Changes in telepsychiatry regulations during the COVID-19 pandemic: 17 countries and regions' approaches to an evolving healthcare landscape.

BACKGROUND: During the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemedicine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic. METHODS: We used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020. RESULTS: Thirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations v. in-person consultations were reevaluated in four regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic. CONCLUSIONS: Our results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, which facilitate greater scale and spread of telepsychiatry globally.

The Characteristics Analysis of a Microfluid-Based EGFET Biosensor with On-Chip Sensing Film for Lactic Acid Detection.

In this research, a microfluid-based extended gate field-effect transistor (EGFET) biosensor with an on-chip sensing window (OCSW) was fabricated. The detection window was composed of six metal layers, and a ruthenium dioxide (RuO2) film was spattered on the surface and functionalized with lactase to detect lactic acid (LA). To detect LA in a more diversified way, a microfluidic system was integrated with the biosensor. Moreover, a special package was used to seal the sensing window and microfluidic tube and insulate it from other parts to prevent water molecule invasion and chip damage. The sensitivity analysis of the EGFET biosensor was studied by a semiconductor parameter analyzer (SPA). The static and dynamic measurements of the EGFET with sensing windows on a chip were analyzed. The sensing characteristics of the EGFET biosensor were verified by the experimental results. The proposed biosensor is suitable for wearable applications due to the advantages of its low weight, low voltage, and simple manufacturing process.

Machine Learning and Novel Biomarkers for the Diagnosis of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on cognitive tests, imaging techniques and cerebrospinal fluid (CSF) levels of amyloid-ß1-42 (Aß42), total tau protein and hyperphosphorylated tau (p-tau). However, the available methods are expensive and relatively invasive. Artificial intelligence techniques like machine learning tools have being increasingly used in precision diagnosis. METHODS: We conducted a meta-analysis to investigate the machine learning and novel biomarkers for the diagnosis of AD. METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews for reviews and trials that investigated the machine learning and novel biomarkers in diagnosis of AD. RESULTS: In additional to Aß and tau-related biomarkers, biomarkers according to other mechanisms of AD pathology have been investigated. Neuronal injury biomarker includes neurofiliament light (NFL). Biomarkers about synaptic dysfunction and/or loss includes neurogranin, BACE1, synaptotagmin, SNAP-25, GAP-43, synaptophysin. Biomarkers about neuroinflammation includes sTREM2, and YKL-40. Besides, d-glutamate is one of coagonists at the NMDARs. Several machine learning algorithms including support vector machine, logistic regression, random forest, and naïve Bayes) to build an optimal predictive model to distinguish patients with AD from healthy controls. CONCLUSIONS: Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics.

Photon-number-resolving segmented detectors based on single-photon avalanche-photodiodes.

We investigate the feasibility and performance of photon-number-resolved photodetection employing single-photon avalanche photodiodes (SPADs) with low dark counts. While the main idea, to split n photons into m detection modes with a vanishing probability of more than one photon per mode, is not new, we investigate here a important variant of this situation where SPADs are side-coupled to the same waveguide rather than terminally coupled to a propagation tree. This prevents the nonideal SPAD quantum efficiency from contributing to photon loss. We propose a concrete SPAD segmented waveguide detector based on a vertical directional coupler design, and characterize its performance by evaluating the purities of Positive-Operator-Valued Measures (POVMs) in terms of number of SPADs, photon loss, dark counts, and electrical cross-talk.

d-glutamate and Gut Microbiota in Alzheimer's Disease.

