Peptide-nucleic acid-mediated enriched polymerase chain reaction as a key point for non-invasive prenatal diagnosis of β-thalassemia

The presence of fetal DNA in maternal plasma can be exploited to develop new procedures for non-invasive prenatal diagnosis. Tests to detect 7 frequent beta-globin gene mutations in people of Mediterranean origin were applied to the analysis of maternal plasma in couples where parents carried different mutations. A mutant enrichment amplification protocol was optimized by using peptide nucleic acids (PNAs) to clamp maternal wild-type alleles. By this approach, 41 prenatal diagnoses were performed by microelectronic microchip analysis, with total concordance of results obtained on fetal DNA extracted from chorionic villi. Among these, 27/28 were also confirmed by direct sequencing and 4 by pyrosequencing

Genetic and nongenetic variation of heifer fertility in Italian Holstein cattle

Excellent fertility performance is important to maximize farmers’ profit and to reduce the number of culled animals. Although female fertility of adult cows has been included in Italian Holstein breeding objectives since 2009, little has been done to quantify genetic variation of heifer fertility characteristics so far. The aim of the present study was to estimate genetic parameters of 4 fertility traits in nulliparous Italian Holstein heifers and to develop an aggregate selection index to improve heifer fertility. Data were retrieved from the national fertility database and included information on insemination, calving, and pregnancy diagnosis dates. The investigated phenotypes (mean ± standard deviation) were age at first insemination (AFI, mo; 17.25 ± 2.89), nonreturn rate at 56 d from the first insemination (NRR56, binary; 0.78 ± 0.41), conception rate at first insemination (CR, binary; 0.61 ± 0.49), and interval from first to last insemination (IFL, d; 26.09 ± 51.85). Genetic parameters were estimated using a 4-trait animal model that included the following fixed effects: herd-year of birth and month of birth for AFI, and herd-year-season of birth and month-year of insemination for IFL, NRR56, and CR; the animal additive genetic effect (fitted to the pedigree-based relationship matrix) was considered as a random term. An aggregate index was developed from the estimated additive genetic (co)variance matrix by considering CR as the breeding goal and AFI, NRR56, and IFL as selection criteria. Heritability estimates from average covariance matrices ranged from 0.012 (CR) to 0.015 (IFL), with the exception of AFI (0.071). Conception rate at first insemination was strongly correlated with both IFL (−0.730) and NRR56 (0.668), and weakly to AFI (−0.065), and the relative emphasis placed on each selection criteria in the aggregate index was 10%, 47%, and 43% for AFI, IFL, and NRR56, respectively. The results of the present study suggest that heifer fertility should be considered as an additional trait in the breeding objectives of Italian Holstein

Genotype/Phenotype Relationship in a Consanguineal Family With Brugada Syndrome Harboring the R1632C Missense Variant in the SCN5A Gene

Brugada syndrome (BrS) is a known cause of sudden cardiac death. The genetic basis of BrS is not well understood, and no one single gene is linked to even a majority of BrS cases. However, mutations in the gene SCN5A are the most common, although the high amount of phenotypic variability prevents a clear correlation between genotype and phenotype. Research techniques are limited, as most BrS cases still remain without a genetic diagnosis, thus impairing the implementation of experimental models representative of a general pathogenetic mechanism. In the present study, we report the largest family to-date with the segregation of the heterozygous variant NM_198056:c.4894C>T (p.Arg1632Cys) in the SCN5A gene. The genotype-phenotype relationship observed suggests a likely pathogenic effect of this variant. Functional studies to better understand the molecular effects of this variant are warranted

Drug eluting stents are superior to bare metal stents to reduce clinical outcome and stent-related complications in CKD patients, a systematic review, meta-analysis and network meta-analysis.

AimsTo compare clinical outcome in Chronic kidney disease (CKD) patients receiving coronary stents according to stent type BMS versus DES and 1st generation versus 2nd generation DES.Methods and ResultsPubMed, Cinhal, Cochrane, Embase, and Web of Science were searched for studies including CKD patients. CKD was defined as eGFR < 60 mL/min. We selected n = 35 articles leading to 376 169 patients, of which 76 557 CKD patients receiving BMS n = 35,807, 1st generation DES n = 37,650, or 2nd generation DES n = 3100. Patient receiving DES, compared to BMS, had a 18% lower all‐cause mortality (RR 0.82, 95%CI 0.71‐0.94). The composite of death or myocardial infarction (MI) was lower in DES patients (RR 0.78, 95%CI 0.67‐0.91), as was stent thrombosis (ST) (RR 0.57, 95%CI 0.34‐0.95), target vessel/lesion revascularization (TVR/TLR) (RR 0.69, 95%CI 0.57‐0.84) and death for cardiovascular cause (RR 0.43, 95%CI 0.25‐0.74). We also found a gradient between 1st and 2nd generation DES, through BMS. Second, compared to 1st generation DES, were associated with further relative risk (RR) reduction of −18% in of all‐cause death, and lower incidence of stent‐related clinical events: −39% RR of ST risk; −27 RR of TVR/TLR risk.ConclusionsDES in CKD patients undergoing PCI were superior to BMS in reducing major adverse clinical events. This was possibly explained, by a lower risk of stent‐related events as ST and TVR or TLR. Second, compared to 1st generation DES may furtherly reduce clinical events

