Single-molecule long-read methylation profiling reveals regional DNA methylation regulated by Elongator Complex Subunit 2 in Arabidopsis roots experiencing spaceflight.

BACKGROUND: The Advanced Plant Experiment-04 - Epigenetic Expression (APEX-04-EpEx) experiment onboard the International Space Station examined the spaceflight-altered cytosine methylation in two genetic lines of Arabidopsis thaliana, wild-type Col-0 and the mutant elp2-5, which is deficient in an epigenetic regulator Elongator Complex Subunit 2 (ELP2). Whole-genome bisulfite sequencing (WGBS) revealed distinct spaceflight associated methylation differences, presenting the need to explore specific space-altered methylation at single-molecule resolution to associate specific changes over large regions of spaceflight related genes. To date, tools of multiplexed targeted DNA methylation sequencing remain limited for plant genomes. RESULTS: To provide methylation data at single-molecule resolution, Flap-enabled next-generation capture (FENGC), a novel targeted multiplexed DNA capture and enrichment technique allowing cleavage at any specified sites, was applied to survey spaceflight-altered DNA methylation in genic regions of interest. The FENGC capture panel contained 108 targets ranging from 509 to 704 nt within the promoter or gene body regions of gene targets derived from spaceflight whole-genome data sets. In addition to genes with significant changes in expression and average methylation levels between spaceflight and ground control, targets with space-altered distributions of the proportion of methylated cytosines per molecule were identified. Moreover, trends of co-methylation of different cytosine contexts were exhibited in the same DNA molecules. We further identified significant DNA methylation changes in three previously biological process-unknown genes, and loss-of-function mutants of two of these genes (named as EMO1 and EMO2 for ELP2-regulated Methylation in Orbit 1 and 2) showed enhanced root growth rate. CONCLUSIONS: FENGC simplifies and reduces the cost of multiplexed, targeted, single-molecule profiling of methylation in plants, providing additional resolution along each DNA molecule that is not seen in population-based short-read data such as WGBS. This case study has revealed spaceflight-altered regional modification of cytosine methylation occurring within single DNA molecules of cell subpopulations, which were not identified by WGBS. The single-molecule survey by FENGC can lead to identification of novel functional genes. The newly identified EMO1 and EMO2 are root growth regulators which may be epigenetically involved in plant adaptation to spaceflight.

Spaceflight impacts xyloglucan oligosaccharide abundance in Arabidopsis thaliana root cell walls.

Over the course of more than a decade, space biology investigations have consistently indicated that cell wall remodeling occurs in a variety of spaceflight-grown plants. Here, we describe a mass spectrometric method to study the fundamental composition of xyloglucan, the most abundant hemicellulose in dicot cell walls, in space-grown plants. Four representative Arabidopsis root samples, from a previously conducted spaceflight experiment - Advanced Plant EXperiment - 04 (APEX-04), were used to investigate changes in xyloglucan oligosaccharides abundances in spaceflight-grown plants compared to ground controls. In situ localized enzymatic digestions and surface sampling mass spectrometry analysis provided spatial resolution of the changes in xyloglucan oligosaccharides abundances. Overall, the results showed that oligosaccharide XXLG/XLXG and XXFG branching patterns were more abundant in the lateral roots of spaceflight-grown plants, while XXXG, XLFG, and XLFG/XLFG were more abundant in the lateral roots of ground control plants. In the primary roots, XXFG had a higher abundance in ground controls than in spaceflight plants. This methodology of analyzing the basic components of the cell wall in this paper highlights two important findings. First, that are differences in the composition of xyloglucan oligosaccharides in spaceflight root cell walls compared to ground controls and, second, most of these differences are observed in the lateral roots. Thus, the methodology described in this paper provides insights into spaceflight cell wall modifications for future investigations.

Integrative transcriptomics and proteomics profiling of Arabidopsis thaliana elucidates novel mechanisms underlying spaceflight adaptation.

