Homing of lin/CD117 hematopoietic stem cells

In this report, we describe the homing of hematopoietic stem cells (HSCs) to non-hematopoietic tissues in lethally irradiated (9 Gy) hybrid mice transplanted intravenously with lin⁻/CD117⁺ bone marrow cells from ROSA26 mice. The numbers of CFU-GM in spleen of irradiated transplanted mice were well above the levels found in non-irradiated group as early as day 8 after transplant. On 12th day regeneration of lymphocytes was observed, an increase in granulocytes was detected as late as on 33rd day. Transplanted cells containing lacZ gene were detected in recipient mice by histochemistry and their location in the thymus, liver, stomach and ileum was followed during 33 days post-transplantation. On 8 and 33 days post-transplantation, we found massive presence of donor (lacZ⁺) cells in the thymic cortex. Hematopoietic stem cell transplantation led not only to recovery of hematopoietic and lymphoid tissues but also facilitated recovery of the small intestinal mucosa, which was significantly damaged by ionizing radiation.     

Low Comparability of Nutrition-Related Mobile Apps against the Polish Reference Method—A Validity Study

Nutrition-related mobile applications (apps) are commonly used to provide information about the user’s dietary intake, however, limited research has been carried out to assess to what extent their results agree with those from the reference method (RM). The main aim of this study was to evaluate the agreement of popular nutrition-related apps with the Polish RM (Dieta 6.0). The dietary data from two days of dietary records previously obtained from adults (60 males and 60 females) were compared with values calculated in five selected apps (FatSecret, YAZIO, Fitatu, MyFitnessPal, and Dine4Fit). The selection of apps was performed between January and February 2021 and based on developed criteria (e.g., availability in the Polish language, access to the food composition database, and the number of downloads). The data was entered by experienced clinical dietitians and checked by one more researcher. The mean age of study participants was 41.7 ± 14.8. We observed that all the apps tended to overestimate the energy intake, however, when considering the macronutrient intake, over- and underestimation were observed. According to our assumed criterion (±5% as perfect agreement, ±10% as sufficient agreement), none of the apps can be recommended as a replacement for the reference method both for scientific as well as clinical use. According to the Bland-Altman analysis, the smallest bias was observed in Dine4Fit in relation to energy, protein, and fat intake (respectively: −23 kcal; −0.7 g, 3 g), however, a wide range between the upper and lower limits of agreement were reported. According to the carbohydrate intake, the lowest bias was observed when FatSecret and Fitatu were used. These results indicate that the leading nutrition-related apps present a critical issue in the assessment of energy and macronutrient intake. Therefore, the implementation of validation studies for quality assessment is crucial to develop apps with satisfying quality.     

Diagnosis and treatment response in the asymmetric variant of chronic inflammatory demyelinating polyneuropathy

The objectives were to (a) assess the diagnostic value of testing clinically affected and unaffected limbs with nerve conduction studies (NCS) in patients with the asymmetric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) variant and to define the most useful strategy for diagnosis, and (b) describe treatment response and long‐term outcome. We performed a retrospective study and included patients with a multifocal distribution of symptoms and signs, who met the probable or definite EFNS/PNS diagnostic categories for CIDP. We included 34 patients and 32 NCS datasets were available. Of these 32 patients, 25 (78%) met the electrodiagnostic criteria for definite or probable CIDP and seven (22%) for possible CIDP. Patients fulfilling the possible electrodiagnostic criteria and a supportive criterion were considered as probable CIDP. NCS of the clinically affected forearm and leg led to a probable or definite diagnosis in 13 patients (41%). Measuring both arms up to Erb's point led to a probable or definite diagnosis in 25 patients (78%), after which NCS of both legs did not contribute to additional probable or definite diagnoses. In total, 30% of patients treated with dexamethasone and 94% of patients treated with intravenous immunoglobulins (IVIg) responded. IVIg withdrawal attempts were successful in 21% of patients. After measuring the clinically affected arm up to Erb's point, NCS of the unaffected arm to Erb's point has the highest additional diagnostic yield in patients with asymmetric CIDP. Patients seem to respond better to IVIg than to corticosteroids and long‐term treatment is often required, although IVIg withdrawal was successful in 21%.     

