Transcranial pulse stimulation in the treatment of mild neurocognitive disorders.

OBJECTIVE: There are limited effectiveness and potential side effects of existing pharmacological approach in treating mild neurocognitive disorder (NCD). Transcranial pulse stimulation (TPS) applies repetitive single high-pressure ultrashort shockwave pulses to stimulate the brain, which has been shown to effectively improve cognition in major NCD. However, the effectiveness of TPS in mild NCD patients remained unknown. This study aims to assess the effectiveness and tolerability of TPS with neuro-navigation in old-age adults with mild NCD by both clinical and biochemical assessments. METHODS: An open-label study recruited older adults with mild NCD to receive neuro-navigated TPS intervention for two weeks with three sessions per week. Assessments included detailed cognitive assessments, APOE genotype, and brain-derived neurotrophic factor (BDNF). RESULTS: Nineteen participants (12 females and 7 males) completed the whole TPS interventions with no serious adverse effects reported. Repeated measures ANOVA showed statistically significant effects of time on HK-MoCA (F (3, 54) = 4.99, P = 0.004), 30-sec interval of Verbal Fluency Test (F (3, 54) = 2.94, P = 0.041), Stroop interference (F (3, 54) = 3.46, P = 0.023), and Chinese IADL (F (3, 54) = 2.78, P = 0.050) after receiving the intervention. Bonferroni post hoc comparisons on HK-MoCA showed a significant improvement after intervention. There was no significant change in serum BDNF level. INTERPRETATION: TPS has brought significant improvement in cognition of elderly with mild NCD. It has a great potential to delay the deterioration of cognition in older adults. The long-term effect of TPS in cognition would benefit from further large-scale, randomized, sham-controlled trials.

Psychological impact on healthcare workers, general population and affected individuals of SARS and COVID-19: A systematic review and meta-analysis.

Background: Any infectious disease outbreak may lead to a negative detrimental psychological impact on individuals and the community at large, however; there was no systematic review nor meta-analysis that examined the relationship between the psychological/mental health impact of SARS and COVID-19 outbreak in Asia. Methods and design: A systematic search was conducted using PubMed, EMBASE, Medline, PsycINFO, and CINAHL databases from 1/1/2000 to 1/6/2020. In this systematic review and meta-analysis, we analyzed the psychological impact on confirmed/suspected cases, healthcare workers and the general public during the Severe Acute Respiratory Syndrome (SARS) outbreak and Coronavirus disease (COVID-19) epidemics. Primary outcomes included prevalence of depression, anxiety, stress, post-traumatic stress disorder, aggression, sleeping problems and psychological symptoms. Result: Twenty-three eligible studies (N = 27,325) were included. Random effect model was used to analyze the data using STATA. Of these studies, 11 were related to the SARS outbreak and 12 related to COVID-19 outbreaks. The overall prevalence rate of anxiety during SARS and COVID-19 was 37.8% (95% CI: 21.1-54.5, P < 0.001, I2 = 96.9%) and 34.8% (95% CI: 29.1-40.4), respectively. For depression, the overall prevalence rate during SARS and COVID-19 was 30.9% (95% CI: 18.6-43.1, P < 0.001, I2 = 97.3%) and 32.4% (95% CI: 19.8-45.0, P < 0.001, I2 = 99.8%), respectively. The overall prevalence rate of stress was 9.4% (95% CI: -0.4 -19.2, P = 0.015, I2 = 83.3%) and 54.1% (95% CI: 35.7-72.6, P < 0.001, I2 = 98.8%) during SARS and COVID-19, respectively. The overall prevalence of PTSD was 15.1% (95% CI: 8.2-22.0, P < 0.001) during SARS epidemic, calculated by random-effects model (P < 0.05), with significant between-study heterogeneity (I2 = 93.5%). Conclusion: The SARS and COVID-19 epidemics have brought about high levels of psychological distress to individuals. Psychological interventions and contingent digital mental health platform should be promptly established nationwide for continuous surveillance of the increasing prevalence of negative psychological symptoms. Health policymakers and mental health experts should jointly collaborate to provide timely, contingent mental health treatment and psychological support to those in need to reduce the global disease burden. Systematic review registration: CRD42020182787, identifier PROSPER.

