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1.
J Biol Chem ; 300(3): 105740, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340794

RESUMO

Diseases caused by Leishmania and Trypanosoma parasites are a major health problem in tropical countries. Because of their complex life cycle involving both vertebrate and insect hosts, and >1 billion years of evolutionarily distance, the cell biology of trypanosomatid parasites exhibits pronounced differences to animal cells. For example, the actin cytoskeleton of trypanosomatids is divergent when compared with other eukaryotes. To understand how actin dynamics are regulated in trypanosomatid parasites, we focused on a central actin-binding protein profilin. Co-crystal structure of Leishmania major actin in complex with L. major profilin revealed that, although the overall folds of actin and profilin are conserved in eukaryotes, Leishmania profilin contains a unique α-helical insertion, which interacts with the target binding cleft of actin monomer. This insertion is conserved across the Trypanosomatidae family and is similar to the structure of WASP homology-2 (WH2) domain, a small actin-binding motif found in many other cytoskeletal regulators. The WH2-like motif contributes to actin monomer binding and enhances the actin nucleotide exchange activity of Leishmania profilin. Moreover, Leishmania profilin inhibited formin-catalyzed actin filament assembly in a mechanism that is dependent on the presence of the WH2-like motif. By generating profilin knockout and knockin Leishmania mexicana strains, we show that profilin is important for efficient endocytic sorting in parasites, and that the ability to bind actin monomers and proline-rich proteins, and the presence of a functional WH2-like motif, are important for the in vivo function of Leishmania profilin. Collectively, this study uncovers molecular principles by which profilin regulates actin dynamics in trypanosomatids.


Assuntos
Citoesqueleto de Actina , Actinas , Leishmania major , Parasitos , Profilinas , Animais , Humanos , Citoesqueleto de Actina/química , Citoesqueleto de Actina/metabolismo , Actinas/química , Actinas/metabolismo , Motivos de Aminoácidos , Sítios de Ligação , Sequência Conservada , Cristalização , Cristalografia por Raios X , Leishmania major/citologia , Leishmania major/metabolismo , Parasitos/citologia , Parasitos/metabolismo , Profilinas/química , Profilinas/metabolismo , Ligação Proteica , Domínios Proteicos
2.
BMC Nephrol ; 25(1): 148, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671349

RESUMO

BACKGROUND: The use of tools that allow estimation of the probability of progression of chronic kidney disease (CKD) to advanced stages has not yet achieved significant practical importance in clinical setting. This study aimed to develop and validate a machine learning-based model for predicting the need for renal replacement therapy (RRT) and disease progression for patients with stage 3-5 CKD. METHODS: This was a retrospective, closed cohort, observational study. Patients with CKD affiliated with a private insurer with five-year follow-up data were selected. Demographic, clinical, and laboratory variables were included, and the models were developed based on machine learning methods. The outcomes were CKD progression, a significant decrease in the estimated glomerular filtration rate (eGFR), and the need for RRT. RESULTS: Three prediction models were developed-Model 1 (risk at 4.5 years, n = 1446) with a F1 of 0.82, 0.53, and 0.55 for RRT, stage progression, and reduction in the eGFR, respectively,- Model 2 (time- to-event, n = 2143) with a C-index of 0.89, 0.67, and 0.67 for RRT, stage progression, reduction in the eGFR, respectively, and Model 3 (reduced Model 2) with C-index = 0.68, 0.68 and 0.88, for RRT, stage progression, reduction in the eGFR, respectively. CONCLUSION: The time-to-event model performed well in predicting the three outcomes of CKD progression at five years. This model can be useful for predicting the onset and time of occurrence of the outcomes of interest in the population with established CKD.


Assuntos
Inteligência Artificial , Progressão da Doença , Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Terapia de Substituição Renal , Humanos , Masculino , Feminino , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Aprendizado de Máquina , Idoso , Estudos de Coortes , Adulto
3.
Lett Appl Microbiol ; 77(6)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38816215

