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Article ; Online: Generation of four iPSC lines from four patients with Leigh syndrome carrying homoplasmic mutations m.8993T > G or m.8993T > C in the mitochondrial gene MT-ATP6.

Lorenz, Carmen / Zink, Annika / Henke, Marie-Therese / Staege, Selma / Mlody, Barbara / Bünning, Miriam / Wanker, Erich / Diecke, Sebastian / Schuelke, Markus / Prigione, Alessandro

Stem cell research

2022 Volume 61, Page(s) 102742

Abstract: ... mutations m.8993T > G or m.8993T > C in the mitochondrial gene MT-ATP6. We used Sendai viruses to deliver ... reprogramming factors OCT4, SOX2, KLF4, and c-MYC. The established iPSC lines expressed pluripotency markers ...

Abstract	We report the generation of four human iPSC lines (8993-A12, 8993-B12, 8993-C11, and 8993-D7) from fibroblasts of four patients affected by maternally inherited Leigh syndrome (MILS) carrying homoplasmic mutations m.8993T > G or m.8993T > C in the mitochondrial gene MT-ATP6. We used Sendai viruses to deliver reprogramming factors OCT4, SOX2, KLF4, and c-MYC. The established iPSC lines expressed pluripotency markers, exhibited a normal karyotype, were capable to form cells of the three germ layers in vitro, and retained the MT-ATP6 mutations at the same homoplasmic level of the parental fibroblasts.
MeSH term(s)	Fibroblasts ; Genes, Mitochondrial ; Humans ; Induced Pluripotent Stem Cells ; Leigh Disease/genetics ; Mitochondrial Proton-Translocating ATPases/genetics ; Mutation/genetics
Chemical Substances	MT-ATP6 protein, human ; Mitochondrial Proton-Translocating ATPases (EC 3.6.3.-)
Language	English
Publishing date	2022-03-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2393143-7
ISSN	1876-7753 ; 1873-5061
ISSN (online)	1876-7753
ISSN	1873-5061
DOI	10.1016/j.scr.2022.102742
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Article ; Online: RNA-based generation of iPSCs from a boy carrying the mutation m.9185 T>C in the mitochondrial gene MT-ATP6 and from his healthy mother.

Steiner, Tabea / Zink, Annika / Henke, Marie-Therese / Cecchetto, Giulia / Buenning, Miriam / Rossi, Andrea / Schuelke, Markus / Prigione, Alessandro

Stem cell research

2022 Volume 64, Page(s) 102920

Abstract: ... from a young male carrying the mutation m.9185 T>C in the mitochondrial gene MT-ATP6 (present at virtual ...

Abstract	We used a non-integrative self-replicating RNA vector to establish four iPSC lines: two iPSC lines from a young male carrying the mutation m.9185 T>C in the mitochondrial gene MT-ATP6 (present at virtual homoplasmic level), and two iPSC lines from his healthy mother (carrying the mutation in only about 4 % of mtDNA copies). All iPSC lines exhibited pluripotency characteristics, were capable to give rise to cells of the three germ layers in vitro, and presented a normal karyotype. The derived iPSC lines retained the MT-ATP6 mutation at levels similar to those observed in the parental fibroblasts.
MeSH term(s)	Humans ; Female ; Male ; Induced Pluripotent Stem Cells ; Genes, Mitochondrial ; RNA ; Mothers ; DNA, Mitochondrial/genetics ; Mutation/genetics ; Mitochondrial Proton-Translocating ATPases/genetics
Chemical Substances	RNA (63231-63-0) ; DNA, Mitochondrial ; MT-ATP6 protein, human ; Mitochondrial Proton-Translocating ATPases (EC 3.6.3.-)
Language	English
Publishing date	2022-09-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2393143-7
ISSN	1876-7753 ; 1873-5061
ISSN (online)	1876-7753
ISSN	1873-5061
DOI	10.1016/j.scr.2022.102920
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Article ; Online: Generation of four iPSC lines from four patients with Leigh syndrome carrying homoplasmic mutations m.8993T > G or m.8993T > C in the mitochondrial gene MT-ATP6

Carmen Lorenz / Annika Zink / Marie-Therese Henke / Selma Staege / Barbara Mlody / Miriam Bünning / Erich Wanker / Sebastian Diecke / Markus Schuelke / Alessandro Prigione