Spaceflight presents a unique environment with complex stressors, including microgravity and radiation, that can influence plant physiology at molecular levels. Combining transcriptomics and proteomics approaches, this research gives insights into the coordination of transcriptome and proteome in Arabidopsis' molecular and physiological responses to Spaceflight environmental stress. Arabidopsis seedlings were germinated and grown in microgravity (µg) aboard the International Space Station (ISS) in NASA Biological Research in Canisters - Light Emitting Diode (BRIC LED) hardware, with the ground control established on Earth. At 10 days old, seedlings were frozen in RNA-later and returned to Earth. RNA-seq transcriptomics and TMT-labeled LC-MS/MS proteomic analysis of cellular fractionates from the plant tissues suggest the alteration of the photosynthetic machinery (PSII and PSI) in spaceflight, with the plant shifting photosystem core-regulatory proteins in an organ-specific manner to adapt to the microgravity environment. An overview of the ribosome, spliceosome, and proteasome activities in spaceflight revealed a significant abundance of transcripts and proteins involved in protease binding, nuclease activities, and mRNA binding in spaceflight, while those involved in tRNA binding, exoribonuclease activity, and RNA helicase activity were less abundant in spaceflight. CELLULOSE SYNTHASES (CESA1, CESA3, CESA5, CESA7) and CELLULOSE-LIKE PROTEINS (CSLE1, CSLG3), involved in cellulose deposition and TUBULIN COFACTOR B (TFCB) had reduced abundance in spaceflight. This contrasts with the increased expression of UDP-ARABINOPYRANOSE MUTASEs, involved in the biosynthesis of cell wall non-cellulosic polysaccharides, in spaceflight. Both transcripts and proteome suggested an altered polar auxin redistribution, lipid, and ionic intracellular transportation in spaceflight. Analyses also suggest an increased metabolic energy requirement for plants in Space than on Earth, hence, the activation of several shunt metabolic pathways. This study provides novel insights, based on integrated RNA and protein data, on how plants adapt to the spaceflight environment and it is a step further at achieving sustainable crop production in Space.

Transcriptomic dynamics in the transition from ground to space are revealed by Virgin Galactic human-tended suborbital spaceflight.

The Virgin Galactic Unity 22 mission conducted the first astronaut-manipulated suborbital spaceflight experiment. The experiment examined the operationalization of Kennedy Space Center Fixation Tubes (KFTs) as a generalizable approach to preserving biology at various phases of suborbital flight. The biology chosen for this experiment was Arabidopsis thaliana, ecotype Col-0, because of the plant history of spaceflight experimentation within KFTs and wealth of comparative data from orbital experiments. KFTs were deployed as a wearable device, a leg pouch attached to the astronaut, which proved to be operationally effective during the course of the flight. Data from the inflight samples indicated that the microgravity period of the flight elicited the strongest transcriptomic responses as measured by the number of genes showing differential expression. Genes related to reactive oxygen species and stress, as well as genes associated with orbital spaceflight, were highly represented among the suborbital gene expression profile. In addition, gene families largely unaffected in orbital spaceflight were diversely regulated in suborbital flight, including stress-responsive transcription factors. The human-tended suborbital experiment demonstrated the operational effectiveness of the KFTs in suborbital flight and suggests that rapid transcriptomic responses are a part of the temporal dynamics at the beginning of physiological adaptation to spaceflight.

Hoffman syndrome with the classic sign of myoedema and an unusual finding of systolic heart failure.

A man in his 20s presented with a 6-year history of calf muscle hypertrophy, proximal muscle weakness and muscle cramps. Along with this, he also had patchy hair loss, facial puffiness and slurring of speech. On examination, he had mild symmetrical proximal muscle weakness, a delayed relaxation phase of his deep tendon reflexes and a rare neurological sign of myoedema. His laboratory investigations revealed elevated thyroid-stimulating hormone levels with high creatine kinase levels, and an echocardiogram showed left ventricular systolic dysfunction. He was diagnosed with Hoffman syndrome, a rare pseudohypertrophic myopathy associated with severe and prolonged hypothyroidism. He had an excellent response to thyroid hormone replacement.

