46 registros encontrados - material PRE-PRINT E unidade Faculdade de Ciências Médicas
PRE-PRINT - Inglês
Assunto: Pre-print
Abstract: syndrome (Thyroglobulin-Elevated Negative Iodine Scintigraphy) in differentiated thyroid carcinoma is characterized by reduced expression of...
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Abstract: syndrome (Thyroglobulin-Elevated Negative Iodine Scintigraphy) in differentiated thyroid carcinoma is characterized by reduced expression of sodium-iodine symporter, rising serum thyroglobulin levels (Tg), and negative whole-body [131I]Iodine scans. In such patients, somatostatin receptor imaging with [68Ga]Ga-DOTATATE PET/CT (SSR PET/CT) and [18F]F-FDG PET/CT (FDG PET/CT) can identify metastases. To compare the uptake pattern of SSR PET/CT and FDG PET/CT in papillary thyroid carcinoma (PTC) patients with TENIS Syndrome under two conditions: elevated (eTSH) and suppressed (sTSH) TSH serum levels. Based on imaging findings in these patients, we intend to identify potential candidates for peptide receptor radionuclide therapy (PRRNT). Fifteen patients with PTC and TENIS Syndrome were prospectively enrolled. All patients underwent both SSR PET/CT and FDG PET/CT with sTSH and eTSH. Images were blindly evaluated for differences in SUVmax values and lesion detectability. The reference standard consisted of neck ultrasound, CT, MRI, PET/CT, biopsy, and follow-up. Three patients were selected for PRRNT due to lesion uptake similar or higher than the liver.RESULTS On a per-patient and on a per-lesion based analysis, sTSH SSR PET/CT detected a greater number of cervical and distant LNs (both p?=?0.0253 on per-patient and p?=?0.0176 and p?=?0.0391 on per-lesion, respectively) when compared to sTSH FDG PET/CT. Likewise, eTSH SSR PET/CT detected a greater number of patients with local recurrences (p?=?0.0455) and distant LN metastases (p?=?0.0143) and in a per-lesion based analysis greater number of cervical and distant LNs (p?=?0.0337 and p?=?0.0039, respectively) when compared to eTSH FDG PET/CT. No differences were found for lung and bone metastases. One of three patients submitted to 3 cycles of PRRNT presented with a visual partial response, a 20% reduction in quantitative analyses and stable disease regarding Tg and TgAb levels.CONCLUSIONS In patients with PTC and TENIS Syndrome, SSR PET/CT detected a greater number of loco-regional and distant LN metastases than FDG PET/CT with both sTSH and eTSH. One of 3 patients submitted to PRRNT presented a partial response to treatment. Our findings may impact in patient restaging, management and theranostics strategies with radiolabeled somatostatin analogs
PRE-PRINT - Inglês
Assunto: Pre-print
Abstract: 6-Nitrodopamine (6-ND) is released from isolated atria of rabbit, rat and mice and has significant positive chronotropic action. The...
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Abstract: 6-Nitrodopamine (6-ND) is released from isolated atria of rabbit, rat and mice and has significant positive chronotropic action. The positive chronotropic effect induced by 6-ND is selectively blocked by ß1-adrenoceptor antagonists at concentrations that do not affect the positive chronotropic effect induced by dopamine, noradrenaline, and adrenaline. Here the effects of propranolol, 4-NO2-propranolol and 7-NO2-propranolol were investigated in the rat isolated right atrium. The right atrium was mounted between two metal hooks in 10-mL custom designed glass chambers containing Krebs-Henseleit’s solution, continuously gassed (95%O2:5%CO2) and heated (37°C). Tissues were allowed to equilibrate under a resting tension of 10 mN for one hour, and the isometric tension was registered using a PowerLab system. 4-NO2-propranol was more potent than propranolol as a negative chronotropic agent. At 30 nM, 4-NO2-propranolol did not affect the chronotropic effect of dopamine, noradrenaline, and adrenaline. The S-isomer of 4- NO2-propranolol, but not the R-isomer, was active. Propranolol induced fall in atrial rate at concentrations higher than those required to block the chronotropic effects of dopamine, noradrenaline and adrenaline, but enough to block the 6-ND effect. 7-NO2-propranolol was only active at very high concentration, and the effect was not stereoselective. The negative chronotropic effects induced by 4-NO2-propranolol (100 nM) and propranolol (300 nM) were not observed in L-NAME treated atria, whereas that induced by 7-NO2-propranolol (10 mM) was unaffected. The potent and selective inhibition observed with (±)-4-NO2-propranolol reinforces the concept that 6-ND is a major mediator of heart chronotropism and the main target of the so-called b-blockers
PRE-PRINT - Inglês
Assunto: Atropina
Abstract: 6-Nitrodopamine (6-ND) is a novel endogenous catecholamine that is released from the rat isolated vas deferens, and has been characterized...
