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Background: Proper positioning of a total hip arthroplasty (THA) plays a crucial role in the success and long-term survivorship of the implant. Cup positioning within the Lewinnek Safe Zone (LSZ) does not, however, avoid implant dislocation. Thus, the concept of a functional cup position has been introduced. The purpose of this study was to assess the discrepancy between LSZ and the acetabular cup position suggested by the patient's specific functional planning. The hypothesis was that a mismatch does exist., Methods: One hundred consecutive patients with primary hip osteoarthritis undergoing primary THA with a personalized functional preoperative planning and patient-specific cup implantation system were enrolled. Anatomical and spino-pelvic functional parameters were recorded and, for each patient, a "safe cup orientation" was suggested. The suggested functional safe zone was compared to the LSZ., Results: The mean suggested inclination was 39° ± 3° (range 32°-45°). The mean suggested anteversion was 21° ± 3° (range 12°-28°). The patient's functional acetabular inclination (AI) corresponded to the LSZ in one of the 100 patients, whereas the acetabular anteversion (AV) was outside the LSZ in 8 of the 100 patients. The mean pelvic tilt while standing and sitting were 0.5° ± 7° (range 21°-45°) and -6° ± 16.7° (range -63°-33°), respectively. The mean pelvic incidence was 52° ± 9.7° (range 33°-83°)., Conclusion: When a functional patient's specific preoperative planning is performed, the LZS does not correspond to the patient's functional safe zone in about 8% of patients. The concept of a universal safe zone should be revisited, and a functional personalized safe zone may have to be more widely considered., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by our University ethics committee and conducted in accordance with the ethical standards in the 1964 Declaration of Helsinki. Consent for publication: All participants provided informed consent for their inclusion in the study, which was approved by the university's ethics committee. Competing interests: All authors declared that there are no conflicts of interest., (© 2025. The Author(s).)

The noncarious cervical lesions (NCCLs) recognize an etiological framework of onset very different from the carious processes with etiology whose bacteria aggregated in a biofilm play a predominant role, leading in this way to the loss of the mineralized structure of the tooth. The pathological picture of the NCCLs, which manifests itself with a clinical picture of dental wear, differs from caries because it mainly recognizes a series of pathological processes, such as erosion, through the action of generally acidic chemical agents and abrasion, which is basically expressed through repeated mechanical trauma characteristic of tooth brushing. However, in the literature, there is no unanimous agreement in identifying only these two mechanisms, but there are some who propose a more marked role of anomalous occlusal loads, which would be unloaded on some teeth which, in addition to both erosive and abrasive mechanisms, would give rise to abfraction. Therefore, the aim of this review was to collect literature etio-pathological information and discuss the mechanisms underlying NCCLs., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Mario Dioguardi et al.)

Purpose: To compare liver MRI with AIR Recon Deep Learning™(ARDL) algorithm applied and turned-off (NON-DL) with conventional high-resolution acquisition (NAÏVE) sequences, in terms of quantitative and qualitative image analysis and scanning time., Material and Methods: This prospective study included fifty consecutive volunteers (31 female, mean age 55.5 ± 20 years) from September to November 2021. 1.5 T MRI was performed and included three sets of images: axial single-shot fast spin-echo (SSFSE) T2 images, diffusion-weighted images(DWI) and apparent diffusion coefficient(ADC) maps acquired with both ARDL and NAÏVE protocol; the NON-DL images, were also assessed. Two radiologists in consensus drew fixed regions of interest in liver parenchyma to calculate signal-to-noise-ratio (SNR) and contrast to-noise-ratio (CNR). Subjective image quality was assessed by two other radiologists independently with a five-point Likert scale. Acquisition time was recorded., Results: SSFSE T2 objective analysis showed higher SNR and CNR for ARDL vs NAÏVE, ARDL vs NON-DL(all P < 0.013). Regarding DWI, no differences were found for SNR with ARDL vs NAÏVE and, ARDL vs NON-DL (all P > 0.2517).CNR was higher for ARDL vs NON-DL(P = 0.0170), whereas no differences were found between ARDL and NAÏVE(P = 1). No differences were observed for all three comparisons, in terms of SNR and CNR, for ADC maps (all P > 0.32). Qualitative analysis for all sequences showed better overall image quality for ARDL with lower truncation artifacts, higher sharpness and contrast (all P < 0.0070) with excellent inter-rater agreement (k ≥ 0.8143). Acquisition time was lower in ARDL sequences compared to NAÏVE (SSFSE T2 = 19.08 ± 2.5 s vs. 24.1 ± 2 s and DWI = 207.3 ± 54 s vs. 513.6 ± 98.6 s, all P < 0.0001)., Conclusion: ARDL applied on upper abdomen showed overall better image quality and reduced scanning time compared with NAÏVE protocol., (© 2022. The Author(s).)

Iterative reconstructions (IR) might alter radiomic features extraction. We aim to evaluate the influence of Adaptive Statistical Iterative Reconstruction-V (ASIR-V) on CT radiomic features. Patients who underwent unenhanced abdominal CT (Revolution Evo, GE Healthcare, USA) were retrospectively enrolled. Raw data of filtered-back projection (FBP) were reconstructed with 10 levels of ASIR-V (10-100%). CT texture analysis (CTTA) of liver, kidney, spleen and paravertebral muscle for all datasets was performed. Six radiomic features (mean intensity, standard deviation (SD), entropy, mean of positive pixel (MPP), skewness, kurtosis) were extracted and compared between FBP and all ASIR-V levels, with and without altering the spatial scale filter (SSF). CTTA of all organs revealed significant differences between FBP and all ASIR-V reconstructions for mean intensity, SD, entropy and MPP (all p < 0.0001), while no significant differences were observed for skewness and kurtosis between FBP and all ASIR-V reconstructions (all p > 0.05). A per-filter analysis was also performed comparing FBP with all ASIR-V reconstructions for all six SSF separately (SSF0-SSF6). Results showed significant differences between FBP and all ASIR-V reconstruction levels for mean intensity, SD, and MPP (all filters p < 0.0315). Skewness and kurtosis showed no differences for all comparisons performed (all p > 0.05). The application of incremental ASIR-V levels affects CTTA across various filters. Skewness and kurtosis are not affected by IR and may be reliable quantitative parameters for radiomic analysis.

Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA binders. TFOs provide a tool for controlling gene expression or, when attached to an appropriate chemical reagent, for directing DNA damage. Here, we report a set of rules for predicting the best out of five different triple-helical binding motifs (TM, UM, GA, GT, and GU, where M is 5-methyldeoxycytidine and U is deoxyuridine) by taking into consideration the sequence composition of the underlying duplex target. We tested 11 different triplex targets present in genes having an oncogenic role. The rules have predictive power and are very useful in the design of TFOs for antigene applications. Briefly, we retained motifs GU and TM, and when they do form a triplex, TFOs containing G and U are preferred over those containing T and M. In the case of the G-rich TFOs, triplex formation is principally dependent on the percentage of G and the length of the TFO. In the case of the pyrimidine motif, replacement of T with U is destabilizing; triplex formation is dependent on the percentage of T and destabilized by the presence of several contiguous M residues. An equation to choose between a GU and TM motif is given.

Gene regulation networks control differentiation and function of hundreds of cell types. Dysfunctions of transcription factors, which are key elements in the regulation pathways, are involved in numerous pathologies. The recent development of genomics technologies allows the study of gene regulation mechanisms and help us understand their impact on the cells. Bioinformatic tools are needed to fully exploit data obtained by genomics approaches. Thus, bioinformatics play an essential role in the characterisation of the transcription factors binding sites and their target genes. In this review we will introduce the main breakthroughs in bioinformatics area for the comprehension of regulation mechanisms. We will insist on i) the approaches "with a priori" for the genome annotation based on known transcription factors binding sites, ii) the approaches "without a priori" for the discovery of new binding sites and iii) the functional annotation of the target genes of those transcription factors. Finally, we will present recent examples of the fruitful use of in silico studies for the comprehension of regulation mechanisms and of the consequences of their dysfunction.

The formation of triple-helical structures of DNA is based on sequence-specific recognition of oligopyrimidine.oligopurine stretches of double-helical DNA. Triple-helical structures can be stabilized by DNA-binding ligands. Benzoquinoquinoxaline (BQQ) derivatives are among the most potent intercalating-type agents known to stabilize DNA triple-helical structures. We previously reported the conversion of BQQ into a triplex-directed DNA cleaving agent, namely BQQ-ethylenediaminetetraacetic acid (EDTA), by coupling of 6-(3-aminopropylamino)BQQ to a suitable ethylenediaminetetraacetic acid derivative, and we demonstrated the ability of this conjugate to cause double-stranded cleavage of DNA at the triplex site. However, this prototype derivative BQQ-EDTA conjugate showed lower affinity towards triplex DNA than BQQ itself. In the light of this observation, and guided by molecular modeling studies, we synthesized a second generation of BQQ-EDTA conjugates based on 6-[bis(2-aminoethyl)amino]- and 6-(3,3'-diamino-N-methyldipropylamino)-BQQ derivatives. We confirmed by DNA melting experiments that the new conjugates displayed an increased specific affinity towards triple helices when compared to the previously synthesized BQQ-EDTA. In addition, the efficiency of these new agents in triplex-specific binding and cleavage was demonstrated by triplex-directed double-stranded cleavage of plasmid DNA.

Amino-p-quinacridine compounds (PQs) have been shown to stabilize strongly and specifically triple-helical DNA. Moreover, these derivatives display photoactive properties that make them efficient DNA cleavage agents. We exploited these two properties (triplex-specific binding and photoactivity) to selectively cleave a double-stranded (ds)DNA sequence present in the HIV-1 genome. Cleavage was first carried out on a linearized plasmid (3300 bp) containing the HIV polypurine tract (PPT) that allowed targeting by a triplex-forming oligonucleotide (TFO). PQ(3)(), the most active compound of the series, efficiently cleaved double-stranded DNA in the vicinity of the PPT when this sequence had formed a triplex with a 16-mer TFO. Investigation of the cleavage at the molecular level was addressed on a short DNA fragment (56 bp); the photoinduced cleavage by PQ(3)() occurred only in the presence of the triple helix. Nevertheless, unusual cleavage patterns were observed: damage was observed at guanines located 6-9 bp away from the end of the triple helical site. This cleavage is very efficient (up to 60%), does not require alkaline treatment, and is observed on both strands. A quinacridine-TFO conjugate produced the same cleavage pattern. This observation, along with others, excludes the hypothesis of a triplex-induced allosteric binding site of PQ(3 )()adjacent to the damaged sequence and indicates that PQ(3 )()preferentially binds in the vicinity of the 5'-triplex junction. Irradiation in the presence of TFO-conjugates with acridine (an intercalative agent) and with the tripeptide lys-tryp-lys led to a complete inhibition of the photocleavage reaction. These results are interpreted in terms of competitive binding and of electron-transfer quenching. Together with the findings of simple mechanistic investigations, they led to the conclusion that the photoinduced damage proceeds through a direct electron transfer between the quinacridine and the guanines. This study addresses the chemical mechanism leading to strand breakage and characterizes the particular photosensitivity of the HIV-DNA target sequence which could be an oxidative hot spot for addressed photoinduced strand scission by photosensitizers.