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BMC Psychiatry Jun 202322q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal interstitial-deletion disorder, occurring in approximately 1 in 2000 to 6000 live births. Affected...
BACKGROUND
22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal interstitial-deletion disorder, occurring in approximately 1 in 2000 to 6000 live births. Affected individuals exhibit variable clinical phenotypes that can include velopharyngeal anomalies, heart defects, T-cell-related immune deficits, dysmorphic facial features, neurodevelopmental disorders, including autism, early cognitive decline, schizophrenia, and other psychiatric disorders. Developing comprehensive treatments for 22q11.2DS requires an understanding of both the psychophysiological and neural mechanisms driving clinical outcomes. Our project probes the core psychophysiological abnormalities of 22q11.2DS in parallel with molecular studies of stem cell-derived neurons to unravel the basic mechanisms and pathophysiology of 22q11.2-related psychiatric disorders, with a primary focus on psychotic disorders. Our study is guided by the central hypothesis that abnormal neural processing associates with psychophysiological processing and underlies clinical diagnosis and symptomatology. Here, we present the scientific background and justification for our study, sharing details of our study design and human data collection protocol.
METHODS
Our study is recruiting individuals with 22q11.2DS and healthy comparison subjects between the ages of 16 and 60 years. We are employing an extensive psychophysiological assessment battery (e.g., EEG, evoked potential measures, and acoustic startle) to assess fundamental sensory detection, attention, and reactivity. To complement these unbiased measures of cognitive processing, we will develop stem-cell derived neurons and examine neuronal phenotypes relevant to neurotransmission. Clinical characterization of our 22q11.2DS and control participants relies on diagnostic and research domain criteria assessments, including standard Axis-I diagnostic and neurocognitive measures, following from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and the North American Prodrome Longitudinal Study (NAPLS) batteries. We are also collecting measures of autism spectrum (ASD) and attention deficit/hyperactivity disorder (ADHD)-related symptoms.
DISCUSSION
Studying 22q11.2DS in adolescence and adulthood via deep phenotyping across multiple clinical and biological domains may significantly increase our knowledge of its core disease processes. Our manuscript describes our ongoing study's protocol in detail. These paradigms could be adapted by clinical researchers studying 22q11.2DS, other CNV/single gene disorders, or idiopathic psychiatric syndromes, as well as by basic researchers who plan to incorporate biobehavioral outcome measures into their studies of 22q11.2DS.
Topics: Adolescent; Adult; Humans; Child; Young Adult; Middle Aged; DiGeorge Syndrome; Longitudinal Studies; Psychotic Disorders; Autistic Disorder; Child Development Disorders, Pervasive; Chromosome Deletion
PubMed: 37312091
DOI: 10.1186/s12888-023-04888-5 -
Frontiers in Cell and Developmental... 2022Chromatinopathies are defined as genetic disorders caused by mutations in genes coding for protein involved in the chromatin state balance. So far 82 human conditions... (Review)
Review
Chromatinopathies are defined as genetic disorders caused by mutations in genes coding for protein involved in the chromatin state balance. So far 82 human conditions have been described belonging to this group of congenital disorders, sharing some molecular features and clinical signs. For almost all of these conditions, no specific treatment is available. For better understanding the molecular cascade caused by chromatin imbalance and for envisaging possible therapeutic strategies it is fundamental to combine clinical and basic research studies. To this end, animal modelling systems represent an invaluable tool to study chromatinopathies. In this review, we focused on available data in the literature of animal models mimicking the human genetic conditions. Importantly, affected organs and abnormalities are shared in the different animal models and most of these abnormalities are reported as clinical manifestation, underlying the parallelism between clinics and translational research.
PubMed: 36225316
DOI: 10.3389/fcell.2022.979512 -
PeerJ 2022Thyroid-associated ophthalmopathy (TAO) is a common orbital inflammatory disease, but the abnormal expression of proteins in tears of TAO patients has not been...
BACKGROUND
Thyroid-associated ophthalmopathy (TAO) is a common orbital inflammatory disease, but the abnormal expression of proteins in tears of TAO patients has not been systematically studied. The purpose of this study is to compare and analyze the total tear protein profile of TAO patients and to provide protein cues for TAO pathogenesis.
