Diagnosis of Epstein-Barr and cytomegalovirus infections using decision trees: an effective way to avoid antibiotic overuse in paediatric tonsillopharyngitis.

BACKGROUND: The incidence of tonsillopharyngitis is especially prevalent in children. Despite the fact that viruses cause the majority of infections, antibiotics are frequently used as a treatment, contrary to international guidelines. This is not only an inappropriate method of treatment for viral infections, but it also significantly contributes to the emergence of antibiotic-resistant strains. In this study, EBV and CMV-related tonsillopharyngitis were distinguished from other pathogens by using machine learning techniques to construct a classification tree based on clinical characteristics. MATERIALS AND METHODS: In 2016 and 2017, we assessed information regarding 242 children with tonsillopharyngitis. Patients were categorized according to whether acute cytomegalovirus or Epstein-Barr virus infections were confirmed (n = 91) or not (n = 151). Based on symptoms and blood test parameters, we constructed decision trees to discriminate the two groups. The classification efficiency of the model was characterized by its sensitivity, specificity, positive predictive value, and negative predictive value. Fisher's exact and Welch's tests were used to perform univariable statistical analyses. RESULTS: The best decision tree distinguished EBV/CMV infection from non-EBV/CMV group with 83.33% positive predictive value, 88.90% sensitivity and 90.30% specificity. GPT (U/l) was found to be the most discriminatory variable (p < 0.0001). Using the model, unnecessary antibiotic treatment could be reduced by 66.66% (p = 0.0002). DISCUSSION: Our classification model can be used as a diagnostic decision support tool to distinguish EBC/CMV infection from non EBV/CMV tonsillopharyngitis, thereby significantly reducing the overuse of antibiotics. It is hoped that the model may become a tool worth considering in routine clinical practice and may be developed to differentiate between viral and bacterial infections.

The nuclear receptor tailless induces long-term neural stem cell expansion and brain tumor initiation.

Malignant gliomas are the most common primary brain tumors, and are associated with frequent resistance to therapy as well as poor prognosis. Here we demonstrate that the nuclear receptor tailless (Tlx), which in the adult is expressed exclusively in astrocyte-like B cells of the subventricular zone, acts as a key regulator of neural stem cell (NSC) expansion and brain tumor initiation from NSCs. Overexpression of Tlx antagonizes age-dependent exhaustion of NSCs in mice and leads to migration of stem/progenitor cells from their natural niche. The increase of NSCs persists with age, and leads to efficient production of newborn neurons in aged brain tissues. These cells initiate the development of glioma-like lesions and gliomas. Glioma development is accelerated upon loss of the tumor suppressor p53. Tlx-induced NSC expansion and gliomagenesis are associated with increased angiogenesis, which allows for the migration and maintenance of brain tumor stem cells in the perivascular niche. We also demonstrate that Tlx transcripts are overexpressed in human primary glioblastomas in which Tlx expression is restricted to a subpopulation of nestin-positive perivascular tumor cells. Our study clearly demonstrates how NSCs contribute to brain tumorgenesis driven by a stem cell-specific transcription factor, thus providing novel insights into the histogenesis and molecular pathogenesis of primary brain tumors.

Epidemiology and clinical features of SARS-CoV-2 infection in hospitalized children across four waves in Hungary: A retrospective, comparative study from March 2020 to December 2021.

Background and Aims: From 2019 till the present, infections induced by the novel coronavirus and its mutations have posed a new challenge for healthcare. However, comparative studies on pediatric infections throughout waves are few. During four different pandemic waves, we intended to investigate the clinical and epidemiological characteristic of the pediatric population hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infection. Methods: Between March 2020 and December 2021, we performed our retrospective research on children infected with the SARS-CoV-2 virus at the University of Szeged. We analyzed the data of all patients who required hospitalization due to positive results of SARS-CoV-2 tests (Nucleic Acid Amplification Test or rapid antigen test). Data analysis included demographic data, medical history, clinical findings, length of hospitalization, and complications, using medical records. Results: In this study, data from 358 coronavirus-infected children were analyzed. The most affected age group was children over 1 month and under 1 year (30.2%). The highest number of cases was recorded in the fourth wave (53.6%). Fever (65.6%), cough (51.4%), nasal discharge (35.3%), nausea and vomiting (31.3%), and decreased oral intake (28.9%) were the most common symptoms. The most common complications were dehydration (50.5%), pneumonia (14.9%), and bronchitis/bronchiolitis (14.5%). Based on RR values, there are considerable differences in the prevalence of the symptoms and complications between the different age groups and waves. Cox proportional hazard model analyzes showed that fever and tachypnoea had a relevant effect on days to recovery. Conclusions: We found trends similar to those previously published, overall statistics. The proportion of children requiring hospitalization varied from wave to wave, with the fourth wave affecting the Hungarian child population the most. Our findings suggest that hospitalization time is unrelated to age, but that certain symptoms (fever and tachypnoea) are associated with longer hospitalization. The onset of certain symptoms may differ by age group.

