Dose- and time-dependent changes in viability and IL-6, CXCL8 and CCL2 production by HaCaT-cells exposed to cobalt. Effects of high and low calcium growth conditions

Background Sensitization requires exposure to an allergen with subsequent production of a “danger “signal. In the skin, keratinocytes are the main producers of these signals. Objective To compare dose- and time-effects of cobalt on the viability of and cytokine release from HaCaT cells cultured at low or high calcium. Method To model two separate states of differentiation of keratinocytes, HaCaT cells were cultured under low or high calcium conditions. HaCaT were exposed to different concentrations of cobalt chloride (10 μm to 5 mM) over time (30 minutes– 48 hours). Cell viability was measured with the Cell-Titer Blue Viability assay. Cytokine production was measured using a bead-based immunoassay and flow cytometry. Gene expression was quantified using qPCR. Data was analyzed by ANOVA and linear mixed model. Results Viability of the cells was dose- and time-dependent. A linear mixed statistical model showed that cobalt exposure induces increase in IL-6, CXCL8 and CCL2 production over time and whereas increase of IL-6 and a decrease of CCL2 was associated with increasing cobalt chloride concentrations. When comparing the cells incubated under high and low calcium conditions, the more differentiated cells in the high concentration were found to exert a stronger response in terms of IL-6 release. Conclusions Our data suggest that cobalt chloride triggered an alarm system in HaCaT cells, and proinflammatory cytokines/chemokines were secreted in a dose- and time-dependent manner. When high and low calcium incubations were compared, the difference was seen only for IL-6. These findings indicate that the effect of cobalt chloride on cell toxicity occurs throughout the living epidermis.

Download Full-text

Factors associated with professional identity formation within psychiatry residency training: A longitudinal study

Perspectives on Medical Education ◽

10.1007/s40037-021-00673-w ◽

2021 ◽

Author(s):

Qian Hui Chew ◽

Yvonne Steinert ◽

Kang Sim

Keyword(s):

Professional Identity ◽

Identity Formation ◽

Psychiatry Residency ◽

Mixed Model ◽

Linear Mixed Model ◽

Developmental Stages ◽

Rate Of Change ◽

Psychiatry Residents ◽

Factors Associated ◽

Over Time

Abstract Introduction Conceptual frameworks for professional identity (PI) formation highlight the importance of developmental stages and socialization as the learner progresses from legitimate peripheral to full participation. Based on extant literature and clinical impressions, the authors aimed to explore factors associated with PI formation in psychiatry residents over time, and hypothesized that time in training, seniority status, and duration of exposure to psychiatry prior to residency would be associated with PI formation. Methods Eighty out of 96 psychiatry residents (response rate, 83.3%) from the National Psychiatry Residency Program in Singapore participated and rated their PI development using the Professional Self Identity Questionnaire (PSIQ) across four timepoints from January 2016–December 2019. The residents were classified as junior (first 3 years) or senior residents (years 4–5). Linear mixed model analyses were conducted, with time in training, seniority status (junior versus senior residents), duration of psychiatry postings prior to residency, and their interaction as associated factors with PI over time. Results Time in training, seniority, and duration of psychiatry postings before residency (all p < 0.01) were significantly associated with higher PSIQ scores at baseline. Over time, although all residents had increases in PSIQ scores, this rate of change did not differ significantly between junior and senior residents. Discussion Exposure to psychiatry postings before residency, time in learning, and seniority are factors which influence PI development in residents. This has implications for psychiatry residency selection and training, adequate clinical exposure during training rotations, and continual support for new and senior residents to foster PI formation over time.

