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1.
Clin Psychol Psychother ; 31(3): e2985, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706162

RESUMO

BACKGROUND: Taking patient preference into consideration has received increased attention in the last decades. We conducted a meta-analysis to estimate the effects of patient preference on clinical outcome, satisfaction and adherence regarding treatment of depression and anxiety. METHODS: Pubmed, Embase, PsycINFO and Scopus were searched for (cluster) randomized controlled trials. Twenty-six randomized controlled clinical trials were included, comprising 3670 participants, examining the effect of patient preference regarding treatment of anxiety and depression on clinical outcome, satisfaction and/or adherence. RESULTS: No effect of patient preference was found on clinical outcome [d = 0.06, 95% CI = (-0.03, 0.15), p = 0.16, n = 23 studies]. A small effect of patient preference was found on treatment satisfaction [d = 0.33, 95% CI = (0.08, 0.59), p = 0.01, n = 6 studies] and on treatment adherence [OR = 1.55, 95% CI = (1.28, 1.87), p < 0.001, n = 22 studies]. LIMITATIONS: Patient preference is a heterogeneous concept, future studies should strive to equalize operationalization of preference. Subgroup analyses within this study should be interpreted with caution because the amount of studies per analysed subgroup was generally low. Most studies included in this meta-analysis focused on patients with depression. The small number of studies (n = 6) on satisfaction, prevents us from drawing firm conclusions. CONCLUSIONS: While this meta-analysis did not find a positive effect of considering patient preference on clinical outcome, it was associated with slightly better treatment satisfaction and adherence. Accommodating preference of patients with anxiety and depression can improve treatment. TRIAL REGISTRATION: PROSPERO: CRD42020172556.


Assuntos
Transtornos de Ansiedade , Transtorno Depressivo , Preferência do Paciente , Satisfação do Paciente , Humanos , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/terapia , Transtorno Depressivo/psicologia , Transtorno Depressivo/terapia , Preferência do Paciente/psicologia , Preferência do Paciente/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Cooperação e Adesão ao Tratamento/psicologia , Cooperação e Adesão ao Tratamento/estatística & dados numéricos , Resultado do Tratamento
2.
Microbiology (Reading) ; 170(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38739436

RESUMO

Endolysins are bacteriophage (or phage)-encoded enzymes that catalyse the peptidoglycan breakdown in the bacterial cell wall. The exogenous action of recombinant phage endolysins against Gram-positive organisms has been extensively studied. However, the outer membrane acts as a physical barrier when considering the use of recombinant endolysins to combat Gram-negative bacteria. This study aimed to evaluate the antimicrobial activity of the SAR-endolysin LysKpV475 against Gram-negative bacteria as single or combined therapies, using an outer membrane permeabilizer (polymyxin B) and a phage, free or immobilized in a pullulan matrix. In the first step, the endolysin LysKpV475 in solution, alone and combined with polymyxin B, was tested in vitro and in vivo against ten Gram-negative bacteria, including highly virulent strains and multidrug-resistant isolates. In the second step, the lyophilized LysKpV475 endolysin was combined with the phage phSE-5 and investigated, free or immobilized in a pullulan matrix, against Salmonella enterica subsp. enterica serovar Typhimurium ATCC 13311. The bacteriostatic action of purified LysKpV475 varied between 8.125 µg ml-1 against Pseudomonas aeruginosa ATCC 27853, 16.25 µg ml-1 against S. enterica Typhimurium ATCC 13311, and 32.50 µg ml-1 against Klebsiella pneumoniae ATCC BAA-2146 and Enterobacter cloacae P2224. LysKpV475 showed bactericidal activity only for P. aeruginosa ATCC 27853 (32.50 µg ml-1) and P. aeruginosa P2307 (65.00 µg ml-1) at the tested concentrations. The effect of the LysKpV475 combined with polymyxin B increased against K. pneumoniae ATCC BAA-2146 [fractional inhibitory concentration index (FICI) 0.34; a value lower than 1.0 indicates an additive/combined effect] and S. enterica Typhimurium ATCC 13311 (FICI 0.93). A synergistic effect against S. enterica Typhimurium was also observed when the lyophilized LysKpV475 at ⅔ MIC was combined with the phage phSE-5 (m.o.i. of 100). The lyophilized LysKpV475 immobilized in a pullulan matrix maintained a significant Salmonella reduction of 2 logs after 6 h of treatment. These results demonstrate the potential of SAR-endolysins, alone or in combination with other treatments, in the free form or immobilized in solid matrices, which paves the way for their application in different areas, such as in biocontrol at the food processing stage, biosanitation of food contact surfaces and biopreservation of processed food in active food packing.