RESUMO

γ-Aminobutyric acid (GABA) is an inhibitory neurotransmitter of the central nervous system that impacts physical and mental health. Low GABA levels have been documented in several diseases, including multiple sclerosis and depression, and studies suggest that GABA could improve disease outcomes in those conditions. Probiotic bacteria naturally produce GABA and have been engineered to enhance its synthesis. Strains engineered thus far use inducible expression systems that require the addition of exogenous molecules, which complicates their development as therapeutics. This study aimed to overcome this challenge by engineering Lactococcus lactis with a constitutive GABA synthesis gene cassette. GABA synthesizing and transport genes (gadB and gadC) were cloned onto plasmids downstream of constitutive L. lactis promoters [P2, P5, shortened P8 (P8s)] of different strengths and transformed into L. lactis. Fold increase in gadCB expression conferred by these promoters (P2, P5, and P8s) was 322, 422, and 627, respectively, compared to the unmodified strain (P = 0.0325, P8s). GABA synthesis in the highest gadCB expressing strain, L. lactis-P8s-glutamic acid decarboxylase (GAD), was dependent on media supplementation with glutamic acid and significantly higher than the unmodified strain (P < 0.0001, 125 mM, 200 mM glutamic acid). Lactococcus lactis-P8s-GAD is poised for therapeutic testing in animal models of low-GABA-associated disease.


Assuntos
Glutamato Descarboxilase , Lactococcus lactis , Regiões Promotoras Genéticas , Ácido gama-Aminobutírico , Lactococcus lactis/genética , Lactococcus lactis/metabolismo , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/biossíntese , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Engenharia Genética , Plasmídeos/genética , Ácido Glutâmico/metabolismo , Engenharia Metabólica , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
4.
BMC Health Serv Res ; 24(1): 29, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178131

RESUMO

BACKGROUND: One practice in healthcare implementation is patient engagement in quality improvement and systems redesign. Implementers in healthcare systems include clinical leadership, middle managers, quality improvement personnel, and others facilitating changes or adoption of new interventions. Patients provide input into different aspects of health research. However, there is little attention to involve patients in implementing interventions, especially in the United States (U.S.), and this might be essential to reduce inequities. Implementers need clear strategies to overcome challenges, and might be able to learn from countries outside the U.S. METHODS: We wanted to understand existing work about how patients are being included in implementation activities in real world U.S. healthcare settings. We conducted an environmental scan of three data sources: webinars, published articles, and interviews with implementers who engaged patients in implementation activities in U.S. healthcare settings. We extracted, categorized, and triangulated from data sources the key activities, recurring challenges, and promising solutions using a coding template. RESULTS: We found 27 examples of patient engagement in U.S. healthcare implementation across four webinars, 11 published articles, and seven interviews, mostly arranging patient engagement through groups and arranging processes for patients that changed how engaged they were able to be. Participants rarely specified if they were engaging a population experiencing healthcare inequities. Participants described eight recurring challenges; the two most frequently identified were: (1) recruiting patients representative of those served in the healthcare system; and (2) ensuring processes for equitable communication among all. We matched recurring challenges to promising solutions, such as logistic solutions on how to arrange meetings to enhance engagement or training in inclusivity and power-sharing. CONCLUSION: We clarified how some U.S. implementers are engaging patients in healthcare implementation activities using less and more intensive engagement. It was unclear whether reducing inequities was a goal. Patient engagement in redesigning U.S. healthcare service delivery appears similar to or less intense than in countries with more robust infrastructure for this, such as Canada and the United Kingdom. Challenges were common across jurisdictions, including retaining patients in the design/delivery of implementation activities. Implementers in any region can learn from those in other places.


Assuntos
Atenção à Saúde , Instalações de Saúde , Humanos , Estados Unidos , Comunicação , Melhoria de Qualidade , Canadá
5.
Dig Dis Sci ; 67(11): 5262-5271, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35122190

