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Exposure to the non-protein amino acid cyanotoxin ß-N-methylamino-L-alanine (BMAA), released by cyanobacteria found in many water reservoirs has been associated with neurodegenerative diseases. We previously demonstrated that BMAA induced cell death in both retina photoreceptors (PHRs) and amacrine neurons by triggering different molecular pathways, as activation of NMDA receptors and formation of carbamate-adducts was only observed in amacrine cell death. We established that activation of Retinoid X Receptors (RXR) protects retinal cells, including retina pigment epithelial (RPE) cells from oxidative stress-induced apoptosis. We now investigated the mechanisms underlying BMAA toxicity in these cells and those involved in RXR protection. BMAA addition to rat retinal neurons during early development in vitro increased reactive oxygen species (ROS) generation and polyADP ribose polymers (PAR) formation, while pre-treatment with serine (Ser) before BMAA addition decreased PHR death. Notably, RXR activation with the HX630 agonist prevented BMAA-induced death in both neuronal types, reducing ROS generation, preserving mitochondrial potential, and decreasing TUNEL-positive cells and PAR formation. This suggests that BMAA promoted PHR death by substituting Ser in polypeptide chains and by inducing polyADP ribose polymerase activation. BMAA induced cell death in ARPE-19 cells, a human epithelial cell line; RXR activation prevented this death, decreasing ROS generation and caspase 3/7 activity. These findings suggest that RXR activation prevents BMAA harmful effects on retinal neurons and RPE cells, supporting this activation as a broad-spectrum strategy for treating retina degenerations.

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Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.

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Introduction: Image quality and acquisition protocol adherence assessment is a neglected area in teledermatology. We examine if it is feasible to use deep learning methods to automate the assessment of the adherence of examinations to image acquisition protocols. In this study, we focused on the quality criteria of two image acquisition protocols: (1) approximation image and (2) panoramic image, as these are present in all teledermatology examination protocols currently used by the Santa Catarina State Integrated Telemedicine and Telehealth System (STT/SC). Methods: We use a data set of 36,102 teledermatological examinations performed at the STT/SC during 2021. As our validation process, we adopted standard machine learning metrics and an inter-rater agreement (IRA) study with 11 dermatologists. For the approximation image protocol, we used the Mask-Region based Convolutional Neural Network (RCNN) Object Detection Deep Learning (DL) architecture to identify the presence of a lesion identification tag and a ruler used to provide a frame reference of the lesion. For the panoramic image protocol, we used DensePose, a pose estimation DL, architecture to assess the presence of a whole patient body and its orientation. A combination of the two approaches was additionally validated through an IRA study between specialists. Results: Mask-RCNN achieved a score of 96% mean average precision (mAP), while DensePose presented 75% mAP. IRA achieved a level of agreement of 96.68% with the Krippendorff alpha score. Conclusions: Our results show the feasibility of using deep learning to automate the image quality and protocol adherence assessment in teledermatology, before the specialist's manual analysis of the examination.

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The objective of this study was to determine the effects of growing stage (GS) on morphological and chemical composition of whole-plant soybean (WPS), and fermentative profile and chemical composition of whole-plant soybean silage (SS). This study was divided into two trials conducted in a complete randomised block design. The first trial evaluated the effect of GS from R1 to R8 (59-135 d after sowing) on morphological and chemical composition of WPS and its botanical components. The second trial determined the effects of GS from R3 (71 d after sowing) to R7 (124 d after sowing) on dry matter (DM) losses, fermentative profile, chemical composition and aerobic stability of SS. The proportion of leaves in WPS was reduced, while stem and pod proportions were increased as the GS progressed. Ensiling WPS at R6 and R7 decreased the contents of acetic acid, lactic acid and branched-chain fatty acids, and ethanol, and increased the contents of propionic acid and NH3-N. However, silage butyric acid concentrations in R6 and R7 were relatively high (18.1 and 19.9 g/kg DM, respectively). Butyric acid and buffering capacity varied according to GS with the lowest values observed in silages derived from GS R3, R5 and R7, and the highest values observed in silages made from GS R5. Later GS resulted in greater contents of DM, crude protein and ether extract, and lower contents of acid detergent fibre and non-fibre carbohydrate in SS. The high fat of SS produced from later GS limits high inclusion levels in ruminant diets. Morphological components impacted chemical composition of SS, whereas the R7 stage improved fermentative profile and resulted in an SS with greater in situ degradability of DM and neutral detergent fibre.

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Plastic pollution is a critical environmental issue with far-reaching and not yet fully explored consequences. This study uncovered a significant source of plastic contamination arising from improper application and management of expanded polystyrene (EPS) utilised as expansion joints at a construction site near the coast of Antofagasta, Chile. Through meticulous field observations and calculations, we estimate that a staggering 82.9 million EPS spheres have the potential to be released into the environment from the 7.62 m3 of this material used for the construction of this coastal promenade, constituting a chronic source of pollution. Despite the ongoing construction, we have already evidenced mechanical fragmentation and dispersion of EPS microplastic pollution in the surrounding natural environment. To our knowledge, this is the first study that documents misused construction materials contributing to plastic pollution. In addition to the EPS pollution, our findings reveal an alarming accumulation of litter - an acute pollution source - including plastic cups, bottles, carrier bags, and several other construction materials (e.g. plastic nets, films) that are exacerbating the pollution problems within the region and potentially endangering marine and terrestrial organisms. These observations highlight the urgent need for mitigating measures and intervention policies targeting construction-related plastic and microplastic pollution, along with a more robust regulatory framework for construction activities as well as adequate surveillance and enforcement.

