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The safety of long-term PDE5Is in LVAD patients remains unclear and needs to be further clarified in prospective studies with randomized study design.
To explore whether the existence and pattern of distribution of macular haemorrhage or exudate can be valuable diagnostic markers for macular neovascularization type 3 (MNV3) in patients with neovascular age-related macular degeneration.
Eighty-three eyes of 83 consecutive treatment naïve patients with stage 3 MNV3 were enrolled. The diagnosis was based on fluorescein angiography (FA) and optical coherence tomography (OCT). Subretinal and intraretinal haemorrhage and dense exudates were evaluated on colour fundus photography. Fluorescein angiography (FA) images and OCT scans were used to identify the axial location of the haemorrhage. 83 patients with MNV1 and 83 with MNV2 were included as two control groups.
In the MNV3 group, 62 (75%) eyes had intraretinal haemorrhage and 52 (63%) had dense exudates. 73 (88%) eyes had intraretinal haemorrhage and/or dense exudates. 41 (49%) had both pathologies. The intraretinal haemorrhage was flame shaped over the lesion and punctate or semi-punctate further away from it and directed to the fovea. No subretinal haemorrhage was noticed. In the MNV1 and MNV2 groups, 11 (13%) and 24 (29%) eyes had subretinal haemorrhage or dense exudates, respectively. No intraretinal haemorrhage was seen in the two control groups. selleck products The prevalence of exudates and haemorrhage (irrespective of its location) was greater in MNV3 than in MNV1 or 2 (p<0.0001).
The existence and pattern of distribution of intraretinal haemorrhage is pathognomonic of MNV3. It makes (alone or with dense exudates) the diagnose MNV3 possible using fundoscopy or colour fundus photo and without further diagnostic expenditure.
The existence and pattern of distribution of intraretinal haemorrhage is pathognomonic of MNV3. It makes (alone or with dense exudates) the diagnose MNV3 possible using fundoscopy or colour fundus photo and without further diagnostic expenditure.
Neoadjuvant radiotherapy (NART) as part of a multi-modality approach for locally advanced breast cancer (LABC) requires further investigation. Importantly, this approach may allow for a single-staged surgical procedure, with mastectomy and immediate autologous reconstruction. Multiple other potential benefits of NART include improved pathological downstaging of breast disease, reduced overall treatment time, elimination of time period with breast tissue deficit and improved patient satisfaction.
This is a retrospective multi-institutional review of patients with LABC and high-risk breast disease undergoing NART. Eligible patients sequentially underwent neoadjuvant chemotherapy (NACT) with or without HER2-targeted therapy, NART, followed by mastectomy with immediate autologous breast reconstruction (BR) 4- to 6 weeks post-completion of radiotherapy. Patient and tumour characteristics were analysed using descriptive statistics. Surgical complications were assessed using the Clavien-Dindo Classification (Ann to reconstructive surgery and thus shortening a woman's breast cancer journey. The findings of this review support the use of NART, with comparable rates of surgical complications to standard sequencing.
Despite the acknowledgment that holmium laser enucleation of the prostate (HoLEP) is a safe, efficacious procedure with benefits over traditional treatments, it is not widely adopted. Its steep learning curve is considered responsible, and the new en bloc technique (EBT) aims to improve this.
A retrospective analysis of 268 consecutive patients (215 lobe technique [LT] and 53 EBT) who underwent HoLEP between May 2016 and April 2020 was performed. Data were collected on patient demographics, prostate volume, enucleation time, prostatic weight, and length of stay.
There was no difference in mean prostate volume and enucleated prostatic weight between the LT and EBT (99.2 mL vs 98.5 mL, P= .95216, and 71.7 g vs 69.3 g, P= .92034, respectively). There was a reduction in mean enucleation time with the EBT to 37.7 minutes compared with 53.3 minutes (LT) (P< .00001). This translated to an improved operative efficiency of 1.84 g/min (EBT) compared to 1.33 g/min (LT) (P< .00001). The EBT demonstrated a continuous improvement in operative efficiency with increasing prostate size unlike the LT where efficiency plateaus.
The EBT for HoLEP demonstrates a significant improvement in operative efficiency which has the potential to reduce the surgeons' learning curve and lead to more widespread adoption.