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Abstract: 6-Nitrodopamine (6-ND) is a novel endogenous catecholamine that is released from the rat isolated vas deferens, and has been characterized as a major modulator of the contractility of rat isolated epididymal vas deferens (RIEVD). Drugs such as tricyclic antidepressants, a1 and ß1ß2 adrenoceptor blockers, act as selective antagonists of the 6-ND receptor in the RIEVD. In the rat isolated atria, 6-ND has a potent positive chronotropic action and causes remarkable potentiation of the positive chronotropic effects induced by dopamine, noradrenaline, and adrenaline. Here, whether 6-ND interacts with the classical catecholamines in the rat isolated vas deferens was investigated. Incubation with 6-ND (0.1 and 1 nM; 30min) caused no contractions in the RIEVD but provoked significant leftward shifts in the concentration-response curves to noradrenaline, adrenaline, and dopamine. Pre-incubation of the RIEVD with 6-ND (1 nM), potentiated the contractions induced by electric-field stimulation (EFS), whereas pre-incubation with 1 nM of dopamine, noradrenaline or adrenaline, did not affect EFS-induced contractions. In tetrodotoxin (1 µM) pre-treated (30 min) RIEVD, pre-incubation with 6-ND (0.1 nM) did not cause leftward shifts in the concentration-dependent contractions induced by noradrenaline, adrenaline, or dopamine. Pre-incubation of the RIEVD with the a2A-adrenoceptor antagonist idazoxan (30 min, 10 nM) did not affect dopamine, noradrenaline, adrenaline, and EFS-induced contractions. However, when idazoxan (10 nM) and 6-ND (0.1 nM) were simultaneously pre-incubated (30 min), a significant potentiation of the EFS-induced contractions of the RIEVD was observed. 6-nitrodopamine causes remarkable potentiation of dopamine, noradrenaline, and adrenaline contractions on the RIEVD, due to activation of adrenergic terminals, possibly via pre-synaptic adrenoceptors
A brazilian nationwide multicenter study on deficiency of deaminase-2 (DADA2)
PRE-PRINT - Inglês
Assunto: Adenosina desaminase
Abstract: The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion....
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Abstract: The deficiency of ADA2 (DADA2) is a rare autoinflammatory disease provoked by mutations in the ADA2 gene inherited in a recessive fashion. Up to this moment there is no consensus for the treatment of DADA2 and anti-TNF is the therapy of choice for chronic management whereas bone marrow transplantation is considered for refractory or severe phenotypes. Data from Brazil is scarce and this multicentric study reports 18 patients with DADA2 from Brazil. Patients and methods: This is a multicentric study proposed by the Center for Rare and Immunological Disorders of the Hospital 9 de Julho - DASA, São Paulo - Brazil. Patients of any age with a confirmed diagnosis of DADA2 were eligible for this project and data on clinical, laboratory, genetics and treatment were collected. Results: Eighteen patients from 10 different centers are reported here. All patients had disease onset at the pediatric age (median of 5 years) and most of them from the state of São Paulo. Vasculopathy with recurrent stroke was the most common phenotype but atypical phenotypes compatible with ALPS-like and Common Variable Immunodeficiency (CVID) was also found. All patients carried pathogenic mutations in the ADA2 gene. Acute management of vasculitis was not satisfactory with steroids in many patients and all those who used anti-TNF had favorable responses. Conclusion: The low number of patients diagnosed with DADA2 in Brazil reinforces the need for disease awareness for this condition. Moreover, the absence of guidelines for diagnosis and management is also necessary to guide diagnosis and treatment of this disorder
A diabetic mice model for studying skin wound healing
PRE-PRINT - Inglês
Assunto: Modelos animais
Abstract: Advances in wound treatment depend on the availability of suitable animal models. All animal models try to reflect human wound healing...
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Abstract: Advances in wound treatment depend on the availability of suitable animal models. All animal models try to reflect human wound healing problems. For acute wounds, it is easier to obtain adequate animal models, however, for chronic wounds such as those found in individuals with diabetic foot ulcer, approximations of the clinical picture become a challenge. Nowadays, the key points of wound healing processes are better understood, and therefore, therapeutic strategies can be developed to manipulate wound repair. Research efforts involves the development of therapies to aid in the treatment of impaired wound healing and, to improving normal wound healing to drive a process close to regenerative. To achieve a better animal model that is more appropriate for studying wound healing, six-week- old male C57BL/6 mice were separated into groups fed a Chow and High-Fat Diet for 0.5, 3, and 6 months, when part of the animals were induced to diabetes by streptozotocin. Then, mice were submitted to metabolic, molecular, and morphological analyses. We show that this model results in a severe metabolic phenotype with insulin resistance, reduced insulin expression, and glucose intolerance associated with obesity and, more importantly, skin changes. Furthermore, the skin phenotype, both structurally and transcriptionally, overlapped with conditions found in elderly patients with DM that reproduce the phenotype of most patients who develop diabetic foot ulcers
PRE-PRINT - Inglês
Assunto: Produtos biológicos
Abstract: Synthetic cannabinoids are still a growing trend among drug users and consist of a group of hundreds of highly potent compounds. To...
