Breast Implant Removal-Only: The Role of Targeted Compression.

BACKGROUND: The number of women seeking explantation of their breast implants has increased in recent years. Anxiety due to potential health problems has been one of the major catalysts. Mastopexy with or without autoaugmentation and fat grafting are the main techniques used in breast implant removal surgery. OBJECTIVES: To analyse the aesthetic and satisfactory outcomes after simple breast implant removal assisted by targeted compression. METHODS: Twenty-eight patients were included in the series. Targeted compression of the breast after implant removal was performed during the 1st month. A satisfaction survey using a Likert scale was used before and after the final visit. The patients were followed up for 1 year. RESULTS: The mean age of the patients was 41 years old, and the mean time between implantation and removal was 10 years. Subjective reasons for removal (46.4% of the patients) were more frequent in women with less time since implantation (5 years) versus 15 years for implant-related problems. A total of 57.14% of the women were satisfied with the aesthetic result, and 42.86% were very satisfied. Only 17.8% of the total would consider an aesthetic refinement. CONCLUSIONS: Simple breast implant removal yields good aesthetic outcomes, and patients are satisfied with the results. Good management of compression of the breast and close follow-up to treat any collection in the pocket provides good adhesion and allows for effective management of the process of deflation and setting of the breast mound. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen.

Collagen, a versatile family of proteins with 28 members and 44 genes, is pivotal in maintaining tissue integrity and function. It plays a crucial role in physiological processes like wound healing, hemostasis, and pathological conditions such as fibrosis and cancer. Collagen is a target in these processes. Direct methods for collagen modulation include enzymatic breakdown and molecular binding approaches. For instance, Clostridium histolyticum collagenase is effective in treating localized fibrosis. Polypeptides like collagen-binding domains offer promising avenues for tumor-specific immunotherapy and drug delivery. Indirect targeting of collagen involves regulating cellular processes essential for its synthesis and maturation, such as translation regulation and microRNA activity. Enzymes involved in collagen modification, such as prolyl-hydroxylases or lysyl-oxidases, are also indirect therapeutic targets. From another perspective, collagen is also a natural source of drugs. Enzymatic degradation of collagen generates bioactive fragments known as matrikines and matricryptins, which exhibit diverse pharmacological activities. Overall, collagen-derived peptides present significant therapeutic potential beyond tissue repair, offering various strategies for treating fibrosis, cancer, and genetic disorders. Continued research into specific collagen targeting and the application of collagen and its derivatives may lead to the development of novel treatments for a range of pathological conditions.

Classification performance assessment for imbalanced multiclass data.

The evaluation of diagnostic systems is pivotal for ensuring the deployment of high-quality solutions, especially given the pronounced context-sensitivity of certain systems, particularly in fields such as biomedicine. Of notable importance are predictive models where the target variable can encompass multiple values (multiclass), especially when these classes exhibit substantial frequency disparities (imbalance). In this study, we introduce the Imbalanced Multiclass Classification Performance (IMCP) curve, specifically designed for multiclass datasets (unlike the ROC curve), and characterized by its resilience to class distribution variations (in contrast to accuracy or F ß -score). Moreover, the IMCP curve facilitates individual performance assessment for each class within the diagnostic system, shedding light on the confidence associated with each prediction-an aspect of particular significance in medical diagnosis. Empirical experiments conducted with real-world data in a multiclass context (involving 35 types of tumors) featuring a high level of imbalance demonstrate that both the IMCP curve and the area under the IMCP curve serve as excellent indicators of classification quality.

Arrest of labor secondary to large uterine fibroid.

Key Clinical Message: Large uterine fibroids during pregnancy are associated with increased maternal and fetal complications. Large uterine fibroids should be kept in mind as a cause for arrest of labor and the need for cesarean delivery. Abstract: Uterine fibroids >5 cm in diameter are more likely to grow during pregnancy and cause obstetrical complications. We report a case of a large 9 cm subserosal uterine fibroid as the cause for the arrest of labor and the need for cesarean delivery.

