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1.
Nat Immunol ; 24(11): 1947-1959, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37845489

RESUMO

Age-associated changes in the T cell compartment are well described. However, limitations of current single-modal or bimodal single-cell assays, including flow cytometry, RNA-seq (RNA sequencing) and CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), have restricted our ability to deconvolve more complex cellular and molecular changes. Here, we profile >300,000 single T cells from healthy children (aged 11-13 years) and older adults (aged 55-65 years) by using the trimodal assay TEA-seq (single-cell analysis of mRNA transcripts, surface protein epitopes and chromatin accessibility), which revealed that molecular programming of T cell subsets shifts toward a more activated basal state with age. Naive CD4+ T cells, considered relatively resistant to aging, exhibited pronounced transcriptional and epigenetic reprogramming. Moreover, we discovered a novel CD8αα+ T cell subset lost with age that is epigenetically poised for rapid effector responses and has distinct inhibitory, costimulatory and tissue-homing properties. Together, these data reveal new insights into age-associated changes in the T cell compartment that may contribute to differential immune responses.


Assuntos
Subpopulações de Linfócitos T , Transcriptoma , Criança , Humanos , Idoso , Envelhecimento/genética , Epitopos/metabolismo , Análise de Célula Única
3.
J Membr Biol ; 257(3-4): 165-205, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38990274

RESUMO

Scorpion venoms have proven to be excellent sources of antimicrobial agents. However, although many of them have been functionally characterized, they remain underutilized as pharmacological agents, despite their evident therapeutic potential. In this review, we discuss the physicochemical properties of short scorpion venom antimicrobial peptides (ssAMPs). Being generally short (13-25 aa) and amidated, their proven antimicrobial activity is generally explained by parameters such as their net charge, the hydrophobic moment, or the degree of helicity. However, for a complete understanding of their biological activities, also considering the properties of the target membranes is of great relevance. Here, with an extensive analysis of the physicochemical, structural, and thermodynamic parameters associated with these biomolecules, we propose a theoretical framework for the rational design of new antimicrobial drugs. Through a comparison of these physicochemical properties with the bioactivity of ssAMPs in pathogenic bacteria such as Staphylococcus aureus or Acinetobacter baumannii, it is evident that in addition to the net charge, the hydrophobic moment, electrostatic energy, or intrinsic flexibility are determining parameters to understand their performance. Although the correlation between these parameters is very complex, the consensus of our analysis suggests that there is a delicate balance between them and that modifying one affects the rest. Understanding the contribution of lipid composition to their bioactivities is also underestimated, which suggests that for each peptide, there is a physiological context to consider for the rational design of new drugs.


Assuntos
Peptídeos Antimicrobianos , Venenos de Escorpião , Venenos de Escorpião/química , Venenos de Escorpião/farmacologia , Peptídeos Antimicrobianos/química , Peptídeos Antimicrobianos/farmacologia , Animais , Humanos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Interações Hidrofóbicas e Hidrofílicas , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Termodinâmica
4.
Vet Res ; 55(1): 53, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658996

RESUMO

Gene expression for Th1/Th2 cytokines (IL-4 and IFN-É£), regulatory cytokines (TGF-ß and IL-10) and the transcriptional factor FoxP3 was analyzed in the liver and hepatic lymph nodes (HLN) from sheep immunized with partially protective and non-protective vaccine candidates and challenged with Fasciola hepatica. FoxP3 T cells were also evaluated by immunohistochemistry (IHQ). The most remarkable difference between the partially protected vaccinated (V1) group and the non-protected vaccinated (V2) group was a more severe expansion of FoxP3 T cells recorded by IHQ in both the liver and HLN of the V2 group as compared to the V1 group, whereas no differences were found between the V2 group and the infected control (IC) group. Similar results were recorded for FoxP3 gene expression although significant differences among V1 and V2 groups were only significant in the HLN, while FoxP3 gene expression was very similar in the V2 and IC groups both in the liver and HLN. No significant differences for the remaining cytokines were recorded between the V1 and V2 groups, but in the liver the V2 group shows significant increases of IFN-É£ and IL-10 as compared to the uninfected control (UC) group whereas the V1 group did not. The lower expansion of FoxP3 T cells and lower increase of IFN-É£ and IL-10 in the partially protected vaccinated group may be related with lower hepatic lesions and fluke burdens recorded in this group as compared to the other two infected groups. The most relevant change in regulatory cytokine gene expression was the significant increase of TGF-ß in the liver of IC, V1 and V2 groups as compared to the UC group, which could be related to hepatic lesions.