Download Full-text

Decline of ovarian function in patients with rheumatoid arthritis: serum anti-Müllerian hormone levels in a longitudinal cohort

RMD Open ◽

10.1136/rmdopen-2020-001307 ◽

2020 ◽

Vol 6 (3) ◽

pp. e001307

Author(s):

Jenny Brouwer ◽

Radboud J E M Dolhain ◽

Johanna M W Hazes ◽

Nicole S Erler ◽

Jenny A Visser ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mixed Model ◽

Linear Mixed Model ◽

Ovarian Function ◽

Reproductive Function ◽

Related Factors ◽

Original Cohort ◽

Primordial Follicles ◽

Age At Menopause ◽

Over Time

ObjectiveRheumatoid arthritis (RA) often affects women in their fertile age, and is known to compromise female fertility. Serum anti-Müllerian hormone (AMH) levels are a proxy for the total number of primordial follicles, and a reliable predictor of the age at menopause. Our objective was to study the longitudinal intra-individual decline of serum AMH levels in female RA patients.MethodsFemale RA patients from a nationwide prospective cohort (2002–2008) were re-assessed in 2015–2016. Serum AMH levels were measured using the picoAMH assay and compared with healthy controls. A linear mixed model (LMM) was built to assess the effect of RA-related clinical factors on the decline of AMH levels.ResultsA group of 128 women were re-assessed at an age of 42.6±4.4 years, with a median disease duration of 15.8 (IQR 12.7–21.5) years. The time between first and last AMH assessments was 10.7±1.8 (range 6.4–13.7) years. Participants represented a more fertile selection of the original cohort. At follow-up, 39% of patients had AMH levels below the 10th percentile of controls (95% CI 31% to 48%), compared with 16% (95% CI 9.3% to 22%) at baseline. The LMM showed a significant decline of AMH with increasing age, but no significant effect of RA-related factors on AMH.ConclusionAMH levels in RA patients showed a more pronounced decline over time than expected, supporting the idea that in chronic inflammatory conditions, reproductive function is compromised, resulting in a faster decline of ovarian function over time and probably an earlier age at menopause.

Download Full-text

Environmental Surveillance Can Dynamically Track Ecological Changes in Enteroviruses

Applied and Environmental Microbiology ◽

10.1128/aem.01604-19 ◽

2019 ◽

Vol 85 (24) ◽

Cited By ~ 2

Author(s):

Hiroki Ozawa ◽

Hiromu Yoshida ◽

Shuzo Usuku

Keyword(s):

Multidimensional Scaling ◽

Large Scale ◽

Local Community ◽

Amino Acid Sequences ◽

Time Dependent ◽

Small Scale ◽

Dependent Manner ◽

Environmental Surveillance ◽

Ecological Changes ◽

Over Time

ABSTRACT Environmental surveillance can be used to trace enteroviruses shed from human stool using a sewer network that is independent of symptomatic or asymptomatic infection. In this study, the local transmission of enteroviruses was analyzed using two wastewater treatment plants, which were relatively close to each other (15 km), designated as sentinels. Influent was collected at both sentinels once a month from 2013 to 2016, and viruses were isolated. Using neutralizing tests with type-specific polyclonal antisera and molecular typing, 933 isolates were identified as enteroviruses. Our results showed that the frequency of virus isolation varied for each serotype at the two sentinels in a time-dependent manner. Because echovirus 11 (Echo11) and coxsackievirus B5 isolates showed a high frequency and were difficult to distinguish, they were further grouped into various lineages based on the VP1 amino acid sequences. The prevalence of each lineage was visualized using multidimensional scaling. The results showed that Echo11 isolates of the same lineage were isolated continuously, similar to coxsackievirus B5 isolates of three lineages. Conversely, Echo1, Echo13, Echo18, Echo19, Echo20, Echo29, and Echo33 were isolated only once each. Our findings suggested that if an enterovirus is imported into the population, it may result in small-scale transmission, whereas if there are initially many infected individuals, it may be possible for the virus to spread to a wide area, beyond the local community, over time. In addition, our findings could provide insights into risk assessment of transmission for importation of poliovirus in polio-free countries and regions. IMPORTANCE In this study, we showed that environmental enterovirus surveillance can be used to monitor the propagation of nonpolio enteroviruses in addition to poliovirus detection. Since epidemiological studies of virus transmission based on the past were performed using specimens from humans, there were limitations to research design, such as specimen collection for implementation on a large-scale target population. However, environmental monitoring can dynamically track the ecological changes in enteroviruses in the region by monitoring viruses in chronological order and targeting the population within the area by monitoring viruses over time. We observed differences in the transmission of echovirus 11 and coxsackievirus B5 in the region according to lineage in a time-dependent manner and with a multidimensional scaling pattern.

