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Background Retrospective studies have suggested that patients with dementia have higher prevalence of atopic dermatitis (AD) than those without dementia. However, the temporal association of AD with subsequent dementia remains unknown. Objective To assess the temporal association of AD with subsequent dementia. Methods We included data of patients with AD aged 45 years and older (n = 1059) and 1:10 age, sex, residence, income, and dementia-related comorbidity–matched controls (n = 10,590) from the Taiwan National Health Insurance Research Database and reviewed their subsequent dementia development from the enrollment date to the end of 2013. Results After adjustments for dementia-related comorbidities, patients with AD were found to be more likely to develop any dementia (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.24-3.29), particularly Alzheimer's disease (HR, 3.74; 95% CI, 1.17-11.97), during the follow-up period than those in the control group. Moderate-to-severe AD was associated with a high subsequent dementia risk (HR, 4.64; 95% CI, 2.58-8.33). Sensitivity analyses with the exclusion of the first 3 (HR, 2.20; 95% CI, 1.28-3.80) or 5 (HR, 2.05; 95% CI, 1.08-3.89) years of observation revealed consistent findings. Conclusion AD may be an independent risk factor for new-onset dementia. Clinicians may monitor the trajectory of neurocognitive function among elderly patients with AD. Additional studies elucidating the pathomechanisms between AD and subsequent dementia are warranted.

Background and Purpose: Patients with obsessive-compulsive disorder (OCD) tend to be comorbid with stroke-related risk factors, including obesity, hypertension, and diabetes. However, the temporal association between OCD and subsequent stroke risk is unclear. Methods: Using data collected between 2001 and 2010 by Taiwan’s National Health Insurance Research Database, 28 064 adult patients with OCD (International Classification of Diseases, Ninth Revision, Clinical Modification [ ICD-9-CM ] code: 300.3) and 28 064 age-, sex-, and comorbidity-matched controls were included in this study. Patients who developed ischemic ( ICD-9-CM codes: 433, 434, and 435) and hemorrhagic ( ICD-9-CM codes: 430, 431, and 432) stroke during follow-up (from enrollment to end of 2011) were identified. Moreover, medications used for treating OCD were assessed. Results: Patients with OCD (hazard ratio [HR], 3.02 [95% CI, 1.91–4.77]), especially middle-aged (HR, 2.66 [95% CI, 1.34–5.29]) and elderly adults (HR, 3.46 [95% CI, 1.70–7.05]), had an elevated risk of developing ischemic stroke during the follow-up period compared with non-OCD controls. The cumulative HR of hemorrhagic stroke did not differ (HR, 0.87 [95% CI, 0.42–1.80]) between the OCD and non-OCD groups. In patients with OCD, both short- (HR, 1.69 [95% CI, 0.74–3.88]; HR, 0.31 [95% CI, 0.05–1.95]) and long-term use (HR, 1.37 [95% CI, 0.60–3.16]; HR, 0.90 [95% CI, 0.22–3.76]) of OCD medications were not correlated with ischemic and hemorrhagic stroke compared with nonuse. Conclusions: Clinicians should closely monitor cerebrovascular disease and related risks in patients with OCD. The pathomechanism of OCD with an increased risk of ischemic stroke warrants further investigation.

Evidence suggests that levels of treatment refractoriness and brain-derived neurotrophic factor (BDNF) rs6265 polymorphism are related to the antidepressant effects of conventional antidepressants and repetitive transcranial magnetic stimulation. However, whether these factors are associated with the antidepressant effects of low-dose ketamine remains unclear. In total, 71 patients with treatment-resistant depression (TRD) were randomized to 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline control infusion groups. They were further divided into three treatment refractoriness groups according to the Maudsley staging method and were genotyped for Val66Met BDNF polymorphism. Participants’ Hamilton Depression Rating Scale (HDRS) scores were assessed preinfusion, at 40, 80, 120, and 240 min postinfusion, and sequentially on days 2–7 and 14 after infusion. Patients with any Val allele exhibited an antidepressant response (p = 0.029) to 0.5 mg/kg ketamine vs. 0.2 mg/kg ketamine vs. saline control infusions. However, the trajectory of HDRS scores did not differ (p = 0.236) between the treatment groups among Met/Met carriers. In the low treatment refractoriness group, the 0.2 mg/kg ketamine infusion exhibited the optimal antidepressant effect (p = 0.002); in the moderate treatment refractoriness group, the 0.5 mg/kg ketamine infusion achieved the strongest antidepressant effect (p = 0.006); however, in the high treatment refractoriness group, the trajectory of depressive symptoms did not differ between treatments (p = 0.325). In future clinical practice, ketamine dose may be adjusted according to the level of treatment refractoriness and BDNF rs6265 polymorphism to achieve the optimal antidepressant effect for patients with TRD.

Background: Evidence suggests that clinical markers, such as comorbid anxiety, body weight, and others can assist in predicting response to low-dose ketamine infusion in treatment resistant depression patients. However, whether a composite of clinical markers may improve the predicted probability of response is uncertain. Methods: The current study investigated the results of our previous randomized placebo-controlled and open-label trials in which 73 patients with treatment-resistant depression (TRD) received a single ketamine infusion of 0.5 mg/kg. Clinical characteristics at baseline, including depression severity, duration of the current episode, obesity, comorbidity of anxiety disorder, and current suicide risk, were assessed as potential predictors in a classification and regression tree model for treatment response to ketamine infusion. Results: The predicted probability of a composite of age at disease onset, depression severity, duration of current episode, and obesity/overweight was significantly greater (area under curve = .736, p = .001) than that of any one marker (all p > .05). The most powerful predictors of treatment response to ketamine infusion were younger age at disease onset and obesity/overweight. The strongest predictors of treatment nonresponse were longer duration of the current episode and greater depression severity at baseline. Discussion: Depression severity, duration of the current episode, obesity, and age at disease onset may predict treatment response versus nonresponse to low-dose ketamine infusion. However, whether our predicted probability for a single infusion may be applied to repeated infusions would require further investigation. Clinical trial registration: UMIN Clinical Trials Registry (UMIN000023581 and UMIN000016985).

Interest and activity are part of the positive mood domain. Evidence suggests the symptom domain of interest-activity at baseline as a clinical predictor for treatment response to traditional antidepressants. However, whether this domain is related to the response to a single low-dose ketamine infusion remains unclear. Seventy-one patients with treatment-resistant depression were randomized to 3 treatment groups: a single 0.5 or 0.2 mg/kg ketamine or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale before infusions and at postinfusion period (at 40 min and up to 2 weeks). Low (mild) versus medium versus high (severe) interest-activity symptom domain groups were classified on the basis of the cutoff point of ± 0.4 standard deviation. The effect of baseline interest-activity symptoms on outcomes was tested using generalized estimating equation models. The interest-activity symptom domain as a continuous variable (β = 8.413, p = .016) was related to the trajectory of depressive symptoms. Stratified by levels of the interest-activity symptom domain, in the low interest-activity, 0.2 mg/kg ketamine infusion (β = 0.013) demonstrated the greatest antidepressant effect (p

Background/Purpose Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) disorder that causes relapsing inflammation and severe mucosal damage in the intestine. Crohn’s disease (CD)-related stricturing complications are a major cause of surgery, disability, and reduced quality of life. Endoscopic balloon dilation (EBD) has been shown to reliably delay or prevent surgery in patients with stricturing CD. However, cases of EBD performed for stricture in CD in Taiwan are rare. In this study, we want to evaluate the experiences regarding EBD for stricturing CD in Taiwan. Methods We conducted a retrospective analysis of 9 medical centers in Taiwan. Patients with CD-related strictures who were treated with EBD were included and analyzed. Results In nine medical centers, a total of 26 CD patients (19 male, 7 female, mean disease duration 75.4 ± 65.2 months) underwent 42 EBD procedures during the study period. Among the subjects, an 83.3% (35/42) EBD success rate was seen, but 26.9% (7/26) patients underwent surgery after ineffective EBD. In the surgery group, the the small bowel strictures was high compared with the non-surgery group (p = 0.01). There were no significant differences in disease phenotype, disease duration or history of fistulizing disease. In the surgery group, immunosuppressant use was high, and 5-aminosalicylic acid (5-ASA) use was low compared with the non-surgery group. After EBD, the physicians tended to change the drugs, especially increasing the use of biologic agents. Conclusion EBD is a safe and effective procedure for CD-related stricture, with a 83.3% success rate in Taiwan.

