Notes

Optimistic suggestions amplification in excitedly pushing immune cell communities.
from clinic-based populations with relatively young patients. Greater inclusivity and deeper phenotyping in unselected cohorts could improve generalizability as well as diagnosis and development of effective treatments for all patients with dementia.
Contemporary dementia research is limited in terms of racial and geographic diversity and draws largely from clinic-based populations with relatively young patients. Greater inclusivity and deeper phenotyping in unselected cohorts could improve generalizability as well as diagnosis and development of effective treatments for all patients with dementia.
Disability and mortality are common among older adults with critical illness. Older adults who are socially isolated may be more vulnerable to adverse outcomes for various reasons, including fewer supports to access services needed for optimal recovery; however, whether social isolation is associated with post-intensive care unit (ICU) disability and mortality is not known.

To evaluate whether social isolation is associated with disability and with 1-year mortality after critical illness.

This observational cohort study included community-dwelling older adults who participated in the National Health and Aging Trends Study (NHATS) from May 2011 through November 2018. Hospitalization data were collected through 2017 and interview data through 2018. Data analysis was conducted from February 2020 through February 2021. The mortality sample included 997 ICU admissions of 1 day or longer, which represented 5 705 675 survey-weighted ICU hospitalizations. Of these, 648 ICU stays, representing 3 821 611 ICU hospical illness.
In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

We examined the prevalence of, and factors associated with, serious opioid-related adverse drug events (ORADEs) that led to an emergency department (ED) visit or hospitalization among patients with chronic gastrointestinal (GI) symptoms and disorders dually enrolled in the Department of Veterans Affairs (VA) and Medicare Part D.

In this retrospective cohort study, we used linked national patient-level data (April 1, 2011, to December 31, 2014) from the VA and Centers for Medicare and Medicaid Services to identify serious ORADEs among dually enrolled veterans with a chronic GI symptomnd disorders. Future quality improvement efforts should target this vulnerable population.
There may be a considerable burden of serious ORADEs among patients with chronic GI symptoms and disorders. Future quality improvement efforts should target this vulnerable population.Relatively little is known about visual processing during free-viewing visual search in realistic dynamic environments. Free-viewing is characterized by frequent saccades. During saccades, visual processing is thought to be suppressed, yet we know that the presaccadic visual content can modulate postsaccadic processing. To better understand these processes in a realistic setting, we study here saccades and neural responses elicited by the appearance of visual targets in a realistic virtual environment. While subjects were being driven through a 3D virtual town, they were asked to discriminate between targets that appear on the road. Using a system identification approach, we separated overlapping and correlated activity evoked by visual targets, saccades, and button presses. We found that the presence of a target enhances early occipital as well as late frontocentral saccade-related responses. The earlier potential, shortly after 125 ms post-saccade onset, was enhanced for targets that appeared in the peripheral vision as compared to the central vision, suggesting that fast peripheral processing initiated before saccade onset. The later potential, at 195 ms post-saccade onset, was strongly modulated by the visibility of the target. Together these results suggest that, during natural viewing, neural processing of the presaccadic visual stimulus continues throughout the saccade, apparently unencumbered by saccadic suppression.
In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings.

To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.

This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Rapamycin Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021.

Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cuperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.
It is unknown if there is a difference in outcome in asleep vs awake deep brain stimulation (DBS) of the subthalamic nucleus for advanced Parkinson disease.

To determine the difference in adverse effects concerning cognition, mood, and behavior between awake and asleep DBS favoring the asleep arm of the study.

This study was a single-center prospective randomized open-label blinded end point clinical trial. A total of 187 persons with Parkinson disease were referred for DBS between May 2015 to March 2019. Analysis took place from January 2016 to January 2020. The primary outcome follow-up visit was conducted 6 months after DBS.

Bilateral subthalamic nucleus DBS was performed while the patient was asleep (under general anesthesia) in 1 study arm and awake in the other study arm. Both arms of the study used a frame-based intraoperative microelectrode recording technique to refine final target placement of the DBS lead.

