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1.
J Mol Cell Cardiol ; 195: 55-67, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39089571

ABSTRACT

Acute lung injury (ALI) including acute respiratory distress syndrome (ARDS) is a major complication and increase the mortality of patients with cardiac surgery. We previously found that the protein cargoes enriched in circulating extracellular vesicles (EVs) are closely associated with cardiopulmonary disease. We aimed to evaluate the implication of EVs on cardiac surgery-associated ALI/ARDS. The correlations between "oncoprotein-induced transcript 3 protein (OIT3) positive" circulating EVs and postoperative ARDS were assessed. The effects of OIT3-overexpressed EVs on the cardiopulmonary bypass (CPB) -induced ALI in vivo and inflammation of human bronchial epithelial cells (BEAS-2B) were detected. OIT3 enriched in circulating EVs is reduced after cardiac surgery with CPB, especially with postoperative ARDS. The "OIT3 positive" EVs negatively correlate with lung edema, hypoxemia and CPB time. The OIT3-overexpressed EVs can be absorbed by pulmonary epithelial cells and OIT3 transferred by EVs triggered K48- and K63-linked polyubiquitination to inactivate NOD-like receptor protein 3 (NLRP3) inflammasome, and restrains pro-inflammatory cytokines releasing and immune cells infiltration in lung tissues, contributing to the alleviation of CPB-induced ALI. Overexpression of OIT3 in human bronchial epithelial cells have similar results. OIT3 promotes the E3 ligase Cbl proto-oncogene B associated with NLRP3 to induce the ubiquitination of NLRP3. Immunofluorescence tests reveal that OIT3 is reduced in the generation from the liver sinusoids endothelial cells (LSECs) and secretion in liver-derived EVs after CPB. In conclusion, OIT3 enriched in EVs is a promising biomarker of postoperative ARDS and a therapeutic target for ALI after cardiac surgery.

2.
Ann Acad Med Singap ; 53(7): 410-419, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39132958

ABSTRACT

Introduction: This study aimed to determine patterns of screen viewing time (SVT) in preschool children with developmental, behavioural or emotional (DBE) issues, and to identify its relationship with social-emotional development. Method: This cross-sectional study involved children aged 0-5 years who were referred to a developmental paediatric clinic for DBE issues. Parents completed a screen time questionnaire, and the Devereux Early Childhood Assessment-Clinical (DECA-C) question-naire which assessed the social-emotional competence of the children. Data were analysed using logistic regression, correlational analyses and tests of comparison. Results: Among 225 children (mean age: 32.4 months), mean daily SVT was 138 minutes. More than half (51.1%) of the children had clinical features of language delay, while 26.6% had features suggestive of autism spectrum disorder. Screen time was first introduced at a mean age of 13.8 months, with 32.4% of children previously experiencing higher SVT. Compared to SVT introduction after 1 year of age, SVT in the first 12 months was primarily to facilitate feeding (P<0.05). Children with higher past SVT had poorer attention, more aggression, and increased behavioural concerns. Children with DBE issues have significantly more screen time than same-aged peers. Conclusion: Children with DBE issues are exposed to SVT at a very young age and have significantly more screen time than their peers. It is crucial to guide parents to reduce SVT in early childhood, particularly around mealtimes.


Subject(s)
Screen Time , Humans , Child, Preschool , Singapore/epidemiology , Cross-Sectional Studies , Male , Female , Infant , Autism Spectrum Disorder/psychology , Social Skills , Language Development Disorders/psychology , Language Development Disorders/epidemiology , Emotions , Surveys and Questionnaires , Child Behavior Disorders/epidemiology , Child Behavior Disorders/diagnosis , Child Behavior Disorders/psychology
3.
J Pain Res ; 17: 2605-2628, 2024.
Article in English | MEDLINE | ID: mdl-39139997

