Somatic hypermutation defects in two adult hyper immunoglobulin M patients

Immunologic Research - Hyper immunoglobulin M (HIGM) syndrome is a rare disorder of the immune system with impaired antibody functions. The clinical picture of the patients varies according to the...     

Unique and redundant roles of SOX2 and SOX17 in regulating the germ cell tumor fate

Embryonal carcinomas (ECs) and seminomas are testicular germ cell tumors. ECs display expression of SOX2, while seminomas display expression of SOX17. In somatic differentiation, SOX17 drives endodermal cell fate. However, seminomas lack expression of endoderm markers, but show features of pluripotency. Here, we use chromatin immunoprecipitation sequencing to report and compare the binding pattern of SOX17 in seminoma-like TCam-2 cells to SOX17 in somatic cells and SOX2 in EC-like 2102EP cells. In seminoma-like cells, SOX17 was detected at canonical (SOX2/OCT4), compressed (SOX17/OCT4) and noncomposite SOX motifs. SOX17 regulates TFAP2C, PRDM1 and PRDM14, thereby maintaining latent pluripotency and suppressing somatic differentiation. In contrast, in somatic cells canonical motifs are rarely bound by SOX17. In sum, only 12% of SOX17-binding sites overlap in seminoma-like and somatic cells. This illustrates that binding site choice is highly dynamic and cell type specific. Deletion of SOX17 in seminoma-like cells resulted in loss of pluripotency, marked by a reduction of OCT4 protein level and loss of alkaline phosphatase activity. Furthermore, we found that in EC-like cells SOX2 regulates pluripotency-associated genes, most likely by partnering with OCT4. In conclusion, SOX17 (in seminomas) functionally replaces SOX2 (in ECs) to maintain expression of the pluripotency cluster.     

Assessment of proadrenomedullin as diagnostic or prognostic biomarker of acute appendicitis in children with acute abdominal pain

BackgroundAcute appendicitis (AA) is one of the most frequent surgical pathologies in pediatrics.ObjectivesTo investigate the utility of proadrenomedullin (pro-ADM) for the diagnosis of AA.MethodsProspective, analytical, observational, and multicenter study conducted in 6 pediatric emergency departments. Children up to 18 years of age with suspected AA were included. Clinical, epidemiological, and analytical data were collected.ResultsWe studied 285 children with an average age of 9.5 years (95% confidence interval [CI], 9.1–9.9). AA was diagnosed in 103 children (36.1%), with complications in 10 of them (9.7%). The mean concentration of pro-ADM (nmol/L) was higher in children with AA (0.51 nmol/L, SD 0.16) than in children with acute abdominal pain (AAP) of another etiology (0.44 nmol/L, SD 0.14; p < 0.001). This difference was greater in complicated cases compared with uncomplicated AA (0.64 nmol/L, SD 0.17 and 0.50 nmol/L, SD 0.15, respectively; p = 0.005). The areas under the receiver-operating characteristic curves were 0.66 (95% CI, 0.59–0.72) for pro-ADM, 0.70 (95% CI, 0.63–0.76) for C-reactive protein (CRP), 0.84 (95% CI, 0.79–0.89) for neutrophils, and 0.84 (95% CI, 0.79–0.89) for total leukocytes. The most reliable combination to rule out AA was CRP ≤1.25 mg/dL and pro-ADM ≤0.35 nmol/L with a sensitivity of 96% and a negative predictive value of 93%.ConclusionChildren with AA presented higher pro-ADM values than children with AAP of other etiologies, especially in cases of complicated AA. The combination of low values of pro-ADM and CRP can help to select children with low risk of AA.     

Los ingresos ectópicos y su relación con la aparición de complicaciones y estancias prolongadas

Objective

To analyze the relationship between the type of hospital admission (outlier and non-outlier admissions) and the appearance of clinical complications and the average stay.

Effects of 2,4-dichlorophenoxyacetic acid on the ventral prostate of rats during the peri-pubertal,pubertal and adult stage

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is used on a wide variety of terrestrial and aquatic broadleaf weeds. 2,4-D has been shown to produce a wide range of adverse effects on animal and human health. The aim of the current study was to evaluate the effects of pre- and postnatal exposure to 2,4-D on rat ventral prostate (VP). Pregnant rats were exposed daily to oral doses of 70?mg/kg/day of 2,4-D from 16 days of gestation up to 23 days after delivery. Then, the treated groups (n?=?8) were fed with a 2,4-D added diet until sacrificed by decapitation on postnatal day (PND) 45, 60, or 90. Morphometric studies were performed and androgen receptor (AR) protein levels in the VP were determined. AR, insulin-like growth factor-I (IGF-1) and insulin-like growth factor-I receptor (IGF-1R) mRNA expression in the VP along with testosterone (T), dihydroxytestosterone (DHT), growth hormone (GH) and IGF-1 serum levels were also determined to ascertain whether these parameters were differentially affected. Results of this study showed that 2,4-D exposure during gestation and until adulthood altered development of the prostate gland in male rats, delaying it at early ages while increasing its size in adults, indicate that 2,4-D could behave as endocrine disruptors (EDs).     

Extraction of artefactual MRS patterns from a large database using non-negative matrix factorization

Despite the success of automated pattern recognition methods in problems of human brain tumor diagnostic classification, limited attention has been paid to the issue of automated data quality assessment in the field of MRS for neuro-oncology. Beyond some early attempts to address this issue, the current standard in practice is MRS quality control through human (expert-based) assessment. One aspect of automatic quality control is the problem of detecting artefacts in MRS data. Artefacts, whose variety has already been reviewed in some detail and some of which may even escape human quality control, have a negative influence in pattern recognition methods attempting to assist tumor characterization. The automatic detection of MRS artefacts should be beneficial for radiology as it guarantees more reliable tumor characterizations, as well as the development of more robust pattern recognition-based tumor classifiers and more trustable MRS data processing and analysis pipelines. Feature extraction methods have previously been used to help distinguishing between good and bad quality spectra to apply subsequent supervised pattern recognition techniques. In this study, we apply feature extraction differently and use a variant of a method for blind source separation, namely Convex Non-Negative Matrix Factorization, to unveil MRS signal sources in a completely unsupervised way. We hypothesize that, while most sources will correspond to the different tumor patterns, some of them will reflect signal artefacts. The experimental work reported in this paper, analyzing a combined short and long echo time ¹H-MRS database of more than 2000 spectra acquired at 1.5T and corresponding to different tumor types and other anomalous masses, provides a first proof of concept that points to the possible validity of this approach.     

Persistent Organochlorine Contaminant Residues in Tissues of Hedgehogs from Turkey

The residues of persistent organochlorinated pollutants (POPs), namely polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) (HCHs, CHLs, HCCPs, DDTs, and dicofol congeners) were investigated in the hair and muscle of road-killed Erinaceus roumanicus and E. concolor in Turkey. Mean residue levels were as follows: in hair, PCBs?=?7.43?±?4.88 ng/g and OCPs?=?9.21?±?1.27 ng/g; in muscle, PCBs?=?30.73?±?2.51 ng/g and OCPs?=?145.04?±?16.59 ng/g. There was no significant difference between species and sex, while there was significant difference between habitats and regions in terms of either total PCB and OCP levels, or POP levels (p?<?0.05). Age was a determinative factor for the bio-accumulation of POPs. The contaminant levels were high in the species, sample areas, and habitats. The data also showed that tissues of hedgehogs are suitable for monitoring and evaluating the bioaccumulation of POP levels in Turkey.