Wnt/ß-Catenin-Signaling Modulates Megakaryopoiesis at the Megakaryocyte-Erythrocyte Progenitor Stage in the Hematopoietic System.

The bone marrow (BM) hematopoietic system (HS) gives rise to blood cells originating from hematopoietic stem cells (HSCs), including megakaryocytes (MKs) and red blood cells (erythrocytes; RBCs). Many steps of the cell-fate decision remain to be elucidated, being important for cancer treatment. To explore the role of Wnt/ß-catenin for MK and RBC differentiation, we activated ß-catenin signaling in platelet-derived growth factor b (Pdgfb)-expressing cells of the HS using a Cre-lox approach (Ctnnb1BM-GOF). FACS analysis revealed that Pdgfb is mainly expressed by megakaryocytic progenitors (MKPs), MKs and platelets. Recombination resulted in a lethal phenotype in mutants (Ctnnb1BM-GOFwt/fl, Ctnnb1BM-GOFfl/fl) 3 weeks after tamoxifen injection, showing an increase in MKs in the BM and spleen, but no pronounced anemia despite reduced erythrocyte counts. BM transplantation (BMT) of Ctnnb1BM-GOF BM into lethally irradiated wildtype recipients (BMT-Ctnnb1BM-GOF) confirmed the megakaryocytic, but not the lethal phenotype. CFU-MK assays in vitro with BM cells of Ctnnb1BM-GOF mice supported MK skewing at the expense of erythroid colonies. Molecularly, the runt-related transcription factor 1 (RUNX1) mRNA, known to suppress erythropoiesis, was upregulated in Ctnnb1BM-GOF BM cells. In conclusion, ß-catenin activation plays a key role in cell-fate decision favoring MK development at the expense of erythroid production.

Innovative biodegradable dibutyrylchitin dressing for the treatment of ulcers occurring during chronic venous insufficiency in patients with type 2 diabetes.

The aim of this study was to assess the course of the healing process following the use of dibutyrylchitin (DBC) dressing, a fully degradable material used in the treatment of ulcers which occur during chronic venous insufficiency common in patients suffering from type 2 diabetes. These diseases have a significant impact on the patients' standard of living, including the potential employment, and on the declining attendance at the current workplace. The implementation of this innovative therapeutic solution may positively affect the above-mentioned difficulties. An analysis of the healing process, following the application of the DBC dressing, was performed. Once the dressing was positioned on the wound, the analysis indicated that it underwent a process of degradation facilitated by the enzymes occurring naturally in the wound. When fully degraded, a further layer was applied. This process was repeated until the wound was fully healed. The study group consisted of 4 patients previously diagnosed with type 2 diabetes. During the observation period, the ulcers in all 4 cases had healed. The examined wound dressings adhered well to the wound surface and degraded within it. No side effects or adverse effects of the applied innovative therapy were observed. An addition of the biodegradable DBC dressing to the standard therapy procedure of ulcers occurring during chronic venous insufficiency among patients with type 2 diabetes indicate safe and effective treatment, which may have a direct reflection in the patient's professional capacity enhancement. It resulted in the complete healing of all ulcers in each of the observed cases. Int J Occup Med Environ Health. 2021;34(4):565-73.

Evaluation of the effectiveness of iodine prophylaxis in Poland based on over 20 years of observations of iodine supply in school-aged children in the central region of the country.

INTRODUCTION: Due to the mild-to-moderate iodine deficiency in Poland, in 1997 iodine prophylaxis based on obligatory salt iodization was introduced. We attempted to evaluate the effectiveness of such prophylaxis, based on over 20 years of observations of iodine supply in school-aged children in Opoczno district (Central Poland). MATERIAL AND METHODS: A group of 603 children (316 girls and 287 boys), aged 6-14, was examined at 4 time points: in the years 1994, 1999, 2010 and 2016. The children were tested for urine iodine concentration (UIC) and in each child the thyroid volume was measured ultrasonographically. RESULTS: The median UIC in 1994 (45.5 µg/l) indicated moderate iodine deficiency, while after introducing prophylaxis it corresponded to adequate values (1999 - 101.1 µg/l, 2010 - 100.6 µg/l, 2016 - 288.3 µg/l); however, the last value was higher than the previous two. The thyroid size, assessed by ultrasonography and presented as volume/body surface area (V/BSA), in 1994 was 6.55 × 10-6 m; this value was higher than at other time points (2.73 × 10-6 m in 1999, 2.73 × 10-6 m in 2010, and 2.70 × 10-6 m in 2016). CONCLUSIONS: Iodine prophylaxis has proved effective in eliminating iodine deficiency. In recent years, the diversification of iodine sources, despite the reduction of salt consumption, has led to an increase in median UIC to values close to the upper limit of UIC, accepted as normal. Further increase in iodine supply may be unfavourable for health; therefore constant monitoring of iodine prophylaxis is required.

Two-Dimensional Speckle Tracking Versus Applanation Tonometry in Evaluation of Subclinical Atherosclerosis in Children with Type 1 Diabetes Mellitus.