BACKGROUND: An increasing number of studies have shown that the brain-gut-microbiota axis may significantly contribute to Alzheimer's disease (AD) pathogenesis. Moreover, impaired memory and learning involve the dysfunction neurotransmission of glutamate, the agonist of the N-methyl-d-aspartate receptor and a major excitatory neurotransmitter in the brain. This systematic review aimed to summarize the current cutting-edge research on the gut microbiota and glutamate alterations associated with dementia. METHODS: PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews were reviewed for all studies on glutamate and gut microbiota in dementia published up until Feb 2020. RESULTS: Several pilot studies have reported alterations of gut microbiota and metabolites in AD patients and other forms of dementia. Gut microbiota including Bacteroides vulgatus and Campylobacter jejuni affect glutamate metabolism and decrease the glutamate metabolite 2-keto-glutaramic acid. Meanwhile, gut bacteria with glutamate racemase including Corynebacterium glutamicum, Brevibacterium lactofermentum, and Brevibacterium avium can convert l-glutamate to d-glutamate. N-methyl-d-aspartate glutamate receptor (NMDAR)-enhancing agents have been found to potentially improve cognition in AD or Parkinson's disease patients. These findings suggest that d-glutamate (d-form glutamate) metabolized by the gut bacteria may influence the glutamate NMDAR and cognitive function in dementia patients. CONCLUSIONS: Gut microbiota and glutamate are potential novel interventions to be developed for dementia. Exploring comprehensive cognitive functions in animal and human trials with glutamate-related NMDAR enhancers are warranted to examine d-glutamate signaling efficacy in gut microbiota in patients with AD and other neurodegenerative dementias.

Computer simulations of thermal tissue remodeling during transvaginal and transurethral laser treatment of female stress urinary incontinence.

BACKGROUND AND OBJECTIVES: A non-surgical method is being developed for treating female stress urinary incontinence by laser thermal remodeling of subsurface tissues with applied surface tissue cooling. Computer simulations of light transport, heat transfer, and thermal damage in tissue were performed, comparing transvaginal and transurethral approaches. STUDY DESIGN/MATERIALS AND METHODS: Monte Carlo (MC) simulations provided spatial distributions of absorbed photons in the tissue layers (vaginal wall, endopelvic fascia, and urethral wall). Optical properties (n,µa ,µs ,g) were assigned to each tissue at λ = 1064 nm. A 5-mm-diameter laser beam and incident power of 5 W for 15 seconds was used, based on previous experiments. MC output was converted into absorbed energy, serving as input for finite element heat transfer simulations of tissue temperatures over time. Convective heat transfer was simulated with contact probe cooling temperature set at 0°C. Variables used for thermal simulations (κ,c,ρ) were assigned to each tissue layer. MATLAB code was used for Arrhenius integral thermal damage calculations. A temperature matrix was constructed from ANSYS output, and finite sum was incorporated to approximate Arrhenius integral calculations. Tissue damage properties (Ea ,A) were used to compute Arrhenius sums. RESULTS: For the transvaginal approach, 37% of energy was absorbed in the endopelvic fascia target layer with 0.8% deposited beyond it. Peak temperature was 71°C, the treatment zone was 0.8-mm-diameter, and 2.4 mm of the 2.7-mm-thick vaginal wall was preserved. For transurethral approach, 18% energy was absorbed in endopelvic fascia with 0.3% deposited beyond the layer. Peak temperature was 80°C, treatment zone was 2.0-mm-diameter, and 0.6 mm of 2.4-mm-thick urethral wall was preserved. CONCLUSIONS: Computer simulations suggest that transvaginal approach is more feasible than transurethral approach. Lasers Surg. Med. 49:198-205, 2017. © 2016 Wiley Periodicals, Inc.

Temperature dependence of the reaction of anti-CH3CHOO with water vapor.

The kinetics of the reaction of anti-CH3CHOO with water vapor were investigated using transient UV absorption spectroscopy at temperatures from 288 to 328 K and 500 Torr. We found that both the water monomer and the water dimer react with anti-CH3CHOO. The rate coefficients of the reaction of the water monomer and dimer with anti-CH3CHOO at 298 K were determined to be (1.31 ± 0.26) × 10-14 cm3 s-1 and (4.40 ± 0.29) × 10-11 cm3 s-1, respectively. Furthermore, for the water dimer reaction, we observed very large negative temperature dependence with an activation energy of -12.17 ± 0.66 kcal mol-1. On the other hand, the monomer reaction showed minimal temperature dependence with nearly zero activation energy. At atmospherically relevant humidity, in opposition to previous experiments conducted for CH2OO in which water dimer reaction predominates at room temperature, for anti-CH3CHOO, the water monomer reaction can contribute significantly (∼30% of the reaction with water vapor at relative humidity RH = 40% and 298 K). These results show that substitution of an alkyl group can greatly affect the reaction of Criegee intermediates with water vapor, especially changing the contributions of water monomer and dimer reactions.

