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Immunity & Ageing : I & A Jun 2024Age > 65 years is a key risk factor for poor outcomes after human influenza infection. Specifically, in addition to respiratory disease, non-neurotropic influenza A...
BACKGROUND
Age > 65 years is a key risk factor for poor outcomes after human influenza infection. Specifically, in addition to respiratory disease, non-neurotropic influenza A virus (IAV) causes neuro-cognitive complications, e.g. new onset depression and increases the risk of dementia after hospitalization. This study aimed to identify potential mechanisms of these effects by determining differences between young and old mice in brain gene expression in a mouse model of non-neurotropic IAV infection.
METHODS
Young (12 weeks) and old (70 weeks) C57Bl/6J mice were inoculated intranasally with 200 PFU H1N1 A/PR/34/8 (PR8) or sterile PBS (mock). Gene expression in lung and brain was measured by qRT-PCR and normalized to β-actin. Findings were confirmed using the nCounter Mouse Neuroinflammation Array (NanoString) and analyzed with nSolver 4.0 and Ingenuity Pathway Analysis (IPA, Qiagen).
RESULTS
IAV PR8 did not invade the central nervous system. Young and old mice differed significantly in brain gene expression at baseline and during non-neurotropic IAV infection. Expression of brain Ifnl, Irf7, and Tnf mRNAs was upregulated over baseline control at 3 days post-infection (p.i.) only in young mice, but old mice expressed more Ifnl than young mice 7 days p.i. Gene arrays showed down-regulation of the Epigenetic Regulation, Insulin Signaling, and Neurons and Neurotransmission pathways in old mice 3 days p.i. while young mice demonstrated no change or induction of these pathways at the same time point. IPA revealed marked baseline differences between old and young mice. Gene expression related to Cognitive Impairment, Memory Deficits and Learning worsened in old mice relative to young mice during IAV infection. Aged mice demonstrate more severe changes in gene expression related to memory loss and cognitive dysfunction by IPA.
CONCLUSIONS
These data suggest the genes and pathways related to learning and cognitive performance that were worse at baseline in old mice were further worsened by IAV infection, similar to old patients. Early events in the brain triggered by IAV infection portend downstream neurocognitive pathology in old adults.
PubMed: 38907247
DOI: 10.1186/s12979-024-00447-y -
Thrombosis Journal Jun 2024The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact, with millions...
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact, with millions of confirmed cases and deaths worldwide. While most cases are mild, a subset progresses to severe respiratory complications and death, with factors such as thromboembolism, age, and underlying health conditions increasing the risk. Vascular endothelial damage has been implicated in severe outcomes, but specific biomarkers remain elusive. This study investigated syndecan-1 (SDC-1), a marker of endothelial damage, as a potential prognostic factor for COVID-19, focusing on the Japanese population, which is known for its aging demographics and high prevalence of comorbidities.
METHODS
A multicenter retrospective study of COVID-19 patients in Fukushima Prefecture in Japan who were admitted between February 2020 and August 2021 was conducted. SDC-1 levels were measured along with other clinical and laboratory parameters. Outcomes including thrombosis, 28-day survival, and disease severity were assessed, and disease severity was categorized according to established guidelines.
RESULTS
SDC-1 levels were correlated with disease severity. Patients who died from COVID-19 had greater SDC-1 levels than survivors, and the area under the receiver operating characteristic curve (AUC) analysis suggested the potential of the SDC-1 level as a predictor of mortality (AUC 0.714). K‒M analysis also revealed a significant difference in survival based on an SDC-1 cutoff of 10.65 ng/mL.
DISCUSSION
This study suggested that SDC-1 may serve as a valuable biomarker for assessing COVID-19 severity and predicting mortality within 28 days of hospitalization, particularly in the Japanese population. However, further investigations are required to assess longitudinal changes in SDC-1 levels, validate its predictive value for long-term survival, and consider its applicability to new viral variants.
CONCLUSIONS
SDC-1 is emerging as a potential biomarker for assessing the severity and life expectancy of COVID-19 in the Japanese population, offering promise for improved risk stratification and patient management in the ongoing fight against the virus.
PubMed: 38907229
DOI: 10.1186/s12959-024-00619-2 -
BMC Geriatrics Jun 2024Increase in functional disability in aging societies is an international medical and public health issue. Masticatory function may be a potential risk factor for... (Observational Study)
Observational Study
BACKGROUND
Increase in functional disability in aging societies is an international medical and public health issue. Masticatory function may be a potential risk factor for functional disability, but the role of frailty in the association has not been clarified.
