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Songbirds have one special accessory chromosome, the so-called germline-restricted chromosome (GRC), which is only present in germline cells and absent from all somatic tissues. Earlier work on the zebra finch (Taeniopygia guttata castanotis) showed that the GRC is inherited only through the female line-like the mitochondria-and is eliminated from the sperm during spermatogenesis. Here, we show that the GRC has the potential to be paternally inherited. Confocal microscopy using GRC-specific fluorescent in situ hybridization probes indicated that a considerable fraction of sperm heads (1 to 19%) in zebra finch ejaculates still contained the GRC. In line with these cytogenetic data, sequencing of ejaculates revealed that individual males from two families differed strongly and consistently in the number of GRCs in their ejaculates. Examining a captive-bred male hybrid of the two zebra finch subspecies (T. g. guttata and T. g. castanotis) revealed that the mitochondria originated from a castanotis mother, whereas the GRC came from a guttata father. Moreover, analyzing GRC haplotypes across nine castanotis matrilines, estimated to have diverged for up to 250,000 y, showed surprisingly little variability among GRCs. This suggests that a single GRC haplotype has spread relatively recently across all examined matrilines. A few diagnostic GRC mutations that arose since this inferred spreading suggest that the GRC has continued to jump across matriline boundaries. Our findings raise the possibility that certain GRC haplotypes could selfishly spread through the population via occasional paternal transmission, thereby outcompeting other GRC haplotypes that were limited to strict maternal inheritance, even if this was partly detrimental to organismal fitness.
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Cromosomas , Células Germinativas , Herencia Paterna , Pájaros Cantores/genética , Animales , Análisis Citogenético , ADN Mitocondrial , Evolución Molecular , Femenino , Haplotipos , Masculino , Filogenia , Pájaros Cantores/clasificación , EspermatozoidesRESUMEN
The protein encoded by COQ7 is required for CoQ10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However, the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptional remodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies.
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PURPOSE: Investigation of undiagnosed cases of infectious neurological diseases, especially in the paediatric population, remains a challenge. This study aimed to enhance understanding of viruses in CSF from children with clinically diagnosed meningitis and/or encephalitis (M/ME) of unknown aetiology using shotgun sequencing enhanced by hybrid capture (HCSS). METHODS: A single-centre prospective study was conducted at Sant Joan de Déu University Hospital, Barcelona, involving 40 M/ME episodes of unknown aetiology, recruited from May 2021 to July 2022. All participants had previously tested negative with the FilmArray Meningitis/Encephalitis Panel. HCSS was used to detect viral nucleic acid in the patients' CSF. Sequencing was performed on Illumina NovaSeq platform. Raw sequence data were analysed using CZ ID metagenomics and PikaVirus bioinformatics pipelines. RESULTS: Forty episodes of M/ME of unknown aetiology in 39 children were analysed by HCSS. A significant viral detection in 30 CSF samples was obtained, including six parechovirus A, three enterovirus ACD, four polyomavirus 5, three HHV-7, two BKV, one HSV-1, one VZV, two CMV, one EBV, one influenza A virus, one rhinovirus, and 13 HERV-K113 detections. Of these, one sample with BKV, three with HHV-7, one with EBV, and all HERV-K113 were confirmed by specific PCR. The requirement for Intensive Care Unit admission was associated with HCSS detections. CONCLUSION: This study highlights HCSS as a powerful tool for the investigation of undiagnosed cases of M/ME. Data generated must be carefully analysed and reasonable precautions must be taken before establishing association of clinical features with unexpected or novel virus findings.