BACKGROUND Patients with type 1 diabetes mellitus (T1DM) often develop atherosclerosis at an early age. In the subclinical stage of the process, minimal/non-morphological changes can be noticed, but the arterial wall function can be impaired. Applanation tonometry allows to assess the arterial tree stiffness; however, the Two-Dimensional Speckle Tracking (2DST) is an increasingly accepted alternative. This study evaluated arterial wall stiffness using these 2 techniques in children with T1DM. MATERIAL AND METHODS We performed applanation tonometry and carotid arteries sonography with evaluation of the carotid intima-media thickness (cIMT) and use of the 2DST in 50 children with T1DM and in 50 healthy sex- and age-matched controls. We also assessed the reliability of 2DST in 10 random subjects. RESULTS Children with T1DM had increased arterial wall stiffness, which was confirmed by tonometry (PWV: p=0.0386) and 2DST (Strain: p=0.0004; Strain rate: p=0.0081). There was no significant difference in cIMT between groups (0.45±0.06 vs. 0.43±0.05, p=0.073 in children with T1DM and controls, respectively). 2DST presented good intraclass correlation coefficient between researchers and within a single researcher. CONCLUSIONS Children with T1DM presenting with subclinical stage of atherosclerosis were found to have arterial wall stiffening. The 2DST, the same as applanation tonometry, allows to recognize this condition but in a more accessible and reproducible manner.

Limitations of insulin resistance assessment in polycystic ovary syndrome.

BACKGROUND: Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable. SUBJECTS AND METHODS: In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices). RESULTS: There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, r = -0.999, HOMA-IR/McAuley index, r = -0.849 and between all OGTT-derived IR indices (e.g. r = -0.876, for IRI/Matsuda, r = -0.808, for IRI/Stumvoll, and r = 0.947, for Matsuda/Stumvoll index, P < 0.001 for all), contrasting with a significant (P < 0.001), but highly variable correlation between IR indices derived from fasting vs OGTT-derived variables, ranging from r = -0.881 (HOMA-IR/Matsuda), through r = 0.58, or r = -0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to r = 0.41 (QUICKI/Stumvoll), and r = 0.386 for QUICKI/Matsuda indices. Detailed comparison between HOMA-IR and IRI revealed that concordance between HOMA and IRI was poor for HOMA-IR/IRI values above 75th and 90th percentile. For instance, only 53% (70/132) women with HOMA-IR >75th percentile had IRI value also above 75th percentile. There was a significant, but weak correlation of all IR indices with testosterone concentrations. CONCLUSIONS: Significant number of women with PCOS can be classified as being either insulin sensitive or insulin resistant depending on the method applied, as correlation between various IR indices is highly variable. Clinical application of surrogate indices for assessment of IR in PCOS must be therefore viewed with an extreme caution.

Gestational diabetes - is diet and insulin the only solution?

Gestational diabetes (GDM) is a relatively common complication of pregnancy. Maternal hyperglycemia causes many serious side effects for mothers, fetuses and newborns. In 90% of women diagnosed with GDM, a dietary treatment results in satisfactory levels of blood glucose. The remaining 10% require insulin therapy to achieve the recommended glycemic levels. The majority of recent studies show the efficiency of metformin in gestational diabetes and prove that it is not a cause for any harmful side effects to the embryo and/or fetus. Metformin is an effective alternative to insulin in glycemic control in pregnant women. The implementation of metformin, as a routine procedure in gestational diabetes, requires further research, the results of which would unequivocally confirm its efficacy and safety for pregnant women and their offspring.

Working Group Guidelines on the nursing roles in caring for patients with Crohn's disease and ulcerative colitis in Poland.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, present a major challenge for present-day gastroenterology due to their increasing incidence, chronic nature, risk of permanent worsening of quality of life of patients, and the costs of conservative and invasive treatment. Basic and advanced nursing care are important parts of the multidisciplinary care for patients. The developed guidelines on the nursing care, which are compliant with the European guidelines published by Nurses-European Crohn's & Colitis Organisation (N-ECCO), were adjusted to the current situation in Poland. Significant issues that are important for nursing teams have been identified, with particular emphasis on the specificity of working in centres specialising in the care of IBD patients. The Working Group paid attention to the conditions that should be satisfied in order to optimise the nursing care for IBD patients, and the necessity to develop professional and scientific cooperation with European centres within European Crohn's & Colitis Organisation (ECCO) and N-ECCO.

The usefulness of psychometric tests in dental treatment of patients aged above 65.