[Mind-body medicine in pain management]. / Mind-body-Medizin in der Schmerztherapie.

Chronic pain affects around 3 million people in Germany. The drug therapies used are only effective to a limited extent and sometimes have considerable side effects. Methods of mind-body medicine (MBM) including especially mindfulness-based stress reduction (MBSR), meditation and yoga, can significantly reduce the perceived intensity of the pain. Combined with evidence-based complementary medicine, MBM as mind-body medicine in integrative and complementary medicine (MICOM) is an effective instrument for self-efficacy and self-care with very few side effects. The reduction of stress plays a key role in this process.

Advancing the automation of plant nucleic acid extraction for rapid diagnosis of plant diseases in space.

Human space exploration missions will continue the development of sustainable plant cultivation in what are obviously novel habitat settings. Effective pathology mitigation strategies are needed to cope with plant disease outbreaks in any space-based plant growth system. However, few technologies currently exist for space-based diagnosis of plant pathogens. Therefore, we developed a method of extracting plant nucleic acid that will facilitate the rapid diagnosis of plant diseases for future spaceflight applications. The microHomogenizer™ from Claremont BioSolutions, originally designed for bacterial and animal tissue samples, was evaluated for plant-microbial nucleic acid extractions. The microHomogenizer™ is an appealing device in that it provides automation and containment capabilities that would be required in spaceflight applications. Three different plant pathosystems were used to assess the versatility of the extraction process. Tomato, lettuce, and pepper plants were respectively inoculated with a fungal plant pathogen, an oomycete pathogen, and a plant viral pathogen. The microHomogenizer™, along with the developed protocols, proved to be an effective mechanism for producing DNA from all three pathosystems, in that PCR and sequencing of the resulting samples demonstrated clear DNA-based diagnoses. Thus, this investigation advances the efforts to automate nucleic acid extraction for future plant disease diagnosis in space.

Role of Neutrophil Gelatinase-associated Lipocalin (NGAL) and Other Clinical Parameters as Predictors of Bacterial Sepsis in Patients Presenting to the Emergency Department with Fever.

Background: Bacterial sepsis is associated with significant morbidity and mortality. However, to date, there is no single test that predicts sepsis with reproducible results. We proposed that using a combination of clinical and laboratory parameters and a novel biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL) may aid in early diagnosis. Method: A prospective cohort study was conducted at a tertiary care center in South India (June 2017 to April 2018) on patients with acute febrile episodes fulfilling the Systemic Inflammatory Response Syndrome (SIRS) criteria. Plasma NGAL and standard clinical and laboratory parameters were collected at the admission. Bacterial sepsis was diagnosed based on blood culture positivity or clinical diagnosis. Clinically relevant plasma NGAL cut-off values were identified using the receive operating characteristic (ROC) curve. Clinically relevant clinical parameters along with plasma NGAL's risk ratios estimated from the multivariable Poisson regression model were rounded and used as weights to create a new scoring tool. Results: Of 100 patients enrolled, 37 had bacterial sepsis. The optimal plasma NGAL cut-off value to predict sepsis was 570 ng/mL [area under the curve (AUC): 0.69]. The NGAL sepsis screening tool consists of the following clinical parameter: diabetes mellitus, the presence of rigors, quick sequential organ failure assessment (qSOFA) >2, a clear focus of infection, and the plasma NGAL >570 ng/mL. A score of <3 ruled out bacterial sepsis and a score >7 were highly suggestive of bacterial sepsis with an interval likelihood ratio (LR) of 7.77. Conclusion: The NGAL sepsis screening tool with a score >7 can be used in the emergency department (ED) to identify bacterial sepsis. How to cite this article: Paul A, Newbigging NS, Lenin A, Gowri M, Varghese JS, Nell AJ, et al. Role of Neutrophil Gelatinase-associated Lipocalin (NGAL) and Other Clinical Parameters as Predictors of Bacterial Sepsis in Patients Presenting to the Emergency Department with Fever. Indian J Crit Care Med 2023;27(3):176-182.