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Abstract: Synthetic cannabinoids are still a growing trend among drug users and consist of a group of hundreds of highly potent compounds. To investigate the use of such substances, sample preparation of biological matrices is a crucial step prior to instrumental analysis. Although different efficient extraction techniques have been proposed for that aim, they usually do not fit eco-friendly guidelines that have been gaining popularity in recent years, such as Green Analytical Toxicology. This work uses describes for the first time the use of switchable hydrophilicity solvent-based homogenous liquid-liquid microextraction (SHS-HLLME) for synthetic cannabinoids. This is a green technique that replaces highly toxic organic reagents for switchable hydrophilicity solvents (SHS), substances that can be either water-miscible or immiscible depending on their protonation. Thus, by simply adjusting the pH of the system, these SHS can be used as extraction solvents. A full optimization study including type of SHS, volume of protonated SHS, volume of NaOH, salting-out effect, and extraction time was perfomed. The optimized procedure consisted of precipitating the proteins of 300 ?L of plasma with 300 ?L of acetonitrile followed by centrifugation; evaporation of the organic solvent under N2 stream; addition of 500 ?L of the protonated DPA, DPA-HCl (6 M) (1:1, v/v); addition of 500 ?L of NaOH (10 M); and finally centrifugation and evaporation. Validation results showed determination coefficients ? 0.99 for the 0.1-10 ng/mL linear range; 0.01-0.08 ng/mL as limit of detection; 0.1 ng/mL as limit of quantitation; accuracy and imprecision were within acceptable ranges; matrix effect, recovery, and process efficiency ranged from -55.6% to 185.9%, 36% to 56.7%, and 18.5% to 148.4%, respectively. The SHS-HLLME herein described was fully optimized providing satisfactory recoveries of 31 synthetic cannabinoids at low concentrations requiring only 300 ?L of plasma. In addition, the validation results showed that the technique is a reliable eco-friendly alternative for clinical and toxicological analysis
PRE-PRINT - Inglês
Assunto: Camundongo
Abstract: Annually, millions of animals are used for experimental purposes. Despite the recommended anesthetic doses being well-known worldwide, the...
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Abstract: Annually, millions of animals are used for experimental purposes. Despite the recommended anesthetic doses being well-known worldwide, the final amounts applied to mice could be different than those calculated. Here, we developed, tested, and validated a mobile app where researchers and operators were able to use personal devices to process body weight, calculate a master anesthetic cocktail, and then apply the individual volume to each mouse. Our objective was to refine anesthesia procedures using information technologies. Our data showed that the "Labinsane" mobile app decreased anesthetic-related deaths upon using weight-adjusted doses of ketamine and xylazine. Also, we validated that the Labinsane mobile app matched all calculations of anesthetic doses. To our knowledge, this is the first report with hundreds of anesthetized mice records and validation and implementation of a mobile app to solve an old but transversal challenge for researchers working with experimental mice
Acupuncture as a complementary treatment for leg ulcers in sickle-cell disease
PRE-PRINT - Inglês
Assunto: Anemia falciforme
Abstract: Sickle-cell diseases (SCD) are a group of hereditary disorders in which a specific mutation in the gene that encodes the hemoglobin ß chain...
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Abstract: Sickle-cell diseases (SCD) are a group of hereditary disorders in which a specific mutation in the gene that encodes the hemoglobin ß chain leads to formation of an anomalous hemoglobin molecule (HbS) with high polymerization power. This leads to sickling of erythrocytes in situations of low oxygen tension, such as in microcirculation, resulting in peripheral microvasculature occlusion, chronic hemolysis, inflammation, and damage to several target organs. Malleolar ulcers are among the most-debilitating complications of the disease, as they are associated with significant pain, secondary infections, and social impact due to their aesthetic impairment. There are no completely satisfactory therapeutic options for this complication; local healing agents, antibiotics, and dressings are used, with high rates of recurrence and complications, such as osteomyelitis and even limb amputation
Advancing gaba-edited mrs research through a reconstruction challenge
PRE-PRINT - Inglês
Assunto: Pre-print
Abstract: Purpose To create a benchmark for the comparison of machine learning-based Gamma-Aminobutyric Acid (GABA)-edited Magnetic Resonance...