The primary outcome variable was the between-group difference in cognitive, mood, a to 4.2]). Asleep surgery was experienced as less burdensome by patients and was 26 minutes shorter than awake surgery.

There was no difference in the primary outcome of asleep vs awake DBS. Future large randomized clinical trials should examine some of the newer asleep based DBS technologies because this study was limited to frame-based microelectrode-guided procedures.

trialregister.nl Identifier NTR5809.
trialregister.nl Identifier NTR5809.Blood transcriptomics have revealed major characteristics of the immune response in active TB, but the signature early after infection is unknown. In a unique clinically and temporally well-defined cohort of household contacts of active TB patients that progressed to TB, we define minimal changes in gene expression in incipient TB increasing in subclinical and clinical TB. While increasing with time, changes in gene expression were highest at 30 d before diagnosis, with heterogeneity in the response in household TB contacts and in a published cohort of TB progressors as they progressed to TB, at a bulk cohort level and in individual progressors. Blood signatures from patients before and during anti-TB treatment robustly monitored the treatment response distinguishing early and late responders. Blood transcriptomics thus reveal the evolution and resolution of the immune response in TB, which may help in clinical management of the disease.In this issue of JEM, Gschwend et al. (2021. J. Exp. Med.https//doi.org/10.1084/jem.20210745) reveal the indispensable role of alveolar epithelial cells type 2 in controlling the density of alveolar macrophages. This study highlights the intricate crosstalk that lung stroma and macrophages undergo to maintain homeostasis.
The purpose of this study was to observe changes of the retinal pigment epithelium (RPE) on the transition from dysmorphia to atrophy in age-related macular degeneration (AMD) by fluorescence lifetime imaging ophthalmoscopy (FLIO).

Multimodal imaging including color fundus photography (CFP), optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, and FLIO was performed in 40 eyes of 37 patients with intermediate AMD and no evidence for geographic atrophy or macular neovascularization (mean age = 74.2 ± 7.0 years). Twenty-three eyes were followed for 28.3 ± 18.3 months. Seven eyes had a second follow-up after 46.6 ± 9.0 months. Thickened RPE on OCT, hyperpigmentation on CFP, hyper-reflective foci (HRF) on OCT, attributed to single or clustered intraretinal RPE, were identified. Fluorescence lifetimes in two spectral channels (short-wavelength spectral channel [SSC] = 500-560 nm, long-wavelength spectral channel [LSC] = 560-720 nm) as well as emission spectrum intensity ratio (ESIR) of thbserved by FLIO. Thus, FLIO might provide early biomarkers for AMD progression and contribute to our understanding of RPE pathology.Severe liver disease is one of the most common causes of death globally. Currently, whole organ transplantation is the only therapeutic method for end-stage liver disease treatment, however, the need for donor organs far outweighs demand. Recently liver tissue engineering is starting to show promise for alleviating part of this problem. Electrospinning is a well-known method to fabricate a nanofibre scaffold which mimics the natural extracellular matrix that can support cell growth. This study aims to investigate liver cell responses to topographical features on electrospun fibres. Scaffolds with large surface depression (2 μm) (LSD), small surface depression (0.37 μm) (SSD), and no surface depression (NSD) were fabricated by using a solvent-nonsolvent system. A liver cell line (HepG2) was seeded onto the scaffolds for up to 14 days. The SSD group exhibited higher levels of cell viability and DNA content compared to the other groups. Additionally, the scaffolds promoted gene expression of albumin, with all cases having similar levels, while the cell growth rate was altered. Furthermore, the scaffold with depressions showed 0.8 MPa higher ultimate tensile strength compared to the other groups. These results suggest that small depressions might be preferred by HepG2 cells over smooth and large depression fibres and highlight the potential for tailoring liver cell responses.We report herein the first example of the N3 radical-mediated azidosulfonylation of alkynes, affording the β-azidovinyl sulfone products with a broad substrate scope, excellent functional group compatibility, and high yield. DFT calculations suggest that the mechanism of the reaction proceeds through an unprecedented sequential N3 radical addition and sulfonyl radical coupling pathway.
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