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Metagenómica , Virus , Humanos , Preescolar , Estudios Prospectivos , Femenino , Masculino , Niño , Virus/genética , Virus/aislamiento & purificación , Virus/clasificación , Lactante , Metagenómica/métodos , Encefalitis/virología , Encefalitis/líquido cefalorraquídeo , Encefalitis/diagnóstico , Líquido Cefalorraquídeo/virología , Meningitis Viral/virología , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/diagnóstico , Adolescente , Secuenciación de Nucleótidos de Alto Rendimiento , España , Meningitis/virología , Meningitis/líquido cefalorraquídeo , Meningitis/diagnóstico , Encefalitis Viral/virología , Encefalitis Viral/líquido cefalorraquídeo , Encefalitis Viral/diagnósticoRESUMEN
The role of locoregional therapy in the management of thyroid pathology is rapidly evolving. The Society of Interventional Radiology Foundation commissioned an international research consensus panel consisting of physicians from multiple disciplines with expertise in the management of benign and malignant thyroid disease. The panel focused on identifying gaps in the current body of literature to establish research priorities that have the potential to shape the landscape of minimally invasive thyroid interventions. The topics discussed were centered on the emerging role of ablation for malignant thyroid tumors and the treatment of large functioning nodules with embolization and ablation. Specifically, the panel prioritized identifying nodule characteristics, including size and location, that are associated with ideal outcomes following thermal ablation for papillary thyroid microcarcinoma through the development of an international registry or a prospective, multi-institutional trial. The panel also prioritized evaluating the role of locoregional therapy in Stage T1b papillary thyroid cancer through a sequence of two studies: a Phase I study of ablation followed by immediate resection of Stage T1b papillary thyroid cancer, which may lead to a Phase II prospective, multi-institutional study of ablation followed by biopsy for Stage T1b papillary thyroid cancer. Lastly, the panel prioritized investigating the treatment of large, functioning thyroid nodules greater than 20 ml in volume through a randomized clinical trial or prospective registry comparing embolization alone with embolization followed by ablation.
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To develop and validate a 3D simulation model to calculate laser ablation (LA) zone size and estimate the volume of treated tissue for thyroid applications, a model was developed, taking into account dynamic optical and thermal properties of tissue change. For validation, ten Yorkshire swines were equally divided into two cohorts and underwent thyroid LA at 3 W/1,400 J and 3 W/1,800 J respectively with a 1064-nm multi-source laser (Echolaser X4 with Orblaze™ technology; ElEn SpA, Calenzano, Italy). The dataset was analyzed employing key statistical measures such as mean and standard deviation (SD). Model simulation data were compared with animal gross histology. Experimental data for longitudinal length, width (transverse length), ablation volume and sphericity were 11.0 mm, 10.0 mm, 0.6 mL and 0.91, respectively at 1,400 J and 14.6 mm, 12.4 mm, 1.12 mL and 0.83, respectively at 1,800 J. Gross histology data showed excellent reproducibility of the ablation zone among same laser settings; for both 1,400 J and 1,800 J, the SD of the in vivo parameters was ≤ 0.7 mm, except for width at 1,800 J, for which the SD was 1.1 mm. Simulated data for longitudinal length, width, ablation volume and sphericity were 11.6 mm, 10.0 mm, 0.62 mL and 0.88, respectively at 1,400 J and 14.2 mm, 12.0 mm, 1.06 mL and 0.84, respectively at 1,800 J. Experimental data for ablation volume, sphericity coefficient, and longitudinal and transverse lengths of thermal damaged area showed good agreement with the simulation data. Simulation datasets were successfully incorporated into proprietary planning software (Echolaser Smart Interface, Elesta SpA, Calenzano, Italy) to provide guidance for LA of papillary thyroid microcarcinomas. Our mathematical model showed good predictability of coagulative necrosis when compared with data from in vivo animal experiments.
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Terapia por Láser , Glándula Tiroides , Animales , Terapia por Láser/métodos , Terapia por Láser/instrumentación , Glándula Tiroides/cirugía , Glándula Tiroides/patología , Porcinos , Simulación por Computador , Modelos Teóricos , Reproducibilidad de los ResultadosRESUMEN
Acetic acid bacteria (AAB) and other members of the complex microbiotas, whose activity is essential for vinegar production, display biodiversity and richness that is difficult to study in depth due to their highly selective culture conditions. In recent years, liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has emerged as a powerful tool for rapidly identifying thousands of proteins present in microbial communities, offering broader precision and coverage. In this work, a novel method based on LC-MS/MS was established and developed from previous studies. This methodology was tested in three studies, enabling the characterization of three submerged acetification profiles using innovative raw materials (synthetic alcohol medium, fine wine, and craft beer) while working in a semicontinuous mode. The biodiversity of existing microorganisms was clarified, and both the predominant taxa (Komagataeibacter, Acetobacter, Gluconacetobacter, and Gluconobacter) and others never detected in these media (Asaia and Bombella, among others) were identified. The key functions and adaptive metabolic strategies were determined using comparative studies, mainly those related to cellular material biosynthesis, energy-associated pathways, and cellular detoxification processes. This study provides the groundwork for a highly reliable and reproducible method for the characterization of microbial profiles in the vinegar industry.