ABSTRACT

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) still lacks efficient therapeutic drugs. This study aimed to systematically evaluate the effects of Huangqi Guizhi Wuwu Decoction (HGWD) alone or combined with positive drugs on CIPN prevention and treatment. Methods: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI), Wan Fang Data, China Science and Technology Journal (VIP) and Chinese Biomedical (CBM) databases were searched for randomized controlled trials (RCTs) of HGWD for CIPN prevention and treatment. The search time ranged from database establishment to October 17, 2023. The Cochrane risk-of-bias assessment tool was used for quality assessment, Review Manager 5.3 and STATA 12.0 were used for meta-analysis, and GRADEprofiler was used for evidence level assessment. Results: A total of 32 RCTs involving 1987 patients were included. The meta-analysis results revealed the following: 1. In terms of the total CIPN incidence, that in the HGWD group was lower than that in the blank control group. The incidence in both the HGWD and HGWD+positive drug groups was lower than that in the monotherapy-positive drug group. 2. In terms of the incidence of severe CIPN, that in the HGWD group was lower than that in the blank control and positive drug groups. There was no statistically significant difference between the HGWD+positive drug and positive drug groups. Sensitivity analysis revealed that the results of severe incidence in the HGWD group was lower than that in the positive drug group were unstable 3. HGWD did not increase the number of chemotherapy-related adverse events. Conclusion: HGWD can safely and effectively prevent CIPN, reduce symptoms, improve quality of life and reduce the impact of chemotherapy drugs on sensory nerve conduction. However, more high-quality RCTs are needed to compare the efficacy of HGWD with that of positive control drugs in preventing severe CIPN.

4.
Stat Methods Med Res ; : 9622802241262525, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39053567

ABSTRACT

Individualized treatment rules inform tailored treatment decisions based on the patient's information, where the goal is to optimize clinical benefit for the population. When the clinical outcome of interest is survival time, most of current approaches typically aim to maximize the expected time of survival. We propose a new criterion for constructing Individualized treatment rules that optimize the clinical benefit with survival outcomes, termed as the adjusted probability of a longer survival. This objective captures the likelihood of living longer with being on treatment, compared to the alternative, which provides an alternative and often straightforward interpretation to communicate with clinicians and patients. We view it as an alternative to the survival analysis standard of the hazard ratio and the increasingly used restricted mean survival time. We develop a new method to construct the optimal Individualized treatment rule by maximizing a nonparametric estimator of the adjusted probability of a longer survival for a decision rule. Simulation studies demonstrate the reliability of the proposed method across a range of different scenarios. We further perform data analysis using data collected from a randomized Phase III clinical trial (SWOG S0819).

5.
World J Clin Cases ; 12(21): 4807-4812, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39070838

ABSTRACT

BACKGROUND: Paragonimiasis is a typical food-borne zoonotic disease. Hosts acquire Paragonimus infection through the ingestion of raw or undercooked crayfish and crab. The clinical manifestations of the disease are varied, and it is often misdiagnosed or missed. The diagnosis of paragonimiasis should be considered comprehensively. Praziquantel is the first choice for treatment, and albendazole can be used in combination with repeated courses in severe cases. CASE SUMMARY: We report a case of liver paragonimiasis that was misdiagnosed as an abscess. The patient presented with fatigue and poor appetite for 2 months, and was diagnosed with liver abscess in the local hospital. After 6 months, the patient visited our hospital because of recurrent abdominal pain and was diagnosed with liver paragonimiasis based on epidemiological history, clinical presentations, and laboratory findings. He was treated with praziquantel (25 mg/kg) three times a day for 3 days; however, the symptoms still presented after treatment. He was treated with oral praziquantel and albendazole for one further course. Follow-up suggested that the treatment was effective and the symptoms improved. CONCLUSION: The combination of albendazole and praziquantel may improve the therapeutic efficacy of paragonimiasis.

