Construction of Multiply Guaranteed DNA Sensors for Biological Sensing and Bioimaging Applications.

Nucleic acids exhibit exceptional functionalities for both molecular recognition and catalysis, along with the capability of predictable assembly through strand displacement reactions. The inherent programmability and addressability of DNA probes enable their precise, on-demand assembly and accurate execution of hybridization, significantly enhancing target detection capabilities. Decades of research in DNA nanotechnology have led to advances in the structural design of functional DNA probes, resulting in increasingly sensitive and robust DNA sensors. Moreover, increasing attention has been devoted to enhancing the accuracy and sensitivity of DNA-based biosensors by integrating multiple sensing procedures. In this review, we summarize various strategies aimed at enhancing the accuracy of DNA sensors. These strategies involve multiple guarantee procedures, utilizing dual signal output mechanisms, and implementing sequential regulation methods. Our goal is to provide new insights into the development of more accurate DNA sensors, ultimately facilitating their widespread application in clinical diagnostics and assessment.

Carbon nanotubes: a powerful bridge for conductivity and flexibility in electrochemical glucose sensors.

The utilization of nanomaterials in the biosensor field has garnered substantial attention in recent years. Initially, the emphasis was on enhancing the sensor current rather than material interactions. However, carbon nanotubes (CNTs) have gained prominence in glucose sensors due to their high aspect ratio, remarkable chemical stability, and notable optical and electronic attributes. The diverse nanostructures and metal surface designs of CNTs, coupled with their exceptional physical and chemical properties, have led to diverse applications in electrochemical glucose sensor research. Substantial progress has been achieved, particularly in constructing flexible interfaces based on CNTs. This review focuses on CNT-based sensor design, manufacturing advancements, material synergy effects, and minimally invasive/noninvasive glucose monitoring devices. The review also discusses the trend toward simultaneous detection of multiple markers in glucose sensors and the pivotal role played by CNTs in this trend. Furthermore, the latest applications of CNTs in electrochemical glucose sensors are explored, accompanied by an overview of the current status, challenges, and future prospects of CNT-based sensors and their potential applications.

Outcomes of critically ill older adults with COVID-19: a multicentre retrospective cohort study.

PURPOSE: Older adults with COVID-19 have a high prevalence of complications and mortality during hospitalization. Given the large proportion of older adults requiring admission to an intensive care unit (ICU), we aimed to describe the management and outcomes of older adults with COVID-19 requiring ICU care and identify predictors of hospital mortality. METHODS: We included consecutive patients ≥ 65 yr of age who were admitted between 11 March 2020 and 30 June 2021 to one of five Toronto (ON, Canada) ICUs with a primary diagnosis of SARS-CoV-2 infection in a retrospective cohort study. Patient characteristics, ICU treatment, and outcomes were recorded. We used multivariable logistic regression to identify predictors of in-hospital mortality. RESULTS: Of the 273 patients, the median [interquartile range] age was 74 [69-80] yr, 104 (38.1%) were female, and 164 (60.1%) required invasive mechanical ventilation. One hundred and forty-two patients (52.0%) survived their hospital stay. Compared with survivors, nonsurvivors were older (74 [70-82] yr vs 73 [68-78] yr; P = 0.03), and a smaller proportion was female (39/131, 29.8% vs 65/142, 45.8%; P = 0.01). Patients had long hospital (19 [11-35] days) and ICU (9 [5-22] days) stays, with no significant differences in ICU length of stay or duration of invasive mechanical ventilation between the two groups. Higher APACHE II score, increasing age, and the need for organ support were independently associated with higher in-hospital mortality while female sex was associated with lower mortality. CONCLUSIONS: Older critically ill COVID-19 patients had long ICU and hospital stays, and approximately half died in hospital. Further research is needed to identify individuals who will benefit most from an ICU admission and to evaluate posthospitalization outcomes.

