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Strong and consistent findings suggest that a positive school climate is related to improved student outcomes. However, assessment of the school climate rarely considers the environmental fit (or misfit) between individuals' actual or lived experiences and their preferred environment. This study drew on a person-environment fit perspective to examine whether: students' experiences of the school climate (actual environment) differed from their views of their ideal school climate (preferred environment); the views of the actual and preferred environment differed between schools; and the actual-preferred discrepancy (as a measure of the environmental fit) was related to student wellbeing, resilience and reports of bullying. The results from the analysis of data collected from 993 upper primary school students suggest that outcomes were enhanced when the perceived environment more closely matched the preferred environment. Our study's findings support using a person-environment fit perspective alongside a socio-ecological approach to inform strategic decisions for school improvement efforts.

Although the role of leadership in school improvement is widely recognized, there is less understanding of what leaders can do to support (and mitigate barriers to) the implementation of mandated educational change. This systematic literature review analyzed findings from 191 relevant primary studies published between 2000 and 2020 and identified four broad themes: developing a reform-ready school climate, comprehensive planning, preparation for implementation, and building capacity. These results offer practical information about malleable school-level factors to which school leaders can attend (before implementing mandated reform) to support the school's capacity for change.

Summary: Background: Sudden Infant Death Syndrome (SIDS) is a leading cause of postneonatal mortality. The absence of specific biomarkers of SIDS diagnosis and risk leaves a significant gap in understanding SIDS pathophysiology. Metabolomics offers an avenue to better understand SIDS biology and identifying potential biomarkers. Methods: Using Metabolon Inc., global discovery panel, we analysed 828 metabolites from post-mortem serum samples of infants from the Chicago Infant Mortality Study (CIMS) and the NIH NeuroBioBank (NBB). In total, 300 infants (195 SIDS; 105 non-SIDS) across multiple race/ethnicities (70% Black, 13% White, and 16% Hispanic) were included. Metabolite associations with SIDS were performed using Welch’s t-tests, linear and logistic regression, and network-cluster analyses. Findings: We identified thirty-five significant metabolite predictors of SIDS after adjustment for age, sex, race and ethnicity, and post-mortem interval, including ornithine (OR 21.98; p-value 6.44e-7), 5-hydroxylysine (OR 19.48; p-value 6.78e-7), 1-stearoyl-2-linoleoyl-GPC (18:0/18:2) (OR 16.80; p-value 3.4e-7), ribitol (OR 8.19; p-value 4.2e-8), and arabitol/xylitol. Using Weighted Gene Co-expression Network Analysis (WGCNA), ten metabolite clusters were identified. Four exhibited significant associations with SIDS. The two most correlated clusters were enriched for metabolites in the tyrosine metabolism pathway and lipid (sphingomyelins) pathways. Interpretation: We identified metabolite biomarkers within key biological pathways and processes (e.g., nitrogen metabolism, lipid and fatty acid metabolism, stress response, nerve cell communication, hormone regulation, oxidative stress) with potential implications in SIDS pathology. Further research is needed to validate these biomarkers in additional SIDS cohorts. Funding: The Chicago Infant Mortality Study was funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute on Deafness and Other Communication Disorders under contract number NO1-HD-3-3188, the Centers for Disease Control and Prevention and the Association of Teachers of Preventive Medicine under cooperative agreement number U50/CCU300860-06, and the Playmates in Heaven Foundation. The current analyses were funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development under 5R01HD101518-04.