The association between systemic inflammation, executive dysfunction, and gray matter (GM) volume difference in first-episode affective disorders, including bipolar and major depressive disorders, is unclear.Twenty-two patients with first-episode bipolar disorder, 22 age- and sex-matched patients with first-episode major depressive disorder, and 22 matched controls were enrolled in our study; all patients underwent comprehensive assessments, including clinical assessment, executive function examination (Wisconsin card sorting test [WCST]), proinflammatory cytokine receptors (soluble interleukin-6 receptor and tumor necrosis factor-α receptor 1 [TNFR1]), and brain magnetic resonance imaging. Voxel-based morphometry was performed to analyze the GM volume difference between bipolar and major depressive disorders.Patients with bipolar disorder were more likely to exhibit higher levels of TNFR1 (P = .038), more number of deficits in WCST (P.05), and smaller GM volume in the middle frontal cortex (uncorrected voxel level P.001) compared with those with major depressive disorder and healthy controls. Positive associations were observed between the middle frontal cortex volume, executive function, and the TNFR1 level.GM volume reduction in the middle frontal cortex, a greater level of systemic inflammation, and executive dysfunction were observed in first-episode affective disorders, especially bipolar disorder. A positive correlation between middle frontal cortex volume, executive function, and the TNFR1 level may indicate a divergent effect of brain and systemic inflammation functioning in the early phase (first episode) of affective disorder.

Background Frontostriatal disconnectivity plays a crucial role in the pathophysiology of major depressive disorder. However, whether the baseline functional connectivity of the frontostriatal network could predict the treatment outcome of low-dose ketamine infusion remains unknown. Methods In total, 48 patients with treatment-resistant depression were randomly divided into 3 treatment groups (a single-dose 40-minute i.v. infusion) as follows: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline placebo infusion. Patients were subsequently followed-up for 2 weeks. Resting-state functional magnetic resonance imaging was performed for each patient before infusion administration. In addition, the baseline frontostriatal functional connectivity of patients with treatment-resistant depression was also compared with that of healthy controls. Results Compared with the healthy controls, patients with treatment-resistant depression had a decreased functional connectivity in the frontostriatal circuits, especially between the right superior frontal cortex and executive region of the striatum and between the right paracingulate cortex and rostral-motor region of the striatum. The baseline hypoconnectivity of the bilateral superior frontal cortex to the executive region of the striatum was associated with a greater reduction of depression symptoms after a single 0.2-mg/kg ketamine infusion. Conclusion Reduced connectivity of the superior frontal cortex to the striatum predicted the response to ketamine infusion among patients with treatment-resistant depression.

Studies have demonstrated that conduct disorder is related to risky sexual behaviors, the dominant risk factor for contracting a sexually transmitted infection (STI). However, the association between conduct disorder and STIs remains unclear. Using the Taiwan National Health Insurance Research Database, 5733 adolescents with conduct disorder and 22,932 age- and sex-matched controls without conduct disorder were enrolled from 2001 to 2009 and were subject to follow-up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was performed to examine the likelihood of subsequently contracting an STI for patients and controls. Patients with conduct disorder were more likely than controls to develop any STI (HR 3.95, 95% CI 2.97–5.26) after adjusting for demographic data, psychiatric comorbidities, and use of medications. Long-term use of second-generation antipsychotics (SGAs) was related to a reduced risk (HR 0.36, 95% CI 0.14–0.91) of developing an STI among patients with conduct disorder. Adolescents with conduct disorder had an increased risk of developing any STI later in life compared with those without conduct disorder. Long-term use of SGAs was associated with a lower risk of subsequent STI.

BackgroundThe antidepressant effect of low-dose ketamine infusion on Taiwanese patients with anxious vs nonanxious treatment-resistant depression (ANX-TRD vs NANX-TRD) has remained unknown.MethodsIn total, 71 patients with TRD were randomized to three groups. Each group had participants who received saline infusions mixed with 0 (a normal saline infusion), 0.2, and 0.5 mg/kg of ketamine. Participants were followed up for 2 weeks. Anxious depression was defined as major depressive disorder with a total score of 7 or more on the 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor. Generalized estimating equation models were used to investigate the effects of treatment (ketamine vs placebo) and depression type (ANX-TRD vs NANX-TRD) in the reduction of depressive symptoms during the follow-up period.ResultsPatients with ANX-TRD were less likely to respond to a single low-dose ketamine infusion than those with NANX-TRD. Among patients with NANX-TRD, low-dose ketamine infusion was significantly superior to placebo for reducing depressive symptoms. However, among patients with ANX-TRD, ketamine was not superior to placebo; nonetheless, approximately 30% of the patients responded to ketamine infusion compared to 13% who responded to the placebo.ConclusionsLow-dose ketamine infusion was effective for Taiwanese patients with NANX-TRD but not so effective for those with ANX-TRD. A higher level of anxiety severity accompanying depression was related to greater depression severity. This may confound and reduce the antidepressant effect of ketamine infusion.

Prolonged intermittent theta burst stimulation (piTBS) with triple doses of the standard protocol is an updated form of repetitive transcranial magnetic stimulation, and it is an effective add-on intervention for major depressive disorder. In the present study, our objective was to investigate the antidepressant efficacy of piTBS monotherapy. Efficacy between the standard 5-cm method and magnetic resonance imaging (MRI)-guided coil positioning to the left dorsolateral prefrontal cortex method was also compared.In the present double-blind, randomized, sham-controlled trial, 105 patients with recurrent depression who exhibited no responses to at least one adequate antidepressant treatment for the prevailing episode were assigned randomly to one of three groups: piTBS monotherapy (n = 35), repetitive transcranial magnetic stimulation monotherapy (n = 35), or sham stimulation (n = 35). The acute treatment period was 2 weeks. Half of the patients were randomized to MRI navigation in each group.No serious adverse events were observed. The piTBS group exhibited significantly greater decreases in depression scores than the sham group at week 2 (-40.0% vs. -13.9%; p.001 after correcting for multiple comparisons by Bonferroni [effect size (Cohen's d) = 1.12]), and the odds ratio for responses was high. The MRI navigation method (-32.4%) did not yield better antidepressant effects than the standard method (-40.6%). Brain stimulation and 17-item Hamilton Depression Rating Scale changes in the first week were the most important variables for predicting antidepressant responses.Left prefrontal piTBS monotherapy is effective for the treatment of recurrent depression, and the MRI-guided method of coil targeting is not better than the standard method.