RéSUMé: OBJECTIF: Les personnes âgées atteintes de la COVID-19 ont une prévalence élevée de complications et de mortalité pendant l'hospitalisation. Compte tenu de la forte proportion de personnes âgées nécessitant une admission dans une unité de soins intensifs (USI), nous avons cherché à décrire la prise en charge et les devenirs des personnes âgées atteintes de COVID-19 nécessitant des soins intensifs et à identifier les prédicteurs de mortalité hospitalière. MéTHODE: Nous avons inclus des patient·es consécutif·ves âgé·es de ≥ 65 ans admis·es entre le 11 mars 2020 et le 30 juin 2021 dans l'une des cinq unités de soins intensifs de Toronto (ON, Canada) avec un diagnostic primaire d'infection par le SRAS-CoV-2 dans une étude de cohorte rétrospective. Les caractéristiques des patient·es, le traitement en USI et les devenirs ont été enregistrés. Nous avons utilisé une régression logistique multivariable pour identifier les prédicteurs de mortalité hospitalière. RéSULTATS: Parmi les 273 patient·es, l'âge médian [écart interquartile] était de 74 [69-80] ans, 104 (38,1 %) étaient des femmes et 164 (60,1 %) ont nécessité une ventilation mécanique invasive. Cent quarante-deux personnes (52,0 %) ont survécu à leur séjour à l'hôpital. Comparativement aux personnes survivantes, les personnes qui n'ont pas survécu étaient plus âgées (74 [70-82] ans vs 73 [68­78] ans; P = 0,03), et une plus faible proportion était de sexe féminin (39/131, 29,8 % vs 65/142, 45,8 %; P = 0,01). Les séjours des patient·es à l'hôpital (19 [11-35] jours) et à l'USI (9 [5-22] jours) étaient longs, sans différence significative dans la durée du séjour en USI ou la durée de la ventilation mécanique invasive entre les deux groupes. Un score APACHE II plus élevé, un âge plus avancé et le besoin de mesures de soutien d'organes étaient indépendamment associés à une mortalité plus élevée à l'hôpital, tandis que le sexe féminin était associé à une mortalité plus faible. CONCLUSION : Les personnes plus âgées gravement malades atteintes de la COVID-19 ont eu de longs séjours en soins intensifs et à l'hôpital, et environ la moitié sont décédées à l'hôpital. D'autres recherches sont nécessaires pour identifier les personnes qui bénéficieraient le plus d'une admission à l'USI et pour évaluer les devenirs post-hospitalisation.

Psychopathology in the Offspring of Indigenous Parents with Mental Health Challenges: A Systematic Review: Psychopathologie des descendants de parents autochtones ayant des problèmes de santé mentale: Une revue systématique.

OBJECTIVE: Parental psychopathology is a significant risk factor for mental health challenges in offspring, but the nature and magnitude of this link in Indigenous Peoples is not well understood. This systematic review examined the emotional and behavioral functioning of the offspring of Indigenous parents with mental health challenges. METHOD: We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and Web of Science from their inceptions until April 2020. Studies were included if they included assessments of emotional, behavioral, or other psychological outcomes in the offspring of Indigenous parents with a mental health challenge. RESULTS: The 14 studies eligible for review were focused on parental substance misuse (n = 8), maternal internalizing (i.e., depression, anxiety) issues (n = 5), and poor overall parental mental health (n = 4). In 11 studies, parental substance misuse, depression, and/or overall mental health challenges were associated with 2 to 4 times the odds of offspring externalizing and internalizing behaviors as compared to offspring of Indigenous parents without mental health challenges. CONCLUSION: The findings suggest higher risks of mental health challenges among offspring of Indigenous parents with psychiatric difficulties than among Indigenous children of parents without similar difficulties. Knowledge of these phenomena would be improved by the use of larger, more representative samples, culturally appropriate measures, and the engagement of Indigenous communities. Future studies should be focused on both risk and resilience mechanisms so that cycles of transmission can be interrupted and resources aimed at detection, prevention, and treatment optimally allocated.

The care experiences of patients who die in residential hospice: A qualitative analysis of the last three months of life from the views of bereaved caregivers.

OBJECTIVE: Despite the increasing prominence of residential hospices as a place of death and that, in many regards, this specialized care represents a gold standard, little is known about the care experience in this setting. Using qualitative survey data, we examined the positive and negative perceptions of care in hospices and in other prior settings. METHOD: Qualitative comments were extracted from the CaregiverVoice survey completed by bereaved caregivers of decedents who had died in 16 residential hospices in Ontario, Canada. On this survey, caregivers reported what was good and bad about the services provided during the last three months of life as separate open-text questions. A constant-comparison method was employed to derive themes from the responses. RESULTS: A total of 550 caregivers completed the survey, 94% (517) of whom commented on either something good (84%) and/or bad (49%) about the care experience. In addition to residential hospice, the majority of patients represented also received palliative care in the home (69%) or hospital (59%). Overall, most positive statements were about care in hospice (71%), whereas the negative statements tended to refer to other settings (81%). The hospice experience was found to exemplify care that was compassionate and holistic, in a comforting environment, offered by providers who were personable, dedicated, and informative. These humanistic qualities of care and the extent of support were generally seen to be lacking from the other settings. SIGNIFICANCE OF RESULTS: Our examination of the good and bad aspects of palliative care received is unique in qualitatively exploring palliative care experiences across multiple settings, and specifically that in hospices. Investigation of these perspectives affirmed the elements of care that dying patients and their family caregivers most value and that the hospices were largely effective at addressing. These findings highlight the need for reinforcing these qualities in other end-of-life settings to create comforting and supportive environments.