Background: Invasive fungal infections are responsible for a large number of infections in hospitalized patients annually and are responsible for high morbidity and mortality. Familiarity with novel agents or strategies in this area can be challenging. Objectives: To identify the top 10 manuscripts on the treatment of invasive fungal infections from 2018 to 2023. Design: Modified Delphi consensus-building technique. Methods: A three-stage consensus-building approach was used comprised of (1) identifying relevant articles; (2) voting by a panel of experts to establish consensus on the importance of these articles; and (3) finalizing the list of top articles by a small group. Members of the Southeastern Research Group Endeavor network served as content experts. Publications from 2018 to 2023 were evaluated if articles met the following inclusion criteria: (1) published between 2018 and 2023, (2) contained content related to fungal infections, and (3) included an actionable intervention. Results: A total of 6518 potential publications were assessed. After applying inclusion and exclusion criteria, 82 articles were reviewed. The top 10 publications related to invasive fungal infections, selected by a panel of experts, are summarized in this manuscript and include publications related to the treatment of invasive aspergillosis, candidiasis, and cryptococcosis. Conclusion: This article highlights the selected publications and may serve as a key resource for teaching and training. Clinicians may also employ these reported interventions to identify new opportunities to optimize antifungal therapeutic strategies within one’s institution.

IntroductionStroke is a leading cause of death and disability worldwide. Recurrent strokes are seven times more lethal than initial ones, with 54% leading to long-term disability. Substantial recurrent stroke risk disparities exist among ancestral groups. Notably, Africans face double the risk and higher fatality rates compared to Europeans. Although genetic studies, particularly GWAS, hold promise for uncovering biological insights into recurrent stroke, they remain underexplored. Our study addresses this gap through meta-analyses of recurrent stroke GWAS, considering specific ancestral groups and a combined approach.MethodsWe utilized four independent study cohorts for African, European, and Combined ancestry recurrent stroke GWAS with genotyping, imputation, and strict quality control. We harmonized recurrent stroke phenotype and effect allele estimates across cohorts. The logistic regression GWAS model was adjusted for age, sex, and principal components. We assessed how well genetic risk of stroke informs recurrent stroke risk using Receiver Operating Characteristic (ROC) curve analysis with the GIGASTROKE Consortium's polygenic risk scores (PRS).ResultsHarmonization included 4,420 participants (818 African ancestry and 3,602 European ancestry) with a recurrent stroke rate of 16.8% [median age 66.9 (59.1, 73.6) years; 56.2% male]. We failed to find genome-wide significant variants (p < 5e−8). However, we found 18 distinct suggestive (p < 5e−6) genetic loci with high biological relevance consistent across African and European ancestries, including PPARGC1B, CCDC3, OPRL1, and MYH11 genes. These genes affect vascular stenosis through constriction and dilation. We also observed an association with SDK1 gene, which has been previous linked with hypertension in Nigerian and Japanese populations). ROC analysis showed poor performance of the ischemic stroke PRS in discriminating recurrent stroke status (area under the curve = 0.48).DiscussionOur study revealed genetic associations with recurrent stroke not previously associated with incident ischemic stroke. We found suggestive associations in genes previously linked with hypertension. We also determined that knowing the genetic risk of incident stroke does currently not inform recurrent stroke risk. We urgently need more studies to understand better the overlap or lack thereof between incident and recurrent stroke biology.

Abstract Terazosin is an α1-adrenergic receptor antagonist that enhances glycolysis and increases cellular ATP by binding to the enzyme phosphoglycerate kinase 1 (PGK1). Recent work has shown that terazosin is protective against motor dysfunction in rodent models of Parkinson’s disease (PD) and is associated with slowed motor symptom progression in PD patients. However, PD is also characterized by profound cognitive symptoms. We tested the hypothesis that terazosin protects against cognitive symptoms associated with PD. We report two main results. First, in rodents with ventral tegmental area (VTA) dopamine depletion modeling aspects of PD-related cognitive dysfunction, we found that terazosin preserved cognitive function. Second, we found that after matching for demographics, comorbidities, and disease duration, PD patients newly started on terazosin, alfuzosin, or doxazosin had a lower hazard of being diagnosed with dementia compared to tamsulosin, an α1-adrenergic receptor antagonist that does not enhance glycolysis. Together, these findings suggest that in addition to slowing motor symptom progression, glycolysis-enhancing drugs protect against cognitive symptoms of PD.