Assuntos
Antibacterianos , Endopeptidases , Glucanos , Polimixina B , Fagos de Salmonella , Endopeptidases/farmacologia , Endopeptidases/química , Endopeptidases/metabolismo , Polimixina B/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Fagos de Salmonella/genética , Fagos de Salmonella/fisiologia , Fagos de Salmonella/química , Glucanos/química , Glucanos/farmacologia , Animais , Testes de Sensibilidade Microbiana , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/virologia , Camundongos , Salmonella typhimurium/virologia , Salmonella typhimurium/efeitos dos fármacos , Bacteriófagos/fisiologia , Bacteriófagos/genética , Proteínas Virais/genética , Proteínas Virais/metabolismo , Proteínas Virais/farmacologia , Proteínas Virais/química
3.
Curr Issues Mol Biol ; 46(4): 3424-3437, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38666945

RESUMO

Escherichia coli phytase (AppA) is widely used as an exogenous enzyme in monogastric animal feed mainly because of its ability to degrade phytic acid or its salt (phytate), a natural source of phosphorus. Currently, successful recombinant production of soluble AppA has been achieved by gene overexpression using both bacterial and yeast systems. However, some methods for the biomembrane immobilization of phytases (including AppA), such as surface display on yeast cells and bacterial spores, have been investigated to avoid expensive enzyme purification processes. This study explored a homologous protein production approach for displaying AppA on the cell surface of E. coli by engineering its outer membrane (OM) for extracellular expression. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of total bacterial lysates and immunofluorescence microscopy of non-permeabilized cells revealed protein expression, whereas activity assays using whole cells or OM fractions indicated functional enzyme display, as evidenced by consistent hydrolytic rates on typical substrates (i.e., p-nitrophenyl phosphate and phytic acid). Furthermore, the in vitro results obtained using a simple method to simulate the gastrointestinal tract of poultry suggest that the whole-cell biocatalyst has potential as a feed additive. Overall, our findings support the notion that biomembrane-immobilized enzymes are reliable for the hydrolysis of poorly digestible substrates relevant to animal nutrition.

4.
Arch Endocrinol Metab ; 68: e230502, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578472

RESUMO

Hyperprolactinemia is a frequent cause of menstrual irregularity, galactorrhea, hypogonadism, and infertility. The most common etiologies of hyperprolactinemia can be classified as physiological, pharmacological, and pathological. Among pathological conditions, it is essential to distinguish prolactinomas from other tumors and pituitary lesions presenting with hyperprolactinemia due to pituitary stalk disconnection. Proper investigation considering clinical data, laboratory tests, and, if necessary, imaging evaluation, is important to identify the correctcause of hyperprolactinemia and manage the patient properly. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Societyof Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and medication-induced hyperprolactinemia in women.


Assuntos
Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Gravidez , Humanos , Feminino , Hiperprolactinemia/diagnóstico , Neoplasias Hipofisárias/diagnóstico , Brasil , Prolactina , Prolactinoma/diagnóstico
5.
Arch Endocrinol Metab ; 68: e230504, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578473

RESUMO

Dopamine agonists are the first line of treatment for patients with symptomatic hyperprolactinemia due to prolactinomas and in those with idiopathic hyperprolactinemia. Treatment with these agents is effective in 80%-90% of the cases. Infertility treatment of patients with hyperprolactinemia is also carried out with dopamine agonists, aiming for the normalization of prolactin levels. The risk of symptomatic growth of prolactinomas during pregnancy is dependent on the tumor's size, duration of previous treatments, and prolactin levels. Notably, the corresponding risk is relatively low in cases of microprolactinomas (<5%). Remission of hyperprolactinemia occurs in about 30% of the patients after drug treatment and may also occur after pregnancy and menopause. The use of some drugs, such as antidepressants and antipsychotics, is a frequent cause of hyperprolactinemia, and managing this occurrence involves unique considerations. This position statement by the Brazilian Federation of Gynecology and Obstetrics Associations (Febrasgo) and Brazilian Society of Endocrinology and Metabolism (SBEM) addresses the recommendations for measurement of serum prolactin levels and the investigations of symptomatic and asymptomatic hyperprolactinemia and drug-induced hyperprolactinemia in women.