METHODS
Forty thousand five hundred sixty-two community-dwelling older adults aged 65 years and over who were insured by public health insurance as of April 2018 were followed up for a median of 3.0 years. Masticatory function was categorized as good, moderate, or poor based on a self-reported questionnaire. The development of functional disability was defined as a new certification of the need for long-term care. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs).
RESULTS
During the follow-up period, 1,397 individuals experienced functional disability. After adjusting for age, sex, comorbidities, medical history, and lifestyle behaviors, the HR for incident functional disability was significantly higher in the moderate and poor groups compared to the good group (moderate, HR 1.21 [95% CI, 1.07-1.37]; poor, HR 1.64 [95% CI, 1.03-2.62]). However, after additional adjustment for frailty-related factors-namely, underweight, regular exercise, and gait speed-the association was attenuated in both the moderate group (HR 1.06 [95% CI, 0.94-1.21]) and the poor group (HR 1.51 [95% CI, 0.94-2.41]).
CONCLUSIONS
Masticatory dysfunction was significantly associated with incident functional disability in a community-dwelling older Japanese population. Our findings suggest that masticatory dysfunction may be a surrogate of frailty rather than a direct cause of functional disability.
Topics: Humans; Aged; Male; Female; Frailty; Mastication; Aged, 80 and over; Independent Living; Frail Elderly; Disabled Persons; Disability Evaluation; Risk Factors; Geriatric Assessment; Japan
PubMed: 38907214
DOI: 10.1186/s12877-024-05131-w -
BMC Medical Informatics and Decision... Jun 2024Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex...
BACKGROUND
Patient-reported outcome (PRO) is a distinct and indispensable dimension of clinical characteristics and recent advances have made remote PRO measurement possible. Sex difference in PRO of Parkinson's disease (PD) is hardly extensively researched.
METHODS
A smartphone-based self-management platform, offering remote PRO measurement for PD patients, has been developed. A total of 1828 PD patients, including 1001 male patients and 827 female patients, were enrolled and completed their PRO submission through this platform.
RESULTS
Sex differences in PROs have been identified. The female group had a significantly lower height, weight, and body mass index (BMI) than the male group (P < 0.001). For motor symptoms, a higher proportion of patients reporting dyskinesia was observed in the female group. For non-motor symptoms, there is a higher percentage (P < 0.001) as well as severity (P = 0.016) of depression in the female group. More male patients reported hyposmia, lisp, drooling, dysuria, frequent urination, hypersexuality, impotence, daytime sleepiness, and apathy than females (P < 0.05). In contrast, more female patients reported headache, palpation, body pain, anorexia, nausea, urinal incontinence, anxiety, insomnia (P < 0.05) than males.
CONCLUSIONS
We provide evidence for sex differences in PD through the data collected from our platform. These results highlighted the importance of gender in clinical decision-making, and also support the feasibility of remote PRO measurement through a smartphone-based self-management platform in patients with PD.
Topics: Humans; Parkinson Disease; Male; Female; Smartphone; Pilot Projects; Self-Management; Cross-Sectional Studies; Middle Aged; Aged; Patient Reported Outcome Measures; Sex Factors; Mobile Applications
PubMed: 38907208
DOI: 10.1186/s12911-024-02569-1 -
BMC Public Health Jun 2024With the conflict between the promise of ageing in health and longevity and the limited availability of health resources and social support, older adults in China...
BACKGROUND
With the conflict between the promise of ageing in health and longevity and the limited availability of health resources and social support, older adults in China inevitably experience anxieties surrounding health risks. This study aims to investigate how older adults perceive the health risks that come with getting older, explore the degree to which health risks affect older adults, and advocate for active engagement in practices for managing health risks.
METHODS
Using purposive sampling, three districts of Beijing (Xicheng District, Fengtai District, and Daxing District, respectively) were selected for the research. Qualitative semi-structured and in-depth interviews were conducted with 70 community-dwelling older adults who participated in the study. Data were extracted and analyzed based on a thematic framework approach.
RESULTS
Three main themes were identified: (i) the anxieties of older adults concerning health risks in ageing; (ii) the priorities of older adults for health risk management in ageing; (iii) the expectations of older adults for health risk management in ageing. The primary health concerns among older adults included disease incidence and function decline. It was found that basic health management emerged as a critical need for older adults to mitigate health risks. Moreover, it was observed that healthcare support for older adults from familial, institutional, and governmental levels exhibited varying degrees of inadequacy.