Utilizing the KSC Fixation Tube to Conduct Human-Tended Plant Biology Experiments on a Suborbital Spaceflight.

Suborbital spaceflights now enable human-tended research investigating short-term gravitational effects in biological systems, eliminating the need for complex automation. Here, we discuss a method utilizing KSC Fixation Tubes (KFTs) to both carry biology to suborbital space as well as fix that biology at certain stages of flight. Plants on support media were inserted into the sample side of KFTs preloaded with RNAlater in the fixation chamber. The KFTs were activated at various stages of a simulated flight to fix the plants. RNA-seq analysis conducted on tissue samples housed in KFTs, showed that plants behaved consistently in KFTs when compared to petri-plates. Over the time course, roots adjusted to hypoxia and leaves adjusted to changes in photosynthesis. These responses were due in part to the environment imposed by the encased triple containment of the KFTs, which is a requirement for flight in human spacecraft. While plants exhibited expected reproducible transcriptomic alteration over time in the KFTs, responses to clinorotation during the simulated flight suggest that transcriptomic responses to suborbital spaceflight can be examined using this approach.

A Randomized Controlled Trial of Fasting and Lifestyle Modification in Patients with Metabolic Syndrome: Effects on Patient-Reported Outcomes.

Lifestyle interventions can have a positive impact on quality of life and psychological parameters in patients with metabolic syndrome (MetS). In this randomized controlled trial, 145 participants with MetS (62.8% women; 59.7 ± 9.3 years) were randomized to (1) 5-day fasting followed by 10 weeks of lifestyle modification (F + LM; modified DASH diet, exercise, mindfulness; n = 73) or (2) 10 weeks of lifestyle modification only (LM; n = 72). Outcomes were assessed at weeks 0, 1, 12, and 24, and included quality of life (Short-Form 36 Health Survey Questionnaire, SF-36), anxiety/depression (Hospital Anxiety and Depression Scale, HADS), stress (Cohen Perceived Stress Scale, CPSS), mood (Profile of Mood States, POMS), self-efficacy (General Self-Efficacy Scale, GSE), mindfulness (Mindfulness Attention Awareness Scale, MAAS), and self-compassion (Self-Compassion Scale, SCS). At week 1, POMS depression and fatigue scores were significantly lower in F + LM compared to LM. At week 12, most self-report outcomes improved in both groups-only POMS vigor was significantly higher in F + LM than in LM. Most of the beneficial effects within the groups persisted at week 24. Fasting can induce mood-modulating effects in the short term. LM induced several positive effects on quality of life and psychological parameters in patients with MetS.

SARS-CoV-2 vaccination and new-onset myasthenia gravis: A report of 7 cases and review of the literature.

Myasthenia gravis (MG) is an antibody-mediated immune disorder of the neuromuscular junction. SARS-CoV-2 is now recognised as a trigger factor for autoimmune diseases and to cause immune-mediated dysregulation, likely due to molecular mimicry induced by viral antigens. SARS-CoV-2 vaccination, similarly, results in exposure to viral antigen. Here we report 7 cases of new-onset myasthenia gravis in timely association with SARS-CoV-2 vaccination, including the first paediatric case identified to date. We also reviewed the literature for other new-onset MG cases reported within 4 weeks of SARS-CoV-2 vaccination and discuss our findings in the context of altered (auto)immunity following SARS-CoV-2 vaccination and/or infection.

Effects of Fasting and Lifestyle Modification in Patients with Metabolic Syndrome: A Randomized Controlled Trial.

