Who Benefited Most from the Internet-Based Conversational Engagement RCT (I-CONECT)? Application of the Personalized Medicine Approach to a Behavioral Intervention Study.

BACKGROUND: Many Alzheimer's Disease (AD) clinical trials have failed to demonstrate treatment efficacy on cognition. It is conceivable that a complex disease like AD may not have the same treatment effect due to many heterogeneities of disease processes and individual traits. OBJECTIVES: We employed an individual-level treatment response (ITR) approach to determine the characteristics of treatment responders and estimated time saved in cognitive decline using the Internet-based Conversational Engagement Clinical Trial (I-CONECT) behavioral intervention study as a model. DESIGN AND SETTING: I-CONECT is a multi-site, single-blind, randomized controlled trial aimed to improve cognitive functions through frequent conversational interactions via internet/webcam. The experimental group engaged in video chats with study staff 4 times/week for 6 months; the control group received weekly 10-minute check-in phone calls. PARTICIPANTS: Out of 186 randomized participants, current study used 139 participants with complete information on both baseline and 6-month follow-up (73 with mild cognitive impairment (MCI), 66 with normal cognition; 64 in the experimental group, and 75 in the control group). MEASUREMENTS: ITR scores were generated for the Montreal Cognitive Assessment (MoCA) (global cognition, primary outcome) and Category Fluency Animals (CFA) (semantic fluency, secondary outcome) that showed significant efficacy in the trial. ITR scores were generated through 300 iterations of 3-fold cross-validated random forest models. The average treatment difference (ATD) curve and the area between the curves (ABC) were estimated to measure the heterogeneity of treatment responses. Responder traits were identified using SHapley Additive exPlanations (SHAP) and decision tree models. The time saved in cognitive decline was explored to gauge clinical meaningfulness. RESULTS: ABC statistics showed substantial heterogeneity in treatment response with MoCA but modest heterogeneity in treatment response with CFA. Age, cognitive status, time spent with family and friends, education, and personality were important characteristics that influenced treatment responses. Intervention group participants in the upper 30% of ITR scores demonstrated potential delays of 3 months in semantic fluency (CFA) and 6 months in global cognition (MoCA), assuming a 5-fold faster natural cognitive decline compared to the control group during the post-treatment period. CONCLUSIONS: ITR-based analyses are valuable in profiling treatment responders for features that can inform future trial design and clinical practice. Reliably measuring time saved in cognitive decline is an area of ongoing research to gain insight into the clinical meaningfulness of treatment.

A comprehensive analysis of nucleotide excision repair characteristics defines a novel prognostic signature for acute myeloid leukemia.

OBJECTIVE: Nucleotide excision repair (NER) has been associated with various types of malignant tumors. However, the precise roles of nucleotide excision repair-related genes (NERGs) in acute myeloid leukemia (AML) remain incompletely understood. Hence, this study aimed to develop a prognostic signature incorporating NERGs in AML, which could potentially predict patient outcomes. MATERIALS AND METHODS: By querying the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases, we acquired RNA-seq data and clinical information pertaining to AML. To identify differentially expressed NERGs (DE-NERGs), we employed the Wilcoxon rank-sum test. Based on the expression patterns of DE-NERGs with prognostic significance, patients were categorized into two subgroups. A prognostic signature was developed through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to compare the differentially expressed genes (DEGs) between these two groups. Additionally, a nomogram was constructed using multivariate analysis. The biological pathways involved were elucidated through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA). RESULTS: We developed a prognostic model based on an 11-gene signature. Furthermore, the risk score derived from this model was demonstrated to independently serve as a prognostic marker for patients diagnosed with AML. CONCLUSIONS: Our prognostic model, based on NERGs, was developed and validated to provide insights into the onset and progression of AML and establish a foundation for more effective treatment. Our findings not only contribute to clinical decision-making but also underscore the significance of nucleotide excision repair. Furthermore, they may pave the way for the development of targeted therapeutic strategies specifically focused on this process.

Hysterectomy and risk of osteoarthritis in women: a nationwide nested case-control study.