BackgroundWhether the first-degree relatives (FDRs) of patients with obsessive-compulsive disorder (OCD) have an increased risk of the major psychiatric disorders, namely schizophrenia, bipolar disorder, OCD, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), remains unclear.MethodsUsing the Taiwan National Health Insurance Research Database with the whole population sample size (n = 23 258 175), 89 500 FDRs, including parents, offspring, siblings, and twins, of patients with OCD were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with OCD.ResultsFDRs of patients with OCD had higher RRs of major psychiatric disorders, namely OCD (RR 8.11, 95% confidence interval (CI) 7.68–8.57), bipolar disorder (RR 2.85, 95% CI 2.68–3.04), MDD (RR 2.67, 95% CI 2.58–2.76), ASD (RR 2.38, 95% CI 2.10–2.71), ADHD (RR 2.19, 95% CI 2.07–2.32), and schizophrenia (RR 1.97, 95% CI 1.86–2.09), compared with the total population. Different familial kinships of FDRs, such as parents, offspring, siblings, and twins consistently had increased risks for these disorders. In addition, a dose-dependent relationship was found between the numbers of OCD probands and the risk of each major psychiatric disorder.ConclusionsThe FDRs, including parents, offspring, siblings, and twins, of patients with OCD have a higher risk of OCD, schizophrenia, bipolar disorder, MDD, ADHD, and ASD. The familial co-aggregation of OCD with OCD and other major psychiatric disorders was existent in a dose-dependent manner. Given the increased risks of psychiatric disorders, medical practitioners should closely monitor the mental health of the FDRs of patients with OCD.

Background GEMINI trials and real-world studies in Western population have demonstrated the effectiveness and safety of vedolizumab (VDZ) for IBD. However, long-term real-world evidence of VDZ in Asian populations remains limited. This study aimed to investigate the effectiveness and safety of VDZ in Taiwan CD and UC patients, and the IBD relapse after VDZ discontinuation. Methods Data were prospectively collected (January 2018-May 2020) from the Taiwan Society of IBD (TSIBD) registry, one of the largest real-world Asian IBD cohorts. Patients (>18 years old) receiving ≥1 dose of VDZ with up to a 1-year follow-up period were analyzed. Effectiveness at 6 month and 1 year including clinical response (CRS), clinical remission (CRM), steroid-free remission (SRM) and mucosal healing (MH);and safety outcome were analyzed descriptively. IBD relapse after VDZ treatment discontinuation was assessed since the reimbursement period in Taiwan is limited due to drug holiday required by government. Results A total of 274 patients (CD:127, UC:147) were included. At VDZ initiation, average [SD] age (year): 33.4 [14.6] in CD and 42.4 [14.3] in UC; median disease duration (years): 3.1 in CD and 3.9 in UC; 50.4% of CD and 70.7% of UC patients were biologics (bio)-naïve. Treatment effectiveness was analyzed (Figure 1-4). At 6 months, effectiveness in the CD bio-naïve group was significantly higher than the bio-exposed patients in CRS (67.4% vs 43.9%, p=0.047), CRM (62.8% vs 39.0%, p=0.025), and SRM (43.3% vs 4.3%, p=0.001), respectively. At 1 year, the CD bio-naïve group had higher CRS (82.1% vs 60.7%, p=0.026) than the bio-exposed group. There was no difference in effectiveness between bio-naïve and bio-exposed groups in UC at both 6 months and 1 year. Three patients (1.1%) reported serious infections (respiratory infection, intractable infection with underlying myelodysplastic syndrome and intestinal perforation due to endoscopy) and two (0.7%) had infusion-related reactions. No malignancies or hepatic injuries were reported. After limited treatment up to one year due to reimbursement, 58% (54/93) of patients had IBD relapse (CD: 27 [62.8%], UC: 27 [54%]). After cessation of VDZ, the mean [SD] time to IBD relapse was 5.5 [4.0] months in CD, and 5.8 [5.7] months for UC. Conclusion This study has shown the effectiveness and safety of VDZ therapy for Taiwan IBD patients. Better outcomes were observed in bio-naïve CD patients, whereas bio-naïve and bio-exposed UC patients have comparable outcomes. After a limited VDZ treatment duration, over one-half of patients had IBD relapse, with the majority occurring within 5 months of VDZ discontinuation. These data suggest that continued VDZ therapy would benefit the majority of IBD patients in Taiwan.

Adiponectin has an important role in obesity, insulin resistance, and cardiovascular disease. We investigated the association between serum adiponectin levels and endothelial function in kidney transplant patients.Fasting blood samples were obtained from 70 kidney transplant patients. The vascular reactivity index was measured with a digital thermal monitoring test. Serum adiponectin levels were measured with a commercially available enzyme immunoassay kit. A vascular reactivity index1.0 was defined as poor, 1.0 or greater but less than 2.0 was intermediate, and 2.0 or greater was good.The results showed that 10 kidney transplant patients (13.3%) were categorized with a vascular reactivity index of poor, 25 (35.7%) were intermediate, and 35 (50%) were good. Increased waist circumference (P = .037), increased serum alkaline phosphatase (P = .026), and lower serum adiponectin (P = .001) were associated with poor vascular reactivity index. Advanced age (r = -0.300; P = .012), waist circumference (r = -0.372; P = .002), serum alkaline phosphatase (r = -0.323; P = .006), and logarithmically transformed serum triglycerides (r = -0.317; P = .007) were negatively correlated with the vascular reactivity index, whereas serum adiponectin (r = 0.332; P = .005) was positively correlated with the vascular reactivity index. Multi variable forward stepwise linear regression analysis showed that waist circumference, serum alkaline phosphatase, and serum adiponectin were significantly and independently associated with the vascular reactivity index.Fasting serum adiponectin levels were positively associated with the vascular reactivity index and negatively associated with endothelial function in kidney transplant patients.

Acanthamoeba spp. are free-living parasites that can cause severe infections such as granulomatous amoebic encephalitis (GAE) and amoebic keratitis (AK). Polyhexamethylene biguanide (PHMB) is a topical application for AK treatment. However, PHMB is not entirely effective against all Acanthamoeba strains or isolates. The mechanisms by which Acanthamoeba protects itself against extreme drug conditions without encystation are still unknown. According to a previous study, cytochrome P450 monooxygenase (CYP450MO) plays an important role in the oxidative biotransformation of numerous drugs related to metabolism. In this study, a CYP450MO fragment was inserted into the pGAPDH-EGFP vector and transfected into Acanthamoeba castellanii. We found that CYP450MO-overexpressing Acanthamoeba had higher survival rates than those of the control cells after PHMB treatment. Moreover, we also found that encystation-related genes such as cellulose synthase I (CSI), encystation-mediating serine proteinase (EMSP), and autophagy-related protein 8 (ATG8) expression levels were not significantly different between Acanthamoeba transfected by pGAPDH-EGFP or pGAPDH-EGFP-CYP450MO. We suggest that Acanthamoeba transfected by pGAPDH-EGFP-CYP450MO may not induce encystation-related genes to resist PHMB treatment. In conclusion, these findings indicate that CYP450MO may be an additional target when PHMB is used for treatment of amoebic keratitis.La monooxygénase du cytochrome P450 d’Acanthamoeba castellanii participe à la résistance au traitement par le polyhexaméthylène biguanide.Les Acanthamoeba spp. sont des parasites libres qui peuvent provoquer des infections graves telles que l’encéphalite amibienne granulomateuse (EAG) et la kératite amibienne (KA). Le polyhexaméthylène biguanide (PHMB) est une application topique pour le traitement de la KA. Cependant, le PHMB n’est pas entièrement efficace contre toutes les souches ou isolats d’Acanthamoeba. Les mécanismes par lesquels Acanthamoeba se protège contre des conditions médicamenteuses extrêmes sans enkystation sont encore inconnus. Selon une étude précédente, la monooxygénase du cytochrome P450 (CYP450MO) joue un rôle important dans la biotransformation oxydative de nombreux médicaments liés au métabolisme. Dans cette étude, un fragment CYP450MO a été inséré dans le vecteur pGAPDH-EGFP et transfecté dans Acanthamoeba castellanii. Nous avons constaté que les Acanthamoeba surexprimant le CYP450MO avaient des taux de survie plus élevés que ceux des cellules témoins après un traitement au PHMB. De plus, nous avons également constaté que les gènes liés aux enkystations tels que la cellulose synthase I (CSI), la sérine protéinase médiatrice de l’enkystation (EMSP) et les niveaux d’expression de la protéine 8 liée à l’autophagie (ATG8) n’étaient pas significativement différents entre les Acanthamoeba transfectés par pGAPDH-EGFP ou par pGAPDH-EGFP-CYP450MO. Nous suggérons que les Acanthamoeba transfectés par pGAPDH-EGFP-CYP450MO ne peuvent pas induire les gènes liés à l’enkystation pour résister au traitement PHMB. En conclusion, ces résultats peuvent indiquer que la monooxygénase du cytochrome P450 peut être une cible potentielle pour le traitement par PHMB de la kératite amibienne.

