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A simple and effective strategy is proposed for fabricating honeycomb-patterned ethyl cellulose (EC) films via a combination of the dip-coating and breath figure methods under a wide humidity range (40–90%). A mixture of toluene and methanol as a volatile solvent/nonsolvent pair was used to effectively control the surface morphology. Additionally, honeycomb patterns were successfully formed via dip-coating under a low humidity (relative humidity less than 40%), when water was directly added into the mixed solution. The important factors that influenced the morphology of EC honeycomb-patterned films were investigated, such as the humidity, solution concentration, and the withdrawal speed during dip-coating. The pore sizes could be controlled by changing the film-formation conditions. Water contact angle enables a transition from hydrophilic to hydrophobic. The possible mechanisms of honeycomb pattern formation are discussed. The fabrication of an ordered honeycomb-patterned film in a cost-effective and convenient manner will have broad application potential in the future.
The upsurge in the number of people affected by the COVID-19 is likely to lead to increased rates of emotional trauma and mental illnesses. This article systematically reviewed the available data on the benefits of interventions to reduce adverse mental health sequelae of infectious disease outbreaks, and to offer guidance for mental health service responses to infectious disease pandemic. PubMed, Web of Science, Embase, PsycINFO, WHO Global Research Database on infectious disease, and the preprint server medRxiv were searched. Of 4278 reports identified, 32 were included in this review. Most articles of psychological interventions were implemented to address the impact of COVID-19 pandemic, followed by Ebola, SARS, and MERS for multiple vulnerable populations. Increasing mental health literacy of the public is vital to prevent the mental health crisis under the COVID-19 pandemic. Group-based cognitive behavioral therapy, psychological first aid, community-based psychosocial arts program, and other culturally adapted interventions were reported as being effective against the mental health impacts of COVID-19, Ebola, and SARS. Culturally-adapted, cost-effective, and accessible strategies integrated into the public health emergency response and established medical systems at the local and national levels are likely to be an effective option to enhance mental health response capacity for the current and for future infectious disease outbreaks. Tele-mental healthcare services were key central components of stepped care for both infectious disease outbreak management and routine support; however, the usefulness and limitations of remote health delivery should also be recognized.
There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia.
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.
Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.
This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).
FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50–19.67), ADHD 3.94 (CI 3.72–4.17), schizophrenia 3.05 (CI 2.74–3.40), BD 2.22 (CI 1.98–2.48) and MDD 1.88 (CI 1.76–2.00). Higher RRs of schizophrenia (4.47, CI 3.95–5.06) and ASD (18.54, CI 16.18–21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.
The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.
Studies 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.
Overall, 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.
Patients 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 < .05) but not affective disorder diagnosis or obesity/overweight was significantly associated with cognitive function deficits, although obesity/overweight and diagnosis were significantly associated with increased TNF-α level.
Our 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.
An atomistic kinetic Monte Carlo coupled with the embedded-atom method is used to simulate film growth and morphology evolution of a Cu–Zn–Sn precursor of Cu2ZnSnS4 solar cells by single-step electrodeposition. The deposition and diffusion events of three different metallic atoms are described by the simulation. Moreover, the multibody Cu–Zn–Sn potential is used to calculate diffusion barrier energy. The effects of process factors, including temperature and electrode potential, on the cross-section morphology and surface roughness are explored, while keeping the elemental composition ratios constant. The lowest roughness with the smoothest morphology is obtained at the optimal parameters. The distribution and transformation behaviors of cluster sizes are investigated to describe the alloy film growth process. Furthermore, the comparison between deposition events and diffusion events reveals that deposition events depend primarily on individual deposition rates of different metallic atoms, but diffusion events are mainly dependent on the interaction of metallic atoms. The film morphology evolution is visualized by three-dimensional configuration with increasing numbers of atoms, which suggests a competing mechanism between nucleation and growth of the thin film alloy.
Compared with the general population, individuals with schizophrenia have a higher risk of periodontal disease, which can potentially reduce their life expectancy. However, evidence for the early development of periodontal disease in schizophrenia is scant. The current study investigated risk factors for periodontal disease in patients newly diagnosed with schizophrenia.
