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1.
Int J Mol Sci ; 25(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38673947

RESUMO

Phyllotreta striolata, the striped flea beetle, is one of the most destructive pests in Brassicaceae plants worldwide. Given the drawbacks associated with long-term use of chemical insecticides, green strategies based on chemical ecology are an effective alternative for beetle control. However, the lack of information on beetle ecology has hindered the development of effective biocontrol strategies. In this report, we identified two odorants, (S)-cis-verbenol and (-)-verbenone, which displayed significant attraction for P. striolata (p < 0.05), indicating their great potential for P. striolata management. Using the Drosophila "empty neuron" system, an antenna-biased odorant receptor, PstrOR17, was identified as responsible for the detection of (-)-verbenone and (S)-cis-verbenol. Furthermore, the interactions between PstrOR17 and (-)-verbenone or (S)-cis-verbenol were predicted via modeling and molecular docking. Finally, we used RNAi to confirm that PstrOR17 is essential for the detection of (-)-verbenone and (S)-cis-verbenol to elicit an attraction effect. Our results not only lay a foundation for the development of new and effective nonchemical insecticide strategies based on (S)-cis-verbenol and (-)-verbenone, but also provide new insight into the molecular basis of odorant recognition in P. striolata.


Assuntos
Monoterpenos Bicíclicos , Besouros , Receptores Odorantes , Animais , Antenas de Artrópodes/efeitos dos fármacos , Antenas de Artrópodes/metabolismo , Monoterpenos Bicíclicos/farmacologia , Besouros/efeitos dos fármacos , Besouros/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , Simulação de Acoplamento Molecular , Monoterpenos/química , Monoterpenos/farmacologia , Odorantes , Receptores Odorantes/genética , Receptores Odorantes/metabolismo
2.
Pest Manag Sci ; 80(7): 3603-3611, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38458148

RESUMO

BACKGROUND: The Asian tiger mosquito, Aedes albopictus, is a competent vector for the spread of several viral arboviruses including dengue, chikungunya, and Zika. Several vital mosquito behaviors linked to survival and reproduction are primarily dependent on a sophisticated olfactory system for semiochemical perception. However, a limited number of studies has hampered our understanding of the relationship between the A. albopictus acute olfactory system and the complex chemical world. RESULTS: Here, we performed a qRT-PCR assay on antennae from A. albopictus of differing sex, age and physiological states, and found that AalbOr10 was enriched in blood-fed female mosquitoes. We then undertook single sensillum recording to de-orphan AalbOr10 using a panel of physiologically and behaviorally relevant odorants in a Drosophila 'empty neuron' system. The results indicated that AalbOr10 was activated by seven aromatic compounds, all of which hampered egg-laying in blood-fed mosquitoes. Furthermore, using a post-RNA interference oviposition assay, we found that reducing the transcript level of AalbOr10 affected repellent activity mediated by 2-ethylphenol at low concentrations (10-4 vol/vol). Computational modeling and molecular docking studies suggested that hydrogen bonds to Y68 and Y150 mediated the interaction of 2-ethylphenol with AalbOr10. CONCLUSION: We reveal a potential link between aromatics-induced oviposition repellency behaviors and a specific odorant receptor in A. albopictus. Our findings provide a foundation for identifying active semiochemicals for the monitoring or controlling of mosquito populations. © 2024 Society of Chemical Industry.


Assuntos
Aedes , Repelentes de Insetos , Oviposição , Receptores Odorantes , Animais , Aedes/efeitos dos fármacos , Aedes/genética , Aedes/fisiologia , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Oviposição/efeitos dos fármacos , Feminino , Repelentes de Insetos/farmacologia , Masculino , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Simulação de Acoplamento Molecular , Antenas de Artrópodes/efeitos dos fármacos , Antenas de Artrópodes/fisiologia
3.
Pestic Biochem Physiol ; 194: 105490, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532317

