Assay Development for High-Throughput Drug Screening Against Mycobacteria.

Mycobacterium abscessus (Mab) infections are challenging to treat due to high intrinsic drug resistance, comparable to multidrug-resistant tuberculosis. Treatments are extremely ineffective and based on a multi-drug regimen, resulting in low patient compliance. Consequently, the scientific community is urged to identify new and effective drugs to treat these infections.

E-cadherin variants associated with oral facial clefts trigger aberrant cell motility in a REG1A-dependent manner.

Background: Germline mutations of E-cadherin contribute to hereditary diffuse gastric cancer (HDGC) and congenital malformations, such as oral facial clefts (OFC). However, the molecular mechanisms through which E-cadherin loss-of-function triggers distinct clinical outcomes remain unknown. We postulate that E-cadherin-mediated disorders result from abnormal interactions with the extracellular matrix and consequent aberrant intracellular signalling, affecting the coordination of cell migration.

Atypical pattern of ocular toxoplasmosis: recurrent inner foveal toxoplasmic retinitis (rifter).

Failure to recognize the different possible clinical presentations of ocular toxoplasmosis may delay diagnosis and treatment, compromising visual prognosis. The aim of this paper is to describe an atypical pattern of ocular toxoplasmosis, not yet described. Five Brazilian patients, from 4 different referral centers, presented similar atypical pattern of ocular toxoplasmosis characterized by mild vitritis, foveal cavitation involving predominantly all retinal layers associated with adjacent inner retinal necrosis (a necrotizing retinitis with a persisting inner retinal tissue bridge and loss of subjacent retinal layers).

High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells.

Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties.

Real-Life Data on Readmissions of Worsening Heart Failure Outpatients in a Heart Failure Clinic.

Introduction Recurrent hospitalizations for worsening heart failure (WHF) represent a major global public health concern, resulting in significant individual morbimortality and socioeconomic costs. This real-life study aimed to determine the rate and predictors of readmission for WHF in a cohort of outpatients with chronic heart failure (CHF) followed in a heart failure clinic (HFC) at a university hospital. Methods We conducted a longitudinal, observational, and retrospective study of all consecutive CHF patients seen at the HFC of the São Francisco Xavier Hospital, Lisbon, by a multidisciplinary team in 2019.

DIRECT MACULAR HOLE MANIPULATION RESULTS IN HIGH SUCCESS RATE IN SECONDARY MACULAR HOLE REPAIR.

Purpose: To investigate closure rates and functional outcomes of surgery for refractory and recurrent macular holes (MHs) in a real-world setting.

Methods: Retrospective review of secondary MH surgeries.

Results: A total of 72 eyes from 72 patients were included.

Mechanical Properties of Colorectal Cancer Cells Determined by Dynamic Atomic Force Microscopy: A Novel Biomarker.

Colorectal cancer (CRC) has been addressed in the framework of molecular, cellular biology, and biochemical traits. A new approach to studying CRC is focused on the relationship between biochemical pathways and biophysical cues, which may contribute to disease understanding and therapy development. Herein, we investigated the mechanical properties of CRC cells, namely, HCT116, HCT15, and SW620, using static and dynamic methodologies by atomic force microscopy (AFM).

Point-of-Care Ultrasound Protocol for Insertion and Confirmation of Central Venous Catheter Placement.

Central venous catheterization is a common procedure in the management of critically ill patients, in the context of medical emergencies, and before surgical interventions. Placing a central venous catheter (CVC) in the internal jugular vein (IJV) using anatomical references is associated with a high risk of complications, in particular pneumothorax and arterial puncture. Thus, the placement of CVCs with ultrasound support is recommended by several medical societies and health regulators at the international level.

Outcomes of Pars Plana Vitrectomy and 4-Point Sutured Scleral Fixation of Akreos AO60 Intraocular Lens in Clinical Settings: A Case Series.

Purpose: To determine the long-term anatomic outcomes and surgical complications of pars plana vitrectomy (PPV) and 4-point Gore-Tex-sutured Akreos AO60 intraocular lens (IOL) scleral fixation.

Design: Retrospective, multicenter, multisurgeon case series.

Participants: Ninety-seven patients in tertiary eye care centers.

The first gene therapy for biallelic dystrophy with voretigene neparvovec-rzyl in Brazil.

Purpose: To report the first Brazilian patient with deficiency-inherited retinal dystrophy (-IRD) treated with (VN).

