Daily age, growth rate, and pelagic larval duration of commercially important snapper species in Abrolhos National Marine Park.

The age and daily growth of fish are registered through the deposition of increments in their otoliths, which are concretions formed by the precipitation of substances present in the endolymphatic fluid, mainly calcium carbonate (CaCO3). Faced with the need to fill some of the gaps in the knowledge on the occurrence and duration of the initial stages of snapper species' life cycles in the Abrolhos Bank, this study aimed to describe the growth rates, age, and period of pelagic larval duration (PLD) of three snapper species during the larval pre-settlement phase, in the Abrolhos Bank region. The post-larvae were captured using light traps. Otoliths were removed from 117 samples of snapper species; however, only 69 were viable for age estimation, of which 15 were Lutjanus analis, 25 were Lutjanus jocu, and 29 were Lutjanus synagris. Together, the samples presented individuals with total lengths ranging from 16.14 to 24.76 mm and ages from 21 to 39 days. Settlement marks were found for all three species, and the average PLD was ~25 days. The somatic growth of the snapper species was positively correlated with otolith growth. L. jocu presented the greatest daily growth compared to the other species. The three species use the Abrolhos Bank as a larval settlement site, demonstrating plasticity by using different habitats throughout their lives.

Accuracy of cone-beam computed tomography in determining gingival thickness: a systematic review and meta-analysis.

OBJECTIVE: To assess the accuracy of cone-beam computed tomography (CBCT) for determining gingival thickness. MATERIAL AND METHODS: Searches were undertaken in PubMed/MEDLINE, EMBASE, LILACS, Web of Science, Scopus, LIVIVO, and gray literature (Google Scholar and ProQuest) for studies considered eligible according to the following criteria: cross-sectional observational studies, which compared CBCT accuracy with that of transgingival probing when determining gingival thickness, in adult patients with good periodontal health. No language or time restrictions were applied in this systematic review. The risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for analytical cross-sectional studies. RESULTS: Six articles were included for qualitative synthesis, involving a pooled sample of 132 patients with a mean age of 29 years (18-51 years). Of these 6 studies, 5 were eligible for quantitative analysis. The meta-analysis showed no statistically significant difference between CBCT and transgingival probing measures of gingival tissue (mean difference of 0.10 (95% CI-0.17-0.38). No significant level of heterogeneity was detected (Tau2-P = 0.0662; I2 = 0%; H2-P = 1.000; Q-P = 1.134). According to the GRADE criterion, confidence in the cumulative evidence was considered low. CONCLUSIONS: CBCT is an accurate method for determining gingival tissue thickness, comparable to the reference standard (transgingival probing). CLINICAL RELEVANCE: CBCT could be considered for gingival thickness measurement when bone thickness is also needed, and thereby aid in the assessment of gingival biotype without the discomfort and anesthesia needed in transgingival probing. TRIAL REGISTRATION: This protocol was registered at the PROSPERO database (International Prospective Register of Systematic Review) under registration number CRD42022326970. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326970 .

Inactivation of Lgi1 in murine neuronal precursor cells leads to dysregulation of axon guidance pathways.

LGI1 mutations predispose to a rare epilepsy syndrome and when inactivated in mice leads to early onset seizures and premature death. Histopathology of the mature brain soon after birth shows cortical dysplasia in Lgi1 null mice with hypercellularity in the outer cortical layers. Here we show extensive gene expression changes in neuronal precursor cells from Lgi1 null mice compared with wild type mice. The most significantly dysregulated pathway involves canonical axon guidance signaling with multiple networks involved in cell movement, adhesion and invasion related to actin cytoskeleton reorganization. The Lgi1 null NPCs show increased cell motility in vitro compared with normal counterparts. Dysregulation of genes critical to cell movement/migration and critical transcription factors involved in early neuronal development is a prominent feature. These studies provide a critical mechanistic link to the observation of increased cellularity in the outer layers of the developing cortex in Lgi1 null mice.

Distinct signaling programs associated with progression of FGFR1 driven leukemia in a mouse model of stem cell leukemia lymphoma syndrome.