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Ácido Acético , Proteínas Bacterianas , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Ácido Acético/metabolismo , Ácido Acético/análisis , Ácido Acético/química , Cromatografía Liquida/métodos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/análisis , Bacterias/metabolismoRESUMEN
In situ activation of Pt(IV) to Pt(II) species is a promising strategy to control the anticancer activity and overcome the off-target toxicity linked to classic platinum chemotherapeutic agents. Herein, we present the design and synthesis of two new asymmetric Pt(IV) derivatives of cisplatin and oxaliplatin (1·TARF and 2·TARF, respectively) bearing a covalently bonded 2',3',4',5'-tetraacetylriboflavin moiety (TARF). 1H and 195Pt NMR spectroscopy shows that 1·TARF and 2·TARF can be effectively activated into toxic Pt(II) species, when incubated with nicotinamide adenine dinucleotide, sodium ascorbate, and glutathione in the dark and under light irradiation. Density functional theory studies of the dark Pt(IV)-to-Pt(II) conversion of 2·TARF indicate that the process involves first hydride transfer from the donor to the flavin moiety of the complex, followed by electron transfer to the Pt(IV) center. When administered to MDA-MB-231 breast cancer cells preincubated with nontoxic amounts of ascorbate, 2·TARF displays enhanced toxicity (between 1 and 2 orders of magnitude), suggesting that the generation of oxaliplatin can selectively be triggered by redox activation. Such an effect is not observed when 2 and TARF are coadministered under the same conditions, demonstrating that covalent binding of the flavin to the Pt complex is pivotal.
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Antineoplásicos , Profármacos , Oxaliplatino/farmacología , Antineoplásicos/química , Cisplatino/química , Platino (Metal)/química , Espectroscopía de Resonancia Magnética , Profármacos/química , Línea Celular TumoralRESUMEN
Selfish genetic elements (SGE) get a transmission advantage (drive) thanks to their non-Mendelian inheritance. Here I identify eight steps during the reproductive cycle that can be subverted by SGEs to thrive in natural populations. Even though only three steps occur during meiosis, most cases of segregation distortion are considered "meiotic drive sensu lato." As this is a source of unnecessary contradictions, I suggest always using the term "transmission ratio distortion" (TRD). Chromosomal SGEs (e.g., B chromosomes) exhibit almost all types of TRD. In plants, the best-studied type of TRD for B chromosomes occurs post-meiotically during male gametophyte maturation. However, in animals, the two main types are pre-meiotic and meiotic TRDs, in all cases associated with gonotaxis (i.e., a preference of B chromosomes for germ cells). Frequently, TRD drivers in genic SGEs (e.g., t-alleles and segregation distorters in Drosophila) are paralogous copies of genes from the standard genome, whereas their targets can be other genes or satellite DNA (satDNA). As B chromosomes are often rich in satDNA and contain paralogous copies of A chromosome genes, perhaps their drive mechanisms are similar to those of genic SGEs. So far, the only association between a B chromosome gene and TRD is the gene haplodizer in Nasonia vitripennis. The discovery of B-genes controlling B-drive in other species does not appear to be far off, but experimental crosses will be needed to simultaneously test the TRD of a given B chromosome and the expression of its genes.
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Cromosomas , ADN Satélite , Alelos , Animales , Cromosomas/genética , Drosophila/genética , Meiosis , Secuencias Repetitivas de Ácidos NucleicosRESUMEN
AIMS: Viral diseases can be indirectly transmitted by contaminated non-food contact surfaces to final food products by cross-contamination. The interaction of metal surfaces and viruses, MS2 coliphage and hepatitis A virus (HAV), was investigated for strategy development in decreasing this transmission risk. METHODS AND RESULTS: MS2 deposited onto stainless-steel surface was stable but inactivated at 0.95 log10 PFU min-1 on 99.9% copper surfaces. Greater copper-inactivation of MS2 was observed in (a) simple media (phosphate buffered saline, PBS) than protein-rich media (beef extract buffer), and (b) acidic than pH ≥ 6.8 environments. Among food matrices (strawberry juices and beef broth), the greatest MS2 inactivation by copper occurred in filtered strawberry juice at pH 3.5. At a reduction of 0.17 log10 PFU min-1, HAV survived longer than MS2 on copper by FRhK-4 cell infectivity assay. CONCLUSIONS: The inactivation of virus on copper surfaces was greater in acidic viral surrounding environments and in simple PBS medium. In the same 99% PBS medium, MS2 may not be an appropriate surrogate for HAV when assessing viral inactivation on copper surfaces.