Competition between H2O and (H2O)2 reactions with CH2OO/CH3CHOO.

In this study, we performed ab initio calculations and obtained the bimolecular rate coefficients for the CH2OO/CH3CHOO reactions with H2O/(H2O)2. The energies were calculated with QCISD(T)/CBS//B3LYP/6-311+G(2d,2p) and the partition functions were estimated with anharmonic vibrational corrections by using the second order perturbation theory. Furthermore, we directly measured the rate of the CH2OO reaction with water vapor at high temperatures (348 and 358 K) to reveal the contribution of the water monomer in the CH2OO decay kinetics. We found that the theoretical rate coefficients reproduce the experimental results of CH2OO for a wide range of temperatures. For anti- (syn-) CH3CHOO, we obtained theoretical rate coefficients of 1.60 × 10(-11) (2.56 × 10(-14)) and 3.40 × 10(-14) (1.98 × 10(-19)) cm(3) s(-1) for water dimer and monomer reactions at room temperature. From the detailed analysis of the quantum chemistry and approximations for the thermochemistry calculations, we conclude that our calculated values would be within a factor of 3 of the correct values. Furthermore, at [H2O] = 1 × 10(17) to 5 × 10(17) cm(-3), we estimate that the effective first-order rate coefficients for CH2OO, anti- and syn-CH3CHOO reactions with water vapor will be ∼10(3), ∼10(4), and ∼10(1) s(-1), respectively. Thereby, for Criegee intermediates with a hydrogen atom on the same side as the terminal oxygen atom, the reaction with water vapor will likely dominate the removal processes of these CIs in the atmosphere.

Neonatal jaundice and increased risk of attention-deficit hyperactivity disorder: a population-based cohort study.

BACKGROUND: Previous studies have posited conflicting results regarding the relationship between neonatal jaundice and the subsequent risk of attention-deficit hyperactivity disorder (ADHD). We therefore performed a large population study with a defined neonatal jaundice cohort to investigate the incidence and risk of physician-diagnosed ADHD in Taiwan. METHODS: From 2000 to 2004, 24,950 neonatal jaundice cases and 69,964 matched nonjaundice controls were identified. At the end of 2008, the incidence rate and hazard ratios (HRs) of physician-diagnosed ADHD were calculated. RESULTS: The incidence of ADHD was 2.48-fold greater in the jaundice cohort than in the nonjaundice cohort (3.84 vs. 1.51 per 100,000 person-years) in the study period. The HR of ADHD was substantially greater for male, preterm, and low-birth-weight infants with neonatal jaundice. The risk of developing ADHD in the jaundice cohort was greater after a diagnosis of neonatal jaundice for more than 6 years (HR: 2.64; 95% confidence interval: 2.13-3.28). The risk of ADHD increased for neonates with higher serum bilirubin levels requiring phototherapy and with longer admission days. CONCLUSION: Neonates with jaundice are at high risk for developing physician-diagnosed ADHD during their growth period. A risk alert regarding neurologic consequences is urgently required after a neonatal jaundice diagnosis. Additional studies should be conducted to clarify the pathogenesis of these relationships.

Detailed mechanism of the CH2I + O2 reaction: yield and self-reaction of the simplest Criegee intermediate CH2OO.