We identified a population-based cohort of patients in Taiwan with newly diagnosed schizophrenia who developed periodontal disease within 1 year of their schizophrenia diagnosis. Treatment with antipsychotics and other medications was categorised according to medication type and duration, and the association between medication use and the treated periodontal disease was assessed through logistic regression.
Among 3610 patients with newly diagnosed schizophrenia, 2373 (65.7%) had an incidence of treated periodontal disease during the 1-year follow-up. Female sex (adjusted odds ratios [OR] 1.40; 95% confidence interval [CI] 1.20–1.63); young age (adjusted OR 0.99; 95% CI 0.98–0.99); a 2-year history of periodontal disease (adjusted OR 2.45; 95% CI 1.84–3.26); high income level (adjusted OR 2.24; 95% CI 1.64–3.06) and exposure to first-generation (adjusted OR 1.89; 95% CI 1.54–2.32) and secondary-generation (adjusted OR 1.33; 95% CI 1.11–1.58) antipsychotics, anticholinergics (adjusted OR 1.24; 95% CI 1.03–1.50) and antihypertensives (adjusted OR 1.91; 95% CI 1.64–2.23) were independent risk factors for periodontal disease. Hyposalivation – an adverse effect of first-generation antipsychotics (FGAs) (adjusted OR 2.00; 95% CI 1.63–2.45), anticholinergics (adjusted OR 1.27; 95% CI 1.05–1.53) and antihypertensives (adjusted OR 1.90; 95% CI 1.63–2.22) – was associated with increased risk of periodontal disease. Therefore, hypersalivation due to FGA use (adjusted OR 0.72; 95% CI 0.59–0.88) was considered a protective factor.
The current study highlights that early prevention of periodontal disease in individuals with schizophrenia is crucial. Along with paying more attention to the development of periodontal disease, assessing oral health regularly, helping with oral hygiene, and lowering consumption of sugary drinks and tobacco, emphasis should also be given by physicians to reduce the prescription of antipsychotics to the extent possible under efficacious pharmacotherapy for schizophrenia.
The initial classic Fontan utilising a direct right atrial appendage to pulmonary artery anastomosis led to numerous complications. Adults with such complications may benefit from conversion to a total cavo-pulmonary connection, the current standard palliation for children with univentricular hearts.
A single institution, retrospective chart review was conducted for all Fontan conversion procedures performed from July, 1999 through January, 2017. Variables analysed included age, sex, reason for Fontan conversion, age at Fontan conversion, and early mortality or heart transplant within 1 year after Fontan conversion.
A total of 41 Fontan conversion patients were identified. Average age at Fontan conversion was 24.5 ± 9.2 years. Dominant left ventricular physiology was present in 37/41 (90.2%) patients. Right-sided heart failure occurred in 39/41 (95.1%) patients and right atrial dilation was present in 33/41 (80.5%) patients. The most common causes for Fontan conversion included atrial arrhythmia in 37/41 (90.2%), NYHA class II HF or greater in 31/41 (75.6%), ventricular dysfunction in 23/41 (56.1%), and cirrhosis or fibrosis in 7/41 (17.1%) patients. Median post-surgical follow-up was 6.2 ± 4.9 years. Survival rates at 30 days, 1 year, and greater than 1-year post-Fontan conversion were 95.1, 92.7, and 87.8%, respectively. Two patients underwent heart transplant: the first within 1 year of Fontan conversion for heart failure and the second at 5.3 years for liver failure.
Fontan conversion should be considered early when atrial arrhythmias become common rather than waiting for severe heart failure to ensue, and Fontan conversion can be accomplished with an acceptable risk profile.
Research suggests an association between metabolic disorders, such as type 2 diabetes mellitus (T2DM), and schizophrenia. However, the risk of metabolic disorders in the unaffected siblings of patients with schizophrenia remains unclear.
Using the Taiwan National Health Insurance Research Database, 3135 unaffected siblings of schizophrenia probands and 12,540 age-/sex-matched control subjects were included and followed up to the end of 2011. Individuals who developed metabolic disorders during the follow-up period were identified.