OBJECTIVE: Hysterectomy is the most common gynaecological surgery, performed mainly for benign uterine pathologies in women. Studies have suggested that hysterectomy is associated with osteoarthritis (OA); however, the association remains controversial. This study aimed to investigate the association between hysterectomy and the risk of OA. METHOD: We performed a population-based nested case-control study using the National Health Insurance programme database from 2000 to 2016 in Taiwan. All medical conditions for each case and control were categorized using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and ICD-10. A multiple conditional logistic regression model was applied to analyse the adjusted odds ratio (aOR) and 95% confidence interval (CI) for the association between hysterectomy and OA. RESULTS: Our analyses included 16 592 patients with OA and 66 368 matched controls. After adjustment for possible confounders, hysterectomy had a significant association with OA (aOR = 1.19, 95% CI = 1.09-1.30), especially knee OA (aOR = 1.25, 95% CI = 1.13-1.38). Furthermore, women who received oestrogen therapy (ET) alone and patients who underwent hysterectomy without ET showed a greater risk of OA development compared to women who did not receive ET (aOR = 1.14, 95% CI = 1.07-1.23, and aOR = 1.19, 95% CI = 1.08-1.31, respectively). CONCLUSION: Our findings indicate that hysterectomy is associated with OA, especially knee OA. We also found that women who received ET alone and patients who underwent hysterectomy without ET had an increased risk of OA.

Association between sensorineural hearing loss and vitiligo: a nationwide population-based cohort study.

BACKGROUND: Vitiligo is an acquired depigmentation disease of the skin due to melanocyte destruction. A shared pathogenesis affecting melanocytes in the cochlea has been postulated. However, the association between vitiligo and sensorineural hearing loss (SNHL) is unclear. OBJECTIVE: To identify the association between vitiligo and SNHL. METHODS: This retrospective, nationwide cohort study included patients with vitiligo and age-, sex- and comorbidities-matched controls (propensity score matching; 1:4 ratio) from the National Health Insurance Research Database in Taiwan from 1 January 2000 to 31 December 2013. RESULTS: In total, 13 048 patients with vitiligo and 52 192 controls were included. SNHL developed in 0.61% patients with vitiligo and 0.29% controls. After adjusting for sex, age and comorbidities, a significant association between vitiligo and SNHL was found (adjusted hazard ratio, 2.18; 95% CI, 1.66-2.86). The other risk factors for developing SNHL included increased age, male sex, hyperlipidaemia, coronary artery disease and diffuse connective tissue diseases. In subgroup analysis, the association between vitiligo and SNHL remained significant in almost all the subgroups. CONCLUSION: A 2.2-fold increased risk of developing SNHL was found in patients with vitiligo. Proper referral to otologists for early screening and closer follow-up of SNHL should be considered for patients with vitiligo, especially for patients with older age.

Early-life infections in association with the development of atopic dermatitis in infancy and early childhood: a nationwide nested case-control study.

BACKGROUND: Microbial dysbiosis has been implicated in the development of atopic dermatitis (AD). The risk of development of AD following early-life infections remains unclear. OBJECTIVE: To investigate the impact of early-life infections on AD development. METHODS: This population-based nested case-control study was conducted using the Taiwan's National Health Insurance Research Database. A total of 5454 AD patients and 16 362 control subjects without AD were identified, for the period 1997 to 2013. Demographic characteristics, comorbidities and maternal factors were compared. Adjusted odds ratio (aOR) was calculated to examine the associations between early-life infections and subsequent AD by conditional stepwise logistic regression analysis. RESULTS: Mean age was 2.6 ± 2.9 years in both groups. Overall infections (41.8% vs. 28.9%) before the diagnosis of AD were more common in AD patients than in control subjects (P < 0.001). Infectious diseases [aOR, 1.40; 95% confidence interval (CI), 1.29-1.51], skin infections (aOR, 1.55; 95% CI, 1.40-1.71) and systemic antibiotic exposure (aOR 1.67, 95% CI 1.55-1.79) before AD diagnosis were independently associated with AD development on multivariate analyses. These results were consistent across observation periods (0-1, 1-2 and >2 years after birth) and sensitivity analyses after redefining the index date as 3 or 6 months before the date of AD diagnosis. Other independent risk factors included asthma, allergic rhinitis, intussusception and neonatal hyperbilirubinemia. No association with subsequent AD was found for maternal age at delivery, Caesarean delivery or prenatal antibiotic exposure. CONCLUSION: Infections in early life are associated with AD development in infancy and early childhood.

Lymphoepithelial carcinoma in the sublingual gland.