CONCLUSIONS
The primary source of anxieties among older adults regarding health risks predominantly stems from a perceived sense of health deprivation. It is often compounded by persistent barriers to primary care of priorities in managing health risks among older adults. In addition, the expectations of older adults for health risk management emphasize the necessity for integrated care approaches. Therefore, further research should give priority to the prevention and management of health risks, aim to reduce anxieties, provide integrated care to meet the primary needs and expectations of older adults, and ultimately strive toward the overarching goal of promoting health and longevity.
Topics: Humans; Aged; Female; Male; Qualitative Research; Independent Living; Aged, 80 and over; Anxiety; Middle Aged; Aging; Interviews as Topic; China; Risk Assessment; Health Priorities
PubMed: 38907192
DOI: 10.1186/s12889-024-18878-z -
Scientific Reports Jun 2024Astrocytes play a role in healthy cognitive function and Alzheimer's disease (AD). The transcriptional factor nuclear factor-κB (NF-κB) drives astrocyte diversity, but...
Astrocytes play a role in healthy cognitive function and Alzheimer's disease (AD). The transcriptional factor nuclear factor-κB (NF-κB) drives astrocyte diversity, but the mechanisms are not fully understood. By combining studies in human brains and animal models and selectively manipulating NF-κB function in astrocytes, we deepened the understanding of the role of astrocytic NF-κB in brain health and AD. In silico analysis of bulk and cell-specific transcriptomic data revealed the association of NF-κB and astrocytes in AD. Confocal studies validated the higher level of p50 NF-κB and phosphorylated-p65 NF-κB in glial fibrillary acidic protein (GFAP)-astrocytes in AD versus non-AD subjects. In the healthy mouse brain, chronic activation of astrocytic NF-κB disturbed the proteomic milieu, causing a loss of mitochondrial-associated proteins and the rise of inflammatory-related proteins. Sustained NF-κB signaling also led to microglial reactivity, production of pro-inflammatory mediators, and buildup of senescence-related protein p16 in neurons. However, in an AD mouse model, NF-κB inhibition accelerated β-amyloid and tau accumulation. Molecular biology studies revealed that astrocytic NF-κB activation drives the increase in GFAP and inflammatory proteins and aquaporin-4, a glymphatic system protein that assists in mitigating AD. Our investigation uncovered fundamental mechanisms by which NF-κB enables astrocytes' neuroprotective and neurotoxic responses in the brain.
Topics: Astrocytes; Alzheimer Disease; Animals; Humans; Mice; Brain; NF-kappa B; Disease Models, Animal; Male; Signal Transduction; Female; Glial Fibrillary Acidic Protein; Amyloid beta-Peptides
PubMed: 38906984
DOI: 10.1038/s41598-024-65248-1 -
Scientific Reports Jun 2024Ischemic colitis (IC) and sarcopenia are associated with aging and multiple comorbidities. We aimed to investigate the prevalence and predictive role of sarcopenia in...
Ischemic colitis (IC) and sarcopenia are associated with aging and multiple comorbidities. We aimed to investigate the prevalence and predictive role of sarcopenia in patients with IC. We retrospectively analyzed 225 hospitalized patients (median age, 72 years; women, 67.1%; severe IC, 34.2%) who were diagnosed with IC between January 2007 and February 2022. Sarcopenia was defined as the skeletal muscle index at the third lumbar vertebra determined by computed tomography. It was present in 49.3% (n = 111) of the patients and was significantly associated with severe IC compared to those without sarcopenia (48.6% vs. 20.2%, P < 0.001). Sarcopenia was associated with extended hospitalization (median: 8 vs. 6 days, P < 0.001) and fasting periods (4 vs. 3 days, P = 0.004), as well as prolonged antibiotic use (9 vs. 7 days, P = 0.039). Sarcopenia was linked to a higher risk of surgery or mortality (9.0% vs. 0%, P = 0.001) and independently predicted this outcome (odds ratio [OR], 11.17; 95% confidence interval [CI], 1.24‒1467.65, P = 0.027). It was prevalent among hospitalized patients with IC, potentially indicating severe IC and a worse prognosis. This underscores the importance of meticulous monitoring, immediate medical intervention, and timely surgical consideration.
Topics: Humans; Sarcopenia; Female; Male; Aged; Prevalence; Colitis, Ischemic; Retrospective Studies; Hospitalization; Middle Aged; Aged, 80 and over; Tomography, X-Ray Computed; Prognosis; Risk Factors
PubMed: 38906968
DOI: 10.1038/s41598-024-65243-6 -
Scientific Reports Jun 2024Diabetic retinopathy (DR) is a multifactorial disease displaying vascular-associated pathologies, including vascular leakage and neovascularization, ultimately leading...
