Immune transcriptomes of highly exposed SARS-CoV-2 asymptomatic seropositive versus seronegative individuals from the Ischgl community

Abstract To investigate prevalence of ongoing activation of inflammation following asymptomatic SARS-CoV-2 infection we characterized immune cell transcriptomes from 43 asymptomatic seropositive and 52 highly exposed seronegative individuals with few underlying health issues following a community superspreading event. Four mildly symptomatic seropositive individuals examined three weeks after infection as positive controls demonstrated immunological activation. Approximately four to six weeks following the event, the two asymptomatic groups showed no significant differences. Two seropositive patients with underlying genetic disease impacting immunological activation were included (Cystic Fibrosis (CF), Nuclear factor-kappa B Essential Modulator (NEMO) deficiency). CF, but not NEMO, associated with significant immune transcriptome differences including some associated with severe SARS-CoV-2 infection (IL1B, IL17A, respective receptors). All subjects remained in their usual state of health from event through five-month follow-up. Here, asymptomatic infection resolved without evidence of prolonged immunological activation. Inclusion of subjects with underlying genetic disease illustrated the pathophysiological importance of context on impact of immunological response.

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Immune transcriptomes of highly exposed SARS-CoV-2 asymptomatic seropositive versus seronegative individuals from the Ischgl community

10.1101/2020.09.01.20185884 ◽

2020 ◽

Author(s):

Hye Kyung Lee ◽

Ludwig Knabl ◽

Lisa Pipperger ◽

Andre Volland ◽

Priscilla A. Furth ◽

...

Keyword(s):

Genetic Disease ◽

Nuclear Factor Kappa B ◽

Immune Cell ◽

Immunological Response ◽

Asymptomatic Infection ◽

Health Issues ◽

Immunological Activation ◽

Usual State ◽

Positive Controls

To investigate prevalence of ongoing activation of inflammation following asymptomatic SARS-CoV-2 infection we characterized immune cell transcriptomes from 43 asymptomatic seropositive and 52 highly exposed seronegative individuals with few underlying health issues following a community superspreading event. Four mildly symptomatic seropositive individuals examined three weeks after infection as positive controls demonstrated immunological activation. Approximately four to six weeks following the event, the two asymptomatic groups showed no significant differences. Two seropositive patients with underlying genetic disease impacting immunological activation were included (Cystic Fibrosis (CF), Nuclear factor-kappa B Essential Modulator (NEMO) deficiency). CF, but not NEMO, associated with significant immune transcriptome differences including some associated with severe SARS-CoV-2 infection (IL1B, IL17A, respective receptors). All subjects remained in their usual state of health from event through five-month follow-up. Here, asymptomatic infection resolved without evidence of prolonged immunological activation. Inclusion of subjects with underlying genetic disease illustrated the pathophysiological importance of context on impact of immunological response.

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Immune transcriptomes of highly exposed SARS-CoV-2 asymptomatic seropositive versus seronegative individuals from the Ischgl community

Scientific Reports ◽

10.1038/s41598-021-83110-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hye Kyung Lee ◽

Ludwig Knabl ◽

Lisa Pipperger ◽

Andre Volland ◽

Priscilla A. Furth ◽

...

Keyword(s):

Cystic Fibrosis ◽

Immune Activation ◽

Immune Cell ◽

Comparative Investigation ◽

Asymptomatic Infection ◽

Incontinentia Pigmenti ◽

Health Issues ◽

Sample Collection ◽

Seropositive Individual ◽

Negative Controls

AbstractSARS-CoV-2 infection ranges from asymptomatic to severe with lingering symptomatology in some. This prompted investigation of whether or not asymptomatic disease results in measurable immune activation post-infection. Immune activation following asymptomatic SARS-CoV-2 infection was characterized through a comparative investigation of the immune cell transcriptomes from 43 asymptomatic seropositive and 52 highly exposed seronegative individuals from the same community 4–6 weeks following a superspreading event. Few of the 95 individuals had underlying health issues. One seropositive individual reported Cystic Fibrosis and one individual reported Incontinentia pigmenti. No evidence of immune activation was found in asymptomatic seropositive individuals with the exception of the Cystic Fibrosis patient. There were no statistically significant differences in immune transcriptomes between asymptomatic seropositive and highly exposed seronegative individuals. Four positive controls, mildly symptomatic seropositive individuals whose blood was examined 3 weeks following infection, showed immune activation. Negative controls were four seronegative individuals from neighboring communities without COVID-19. All individuals remained in their usual state of health through a five-month follow-up after sample collection. In summary, whole blood transcriptomes identified individual immune profiles within a community population and showed that asymptomatic infection within a super-spreading event was not associated with enduring immunological activation.