Assuntos
Citocinas , Fasciola hepatica , Fasciolíase , Fatores de Transcrição Forkhead , Doenças dos Ovinos , Animais , Fasciolíase/veterinária , Fasciolíase/prevenção & controle , Fasciolíase/imunologia , Fasciola hepatica/imunologia , Ovinos , Fatores de Transcrição Forkhead/metabolismo , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/imunologia , Doenças dos Ovinos/parasitologia , Citocinas/metabolismo , Fígado/parasitologia , Fígado/imunologia , Vacinas/imunologia , Vacinas/administração & dosagem , Células Th1/imunologia , Linfonodos/imunologia , Feminino , Células Th2/imunologia
5.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731872

RESUMO

Numerous studies suggest the involvement of adenosine-5'-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5'-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y2 and P2Y4 receptors and K+ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K+ (KV) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K+ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K+ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). KV channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y2), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K+ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y4 receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of KV1.2 and KV1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y4 signaling and KV channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.


Assuntos
Trifosfato de Adenosina , Adenilil Ciclases , Relaxamento Muscular , Músculo Liso , Testosterona , Traqueia , Uridina Trifosfato , Animais , Uridina Trifosfato/farmacologia , Uridina Trifosfato/metabolismo , Cobaias , Relaxamento Muscular/efeitos dos fármacos , Masculino , Trifosfato de Adenosina/metabolismo , Traqueia/metabolismo , Traqueia/efeitos dos fármacos , Testosterona/farmacologia , Testosterona/metabolismo , Adenilil Ciclases/metabolismo , Músculo Liso/metabolismo , Músculo Liso/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptores Purinérgicos P2/metabolismo
6.
Cytometry A ; 103(6): 500-517, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36571245

RESUMO

Immunophenotyping using high dimensional flow cytometry is a central component of human immune system multi-omic studies. We present four high parameter flow cytometry panels for deep immunophenotyping of human peripheral blood mononuclear cells (PBMC). This set of four 25+ color panels include 64 cell surface markers to resolve broad immune compartment populations, as well as activation and memory of specific T, B, natural killer (NK), and myeloid lineages. Common lineage bridging markers are integrated into each panel to allow for inter-panel quality control through major lineage frequency verification. These panels were developed using a five laser BD Symphony A5 conventional cytometer and successfully transferred to a five laser Cytek Aurora spectral cytometer capable of acquiring the panels. Nine representative PBMC samples were stained with the four phenotyping panels and acquired on both instruments to evaluate population frequency and visual staining patterns for gating between the systems. Both instruments produced comparable high quality flow cytometry data and supported our decision to acquire samples on the spectral cytometer moving forward. This modular set of panels and instrument performance metrics provide guidelines for designing flow cytometry experiments suitable for longitudinal or cross-sectional immune profiling.


Assuntos
Confiabilidade dos Dados , Leucócitos Mononucleares , Humanos , Estudos Transversais , Citometria de Fluxo , Imunofenotipagem
7.
Int Microbiol ; 26(2): 389-396, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36478540

