ABSTRACT
Selective serotonin re-uptake inhibitors (SSRI) widely used in the treatment of depression, anxiety, obsessive compulsive disorder, fibromyalgia, and migraine are among the most heavily prescribed drug class in the United States (US). Along with an overall rise in SSRI use, these medications are increasingly used by pregnant individuals and recent preclinical and clinical studies have indicated that SSRIs may increase the prevalence of congenital abnormalities and birth defects of the craniofacial region. Our group has developed pre-clinical models of study, including those that mimic the clinical use of SSRI in mice. Here we designed a study to interrogate a commonly prescribed SSRI drug, Citalopram, for its effects on craniofacial and dental development when introduced in utero. Pre-natal exposure to a clinically relevant dose of citalopram resulted in changes in craniofacial form identified by an increase in endocast volume in SSRI exposed postnatal day 15 mouse pups. More specifically, cranial length and synchondrosis length increased in SSRI exposed pups as compared to control pups of the same age. Additionally, growth center (synchondrosis) height and width and palate length and width decreased in SSRI exposed pups as compared to control un-exposed pups. Effects of SSRI on the molars was minimal. Craniofacial growth and development continue to be an area of interest in the investigation of in utero pharmaceutical drug exposure. Altogether these data indicate that prenatal SSRI exposure affects craniofacial form in multiple tissues and specifically at growth sites and centers of the skull.
Subject(s)
Citalopram , Craniofacial Abnormalities , Selective Serotonin Reuptake Inhibitors , Skull , Animals , Selective Serotonin Reuptake Inhibitors/pharmacology , Selective Serotonin Reuptake Inhibitors/adverse effects , Mice , Female , Pregnancy , Citalopram/pharmacology , Skull/drug effects , Craniofacial Abnormalities/chemically induced , Prenatal Exposure Delayed Effects/chemically induced , Disease Models, Animal , MaleABSTRACT
Increased temperatures associated with urbanization (the "urban heat island" effect) have been shown to impact a wide range of traits across diverse taxa. At the same time, climatic conditions vary at fine spatial scales within habitats due to factors including shade from shrubs, trees, and built structures. Patches of shade may function as microclimate refugia that allow species to occur in habitats where high temperatures and/or exposure to ultraviolet radiation would otherwise be prohibitive. However, the importance of shaded microhabitats for interactions between species across urbanized landscapes remains poorly understood. Weedy plants and their foliar pathogens are a tractable system for studying how multiple scales of climatic variation influence infection prevalence. Powdery mildew pathogens are particularly well suited to this work, as these fungi can be visibly diagnosed on leaf surfaces. We studied the effects of shaded microclimates on rates of powdery mildew infection on Plantago host species in (1) "pandemic pivot" surveys in which undergraduate students recorded shade and infection status of thousands of plants along road verges in urban and suburban residential neighborhoods, (2) monthly surveys of plant populations in 22 parks along an urbanization gradient, and (3) a manipulative field experiment directly testing the effects of shade on the growth and transmission of powdery mildew. Together, our field survey results show strong positive effects of shade on mildew infection in wild Plantago populations across urban, suburban, and rural habitats. Our experiment suggests that this relationship is causal, where microclimate conditions associated with shade promote pathogen growth. Overall, infection prevalence increased with urbanization despite a negative association between urbanization and tree cover at the landscape scale. These findings highlight the importance of taking microclimate heterogeneity into account when establishing links between macroclimate or land use context and prevalence of disease.