The unaffected siblings of schizophrenia probands had a higher prevalence of T2DM (3.4% vs. 2.6%, p = 0.010) than the controls. Logistic regression analyses with the adjustment of demographic data revealed that the unaffected siblings of patients with schizophrenia were more likely to develop T2DM (odds ratio [OR]: 1.39, 95% confidence interval [CI]: 1.10–1.75) later in life compared with the control group. Moreover, only female siblings of schizophrenia probands had an increased risk of hypertension (OR: 1.47, 95% CI: 1.07–2.01) during the follow-up compared with the controls.
The unaffected siblings, especially sisters, of schizophrenia probands had a higher prevalence of T2DM and hypertension compared with the controls. Our study revealed a familial link between schizophrenia and T2DM in a large sample. Additional studies are required to investigate the shared pathophysiology of schizophrenia and T2DM.
This paper explores the characteristics of health technology assessment (HTA) systems and practices in Asia. Representatives from nine countries were surveyed to understand each step of the HTA pathway. The analysis finds that although there are similarities in the processes of HTA and its application to inform decision making, there is variation in the number of topics assessed and the stakeholders involved in each step of the process. There is limited availability of resources and technical capacity and countries adopt different means to overcome these challenges by accepting industry submissions or adapting findings from other regions. Inclusion of stakeholders in the process of selecting topics, generating evidence, and making funding recommendations is critical to ensure relevance of HTA to country priorities. Lessons from this analysis may be instructive to other countries implementing HTA processes and inform future research on the feasibility of implementing a harmonized HTA system in the region.
The nucleocapsid protein NC is a crucial component in the human immunodeficiency virus type 1 life cycle. It functions both in its processed mature form and as part of the polyprotein Gag that plays a key role in the formation of new viruses. NC can protect nucleic acids (NAs) from degradation by compacting them to a dense coil. Moreover, through its NA chaperone activity, NC can also promote the most stable conformation of NAs. Here, we explore the balance between these activities for NC and Gag by confining DNA–protein complexes in nanochannels. The chaperone activity is visualized as concatemerization and circularization of long DNA via annealing of short single-stranded DNA overhangs. The first ten amino acids of NC are important for the chaperone activity that is almost completely absent for Gag. Gag condenses DNA more efficiently than mature NC, suggesting that additional residues of Gag are involved. Importantly, this is the first single DNA molecule study of full-length Gag and we reveal important differences to the truncated Δ-p6 Gag that has been used before. In addition, the study also highlights how nanochannels can be used to study reactions on ends of long single DNA molecules, which is not trivial with competing single DNA molecule techniques.
We hypothesize that the tumor necrosis factor-α (TNF-α) may play a role in disturbing the effect of selective serotonin reuptake inhibitor (SSRI) on the striatal connectivity in patients with major depressive disorder (MDD).
We performed a longitudinal observation by combining resting-state functional magnetic resonance imaging (rs-fMRI) and biochemical analyses to identify the abnormal striatal connectivity in MDD patients, and to evaluate the effect of TNF-α level on these abnormal connectivities during SSRI treatment. Eighty-five rs-fMRI scans were collected from 25 MDD patients and 35 healthy controls, and the scans were repeated for all the patients before and after a 6-week SSRI treatment. Whole-brain voxel-wise functional connectivity (FC) was calculated by correlating the rs-fMRI time courses between each voxel and the striatal seeds (i.e. spherical regions placed at the striatums). The level of TNF-α in serum was evaluated by Milliplex assay. Factorial analysis was performed to assess the interaction effects of ‘TNF-α × treatment’ in the regions with between-group FC difference.
Compared with controls, MDD patients showed significantly higher striatal FC in the medial prefrontal cortex (MPFC) and bilateral middle/superior temporal cortices before SSRI treatment (p < 0.001, uncorrected). Moreover, a significant interaction effect of ‘TNF-α × treatment’ was found in MPFC-striatum FC in MDD patients (p = 0.002), and the significance remained after adjusted for age, gender, head motion, and episode of disease.