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Abstract: Purpose To create a benchmark for the comparison of machine learning-based Gamma-Aminobutyric Acid (GABA)-edited Magnetic Resonance Spectroscopy (MRS) reconstruction models using one quarter of the transients typically acquired during a complete scan. Methods The Edited-MRS reconstruction challenge had three tracks with the purpose of evaluating machine learning models trained to reconstruct simulated (Track 1), homogeneous in vivo (Track 2), and heterogeneous in vivo (Track 3) GABA-edited MRS data. Four quantitative metrics were used to evaluate the results: mean squared error (MSE), signal-to-noise ratio (SNR), linewidth, and a shape score metric that we proposed. Challenge participants were given three months to create, train and submit their models. Challenge organizers provided open access to a baseline U-NET model for initial comparison, as well as simulated data, in vivo data, and tutorials and guides for adding synthetic noise to the simulations. Results The most successful approach for Track 1 simulated data was a covariance matrix convolutional neural network model, while for Track 2 and Track 3 in vivo data, a vision transformer model operating on a spectrogram representation of the data achieved the most success. Deep learning (DL) based reconstructions with reduced transients achieved equivalent or better SNR, linewidth and fit error as conventional reconstructions with the full amount of transients. However, some DL models also showed the ability to optimize the linewidth and SNR values without actually improving overall spectral quality, pointing to the need for more robust metrics. Conclusion The edited-MRS reconstruction challenge showed that the top performing DL based edited-MRS reconstruction pipelines can obtain with a reduced number of transients equivalent metrics to conventional reconstruction pipelines using the full amount of transients. The proposed metric shape score was positively correlated with challenge track outcome indicating that it is well-suited to evaluate spectral quality
Alpha1-adrenergic antagonists act as 6-nitrodopamine receptor antagonists in the human vas deferens
PRE-PRINT - Inglês
Assunto: Pre-print
Abstract: 6-Nitrodopamine (6-ND) is released from human vas deferens and plays a modulatory role in the male ejaculation. Therapeutical use of...
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Abstract: 6-Nitrodopamine (6-ND) is released from human vas deferens and plays a modulatory role in the male ejaculation. Therapeutical use of a1-adrenoceptor antagonists is associated with ejaculatory abnormalities. Objectives: To evaluate the effect of a1-adrenoceptor antagonists on the contractions induced by 6-ND, dopamine, noradrenaline, and adrenaline in the human epididymal vas deferens (HEVD). Methods: HEVD strips were suspended in glass chambers containing heated and oxygenated Krebs-Henseleit’s solution. Cumulative concentration-response curves to catecholamines (10 nM-300 mM) were constructed in HEVD strips pre-incubated (30 min) with doxazosin (0.1-1nM), tamsulosin (1-10 nM), prazosin (10-100 nM) and/or silodosin (0.1-10 nM). The effects of these a1-adrenoceptor antagonists were also evaluated in the electric-field stimulation (EFS, 2-32 Hz)-induced contractions. Results: Doxazosin (0.1 nM) caused significant reductions in 6-ND-induced HEVD contractions without affecting the contractions induced by dopamine, noradrenaline, and adrenaline. Similar results were observed with tamsulosin (1 nM) and prazosin (10 nM). At these concentrations, these a1-adrenoceptor antagonists largely reduced the EFS-induced contractions. Silodosin (1 nM) caused concentration-dependent rightward shifts of the concentration-response curves to 6-ND but had no effect on the contractions induced by dopamine and adrenaline. Silodosin (0.1 nM) only inhibited the contractions induced by noradrenaline. Silodosin at 1 nM, but not at 0.1 nM, caused significant reductions in the EFS-induced contractions. Discussion and conclusion: The results indicate that 6-ND plays a major role in the human vas deferens contractility and doxazosin, tamsulosin, prazosin and silodosin cause ejaculation disorders in man by blocking the 6-ND receptor rather than a1-adrenoceptors
PRE-PRINT - Inglês
Assunto: Clonagem
Abstract: We aim to develop a method for cloning highly unstable plasmids encoding sodium channel subunits expressed in the brain. NEB Stable...
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Abstract: We aim to develop a method for cloning highly unstable plasmids encoding sodium channel subunits expressed in the brain. NEB Stable competent cells (NSCC) were transformed with the native plasmid. After purification, plasmids with the expected profile of enzymatic digestion were sequenced. Finally, mutant linear plasmids (MLP) created by site-directed mutagenesis were used to transform NSCC. We found that choosing a suitable host for transformation and subcloning, the controlled temperature during cell growth, and a small volume of Luria Bertani (LB) medium allowed the generation of plasmids without undesirable mutations or structural alterations. At present, there is little information on a detailed method for cloning plasmids carrying the SCN1A gene. Using the method proposed here, we observed increased cell growth and precision in the sequence of the obtained plasmids. We have developed an optimized strategy for replicating unstable plasmids using NSCC with an appropriate volume of culture medium and an adequate temperature in the cloning and subcloning phases. We have also demonstrated how to create the desired plasmid constructs by using site-directed mutagenesis. We expect that our protocol will assist investigators interested in functional studies of sodium channels expressed in the brain
Anxiety and depression during the covid-19 pandemic in healthcare students
PRE-PRINT - Inglês
Assunto: Pre-print
Abstract: The coronavirus (COVID-19) pandemic corroborated a state of mental stress worldwide, in health students like health professionals, so it is...