Diabetic retinopathy (DR) is a multifactorial disease displaying vascular-associated pathologies, including vascular leakage and neovascularization, ultimately leading to visual impairment. However, animal models accurately reflecting these pathologies are lacking. Vascular endothelial growth factor A (VEGF-A) is an important factor in the development of micro- and macro-vascular pathology in DR. In this study, we evaluated the feasibility of using a cumate-inducible lentivirus (LV) mediated expression of vegf-a to understand DR pathology in vitro and in vivo. Retinal pigment epithelial cells (ARPE-19) were transduced with cumate-inducible LV expressing vegf-a, with subsequent analysis of vegf-a expression and its impact on cell proliferation, viability, motility, and permeability. Cumate tolerability in adult Wistar rat eyes was assessed as an initial step towards a potential DR animal model development, by administering cumate via intravitreal injections (IVT) and evaluating consequent effects by spectral domain optical coherence tomography (SD-OCT), flash electroretinography (fERG), ophthalmic examination (OE), and immunohistochemistry. Transduction of ARPE-19 cells with cumate-inducible LV resulted in ~ 2.5-fold increase in vegf-a mRNA and ~ threefold increase in VEGF-A protein secretion. Transduced cells displayed enhanced cell proliferation, viability, permeability, and migration in tube-like structures. However, IVT cumate injections led to apparent retinal toxicity, manifesting as retinal layer abnormalities, haemorrhage, vitreous opacities, and significant reductions in a- and b-wave amplitudes, along with increased microglial activation and reactive gliosis. In summary, while cumate-inducible LV-mediated vegf-a expression is valuable for in vitro mechanistic studies in cellular drug discovery, its use is not a feasible approach to model DR in in vivo studies due to cumate-induced retinal toxicity.
Topics: Animals; Vascular Endothelial Growth Factor A; Diabetic Retinopathy; Lentivirus; Rats; Retinal Pigment Epithelium; Humans; Rats, Wistar; Cell Proliferation; Disease Models, Animal; Cell Line; Intravitreal Injections; Male; Cell Movement; Cell Survival; Tomography, Optical Coherence; Genetic Vectors
PubMed: 38906906
DOI: 10.1038/s41598-024-63590-y -
Nature Communications Jun 2024While TGF-β signaling is essential for microglial function, the cellular source of TGF-β1 ligand and its spatial regulation remains unclear in the adult CNS. Our data...
While TGF-β signaling is essential for microglial function, the cellular source of TGF-β1 ligand and its spatial regulation remains unclear in the adult CNS. Our data supports that microglia but not astrocytes or neurons are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia-Tgfb1 KO leads to the activation of microglia featuring a dyshomeostatic transcriptome that resembles disease-associated, injury-associated, and aged microglia, suggesting microglial self-produced TGF-β1 ligands are important in the adult CNS. Astrocytes in MG-Tgfb1 inducible (i)KO mice show a transcriptome profile that is closely aligned with an LPS-associated astrocyte profile. Additionally, using sparse mosaic single-cell microglia KO of TGF-β1 ligand we established an autocrine mechanism for signaling. Here we show that MG-Tgfb1 iKO mice present cognitive deficits, supporting that precise spatial regulation of TGF-β1 ligand derived from microglia is required for the maintenance of brain homeostasis and normal cognitive function in the adult brain.
Topics: Animals; Microglia; Transforming Growth Factor beta1; Homeostasis; Mice, Knockout; Mice; Autocrine Communication; Cognition; Astrocytes; Signal Transduction; Brain; Male; Transcriptome; Mice, Inbred C57BL; Neurons
PubMed: 38906887
DOI: 10.1038/s41467-024-49596-0 -
Scientific Data Jun 2024Monitoring health is key for identifying priorities in public health planning and improving healthcare services. Life expectancy has conventionally been regarded as a...
Monitoring health is key for identifying priorities in public health planning and improving healthcare services. Life expectancy has conventionally been regarded as a valuable indicator to compare the health status of different populations. However, this measure is simply the mean of the distribution of the length of life and, as such, neglects individual disparities in health outcomes. In this paper, we use life tables from the UN World Population Prospects to develop the most comprehensive dataset of lifespan inequality and polarization for 258 countries and areas for the period 1950-2021. These extensive series on lifespan distributions provide access to crucial information for researchers, practitioners, and the general public, thus contributing to a better understanding of health differences within and between nations.
Topics: Life Expectancy; Humans; Longevity; Health Status Disparities; Life Tables
PubMed: 38906878
DOI: 10.1038/s41597-024-03426-6