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1.
Hepatology ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441908

RESUMO

BACKGROUND AND AIMS: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described. APPROACH AND RESULTS: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18]). CONCLUSIONS: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH.

2.
Plant Physiol ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669447

RESUMO

Flowers, and hence, fruits and seeds, are produced by the activity of the inflorescence meristem after the floral transition. In plants with indeterminate inflorescences the final number of flowers produced by the inflorescence meristem is determined by the length of the flowering period, which ends with inflorescence arrest. Inflorescence arrest depends on many different factors, such as the presence of seeds, the influence of the environment, or endogenous factors such as phytohormone levels and age, which modulate inflorescence meristem activity. The FRUITFULL-APETALA2 (FUL-AP2) pathway plays a major role in regulating the end of flowering, likely integrating both endogenous cues and those related to seed formation. Among AP2 targets, HOMEOBOX PROTEIN21 (HB21) has been identified as a putative mediator of AP2 function in the control of inflorescence arrest. HB21 is a homeodomain leucine zipper transcription factor involved in establishing axillary bud dormancy. Here we characterized the role of HB21 in the control of the inflorescence arrest at the end of flowering in Arabidopsis (Arabidopsis thaliana). HB21, together with HB40 and HB53, are upregulated in the inflorescence apex at the end of flowering, promoting floral bud arrest. We also show that abscisic acid (ABA) accumulation occurs in the inflorescence apex in an HB-dependent manner. Our work suggests a physiological role of ABA in floral bud arrest at the end of flowering, pointing to ABA as a regulator of inflorescence arrest downstream of the HB21/40/53 genes.

3.
Cell Commun Signal ; 22(1): 36, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216942

RESUMO

Prostate cancer, as one of the most prevalent malignancies in males, exhibits an approximate 5-year survival rate of 95% in advanced stages. A myriad of molecular events and mutations, including the accumulation of oncometabolites, underpin the genesis and progression of this cancer type. Despite growing research demonstrating the pivotal role of oncometabolites in supporting various cancers, including prostate cancer, the root causes of their accumulation, especially in the absence of enzymatic mutations, remain elusive. Consequently, identifying a tangible therapeutic target poses a formidable challenge. In this review, we aim to delve deeper into the implications of oncometabolite accumulation in prostate cancer. We center our focus on the consequential epigenetic alterations and impacts on cancer stem cells, with the ultimate goal of outlining novel therapeutic strategies.


Assuntos
Neoplasias , Neoplasias da Próstata , Masculino , Humanos , Epigênese Genética , Microambiente Tumoral , Neoplasias da Próstata/genética , Neoplasias/patologia , Mutação , Células-Tronco Neoplásicas/patologia
4.
Transpl Int ; 37: 12791, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681973

RESUMO

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.


Assuntos
Cuidados Críticos , Obtenção de Tecidos e Órgãos , Humanos , Estudos Prospectivos , Masculino , Feminino , Obtenção de Tecidos e Órgãos/métodos , Pessoa de Meia-Idade , Idoso , Espanha , Adulto , Lesões Encefálicas , Morte Encefálica , Unidades de Terapia Intensiva
5.
Pestic Biochem Physiol ; 201: 105907, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685228

RESUMO

The use of essential oils (EOs) in the development of alternative management methods for bruchid control under storage conditions aroused great interest because they have proven to be effective, less toxic, and less persistent in the ecosystem than synthetic pesticides. In this sense, leaves of Lippia turbinata (Griseb.) Moldenke EO were studied in the present work. The monoterpene limonene and the monoterpenoid eucalyptol were its main constituents. EO showed a potent insecticidal activity, both in contact and fumigant conditions, against Rhipibruchus picturatus (F.) which is one of the main pests of Prosopis alba pods in stored conditions. Moreover, the EO produces repellency in these insects. Additionally, the toxicity mechanism of action was studied. In this regard, the EO inhibits the acetylcholinesterase enzyme in in vitro assays, alters the activity of the antioxidant enzymes superoxide dismutase and catalase, and produces an increase in the lipid peroxidation reactions. This is the first report of the use of the L. turbinata EO against R. picturatus insect pest. The data obtained demonstrate its potential for developing more efficient and natural storage pest control strategies.