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Abstract: The coronavirus (COVID-19) pandemic corroborated a state of mental stress worldwide, in health students like health professionals, so it is essential to analyze the emotional stability of these students. To evaluate depression and anxiety among undergraduate healthcare students using validated scales, in addition to knowing their reactions and perceptions about the implementation of emergency remote education (ERS) in this period of isolation due to the COVID-19 pandemic. We invited by institutional e-mail, healthcare students regularly enrolled at the University of Campinas. After agreement and consent, a google form link was sent to access the data collection form. We sent 1204 invitations and 270 (22.4%) students agreed to participate (medicine 17.4%, nursing 19.3%, pharmacy 36.3%, and phonoaudiology 27%). Most participants were female (83%), up to 22 years of age (63%), white (69%), and between the first and third years of the course (64. 5%). Regarding remote education, 51.1% of participants reported having some degree of difficulty to follow up. Regarding the perception of social relationships, 37.8% considered themselves to be compromised, and 72.2% reported not feeling able to act in the COVID pandemic. Regarding mental health, 74% had high levels of anxiety, and 37% had moderate or severe depression. Healthcare students had high levels of severe anxiety and moderate/severe depression. Dissatisfaction with remote education contributed to the increase in depression rates in all courses. Healthcare students’ needs future strategies for mental health during pandemic conditions
Assessment of metabolic tumor burden in primary staging of rectal cancers using fdg pet/ct
PRE-PRINT - Inglês
Assunto: Pre-print
Abstract: The prognostic value of FDG PET/CT metabolic tumor burden has been established in various solid tumors, but its significance in the staging...
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Abstract: The prognostic value of FDG PET/CT metabolic tumor burden has been established in various solid tumors, but its significance in the staging of rectal cancer remains underexplored. This study aimed to investigate the prognostic role of FDG PET/CT metabolic tumor burden in the primary staging of rectal cancer. A retrospective analysis was conducted on 82 consecutive histology-proven rectal cancer patients, including 29 females (37%), with a mean age of 60.8 years. These patients underwent staging FDG PET/CT, and various metabolic tumor burden parameters (hSUVmax, tuMTV, wbMTV, tuTLG, wbTLG) were calculated. The study assessed the correlation between metabolic tumor burden parameters and overall survival (OS), progression-free survival (PFS), as well as histopathology, clinical staging, performance status, bone-mineral indexes, hematology, and therapy management strategies. The study revealed that metabolic tumor burden, along with the presence of sarcopenia and absence of surgery, were significantly and independently associated with overall survival. Notably, a wbTLG cutoff value of 354 effectively discriminated survivors from non-survivors (p?=?0.0007) with 83% specificity. Furthermore, higher whole-body tumor burden (wbTLG: p?=?0.0090) and low body mass index (p?=?0.0231) were significantly linked to an increased risk of disease progression. This research suggests that whole-body tumor burden assessed through staging FDG PET/CT can serve as an independent imaging biomarker for prognostication in rectal cancer patients
Caloric restriction prevents inflammation and insulin dysfunction in middle-aged ovariectomized mice
PRE-PRINT - Inglês
Assunto: Restrição calórica
Abstract: Loss of ovarian function is associated with increased visceral fat. In this study, we aimed to study the effects of caloric restriction (CR)...
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Abstract: Loss of ovarian function is associated with increased visceral fat. In this study, we aimed to study the effects of caloric restriction (CR) on metabolism in ovariectomized mice. Female, 8–12-month-old mice were divided into three groups: OVX (ovariectomized mice), OVXR (40% CR) and Sham. CR increased insulin sensitivity and glucose tolerance. AMPK phosphorylation was observed in the liver of OVXR mice. CR also increased hepatic cholesterol and triglyceride levels. The reductions in the level of TBARS in the serum and liver and of H2O2 in the liver of OVXR mice suggested alterations in the redox state of the liver. Although expression of catalase protein was reduced by CR, expression of superoxide dismutase was not altered by CR. Although interleukin IL-6 and IL-10 levels in OVXR mice were similar to those in Sham mice, macrophage infiltration was reduced in OVXR mice. OVXR mice had increased sirtuin1 levels and decreased sirtuin3 levels in the liver.In conclusion, CR improved the condition of ovariectomized mice by reducing adiposity and increasing insulin sensitivity and glucose tolerance through a mechanism that may involve AMPK
PRE-PRINT - Inglês
Assunto: ODS: 3. Saúde e bem-estar
Abstract: The 22q11.2 Deletion Syndrome (22q11.2 DS) presents unique healthcare challenges for affected individuals, families, and healthcare systems....
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Abstract: The 22q11.2 Deletion Syndrome (22q11.2 DS) presents unique healthcare challenges for affected individuals, families, and healthcare systems. Despite its rarity, 22q11.2 DS is the most common microdeletion syndrome in humans, emphasizing the need to understand and address the distinctive healthcare requirements of those affected. This paper examines the multifaceted issue of health service access and caregivers’ quality of life in the context of 22q11.2 DS in Brazil, a condition with diverse signs and symptoms demanding multidisciplinary care. This study employs a comprehensive approach to evaluate health service accessibility and the quality of life of caregivers of individuals with 22q11.2 DS. It utilizes a structured Survey and the WHOQOL-bref questionnaire for data collection.Results Individuals with 22q11.2 DS continue to receive incomplete clinical management after obtaining the diagnosis, even in the face of conditions that enabled an average age of diagnosis that precedes that found in sample groups that are more representative of the Brazilian population (mean of 3.2 versus 10, respectively). In turn, caring for individuals with 22q11.2 DS who face difficulty accessing health services impacts the perception of quality of life associated with the caregivers' environment of residence.Conclusions Results obtained help bridge the research gap in understanding how caring for individuals with multisystem clinical conditions such as 22q11.2 DS and difficulties in accessing health are intertwined with aspects of quality of life in Brazil. This research paves the way for more inclusive healthcare policies and interventions to enhance the quality of life for families affected by this syndrome
D-lysergic acid diethylamide has major potential as a cognitive enhancer
PRE-PRINT - Inglês
Assunto: Receptores de serotonina
Abstract: Psychedelic agonists of serotonin receptors induce neural plasticity and synaptogenesis, but their potential to enhance learning remains...