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BACKGROUND: Survival in multiple myeloma (MM) has improved in the past years with the introduction of immunomodulators and proteasome inhibitors. However, chemotherapy-induced peripheral neuropathy (CIPN) is associated with both drug classes affecting Health-Related Quality of Life (HRQoL) and activities of daily living (ADL). OBJECTIVE: We evaluated CIPN in MM patients to identify associated factors and impacts on HRQoL and ADL. METHODS: This is a cross-sectional study with Brazilian patients from public and private health services. Patients were interviewed using validated tools to measure CIPN and HRQoL, along with sociodemographic and clinical questions. Logistic regression was used to assess the association of CIPN with sociodemographic, clinical, and HRQoL variables. RESULTS: In total, 217 patients were eligible for the study. The median age was 67, 50.9% were women, 51.6% had low income, 47.5% had low education, and 55.3% attended private health services. The chemotherapy regimen most used was the combination of cyclophosphamide, thalidomide, and dexamethasone (17.5%) among the 24 types of regimens found. Most patients (90.3%) had at least one CIPN symptom: 62.7% were severe, and 51.62% were extremely bothered ADL. Numbness was the most common symptom (40.6%). CIPN was independently associated with education, hospitalization, chemotherapy, side effects, disease symptoms, and global health status in HRQoL. CONCLUSION: MM patients showed a high frequency of CIPN, which affected ADL and impaired HRQoL. Early and accurate detection of CIPN and dose management in patients with thalidomide and bortezomib-based regimens should be performed to provide better treatment outcomes and avoid permanent disabilities.

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BACKGROUND: Several systemic conditions can result in distinct degrees of salivary gland damage and consequent hypofunction. The development of successful management schemes is highly challenging due to the complexity of saliva. This study aimed to systematically map the literature on the physical stimulation of salivary glands for hyposalivation management and the response of individuals according to different systemic conditions causing salivary impairment. METHODS: A systematic search in the literature was performed. Two reviewers independently selected clinical trials, randomized or not, that used physical stimulation to treat hyposalivation caused by systemic conditions. Studies evaluating healthy subjects without hyposalivation were included as controls. Single-arm clinical studies or case series were also included for protocol mapping (PRISMA extension for scoping reviews). RESULTS: Out of 24 included studies, 10 evaluated healthy subjects, from which 9 tested transcutaneous electrical nerve stimulation (TENS) and 1 tested acupuncture and electroacupuncture. Fourteen studies evaluated individuals with hyposalivation: 6 applied TENS, 6 applied low-level laser therapy (LLLT), and 2 applied acupuncture, carried out in post-chemotherapy, medication use, postmenopausal women, hemodialysis patients, smokers, diabetics, Sjögren's syndrome (SS). All showed increased salivation after treatment, except for two LLLT studies in individuals with SS. CONCLUSIONS: Among the different patient groups, individuals with Sjögren's syndrome (SS) exhibited the poorest responses, while those with medication-induced hyposalivation demonstrated the most favorable treatment outcomes, independently of the management strategy for saliva stimulation. It means that physical stimulation of salivary glands holds promise as an alternative for managing hyposalivation in cases of reversible gland damage. However, to make informed decisions in current practice, it is necessary to conduct new well-designed randomized clinical trials with appropriate methodologies.

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The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival.

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OBJECTIVE(S): This scoping review aims to map the scientific literature on the therapies currently available for physical salivary stimulation in individuals with hyposalivation caused by radiotherapy. STUDY DESIGN: Studies were included when they comprised the target population of adult individuals receiving radiotherapy of the head and neck region and who developed or were at risk of developing hyposalivation. Two reviewers selected the studies and extracted data on the type of physical salivary stimulation therapy used, the degree of glandular tissue involvement, and the percentage of salivary flow alteration. Therapies were classified according to either prophylactic application (before/during radiotherapy) or therapeutic application (post-radiotherapy). RESULTS: Sixteen articles were included: 4 tested transcutaneous electrical nerve stimulation (TENS), 3 studied low-level lasers, 7 researched acupunctures, and 2 investigated acupuncture-like TENS. The outcomes of the prophylactic studies indicated beneficial effects (similar salivary flow or reduced salivary flow loss), although most studies did not include a comparable control group. Therapeutic studies presented conflicting results. CONCLUSION(S): Prophylactic therapies of physical salivary stimulation may produce better effects than therapeutic applications. However, the protocols best indicated could not be defined. Well-designed, controlled clinical trials should be researched in the future to support the clinical recommendation of any of these treatments.

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