RESUMO

Using sphygmomanometers to measure blood pressure is a common practice in the healthcare context. The disinfection and maintenance of these devices is essential in clinical practice to prevent the proliferation of microorganisms. The aim of this study was to determine the presence of pathogenic microorganisms in sphygmomanometer cuffs in the clinical setting. A cross-sectional study was carried out. Five types of healthcare centers, selected through convenience sampling, participated in this study. Samples were collected from the inside of sphygmomanometer cuffs, and labeled and delivered to the laboratory for analysis. The samples were incubated in an oven at 35.5 °C for 24 h. A total CFU count was carried out on the plates that were cataloged as positive. Colonies that showed growth were identified using the matrix-assisted laser desorption/ionization-mass spectrometry technology. Of the total sample, (N = 372), 69.1% were positive and were isolated. In 30.9% (n = 115), no bacterial development was found within 48 h. A total of 257 microorganisms were found. The mean number of colony-forming units was 29.62 (SD = 32.33). The socio-health centers had the highest amount of bacterial contamination in the cuffs. In regards to the type of microorganisms, 31.5% (n = 81) found were Bacillus cereus, followed by 26.8% (n = 69) of Staphylococcus hominis and 9.7% (n = 25) were Pantoea agglomerans, among others. Statistically significant differences were found between the type of microorganism and the hours elapsed since the last disinfection (X2(19) = 44.582; p = 0.001). Statistically significant differences were found between the time elapsed since the last disinfection and the type of sphygmomanometer (X2 (2) = 117.752; p = 0.000). Despite the fact that most hospitals and health centers have established infection control policies and protocols, the results of this study indicate the presence of pathogenic microorganisms in blood pressure cuffs in the clinical setting.


Assuntos
Determinação da Pressão Arterial , Esfigmomanômetros , Pressão Sanguínea/fisiologia , Estudos Transversais , Determinação da Pressão Arterial/métodos , Esfigmomanômetros/microbiologia , Bacillus cereus
8.
Vet Res ; 54(1): 2, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627694

RESUMO

The expression of proinflammatory (IL-1ß, IFN-γ, TNF-α) and regulatory (IL-10, TGF-ß, IL-4) cytokines, as well as the transcription factor FoxP3, was quantified in the liver and hepatic lymph node (HLN) of sheep primoinfected and reinfected with Fasciola hepatica at early (4, 8 and 16 days post-infection [dpi]) and late (100 dpi) stages. The liver exerted a Th2 immune response at very early stages after the primoinfection with F. hepatica that induced the downregulation of IFN-γ, followed by a Th1/Th2/Treg response although the late stages were characterised by the expression of Th1/Th2 immune mediators. Contrarily, in reinfected sheep a robust mixed Th1/Th2/Treg immune response was found at very early stages meanwhile at late stages we observed a Th2/Treg immune response overcoming the expression of Th1 immune mediators. However, the HLN displayed a completely different Th1/Th2/Treg expression profile compared to the liver. Primoinfections with F. hepatica in HLN induced a mixed Th1/Th2/Treg environment from early stages, establishing a Th2 immune response at a late stage. However, the reinfected sheep exerted a Th2 immune response at early stages led by the IL-4 expression in opposition to the Th1/Th2/Treg found in the liver, meanwhile at late stages the HLN of reinfected sheep exerted a mixed Th1/Th2/Treg immune response. This is the first work publishing the expression of immune mediators in the liver and HLN from reinfected sheep with F. hepatica. The study of the immune responses exerted by the natural host in the target organs directly implied in the development of F. hepatica are crucial to better understand the immunopathogenesis of the fasciolosis being a key factor to develop effective vaccines.


Assuntos
Fasciola hepatica , Fasciolíase , Doenças dos Ovinos , Ovinos , Animais , Fasciola hepatica/fisiologia , Interleucina-4 , Reinfecção/patologia , Reinfecção/veterinária , Linfócitos T Reguladores , Fasciolíase/veterinária , Fígado/patologia , Fatores de Transcrição , Imunidade , Linfonodos , Doenças dos Ovinos/patologia
9.
Environ Res ; 226: 115671, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36907345