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Abstract: Psychedelic agonists of serotonin receptors induce neural plasticity and synaptogenesis, but their potential to enhance learning remains uncharted. Here we show that a single dose of d-LSD, a potent serotonergic agonist, increased novel object preference in young and adult rats several days after treatment. d-LSD alone did not increase preference in old animals, but could rescue it to young levels when followed by a 6-day exposure to enriched environment (EE). Mass spectrometry-based proteomics in human brain organoids treated with d-LSD showed upregulation of proteins from the presynaptic active zone. A computational model of synaptic connectivity in the hippocampus and prefrontal cortex suggests that d-LSD enhances novelty preference by combining local synaptic changes in mnemonic and executive regions, with alterations of long-range synapses. Better pattern separation within EE explained its synergy with d-LSD in rescuing novelty preference in old animals. These results advance the use of d-LSD in cognitive enhancement
DOI: https://doi.org/10.1101/866814
Texto completo: https://www.biorxiv.org/content/10.1101/866814v1
PRE-PRINT - Inglês
Assunto: ODS: 3. Saúde e bem-estar
Abstract: Sodium glucose co-transporter 2 inhibitors (SGLT2i) remarkably reduced the incidence of hospitalization for heart failure and cardiovascular...
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Abstract: Sodium glucose co-transporter 2 inhibitors (SGLT2i) remarkably reduced the incidence of hospitalization for heart failure and cardiovascular death of conservatively managed chronic kidney disease. We hypothesized that adding SGLT2i to standard treatment would yield cardiovascular benefits also in end-stage kidney disease (ESKD) individuals on dialysis. The DARE-ESKD-2 Trial (NCT05685394) is an ongoing, single-center, open-label, controlled trial aimed at assessing the cardiovascular effects of dapagliflozin in ESKD on dialysis. Eligible patients are adults on renal replacement therapy for more than 3 prior to enrollment. Exclusion criteria encompass pregnancy, liver failure, and current use of a SGLT2i. After signing an informed consent form, participants are randomized 1:1 to either dapagliflozin 10mg PO plus standard treatment or standard treatment alone for 6 months. Echocardiogram, anthropometry, blood sample collection, 6-min walk test, gait speed, and Kansas City Cardiomyopathy Questionnaire (KCCQ), are performed at baseline and at study termination. Participants are contacted monthly during treatment for outcomes disclosure. The primary endpoint of our study is the between-groups differences in posttreatment changes in plasma levels of N-terminal pro-B natriuretic peptide. Secondary endpoints include the differences between groups in the changes of echocardiography measurements, cardiopulmonary tests performance, body composition. The incidence of safety endpoints will also be diligently compared between study arms. The DARE-ESKD-2 trial will provide unprecedented data on the cardiovascular safety and efficacy of SGLT2i in ESKD individuals on dialysis. This study will pave the grounds for improving clinical outcomes of dialysis recipients
PRE-PRINT - Inglês
Assunto: Saliva
Abstract: Clobenzorex (CBZ) is a stimulant drug, recognized for its anorectic potential, legally used in some countries for obesity treatment....
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Abstract: Clobenzorex (CBZ) is a stimulant drug, recognized for its anorectic potential, legally used in some countries for obesity treatment. However, CBZ is banned in much of the world and has been often used illegally by drivers needing to stay alert for extended periods. Therefore, the rapid identification of CBZ in forensic samples is of paramount importance for public health and safety. In this context, we introduce an innovative electroanalytical screening method for detecting CBZ in seized tablet samples and human oral fluid using voltammetry with a graphite screen-printed electrode (SPE-Gr). The electrochemical detection was optimized in phosphate buffer solution (0.1 mol L-1, pH 7.0) using square wave voltammetry (SWV). The SPE-Gr combined with SWV exhibited a good stability of the electrochemical responses for CBZ detection, with a relative standard deviation of less than 5% across different days (N=5) and using different SPEs (N=3). A linear detection range of 2.5 to 100.0 ?mol L?1 (R² = 0.992) was achieved, with a low limit of detection (LOD) of 0.32 ?mol L?1. Interference studies with other illicit drugs and adulterants confirmed the selectivity of the proposed method for CBZ detection. In addition, the presence of CBZ in seized tablet samples and authentic oral fluids, collected from drivers, was detected and identified using the proposed method, which results were also confirmed by HPLC-MS. Consequently, integrating SPE-Gr with SWV offers a reliable, rapid, sensitive, selective, reproducible, and direct approach for the preliminary qualitative and quantitative analysis of CBZ in forensic contexts. Furthermore, the proposed method provides an efficient oral fluid test for CBZ screening in drivers under the influence of drugs
PRE-PRINT - Inglês
Assunto: Monitoramento de medicamentos
Abstract: Lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC). Among the existing therapies for NSCLC,...
