Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury

Background Birth-related acute profound hypoxic–ischaemic brain injury has specific patterns of damage including the paracentral lobules. Objective To test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality. Materials and methods Study subjects included 13 children with proven acute profound hypoxic–ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups. Results There was statistically significant narrowing of the mid–posterior body and genu of the corpus callosum in children with hypoxic–ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths. Conclusion Focal volume loss is seen in the corpus callosum of children with hypoxic–ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic–ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic–ischaemic brain injur

Mycological and enzymatic studies on fresh beef meat sold in Taiz City, Yemen

The mycological analysis of 30 fresh beef meat samples on Czapek’s agar at 7º and 28ºC revealed that, heavily contamination with moulds was observed especially at 28ºC. A total of 234 and 400 colonies ⁄ 450 g meat were collected on both temperatures, respectively. Sixty-seven species belonging to 20 genera were identified. Members of Aspergillus, Mucor, Penicillium and Trichoderma were the most prevalent fungi. At 7°C was highly spoilage by yeasts fungi, while filamentous fungi predominated at 28°C. The ability of the common fungal isolates to produce protease and lipase enzymes revealed that most of them were positive. Among 152 isolates tested, 103 (67.8%) and 96 (63.2%) could respectively produce these enzymes. Because the deteriorative effects of the above fungi, food should be frequently and routinely analyzed. Also, it is essential to store the meat at lower temperature immediately after slaughtering and during transport and storage to reduce or prevent mould growth. DOI: http://dx.doi.org/10.5281/zenodo.103723

Patterns of Fetal Lamb Regional Cerebral Blood Flow during and after Prolonged Hypoxia

[Abstract not included] Speculation: In the fetal lamb during prolonged intrauterine hypoxia, total and regional cerebral blood flows increase to the same extent without evidence of preferential shunting to critical brainstem or subcortical areas. Neuropathologic studies have indicated relative sparing of these areas during similar animal experimental or human neonatal conditions. This suggests that the pattern of hypoxic ischemic insult to the neonatal central nervous system associated with asphyxia may differ from that produced by hypoxia alone. In addition, during asphyxia these pathologic changes may result primarily from hypotension and decreased regional cerebral blood flow, or from regional metabolic derangements in the cerebral tissue

Alternative polyadenylation factor CPSF6 regulates temperature compensation of the mammalian circadian clock

A defining property of circadian clocks is temperature compensation, characterized by the resilience of their near 24-hour free-running periods against changes in environmental temperature within the physiological range. While temperature compensation is evolutionary conserved across different taxa of life and has been studied within many model organisms, its molecular underpinnings remain elusive. Posttranscriptional regulations such as temperature-sensitive alternative splicing or phosphorylation have been described as underlying reactions. Here, we show that knockdown of cleavage and polyadenylation specificity factor subunit 6 (CPSF6), a key regulator of 3′-end cleavage and polyadenylation, significantly alters circadian temperature compensation in human U-2 OS cells. We apply a combination of 3′-end-RNA-seq and mass spectrometry–based proteomics to globally quantify changes in 3′ UTR length as well as gene and protein expression between wild-type and CPSF6 knockdown cells and their dependency on temperature. Since changes in temperature compensation behavior should be reflected in alterations of temperature responses within one or all of the 3 regulatory layers, we statistically assess differential responses upon changes in ambient temperature between wild-type and CPSF6 knockdown cells. By this means, we reveal candidate genes underlying circadian temperature compensation, including eukaryotic translation initiation factor 2 subunit 1 (EIF2S1).Peer Reviewe

Practice Parameter: Diagnostic assessment of the child with cerebral palsy: Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. For this parameter the authors reviewed available evidence on the assessment of a child suspected of having cerebral palsy (CP), a nonprogressive disorder of posture or movement due to a lesion of the developing brain. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: CP is a common problem, occurring in about 2 to 2.5 per 1,000 live births. In order to establish that a brain abnormality exists in children with CP that may, in turn, suggest an etiology and prognosis, neuroimaging is recommended with MRI preferred to CT (Level A). Metabolic and genetic studies should not be routinely obtained in the evaluation of the child with CP (Level B). If the clinical history or findings on neuroimaging do not determine a specific structural abnormality or if there are additional and atypical features in the history or clinical examination, metabolic and genetic testing should be considered (Level C). Detection of a brain malformation in a child with CP warrants consideration of an underlying genetic or metabolic etiology. Because the incidence of cerebral infarction is high in children with hemiplegic CP, diagnostic testing for coagulation disorders should be considered (Level B). However, there is insufficient evidence at present to be precise as to what studies should be ordered. An EEG is not recommended unless there are features suggestive of epilepsy or a specific epileptic syndrome (Level A). Because children with CP may have associated deficits of mental retardation, ophthalmologic and hearing impairments, speech and language disorders, and oral-motor dysfunction, screening for these conditions should be part of the initial assessment (Level A). CONCLUSIONS: Neuroimaging results in children with CP are commonly abnormal and may help determine the etiology. Screening for associated conditions is warranted as part of the initial evaluation