Download Full-text

Effects of Exercise Restriction on Patients With Anomalous Aortic Origin of a Coronary Artery

World Journal for Pediatric and Congenital Heart Surgery ◽

10.1177/2150135116674444 ◽

2016 ◽

Vol 8 (1) ◽

pp. 18-24 ◽

Cited By ~ 6

Author(s):

Matthew D. Elias ◽

James Meza ◽

Brian W. McCrindle ◽

Julie A. Brothers ◽

Stephen Paridon ◽

...

Keyword(s):

Coronary Artery ◽

Exercise Capacity ◽

Repeated Measures ◽

Mixed Model ◽

Linear Mixed Model ◽

Multivariable Analysis ◽

Young Patients ◽

Significant Difference ◽

Exercise Restriction ◽

Over Time

Background: Management of young patients with anomalous aortic origin of a coronary artery (AAOCA) may involve exercise restriction. We sought to identify the association of exercise restriction with changes over time in body mass index (BMI) and exercise capacity in this cohort. Methods: We performed a retrospective review of patients with AAOCA seen at The Children’s Hospital of Philadelphia between January 1, 1998, and August 31, 2014. Linear mixed model repeated-measures analysis assessed changes in BMI and exercise capacity. Results: We included 72 patients with a median age at presentation of 12.6 years (interquartile range: 10.1-15.8) and mean follow-up of 3.6 ± 3.0 years. The majority had an anomalous right coronary artery (71%) and interarterial ± intramural coronary course (90%). Surgery was performed in 54%, more often in those with interarterial/intramural course ( P < .001) and symptoms ( P = .003). Most patients (82%) were exercise-restricted on presentation, and restricted patients were older than those who were not restricted ( P = .01). There was no significant difference between restricted and nonrestricted patients in initial BMI z scores, percentage of patients with BMI over 85th percentile (26%) or exercise capacity variables. In univariable analysis, exercise restriction over time was not associated with change in BMI z score ( P = .25) or change in exercise variables. Restriction was not associated with significant change in these variables in multivariable analysis. Conclusions: Although further investigation is warranted to determine the degree of adherence to exercise restriction, the recommendation of restriction alone is not associated with increasing BMI or decreasing exercise performance in the short-term.

Download Full-text

Substance Use Among Patients Receiving Out- and Inpatient Dependence Care: a Prospective Norwegian Cohort Study From 2016 to 2020

10.21203/rs.3.rs-566225/v1 ◽

2021 ◽

Author(s):

Jørn Henrik Vold ◽

Fatemeh Chalabianloo ◽

Christer F. Aas ◽

Else-Marie Løberg ◽

Kjell Arne Johansson ◽

...

Keyword(s):