Assuntos
Repelentes de Insetos , Inseticidas , Lippia , Óleos Voláteis , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Lippia/química , Inseticidas/farmacologia , Inseticidas/química , Inseticidas/toxicidade , Repelentes de Insetos/farmacologia , Repelentes de Insetos/química , Besouros/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Acetilcolinesterase/metabolismo , Catalase/metabolismo , Folhas de Planta/química
6.
J Circadian Rhythms ; 22: 2, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617710

RESUMO

Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.

7.
J Environ Manage ; 353: 120088, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38295640

RESUMO

Assessing the impact of greenhouse gas (GHG) emissions on agricultural soils is crucial for ensuring food production sustainability in the global effort to combat climate change. The present study delves to comprehensively assess GHG emissions in Cuba's agricultural soil and analyze its implications for rice production and climate change because of its rich agriculture cultivation tradition and diverse agro-ecological zones from the period of 1990-2022. In this research, based on Autoregressive Distributed Lag (ARDL) approach the empirical findings depicts that in short run, a positive and significant impact of 1.60 percent % in Cuba's rice production. The higher amount of atmospheric carbon dioxide (CO2) levels improves photosynthesis, and stimulates the growth of rice plants, resulting in greater grain yields. On the other hand, rice production index raising GHG emissions from agriculture by 0.35 % in the short run. Furthermore, a significant and positive impact on rice production is found in relation to the farm machinery i.e., 3.1 %. Conversely, an adverse and significant impact of land quality was observed on rice production i.e., -5.5 %. The reliability of models was confirmed by CUSUM and CUSUM square plot. Diagnostic tests ensure the absence of serial correlation and heteroscedasticity in the models. Additionally, the forecasting results are obtained from the three machine learning models i.e. feed forward neural network (FFNN), support vector machines (SVM) and adaptive boosting technique (Adaboost). Through the % MAPE criterion, it is evident that FFNN has achieved high precision (91 %). Based on the empirical findings, the study proposed the adoption of sustainable agricultural practices and incentives should be given to the farmers so that future generations inherit a world that is sustainable, and healthy.


Assuntos
Gases de Efeito Estufa , Oryza , Solo , Gases de Efeito Estufa/análise , Mudança Climática , Reprodutibilidade dos Testes , Metano/análise , Agricultura/métodos , Dióxido de Carbono/análise , Óxido Nitroso/análise
8.
Gastroenterol Hepatol ; : 502222, 2024 Jun 20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38908682

RESUMO

BACKGROUND AND AIMS: Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated HDV prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. METHOD: Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. RESULTS: We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. CONCLUSION: One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present.

9.
Rev Invest Clin ; 76(1): 18-28, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38262366

RESUMO

Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.


Assuntos
Hemocromatose , Sobrecarga de Ferro , Hepatopatias , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Hemocromatose/complicações , Hemocromatose/epidemiologia , Hemocromatose/patologia , Estudos Retrospectivos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/complicações , Hepatopatias/complicações , Hepatopatias/metabolismo , Hepatopatias/patologia , Fígado/metabolismo
10.
J Infect Dis ; 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38064677

RESUMO

Nipah virus (NiV) is a highly pathogenic paramyxovirus. The Syrian hamster model recapitulates key features of human NiV disease and is a critical tool for evaluating antivirals and vaccines. Here we describe longitudinal humoral immune responses in NiV-infected Syrian hamsters. Samples were obtained 1-28 days after infection and analyzed by ELISA, neutralization, and Fc-mediated effector function assays. NiV infection elicited robust antibody responses against the nucleoprotein and attachment glycoprotein. Levels of neutralizing antibodies were modest and only detectable in surviving animals. Fc-mediated effector functions were mostly observed in nucleoprotein-targeting antibodies. Antibody levels and activities positively correlated with challenge dose.