Assuntos
Hiperprolactinemia , Neoplasias Hipofisárias , Prolactinoma , Gravidez , Humanos , Feminino , Hiperprolactinemia/tratamento farmacológico , Prolactinoma/terapia , Agonistas de Dopamina/efeitos adversos , Prolactina , Neoplasias Hipofisárias/terapia , Brasil
6.
J Sex Marital Ther ; 50(4): 542-553, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38482856

RESUMO

Hypoactive sexual desire dysfunction (HSDD) is prevalent among women. This retrospective cohort study aimed to verify the results of the strategies used by Gynecologists and Obstetricians (Ob-gyn) residents in the management of female HSDD. For this, we conducted a data collection of patient medical records of women with HSDD from the Human Sexuality Studies outpatient clinic of the Human Reproduction Center, Department of Gynecology and Obstetrics of FMRP-USP, from 2005 to 2019. Among the 437 women included, 361 (82.6%) answered the question concerning the effect of the protocol to which they were submitted, whereas 234 (64.8%) reported improvements in sexual desire. The univariate model showed that patients without chronic pelvic pain were 19.0% less likely to report improvements in HSDD than those with chronic pelvic pain (p = 0.03). Patients without depression and without orgasmic dysfunction were, respectively 32% and 23% more likely to show improvements in their HSDD than those who had depression or orgasmic dysfunction (respectively p = 0.001, p = 0.008). However, the multivariate model did not identify any associations. The assistance regarding HSDD by the Ob-gyn resident in training to deal with female sexual complaints may be effective in improving sexual complaints.


Assuntos
Disfunções Sexuais Psicogênicas , Saúde Sexual , Humanos , Feminino , Disfunções Sexuais Psicogênicas/terapia , Adulto , Estudos Retrospectivos , Saúde da Mulher , Ginecologia , Pessoa de Meia-Idade , Libido , Disfunções Sexuais Fisiológicas/terapia , Obstetrícia , Dor Pélvica/terapia
7.
JBRA Assist Reprod ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546118

RESUMO

OBJECTIVE: To evaluate the impact of possible maternal and paternal prognostic factors and ovarian stimulation protocols on clinical pregnancy and live birth rates in intrauterine insemination (IUI) cycles. METHODS: Retrospective observational study of 341 IUI cycles performed from January 2016 to November 2020 at the Assisted Reproduction Service of the Clinics Hospital of the Ribeirão Preto Medical School, University of São Paulo. Clinical pregnancy and live birth rates and their potential prognostic factors were evaluated. Wilcoxon's non-parametric test was used to compare quantitative variables, and the chi-square test to compare qualitative variables, adopting a significance level of p<0.05. A logistic regression model was performed to verify which exploratory variables are predictive factors for pregnancy outcome. RESULTS: The ovulation induction protocol using gonadotropins plus letrozole (p=0.0097; OR 4.3286, CI 1.3040 - 14.3684) and post-capacitation progressive sperm ≥ 5million/mL (p=0.0253) showed a statistically significant correlation with the live birth rate. Female and male age, etiology of infertility, obesity, multifollicular growth, endometrial thickness ≥ 7 mm, and time between human chorionic gonadotropin administration and IUI performance were not associated with the primary outcomes. In the group of patients with ideal characteristics (women aged< 40 years, BMI < 30 kg/m2, antral follicle count ≥ 5, partner aged< 45 years, and post-capacitation semen with progressive spermatozoa ≥ 5 million/mL), the rate of clinical pregnancy was 14.8%, while that of live birth, 9.9%. CONCLUSIONS: In this study, the ovulation induction protocol with gonadotropins plus letrozole and post-capacitation progressive sperm ≥ 5 million/mL were the only variables that significantly correlated with intrauterine insemination success.

8.
Neurología (Barc., Ed. impr.) ; 39(2): 105-116, Mar. 2024. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-230865

RESUMO

Introducción El síndrome de pseudotumor cerebri (SPTC) en pacientes prepuberales presenta características que lo diferencian respecto a su presentación en la etapa pospuberal. Nuestro objetivo es describir las características de los pacientes diagnosticados de SPTC pediátrico en nuestro centro y compararlas en función de su estado puberal. Pacientes y métodos Se incluyeron a los pacientes diagnosticados de SPTC en un hospital de tercer nivel entre los años 2006 y 2019 con edades comprendidas entre uno y 18 años que cumplieran los criterios diagnósticos actualizados del SPTC. Se clasificaron en función de su estado puberal y peso corporal. Posteriormente, se analizaron los datos de las punciones lumbares, estudios de neuroimagen, valoraciones oftalmológicas, así como el régimen terapéutico recibido a lo largo de su seguimiento. Resultados Se recogieron 28 pacientes, 22 prepuberales y seis pospuberales, con edad media de 9,04 ± 2,86 años. El 83,3% de los pacientes pospuberales eran varones presentando sobrepeso/obesidad en el 66,7%. Eran varones el 27% de los pacientes prepuberales, de ellos asociaban sobrepeso el 31,8%. La sintomatología más frecuente fue cefalea (89,9%) y visión borrosa (42,9%). Todos los pacientes presentaron papiledema; un 21,4% de los casos presentaron parálisis del VI par. Se identificó un posible desencadenante en un 28,6%. El 19% presentaron recurrencia clínica, siendo todos ellos prepuberales. La resolución clínica completa se produjo en el 55,6% de los pacientes. Conclusión Pacientes con SPTC presentan menor prevalencia de obesidad en la etapa prepuberal, junto con un mayor porcentaje de etiologías secundarias y tasa de recurrencia que los pacientes pospuberales. (AU)


Introduction Pseudotumor cerebri (PC) in prepubertal patients displays certain characteristics that differentiate it from its presentation at the postpubertal stage. The aim of this study is to describe the characteristics of paediatric patients diagnosed with PC at our centre and to compare them according to their pubertal status. Patients and methods We included patients aged between 1 and 18 years who were diagnosed with PC in a tertiary-level hospital between 2006 and 2019 and who met the updated diagnostic criteria for PC. They were classified according to body weight and pubertal status. Subsequently, we analysed results from lumbar punctures, neuroimaging studies, ophthalmological assessments, and treatments received during follow-up. Results We included 28 patients, of whom 22 were of prepubertal age and 6 were of postpubertal age. The mean age (standard deviation) was 9.04 (2.86) years. Among the postpubertal patients, 83.3% were boys, 66.7% of whom presented overweight/obesity. In the group of prepubertal patients, 27% were boys, 31.8% of whom were overweight. The most frequent symptoms were headache (89.9%) and blurred vision (42.9%). All patients presented papilloedema, and 21.4% manifested sixth nerve palsy. Possible triggers were identified in 28.6% of cases. Nineteen percent of patients presented clinical recurrence, all of whom were prepubertal patients. Complete clinical resolution was achieved in 55.6% of patients. Conclusion Prepubertal patients with PC show lower prevalence of obesity, higher prevalence of secondary aetiologies, and higher recurrence rates than postpubertal patients. (AU)


Assuntos
Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Pseudotumor Cerebral , Obesidade , Puberdade , Estudos Longitudinais , Estudos Retrospectivos
9.
Neurologia (Engl Ed) ; 39(2): 105-116, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38272258

RESUMO

INTRODUCTION: Pseudotumor cerebri (PC) in prepubertal patients displays certain characteristics that differentiate it from its presentation at the postpubertal stage. The aim of this study is to describe the characteristics of paediatric patients diagnosed with PC at our centre and to compare them according to their pubertal status. PATIENTS AND METHODS: We included patients aged between 1 and 18 years who were diagnosed with PC in a tertiary-level hospital between 2006 and 2019 and who met the updated diagnostic criteria for PC. They were classified according to body weight and pubertal status. Subsequently, we analysed results from lumbar punctures, neuroimaging studies, ophthalmological assessments, and treatments received during follow-up. RESULTS: We included 28 patients, of whom 22 were of prepubertal age and 6 were of postpubertal age. The mean age (standard deviation) was 9.04 (2.86) years. Among the postpubertal patients, 83.3% were boys, 66.7% of whom presented overweight/obesity. In the group of prepubertal patients, 27% were boys, 31.8% of whom were overweight. The most frequent symptoms were headache (89.9%) and blurred vision (42.9%). All patients presented papilloedema, and 21.4% manifested sixth nerve palsy. Possible triggers were identified in 28.6% of cases. Nineteen percent of patients presented clinical recurrence, all of whom were prepubertal patients. Complete clinical resolution was achieved in 55.6% of patients. CONCLUSION: Prepubertal patients with PC show lower prevalence of obesity, higher prevalence of secondary aetiologies, and higher recurrence rates than postpubertal patients.


Assuntos
Pseudotumor Cerebral , Masculino , Humanos , Criança , Lactente , Pré-Escolar , Adolescente , Feminino , Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/epidemiologia , Sobrepeso/complicações , Estudos Retrospectivos , Prognóstico , Obesidade/complicações
10.
Environ Res ; 247: 118235, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266904

RESUMO

BACKGROUND: Since 2011, over 30 tropical Atlantic nations have experienced substantial landings of holopelagic Sargassum spp. Its decomposition results in the production of hydrogen sulfide (H2S), which, in elevated concentrations, can pose a threat to human health. This study aims to enhance our understanding of the temporal and spatial variability in H2S emissions during the decomposition of Sargassum on beaches. The primary objective is to assess potential exposure risks for local populations, tourists, and cleanup workers. METHODS: H2S levels were monitored using a SENKO sensor (SGTP-H2S; limit of detection 0.1-100 ppm; resolution 0.1 ppm) at four distances from Sargassum accumulation points of (0, 10, 30, and 40 m) in Puerto Morelos, Mexico, during 2022 and 2023. RESULTS: Elevated concentrations of H2S were detected beneath the Sargassum piles, with 23.5% of readings exceeding 5 ppm and occasional spikes above 100 ppm. Above the piles, 87.3% of the measurements remained below 2 ppm, and the remainder fell between 2.1 and 5.2 ppm. At 10 m from the shoreline, 90% of measurements registered below 0.1 ppm, and the remaining 10% were below 2 ppm. Readings at 30 and 40 m consistently recorded levels below 0.1 ppm. H2S concentrations positively correlated with Sargassum pile height, the temperature beneath the piles, and wind speed. CONCLUSIONS: Our findings suggest no immediate and significant exposure risk for residents or tourists. However, Sargassum cleanup workers face a higher exposure risk, potentially encountering concentrations above 5 ppm for nearly one-fourth of the working time.


Assuntos
Sulfeto de Hidrogênio , Sargassum , Humanos , Vento , Temperatura , México
11.
Int J Biol Macromol ; 259(Pt 2): 129330, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38218270

RESUMO

DEAD-box helicases are global regulators of liquid-liquid phase separation (LLPS), a process that assembles membraneless organelles inside cells. An outstanding member of the DEAD-box family is DDX3X, a multi-functional protein that plays critical roles in RNA metabolism, including RNA transcription, splicing, nucleocytoplasmic export, and translation. The diverse functions of DDX3X result from its ability to bind and remodel RNA in an ATP-dependent manner. This capacity enables the protein to act as an RNA chaperone and an RNA helicase, regulating ribonucleoprotein complex assembly. DDX3X and its orthologs from mouse, yeast (Ded1), and C. elegans (LAF-1) can undergo LLPS, driving the formation of neuronal granules, stress granules, processing bodies or P-granules. DDX3X has been related to several human conditions, including neurodevelopmental disorders, such as intellectual disability and autism spectrum disorder. Although the research into the pathogenesis of aberrant biomolecular condensation in neurodegenerative diseases is increasing rapidly, the role of LLPS in neurodevelopmental disorders is underexplored. This review summarizes current findings relevant for DDX3X phase separation in neurodevelopment and examines how disturbances in the LLPS process can be related to neurodevelopmental disorders.


Assuntos
Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Humanos , Animais , Camundongos , Transtorno do Espectro Autista/genética , Caenorhabditis elegans/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Transtornos do Neurodesenvolvimento/genética , RNA/metabolismo , Saccharomyces cerevisiae/metabolismo
12.
Antioxidants (Basel) ; 13(1)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38275659

RESUMO

Ultraviolet (UV) radiation harms the skin, causing oxidative damage, inflammation, and disruption of the skin's barrier function. There is considerable interest in identifying new natural ingredients with antioxidant and anti-inflammatory properties to serve as adjuvants in sunscreens. The flavonoid morin (1) can undergo structural modifications to enhance its biological properties. The aim of this study was to synthesize two new morin-Schiff base derivatives, morin oxime (2) and morin semicarbazone (3), comparing their photoprotective effects with that of the parent compound on UVB-exposed HaCaT keratinocytes. The chemical structure of the novel compounds was revealed based on spectroscopic data analysis. Our findings demonstrated that derivatives 2 and 3 enhanced the light absorption capability in the UV-visible (vis) range compared to 1. Tested compounds exhibited a higher scavenger capacity than Trolox. Moreover, pre-treatment with all compounds protected HaCaT cells from UVB-induced cell death. Compound 3 demonstrated the strongest antioxidant effect, reducing reactive oxygen species (ROS) generation and, subsequently, malondialdehyde (MDA) levels. Additionally, compounds 2 and 3 exhibited greater anti-inflammatory effects than compound 1, significantly reducing interleukin (IL)-6 production levels at all tested concentrations. These findings have demonstrated, for the first time, a promising photoprotective activity of two new Schiff base derivatives and suggest their use as natural sunscreen ingredients.

13.
Appl Microbiol Biotechnol ; 108(1): 152, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38183477

RESUMO

Trichothecenes are a structurally diverse family of toxic secondary metabolites produced by certain species of multiple fungal genera. All trichothecene analogs share a core 12,13-epoxytrichothec-9-ene (EPT) structure but differ in presence, absence and types of substituents attached to various positions of EPT. Formation of some of the structural diversity begins early in the biosynthetic pathway such that some producing species have few trichothecene biosynthetic intermediates in common. Cytochrome P450 monooxygenases (P450s) play critical roles in formation of trichothecene structural diversity. Within some species, relaxed substrate specificities of P450s allow individual orthologs of the enzymes to modify multiple trichothecene biosynthetic intermediates. It is not clear, however, whether the relaxed specificity extends to biosynthetic intermediates that are not produced by the species in which the orthologs originate. To address this knowledge gap, we used a mutant complementation-heterologous expression analysis to assess whether orthologs of three trichothecene biosynthetic P450s (TRI11, TRI13 and TRI22) from Fusarium sporotrichioides, Trichoderma arundinaceum, and Paramyrothecium roridum can modify trichothecene biosynthetic intermediates that they do not encounter in the organism in which they originated. The results indicate that TRI13 and TRI22 could not modify the intermediates that they do not normally encounter, whereas TRI11 could modify an intermediate that it does not normally encounter. These findings indicate that substrate promiscuity varies among trichothecene biosynthetic P450s. One structural feature that likely impacts the ability of the P450s to use biosynthetic intermediates as substrates is the presence and absence of an oxygen atom attached to carbon atom 3 of EPT.


Assuntos
Sistema Enzimático do Citocromo P-450 , Tricotecenos , Especificidade por Substrato , Sistema Enzimático do Citocromo P-450/genética , Metabolismo Secundário
14.
Ecology ; 105(1): e4198, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37897690

RESUMO

Belowground niche partitioning presents a key mechanism for maintaining species coexistence and diversity. Its importance is currently reinforced by climate change that alters soil hydrological conditions. However, experimental tests examining the magnitude of its change under climate change are scarce. We combined measurements of oxygen stable isotopes to infer plant water-uptake depths and extreme drought manipulation in grasslands. Belowground niche partitioning was evidenced by different water-uptake depths of co-occurring species under ambient and extreme drought conditions despite an increased overlap among species due to a shift to shallower soil layers under drought. A co-occurrence of contrasting strategies related to the change of species water-uptake depth distribution was likely to be key for species to maintain some extent of belowground niche partitioning and could contribute to stabilizing coexistence under drought. Our results suggest that belowground niche partitioning could mitigate negative effects on diversity imposed by extreme drought under future climate.


Assuntos
Secas , Plantas , Solo , Água , Mudança Climática , Pradaria
15.
Cancer Immunol Res ; 12(1): 91-106, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-37931247

RESUMO

Pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. The poor survival of patients with PDA has been attributed to a high rate of early metastasis and low efficacy of current therapies, which partly result from its complex immunosuppressive tumor microenvironment. Previous studies from our group and others have shown that tumor-associated macrophages (TAM) are instrumental in maintaining immunosuppression in PDA. Here, we explored the role of Notch signaling, a key regulator of immune response, within the PDA microenvironment. We identified Notch pathway components in multiple immune cell types within human and mouse pancreatic cancer. TAMs, the most abundant immune cell population in the tumor microenvironment, expressed high levels of Notch receptors, with cognate ligands such as JAG1 expressed on tumor epithelial cells, endothelial cells, and fibroblasts. TAMs with activated Notch signaling expressed higher levels of immunosuppressive mediators, suggesting that Notch signaling plays a role in macrophage polarization within the PDA microenvironment. Genetic inhibition of Notch in myeloid cells led to reduced tumor size and decreased macrophage infiltration in an orthotopic PDA model. Combination of pharmacologic Notch inhibition with PD-1 blockade resulted in increased cytotoxic T-cell infiltration, tumor cell apoptosis, and smaller tumor size. Our work implicates macrophage Notch signaling in the establishment of immunosuppression and indicates that targeting the Notch pathway may improve the efficacy of immune-based therapies in patients with PDA.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Macrófagos Associados a Tumor/metabolismo , Células Endoteliais/metabolismo , Transdução de Sinais , Microambiente Tumoral
16.
Behav Brain Res ; 460: 114817, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38122904

RESUMO

Environmental factors such as undernutrition and environmental enrichment can promote changes in the molecular and behavioural mechanisms related to cognition. Herein, we investigated the effect of enriched environment stimulation in rats that were malnourished in the pre- and postnatal periods on changes in the gene expression of brain-derived neurotrophic factor and its receptor in the hippocampus, as well as on anxiety traits and memory. Early undernutrition promoted weight reduction, increased the risk analysis, reduced permanence in the open arm of the elevated plus-maze and induced a reduction in the gene expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B. However, exposure to an enriched environment from 30 to 90 days' old maintained the malnourished phenotype, leading to weight reduction in the control group. In addition, the enriched environment did not alter the risk assessment in the undernourished group, but it did increase the frequency of labyrinth entries. Sixty-day exposure to the enriched environment resulted in a reversal in the gene expression of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus of malnourished rats and favoured of long-term memory in the object recognition test in the open-field. These results suggest that an enriched environment may have a protective effect in adult life by inducing changes in long-term memory and anxiety traits in animals that were undernourished in early life. Furthermore, reversing these effects of undernutrition involves mechanisms linked to the molecular signalling of brain-derived neurotrophic factor and tropomyosin receptor kinase B in the hippocampus.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Desnutrição , Gravidez , Feminino , Ratos , Animais , Masculino , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Tropomiosina/metabolismo , Meio Ambiente , Ansiedade , Vitaminas , Desnutrição/complicações , Desnutrição/metabolismo , Hipocampo/metabolismo , Redução de Peso , Receptor trkB/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-37962996

RESUMO

Interpretability of neural networks (NNs) and their underlying theoretical behavior remain an open field of study even after the great success of their practical applications, particularly with the emergence of deep learning. In this work, NN2Poly is proposed: a theoretical approach to obtain an explicit polynomial model that provides an accurate representation of an already trained fully connected feed-forward artificial NN a multilayer perceptron (MLP). This approach extends a previous idea proposed in the literature, which was limited to single hidden layer networks, to work with arbitrarily deep MLPs in both regression and classification tasks. NN2Poly uses a Taylor expansion on the activation function, at each layer, and then applies several combinatorial properties to calculate the coefficients of the desired polynomials. Discussion is presented on the main computational challenges of this method, and the way to overcome them by imposing certain constraints during the training phase. Finally, simulation experiments as well as applications to real tabular datasets are presented to demonstrate the effectiveness of the proposed method.