Usnea aurantiaco-atra (Jacq) Bory: Metabolites and Biological Activities.

BACKGROUND: Lichens are complex symbiotic associations between a fungus and an alga or cyanobacterium. Due to their great adaptability to the environment, they have managed to colonize many terrestrial habitats, presenting a worldwide distribution from the poles to the tropical regions and from the plains to the highest mountains. In the flora of the Antarctic region, lichens stand out due to their variety and development and are a potential source of new bioactive compounds. METHODS: A phytochemical study of the Antarctic lichen Usnea aurantiaco-atra (Jacq) Bory was conducted with the intention of determining the most important metabolites. In addition, the cytotoxic and antioxidant activities of its extracts were determined. RESULTS: Cytotoxicity studies revealed that the hexane extract contains usnic acid as a majority metabolite, in addition to linoleic acid, ergosterols and terpenes, and demonstrates cytotoxic activity against an A375 melanoma cell line. On the other hand, the presence of total phenols in the extracts did not influence their antioxidant activity. CONCLUSIONS: U. aurantiaco-atra contains mainly usnic acid, although there are terpenes and ergosta compounds that could be responsible for its cytotoxic activity. The presence of phenols did not confer antioxidant properties.

Value of Prostate-Specific Antigen Kinetics in Patients with Low-Risk Prostate Cancer under Active Surveillance.

INTRODUCTION: This study analyzes the value of PSA kinetics, PSA speed (vPSA), and PSA doubling time (PSAdt), in patients with low-risk prostate cancer who are in an active surveillance (AS) program. METHODS: An observational, retrospective, and longitudinal study of a sample of 86 patients included in AS program between January 2014 and October 2021 was conducted. A review of their medical records was performed, and PSA kinetics were calculated, analyzing the causes of discontinuation of the AS program and its relationship with PSA kinetics. RESULTS: The mean age was 63.39 years, and the median follow-up was 62.55 months. The mean PSA at diagnosis was 8.27 ng/mL. A median of PSAdt of 62.55 months and 1.3 ng/mL/year for vPSA was obtained. 35 patients left the program, with a higher percentage of patients leaving with a PSAdt less than 36 months (73.7 vs. 31.1%) and a vPSA greater than 2 ng/mL/year (68.2 vs. 31.3%). The probability of permanence and the time of permanence in AS were statistically significantly higher for those patients with favorable kinetic parameters. CONCLUSION: PSA kinetics is a parameter to take into account when making decisions to keep patients in an AS program.

The Position of the Nipple-Areola Complex in Breast Augmentation.

BACKGROUND: There is some controversy regarding whether the nipple-areola complex (NAC) is elevated, remains stable, or is lowered in breast augmentation. There is a general belief that one can modulate its position depending on the implant chosen. In addition, many preoperative markings include elevating the arms to predict the final position of the NAC. OBJECTIVES: The aim of this study was to investigate changes in the position of the NAC and determine whether the postoperative position of the NAC can be predicted preoperatively by elevating the arms. METHODS: The study included 45 patients. A 3-dimensional scan was performed to take basal (preoperative) and 12-month measurements with the patient's arms in abduction and elevated over the head. The distances measured were the sternal notch-nipple (SN-Ni), nipple-nipple (Ni-Ni), and nipple-inframammary fold (Ni-IMF) distances. RESULTS: With arms abducted, the SN-Ni distance increased by 6% when measured linearly, 8.5% when measured on the skin surface, and 1% to 2% when measured on the sternal line. The Ni-Ni distance increased by 9% (linear) and 15% (over the surface). The Ni-IMF increased by 44%. With arms adducted, the SN-Ni distance increased by 9% (linear), 12% (on the skin surface), and 0.5% at the sternal midline projection. The Ni-Ni distance increased 11% (linear) and 19% (on the surface). The Ni-IMF distance increased by 53%. The postoperative position of the NAC with the arms abducted increased by 17% compared with the preoperative position in adduction. CONCLUSIONS: Implants do not elevate the NAC; its position remains nearly unaltered. The SN-Ni distance was increased in 90% of the patients. Lifting the arms for preoperative markings does not help to predict the postoperative position of the NAC.