11.
Biochem Biophys Res Commun ; 682: 85-90, 2023 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-37804591

RESUMO

Acylphosphatase (AcP, EC 3.6.1.7) is a small model protein conformed by a ferredoxin-like fold, profoundly studied to get insights into protein folding and aggregation processes. Numerous studies focused on the aggregation and/or amyloidogenic properties of AcPs suggest the importance of edge-ß-strands in the process. In this work, we present the first crystallographic structure of Escherichia coli AcP (EcoAcP), showing notable differences with the only available NMR structure for this enzyme. EcoAcP is crystalised as an intertwined dimer formed by replacing a single C-terminal ß-strand between two protomers, suggesting a flexible character of the C-terminal edge of EcoAcP. Despite numerous works where AcP from different sources have been used as a model system for protein aggregation, our domain-swapped EcoAcP structure is the first 3-D structural evidence of native-like aggregated species for any AcP reported to date, providing clues on molecular determinants unleashing aggregation.


Assuntos
Hidrolases Anidrido Ácido , Dobramento de Proteína , Modelos Moleculares , Hidrolases Anidrido Ácido/metabolismo , Cristalografia , Acilfosfatase
12.
Arch Biochem Biophys ; 744: 109670, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37336342

RESUMO

The essential oil (EO) of Schinus areira L. (Anacardiaceae) leaves has shown antibacterial activity against Staphylococcus aureus. In this study, we aimed to unravel the mechanisms of its antibacterial action by using bacterial cells and model membranes. First, the integrity of the S. aureus membrane was evaluated by fluorescence microscopy. It was observed that there was an increase in the permeability of cells that was dependent on the EO concentration as well as the incubation time. For a deep comprension of the action of the EO on the lipids, its effect on the membrane fluidity was evaluated on DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine): DMPG (1,2-dimyristoyl-sn-glycero-3-phospho-1'-rac-glycerol) (5:1) liposomes by dynamic light scattering and by using Laurdan doped liposomes. The results indicate that EO produces changes in lipid membrane packing, increasing the fluidity, reducing the cooperative cohesive interaction between phospholipids and increasing access of water or the insertion of some components of the EO to the interior of the membrane. In addition, the potential effect of EO on intracellular targets, such as the increase of cytosolic reactive oxygen species (ROS) and DNA damage, were analyzed. The EO was capable of increasing the production of ROS as well as inducing a partial DNA degradation. Finally, the effect of EO on S. aureus biofilm was tested. These assays showed that EO was able to inhibit the biofilm formation, and also eradicate preformed biofilms. The results show, that the EO seems to have several bacterial targets involved in its antibacterial activity, from the bacterial membrane to DNA. Furthermore, the antibacterial action affects not only planktonic cells but also biofilms; reinforcing the potential application of this EO.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Óleos Voláteis , Staphylococcus aureus , Óleos Voláteis/farmacologia , Schinus , Lipossomos , Plâncton , Espécies Reativas de Oxigênio , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Biofilmes , Testes de Sensibilidade Microbiana
13.
J Gen Intern Med ; 38(3): 600-609, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35941492

