A growing number of cancer patients use complementary and alternative therapies during and after conventional cancer treatment. Patients are often reluctant to discuss these therapies with their ...oncologist, and oncologists may have limited knowledge and confidence on how to advise patients on the appropriate use. Integrative oncology is a patient-centered, evidence-informed field that utilizes mind-body practices, lifestyle modifications and/or natural products interwoven with conventional cancer treatment. It prioritizes safety and best available evidence to offer appropriate interventions alongside conventional care. There are few opportunities for oncologists to learn about integrative oncology. In this commentary, we highlight the Integrative Oncology Scholars (IOS) program as a means to increase competency in this growing field. We provide an overview of several integrative oncology modalities that are taught through this program, including lifestyle modifications, physical activity, and mind-body interventions. We conclude that as more evidence is generated in this field, it will be essential that oncology healthcare providers are aware of the prevalent use of these modalities by their patients and cancer centers include Integrative Oncology trained physicians and other healthcare professionals in their team to discuss and recommend evidence-based integrative oncology therapies alongside conventional cancer treatments to their patients.
Objective To determine the relative sensitivities of embryos from different strains of mice to in vitro stress. Design Laboratory experiment with embryos from different mouse strains. Setting ...University hospital–based fertility clinic. Animal(s) Mice. Intervention(s) Fresh one-cell embryos from outbred (CF1), inbred (FVB), F1 hybrid (B6/CBA), and cryopreserved F2 hybrid embryos (bcl/B6 × B6/bcl) compared in a mouse embryo assay (MEA) using six doses of each of three in vitro stressors: cumene hydroperoxide in mineral oil, Triton X-100 (TX-100) in media, and hyperosmolality. Main Outcome Measure(s) Blastocyst rate at 96 hours. Result(s) All studies were conducted in triplicate; data were analyzed with chi-square analysis based on fitting a logistic regression model. Both cumene hydroperoxide and Triton X-100 affected blastocyst formation in the outbred strain at concentrations that were less than half of the concentration that affected the other strains. The total number of cells was affected by the treatments in all strains. Conclusion(s) Outbred CF1 embryos are genetically diverse and more sensitive to toxins than either inbred or hybrid mouse embryos. Outbred embryos provide an additional tool for effective quality-control testing.
In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum
Negarnaviricota
was amended and emended. At the genus ...rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of
Negarnaviricota
as now accepted by the ICTV.
2H−TaS2 undergoes a charge density wave (CDW) transition at TCDW∼75 K, however key questions regarding the onset of CDW order remain under debate. In this study, we explore the CDW transition through ...a combination of temperature and excitation-dependent Raman spectroscopy, angle resolved photoemission spectroscopy (ARPES), and density functional theory (DFT). Below TCDW we identify two CDW amplitude modes that redshift and broaden with increasing temperature and one zone-folded mode that disappears above TCDW. Above TCDW, we observe a strong two-phonon mode that softens substantially upon cooling, which suggests the presence of substantial lattice distortions at temperatures as high as 250 K. This correlates with the ARPES observation of the persistence of a CDW energy gap above TCDW and finite-temperature DFT calculations of the phonon band structure that indicate an instability occurring well above the CDW transition temperature. DFT also provides the atomic displacements of the CDW amplitude modes and reproduces their temperature dependence. From these observations we suggest that short range CDW order exists well above TCDW, which poses new questions regarding the interplay between electronic structure and vibrational modes in layered CDW materials.