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Abstract: Lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC). Among the existing therapies for NSCLC, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can be mentioned. Gefitinib is one of the first first-generation reversible EGFR-TKIs and its main metabolite is O-desmethyl-gefitinib. The therapeutic range upper limit for gefitinib has not yet been clearly established despite being an indication of its toxicity, and its adverse drug reaction may be unpredictable. Therefore, therapeutic drug monitoring (TDM) can be applied by measuring gefitinib concentration in blood and its fractions. Solid phase microextraction (SPME) is a miniaturized sample preparation technique, and SPME LC tips represent a variation of SPME. This technique utilizes an inert support coated with HPLC-type silica particles, presenting several advantages. Here, we successfully developed, optimized, and validated a green analytical method for the quantification of gefitinib and its metabolite, O-desmethylgefitinib, in plasma samples, by SPME LC tips and LC-MS/MS. Linearity was achieved from 20 to 800 ng/mL and LLOQ of 20 ng/mL. No interferences were seen at selectivity tests. Matrix effect was lower than 22.9% and inaccuracy, intra-, and inter-run imprecision were better than 15.4%. No carryover was observed and stability study was successfully applied for processed samples maintained in the autosampler at 10°C for 24 h. The method was applied for four authentic samples from individuals under gefitinib treatment, detecting gefitinib from 104.6 ng/mL to 777.1 ng/mL and O-desmethyl-gefitinib from 85.2 ng/mL to 499.2 ng/mL. Finally, the greenness characteristic was evaluated by three tools, achieving satisfactory results that confirm its compliance to GAC principles
PRE-PRINT - Inglês
Assunto: Pre-print
Abstract: The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) study is a prospective multicenter clinical observational study...
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Abstract: The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) study is a prospective multicenter clinical observational study to identify early biomarkers of epileptogenesis after moderate-to-severe traumatic brain injury (TBI). In this preliminary analysis of 37 patients, using a seed-based approach applied to acute (i.e., = 14 days) functional magnetic resonance (MRI) imaging data, we directly test the hypothesis that the epileptogenic process following brain trauma is associated with functional changes within hippocampal and thalamo-cortical networks. Additionally, we hypothesize that the network connectivity involving thalamic and hippocampal circuits underlying early and late-onset epileptogenesis would differ. The three groups did not differ by sex distribution ( ? 2 (2) = 1.8, p = .407), age ( H (2) = 4.227, p = .121), admission Glasgow Coma Scale ( H (2) = 3.850, p = .146) or postinjury day of the MRI session ( H (2) = .695, p = .706). The primary finding is that patients with early seizures, a sign of early epileptogenesis, exhibited pattern 1, namely, an increased positive connectivity in thalamic and hippocampal networks, as compared to patients who had no epileptogenesis, or late epileptogenesis ( p < .05, FWE-corrected at the cluster level). In contrast, this finding was absent in those patients who exhibited late seizures, with the latter group displayed pattern 2, namely, a lower positive and higher negative connectivity in the hippocampal network, as compared to patients who had no signs of epileptogenesis ( p < .05, FWE-corrected at the cluster level). Patients with either pattern 1 or pattern 2 connectivity profiles in thalamic and hippocampal networks were significantly predictive of late ( i.e ., between 7 days and 2 years) epileptogenesis following brain trauma. A Receiver Operating Characteristic (ROC) Curve analysis model that included thalamic and hippocampal functional connectivity values presented an Area Under the Curve (AUC) 87.7, specificity 86.7, and sensitivity 84.6. Our results indicate that dysfunction in hippocampal and thalamo-cortical networks are potential biomarkers for early and late epileptogenesis following a TBI
PRE-PRINT - Inglês
Assunto: Urina
Abstract: Paracetamol or acetaminophen (APAP), or acetaminophen, is a widely used medication for pain relief and fever reduction due to its analgesic...