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Antivirales , Virus de la Hepatitis A , Animales , Bovinos , Cobre/farmacología , Colifagos , Inactivación de Virus , Levivirus/fisiologíaRESUMEN
Skeletal muscle development and regeneration is governed by the combined action of Myf5, MyoD, Mrf4 and MyoG, also known as the myogenic regulatory factors (MRFs). These transcription factors are expressed in a highly spatio-temporal restricted manner, ensuring the significant functional and metabolic diversity observed between the different muscle groups. In this review, we will discuss the multiple layers of regulation that contribute to the control of the exquisite expression patterns of the MRFs in particular, and of myogenic genes in general. We will highlight all major regulatory processes that play a role in myogenesis: from those that modulate chromatin status and transcription competence, such as DNA methylation, histone modification, chromatin remodeling, or non-coding RNAs, to those that control transcript and protein processing and modification, such as alternative splicing, polyadenylation, other mRNA modifications, or post-translational protein modifications. All these processes are exquisitely and tightly coordinated to ensure the proper activation, maintenance and termination of the myogenic process.
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Desarrollo de Músculos , Factores Reguladores Miogénicos , Ensamble y Desensamble de Cromatina , Expresión Génica , Regulación de la Expresión Génica , Músculo Esquelético , Factores de TranscripciónRESUMEN
Collet-Sicard syndrome (CSS) is the unilateral palsy of the cranial nerves (CN) IX, X, XI, and XII. To our knowledge, no review describes the characteristics of patients diagnosed with CSS. Therefore, this review aims to collect and describe all cases in the literature labeled as CSS. We performed a scoping review of the literature and conducted a database search in Embase and PubMed. We included articles and abstracts with case reports or case series of patients with CSS diagnosis. We classified the cases into two groups: "CSS", referring to patients presenting exclusively with IX-XII nerve involvement, and "CSS-plus", which corresponds to cases with CSS and other neurological impairments. We included 135 patients from 126 articles, of which 84 (67.7%) were male. The most common clinical manifestations reported were dysphagia and dysphonia. The most common etiology was tumoral in 53 cases (39.6%) and vascular in 37 cases (27.6%). The majority of patients showed partial or total improvement, with just over half receiving conservative treatment. The most frequent anatomic space was the jugular foramen (44.4%) and the parapharyngeal retrostyloid space (28.9%). Approximately 21% of the patients had other CN impairments, with the seventh and eighth CN most frequently compromised. We conclude that although there is a need for greater rigor in CSS reporting, the syndrome has a clear utility in identifying the localization of jugular foramen and parapharyngeal retrostyloid space pathology.
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Trastornos de Deglución , Enfermedades del Nervio Glosofaríngeo , Humanos , Masculino , Femenino , Nervio Glosofaríngeo , Tratamiento Conservador , Bases de Datos Factuales , Trastornos de Deglución/etiologíaRESUMEN
BACKGROUND: The full catalog of satellite DNA (satDNA) within a same genome constitutes the satellitome. The Library Hypothesis predicts that satDNA in relative species reflects that in their common ancestor, but the evolutionary mechanisms and pathways of satDNA evolution have never been analyzed for full satellitomes. We compare here the satellitomes of two Oedipodine grasshoppers (Locusta migratoria and Oedaleus decorus) which shared their most recent common ancestor about 22.8 Ma ago. RESULTS: We found that about one third of their satDNA families (near 60 in every species) showed sequence homology and were grouped into 12 orthologous superfamilies. The turnover rate of consensus sequences was extremely variable among the 20 orthologous family pairs analyzed in both species. The satDNAs shared by both species showed poor association with sequence signatures and motives frequently argued as functional, except for short inverted repeats allowing short dyad symmetries and non-B DNA conformations. Orthologous satDNAs frequently showed different FISH patterns at both intra- and interspecific levels. We defined indices of homogenization and degeneration and quantified the level of incomplete library sorting between species. CONCLUSIONS: Our analyses revealed that satDNA degenerates through point mutation and homogenizes through partial turnovers caused by massive tandem duplications (the so-called satDNA amplification). Remarkably, satDNA amplification increases homogenization, at intragenomic level, and diversification between species, thus constituting the basis for concerted evolution. We suggest a model of satDNA evolution by means of recursive cycles of amplification and degeneration, leading to mostly contingent evolutionary pathways where concerted evolution emerges promptly after lineages split.