Alcohol misuse is common in many societies worldwide and is associated with extensive morbidity and mortality, often leading to alcohol use disorders (AUD) and alcohol-related end-organ damage. The ...underlying mechanisms contributing to the development of AUD are largely unknown; however, growing evidence suggests that alcohol consumption is strongly associated with alterations in DNA methylation. Identification of alcohol-associated methylomic variation might provide novel insights into pathophysiology and novel treatment targets for AUD. Here we performed the largest single-cohort epigenome-wide association study (EWAS) of alcohol consumption to date (N = 8161) and cross-validated findings in AUD populations with relevant endophenotypes, as well as alcohol-related animal models. Results showed 2504 CpGs significantly associated with alcohol consumption (Bonferroni p value < 6.8 × 10
) with the five leading probes located in SLC7A11 (p = 7.75 × 10
), JDP2 (p = 1.44 × 10
), GAS5 (p = 2.71 × 10
), TRA2B (p = 3.54 × 10
), and SLC43A1 (p = 1.18 × 10
). Genes annotated to associated CpG sites are implicated in liver and brain function, the cellular response to alcohol and alcohol-associated diseases, including hypertension and Alzheimer's disease. Two-sample Mendelian randomization confirmed the causal relationship of consumption on AUD risk (inverse variance weighted (IVW) p = 5.37 × 10
). A methylation-based predictor of alcohol consumption was able to discriminate AUD cases in two independent cohorts (p = 6.32 × 10
and p = 5.41 × 10
). The top EWAS probe cg06690548, located in the cystine/glutamate transporter SLC7A11, was replicated in an independent cohort of AUD and control participants (N = 615) and showed strong hypomethylation in AUD (p < 10
). Decreased CpG methylation at this probe was consistently associated with clinical measures including increased heavy drinking days (p < 10
), increased liver function enzymes (GGT (p = 1.03 × 10
), ALT (p = 1.29 × 10
), and AST (p = 1.97 × 10
)) in individuals with AUD. Postmortem brain analyses documented increased SLC7A11 expression in the frontal cortex of individuals with AUD and animal models showed marked increased expression in liver, suggesting a mechanism by which alcohol leads to hypomethylation-induced overexpression of SLC7A11. Taken together, our EWAS discovery sample and subsequent validation of the top probe in AUD suggest a strong role of abnormal glutamate signaling mediated by methylomic variation in SLC7A11. Our data are intriguing given the prominent role of glutamate signaling in brain and liver and might provide an important target for therapeutic intervention.
Identification of specific antibodies in patient plasma is an essential part of many diagnostic procedures and is critical for safe blood transfusion. Current techniques require laboratory ...infrastructure and long turnaround times which limits access to those nearby tertiary healthcare providers. Addressing this challenge, a novel and rapid paper-based antibody test is reported. We validate antibody detection with reverse blood typing using IgM antibodies and then generalise the validity by adapting to detect SARS CoV-2 (COVID-19) antibodies in patient serum samples. Reagent red blood cells (RBC) are first combined with the patient plasma containing the screened antibody and a droplet of the mixture is then deposited onto paper. The light intensity profile is analyzed to identify test results, which can be detected by eye and/or with image processing to allow full automation. The efficacy of this test to perform reverse blood typing is demonstrated and the performance and sensitivity of this test using different paper types and RBC reagents was investigated using clinical samples. As an example of the flexibility of this approach, we labeled the RBC reagent with an antibody-peptide conjugate to detect SARS CoV-2 (COVID-19) antibodies in patient serum samples. This concept could be generalized to any agglutination-based antibody diagnostics with blood plasma.
Identification of specific antibodies in patient plasma is an essential part of many diagnostic procedures and is critical for safe blood transfusion.
Abstract
The primary targets for HIV infection are CD4 T cells, however macrophages (MΦ) are also infected and persist despite antiretroviral therapy, suggesting evasion of immune responses. Our ...previous work shows that while HIV-infected MΦ are recognized by cytolytic CD8 T lymphocytes (CTL), killing is inefficient and causes hypersecretion of CTL cytokines that propagate inflammation, emphasizing the need for rapid killing to limit inflammation. Thus, we hypothesized that NK cells would be able to rapidly kill HIV-infected MΦ while limiting inflammation. To test this hypothesis, innate interactions between NK cells and HIV-infected MΦ or CD4 T cells were assessed via flow cytometry-based recognition/killing assays. To characterize the potential for antibody-dependent cellular cytotoxicity (ADCC), HIV envelope expression on MΦ was characterized by flow cytometry and HIV-specific CAR T cells. Finally, ADCC responses against infected CD4 T cells and MΦ were assessed via flow cytometry. Despite similar levels of recognition of HIV-infected CD4 T cells and MΦ (degranulation and TNF-α production), NK responses to MΦ were significantly skewed towards non-cytolytic, cytokine production (p<0.0001), which was associated with poor elimination (p<0.0001). Surface HIV envelope is equally accessible on both MΦ and CD4 T cells, as determined by CAR T cell recognition. While ADCC enhanced NK cell responses to both cell types, responses to MΦ were significantly lower compared to that of CD4 T cells (p<0.05). Together, these data suggest HIV-infected MΦ employ a unique mechanism to evade cytolytic NK cell recognition while preserving inflammatory cytokine responses, emphasizing the need to develop alternative strategies to eliminate infected MΦ.