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Abstract: Paracetamol or acetaminophen (APAP), or acetaminophen, is a widely used medication for pain relief and fever reduction due to its analgesic and antipyretic properties. However, excessive APAP consumption can lead to severe hepatotoxicity and nephrotoxicity, posing overdose risks. Consequently, the development of analytical methods for an accurate and rapid detection of APAP in biological matrices is of great interest in the health-related fields. Electrochemical methods have emerged as efficient, cost-effective, and sensitive tools for APAP detection in biological samples. In the light of the reported insights, this review examines critically diverse electrochemical methods for PAR detection in different biological matrices, including serum, urine, oral fluid, and sweat. Results: The claimed benefits of chemically-modified electrodes towards the selective determination of paracetamol in such complex sample matrices are discussed. On the other hand, the possible use of unmodified carbon-based electrodes combined with flow methods is highlighted as an alternative that can find relevance in the analysis of biological fluids suspected of PAR overdose occurring in the forensic scenario. Furthermore, the details regarding the distinct techniques and working electrodes for APAP determination are presented, compared and discussed in separate sections for each biological sample (serum, urine, and oral fluid). Another aspect herein debated is the selective determination of APAP in the presence of electroactive drugs naturally found in biological samples, as uric acid, and ascorbic acid, are evaluated. In addition, we have discussed and emphasized the significance of matrix selection to ensure precise results, especially in potential overdose scenarios
PRE-PRINT - Inglês
Assunto: ODS: 3. Saúde e bem-estar
Abstract: Health literacy enables individuals to access, comprehend, and utilize essential health information and services to make informed decisions...
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Abstract: Health literacy enables individuals to access, comprehend, and utilize essential health information and services to make informed decisions about their well-being. In Brazil, disparities in access to education persist, raising concerns regarding health literacy, particularly in the complex context of rare genetic diseases. One such condition is the 22q11.2 Deletion Syndrome (22q11.2 DS), a rare and heterogeneous genetic disorder that demands multidisciplinary lifelong healthcare support. This paper addresses the health literacy of Brazilian individuals with 22q11.2 DS and their caregivers. It explores the potential use of teleorientation and social media accounts for disseminating scientific knowledge about 22q11.2 DS, addressing families' doubts, and surveying to assess comprehension of the disease. Results The findings underscore the knowledge gap among caregivers of people with 22q11.2. The main doubts of the families remain on recognition and care of 22q11.2 DS clinical signs. The gap of knowledge about 22q11.2 DS, in turn, significantly affects aspects of the quality of life of caregivers associated with the environment of residence. This study highlights the intricate correlation between education, health literacy, access to healthcare, and quality of life in families affected by 22q11.2 DS. Within this context, this article brings a set of strategies that can contribute to improving health literacy regarding 22q11.2 DS in Brazil
PRE-PRINT - Inglês
Assunto: Pre-print
Abstract: The rapid and constant development of deep learning (DL) strategies is pushing forward the quality of object segmentation in images from...
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Abstract: The rapid and constant development of deep learning (DL) strategies is pushing forward the quality of object segmentation in images from diverse fields of interest. In particular, these algorithms can be very helpful in delineating brain abnormalities (lesions, tumors, lacunas, etc), enabling the extraction of information such as volume and location, that can inform doctors or feed predictive models. In this study, we describe ResectVol DL, a fully automatic tool developed to segment resective lacunas in brain images of patients with epilepsy. ResectVol DL relies on the nnU-Net framework that leverages the 3D U-Net deep learning architecture. T1-weighted MRI datasets from 120 patients (57 women; 31.5 ± 15.9 years old at surgery) were used to train (n=78) and test (n=48) our tool. Manual segmentations were carried out by five different raters and were considered as ground truth for performance assessment. We compared ResectVol DL with two other fully automatic methods: ResectVol 1.1.2 and DeepResection, using the Dice similarity coefficient (DSC), Pearson's correlation coefficient, and relative difference to manual segmentation. ResectVol DL presented the highest median DSC (0.92 vs. 0.78 and 0.90), the highest correlation coefficient (0.99 vs. 0.63 and 0.94) and the lowest median relative difference (9 vs. 44 and 12 %). Overall, we demonstrate that ResectVol DL accurately segments brain lacunas, which has the potential to assist in the development of predictive models for postoperative cognitive and seizure outcomes
PRE-PRINT - Inglês
Assunto: COVID-19 (Doença)
Abstract: Little is known about the underpinning mechanisms of neurological dysfunction in post-COVID syndrome. We conducted a cross-sectional study...
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Abstract: Little is known about the underpinning mechanisms of neurological dysfunction in post-COVID syndrome. We conducted a cross-sectional study of 87 consecutive subjects after a mild infection, with a median of 54 days after diagnosis of COVID-19. We performed structured interviews, neurological examinations, 3T-MRI scans, and neuropsychological assessments. The MRI study included white matter investigation with diffusion tensor images (DTI) and functional connectivity with resting-state functional MRI (RS-fMRI). Subjects self-reported headaches (40%) and memory difficulties (33%). The quantitative analyses confirmed symptoms of fatigue (68% of participants), excessive somnolence (35%), symptoms of anxiety (29%), impaired cognitive flexibility (40%), and language dysfunction (33%). Besides, we observed a correlation between DTI fractional anisotropy (FA) and abnormal attention and cognitive flexibility in the Trail Making Test part B. Elevated levels of fatigue and somnolence associated with higher connectivity of the posterior cingulate cortex (PCC) in the RS-fMRI study of the default mode network. While higher connectivity of the PCC with bilateral angular gyri was associated with higher fatigue levels, the elevated levels of somnolence correlated with higher connectivity between the PCC and both the left thalamus and putamen. COVID-19 is associated with long-term neuropsychiatric symptoms and cerebral functional and microstructural alterations