RESUMO

Aedes aegypti is responsible for transmitting a variety of arboviral infectious diseases such as dengue and chikungunya. Insecticides, particularly pyrethroids, are used widely for mosquito control. However, intensive used of pyrethroids has led to the selection of kdr mutations on sodium channels. L982W, locating in the PyR1 (Pyrethroid receptor site 1), was first reported in Ae. aegypti populations collected from Vietnam. Recently, the high frequency of L982W was detected in pyrethroid-resistant populations of Vietnam and Cambodia, and also concomitant mutations L982W + F1534C was detected in both countries. However, the role of L982W in pyrethroid resistance remains unclear. In this study, we examined the effects of L982W on gating properties and pyrethroid sensitivity in Xenopus oocytes. We found that mutations L982W and L982W + F1534C shifted the voltage dependence of activation in the depolarizing direction, however, neither mutations altered the voltage dependence of inactivation. L982W significantly reduced channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, and Type II pyrethroids, deltamethrin and cypermethrin. No enhancement was observed when synergized with F1534C. In addition, L982W and L982W + F1534C mutations reduced the channel sensitivity to DDT. Our results illustrate the molecular basis of resistance mediates by L982W mutation, which will be helpful to understand the interacions of pyrethroids or DDT with sodium channels and develop molecular markers for monitoring pest resistance to pyrethroids and DDT.


Assuntos
Aedes , Inseticidas , Piretrinas , Animais , DDT/farmacologia , Leucina , Piretrinas/farmacologia , Inseticidas/farmacologia , Canais de Sódio/genética , Mutação , Resistência a Inseticidas/genética , Aedes/genética , Mosquitos Vetores/genética
4.
J Child Adolesc Psychiatr Nurs ; 36(2): 95-104, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36647840

RESUMO

PURPOSE: To systematically assess the main sociodemographic factors associated with weight perception of adolescents. METHODOLOGY: All studies related to adolescents' weight perception were retrieved from seven databases from January 2001 to July 2022. A total of 13 Medical Subject Headings (MeSH) and keywords were used to identify qualified studies, and reference lists included in the retrieved studies were manually searched to identify potentially relevant publications. Two evaluators independently assessed the eligibility and extracted data of each study. Agency for Healthcare Research and Quality (AHRQ) risk of bias evaluation tool was used to evaluate the quality and bias risk of included studies. RevMan (version: 5.3) software was used to conduct heterogeneity test and meta-analysis. RESULTS: A total of 12 studies, published between 2003 and 2020, were selected and included in the systematic review and meta-analysis, consisting of 325,367 adolescents from five countries. The risk of bias evaluation indicated that risk of bias was low in five studies and moderate in seven studies. The results of meta-analysis showed that there were no differences in the weight perception accuracy among adolescents under different gender (odds ratio [OR] = 1.00, 95% confidence interval [CI]: 0.88-1.15, p = 0.940), place of residence (OR = 0.98, 95% CI: 0.83-1.16, p = 0.800), grade (OR = 1.73, 95% CI: 0.68-4.42, p = 0.250), and family economic level (OR = 0.94, 95% CI: 0.86-1.02, p = 0.140). Egger's linear regression showed that there was no significant publication bias in the primary analysis. CONCLUSIONS: The current analysis indicates that gender, place of residence, grade, and family economic level were not identified as influencing factors for adolescents' weight perception accuracy. Due to the limitations of the review and included studies, more robust trials are warranted in different social and economic environments to confirm our findings.


