Search

Antenatal genetic diagnostics in the context of genetic counselling: a medical, ethical and legal perspective in Europe

Surrogacy presents itself as a major ethical and legal problem in Spain. On the one hand, this practice is forbidden in Spain, however, Spanish couples go to other countries to carry it out and subsequently want to register their children as their own. Spanish society is constantly demanding this practice so the law will have to be modified: regulated permission or prohibition with criminal liability. A legal solution must be found in the best interests of the children.

Renal cancer cells constitute a paradigm of tumor cells with a glycolytic reprogramming which drives metabolic alterations favouring cell survival and transformation. We studied the expression and activity of pyruvate dehydrogenase kinases (PDK1-4), key enzymes of the energy metabolism, in renal cancer cells. We analysed the expression, subcellular distribution and clinicopathological correlations of PDK1-4 by immunohistochemistry of tumor tissue microarray samples from a cohort of 96 clear cell renal cell carcinoma (ccRCC) patients. Gene expression analysis was performed on whole tumor tissue sections of a subset of ccRCC samples. PDK2 and PDK3 protein expression in tumor cells correlated with lower patient overall survival, whereas PDK1 protein expression correlated with higher patient survival. Gene expression analysis revealed molecular association of PDK2 and PDK3 expression with PI3K signalling pathway, as well as with T cell infiltration and exhausted CD8 T cells. Inhibition of PDK by dichloroacetate in human renal cancer cell lines resulted in lower cell viability, which was accompanied by an increase in pAKT. Together, our findings suggest a differential role for PDK enzymes in ccRCC progression, and highlight PDK as actionable metabolic proteins in relation with PI3K signalling and exhausted CD8 T cells in ccRCC. This work has been funded by Instituto de Salud Carlos III (ISCIII) through the projects CP20/00008 and PI22/00386, and co-funded by European Union, Stiftelsen til fremme av forskning innen nyresykdommer (Unifor 2021 and 2022), and NanoString Science Never Stop in the Nordics, nCounter Grant, to CENX. We thank Arantza Perez Dobaran (University of the Basque Country, UPV/EHU, Leioa, Bizkaia, Spain) for expert IHC technical support. We are grateful for the expert services provided on running the NanoString panels by the Helse Sør-Øst Genomics Core Facility at Oslo University Hospital.

Polycarboxylic ethers or polycarboxylate (PCEs) are one of the most employed superplasticizers in construction. However, the understanding of their microstructure–property relationship is still incomplete. Recently, a theoretical model was proposed that relates the microstructure–conformation of the PCE to its effect on the adsorption onto cement particles and cement hydration time. In this work, the effects of a wide range of PCEs with different side chain lengths (P = 5, Group 1; P = 20, Group 2; and P = 45 and 113, Group 3) having flexible backbone worm conformation except one which has stretch backbone worm conformation (P = 113) were experimentally investigated for their effect on adsorption and cement hydration. It is found that PCEs from Group 1 show electrostatic repulsion as dispersing mechanism, unlike PCEs from Groups 2 and 3. Furthermore, the prediction of the theoretical model is also assessed for all the studied PCEs. Only Group 1 PCEs (shortest side chains) showed deviation from the theoretical predictions, and it was attributed to their different behaviors from the standard PCEs for which the theoretical model was developed., The authors thank the financial support received from EUSKAMPUS Fundazioa, POLYMAT (UPV/EHU), and Tecnalia to carry out the project. The work was carried out under the umbrella of the LTC “Green Concrete”. The authors would like to acknowledge the funding from Misiones Euskampus 1.0 (project “HEMEN”). J. R. Leiza and I. Emaldi also acknowledge the funding from Basque Government (Project IT-1512-22) and MINECO (PID2021-123146OB-I00), and J. S. Dolado acknowledges the funding from the Gobierno Vasco UPV/EHU (Project No. IT-1246-19).

Prostate cancer diagnosis and early stratification is an important aspect to avoid undertreatment of high-risk prostate cancer patients. Major Vault Protein (MVP) has been proposed as a prognostic biomarker in prostate cancer. PTEN and the immune checkpoint protein B7-H3 interact with MVP and are important in prostate cancer progression and therapy response. We evaluated the expression of MVP by immunohistochemistry of tissue microarray samples from a retrospective cohort consisting of 119 prostate cancer patients. We correlated the protein expression of MVP with clinicopathological characteristics, and protein expression of androgen receptor (AR), PTEN, immune checkpoint proteins B7-H3 and PD-L1. We found MVP to be expressed in 53 % of prostate tumors, and correlated positively with biochemical recurrence (ρ = 0.211/p = 0.021). Furthermore, we found positive correlation of MVP expression with expression of AR (ρ = 0.244/p = 0.009) and the immune checkpoint protein B7-H3 (ρ = 0.200/p = 0.029), but not with PD-L1 (ρ = 0.152/p = 0.117) or PTEN expression (ρ = − 0.034/p = 0.721). Our findings support the notion that expression of MVP is associated with poor prognosis in prostate cancer. The correlation between MVP and immune checkpoint protein B7-H3 in prostate cancer suggests a role for MVP in immunoregulation and drug resistance.