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ADN Satélite , Saltamontes , Animales , ADN Satélite/genética , Evolución Molecular , Biblioteca de Genes , Saltamontes/genética , Humanos , FilogeniaRESUMEN
Vandenboschia speciosa is an endangered tetraploid fern species with a large genome (10.5 Gb). Its geographical distribution is characterized by disjoined tertiary flora refuges, with relict populations that survived past climate crises. Here, we analyzed the transposable elements (TEs) and found that they comprise approximately 76% of the V. speciosa genome, thus being the most abundant type of DNA sequence in this gigantic genome. The V. speciosa genome is composed of 51% and 5.6% of Class I and Class II elements, respectively. LTR retrotransposons were the most abundant TEs in this species (at least 42% of the genome), followed by non-LTR retrotransposons, which constituted at least 8.7% of the genome of this species. We introduce an additional analysis to identify the nature of non-annotated elements (19% of the genome). A BLAST search of the non-annotated contigs against the V. speciosa TE database allowed for the identification of almost half of them, which were most likely diverged sequence variants of the annotated TEs. In general, the TE composition in V. speciosa resembles the TE composition in seed plants. In addition, repeat landscapes revealed three episodes of amplification for all TEs, most likely due to demographic changes associated with past climate crises.
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Helechos , Elementos Transponibles de ADN/genética , Evolución Molecular , Helechos/genética , Genoma de Planta , RetroelementosRESUMEN
PURPOSE: To validate an immunofluorescence assay (IFA) detecting residual viable tumor (VT) as intraprocedural thermal ablation (TA) zone assessment and demonstrate its prognostic value for local tumor progression (LTP) after colorectal liver metastasis (CLM) TA. MATERIALS AND METHODS: This prospective study, approved by the institutional review board, included 99 patients with 155 CLMs ablated between November 2009 and January 2019. Tissue samples from the ablation zone (AZ) center and minimal margin underwent immunofluorescent microscopic examination interrogating cellular morphology and mitochondrial viability (IFA) within 30 minutes after ablation. The same tissue samples were subsequently evaluated with standard morphologic and immunohistochemical methods. The sensitivity, specificity, and overall accuracy of IFA versus standard morphologic and immunohistochemical examination were calculated. The LTP-free survival rates were evaluated for the 12-month follow-up period. RESULTS: Of the 311 tissue samples stained, 304 (98%) were deemed evaluable. Of these specimens, 27% (81/304) were considered positive for the presence of VT. The accuracy of IFA was 94% (286/304). The sensitivity and specificity were 100% (63/63) and 93% (223/241), respectively. The 18 false-positive IFA assessments corresponded to samples that included viable cholangiocytes. The 12-month LTP-free survival was 59% versus 78% for IFA positive versus negative for VT AZs, respectively (P < .001). There was no difference in LTP between margin positive only and central AZ-positive tumors (25% vs 31%, P = 1). CONCLUSIONS: The IFA assessment of the AZ can be completed intraprocedurally and serve as a valid real-time biomarker of complete tumor eradication or detect residual VT after TA. This method could improve tumor control by TA.