The EBT for HoLEP demonstrates a significant improvement in operative efficiency which has the potential to reduce the surgeons' learning curve and lead to more widespread adoption.Use of electronic nicotine delivery systems (ENDS), also known as e-cigarettes, in the adolescent population has significantly increased over the past several years. This rise led to an outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) in the summer of 2019. Since that time, numerous case reports and case series on vaping and EVALI have been published but the majority of literature highlights the adult population with few articles focusing on pediatric patients. Given the addictive nature of these products and the lack of full understanding of the human health effects, there is concern that use of ENDS may have lasting impacts on users, especially adolescents and young adults. The goal of this review is to critically assess published data on ENDS use in children, report our institutional experience, discuss the reasons why the use of ENDS have increased among young individuals, outline the current understanding of EVALI as it pertains to the pediatric population, and discuss future opportunities for health policy implementation.Weight bias internalization has received considerable attention in recent years and has been associated with serious psychological and physical consequences in Westernized societies. The modified weight bias internalization scale (WBIS-M) is one of the most frequently used instruments for assessing internalized weight stigma across different body weight categories. The aim of this study was to adapt the WBIS-M for use in Spanish adult populations. The sample consisted of 678 participants from the Spanish general population recruited through the internet, 79.6% of whom were women. The scale was translated into Spanish and then backtranslated. To study the internal structure, a cross-validation analysis was carried out including both exploratory and confirmatory factor analyses to assess the scale's psychometric properties. Internal consistency was evaluated using Cronbach's alpha and McDonald's omega and a test-retest was conducted to assess one-month stability. Results confirmed that the Spanish adaptation of the WBIS-M is an 11-item unidimensional scale, like the original version and shows excellent psychometric properties. In conclusion, the Spanish WBIS-M version seems to be a robust psychometric tool for use in clinical and research settings.Pancreatic beta cells undergo compensatory proliferation in the early phase of type 2 diabetes. While pathways such as FoxM1 are involved in regulating compensatory beta cell proliferation, given the lack of therapeutics effectively targeting beta cell proliferation, other targetable pathways need to be identified. Herein, we show that Pbk, a serine/threonine protein kinase, is essential for high fat diet (HFD)-induced beta cell proliferation in vivo using a Pbk kinase deficiency knock-in mouse model. Mechanistically, JunD recruits menin and HDAC3 complex to the Pbk promoter to reduce histone H3 acetylation, leading to epigenetic repression of Pbk expression. Moreover, menin inhibitor (MI) disrupts the menin-JunD interaction and augments Pbk transcription. Importantly, MI administration increases beta cell proliferation, ameliorating hyperglycemia, and impaired glucose tolerance (IGT) in HFD-induced diabetic mice. Notably, Pbk is required for the MI-induced beta cell proliferation and improvement of IGT. Together, these results demonstrate the repressive role of the menin/JunD/Pbk axis in regulating HFD-induced compensatory beta cell proliferation and pharmacologically regulating this axis may serve as a novel strategy for type 2 diabetes therapy.Sample multiplexing facilitates single-cell sequencing by reducing costs, revealing subtle difference between similar samples, and identifying artifacts such as cell doublets. However, universal and cost-effective strategies are rather limited. Here, we reported a concanavalin A-based sample barcoding strategy (CASB), which could be followed by both single-cell mRNA and ATAC (assay for transposase-accessible chromatin) sequencing techniques. The method involves minimal sample processing, thereby preserving intact transcriptomic or epigenomic patterns. We demonstrated its high labeling efficiency, high accuracy in assigning cells/nuclei to samples regardless of cell type and genetic background, and high sensitivity in detecting doublets by three applications 1) CASB followed by scRNA-seq to track the transcriptomic dynamics of a cancer cell line perturbed by multiple drugs, which revealed compound-specific heterogeneous response; 2) CASB together with both snATAC-seq and scRNA-seq to illustrate the IFN-γ-mediated dynamic changes on epigenome and transcriptome profile, which identified the transcription factor underlying heterogeneous IFN-γ response; and 3) combinatorial indexing by CASB, which demonstrated its high scalability.Nucleic acid-based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications, but many others are still awaiting their eureka moment. Here, we cover the variety of methods developed to deliver nucleic acid-based therapeutics across biological barriers and the model systems used to test them. We discuss important safety considerations and regulatory requirements for synthetic oligonucleotide chemistries and the hurdles for translating laboratory breakthroughs to the clinic. Recent advances in the delivery of nucleic acid-based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide-based therapeutics.In the midst of the ongoing Covid-19 pandemic, researchers across the globe are still working to develop effective vaccines. To expedite this process even further, human challenge trials have been proposed by the World Health Organization (WHO) as an alternative to conventional approaches. In such trials, healthy volunteers are deliberately infected with the pathogen of interest, enabling scientists to study the infection process and facilitate further research on treatments or prophylactics, including vaccines. While human challenge trials would offer a collective benefit to society, minimizing the risks is always difficult. Ethical controversy thus inevitably surrounds these trials. Typically, healthy young adults are recruited to serve as the first candidate subjects for human challenge trials because they are generally considered to represent a low-risk population. Here, we present three reasons for doubt about this healthy-young-adults-first criterion and give justification for also recruiting healthy older adults (or not-young adults), meaning those over 30 years of age, to participate in such trials for SARS-CoV-2.
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