BACKGROUND: Lifestyle interventions, such as fasting, diet, and exercise, are increasingly used as a treatment option for patients with metabolic syndrome (MS). This study assesses the efficacy and safety of fasting followed by lifestyle modification in patients with MS compared to lifestyle modification only. METHODS: Single-blind, multicenter, parallel, randomized controlled trial in two German tertiary referral hospitals in metropolitan areas. INTERVENTIONS: (a) 5-day fasting followed by 10 weeks of lifestyle modification (modified DASH diet, exercise, mindfulness; n = 73); (b) 10 weeks of lifestyle modification only (n = 72). MAIN OUTCOMES AND MEASURES: Co-primary outcomes were ambulatory systolic blood pressure and the homeostasis model assessment (HOMA) index at week 12. Further outcomes included anthropometric, laboratory parameters, and the PROCAM score at weeks 1, 12, and 24. RESULTS: A total of 145 patients with metabolic syndrome (62.8% women; 59.7 ± 9.3 years) were included. No significant group differences occurred for the co-primary outcomes at week 12. However, compared to lifestyle modification only, fasting significantly reduced HOMA index (Δ = -0.8; 95% confidence interval [CI] = -1.7, -0.1), diastolic blood pressure (Δ = -4.8; 95% CI = -5.5, -4.1), BMI (Δ = -1.7; 95% CI = -2.0, -1.4), weight (Δ = -1.7; 95% CI = -2.0, -1.4), waist circumference (Δ = -2.6; 95% CI = -5.0, -0.2), glucose (Δ = -10.3; 95% CI = -19.0, -1.6), insulin (Δ = -2.9; 95% CI = -5.3, -0.4), HbA1c (Δ = -0.2; 95% CI = -0.4, -0.05;), triglycerides (Δ = -48.9; 95% CI = -81.0, -16.9), IL-6 (Δ = -1.2; 95% CI = -2.5, -0.005), and the 10-year risk of acute coronary events (Δ = -4.9; 95% CI = -9.5, -0.4) after week 1. Fasting increased uric acid levels (Δ = 1.0; 95% CI = 0.1, 1.9) and slightly reduced eGRF (Δ = -11.9; 95% CI = -21.8, -2.0). Group differences at week 24 were found for weight (Δ = -2, 7; 95% CI = -4.8, -0.5), BMI (Δ = -1.0; 95% CI = -1.8, -0.3), glucose (Δ = -7.7; 95% CI = -13.5, -1.8), HDL (Δ = 5.1; 95% CI = 1.5, 8.8), and CRP (Δ = 0.2; 95% CI = 0.03, 0.4). No serious adverse events occurred. CONCLUSIONS: A beneficial effect at week 24 was found on weight; fasting also induced various positive short-term effects in patients with MS. Fasting can thus be considered a treatment for initializing lifestyle modification for this patient group; however, it remains to be investigated whether and how the multilayered effects of fasting can be maintained in the medium and longer term.

Plants grown in Apollo lunar regolith present stress-associated transcriptomes that inform prospects for lunar exploration.

The extent to which plants can enhance human life support on other worlds depends on the ability of plants to thrive in extraterrestrial environments using in-situ resources. Using samples from Apollo 11, 12, and 17, we show that the terrestrial plant Arabidopsis thaliana germinates and grows in diverse lunar regoliths. However, our results show that growth is challenging; the lunar regolith plants were slow to develop and many showed severe stress morphologies. Moreover, all plants grown in lunar soils differentially expressed genes indicating ionic stresses, similar to plant reactions to salt, metal and reactive oxygen species. Therefore, although in situ lunar regoliths can be useful for plant production in lunar habitats, they are not benign substrates. The interaction between plants and lunar regolith will need to be further elucidated, and likely mitigated, to best enable efficient use of lunar regolith for life support within lunar stations.

Effects of oxygen fertilization on damage reduction in flooded snap bean (Phaseolus vulgaris L.).