RETINOBLASTOMA-RELATED interactions with key factors of the RNA-directed DNA methylation (RdDM) pathway and its influence on root development.

MAIN CONCLUSION: Our study presents evidence for a novel mechanism for RBR function in transcriptional gene silencing by interacting with key players of the RdDM pathway in Arabidopsis and several plant clades. Transposable elements and other repetitive elements are silenced by the RNA-directed DNA methylation pathway (RdDM). In RdDM, POLIV-derived transcripts are converted into double-stranded RNA (dsRNA) by the activity of RDR2 and subsequently processed into 24 nucleotide short interfering RNAs (24-nt siRNAs) by DCL3. 24-nt siRNAs serve as guides to direct AGO4-siRNA complexes to chromatin-bound POLV-derived transcripts generated from the template/target DNA. The interaction between POLV, AGO4, DMS3, DRD1, RDM1 and DRM2 promotes DRM2-mediated de novo DNA methylation. The Arabidopsis Retinoblastoma protein homolog (RBR) is a master regulator of the cell cycle, stem cell maintenance, and development. We in silico predicted and explored experimentally the protein-protein interactions (PPIs) between RBR and members of the RdDM pathway. We found that the largest subunits of POLIV and POLV (NRPD1 and NRPE1), the shared second largest subunit of POLIV and POLV (NRPD/E2), RDR1, RDR2, DCL3, DRM2, and SUVR2 contain canonical and non-canonical RBR binding motifs and several of them are conserved since algae and bryophytes. We validated experimentally PPIs between Arabidopsis RBR and several of the RdDM pathway proteins. Moreover, seedlings from loss-of-function mutants in RdDM and RBR show similar phenotypes in the root apical meristem. We show that RdDM and SUVR2 targets are up-regulated in the 35S:AmiGO-RBR background.

SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer.

The Polyribonucleotide nucleotidyltransferase 1 gene (PNPT1) encodes polynucleotide phosphorylase (PNPase), a 3'-5' exoribonuclease involved in mitochondrial RNA degradation and surveillance and RNA import into the mitochondrion. Here, we have characterized the PNPT1 promoter by in silico analysis, luciferase reporter assays, electrophoretic mobility shift assays (EMSA), chromatin immunoprecipitation (ChIP), siRNA-based mRNA silencing and RT-qPCR. We show that the Specificity protein 1 (SP1) transcription factor and Nuclear transcription factor Y (NFY) bind the PNPT1 promoter, and have a relevant role regulating the promoter activity, PNPT1 expression, and mitochondrial activity. We also found in Kaplan-Meier survival curves that a high expression of either PNPase, SP1 or NFY subunit A (NFYA) is associated with a poor prognosis in liver cancer. In summary, our results show the relevance of SP1 and NFY in PNPT1 expression, and point to SP1/NFY and PNPase as possible targets in anti-cancer therapy.

Predicted landscape of RETINOBLASTOMA-RELATED LxCxE-mediated interactions across the Chloroplastida.

