Multidisciplinary management of anemia behind epistaxis in HHT

HHT affects one in 5000 people and occurs in all the ethnic groups and areas. It is also known as the Rendu-Osler-Weber disease and it is an inherited autosomal dominant genetic disorder, characterized by vascular abnormalities. Epistaxis, specifically recurrent and spontaneous nosebleeds, has been assessed as one of the most common, if not the most common clinical manifestation in HHT patients. The burden related to this manifestation has both psychological and physical consequences, especially since the treatment options follow a ladder that might bring to surgery and more invasive therapies. The EQ-VAS questionnaire allows us to adequately assess and classify HHT patients based on the intensity and type of epistaxis-related symptoms. This same questionnaire, which is submitted to patients during each evaluation for the benefit of anamnestic supplementation, includes both a question about the presence or absence of anemia and one about whether a red cell transfusion has been performed in the past months or since the last outpatient visit. As a matter of fact, chronic nosebleed, although mild to moderate, can lead to anemia within months or years and, in general, to a poor quality of life. Patients who have to undergo iron supplementation treatments often face the almost inevitable side effects that this therapy entails (diarrhea, constipation, nausea, persistent metallic taste, abdominal pain, etc.). Although numerous treatment options are available for patients with epistaxis phenotype, from topical to surgical, we believe, based on the successes achieved in the follow up of HHT patients at our center, that a multidisciplinary collaboration is essential to identify the patients who can benefit most from each treatment

Human Cancer Cells Signal Their Competitive Fitness Through MYC Activity

MYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development from Drosophila to mammals. Cells expressing low levels of MYC, called losers, are committed to die by nearby cells with high MYC activity, called winners, that overproliferate to compensate for cell loss, so that the fittest cells be selected for organ formation. Given MYC's consolidated role in oncogenesis, cell competition is supposed to be relevant to cancer, but its significance in human malignant contexts is largely uncharacterised. Here we show stereotypical patterns of MYC-mediated cell competition in human cancers: MYC-upregulating cells and apoptotic cells were indeed repeatedly found at the tumour-stroma interface and within the tumour parenchyma. Cell death amount in the stromal compartment and MYC protein level in the tumour were highly correlated regardless of tumour type and stage. Moreover, we show that MYC modulation in heterotypic co-cultures of human cancer cells is sufficient as to subvert their competitive state, regardless of genetic heterogeneity. Altogether, our findings suggest that the innate role of MYC-mediated cell competition in development is conserved in human cancer, with malignant cells using MYC activity to colonise the organ at the expense of less performant neighbours

Targeting the autosomal Ceratitis capitata transformer gene using Cas9 or dCas9 to masculinize XX individuals without inducing mutations

Background: Females of the Mediterranean fruit fly Ceratitis capitata (Medfly) are major agricultural pests, as they lay eggs into the fruit crops of hundreds of plant species. In Medfly, female sex determination is based on the activation of Cctransformer (Cctra). A maternal contribution of Cctra is required to activate Cctra itself in the XX embryos and to start and epigenetically maintain a Cctra positive feedback loop, by female-specific alternative splicing, leading to female development. In XY embryos, the male determining Maleness-on-the-Y gene (MoY) blocks this activation and Cctra produces male-specific transcripts encoding truncated CcTRA isoforms and male differentiation occurs. Results: With the aim of inducing frameshift mutations in the first coding exon to disrupt both female-specific and shorter male-specific CcTRA open reading frames (ORF), we injected Cas9 ribonucleoproteins (Cas9 and single guide RNA, sgRNA) in embryos. As this approach leads to mostly monoallelic mutations, masculinization was expected only in G1 XX individuals carrying biallelic mutations, following crosses of G0 injected individuals. Surprisingly, these injections into XX-only embryos led to G0 adults that included not only XX females but also 50% of reverted fertile XX males. The G0 XX males expressed male-specific Cctra transcripts, suggesting full masculinization. Interestingly, out of six G0 XX males, four displayed the Cctra wild type sequence. This finding suggests that masculinization by Cas9-sgRNA injections was independent from its mutagenic activity. In line with this observation, embryonic targeting of Cctra in XX embryos by a dead Cas9 (enzymatically inactive, dCas9) also favoured a male-specific splicing of Cctra, in both embryos and adults. Conclusions: Our data suggest that the establishment of Cctra female-specific autoregulation during the early embryogenesis has been repressed in XX embryos by the transient binding of the Cas9-sgRNA on the first exon of the Cctra gene. This hypothesis is supported by the observation that the shift of Cctra splicing from female to male mode is induced also by dCas9. Collectively, the present findings corroborate the idea that a transient embryonic inactivation of Cctra is sufficient for male sex determination

Improving sleep quality in cancer patients. a literature review on non-pharmacologic interventions

Objective: Disrupted sleep-in cancer patients is due to several factors. Pre-existing sleep disorders, mental status in cancer, or side effects of cancer treatment are all potential predictors of sleep disturbances in this vulnerable population. This review aims to evaluate and synthesise non-pharmaco-logic interventions for improving sleep quality and the associated benefits in cancer patients. Materials and Methods: A literature review was performed according to PRISMA guidelines. PubMed, Google Scholar, MEDLINE, CINAHL, and Embase databases were interrogated, selected the article with cancer, neoplasm, oncology, sleep-wake disorders, sleep disturbance, sleep problem, strategies, treat-ment, and intervention such as keywords. No time and geographic restrictions but paediatrics, children, and interventions unrelated to sleep improvement in cancer were excluded. Results: Overall, twenty-nine articles were included in the review after selection. The included studies analysed different types of cancer, like breast, lung, and prostate cancer and acute leukaemia. Most of the data gathered from the relevant research suggest that nonpharmacologic interventions significantly improved cancer patients’ sleep quality. Conclusions: Cancer survival rates are increasing; researchers and healthcare professionals should aim not just at survival but also to allow cancer patients just comfortably to live, considering the best quality of life possible. Nurses have a crucial role in the care of this patient population. Nursing implies an intimate relationship with patients and educating the patient to improve their mental and physical condition through non-pharmacological approaches, which should be considered a specific competence