18.
Rev Bras Ginecol Obstet ; 45(10): e575-e583, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37944924

RESUMO

OBJECTIVE: In the present study, our aim was to translate, adapt, and validate the Pelvic Health History Form (a quality of life [QoL] questionnaire) of the International Pelvic Pain Society (IPPS) from English to Portuguese. METHODS: The study was approved by the Ethics and Research Committee (CEP, in the Portuguese acronym) and the IPPS. The "Transcultural Adaptation" method comprised 5 stages: translation, synthesis, backtranslation, expert review, and pretest. Cultural adaptation and validation included cognitive interviews and statistical analysis of unanswered items (> 15%) in 14 clinic patients from CPP and endometriosis clinic at Santa Casa de São Paulo. RESULTS: Strong equivalences were established between the USA and Brazil questionnaires in terms of semantics, idioms, experiences, and concepts. Eighteen culturally inappropriate items were identified and adjusted using the revised response rate index. The subjective form underwent rigorous assessments, confirming its accurate measurement of intended targets. CONCLUSION: The methodology showed efficiency and equivalence, confirming its validity. The user-friendly format and inclusion of translated, adapted, and validated instruments in Portuguese make the form valuable for evaluating pelvic health, with potential for future research.


OBJETIVO: Realizar a tradução, adaptação e validação do questionário de qualidade de vida Pelvic Health History Form da International Pelvic Pain Society (IPPS, na sigla em inglês) para a língua portuguesa. MéTODOS: Aprovação do Comitê de Ética e Pesquisa (CEP) e consentimento do IPPS. A metodologia "Adaptação Transcultural" foi utilizada em cinco etapas: (I) tradução; (II) síntese; (III) retradução; (IV) revisão pelo comitê de especialistas; (V) pré-teste, seguido de adaptação cultural e validação por meio de entrevista cognitiva e análise estatística da taxa de ausência de respostas > 15% após aplicação do instrumento em 14 pacientes do ambulatório de DPC e endometriose da Santa Casa de São Paulo. RESULTADOS: Equivalências semântica, idiomática, experiencial e conceitual entre o questionário de país fonte (EUA) e alvo (Brasil) foram bem estabelecidas. Dezoito itens culturalmente impróprios, de acordo com o índice de ausência de respostas revisados, adaptados e realizada validade de face e de constructo, avaliando forma subjetiva, confiável que o instrumento mede o que pretende medir. CONCLUSãO: A metodologia utilizada foi eficiente, com boa equivalência com o material de origem concluindo a sua validade. Formulário de formato simples, fácil aplicação e compreensão, composto por diversos instrumentos já traduzidos, adaptados e validados em nossa língua. O formulário auxilia avaliação multidimensional da saúde pélvica destas pacientes e poderá ser utilizado em estudos futuros.


Assuntos
Dor Pélvica , Qualidade de Vida , Feminino , Humanos , Portugal , Brasil , Inquéritos e Questionários , Dor Pélvica/diagnóstico
20.
PeerJ ; 11: e16345, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37953770

RESUMO

Southern Mexico's tropical forests are home to the country's highest richness of mammal species; La Chinantla region is situated within this area, its name from the indigenous group residing in the area and holding territorial ownership, namely the Chinantecos. In La Chinantla, there are no Protected Areas; instead, there are Areas Destined Voluntarily for Conservation (ADVC) and "Voluntary Conservation Areas" (VCA), that are managed by local inhabitants through social consensus. These ADVC may function as an archipelago reserve, which represents regional diversity, including the social context, through complementarity. To verify its biodiversity, we analyzed the richness, composition, distribution, and conservation of wild mammals in the region. Records were obtained from four sources-primary data collection, databases, scientific literature, and community monitoring-and were organized into four zones based on altitudinal and vegetation gradients. We compared the diversity between zones for three categories of mammals: small (<100 gr.), bats, and medium and large (>100 gr.). 134 species were identified comprising 11 orders, 26 families and 86 genera. The zone with highest elevation presented the greatest species richness for the assemblage of mammals and terrestrial mammals, while the zone with the lowest elevation had the highest richness of bats. For each mammal category, the zone with the most species also registered the highest number of exclusive species. For the assemblage of mammals and for medium and large mammals, the similarity index was highest between the two intermediate zones, while for small mammals and bats, the greatest similarity occurred between the areas of higher altitude. The study region was found to have the second highest richness of mammals in Mexico. Finally, we suggest that the conservation proposals by indigenous people could function as a set of "islands" that promote the conservation of biodiversity, possibly as an Archipelago Reserve.


Assuntos
Quirópteros , Humanos , Animais , México , Biodiversidade , Mamíferos , Florestas
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