Subject(s)
Microclimate , Plant Diseases , Urbanization , Plant Diseases/microbiology , Ascomycota/physiologyABSTRACT
Neuronal dendrite patterning and synapse formation are tightly regulated during development to promote proper connectivity. Astrocyte-secreted proteins act as guidance and pro-synaptogenic factors during development, but little is known about how astrocytes may contribute to neurodevelopmental disorders. Here we identify down-regulation of the astrocyte-secreted molecule pleiotrophin as a major contributor to neuronal morphological alterations in the Ts65Dn mouse model of Down Syndrome. We find overlapping deficits in neuronal dendrites, spines and intracortical synapses in Ts65Dn mutant and pleiotrophin knockout mice. By targeting pleiotrophin overexpression to astrocytes in adult Ts65Dn mutant mice in vivo , we show that pleiotrophin can rescue dendrite morphology and spine density and increase excitatory synapse number. We further demonstrate functional improvements in behavior. Our findings identify pleiotrophin as a molecule that can be used in Down Syndrome to promote proper circuit connectivity, importantly at later stages of development after typical periods of circuit refinement have completed.
ABSTRACT
OBJECTIVES: A growing body of research is emerging regarding the relationship between parental adverse childhood experiences (ACEs) and negative health, well-being and developmental outcomes in their children. This systematic review seeks to understand the relationship between parental ACEs and the health, well-being and developmental outcomes of their children and whether the relationships differ according to the number and type of parental ACEs. STUDY DESIGN: Systematic review. METHOD: The review includes articles published between 2000 and 2021 from studies using quantitative longitudinal methods and multivariate analysis to investigate the relationship between parental ACEs and their offspring's outcomes. Relevant studies were identified through a systematic search of five databases and findings synthesised using a narrative synthesis. This review was registered on PROSPERO (CRD42021274068). RESULTS: Nineteen studies met the inclusion criteria and were included in the review. This resulted in a combined population sample of 124,043 parents and 128,400 children. Diversity in measurement of parental ACE exposure and in the type of ACEs measured within the studies precluded a meta-analysis. Offspring of parents exposed to ACEs had a higher risk of a range of negative health, well-being and developmental outcomes. This relationship differs according to the number and type of parental ACEs, with a positive relationship observed between the number of parental ACEs and the risk of negative health, well-being and development outcomes in their children. CONCLUSIONS: These findings indicate that screening for parental ACEs by health visitors, midwives and other health or social care staff may identify an at-risk population of infants, children and adolescents and improve child outcomes.
Subject(s)
Adverse Childhood Experiences , Infant , Adolescent , Child , Humans , Parents , Risk Factors , Surveys and QuestionnairesABSTRACT
Introduction Childhood poverty has life-long adverse impacts. We aimed to assess perceptions of parents of a cohort of children attending a paediatric emergency department regarding the impact of their housing on their child and family Methods From 01/11/2020 - 08/01/2021 a cross-sectional study was performed in a paediatric emergency department in Dublin Results Of 312 parents who completed a questionnaire, 4.5% (n = 14) reported themselves to be homeless. Homeless children were less likely to be registered with general practitioners (78.6% vs. 97.5%, p = .009) or be fully vaccinated (71.4% vs. 92.4%, p = .024). Homeless parents were more likely to feel unsafe at home (35.7% vs. 3.4%, p <.001), and to report that their housing negatively impacted their child's education (58.3% vs 10.7%, p <.001), physical health (45.5% vs 11.7, p = .007), and mental health (61.5% vs 12.6%, p <.001). Ten percent of non-homeless parents were concerned about losing their home. A lack of landlord permission to install child safety measures in the home was reported by 28% of all parents. Conclusion Homeless parents were more likely to report that their living situation negatively impacted their child's play, development, education, safety, and health.
Subject(s)
Housing , Ill-Housed Persons , Humans , Child , Child Health , Cross-Sectional Studies , Parents/psychologyABSTRACT
We present a case of spontaneous nontraumatic retrobulbar hemorrhage associated with anti-coagulation therapy and a new diagnosis of scurvy. A 68-year-old male on chronic anti-coagulation therapy presented with a retrobulbar hemorrhage requiring urgent canthotomy and cantholysis. Despite the absence of a supratherapeutic INR and normal clotting factors, the patient continued to have spontaneous hemorrhages within the orbit and elsewhere. Workup revealed a severe vitamin C deficiency consistent with scurvy. Further investigation of dietary history demonstrated an avoidance of all citrus fruit upon starting warfarin due to misunderstanding in medication counseling on avoidance of grapefruit. With repletion of vitamin C and further medication counseling, the patient had no further episodes of spontaneous hemorrhage.