Stem Cell Research, Vol 61, Iss , Pp 102742- (2022)

2022

Abstract	We report the generation of four human iPSC lines (8993-A12, 8993-B12, 8993-C11, and 8993-D7) from fibroblasts of four patients affected by maternally inherited Leigh syndrome (MILS) carrying homoplasmic mutations m.8993T > G or m.8993T > C in the mitochondrial gene MT-ATP6. We used Sendai viruses to deliver reprogramming factors OCT4, SOX2, KLF4, and c-MYC. The established iPSC lines expressed pluripotency markers, exhibited a normal karyotype, were capable to form cells of the three germ layers in vitro, and retained the MT-ATP6 mutations at the same homoplasmic level of the parental fibroblasts.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: The Influence of Strength and Sport Exposure on Psychological Readiness After ACL Reconstruction.

Zink, Griffin P / Zwolski, Christin M / Thomas, Staci M / Paterno, Mark V / Schmitt, Laura C

Sports health

2024 Volume 16, Issue 2, Page(s) 239–246

Abstract: Background: Among young athletes returning to sport after anterior cruciate ligament reconstruction (ACLR), the extent to which psychological readiness is influenced by factors beyond the psychological domain is largely unknown.: Hypothesis: Young ... ...

Abstract	Background: Among young athletes returning to sport after anterior cruciate ligament reconstruction (ACLR), the extent to which psychological readiness is influenced by factors beyond the psychological domain is largely unknown. Hypothesis: Young athletes with recent sport exposure and higher quadriceps strength will demonstrate higher psychological readiness within 8 weeks of medical clearance to return to sport (RTS) after ACLR. Study design: Cross-sectional study. Level of evidence: Level 3. Methods: A total of 38 young athletes after primary ACLR completed testing within 8 weeks of medical clearance to RTS. All participants completed isometric knee extension strength testing, in addition to the ACL Return to Sport after Injury (ACL-RSI) questionnaire. Athletes who participated in sport between time of medical clearance to RTS and date of study enrollment were categorized as SPORT-YES. Those who had not yet participated in sports were categorized as SPORT-NO. Multiple linear regression analyses were used to determine differences in ACL-RSI scores based on quadriceps strength and sport exposure status, while adjusting for age and sex. Results: Of the 38 participants, 20 (52.6%) were categorized as SPORT-YES. The regression model estimating overall ACL-RSI score ( Conclusion: In partial accordance with our hypothesis, recent sport exposure was significantly associated with higher ACL-RSI scores among young athletes in the weeks after medical clearance to RTS after ACLR, while quadriceps strength was not. Clinical relevance: Future prospective work is needed to determine the existence and direction of causal relationships between exposure to sport environment and psychological readiness among young athletes after ACLR.
MeSH term(s)	Humans ; Male ; Anterior Cruciate Ligament Injuries/surgery ; Anterior Cruciate Ligament Injuries/psychology ; Cross-Sectional Studies ; Sports ; Return to Sport/psychology ; Athletes
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2508802-6
ISSN	1941-0921 ; 1941-7381
ISSN (online)	1941-0921
ISSN	1941-7381
DOI	10.1177/19417381231223522
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Article ; Online: Vasectomy and ovary-sparing spay in dogs: comparison of health and behavior outcomes with gonadectomized and sexually intact dogs.

Zink, Chris / Delgado, Mikel M / Stella, Judith L

Journal of the American Veterinary Medical Association

2023 Volume 261, Issue 3, Page(s) 366–374

Abstract: Objective: To compare health and behavior outcomes for dogs that underwent vasectomy or ovary-sparing spay (hysterectomy) with sexually intact dogs or dogs that had undergone traditional castration or spay.: Sample: 6,018 dog owners responded to a ... ...