Lymphoepithelial carcinoma is rare in the salivary glands, with an incidence of 0.4%. The most commonly affected site is the parotid gland, followed by the submandibular gland. Lymphoepithelial carcinoma in the sublingual gland has been reported only four times in the existing English-language literature. Such tumours are characterized by the presence of a poorly differentiated carcinoma that is surrounded and infiltrated by lymphocytes, and they are strongly associated with Epstein-Barr virus infection, patient ethnicity, and prominent radiosensitivity. Wide surgical excision combined with adjuvant therapy has been suggested as the first-choice therapeutic regimen. This report describes the case of a 34-year-old Indonesian woman who was evaluated and treated in Taipei Medical University Hospital. She had a tumour that presented as a painless swelling on the floor of the mouth. The diagnosis was confirmed by conducting an incisional biopsy, and a wide surgical excision with bilateral supraomohyoid neck dissection and free flap reconstruction was performed. The patient also underwent adjuvant chemoradiotherapy. No evidence of local recurrence or distant metastasis was detected during the 6 months of follow-up. Subsequently, the patient returned to her home country, and further follow-ups were not conducted.

Cigarette smoking and risk of herpes zoster: a population-based cohort study in Taiwan.

The effects of cigarette smoking on the risk of herpes zoster (HZ) infection remain unclear. This study aimed to examine the association between cigarette smoking and HZ. Participants were collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of HZ were identified from the Taiwanese National Health Insurance database. Of the 57 641 participants, 3346 developed HZ during the observation period. After controlling for confounders, current smokers had a lower risk of incident HZ than never-smokers (adjusted hazard ratio 0.69; 95% CI 0.62-0.77). There was a trend toward a decreased risk of HZ with increasing numbers of cigarettes per day, years of smoking and cumulative pack-years of smoking among current smokers (Ptrend < 0.001). Former smoking was not associated with risk of HZ. In conclusion, current smoking was significantly associated with a decreased risk of developing HZ.

The potential mechanism of PPP2R3A in myocardial cells and its interacting proteins.

OBJECTIVE: PPP2R3A plays a key role in the cardiac pathological and physiological processes, yet little is known about how the protein involved in normal myocardium formation and the protein-protein interaction pathways involved. To address this issue, we investigated the role of PPP2R3A in cardiac myocytes and identify PPP2R3A specific protein interaction partners to accelerate the developmental process of the mechanistic studies. MATERIALS AND METHODS: PPP2R3A-silenced primary myocardial cell of neonatal rats and H9c2 cells were established by infecting shRNA lentiviral particles. RT-PCR and Western blot were used to determine the expression of PPP2R3A and silencing efficiency. The cell viability was analyzed by CCK-8 kit, then the cell cycles and apoptosis assays were detected by flow cytometry. Novel protein-protein interactions of PPP2R3A were detected by Yeast Two-Hybrid assays using a high-quality human primary cardiomyocyte cDNA library. RESULTS: PPP2R3A-silencing rat primary cardiomyocytes and H9c2 cells were established successfully, and the expression of PPP2R3A was downregulated significantly as confirmed by RT-PCR and Western blot. PPP2R3A silencing can inhibit the myocardial cell proliferation, arrest the cell cycle in the S phase and promote the cardiomyocytes apoptosis. 19 potential candidates like COL1A2, GIPC1and BCL6 specifically interact with PPP2R3A, and COL1A2 was the highest screening frequency, covering 12.5% of the 24 clones. These partners are highly enriched in signaling pathways associated with a variety of cellular processes. CONCLUSIONS: A series of studies have discovered that PPP2R3A was closely associated with heart failure and arrhythmia. Our data further confirmed PPP2R3A plays an important role in the cardiomyocytes and PPP2R3A in the regulation of cardiac events via its interaction partners. Therefore, it is a potential therapeutic target for the disease.

Antibiotic resistance in acne: changes, consequences and concerns.