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Data Driven Mathematical Model of FOLFIRI Treatment for Colon Cancer

Cancers ◽

10.3390/cancers13112632 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2632

Author(s):

Aparajita Budithi ◽

Sumeyye Su ◽

Arkadz Kirshtein ◽

Leili Shahriyari

Keyword(s):

Mathematical Model ◽

Colon Cancer ◽

Cancer Patients ◽

Immune Cell ◽

Treatment Options ◽

Data Driven ◽

T Helper ◽

Primary Tumors ◽

Cell Fractions

Many colon cancer patients show resistance to their treatments. Therefore, it is important to consider unique characteristic of each tumor to find the best treatment options for each patient. In this study, we develop a data driven mathematical model for interaction between the tumor microenvironment and FOLFIRI drug agents in colon cancer. Patients are divided into five distinct clusters based on their estimated immune cell fractions obtained from their primary tumors’ gene expression data. We then analyze the effects of drugs on cancer cells and immune cells in each group, and we observe different responses to the FOLFIRI drugs between patients in different immune groups. For instance, patients in cluster 3 with the highest T-reg/T-helper ratio respond better to the FOLFIRI treatment, while patients in cluster 2 with the lowest T-reg/T-helper ratio resist the treatment. Moreover, we use ROC curve to validate the model using the tumor status of the patients at their follow up, and the model predicts well for the earlier follow up days.

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Grandparent Resilience: Improving Self-Efficacy in Grandparents Raising Grandchildren

Innovation in Aging ◽

10.1093/geroni/igaa057.1647 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 510-510

Author(s):

Aimee Fox ◽

Nathaniel Riggs ◽

Loriena Yancura ◽

Christine Fruhauf

Keyword(s):

Self Efficacy ◽

Emotional Health ◽

Well Being ◽

Individual Variability ◽

Health Issues ◽

Grandparents Raising Grandchildren ◽

Post Intervention ◽

Paired Samples ◽

Post Test

Abstract Grandparents often protect against childhood trauma and promote resilience through their nurturance, love, and support when raising grandchildren. Despite the beneficial role grandparents have on their grandchildren, grandparents may experience challenges of their own, including physical, mental, and emotional health issues, lack of resources, and social isolation. Few interventions exist to help grandparents successfully adapt to the challenges they face as primary parenting figures. The purpose of this study was to test preliminary efficacy of a strengths-based intervention for grandparents raising grandchildren aimed at increasing self-care behaviors, managing emotions, and connecting to community resources. Grandparents (N = 137) providing primary care to grandchildren were recruited to participate in a single-group, pre- and post-test design, 6-week intervention. Self-efficacy was assessed at baseline, post-intervention, and at a 6-month follow-up. To evaluate who the intervention might be most beneficial for, grandparents’ service knowledge, perceived support from others, and length of care provided, measured at baseline, were analyzed for moderating effects. Results of paired-samples t-tests reveal significant increases in self-efficacy (p = .013) from baseline to post-test, which were maintained at the 6-month follow-up (p = .010). Hierarchical multiple regression showed interaction effects of the hypothesized moderators were not significant, indicating improvements in self-efficacy regardless of individual variability at baseline. As demonstrated, interventions can be effective at increasing self-efficacy in grandparents raising grandchildren and strengths-based approaches have the potential to provide universal benefits to grandparents, thus improving functioning in grandfamilies and promoting the health and well-being of grandparents and their grandchildren.

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Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines

Pharmaceutics ◽

10.3390/pharmaceutics13010045 ◽

2020 ◽

Vol 13 (1) ◽

pp. 45

Author(s):

Iman M. Alfagih ◽

Basmah Aldosari ◽

Bushra AlQuadeib ◽

Alanood Almurshedi ◽

Mariyam M. Alfagih

Keyword(s):

Messenger Rna ◽

Immune Cell ◽

Natural Infection ◽

Immunological Response ◽

Infection Process ◽

Dual Function ◽

Therapeutic Vaccines ◽

Non Invasive ◽

Recent Developments

Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines are being evaluated in clinical trials as prophylactic and therapeutic vaccines. However, until recently, their development has been limited by their instability and inefficient in vivo transfection. The nanodelivery system plays a dual function in RNA-based vaccination by acting as a carrier system and as an adjuvant. That is due to its similarity to microorganisms structurally and size-wise; the nanodelivery system can augment the response by the immune system via simulating the natural infection process. Nanodelivery systems allow non-invasive mucosal administration, targeted immune cell delivery, and controlled delivery, reducing the need for multiple administrations. They also allow co-encapsulating with immunostimulators to improve the overall adjuvant capacity. The aim of this review is to discuss the recent developments and applications of biodegradable nanodelivery systems that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases.