Subject(s)
Retrobulbar Hemorrhage , Scurvy , Aged , Hemorrhage , Humans , Male , Orbit , Retrobulbar Hemorrhage/diagnosis , Retrobulbar Hemorrhage/diagnostic imaging , Scurvy/diagnosis , Scurvy/drug therapy , Warfarin/adverse effectsABSTRACT
In this synthesis, we assess present research and anticipate future development needs in modeling water quality in watersheds. We first discuss areas of potential improvement in the representation of freshwater systems pertaining to water quality, including representation of environmental interfaces, in-stream water quality and process interactions, soil health and land management, and (peri-)urban areas. In addition, we provide insights into the contemporary challenges in the practices of watershed water quality modeling, including quality control of monitoring data, model parameterization and calibration, uncertainty management, scale mismatches, and provisioning of modeling tools. Finally, we make three recommendations to provide a path forward for improving watershed water quality modeling science, infrastructure, and practices. These include building stronger collaborations between experimentalists and modelers, bridging gaps between modelers and stakeholders, and cultivating and applying procedural knowledge to better govern and support water quality modeling processes within organizations.
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Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) is an invasive pest that has established in much of the United States. Adventive populations of an effective Asian egg parasitoid of H. halys, Trissolcus japonicus (Ashmead) (Hymenoptera: Scelionidae), have been detected in several states, including Virginia, and its geographic range is expanding. Documenting changes in its distribution and abundance have thus become key research priorities. For these specific purposes, surveillance of T. japonicus over large geographic areas using sentinel H. halys egg masses may not be optimally efficient, and examination of alternative sampling tactics is warranted. In 2016, sentinel H. halys egg masses were deployed as vertical transects in the canopy of female Ailanthus altissima (Mill.) Swingle (Sapindales: Simaroubaceae) in Virginia. A brief follow-up study in 2016 using yellow sticky traps deployed in the same trees yielded captures of T. japonicus, leading to a comparison of vertical transects of sentinel eggs and yellow sticky traps in 2017. Both methods yielded T. japonicus detections only in the middle and upper tree canopies, whereas other known H. halys parasitoids were detected in the lower, middle, or upper canopies. Based on this information, a method for deploying yellow sticky traps in the middle canopy of H. halys host trees was assessed in 2017, yielding T. japonicus captures. A comparison of estimated time inputs revealed that traps were more efficient than sentinel eggs in this regard. Results are discussed in relation to the utility of each sampling method to address specific questions about the range expansion and ecology of T. japonicus.
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Heteroptera , Hymenoptera , Animals , Female , Follow-Up Studies , Trees , VirginiaABSTRACT
The comparatively high cost of laboratory detection methods for Clostridium difficile infection (CDI) coupled to a low prevalence rate has resulted in testing algorithms that use cheaper and relatively sensitive screening methods, followed by more specific confirmatory methods. The aim of this prospectively-conducted study from two centres in the UK, and one in the Republic of Ireland was to determine the efficacy of the EntericBio® realtime C. difficile Assay (EBCD) for the detection of toxigenic C. difficile in stool samples. The EBCD was compared to the in-use testing methods for Clostridium difficile (CD) detection in each centre. In the two UK centres, the EBCD was compared to the C.diff Quik Chek Complete® kit (Techlab), and discrepancies were tested further using The Xpert®C. difficile PCR assay (Cepheid) and PCR ribotyping after cultivation using the spore culture method, respectively. In the Irish centre, EBCD comparison was to an algorithm of C. DIFF CHEK™-60 test (Techlab) for screening followed by C. difficile Premier ™ Toxins A&B assay (Meridian Bioscience®) in the case of positive results; discrepancies were tested using the Xpert®C. difficile PCR assay. In a retrospective analysis of data, a total of 947 stool samples were tested, of which eight (0.8%) proved inhibitory to the EBCD assay. Of the 939 valid tests conducted, reported sensitivities of the EBCD were 94.7%, 100% and 97.9%, respectively; specificities were 99.6%, 100% and 100%, respectively; positive predictive values were 94.7%, 100% and 100%, respectively, and negative predictive values were 99.6%, 100% and 99.8%, respectively. The CD positivity rates in the current study ranged between 6.6% and 8.2%.