Constitutive activation of FGFR1 as a result of chromosome translocations is responsible for the development of a hematopoietic stem cell disorder that progresses to AML. We have developed a syngeneic mouse model of BCR-FGFR1 driven AML and used RNASeq to define gene expression signatures associated with disease progression. The development of the leukemic stem cells (LSC) is associated with a profound downregulation of specific transcription factors that normally maintain stem cell quiescence as well as cell adhesion and motility gene sets related to confinement to the stem cell niche. A prominent feature of the LSCs is the upregulation of genes involved in T-cell function, activation, migration and development. Despite this apparent T-cell priming in the LSCs, however, the majority of these genes are subsequently inactivated in the leukemic blast cells that derive from them. These studies provide insights into the molecular etiology of development and progression of FGFR1 driven AML.

Selective inactivation of LGI1 in neuronal precursor cells leads to cortical dysplasia in mice.

Constitutional mutations in Leucine-rich glioma inactivated 1 (LGI1) predispose to an autosomal dominant epilepsy syndrome in humans and germline inactivation of LGI1 in mice leads to early onset seizures. LGI1 is highly expressed in the regions involved in neuronal stem cell generation and migration and detailed analysis of the brains in these mice reveals a subtle cortical dysplasia characterized by hypercellularity in the outer cortical layers. To investigate the cellular origin for this cortical dysplasia, we created mice that allow cell-specific, conditional inactivation of LGI1. Exons 3-4, which contain critical motifs for LGI1 function, were targeted for deletion and, using a CMV-cre mouse strain, global inactivation of LGI1 led to early onset seizures and the same cortical dysplasia seen in the constitutionally null mice. Similarly, inactivation of LGI1 in cells expressing Nestin, expressed primarily in neuronal precursor cells, led to early onset seizures and cortical dysplasia. In contrast, targeting inactivation of LGI1 in cells expressing Gfap, Camk2a, and parvalbumin, did not lead to cortical dysplasia. This strain of mouse, therefore, allows for a more refined investigation of the cell types involved in the cortical dysplasia seen following inactivation of LGI1 and potentially a better understanding of the molecular mechanisms behind LGI1-induced epilepsy.

YM155 inhibits topoisomerase function.

YM155 (sepantronium bromide) has been evaluated in clinical trials as a survivin suppressant, but despite positive signals from early work, later studies were negative. Clarification of the mechanism of action of YM155 is important for its further development. YM155 affects cells in a cell cycle-specific manner. When cells are in G1, YM155 prevented their progression through the S phase, leaving the cells at G1/S when exposed to YM155. Passage through mitosis from G2 is also defective following YM155 exposure. In this study, YM155 did not behave like a typical DNA intercalator in viscosity, circular dichroism, and absorption spectroscopy studies. In addition, molecular modeling experiments ruled out YM155 DNA interaction to produce DNA intercalation. We show that YM155 inhibited topoisomerase 2α decatenation and topoisomerase 1-mediated cleavage of DNA, suggesting that YM155 inhibits the enzyme function. Consistent with these findings, DNA double-strand break repair was also inhibited by YM155.

Association between cell cycle gene transcription and tumor size in oral squamous cell carcinoma.

Higher tumor size correlates with poor prognosis and is an independent predictive survival factor in oral squamous cell carcinoma (OSCC) patients. However, the molecular events underlining OSCC tumor evolution are poorly understood. We aimed to investigate if large OSCC tumors show different cell cycle gene transcriptional signature compared to small tumors. Seventeen fresh OSCC tumor samples with different tumor sizes (T) were included in the study. Tumors were from the tongue or from the floor of the mouth, and only three patients were nonsmokers. Samples were categorized according to clinical tumor size in tumors ≤2 cm (T1, n = 5) or tumors >2 cm (T2, n = 9; T3, n = 2; T4, n = 1). The group of tumors ≤2 cm was considered the reference group, while the larger tumors were considered the test group. We assessed the expression of 84 cell cycle genes by qRT-PCR array and normalized it to the expression of two housekeeping genes. Results were analyzed according to the formula 2(^-DeltaCt). A five-fold change cutoff was used, and p values <0.05 were considered statistically significant. Ki-67 immunohistochemistry was performed to estimate cell proliferation index. Twenty-nine genes were downregulated in the test group (larger tumors) compared to the reference group (smaller tumors). Among these genes, 13 reached statistical significance: ANAPC4, CUL1, SUMO1, KPNA2, MAD2L2, CCNG2, E2F4, NBN, CUL2, PCNA, TFDP1, KNTC1, and ATR. Ki-67 labeling index was similar in both tumor groups. Our findings suggest that the transcriptional activity of specific cell cycle genes varies according to the size of OSCC tumor, which probably reflects tumor molecular evolution and adaptation to the microenvironment.

