Health-related quality of life (HRQOL) of caregivers of children with disabilities (CWD) is important for both children’s rehabilitation and caregivers’ life, but the corresponding attention is far from enough in mainland China. Thus, we investigated the HRQOL of 170 caregivers and related factors in Shanghai. The 12-item Short Form Health Survey (SF-12) was used to measure HRQOL. The potential factors were collected, including child characteristics, caregiver characteristics, and environmental factors. Univariate analysis and multiple linear regression were performed to identify the key factors that could be intervened. Compared with the general population, caregivers of CWD had a slightly higher score on the physical component summary (PCS, 52.57 ± 8.41), but the score of mental component summary (MCS, 31.58 ± 7.72) was extremely low. Caregiver’s illness condition, family size, and household income were significant factors of physical HRQOL. Caregivers with illness and caregivers living in an extended family were associated with higher mental HRQOL. Whereas these two factors had opposite effects on physical HRQOL. This finding indicated poor mental HRQOL among caregivers of CWD in Shanghai and thus requiring urgent attention and intervention. Improving physical fitness, maintaining family integration, and providing financial support should be considered when developing intervention for this population.
by
Steve CN Hui;
Mark Mikkelsen;
Helge J Zollner;
Vishwadeep Ahluwalia;
Sarael Alcauter;
Laima Baltusis;
Deborah A Barany;
Laura R Barlow;
Robert Becker;
Jeffrey Berman;
Adam Berrington;
Pallab K Bhattacharyya;
Jakob Udby Blicher;
Wolfgang Bogner;
Mark S Brown;
Vince D Calhoun;
Ryan Castillo;
Kim M Cecil;
Yeo B Choi;
Winnie CW Chu;
William T Clarke;
Alexander R Craven;
Koen Cuypers;
Michael Dacko;
Camilo de la Fuente-Sandoval;
Patricia Desmond;
Aleksandra Domagalik;
Julien Dumont;
Niall W Duncan;
Ulrike Dydak;
Katherine Dyke;
David A Edmondson;
Gabriele Ende;
Lars Ersland;
John C Evans;
Alan SR Fermin;
Antonio Ferretti;
Ariane Fillmer;
Tao Gong;
Ian Greenhouse;
James T Grist;
Meng Gu;
Ashley D Harris;
Katarzyna Hatz;
Stefanie Heba;
Eva Heckova;
John P Hegarty;
Kristin-Freiderike Heise;
Shiori Honda;
Aaron Jacobson;
Jacobus FA Jansen;
Chrsitopher W Jenkins;
Stephen J Johnston;
Christoph Juchem;
Alayar Kangarlu;
Adam B Kerr;
Karl Landheer;
Thomas Lange;
Phil Lee;
Swati Rane Levendovszky;
Catherine Limperopoulos;
Feng Liu;
William Lloyd;
David J Lythgoe;
Maro G Machizawa;
Erin L MacMillan;
Richard J Maddock;
Andrei Manzhurtsev;
María L Martinez-Gudino;
Jack J Miller;
Heline Mirzakhanian;
Marta Moreno-Ortega;
Paul G Mullins;
Shinichiro Nakajima;
Jamie Near;
Ralph Noeske;
Wibeke Nordhoy;
Georg Oeltzschner;
Raul Osorio-Duran;
Maria CG Otaduy;
Erick H Pasaye;
Ronald Peeters;
Scott J Peltier;
Ulrich Pilatus;
Nenad Polomac;
Eric C Porges;
Subechhya Pradhan;
James Joseph Prisciandaro;
Nicolaas A Puts;
Caroline D Rae;
Francisco Reyes-Madrigal;
Timothy PL Roberts;
Caroline E Robertson;
Jens T Rosenberg;
Diana-Georgiana Rotaru;
Ruth L O'Gorman Tuura Tuura;
Muhammad G Saleh;
Kristian Sandberg;
Ryan Sangill;
Keith Schembri;
Anouk Schrantee;
Natalia A Semenova;
Debra Singel;
Rouslan Sitnikov;
Jolinda Smith;
Yulu Song;
Craig Stark;
Diederick Stoffers;
Stephan P Swinnen;
Rongwen Tain;
Costin Tanase;
Sofie Tapper;
Martin Tegenthoff;
Thomas Thiel;
Marc Thioux;
Peter Truong;
Pim van Dijk;
Nolan Vella;
Rishma Vidyasagar;
Andrej Vovk;
Guangbin Wang;
Lars T Westlye;
Timothy K Wilbur;
William R Willoughby;
Martin Wilson;
Hans-Jörg Wittsack;
Adam J Woods;
Yen-Chien Wu;
Junqian Xu;
Maria Yanez Lopez;
David KW Yeung;
Qun Zhao;
Xiaopeng Zhou;
Gasper Zupan;
Richard AE Edden
Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. Method: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). Results: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.