The colonization of land by a single streptophyte algae lineage some 450 million years ago has been linked to multiple key innovations such as three-dimensional growth, alternation of generations, the presence of stomata, as well as innovations inherent to the birth of major plant lineages, such as the origins of vascular tissues, roots, seeds and flowers. Multicellularity, which evolved multiple times in the Chloroplastida coupled with precise spatiotemporal control of proliferation and differentiation were instrumental for the evolution of these traits. RETINOBLASTOMA-RELATED (RBR), the plant homolog of the metazoan Retinoblastoma protein (pRB), is a highly conserved and multifunctional core cell cycle regulator that has been implicated in the evolution of multicellularity in the green lineage as well as in plant multicellularity-related processes such as proliferation, differentiation, stem cell regulation and asymmetric cell division. RBR fulfills these roles through context-specific protein-protein interactions with proteins containing the Leu-x-Cys-x-Glu (LxCxE) short-linear motif (SLiM); however, how RBR-LxCxE interactions have changed throughout major innovations in the Viridiplantae kingdom is a question that remains unexplored. Here, we employ an in silico evo-devo approach to predict and analyze potential RBR-LxCxE interactions in different representative species of key Chloroplastida lineages, providing a valuable resource for deciphering RBR-LxCxE multiple functions. Furthermore, our analyses suggest that RBR-LxCxE interactions are an important component of RBR functions and that interactions with chromatin modifiers/remodelers, DNA replication and repair machinery are highly conserved throughout the Viridiplantae, while LxCxE interactions with transcriptional regulators likely diversified throughout the water-to-land transition.

Type 2 Diabetes-Related Variants Influence the Risk of Developing Prostate Cancer: A Population-Based Case-Control Study and Meta-Analysis.

In this study, we have evaluated whether 57 genome-wide association studies (GWAS)-identified common variants for type 2 diabetes (T2D) influence the risk of developing prostate cancer (PCa) in a population of 304 Caucasian PCa patients and 686 controls. The association of selected single nucleotide polymorphisms (SNPs) with the risk of PCa was validated through meta-analysis of our data with those from the UKBiobank and FinnGen cohorts, but also previously published genetic studies. We also evaluated whether T2D SNPs associated with PCa risk could influence host immune responses by analysing their correlation with absolute numbers of 91 blood-derived cell populations and circulating levels of 103 immunological proteins and 7 steroid hormones. We also investigated the correlation of the most interesting SNPs with cytokine levels after in vitro stimulation of whole blood, peripheral mononuclear cells (PBMCs), and monocyte-derived macrophages with LPS, PHA, Pam3Cys, and Staphylococcus Aureus. The meta-analysis of our data with those from six large cohorts confirmed that each copy of the FTOrs9939609A, HNF1Brs7501939T, HNF1Brs757210T, HNF1Brs4430796G, and JAZF1rs10486567A alleles significantly decreased risk of developing PCa (p = 3.70 × 10-5, p = 9.39 × 10-54, p = 5.04 × 10-54, p = 1.19 × 10-71, and p = 1.66 × 10-18, respectively). Although it was not statistically significant after correction for multiple testing, we also found that the NOTCH2rs10923931T and RBMS1rs7593730 SNPs associated with the risk of developing PCa (p = 8.49 × 10-4 and 0.004). Interestingly, we found that the protective effect attributed to the HFN1B locus could be mediated by the SULT1A1 protein (p = 0.00030), an arylsulfotransferase that catalyzes the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. In addition to these results, eQTL analysis revealed that the HNF1Brs7501939, HNF1Brs757210, HNF1Brs4430796, NOTCH2rs10923931, and RBMS1rs7593730 SNPs influence the risk of PCa through the modulation of mRNA levels of their respective genes in whole blood and/or liver. These results confirm that functional TD2-related variants influence the risk of developing PCa, but also highlight the need of additional experiments to validate our functional results in a tumoral tissue context.

Risk Factors for Acute Kidney Injury Following Cardiac Surgery and Performance of Leicester Score in a Spanish Cohort.