METHODS
Tear samples were isolated from 30 TAO patients with obvious ocular surface damage and 30 healthy control subjects. Tear samples from 30 individuals were mixed and divided into three sample pools. Easy nano-scale LC-MS/MS based on labeling-free quantitative technology was utilized to profile tear proteome.
RESULTS
Here, electrospray ionization mass spectra and SDS-PAGE results confirmed the good parallelisms among samples. A total of 313 proteins were obtained from six tear pools, among them, 103 differential abundance proteins (DAPs) were identified, including 99 up-regulated DAPs (including APOA1, HV103, IGH, and Transferrin variant) and four down-regulated DAPs (including FABA, VCC1, NUCB2, and E-cadherin) in the TAO group compared with the control group. GO analysis showed that up-regulated DAPs were mainly enriched in lipid metabolism and platelet molecular function, and down-regulated DAPs were involved in binding, cell junction, and cellular process. KEGG results indicated that DAPs were involved in 117 kinds of signal transduction pathways, among which the immune-related pathway of complement and coagulation cascades had the greatest relevance.
CONCLUSION
In conclusion, label-free LC-MS/MS is an effective strategy for profiling tear proteins component. Our study provides proteins and pathways altered in TAO and provides protein cues for further study on the precise mechanism of TAO pathogenesis.
Topics: Humans; Graves Ophthalmopathy; Proteome; Chromatography, Liquid; Tandem Mass Spectrometry; Tears; Lacerations
PubMed: 35846879
DOI: 10.7717/peerj.13701 -
BMC Medical Education Mar 2022Compared to other road users, ambulance drivers are at a higher accident risk while driving with warning lights and sirens. No standard exists for training or education...
BACKGROUND
Compared to other road users, ambulance drivers are at a higher accident risk while driving with warning lights and sirens. No standard exists for training or education for emergency medical service employees driving ambulances. Training programs should positively influence knowledge. However, knowledge gain can be influenced by several different factors. This study developed a knowledge test for ambulance drivers to determine influencing factors on knowledge and its gain by simulator-based training.
METHODS
Two parallel knowledge test forms with 20 questions each were designed in several steps and tested on up to 174 participants. Questionnaires were used to study associated and influencing factors, such as objective experience, subjective attitudes, personality, motivation and demographic data.
RESULTS
Test construction showed good overall parallelism of the two tests as well as reliability and sensitivity. There was no correlation between subjective and objective knowledge gain, but participants with higher subjective knowledge gain showed a higher variation in objective knowledge. Younger age, higher qualification, higher number of license classes, fewer traffic violations, and more traffic safety trainings were positively associated with knowledge, whereas less yearly driving mileage, more traffic safety trainings, and higher risk sensitivity positively influenced knowledge gain through the training.
CONCLUSION
Knowledge and its gain through training are very low. Reasons for the lack of predictive power of some variables, such as motivation, personality and attitudes, are discussed. This study presents a new tool for testing knowledge on driving with warning lights and sirens. It shows the need for objective testing and for further research in this special area.
Topics: Accidents, Traffic; Ambulances; Automobile Driving; Humans; Licensure; Reproducibility of Results
PubMed: 35354466
DOI: 10.1186/s12909-022-03279-w -
International Journal of Molecular... Jan 2022As part of a complex network of genome control, long regulatory RNAs exert significant influences on chromatin dynamics. Understanding how this occurs could illuminate... (Review)
Review
As part of a complex network of genome control, long regulatory RNAs exert significant influences on chromatin dynamics. Understanding how this occurs could illuminate new avenues for disease treatment and lead to new hypotheses that would advance gene regulatory research. Recent studies using the model fission yeast () and powerful parallel sequencing technologies have provided many insights in this area. This review will give an overview of key findings in that relate long RNAs to multiple levels of chromatin regulation: histone modifications, gene neighborhood regulation in and higher-order chromosomal ordering. Moreover, we discuss parallels recently found in mammals to help bridge the knowledge gap between the study systems.