Experts recommend reporting environmental exposure results back to research participants and communities, yet environmental health researchers need further guidance to improve the practice of reporting back. We present the results of a workshop developed to identify pertinent issues and areas for action in reporting back environmental health research results. Thirty-five attendees participated, brainstorming responses to the prompt: “What are some specific issues that are relevant to reporting back research results to individuals or the larger community?”, and then grouping responses by similarity and rating their importance. Based on a combined theoretical foundation of grounded theory and qualitative content analysis, we used concept mapping to develop a collective understanding of the issues. Visual maps of the participants’ responses were created using nonmetric multidimensional scaling and hierarchical cluster analysis. The resulting concept map provided a spatial depiction of five issue areas: Effective Communication Strategies, Community Knowledge and Concerns, Uncertainty, Empowering Action, and Institutional Review and Oversight (listed from highest to lowest rating). Through these efforts, we disentangled the complex issues affecting how and whether environmental health research results are reported back to participants and communities, by identifying five distinct themes to guide recommendations and action. Engaging community partners in the process of reporting back emerged as a unifying global theme, which could improve how researchers report back research results by understanding community context to develop effective communication methods and address uncertainty, the ability to act, and institutional concerns about beneficence and justice.
Triple negative breast cancer (TNBC) is a significant clinical problem to which immunotherapeutic strategies have been applied with limited success. Using the syngeneic E0771 TNBC mouse model, this work explores the potential for anti-tumor CD8+ T cell immunity to be primed extratumorally in lymphoid tissues and therapeutically leveraged. CD8+ T cell viability and responses within the tumor microenvironment (TME) were found to be severely impaired, effects coincident with local immunosuppression that is recapitulated in lymphoid tissues in late stage disease. Prior to onset of a locally suppressed immune microenvironment, however, CD8+ T cell priming within lymph nodes (LN) that depended on tumor lymphatic drainage remained intact. These results demonstrate tumor-draining LNs (TdLN) to be lymphoid tissue niches that support the survival and antigenic priming of CD8+ T lymphocytes against lymph-draining antigen. The therapeutic effects of and CD8+ T cells response to immune checkpoint blockade were furthermore improved when directed to LNs within the tumor-draining lymphatic basin. TdLNs therefore represent a unique potential tumor immunity reservoir in TNBC for which strategies may be developed to improve the effects of ICB immunotherapy.
Precís
Here, we show that tumor-draining lymph nodes are niches that support the survival and antigenic priming of CD8+ T cells and show an easily implementable method of leveraging lymph nodes within the tumor basin to improve breast cancer immunotherapy outcomes.
Traumatic brain injury (TBI) remains a major cause of disability among young adults in both civilian and military settings contributing to a high burden on healthcare systems (Badhiwala et al., 2019). Sequel of TBI, even mild injuries, include motor and sensory dysfunction, neurocognitive decline, neuropsychiatric complications, as well as increased risk of neurodegenerative and neurovascular events such as Alzheimer’s disease and stroke (Breunig et al., 2013; Burke et al., 2013; Li et al., 2017). Despite the acute nature of the insult in TBI, pathological changes in the traumatized brain are better recognized as a chronic rather than an acute neurological disease, a phenomenon that remains under-investigated. Robust clinical data support the role of neuroinflammation in propagating neurodegenerative changes following TBI with a pivotal role of the complement system as an early trigger and chronic propagator of this response (Alawieh et al., 2018, 2021; Mallah et al., 2021). Hereby, we discuss how the role of complement pathways in different phases of injury after TBI was investigated using clinically relevant targeted complement inhibitors (Alawieh and Tomlinson, 2016; Alawieh et al., 2018, 2021; Mallah et al., 2021).
