Coracoid Abnormalities and Their Relationship with Glenohumeral Deformities in Children with Obstetric Brachial Plexus Injury

<p>Abstract</p> <p>Background</p> <p>Patients with incomplete recovery from obstetric brachial plexus injury (OBPI) usually develop secondary muscle imbalances and bone deformities at the shoulder joint. Considerable efforts have been made to characterize and correct the glenohumeral deformities, and relatively less emphasis has been placed on the more subtle ones, such as those of the coracoid process. The purpose of this retrospective study is to determine the relationship between coracoid abnormalities and glenohumeral deformities in OBPI patients. We hypothesize that coracoscapular angles and distances, as well as coracohumeral distances, diminish with increasing glenohumeral deformity, whereas coracoid overlap will increase.</p> <p>Methods</p> <p>39 patients (age range: 2-13 years, average: 4.7 years), with deformities secondary to OBPI were included in this study. Parameters for quantifying coracoid abnormalities (coracoscapular angle, coracoid overlap, coracohumeral distance, and coracoscapular distance) and shoulder deformities (posterior subluxation and glenoid retroversion) were measured on CT images from these patients before any surgical intervention. Paired Student t-tests and Pearson correlations were used to analyze different parameters.</p> <p>Results</p> <p>Significant differences between affected and contralateral shoulders were found for all coracoid and shoulder deformity parameters. Percent of humeral head anterior to scapular line (PHHA), glenoid version, coracoscapular angles, and coracoscapular and coracohumeral distances were significantly lower for affected shoulders compared to contralateral ones. Coracoid overlap was significantly higher for affected sides compared to contralateral sides. Significant and positive correlations were found between coracoscapular distances and glenohumeral parameters (PHHA and version), as well as between coracoscapular angles and glenohumeral parameters, for affected shoulders. Moderate and positive correlations existed between coracoid overlap and glenohumeral parameters for affected shoulders. On the contrary, all correlations between the coracoid and glenohumeral parameters for contralateral shoulders were only moderate or relatively low.</p> <p>Conclusions</p> <p>These results indicate that the spatial orientation of the coracoid process differs significantly between affected and contralateral shoulders, and it is highly correlated with the glenohumeral deformity. With the progression of glenohumeral deformity, the coracoid process protrudes more caudally and follows the subluxation of the humeral head which may interfere with the success of repositioning the posteriorly subluxed humeral head anteriorly to articulate with the glenoid properly.</p

Lead exposure in adult males in urban Transvaal Province, South Africa during the apartheid era

Human exposure to lead is a substantial public health hazard worldwide and is particularly problematic in the Republic of South Africa given the country’s late cessation of leaded petrol. Lead exposure is associated with a number of serious health issues and diseases including developmental and cognitive deficiency, hypertension and heart disease. Understanding the distribution of lifetime lead burden within a given population is critical for reducing exposure rates. Femoral bone from 101 deceased adult males living in urban Transvaal Province (now Gauteng Province), South Africa between 1960 and 1998 were analyzed for lead concentration by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Of the 72 black and 29 white individuals sampled, chronic lead exposure was apparent in nearly all individuals. White males showed significantly higher median bone lead concentration (ME = 10.04 µg·g−1), than black males (ME = 3.80 µg·g−1) despite higher socioeconomic status. Bone lead concentration covaries significantly, though weakly, with individual age. There was no significant temporal trend in bone lead concentration. These results indicate that long-term low to moderate lead exposure is the historical norm among South African males. Unexpectedly, this research indicates that white males in the sample population were more highly exposed to lead

Combinations of newly confirmed Glioma-Associated loci link regions on chromosomes 1 and 9 to increased disease risk

<p>Abstract</p> <p>Background</p> <p>Glioblastoma multiforme (GBM) tends to occur between the ages of 45 and 70. This relatively early onset and its poor prognosis make the impact of GBM on public health far greater than would be suggested by its relatively low frequency. Tissue and blood samples have now been collected for a number of populations, and predisposing alleles have been sought by several different genome-wide association (GWA) studies. The Cancer Genome Atlas (TCGA) at NIH has also collected a considerable amount of data. Because of the low concordance between the results obtained using different populations, only 14 predisposing single nucleotide polymorphism (SNP) candidates in five genomic regions have been replicated in two or more studies. The purpose of this paper is to present an improved approach to biomarker identification.</p> <p>Methods</p> <p>Association analysis was performed with control of population stratifications using the EIGENSTRAT package, under the null hypothesis of "no association between GBM and control SNP genotypes," based on an additive inheritance model. Genes that are strongly correlated with identified SNPs were determined by linkage disequilibrium (LD) or expression quantitative trait locus (eQTL) analysis. A new approach that combines meta-analysis and pathway enrichment analysis identified additional genes.</p> <p>Results</p> <p>(i) A meta-analysis of SNP data from TCGA and the Adult Glioma Study identifies 12 predisposing SNP candidates, seven of which are reported for the first time. These SNPs fall in five genomic regions (5p15.33, 9p21.3, 1p21.2, 3q26.2 and 7p15.3), three of which have not been previously reported. (ii) 25 genes are strongly correlated with these 12 SNPs, eight of which are known to be cancer-associated. (iii) The relative risk for GBM is highest for risk allele combinations on chromosomes 1 and 9. (iv) A combined meta-analysis/pathway analysis identified an additional four genes. All of these have been identified as cancer-related, but have not been previously associated with glioma. (v) Some SNPs that do not occur reproducibly across populations are in reproducible (invariant) pathways, suggesting that they affect the same biological process, and that population discordance can be partially resolved by evaluating processes rather than genes.</p> <p>Conclusion</p> <p>We have uncovered 29 glioma-associated gene candidates; 12 of them known to be cancer related (<it>p </it>= 1. 4 × 10^-6), providing additional statistical support for the relevance of the new candidates. This additional information on risk loci is potentially important for identifying Caucasian individuals at risk for glioma, and for assessing relative risk.</p