The Use of an Electronic Painting Platform by Family Caregivers of Persons with Dementia: A Feasibility and Acceptability Study.

Painting is a well-known method for alleviating stress, but it is uncertain whether family caregivers can use an electronic painting platform at home for this purpose. Aim. The aim in this study was to assess the feasibility and acceptability of having family caregivers of persons with dementia (FCPWD) draw electronic paintings using a mobile app, and to assess the preliminary effect of the intervention on their well-being. Methods. This was a two-phase feasibility and acceptability study, with qualitative interviews conducted in Phase 1 and qualitative interviews and a quantitative survey conducted in Phase 2. Caregiving burden, depressive symptoms, self-rated health, and social support were measured before and after the intervention. Participants were asked to draw electronic paintings at any time they liked, and to share the paintings with friends or relatives if they wished. Result. The recruitment rate in Phase 2 was 87.5% (28 out of 32), with 78.6% participants (22 out 28) completing all activities in 8 weeks. The FCPWD regarded the e-painting app as an appropriate channel for expressing their emotions. They found the layout of the app to be easy to use and were satisfied with it. A total of 116 pictures were produced. Log-in frequency was significantly correlated with the sharing of paintings with friends or relatives (r = 0.72, p < 0.001). Conclusion. FCPWD considered the e-painting mobile app to be a feasible and acceptable technology-based psychosocial platform. A further investigation with a larger sample in a full-scale randomized controlled trial is warranted.

Effects of Transcranial Pulse Stimulation (TPS) on Young Adults With Symptom of Depression: A Pilot Randomised Controlled Trial Protocol.

Background: Since the emergence of the COVID-19 pandemic, there have been lots of published work examining the association between COVID-19 and mental health, particularly, anxiety and depression in the general populations and disease subpopulations globally. Depression is a debilitating disorder affecting individuals' level of bio-psychological-social functioning across different age groups. Since almost all studies were cross-sectional studies, there seems to be a lack of robust, large-scale, and technological-based interventional studies to restore the general public's optimal psychosocial wellbeing amidst the COVID-19 pandemic. Transcranial pulse stimulation (TPS) is a relatively new non-intrusive brain stimulation (NIBS) technology, and only a paucity of studies was conducted related to the TPS treatment on older adults with mild neurocognitive disorders. However, there is by far no study conducted on young adults with major depressive disorder nationwide. This gives us the impetus to execute the first nationwide study evaluating the efficacy of TPS on the treatment of depression among young adults in Hong Kong. Methods: This study proposes a two-armed single-blinded randomised controlled trial including TPS as an intervention group and a waitlist control group. Both groups will be measured at baseline (T1), immediately after the intervention (T2), and at the 3- month follow-up (T3). Recruitment: A total of 30 community-dwelling subjects who are aged 18 and above and diagnosed with major depressive disorder (MDD) will be recruited in this study. All subjects will be computer randomised into either the intervention group or the waitlist control group, balanced by gender and age on a 1:1 ratio. Intervention: All subjects in each group will have to undertake functional MRI (fMRI) before and after six 30-min TPS sessions, which will be completed in 2 weeks' time. Outcomes: Baseline measurements and post-TPS evaluation of the psychological outcomes (i.e., depression, cognition, anhedonia, and instrumental activities of daily living) will also be conducted on all participants. A 3-month follow-up period will be usedto assess the long-term sustainability of the TPS intervention. For statistical analysis, ANOVA with repeated measures will be used to analyse data. Missing data were managed by multiple mutations. The level of significance will be set to p < 0.05. Significance of the Study: Results of this study will be used to inform health policy to determine whether TPS could be considered as a top treatment option for MDD. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT05006365.