Background
Dolutegravir (DTG) monotherapy results in virologic failure and the development of DTG resistance. Here, we evaluated virologic outcomes of patients switched to DTG functional mono- or dual therapy with a non-cytosine nucleoside analog (NA).
Methods
This retrospective, single center study included treatment-experienced patients switched to regimens containing ≥ 2 antiretrovirals between 8/13/13–11/22/14 who were later found to be on DTG functional mono- or dual therapy with a non-cytosine NA based on historical genotypes. Eligible patients were either suppressed or viremic at baseline and had ≥ 2 HIV-1 RNA measurements at least 4 weeks apart following switch. Demographics, laboratory values and clinical parameters were extracted from the charts of all eligible patients during study treatment until 12/31/2018 and were summarized using descriptive statistics. The primary endpoint was the proportion of patients with HIV-1 RNA < 50 copies/mL following switch.
Results
Of 70 patients switched to DTG functional mono- or dual therapy, 39 were eligible; 19 (49%) were on DTG functional monotherapy and 20 (51%) were on DTG functional dual therapy with a non-cytosine NA. Historical genotypes indicated that all had an M184V/I, and 23 (59%) had an M184V/I and ≥ 1 additional NA mutation. The median duration of follow-up on study treatment was 50 weeks (range 12–244). Following switch, 32/39 (82%) patients achieved or maintained an HIV-1 RNA < 50 copies/mL and 7 (18%) had persistent HIV-1 RNA ≥ 50 copies/mL. Five viremic patients were found to be on functional dual therapy with DTG plus a non-cytosine NA and 2 were on DTG functional monotherapy. Five of these patients had post-switch genotypes ordered as a part of routine clinical care and there was no evidence of treatment-emergent resistance. Five were switched to a different DTG-containing regimen and achieved HIV-1 RNA < 50 copies/mL, 1 was switched to a non-DTG containing regimen and achieved HIV-1 RNA < 50 copies/mL and 1 was lost-to-follow up at week 36.
Conclusions
In this real-world cohort, the majority of whom had virus with the M184V/I and ≥ 1 additional NA mutation, switching to DTG functional mono-or dual therapy with a non-cytosine NA resulted in persistent HIV-1 RNA ≥ 50 copies/mL in 18%. None with post-switch genotypes developed treatment-emergent resistance.
Pseudomonas aeruginosa is a prevalent pathogen in cystic fibrosis (CF) lungs which displays strong resistance to various antibiotic classes, contributing to antimicrobial resistance (AMR). P aeruginosa populations in CF lungs exhibit considerable genetic and phenotypic diversity, raising questions about their susceptibility to non-traditional antimicrobials, such as bacteriocins. R-pyocins, bacteriocins produced by P. aeruginosa, are highly potent, non-replicating phage tail-like protein complexes with a narrow killing spectrum. The diversity of P. aeruginosa variants within CF lung infections may lead to varying susceptibility to R-pyocins due to changes in the lipopolysaccharide (LPS) structure, which acts as the R-pyocin receptor. However, the extent of susceptibility to the five known R-pyocin subtypes (R1-R5) remains unknown, especially considering the diverse P. aeruginosa populations in CF lungs. Additionally, the connection between LPS phenotype and R-pyocin susceptibility is not well understood. We tested 139 P. aeruginosa variants from 17 sputum samples of seven CF patients for R2-pyocin susceptibility and analyzed their LPS phenotypes. Our findings revealed that approximately 83% of sputum samples contained diverse P. aeruginosa populations without R2-pyocin resistant variants, while all samples had some susceptible variants. Moreover, there was no clear correlation between LPS phenotypes and R-pyocin susceptibility. The absence of a clear correlation between LPS phenotypes and R-pyocin susceptibility suggests that LPS packing density may significantly influence R-pyocin susceptibility among CF variants. Our research supports the potential use of R-pyocins as therapeutic agents, as numerous infectious CF variants appear to be susceptible to R2-pyocins, even within diverse P. aeruginosa populations.