Flooding is one of the major abiotic stresses for vegetable production in Florida. Hydroponic and pot trials were conducted with snap bean to evaluate the effects of oxygen fertilization on the biochemical and physiological status of flooded snap bean plants. There were three treatments in the hydroponic trials were: (1) flooded (control), (2) bubble aeration with ambient air, and (3) hydrogen peroxide (H2O2) applied at the beginning of the trial. Plant health was evaluated by determining nitrogen (N) and phosphorus (P) uptake rates. The greenhouse pot trials were used to quantify the effects of three different application rates of solid oxygen fertilizers as calcium peroxide (CaO2) and magnesium peroxide (MgO2). The results showed that plant N and P uptake rates were significantly greater (p < 0.05) with H2O2 than without H2O2. The N uptake rates with H2O2 were like that of those with bubbling. The uptake rate of NH4+ was significantly greater than that of NO3- with the bubbling and H2O2 conditions, but the uptake rate of NO3- was significantly greater than that of NH4+ in the flooding condition. The plant height, leaf greenness, shoot biomass, and yield were all significantly greater with CaO2 or MgO2 than without either solid oxygen fertilizer. The minimum damage of flooded snap bean was found with 2 g CaO2 or 4 g MgO2 per pot. These results indicated that oxygen fertilization may potentially improve yield of flooded snap bean plants.

Estimation of patent foramen ovale size using transcranial Doppler ultrasound in patients with ischemic stroke.

BACKGROUND AND PURPOSE: Patent foramen ovale (PFO)is associated with cryptogenic stroke, especially in young adults. Transcranial Doppler (TCD) ultrasound is used as a screening tool before transesophageal echocardiography (TEE). However, the use of Valsalva maneuver (VM) to identify a right-to-left-shunt underlies interindividual variability. Here, we aimed to assess whether a pressure-controlled standardization of VM is useful to estimate PFO size. METHODS: We included patients aged 18-80 years with a PFO according to TEE. Subjects underwent TCD with microembolic signals (MES) counted under four pressure conditions (i.e., at rest, 15 mbar, 40 mbar, and maximum expiratory pressure). Findings were correlated with TEE-based PFO size. The predictive value of TCD at rest and VM-based TCD for PFO size estimation was assessed by stepwise multivariate linear regression models and multiple cross-tab-analyses. RESULTS: We screened 203 subjects after a cerebrovascular event, of which 78 (48 males [61.5%], median age 55 years [22-80]) with PFO were included. We found an association between MES count and expiratory pressure (p < .001). Predefined MES count categories at TCD pressure conditions correlated significantly with PFO size measured by TEE. We propose a PFO size estimation model based on TCD at rest and under VM, which classified PFO size correctly in 64.1% with the highest accuracy for small PFOs. CONCLUSION: Our data provide evidence that TCD with step-wise barometric standardization allows an estimation of PFO size with good accuracy. Though TCD will not replace TEE in future, this might be of clinical value in circumstances where TEE cannot be easily performed.

Epigenomic Regulators Elongator Complex Subunit 2 and Methyltransferase 1 Differentially Condition the Spaceflight Response in Arabidopsis.

Background: Plants subjected to the novel environment of spaceflight show transcriptomic changes that resemble aspects of several terrestrial abiotic stress responses. Under investigation here is whether epigenetic modulations, similar to those that occur in terrestrial stress responses, have a functional role in spaceflight physiological adaptation. The Advanced Plant Experiment-04 - Epigenetic Expression experiment examined the role of cytosine methylation in spaceflight adaptation. The experiment was conducted onboard the International Space Station, and evaluated the spaceflight-altered, genome-wide methylation profiles of two methylation-regulating gene mutants [methyltransferase 1 (met1-7) and elongator complex subunit 2 (elp2-5)] along with a wild-type Col-0 control. Results: The elp2-5 plants suffered in their physiological adaptation to spaceflight in that their roots failed to extend away from the seed and the overall development of the plants was greatly impaired in space. The met1-7 plants suffered less, with their morphology affected by spaceflight in a manner similar to that of the Col-0 controls. The differentially expressed genes (DEGs) in spaceflight were dramatically different in the elp2-5 and met1-7 plants compared to Col-0, indicating that the disruptions in these mutants resulted in a reprogramming of their spaceflight responses, especially in elp2-5. Many of the genes comprising the spaceflight transcriptome of each genotype were differentially methylated in spaceflight. In Col-0 the majority of the DEGs were representative of the now familiar spaceflight response, which includes genes associated with cell wall remodeling, pathogen responses and ROS signaling. However, the spaceflight transcriptomes of met1-7 and elp2-5 each presented patterns of DEGs that are almost completely different than Col-0, and to each other. Further, the DEGs of the mutant genotypes suggest a more severe spaceflight stress response in the mutants, particularly in elp2-5. Conclusion: Arabidopsis physiological adaptation to spaceflight results in differential DNA methylation in an organ-specific manner. Disruption of Met1 methyltransferase function does not dramatically affect spaceflight growth or morphology, yet met1-7 reprograms the spaceflight transcriptomic response in a unique manner. Disruption of elp2-5 results in poor development in spaceflight grown plants, together with a diminished, dramatically reprogrammed transcriptomic response.

