Genetic Background Influences Severity of Colonic Aganglionosis and Response to GDNF Enemas in the Holstein Mouse Model of Hirschsprung Disease

Hirschsprung disease is a congenital malformation where ganglia of the neural crest-derived enteric nervous system are missing over varying lengths of the distal gastrointestinal tract. This complex genetic condition involves both rare and common variants in dozens of genes, many of which have been functionally validated in animal models. Modifier loci present in the genetic background are also believed to influence disease penetrance and severity, but this has not been frequently tested in animal models. Here, we addressed this question using Holstein mice in which aganglionosis is due to excessive deposition of collagen VI around the developing enteric nervous system, thereby allowing us to model trisomy 21-associated Hirschsprung disease. We also asked whether the genetic background might influence the response of Holstein mice to GDNF enemas, which we recently showed to have regenerative properties for the missing enteric nervous system. Compared to Holstein mice in their original FVB/N genetic background, Holstein mice maintained in a C57BL/6N background were found to have a less severe enteric nervous system defect and to be more responsive to GDNF enemas. This change of genetic background had a positive impact on the enteric nervous system only, leaving the neural crest-related pigmentation phenotype of Holstein mice unaffected. Taken together with other similar studies, these results are thus consistent with the notion that the enteric nervous system is more sensitive to genetic background changes than other neural crest derivatives.

The influence of signal noise to measurements at bridge structure

Bridge weight-in-motion (BWIM) system is a method, that provides to identify axle weights. It is a non-destructive method, which allows not only to identify the axle weight, but it can show current shape of the structure, so it has a great potential. There are various methods to do measurements for this system. Mostly, accelerometers or strain gauge are used. Signal noise has significant effects to the results. It could be resonance of the bridge, wind, defect at the support system, defect at the roadway, etc. It is necessary to filter all this effects, to get clear data. There are many ways to do the filtering. Digital filters allow it. Sometimes, this type of filtering could remove important data about the crossing of the vehicle. It could generate inaccuracy of the whole system and create major errors to identified vehicles. It is necessary to find the optimal way, to keep important data and remove all dynamic noise. This paper will investigate the previously mentioned problems. Measurements will be accomplished on a small-scale model of the bridge. Vehicle will be crossing over the bridge, while the bridge will be awakened to the first vibration shape and other frequencies, that will have a great impact to the measurements.

Localization System for Lightweight Unmanned Aerial Vehicles in Inspection Tasks

This paper presents a localization system for Unmanned Aerial Vehicles (UAVs) especially designed to be used in infrastructure inspection, where the UAVs have to fly in challenging conditions, such as relatively high altitude (e.g., 15 m), eventually with poor or absent GNSS (Global Navigation Satellite System) signal reception, or the need for a BVLOS (Beyond Visual Line of Sight) operation in some periods. In addition, these infrastructure inspection applications impose the following requirements for the localization system: defect traceability, accuracy, reliability, and fault tolerance. Our system proposes a lightweight solution combining multiple stereo cameras with a robotic total station to comply with these requirements, providing full-state estimation (i.e., position, orientation, and linear and angular velocities) in a fixed and time-persistent reference frame. Moreover, the system can align and fuse all sensor measurements in real-time at high frequency. We have integrated this localization system in our aerial platform, and we have tested its performance for inspection in a real-world viaduct scenario, where the UAV has to operate with poor or absent GNSS signal at high altitude.