DNA methylation (DNAm) is associated with time-varying environmental factors that contribute to major depressive disorder (MDD) risk. We sought to test whether DNAm signatures of lifestyle and ...biochemical factors were associated with MDD to reveal dynamic biomarkers of MDD risk that may be amenable to lifestyle interventions.
Here, we calculated methylation scores (MS) at multiple p-value thresholds for lifestyle (BMI, smoking, alcohol consumption, and educational attainment) and biochemical (high-density lipoprotein (HDL) and total cholesterol) factors in Generation Scotland (GS) (N=9,502) and in a replication cohort (ALSPACadults, N=565), using CpG sites reported in previous well-powered methylome-wide association studies. We also compared their predictive accuracy for MDD to a MDD MS in an independent GS sub-sample (N=4,432).
Each trait MS was significantly associated with its corresponding phenotype in GS (βrange=0.089–1.457) and in ALSPAC (βrange=0.078–2.533). Each MS was also significantly associated with MDD before and after adjustment for its corresponding phenotype in GS (βrange=0.053–0.145). After accounting for relevant lifestyle factors, MS for educational attainment (β=0.094) and alcohol consumption (MSp-value<0.01–0.5; βrange=-0.069–0.083) remained significantly associated with MDD in GS. Smoking (AUC=0.569) and educational attainment (AUC=0.585) MSs could discriminate MDD from controls better than the MDD MS (AUC=0.553) in the independent GS sub-sample. Analyses implicating MDD did not replicate across ALSPAC, although the direction of effect was consistent for all traits when adjusting for the MS corresponding phenotypes.
We showed that lifestyle and biochemical MS were associated with MDD before and after adjustment for their corresponding phenotypes (pnominal<0.05), but not when smoking, alcohol consumption, and BMI were also included as covariates. MDD results did not replicate in the smaller, female-only independent ALSPAC cohort (NALSPAC=565; NGS=9,502), potentially due to demographic differences or low statistical power, but effect sizes were consistent with the direction reported in GS. DNAm scores for modifiable MDD risk factors may contribute to disease vulnerability and, in some cases, explain additional variance to their observed phenotypes.
Wellcome Trust.
The Relatives Education And Coping Toolkit (REACT) is an online supported self-management toolkit for relatives of people with psychosis or bipolar designed to improve access to NICE recommended ...information and emotional support.
Our aim was to determine clinical and cost-effectiveness of REACT including a Resource Directory (RD), versus RD-only.
A primarily online, observer-blind randomised controlled trial comparing REACT (including RD) with RD only (registration ISRCTN72019945). Participants were UK relatives aged > = 16, with high distress (assessed using the GHQ-28), and actively help-seeking, individually randomised, and assessed online. Primary outcome was relatives' distress (GHQ-28) at 24 weeks. Secondary outcomes were wellbeing, support, costs and user feedback.
We recruited 800 relatives (REACT = 399; RD only = 401) with high distress at baseline (GHQ-28 REACT mean 40.3, SD 14.6; RD only mean 40.0, SD 14.0). Median time spent online on REACT was 50.8 min (IQR 12.4-172.1) versus 0.5 min (IQR 0-1.6) on RD only. Retention to primary follow-up (24 weeks) was 75% (REACT n = 292 (73.2%); RD-only n = 307 (76.6%)). Distress decreased in both groups by 24 weeks, with no significant difference between the two groups (- 1.39, 95% CI -3.60, 0.83, p = 0.22). Estimated cost of delivering REACT was £62.27 per person and users reported finding it safe, acceptable and convenient. There were no adverse events or reported side effects.
