Genetics and epidemiology of adult-type hypolactasia with emphasis on the situation in Europe

Background : There is no data available on the best insulin treatment to counteract the effects of glucose excursions due to a moderate alcohol intake associated with portions of slight fat and protein-containing food, as often the case during social happenings or “happy hours”. Introduction: This study analyzes the glycemic control and quality of life in 8 adult type 1 diabetic (T1D) patients on insulin-pump therapy which were invited to consume a traditional Italian aperitif (“Spritz” and chips). Introduction : This study analyzes the glycemic control and quality of life in 8 adult type 1 diabetic (T1D) patients on insulin-pump therapy which were invited to consume a traditional Italian aperitif (“Spritz” and chips). Methods: Patients consumed Spritz aperitif twice: using their habitual bolus, based on carbohydrates (CHO) counting (V1), or with a personalized, advanced bolus (V2) calculated from insulin/Kcal derived from Fats and Proteins (FPU). Post-prandial glucose was continuously monitored; glucose incremental areas (iAUC), glucose peak and time to peak, and estimated change from V1 to V2 from repeated- measures models were computed. Each patient fulfilled validated questionnaires on quality of life, knowledge about diabetes and CHO counting. Results : After the educational program, a reduced iAUC (0-80 min: -306, p=ns; 40-80 min: -400, p=0.07) due to greater (p=0.03) and prolonged double-wave insulin boluses was observed. Blood glucose peak and time to peak were also reduced. Moreover, improvements in the psycho-affective dimension, as well as in the alimentary knowledge were detected. Conclusion: Therefore, a personalized educational program on CHO + FPU counting together with insulin bolus management can improve glycemic control during social consumption of alcohol, with positive reflections on the psycho-affective dimension. Further studies are mandatory to confirm such preliminary results.

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FOXL2 in adult‐type granulosa cell tumour of the ovary: oncogene or tumour suppressor gene?

The Journal of Pathology ◽

10.1002/path.5771 ◽

2021 ◽

Author(s):

Jessica A. Pilsworth ◽

Anne‐Laure Todeschini ◽

Samantha J. Neilson ◽

Dawn R. Cochrane ◽

Daniel Lai ◽

...

Keyword(s):

Granulosa Cell ◽

Suppressor Gene ◽

Tumour Suppressor Gene ◽

Tumour Suppressor ◽

Cell Tumour ◽

Granulosa Cell Tumour ◽

Adult Type

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Expression of BARD1 β Isoform in Selected Pediatric Tumors

Genes ◽

10.3390/genes12020168 ◽

2021 ◽

Vol 12 (2) ◽

pp. 168

Author(s):

Anna Jasiak ◽

Natalia Krawczyńska ◽

Mariola Iliszko ◽

Katarzyna Czarnota ◽

Kamil Buczkowski ◽

...

Keyword(s):

Pediatric Cancer ◽

Genome Stability ◽

Cell Cycle Control ◽

Reverse Transcriptase Gene ◽

Neoplastic Tissue ◽

Adult Type ◽

Qpcr Method ◽

New Treatments ◽

First Time ◽

Work Supports

Currently, many new possible biomarkers and mechanisms are being searched and tested to analyse pathobiology of pediatric tumours for the development of new treatments. One such candidate molecular factor is BARD1 (BRCA1 Associated RING Domain 1)—a tumour-suppressing gene involved in cell cycle control and genome stability, engaged in several types of adult-type tumours. The data on BARD1 significance in childhood cancer is limited. This study determines the expression level of BARD1 and its isoform beta (β) in three different histogenetic groups of pediatric cancer—neuroblastic tumours, and for the first time in chosen germ cell tumours (GCT), and rhabdomyosarcoma (RMS), using the qPCR method. We found higher expression of beta isoform in tumour compared to healthy tissue with no such changes concerning BARD1 full-length. Additionally, differences in expression of BARD1 β between histological types of neuroblastic tumours were observed, with higher levels in ganglioneuroblastoma and ganglioneuroma. Furthermore, a higher expression of BARD1 β characterized yolk sac tumours (GCT type) and RMS when comparing with non-neoplastic tissue. These tumours also showed a high expression of the TERT (Telomerase Reverse Transcriptase) gene. In two RMS cases we found deep decrease of BARD1 β in post-chemotherapy samples. This work supports the oncogenicity of the beta isoform in pediatric tumours, as well as demonstrates the differences in its expression depending on the histological type of neoplasm, and the level of maturation in neuroblastic tumours.

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HGG-21. GERMLINE MUTATIONS IN MSH2 GENE IN PEDIATRIC PATIENTS WITH CONGENITAL AND SPORADIC GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noaa222.308 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii348-iii348

Author(s):

Maria Ejmont ◽

Małgorzata Rydzanicz ◽

Wiesława Grajkowska ◽

Marta Perek-Polnik ◽

Agnieszka Sowińska ◽

...