BACKGROUND Whether a single low-dose ketamine infusion may have rapid antidepressant and antisuicidal effects in patients with treatment-resistant double depression remains unclear. METHODS This study enrolled 35 patients with treatment-resistant double depression, 12 of whom received 0.5 mg/kg ketamine, 11 received 0.2 mg/kg ketamine, and 12 received normal saline as a placebo. The patients were assessed using the 17-item Hamilton Rating Scale for Depression (HDRS) prior to the initiation of infusions, at 40 and 240 min post-infusion, and sequentially on Days 2-7 and on Day 14 after ketamine or placebo infusions. RESULTS A single 0.5 mg/kg ketamine infusion had rapid antidepressant (p = 0.031, measured by the HDRS) and antisuicidal (p = 0.033, measured by the HDRS item 3 scores) effects in patients with treatment-resistant double depression. However, 0.2 mg/kg ketamine was insufficient to exert rapid antidepressant and antisuicidal effects in this patient population with severe and chronic illness. DISCUSSION In this patient population, the commonly used dose of 0.5 mg/kg was sufficient. Additional studies are required to investigate whether repeated infusions of low-dose ketamine may also maintain antidepressant and antisuicidal effects in patients with treatment-resistant double depression.

Background Cardiometabolic diseases are suggested to be associated with bipolar disorder. However, the risk of metabolic disorders in unaffected siblings of patients with bipolar disorder remains unclear. Methods From the Taiwan National Health Insurance Research Database, 7,225 unaffected siblings of bipolar probands and 28,900 age-/sex-/income-/residence-matched control individuals were included and followed until the end of 2011. Individuals who developed metabolic disorders during the follow-up period were identified. Results The unaffected siblings of bipolar probands had a higher prevalence of dyslipidemia (5.4% vs. 4.5%, p = 0.001), younger age at diagnosis of type 2 diabetes mellitus (34.81 vs. 37.22, p = 0.024), and higher prevalence of any stroke (1.5% vs. 1.1%, p = 0.007) than the controls. Moreover, only male siblings of bipolar probands had an increased risk of dyslipidemia (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.10–1.48) and higher rates of any stroke (OR: 1.38, 95% CI: 1.02–1.85) and ischemic stroke (OR: 2.43, 95% CI: 1.60–3.70) during the follow-up compared with the controls. Discussion Unaffected siblings of bipolar patients, particularly brothers, had a higher prevalence of dyslipidemia and ischemic stroke compared with the controls. The result suggests the familial association between cardiometabolic diseases and bipolar disorder. Further research may be necessary to identify this shared etiology between the disorders.

Acanthamoeba is a free-living pathogenic protozoan that is distributed in different environmental reservoirs, including lakes and soil. Pathogenic Acanthamoeba can cause severe human diseases, such as blinding keratitis and granulomatous encephalitis. Therefore, it is important to understand the pathogenic relationship between humans and Acanthamoeba. By comparison of systemic analysis results for Acanthamoeba isolates, we identified a novel secreted protein of Acanthamoeba, an M28 aminopeptidase (M28AP), which targets of the human innate immune defense. We investigated the molecular functions and characteristics of the M28AP protein by anti-M28 antibodies and a M28AP mutant strain generated by the CRISPR/Cas9 system. Human complement proteins such as C3b and iC3b were degraded by Acanthamoeba M28AP. We believe that M28AP is an important factor in human innate immunity. This study provides new insight for the development of more efficient medicines to treat Acanthamoeba infection.

Background Gray matter volume reduction in specific brain regions, such as the prefrontal cortex, was found in patients with bipolar disorder and those with unipolar depression. However, few studies have directly compared gray matter volumes between bipolar disorder and unipolar depression. In addition, it is unknown whether proinflammatory cytokines play a role in the gray matter volume difference between bipolar disorder and unipolar depression. Methods Twenty-three patients with bipolar disorder and 23 with unipolar depression in a mildly ill state (Clinical Global Impression-Severity ≤ 3) were enrolled in our study. Each participant underwent structural magnetic resonance imaging and proinflammatory cytokines examination. Voxel-based morphometry was performed to investigate the gray matter volume difference between bipolar disorder and unipolar depression. Correlations of the proinflammatory cytokines and the gray matter volume difference were analyzed. Results Several brain regions, including the orbitofrontal cortex, lingual gyrus, inferior frontal cortex, middle frontal cortex, and planum polare, were significantly smaller in patients with bipolar disorder than in those with unipolar depression. These gray matter volume differences between bipolar disorder and unipolar depression were negatively correlated with soluble IL-6 receptor levels. Discussion Proinflammatory cytokines, especially IL-6, were associated with the gray matter volumes in bipolar disorder and unipolar depression. However, the complicated associations between proinflammatory cytokines, neurocognitive function, and gray matter volumes require further investigation.

Objective: We intended to investigate the risk of developing migraine among patients with posttraumatic stress disorder (PTSD). Methods: With the Taiwan's National Health Insurance Research Database, we examined 5,644 patients with PTSD and 22,576 age- and sex-matched controls between 2002 and 2009 and followed them to the end of 2011. Individuals who developed migraine during the follow-up period were identified. Results: Patients with PTSD had a significantly higher incidence of developing migraine (5.74 vs. 1.22 per 1,000 person-years, p < 0.001) during the follow-up period than the controls. We did Cox regression analysis with adjustments of demographic data and medical comorbidities and found that patients with PTSD were more likely to develop migraine (hazard ratio [HR] = 3.83, 95% confidence interval [CI] = 2.82–5.20) than the control group. Sensitivity analyses after excluding the 1st year (HR = 2.89; 95% CI = 2.04–4.08) or the first 3 years (HR = 2.07; 95% CI = 1.32–3.24) of observation showed consistent findings. Moreover, a high frequency of psychiatric clinics visiting for PTSD was associated with an increased risk of developing migraine. Conclusion: Patients with PTSD had a higher risk of migraine than the controls. The symptom severity of PTSD may be associated with an increased risk of migraine. Further studies are required to investigate the underlying pathophysiology between PTSD and migraine.