6.
Front Cell Dev Biol ; 12: 1415621, 2024.
Article in English | MEDLINE | ID: mdl-39071800

ABSTRACT

Introduction: Mouse embryonic stem cell (ESC) self-renewal can be maintained through dual inhibition of GSK3 and MEK kinases. MEK has two highly homologous downstream kinases, extracellular signal-regulated kinase 1 and 2 (ERK1/2). However, the exact roles of ERK1/2 in mouse ESC self-renewal and differentiation remain unclear. Methods: We selectively deleted or inhibited ERK1, ERK2, or both using genetic and chemical genetic approaches combined with small molecule inhibitors. The effects of ERK paralog-specific inhibition on mouse ESC self-renewal and differentiation were then assessed. Results: ERK1/2 were found to be dispensable for mouse ESC survival and self-renewal. The inhibition of both ERK paralogs, in conjunction with GSK3 inhibition, was sufficient to maintain mouse ESC self-renewal. In contrast, selective deletion or inhibition of only one ERK paralog did not mimic the effect of MEK inhibition in promoting mouse ESC self-renewal. Regarding ESC differentiation, inhibition of ERK1/2 prevented mesendoderm differentiation. Additionally, selective inhibition of ERK1, but not ERK2, promoted mesendoderm differentiation. Discussion: These findings suggest that ERK1 and ERK2 have both overlapping and distinct roles in regulating ESC self-renewal and differentiation. This study provides new insights into the molecular mechanisms of ERK1/2 in governing ESC maintenance and lineage commitment, potentially informing future strategies for controlling stem cell fate in research and therapeutic applications.

7.
Exp Ther Med ; 28(2): 330, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38979021

ABSTRACT

Chrysanthemum indicum Linnén (C. indicum), a medicinal and food herb with various bioactive components, may be of beneficial use in cosmetics and the treatment of skin-related diseases. However, to date, few studies have been reported on its potential preventive and therapeutic effects on skin cancer. Therefore, the present study aimed to investigate the effect and potential mechanism of action of supercritical carbon dioxide extract from C. indicum (CISCFE) on UV-induced skin cancer in a mouse model. Kunming mice were allocated randomly to five treatment groups: Sham, model, low concentration CISCFE, high concentration CISCFE and positive control nicotinamide groups. The dorsal skin of mice was irradiated with UV light for 31 weeks. Histopathological changes, ELISA assays, immunohistochemical analysis and western blotting were performed to investigate the potential therapeutic effects of CISCFE. The results showed that CISCFE alleviated skin oxidative and inflammatory damage in a UV-induced mouse model of skin cancer. Moreover, CISCFE suppressed abnormal activation of proto-oncogene c-Myc and the overexpression of Ki-67 and VEGF, and increased expression of the anti-oncogene PTEN, thereby reducing abnormal proliferation of the epidermis and blood vessels. Additionally, CISCFE increased the protein expression levels of NAD-dependent protein deacetylase sirtuin-1 (SIRT1), Kelch-like ECH associated protein 1 (Keap1) and inhibited the expression of nuclear factor 2 erythroid 2-related factor 2 (Nrf2), phosphorylated (p)-p62 (Ser 349), p-p65 and acetyl-p65 proteins in a UV-induced skin cancer mouse model. In summary, CISCFE exhibited potent anti-skin cancer activity, which may be attributed its potential effects on the p62/Keap1-Nrf2 and SIRT1/NF-κB pathways.

8.
Angew Chem Int Ed Engl ; : e202403432, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023052

ABSTRACT

In the pursuit of next-generation ultrahigh-energy-density Li-O2 batteries, it is imperative to develop an electrolyte with stability against the strong oxidation environments. N,N-dimethylacetamide (DMA) is a recognized solvent known for its robust resistance to the highly reactive reduced oxygen species, yet its application in Li-O2 batteries has been constrained due to its poor compatibility with the Li metal anode. In this study, a rationally selected hydrofluoroether diluent, methyl nonafluorobutyl ether (M3), has been introduced into the DMA-based electrolyte to construct a localized high concentration electrolyte. The stable -CH3 and C-F bonds within the M3 structure could not only augment the fundamental properties of the electrolyte but also fortify its resilience against attacks from O2- and 1O2. Additionally, the strong electron-withdrawing groups (-F) presented in the M3 diluent could facilitate coordination with the electron-donating groups (-CH3) in the DMA solvent. This intermolecular interaction promotes more alignment of Li+-anions with a small amount of M3 addition, leading to the construction of an anion-derived inorganic-rich SEI that enhances the stability of the Li anode. As a result, the Li-O2 batteries with the DMA/M3 electrolyte exhibit superior cycling performance at both 30 °C (359th) and -10 °C (120th).