Lipocalin 13 enhances insulin secretion but is dispensable for systemic metabolic control.

Members of the lipocalin protein family serve as biomarkers for kidney disease and acute phase inflammatory reactions, and are under preclinical development for the diagnosis and therapy of allergies. However, none of the lipocalin family members has made the step into clinical development, mostly due to their complex biological activity and the lack of in-depth mechanistic knowledge. Here, we show that the hepatokine lipocalin 13 (LCN13) triggers glucose-dependent insulin secretion and cell proliferation of primary mouse islets. However, inhibition of endogenous LCN13 expression in lean mice did not alter glucose and lipid homeostasis. Enhanced hepatic secretion of LCN13 in either diet-induced or genetic obesity led to no discernible impact on systemic glucose and lipid metabolism, neither in preventive nor therapeutic setting. Of note, loss or forced LCN13 hepatic secretion did not trigger any compensatory regulation of related lipocalin family members. Together, these data are in stark contrast to the suggested gluco-regulatory and therapeutic role of LCN13 in obesity, and imply complex regulatory steps in LCN13 biology at the organismic level mitigating its principal insulinotropic effects.

[Exudative tonsillitis in children. How can we reduce the unnecessary antibiotic consumption?] / Lepedékes tonsilla gyermekkorban. Hogyan csökkentheto az indokolatlan antibiotikumfelhasználás?

Introduction: Exudative tonsillitis is a common clinical picture during childhood. The majority of these cases are caused by viruses (Epstein-Barr virus [EBV], cytomegalovirus [CMV], influenza virus, parainfluenza virus, and adenovirus), and only some infections are caused by bacteria, mainly group A streptococci (GAS). On the basis of international guidelines, routine use of early antibiotic treatment is not recommended in these cases, because it seems not to prevent GAS-associated complications. Aim: Our aim was to determine those laboratory results which are useful to distinguish between bacterial and viral infections in children with exudative tonsillitis to reduce antibiotic overuse. Method: In our study, we evaluated 135 clinical data from 133 children with exudative tonsillitis. Patients were grouped according to the following criteria: the first group contained patients with acute CMV or EBV infections, while in the second group, CMV or EBV infections were not confirmed using serology. Results: On the basis of our results, EBV or CMV infections (66/135, 48.8%) were serologically confirmed in the majority of cases with exudative tonsillitis between 2016 and 2017, while the causative role of GAS was minimal in this patient group (3/65, 4.61%). In spite of this finding, the majority of patients (92%) were treated with antibiotics. Conclusion: Our retrospective findings confirmed that it is not possible to determine the causative agent of this clinical picture on the basis of symptoms, and physical findings, moreover laboratory results, such as high white blood cell count could not confirm bacterial infection. At the same time, elevated transaminase levels may refer to viral origin of infection, especially EBV or CMV with high predictive value; the use of extended laboratory tests may reduce the unnecessary antibiotic consumption. Orv Hetil. 2020; 161(2): 50-55.

The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone.

The tailless (Tlx) gene encodes an orphan nuclear receptor that is expressed by neural stem/progenitor cells in the adult brain of the subventricular zone (SVZ) and the dentate gyrus (DG). The function of Tlx in neural stem cells of the adult SVZ remains largely unknown. We show here that in the SVZ of the adult brain Tlx is exclusively expressed in astrocyte-like B cells. An inducible mutation of the Tlx gene in the adult brain leads to complete loss of SVZ neurogenesis. Furthermore, analysis indicates that Tlx is required for the transition from radial glial cells to astrocyte-like neural stem cells. These findings demonstrate the crucial role of Tlx in the generation and maintenance of NSCs in the adult SVZ in vivo.

Inactivation of the gene for the nuclear receptor tailless in the brain preserving its function in the eye.

During embryogenesis, tailless, an orphan member of the nuclear receptor family, is expressed in the germinal zones of the brain and the developing retina, and is involved in regulating the cell cycle of progenitor cells. Consequently, a deletion of the tailless gene leads to decreased cell number with associated anatomical defects in the limbic system, the cortex and the eye. These structural abnormalities are associated with blindness, increased aggressiveness, poor performance in learning paradigms and reduced anxiousness. In order to assess the contribution of blindness to the behavioural changes, we established tailless mutant mice with intact visual abilities. We generated a mouse line in which the second exon of the tailless gene is flanked by loxP sites and crossed these animals with a transgenic line expressing the Cre recombinase in the neurogenic area of the developing brain, but not in the eye. The resulting animals have anatomically indistinguishable brains compared with tailless germline mutants, but are not blind. They are less anxious and much more aggressive than controls, like tailless germline mutants. In contrast to germline mutants, the conditional mutants are not impaired in fear conditioning. Furthermore, they show good performance in the Morris water-maze despite severely reduced hippocampal structures. Thus, the pathological aggressiveness and reduced anxiety found in tailless germline mutants are due to malformations caused by inactivation of the tailless gene in the brain, but the poor performance of tailless null mice in learning and memory paradigms is dependent on the associated blindness.