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Health assessments for Indigenous Australians at Orange Aboriginal Medical Service: health problems identified and subsequent follow up

Australian Journal of Primary Health ◽

10.1071/py14120 ◽

2016 ◽

Vol 22 (3) ◽

pp. 233 ◽

Cited By ~ 1

Author(s):

Tegan Dutton ◽

Wendy Stevens ◽

Jamie Newman

Keyword(s):

Medical Service ◽

Pap Smear ◽

Aboriginal Health ◽

Indigenous Australians ◽

Adult Women ◽

Health Issues ◽

Retrospective Audit ◽

Health Assessments ◽

Clinical Records

This study aimed to document the types, management and follow up of health issues identified by all Aboriginal Health Assessments (AHA) performed at Orange Aboriginal Medical Service from 1 January 2011 to 31 December 2012. This was done with a retrospective audit of clinical records. In total, 1169 AHAs were performed: 41% child, 53% adult and 6% older person AHAs. Newly identified health issues were documented in 85% (984). Being overweight (41%; 476) and smoking (26%; 301) were the common risk factors identified. As a result of the AHA, most children who were not up-to-date with their vaccinations received catch-up immunisations; 11% (36) of adult women (n=314) received a Pap smear, although Pap smear status was unknown or not up-to-date for 61% (192); 27% (311) of cases were prescribed new medication; and 1239 referrals were made but only 40% were attended. At 6 months following the AHA, 26% (240) of cases with newly identified health issues were completely managed and followed up, whereas 25% (226) received no follow up. The AHAs are useful for identifying new health issues; however, follow up of the identified health issues should be improved. If AHAs are to improve health outcomes, appropriate management and follow up of the identified health issues are essential.

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Effects of choral singing on salivary cortisol levels and self-reported stress in university students

Music and Medicine ◽

10.47513/mmd.v13i4.794 ◽

2021 ◽

Vol 13 (4) ◽

Author(s):

Gunnar Glauco De Cunto Carelli Taets ◽

Ramon Werner Heringer Gutierrez ◽

Leila Brito Bergold ◽

Luana Silva Monteiro

Keyword(s):

University Students ◽

Salivary Cortisol ◽

Health Issues ◽

Group Approach ◽

Choral Singing ◽

Before And After ◽

Quasi Experimental ◽

Potential Impact ◽

Cortisol Levels

Although mental disorders are common among university students, the majority of students with mental health issues do not seek out treatment during their academic life. The aim of this study was to evaluate the effects of a novel group approach- choir singing, and its potential impact on stress, via salivary cortisol levels and self-reported stress levels in university students during 4 sessions of choir singing. It was based on a quasi-experimental research conducted with 25 Brazilian university students. Each choir singing session lasted 60 minutes. A question was asked before and after the intervention: what is the level of your stress? Salivary cortisol was collected before and after the intervention. After the choir singing intervention, there was a statistically significant reduction in self-reported stress (p<0.0001) and salivary cortisol levels (p<0.0001). This research suggests that choir singing can reduce the self-reported stress of university students after 4 weeks of follow-up with ∆= 45.83% and salivary cortisol levels in the first week with ∆= 3.57%.

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Association of Heavy Metals with Overall Mortality in a Taiwanese Population

10.21203/rs.3.rs-277882/v1 ◽

2021 ◽

Author(s):

Yi-hsueh Liu ◽

Chih-Wen Wang ◽

Da-Wei Wu ◽

Wen-Hsien Lee ◽

Ying-Chih Chen ◽

...