Substance Use ◽

Mixed Model ◽

Linear Mixed Model ◽

Severity Index ◽

Future Research ◽

Opioid Agonist ◽

Low Threshold ◽

The Mean ◽

The Impact ◽

Over Time

Abstract BackgroundContinuous use of amphetamines, alcohol, benzodiazepines, cannabis, cocaine, or opioids contributes to health impairments, increased morbidity, and overdose deaths among patients with substance use disorders (SUDs). This study evaluates the impact of inpatient detoxification, specialized opioid agonist therapy (OAT), and low-threshold municipality care on substance use over time. MethodsWe used data from a cohort of SUD patients in Norway through health assessments of self-reported substance use and sociodemographic and clinical factors. A total of 881 substance use measurements, including type and amount of substances, were assessed from 708 SUD patients in 2016-2020. Substance use for individual and total substances was calculated, creating a substance use severity index (SUSI) ranging from zero (no use) to one (daily use). We defined baseline as the first substance use measurement when the measurements were listed chronologically. Time was defined as years from baseline. We used a linear mixed model to analyze associations between the SUSI and inpatient detoxification, specialized OAT compared with low-threshold municipality care, as well as the factors like injecting substance use, gender, and age, presented with coefficients and 95% confidence intervals (CI).ResultsNeither inpatient detoxification (mean SUSI change: 0.01, -0.03;0.04) nor specialized OAT (0.03, -0.09;0.14) compared with low-threshold municipality care were associated with changes in substance use over time. Patients who were over 60 years of age (mean SUSI difference: -0.06, -0.13;0.00) had a lower SUSI than those under 30 years of age, while patients who injected substances had a higher SUSI than those who did not inject substances (0.18, 0.15;0.20) at baseline. The mean SUSI for the individual substances were 0.50 (standard deviation (SD): 0.38) for cannabis, 0.40 (0.37) for benzodiazepines, 0.33 (0.34) for amphetamines and cocaine, 0.31 (0.29) for alcohol, and 0.22 (0.31) for opioids at baseline. The mean SUSI of all substances was 0.35 (0.20). Conclusion The present study demonstrates that neither inpatient detoxification nor specialized OAT compared to low-threshold municipality care were associated with changes in substance use over time. Future research needs to evaluate the impact on substance use and healthy survival of multiple health care interventions to this patient group.

Download Full-text

How nursing students’ placement preferences and perceptions of community care develop in a more ‘community-oriented’ curriculum; A longitudinal cohort study

10.21203/rs.2.22660/v1 ◽

2020 ◽

Author(s):

Margriet van Iersel ◽

Corine Latour ◽

Marjon van Rijn ◽

Rien de Vos ◽

Paul A. Kirschner ◽

...

Keyword(s):

Nursing Students ◽

Labour Market ◽

Nursing Student ◽

Mixed Model ◽

Linear Mixed Model ◽

Community Care ◽

Individual Level ◽

Nursing Curricula ◽

Marginal Means ◽

Over Time

Abstract Background: Extramuralisation in healthcare has influenced medical and nursing curricula internationally with the incorporation of themes related to primary/ community care. Despite this, students do not easily change their career preferences. The hospital is still favourite, leading to labour market shortages in extramural care. This study investigates how baccalaureate nursing students’ perceptions of community care and placement preferences develop over time in a more 'community-care-oriented' curriculum, to gain insights on which curriculum elements potentially influence career choices. Methods: A nursing student cohort of a University of Applied Sciences in the Netherlands ( n = 273) underwent a new four-year curriculum containing extended elements of community care. The primary outcome was assessed with the Scale on Community Care Perceptions (SCOPE). Data were collected each year of study. Descriptive statistics were used to investigate students’ placement preferences and perceptions, and linear mixed model techniques (LMMs) for measuring how students’ perceptions develop over time. Patterns of placement preferences at individual level were visualised. Results: Students’ perceptions of community care, as measured with SCOPE, show a slight decrease between year 1 and 4, while items mutually differ substantially. In contrast, the preference of community care for a placement increases from 2.6% in year 1 tot 8.2% in year 4. The hospital is favourite in year 1 (79.8%), and remains most popular. At individual level, students often change placement preferences, although a preference for the hospital is more consistent. The LMMs indicates that, at the four time-points, the estimated marginal means of students’ perceptions fluctuate between 6 and 7 (range 1-10). A placement in community care did not positively influence students’ perceptions, and an intensive one week theoretical programme was only temporarily influential. Conclusion: Although interest for placement in community care increased substantially, it was not clear which curriculum elements stimulated this, nor did the curriculum positively influence students’ perceptions. As most students do not look forward to the high responsibility of the field, other curricula with educational tracks for more mature students/ nurses with a vocational training may be an alternative contribution to solving the labour market problems in community care.