9.
Mol Ther Oncol ; 32(3): 200823, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39006946

ABSTRACT

In the field of innovative cancer treatment strategies, oncolytic vaccinia virus (VV)es have gained traction as promising vectors. In the current study, we inserted the human C-type lectin domain family 2 member A (CLEC2A) gene into VV, creating a replicating therapeutic, oncoVV-CLEC2A. The findings reveal that oncoVV-CLEC2A effectively suppresses colorectal proliferation of mouse xenografts and a range of human cancer cell lines by augmenting viral reproduction capabilities, including the lung cancer H460 cell line, colorectal cancer cell lines (HCT116 and SW620), and hepatocellular carcinoma HuH-7 cell line. Moreover, it is evident that oncoVV-CLEC2A can induce antitumor immunity by boosting cytokine production but not antivirus response, and enhancing calreticulin expression. Further investigation indicates that oncoVV-CLEC2A can enhance antitumor capabilities by activating natural killer cells to produce interferon-γ and induce M1-like macrophage polarization. These findings shed light on the antitumor mechanisms of oncoVV-CLEC2A, provide a theoretical basis for oncolytic therapies, and lay the groundwork for novel strategies for modifying VVs.

10.
Sci Total Environ ; 945: 173856, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38871315

ABSTRACT

Regional transport plays a crucial role in the pollution of fine particulate matter (PM2.5) over the Yangtze River Delta region (YRD). A practical joint regional emission control strategy requires quantitative assessment of the contribution of regional transport. In this study, the contribution of inter-city transport to PM2.5 among the 41 cities in the YRD region were quantitatively estimated using a source-oriented chemical transport model, and then the relationship between the cumulative contribution of regional transport and the distance was examined using the Michaelis-Menten equation. The results show that the Michaelis-Menten equation is suitable to represent the relationship between the cumulative contribution and transport distance. The coefficient of determination (r2) of the fittings is greater than 0.9 in 71 % of the cases in the six subregions and four seasons in YRD. Two key parameters in the Michaelis-Menten eq. K1, indicating the maximum contribution of regional transport, and K2, indicating the distance to which the regional transport contribution reach half the maximum contribution, show substantial regional and seasonal variations. The average K1 is 73.6 %, with lower values observed in the northern part of the YRD and higher values in central Jiangsu. K2 is larger in northern Jiangsu, as well as central and southern Zhejiang. The local contribution in autumn and winter is lower than that in spring and summer in the northern part of the YRD. Particularly in northern Jiangsu, the local contribution reaches 90.4 % in summer but drops to 53.0 % in autumn and winter, illustrating significant impacts of regional transport to PM2.5 in autumn and winter in this area. K2 is larger on polluted days, compared to clean days, indicating greater contributions from regional transport to PM2.5 in YRD. The results can serve as a scientific foundation for implementing regional joint prevention and control measures in the YRD region.

11.
Environ Health Perspect ; 132(6): 67010, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38922331

ABSTRACT

BACKGROUND: Evidence linking gaseous air pollution to late-life brain health is mixed. OBJECTIVE: We explored associations between exposure to gaseous pollutants and brain magnetic resonance imaging (MRI) markers among Atherosclerosis Risk in Communities (ARIC) Study participants, with attention to the influence of exposure estimation method and confounding by site. METHODS: We considered data from 1,665 eligible ARIC participants recruited from four US sites in the period 1987-1989 with valid brain MRI data from Visit 5 (2011-2013). We estimated 10-y (2001-2010) mean carbon monoxide (CO), nitrogen dioxide (NO2), nitrogen oxides (NOx), and 8- and 24-h ozone (O3) concentrations at participant addresses, using multiple exposure estimation methods. We estimated site-specific associations between pollutant exposures and brain MRI outcomes (total and regional volumes; presence of microhemorrhages, infarcts, lacunes, and severe white matter hyperintensities), using adjusted linear and logistic regression models. We compared meta-analytically combined site-specific associations to analyses that did not account for site. RESULTS: Within-site exposure distributions varied across exposure estimation methods. Meta-analytic associations were generally not statistically significant regardless of exposure, outcome, or exposure estimation method; point estimates often suggested associations between higher NO2 and NOx and smaller temporal lobe, deep gray, hippocampal, frontal lobe, and Alzheimer disease signature region of interest volumes and between higher CO and smaller temporal and frontal lobe volumes. Analyses that did not account for study site more often yielded significant associations and sometimes different direction of associations. DISCUSSION: Patterns of local variation in estimated air pollution concentrations differ by estimation method. Although we did not find strong evidence supporting impact of gaseous pollutants on brain changes detectable by MRI, point estimates suggested associations between higher exposure to CO, NOx, and NO2 and smaller regional brain volumes. Analyses of air pollution and dementia-related outcomes that do not adjust for location likely underestimate uncertainty and may be susceptible to confounding bias. https://doi.org/10.1289/EHP13906.