Keyword(s):

Heavy Metals ◽

Multivariate Analysis ◽

General Population ◽

Confidence Interval ◽

Health Issues ◽

Taiwanese Population ◽

Southern Taiwan ◽

The Relationship ◽

Overall Mortality

Abstract Previous studies have shown links between heavy metals and many health issues. However, data on the association between heavy metals and mortality in the general population are still limited. Therefore, the aim of this study was to investigate the relationship between heavy metals and overall mortality in the general population. We enrolled 2,497 participants (1,001 males and 1,496 females) living in southern Taiwan, and measured levels of seven heavy metals: lead (Pb) in blood and cadmium (Cd), nickel (Ni), copper (Cu), chromium (Cr), manganese (Mn) and arsenic (As) in urine. The median follow-up period was 41.8 (4-50) months, during which 40 (1.6%) patients died. Compared to the participants who survived, those who died had higher urine Cd, higher urine Cu and lower urine Mn levels. Multivariate analysis showed that high urine Cd (per 1 mg/L; hazard ratio [HR], 1.352; 95% confidence interval [CI], 1.089-1.680; p = 0.006), high urine Cu (per 1 mg/dL; HR, 1.350; 95% CI, 1.151-1.583; p < 0.001), and low urine Mn (per 1 mg/L; HR, 0.717; 95% CI, 0.557-0.923; p = 0.010) were associated with increased overall mortality. In conclusion, our results demonstrated that high levels of urine Cd and Cu and low urine Mn level were associated with increased overall mortality in general population.

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26 Introducing the Sherpa Model for Managing Multi-Morbidity to Trainee GPS: Outcomes and Relevance to Elderly CareÂ

Age and Ageing ◽

10.1093/ageing/afab029.05 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

pp. i7-i11

Author(s):

D Swancutt ◽

E Jack ◽

H Neve ◽

J Tredinnick-Rowe ◽

N Axford ◽

...

Keyword(s):

Qualitative Data ◽

Geriatric Medicine ◽

Training Programme ◽

Case Mix ◽

Shared Decision ◽

Health Issues ◽

Number Of Patients ◽

Consultation Model ◽

Framework Approach

Abstract Background Primary care trainees are traditionally taught to use a consultation model which focuses on eliciting the patients’ main reason for consulting “today”. As the number of patients with multi-morbidity increases, this approach is often inappropriate or unhelpful. Patients can be left without an understanding of their interacting health issues. The SHERPA model provides a biopsychosocial framework for consulting patients with multi-morbidity. We aimed to examine the responses to this model when integrated into a training programme for newly registered GPs. Methods Sixteen participants provide qualitative data on their experience and follow-up use of SHERPA. Four hours of teaching were observed. Twenty-four feedback templates on training (n = 18) and SHERPA application (n = 6) were collected. Individual semi-structured one-to-one interviews were conducted with trainees (n = 5) and trainers (n = 3). Data were transcribed and, using the Framework approach, systematically analysed focussing on the trainees’ reaction to the teaching sessions and their ability to use the SHERPA consultation model. Results Participants engaged well with the teaching sessions, enjoying the scenarios and bringing observations from their own experience. Five participants went on to apply SHERPA successfully with their patients. Barriers to using this approach were: not seeing appropriate patients with multi-morbidities (due to current placement or patient type); time; lack of confidence and familiarity; concern about missing important immediate clinical issues; and viewing the approach as “in addition” rather than key to shared decision-making. Conclusion The SHERPA model was viewed as a helpful addition by trainee GPs, although practical issues, fears and not seeing it as their priority for their case-mix, limited their application of it. Regular support from trainers, where trainees reflect on their experience of using SHERPA, could increase their confidence and familiarity with this method. These findings suggest that SHERPA may be relevant to other specialities such as geriatric medicine, where multi-morbidity is common.

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Genetics of cardiomyopathies: myocardial infiltration

ESC CardioMed ◽

10.1093/med/9780198784906.003.0159 ◽

2018 ◽

pp. 710-713

Author(s):

Frank Weidemann

Keyword(s):

Heart Failure ◽

Pompe Disease ◽

Genetic Disease ◽

Neurological Disease ◽

Diastolic Filling ◽

Potential Treatment ◽

Infiltrative Cardiomyopathy ◽

Storage Products ◽

Storage Disorders

Genetic disease can lead to myocardial infiltration which results in a cardiomyopathy characterized by the deposition of storage products within ventricular walls. The storage is inducing diastolic filling abnormalities which are finally responsible for the symptoms such as dyspnoea. During follow-up most patients die because of heart failure. Transthyretin-related amyloidosis is the most common infiltrative cardiomyopathy. Rarer diseases are storage disorders such as Fabry disease and Pompe disease. The primary neurological disease Friedreich’s ataxia can in addition induce an infiltrative cardiomyopathy. This chapter focuses on the pathophysiology, the symptoms, the typical image findings, and the potential treatment of these different rare genetic infiltrative diseases.

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