The application of a new reaction scheme using CH2I + O2 to generate the simplest Criegee intermediate, CH2OO, has stimulated lively research; the Criegee intermediates are extremely important in atmospheric chemistry. The detailed mechanism of CH2I + O2 is hence important in understanding kinetics involving CH2OO. We employed ultraviolet absorption to probe simultaneously CH2I2, CH2OO, CH2I, and IO in the reaction system of CH2I + O2 upon photolysis at 248 nm of a flowing mixture of CH2I2, O2, and N2 (or SF6) in the pressure range 7.6-779 Torr to investigate the reaction kinetics. With a detailed mechanism to model the observed temporal profiles of CH2I, CH2OO, and IO, we found that various channels of the reaction CH2I + O2 and CH2OO + I play important roles; an additional decomposition channel of CH2I + O2 to form products other than CH2OO or ICH2OO becomes important at pressure less than 60 Torr. The pressure dependence of the derived rate coefficients of various channels of reactions of CH2I + O2 and CH2OO + I has been determined. We derived a rate coefficient also for the self-reaction of CH2OO as k = (8 ± 4) × 10(-11) cm(3) molecule(-1) s(-1) at 295 K. The yield of CH2OO from CH2I + O2 was found to have a pressure dependence on N2 and O2 smaller than in previous reports; for air under 1 atm, the yield of ~30% is about twice of previous estimates.

UV absorption spectrum of the C2 Criegee intermediate CH3CHOO.

The UV spectrum of CH3CHOO was measured by transient absorption in a flow cell at 295 K. The absolute absorption cross sections of CH3CHOO were measured by laser depletion in a molecular beam to be (1.06 ± 0.09) × 10(-17) cm(2) molecule(-1) at 308 nm and (9.7 ± 0.6) × 10(-18) cm(2) molecule(-1) at 352 nm. After scaling the UV spectrum of CH3CHOO to the absolute cross section at 308 nm, the peak UV cross section is (1.27 ± 0.11) × 10(-17) cm(2) molecule(-1) at 328 nm. Compared to the simplest Criegee intermediate CH2OO, the UV absorption band of CH3CHOO is similar in intensity but blue shifted by 14 nm, resulting in a 20% slower photolysis rate estimated for CH3CHOO in the atmosphere.

Comparative Effectiveness of Different Exercises for Reducing Pain Intensity in Primary Dysmenorrhea: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Studies have demonstrated that exercise can mitigate the intensity of menstrual pain in primary dysmenorrhea, but the most effective type of exercise remains unclear. The objective of this systematic review and network meta-analysis was to evaluate the effectiveness of different exercise regimens in reducing pain associated with primary dysmenorrhoea. METHODS: Randomized controlled trials investigating the relationship between menstrual pain and exercise were selected from major electronic databases until February 2, 2024. The primary outcome was the effect of exercise on pain intensity measured by the mean difference on a 10-cm visual analogue scale at 4 and 8 weeks after intervention. The secondary outcome was the difference in risk of dropout at 8 weeks. The study protocol was registered as INPLASY202330050. RESULTS: This systematic review and network meta-analysis included 29 randomized controlled trials, which involved 1808 participants with primary dysmenorrhea. Exercise interventions included relaxation exercise, strength training, aerobic activity, yoga, mixed exercise, and the Kegel maneuver. Relaxation exercise was the most effective in reducing menstrual pain in 4 weeks (- 3.56; 95% confidence interval: - 5.03 to - 2.08). All exercise interventions were effective in reducing menstrual pain at 8 weeks, with reductions ranging from - 3.87 (95% CI - 5.51 to - 2.22) for relaxation exercise to - 2.75 (95% CI - 4.00 to - 1.51) for yoga, compared to the control group. Relaxation exercises were found to have a significantly lower dropout risk (- 0.11; 95% CI - 0.20 to 0.02), while none of the exercise types was associated with a higher dropout risk than the control group. CONCLUSION: All exercise interventions were effective in reducing menstrual pain in primary dysmenorrhea after 8 weeks of intervention. However, relaxation exercise was found to be the most effective intervention at 4 and 8 weeks and had the lowest risk of dropout.