IL-17 genetic and immunophenotypic evaluation in chronic graft-versus-host disease.

Although interleukin-17 (IL-17) is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD) was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4(+) T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD.

Review of the limitations of current biomarkers in acute kidney injury clinical practices.

Acute kidney injury is a prevalent disease in hospitalized patients and is continuously increasing worldwide. Various efforts have been made to define and classify acute kidney injury to understand the progression of this disease. Furthermore, deviations from structure and kidney function and the current diagnostic guidelines are not adequately placed due to baseline serum creatinine values, which are rarely known and estimated based on glomerular function rate, resulting in misclassification of acute kidney injury staging. Hence, the current guidelines are still developing to improve and understand the clinical implications of risk factors and earlier predictive biomarkers of acute kidney injury. Yet, studies have indicated disadvantages and limitations with the current acute kidney injury biomarkers, including lack of sensitivity and specificity. Therefore, the present narrative review brings together the most current evidenced-based practice and literature associated with the limitations of the gold standard for acute kidney injury diagnoses, the need for novel acute kidney injury biomarkers, and the process for biomarkers to be qualified for diagnostic use under the following sections and themes. The introduction section situates the anatomy and normal and abnormal kidney functions related to acute kidney injury disorders. Guidelines in providing acute kidney injury definitions and classification are then considered, followed by a discussion of the disadvantages of standard markers used to diagnose acute kidney injury. Characteristics of an ideal acute kidney injury biomarker are discussed concerning sensitivity, specificity, and anatomic location of injury. A particular focus on the role and function of emerging biomarkers is discussed in relation to their applications and significance to the prognosis and severity of acute kidney injury. Findings show emerging markers are early indicators of acute kidney injury prediction in different clinical settings. Finally, the process required for a biomarker to be applied for diagnostic use is explained.

Transcription factor STAT1 gene polymorphism is associated with the development of severe forms of periodontal disease.

INTRODUCTION: Periodontal disease (PD) is one of the most common inflammatory diseases, affecting about 10 % of the world population. The establishment of PD is influenced by polymorphisms in genes involved with the inflammatory response. Signal Transducer and Activator of Transcription (STAT)-1 is a transcription factor that plays a key role in the intracellular signaling triggered by cytokines and, thus, its activation is critical in inflammatory diseases. AIM AND METHODS: We aim to evaluate the occurrence of association between STAT-1 (rs3771300) polymorphism and distinct clinical forms and severity of PD; we genotyped 180 subjects using realtime PCR. RESULTS AND CONCLUSION: We observed that the presence of the G allele for STAT-1 was associated with twice as high of a chance to develop aggressive periodontitis, and the most severe form of the disease.

Identification of small molecules that suppress cell invasion and metastasis promoted by WASF3 activation.

The WASF3 gene promotes cancer cell invasion and metastasis, and genetic inactivation leads to suppression of metastasis. To identify small molecules that might interfere with WASF3 function, we performed an in silico docking study to the regulatory pocket of WASF3 using the National Cancer Institute (NCI) diversity set VI small molecule library. Compounds that showed the maximum likelihood of interaction with WASF3 were screened for their effect on cell movement in breast and prostate cancer cells, a well-established predictor of invasion and metastasis. Three hit compounds were identified that affected cell movement, and the same compounds also suppressed cell migration and invasion in vitro in both MDA-MB-231 breast cancer cells and Du145 prostate cancer cells. Using a zebrafish metastasis assay, one of these compounds, NSC670283, showed significant suppression of metastasis in vivo while not affecting cell proliferation. NSC670283 showed a consistent effect on suppression of invasion and metastasis, and cellular temperature shift assays provided support for physical interaction with WASF3. In addition, suppression of cell movement and invasion was accompanied by a decrease in actin filament polymerization. The data in this study suggest that these small molecules inhibit cancer cell invasion and metastasis, and to our knowledge, it is the first identification of a small molecule that can potentially inhibit WASF3-directed metastasis, laying the foundation for medicinal chemistry approaches to enhance the potency of the identified compounds.

Impact of the COVID-19 Pandemic on National Institutes of Health-Funded Researchers and Their Projects: The Role of Age, Sex, Experience, and Team Size.