Hypocretin/orexin (HCRT) is a neuropeptide that is associated with both stress and reward systems in humans and rodents. The different contributions of signaling at hypocretin-receptor 1 (HCRT-R1) and hypocretin-receptor 2 (HCRT-R2) to compulsive alcohol drinking are not yet fully understood. Thus, the current studies used pharmacological and viral-mediated targeting of HCRT to determine participation in compulsive alcohol drinking and measured HCRT-receptor mRNA expression in the extended amygdala of both alcohol-dependent and non-dependent male rats. Rats were made dependent through chronic intermittent exposure to alcohol vapor and were tested for the acute effect of HCRT-R1-selective (SB-408124; SB-R1), HCRT-R2-selective (NBI-80713; NB-R2), or dual HCRT-R1/2 (NBI-87571; NB-R1/2) antagonism on alcohol intake. NB-R2 and NB-R1/2 antagonists each dose-dependently decreased overall alcohol drinking in alcohol-dependent rats, whereas, SB-R1 decreased alcohol drinking in both alcohol-dependent and non-dependent rats at the highest dose (30 mg/kg). SB-R1, NB-R2, and NB-R1/2 treatment did not significantly affect water drinking in either alcohol-dependent or non-dependent rats. Additional PCR analyses revealed a significant decrease in Hcrtr1 mRNA expression within the central amygdala (CeA) of dependent rats under acute withdrawal conditions compared to non-dependent rats. Lastly, a shRNA-encoding adeno-associated viral vector with retrograde function was used to knockdown HCRT in CeA-projecting neurons from the lateral hypothalamus (LH). LH-CeA HCRT knockdown significantly attenuated alcohol self-administration in alcohol-dependent rats. These observations suggest that HCRT signaling in the CeA is necessary for alcohol-seeking behavior during dependence. Together, these data highlight a role for both HCRT-R1 and -R2 in dependent alcohol-seeking behavior.

BackgroundCurrent EMS stroke screening tools facilitate early detection and triage, but the tools' accuracy and reliability are limited and highly variable. An automated stroke screening tool could improve stroke outcomes by facilitating more accurate prehospital diagnosis and delivery. We hypothesize that a machine learning algorithm using video analysis can detect common signs of stroke. As a proof-of-concept study, we trained a computer algorithm to detect presence and laterality of facial weakness in publically available videos with comparable accuracy, sensitivity, and specificity to paramedics.Methods and ResultsWe curated videos of people with unilateral facial weakness (n = 93) and with a normal smile (n = 96) from publicly available web-based sources. Three board certified vascular neurologists categorized the videos according to the presence or absence of weakness and laterality. Three paramedics independently analyzed each video with a mean accuracy, sensitivity and specificity of 92.6% [95% CI 90.1–94.7%], 87.8% [95% CI 83.9–91.7%] and 99.3% [95% CI 98.2–100%]. Using a 5-fold cross validation scheme, we trained a computer vision algorithm to analyze the same videos producing an accuracy, sensitivity and specificity of 88.9% [95% CI 83.5–93%], 90.3% [95% CI 82.4–95.5%] and 87.5 [95% CI 79.2–93.4%].ConclusionsThese preliminary results suggest that a machine learning algorithm using computer vision analysis can detect unilateral facial weakness in pre-recorded videos with an accuracy and sensitivity comparable to trained paramedics. Further research is warranted to pursue the concept of augmented facial weakness detection and external validation of this algorithm in independent data sets and prospective patient encounters.

The development of nanomaterials for imaging and drug delivery has been of great interest to the field. Here, the authors synthesized multifunctional enzyme-responsive hydrogels with self-assembling quantum dots for nucleic acid and drug delivery as well as having imaging capability.