The INTREST registry: protocol of a multicenter prospective cohort study of predictors of women's response to integrative breast cancer treatment.

BACKGROUND: Cancer registries usually assess data of conventional treatments and/or patient survival. Beyond that, little is known about the influence of other predictors of treatment response related to the use of complementary therapies (CM) and lifestyle factors affecting patients' quality and quantity of life. METHODS: INTREST is a prospective cohort study collecting register data at multiple German certified cancer centers, which provide individualized, integrative, in- and outpatient breast cancer care. Patient-reported outcomes and clinical cancer data of anticipated N = 715 women with pTNM stage I-III breast cancer are collected using standardized case report forms at the time of diagnosis, after completing neo-/adjuvant chemotherapy, after completing adjuvant therapy (with the exception of endocrine therapy) as well as 1, 2, 5, and 10 years after baseline. Endpoints for multivariable prediction models are quality of life, fatigue, treatment adherence, and progression-based outcomes/survival. Predictors include the study center, sociodemographic characteristics, histologic cancer and comorbidity data, performance status, stress perception, depression, anxiety, sleep quality, spirituality, social support, physical activity, diet behavior, type of conventional treatments, use of and belief in CM treatments, and participation in a clinical trial. Safety is recorded following the Common Terminology Criteria for Adverse Events. DISCUSSION: This trial is currently recruiting participants. Future analyses will allow to identify predictors of short- and long-term response to integrative breast cancer treatment in women, which, in turn, may improve cancer care as well as quality and quantity of life with cancer. TRIAL REGISTRATION: German Clinical Trial Register DRKS00014852 . Retrospectively registered at July 4th, 2018.

Switching anti-VEGF agent for wet AMD: evaluation of impact on visual acuity, treatment frequency and retinal morphology in a real-world clinical setting.

PURPOSE: The aim of the present cross-sectional real-world study is to evaluate the impact of switch of anti-VEGF agent from ranibizumab to aflibercept on visual acuity, treatment frequency and retinal morphology after 12 months in eyes with ongoing chronic treatment for wet age-related macular degeneration (AMD) compared to eyes not subjected to switch of anti-VEGF agent. METHODS: Data was obtained retrospectively from the Swedish Macular Register, spectral-domain optical coherence tomography (OCT) images and electronic patient charts. All eyes included were treated in the same clinical setting at the Department of Ophthalmology at the county hospital of Västmanland in Västerås, Sweden. RESULTS: In total, 282 and 359 eyes were included in the non-switch and switch cohorts, respectively. The cohorts were well balanced. Visual acuity remained stable during the observation period in both cohorts of eyes. The number of anti-VEGF treatments slowly declined over time in both cohorts of eyes and, consequently, the treatment intervals increased during the observation period. In eyes subjected to switch of anti-VEGF agent, planned treatment interval at 12 months was 7.6 (mean; SD 2.9) weeks compared to 6.8 (mean; SD 2.7) in the non-switch cohort (P = 0.001). OCT images demonstrated lower prevalence of intraretinal and subretinal fluid as well as pigment epithelial detachment at 12 months in eyes subjected to switch of anti-VEGF agent compared to non-switch eyes. CONCLUSION: Switch of anti-VEGF agent from ranibizumab to aflibercept did not affect visual function whereas improvement in retinal morphology was observed. These findings suggest a beneficial effect of switching from ranibizumab to aflibercept in eyes with ongoing chronic anti-VEGF treatment irrespective of previous response to ranibizumab. Longer follow-up is required to further evaluate the potential clinical significance of this finding.