Topics: Chromatin; Histone Code; Protein Processing, Post-Translational; RNA, Fungal; RNA, Long Noncoding; Schizosaccharomyces; Schizosaccharomyces pombe Proteins
PubMed: 35055152
DOI: 10.3390/ijms23020968 -
JCO Clinical Cancer Informatics Feb 2022This is an update to a previously published report characterizing the impact that efforts to control the COVID-19 pandemic have had on the normal course of...
PURPOSE
This is an update to a previously published report characterizing the impact that efforts to control the COVID-19 pandemic have had on the normal course of cancer-related encounters.
METHODS
Data were analyzed from 22 US health care organizations (members of the TriNetX global network) having relevant, up-to-date encounter data. Although the original study compared encounter data pre-COVID-19 (January-April 2019) with the corresponding months in 2020, this update considers data through April 2021. As before, cohorts were generated for all neoplasm patients (malignant, benign, in situ, and of unspecified behavior), all new incidence neoplasm patients, exclusively malignant neoplasm patients, and new incidence malignant neoplasm patients. Data on the initial cancer stage were available for calendar year 2020 from about one third of the study's organizations.
RESULTS
Although COVID-19 cases fluctuated through 2021, newly diagnosed cancers closely paralleled the prepandemic base year 2019. Similarly, screening for breast, colorectal, and cervical cancers quickly recovered beginning in May 2020 to prepandemic numbers. Preliminary data for the initial cancer stage showed no significant difference ( > .10) in distribution for breast or colon cancers between 2019 and 2020.
CONCLUSION
Although the number of COVID-19 cases fluctuated, the steep declines observed during March and April 2020 in screening for breast and colon cancer and patients with newly diagnosed cancer did not continue through the rest of 2020 and into April 2021. Screening and new incidence cancer numbers quickly rose compared with prepandemic levels. The concern that more patients with advanced-stage cancer would be seen in the months following the drastic dips of March-April 2020 was not realized as the major disruption to normal cancer care was limited to these 2 months.
Topics: COVID-19; Humans; Incidence; Neoplasms; Pandemics; SARS-CoV-2
PubMed: 35258986
DOI: 10.1200/CCI.21.00200 -
Nutrients Jul 2023Vitamin D intervention studies are designed to evaluate the impact of the micronutrient vitamin D on health and disease. The appropriate design of studies is essential... (Review)
Review
Vitamin D intervention studies are designed to evaluate the impact of the micronutrient vitamin D on health and disease. The appropriate design of studies is essential for their quality, successful execution, and interpretation. Randomized controlled trials (RCTs) are considered the "gold standard" for intervention studies. However, the most recent large-scale (up to 25,000 participants), long-term RCTs involving vitamin D did not provide any statistically significant primary results. This may be because they are designed similarly to RCTs of a therapeutic drug but not of a nutritional compound and that only a limited set of parameters per individual were determined. We propose an alternative concept using the segregation of study participants into different groups of responsiveness to vitamin D supplementation and in parallel measuring a larger set of genome-wide parameters over multiple time points. This is in accordance with recently developed mechanistic modeling approaches that do not require a large number of study participants, as in the case of statistical modeling of the results of a RCT. Our experience is based on the vitamin D intervention trials VitDmet, VitDbol, and VitDHiD, which allowed us to distinguish the study participants into high, mid, and low vitamin D responders. In particular, investigating the vulnerable group of low vitamin D responders will provide future studies with more conclusive results both on the clinical and molecular benefits of vitamin D supplementation. In conclusion, our approach suggests a paradigm shift towards detailed investigations of transcriptome and epigenome-wide parameters of a limited set of individuals, who, due to a longitudinal design, can act as their own controls.
Topics: Humans; Cholecalciferol; Vitamin D; Vitamins; Research Design; Dietary Supplements
PubMed: 37571318
DOI: 10.3390/nu15153382 -
American Journal of Pharmaceutical... Aug 2022The primary objective of this study was to gain an understanding of student pharmacist learning that occurs during international advanced pharmacy practice experiences...