The De-Etiolated 1 Homolog of Arabidopsis Modulates the ABA Signaling Pathway and ABA Biosynthesis in Rice.

DEETIOLATED1 (DET1) plays a critical role in developmental and environmental responses in many plants. To date, the functions of OsDET1 in rice (Oryza sativa) have been largely unknown. OsDET1 is an ortholog of Arabidopsis (Arabidopsis thaliana) DET1 Here, we found that OsDET1 is essential for maintaining normal rice development. The repression of OsDET1 had detrimental effects on plant development, and leaded to contradictory phenotypes related to abscisic acid (ABA) in OsDET1 interference (RNAi) plants. We found that OsDET1 is involved in modulating ABA signaling in rice. OsDET1 RNAi plants exhibited an ABA hypersensitivity phenotype. Using yeast two-hybrid (Y2H) and bimolecular fluorescence complementation assays, we determined that OsDET1 interacts physically with DAMAGED-SPECIFIC DNA-BINDING PROTEIN1 (OsDDB1) and CONSTITUTIVE PHOTOMORPHOGENIC10 (COP10); DET1- and DDB1-ASSOCIATED1 binds to the ABA receptors OsPYL5 and OsDDB1. We found that the degradation of OsPYL5 was delayed in OsDET1 RNAi plants. These findings suggest that OsDET1 deficiency disturbs the COP10-DET1-DDB1 complex, which is responsible for ABA receptor (OsPYL) degradation, eventually leading to ABA sensitivity in rice. Additionally, OsDET1 also modulated ABA biosynthesis, as ABA biosynthesis was inhibited in OsDET1 RNAi plants and promoted in OsDET1-overexpressing transgenic plants. In conclusion, our data suggest that OsDET1 plays an important role in maintaining normal development in rice and mediates the cross talk between ABA biosynthesis and ABA signaling pathways in rice.

Mortality in hospitalized older adults with COVID-19 during three waves: A multicenter retrospective cohort study.

Background: The waves of COVID-19 infections in Ontario, Canada, were marked by differences in patient characteristics and treatment. Our objectives were to (i) describe patient characteristics, treatment, and outcomes of hospitalized older adults with COVID-19 between waves 1, 2, and 3, (ii) determine if there was an improvement in in-hospital mortality in waves 2 and 3 after adjusting for covariates. Methods: This retrospective cohort study was done in five acute care hospitals in Toronto, Ontario. Consecutive hospitalized older adults aged ≥65 years with confirmed COVID-19 infection were included. Wave 1 extended from March 11 to July 31, 2020, wave 2 from August 1, 2020 to February 20, 2021, and wave 3 from February 21 to June 30, 2021. Patient characteristics and outcomes were abstracted from charts. A logistic regression model was used to determine the association between COVID-19 and in-hospital mortality in waves 2 and 3 compared with wave 1. Results: Of the 1671 patients admitted to acute care, 297 (17.8%) were admitted in wave 1, 751 (44.9%) in wave 2, and 623 (37.3%) in wave 3. The median age of our cohort was 77.0 years (interquartile range: 71.0-85.0) and 775 (46.4%) were female. The prevalence of frailty declined in progressive waves. The use of dexamethasone, remdesivir, and tocilizumab was significantly higher in waves 2 and 3 compared with wave 1. In the unadjusted analysis, in-hospital mortality was unchanged between waves 1 and 2, but it was lower in wave 3 (18.3% vs. 27.4% in wave 1). After adjustment, in-hospital mortality was unchanged in waves 2 and 3 compared with wave 1. Conclusion: In-hospital mortality in hospitalized older adults with COVID-19 was similar between waves 1 and 3. Further research should be done to determine if COVID-19 therapies have similar benefits for older adults compared with younger adults.

Characteristics, treatment and delirium incidence of older adults hospitalized with COVID-19: a multicentre retrospective cohort study.

