Cerebral small vessel disease burden is associated with poststroke depressive symptoms: A 15-month prospective study

Objective: All types of cerebral small vessel disease (SVD) markers including lacune, white matter hyperintensities (WMH), cerebral microbleeds, and perivascular spaces were found to be associated with poststroke depressive symptoms (PDS). This study explored whether the combination of the four markers constituting an overall SVD burden was associated with PDS. Methods: A cohort of 563 patients with acute ischemic stroke were followed over a 15-month period after the index stroke. A score of _7 on the 15-item Geriatric Depression Scale was defined as clinically significant PDS. Scores of the four SVD markers ascertained on magnetic resonance imaging were summed up to represent total SVD burden. The association between SVD burden and PDS was assessed with generalized estimating equation models. Results: The study sample had a mean age of 67.0 _ 10.2 years and mild-moderate stroke [National Institutes of Health Stroke Scale score: 3, interquartile, 1–5]. PDS were found in 18.3%, 11.6%, and 12.3% of the sample at 3, 9, and 15 months after stroke, respectively. After adjusting for demographic characteristics, vascular risk factors, social support, stroke severity, physical and cognitive functions, and size and locations of stroke, the SVD burden was associated with an increased risk of PDS [odds ratio = 1.30; 95% confidence interval = 1.07–1.58; p = 0.010]. Other significant predictors of PDS were time of assessment, female sex, smoking, number of acute infarcts, functional independence, and social support. Conclusion: SVD burden was associated with PDS examined over a 15-month follow-up in patients with mild to moderate acute ischemic stroke

Accurate Modeling of the Effects of Fringing Area Interface Traps on Scanning Capacitance Microscopy Measurement

Scanning capacitance microscopy (SCM) is a dopant profile extraction tool with nanometre spatial resolution. While it is based on the high-frequency MOS capacitor theory, there are crucial second-order effects which make the extraction of dopant profile from SCM data a challenging task. Due to small size of the SCM probe, the trapped charges in the interface traps at the oxide-silicon dioxide interface surrounding the probe significantly affect the measured SCM data through the fringing electric field created by the trapped charges. In this paper, we present numerical simulation results to investigate the nature of SCM dC/dV data in the presence of interface traps. The simulation takes into consideration the traps response to the ac signal used to measure dC/dV as well as the fringing field of the trapped charge surrounding the probe tip. In the study, we present an error estimation of experimental SCM dopant concentration extraction when the interface traps and fringing field are ignored. The trap distribution in a typical SCM sample is also investigated

Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells

<p>Abstract</p> <p>Background</p> <p>Polysaccharopeptide (PSP) from <it>Coriolus versicolor </it>(<it>Yunzhi</it>) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT).</p> <p>Methods</p> <p>We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT.</p> <p>Results</p> <p>PSP reduced cellular proliferation; inhibited cells progression through both S and G₂phase, reduced ³H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G₂phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT.</p> <p>Conclusion</p> <p>The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.</p

Association of cerebral small vessel disease burden and health-related quality of life after acute ischemic stroke