RESUMO

OBJECTIVE: To investigate the relationship between ambient temperature and atmospheric pressure (AP) and the severity of heart failure (HF) decompensations. METHODS: We analysed patients coming from the Epidemioloy Acute Heart Failure Emergency (EAHFE) Registry, a multicentre prospective cohort study enrolling patients diagnosed with decompensated HF in 26 emergency departments (EDs) of 16 Spanish cities. We recorded patient and demographic data and maximum temperature (Tmax) and AP (APmax) the day before ED consultation. Associations between temperature and AP and severity endpoints were explored by logistic regression. We used restricted cubic splines to model continuous non-linear associations of temperature and AP with each endpoint. RESULTS: We analysed 16,545 patients. Daily Tmax and APmax (anomaly) of the day before patient ED arrival ranged from 0.8 to 41.6° and from - 61.7 to 69.9 hPa, respectively. A total of 12,352 patients (75.2%) were hospitalised, with in-hospital mortality in 1171 (7.1%). The probability of hospitalisation by HF decompensation showed a U-shaped curve versus Tmax and an increasing trend versus APmax. Regarding temperature, hospitalisation significantly increased from 20 °C (reference) upwards (25 °C: OR = 1.12, 95% CI = 1.04-1.21; 40 °C: 1.65, 1.13-2.40) and below 5.4 °C (5 °C: 1.21, 1.01-1.46). Concerning the mean AP of the city (anomaly = 0 hPa), hospitalisation increased when APmax (anomaly) was above + 7.0 hPa (atmospheric anticyclone; + 10 hPa: 1.14, 1.05-1.24; + 30 hPa: 2.02. 1.35-3.03). The lowest probability of mortality also corresponded to cold-mild temperatures and low AP, with a significant increased risk only found for Tmax above 24.3 °C (25 °C: 1.13, 1.01-1.27; 40 °C: 2.05, 1.15-3.64) and APmax (anomaly) above + 3.4 hPa (+ 10 hPa: 1.21, 1.07-1.36; + 30 hPa: 1.73, 1.06-2.81). Sensitivity analysis confirmed the main analysis results. CONCLUSION: Temperature and AP are independently associated with the severity of HF decompensations, with possible different effects on the need for hospitalisation and in-hospital mortality.


Assuntos
Insuficiência Cardíaca , Humanos , Temperatura , Estudos Prospectivos , Insuficiência Cardíaca/diagnóstico , Serviço Hospitalar de Emergência , Hospitalização
14.
Ann Hematol ; 102(9): 2309-2315, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37439893

RESUMO

Splenectomy remains an effective treatment for refractory immune cytopenia (RIC), which encompasses immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Accessory spleens (AS) have been described without identifying specific risk factors. We retrospectively analyzed patients with RIC after splenectomy who underwent splenic scintigraphy (SS) at our institution. Seventy-one patients were included. Sixty-two patients had ITP, five had AIHA, and four had Evans syndrome. Seventy-five percent (n = 53) were women. Eleven patients (15.5%) had an AS detected by SS. A complete response (CR) to first-line steroids (odds ratio (OR) 5.75, 95% confidence interval (CI) 1.37-24.14, p = 0.017) and the absence of Howell-Jolly bodies (HJB) in peripheral blood smear (PBS) (OR 11.37, 95% CI 2.70-47.85, p = 0.001) were found to be risk factors. Patients with both elements had a higher rate of AS (83.3%) when compared to those with one or no factors (p < 0.001). Eight patients (73%) underwent an accessory splenectomy: seven (87.5%) achieved a CR, and none had perioperative complications. The presence of HJB in PBS changed from 25 to 87.5% after accessory splenectomy. We recommend the search for an AS via SS in patients with RIC due to ITP, who had a CR to corticosteroids and the absence of HJB in PBS. Accessory splenectomy is a safe and effective procedure.