Subject(s)
Air Pollutants , Air Pollution , Dementia , Environmental Exposure , Magnetic Resonance Imaging , Neuroimaging , Humans , Air Pollutants/analysis , Air Pollution/statistics & numerical data , Male , Female , Environmental Exposure/statistics & numerical data , Dementia/epidemiology , Aged , Middle Aged , Nitrogen Oxides/analysis , Cohort Studies , Brain/diagnostic imaging , Nitrogen Dioxide/analysis , Ozone/analysis , United States/epidemiology
12.
Exp Dermatol ; 33(6): e15097, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38840370

ABSTRACT

Surgical management of basal cell carcinoma (BCC) typically involves surgical excision with post-operative margin assessment using the bread-loafing technique; or gold-standard Mohs micrographic surgery (MMS), where margins are iteratively examined for residual cancer after tumour removal, with additional excisions performed upon detecting residual tumour at margins. There is limited sampling of resection margins with bread loafing, with detection of positive margins 44% of the time using 2 mm intervals. To resolve this, we have developed three-dimensional (3D) Tissue Imaging for: (1) complete examination of cancer margins and (2) detection of tumour proximity to nerves and blood vessels. 3D Tissue optical clearing with a light sheet imaging protocol was developed for margin assessment in two datasets assessed by two independent evaluators: (1) 48 samples from 29 patients with varied BCC subtypes, sizes and pigmentation levels; (2) 32 samples with matching Mohs' surgeon reading of tumour margins using two-dimensional haematoxylin & eosin-stained sections. The 3D Tissue Imaging protocol permits a complete examination of deeper and peripheral margins. Two independent evaluators achieved negative predictive values of 92.3% and 88.24% with 3D Tissue Imaging. Images obtained from 3D Tissue Imaging recapitulates histological features of BCC, such as nuclear crowding, palisading and retraction clefting and provides a 3D context for recognising normal skin adnexal structures. Concurrent immunofluorescence labelling of nerves and blood vessels allows visualisation of structures closer to tumour-positive regions, which may have a higher risk for neural and vascular infiltration. Together, this method provides more information in a 3D spatial context, enabling better cancer management by clinicians.


Subject(s)
Carcinoma, Basal Cell , Imaging, Three-Dimensional , Margins of Excision , Mohs Surgery , Skin Neoplasms , Humans , Carcinoma, Basal Cell/diagnostic imaging , Carcinoma, Basal Cell/surgery , Carcinoma, Basal Cell/pathology , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/surgery , Skin Neoplasms/pathology
13.
Stem Cell Res Ther ; 15(1): 187, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937829

ABSTRACT

Due to the advanced studies on stem cells in developmental biology, the roles of stem cells in the body and their phenotypes in related diseases have not been covered clearly. Meanwhile, with the intensive research on the mechanisms of stem cells in regulating various diseases, stem cell therapy is increasingly being attention because of its effectiveness and safety. As one of the most widely used stem cell in stem cell therapies, hematopoietic stem cell transplantation shows huge advantage in treatment of leukemia and other blood-malignant diseases. Besides, due to the effect of anti-inflammatory and immunomodulatory, mesenchymal stem cells could be a potential therapeutic strategy for variety infectious diseases. In this review, we summarized the effects of Staphylococcus aureus (S. aureus) and its components on different types of adult stem cells and their downstream signaling pathways. Also, we reviewed the roles of different kinds of stem cells in various disease models caused by S. aureus, providing new insights for applying stem cell therapy to treat infectious diseases.