Depression, Anxiety and Stress on Caregivers of Persons with Dementia (CGPWD) in Hong Kong amid COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) contributed to increasing prevalence of depressive symptoms and other psychological repercussions, particularly in the disease population in Hong Kong. Nonetheless, the caregiver burden of caregivers of persons with dementia (CGPWD), has been under-investigated. AIMS: This study examined the psychological impact and its correlates on the CGPWD in Hong Kong amid the COVID-19 outbreak. METHODS: CGPWD referred from rehabilitation clinics and online seminar were used to recruit participants to complete an online questionnaire by the end of the second-wave of the COVID-19 outbreak (June 2021). To be eligible, either full-time or part-time CGPWD, aged 18 or above, can understand Cantonese, currently reside in Hong Kong and offering care to PWD for at least one year, were recruited. Those CGPWD diagnosed with any type of psychiatric disorder were excluded from this study. The Chinese Center for Epidemiologic Studies Depression Scale (CES-D), Perceived Stress Scale (PSS-10), Generalized Anxiety Disorder (GAD-7), Zarit Burden Interview (ZBI-22), and Nonattachment Scale (NAS-7) were used to measure participants' depression, perceived stress, anxiety symptoms, caregiver burden and wisdom in subjective feelings of internal stress. The modified Medical Outcomes Study Social Support Survey (mMOS-SS) and the SARS Appraisal Inventory (SAI) were also administered to measure participants' perceived support and coping efficacy. Follow-up responses were gathered by the end of third-wave outbreak (October 2021). RESULTS: A total of 51 CGPWD participated, of which, 33 (64.7%) suffered from probable depression (CES-D score ≥ 16). Participants also showed a significant increase in depression symptom scores at the three-month follow-up period (t = 2.25, p = 0.03). CGPWD with probable depression had less non-attachment awareness and higher scores in anxiety, stress, caregiving burden, and coronavirus impact (all p < 0.05) than those without. CONCLUSIONS: High prevalence of depressive symptoms was noted among our CGPWD sample and these symptoms seemed to worsen substantially. Contingent online mental health support should be prioritized to those CGPWD to reduce psychiatric morbidity and the global disease burden.

Association Between Depression, Health Beliefs, and Face Mask Use During the COVID-19 Pandemic.

The 2019 novel coronavirus (COVID-19) pandemic is associated with increases in psychiatric morbidity, including depression. It is unclear if people with depressive symptoms understand or apply COVID-19 information differently to the general population. Therefore, this study aimed to examine associations between depression, health beliefs, and face mask use during the COVID-19 pandemic among the general population in Hong Kong. This study gathered data from 11,072 Hong Kong adults via an online survey. Respondents self-reported their demographic characteristics, depressive symptoms (PHQ-9), face mask use, and health beliefs about COVID-19. Hierarchical logistic regression was used to identify independent variables associated with depression. The point-prevalence of probable depression was 46.5% (n = 5,150). Respondents reporting higher mask reuse (OR = 1.24, 95%CI 1.17-1.34), wearing masks for self-protection (OR = 1.03 95%CI 1.01-1.06), perceived high susceptibility (OR = 1.15, 95%CI 1.09-1.23), and high severity (OR = 1.33, 95%CI 1.28-1.37) were more likely to report depression. Depression was less likely in those with higher scores for cues to action (OR = 0.82, 95%CI 0.80-0.84), knowledge of COVID-19 (OR = 0.95, 95%CI 0.91-0.99), and self-efficacy to wear mask properly (OR = 0.90 95%CI 0.83-0.98). We identified a high point-prevalence of probable major depression and suicidal ideation during the COVID-19 outbreak in Hong Kong, but this should be viewed with caution due to the convenience sampling method employed. Future studies should recruit a representative probability sample in order to draw more reliable conclusions. The findings highlight that COVID-19 health information may be a protective factor of probable depression and suicidal ideation during the pandemic. Accurate and up-to-date health information should be disseminated to distressed and vulnerable subpopulations, perhaps using digital health technology, and social media platforms to prompt professional help-seeking behavior.

Cyclometalated Palladium(II) N-Heterocyclic Carbene Complexes: Anticancer Agents for Potent In†Vitro Cytotoxicity and In†Vivo Tumor Growth Suppression.