Objective: Cerebral small vessel disease (SVD) is associated with increased mortality, disability and cognitive decline, depression in stroke survivors. This study examined the association between SVD burden, defined by a combination of SVD markers, and health-related quality of life (HRQoL) in acute ischemic stroke. Methods: Patients admitted with acute ischemic stroke of any etiology were prospectively screened between January 2010 to December 2014 and enrolled in the study if they met study entry criteria. HRQoL was evaluated with the 12-item Stroke Specific Quality of Life (SSQoL) at 3 months after the onset of acute ischemic stroke. SVD was ascertained by the presence of any of the SVD markers including lacune, white matter hyperintensities (WMH), cerebral microbleeds (CMB) and enlarged perivascular spaces (EPVS) in the basal ganglia or their combinations on brain magnetic resonance imaging (MRI). The presence of each individual marker scored 1 point and was summed up to generate an ordinal “SVD score” (0–4) capturing total SVD burden. Linear regression was used to determine the associations between SVD burden and HRQoL. Results: Of the743 acute ischemic stroke patients that formed he study sample (mean age: 66.3 ± 10.6 years; 41.7% women), 49.3%, 22.5%, 16.0%, 9.2% and 3.1% had SVD scores of 0, 1, 2, 3 and 4, respectively. After adjusting for demographic, clinical and imaging variables, the SVD score was independently associated with lower overall score of SSQoL (B = − 1.39, SE = 0.56, p = 0.01), and its domains of mobility (B = − 0.41, SE = 0.10, p \u3c 0.001) and vision (B = − 0.12, SE = 0.06, p = 0.03). Acute infract volume (B = − 1.44, SE = 0.54, p = 0.01), functional independence (B = 5.69, SE = 0.34, p \u3c 0.001) and anxious (B = − 1.13, SE = 0.23, p \u3c 0.001) and depressive symptoms (B = − 3.41, SE = 0.22, p \u3c 0.001) were also the significant predictors of the overall score of SSQoL. Conclusion: The brain’s SVD burden predicts lower HRQoL, predominantly in domains of mobility and vision at 3 months after acute ischemic stroke. The evaluation of SVD burden could facilitate developing individual treatment strategies

Development and validation of a quantitative measure for parent empowerment via transformative learning

Although current literature demonstrates how parents benefit from parent empowerment programs, the development of a quantitative measure of parent empowerment has garnered limited attention in parenting research. The goal of this research was therefore to develop and validate a quantitative measure for the assessment of practitioners’ attitudes and competence in parent empowerment. In the process of item generation, the qualitative findings derived from four studies in relation to the perceived outcomes and experiences in parent empowerment were synthesized in the first stage. In the second stage, a list of narratives that articulated different themes of parent empowerment was generated, which resulted in an item pool containing 28 items. In the third stage, the research team converted the 28 items into a survey instrument. In the fourth stage, a first-scale validation study was conducted to explore the factor structure of the initial 28-item questionnaire. The exploratory factor analysis on the first sample of 366 practitioners yielded a twofold factor structure with 17 items, including practitioners’ attitudes in parent empowerment and practitioners’ competence in parent empowerment. In the final stage, a second-scale validation study was undertaken to verify the fit of the twofold factor structure. A confirmatory factor analysis on the second sample of 170 practitioners demonstrated a good model fit. The results of reliability tests for the whole scale and two subscales also indicate satisfactory internal consistency. The Parent Empowerment via Transformative Learning Questionnaire (PETLQ) was thus developed and confirmed as a scale with sufficient factorial validity and internal consistency to be used for assessing parenting practitioners’ attitudes and competence in parent empowerment and for evaluating the effectiveness of parent empowerment programs

Projecting the 10-year costs of care and mortality burden of depression until 2032: a Markov modelling study developed from real-world data

Background Based on real-world data, we developed a 10-year prediction model to estimate the burden among patients with depression from the public healthcare system payer's perspective to inform early resource planning in Hong Kong. Methods We developed a Markov cohort model with yearly cycles specifically capturing the pathway of treatment-resistant depression (TRD) and comorbidity development along the disease course. Projected from 2023 to 2032, primary outcomes included costs of all-cause and psychiatric care, and secondary outcomes were all-cause deaths, years of life lived, and quality-adjusted life-years. Using the territory-wide electronic medical records, we identified 25,190 patients aged ≥10 years with newly diagnosed depression from 2014 to 2016 with follow-up until 2020 to observe the real-world time-to-event pattern, based on which costs and time-varying transition inputs were derived using negative binomial modelling and parametric survival analysis. We applied the model as both closed cohort, which studied a fixed cohort of incident patients in 2023, and open cohort, which introduced incident patients by year from 2014 to 2032. Utilities and annual new patients were from published sources. Findings With 9217 new patients in 2023, our closed cohort model projected the 10-year cumulative costs of all-cause and psychiatric care to reach US$309.0 million and US$58.3 million, respectively, with 899 deaths (case fatality rate: 9.8%) by 2032. In our open cohort model, 55,849–57,896 active prevalent cases would cost more than US$322.3 million and US$60.7 million, respectively, with more than 943 deaths annually from 2023 to 2032. Fewer than 20% of cases would live with TRD or comorbidities but contribute 31–54% of the costs. The greatest collective burden would occur in women aged above 40, but men aged above 65 and below 25 with medical history would have the highest costs per patient-year. The key cost drivers were relevant to the early disease stages. Interpretation A limited proportion of patients would develop TRD and comorbidities but contribute to a high proportion of costs, which necessitates appropriate attention and resource allocation. Our projection also demonstrates the application of real-world data to model long-term costs and mortality, which aid policymakers anticipate foreseeable burden and undertake budget planning to prepare for the care need in alternative scenarios