Background Several case reports have suggested an association between obsessive-compulsive disorder (OCD) and dementia. However, the exact relationship remains unclear. Methods Using the Taiwan National Health Insurance Research Database, 1,347 patients with OCD (ICD-9-CM code 300.3) aged ≥ 45 years and 13,470 controls matched for age, sex, residence, income, and dementia-related comorbidities were included between 1996 and 2013 for investigation of subsequent dementia from enrollment to the end of 2013. Stratified Cox regression analysis on each matched pair was applied to assess the dementia risk between the OCD and control groups. The analysis for the current study was performed in 2018. Results Patients with OCD had increased risk of developing any dementia (hazard ratio [HR] = 4.28; 95% confidence interval [CI], 2.96-6.21), Alzheimer's disease (HR = 4.04; 95% CI, 1.55-10.54), and vascular dementia (HR = 3.95; 95% CI, 1.70-9.18) compared with controls. Discussion Future research on the pathogenic mechanisms and molecular underpinnings of the relationship between OCD and dementia may lead to the development of novel therapeutics.

Acanthamoeba spp. are free-living protozoans that cause a serious human eye disease called Acanthamoeba keratitis (AK). Several new and effective medical therapies for AK patients remain highly debated, and therefore, chlorhexidine digluconate (CHG) is still considered one of the first lines of treatment for AK patients. We hypothesized that ocular microenvironmental factors are responsible for Acanthamoeba drug resistance and clinical AK treatment failure. To investigate the influence of the ocular surface on CHG treatment, we tested the effect of several ocular elements on the antiamoeba activity of CHG. The suspected inhibitory elements, including mucin, albumin, human and amoeba cell lysates, live and heat-killed bacteria, and cornea, were added to the amoebicidal activity platform, where amoebae were incubated with CHG at various concentrations. Mucin showed a significant inhibitory effect on CHG activity against Acanthamoeba castellanii. In contrast, albumin did not affect CHG treatment. Furthermore, human and amoeba cell lysates and live and heat-killed bacterial suspensions also significantly inhibited CHG activity. Additionally, we found that pig corneas also reduced CHG activity. In contrast, dry-eye drops and their major component, propylene glycol, which is commonly used as eyewash material, did not have an impact on CHG activity. Our results demonstrate the effect of ocular microenvironmental factors on CHG activity and suggest that these factors may play a role in the development of amoeba resistance to CHG and treatment failure.

Acanthamoeba act as hosts for various microorganisms and pathogens, causing Acanthamoeba Keratitis (AK). To investigate the association between endosymbionts and AK progression, we performed a metagenomics study to characterize the intracellular microbiome from five lenses associated with AK isolates and standard strains to characterize the role of ocular flora in AK progression. The used clinical isolates were axenic cultured from lenses associated with AK patients. AK isolates and standard controls such as 16S ribosomal RNA sequencing techniques were used for analysis. The microbiome compositions and relative abundance values were compared. The orders of Clostridiales and Bacteroidales presented major populations of intracellular microbes belonging to all isolates. Comparison of the different source isolates showed that most of the abundance in keratitis isolates came from Ruminococcus gnavus (121.0 folds), Eubacterium dolichum (54.15 folds), Roseburia faecis (24.51 folds), and Blautia producta (3.15 folds). Further analysis of the relative abundance data from keratitis isolates showed that Blautia producta was positively correlated with the disease course. In contrast, Bacteroides ovatus was found to be abundant in early-stage keratitis isolates. This study reveals the abundant anaerobic Gram-positive rods present in severe keratitis isolate and characterize the association between Acanthamoeba and ocular flora in AK progression.

Background Recent imaging studies of large datasets suggested that psychiatric disorders have common biological substrates. This study aimed to identify all the common neural substrates with connectomic abnormalities across four major psychiatric disorders by using the data-driven connectome-wide association method of multivariate distance matrix regression (MDMR). Methods This study analyzed a resting functional magnetic resonance imaging dataset of 100 patients with schizophrenia, 100 patients with bipolar I disorder, 100 patients with bipolar II disorder, 100 patients with major depressive disorder, and 100 healthy controls (HCs). We calculated a voxel-wise 4,330 × 4,330 matrix of whole-brain functional connectivity (FC) with 8-mm isotropic resolution for each participant and then performed MDMR to identify structures where the overall multivariate pattern of FC was significantly different between each patient group and the HC group. A conjunction analysis was performed to identify common neural regions with FC abnormalities across these four psychiatric disorders. Results The conjunction of the MDMR maps revealed that the four groups of patients shared connectomic abnormalities in distributed cortical and subcortical structures, which included bilateral thalamus, cerebellum, frontal pole, supramarginal gyrus, postcentral gyrus, lingual gyrus, lateral occipital cortex, and parahippocampus. The follow-up analysis based on pair-wise FC of these regions demonstrated that these psychiatric disorders also shared similar patterns of FC abnormalities characterized by sensory/subcortical hyperconnectivity, association/subcortical hypoconnectivity, and sensory/association hyperconnectivity. Conclusions These findings suggest that major psychiatric disorders share common connectomic abnormalities in distributed cortical and subcortical regions and provide crucial support for the common network hypothesis of major psychiatric disorders.

Backgrounds Evidence suggested the crucial roles of brain-derived neurotrophic factor (BDNF) and glutamate system functioning in the antidepressant mechanisms of low-dose ketamine infusion in treatment-resistant depression (TRD). Methods 65 patients with TRD were genotyped for 684,616 single nucleotide polymorphisms (SNPs). Twelve ketamine-related genes were selected for the gene-based genome-wide association study on the antidepressant effect of ketamine infusion and the resulting serum ketamine and norketamine levels. Results Specific SNPs and whole genes involved in BDNF–TrkB signaling (i.e., rs2049048 in BDNF and rs10217777 in NTRK2) and the glutamatergic and GABAergic systems (i.e., rs16966731 in GRIN2A) were associated with the rapid (within 240 min) and persistent (up to 2 weeks) antidepressant effect of low-dose ketamine infusion and with serum ketamine and norketamine levels. Discussion Our findings confirmed the predictive roles of BDNF–TrkB signaling and glutamatergic and GABAergic systems in the underlying mechanisms of low-dose ketamine infusion for TRD treatment.

Studies have suggested an association between metabolic and cerebrocardiovascular diseases and major depressive disorder (MDD). However, the risk of metabolic and cerebrocardiovascular diseases in the unaffected siblings of patients with MDD remains uncertain. Using the Taiwan National Health Insurance Research Database, 22,438 unaffected siblings of patients with MDD and 89,752 age-/sex-matched controls were selected and followed up from 1996 to the end of 2011. Individuals who developed metabolic and cerebrocardiovascular diseases during the follow-up period were identified. Compared with the controls, the unaffected siblings of patients with MDD had a higher prevalence of metabolic diseases, such as hypertension (5.0% vs. 4.5%, p = 0.007), dyslipidemia (5.6% vs. 4.8%, p < 0.001), and obesity (1.7% vs. 1.5%, p = 0.028), and cerebrocardiovascular diseases, such as ischemic stroke (0.6% vs. 0.4%, p < 0.005) and ischemic heart disease (2.1% vs. 1.7%, p < 0.001). Logistic regression analyses revealed that the unaffected siblings of patients with MDD were more likely to develop hypertension, dyslipidemia, ischemic stroke, and ischemic heart diseases during the follow-up period than the controls. Our study revealed a familial coaggregation between MDD and metabolic and cerebrocardiovascular diseases. Additional studies are required to investigate the shared pathophysiology of MDD and metabolic and cerebrocardiovascular diseases.