Abstract	Objective: To compare health and behavior outcomes for dogs that underwent vasectomy or ovary-sparing spay (hysterectomy) with sexually intact dogs or dogs that had undergone traditional castration or spay. Sample: 6,018 dog owners responded to a web-based survey between November 3, 2021, and January 7, 2022. Procedures: Participants were asked demographic questions and to provide information about 1 or more dogs (living or deceased). Options for reproductive status were as follows: sexually intact, castrated, spayed (ovariohysterectomy or ovariectomy), vasectomy, or ovary-sparing spay (hysterectomy). Participants were asked questions about orthopedic and other health problems, cancer, and problematic behavior. Logistic regression models, survival analyses, and descriptive statistics were used to assess relationships between reproductive status and outcomes. Results: Owners provided valid surveys for 6,018 dogs, including 1,056 sexually intact, 1,672 castrated, and 58 vasectomized male dogs and 792 sexually intact, 2,281 spayed, and 159 female dogs that had undergone ovary-sparing spay. Longer exposure to gonadal hormones, regardless of reproductive status, was associated with reduced odds of general health problems and both problematic and nuisance behaviors. Clinical relevance: To our knowledge, this study provides the first data on health and behavior outcomes of vasectomy and ovary-sparing spay in dogs and is the first to compare these outcomes to sexually intact and gonadectomized dogs. It adds to accumulating data on the mixed benefits and risks of removing the gonads to prevent reproduction and emphasizes the importance of developing an informed, case-by-case assessment of each patient, taking into consideration the potential risks and benefits of spaying or neutering and alternative reproductive surgeries.
MeSH term(s)	Dogs ; Male ; Female ; Animals ; Ovary ; Vasectomy/veterinary ; Ovariectomy/veterinary ; Hysterectomy/veterinary ; Health Behavior
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	390811-2
ISSN	1943-569X ; 0003-1488
ISSN (online)	1943-569X
ISSN	0003-1488
DOI	10.2460/javma.22.08.0382
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Article ; Online: Family discussions and demographic factors influence adolescent's knowledge and attitude towards organ donation after brain death: a questionnaire study.

Stadlbauer, Vanessa / Zink, Christoph / Likar, Paul / Zink, Michael

BMC medical ethics

2020 Volume 21, Issue 1, Page(s) 57

Abstract: Background: Knowledge and attitude towards organ donation are critical factors influencing organ donation rate. We aimed to assess the knowledge and attitude towards organ donation in adolescents in Austria and Switzerland.: Methods: A paper-based ... ...

Abstract	Background: Knowledge and attitude towards organ donation are critical factors influencing organ donation rate. We aimed to assess the knowledge and attitude towards organ donation in adolescents in Austria and Switzerland. Methods: A paper-based survey was performed in two secondary schools (age range 11-20 years) in Austria and Switzerland. 354/400 surveys were sufficiently answered and analyzed. Results: Our study found that knowledge on organ donation is scarce in adolescents. Less than 60% of those surveyed thinks that a person is dead when declared brain dead. 84.6% would authorize organ donation after brain death for themselves, but only 69% would authorize organ donation after brain death for a close relative. 93.7% would accept a donor organ if they needed one. Family discussions, rather than school discussions, influenced knowledge on organ donation, the percentage of respondents who have a firm opinion on organ donation and the rate of declaration of this opinion. Age, gender, nationality and religion also influenced knowledge and attitude towards organ donation. Nearly one third of adolescents are of the opinion that selling non-vital organs should be legalized. Conclusion: Since having had family discussions, a potentially modifiable factor, was positively associated with knowledge and attitude towards organ donation, we postulate that educational programs stimulating family discussions on organ donation may be a promising strategy to increase knowledge.
MeSH term(s)	Adolescent ; Adult ; Austria ; Brain Death ; Child ; Demography ; Health Knowledge, Attitudes, Practice ; Humans ; Surveys and Questionnaires ; Switzerland ; Tissue and Organ Procurement ; Young Adult
Language	English
Publishing date	2020-07-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2041552-7
ISSN	1472-6939 ; 1472-6939
ISSN (online)	1472-6939
ISSN	1472-6939
DOI	10.1186/s12910-020-00499-x
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Article ; Online: Effects of water quality on palladium-induced olfactory toxicity and bioaccumulation in rainbow trout (Oncorhynchus mykiss).

Simonis, Carolyn / Zink, Lauren / Johnston, Sarah E / Bogard, Matthew / Pyle, Gregory G

Integrated environmental assessment and management

2024

Abstract: Through emission processes, palladium (Pd) particulates from industrial sources are introduced into a range of ecosystems including freshwater environments. Despite this, research on Pd-induced bioaccumulation, uptake, and toxicity is limited for ... ...