RESUMO

Potential endocrine-disrupting properties of cyanotoxins, such as microcystin-LR (MC-LR) and cylindrospermopsin (CYN) are of concern due to their increasing occurrence, the scarcity of reports on the topic (particularly for CYN) and the impact of human's health at different levels. Thus, this work performed for the first time the uterotrophic bioassay in rats, following the Organization for Economic Cooperation and Development (OECD) Test Guideline 440, to explore the oestrogenic properties of CYN and MC-LR (75, 150, 300 µg/kg b.w./day) in ovariectomized (OVX) rats. Results revealed neither changes in the wet and blotted uterus weights nor in the morphometric study of uteri. Moreover, among the steroid hormones analysed in serum, the most remarkable effect was the dose-dependent increase in progesterone (P) levels in rats exposed to MC-LR. Additionally, a histopathology study of thyroids and serum levels of thyroids hormones were determined. Tissue affectation (follicular hypertrophy, exfoliated epithelium, hyperplasia) was observed, as well as increased T3 and T4 levels in rats exposed to both toxins. Taken together, these results point out that CYN and MC-LR are not oestrogenic compounds at the conditions tested in the uterotrophic assay in OVX rats, but, however, thyroid disruption effects cannot be discarded.


Assuntos
Toxinas Bacterianas , Glândula Tireoide , Humanos , Animais , Ratos , Organização para a Cooperação e Desenvolvimento Econômico , Estrogênios/toxicidade , Toxinas Bacterianas/toxicidade , Toxinas de Cianobactérias , Microcistinas/toxicidade , Microcistinas/análise
10.
Knee Surg Sports Traumatol Arthrosc ; 31(7): 2944-2955, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36598512

RESUMO

PURPOSE: Articular cartilage is vulnerable to multiple types of damage and it has limited reparative and regenerative capacities due to its absence of vascularity. Although a large number of therapeutic strategies exist to treat chondral defects, they have some limitations, such as fibrocartilage formation. Therefore, the goal of the present study was to evaluate the chondrogenic regenerative properties of an autologous-made matrix of particulated cartilage and platelet-rich plasma (PACI + PRP) implantation for the treatment of full-thickness chondral defects in sheep. METHODS: A full-thickness 8 mm diameter cartilage defect was created in the weight-bearing area of the medial femoral condyle in both knees of 16 sheep. The right knees of all animals were treated with particulated autograft cartilage implantation and platelet-rich plasma, while the left knees were injected with Ringer's lactate solution or hyaluronic acid. The sheep were killed 9 or 18 months after surgery. Macroscopic evaluations were performed using three different scoring systems, and histopathological evaluations were performed using a modified scoring system based on different scoring systems. RESULTS: The PACI + PRP groups showed statistically significant differences in the percentage of defect repair and chondrocytes in the newly formed cartilage tissue at 18 months compared to 9 months. CONCLUSIONS: The results suggest that macroscopic appearance, histological structure and chondrocyte repair were improved when using PACI + PRP treatment for chondral defects, producing an outcome similar to the surrounding healthy cartilage. PACI + PRP is a totally autologous, easy, and unexpensive treatment that can be performed in one-step procedure and is useful as a therapeutic option for knee chondral defects.


Assuntos
Doenças das Cartilagens , Cartilagem Articular , Plasma Rico em Plaquetas , Animais , Ovinos , Articulação do Joelho/cirurgia , Cartilagem Articular/patologia , Doenças das Cartilagens/patologia , Condrócitos/transplante
11.
Pediatr Emerg Care ; 39(12): 940-944, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37079583

RESUMO

OBJECTIVES: The use of intraosseous (IO) access is recommended in cardiac arrest when peripheral venous access is not accessible. Various methodologies exist that are used for teaching and learning about cannulation of the IO route both in education and in research. The purpose of the present study was to compare self-efficacy in the cannulation technique for IO access through different techniques. METHODS: A randomized comparative study was conducted. A total of 118 nursing students participated. The participants were randomly distributed into 2 intervention groups: chicken bone and egg. A checklist was used for data collection to evaluate the IO cannulation technique in nursing students and another to analyze self-efficacy. RESULTS: The average total score of self-efficacy for all participants was 8.84 (standard deviation (SD) = 0.98). No statistically significant differences were found when comparing the total self-efficacy score and the intervention group ( U = 1604.500; z = -0.733; P = 0.463). No statistically significant differences were found between both groups for the average total score of the procedure ( U = 6916.500; z = -0.939; P = 0.348). The egg group carried out the IO cannulation procedure in a significantly less amount of time (M = 126.88, SD = 82.18) than the chicken bone group (M = 183.77, SD = 108.28), finding statistically significant differences ( U = 4983.500; z = -5.326; P < 0.001). CONCLUSIONS: Using an egg to teach and learn about IO access could be considered a methodology that is equally effective as using a chicken bone, with the advantage of achieving IO access in a lesser amount of time.