Assuntos
Percepção de Peso , Adolescente , Humanos , Fatores Sociodemográficos , Masculino , Feminino , Criança , Adulto Jovem
5.
Neurol India ; 70(5): 2047-2052, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352607

RESUMO

Background: Hypertensive intracerebral hemorrhage (HICH) seriously endangers the quality of life of patients and can even lead to death. Craniotomy is a common treatment method for HICH. Objective: The aim of this study was to investigate the efficacy of two different sizes of craniotomy in patients with HICH, as well as to evaluate their effects on C-reactive protein (CRP) and blood lactate levels. Materials and Methods: A total of 72 patients with HICH in the basal ganglia were operated on in our hospital from February 2017 to March 2019 and randomly divided into two groups: the small bone window (SBW) group (n = 37) and the large bone flap group (n = 35). The curative effects of the two kinds of operations were evaluated by the length of operation, the days of hospitalization, the rate of hematoma clearance, the rate of rebleeding, and the incidence of complications. Additionally, the levels of CRP and lactate were compared between the two groups. Results: The results showed that the average intraoperative time, hospital stay, rebleeding rate, and postoperative complications of patients in the SBW group were less than those in the large bone flap group. Moreover, the number of patients in the SBW group with good postoperative recovery, including class V and class IV, was higher than that in the large bone flap group. Minimally invasive craniotomy with SBW reduced the lactic acid and CRP levels more quickly than the large bone flap group. Conclusions: An SBW was superior to a large bone flap in terms of the operative effect and lactate and CRP levels. It is concluded that an SBW has significant advantages over a large bone flap.


Assuntos
Hemorragia Intracraniana Hipertensiva , Humanos , Hemorragia Intracraniana Hipertensiva/cirurgia , Hemorragia Intracraniana Hipertensiva/complicações , Proteína C-Reativa , Ácido Láctico , Qualidade de Vida , Resultado do Tratamento , Estudos Retrospectivos , Craniotomia/métodos , Gânglios da Base/cirurgia
6.
Insects ; 13(11)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36421975

RESUMO

The striped flea beetle, Phyllotreta striolata, is one of the most destructive pests of Cruciferae crops worldwide. RNA interference (RNAi) is a promising alternative strategy for pest biological control, which overcomes the weakness of synthetic insecticides, such as pest resistance, food safety problems and toxicity to non-target insects. The homolog of Spt16/FACT, dre4 plays a critical role in the process of gene transcription, DNA repair, and DNA replication; however, the effects of dre4 silencing in P. striolata remain elusive. In this study, we cloned and characterized the full-length dre4 from P. striolata and silenced Psdre4 through microinjection and oral delivery; it was found that the silencing of dre4 contributed to the high mortality of P. striolata in both bioassays. Moreover, 1166 differentially regulated genes were identified after Psdre4 interference by RNA-seq analysis, which might have been responsible for the lethality. The GO analysis indicated that the differentially regulated genes were classified into three GO functional categories, including biological process, cellular component, and molecular function. The KEGG analysis revealed that these differentially regulated genes are related to apoptosis, autophagy, steroid hormone biosynthesis, cytochrome P450 and other signaling pathways. Our results suggest that Psdre4 is a fatal RNAi target and has significant potential for the development of RNA pesticides for P. striolata management.

7.
Bioengineered ; 13(2): 3969-3980, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35113000

RESUMO

Studies have demonstrated that long noncoding RNAs (lncRNAs) are important regulators of intracerebral hemorrhage (ICH) and participants in ICH pathogenesis. We designed this study to probe the potential functions and mechanisms of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in ICH. The ICH model was established and the rats were treated with MALAT1-shRNA or MALAT1-shRNA+miR-146a inhibitor 1 h after ICH induction. A dual-luciferase reporter assay was employed to examine the relationship between MALAT1 and miR-146a. In addition, rat neurobehavioral changes, brain water content, and neuronal apoptosis were measured in this study. Furthermore, the pro­inflammatory markers tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß were determined by enzyme-linked immunosorbent assays (ELISAs), while the oxidative stress factors, including malondialdehyde (MDA) and superoxide dismutase (SOD), were also evaluated. Lastly, a Western blot assay was employed to examine the protein levels of phosphorylated (p)-p65 and p65. First, we found that MALAT1 was expressed at higher levels in ICH rats. miR-146a is a target gene of MALAT1 and is downregulated in ICH rats. Downregulation of MALAT1 inhibited the neurological scores, brain water content, and neuronal apoptosis, reduced the levels of pro-inflammatory cytokines, and prevented oxidative stress in ICH rats. In addition, the protein level of p-p65 and the ratio of p-p65/p65 were decreased in the MALAT1-shRNA group. All the effects of MALAT1-shRNA on ICH rats were reversed by miR-146a inhibitor co-treatment. In conclusion, downregulation of MALAT1 protected against ICH by suppressing inflammation and oxidative stress by upregulating miR-146a.