Keyword(s):

Germline Mutations ◽

Response To Therapy ◽

Msh2 Gene ◽

Illumina Hiseq ◽

Adult Type ◽

Targeted Next Generation Sequencing ◽

Pathogenic Variants ◽

New Treatment ◽

Next Generation Sequencing Ngs ◽

Ngs Data

Abstract INTRODUCTION Glioblastoma (GBM) remains one of the biggest therapeutic challenges in neuro-oncology. In spite of multimodal treatment approaches the prognosis of GBM is extremely poor, median survival is estimated about 12–16 months. Although GBM is one of the most common and malignant primary brain tumors, pediatric glioblastoma, including congenital is a very rare tumor, with an incidence of about 1.1–3.4 per million live births. Moreover, the mode of presentation, behavior, response to therapy and molecular background of pediatric glioblastomas differs from adult type of GBM. Until now, about ten patients with congenital glioblastoma have been described and in none of them germline markers were examined. Here we report two patients with GBM, one with congenital tumor with germline mutations in MSH2 gene. METHODS Targeted Next-Generation Sequencing (NGS) of the probands DNA extracted from leucocytes was performed using the TruSight One sequencing panel on an Illumina HiSeq 1500. Applied gene panel investigated the coding sequence and splice sites of 4813 genes associated with known disease phenotypes. The NGS data were analyzed using an in-house procedure. Identified variants were validated by Sanger sequencing. RESULTS NGS analysis of patients constitutional DNA revealed know, pathogenic variants c.940C>T and c.942 + 3A>T in MSH2 gene (NM_000251.3) associated with MMR-dependent hereditary cancer syndromes. CONCLUSION Molecular analysis are heavily needed for better understanding of pediatric GBM etiology and new treatment modality implementation. Identification of this oncogenic driver may provide insight into the pathogenesis of GBM, including congenital cases. Funded by National Science Centre, Poland (2016/23/B/NZ2/03064 and 2016/21/B/NZ2/01785).

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Therapeutic Potential of αS Evolvability for Neuropathic Gaucher Disease

Biomolecules ◽

10.3390/biom11020289 ◽

2021 ◽

Vol 11 (2) ◽

pp. 289 ◽

Cited By ~ 1

Author(s):

Jianshe Wei ◽

Yoshiki Takamatsu ◽

Ryoko Wada ◽

Masayo Fujita ◽

Gilbert Ho ◽

...

Keyword(s):

Gaucher Disease ◽

Therapeutic Potential ◽

Amyloid Β ◽

Lysosomal Storage ◽

Adult Type ◽

Recessive Mutations ◽

Lysosomal Dysfunction ◽

Increased Risk ◽

Rational Therapy ◽

Novel Therapeutic Strategies

Gaucher disease (GD), the most common lysosomal storage disorder (LSD), is caused by autosomal recessive mutations of the glucocerebrosidase gene, GBA1. In the majority of cases, GD has a non-neuropathic chronic form with adult onset (GD1), while other cases are more acute and severer neuropathic forms with early onset (GD2/3). Currently, no radical therapies are established for GD2/3. Notably, GD1, but not GD2/3, is associated with increased risk of Parkinson’s disease (PD), the elucidation of which might provide a clue for novel therapeutic strategies. In this context, the objective of the present study is to discuss that the evolvability of α-synuclein (αS) might be differentially involved in GD subtypes. Hypothetically, aging-associated PD features with accumulation of αS, and the autophagy-lysosomal dysfunction might be an antagonistic pleiotropy phenomenon derived from αS evolvability in the development in GD1, without which neuropathies like GD2/3 might be manifested due to the autophagy-lysosomal dysfunction. Supposing that the increased severity of GD2/3 might be attributed to the decreased activity of αS evolvability, suppressing the expression of β-synuclein (βS), a potential buffer against αS evolvability, might be therapeutically efficient. Of interest, a similar view might be applicable to Niemann-Pick type C (NPC), another LSD, given that the adult type of NPC, which is comorbid with Alzheimer’s disease, exhibits milder medical symptoms compared with those of infantile NPC. Thus, it is predicted that the evolvability of amyloid β and tau, might be beneficial for the adult type of NPC. Collectively, a better understanding of amyloidogenic evolvability in the pathogenesis of LSD may inform rational therapy development.

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Role of Oral Antioxidant Supplementation in the Current Management of Diabetic Retinopathy

International Journal of Molecular Sciences ◽

10.3390/ijms22084020 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4020

Author(s):

Enrique Antonio Alfonso-Muñoz ◽

Raquel Burggraaf-Sánchez de las Matas ◽

Jorge Mataix Boronat ◽

Julio César Molina Martín ◽

Carmen Desco

Keyword(s):

Diabetic Retinopathy ◽

Diabetic Macular Oedema ◽

Complementary Therapy ◽

Antioxidant Supplementation ◽

Current Management ◽

Adult Type ◽

Aged People

Oxidative stress has been postulated as an underlying pathophysiologic mechanism of diabetic retinopathy (DR), the main cause of avoidable blindness in working-aged people. This review addressed the current daily clinical practice of DR and the role of antioxidants in this practice. A systematic review of the studies on antioxidant supplementation in DR patients was presented. Fifteen studies accomplished the inclusion criteria. The analysis of these studies concluded that antioxidant supplementation has a IIB level of recommendation in adult Type 1 and Type 2 diabetes mellitus subjects without retinopathy or mild-to-moderate nonproliferative DR without diabetic macular oedema as a complementary therapy together with standard medical care.

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