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Ablación por Catéter , Neoplasias Colorrectales , Neoplasias Hepáticas , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Técnica del Anticuerpo Fluorescente , Secciones por Congelación , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND. Digital breast tomosynthesis (DBT) has led to increased detection and biopsy of architectural distortion, which may yield malignancy, radial scar, or other benign pathologies. Management of nonmalignant architectural distortion on DBT remains controversial. OBJECTIVE. The purpose of this study was to determine upgrade rates of architectural distortion on DBT from nonmalignant pathology at biopsy to malignancy at surgery. METHODS. This retrospective study included cases of mammographically detected architectural distortion from July 1, 2016, to June 30, 2019, that were nonmalignant at image-guided needle biopsy and underwent surgical excision. Mammographic examinations included digital 2D mammography and DBT. Imaging data were extracted from radiology reports. Upgrade rates were summarized using descriptive statistics. Features of upgraded and nonupgraded cases were compared using Pearson chi-square test and Wilcoxon signed rank test. RESULTS. The study included 129 cases of architectural distortion with nonmalignant pathology at biopsy that underwent excision in 125 women (mean age, 54 years; range, 23-90 years). At biopsy, 92 (71.3%) were radial scars and 37 (28.7%) were other nonmalignant pathologies. Of 66 radial scars without atypia at biopsy, one (1.5%) was upgraded to ductal carcinoma in situ (DCIS) at surgery and none to invasive cancer. Of 24 benign pathologies without atypia at biopsy, one was considered discordant. Of the 23 remaining concordant cases, one (4.3%) was upgraded to DCIS at surgery and none to invasive cancer. The overall upgrade rate to cancer of architectural distortion with concordant nonmalignant pathology at biopsy was 10.2% (13/128). The upgrade rate to cancer of architectural distortion without atypia was 2.2% (2/89) and with atypia was 28.2% (11/39). Explored features (age, personal or family breast cancer history, presentation by screening vs diagnostic mammography, breast density, associated mammographic findings, presence and size of ultrasound correlate, biopsy modality) showed no signifi-cant associations with upgrade risk (p > .05). CONCLUSION. Architectural distortion on DBT with concordant nonmalignant pathology at biopsy has an overall upgrade rate to malignancy at surgery of 10.2%. Architectural distortion without atypia has a low upgrade rate of 2.2%. CLINICAL IMPACT. Imaging surveillance can be considered for architectural distortion on DBT yielding radial scar without atypia or other concordant benign pathologies without atypia at biopsy.
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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Enfermedad Fibroquística de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Cicatriz/diagnóstico por imagen , Femenino , Humanos , Biopsia Guiada por Imagen , Mamografía/métodos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE OF REVIEW: To provide an overview of the classifications and clinical hallmarks of common cancer-related conditions that contribute to the high incidence of portal hypertension in this population and provide an update on currently available interventional radiology therapeutic approaches. RECENT FINDINGS: In the last few decades, there have been significant advancements in understanding the pathophysiology of portal hypertension. This knowledge has led to the development of safer and more effective minimally invasive approaches. The main objective is to provide alternatives to prevent life-threatening complications from clinically significant portal hypertension and to allow the continuation of cancer treatment interventions that would otherwise be stopped. Clinicians involved in cancer care should be aware of risk factors, associated complications, and management of portal hypertension in cancer patients. Interventional radiology offers minimally invasive alternatives that play a central role in improving clinical outcomes and survival of these patients, allowing the continuation of cancer treatments.
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Várices Esofágicas y Gástricas , Hipertensión Portal , Neoplasias , Humanos , Várices Esofágicas y Gástricas/complicaciones , Hipertensión Portal/complicaciones , Hipertensión Portal/terapia , Factores de Riesgo , Hemorragia Gastrointestinal/complicaciones , Neoplasias/complicaciones , Neoplasias/terapiaRESUMEN
Everolimus is an immunosuppressant agent used in organ transplantation and, more recently, in cancer therapy. It has demonstrated beneficial effects in breast cancer, renal cancer, and neuroendocrine tumours. However, the treatment is not without side effects, some of which are still little known. We report the case of a 56 year-old man with a diagnosis of neuroendocrine tumour who developed a complex regional pain syndrome (CRPS) secondary to treatment with everolimus. CRPS has been linked to treatments with everolimus in renal and breast cancer patients as well as in renal transplant patients. To our knowledge, this is the first case of CRPS in a neuroendocrine tumour patient on everolimus treatment.
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Síndromes de Dolor Regional Complejo , Tumores Neuroendocrinos , Distrofia Simpática Refleja , Síndromes de Dolor Regional Complejo/inducido químicamente , Síndromes de Dolor Regional Complejo/tratamiento farmacológico , Everolimus/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/tratamiento farmacológicoRESUMEN
Arthrofibrosis is a prevalent condition affecting greater than 5% of the general population and leads to a painful decrease in joint range of motion (ROM) and loss of independence due to pathologic accumulation of periarticular scar tissue. Current treatment options are limited in effectiveness and do not address the underlying cause of the condition: accumulation of fibrotic collagenous tissue. Herein, the naturally occurring peptide hormone relaxin-2 is administered for the treatment of adhesive capsulitis (frozen shoulder) and to restore glenohumeral ROM in shoulder arthrofibrosis. Recombinant human relaxin-2 down-regulates type I collagen and α smooth muscle actin production and increases intracellular cAMP concentration in human fibroblast-like synoviocytes, consistent with a mechanism of extracellular matrix degradation and remodeling. Pharmacokinetic profiling of a bolus administration into the glenohumeral joint space reveals the brief systemic and intraarticular (IA) half-lives of relaxin-2: 0.96 h and 0.62 h, respectively. Furthermore, using an established, immobilization murine model of shoulder arthrofibrosis, multiple IA injections of human relaxin-2 significantly improve ROM, returning it to baseline measurements collected before limb immobilization. This is in contrast to single IA (sIA) or multiple i.v. (mIV) injections of relaxin-2 with which the ROM remains constrained. The histological hallmarks of contracture (e.g., fibrotic adhesions and reduced joint space) are absent in the animals treated with multiple IA injections of relaxin-2 compared with the untreated control and the sIA- and mIV-treated animals. As these findings show, local delivery of relaxin-2 is an innovative treatment of shoulder arthrofibrosis.