Subject(s)
Bacterial Toxins/genetics , Clostridioides difficile/isolation & purification , Clostridium Infections/microbiology , Polymerase Chain Reaction/methods , Adolescent , Algorithms , Bacterial Toxins/metabolism , Child , Child, Preschool , Clostridioides difficile/classification , Clostridioides difficile/genetics , Feces/microbiology , Female , Humans , Male , Prospective Studies , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Warming at nearly twice the global rate, higher than average air temperatures are the new 'normal' for Arctic ecosystems. This rise in temperature has triggered hydrological and geochemical changes that increasingly release carbon-rich water into the coastal ocean via increased riverine discharge, coastal erosion, and the thawing of the semi-permanent permafrost ubiquitous in the region. To determine the biogeochemical impacts of terrestrially derived dissolved organic matter (tDOM) on marine ecosystems we compared the nutrient stocks and bacterial communities present under ice-covered and ice-free conditions, assessed the lability of Arctic tDOM to coastal microbial communities from the Chukchi Sea, and identified bacterial taxa that respond to rapid increases in tDOM. Once thought to be predominantly refractory, we found that â¼7% of dissolved organic carbon and â¼38% of dissolved organic nitrogen from tDOM was bioavailable to receiving marine microbial communities on short 4 - 6 day time scales. The addition of tDOM shifted bacterial community structure toward more copiotrophic taxa and away from more oligotrophic taxa. Although no single order was found to respond universally (positively or negatively) to the tDOM addition, this study identified 20 indicator species as possible sentinels for increased tDOM. These data suggest the true ecological impact of tDOM will be widespread across many bacterial taxa and that shifts in coastal microbial community composition should be anticipated.
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Natural enemies and pollinators require nutritional and habitat resources that are often not found in conventional agricultural fields. The addition of flowering plants within agroecosystems may provide the resources necessary to support beneficial insects at the local scale. We hypothesized that insect pollinator and natural enemy abundance would increase in cucumber (Cucumis sativus) plots containing flower strips and that the effect would be greatest in the crop rows closest to the flower strips. Three flower treatments were tested: 1) buckwheat (Fagopyrum esculentum), 2) yellow mustard (Brassica hirta), 3) sweet alyssum (Lobularia maritima), and cucumbers as a control. Flowers were planted within a commercial cucumber field in 20-m-long strips in a randomized complete block design with six replications in the 2014 and 2015 growing seasons. Some floral treatments successfully attracted more beneficial insects than others, but the beneficials did not disperse out to the cucumber plants. Cucumber yield was unaffected by flowers with one exception: in 2015, cucumber yield in the sweet alyssum plots were greater than those in plots with no flowers. Our research indicates that adding flowers to cucumber fields to increase services from beneficial insects needs to be further investigated to better understand the effect of factors such as relative flowering strip size.