These findings provide evidence that treatment-related brain connectivity change is dependent on the TNF-α level in MDD patients, and the MPFC-striatum connectivities possibly serve as an important target in the brain.
Environmental characteristics (for example, temperature, photoperiod) as seasonal cues can affect the offspring sex ratio and reproductive tactics of many hymenopteran insects. Leptocybe invasa Fisher & La Salle is the most critical invasive insect pest of Eucalyptus spp. in the world and displays thelytokous reproduction. In the current study, we studied the effects of temperature and photoperiod on offspring sex ratio and reproductive tactics in L. invasa. Results show that sex ratio (female: male) of L. invasa was under 15, 25 and 35 °C with both L 12: D 12 and L 16: D 8, and cold and thermal acclimation were 74.5:1, 71.0:1, 59.0:0, 17.3:1, 53.0:0, 64.0:0, 47.0:1 and 56.0:0, respectively, which was highly significantly female biased and with no significant difference due to temperature or photoperiod. Offspring virgin females oviposited and induced the bump-shaped galls on plants under the same conditions as described above. Constant temperature, photoperiod and their interaction, and cold and thermal acclimation had no significant effect on the infestation rates of Eucalyptus branches induced by offspring virgin females. Thus, temperature, photoperiod and cold and thermal acclimation did not influence female-biased sex ratio and tactics with thelytokous reproduction of offspring females in L. invasa.
Attention-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.
To evaluate the risk of suicide attempt in adolescents and young adults with ADHD.
Using 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.
ADHD 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).
ADHD 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.
Van der Waals (vdW) heterojunctions consisting of vertically-stacked individual or multiple layers of two-dimensional layered semiconductors, especially the transition metal dichalcogenides (TMDs), show novel optoelectronic functionalities due to the sensitivity of their electronic and optical properties to strong quantum confinement and interfacial interactions. Here, monolayers of n-type MoSe2 and p-type Mo1−xWxSe2 are grown by vapor transport methods, then transferred and stamped to form artificial vdW heterostructures with strong interlayer coupling as proven in photoluminescence and low-frequency Raman spectroscopy measurements. Remarkably, the heterojunctions exhibit an unprecedented photoconductivity effect that persists at room temperature for several days. This persistent photoconductivity is shown to be tunable by applying a gate bias that equilibrates the charge distribution. These measurements indicate that such ultrathin vdW heterojunctions can function as rewritable optoelectronic switches or memory elements under time-dependent photo-illumination, an effect which appears promising for new monolayer TMDs-based optoelectronic devices applications.
Objective: To study the relationship of Nε-(carboxymethyl)-lysine level (CML)
with microstructure changes of white matter (WM), and cognitive impairment
in patients with type 2 diabetes mellitus (T2DM) and to discuss the
potential mechanism underlying T2DM-associated cognitive impairment. Methods: The study was performed in T2DM patients (n=22) with disease course
≥5 years and age ranging from 65 to 75 years old. A control group consisted
of 25 sex- and age-matched healthy volunteers. Fractional anisotropy (FA) of
several WM regions was analyzed by diffusion tensor imaging scan. Plasma CML
levels were measured by enzyme-linked immunosorbent assay, and cognitive
function was assessed by Mini-Mental State Examination and Montreal
cognitive assessment (MoCA). Results: The total Mini-Mental State Examination score in the patient group
(25.72±3.13) was significantly lower than the control group (28.16±2.45)
(p<0.05). In addition, the total MoCA score in the patient group
(22.15±3.56) was significantly lower than the control group 25.63±4.12)
(p<0.01). In the patient group, FA values were significantly decreased in
the corpus callosum, cingulate fasciculus, inferior fronto-occipital
fasciculus, parietal WM, hippocampus, and temporal lobes relative to
corresponding regions of healthy controls (p<0.05). Plasma CML level was
negatively correlated with average FA values in the global brain (r=−0.58,
p<0.01) and MoCA scores (r=−0.47, p<0.05). Conclusions: In T2DM, WM microstructure changes occur in older patients, and
elevations in CML may play a role in the development of cognitive