OBJECTIVE: The aim of this study was to analyze the occurrence of some psychological disorders in elderly people in three different social settings and to evaluate the impact of those problems on the adaptation of denture wearers to removable prostheses. MATERIALS AND METHODS: The study was conducted in three social settings: the geriatric clinic of a university hospital, nursing homes and a Third Age University school (TAU). Each group consisted of 70 randomly selected individuals. Of the total number of 210 subjects, 183 persons wore maxillary removable dentures while 150 had mandibular prostheses. Some symptoms of psychological disorders were diagnosed on the basis of results provided by two tests: GHQ and GDS. For identification of an inter-relationship between the use of removable dentures and the psychic status, the difficulties in adaptation to removable dentures were evaluated. RESULTS: Statistical analysis showed that the number of individuals with depressive symptoms was significantly lower in the group of TAU students than among the nursing home residents. No statistically significant difference in the occurrence of depression was found between the group of hospital patients and the students of TAU. A comparison of the GDS test results with the incidence of denture use difficulties indicated a significant inter-relationship. CONCLUSIONS: The GHQ and GDS tests may prove useful in the prosthetic treatment of those removable denture wearers who complain of oral discomfort without manifesting any visible causes. The proportion of elderly with signs of psychic disorders is significantly lower among TAU students than nursing home residents and hospital patients.

Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension.

RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling. Recent studies have revealed that immune and inflammatory responses play a crucial role in pathogenesis of idiopathic PAH. OBJECTIVES: To systematically evaluate the number and cross-sectional distribution of inflammatory cells in different sizes of pulmonary arteries from explanted lungs of patients with idiopathic PAH versus healthy donor lungs and to demonstrate functional relevance by blocking stromal-derived factor-1 by the Spiegelmer NOX-A12 in monocrotaline-induced pulmonary hypertension in rats. METHODS: Immunohistochemistry was performed on lung tissue sections from patients with idiopathic PAH and healthy donors. All positively stained cells in whole-lung tissue sections, surrounding the vessels, and in the different compartments of the vessels were counted. To study the effects of blocking SDF-1, rats with monocrotaline-induced pulmonary hypertension were treated with NOX-A12 from Day 21 to Day 35 after monocrotaline administration. MEASUREMENTS AND MAIN RESULTS: We found a significant increase of the perivascular number of macrophages (CD68(+)), macrophages/monocytes (CD14(+)), mast cells (toluidine blue(+)), dendritic cells (CD209(+)), T cells (CD3(+)), cytotoxic T cells (CD8(+)), and helper T cells (CD4(+)) in vessels of idiopathic PAH lungs compared with control subjects. FoxP3(+) mononuclear cells were significantly decreased. In the monocrotaline model, the NOX-A12-induced reduction of mast cells, CD68(+) macrophages, and CD3(+) T cells was associated with improvement of hemodynamics and pulmonary vascular remodeling. CONCLUSIONS: Our findings reveal altered perivascular inflammatory cell infiltration in pulmonary vascular lesions of patients with idiopathic pulmonary arterial hypertension. Targeting attraction of inflammatory cells by blocking stromal-derived factor-1 may be a novel approach for treatment of PAH.

Phosphodiesterase 10A upregulation contributes to pulmonary vascular remodeling.

Phosphodiesterases (PDEs) modulate the cellular proliferation involved in the pathophysiology of pulmonary hypertension (PH) by hydrolyzing cAMP and cGMP. The present study was designed to determine whether any of the recently identified PDEs (PDE7-PDE11) contribute to progressive pulmonary vascular remodeling in PH. All in vitro experiments were performed with lung tissue or pulmonary arterial smooth muscle cells (PASMCs) obtained from control rats or monocrotaline (MCT)-induced pulmonary hypertensive (MCT-PH) rats, and we examined the effects of the PDE10 inhibitor papaverine (Pap) and specific small interfering RNA (siRNA). In addition, papaverine was administrated to MCT-induced PH rats from day 21 to day 35 by continuous intravenous infusion to examine the in vivo effects of PDE10A inhibition. We found that PDE10A was predominantly present in the lung vasculature, and the mRNA, protein, and activity levels of PDE10A were all significantly increased in MCT PASMCs compared with control PASMCs. Papaverine and PDE10A siRNA induced an accumulation of intracellular cAMP, activated cAMP response element binding protein and attenuated PASMC proliferation. Intravenous infusion of papaverine in MCT-PH rats resulted in a 40%-50% attenuation of the effects on pulmonary hypertensive hemodynamic parameters and pulmonary vascular remodeling. The present study is the first to demonstrate a central role of PDE10A in progressive pulmonary vascular remodeling, and the results suggest a novel therapeutic approach for the treatment of PH.

The impact of positron emission tomography/computed tomography in edge delineation of gross tumor volume for head and neck cancers.

PURPOSE: To study anatomic biologic contouring (ABC), using a previously described distinct halo, to unify volume contouring methods in treatment planning for head and neck cancers. METHODS AND MATERIALS: Twenty-five patients with head and neck cancer at various sites were planned for radiation therapy using positron emission tomography/computed tomography (PET/CT). The ABC halo was used in all PET/CT scans to contour the gross tumor volume (GTV) edge. The CT-based GTV (GTV-CT) and PET/CT-based GTV (GTV-ABC) were contoured by two independent radiation oncologists. RESULTS: The ABC halo was observed in all patients studied. The halo had a standard unit value of 2.19 +/- 0.28. The mean halo thickness was 2.02 +/- 0.21 mm. Significant volume modification (>or=25%) was seen in 17 of 25 patients (68%) after implementation of GTV-ABC. Concordance among observers was increased with the use of the halo as a guide for GTV determination: 6 patients (24%) had a