The Significance of NOTCH Pathway in the Development of Fibrosis in Systemic Sclerosis

Systemic sclerosis (SSc) is an autoimmune disorder characterized by the fibrosis of skin, heart, lung, and kidney as well. Excessive activation of fibroblasts is associated with higher expression of Notch1 and/or Notch3 genes. The constitutive expression of NOTCH genes was described in epithelial cells: epidermal keratinocytes, hair follicle cells and sebaceous glands. The NOTCH signalling pathway may be involved in the development of fibrosis, myofibroblast formation and the process of epithelial-mesenchymal transition. Activation of the NOTCH pathway leads to morphological, phenotypic and functional changes in epithelial cells. Furthermore, inhibition of Notch signalling prevent the development of fibrosis in different models, among them, bleomycin-induced fibrosis and in the Task-1 mause model. Molecular mechanisms, including the role of NOTCH signaling pathway, associated with fibrosis in SSc have not been completely recognized.     

Relapse following frontofacial advancement using the rigid external distractor

Multisutural synostosis may result in frontofacial hypoplasia. The aesthetic and function problems arising from this can be corrected by frontofacial advancement, either by monobloc or bipartition osteotomy. Significantly larger, safer advancements can be achieved using distraction osteogenesis when compared to conventional osteotomy. However, the stability of this technique has been questioned. A retrospective study of 21 patients with craniofacial dysostosis who underwent frontofacial advancement osteotomies using the rigid external distractor system was undertaken. Twelve were distracted on protocol 1 (24 hours after surgery at 1.5 mm/d). Nine were distracted on protocol 2 (7 days after surgery at 1 mm/d). A 6-week consolidation period was used. Changes in frontofacial advancement in the sagittal plane were measured preoperatively, immediately, at 6 months, and where possible thereafter annually using lateral cephalograms and three-dimensional computed tomography scans. The midface was distracted an average of 16.4 mm with a range of 12 to 22 mm as measured in the sagittal plain. Relapse was seen only in 3 of 21 patients, and all of these patients were distracted using protocol 1. Distraction osteogenesis of the frontofacial skeleton using the rigid external distractor frame is generally stable. In this series, a longer latency period and reduced distraction rate resulted in greater stability. Overdistraction in the growing infant is recommended to allow for completion of growth. Overdistraction is not needed to compensate for potential relapse.     

Increased expression of the microRNA 106b~25 cluster and its host gene MCM7 in corticotroph pituitary adenomas is associated with tumor invasion and Crooke’s cell morphology

Purpose

MCM7 (minichromosome maintenance complex component 7), a DNA replication licensing factor, is a host gene for the oncogenic miR-106b~25 cluster. It has been recently revealed as a relevant prognostic biomarker in a variety of cancers, including pituitary adenomas. The purpose of this study was to assess whether miR-106b~25 and MCM7 levels correlate with tumor invasiveness in a cohort of ACTH-immunopositive adenomas.

Methods

Tissue samples were obtained intraoperatively from 25 patients with pituitary adenoma. Tumor invasiveness was assessed according to the Knosp grading scale. MCM7, Ki-67 and TP53 levels were assessed by immunohistochemical staining, while the expression of miR-106b-5p, miR-93-5p, miR-93-3p and miR-25-3p were measured using quantitative real-time PCR performed on RNA isolated from FFPE tissues.

Results

We have found a significant increase in MCM7 and Ki-67 labeling indices in invasive ACTHomas. Moreover, MCM7 was ubiquitously overexpressed in Crooke’s cell adenomas. The expression of miR-93-5p was significantly elevated in invasive compared to noninvasive tumors. In addition, all four microRNAs from the miR-106b~25 cluster displayed marked upregulation in Crooke’s cell adenomas. Remarkably, MCM7 and miR-106b-5p both strongly correlated with Knosp grade. A combination of MCM7 LI and miR-106b~25 cluster expression was able to accurately differentiate invasive from noninvasive tumors and had a significant discriminatory ability to predict postoperative tumor recurrence/progression.

Conclusions

miR-106b~25 and its host gene MCM7 are potential novel biomarkers for invasive ACTH-immunopositive pituitary adenomas. Additionally, they are both significantly upregulated in rare Crooke’s cell adenomas and might therefore contribute to their aggressive phenotype.