Abstract	Through emission processes, palladium (Pd) particulates from industrial sources are introduced into a range of ecosystems including freshwater environments. Despite this, research on Pd-induced bioaccumulation, uptake, and toxicity is limited for freshwater fishes. Unlike other metals, there are currently no regulations or protective guidelines to limit Pd release into aquatic systems, indicating a global absence of measures addressing its environmental impact. To assess the olfactory toxicity potential of Pd, the present study aimed to explore Pd accumulation in olfactory tissues, olfactory disruption, and oxidative stress in rainbow trout (Oncorhynchus mykiss) following waterborne Pd exposure. Olfactory sensitivity, measured by electro-olfactography, demonstrated that Pd inhibits multiple pathways of the olfactory system following 96 h of Pd exposure. In this study, the concentrations of Pd for inhibition of olfactory function by 20% (2.5 μg/L; IC20) and 50% (19 μg/L; IC50) were established. Rainbow trout were then exposed to IC20 and IC50 Pd concentrations in combination with varying exposure conditions, as changes in water quality alter the toxicity of metals. Independent to Pd, increased water hardness resulted in decreased olfactory perception owing to ion competition at the olfactory epithelium. No other environmental parameter in this study significantly influenced Pd-induced olfactory toxicity. Membrane-associated Pd was measured at the olfactory rosette and gill following exposure; however, this accumulation did not translate to oxidative stress as measured by the production of malondialdehyde. Our data suggest that Pd is toxic to rainbow trout via waterborne contamination near field-measured levels. This study further demonstrated Pd bioavailability and uptake at water-adjacent tissues, adding to our collective understanding of the toxicological profile of Pd. Taken together, our results provide novel insights into the olfactory toxicity in fish following Pd exposure. Integr Environ Assess Manag 2024;00:1-13. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2234931-5
ISSN	1551-3793 ; 1551-3777
ISSN (online)	1551-3793
ISSN	1551-3777
DOI	10.1002/ieam.4900
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Article ; Online: How effective is drinking natural mineral water against heartburn from functional dyspepsia, gastroesophageal reflux disease or other causes? A systematic review of clinical intervention studies.

D'Souza, Arun / Zink, Katharina / Langhorst, Jost / Wildner, Manfred / Stupp, Carolin / Keil, Thomas

Complementary medicine research

2024

Abstract: Background For centuries, spring and other natural waters have been recommended as external or internal remedies for numerous diseases. For studies that examined the effects of drinking mineral waters against heartburn, gastroesophageal reflux disease ( ... ...

Abstract	Background For centuries, spring and other natural waters have been recommended as external or internal remedies for numerous diseases. For studies that examined the effects of drinking mineral waters against heartburn, gastroesophageal reflux disease (GERD), or functional dyspepsia a systematic review is lacking. Objectives The main aim of this systematic review was to examine the effects of drinking natural mineral waters on heartburn from various causes by identifying all published intervention studies and critically appraising their methods as well as summarizing their results. Methods We systematically searched the largest medical literature database MEDLINE, further relevant web sources and gray literature for randomized and non-randomized trials, with or without control groups, up to September 2021 and no language restrictions. Further inclusion criteria were adult patients with heartburn, drinking cure with natural mineral water as intervention, compared to no or other interventions (care-as-usual, waiting list). We defined the reduction of heartburn symptoms and duration of disease episodes as primary and quality of life as secondary outcomes. Two reviewers independently carried out the study quality assessments (risk of bias) using the National Institutes of Health-Study Quality Assessment Tools. Results Nine trials comprising 393 patients from Italy, Russia, Ukraine, and Germany fulfilled all inclusion criteria. We identified three randomized controlled trials (all with poor methodological quality), plus six before-after (pre/post) intervention studies without a control group. The intervention groups of the three comparative trials seemed to show a stronger reduction of self-reported heartburn symptoms, and duration of heartburn episodes than the respective control groups, however they all had a poor methodological quality. Conclusion Based on the best available evidence of clinical studies, we cannot recommend or advise against drinking natural mineral waters as a treatment for heartburn. The potential benefits of natural mineral waters that were reported in some studies with a lower evidence level (e.g., lacking a control group) should be verified by good quality randomized clinical trials with adequate comparison groups and longer follow-up periods. .
Language	English
Publishing date	2024-03-12
Publishing country	Switzerland
Document type	Systematic Review
ZDB-ID	2885931-5
ISSN	2504-2106 ; 2504-2092
ISSN (online)	2504-2106
ISSN	2504-2092
DOI	10.1159/000536528
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Article ; Online: Association of behavioural and social-communicative profiles in children with 16p11.2 copy number variants: a multi-site study.