OBJECTIVES: The COVID-19 pandemic has disrupted the social life, work environment, and well-being of millions of people. We examined COVID-19's impact on National Institutes of Health (NIH)-funded extramural principal investigators (PIs) affiliated with public health and preventive medicine departments across the country and their projects; assessed PIs' confidence in achieving project goals; and investigated the role of age, sex, experience, and team size on PIs' confidence in achieving project goals during the pandemic. METHODS: We sent an anonymous online survey in January 2021 to 1076 extramural PIs affiliated with public health and preventive medicine departments at US institutions; 133 (12.4%) responded. We examined the impact of COVID-19 on the PIs, their project team operations, and their confidence that project objectives would be met, using Likert scales based on age, sex, team size, and PI experience. RESULTS: Of 126 PIs, 94 (74.6%) felt that their day-to-day professional life was impacted a lot or a great deal by COVID-19. More female PIs than male PIs reported that their level of stress changed because of the COVID-19 pandemic. Of 125 PIs, 67 (53.6%) made major adjustments to research operations, 46 (36.8%) made minor adjustments, 5 (4.0%) halted research, and 7 (5.6%) reported not being affected. Of 123 PIs, 89 (72.4%) reported not using NIH COVID-19 accommodations. PIs who led projects 4 or 5 times felt more confident about meeting their research objectives than PIs who led projects 2 or 3 times. CONCLUSIONS: Future studies should investigate how to develop more engaging support and communication strategies to assist NIH researchers in mitigating the effects of pandemics or large-scale emergencies.

Design and development of a Telemedicine Assessment Toolkit (TAT) for the assessment of audiovisual telemedicine encounters.

Although the use of audiovisual telemedicine has grown in recent years especially during recent COVID-19-related lockdowns, evidence shows there is still a lack of tools that can be used for the assessment of telemedicine encounters. The few validated questionnaires that are available for assessing telemedicine encounters are not often used. Non-validated questionnaires dominate research, leading to results that cannot be compared or extrapolated to other research or medical sites. Development of standard measures for the assessment of telemedicine encounters has been advocated by stakeholders. The objective of this study is to provide a comprehensive set of measures by developing a conceptual approach and a preliminary Telemedicine Assessment Toolkit (TAT) for the assessment of audiovisual telemedicine encounters. A two-step conceptual approach was used to identify potential domains and sub-domains by qualitative analysis of a pool of questions from studies published from 2016 to 2021. Questions were adopted from validated questionnaires or generated to represent the underlying concept of each sub-domain, resulting in a core block of comprehensive questions. A toolkit is proposed with question-measures that cover the sub-domains relevant to the assessment of telemedicine encounters. This study recommended 11 domains to be used for the assessment of telemedicine encounters: "usability," "patient satisfaction," "patient-provider interaction," "patient perspectives," "telemedicine readiness," "qualitative feedback," "comparison to standard (in-person) care," "privacy," "technology," "patient feeling," and "patient costs." Of the 11 domains, 26 underlying sub-domains were created. From the subdomains, a 30-question core block was proposed. The core-block together with a precursor block aimed to retrieve demographic/patient characteristics and, together with a customizable clinical outcomes block, complete the comprehensive toolkit. The toolkit, upon testing and validation, would enable researchers and system owners to assess patient-oriented aspects of audiovisual telemedicine encounters more accurately and accelerate the adoption of common audiovisual telemedicine assessment measures.

Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability.

LGI1 in humans is responsible for a predisposition to autosomal dominant partial epilepsy with auditory features (ADPEAF). However, mechanisms of how LGI1 mutations cause epilepsy remain unclear. We have used a mouse chromosome engineering strategy to create a null mutation for the gene ortholog encoding LGI1. The Lgi1 null mutant mice show no gross overall developmental abnormalities from routine histopathological analysis. After 12-18 days of age, the homozygous mutant mice all exhibit myoclonic seizures accompanied by rapid jumping and running and die shortly thereafter. The heterozygous mutant mice do not develop seizures. Electrophysiological analysis demonstrates an enhanced excitatory synaptic transmission by increasing the release of the excitatory neurotransmitter glutamate, suggesting a basis for the seizure phenotype. This mouse model, therefore, provides novel insights into the mechanism behind ADPEAF and offers a new opportunity to study the mechanism behind the role of LGI1 in susceptibility to myoclonic seizures.

Association between polymorphisms in interleukin-17A and -17F genes and chronic periodontal disease.