Antibiotic resistance in acne was first observed in the 1970s and has been a major concern in dermatology since the 1980s. The resistance rates and types of antimicrobials have subsequently shown great variations in regions and countries. Illustrative of this is the resistance to topical erythromycin and clindamycin which continues to be a problem worldwide, while resistance to systemic treatment with tetracyclines has remained low during the past decade. The resistance for the newer macrolides like azithromycin and clarithromycin has been increasing. The results of antibiotic resistance may include treatment failure of acne, disturbance of skin microbiota, induction of opportunistic pathogens locally and systemically, and dissemination of resistant strains to both healthcare personnel and the general population. The ensuing complications, such as aggravated opportunistic infections caused by Propionibacterium acnes and the emergence of multiresistant superbugs, have not yet been confirmed.

Cigarette smoking and risk of rosacea: a nationwide population-based cohort study.

BACKGROUND: Most evidence regarding the relationship between cigarette smoking and risk of rosacea is obtained from cross-sectional or case-control studies. OBJECTIVE: To examine the association between smoking and risk of developing rosacea. METHODS: Participants were collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of rosacea were identified from the National Health Insurance database. Cox proportional hazard model was used for the analyses. RESULTS: Of the 59 973 participants, 379 developed rosacea during a mean follow-up of 10.8 years. After adjustment for potential confounders, current smokers had a lower risk of rosacea than never smokers [adjusted hazard ratio (aHR) 0.60; 95% confidence interval (CI) 0.39-0.92]. An increase in smoking intensity was associated with a decreased risk of rosacea among current smokers (Ptrend  = 0.0101). Compared with never smokers, current smokers of >15 cigarettes/day had an aHR of 0.51 (95% CI: 0.26-0.99) for rosacea. For incident rosacea, the aHRs (95% CIs) of current smokers of ≤10 years of smoking and ≤10 pack-years of smoking were 0.44 (0.22-0.88) and 0.51 (0.29-0.89), respectively. Former smoking was not associated with rosacea risk. CONCLUSION: Current smoking was significantly associated with a decreased risk of rosacea.

Progression of chronic kidney disease and the risk of tuberculosis: an observational cohort study.

Little is known about tuberculosis (TB) risk in the earlier stages of chronic kidney disease (CKD). To investigate the relationship between CKD at all stages and the risk of incident TB. We conducted a cohort study using 100 058 participants of a community-based health screening programme in northern Taiwan, 2005-2008. Renal function was ascertained at baseline using serum creatinine level and the urine dipstick test. The occurrence of active TB was ascertained using the National Tuberculosis Registry. Cox proportional hazards regression was used to estimate the association between CKD and TB. During a median follow-up of 7.5 years, TB incidence was 472. In the Cox regression analyses, individuals with Stage 1-4 CKD had a 25% increase in TB hazard than those without disease (adjusted hazard ratio [aHR] 1.25, 95%CI 1.02-1.54). A positive correlation between CKD stage and TB was observed (P = 0.02 for trend). TB risk increased by 5.1% with every 10 ml/min/1.73 m² decrease in the estimated glomerular filtration rate (aHR 1.05, 95%CI 0.99-1.12). Our results suggested an increased risk of TB in early-stage CKD. TB prevention efforts should consider individuals with earlier stages of CKD. .

Collection, particle sizing and detection of airborne viruses.

Viruses that affect humans, animals and plants are often dispersed and transmitted through airborne routes of infection. Due to current technological deficiencies, accurate determination of the presence of airborne viruses is challenging. This shortcoming limits our ability to evaluate the actual threat arising from inhalation or other relevant contact with aerosolized viruses. To improve our understanding of the mechanisms of airborne transmission of viruses, air sampling technologies that can detect the presence of aerosolized viruses, effectively collect them and maintain their viability, and determine their distribution in aerosol particles, are needed. The latest developments in sampling and detection methodologies for airborne viruses, their limitations, factors that can affect their performance and current research needs, are discussed in this review. Much more work is needed on the establishment of standard air sampling methods and their performance requirements. Sampling devices that can collect a wide size range of virus-containing aerosols and maintain the viability of the collected viruses are needed. Ideally, the devices would be portable and technology-enabled for on-the-spot detection and rapid identification of the viruses. Broad understanding of the airborne transmission of viruses is of seminal importance for the establishment of better infection control strategies.

Assessing Vascularity of Osseous Spinal Metastases with Dual-Energy CT-DSA: A Pilot Study Compared with Catheter Angiography.