Assuntos
Púrpura Trombocitopênica Idiopática , Esplenopatias , Trombocitopenia , Humanos , Feminino , Masculino , Estudos Retrospectivos , Esplenectomia/métodos , Trombocitopenia/etiologia , Púrpura Trombocitopênica Idiopática/cirurgia , Púrpura Trombocitopênica Idiopática/etiologia , Esplenopatias/etiologia
15.
Phys Chem Chem Phys ; 25(9): 6891-6901, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36799657

RESUMO

An important point to take advantage of the use of antioxidants in industrial applications in a more efficient way is to know in depth their oxidation mechanism. This is not always a simple task and requires an in-depth study that is often insufficient to precisely describe all the structures and processes involved. This is the case of betanidin, a natural pigment employed in the drug, food, and cosmetic industries. In the present work, we seek to unravel the complete oxidation mechanism of betanidin with the use of computational techniques, supported by experimental data. For this aim, the pKas and oxidation potentials of the reactions involved at different pHs were analyzed using density functional theory (DFT) with the B3LYP/6-31+G(d,p)/SMD approach. Moreover, the decomposition mechanism of the intermediate products (decarboxylation reactions) was studied deeply. The analysis of DFT results allowed the proposal of a tentative mechanism that was put to test using the digital simulations of cyclic voltammetry by comparing the results of these simulations with an experimental case. Based on the rigorous experimental analysis, DFT, and simulations of cyclic voltammetry, the complete mechanism of the oxidation of betanidin in an aqueous medium was proposed. The dimerization of the oxidation products was also considered to explain the voltammetric response of betanidin.

16.
Vet Pathol ; 60(5): 560-577, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37458195

RESUMO

Disease outbreaks in several ecologically or commercially important invertebrate marine species have been reported in recent years all over the world. Mass mortality events (MMEs) have affected the noble pen shell (Pinna nobilis), causing its near extinction. Our knowledge of the dynamics of diseases affecting this species is still unclear. Early studies investigating the causative etiological agent focused on a novel protozoan parasite, Haplosporidium pinnae, although further investigations suggested that concurrent polymicrobial infections could have been pivotal in some MMEs, even in the absence of H. pinnae. Indeed, moribund specimens collected during MMEs in Italy, Greece, and Spain demonstrated the presence of a bacteria from within the Mycobacterium simiae complex and, in some cases, species similar to Vibrio mediterranei. The diagnostic processes used for investigation of MMEs are still not standardized and require the expertise of veterinary and para-veterinary pathologists, who could simultaneously evaluate a variety of factors, from clinical signs to environmental conditions. Here, we review the available literature on mortality events in P. nobilis and discuss approaches to define MMEs in P. nobilis. The proposed consensus approach should form the basis for establishing a foundation for future studies aimed at preserving populations in the wild.


Assuntos
Bivalves , Haplosporídios , Mycobacterium , Animais , Bivalves/microbiologia , Bivalves/parasitologia , Itália , Surtos de Doenças
17.
Sensors (Basel) ; 23(20)2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37896442

RESUMO

Artificial neural networks are a powerful tool for managing data that are difficult to process and interpret. This article presents the design and implementation of backpropagated multilayer artificial neural networks, structured with a vector input, hidden layers, and an output node, for information processing generated by an optical encoder based on the polarization of light. A machine learning technique is proposed to train the neural networks such that the system can predict with remarkable accuracy the angular position in which the rotating element of the neuro-encoder is located based on information provided by light's phase-shifting arrangements. The proposed neural designs show excellent performance in small angular intervals, and a methodology was proposed to avoid losing this remarkable characteristic in measurements from 0 to 180° and even up to 360°. The neuro-encoder was implemented in the simulation stage to obtain performance results, where the main evaluation metric employed to assess the performance is the total error. This proposal can be useful to improve the capabilities of resolvers or other polyphasic sensors used to obtain outstanding precision and accurate data, even when working under hard and noisy industrial conditions.