This analysis aimed to see how effective different types of exercise are in reducing pain in women with primary dysmenorrhea. The researchers looked at 29 studies involving 1808 participants and evaluated six different types of exercise. The main outcome was the effect of pain reduction after 4 and 8 weeks of exercise. The researchers found that all types of exercise were effective in reducing menstrual pain after 8 weeks, with relaxation exercises being the most effective at both 4 and 8 weeks. None of the exercise types were associated with higher dropout risks than the control group, and relaxation exercise had a lower dropout risk than the other types of exercise.

TBK1-associated protein in endolysosomes (TAPE)/CC2D1A is a key regulator linking RIG-I-like receptors to antiviral immunity.

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are key RNA viral sensors for triggering antiviral immunity. The underlying mechanisms for RLRs to trigger antiviral immunity have yet to be explored. Here we report the identification of TAPE (TBK1-associated protein in endolysosomes) as a novel regulator of the RLR pathways. TAPE functionally and physically interacts with RIG-I, MDA5, and IPS-1 to activate the IFN-ß promoter. TAPE knockdown impairs IFN-ß activation induced by RLRs but not IPS-1. TAPE-deficient cells are defective in cytokine production upon RLR ligand stimulation. During RNA virus infection, TAPE knockdown or deficiency diminishes cytokine production and antiviral responses. Our data demonstrate a critical role for TAPE in linking RLRs to antiviral immunity.

A 30-Year-Old Woman with an 8-Week History of Anxiety, Depression, Insomnia, and Mild Cognitive Impairment Following COVID-19 Who Responded to Accelerated Bilateral Theta-Burst Transcranial Magnetic Stimulation Over the Prefrontal Cortex.

BACKGROUND This report is of a 30-year-old woman with an 8-week history of anxiety, depression, insomnia, and mild cognitive impairment following COVID-19 infection, who responded to accelerated bilateral theta-burst transcranial magnetic stimulation (TBS) over the prefrontal cortex. CASE REPORT A previously healthy 30-year-old woman visited our psychiatric clinic for symptoms including anxiety, depression, insomnia, and brain fog (mild cognitive impairment) for more than 8 weeks after being diagnosed with COVID-19 on May 9, 2022. Continuous TBS of the right dorsolateral prefrontal cortex (DLPFC), followed by intermittent TBS of the left DLPFC, was performed twice daily over 5 days for a total of 10 sessions. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), and subsets of the Wechsler Memory Scale (WMS)-Third Edition were administered at baseline and at the end of treatment. After 10 sessions of treatment, her BAI, BDI, HAMD, PSQI, WMS-Logical Memory, WMS-Faces, WMS-Verbal Paired Associates, and WMS-Family Pictures scores had improved from 4, 18, 10, 14, 8, 10, 12, and 8, respectively, to 0, 7, 1, 10, 15, 15, 15, and 10, respectively. CONCLUSIONS Accelerated TBS over the bilateral DLPFC may ameliorate long-COVID-associated neuropsychiatric symptoms. Additional trials are warranted to evaluate the effect of neuropsychiatric symptoms following COVID-19.

Accelerated theta-burst transcranial magnetic stimulation of the bilateral dorsolateral prefrontal cortex in a patient with post-traumatic stress disorder and major depressive disorder: Case report.

Background: Theta-burst transcranial magnetic stimulation has demonstrated promising effectiveness as treatment for post-traumatic stress disorder (PTSD) and depression. However, the effect of accelerated theta-burst stimulation (TBS) in comorbid with PTSD and depression remains unknown. Case presentation: We report a case of a 25-year-old woman with PTSD and depression whose symptoms markedly improved after continuous TBS of the right dorsolateral prefrontal cortex (DLPFC) and intermittent TBS (iTBS) over the left DLPFC, and then with 20 min break before the 2nd iTBS session. Conclusions: Accelerated TBS over the bilateral DLPFC may improve severe PTSD and depression. Accelerated TBS may have more improvement of depression symptoms than PTSD symptoms. Further trials are warranted to investigate the effect and safety for patients with complicated PTSD and depression.