The bracteatus pineapple genome and domestication of clonally propagated crops

Domestication of clonally propagated crops such as pineapple from South America was hypothesized to be a 'one-step operation'. We sequenced the genome of Ananas comosus var. bracteatus CB5 and assembled 513 Mb into 25 chromosomes with 29,412 genes. Comparison of the genomes of CB5, F153 and MD2 elucidated the genomic basis of fiber production, color formation, sugar accumulation and fruit maturation. We also resequenced 89 Ananas genomes. Cultivars 'Smooth Cayenne' and 'Queen' exhibited ancient and recent admixture, while 'Singapore Spanish' supported a one-step operation of domestication. We identified 25 selective sweeps, including a strong sweep containing a pair of tandemly duplicated bromelain inhibitors. Four candidate genes for self-incompatibility were linked in F153, but were not functional in self-compatible CB5. Our findings support the coexistence of sexual recombination and a one-step operation in the domestication of clonally propagated crops. This work guides the exploration of sexual and asexual domestication trajectories in other clonally propagated crops

Highly efficient cash sterilization with ultrafast and flexible Joule‐heating strategy by laser patterning

Since ancient times, humans have learned to use fire and other heating methods to fight against dangerous pathogens, like cooking raw food, sterilizing surgical tools, and disinfecting other pathogen transmission media. However, it remains difficult for current heating methods to achieve extremely fast and highly efficient sterilization simultaneously. Herein, an ultrafast and uniform heating‐based strategy with outstanding bactericidal performance is proposed. Ultra‐precise laser manufacturing is used to fabricate the Joule heater which can be rapidly heated to 90 °C in 5 s with less than 1 °C fluctuation in a large area by real‐time temperature feedback control. An over 98% bactericidal efficiency on S. aureus for 30 s and on E. coli for merely 5 s is shown. The heating strategy shows a 360 times faster acceleration compared to the commonly used steam sterilization from the suggested guidelines by the Centers for Disease Control and Prevention (CDC), indicating that high temperatures with short duration can effectively disinfect microorganisms. As a proof of concept, this heating strategy can be widely applied to sterilizing cash and various objects to help protect the public from bacteria in daily life

Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death

Glaucoma, a major cause of blindness worldwide, is a neurodegenerative optic neuropathy in which vision loss is caused by loss of retinal ganglion cells (RGCs). To better define the pathways mediating RGC death and identify targets for the development of neuroprotective drugs, we developed a high-throughput RNA interference screen with primary RGCs and used it to screen the full mouse kinome. The screen identified dual leucine zipper kinase (DLK) as a key neuroprotective target in RGCs. In cultured RGCs, DLK signaling is both necessary and sufficient for cell death. DLK undergoes robust posttranscriptional up-regulation in response to axonal injury in vitro and in vivo. Using a conditional knockout approach, we confirmed that DLK is required for RGC JNK activation and cell death in a rodent model of optic neuropathy. In addition, tozasertib, a small molecule protein kinase inhibitor with activity against DLK, protects RGCs from cell death in rodent glaucoma and traumatic optic neuropathy models. Together, our results establish a previously undescribed drug/drug target combination in glaucoma, identify an early marker of RGC injury, and provide a starting point for the development of more specific neuroprotective DLK inhibitors for the treatment of glaucoma, nonglaucomatous forms of optic neuropathy, and perhaps other CNS neurodegenerations