Palladium(II) complexes are generally reactive toward substitution/reduction, and their biological applications are seldom explored. A new series of palladium(II) N-heterocyclic carbene (NHC) complexes that are stable in the presence of biological thiols are reported. A representative complex, [Pd(C^N^N)(N,N'-nBu2 NHC)](CF3 SO3 ) (Pd1 d, HC^N^N=6-phenyl-2,2'-bipyridine, N,N'-nBu2 NHC=N,N'-di-n-butylimidazolylidene), displays potent killing activity toward cancer cell lines (IC50 =0.09-0.5 µm) but is less cytotoxic toward a normal human fibroblast cell line (CCD-19Lu, IC50 =11.8 µm). In vivo anticancer studies revealed that Pd1 d significantly inhibited tumor growth in a nude mice model. Proteomics data and in vitro biochemical assays reveal that Pd1 d exerts anticancer effects, including inhibition of an epidermal growth factor receptor pathway, induction of mitochondrial dysfunction, and antiangiogenic activity to endothelial cells.

Luminescent rhenium(I) polypyridine fluorous complexes as novel trifunctional biological probes.

We present the synthesis, characterization, and photophysical properties of three luminescent rhenium(I) polypyridine fluorous complexes [Re(Me(2)bpy)(CO)(3)(L)](PF(6)) (Me(2)bpy = 4,4'-dimethyl-2,2'-bipyridine; L = 3-amino-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine (py-Rf-NH(2)) (1), 3-isothiocyanato-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine (py-Rf-NCS) (2), 3-ethylthioureidyl-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine (py-Rf-TU-C(2)H(5)) (3)). The isothiocyanate complex 2 has been used to label bovine serum albumin (BSA) and glutathione (GSH). The photophysical properties of the resultant bioconjugates have been studied. The isolation of the luminescent fluorous rhenium-GSH conjugate from a mixture of 20 amino acids has been demonstrated using fluorous solid-phase extraction (FSPE). Additionally, the cytotoxicity of complexes 1 and 3 toward HeLa cells has been examined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cellular uptake properties of complex 3 have also been investigated by laser-scanning confocal microscopy.

Luminescent dendritic cyclometalated iridium(III) polypyridine complexes: synthesis, emission behavior, and biological properties.

Luminescent dendritic cyclometalated iridium(III) polypyridine complexes [{Ir(N--C)(2)}(n)(bpy-n)](PF(6))(n) (HN--C = 2-phenylpyridine, Hppy, n = 8 (ppy-8), 4 (ppy-4), 3 (ppy-3); HN--C = 2-phenylquinoline, Hpq, n = 8 (pq-8), 4 (pq-4), 3 (pq-3)) have been designed and synthesized. The properties of these dendrimers have been compared to those of their monomeric counterparts [Ir(N--C)(2)(bpy-1)](PF(6)) (HN--C = Hppy (ppy-1), Hpq (pq-1)). Cyclic voltammetric studies revealed that the iridium(IV/III) oxidation and bpy-based reduction occurred at about +1.24 to +1.29 V and -1.21 to -1.27 V versus SCE, respectively, for all the complexes. The molar absorptivity of the dendritic iridium(III) complexes is approximately proportional to the number of [Ir(N--C)(2)(N--N)] moieties in one complex molecule. However, the emission lifetimes and quantum yields are relatively independent of the number of [Ir(N--C)(2)(N--N)] units, suggesting negligible electronic communications between these units. Upon photoexcitation, the complexes displayed triplet metal-to-ligand charge-transfer ((3)MLCT) (dpi(Ir) --> pi*(bpy-n)) emission. The interaction of these complexes with plasmid DNA has been investigated by agarose gel retardation assays. The results showed that the dendritic iridium(III) complexes, unlike their monomeric counterparts, bound to the plasmid, and the interaction was electrostatic in nature. The lipophilicity of all the complexes has been determined by reversed-phase high-performance liquid chromatography (HPLC). Additionally, the cellular uptake of the complexes by the human cervix epithelioid carcinoma (HeLa) cell line has been examined by inductively coupled plasma mass spectrometry (ICP-MS), laser-scanning confocal microscopy, and flow cytometry. Upon internalization, all the complexes were localized in the perinuclear region, forming very sharp luminescent rings surrounding the nuclei. Interestingly, in addition to these rings, HeLa cells treated with the dendritic iridium(III) complexes showed specific labeled compartments, which have been identified to be the Golgi apparatus. Furthermore, the cytotoxicity of these iridium(III) complexes has been evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay.