Objective:Prostate cancer is a common malignancy in men over 50 years old,and radical prostatectomy,particularly via laparoscopic and robotic-assisted techniques,significantly impacts quality of life,especially in ter...Objective:Prostate cancer is a common malignancy in men over 50 years old,and radical prostatectomy,particularly via laparoscopic and robotic-assisted techniques,significantly impacts quality of life,especially in terms of erectile dysfunction.This systematic review and meta-analysis aimed to evaluate the preservation of erectile function following robotic-assisted and laparoscopic radical prostatectomy,with a separate analysis of randomized clinical trials and non-randomized studies.Methods:This review was carried out using randomized and non-randomized studies involving adult patients diagnosed with localized prostate cancer undergoing radical prostatectomy,according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered in PROSPERO.Applicable literature from PubMed,Cochrane,Embase,and the Latin American and Caribbean Health Sciences Literature database was analysed.The bias in randomized clinical trials was assessed using the Cochrane Risk of Bias 2.0 tool,and observational studies were evaluated via the Newcastle-Ottawa Scale.The statistical analysis was performed using Review Manager version 5.4.Results:Our analysis included 13 studies involving 6281 patients.Comparative meta-analysis of non-randomized studies demonstrated that robotic techniques were significantly more effective in preserving erectile function at 3 months(risk difference[RD]0.05,95%confidence interval[CI]0.00-0.11;p=0.040),6 months(RD 0.10,95%CI 0.03-0.17;p=0.006),and 12 months postoperatively(RD 0.06,95%CI 0.02-0.10;p=0.002).Conclusion:Robotic-assisted surgery showed greater preservation of erectile function 3 months,6 months,and 12 months after radical prostatectomy.However,additional studies with meticulous methodological criteria are necessary for future analysis.展开更多
AIM:To determine initial medication adherence in newly diagnosed glaucoma patients treated with anti-glaucoma drugs.METHODS:This retrospective and observational study included all patients diagnosed with glaucoma in t...AIM:To determine initial medication adherence in newly diagnosed glaucoma patients treated with anti-glaucoma drugs.METHODS:This retrospective and observational study included all patients diagnosed with glaucoma in the Primary Health Care units in Portugal during the years 2012 and 2013,which in consequence received a first prescription for anti-glaucoma drugs.Data was collected from electronic prescribing records of the primary care units and from pharmacy claims records.Initiation of glaucoma treatment and early discontinuation were measured,and the combination of(non)-initiation and early discontinuation accounted for initial medication(non)-adherence.RESULTS:A total of 3548 new glaucoma patients(40.1%male;59.9%female)were included.The 1133(31.9%)patients were initially classified as non-users,since there was no pharmacy claim found for their first prescription for glaucoma treatment.Additionally,277(11.5%)patients early discontinued their treatment,acquiring only their first prescription.Overall,the initial medication non-adherence rate was 39.7%since 1410 patients either didn’t initiate treatment or discontinued it early.CONCLUSION:This study,reveals a major opportunity to improve glaucoma treatment and its control,since a large proportion of patients fail to engage with their prescribed therapy,which implies that implementation of individual or group strategies that enable patients with glaucoma to correctly perform their treatment is still needed.展开更多
AIM: To assess our experience with the use and management of everolimus-based regimens post-liver transplantation and to redefine the potential role of this drug in current clinical practice.METHODS: From October 1988...AIM: To assess our experience with the use and management of everolimus-based regimens post-liver transplantation and to redefine the potential role of this drug in current clinical practice.METHODS: From October 1988 to December 2012, 1023 liver transplantations were performed in 955 patients in our Unit. Seventy-four patients(7.74%) received immunosuppression with everolimus at some time post-transplantation. Demographic characteristics, everolimus indication, time elapsed from transplantation to the introduction of everolimus, doses and levels administered, efficacy, side effects, discontinuation andpost-conversion survival were analyzed. RESULTS: Mean age at the time of conversion to everolimus was 57.7 ± 10 years. Indications for conversion were: refractory rejection 31.1%, extended hepatocellular carcinoma in explanted liver 19%, post-transplant hepatocellular carcinoma recurrence 8.1%, de novo tumour 17.6%, renal insufficiency 8.1%, severe neurotoxicity 10.8%, and others 5.4%. Median time from transplantation to introduction of everolimus was 6 mo(range: 0.10-192). Mean follow-up post-conversion was 22 ± 19 mo(range: 0.50-74). The event for which the drug was indicated was resolved in 60.8% of patients, with the best results in cases of refractory rejection, renal insufficiency and neurotoxicity. Results in patients with cancer were similar to those of a historical cohort treated with other immunosuppressants. The main side effects were dyslipidemia and infections. Post-conversion acute rejection occurred in 14.9% of cases. The drug was discontinued in 28.4% of patients.CONCLUSION: Everolimus at low doses in combination with tacrolimus is a safe immunosuppressant with multiple early and late indications post-liver transplantation.展开更多
Background: Measures to contain the COVID-19 transmission reached teaching routines of universities worldwide with possible mental health consequences for anxiety. This study assessed prevalence and risk factors for s...Background: Measures to contain the COVID-19 transmission reached teaching routines of universities worldwide with possible mental health consequences for anxiety. This study assessed prevalence and risk factors for stress, depression, and anxiety (SDA) in medical students during quarantine by COVID-19. Methods: A cross-sectional observational study of medical students by means of the DASS-21 questionnaire. Risk factors for SDA were assessed based on epidemiologic questions related to COVID-19. Receiver Operating Characteristics (ROC) curves were calculated for each predictor, as well as sensitivity and specificity. Results: This survey reached 1009 responses. A prevalence of 77.5% for some SDA disorder was found, 63% being severe. Previous diagnosis of psychiatric disorder was a factor of risk for anxiety (OR 2.78 CI95% 1.44 - 14.25, p = 0.044), as well as for depression (OR 3.37 CI95% 1.98 - 6.02, p Conclusion: Psychiatric conditions as well as chronic illnesses were risk factors for high prevalence of anxiety, depression and stress during the COVID-19 pandemic among medical students.展开更多
Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs...Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.展开更多
Diazotrophic bacteria applied as a seed inoculant can improve the grain yield of several crops including maize. The current study aimed to test the agronomic efficiency and contribution of biological nitrogen fixation...Diazotrophic bacteria applied as a seed inoculant can improve the grain yield of several crops including maize. The current study aimed to test the agronomic efficiency and contribution of biological nitrogen fixation(BNF) of the endophytic diazotroph Herbaspirillum seropedicae strain ZAE94 to maize under field conditions. Eighteen field assays were conducted in four different locations during consecutive years on two hybrids and two varieties of maize in a random block design with four replicates using a peat-based inoculant. The inoculant containing the ZAE94 strain was applied without nitrogen(N)fertilization or with 40 kg N ha^(-1) and was compared to the application of 40 and 80 kg N ha^(-1) without inoculation. Crop productivity and N accumulation in the grain were evaluated in addition to ^(15)N natural abundance(δ^(15)N) to evaluate BNF in the treatments without N fertilization. Fertilization at 40 kg N ha^(-1) plus bacterial inoculation produced crop yields similar to the treatment with 80 kg N ha^(-1) and increased grain N content, especially in the off-season with 40 kg N ha^(-1). The inoculation treatments showed lower δ^(15)N values than the non-inoculated treatments, which was most evident in the off-season. The BNF contributed about 30% of N accumulated in plants inoculated with ZAE94. On average, 64% of the N fertilized plots showed an increase of the parameters evaluated in the inoculated treatments, compared with the control. Inoculation also increased root length, root volume, and leaf area, and these parameters were positively correlated with plant weight using a hydroponic assay. This study revealed that the application of H. seropedicae inoculant increased the amount of N in plants owing to BNF, and there is a better chance of yield response to inoculation under low N fertilizer application in the off-season.展开更多
AIM： To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica （Cactaceae） on the healing of ethanol-induced gastritis in rats. METHODS： Chronic gastric mucosa injury was treated with mucilage...AIM： To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica （Cactaceae） on the healing of ethanol-induced gastritis in rats. METHODS： Chronic gastric mucosa injury was treated with mucilage （5 mg/kg per day） after it was induced by ethanol. Lipid composition, activity of 5＇-nucleotidase （a membrane-associated ectoenzyme） and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS： Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine （PC） decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5＇-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION： The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine （PE）, may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.展开更多
The aim of this work was to evaluate arbuscular mycorrhizal(AM)fungi as soil indicators and the mycorrhization of native and exotic tree species planted in the Acaraúbasin,a transition area from the coast to the ...The aim of this work was to evaluate arbuscular mycorrhizal(AM)fungi as soil indicators and the mycorrhization of native and exotic tree species planted in the Acaraúbasin,a transition area from the coast to the Brazilian semiarid region.Plots with 6-year-old trees of four native and three non-native species as well as one non-forested area were evaluated in terms of the diversity of AM fungi in the mycorrhizosphere and the root colonization by AM and ectomycorrhizal(EcM)fungi.Twenty-four AM fungi were identified;Claroideoglomus etunicatum,Glomus sinuosum,Paraglomus albidum,Acaulospora laevis,and Acaulospora brasiliensis were abundant in the forest soil.Diversity,dominance,evenness and richness indices of AM fungi were higher in plots with native trees.All root samples were colonized by AM fungi and only A nadenanthera colubrina,Acacia mangium,Casuarina equisetifolia and Eucalyptus urophylla formed associations with EcM fungi.Acaulospora morphotypes served as soil indicators for coverings with the native species Astronium fraxinifolium and Colubrina glandulosa.Exotic species may favor the proliferation of rarer AM fungi.These fungi–plant relationships may be important in the management of forest systems,and the evidence with mycorrhizal associations allows the inclusion of Brazilian species in tropical reforestation.展开更多
Bamboo fibers were used as source to prepare cellulose hydrogel films for cell cultivation scaffold. The preparation of cellulose solutions was carried out by three different dissolving methods with NaOH-based and NaO...Bamboo fibers were used as source to prepare cellulose hydrogel films for cell cultivation scaffold. The preparation of cellulose solutions was carried out by three different dissolving methods with NaOH-based and NaOH/urea aqueous solutions and DMAc/LiCl solution. Several hydrogel films were elaborated and their properties were compared to evaluate the effect of the dissolving method. It was found that tensile strength of the resultant hydrogel films increased from 21 to 66 N/mm2 when DMAc/LiCl was used instead of the NaOH/urea solution. The same tendency was observed in the obtained elongation values. Moreover, a remarkable difference in fibroblast cell cultivation was observed in higher cell density, when DMAc/LiCl method was used. The obtained results with DMAc/LiCl also were seen to be higher than the results for PS dish used as control. However, low cytocompatibility was observed when NaOH and NaOH/urea methods were used. The obtained results showed that hydrogel films elaborated with cellulose solution prepared with DMAc/LiCl method exhibited good cytocompatibility for the cell cultivation scaffold.展开更多
Polarimetry encompasses a collection of optical techniques broadly used in a variety of fields.Nowadays,such techniques have provided their suitability in the biomedical field through the study of the polarimetric res...Polarimetry encompasses a collection of optical techniques broadly used in a variety of fields.Nowadays,such techniques have provided their suitability in the biomedical field through the study of the polarimetric response of biological samples(retardance,dichroism and depolarization)by measuring certain polarimetric observables.One of these features,depolarization,is mainly produced by scattering on samples,which is a predominant efiect in turbid media as biological tissues.In turn,retardance and dichroic efiects are produced by tissue anisotropies and can lead to depolarization too.Since depolarization is a predominant efiect in tissue samples,we focus on studying difierent depolarization metrics for biomedical applications.We report the suitability of a set of depolarizing observables,the indices of polarimetric purity(IPPs),for biological tissue inspection.We review some results where we demonstrate that IPPs lead to better performance than the depolarization index,which is a well-established and commonly used depolarization observable in the literature.We also provide how IPPs are able to significantly enhance contrast between difierent tissue structures and even to reveal structures hidden by using standard intensity images.Finally,we also explore the classificatory potential of IPPs and other depolarizing observables for the discrimination of difierent tissues obtained from ex vivo chicken samples(muscle,tendon,myotendinous junction and bone),reaching accurate models for tissue classification.展开更多
Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic ...Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.展开更多
Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid compositi...Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).展开更多
BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
Aortic regurgitation(AR)poses distinct challenges in interventional cardiology,necessitating novel approaches for treatment.This editorial examined the evolving landscape of transcatheter aortic valve replacement(TAVR...Aortic regurgitation(AR)poses distinct challenges in interventional cardiology,necessitating novel approaches for treatment.This editorial examined the evolving landscape of transcatheter aortic valve replacement(TAVR)as an alternative therapeutic strategy for AR,particularly in patients deemed high risk for surgery.We explored the anatomical and patho-physiological disparities between AR and aortic stenosis(AS)and elucidates the technical nuances of TAVR procedures in AR pa-tients,emphasizing the need for precise prosthesis positioning and considerations for excessive stroke volume.Additionally,we discussed the safety and efficacy of TAVR compared to SAVR in AR management,drawing insights from recent case series and registry data.Notably,dedicated TAVR devices tailored for AR,such as the J-Valve and JenaValve,demonstrate promising out-comes in reducing residual AR and ensuring procedural success.Conversely,“off-label”TAVR devices,including balloon-ex-pandable and self-expandable platforms,offer feasible alternatives-particularly for large aortic annuli-with favorable device suc-cess rates and low residual AR rates.We highlighted the need for further research,including randomized trials,to delineate the definitive role of TAVR in AR treatment and to address remaining questions regarding device selection and long-term outcomes.In conclusion,TAVR emerges as a viable option for patients with AR,particularly those facing high surgical risks or frailty,with ongoing investigations poised to refine its position in the therapeutic armamentarium.展开更多
Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and function.This cellular process is evolutionarily highly conserved to quality control of many pr...Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and function.This cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino acids.This process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein markers.Some of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).展开更多
BACKGROUND Autoimmune liver disease(AILD)recurrence is common after liver transplantation(LT).While several risk factors for recurrence have been identified,their combined predictive value has yet to be thoroughly inv...BACKGROUND Autoimmune liver disease(AILD)recurrence is common after liver transplantation(LT).While several risk factors for recurrence have been identified,their combined predictive value has yet to be thoroughly investigated.AIM To evaluate the combined predictive value of clinical and laboratory risk factors for AILD recurrence after LT.METHODS This retrospective cohort study included 79 patients with AILD who underwent LT at a single liver transplant center.We compared clinical and laboratory variables between patients with and without recurrent disease and assessed the predictive performance of these factors using four logistic regression models and their corresponding area underthe receiver operating characteristic curve (AUC).RESULTSRecurrent AILD occurred in 26.58% of patients (95%CI: 17-38), the median time to recurrence was 28 months(interquartile range: 16-38). Patients with recurrent AILD had significantly higher pre-transplant Child-Pugh scores[11.61 ± 1.16 vs 10.58 ± 1.96 points;odds ratio (OR) = 1.43, 95%CI: 1.03-2.00;P = 0.032] and model for end-stage liverdisease score (MELD) (22.76 ± 5.47 vs 18.81 ± 7.24 points;OR = 1.08, 95%CI: 1.01-1.16;P = 0.032), compared to thosewithout recurrence. Additionally, baseline alanine aminotransferase (ALT) > 2 times the upper limit of normal(ULN) was significantly associated with recurrence (31% vs 57.1%;OR = 2.96, 95%CI: 1.06-8.28;P = 0.038). Ourmodels, incorporating several risk variables, demonstrated moderate predictive ability for AILD recurrence. TheAUCs were as follows: (1) Model 1 (AUC = 0.75, 95%CI: 0.58-0.87);(2) Model 2 (AUC = 0.74, 95%CI: 0.59-0.90);(3)Model 3 (AUC = 0.72, 95%CI: 0.58-0.88);and (4) Model 4 (AUC = 0.63, 95%CI: 0.40-0.76), with no statisticallysignificant difference between the models (P = 0.488).CONCLUSIONHigher pre-transplant Child-Pugh and MELD scores, as well as ALT > 2 ULN, were associated with an increasedrisk of AILD recurrence.展开更多
The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves gl...The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.展开更多
Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy ...Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.展开更多
BACKGROUND Neonatal screening(NS)is a public health policy to identify genetic pathologies such as cystic fibrosis(CF),sickle cell disease,and other diseases.Sickle cell disea-se is the comprehensive term for a group ...BACKGROUND Neonatal screening(NS)is a public health policy to identify genetic pathologies such as cystic fibrosis(CF),sickle cell disease,and other diseases.Sickle cell disea-se is the comprehensive term for a group of hemoglobinopathies characterized by the presence of hemoglobin S.CF is an autosomal recessive multisystemic disease with pathophysiology involving deleterious mutations in the transmembrane re-gulatory gene that encodes a protein that regulates the activity of chloride and sodium channels in the cell surface epithelium.NS is crucial for early diagnosis and management,which ensures a better quality of life.AIM To report a case of the coexistence of sickle cell anemia(SCA)and CF and perform an integrative literature review.METHODS This is an observational study and a review of the literature focusing on two rare genetic pathologies identified simultaneously in NS from the perspective of a clinical case.The authors identified only 5 cases of SCA associated with CF.No clinical trials or review articles were identified considering the rarity of the coexistence of these two pathologies.RESULTS Herein,the authors reported the case of a girl who after undergoing NS on day 8 of life was diagnosed with SCA with an alteration in the dosage of immunoreactive trypsin.The diagnosis of CF was confirmed by the Coulometry Sweat Test.The rarity of the co-occurrence of these two severe genetic pathologies(CF and SCA)is a challenge for medical science.CONCLUSION This study adds to the few case reports present in the literature that highlight the identification of two severe diseases via NS.展开更多
The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
文摘Objective:Prostate cancer is a common malignancy in men over 50 years old,and radical prostatectomy,particularly via laparoscopic and robotic-assisted techniques,significantly impacts quality of life,especially in terms of erectile dysfunction.This systematic review and meta-analysis aimed to evaluate the preservation of erectile function following robotic-assisted and laparoscopic radical prostatectomy,with a separate analysis of randomized clinical trials and non-randomized studies.Methods:This review was carried out using randomized and non-randomized studies involving adult patients diagnosed with localized prostate cancer undergoing radical prostatectomy,according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered in PROSPERO.Applicable literature from PubMed,Cochrane,Embase,and the Latin American and Caribbean Health Sciences Literature database was analysed.The bias in randomized clinical trials was assessed using the Cochrane Risk of Bias 2.0 tool,and observational studies were evaluated via the Newcastle-Ottawa Scale.The statistical analysis was performed using Review Manager version 5.4.Results:Our analysis included 13 studies involving 6281 patients.Comparative meta-analysis of non-randomized studies demonstrated that robotic techniques were significantly more effective in preserving erectile function at 3 months(risk difference[RD]0.05,95%confidence interval[CI]0.00-0.11;p=0.040),6 months(RD 0.10,95%CI 0.03-0.17;p=0.006),and 12 months postoperatively(RD 0.06,95%CI 0.02-0.10;p=0.002).Conclusion:Robotic-assisted surgery showed greater preservation of erectile function 3 months,6 months,and 12 months after radical prostatectomy.However,additional studies with meticulous methodological criteria are necessary for future analysis.
文摘AIM:To determine initial medication adherence in newly diagnosed glaucoma patients treated with anti-glaucoma drugs.METHODS:This retrospective and observational study included all patients diagnosed with glaucoma in the Primary Health Care units in Portugal during the years 2012 and 2013,which in consequence received a first prescription for anti-glaucoma drugs.Data was collected from electronic prescribing records of the primary care units and from pharmacy claims records.Initiation of glaucoma treatment and early discontinuation were measured,and the combination of(non)-initiation and early discontinuation accounted for initial medication(non)-adherence.RESULTS:A total of 3548 new glaucoma patients(40.1%male;59.9%female)were included.The 1133(31.9%)patients were initially classified as non-users,since there was no pharmacy claim found for their first prescription for glaucoma treatment.Additionally,277(11.5%)patients early discontinued their treatment,acquiring only their first prescription.Overall,the initial medication non-adherence rate was 39.7%since 1410 patients either didn’t initiate treatment or discontinued it early.CONCLUSION:This study,reveals a major opportunity to improve glaucoma treatment and its control,since a large proportion of patients fail to engage with their prescribed therapy,which implies that implementation of individual or group strategies that enable patients with glaucoma to correctly perform their treatment is still needed.
文摘AIM: To assess our experience with the use and management of everolimus-based regimens post-liver transplantation and to redefine the potential role of this drug in current clinical practice.METHODS: From October 1988 to December 2012, 1023 liver transplantations were performed in 955 patients in our Unit. Seventy-four patients(7.74%) received immunosuppression with everolimus at some time post-transplantation. Demographic characteristics, everolimus indication, time elapsed from transplantation to the introduction of everolimus, doses and levels administered, efficacy, side effects, discontinuation andpost-conversion survival were analyzed. RESULTS: Mean age at the time of conversion to everolimus was 57.7 ± 10 years. Indications for conversion were: refractory rejection 31.1%, extended hepatocellular carcinoma in explanted liver 19%, post-transplant hepatocellular carcinoma recurrence 8.1%, de novo tumour 17.6%, renal insufficiency 8.1%, severe neurotoxicity 10.8%, and others 5.4%. Median time from transplantation to introduction of everolimus was 6 mo(range: 0.10-192). Mean follow-up post-conversion was 22 ± 19 mo(range: 0.50-74). The event for which the drug was indicated was resolved in 60.8% of patients, with the best results in cases of refractory rejection, renal insufficiency and neurotoxicity. Results in patients with cancer were similar to those of a historical cohort treated with other immunosuppressants. The main side effects were dyslipidemia and infections. Post-conversion acute rejection occurred in 14.9% of cases. The drug was discontinued in 28.4% of patients.CONCLUSION: Everolimus at low doses in combination with tacrolimus is a safe immunosuppressant with multiple early and late indications post-liver transplantation.
文摘Background: Measures to contain the COVID-19 transmission reached teaching routines of universities worldwide with possible mental health consequences for anxiety. This study assessed prevalence and risk factors for stress, depression, and anxiety (SDA) in medical students during quarantine by COVID-19. Methods: A cross-sectional observational study of medical students by means of the DASS-21 questionnaire. Risk factors for SDA were assessed based on epidemiologic questions related to COVID-19. Receiver Operating Characteristics (ROC) curves were calculated for each predictor, as well as sensitivity and specificity. Results: This survey reached 1009 responses. A prevalence of 77.5% for some SDA disorder was found, 63% being severe. Previous diagnosis of psychiatric disorder was a factor of risk for anxiety (OR 2.78 CI95% 1.44 - 14.25, p = 0.044), as well as for depression (OR 3.37 CI95% 1.98 - 6.02, p Conclusion: Psychiatric conditions as well as chronic illnesses were risk factors for high prevalence of anxiety, depression and stress during the COVID-19 pandemic among medical students.
基金Part of this manuscript was supported by Grant from the Instituto Mexicano del Seguro Social,projects FIS/IMSS/PROT/G15/1414
文摘Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.
基金funded by Brazilian Agriculture Research Corporation—Embrapa,the National Research Council (CNPq),Brazil (No.465133/2014-2)Newton Fund “Understanding and Exploiting Biological Nitrogen Fixation for Improvement of Brazilian Agriculture” (No.B/N012476/1)+2 种基金the Biotechnology and Biological Sciences Research Council (BBSRC),Brazilthe Brazilian National Council for State Funding Agencies (CONFAP)the Coordination of Improvement of Higher Education Personnel (CAPES),Brazil (No.001)。
文摘Diazotrophic bacteria applied as a seed inoculant can improve the grain yield of several crops including maize. The current study aimed to test the agronomic efficiency and contribution of biological nitrogen fixation(BNF) of the endophytic diazotroph Herbaspirillum seropedicae strain ZAE94 to maize under field conditions. Eighteen field assays were conducted in four different locations during consecutive years on two hybrids and two varieties of maize in a random block design with four replicates using a peat-based inoculant. The inoculant containing the ZAE94 strain was applied without nitrogen(N)fertilization or with 40 kg N ha^(-1) and was compared to the application of 40 and 80 kg N ha^(-1) without inoculation. Crop productivity and N accumulation in the grain were evaluated in addition to ^(15)N natural abundance(δ^(15)N) to evaluate BNF in the treatments without N fertilization. Fertilization at 40 kg N ha^(-1) plus bacterial inoculation produced crop yields similar to the treatment with 80 kg N ha^(-1) and increased grain N content, especially in the off-season with 40 kg N ha^(-1). The inoculation treatments showed lower δ^(15)N values than the non-inoculated treatments, which was most evident in the off-season. The BNF contributed about 30% of N accumulated in plants inoculated with ZAE94. On average, 64% of the N fertilized plots showed an increase of the parameters evaluated in the inoculated treatments, compared with the control. Inoculation also increased root length, root volume, and leaf area, and these parameters were positively correlated with plant weight using a hydroponic assay. This study revealed that the application of H. seropedicae inoculant increased the amount of N in plants owing to BNF, and there is a better chance of yield response to inoculation under low N fertilizer application in the off-season.
文摘AIM： To study the effect of mucilage obtained from cladodes of Opuntia ficus-indica （Cactaceae） on the healing of ethanol-induced gastritis in rats. METHODS： Chronic gastric mucosa injury was treated with mucilage （5 mg/kg per day） after it was induced by ethanol. Lipid composition, activity of 5＇-nucleotidase （a membrane-associated ectoenzyme） and cytosolic activities of lactate and alcohol dehydrogenases in the plasma membrane of gastric mucosa were determined. Histological studies of gastric samples from the experimental groups were included. RESULTS： Ethanol elicited the histological profile of gastritis characterized by loss of the surface epithelium and infiltration of polymorphonuclear leukocytes. Phosphatidylcholine （PC） decreased and cholesterol content increased in plasma membranes of the gastric mucosa. In addition, cytosolic activity increased while the activity of alcohol dehydrogenases decreased. The administration of mucilage promptly corrected these enzymatic changes. In fact, mucilage readily accelerated restoration of the ethanol-induced histological alterations and the disturbances in plasma membranes of gastric mucosa, showing a univocal anti-inflammatory effect. The activity of 5＇-nucleotidase correlated with the changes in lipid composition and the fluidity of gastric mucosal plasma membranes. CONCLUSION： The beneficial action of mucilage seems correlated with stabilization of plasma membranes of damaged gastric mucosa. Molecular interactions between mucilage monosaccharides and membrane phospholipids, mainly PC and phosphatidylethanolamine （PE）, may be the relevant features responsible for changing activities of membrane-attached proteins during the healing process after chronic gastric mucosal damage.
基金Project funding:This work was financially supported by SINDIMóVEIS(Sindicato das Indústrias de Móveis do Ceará)ADECE(Agência de Desenvolvimento do Estado do Ceará)Embrapa(code 12.13.07.006.0002)。
文摘The aim of this work was to evaluate arbuscular mycorrhizal(AM)fungi as soil indicators and the mycorrhization of native and exotic tree species planted in the Acaraúbasin,a transition area from the coast to the Brazilian semiarid region.Plots with 6-year-old trees of four native and three non-native species as well as one non-forested area were evaluated in terms of the diversity of AM fungi in the mycorrhizosphere and the root colonization by AM and ectomycorrhizal(EcM)fungi.Twenty-four AM fungi were identified;Claroideoglomus etunicatum,Glomus sinuosum,Paraglomus albidum,Acaulospora laevis,and Acaulospora brasiliensis were abundant in the forest soil.Diversity,dominance,evenness and richness indices of AM fungi were higher in plots with native trees.All root samples were colonized by AM fungi and only A nadenanthera colubrina,Acacia mangium,Casuarina equisetifolia and Eucalyptus urophylla formed associations with EcM fungi.Acaulospora morphotypes served as soil indicators for coverings with the native species Astronium fraxinifolium and Colubrina glandulosa.Exotic species may favor the proliferation of rarer AM fungi.These fungi–plant relationships may be important in the management of forest systems,and the evidence with mycorrhizal associations allows the inclusion of Brazilian species in tropical reforestation.
文摘Bamboo fibers were used as source to prepare cellulose hydrogel films for cell cultivation scaffold. The preparation of cellulose solutions was carried out by three different dissolving methods with NaOH-based and NaOH/urea aqueous solutions and DMAc/LiCl solution. Several hydrogel films were elaborated and their properties were compared to evaluate the effect of the dissolving method. It was found that tensile strength of the resultant hydrogel films increased from 21 to 66 N/mm2 when DMAc/LiCl was used instead of the NaOH/urea solution. The same tendency was observed in the obtained elongation values. Moreover, a remarkable difference in fibroblast cell cultivation was observed in higher cell density, when DMAc/LiCl method was used. The obtained results with DMAc/LiCl also were seen to be higher than the results for PS dish used as control. However, low cytocompatibility was observed when NaOH and NaOH/urea methods were used. The obtained results showed that hydrogel films elaborated with cellulose solution prepared with DMAc/LiCl method exhibited good cytocompatibility for the cell cultivation scaffold.
基金the financial support of Spanish MINECO(PID2021-126509OB-C21,and Fondos FEDER)Catalan Government(2017-SGR-001500).
文摘Polarimetry encompasses a collection of optical techniques broadly used in a variety of fields.Nowadays,such techniques have provided their suitability in the biomedical field through the study of the polarimetric response of biological samples(retardance,dichroism and depolarization)by measuring certain polarimetric observables.One of these features,depolarization,is mainly produced by scattering on samples,which is a predominant efiect in turbid media as biological tissues.In turn,retardance and dichroic efiects are produced by tissue anisotropies and can lead to depolarization too.Since depolarization is a predominant efiect in tissue samples,we focus on studying difierent depolarization metrics for biomedical applications.We report the suitability of a set of depolarizing observables,the indices of polarimetric purity(IPPs),for biological tissue inspection.We review some results where we demonstrate that IPPs lead to better performance than the depolarization index,which is a well-established and commonly used depolarization observable in the literature.We also provide how IPPs are able to significantly enhance contrast between difierent tissue structures and even to reveal structures hidden by using standard intensity images.Finally,we also explore the classificatory potential of IPPs and other depolarizing observables for the discrimination of difierent tissues obtained from ex vivo chicken samples(muscle,tendon,myotendinous junction and bone),reaching accurate models for tissue classification.
基金supported by Fondo Nacional de Desarrollo Científico y Tecnológico(FONDECYT)#1200836,#1210644,and#1240888,and Agencia Nacional de Investigación y Desarrollo(ANID)-FONDAP#15130011(to LL)FONDECYT#3230227(to MFG).
文摘Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.
基金supported by PTDC-01778/2022-NeuroDev3D,iNOVA4Health(UIDB/04462/2020 and UIDP/04462/2020)LS4FUTURE(LA/P/0087/2020)。
文摘Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no exception.Cell-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these forces.Intrinsic and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse formation.In the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called plasticity.Synaptic plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
文摘Aortic regurgitation(AR)poses distinct challenges in interventional cardiology,necessitating novel approaches for treatment.This editorial examined the evolving landscape of transcatheter aortic valve replacement(TAVR)as an alternative therapeutic strategy for AR,particularly in patients deemed high risk for surgery.We explored the anatomical and patho-physiological disparities between AR and aortic stenosis(AS)and elucidates the technical nuances of TAVR procedures in AR pa-tients,emphasizing the need for precise prosthesis positioning and considerations for excessive stroke volume.Additionally,we discussed the safety and efficacy of TAVR compared to SAVR in AR management,drawing insights from recent case series and registry data.Notably,dedicated TAVR devices tailored for AR,such as the J-Valve and JenaValve,demonstrate promising out-comes in reducing residual AR and ensuring procedural success.Conversely,“off-label”TAVR devices,including balloon-ex-pandable and self-expandable platforms,offer feasible alternatives-particularly for large aortic annuli-with favorable device suc-cess rates and low residual AR rates.We highlighted the need for further research,including randomized trials,to delineate the definitive role of TAVR in AR treatment and to address remaining questions regarding device selection and long-term outcomes.In conclusion,TAVR emerges as a viable option for patients with AR,particularly those facing high surgical risks or frailty,with ongoing investigations poised to refine its position in the therapeutic armamentarium.
基金supported by Grants from Spanish FEDER/Science and Innovation Ministry I+D+i-RETOS-PID2021-124801NB-100Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas(CIBERN ED+1 种基金an initiative of the ISCIII)[PI2016/01]the Fundocion Ramon Areces and Banco Santander to the CBMSO(to FW)。
文摘Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and function.This cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino acids.This process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein markers.Some of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).
文摘BACKGROUND Autoimmune liver disease(AILD)recurrence is common after liver transplantation(LT).While several risk factors for recurrence have been identified,their combined predictive value has yet to be thoroughly investigated.AIM To evaluate the combined predictive value of clinical and laboratory risk factors for AILD recurrence after LT.METHODS This retrospective cohort study included 79 patients with AILD who underwent LT at a single liver transplant center.We compared clinical and laboratory variables between patients with and without recurrent disease and assessed the predictive performance of these factors using four logistic regression models and their corresponding area underthe receiver operating characteristic curve (AUC).RESULTSRecurrent AILD occurred in 26.58% of patients (95%CI: 17-38), the median time to recurrence was 28 months(interquartile range: 16-38). Patients with recurrent AILD had significantly higher pre-transplant Child-Pugh scores[11.61 ± 1.16 vs 10.58 ± 1.96 points;odds ratio (OR) = 1.43, 95%CI: 1.03-2.00;P = 0.032] and model for end-stage liverdisease score (MELD) (22.76 ± 5.47 vs 18.81 ± 7.24 points;OR = 1.08, 95%CI: 1.01-1.16;P = 0.032), compared to thosewithout recurrence. Additionally, baseline alanine aminotransferase (ALT) > 2 times the upper limit of normal(ULN) was significantly associated with recurrence (31% vs 57.1%;OR = 2.96, 95%CI: 1.06-8.28;P = 0.038). Ourmodels, incorporating several risk variables, demonstrated moderate predictive ability for AILD recurrence. TheAUCs were as follows: (1) Model 1 (AUC = 0.75, 95%CI: 0.58-0.87);(2) Model 2 (AUC = 0.74, 95%CI: 0.59-0.90);(3)Model 3 (AUC = 0.72, 95%CI: 0.58-0.88);and (4) Model 4 (AUC = 0.63, 95%CI: 0.40-0.76), with no statisticallysignificant difference between the models (P = 0.488).CONCLUSIONHigher pre-transplant Child-Pugh and MELD scores, as well as ALT > 2 ULN, were associated with an increasedrisk of AILD recurrence.
基金funded by the Alexander von Humboldt Stiftungsupported by DFG (SCH W534/6-1 to SWS)
文摘The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage.The latter involves global alterations,making understanding plastic responses triggered by local damage difficult.One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche,the subgranular zone,and beyond neurogenesis,newly born granule cells may maintain a“young”phenotype throughout life,adding to the plastic nature of the structure.Here,we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells.A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus,which evoked a foreign body reaction of astrocytes,along with the activation of local young neurons expressing doublecortin.Forty-eight hours after foreign body placement,the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body,whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus.Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus.Seven days after foreign body placement in the dentate gyrus,the increase in doublecortin-immunoreactivity was no longer observed,indicating the transient activation of young cells.However,7 days after foreign body placement,the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions.As calbindin is a marker for mature granule cells,this result suggests that activated young cells remain at a more immature stage following foreign body placement.Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement.This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity,specifically of newly born neurons under controlled in vitro conditions.
文摘Alzheimer's disease (AD) is characterized by an imbalance between excitatory and inhibitory brain networks,leading to aberrant homeostatic synaptic plasticity.AD has progressively been recognized as syna ptopathy and syna ptic dysfunction has been identified as a key component of its pathogenesis (Schirinzi et al.,2020).Syna ptic dysfunction is believed to precede synapse loss,a primary biological correlate of cognitive decline in AD,inevita bly associated with neuronal death.
文摘BACKGROUND Neonatal screening(NS)is a public health policy to identify genetic pathologies such as cystic fibrosis(CF),sickle cell disease,and other diseases.Sickle cell disea-se is the comprehensive term for a group of hemoglobinopathies characterized by the presence of hemoglobin S.CF is an autosomal recessive multisystemic disease with pathophysiology involving deleterious mutations in the transmembrane re-gulatory gene that encodes a protein that regulates the activity of chloride and sodium channels in the cell surface epithelium.NS is crucial for early diagnosis and management,which ensures a better quality of life.AIM To report a case of the coexistence of sickle cell anemia(SCA)and CF and perform an integrative literature review.METHODS This is an observational study and a review of the literature focusing on two rare genetic pathologies identified simultaneously in NS from the perspective of a clinical case.The authors identified only 5 cases of SCA associated with CF.No clinical trials or review articles were identified considering the rarity of the coexistence of these two pathologies.RESULTS Herein,the authors reported the case of a girl who after undergoing NS on day 8 of life was diagnosed with SCA with an alteration in the dosage of immunoreactive trypsin.The diagnosis of CF was confirmed by the Coulometry Sweat Test.The rarity of the co-occurrence of these two severe genetic pathologies(CF and SCA)is a challenge for medical science.CONCLUSION This study adds to the few case reports present in the literature that highlight the identification of two severe diseases via NS.
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