Nursing Procedures for the Prevention and Treatment of Mucositis Induced by Cancer Therapies: Clinical Practice Guideline Based on an Interdisciplinary Consensus Process and a Systematic Literature Search.

BACKGROUND: Patients with cancer receiving tumor therapy often suffer from oral mucositis. OBJECTIVES: The aim of this project was to summarize experiences with nursing procedures by experts in integrative oncology and to establish recommendations for nursing interventions that can prevent or cure mucositis. METHODS: The study design was an interdisciplinary consensus process based on a systematic literature search. RESULTS: The panel discussed and agreed on 19 nursing procedures, which included mouthwashes, such as teas, supplements, oil applications, and different kinds of ice cubes to suck, as well as flaxseed solution, propolis, and mare milk. Twelve interventions were classified as effective, with effectiveness for OraLife, propolis, sea buckthorn pulp oil, marshmallow root tea also for xerostomia, Helago chamomile oil, mare milk, and Saliva Natura rated as highly effective in clinical experience. In the systematic literature search, a total of 12 out of 329 randomized controlled trials and meta-analyses on chamomile (n = 3), Calendula (n = 1) and sage (n = 1), propolis (n = 2), and sucking ice cubes (cryotherapy; n = 5) met all inclusion criteria. Trial evidence for effectiveness in oral mucositis was revealed for propolis and cryotherapy. CONCLUSIONS: The current evidence supports the use of some nursing procedures (f.e. propolis for 2 and 3 grade mucositis) for improving oral mucositis during cancer therapies. There is still a need to define general clinical practice guidelines for the supportive treatment of mucositis, as well as for more interdisciplinary research in this area.

Effects of an Integrative Mind-Body-Medicine Group Program on Breast Cancer Patients During Chemotherapy: An Observational Study.

BACKGROUND: Breast cancer is one of the leading cancers in women in the Western world. Cancer treatment, especially chemotherapy, is often associated with physical and psychosocial side effects. OBJECTIVE: To improve the quality of life and manage side effects, a new integrative mind-body-medicine group concept for breast cancer patients receiving chemotherapy was developed and pilot tested. METHODS: Breast cancer patients participated in a 66 hours mind-body-medicine group program tailored to the needs of cancer patients during chemotherapy. The program was integrated into standard care encompassing mindfulness training, yoga, moderate exercise, nutrition, complementary self-help strategies, cognitive restructuring, and acupuncture. Quality of life (EORTC QLQ-C30), depression and anxiety (HADS), stress (PSS-10), and fatigue (BFI) were assessed before and after the program, as well as satisfaction and safety. Analyses were carried out on exploratory basis with paired samples t-tests. RESULTS: Fifty-seven female patients, aged 51.3±10.5 years, with breast cancer diagnoses were enrolled. After completing the program, global EORTC quality of life was improved (D=9.5; 95%-CI=[2.9|16.1]; p=.005), although the EORTC-symptom scales assessing fatigue (D=9.9; 95%-CI=[1|18.8]; p=.030), nausea (D=7.1; 95%- CI=[0.6|13.6]; p=.031), and dyspnea (D=12.5; 95%-CI=[2.9|22.1]; p=.011) were found to be increased. Stress (D=-3.5; 95%-CI=[-5|-2.1]; p=.000), anxiety (D=-3.8; 95%-CI=[-4.9|-2.7]; p=.000) and depression (D=-3.9; 95%-CI=[-4.9|-2.8]; p=.000) were also found to be significantly reduced. Regarding the severity of (D=0.2; 95%- CI=[-0.8|0.5]; p=.644) and the impairment due to fatigue (D=0.1; 95%-CI=[-0.8|0.6]; p=.696), no significant worsening was observed. Patients were satisfied with the program. No serious adverse events were reported. CONCLUSION: Breast cancer patients benefit from an integrative mind-body-medicine group program during chemotherapy regarding the quality of life and psychological symptoms. Randomized controlled trials are warranted.