment has been reported to be effective for treating AD as well as some TGF-ß1-induced fibrotic diseases. OBJECTIVES: To evaluate the effect of tacrolimus on TGF-ß1-stimulated cultured normal human dermal fibroblasts and explore the potential signalling pathways involved. METHODS: Fibroblasts cultured from healthy adult human foreskins were treated with TGF-ß1 with or without tacrolimus. The impact on cell viability and proliferation were assessed by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and BrdU incorporation assay respectively. Reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA) and western blotting were performed to evaluate the relevant expressions of mRNA or proteins in fibroblasts. RESULTS: Our results revealed that the increased expressions of transforming growth factor-ß receptor I (TGF-ßRI) and TGF-ßRII in TGF-ß1-treated fibroblasts were suppressed by tacrolimus treatment. In addition, tacrolimus significantly inhibited fibroblast proliferation enhanced by TGF-ß1. TGF-ß1 increased type I collagen production, and this enhancing effect was suppressed by tacrolimus. The down-regulation of MMP-1 and up-regulation of TIMP-1 induced by TGF-ß1 were reversed by tacrolimus. The increase in phosphorylated p38 mitogen-activated protein kinase (p38MAPK) expression stimulated by TGF-ß1 was down-regulated by tacrolimus. Moreover, the fibroblasts treated with p38MAPK inhibitor significantly reduced type I collagen expression induced by TGF-ß1. CONCLUSIONS: The present results demonstrated that tacrolimus significantly inhibited physiological functions of fibroblasts enhanced by TGF-ß1 in vitro. Clinically, we propose that topical tacrolimus may not only reduce AD recurrence but also ameliorate dermal fibrosis often seen in chronic AD lesions.

Incidence and risk of central nervous system metastases as site of first recurrence in patients with HER2-positive breast cancer treated with adjuvant trastuzumab.

BACKGROUND: Central nervous system (CNS) disease as the site of first relapse after exposure to adjuvant trastuzumab has been reported. We carried out comprehensive meta-analysis to determine the risk of CNS metastases as the first site of recurrence in patients with HER2-positive breast cancer who received adjuvant trastuzumab. METHODS: Eligible studies include randomized trials of adjuvant trastuzumab administered for 1 year to patients with HER2-positive breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the incidence, relative risk (RR), and 95% confidence intervals (CIs) using fixed-effects inverse variance and random-effects models. RESULTS: A total of 9020 patients were included. The incidence of CNS metastases as first site of disease recurrence in HER2-positive patients receiving adjuvant trastuzumab was 2.56% (95% CI 2.07% to 3.01%) compared with 1.94% (95% CI 1.54% to 2.38%) in HER2-positive patients who did not receive adjuvant trastuzumab. The RR of the CNS as first site of relapse in trastuzumab-treated patients was 1.35 (95% CI 1.02-1.78, P = 0.038) compared with control arms without trastuzumab therapy. The ratio of CNS metastases to total number of recurrence events was 16.94% (95% CI 10.85% to 24.07%) and 8.33% (95% CI 6.49% to 10.86%) for the trastuzumab-treated and control groups, respectively. No statistically significant differences were found based on trastuzumab schedule or median follow-up time. No evidence of publication bias was observed. CONCLUSIONS: Adjuvant trastuzumab is associated with a significant increased risk of CNS metastases as the site of first recurrence in HER2-positive breast cancer patients.

Maternal bereavement in the antenatal period and oral cleft in the offspring.

STUDY QUESTION: Is maternal bereavement (emotional stress) due to loss of a close relative in the antenatal period associated with the risk of oral cleft in the offspring? SUMMARY ANSWER: Our study suggests prenatal maternal bereavement is associated with an increased risk of oral cleft in the offspring, especially when the bereavement was due to a sudden death or death of a child. WHAT IS KNOWN ALREADY: The aetiology of oral cleft is unknown but includes both genetic and environmental causes. STUDY DESIGN, SIZE AND DURATION: We performed a population-based cohort study based on several national registers in Denmark from 1978 to 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our final study population consisted of 1 771 663 children. Of these 35 118 (2%) were born to mothers who experienced bereavement in the exposure window from 1 year before pregnancy to the end of the first trimester. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 3043 children were diagnosed with a cleft; 968 with cleft lip, 1206 with cleft lip and palate and 869 with a cleft palate. For overall bereavement the prevalence was 1.7 per 1 000 live born in the unexposed children and 2.2 per 1 000 live born in the exposed children. Overall, maternal bereavement due to the death of a close relative from 1 year before conception to the end of the first trimester was associated with a significantly increased risk of oral cleft [odds ratio (OR): 1.28, 95% confidence interval (CI): 1.01; 1.61). When mothers lost a relative due to a sudden death, the risk of oral cleft in the offspring was higher (OR: 1.76, 95% CI: 1.06; 2.94). Losing a relative in the time period before pregnancy and during the first trimester showed a tendency to an increased risk. The risk increase was 77% when the mother was bereaved due to sudden death and the estimation was robust in different analytical strategies. LIMITATIONS, REASONS FOR CAUTION: It is a limitation that we only studied live born children, but most children with isolated oral cleft would survive their pregnancy and birth. Since oral cleft are rare and despite the large study population, we still had a relatively small number of cases, which results in limited power to detect small differences. We did not have actual measurements of the maternal cortisol concentration, but we believe that bereavement due to death of a close relative produces a strong stress reaction in most people. Also we did not have the opportunity to adjust for intake of folic acid and use of anti-depressant; however, analysis in a subset of the data showed no difference in these intakes between exposed and unexposed mothers. WIDER IMPLICATIONS OF THE FINDINGS: With this study we add a large-scale human cohort study to the body of literature on stress and birth defects. Our study is in agreement with previously published results and can be generalized to similar populations like the native Danish population. Severe stress may be added to the list of potential causes for oral cleft.

Increased risk of psoriasis following chronic rhinosinusitis without nasal polyps: a population-based matched-cohort study.

BACKGROUND: Although chronic rhinosinusitis without nasal polyps (CRSsNP) and psoriasis both share immunological disturbances as pathological factors, no prior study has investigated the risk for psoriasis among patients with CRSsNP. OBJECTIVES: To investigate the subsequent risk for psoriasis following a diagnosis of CRSsNP by utilizing a cohort study design and a population-based dataset in Taiwan. METHODS: In total, 13 242 subjects with CRSsNP were included in the study cohort and 39 726 subjects were randomly extracted for the comparison cohort. We individually tracked each individual in this study (n = 52 968) for a 5-year period following their index date to identify those subjects who received a subsequent diagnosis of psoriasis. Cox proportional hazards regression analysis was conducted to calculate the 5-year risk of subsequent psoriasis following a diagnosis of CRS among the sampled subjects. RESULTS: The incidence rate of psoriasis during the 5-year follow-up period was 1·41 [95% confidence interval (CI) 1·14-1·71] per 1000 person-years and 0·69 (95% CI 0·59-0·81) per 1000 person-years for the study and comparison cohort, respectively. Stratified Cox proportional hazards regression revealed that the hazard ratio for psoriasis during the 5-year follow-up period for subjects with CRSsNP compared with the control group was 2·01 (95% CI 1·54-2·62) after adjusting for monthly income, geographical region, hypertension, diabetes, coronary heart disease and hyperlipidaemia, and censoring the cases who died during the 5-year follow-up period. CONCLUSION: This study detected an increased risk for psoriasis among patients with CRSsNP.