Improvement of the CORS method for Cepheids radii determination based on Stromgren photometry

In this paper we present a modified version of the CORS method based on a new calibration of the Surface Brightness function in the Stromgren photometric system. The method has been tested by means of synthetic light and radial velocity curves derived from nonlinear pulsation models. Detailed simulations have been performed to take into account the quality of real observed curves as well as possible shifts between photometric and radial velocity data. The method has been then applied to a sample of Galactic Cepheids with Stromgren photometry and radial velocity data to derive the radii and a new PR relation. As a result we find log R = (1.19 +- 0.09) + (0.74 +- 0.11) log P (r.m.s=0.07). The comparison between our result and previous estimates in the literature is satisfactory. Better results are expected from the adoption of improved model atmosphere grids.Comment: 13 pages including 12 postscript figures and 3 jpeg figures; accepted for publication on A&

Cardiopulmonary Exercise Testing in Repaired Tetralogy of Fallot: Multiparametric Overview and Correlation with Cardiac Magnetic Resonance and Physical Activity Level

Patients with repaired Tetralogy of Fallot (rToF) typically report having preserved subjective exercise tolerance. Chronic pulmonary regurgitation (PR) with varying degrees of right ventricular (RV) dilation as assessed by cardiac magnetic resonance imaging (MRI) is prevalent in rToF and may contribute to clinical compromise. Cardiopulmonary exercise testing (CPET) provides an objective assessment of functional capacity, and the International Physical Activity Questionnaire (IPAQ) can provide additional data on physical activity (PA) achieved. Our aim was to assess the association between CPET values, IPAQ measures, and MRI parameters. All rToF patients who had both an MRI and CPET performed within one year between March 2019 and June 2021 were selected. Clinical data were extracted from electronic records (including demographic, surgical history, New York Heart Association (NYHA) functional class, QRS duration, arrhythmia, MRI parameters, and CPET data). PA level, based on the IPAQ, was assessed at the time of CPET. Eighty-four patients (22.8 ± 8.4 years) showed a reduction in exercise capacity (median peak VO2 30 mL/kg/min (range 25–33); median percent predicted peak VO2 68% (range 61–78)). Peak VO2, correlated with biventricular stroke volumes (RVSV: β = 6.11 (95%CI, 2.38 to 9.85), p = 0.002; LVSV: β = 15.69 (95% CI 10.16 to 21.21), p < 0.0001) and LVEDVi (β = 8.74 (95%CI, 0.66 to 16.83), p = 0.04) on multivariate analysis adjusted for age, gender, and PA level. Other parameters which correlated with stroke volumes included oxygen uptake efficiency slope (OUES) (RVSV: β = 6.88 (95% CI, 1.93 to 11.84), p = 0.008; LVSV: β = 17.86 (95% CI 10.31 to 25.42), p < 0.0001) and peak O2 pulse (RVSV: β = 0.03 (95%CI, 0.01 to 0.05), p = 0.007; LVSV: β = 0.08 (95% CI 0.05 to 0.11), p < 0.0001). On multivariate analysis adjusted for age and gender, PA level correlated significantly with peak VO2/kg (β = 0.02, 95% CI 0.003 to 0.04; p = 0.019). We observed a reduction in objective exercise tolerance in rToF patients. Biventricular stroke volumes and LVEDVi were associated with peak VO2 irrespective of RV size. OUES and peak O2 pulse were also associated with biventricular stroke volumes. While PA level was associated with peak VO2, the incremental value of this parameter should be the focus of future studies

How to improve educational behaviors for caregivers and patients having Central Venous Access Device (CVAD). a scoping review

Objective: Central venous access devices (CVADs) are essential to the modern management of patients with hematological malignancies and solid tumors. Educational programs play a crucial role in promoting appropriate patient actions to support patient safety during hospitalization and homecare. This review aimed to identify literature concerning educational interventions to promote patients’ actions to overcome CVAD-related problems and improve self-monitoring and self-management. Materials and Methods: Documentary evaluation of international databases, such as PubMed, CINAHL, Scopus and Cochrane. Searching for data on population, context and concept regarding CVAD self-management. The extracted data was subject to thematic analysis. The following scoping reviews were developed using the five-stage framework outlined by Arksey and O’Malley, and advanced by Levac and colleagues. Results: Of the 2802 articles identified, 19 research articles were selected in this review. Educational programs have been shown to improve CVAD self management, to decrease stress and anxiety related to their use, and to reduce the onset of complications. In addition, nurses have proven to be the professional reference figure for educational interventions. Conclusions: The results of the study lead to the conclusion that programs aimed at improving selfcare and reducing the onset of complications in patients living with chronic and debilitating diseases should be made available to a larger portion of individuals. Both generic and specific programs are needed, in the different contexts of home and hospital, for the short and long term, in order to ameliorate participants’ abilities. The results of this study should, therefore, encourage health professionals to plan, carry out, and evaluate the establishment of educational programs with patient participation