The association of appetite hormones with cognitive function in patients with affective disorders remains unknown.All total, 58 adult patients with bipolar I disorder, 36 with bipolar II disorder, 40 with major depressive disorder were enrolled and age and sex-matched with 40 controls. The levels of appetite hormones leptin, ghrelin, insulin and adiponectin were assessed. Wisconsin Card Sorting Test was used to assess executive function.A general linear model, adjusted for demographic data and clinical symptoms, demonstrated the ghrelin levels were higher in patients with bipolar I or II disorder than in those with major depressive disorder and controls (Patients with bipolar I or II disorder were more likely to have high levels of ghrelin than patients with major depressive disorder and controls, which may have a positive correlation on the cognitive function of patients with bipolar I or II disorder.

Background: Evidence suggests a bidirectional association between migraine and depression in individuals and in twins. However, whether a bidirectional association between migraine and depression also occurs among siblings (probands and unaffected nontwin siblings) remains unknown. Methods: Using the Taiwan National Health Insurance Research Database, we examined the data of 1504 probands with migraine, 1595 unaffected siblings, and 6380 nonmigrainous controls born before 2000 to identify new-onset depression for the period between 1996 and 2011. Conversely, 31824 probands with depression, 34325 unaffected siblings, and 137300 nondepressive controls were examined for the identification of new-onset migraine. Results: Logistic regression analyses demonstrated that compared with the controls, patients with migraine (odds ratio [OR]: 4.09; 95% confidence interval [CI]: 3.75–4.46) and unaffected siblings (OR: 1.40; 95% CI: 1.24–1.58) were more likely to develop depression during the follow-up period. Moreover, patients with depression and unaffected siblings had a 4.13-fold (95% CI: 3.18–5.36) and 1.45-fold (95% CI: 1.03–2.05) increased risk of migraine. Discussion: The bidirectional association between migraine and depression among probands and unaffected siblings suggests a familial coaggregation of these two conditions. Additional studies are required to investigate the genetic and environmental etiologies for this coaggregation.

BackgroundStudies have suggested the detrimental effects of obesity and systemic inflammation on the cognitive function of patients with bipolar or major depressive disorder. However, the complex associations between affective disorder, obesity, systemic inflammation, and cognitive dysfunction remain unclear.MethodsOverall, 110 patients with affective disorder (59 with bipolar I disorder and 51 with major depressive disorder) who scored ≥61 on the Global Assessment of Functioning and 51 age- and sex-matched controls were enrolled. Body mass index ≥25 kg/m2 was defined as obesity or overweight. Levels of proinflammatory cytokines—including interleukin-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)—were measured, and cognitive function was assessed using various methods, including the Wisconsin Card Sorting Test (WCST) and go/no-go task.ResultsPatients with bipolar I disorder or major depressive disorder were more likely to be obese or overweight, had higher CRP and TNF-α levels, and had greater executive dysfunction in the WCST than the controls. TNF-α level (P ConclusionsOur findings may indicate that proinflammatory cytokines, but not obesity or overweight, have crucial effects on cognitive function in patients with bipolar I disorder or major depressive disorder, although proinflammatory cytokines and obesity or overweight were found to be strongly associated. The complex relationships between affective disorder diagnosis, proinflammatory cytokine levels, obesity or overweight, and cognitive function require further investigation.

Periodontitis, an inflammatory disease of the oral cavity, was caused by microbes from bacteria to protozoa. In this study, we detected protozoa, Entamoeba gingivalis and other three common pathogenic bacteria, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia by the Polymerase chain reaction (PCR) on patients.

With the introduction of direct-acting antiviral (DAA) agents, hepatitis C virus (HCV) treatment has dramatically improved. However, there are insufficient data on the benefits of DAA therapy in hepatocellular carcinoma (HCC). The purpose of this study was to investigate the outcome of patients who received DAA therapy after HCC treatment. We retrospectively reviewed patients with HCV-related HCC in a single medical center, and the outcome of patients with or without DAA therapy was analyzed. In total, 107 HCC patients were enrolled, of whom 60 had received DAA therapy after treatment for HCC. There were no significant intergroup differences in age, sex, laboratory results, or tumor burden. A more advanced stage was noted in the no DAA group (P = 0.003). In the treatment modality, sorafenib was commonly prescribed in the no DAA group (P = 0.007). The DAA group had a longer overall survival (OS) time than the no DAA group (P

Background Studies have reported that ketamine potentially increases subjective happiness in healthy volunteers. However, whether ketamine-induced happiness can predict the treatment response of ketamine infusion among patients with treatment-resistant depression (TRD) remains unknown. Methods Between 2012 and 2015, 71 adult patients with TRD (based on DSM-IV-TR criteria) were enrolled and randomly assigned to receive a 40-minute ketamine (0.5 mg/kg or 0.2 mg/kg) or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale. Measurements were conducted prior to infusion, at 40 and 240 minutes postinfusion, and, sequentially, on days 2 to 7 and 14 postinfusion. The visual analog scale for happiness (VASH) was used to assess happiness during infusion. The positive symptoms subscale of the Brief Psychiatric Rating Scale (BPRS-P) was used to measure the potential psychotomimetic effects of ketamine. Results For both the 2-factor (ketamine vs placebo) and 3-factor (ketamine 0.5 mg/kg vs 0.2 mg/kg vs placebo) models, a generalized estimating equation model indicated that infusion response type (happiness vs nonhappiness) significantly (P = .008 vs P = .002) predicted the trajectory of depressive symptoms after infusion. Changes in VASH and BPRS-P measures were not associated with each other. Conclusions Subjective happiness during ketamine infusion predicted the antidepressant effect of both 0.5 mg/kg and 0.2 mg/kg ketamine infusion over time. Happiness during ketamine infusion, which was not related to the psychotomimetic effect of ketamine, may be associated with the reduction of depressive symptoms during the follow-up. Trial registration UMIN Clinical Trials Registry registration number: UMIN000016985.

Background Previous individual studies have shown the differences in inflammatory cytokines and gray matter volumes between bipolar disorder (BD) and unipolar depression (UD). However, few studies have investigated the association between pro-inflammatory cytokines and differences in brain gray matter volumes between BD and UD. Methods In this study, 72 BD patients and 64 UD patients were enrolled, with comparable gender and age distributions (33.8% males and an average age of 39.3 ± 13.7 years). Each participant underwent metabolic profiling (including body mass index (BMI), glucose, triglyceride, high-density lipoprotein (HDL), leptin, insulin, adiponectin), pro-inflammatory cytokine (including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1) examinations, and structural magnetic resonance imaging exams. Voxel-based morphometry was performed to investigate the gray matter volume differences between BD and UD patients. Correlations between pro-inflammatory cytokines and the gray matter volume difference were analyzed. Results Compared to UD patients, the BD group had significantly higher BMI, and higher levels of sIL-6R and sTNF-R1 than the UD patients. The BMI significantly correlated with the level of pro-inflammatory cytokines. Adjusted for age, sex, BMI, duration of illness and total intracranial volume, the BD individuals had significantly more reduced gray matter volumes over 12 areas: R. cerebellar lobule VIII, R. putamen, L. putamen, R. superior frontal gyrus, L. lingual gyrus, L. precentral gyrus, R. fusiform gyrus, L. calcarine, R. precuneus, L. inferior temporal gyrus, L. hippocampus, and L. superior frontal gyrus. These 12 gray matter volume differences between BP and UD patients negatively correlated with sIL-6R and sTNF-R1 levels. Conclusions Our results suggested that BD patients had higher BMI and pro-inflammatory cytokine levels in comparison to UD patients, especially IL-6 and sTNF-R1, which may contribute to greater gray matter reductions in BD patients in comparison to UD patients. The results support the neuro-inflammation pathophysiology mechanism in mood disorder. It is clinically important to monitor BMI, which, in this investigation, positively correlated with levels of inflammatory cytokines.