Cryptosporidium animal species in Iran: a systematic review and meta-analysis

Background Cryptosporidiosis is an acute and short-term infection which can lead to severe diarrhea (intestinal cryptosporidiosis) associated with a persistent cough in the host with immune system defect. This systematic review and meta-analysis was conducted to estimate the prevalence of animal Cryptosporidium species and the corresponding epidemiological aspects in Iran. Methods In this study, all original research articles relating to the animal cryptosporidiosis in Iran were collected from reliable databases using keywords. A meta-analysis was conducted separately for each subgroup, and heterogeneity among the studies was performed using the Q and I2 tests. Furthermore, it should be noticed that the significance level in the statistical analysis with the Comprehensive Meta-analysis software was considered to be less than 0.05. Finally, meta-analysis results were shown in forest plot with a 95% CI. Results In total, 4795 studies were included in the initial screening. Duplicated or non-original studies and the ones which did not meet our considered criteria were excluded from the list. Out of the 100 articles included in our first list for the meta-analysis, 40, 16, 13, 10, 9, 7, and 5 were done on cattle and calves, birds, dogs, sheep, rodents, camels, and horses, respectively. The prevalence rate of cryptosporidiosis among the birds, horses, rodents, camels, dogs, cattle, and sheep in Iran was estimated to be 7.5%, 19.5%, 20.8%, 8.4%, 4.9%, 14.4%, and 9.1%, respectively. Conclusion The different Cryptosporidium species have been found in different regions of Iran. Geographical region, climate, and domestic animals are considered as factors responsible for animal cryptosporidiosis prevalence in the area. Moreover, this parasite is zoonotic which causes disease in animals as well as humans which can result in economic loss.

Acute Hematogenous Escherichia coli Osteomyelitis of the Fibula in an Adolescent Girl

Introduction: Acute hematogenous osteomyelitis (AHO) usually occurs in the first two decades of life. Evidence shows that 50% of patients with AHO are younger than five years. This infection typically affects the metaphyseal region of long tubular bones, whereas the fibula is rarely involved. Staphylococcus aureus is the causative agent of AHO in the majority of cases, while Escherichia coli is isolated rather uncommonly beyond the neonatal period. Case Presentation: Herein, we describe the case of an adolescent girl who was treated medically and surgically for AHO with an unusual location in the proximal fibula, caused by E. coli. The source of the causative agent remained unknown after the patient had been evaluated for possible urinary tract infection and underlying immune system defect. Conclusions: The fibula is a rare anatomic location for AHO, and such cases may pose a diagnostic challenge. Lack of response to empiric antibiotic treatment in patients with AHO may indicate the involvement of an uncommon pathogen, which is not susceptible to standard empiric antimicrobials aimed to target S. aureus as the most likely pathogen. In such instances, prompt surgical intervention can help determine the causative pathogen and optimize antimicrobial treatment.

Aggressive Periodontitis with Neutropenia Caused by MMD2 Mutation

Aggressive periodontitis causes rapid periodontal tissue destruction and is a disease that occurs at a young age and runs in the patient’s family. Here, we revealed a heterozygous A116V missense mutation in the gene encoding monocyte to macrophage differentiation associated 2 (MMD2) protein in a Japanese family with aggressive periodontitis and neutropenia. Analyses of patients’ peripheral blood revealed a low number of neutrophils but abundant quantity of CD34+ hematopoietic stem and progenitor cells (HSPCs). Moreover, mutant Mmd2 mice showed severe alveolar bone loss and neutropenia. In patients and mutant Mmd2 mice, differentiation of HSPCs into granulocytes was also impeded, and their granulocytes were functionally impaired. Taken together, A116V mutation in MMD2 gene induced mild neutropenia and slightly limited the immune defense response. Our studies suggested that aggressive periodontitis in association with A116V MMD2 mutation constitutes a new immune system defect that belongs to the same spectrum of severe congenital neutropenia.

Haemophagocytic lymphohisticytosis—an underrecognized hyperinflammatory syndrome

Haemophagocytic lymphohisticytosis (HLH) is a syndrome of uncontrolled, severe systemic inflammation (hyperinflammation) arising either from a genetic immune system defect [primary (pHLH)] or triggered as a complication of malignancy, infection, or rheumatologic disease [secondary (sHLH)]. Patients with HLH often have non-specific symptoms and become progressively and critically unwell, with fever, cytopenia and multi-organ failure. Untreated, HLH is almost universally fatal, but even when treated, mortality is high, particularly when HLH complicates malignancy. HLH is managed with immunosuppression, and this can seem difficult to justify in such unwell patients. This review aims to examine the diagnostic and treatment challenges posed by sHLH and to improve recognition among rheumatologists who, being expert in the management of multisystem diseases and in the use of immunosuppression, are ideally placed to deliver care and build an evidence base for better disease characterization and treatment.