MLPA based detection of mutations in the dystrophin gene of 180 Polish families with Duchenne/Becker muscular dystrophy

Duchenne/Becker muscular dystrophy (DMD/BMD) is a recessive, X-linked disorder caused by a mutation in the dystrophin gene. Deletions account for approximately 60–65% of mutations, duplications for 5–10%. The remaining cases are mainly point mutations. According to Monaco theory clinical form of the disease depends on maintaining or disrupting the reading frame. The purpose of the study was to determine frequency and location of deletions and duplications in the dystrophin gene, to determine the compliance between maintaining/disrupting the reading frame and clinical form of the disease and to check the effectiveness of MLPA (multiplex ligation-dependent probe amplification) in the detection of these mutations in hemizygous patients and heterozygous female carriers. The material is composed of combined results of molecular diagnosis carried out in years 2009–2012 in 180 unrelated patients referred with the diagnosis of DMD/BMD tested by use of MLPA. We identified 110 deletions, 22 duplication (in one patient two different duplications were detected) and 2 point mutations. Deletions involved mainly exons 45–54 and 3–21, whereas most duplications involved exons 3–18. The compliance with Monaco theory was 95% for deletions and 76% for duplications. Most of mutations in the dystrophin gene were localized in the hot spots – different for deletions and duplications. MLPA enabled their quick identification, exact localization and determination whether or not they maintained or disrupted the reading frame. MLPA was also effective in detection of deletions and duplications in female carriers

Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation.

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation

Newly Diagnosed Monostotic Paget’s Disease of Bone during Living Kidney Donor Candidate Evaluation

The popularity of living-donor organ donation has increased recently as an alternative to deceased-organ donation due to the growing need for organs and a shortage of deceased-donor organs. This procedure requires an in-depth health assessment of candidates, who must be in excellent physical and mental health. We present a potential living-kidney donor withdrawn from donation due to a newly diagnosed Paget’s disease of bone (PDB). The patient underwent computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, and bone densitometry with trabecular bone score (TBS) assessment. The sole lumbar vertebra affected by PDB was investigated comprehensively, non-invasively, quantitatively, and qualitatively

Newly Diagnosed Monostotic Paget’s Disease of Bone During Living Kidney Donor Candidate Evaluation

The popularity of living-donor organ donation has increased recently as an alternative to deceased-organ donation due to the growing need for organs and a shortage of deceased-donor organs. This procedure requires an in-depth health assessment of candidates, who must be in excellent physical and mental health. We present a potential living-kidney donor withdrawn from donation due to a newly diagnosed Paget’s disease of bone (PDB). The patient underwent computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, and bone densitometry with trabecular bone score (TBS) assessment. The sole lumbar vertebra affected by PDB was investigated comprehensively, non-invasively, quantitatively, and qualitatively

Is a Patient with Paget’s Disease of Bone Suitable for Living Kidney Donation?—Decision-Making in Lack of Clinical Evidence

Living donor kidney transplantation is a widely performed medical procedure. Living kidney donation requires an in-depth health assessment of candidates. The potential living kidney donor must remain healthy after kidney removal. A consequence of donation can be a decrease in glomerular filtration rate (GFR), and donors can become at risk of developing chronic kidney disease (CKD). We present a rationale for potential living kidney donor withdrawal due to Paget’s disease of bone (PDB) based on a literature review. The treatment for PDB includes the use of, for example, non-steroidal anti-inflammatory drugs (NSAIDs), which can lead to acute kidney injury (AKI) as well as CKD, or bisphosphonates, which are not recommended for patients with decreased GFR

Impact of Graft Size Matching on the Early Post-Transplant Complications and Patients Survival in Children after Living Donor Liver Transplantations