Abstract Background The importance of upper airway structure in the susceptibility of the lower respiratory tract to colonization with potential pathogens is well established. With the advent of rapid, high throughput, next generation sequencing, there is a growing appreciation of the importance of commensal microbial populations in maintaining mucosal health, and a realization that bacteria colonize anatomical locations that were previously considered to be sterile. While upper respiratory tract microbial populations have been described, there are currently no published studies describing the normal microbial populations of the bovine lower respiratory tract. Consequently, we have little understanding of the relationship between upper and lower respiratory tract microbiota in healthy cattle. The primary objective of our study was to characterize the composition, structure and relationship of the lower and upper respiratory microbial communities in clinically healthy feedlot cattle. Nasopharyngeal swabs (NPS), and bronchoalveolar lavage (BAL) fluid, were collected from clinically healthy feedlot calves (n = 8). Genomic DNA from each sample was extracted, and the V3-V4 hypervariable region of the bacterial 16S rRNA gene was amplified and sequenced using Illumina Miseq platform. Results Across all samples, the most predominant phyla were Proteobacteria, Actinobacteria and Firmicutes. The most common genera were Rathayibacter, Mycoplasma, Bibersteinia and Corynebacterium. The microbial community structure was distinct between these two biogeographical sites. Most of the bacterial genera identified in the BAL samples were also present in the NPS, but biogeographical-specific genera were enriched in both the NPS (Rathayibacter) and BAL (Bibersteinia) samples. There were strong associations between the presence of certain taxa at each specific location, and strong correlations between the presence of specific taxa in both the NPS and BAL samples. Conclusions The correlation between the presence of specific taxa in both the NPS and BAL samples, supports the notion of a mutualistic interrelationship between these microbial communities. Future studies, in large cohorts of animals, are needed to determine the role and clinical importance of the relationships of respiratory tract microbial communities with health, productivity, and susceptibility to the development of respiratory disease, in growing cattle.

Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are common causes of dementia worldwide. Although considered separate entities based on the relative temporal onset of motor symptoms vs. diagnosis of dementia, it is unknown if these diseases truly have distinct cognitive profiles. We hypothesized that patients divided into PDD and DLB categories strictly by temporal criteria would have different neuropsychological profiles. We investigated this question via neuropsychological testing of PDD and DLB patients at the University of Iowa. We performed retrospective chart analysis and review of neuropsychological testing of clinically diagnosed patients with PDD or DLB, who had presented to University of Iowa’s dementia and movement disorder clinics. Forty-seven patients diagnosed by the treating neurologist as PDD or DLB were included. Neuropsychological performance was compared between groups, and as a function of the relative timing of the motor diagnosis vs. diagnosis of dementia. We found that both PDD and DLB patients showed severe deficits in executive function, visual–spatial processing, and verbal learning. However, we found no significant differences in neuropsychological performance between groups, and neuropsychological performance could not reliably account for the relative timing of motor diagnosis vs. diagnosis of dementia. Our data support the idea that DLB and PDD are on a neuropsychological spectrum.

Fascioliasis, caused by the liver fluke Fasciola hepatica, is a neglected tropical disease infecting over 1 million individuals annually with 17 million people at risk of infection. Like other helminths, F. hepatica employs mechanisms of immune suppression in order to evade its host immune system. In this study the N-glycosylation of F. hepatica's tegumental coat (FhTeg) and its carbohydrate-dependent interactions with bone marrow derived dendritic cells (BMDCs) were investigated. Mass spectrometric analysis demonstrated that FhTeg N-glycans comprised mainly of oligomannose and to a lesser extent truncated and complex type glycans, including a phosphorylated subset. The interaction of FhTeg with the mannose receptor (MR) was investigated. Binding of FhTeg to MR-transfected CHO cells and BMDCs was blocked when pre-incubated with mannan. We further elucidated the role played by MR in the immunomodulatory mechanism of FhTeg and demonstrated that while FhTeg's binding was significantly reduced in BMDCs generated from MR knockout mice, the absence of MR did not alter FhTeg's ability to induce SOCS3 or suppress cytokine secretion from LPS activated BMDCs. A panel of negatively charged monosaccharides (i.e. GlcNAc-4P, Man-6P and GalNAc-4S) were used in an attempt to inhibit the immunoregulatory properties of phosphorylated oligosaccharides. Notably, GalNAc-4S, a known inhibitor of the Cys-domain of MR, efficiently suppressed FhTeg binding to BMDCs and inhibited the expression of suppressor of cytokine signalling (SOCS) 3, a negative regulator the TLR and STAT3 pathway. We conclude that F. hepatica contains high levels of mannose residues and phosphorylated glycoproteins that are crucial in modulating its host's immune system, however the role played by MR appears to be limited to the initial binding event suggesting that other C-type lectin receptors are involved in the immunomodulatory mechanism of FhTeg.