Assuntos
Hemorragia Cerebral/metabolismo , Inflamação/genética , MicroRNAs/genética , Estresse Oxidativo/genética , RNA Longo não Codificante/genética , Animais , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Masculino , Ratos , Ratos Sprague-Dawley
8.
Parasit Vectors ; 15(1): 43, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35101118

RESUMO

BACKGROUND: The Asian tiger mosquito Aedes albopictus is a competent vector of several viral arboviruses including yellow fever, dengue fever, and chikungunya. Several vital mosquito behaviors (e.g., feeding, host-seeking, mating, and oviposition) are primarily dependent on the olfactory system for semiochemicals detection and discrimination. However, the limited number of studies hampers our understanding of the relationships between the Ae. albopictus olfactory system and the complex chemical world. METHODS: We performed RT-qPCR assay on antennae of Ae. albopictus mosquitoes of different sexes, ages and physiological states, and found odorant receptor 11 (AalbOr11) enriched in non-blood-fed female mosquitoes. Then, we examined the odorant preference with a panel of physiologically and behaviorally relevant odorants in Xenopus oocytes. RESULTS: The results indicated that AalbOr11 could be activated by ten aromatics, seven terpenes, six heterocyclics, and three alcohols. Furthermore, using post-RNA interference (RNAi) hand-in-cage assay, we found that reducing the transcript level of AalbOr11 affected the repellency activity mediated by (+)-fenchone at a lower concentration (0.01% v/v). CONCLUSIONS: Using in vitro functional characterization, we found that AalbOr11 was a broadly tuned receptor. Moreover, we found that AalbOr11 shared a conserved odorant reception profile with homologous Anopheles gambiae Or11. In addition, RNAi and bioassay suggested that AablOr11 might be one of the receptors mediating (+)-fenchone repellency activity. Our study attempted to link odor-induced behaviors to odorant reception and may lay the foundation for identifying active semiochemicals for monitoring or controlling mosquito populations.


Assuntos
Aedes/fisiologia , Mosquitos Vetores/fisiologia , Receptores Odorantes/fisiologia , Aedes/classificação , Aedes/genética , Animais , Canfanos/farmacologia , Feminino , Repelentes de Insetos/farmacologia , Masculino , Mosquitos Vetores/classificação , Mosquitos Vetores/genética , Norbornanos/farmacologia , Interferência de RNA/fisiologia , Receptores Odorantes/genética , Transcrição Gênica
9.
Materials (Basel) ; 14(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576607

RESUMO

Matrix microstructure and texture controlling is an important way to optimize Goss ({110}<001>) abnormal grain growth (AGG) in high magnetic induction grain-oriented silicon (Hi-B) steel during primary recrystallization. In the present work, a matrix with homogeneous grain size and favorable texture components was obtained through two-stage normalized annealing followed by primary recrystallization. Furthermore, secondary recrystallization was performed for sharp Goss orientation by slow heating and purified annealing. It was found that plenty of island grains, which occurred and disappeared gradually, accompanied the process of AGG. Through analyzing the evolution of microstructure and texture, we realized that the formation of island grains was related to the large-size grains in matrix, and the elimination of that was attributed to the special grain boundaries which satisfied both coincident site lattice (CSL) and high-energy (HE) models. It was essential to control grain size and favorable orientations in matrix comprehensively for the high-efficient abnormal growing of sharp Goss orientation, through which excellent magnetic properties could be obtained simultaneously.