Methods: An adult patient with Leber congenital amaurosis-2 with a homozygous mutation in the gene (p.Phe83Leu) was treated bilaterally with VN.

Steroid-Quinoline Hybrids for Disruption and Reversion of Protein Aggregation Processes.

Reversing protein aggregation within cells may be an important tool to fight protein-misfolding disorders such as Alzheimer's, Parkinson's, and cardiovascular diseases. Here we report the design and synthesis of a family of steroid-quinoline hybrid compounds based on the framework combination approach. This set of hybrid compounds effectively inhibited Aβ1-42 self-aggregation by delaying the exponential growth phase and/or reducing the quantity of fibrils in the steady state.

Integrin β1 orchestrates the abnormal cell-matrix attachment and invasive behaviour of E-cadherin dysfunctional cells.

Background: Tumour progression relies on the ability of cancer cells to penetrate and invade neighbouring tissues. E-cadherin loss is associated with increased cell invasion in gastric carcinoma, and germline mutations of the E-cadherin gene are causative of hereditary diffuse gastric cancer. Although E-cadherin dysfunction impacts cell-cell adhesion, cell dissemination also requires an imbalance of adhesion to the extracellular matrix (ECM).

Human amniotic membrane for the treatment of large and refractory macular holes: a retrospective, multicentric, interventional study.

Background: The purpose of the current study is to report the anatomical and functional results of off-label human amniotic membrane graft as primary intervention to repair large to giant macular holes and in reoperations when wide internal limiting membrane peeling was unsuccessful.

Methods: Retrospective chart review was carried out in five different centers to identify all cases that had undergone off-label human amniotic membrane graft for the treatment of large or failed macular holes (MH). Data collected included age, gender, other concomitant diagnosis, symptoms duration, lens status, number of previous surgeries, macular hole measurements (minimum and base linear diameters), mean post-operative follow-up (months), and pre- and post-operative best corrected visual acuity (BCVA).

Role of Vital Dyes in Chromovitrectomy.

Chromovitrectomy, the intraocular application of dyes to assist visualization of preretinal tissues during vitreoretinal surgery, was introduced to avoid ocular complications related to internal limiting membrane peeling, inadequate removal of the vitreous, and incomplete removal of epiretinal membranes. Since 2000, chromovitrectomy has become a popular approach among vitreoretinal specialists. The first vital dye used in chromovitrectomy, indocyanine green, facilitated identification of the fine and transparent internal limiting membrane.

B-scan ultrasound, visual electrophysiology and perioperative videoendoscopy for predicting functional results in keratoprosthesis candidates.

Background/aims: We analysed the ability of B-scan ultrasound, ocular electrophysiology testing and videoendoscopic examination for predicting visual prognosis in Boston Type 1 keratoprosthesis (KPro-1) candidates. Indirect anatomical and electrophysiological findings and results from direct endoscopic evaluations were correlated with postoperative functional data.

Methods: In this prospective and interventional study, we included 13 individuals who had previously been indicated for Kpro-1 surgery.

Fluorescent H Receptor Squaramide-Type Antagonists: Synthesis, Characterization, and Applications.

Fluorescence labeled ligands have been gaining importance as molecular tools, enabling receptor-ligand-binding studies by various fluorescence-based techniques. Aiming at red-emitting fluorescent ligands for the hHR, a series of squaramides labeled with pyridinium or cyanine fluorophores (-) was synthesized and characterized. The highest hHR affinities in radioligand competition binding assays were obtained in the case of pyridinium labeled antagonists - (p : 7.

Orally administrated chitosan microspheres bind Helicobacter pylori and decrease gastric infection in mice.

Persistent Helicobacter pylori (H. pylori) infection is related to 90% of gastric cancers. With bacterial resistance rising and treatment inefficiency affecting 15% of the patients, alternative treatments urge.

A SOX2 Reporter System Identifies Gastric Cancer Stem-Like Cells Sensitive to Monensin.

Gastric cancer remains a serious health burden with few therapeutic options. Therefore, the recognition of cancer stem cells (CSCs) as seeds of the tumorigenic process makes them a prime therapeutic target. Knowing that the transcription factors SOX2 and OCT4 promote stemness, our approach was to isolate stem-like cells in human gastric cancer cell lines using a traceable reporter system based on SOX2/OCT4 activity (SORE6-GFP).