Subject(s)
Agriculture/methods , Cucumis sativus/growth & development , Flowers , Insecta , Animals , Brassica , Brassicaceae , Ecosystem , Environmental Monitoring/methods , Fagopyrum , Michigan , PollinationSubject(s)
Brain/pathology , Frontotemporal Dementia/pathology , Frontotemporal Lobar Degeneration/pathology , Multiple System Atrophy/pathology , Fatal Outcome , Frontotemporal Dementia/diagnosis , Frontotemporal Lobar Degeneration/diagnosis , Humans , Male , Middle Aged , Multiple System Atrophy/diagnosisABSTRACT
Item cloning is increasingly used to generate slight differences in tasks for use in psychological experiments and educational assessments. This paper investigates the psychometric issues that arise when item cloning introduces variation into the difficulty parameters of the item clones. Four models are proposed and evaluated in simulation studies with conditions representing possible types of variation due to item cloning. Depending on the model specified, unaccounted variance in the item clone difficulties propagates to other parameters in the model, causing specific and predictable patterns of bias. Person parameters are largely unaffected by the choice of model, but for inferences related to the item parameters, the choice is critical and can even be leveraged to identify problematic item cloning.
Subject(s)
Models, Statistical , Models, Theoretical , Psychometrics , Educational Measurement , HumansABSTRACT
Conservation tillage combined with cover crops or mulching may enhance natural enemy activity in agroecosystems by reducing soil disturbance and increasing habitat structural complexity. In particular, weed seed predation can increase with vegetation cover and reduced tillage, indicating that mulches may improve the quality of the habitat for weed seed foraging. The purpose of this study was to quantify the effects of tillage and mulching for conservation biological control in cucurbit fields. The effects of mulch and reduced tillage on arthropods and rates of weed seed loss from arenas were examined in field trials on sandy soils in 2014 and 2015. Experimental factors included tillage and cover crop, each with two levels: strip-tillage or full-tillage, and cover crop mulch (rye residue) or no cover crop mulch (unmulched). Arthropod abundance on the crop foliage was not affected by tillage or cover crops. Contrary to expectations, epigeal natural enemies of insects and rates of weed seed removal either did not respond to treatments or were greater in full-tilled plots and plots without mulch. Our study demonstrates the potential importance of weed seed predators in reducing weed seedbanks in vegetable agroecosystems, and suggests that early-season tillage may not be detrimental to epigeal predator assemblages.
Subject(s)
Agriculture/methods , Arthropods/physiology , Crops, Agricultural/growth & development , Cucurbita/growth & development , Herbivory , Plant Weeds/physiology , Seeds/physiology , Animals , Biodiversity , Conservation of Natural Resources , Ecosystem , Food Chain , MichiganABSTRACT
Essentials It is unclear if platelet function differs between preterm and full-term neonates. Platelet behavior was characterized using a flow-based assay on von Willebrand Factor (VWF). Preterms had increased platelet interaction with VWF and glycoprotein Ibα expression. Platelets from preterm neonates behave differently on VWF compared to full-term neonates. SUMMARY: Background Very low birth weight (VLBW) preterm neonates have an increased risk of hemorrhage-related morbidity and mortality as compared with their full-term counterparts. It is unclear whether platelet function differs between preterm and full-term neonates. This is partly because of the large volumes of blood required to perform standard platelet function tests, and the difficulty in obtaining such samples in neonates. Objectives This study was designed to characterize platelet behavior in neonates with a physiologic flow-based assay that quantifies platelet function in microliter volumes of blood under arterial shear. Methods Blood from VLBW preterm neonates of ≤ 32 weeks' gestation (n = 15) and full-term neonates (n = 13) was perfused under arterial shear over surface-immobilized von Willebrand factor (VWF). Platelet behavior was recorded by digital-image microscopy and analyzed. Surface expression of platelet glycoprotein (GP) Ibα and GPIIIa of VLBW preterm and full-term neonates was also measured. Results VLBW preterm neonates had increased numbers of platelets interacting with VWF, and increased GPIbα expression on the platelet surface. Despite the increased numbers of VWF interactions as reflected by flow-driven platelet translocation along the protein surface, no significant differences were observed in the numbers of platelets that adhered in a stationary fashion to VWF. Platelets from VLBW preterm neonates and those from full-term neonates behaved differently on VWF. Conclusions These differences in platelet function may contribute to the higher incidence of bleeding observed in VLBW preterm neonatal populations, or may represent a compensatory mechanism to counteract this risk of bleeding.