The primary objective of this study was to gain an understanding of student pharmacist learning that occurs during international advanced pharmacy practice experiences (APPEs). The secondary objective was to direct the development of suitable predeparture orientation activities for pharmacy students. University of Kentucky College of Pharmacy students authored blogs between 2012 and 2019 describing patient care and non-patient care international APPEs. This study utilized inductive thematic analysis to analyze the blogs and define codes, categories, and themes from the data set. The entire data set was used to generate changes to an orientation program delivered to students before they study abroad (predeparture orientation). The analysis included 47 blogs from which seven pictorial codes and 24 text codes were isolated to ultimately form four categories: Learning About Health Care; My Surroundings; Logistics; and Me, Myself, and I. Two overall themes emerged from the codes and categories: Everything Is Different and Here's What I Think and Feel. Through examining the data and reviewing other studies focusing on study abroad experiences, the results indicate that the themes isolated in this study parallel previously described benefits of studying abroad. Additionally, analysis of the blogs suggested that expanding the predeparture orientation for students and including follow-up discussions may facilitate student understanding prior to travel. This study gives unique insight into thoughts and the relative importance of pharmacy students' experiences while studying abroad. The resulting data, considered along with previously published studies, can guide educators in refining predeparture materials. Further studies are needed to evaluate the effectiveness of revised predeparture orientation.
Topics: Education, Pharmacy; Humans; Pharmaceutical Services; Pharmacists; Pharmacy; Students, Pharmacy
PubMed: 34785494
DOI: 10.5688/ajpe8673 -
Current Research in Food Science 2022Studying the composition of a certain food is not enough to predict its health benefits. Research over the past decades has decisively strengthened the notion that any... (Review)
Review
Studying the composition of a certain food is not enough to predict its health benefits. Research over the past decades has decisively strengthened the notion that any putative health benefit is best related to the fraction of compounds transferred from ingested foods into the body since the absorption may be incomplete after oral consumption. In other words, the bioavailability of food components is crucial information. Therefore, a variety of models have been developed to predict their bioaccessibility and bioavailability in the most diverse food matrices and food products. These models can also be applied to study the impact of several endogenous or exogenous factors on the bioaccessibility and bioavailability of nutrients and bioactive compounds, guiding nutrition and food scientists, technologists, and engineers towards the development of strategies to optimize the positive impact of the diet on well-being and quality of life. While bioavailability is ideally examined in human volunteers, digestion methods, as well as intestinal absorption and microphysiological models, simulate human physiological conditions. Additionally, methods are alternatives to offset ethical, economical, and experimental limitations associated with studies conducted either with individuals or animals. This graphical review draws parallels between models mimicking digestion processes, uptake, absorption, metabolism, and distribution of dietary compounds and human physiology.
PubMed: 35106487
DOI: 10.1016/j.crfs.2022.01.002 -
Ecology and Evolution May 2022Studying the genetics of phenotypic convergence can yield important insights into adaptive evolution. Here, we conducted a comparative genomic study of four lineages...
Studying the genetics of phenotypic convergence can yield important insights into adaptive evolution. Here, we conducted a comparative genomic study of four lineages (species and subspecies) of anadromous shad () that have independently evolved life cycles entirely completed in freshwater. Three naturally diverged (. , .. , and .), and the fourth (. ) was artificially landlocked during the last century. To conduct this analysis, we assembled and annotated a draft of the . genome and generated whole-genome sequencing for 16 anadromous and freshwater populations of shad. Widespread evidence for parallel genetic changes in freshwater populations within lineages was found. In freshwater . , which have only been diverging for tens of generations, this shows that parallel adaptive evolution can rapidly occur. However, parallel genetic changes across lineages were comparatively rare. The degree of genetic parallelism was not strongly related to the number of shared polymorphisms between lineages, thus suggesting that other factors such as divergence among ancestral populations or environmental variation may influence genetic parallelism across these lineages. These overall patterns were exemplified by genetic differentiation involving a paralog of - that appears to be under selection in just two of the more distantly related lineages studied, .. and . . Our findings provide insights into the genetic architecture of adaptation and parallel evolution along a continuum of population divergence.
PubMed: 35646309
DOI: 10.1002/ece3.8908