OBJECTIVE: Interleukin-17 (IL-17) is a cytokine that induces neutrophil recruitment and the release of inflammatory mediators in several inflammatory conditions; nevertheless, the involvement of IL-17 gene polymorphisms in chronic periodontitis (CP) has not been addressed yet. Our aim was to evaluate the association between periodontal status and the polymorphisms IL-17A G197A and IL-17F C7488T in subjects with CP along with their impact on levels of inflammatory mediators. MATERIAL AND METHODS: Genomic DNA was obtained from 30 CP patients and 30 healthy controls (HCs). IL-17A G197A and IL-17F C7488T polymorphisms were determined using PCR-RFLP. Serum and periodontal tissues were collected and processed for ELISA, myeloperoxidase (MPO), and/or microscopic analysis. RESULTS: The frequencies of genotypes in the CP group were significantly different from those of HC. Odds ratio indicated that increased risks for CP were associated with the -197A allele, not with the -7488T allele. In addition, the -197A allele was correlated with worse clinical parameters, higher MPO activity, and increased expression of inflammatory mediators (IL-17A and IL-8) than the other genotypes. CONCLUSIONS: These results indicate that the IL-17A -197A allele is associated with increased risk for CP, likely because this genotype relates to the enhanced inflammation in periodontal tissues.

Oral cGVHD screening tests in the diagnosis of systemic chronic graft-versus-host disease.

To determine the diagnostic properties of oral manifestations and histological features of graft-versus-host disease (GVHD) screening tests in the diagnosis of systemic chronic graft-versus-host disease (cGVHD). Sixty patients having undergone allogeneic haematopoietic stem cell transplantation were selected. The patients were submitted to a clinical oral examination to assess symptoms and clinical changes in the oral mucosa. Histopathologic analysis of the lower lip oral mucosa (LLOM) and salivary glands (SG) was also performed. Systemic cGVHD was used for a comparison to oral cGVHD. The accuracy of oral cGVHD tests was low for all methods (58.4% and 52.6% for white lesions and white/red lesions, respectively, in the clinical analysis; 50.4% for the presence of oral pain; and 66.8% and 55.1% for LLOM and SG histopathologic tests, respectively). However, the presence of oral pain had good diagnostic properties [specificity: 100.0, 95% confidence interval (CI): 88.0-100.0; positive predictive value (PPV): 100.0, 95% CI: 94.4-100.0; and negative predictive value (NPV): 72.0, 95% CI: 57.3-83.3]. Moreover, SG alterations revealed by the histopathological analysis also exhibited good diagnostic properties (sensitivity: 98.6, 95% CI: 81.5-99.8; PPV: 71.1, 95% CI: 62.1-79.7; NPV: 85.9 95% CI: 32.9-99.4). The clinical severity of oral lesions and histophatological changes in the LLOM did not exhibit adequate diagnostic properties, whereas both oral pain and SG histopathological analysis exhibited adequate properties for the diagnosis of systemic cGVHD. Histological changes in lip oral mucosa and salivary glands together with a clinical manifestation of the disease in the oral mucosa can be useful to determining the systemic cGVHD.

Risk of oral cancer in patients with graft-vs-host disease: A systematic review and meta-analysis.

OBJECTIVE: This systematic review was undertaken to determine the risk of oral cancer in patients with chronic graft-vs-host disease (cGvHD). STUDY DESIGN: The search was conducted in 6 electronic databases (PubMed/MEDLINE, EMBASE, LILACS, Web of Science, Scopus, and LIVIVO) and gray literature (Google Scholar, Open Gray, and ProQuest) for studies published up to November 2021. RESULTS: Of the 13 cohorts included in qualitative synthesis, 9 were eligible for the quantitative analysis. The meta-analysis showed that the presence of cGvHD increased the risk of developing oral cancer (risk ratio [RR] = 2.78; 95% CI, 1.27-6.08; I2 = 46%; P = .01). A subgroup meta-analysis revealed a higher risk of oral cancer in Asian samples exposed to cGvHD (RR = 2.50; 95% CI, 1.54-4.04; I2 = 0%; P = .0002), which was not seen in the pooled analysis of European samples (P = .24). The overall methodological quality of most studies included was "good." The cumulative evidence (Grading of Recommendations Assessment, Development and Evaluation) was considered moderate and of very low confidence for Asian and European studies, respectively. CONCLUSIONS: Patients with cGvHD resulting from allogenic hematopoietic stem cell transplantation run an increased risk of developing oral cancer. Hence, it is recommended that patients with cGvHD be monitored to allow for the early detection and treatment of secondary malignant disease.