BACKGROUND: The COVID-19 pandemic has affected older adults disproportionately, and delirium is a concerning consequence; however, the relationship between delirium and corticosteroid use is uncertain. The objective of the present study was to describe patient characteristics, treatments and outcomes among older adults hospitalized with COVID-19, with a focus on dexamethasone use and delirium incidence. METHODS: We completed this retrospective cohort study at 7 sites (including acute care, rehabilitation and long-term care settings) in Toronto, Ontario, Canada. We included adults aged 65 years or older, consecutively hospitalized with confirmed SARS-CoV-2 infection, between Mar. 11, 2020, and Apr. 30, 2021. We abstracted patient characteristics and outcomes from charts and analyzed them descriptively. We used a logistic regression model to determine the association between dexamethasone use and delirium incidence. RESULTS: During the study period, 927 patients were admitted to the acute care hospitals with COVID-19. Patients' median age was 79.0 years (interquartile range [IQR] 72.0-87.0), and 417 (45.0%) were female. Most patients were frail (61.9%), based on a Clinical Frailty Scale score of 5 or greater. The prevalence of delirium was 53.6%, and the incidence was 33.1%. Use of restraints was documented in 20.4% of patients. In rehabilitation and long-term care settings (n = 115), patients' median age was 86.0 years (IQR 78.5-91.0), 72 (62.6%) were female and delirium occurred in 17 patients (14.8%). In patients admitted to acute care during wave 2 of the pandemic (Aug. 1, 2020, to Feb. 20, 2021), dexamethasone use had a nonsignificant association with delirium incidence (adjusted odds ratio 1.38, 95% confidence interval 0.77-2.50). Overall, in-hospital death occurred in 262 (28.4%) patients in acute care settings and 28 (24.3%) patients in rehabilitation or long-term care settings. INTERPRETATION: In-hospital death, delirium and use of restraints were common in older adults admitted to hospital with COVID-19. Further research should be directed to improving the quality of care for this population with known vulnerabilities during continued waves of the COVID-19 pandemic.

The effect of composite PHB coating on the biological properties of a magnesium based alloy.

Magnesium alloys have been widely investigated as biodegradable cardiovascular temporal implants due to their better mechanical properties and biocompatibility, but the rapid degradation limited its application. In this study, the anodic oxidation-Cu structure was used to improve the adhesive strength and stability between poly-ß-hydroxybutyrate (PHB) and magnesium alloys, and the effects of anodic oxidation magnesium alloys with copper film and PHB film (MACP) on human umbilical vein endothelial cells (HUVECs), blood compatibility and antibacterial properties were investigated in this research. As the result, the MACP structure had a stable structure and better corrosion resistance, and significant antibacterial properties. The coating would not affect the original excellent biocompatibility of the magnesium alloy. It was indicated that MACP was a potential surface modification strategy for vascular stents candidate material.

Prevalence and trajectory of erosions, synovitis, and bone marrow edema in feet of patients with early rheumatoid arthritis.

Despite erosions being as prevalent in feet as in hands in patients with rheumatoid arthritis (RA), their development in relation to synovitis and bone marrow edema (BME) have mainly been studied in hands. This study examines the prevalence and longitudinal trajectory of erosions, BME, and synovitis in metatarsophalangeal joints (MTPJs) in patients with early RA over 2 years of treatment. We also describe correlations between erosions, synovitis, and BME at the joint level. Magnetic resonance imaging (MRI) of the most symptomatic forefoot was acquired at baseline, year 1, and ≥ 2 years. Metatarsophalangeal joints 2-5 were scored by a radiologist for erosions, synovitis, and BME according to OMERACT guidelines. Patients were treated per standard of care. Thirty-two patients with early RA were included. Significant reductions in overall synovitis scores, MTPJ2, and MTPJ3 synovitis scores were seen between year 1 and ≥ 2 years. Overall BME scores improved in year 1 and were sustained at ≥ 2 years. BME improved in MTPJ2, MTPJ3, and MTPJ4. Overall erosions did not significantly change. Positive correlations were seen between changes in synovitis and BME in MTPJ2 and MTPJ5. In patients with early RA, standard of care was associated with overall reductions in synovitis by year 2, BME by year 1, and no progression in overall erosion scores on MRI. MTPJ2 and MTPJ3 appeared to be the most active joints. Improvements in synovitis were noted in MTPJ2 and MTPJ3 and reductions in BME in MTPJ2, MTPJ3, and MTPJ4, while other MTPJs did not progress. Key Points • This is one of the few MRI studies that examined longitudinal changes in imaging outcomes in early RA at the joint level in feet. • Erosions, synovitis, and bone marrow edema (BME) visualized on magnetic resonance imaging were most prevalent in metatarsophalangeal joints (MTPJ) 2 and 3 in patients with early rheumatoid arthritis (RA). • Standard of care was associated with improvements in synovitis in MTPJ2 and MTPJ3 and improvements in BME in MTPJ2, MTPJ3, and MTPJ4 over 2 years of treatment.