One of the basic and unresolved puzzles in the chemistry of vision concerns the natural selection of 11-cis-retinal as the light-sensing chromophore in visual pigments. A detailed computational examination of the structure, stability, energetics and spectroscopy of 7-cis, 9-cis, 11-cis and 13-cis-retinal isomers in vertebrate (bovine, monkey) and invertebrate (squid) visual pigments is carried out using hybrid quantum mechanics/molecular mechanics (QM/MM) method. It is shown that the electrostatic interaction between retinal and opsin dominates the natural selection of 11-cis-retinal over other cis-isomers in the dark-state. In all the pigments, 9-cis-retinal is found to be only slightly higher in energy than 11-cis-retinal, which provides strong evidence for the presence of 9-cis-rhodopsin in nature. 7-cis-retinal is suggested to be an “upside-down” version of 11-trans-isomer because structural rearrangements observed for 7-cis-squid rhodopsin is found to be very similar to that of squid bathorhodopsin. The progressive red shift in the calculated absorption wavelength (λmax) of 7-cis- (431 nm), 9-cis- (456 nm), 11-cis- (490 nm) and 13-cis-retinal isomers (508 nm) are attributed to the decrease in bond length alternation of the retinal.
Background: In the United States, racial and ethnic minorities are disproportionately affected by COVID-19, with persistent social and structural factors contributing to these disparities. At the intersection of race/ethnicity and gender, women of color may be disadvantaged in terms of COVID-19 outcomes due to their role as essential workers, their higher prevalence of pre-existing conditions, their increased stress and anxiety from the loss of wages and caregiving, and domestic violence. Objective: The purpose of this study is to examine racial and ethnic differences in the prevalence of COVID-19 outcomes, stressors, fear, and prevention behaviors among adult women residing in the United States. Methods: Between May and June 2020, women were recruited into the Capturing Women’s Experiences in Outbreak and Pandemic Environments (COPE) Study, a web-based cross-sectional study, using advertisements on Facebook; 491 eligible women completed a self-administered internet-based cross-sectional survey. Descriptive statistics were used to examine racial and ethnic differences (White; Asian; Native Hawaiian or other Pacific Islander; Black; Hispanic, Latina, or Spanish Origin; American Indian or Alaskan Native; multiracial or some other race, ethnicity, or origin) on COVID-19 outcomes, stressors, fear, and prevention behaviors. Results: Among our sample of women, 16% (73/470) reported COVID-19 symptoms, 22% (18/82) were concerned about possible exposure from the people they knew who tested positive for COVID-19, and 51.4% (227/442) knew where to get tested; yet, only 5.8% (27/469) had been tested. Racial/ethnic differences were observed, with racial/ethnic minority women being less likely to know where to get tested. Significant differences in race/ethnicity were observed for select stressors (food insecurity, not enough money, homeschooling children, unable to have a doctor or telemedicine appointment) and prevention behaviors (handwashing with soap, self-isolation if sick, public glove use, not leaving home for any activities). Although no racial/ethnic differences emerged from the Fear of COVID-19 Scale, significant racial/ethnic differences were observed for some of the individual scale items (eg, being afraid of getting COVID-19, sleep loss, and heart racing due to worrying about COVID-19). Conclusions: The low prevalence of COVID-19 testing and knowledge of where to get tested indicate a critical need to expand testing for women in the United States, particularly among racial/ethnic minority women. Although the overall prevalence of engagement in prevention behaviors was high, targeted education and promotion of prevention activities are warranted in communities of color, particularly with consideration for stressors and adverse mental health.