Download Full-text

Micronized Palmitoylethanolamide-Polydatin Reduces the Painful Symptomatology in Patients with Interstitial Cystitis/Bladder Pain Syndrome

BioMed Research International ◽

10.1155/2019/9828397 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

M. Cervigni ◽

L. Nasta ◽

C. Schievano ◽

N. Lampropoulou ◽

E. Ostardo

Keyword(s):

Interstitial Cystitis ◽

Pelvic Pain ◽

Mixed Model ◽

Linear Mixed Model ◽

Pain Syndrome ◽

Bladder Pain Syndrome ◽

Symptom Scale ◽

Open Label ◽

Bladder Pain ◽

Over Time

Aims. To assess the efficacy of a micronized-palmitoylethanolamide-polydatin (m-PEA-Pol) based product on chronic pelvic pain and severity of other symptoms in interstitial cystitis/bladder pain syndrome (IC/BPS) patients refractory to conventional therapies. Methods. A pilot, open-label bicentric study was carried out involving 32 IC/BPS patients. Chronic, oral m-PEA-Pol treatment lasted 6 months. Bladder pain was evaluated using the visual analog scale, while changes from baseline in other urinary symptoms were evaluated by means of the O’Leary-Sant Interstitial Cystitis Symptom and Problem Index and the Pelvic Pain and Urgency/Frequency (PUF) symptom scale questionnaires. The generalized linear mixed model was used to evaluate significant mean changes across time. Results. A significant and progressive reduction of pain intensity was observed during m-PEA-Pol treatment (p<0.0001 for reduction over time). The effect was associated with a reduction in severity of patients’ symptoms evaluated with the O’Leary-Sant questionnaire (p=0.0110 and p=0.0014 for cystitis symptoms and problem mean scores, respectively) and the PUF scale (p=0.0163 and p=0.0005 for symptom and bother mean scores, respectively). m-PEA-Pol therapy elicited a significant reduction over time in the urinary frequency evaluated with voiding diary (p=0.0005) and a small but not significant improvement of bladder capacity. Conclusions. These data highlight the potential benefit of m-PEA-Pol in patients with rare pathology such as IC/BPS and confirm the good safety profile of micronized PEA-based products.

Download Full-text

Change Point Detection For Clustered Expression Data In Short Time Series.

10.21203/rs.3.rs-605289/v1 ◽

2021 ◽

Author(s):

Miriam Sieg ◽

Lina Katrin Sciesielski ◽

Karin Kirschner ◽

Jochen Kruppa

Keyword(s):

Time Series ◽

Confidence Intervals ◽

Change Point ◽

Mixed Model ◽

Linear Mixed Model ◽

Change Point Detection ◽

Change Points ◽

Point Detection ◽

Over Time ◽

Time Point

Abstract Background: In longitudinal studies, observations are made over time. Hence, the single observations at each time point are dependent, making them a repeated measurement. In this work, we explore a different, counterintuitive setting: At each developmental time point, a lethal observation is performed on the pregnant or nursing mother. Therefore, the single time points are independent. Furthermore, the observation in the offspring at each time point is correlated with each other because each litter consists of several (genetically linked) littermates. In addition, the observed time series is short from a statistical perspective as animal ethics prevent killing more mother mice than absolutely necessary, and murine development is short anyway. We solve these challenges by using multiple contrast tests and visualizing the change point by the use of confidence intervals.Results: We used linear mixed models to model the variability of the mother. The estimates from the linear mixed model are then used in multiple contrast tests.There are a variety of contrasts and intuitively, we would use the Changepoint method. However, it does not deliver satisfying results. Interestingly, we found two other contrasts, both capable of answering different research questions in change point detection: i) Should a single point with change direction be found, or ii) Should the overall progression be determined? The Sequen contrast answers the first, the McDermott the second. Confidence intervals deliver effect estimates for the strength of the potential change point. Therefore, the scientist can define a biologically relevant limit of change depending on the research question.Conclusion: We present a solution with effect estimates for short independent time series with observations nested at a given time point. Multiple contrast tests produce confidence intervals, which allow determining the position of change points or to visualize the expression course over time. We suggest to use McDermott’s method to determine if there is an overall significant change within the time frame, while Sequen is better in determining specific change points. In addition, we offer a short formula for the estimation of the maximal length of the time series.