We report research into associations between the school-level and classroom-level environment in science classrooms in South Africa. An instrument, developed to assess students' perceptions of their classroom learning environment as a means of monitoring and guiding changes towards outcomes-based education, was administered to 2,638 Grade 8 science students from 50 classes in 50 secondary schools in Limpopo province. In addition, the teachers of each of the 50 classes responded to a questionnaire developed to assess factors in the school-level environment (such as the adequacy of resources, parental involvement and collegiality). Thedata collected using the two questionnaires were analysed to examine whether the environment created at the school level was linked to the likelihood of teachers successfully implementing outcomes-based education at the classroom level.

A 2-month-old Simmental heifer presented for acute onset of neurological behavior. Laboratory tests confirmed the presence of hyponatremia, hypochloremia, and hypokalemia that improved with intravenous fluid therapy. Despite an initial cessation of neurological signs, symptoms re-emerged, and the heifer was euthanized due to poor prognosis. A pituitary abscess (Trueperella pyogenes) was observed on gross necropsy, suggesting that the effects of panhypopituitarism (inappropriate anti-diuretic hormone (ADH), adrenocorticotropic hormone (ACTH), and/or thyroid-stimulating hormone (TSH) secretion) may have resulted in the clinical findings. Pituitary abscess syndrome carries a poor prognosis due to the inability to penetrate the area with systemic antibiotic therapy. These findings highlight the unusual clinical presentations that may occur following pituitary abscess syndrome in cattle that practitioners need to consider when determining prognosis.

Writing often helps people deal with trauma. To see if writing about childhood physical or sexual abuse, or positive experiences, helps, psychology undergraduates wrote for 20 minutes on 4 days about their abuse, a positive experience, or a trivial topic. Among 102 who began and 85 who completed pre-, post-, and 4-week follow-up measures of depression, anxiety, and suicidal ideas, abuse writers were more likely to discontinue, and positive writers were more depressed and anxious. Compared to pretest, all completers were less depressed, anxious, and suicidal at follow-up, but nonsignificantly different in health visits. Completers who wrote about abuse rated the study as more valuable than did those who wrote about positive experiences, College students who wrote about childhood physical or sexual abuse benefited from any type of structured writing assignment (where they interacted with a researcher and got extra credit) in terms of reduced anxiety, depression, and suicidal ideas, but they found value in writing about their trauma more than writing about innocuous topics. Keywords: abuse; writing; Pennebaker; disclosure

The 4-slice CT that forms part of the GE Infinia Hawkeye-4 SPECT-CT scanner (Hawkeye) is evaluated against the diagnostic 16-slice CT that is incorporated in the GE Discovery ST PET-CT system (DST). The x-ray tube of the slow-rotating Hawkeye system (23 s/rotation) operates at approximately a third of the dose of diagnostic systems as used for conventional diagnostic imaging. Image reconstruction is optimized for low noise. High-contrast spatial resolution significantly falls behind diagnostic figures: the average of MTF50 and MTF10 (resolution where the MTF has fallen to 50% and 10%) is 2.8 ± 0.1 cm[?]1 for Hawkeye and 5.3 ± 0.1 cm[?]1 for the DST (standard reconstruction filters). Resolution in the direction of the couch movement (z coordinate) is governed by the fixed Hawkeye slice width of 5 mm. Reconstruction accuracy is found to be increased by reducing the default z increment from 4.4 mm to 2.2 mm. Low-contrast object detectability is superior compared with diagnostic systems operating in the Hawkeye dose range. In the diagnostic dose regime, however, small low-contrast details remain visible in DST that are not detectable with Hawkeye. Although not of diagnostic quality, the low-dose Hawkeye provides appropriate data for SPECT attenuation correction and anatomical localization capability. [ABSTRACT FROM AUTHOR]