The incidence of acute kidney injury following cardiac surgery (CSA-AKI) is up to 30%, and it places patients at an increased risk of death. The Leicester score (LS) is a new score that predicts CSA-AKI of any stage with better discrimination compared to previous scores. The aim of this study was to identify risk factors for CSA-AKI and to assess the performance of LS. A unicentric retrospective study of patients that required cardiac surgery with cardio-pulmonary bypass (CPB) in 2015 was performed. The inclusion criteria were patients over 18 years old who were operated on for cardiac surgery (valve substitution (VS), Coronary Artery Bypass Graft (CABG), or a combination of both procedures and requiring CPB). CSA-AKI was defined with the Kidney Disease Improving Global Outcomes (KDIGO) criteria. In the multivariate analysis, hypertension (odds ratio 1.883), estimated glomerular filtration rate (EGFR) <60 mL/min (2.365), and peripheral vascular disease (4.66) were associated with the outcome. Both discrimination and calibration were better when the LS was used compared to the Cleveland Clinic Score and Euroscore II, with an area under the curve (AUC) of 0.721. In conclusion, preoperative hypertension in patients with CKD with or without peripheral vasculopathy can identify patients who are at risk of CSA-AKI. The LS was proven to be a valid score that could be used to identify patients who are at risk and who could benefit from intervention studies.

Root canal microbiota as an augmented reservoir of antimicrobial resistance genes in type 2 diabetes mellitus patients

Abstract Antimicrobial resistance is a global public health problem. Root canal microbiota associated with apical periodontitis represents a well-known reservoir of antimicrobial resistance genes (ARGs). However, the effect of type 2 diabetes mellitus (T2DM) in this reservoir is unknown. This study aimed to establish if root canal microbiota associated with apical periodontitis in T2DM patients is an augmented reservoir by identifying the prevalence of nine common ARGs and comparing it with the prevalence in nondiabetic patients. Methodology This cross-sectional study included two groups: A T2DM group conformed of 20 patients with at least ten years of living with T2DM and a control group of 30 nondiabetic participants. Premolar or molar teeth with pulp necrosis and apical periodontitis were included. A sample was collected from each root canal before endodontic treatment. DNA was extracted, and ARGs were identified by polymerase chain reaction. Results tetW and tetM genes were the most frequent (93.3 and 91.6%, respectively), while ermA was the least frequent (8.3%) in the total population. The distribution of the ARGs was similar in both groups, but a significant difference (p<0.005) was present in ermB, ermC, cfxA, and tetQ genes, being more frequent in the T2DM group. A total of eighty percent of the T2DM patients presented a minimum of four ARGs, while 76.6% of the control group presented a maximum of three. Conclusions Root canal microbiota associated with apical periodontitis in T2DM patients carries more ARGs. Therefore, this pathological niche could be considered an augmented reservoir.

Safety and Efficacy of Deoxycholic Acid Injection for Hypogastric Fat Reduction: A Pilot Study.

BACKGROUND: Although deoxycholic acid (DCA) has been proposed for use in other areas, it is used primarily for treating moderate-to-severe fat in the submental area. OBJECTIVE: To evaluate the safety and efficacy of DCA for fat reduction in the hypogastric region. MATERIALS AND METHODS: A prospective, longitudinal, nonrandomized, open-label, interventional pilot study was performed. Deoxycholic acid was transcutaneously injected in upper right, upper left, lower right, and lower left hypogastric zones. Fat thickness was assessed using calipers, ultrasound, and 3-dimensional scanning. The primary end point safety was evaluated by laboratory tests and the incidence of adverse events. RESULTS: Fourteen patients (54 treatment sessions) were included. The mean total volume administered was 26.6 mL. The main local adverse events were edema (94.4%), bruising (90.7%), and erythema (79.6%), all being self-limited (the mean duration 9.6, 7, and 2 days, respectively). A DCA dose was significantly associated with erythema duration (p = .0421) but not with edema duration (p = .1611) or bruising incidence (p = .1013). Measurement using calipers, ultrasound, and 3-dimensional scanning revealed significant fat thickness reduction. Patient-reported outcome measure scores revealed a significant improvement in patient satisfaction. CONCLUSION: Deoxycholic acid may be a safe and effective option for reducing fat thickness in the hypogastric region, although given the cost/benefit ratio probably should be reserved for small deposits.