Subject(s)
Platelet Function Tests/methods , Platelet Glycoprotein GPIb-IX Complex/metabolism , von Willebrand Factor/metabolism , Blood Coagulation Tests , Blood Platelets/cytology , Female , Gestational Age , Hemorheology , Hemorrhage/blood , Humans , Infant, Newborn , Infant, Premature , Infant, Very Low Birth Weight , Male , Perfusion , Platelet Activation , Platelet Adhesiveness/physiology , Protein Binding , Shear StrengthABSTRACT
BACKGROUND AND PURPOSE: Rhabdomyosarcoma and Langerhans cell histiocytosis are malignant lesions that can affect the skull base with similar radiographic characteristics on CT and MR imaging. We hypothesized that location within the temporal bone determined radiographically can provide useful adjunctive information in differentiating these distinct neoplasms. MATERIALS AND METHODS: We identified patients with Langerhans cell histiocytosis and rhabdomyosarcoma by using an imaging data base and International Classification of Diseases, Ninth Revision codes at a tertiary care academic medical center. Cross-sectional images were reviewed by a neurotologist and neuroradiologist, who evaluated the location of the lesions and scored each subsite-middle ear, mastoid, petrous apex, retrosigmoid/posterior fossa-on a scale of 0 (no involvement), 1 (partial), or 2 (complete involvement). RESULTS: We identified 12 patients representing 14 cases of Langerhans cell histiocytosis, and 9 patients representing 9 cases of rhabdomyosarcoma. For patients with Langerhans cell histiocytosis, mastoid involvement was rated 23/28 (82%) compared with 6/18 (33%) with rhabdomyosarcoma (P = .001). Langerhans cell histiocytosis was present in only the anterior portion of the temporal bone (petrous apex and middle ear) in 1 case (7.1%) and in the anterior portion of the temporal bone only in 5/9 (55%) cases of rhabdomyosarcoma (P = .018). The cortical bone was more commonly involved in Langerhans cell histiocytosis, 11/28 (39%) of cases compared with 2/18 (11%) cases in rhabdomyosarcoma (P < .05). CONCLUSIONS: These results indicate that lesions involving only the anterior portion of the temporal bone (petrous apex and middle ear) are more likely to be rhabdomyosarcoma. Lesions involving the mastoid are more likely to be Langerhans cell histiocytosis. This difference in primary location may be helpful in predicting the pathology of these lesions on the basis of imaging.
Subject(s)
Histiocytosis, Langerhans-Cell/diagnostic imaging , Rhabdomyosarcoma/diagnostic imaging , Skull Base Neoplasms/diagnostic imaging , Temporal Bone/diagnostic imaging , Child , Cross-Sectional Studies , Diagnosis, Differential , Female , Histiocytosis, Langerhans-Cell/pathology , Humans , Image Interpretation, Computer-Assisted , Male , Rhabdomyosarcoma/pathology , Skull Base Neoplasms/pathology , Temporal Bone/pathology , Tomography, X-Ray ComputedABSTRACT
Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable or multiple variables that may completely or partially mediate the DIF effect. If complete mediation effect is found, the DIF effect is fully accounted for. Through our simulation study, we find that the mediated MIMIC model is very successful in detecting the mediation effect that completely or partially accounts for DIF, while keeping the Type I error rate well controlled for both balanced and unbalanced sample sizes between focal and reference groups. Because it is successful in detecting such mediation effects, the mediated MIMIC model may help explain DIF and give guidance in the revision of a DIF item.
ABSTRACT
MELAS is a rare mitochondrial disorder. We report two cases in Irish males where the characteristics were evident, but the diagnosis not made for a considerable period of time. In one of the cases the symptoms were presumed secondary to prematurity. In the other the symptoms were presumed secondary to epilepsy and he had three respiratory arrests secondary to benzodiazepine administration. This report wishes to highlight MELAS as a differential diagnosis in paediatric patients who present with stroke.