Verbesselt, J / Walsh, L K / Mitchel, M W / Taylor, C M / Finucane, B M / Breckpot, J / Zink, I / Swillen, A

Journal of intellectual disability research : JIDR

2024

Abstract: Background: Despite the established knowledge that recurrent copy number variants (CNVs) at the 16p11.2 locus BP4-BP5 confer risk for behavioural and language difficulties, limited research has been conducted on the association between behavioural and ... ...

Abstract	Background: Despite the established knowledge that recurrent copy number variants (CNVs) at the 16p11.2 locus BP4-BP5 confer risk for behavioural and language difficulties, limited research has been conducted on the association between behavioural and social-communicative profiles. The current study aims to further delineate the prevalence, nature and severity of, and the association between, behavioural and social-communicative features of school-aged children with 16p11.2 deletion syndrome (16p11.2DS) and 16p11.2 duplication (16p11.2Dup). Methods: A total of 68 individuals (n = 47 16p11.2DS and n = 21 16p11.2Dup) aged 6-17 years participated. Standardised intelligence tests were administered, and behavioural and social-communicative skills were assessed by standardised questionnaires. Scores of both groups were compared with population norms and across CNVs. The influence of confounding factors was investigated, and correlation analyses were performed. Results: Compared with the normative sample, children with 16p11.2DS showed high rates of social responsiveness (67%) and communicative problems (69%), while approximately half (52%) of the patients displayed behavioural problems. Children with 16p11.2Dup demonstrated even higher rates of social-communicative problems (80-90%) with statistically significantly more externalising and overall behavioural challenges (89%). In both CNV groups, there was a strong positive correlation between behavioural and social-communicative skills. Conclusions: School-aged children with 16p11.2 CNVs show high rates of behavioural, social responsiveness and communicative problems compared with the normative sample. These findings point to the high prevalence of autistic traits and diagnoses in these CNV populations. Moreover, there is a high comorbidity between behavioural and social-communicative problems. Patients with difficulties in both domains are vulnerable and need closer clinical follow-up and care.
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	1103832-9
ISSN	1365-2788 ; 0964-2633
ISSN (online)	1365-2788
ISSN	0964-2633
DOI	10.1111/jir.13141
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Article ; Online: Ultra-deep sequencing of 45S rDNA to discern intragenomic diversity in three Chrysodeixis species for molecular identification.

Zink, Frida A / Tembrock, Luke R / Timm, Alicia E / Gilligan, Todd M

Scientific reports

2023 Volume 13, Issue 1, Page(s) 13017

Abstract: ... three species of potential concern for United States trade initiatives: C. includens, C. chalcites, and ... C. eriosoma. Here we describe a method to generate robust 45S rDNA profiles using long read ...

Abstract	Species identification is necessary to prevent introductions of exotic plant pests through global trade. Many of these pests are understudied and lack publicly available DNA sequence data on which rapid molecular identification methods can be based. One such lineage is the genus Chrysodeixis, which includes three species of potential concern for United States trade initiatives: C. includens, C. chalcites, and C. eriosoma. Here we describe a method to generate robust 45S rDNA profiles using long read sequencing in order to clarify evolutionary relationships and develop a real-time PCR identification technique. Such an identification tool will be useful in rapidly differentiating between Chrysodeixis species of quarantine concern where traditional morphological identification methods are insufficient. Molecular methods such as this greatly reduce the time spent identifying each specimen, allow for detection of eDNA, vastly increase throughput, and increase the probability of detection. The methods presented here will be generally adaptable to any understudied lepidopteran taxa that necessitates a molecular diagnostic assay and, with adjustment or testing of the primers, could be applied to any group for which development of rDNA profiles in a benchtop setting would prove useful.
MeSH term(s)	Animals ; DNA, Ribosomal/genetics ; Moths/genetics ; High-Throughput Nucleotide Sequencing
Chemical Substances	DNA, Ribosomal
Language	English
Publishing date	2023-08-10
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-39673-7
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