Associations between frontal lobe activity and depressive symptoms in patients with major depressive disorder receiving rTMS treatment: a near-infrared spectroscopy study.

Introduction: The effects of repetitive transcranial magnetic stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC) in patients with major depressive disorder (MDD) have been proved to have antidepressant effects. However, the absence of biomarkers to assess treatment response remains a challenge. This research aims to explore the relationship between frontal lobe activity, measured using near infrared spectroscopy (NIRS), and changes in symptoms among MDD patients following rTMS treatment. Methods: A total of 26 MDD patients underwent 20 sessions of 10 Hz rTMS targeting the left DLPFC. NIRS was used to measure frontal lobe activity during a verbal fluency test at baseline, after 10 rTMS sessions, and after 20 rTMS sessions. Responders were defined as individuals with more than a 50% reduction in symptoms based on the 21-item Hamilton Depression Rating Scale after 20 rTMS sessions. Results: Among the 14 responders, an increase in frontal lobe activity was significantly correlated with improvements in depressive symptoms following 10 (p = 0.0001) and 20 rTMS sessions (p = 0.007). Additionally, frontal lobe activity after 10 rTMS sessions was significantly associated with symptom improvement after 20 sessions (p = 0.001). These associations were not observed among non-responders. Conclusion: The findings from this study indicate distinct patterns of frontal lobe activity between responders and non-responders to rTMS treatment, suggesting that NIRS has the potential to serve as a biomarker for monitoring treatment response in MDD patients undergoing rTMS.

Efficacy of Non-Invasive Brain Stimulation for Treating Depression in Patients with Traumatic Brain Injury: A Meta-Analysis and Meta-Regression of Randomized Controlled Trials.

OBJECTIVE: This meta-analysis aimed to ascertain the efficacy of non-invasive brain stimulation (NIBS)-comprising repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)-for depression in traumatic brain injury (TBI) patients. METHODS: Comprehensive searches were conducted in PubMed, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials up to 28 January 2023. Random-effects models assessed the treatment effects, and heterogeneity was evaluated through I2 statistics and funnel plot inspection. RESULTS: From 10 trials (234 participants; 8 rTMS, 2 tDCS), NIBS was found significantly more effective than sham in alleviating depressive symptoms (SMD: 0.588, 95% CI: 0.264-0.912; p < 0.001). rTMS, specifically, showed higher efficacy (SMD: 0.707, 95% CI: 0.306-1.108; p = 0.001) compared to sham, whereas tDCS outcomes were inconclusive (SMD: 0.271, 95% CI: -0.230 to 0.771; p = 0.289). Meta-regression found no correlation with the number of sessions, treatment intensity, or total dose. Notably, while post-treatment effects were significant, they diminished 1-2 months post intervention. Adverse events associated with NIBS were minimal, with no severe outcomes like seizures and suicide reported. CONCLUSIONS: rTMS emerged as a potent short-term intervention for depression in TBI patients, while tDCS findings remained equivocal. The long-term efficacy of NIBS is yet to be established, warranting further studies. The low adverse event rate reaffirms NIBS's potential safety.

TBK1-associated protein in endolysosomes (TAPE) is an innate immune regulator modulating the TLR3 and TLR4 signaling pathways.

The innate immune system elicits the first wave of immune responses against pathogen infection. Its operational modes are complex and have yet to be defined. Here, we report the identification of an innate immune regulator termed TAPE (TBK1-associated protein in endolysosomes), previously known as CC2D1A/Freud-1/Aki-1, which modulates the TLR3 and TLR4 pathways. We found that TAPE activated the TBK1, NF-κB, and ERK pathways leading to IFN-ß and inflammatory cytokine induction. TAPE was shown to colocalize with endosomal marker Rab5 and lysosomal marker LAMP1 in mammalian cells, suggesting that TAPE resided in endolysosomes. Knockdown of TAPE selectively impaired the TLR3 and endocytic TLR4 pathways to IFN-ß induction. Furthermore, TAPE interacted and synergized with Trif to activate IFN-ß. TAPE knockdown failed to block Trif-mediated IFN-ß induction, whereas Trif knockdown impaired the TLR3 and TAPE cooperation on IFN-ß induction, suggesting that TAPE acts upstream of Trif. Together, our data demonstrate a central role for TAPE in linking TLR3 and TLR4 to innate immune defenses at an early step.