Background Inflammatory bowel disease (IBD) was emerging as a worldwide epidemic disease, and the advanced therapy changed the clinical course and possibly the outcomes. Our previous study reported a higher mortality rate from (IBD) in Taiwan than in Western countries. We proposed to analyze the trend and risk factors of mortality in order to improve the care quality of IBD patients. Methods This retrospective study was conducted to analyze data for January 2001 to December 2015 from a registered database, compiled by the Taiwan’s National Health Insurance. Results Between 2001 and 2015, a total of 3806 IBD patients [Crohn’s disease (CD): 919; ulcerative colitis (UC): 2887] were registered as having catastrophic illness, and 8.2% of these patients died during follow-up. The standardized mortality ratios (SMRs) of CD and UC were 3.72 (95% CI 3.02–4.55) and 1.44 (95% CI 1.26–1.65), respectively, from 2001 to 2015, respectively. A comparison of the periods of 2011–2015 and 2001–2005 revealed a decrease in the mortality rates from both UC and CD. Multivariate Cox proportional hazards analysis identified elderly individuals; sepsis and pneumonia were the risk factors for IBD mortality. The specific risk factors of mortality were liver cancer for UC and surgeries for CD. Conclusion For further decreasing IBD-related mortality in Taiwan, we need to pay special attention toward elderly individuals, infection control, cancer screening and improvement in perioperative care.

ADHD comorbidity has been associated with delayed diagnosis of ASD, but no study has investigated this association in an Asian country. Children with ASD were included and divided into three groups: ADHD before ASD, ADHD same/after ASD, and ASD only. Timing of ASD and ADHD diagnoses were assessed. The logistic regression model was performed to investigate the likelihood of being diagnosed with ASD after 6 years of age between three groups. ADHD before ASD (OR 10.93) group was more likely to being diagnosed with ASD after 6 years of age compared with ADHD same/after ASD (OR: 1.37) and ASD only groups. ADHD comorbidity would delay the diagnosis of ASD in the general clinical settings in Taiwan.

BackgroundAttention-deficit hyperactivity disorder (ADHD) increases the risk of suicidal behaviours through psychiatric comorbidities; however, a significant direct association has not been observed between ADHD and suicide attempts.AimsTo evaluate the risk of suicide attempt in adolescents and young adults with ADHD.MethodUsing a nationwide, population-based insurance claims database, this longitudinal cohort study enrolled 20 574 adolescents and young adults with ADHD and 61 722 age- and gender-matched controls between 2001 and 2009. Any suicide attempt was identified from enrolment to 31 December 2011. The association between ADHD medications and the likelihood of suicide attempt was assessed.ResultsADHD was an independent risk factor for any suicide attempt (hazard ratio = 3.84, 95% CI = 3.19–4.62) and repeated suicide attempts (hazard ratio = 6.52, 95% CI = 4.46–9.53). Subgroup analyses of men, women, adolescents and young adults demonstrated the same trend. Methylphenidate or atomoxetine treatment did not increase the risk of suicide attempt or repeated suicide attempts. Long-term methylphenidate treatment was associated with a significantly decreased risk of repeated suicide attempts in men (hazard ratio = 0.46, 95% CI = 0.22–0.97).ConclusionADHD was a risk factor for suicide attempt and a stronger predictor of repeated suicide attempts, independent of comorbidities. Further investigation is warranted to explore the mechanism underlying the association between ADHD and suicidal behaviours.Declaration of interestNone.

Backgrounds Whether the antidepressant effects of low-dose ketamine infusion and the therapeutic impact of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism vary across different depression symptom domains, namely affective, cognitive, and somatic, remains unclear. Methods We-reanalyzed the data of Adjunctive Ketamine Study of Taiwanese Patients with Treatment-Resistant Depression (TRD). A total of 71 patients with TRD were randomized to three infusion groups: 0.5 and 0.2 mg/kg ketamine groups and the normal saline placebo group. The Beck Depression Inventory-II (BDI-II) was used to obtain self-reported scores prior to infusion and 240 min after infusion and sequentially on days 3, 7, and 14 after infusion. The three-factor model of cognitive, somatic, and affective depressive symptoms that is based on the BDI-II and proposed by Beck et al. was applied in the current study. The Val66Met BDNF polymorphism was genotyped. Results Ketamine infusion exerted rapid and sustained antidepressant effects on the affective (p = 0.014) and cognitive (p = 0.005) depression symptom domains but not on the somatic (p = 0.085) depression symptom domain. Only patients with TRD harboring any Val allele at the BDNF rs6265 polymorphism were more likely to respond (p = 0.011) to low-dose ketamine infusion. Discussion Additional studies should elucidate different mechanisms underlying the effects of ketamine infusion on cognitive, affective, and somatic depression symptom domains in patients with TRD.

A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan’s National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65–4.88), bipolar disorder (3.23, 3.12–3.35), major depressive disorder (2.05, 2.00–2.10), ASD (2.55, 2.35–2.77) and ADHD (1.31, 1.25–1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.

Background/Purpose Acanthamoeba keratitis (AK), a painful infectious corneal disease, is caused by the free-living pathogenic species Acanthamoeba . The symptoms include corneal infiltrate, epithelial, and stromal destruction, and loss of vision. Current treatment generally involves an hourly application of polyhexamethylene biguanide (PHMB) over a period of several days; however, even this is not entirely effective against all strains/isolates. The aims of this study were to confirm the existence of pathogenic strains in Taiwan which are highly resistant to drugs and to characterize the behavior of these strains. Methods An in vitro Acanthamoeba species culture platform was established to observe the effectiveness of treatment and chart the morphological changes that occur under the effects of drugs using a light microscope and time-lapse recording. Changes in gene expression were examined using reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR. Results Over 90% of the standard strain cells (ATCC 30010) were lysed after being treated with PHMB for 1 hour; however, clinical isolates of Acanthamoeba castellanii that differed in their susceptibility to the treatment drug were only partly lysed. Following treatment with PHMB, National Cheng Kung University Hospital isolation B (NCKH_B) transformed into a pseudocyst under the effects of drug stress; however, National Cheng Kung University Hospital isolation D (NCKH_D), an isolate with higher tolerance for PHMB, did not transform. Conclusion Our results confirm the existence of clinical isolates of A. castellanii with high resistance to PHMB in Taiwan and present the alternative drug tolerance of A. castellanii in addition to the transformation of pseudocyst/cyst.