Meiotic Recombination Hotspots of Fission Yeast Are Directed to Loci that Express Non-Coding RNA

Polyadenylated, mRNA-like transcripts with no coding potential are abundant in eukaryotes, but the functions of these long non-coding RNAs (ncRNAs) are enigmatic. In meiosis, Rec12 (Spo11) catalyzes the formation of dsDNA breaks (DSBs) that initiate homologous recombination. Most meiotic recombination is positioned at hotspots, but knowledge of the mechanisms is nebulous. In the fission yeast genome DSBs are located within 194 prominent peaks separated on average by 65-kbp intervals of DNA that are largely free of DSBs.). Furthermore, we tested and rejected the hypothesis that the ncRNA loci and DSB peaks localize preferentially, but independently, to a third entity on the chromosomes.Meiotic DSB hotspots are directed to loci that express polyadenylated ncRNAs. This reveals an unexpected, possibly unitary mechanism for what directs meiotic recombination to hotspots. It also reveals a likely biological function for enigmatic ncRNAs. We propose specific mechanisms by which ncRNA molecules, or some aspect of RNA metabolism associated with ncRNA loci, help to position recombination protein complexes at DSB hotspots within chromosomes

Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected

An Alternate STAT6-Independent Pathway Promotes Eosinophil Influx into Blood during Allergic Airway Inflammation

Enhanced eosinophil responses have critical roles in the development of allergic diseases. IL-5 regulates the maturation, migration and survival of eosinophils, and IL-5 and eotaxins mediate the trafficking and activation of eosinophils in inflamed tissues. CD4⁺ Th2 cells are the main producers of IL-5 and other cells such as NK also release this cytokine. Although multiple signalling pathways may be involved, STAT6 critically regulates the differentiation and cytokine production of Th2 cells and the expression of eotaxins. Nevertheless, the mechanisms that mediate different parts of the eosinophilic inflammatory process in different tissues in allergic airway diseases remain unclear. Furthermore, the mechanisms at play may vary depending on the context of inflammation and microenvironment of the involved tissues. We employed a model of allergic airway disease in wild type and STAT6-deficient mice to explore the roles of STAT6 and IL-5 in the development of eosinophilic inflammation in this context. Quantitative PCR and ELISA were used to examine IL-5, eotaxins levels in serum and lungs. Eosinophils in lung, peripheral blood and bone marrow were characterized by morphological properties. CD4⁺ T cell and NK cells were identified by flow cytometry. Antibodies were used to deplete CD4⁺ and NK cells. We showed that STAT6 is indispensible for eosinophilic lung inflammation and the induction of eotaxin-1 and -2 during allergic airway inflammation. In the absence of these chemokines eosinophils are not attracted into lung and accumulate in peripheral blood. We also demonstrate the existence of an alternate STAT6-independent pathway of IL-5 production by CD4⁺ and NK cells that mediates the development of eosinophils in bone marrow and their subsequent movement into the circulation

Response of the primary auditory and non-auditory cortices to acoustic stimulation: A manganese-enhanced MRI study

Structural and functional features of various cerebral cortices have been extensively explored in neuroscience research. We used manganese-enhanced MRI, a non-invasive method for examining stimulus-dependent activity in the whole brain, to investigate the activity in the layers of primary cortices and sensory, such as auditory and olfactory, pathways under acoustic stimulation. Male Sprague-Dawley rats, either with or without exposure to auditory stimulation, were scanned before and 24-29 hour after systemic MnCl2 injection. Cortex linearization and layer-dependent signal extraction were subsequently performed for detecting layer-specific cortical activity. We found stimulus-dependent activity in the deep layers of the primary auditory cortex and the auditory pathways. The primary sensory and visual cortices also showed the enhanced activity, whereas the olfactory pathways did not. Further, we performed correlation analysis of the signal intensity ratios among different layers of each cortex, and compared the strength of correlations between with and without the auditory stimulation. In the primary auditory cortex, the correlation strength between left and right hemisphere showed a slight but not significant increase with the acoustic simulation, whereas, in the primary sensory and visual cortex, the correlation coefficients were significantly smaller. These results suggest the possibility that even though the primary auditory, sensory, and visual cortices showed enhanced activity to the auditory stimulation, these cortices had different associations for auditory processing in the brain network.open0