BACKGROUND AND PURPOSE: Spine debulking surgery in patients with hypervascular spinal metastasis is associated with massive intraoperative blood loss, but currently, the vascularity of tumor is determined by invasive conventional angiography or dynamic contrast MR imaging. We aimed to investigate the usefulness of noninvasive dual-energy CT-DSA, comparing it with conventional angiography in evaluating the vascularity of spinal metastasis. MATERIALS AND METHODS: We conducted a retrospective study from January to December 2018. A total of 15 patients with spinal metastasis undergoing dual-energy CT, conventional DSA, and subsequent debulking surgery were included. CT-DSA images were produced after rigid-body registration and subtraction between CT phases. Qualitative and quantitative assessments of tumor vascularity were conducted. Correlations between CT-DSA and conventional DSA results were evaluated using the Spearman coefficient. The mean enhancement in the estimated tumor volume and surgical blood loss was compared between hypervascular and nonhypervascular groups using the Wilcoxon rank sum test. RESULTS: The CT-DSA and DSA results were strongly correlated, with ρ = 0.87 (P < .001). The DSA and the quantitative enhancement index also showed a strong correlation with ρ = 0.83 (P < .001). Wilcoxon rank sum testing between hypervascular and nonhypervascular CT-DSA groups showed a difference in enhancement indices (P = .0003). The blood loss between the hypervascular and nonhypervascular groups was nonsignificant (P = .09). CONCLUSIONS: Dual-energy CT-DSA correlates well with conventional DSA in assessing the vascularity of spinal metastasis. It may serve as a noninvasive preoperative evaluation option before debulking surgery.

Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting approximately 45% of male and 16% of female carriers of the FMR1 premutation over the age of 50 years. Currently, no effective treatment is available. We performed an open-label intervention study to assess whether allopregnanolone, a neurosteroid promoting regeneration and repair, can improve clinical symptoms, brain activity, and magnetic resonance imaging (MRI) measurements in patients with FXTAS. Six patients underwent weekly intravenous infusions of allopregnanolone (2-6 mg over 30 min) for 12 weeks. All patients completed baseline and follow-up studies, though MRI scans were not collected from 1 patient because of MRI contraindications. The MRI scans from previous visits, along with scans from 8 age-matched male controls, were also included to establish patients' baseline condition as a reference. Functional outcomes included quantitative measurements of tremor and ataxia and neuropsychological evaluations. Brain activity consisted of event-related potential N400 word repetition effect during a semantic memory processing task. Structural MRI outcomes comprised volumes of the hippocampus, amygdala, and fluid-attenuated inversion recovery hyperintensities, and microstructural integrity of the corpus callosum. The results of the study showed that allopregnanolone infusions were well tolerated in all subjects. Before treatment, the patients disclosed impairment in executive function, verbal fluency and learning, and progressive deterioration of all MRI measurements. After treatment, the patients demonstrated improvement in executive functioning, episodic memory and learning, and increased N400 repetition effect amplitude. Although MRI changes were not significant as a group, both improved and deteriorated MRI measurements occurred in individual patients in contrast to uniform deterioration before the treatment. Significant correlations between baseline MRI measurements and changes in neuropsychological test scores indicated the effects of allopregnanolone on improving executive function, learning, and memory for patients with relatively preserved hippocampus and corpus callosum, while reducing psychological symptoms for patients with small hippocampi and amygdalae. The findings show the promise of allopregnanolone in improving cognitive functioning in patients with FXTAS and in partially alleviating some aspects of neurodegeneration. Further studies are needed to verify the efficacy of allopregnanolone for treating FXTAS.

Enhancing expression of the pseudorabies virus glycoprotein E in yeast and its application in an indirect sandwich ELISA.

AIMS: The purpose of this study was to produce a recombinant pseudorabies virus (PRV) glycoprotein E (gE) protein with the correct antigenicity for use as a low-cost diagnostic antigen. METHODS AND RESULTS: The gene fragment encoding the amino-terminal immunodominant region of PRV gE (codons 31-270) (gEN31-270) was codon optimized and expressed constitutively and secreted using a Pichia pastoris expression system. Yeast-expressed gEN31-270 (ygEN31-270) was harvested from the culture supernatant, and ygEN31-270 was shown to exhibit N-linked glycosylation. An indirect sandwich enzyme-linked immunosorbent assay (ELISA) was developed using ygEN31-270 as a coating antigen, and the results showed that the assay had high sensitivity and specificity, as well as almost perfect concordance with a commercial gE ELISA kit. CONCLUSIONS: The immunodominant region (amino acids 31-270) of gE was expressed successfully in P. pastoris using a codon optimization strategy. ygEN31-270 was secreted and N-glycosylated. The ygEN31-270-based indirect sandwich ELISA showed high sensitivity and specificity to detect gE-specific antibodies in swine serum samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The ygEN31-270-based indirect sandwich ELISA may provide an alternative method for developing a diagnostic kit with easy manipulation and low cost.