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Bursitis/tratamiento farmacológico , Relaxina/uso terapéutico , Animales , Bursitis/patología , Línea Celular , Colágeno/metabolismo , Modelos Animales de Enfermedad , Femenino , Fibrosis , Humanos , Inyecciones Intraarticulares , Masculino , Ratones , Rango del Movimiento Articular/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Relaxina/administración & dosificación , Articulación del Hombro/efectos de los fármacos , Articulación del Hombro/patologíaRESUMEN
BACKGROUND: Eukaryote genomes frequently harbor supernumerary B chromosomes in addition to the "standard" A chromosome set. B chromosomes are thought to arise as byproducts of genome rearrangements and have mostly been considered intraspecific oddities. However, their evolutionary transcendence beyond species level has remained untested. RESULTS: Here we reveal that the large metacentric B chromosomes reported in several fish species of the genus Astyanax arose in a common ancestor at least 4 million years ago. We generated transcriptomes of A. scabripinnis and A. paranae 0B and 1B individuals and used these assemblies as a reference for mapping all gDNA and RNA libraries to quantify coverage differences between B-lacking and B-carrying genomes. We show that the B chromosomes of A. scabripinnis and A. paranae share 19 protein-coding genes, of which 14 and 11 were also present in the B chromosomes of A. bockmanni and A. fasciatus, respectively. Our search for B-specific single-nucleotide polymorphisms (SNPs) identified the presence of B-derived transcripts in B-carrying ovaries, 80% of which belonged to nobox, a gene involved in oogenesis regulation. Importantly, the B chromosome nobox paralog is expressed > 30× more than the A chromosome paralog. This indicates that the normal regulation of this gene is altered in B-carrying females, which could potentially facilitate B inheritance at higher rates than Mendelian law prediction. CONCLUSIONS: Taken together, our results demonstrate the long-term survival of B chromosomes despite their lack of regular pairing and segregation during meiosis and that they can endure episodes of population divergence leading to species formation.
Asunto(s)
Characidae/genética , Cromosomas/genética , Genoma , Polimorfismo de Nucleótido Simple , Animales , Mapeo Cromosómico , Femenino , Masculino , Especificidad de la EspecieRESUMEN
BACKGROUND: To evaluate liver venous deprivation (LVD) outcomes in patients with colorectal liver metastasis (CRLM) heavily pretreated with systemic and hepatic arterial infusion pump (HAIP) chemotherapies that had an anticipated insufficient future liver remnant (FLR) hypertrophy after portal vein embolization (PVE). METHODS: PVE was performed with liquid embolics using a transsplenic or ipsilateral transhepatic approach. Simultaneously and via a trans-jugular approach, the right hepatic vein was embolized with vascular plugs. Liver volumetry was assessed on computed tomography before and 3-6 weeks after LVD. RESULTS: Twelve consecutive CRLM patients that underwent LVD before right hepatectomy or trisectionectomy were included, all previously treated with systemic chemotherapy for a mean of 11.9 months. Six patients had additional HAIP. After embolization, FLR ratio increased from 28.7% ± 5.9 to 42.2% ± 9.0 (P < 0.01). Mean kinetic growth rate (KGR) was 3.56%/week ± 2.3, with a degree of hypertrophy (DH) of 13.8% ± 7.1. In the HAIP subgroup, mean KGR and DH were respectively 3.58%/week ± 2.8 and 14.3% ± 8.7. No severe complications occurred. Ten patients reached surgery after 39 days ± 7.5. CONCLUSION: In heavily pretreated patients, LVD safely stimulated a rapid and effective FLR hypertrophy, with a resultant high rate of resection.