Ultrasonography supplements clinical exam to improve early rheumatoid arthritis disease activity monitoring in metatarsophalangeal joints.

INTRODUCTION: Compared with clinical examination (CE), ultrasonography (US) provides additional and more accurate assessment of inflammation and visualization of structural damage. To better understand the effectiveness of US in metatarsophalangeal joints (MTPJs), we compared disease activity in MTPJs 2-5 assessed by CE and US, with magnetic resonance imaging (MRI) as reference standard. METHOD: Treatment-naïve adult patients with early RA (ACR criteria, disease duration < 2 years) were consecutively recruited. MTPJs 2-5 were assessed for swelling and tenderness, and imaged by US (Esaote MyLab70). The most symptomatic foot was imaged by peripheral MRI (1.0 Tesla). US was semiquantitatively graded for synovial thickening (ST) and power Doppler (PD) (0-3), and erosions (yes/no). MRI was semiquantitatively graded for bone marrow edema (BME), synovitis, and erosions (OMERACT). Kappa agreement, sensitivity, specificity, and predictive values were analyzed using cut-offs at ST ≥ 2, PD ≥ 1, and MRI synovitis and BME at both ≥ 1 and ≥ 2. RESULTS: This study included 39 patients (85% female, mean (SD) age = 51.6 (10.3)). Using MRI synovitis and BME grade ≥ 2 as the reference, PD had superior sensitivity (82%) and kappa agreement (k = 0.43) than swollen joint count (55%, k = 0.20), but similar high specificity (88%, 83%). ST and PD were often observed in clinically asymptomatic MTPJs. US detected very few MRI erosions, but several observed erosions corresponded to grade ≥ 2 MRI erosions. CONCLUSION: Clinical swelling and PD are highly specific for active inflammation in the MTPJs. US supplemented CE by allowing observation of subclinical inflammation and structural damage. Key Points • Ultrasonography detected many subclinical synovial inflammations in metatarsophalangeal joints (MTPJs), many confirmed by MRI • Ultrasonography may best be used clinically to supplement clinical examination by assessing non-swollen joints • Ultrasonography provided quick method of visualizing bone erosions that were grade ≥ 2 on MRI.

Mutation of OsDET1 increases chlorophyll content in rice.

As an important agronomic trait, the chlorophyll (Chl) content is closely related to photosynthesis in plants. A rice mutant Gc (Oryza sativa indica) was characterized previously by its enhanced Chl content (Chl b and total Chl) and exaggerated photosynthetic rate. Here, we describe the enhanced Chl content was caused by a mutation in the rice homolog of the DE-ETIOLATED1 (DET1) known to be involved in light transduction and morphogenesis in Arabidopsis and tomato. Sequence analysis revealed that the Gc mutant carried two fragment-insertions and a fragment-deletion upstream of the start codon of OsDET1, which led to enhance mRNA levels of OsDET1. Besides, the Gc mutant harbored a single T-to-C base transversion in the seventh exon of OsDET1, which resulted in leucine(328) to serine(328) localized in the highly conserved region. Genetic complementation demonstrated that OsDET1 mutation conferred the enhanced Chl content in the Gc mutant leaf. OsDET1 was richly expressed in green tissues, and its expression seems to be under circadian control. OsDET1-GFP fusion protein in onion epidermal cells showed that OsDET1 localized to the nucleus. These results indicated that OsDET1 mutation in Gc mutant increases Chl content in rice, which might be fundamental for enhanced photoresponsiveness.

Photosynthetic and physiological analysis of the rice high-chlorophyll mutant (Gc).

Chlorophyll (Chl) molecules are essential for harvesting light energy in photosynthesis. A rice high-chlorophyll mutant (Gc) with significantly increased Chl b was identified previously in Zhenshan 97B (Oryza sativa indica). However, the mechanism underlying this higher Chl b content and its effects on photosynthetic efficiency are still unclear. Immunoblot and blue native polyacrylamide gel electrophoresis (BN-PAGE) with a second dimension electrophoresis followed by the matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) analysis showed that a few core proteins of photosystem I (PSI) and photosystem II (PSII), and light-harvesting complex II (LHCII) proteins were overexpressed in the mutant plants. Remarkable differences in chloroplast ultrastructure were observed between the wild-type and mutant plants, with the latter having more highly stacked and larger grana. Chl florescence analysis demonstrated that Gc had markedly increased quantum efficiency of photosystem II (ΦPSII), photochemical quenching (qP), non-photochemical quenching (qN) and electron transport rate (ETR). This morphological and physiological adaptation might confer a higher photosynthetic capacity in Gc than the wild-type.