Smoker's paradox in ST-elevation myocardial infarction: Role of inflammation and platelets.

n/

Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4

Genes for familial hemiplegic migraine (FHM) and episodic ataxia type-2 (EA-2) have been mapped to chromosome 19p13. We characterized a brain- specific P/Q-type Ca2+ channel α1-subunit gene, CACNLIA4, covering 300 kb with 47 exons. Sequencing of all exons and their surroundings revealed polymorphic variations, including a (CA)(n)-repeat (D19S1150), a (CAG)(n)- repeat in the 3'-UTR, and different types of deleterious mutations in FHM and EA-2. In FHM, we found four different missense mutations in conserved functional domains. One mutation has occurred on two different haplotypes in unrelated FHM families. In EA-2, we found two mutations disrupting the reading frame. Thus, FHM and EA-2 can be considered as allelic channelopathies. A similar etiology may be involved in common types of migraine

SCN5A Nonsense Mutation and NF1 Frameshift Mutation in a Family With Brugada Syndrome and Neurofibromatosis

In this case series, we report for the first time a family in which the inherited nonsense mutation [c. 3946C &gt; T (p.Arg1316*)] in the SCN5A gene segregates in association with Brugada syndrome (BrS). Moreover, we also report, for the first time, the frameshift mutation [c.7686delG (p.Ile2563fsX40)] in the NF1 gene, as well as its association with type 1 neurofibromatosis (NF1), characterized by pigmentary lesions (café au lait spots, Lisch nodules, freckling) and cutaneous neurofibromas. Both of these mutations and associated phenotypes were discovered in the same family. This genetic association may identify a subset of patients at higher risk of sudden cardiac death who require the appropriate electrophysiological evaluation. This case series highlights the importance of genetic testing not only to molecularly confirm the pathology but also to identify asymptomatic family members who need clinical examinations and preventive interventions, as well as to advise about the possibility of avoiding recurrence risk with medically assisted reproduction

Quantum micro–nano devices fabricated in diamond by femtosecond laser and ion irradiation

Diamond has attracted great interest as a quantum technology platform thanks to its optically active nitrogen vacancy (NV) center. The NV's ground state spin can be read out optically, exhibiting long spin coherence times of ≈1 ms even at ambient temperatures. In addition, the energy levels of the NV are sensitive to external fields. These properties make NVs attractive as a scalable platform for efficient nanoscale resolution sensing based on electron spins and for quantum information systems. Diamond photonics enhance optical interactions with NVs, beneficial for both quantum sensing and information. Diamond is also compelling for microfluidic applications due to its outstanding biocompatibility, with sensing functionality provided by NVs. However, it remains a significant challenge to fabricate photonics, NVs, and microfluidics in diamond. In this Progress Report, an overview is provided of ion irradiation and femtosecond laser writing, two promising fabrication methods for diamond‐based quantum technological devices. The unique capabilities of both techniques are described, and the most important fabrication results of color center, optical waveguide, and microfluidics in diamond are reported, with an emphasis on integrated devices aiming toward high performance quantum sensors and quantum information systems of tomorrow

Pulsed Bessel beam-induced microchannels on a diamond surface for versatile microfluidic and sensing applications

We present a laser machining method based on the use of pulsed Bessel beams to create, by single pass transverse writing, three-dimensional trench-like microstructures on a synthetic monocrystalline diamond substrate. By tuning the laser pulse energy and the writing speed, it is possible to control the features of the surface trenches obtained and to optimize the resulting high aspect-ratio and low roughness microstructures. This work confirms the potentialities of quasi-stationary beams in ultra-fast laser inscription technology. In particular the presented results show the possibility to fabricate deep and precise microfluidic channels on biocompatible diamond substrates, offering a great potential for biomedical sensing applications