An in vivo strategy for knockdown of circular RNAs

Exonic circular RNAs (circRNAs) are highly abundant RNAs generated mostly from exons of protein-coding genes. Assaying the functions of circRNAs is not straightforward as common approaches for circRNA depletion tend to also alter the levels of mRNAs generated from the hosting gene. Here we describe a methodology for specific knockdown of circRNAs in vivo with tissue and cell resolution. We also describe an experimental and computational platform for determining the potential off-target effects as well as for verifying the obtained phenotypes. Briefly, we utilize shRNAs targeted to the circRNA-specific back-splice junction to specifically downregulate the circRNA. We utilized this methodology to downregulate five circRNAs that are highly expressed in Drosophila. There were no effects on the levels of their linear counterparts or any RNA with complementarity to the expressed shRNA. Interestingly, downregulation of circCtrip resulted in developmental lethality that was recapitulated with a second shRNA. Moreover, downregulation of individual circRNAs caused specific changes in the fly head transcriptome, suggesting roles for these circRNAs in the fly nervous system. Together, our results provide a methodological approach that enables the comprehensive study of circRNAs at the organismal and cellular levels and generated for the first time flies in which specific circRNAs are downregulated

Translation of circRNAs

Circular RNAs (circRNAs) are abundant and evolutionarily conserved RNAs of largely unknown function. Here, we show that a subset of circRNAs is translated in vivo. By performing ribosome footprinting from fly heads, we demonstrate that a group of circRNAs is associated with translating ribosomes. Many of these ribo-circRNAs use the start codon of the hosting mRNA, are bound by membrane-associated ribosomes, and have evolutionarily conserved termination codons. In addition, we found that a circRNA generated from the muscleblind locus encodes a protein, which we detected in fly head extracts by mass spectrometry. Next, by performing in vivo and in vitro translation assays, we show that UTRs of ribo-circRNAs (cUTRs) allow cap-independent translation. Moreover, we found that starvation and FOXO likely regulate the translation of a circMbl isoform. Altogether, our study provides strong evidence for translation of circRNAs, revealing the existence of an unexplored layer of gene activity

Recent Trends in Artificial Intelligence-Assisted Coronary Atherosclerotic Plaque Characterization

Coronary artery disease is a major cause of morbidity and mortality worldwide. Its underlying histopathology is the atherosclerotic plaque, which comprises lipid, fibrous and—when chronic—calcium components. Intravascular ultrasound (IVUS) and intravascular optical coherence tomography (IVOCT) performed during invasive coronary angiography are reference standards for characterizing the atherosclerotic plaque. Fine image spatial resolution attainable with contemporary coronary computed tomographic angiography (CCTA) has enabled noninvasive plaque assessment, including identifying features associated with vulnerable plaques known to presage acute coronary events. Manual interpretation of IVUS, IVOCT and CCTA images demands scarce physician expertise and high time cost. This has motivated recent research into and development of artificial intelligence (AI)-assisted methods for image processing, feature extraction, plaque identification and characterization. We performed parallel searches of the medical and technical literature from 1995 to 2021 focusing respectively on human plaque characterization using various imaging modalities and the use of AI-assisted computer aided diagnosis (CAD) to detect and classify atherosclerotic plaques, including their composition and the presence of high-risk features denoting vulnerable plaques. A total of 122 publications were selected for evaluation and the analysis was summarized in terms of data sources, methods—machine versus deep learning—and performance metrics. Trends in AI-assisted plaque characterization are detailed and prospective research challenges discussed. Future directions for the development of accurate and efficient CAD systems to characterize plaque noninvasively using CCTA are proposed.</jats:p

Superior Neuroprotective Efficacy of LAU-0901, a Novel Platelet-Activating Factor Antagonist, in Experimental Stroke

Platelet-activating factor (PAF) accumulates during cerebral ischemia, and inhibition of this process plays a critical role in neuronal survival. Recently, we demonstrated that LAU-0901, a novel PAF receptor antagonist, is neuroprotective in experimental stroke. We used magnetic resonance imaging in conjunction with behavior and immunohistopathology to expand our understanding of this novel therapeutic approach. Sprague–Dawley rats received 2 h middle cerebral artery occlusion (MCAo) and were treated with LAU-0901 (60 mg/kg) or vehicle 2 h from MCAo onset. Behavioral function, T2-weighted imaging (T2WI), and apparent diffusion coefficients were performed on days 1, 3, and 7 after MCAo. Infarct volume and number of GFAP, ED-1, and NeuN-positive cells were conducted on day 7. Behavioral deficit was significantly improved by LAU-0901 treatment compared to vehicle on days 1, 3, and 7. Total lesion volumes computed from T2WI were significantly reduced by LAU-0901 on days 1, 3, and 7 (by 83%, 90%, and 96%, respectively), which was consistent with decreased edema formation. Histopathology revealed that LAU-0901 treatment resulted in significant reduction of cortical and subcortical infarct volumes, attenuated microglial infiltration, and promoted astrocytic and neuronal survival. These findings suggest LAU-0901 is a promising neuroprotectant and provide the basis for future therapeutics in patients suffering ischemic stroke