Subject(s)
Staphylococcus aureus , Humans , Animals , Inflammation/therapy , Staphylococcal Infections/therapy , Signal Transduction , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism
14.
Environ Res ; 258: 119425, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38879108

ABSTRACT

BACKGROUND: Increasing evidence links higher air pollution exposures to increased risk of cognitive impairment. While midlife risk factors are often most strongly linked to dementia risk, few studies have considered associations between midlife roadway proximity or ambient air pollution exposure and incident dementia decades later, in late life. OBJECTIVES: Our objective was to determine if midlife exposures to ambient air pollution or roadway proximity are associated with increased risk of dementia in the Atherosclerosis Risk in Communities (ARIC) study over up to 29 years of follow-up. METHODS: Our eligible sample included Black and White ARIC participants without dementia at Visit 2 (1990-1992). Participants were followed through Visit 7 (2018-2019), with dementia status and onset date defined based on formal dementia ascertainment at study visits, informant interviews, and surveillance efforts. We used adjusted Weibull survival models to assess the associations of midlife ambient air pollution and road proximity with incident dementia. RESULTS: The median age at baseline (1990-1992, Visit 2) of the 12,700 eligible ARIC participants was 57.0 years; 56.0% were female, 24.2% were Black, and 78.9% had at least a high school education. Over up to 29 years of follow-up, 2511 (19.8%) persons developed dementia. No associations were found between ambient air pollutants and proximity to major roadways with risk of incident dementia. In exploratory analyses, living closer to roadways in midlife increased dementia risk in individuals younger at baseline and those without midlife hypertension, and there was evidence of increased risk of dementia with increased midlife exposure to NOx, several PM2.5 components, and trace metals among those with diabetes in midlife. CONCLUSIONS: Midlife exposure to ambient air pollution and midlife roadway proximity was not associated with dementia risk over decades of follow-up. Further investigation to explore potential for greater susceptibility among specific subgroups identified here is needed.


Subject(s)
Air Pollutants , Air Pollution , Dementia , Environmental Exposure , Humans , Middle Aged , Dementia/epidemiology , Dementia/chemically induced , Dementia/etiology , Female , Male , Environmental Exposure/adverse effects , Air Pollution/adverse effects , Air Pollution/analysis , Aged , Air Pollutants/analysis , Air Pollutants/adverse effects , Incidence , Risk Factors , Atherosclerosis/epidemiology , Atherosclerosis/etiology , Particulate Matter/analysis , Particulate Matter/adverse effects , Vehicle Emissions/analysis
15.
Heliyon ; 10(9): e29848, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38699049

ABSTRACT

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

16.
Int J Ophthalmol ; 17(3): 528-536, 2024.
Article in English | MEDLINE | ID: mdl-38721515

ABSTRACT

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

17.
J Autism Dev Disord ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773032

ABSTRACT

This cross-sectional study aimed to assess Quality of life (QoL) of parents of children on the autism spectrum in Singapore and identify its associated factors. Parents of children (age ≥ 5 years) completed the Quality of Life in Autism scale which measures parental self-rated QoL (higher scores denote greater QoL), and the perceived impact of the child's autism-related behaviors on parents (higher scores denote lesser impact). Information on the child's degree of autism (measured by the Social Responsiveness Scale, second edition [SRS-2]), community and social participation and cognitive and adaptive functioning were also obtained. Participants were 86 parents with mean child age 6.3 years (SD 1.0). Univariate analysis results revealed greater participation in community and social events to be two modifiable factors associated with higher parental QoL. However, these factors were not found to be significant in the multivariate model. Higher autism features (represented by higher parent-rated SRS scores) was associated with a greater perceived impact of the child's behaviors by parents in both univariate and multivariate analyses. Of note, child's cognitive or adaptive skills were not significantly associated with either QoL measure. Equipping parents to handle autism-related behaviors can be useful to reduce their impact on parental QoL. Facilitating community participation for these children may positively influence caregiver QoL as well.