Assuntos
Serviços Médicos de Emergência , Parada Cardíaca , Criança , Humanos , Cateterismo , Coleta de Dados , Serviços Médicos de Emergência/métodos , Parada Cardíaca/terapia , Infusões Intraósseas , Autoeficácia
12.
Int J Mol Sci ; 24(6)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36982957

RESUMO

Theophylline is a drug commonly used to treat asthma due to its anti-inflammatory and bronchodilatory properties. Testosterone (TES) has been suggested to reduce the severity of asthma symptoms. This condition affects boys more than girls in childhood, and this ratio reverses at puberty. We reported that guinea pig tracheal tissue chronic exposure to TES increases the expression of ß2-adrenoreceptors and enhances salbutamol-induced K+ currents (IK+). Herein, we investigated whether the upregulation of K+ channels can enhance the relaxation response to methylxanthines, including theophylline. Chronic incubation of guinea pig tracheas with TES (40 nM, 48 h) enhanced the relaxation induced by caffeine, isobutylmethylxanthine, and theophylline, an effect that was abolished by tetraethylammonium. In tracheal myocytes, chronic incubation with TES increased theophylline-induced IK+; flutamide reversed this effect. The increase in IK+ was blocked by 4-aminopyridine by ~82%, whereas iberiotoxin reduced IK+ by ~17%. Immunofluorescence studies showed that chronic TES exposure increased the expression of KV1.2 and KV1.5 in airway smooth muscle (ASM). In conclusion, chronic exposure to TES in guinea pig ASM promotes upregulation of KV1.2 and KV1.5 and enhances theophylline relaxation response. Therefore, gender should be considered when prescribing methylxanthines, as teenage boys and males are likely to respond better than females.


Assuntos
Asma , Teofilina , Masculino , Feminino , Cobaias , Animais , Teofilina/farmacologia , Testosterona/farmacologia , Relaxamento Muscular , Maturidade Sexual , Músculo Liso , Traqueia
13.
Int J Mol Sci ; 24(20)2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37894837

RESUMO

This study performs an analysis that will enable the evaluation of the quality, durability, and structure of repaired cartilaginous extracellular matrix tissue using an autologous-based particulated autograft cartilage and platelet-rich plasma treatment (PACI + PRP). A single-blind controlled experiment was conducted on 28 sheep to evaluate the efficacy of the PACI + PRP treatment for cartilage defects. Full-thickness 8 mm diameter defects were created in the weight-bearing area of both knees. The right knees received PACI + PRP. The left knees were treated with Ringer's lactate solution (RLS) or hyaluronic acid (HA) injections. Sheep were euthanized at 9- or 18-months post-surgery. An extensive immunohistochemical analysis was performed to assess collagen types (I, II, III, V, VI, IX, X, XI) and aggrecan positivity. A semiquantitative scoring system provided a detailed evaluation of immunostaining. Collagens and aggrecan scores in the PACI + PRP groups were similar to healthy cartilage. Significant differences were found in collagens associated with matrix maturity (II and V), degradation (IX), structure and mechanics (VI), and hypertrophy (X) between healthy cartilage and RLS- or HA-repaired cartilage. The PACI + PRP treatment advanced the repair cartilage process in chondral defects with mature hyaline cartilage and enhanced the structural and mechanical qualities with better consistent cartilage, less susceptible to degradation and without hypertrophic formation over time.


Assuntos
Doenças das Cartilagens , Cartilagem Articular , Plasma Rico em Plaquetas , Animais , Ovinos , Cartilagem Articular/cirurgia , Agrecanas/genética , Agrecanas/metabolismo , Método Simples-Cego , Doenças das Cartilagens/metabolismo , Plasma Rico em Plaquetas/metabolismo , Ácido Hialurônico/metabolismo , Colágeno/metabolismo
14.
Nurs Health Sci ; 25(4): 676-684, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37927155

RESUMO

This study aimed to evaluate staff nurses' perspectives on the use of face masks in effective communication and relationship management skills with patients in the hospital setting. The study surveyed registered nurses (RNs) who work with adult patients in different hospital units. An online survey was completed by RNs who were selected by convenience sampling. RNs' communication with patients was perceived as moderately affected by the use of face masks. Statistically significant differences were found when comparing communication with years of professional experience. Participants who had over 10 years of experience reported having greater difficulty in their communication with patients when using face masks. The effect of provider-patient relationship on effective nurse-patient face-mask communication was statistically significant and negative. This study shows that some participants found face masks used in the clinical setting may affect nurse-patient communication, as well as the nurses' ability to manage their relationships with patients. The findings of this study support the need for targeted research into effective communication strategies when face mask use is needed in the healthcare setting.


Assuntos
Comunicação , Relações Enfermeiro-Paciente , Adulto , Humanos , Estudos Transversais , Pacientes , Hospitais
15.
PLoS Pathog ; 16(8): e1008810, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32817704

RESUMO

Sterol 14-α-demethylase (C14DM) is a key enzyme in the biosynthesis of sterols and the primary target of azoles. In Leishmania major, genetic or chemical inactivation of C14DM leads to accumulation of 14-methylated sterol intermediates and profound plasma membrane abnormalities including increased fluidity and failure to maintain ordered membrane microdomains. These defects likely contribute to the hypersensitivity to heat and severely reduced virulence displayed by the C14DM-null mutants (c14dm‾). In addition to plasma membrane, sterols are present in intracellular organelles. In this study, we investigated the impact of C14DM ablation on mitochondria. Our results demonstrate that c14dm‾ mutants have significantly higher mitochondrial membrane potential than wild type parasites. Such high potential leads to the buildup of reactive oxygen species in the mitochondria, especially under nutrient-limiting conditions. Consistent with these mitochondrial alterations, c14dm‾ mutants show impairment in respiration and are heavily dependent on glucose uptake and glycolysis to generate energy. Consequently, these mutants are extremely sensitive to glucose deprivation and such vulnerability can be rescued through the supplementation of glucose or glycerol. In addition, the accumulation of oxidants may also contribute to the heat sensitivity exhibited by c14dm‾. Finally, genetic or chemical ablation of C14DM causes increased susceptibility to pentamidine, an antimicrobial agent with activity against trypanosomatids. In summary, our investigation reveals that alteration of sterol synthesis can negatively affect multiple cellular processes in Leishmania parasites and make them vulnerable to clinically relevant stress conditions.


Assuntos
Leishmania major/enzimologia , Leishmania major/fisiologia , Leishmaniose Cutânea/patologia , Mitocôndrias/fisiologia , Proteínas de Protozoários/metabolismo , Esterol 14-Desmetilase/metabolismo , Esteróis/metabolismo , Humanos , Leishmaniose Cutânea/metabolismo , Leishmaniose Cutânea/parasitologia , Potencial da Membrana Mitocondrial , Proteínas de Protozoários/genética , Espécies Reativas de Oxigênio/metabolismo , Esterol 14-Desmetilase/genética
16.
Arch Gynecol Obstet ; 306(6): 2035-2045, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35997971

RESUMO

PURPOSE: This study aimed to determine the efficacy of non-hormonal therapy with citalopram vs fluoxetine for treating vasomotor syndrome (VMS) and urogenital syndrome of menopause (GSM) in Mexican women. METHODS: A parallel prospective randomized clinical trial was conducted in 91 postmenopausal women with a total score on the Menopause Rating Scale (MRS) ≥ 17 and with the clinical diagnosis of VSM and GSM. Patients were randomly assigned to receive citalopram (n = 49) or fluoxetine (n = 42). Follow-up was carried out at 3 and 6 months. RESULTS: The citalopram group experienced a significant improvement compared to the fluoxetine group in the MRS total score (p < 0.01), as well as in the psychological (p < 0.001) and somatic (p < 0.0001) domains at 3 and 6 months of follow-up. After 6 months of follow-up, the group that received citalopram decreased the relative risk (RR) to present VMS symptoms (RR = 0.30, CI 0.19-0.5, p = 0.0001), depressed mood (RR = 0.31, CI 0.15-0.6, p = 0.0002), irritability (RR = 0.40, CI 0.22-0.73, p = 0.002), anxiety (RR = 0.30, CI 0.13-0.69, p = 0.003), physical and mental exhaustion (RR = 0.35, CI 0.18-0.67, p = 0.001), sexual problems (RR = 0.18, CI 0.06-0.48, p = 0.0001), vaginal dryness (RR = 0.34, CI 0.14-0.80, p = 0.01), and urinary problems (RR = 0.36, CI 0.14-0.92, p = 0.043). CONCLUSION: We conclude that citalopram tends to improve VSM and GSM symptoms in postmenopausal Mexican women. Thus, we recommend the daily use of citalopram 20 mg. However, further studies will be required to support the results of the present work. These should include a larger number of patients and a placebo group. CLINICAL TRIAL REGISTRATION: This clinical trial was retrospectively registered by the United States National Library of Medicine in the www. CLINICALTRIALS: gov database on 04/20/2022. The given test Registration Number is NCT05346445.


Assuntos
Citalopram , Fluoxetina , Humanos , Feminino , Citalopram/uso terapêutico , Estudos Prospectivos , Pós-Menopausa/psicologia , Menopausa/psicologia , Síndrome
17.
J Nurs Manag ; 30(6): 1540-1548, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34595793

RESUMO

AIM: To explore nursing students' perceptions of the identification and medical care of sex trafficking victims and how to improve the care provided based on the identified barriers. BACKGROUND: Despite the fact that more than 87% of sex trafficking victims establish contact with health professionals, their lack of awareness and training hinders their ability to assist victims properly. METHODS: A descriptive qualitative study was carried out using 11 focus groups of nursing students after a simulated case of sex trafficking victim. The analysis of results was conducted through content analysis. RESULTS: A total of 110 fourth-year nursing students participated in this study. After performing the data analysis, three main categories emerged: (i) making a health issue visible, (ii) identifying sex trafficking victims: resources based on evidence-based practice, and (iii) educational resources on sex trafficking in nursing degree. CONCLUSIONS: Our results show that through clinical simulation, integrating content regarding the medical care of vulnerable groups can be useful for developing the skills necessary to provide effective care from a trauma-informed approach. IMPLICATIONS FOR NURSING MANAGEMENT: Health institutions, senior charge nurses, and other health service managers should be aware of the current need for sex trafficking training, structural-level changes, and updated evidence-based guidelines and protocols with other service providers and law enforcement to provide high-quality care.


Assuntos
Bacharelado em Enfermagem , Tráfico de Pessoas , Estudantes de Enfermagem , Bacharelado em Enfermagem/métodos , Grupos Focais , Pessoal de Saúde , Tráfico de Pessoas/prevenção & controle , Humanos , Pesquisa Qualitativa
18.
Aust Crit Care ; 35(4): 445-449, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34456126

RESUMO

BACKGROUND: Prolonged preshock pauses are associated with negative effects on patient outcomes and survival. A greater understanding of these pauses may help to improve the quality of advanced life support (ALS) and clinical outcomes. OBJECTIVE: The objective of this study was to identify the pauses that occur during ALS situations in high-fidelity simulation scenarios and the frequency and duration of these pauses. METHODS: One hundred forty-two nursing students participated in this cross-sectional study, involving high-fidelity simulation scenario of cardiorespiratory arrest in a simulated hospital room. Pauses were assessed using an observation checklist. RESULTS: Students performed the scenario in an average time of 8.32 (standard deviation = 1.13) minutes. Pauses between chest compressions were longer than recommended (mean = 0.36, standard deviation = 1.14). A strong positive correlation was found between the identification of the arrhythmia and the initiation of countershock (rs = 0.613, p < 0.001). CONCLUSIONS: Nursing students generally performed ALS within the time limits recommended by resuscitation guidelines. Early identification of shockable rhythms may lead to early nurse-initiated defibrillation. Strategies to speed up the identification of arrhythmias should be put in place to minimise preshock pauses and improve ALS outcomes.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Treinamento com Simulação de Alta Fidelidade , Estudos Transversais , Cardioversão Elétrica , Parada Cardíaca/terapia , Humanos
19.
Vet Res ; 52(1): 13, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509286