Glioblastoma multiforme (GBM) is one of the most aggressive cancers. Despite recent advances in multimodal therapies, high-grade glioma remains fatal. Temozolomide (TMZ) is an alkylating agent used worldwide for the clinical treatment of GBM; however, the innate and acquired resistance of GBM limits its application. Here, we found that TMZ inhibited the proliferation and induced the G2/M arrest of GBM cells. Therefore, we performed microarrays to identify the cell cycle- and apoptosis-related genes affected by TMZ. Notably, GADD45A was found to be up-regulated by TMZ in both cell cycle and apoptosis arrays. Furthermore, GADD45A knockdown (GADD45Akd) enhanced the cell growth arrest and cell death induced by TMZ, even in natural (T98) and adapted (TR-U373) TMZ-resistant cells. Interestingly, GADD45Akd decreased the expression of O6-methylguanine-DNA methyltransferase (MGMT) in TMZ-resistant cells (T98 and TR-U373). In MGMT-deficient/TMZ-sensitive cells (U87 and U373), GADD45Akd decreased TMZ-induced TP53 expression. Thus, in this study, we investigated the genes influenced by TMZ that were important in GBM therapy, and revealed that GADD45A plays a protective role against TMZ treatment which may through TP53-dependent and MGMT-dependent pathway in TMZ-sensitive and TMZ-resistant GBM, respectively. This protective role of GADD45A against TMZ treatment may provide a new therapeutic strategy for GBM treatment.

Previous studies have demonstrated the association between Cushing's syndrome (CS), obstructive sleep apnea (OSA), and the risk factors for OSA, but rarely provided the evidence within a large population. Using the Taiwan National Health Insurance Research Database, we attempted to investigate the association between CS and OSA, and to provide persuading evidences.In our study, 1612 patients with CS and 1612 age-, sex-, and comorbidities-matched controls were included, and followed up to the end of 2011. Cases of OSA were identified during the follow-up.Among patients with CS, 53 developed OSA (incidence: 4.11 per thousand person-year) compared with 22 in the control group (incidence: 1.70 per thousand person-year) during the follow-up (p 0.001). CS patients had a 2.82-fold higher risk of developing OSA (HR = 2.82; 95% CI: 1.67-4.77) in later life.Our study was the first longitudinal study to support the temporal association between CS and risk of OSA. Patients with CS were associated with an increased likelihood of OSA. Further studies would be required to investigate the exact underlying mechanisms between CS and OSA, and elucidate whether the prompt intervention for CS may reduce the risk of subsequent OSA.

OBJECTIVE Several cross-sectional studies have reported a relationship between posttraumatic stress disorder (PTSD) and epilepsy. However, the temporal association between PTSD and epilepsy has rarely been investigated. We hypothesized that the risk of developing epilepsy later in life would be higher in patients with PTSD than in those without PTSD. METHODS Using the Taiwan National Health Insurance Research Database, 6425 individuals with PTSD and 24,980 age-/sex-matched controls were enrolled between 2002 and 2009 in our study and followed up to the end of 2011. Those who developed epilepsy during the follow-up period were identified. RESULTS Individuals with PTSD had a higher incidence of developing epilepsy (2.65 versus 0.33 per 1000 person-years, p < .001), with an earlier onset of epilepsy (37.53 years [15.80 years] versus 48.11 years [23.97 years], p = .002) than did the controls. Individuals with PTSD had an elevated risk of developing epilepsy (hazard ratio [HR] = 3.72, 95% confidence interval [CI] = 2.27-6.11) during the follow-up after adjustment for demographic data and medical and psychiatric comorbidities. Sensitivity analyses after excluding the observation in the first year (HR = 2.53, 95% CI = 1.44-4.47) and the first 3 years (HR = 2.14, 95% CI = 1.15-4.01) revealed consistent results. CONCLUSIONS These results supported a temporal association between PTSD and the development of epilepsy. Further studies are warranted to investigate the underlying pathophysiological pathways that explain the longitudinal association of PTSD with subsequent epilepsy.

Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.

The antidepressant effects of ketamine are thought to depend on brain-derived neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to characterize the dose-related antidepressant effects of ketamine in patients with treatment-resistant depression drawn from a Chinese population predominately possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a double-blind, randomized, parallel-group, placebo-controlled trial of a single ketamine infusion (saline, 0.2 mg/kg, 0.5 mg/kg). Patients (N=71; BDNF genotype: Val/Val (N=12, 17%), Val/Met (N=40, 56.3%), and Met/Met (N=19, 26.8%)) received mood ratings before infusion, after infusion, and for the subsequent 14 days. Plasma ketamine levels and BDNF genotypes were assessed. This study found a significant dose-related ketamine effect on scores on the Hamilton Depression Rating Scale (HAMD). The responder analysis (>50% reduction from baseline HAMD on at least 2 days between days 2 and 5) also revealed a significant dose-related effect (saline: 12.5%, 0.2 mg/kg: 39.1%; 0.5 mg/kg: 45.8%). This is the first report to our knowledge to demonstrate the dose-related efficacy of R/S-ketamine for treatment-resistant depression and the first to characterize ketamine effects in a genotyped Chinese population in which most (83%) patients possessed at least one copy of the lower functioning Met allele of the BDNF gene.

Spinal dura arteriovenous fistula (SDAVF) is not an uncommon vascular malformation but is rare at craniocervical junction. The initial presentation is usually subarachnoid hemorrhage or cervical myelopathy caused by venous hypertension of the drainage vein. We report a male patient who has sudden onset of paraplegia, anesthesia of bilateral lower limbs, and urine retention. Cervical spinal cord edema and engorgement of posterior and anterior spinal veins were noted on magnetic resonance image study. Angiogram disclosed a SDAVF feeding by meningeal branch of the left vertebral artery and drainage inferiorly through posterior and anterior spinal vein. Complete obliteration of the fistula was achieved by transarterial embolization with n-butyl cyanoacrylate. The muscle power of lower limbs improved after the embolization. In previous studies, functional outcome is most correlated with pretreatment condition. Early diagnosis and treatment of the lesion will prevent permanent neurological deficit.

Objective It was unclear whether older people without dementia who attempted suicide were at increased risk of subsequently developing dementia. Methods Using the Taiwan National Health Insurance Research Database, 1,189 patients aged ≥ 65 years who attempted suicide and 4,756 age- and sex-matched control subjects were enrolled in our study and followed to the end of 2011. Those who developed dementia during the follow-up were identified. Results Cox regression analysis, after adjusting for demographic data and medical comorbidities, found that geriatric suicide attempt was associated with an increased risk of subsequent dementia (HR: 7.40; 95% CI: 6.11–8.97; Wald χ 2 = 414.87, df = 1, p 2 = 312.62, df = 1, p 2 = 97.78, df = 1, p Conclusion The elderly who attempted suicide were prone to developing dementia in later life, independent of depression and medical comorbidities. Further studies are necessary to clarify the underlying mechanisms between geriatric suicide and dementia and whether the prompt intervention for geriatric suicide may reduce this risk.

Pancreatic cancer is the eighth leading cause of cancer-related deaths in Taiwan. Pancreatic cancer has a poor prognosis. Diagnosis of early-stage pancreatic cancer, which can be defined based on resectability, size, or curability, will improve survival. Diagnostic tools for pancreatic cancer include transabdominal ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography (ERCP), and endoscopic ultrasound (EUS). We report the case of a 48-year-old man who presented with progressively yellowing skin. An CT imaging study did not reveal the pancreatic lesion. Further imaging with EUS was performed to search for the organic lesion causing an abrupt distal common bile duct stricture, and a heterogeneous hypoechoic tumor located at the uncinate process was identified. The patient underwent a Whipple operation because malignancy could not be ruled out. The final pathological result was moderate to poorly differentiated adenocarcinoma.