REACT is an inexpensive, acceptable, and safe way to deliver NICE-recommended support for relatives. However, for highly distressed relatives it is no more effective in reducing distress (GHQ-28) than a comprehensive online resource directory.
ISRCTN72019945 prospectively registered 19/11/2015.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Relatives caring for people with severe mental health problems find information and emotional support hard to access. Online support for self-management offers a potential solution.
The objective was ...to determine the clinical effectiveness and cost-effectiveness of an online supported self-management tool for relatives: the Relatives' Education And Coping Toolkit (REACT).
This was a primarily online (UK), single-blind, randomised controlled trial, comparing REACT plus a resource directory and treatment as usual with the resource directory and treatment as usual only, by measuring user distress and other well-being measures at baseline and at 12 and 24 weeks.
A total of 800 relatives of people with severe mental health problems across the UK took part; relatives who were aged ≥ 16 years, were experiencing high levels of distress, had access to the internet and were actively seeking help were recruited.
REACT comprised 12 psychoeducation modules, peer support through a group forum, confidential messaging and a comprehensive resource directory of national support. Trained relatives moderated the forum and responded to messages.
The main outcome was the level of participants' distress, as measured by the General Health Questionnaire-28 items.
Various online and offline strategies, including social media, directed potential participants to the website. Participants were randomised to one of two arms: REACT plus the resource directory (
= 399) or the resource directory only (
= 401). Retention at 24 weeks was 75% (REACT arm,
= 292; resource directory-only arm,
= 307). The mean scores for the General Health Questionnaire-28 items reduced substantially across both arms over 24 weeks, from 40.2 (standard deviation 14.3) to 30.5 (standard deviation 15.6), with no significant difference between arms (mean difference -1.39, 95% confidence interval -3.60 to 0.83;
= 0.22). At 12 weeks, the General Health Questionnaire-28 items scores were lower in the REACT arm than in the resource directory-only arm (-2.08, 95% confidence interval -4.14 to -0.03;
= 0.027), but this finding is likely to be of limited clinical significance. Accounting for missing data, which were associated with higher distress in the REACT arm (0.33, 95% confidence interval -0.27 to 0.93;
= 0.279), in a longitudinal model, there was no significant difference between arms over 24 weeks (-0.56, 95% confidence interval -2.34 to 1.22;
= 0.51). REACT cost £142.95 per participant to design and deliver (£62.27 for delivery only), compared with £0.84 for the resource directory only. A health economic analysis of NHS, health and Personal Social Services outcomes found that REACT has higher costs (£286.77), slightly better General Health Questionnaire-28 items scores (incremental General Health Questionnaire-28 items score adjusted for baseline, age and gender: -1.152, 95% confidence interval -3.370 to 1.065) and slightly lower quality-adjusted life-year gains than the resource directory only; none of these differences was statistically significant. The median time spent online was 50.8 minutes (interquartile range 12.4-172.1 minutes) for REACT, with no significant association with outcome. Participants reported finding REACT a safe, confidential environment (96%) and reported feeling supported by the forum (89%) and the REACT supporters (86%). No serious adverse events were reported.
The sample comprised predominantly white British females, 25% of participants were lost to follow-up and dropout in the REACT arm was not random.
An online self-management support toolkit with a moderated group forum is acceptable to relatives and, compared with face-to-face programmes, offers inexpensive, safe delivery of National Institute for Health and Care Excellence-recommended support to engage relatives as peers in care delivery. However, currently, REACT plus the resource directory is no more effective at reducing relatives' distress than the resource directory only.
Further research in improving the effectiveness of online carer support interventions is required.
Current Controlled Trials ISRCTN72019945.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 24, No. 32. See the NIHR Journals Library website for further project information.
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