18.
Environ Res ; 256: 119178, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38768885

ABSTRACT

BACKGROUND: Reported associations between particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5) and cognitive outcomes remain mixed. Differences in exposure estimation method may contribute to this heterogeneity. OBJECTIVES: To assess agreement between PM2.5 exposure concentrations across 11 exposure estimation methods and to compare resulting associations between PM2.5 and cognitive or MRI outcomes. METHODS: We used Visit 5 (2011-2013) cognitive testing and brain MRI data from the Atherosclerosis Risk in Communities (ARIC) Study. We derived address-linked average 2000-2007 PM2.5 exposure concentrations in areas immediately surrounding the four ARIC recruitment sites (Forsyth County, NC; Jackson, MS; suburbs of Minneapolis, MN; Washington County, MD) using 11 estimation methods. We assessed agreement between method-specific PM2.5 concentrations using descriptive statistics and plots, overall and by site. We used adjusted linear regression to estimate associations of method-specific PM2.5 exposure estimates with cognitive scores (n = 4678) and MRI outcomes (n = 1518) stratified by study site and combined site-specific estimates using meta-analyses to derive overall estimates. We explored the potential impact of unmeasured confounding by spatially patterned factors. RESULTS: Exposure estimates from most methods had high agreement across sites, but low agreement within sites. Within-site exposure variation was limited for some methods. Consistently null findings for the PM2.5-cognitive outcome associations regardless of method precluded empirical conclusions about the potential impact of method on study findings in contexts where positive associations are observed. Not accounting for study site led to consistent, adverse associations, regardless of exposure estimation method, suggesting the potential for substantial bias due to residual confounding by spatially patterned factors. DISCUSSION: PM2.5 estimation methods agreed across sites but not within sites. Choice of estimation method may impact findings when participants are concentrated in small geographic areas. Understanding unmeasured confounding by factors that are spatially patterned may be particularly important in studies of air pollution and cognitive or brain health.


Subject(s)
Air Pollutants , Brain , Cognition , Environmental Exposure , Magnetic Resonance Imaging , Particulate Matter , Particulate Matter/analysis , Humans , Male , Middle Aged , Female , Cognition/drug effects , Air Pollutants/analysis , Brain/diagnostic imaging , Brain/drug effects , Aged , Air Pollution/adverse effects , Air Pollution/analysis
19.
Sci Total Environ ; 938: 173327, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38761930

ABSTRACT

A near-explicit mechanism, the master chemical mechanism (MCMv3.3.1), coupled with the Community Multiscale Air Quality (CMAQ) model (CMAQ-MCM-SOA), was applied to investigate the characteristics of secondary organic aerosol (SOA) during a pollution event in the Yangtze River Delta (YRD) region in summer 2018. Model performances in predicting explicit volatile organic compounds (VOCs), organic aerosol (OA), secondary organic carbon (SOC), and other related pollutants in Taizhou, as well as ozone (O3) and fine particulate matter (PM2.5) in multiple cities in this region, were evaluated against observations and model predictions by the CMAQ model coupled with a lumped photochemical mechanism (SAPRC07tic, S07). MCM and S07 exhibited similar performances in predicting gaseous species, while MCM better captured the observed PM2.5 and inorganic aerosols. Both models underpredicted OA concentrations. When excluding data during biomass burning events, SOC concentrations were underpredicted by the CMAQ-MCM-SOA model (-28.4 %) and overpredicted by the CMAQ-S07 model (134.4 %), with better agreement with observations in the trend captured by the CMAQ-MCM-SOA model. Dicarbonyl SOA accounted for a significant fraction of total SOA in the YRD, while organic nitrates originating from aromatics were the most abundant species contributing to the SOA formation from gas-particle partitioning. The oxygen-to­carbon ratio (O/C) for SOA and OA were 0.68-0.75 and 0.20-0.65, respectively, indicating a higher oxidation state in the areas influenced by biogenic emissions. Finally, the phase state of SOA was examined by calculating the glass transition temperature (Tg) based on its molecular composition. It was found that semi-solid state characterized SOA in the YRD, which could potentially impact their chemical transformation and lifetimes along with those of their precursors.

20.
Blood Rev ; 65: 101196, 2024 May.
Article in English | MEDLINE | ID: mdl-38604819

ABSTRACT

Chronic myeloid leukaemia (CML) is caused by BCR::ABL1. Tyrosine kinase-inhibitors (TKIs) are the initial therapy. Several organizations have reported milestones to evaluate response to initial TKI-therapy and suggest when a change of TKI should be considered. Achieving treatment-free remission (TFR) is increasingly recognized as the optimal therapy goal. Which TKI is the best initial therapy for which persons and what depth and duration of molecular remission is needed to achieve TFR are controversial. In this review we discuss these issues and suggest future research directions.


Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Protein Kinase Inhibitors , Humans , Protein Kinase Inhibitors/therapeutic use , Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/etiology , Remission Induction , Biology
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