Predictive Score for Carbapenem-Resistant Gram-Negative Bacilli Sepsis: Single-Center Prospective Cohort Study.

A clinical-epidemiological score to predict CR-GNB sepsis to guide empirical antimicrobial therapy (EAT), using local data, persists as an unmet need. On the basis of a case-case-control design in a prospective cohort study, the predictive factors for CR-GNB sepsis were previously determined as prior infection, use of mechanical ventilation and carbapenem, and length of hospital stay. In this study, each factor was scored according to the logistic regression coefficients, and the ROC curve analysis determined its accuracy in predicting CR-GNB sepsis in the entire cohort. Among the total of 629 admissions followed by 7797 patient-days, 329 single or recurrent episodes of SIRS/sepsis were enrolled, from August 2015 to March 2017. At least one species of CR-GNB was identified as the etiology in 108 (33%) episodes, and 221 were classified as the control group. The cutoff point of ≥3 (maximum of 4) had the best sensitivity/specificity, while ≤1 showed excellent sensitivity to exclude CR-GNB sepsis. The area under the curve was 0.80 (95% CI: 0.76-0.85) and the number needed to treat was 2.0. The score may improve CR-GNB coverage and spare polymyxins with 22% (95% CI: 17-28%) adequacy rate change. The score has a good ability to predict CR-GNB sepsis and to guide EAT in the future.

The temporal and spatial expression pattern of the LGI1 epilepsy predisposition gene during mouse embryonic cranial development.

BACKGROUND: Mutations in the LGI1 gene predispose to a rare, hereditary form of temporal epilepsy. Currently, little is known about the temporal and spatial expression pattern of Lgi1 during normal embryogenesis and so to define this more clearly we used a transgenic mouse line that expresses GFP under the control of Lgi1 cis-regulatory elements. RESULTS: During embryonic brain growth, high levels of Lgi1 expression were found in the surface ectoderm, the neuroepithelium, mesenchymal connective tissue, hippocampus, and sensory organs, such as eye, tongue, and the olfactory bulb. Lgi1 was also found in the cranial nerve nuclei and ganglia, such as vestibular, trigeminal, and dorsal ganglia. Expression of Lgi1 followed an orchestrated pattern during mouse development becoming more subdued in areas of the neocortex of the mid- and hind-brain in early postnatal animals, although high expression levels were retained in the choroid plexus and hippocampus. In late postnatal stages, Lgi1 expression continued to be detected in many areas in the brain including, hippocampus, paraventricular thalamic nuclei, inferior colliculus, and the cerebral aqueduct. We also showed that Lgi1-expressing cells co-express nestin, DCX, and beta-III tubulin suggesting that Lgi1-expressing cells are migratory neuroblasts. CONCLUSION: These observations imply that Lgi1 may have a role in establishing normal brain architecture and neuronal functions during brain development suggesting that it may be involved in neurogenesis and neuronal plasticity, which become more specifically defined in the adult animal.

Investigation of functional IL-10 gene polymorphism and IL-10 levels in acute graft-versus-host disease.

BACKGROUND: Graft-versus-host disease (GVHD) represents a major complication in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Although studies have been conducted concerning the investigation of cytokine polymorphisms in the development of acute GVHD (aGVHD), the contribution of recipients and donors as regards cytokine levels has not yet been thoroughly assessed. OBJECTIVE: The aim of this study was to investigate the impact of IL-10 polymorphisms on cytokine levels in blood and saliva, in addition to the occurrence and severity of aGVHD. METHODS: Fifty-eight consecutive allo-HSCT recipients and their donors were included in this prospective study. Saliva and/or blood samples were obtained from recipients and donors to determine IL10 polymorphisms. The IL-10 levels in the blood and saliva were also assessed. The samples were collected from seven days before transplant (day -7) to 100 days after allo-HSCT (day +100), once a week or until the death of recipient. RESULTS: No association was found between recipient and donor IL10 polymorphism and IL-10 levels in the saliva with aGVHD. In contrast, IL-10 levels in the blood were associated with the occurrence of aGVHD. The high producer phenotype in the recipient was also associated with high levels of IL-10 in the blood and saliva. CONCLUSION: Although IL10 polymorphisms were not associated with the occurrence and severity of aGVHD, the genetic background of the recipient did in fact influence the production of the cytokine. Furthermore, as IL-10 levels in the blood were associated with the disease development, this parameter may well be a useful predictor of aGVHD development.