18.
Int J Mol Sci ; 24(24)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38139289

RESUMO

Androgenic alopecia (AGA) is the most prevalent type of progressive hair loss and has psychological repercussions. Nevertheless, the effectiveness of current pharmacological treatments remains limited, in part because the molecular basis of the disease has not been fully elucidated. Our group previously highlighted the important roles of aromatase and 5α-reductase (5α-R) in alopecia in young women with female pattern hair loss. Additionally, an association has been proposed between AGA and prostate cancer (PCa), suggesting that genes implicated in PCa would also be involved in AGA. A low-invasive, sensitive, and precise method was used to determine mRNA levels of aromatase, 5α-R isozymes, and 84 PCa-related genes in samples of plucked hair from young men with AGA and controls. Samples were obtained with a trichogram from the vertex scalp, and mRNA levels were quantified using real-time RT-PCR. The men with AGA had significantly higher 5α-R2 mRNA levels in comparison to controls; interestingly, some of them also showed markedly elevated mRNA levels of 5α-R1 or 5α-R3 or of both, which may explain the varied response to 5α-R inhibitor treatments. The men with AGA also showed significant changes versus controls in 6 out of the 84 genes implicated in PCa. This study contributes greater knowledge of the molecular bases of AGA, facilitating early selection of the most appropriate pharmacological therapy and opening the way to novel treatments.


Assuntos
Colestenona 5 alfa-Redutase , Neoplasias da Próstata , Masculino , Humanos , Colestenona 5 alfa-Redutase/genética , Aromatase/genética , Isoenzimas/uso terapêutico , RNA Mensageiro/genética , Cabelo , Alopecia/genética , Alopecia/tratamento farmacológico , Neoplasias da Próstata/genética
19.
Int J Mol Sci ; 24(8)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37108388

RESUMO

Covalent peptidomimetic protease inhibitors have gained a lot of attention in drug development in recent years. They are designed to covalently bind the catalytically active amino acids through electrophilic groups called warheads. Covalent inhibition has an advantage in terms of pharmacodynamic properties but can also bear toxicity risks due to non-selective off-target protein binding. Therefore, the right combination of a reactive warhead with a well-suited peptidomimetic sequence is of great importance. Herein, the selectivities of well-known warheads combined with peptidomimetic sequences suited for five different proteases were investigated, highlighting the impact of both structure parts (warhead and peptidomimetic sequence) for affinity and selectivity. Molecular docking gave insights into the predicted binding modes of the inhibitors inside the binding pockets of the different enzymes. Moreover, the warheads were investigated by NMR and LC-MS reactivity assays against serine/threonine and cysteine nucleophile models, as well as by quantum mechanics simulations.


Assuntos
Peptidomiméticos , Inibidores de Proteases , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , Peptidomiméticos/farmacologia , Simulação de Acoplamento Molecular , Aminoácidos/química , Cisteína/metabolismo
20.
Molecules ; 28(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37894621

RESUMO

Essential oils (EOs) are natural antioxidant alternatives that reduce skin damage. However, EOs are highly volatile; therefore, their nanoencapsulation represents a feasible alternative to increase their stability and favor their residence time on the skin to guarantee their effect. In this study, EOs of Rosmarinus officinalis and Lavandula dentata were nanoencapsulated and evaluated as skin delivery systems with potential antioxidant activity. The EOs were characterized and incorporated into polymeric nanocapsules (NC-EOs) using nanoprecipitation. The antioxidant activity was evaluated using the ferric thiocyanate method. The ex vivo effects on pig skin were evaluated based on biophysical parameters using bioengineering techniques. An ex vivo dermatokinetic evaluation on pig skin was performed using modified Franz cells and the tape-stripping technique. The results showed that the EOs had good antioxidant activity (>65%), which was maintained after nanoencapsulation and purification. The nanoencapsulation of the EOs favored its deposition in the stratum corneum compared to free EOs; the highest deposition rate was obtained for 1,8-cineole, a major component of L. dentata, at 1 h contact time, compared to R. officinalis with a major deposition of the camphor component. In conclusion, NC-EOs can be used as an alternative antioxidant for skin care.


Assuntos
Nanocápsulas , Óleos Voláteis , Animais , Suínos , Óleos Voláteis/farmacologia , Antioxidantes/farmacologia , Pele , Eucaliptol , Polímeros
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