We aimed to assess the impact of the graft-recipient weight ratio (GRWR) on early post-transplant complications and patient survival rates in children after living donor liver transplantation (LDLT). We retrospectively analyzed 321 patients who underwent LDLT from 2004 to 2019. The recipients were categorized into four groups: 37 patients had a GRWR ≤ 1.5% (Group A), 196 patients had a GRWR > 1.5% and ≤3.5% (Group B), 73 patients had a GRWR > 3.5% and <5% (Group C) and 15 patients had a GRWR ≥ 5% (Group D). Incidence of early surgical complications including vascular complications, biliary complications, postoperative bleedings, gastrointestinal perforations and graft loss were comparable among groups with a different GRWR. Delayed abdominal wound closure was more common in patients with a GRWR > 3.5%. Recipients with a GRWR < 5% had a significantly better prognosis concerning patients and graft survival. Using grafts with a GRWR < 5% allows us to expand the donor pool and decrease the risk of mortality while on the waiting list, when patients at the time of transplantation have less advanced liver disease. LDLT with a GRWR ≥ 5% is related to a higher risk of poor outcome, and thus should be an option for treating selected patients when the risk of a delayed transplantation is high and access to deceased donors is limited

Application of Different Compositions of Apple Puree Gels and Drying Methods to Fabricate Snacks of Modified Structure, Storage Stability and Hygroscopicity

The aim of this study was to determine the effect of incorporation of apple puree and maltodextrin to agar sol on the sorption properties and structure of the dried gel. The effect of different drying methods on the sorption behaviour of aerated apple puree gels was also observed. The gels with the addition of 25% and 40% concentration of apple puree and with or without maltodextrin were prepared and dried. The foamed agar gel was subjected to freeze-drying, air-drying and vacuum-drying. The sorption properties of dried gels (adsorption isotherms, water uptake in time) were investigated. The relations between the glass transition temperature, water activity and water content were also obtained for some apple snacks. The increase in apple puree in freeze-dried gels increased the hygroscopicity and decreased the glass transition temperature (Tg). The water content at given activity and hygroscopicity were reduced by the addition of maltodextrin, which also caused the increase in Tg. The application of different drying methods enabled obtaining different structures of material. The open-pore, fragile materials were obtained by freeze-drying, the expanded matrix with big holes was characteristic for vacuum-dried gels, but the closed pores with thick walls were created during the air-drying

The Impact of Hepatic Artery Thrombosis on the Outcome of Pediatric Living Donor Liver Transplantations

The aim of our study was to assess risk factors for hepatic artery thrombosis (HAT) and to evaluate the impact of HAT management on long-term outcomes after pediatric living donor liver transplantation (LDLT). We retrospectively analyzed 400 patients who underwent primary LDLT between 1999 and 2020. We compared preoperative data, surgical factors, complications, and patient and graft survivals in patients with HAT (HAT Group) and without HAT (non-HAT Group). A total of 27 patients (6.75%) developed HAT. Acute liver failure, a hepatic artery (HA) anastomosis diameter below 2 mm, and intraoperative HA flow dysfunction were significantly more common in the HAT Group (p p = 0.02026, and p = 0.0019, respectively). In the HAT Group, 21 patients (77.8%) underwent urgent surgical revision. The incidence of biliary stenosis and retransplantation was significantly higher in the HAT Group (p = 0.00002 and p p < 0.05). The close monitoring of HA flow with Doppler ultrasound during the critical period of 2 to 3 weeks after LDLT and the immediate attempt of surgical revascularization may attenuate the elevated risk of biliary stenosis, graft loss, and the need for retransplantation due to HAT

Risk for Recurrence in Long-Term Follow-Up of Children after Liver Transplantation for Hepatoblastoma or Hepatocellular Carcinoma

The aim of this study was to assess the long-term results of liver transplantation (LT) in pediatric patients with unresectable hepatoblastoma (HB) or hepatocellular carcinoma (HCC) with special reference to the risk of tumor recurrence. We retrospectively analyzed data from 46 HB and 26 HCC patients who underwent LT between 1990 and 2022. In HCC patients, we compared outcomes depending on donor type. We evaluated the impact of a number of risk factors on recurrence-free survival after LT. Estimated patient survival after 5, 10, and 15 years was 82%, 73%, and 73% in the HB group and 79%, 75%, and 75% in the HCC group, respectively (p = 0.76). In the HCC group, living donor LT (LDLT) and deceased donor LT (DDLT) provided similar patient survival (p = 0.09). Estimated recurrence-free survival in patients who had three or fewer risk factors was significantly better than in patients with more than three risk factors (p = 0.0001). Adequate patient selection is necessary when considering LT for primary liver tumors in children. The presence of more than three risk factors is associated with a very high risk of recurrence and indicates poor prognosis, whereas extrahepatic disease may be considered a contraindication for transplantation