Download Full-text

Genetic Variants in the Genes of the Stress Hormone Signalling Pathway and Depressive Symptoms during and after Pregnancy

BioMed Research International ◽

10.1155/2014/469278 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 11

Author(s):

Michael Schneider ◽

Anne Engel ◽

Peter A. Fasching ◽

Lothar Häberle ◽

Elisabeth B. Binder ◽

...

Keyword(s):

Depressive Symptoms ◽

Pregnant Women ◽

Mixed Model ◽

Linear Mixed Model ◽

Depression Scale ◽

Fixed Time ◽

Nucleotide Polymorphisms ◽

Stress Hormone ◽

Time Points ◽

Over Time

Purpose. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes of the stress hormone signaling pathway, specificallyFKBP5,NR3C1, andCRHR1, are associated with depressive symptoms during and after pregnancy.Methods. The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for the assessment of maternal and fetal health including the assessment of depressiveness. The German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) was completed at three time points in this prospective cohort study. Visit 1 was at study entry in the third trimester of the pregnancy, visit 2 was shortly after birth, and visit 3 was 6–8 months after birth. Germline DNA was collected from 361 pregnant women. Nine SNPs in the above mentioned genes were genotyped. After construction of haplotypes for each gene, a multifactorial linear mixed model was performed to analyse the depression values over time.Results. EPDS values were within expected ranges and comparable to previously published studies. Neither did the depression scores differ for comparisons among haplotypes at fixed time points nor did the change over time differ among haplotypes for the examined genes. No haplotype showed significant associations with depressive symptoms severity during pregnancy or the postpartum period.Conclusion. The analysed candidate haplotypes inFKBP5,NR3C1, andCRHR1did not show an association with depression scores as assessed by EPDS in this cohort of healthy unselected pregnant women.

Download Full-text

Retention in Continuous Care and Sustained Viral Suppression

Journal of the International Association of Providers of AIDS Care (JIAPAC) ◽

10.1177/2325957416678929 ◽

2016 ◽

Vol 16 (1) ◽

pp. 42-47 ◽

Cited By ~ 11

Author(s):

Timothy N. Crawford ◽

Alice Thornton

Keyword(s):

Viral Suppression ◽

Mixed Model ◽

Linear Mixed Model ◽

Generalized Linear Mixed Model ◽

Sustained Viral Suppression ◽

Continuous Care ◽

Disease Clinic ◽

Study Population ◽

The Relationship ◽

Over Time

Objectives: To examine the relationship between retention in continuous care and sustained viral suppression. Methods: The authors retrospectively followed 653 persons who were virally suppressed and seeking care at an infectious disease clinic in Kentucky for an average of 6 years to determine the rates of retention in medical care (≥2 visits separated by ≥3 months within a 12-month period) and sustained viral suppression (<400 copies/mL). A generalized linear mixed model was used to determine an association between retention and suppression over time. Results: Approximately 61% of the study population were retained in continuous care and 75% had sustained viral suppression for all patient-years. Persons retained in care were 3 times the odds of sustaining viral suppression over time ( P < .001). Conclusion: Retention is essential to achieving and maintaining viral suppression. Strategies should be set in place that emphasize increasing the rates of retention, which in turn may increase the rates of suppression.

Download Full-text