Hypoxic lung cancer-secreted exosomal miR-23a increased angiogenesis and vascular permeability by targeting prolyl hydroxylase and tight junction protein ZO-1.

Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.

The effectiveness of suicide prevention programmes: urban and gender disparity in age-specific suicide rates in a Taiwanese population.

OBJECTIVE: The effectiveness of suicide prevention programmes is an important issue worldwide today. The impact of urbanization and gender is controversial in suicide rates. Hence, this study adjusted on potential risk factors and secular changes for suicide rates in gender and rural/urban areas. STUDY DESIGN: Observational study. METHODS: A Suicide Prevention Center was established by the Executive Yuan in Taiwan in 2005 and tried to carry out suicidal intervention in the community in every city and town. There were two phases, including the first phase of the programme from 2005 to 2008, and the second phase of the programme from 2009 to 2013. The crude suicide rates data from the period of 1991-2013, which recruited nine urban and 14 rural areas in Taiwan, were extracted from the Taiwanese national mortality data file. The suicide rates in two areas of Taiwan (Taipei city and Yilan County) were further used to compare the differences between urban and rural areas. RESULTS: The results show that unemployment increased the suicide rate in men aged 45-64 years and in women older than 65 years of age in Taiwan. High divorce and unemployment rates resulted in increased suicide rates in men in the city, whereas emotional distress was the main cause of suicides in men in rural areas. The main method of suicide was jumping from a high building for both sexes in the city, whereas drowning was the most common method of suicide for men in rural areas. CONCLUSION: Following the intervention programme, suicide behaviour began to decrease in all urban and rural areas of Taiwan. This study showed the cumulative effect of the intervention programme in decreasing the suicide rate in Taiwan. Moreover, the gender-specific suicidal rate and disparity in suicidal methods in urban and rural areas should be considered in further preventive strategies in Taiwan.

Egr-1 regulates irradiation-induced autophagy through Atg4B to promote radioresistance in hepatocellular carcinoma cells.

Although hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) revealed that Egr-1 binds to the Atg4B promoter to upregulate its expression in HCC cells. Suppression of Egr-1 function by dominant-negative Egr-1 dampens IR-induced autophagy, cell migration, and increases cell sensitivity to radiotherapy. Together, these results suggest that Egr-1 contributes to HCC radioresistance through directly upregulating target gene Atg4B, which may serve as a protective mechanism by preferential activation of the autophagy.

Exosomes and breast cancer: a comprehensive review of novel therapeutic strategies from diagnosis to treatment.

Exosomes are nanosized vesicles, released by various cells, which have essential roles in intercellular communication locally and systemically through transporting their contents such as proteins and lipids as well as RNA. It was clear that the element of contents in exosomes reassembled with the emerging of cancers. Over the past decade, researchers paid more attention to the role of exosomes in breast cancer. The purpose of this review was to discuss the details of the biological characteristics of exosomes in breast cancer. The discussion would focus on the role of exosomes in breast cancer development, progression, metastasis and drug resistance, as well as related therapeutic and diagnostic strategies.

Presence of the Merkel cell polyomavirus in Merkel cell carcinoma combined with squamous cell carcinoma in a patient with chronic arsenism.

We present a case of Merkel cell carcinoma (MCC) coincident with squamous cell carcinoma (SCC) on the breast of a woman with chronic arsenism. This case demonstrates the distinct association of chronic arsenism with two different primary cutaneous carcinomas. Merkel cell polyomavirus (MCPyV) was identified in the lesional skin of the MCC but not in that of the SCC, suggesting there are different interactions of MCPyV in the pathogenesis of SCC and MCC related to arsenic. Physicians need to be vigilant in the occurrence of both SCC and MCC in patients with chronic arsenism. To our knowledge, this is the first study to show the presence of MCPyV in the MCC but not the SCC portion of an arsenic-induced tumour.