10.
Pest Manag Sci ; 77(8): 3706-3712, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33798266

RESUMO

BACKGROUND: Pyrethrum from dry flowers of Chrysanthemum is a well-known botanical insecticide and repellent. Its insecticidal activity attributes to its six insecticidal esters, collectively known as pyrethrins. Pyrethrins and its synthetic analogs pyrethroids exert their toxic action by modifying the function of voltage-gated sodium channels. Aside from insecticidal activity, pyrethrum has also been used to repel mosquitoes for centuries. Today, pyrethrum continues to be used as an active ingredient in mosquito coils and other mosquito-repellent devices globally. However, the mechanism of pyrethrum repellency remains largely unknown. RESULTS: Here we report that pyrethrum vapor induced spatial (non-contact) repellency in Aedes albopictus, a major vector of dengue and West Nile viruses. Using electroantennogram (EAG) recordings from adult antennae, we found that pyrethrum elicited EAG response in a dose-dependent manner. We then isolated the six insecticidal esters, pyrethrins I and II, cinerins I and II, jasmolins I and II from pyrethrum extract and discovered that five of the six esters, except jasmolin I, all elicited EAG responses. Furthermore, pyrethrins I and II, cinerin II and jasmolin II induced repellency, whereas cinerin I and jasmolin I did not. CONCLUSION: Of the six pyrethrins, four of them, pyrethrins I and II, cinerin II and jasmolin II, activate olfactory-receptor neurons and elicit spatial repellency in Ae. albopictus. Our study provided a foundation for future structure-function studies of pyrethrins, their cognate olfactory receptors and efficacies of repellency and for the development of new and more effective mosquito repellents for controlling vector-borne human diseases. © 2021 Society of Chemical Industry.


Assuntos
Aedes , Chrysanthemum cinerariifolium , Repelentes de Insetos , Inseticidas , Piretrinas , Animais , Humanos , Mosquitos Vetores
11.
Insect Biochem Mol Biol ; 123: 103411, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32450204

RESUMO

Voltage-gated sodium channels are the major targets of several classes of insecticides, including pyrethroids. However, sensitivities of many insect pest species to pyrethroids have gradually decreased due to overuse in pest management programs. One major mechanism of pyrethroid resistance known as knockdown resistance (kdr) involves mutations in the sodium channel gene. Three new mutations in helix IIIS6 of sodium channel (I1532T and F1534S/L) are recently detected in several pyrethroid-resistant populations of Aedes albopictus. The roles of these mutations in pyrethroid resistance have not been functionally examined. We introduced mutations I1532T and F1534S/L alone or in combination into the pyrethroid-sensitive sodium channel AaNav1-1 from Aedes aegypti by site-directed mutagenesis and explored effects of these mutations on the channel gating and sensitivity to pyrethroids. No significant modifications in channel properties were detected, except for a slightly changed activation by F1534S and I1532T + F1534S. However, I1532T and F1534S/L substantially reduced the channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, but not to two Type II pyrethroids, deltamethrin and cypermethrin. The double mutations did not increase the channel resistance to permethrin or bifenthrin. We have built a Nav1.4-based homology model of the AaNav1-1 channel and docked pyrethroids in the model to explain different sensitivities of the mutants to Type I and Type II pyrethroids. The results will assist in developing molecular markers for monitoring pest resistance to pyrethroids. They also provide new insight in the molecular basis of different action of Type I and Type II pyrethroids on sodium channels.