Atrial fibrillation (AF) is a common supraventricular arrhythmia. Its automatic identification by standard 12-lead electrocardiography (ECG) is still challenging. Recently, deep learning provided new instruments able to mimic the diagnostic ability of clinicians but only in case of binary classification (AF vs. normal sinus rhythm-NSR). However, binary classification is far from the real scenarios, where AF has to be discriminated also from several other physiological and pathological conditions. The aim of this work is to present a new AF multiclass classifier based on a convolutional neural network (CNN), able to discriminate AF from NSR, premature atrial contraction (PAC) and premature ventricular contraction (PVC). Overall, 2796 12-lead ECG recordings were selected from the open-source "PhysioNet/Computing in Cardiology Challenge 2021" database, to construct a dataset constituted by four balanced classes, namely AF class, PAC class, PVC class, and NSR class. Each lead of each ECG recording was decomposed into spectrogram by continuous wavelet transform and saved as 2D grayscale images, used to feed a 6-layers CNN. Considering the same CNN architecture, a multiclass classifiers (all classes) and three binary classifiers (AF class, PAC class, and PVC class vs. NSR class) were created and validated by a stratified shuffle split cross-validation of 10 splits. Performance was quantified in terms of area under the curve (AUC) of the receiver operating characteristic. Multiclass classifier performance was high (AF class: 96.6%; PAC class: 95.3%; PVC class: 92.8%; NSR class: 97.4%) and preferable to binary classifiers. Thus, our CNN AF multiclass classifier proved to be an efficient tool for AF discrimination from physiological and pathological confounders. Clinical Relevance-Our CNN AF multiclass classifier proved to be suitable for AF discrimination in real scenarios.

Limbah jagung dan padi merupakan limbah pertanian yang banyak ditemukan di Desa Bluri, Kec. Solokuro, Kab. Lamongan, Prov. Jawa Timur. Desa Bluri adalah salah satu desa binaan Direktorat Riset, Teknologi, dan Pengabdian Kepada Masyarakat (DRTPM), Institut Teknologi Sepuluh Nopember (ITS) yang juga memiliki potensi dibidang peternakan khususnya penggemukan sapi yang sampai saat ini masih dikelola secara tradisional. Ketersediaan dan harga pakan menjadi permasalahan utama pada proses penggemukan sapi. Mengingat pakan hijauan akan sulit diperoleh pada musim kemarau, dan pakan yang hanya mengandalkan pada limbah pertanian yang ada mempunyai kualitas (kandungan nutrisi) yang belum memenuhi mutu pakan untuk penggemukan sapi. Oleh karena itu, untuk memenuhi pakan ternak sapi yang secara kualitas dan kuantitas memenuhi kebutuhan yang diperlukan, pada kegiatan abmas berbasis produk sebelumnya telah dilakukan pembuatan pakan ternak setara konsentrat sapi potong dari limbah pertanian setempat secara fermentasi aerob sehingga proses yang ditawarkan lebih murah, mudah, ramah lingkungan dan berkelanjutan. Pakan ternak yang diperoleh dapat dianggap sebagai konsentrat sapi potong penggemukan karena secara nutrisi sesuai dengan SNI 3148-2:2017 yaitu kadar air 12,83% (maks. 14%), kadar protein kasar 16,12% (min. 13%), dan kadar lemak kasar 0,96% (maks. 7%). Namun kadar abu dan TDN yaitu 14,62% dan 57,51%, masih diatas kadar abu dan TDN yang disyaratkan yaitu maks. 12% dan min 68%. Sehingga abmas berbasis produk yang dilakukan bertujuan memperbaiki kulitas pakan melalui penurunan kadar abu dan menaikkan kadar TDN dengan cara (1) modifikasi bahan pakan, (2) modifikasi biakan mikroba dengan menambahkan bakteri/jamur yang mampu mengurai bahan-bahan lignoselulosa, dan (3) memperlama waktu fermentasi. Dengan modifikasi bahan, biakan mikroba dan memperlama waktu fermentasi maka kadar protein kasar meningkat tajam menjadi 23,92% (C2/M2/7 hari fermentasi), kadar abu sedikit naik menjadi 9,52% (C3/M3/7 hari fermentasi), demikian juga TDN menjadi 66,07% (C3/M2/7 hari fermentasi). Uji coba pakan di lapangan menunjukkan kenaikan berat rata-rata sapi perhari yang masih memberikan keuntungan kepada para peternak. Sehingga penggunaan pakan ternak dari limbah pertanian dengan fermentasi aerob menggunakan biakan mikroba dari ITS dapat menjadi solusi para peternak di Desa Bluri yang hingga saat ini belum ada yang berhasil karena mahalnya biaya pakan.

Targeted therapy in combination with immune checkpoint inhibitors has been recently implemented in advanced or metastatic renal cancer treatment. However, many treated patients either do not respond or develop resistance to therapy, making alternative immune checkpoint-based immunotherapies of potential clinical benefit for specific groups of patients. In this study, we analyzed the global expression of B7 immune checkpoint family members (PD-L1, PD-L2, B7-H2, B7-H3, B7-H4, B7-H5, B7-H6, and B7-H7) in human renal cancer cells (Caki-1, A-498, and 786-O cell lines) upon treatment with clinically relevant targeted drugs, including tyrosine kinase inhibitors (Axitinib, Cabozantinib, and Lenvatinib) and mTOR inhibitors (Everolimus and Temsirolimus). Gene expression analysis by quantitative PCR revealed differential expression patterns of the B7 family members in renal cancer cell lines upon targeted drug treatments. B7-H4 gene expression was upregulated after treatment with various targeted drugs in Caki-1 and 786-O renal cancer cells. Knocking down the expression of B7-H4 by RNA interference (RNAi) using small interfering RNA (siRNA) decreased renal cancer cell viability and increased drug sensitivity. Our results suggest that B7-H4 expression is induced upon targeted therapy in renal cancer cells and highlight B7-H4 as an actionable immune checkpoint protein in combination with targeted therapy in advanced renal cancer cases resistant to current treatments.