Pilot study of deep brain stimulation in refractory obsessive-compulsive disorder ethnic Chinese patients.

AIMS: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is a promising alternative to ablative surgery in treatment of refractory obsessive-compulsive disorder (OCD). A pilot study was conducted to assess 15-month outcomes of DBS in patients with refractory OCD in Taiwan. METHODS: Four adult patients with a 3-year or more history of refractory OCD (Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score of at least 28) met the criteria for DBS surgery. DBS electrodes were implanted bilaterally in the VC/VS. Stimulation was adjusted for therapeutic benefit and absence of adverse effects. Psychiatric evaluation was conducted preoperatively, postoperatively, and at follow up at every 3 months for 15 months. Primary outcome measure was Y-BOCS. Secondary outcomes included the Hamilton Depression Rating Scale (HAM-D), and the Global Assessment of Function Scale. RESULTS: Mean severity of OCD was a Y-BOCS score of 36.3 ± 2.1. At the end of 15 months' follow up, there was a 33.06% decrease in OCD severity (P = 0.001). Similar findings were seen for HAM-D (32.51% reduction, P = 0.005), and Global Assessment of Function Scale (31.03% increase, P = 0.026). In terms of adverse effects, two patients suffered from hypomania episodes after several weeks of DBS stimulation, and one had transient hypomania-like syndrome during DBS initial programming. One patient (Case 1) had an allergic reaction to implantation of the pulse generator in the chest, and another patient (Case 3) exhibited vertigo. CONCLUSIONS: We confirm that DBS of the VC/VS appears to be beneficial for improvements in function and mood among patients with treatment-resistant OCD. Compared to previous studies examining the therapeutic effects of DBS, no serious adverse effects were observed.

A Survey of Mobile Apps for the Care Management of Patients with Dementia.

OBJECTIVE: Dementia is a progressive neurocognitive disorder that currently affects approximately 50 million people globally and causes a heavy burden for their families and societies. This study analyzed mobile apps for dementia care in different languages and during the COVID-19 pandemic. METHODS: We searched PubMed, Cochrane Collaboration Central Register of Con-trolled Clinical Trials, Cochrane Systematic Reviews, Google Play Store, Apple App Store, and Huawei App Store for mobile applications for dementia care. The Mobile Application Rating Scale (MARS) was used to assess the quality of applications. RESULTS: We included 99 apps for dementia care. No significant difference in MARS scores was noted between the two language apps (Overall MARS: English: 3.576 ± 0.580, Chinese: 3.569 ± 0.746, p = 0.962). In the subscale analysis, English apps had higher scores of perceived impact than Chinese apps but these were not significant (2.654 ± 1.372 vs. 2.000 ± 1.057, p = 0.061). (2) Applications during the COVID-19 pandemic had higher MARS scores than those before the COVID-19 pandemic but these were not significant (during the COVID-19 pandemic: 3.722 ± 0.416; before: 3.699 ± 0.615, p = 0.299). In the sub-scale analysis, apps during the COVID-19 pandemic had higher scores of engagement than apps before the COVID-19 pandemic but these were not significant (3.117 ± 0.594 vs. 2.698 ± 0.716, p = 0.068). CONCLUSIONS: Our results revealed that there is a minor but nonsignificant difference between different languages and during the COVID-19 pandemic. Further cooperation among dementia professionals, technology experts, and caregivers is warranted to provide evidence-based and user-friendly information to meet the needs of users.