Assuntos
Aedes/genética , Resistência a Inseticidas/genética , Piretrinas/farmacologia , Canais de Sódio Disparados por Voltagem/genética , Animais , Biomarcadores , Técnicas de Silenciamento de Genes/métodos , Proteínas de Insetos/efeitos dos fármacos , Proteínas de Insetos/genética , Inseticidas/farmacologia , Mutação/efeitos dos fármacos , Canais de Sódio Disparados por Voltagem/efeitos dos fármacos
12.
Cancer Biother Radiopharm ; 34(1): 1-6, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30676069

RESUMO

OBJECTIVE: To investigate the expression levels of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in pituitary adenomas (PAs), and to analyze the relationship of the expressions of the two with the prognosis of patients. METHODS: A total of 108 patients with PAs diagnosed in our hospital from May 2010 to May 2012 were selected and divided into the invasive PA (IPA) group (n = 58) and the non-IPA group (n = 50) according to the invasiveness of PAs. Hematoxylin and eosin (H&E) staining was used to observe the pathological state of patients. The expression levels of MMP-9 and TIMP-1 were measured by immunohistochemistry and western blotting at protein level and reverse transcription-polymerase chain reaction at gene level, respectively. The expression levels of MMP-9 and TIMP-1 in serum of patients before operation were tested using enzyme-linked immunosorbent assay, and patients with PAs after operation were followed up. RESULT: The positive expression rate of MMP-9 in IPAs was significantly higher than that in non-IPAs, whereas that of TIMP-1 was relatively high in non-IPAs, and the differences were statistically significant (p < 0.05). At both protein and gene levels, MMP-9 was highly expressed in IPAs, whereas TIMP-1 was highly expressed in non-IPAs, and the differences were statistically significant (p < 0.05 in all comparisons). Before operation, the expression level of MMP-9 in serum of patients with IPAs was relatively high, whereas that of TIMP-1 in serum of patients with non-IPAs was relatively high, and the differences were statistically significant (p < 0.05 in all comparisons). CONCLUSION: The postoperative survival rate of patients with highly expressed MMP-9 was relatively low, whereas that of patients with highly expressed TIMP-1 was relatively high. The abnormal expressions of MMP-9 and TIMP-1 play important roles in the invasion process of PAs. The prognoses of patients with low expression MMP-9 and high expression TIMP-1 are more positive.


Assuntos
Adenoma/enzimologia , Biomarcadores Tumorais/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Neoplasias Hipofisárias/enzimologia , Inibidor Tecidual de Metaloproteinase-1/biossíntese , Adenoma/patologia , Adulto , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/patologia , Prognóstico
13.
Arch Med Res ; 48(7): 638-652, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29548729

RESUMO

BACKGROUND: Prognosis of spontaneous intracerebral hemorrhage (ICH) remains poor worldwide. AIMS OF THE STUDY: To investigate the effect and optimal protocol for hyperbaric-oxygen therapy (HBOT), and reduce incidence of upper gastrointestinal bleeding (UGIB) in ICH. METHODS: This prospective, randomized, controlled trial included 565 patients with acute severe ICH. Participants were randomly assigned to a sham-control group (Group A) and four intervention groups: Groups B and C with 2.0 atmospheres absolute (ATA) pressure and HBOT exposure for 60 or 90 sessions, respectively; and Groups D and E with 1.5 ATA for 60 or 90 sessions, respectively. All patients received emergency craniotomy with hematoma evacuation. Outcome measures were modified Barthel Index (MBI) and modified Rankin Scale (mRS) scores, mortality rates at follow-up six months. UGIB rates were assessed as potential side effect. RESULTS: In four intervention groups, MBI and mRS scores were all significantly improved, and mortality rates were all significantly decreased compared with Group A (all p < 0.005). UGIB rates were 39.25, 60.00, 64.49, 36.79, and 34.26% in Groups A, B, C, D, and E, respectively. UGIB rates in Groups B and C were significantly increased compared with Groups A, D and E (all p < 0.005). None of UGIB were clinically significant. CONCLUSIONS: HBOT significantly improves survival and functional outcomes of ICH. HBOT at 1.5 and 2.0 ATA had the same beneficial effect. A pressure of 1.5 ATA and 60 HBOT exposures represents an optimal protocol for HBOT. Further studies are needed to optimize the protocol per specific patient.


Assuntos
Hemorragia Cerebral/terapia , Oxigenoterapia Hiperbárica , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/mortalidade , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
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