RESUMO

In this work we report the protection found in a vaccination trial performed in sheep with two different vaccines composed each one by a cocktail of antigens (rCL1, rPrx, rHDM and rLAP) formulated in two different adjuvants (Montanide ISA 61 VG (G1) and Alhydrogel®(G2)). The parameters of protection tested were fluke burden, faecal egg count and evaluation of hepatic lesions. In vaccinated group 1 we found a significant decrease in fluke burden in comparison to both unimmunised and infected control group (37.2%; p = 0.002) and to vaccinated group 2 (Alhydrogel®) (27.08%; p = 0.016). The lower fluke burden found in G1 was accompanied by a decrease in egg output of 28.71% in comparison with the infected control group. Additionally, gross hepatic lesions found in vaccine 1 group showed a significant decrease (p = 0.03) in comparison with unimmunised-infected group. The serological study showed the highest level for both IgG1 and IgG2 in animals from group 1. All these data support the hypothesis of protection found in vaccine 1 group.


Assuntos
Fasciola hepatica/imunologia , Fasciolíase/veterinária , Doenças dos Ovinos/prevenção & controle , Vacinação/veterinária , Vacinas Combinadas/farmacologia , Adjuvantes Imunológicos/farmacologia , Animais , Fasciolíase/imunologia , Fasciolíase/prevenção & controle , Ovinos , Doenças dos Ovinos/imunologia , Carneiro Doméstico
20.
J Oral Maxillofac Surg ; 79(5): 1000-1008, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33434521

RESUMO

PURPOSE: The variables involved in prognosis after treatment of internal derangement (ID) of the temporomandibular joint (TMJ) are unclear. The purpose of this study was to estimate the frequency and identify which factors are associated with treatment success (or failure) among patients with ID managed with arthroscopy. MATERIAL AND METHODS: A retrospective cohort study was carried out of patients undergoing TMJ arthroscopy over a 9-year-period. The predictor variable was composed of a set of demographic, clinical, and operative findings, including, as primary variable, the patient's age. The primary outcome variable was based on the American Association of Oral and Maxillofacial Surgery (AAOMS) criteria of pain (measured by visual analogue scale (VAS)) and maximal interincisal opening (MIO) defined as VAS ≤ 3 and MIO greater 35 mm and grouped as success or failure. The improvement in pain and functional values were compared with the age by using the Pearson correlation coefficient, whereas categorical variables were tested using chi-squared analysis, and mean values were compared with Student t-test or ANOVA. Subsequently, a logistic regression model was used, and the odds ratios (OR) of the evaluated comparisons were calculated. RESULTS: A total of 212 patients were included in this study. In terms of arthroscopic findings, the presence of severe chondromalacia, adhesions or disc perforation (P < .001), was related with older patients. However, there was no statistically significant correlation between age and the postoperative improvement referred to pain or MIO. According to the AAOMS criteria, the procedure was successful in 54.24% of the cases. Two factors were related with a favorable outcome in the adjusted regression analysis: a higher presurgical MIO (OR 0.91, P < .001) and the presence of adhesions (OR 0.41, P = .003). CONCLUSION: Age has no influence on the outcome after arthroscopy. A higher presurgical MIO and the presence of adhesions provide, in the long-term, a favorable prognosis.


Assuntos
Luxações Articulares , Transtornos da Articulação Temporomandibular , Artroscopia , Humanos , Medição da Dor , Amplitude de Movimento Articular , Estudos Retrospectivos , Articulação Temporomandibular , Transtornos da Articulação Temporomandibular/cirurgia , Resultado do Tratamento
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