RESUMO

BACKGROUND: Prior drug allergies are common and may increase susceptibility to adverse medication effects. The aim of this study was to compare the frequency, clinical features, and outcomes of DILI among patients with and without a history of prior drug allergy. METHODS: The EMR at a large liver referral center was searched for all DILI encounters using ICD-10 T-codes for drug poisoning/toxicity and K-71 codes for toxic liver injury between 10/1/2015 and 9/30/2019. Clinically significant liver injury was identified using predefined laboratory criteria, and cases were adjudicated using a 5-point expert opinion scale: 1/2/3 = probable DILI and 4/5 = non-DILI. Drug allergy was defined as a history of anaphylaxis, hives, rash, or pruritus after drug exposure. RESULTS: Among 766,930 patient encounters, 127 unique patients met inclusion criteria with 72 (56.7%) cases adjudicated as probable DILI and 55 (43.3%) as non-DILI. In the probable DILI group, the most frequent suspect drug classes were: antimicrobials (41.9%), herbal and dietary supplements (9.5%), and antineoplastics (8.1%). Twenty-three of the 72 DILI patients (31.9%) had a history of drug allergy before the DILI episode compared to 16 (29.1%) of the 55 non-DILI cases (p = 0.89). However, none of the allergy drugs and suspect DILI drugs were the same although many were in the same drug class. DILI patients with a prior drug allergy were more likely to be female (73.9% vs. 44.9%, p = 0.04) and have lower serum bilirubin (4.0 vs. 7.8, p = 0.08) and INR (1.1 vs. 1.6, p = 0.043) levels at presentation. The likelihood of death or liver transplantation among probable DILI cases with prior drug allergy was lower than those without prior drug allergy (0% vs. 8.2%, p = 0.35). The suspect drug was subsequently documented in the "Drug Allergy" section of the EMR in only 23 (31.9%) of the 72 probable DILI patients, and these patients were more likely to present with a rash (7% vs. 2%, p = 0.006) and higher serum bilirubin levels (10.5 vs. 4.7, p = 0.008) compared to those in whom the suspect drug was not listed as "drug allergy." CONCLUSION: A prior drug allergy history was not associated with a greater likelihood of developing DILI compared to other causes of acute liver injury. However, the probable DILI patients with a history of prior drug allergy tended to have less severe liver injury and clinical outcomes. The low rate of suspect drug documentation in the "Drug Allergy" section of EMR after a DILI episode is of concern and could lead to avoidable harm from inadvertent suspect drug re-challenge.


Assuntos
Antineoplásicos , Doença Hepática Induzida por Substâncias e Drogas , Hipersensibilidade a Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Exantema , Adulto , Humanos , Feminino , Masculino , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Bilirrubina
6.
Neurocrit Care ; 35(1): 249-254, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33403586

RESUMO

PURPOSE: Soluble Fas Ligand (sFasL) is one of the main ligands that activates the apoptosis extrinsic pathway. Higher expression of FasL in brain samples and higher cerebrospinal fluid FasL concentrations in traumatic brain injury (TBI) patients than in controls have been found. However, the potential association between blood sFasL concentrations and TBI mortality has not been reported. Therefore, the objective of this study was to determine whether that association exists. METHODS: We included patients with a severe isolated TBI, defined as < 9 points in Glasgow Coma Scale (GCS) and < 10 non-cranial aspects points in Injury Severity Score in this observational and prospective study performed in 5 Intensive Care Units. We measured serum sFasL concentrations on day 1 of TBI. RESULTS: We found that 30-day survivor (n = 59) in comparison to non-survivor patients (n = 24) had higher GCS (p = 0.001), lower age (p = 0.004), lower APACHE-II score (p < 0.001), lower intracranial pressure (ICP) (p = 0.01), lower computer tomography (CT) findings of high risk of death (p = 0.02) and lower serum sFasL concentrations (p < 0.001). The area under the curve for mortality prediction by serum sFasL levels was of 75% (95% CI = 63%-87%; p < 0.001). In Kaplan-Meier analysis was found that patients with serum sFasL levels > 29.2 pg/mL had a higher mortality rate (Hazard ratio = 6.2; 95% CI = 2.6-14.8; p < 0.001). Multiple logistic regression analysis found an association between serum sFasL levels and mortality after controlling for GCS, age and CT findings (OR = 1.055; 95% CI = 1.018-1.094; p = 0.004), and after controlling for APACHE-II, ICP and CT findings (OR = 1.048; 95% CI = 1.017-1.080; p = 0.002). CONCLUSIONS: The association between serum sFasL levels and 30-day mortality in TBI patients was the major novel finding of our study; however, future validation could be interesting to confirm those results.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas , Proteína Ligante Fas , Escala de Coma de Glasgow , Humanos , Estudos Prospectivos
7.
World J Microbiol Biotechnol ; 38(1): 4, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34825262

RESUMO

This review aims to elucidate the state of the art of microalgae-based biostimulants as a tool in agriculture by summarizing the biologically active compounds factors that influence the use of microalgae biostimulants and their application methods in the field. Additionally, we examined the factors that support the use of microalgal biostimulants to face abiotic and biotic stress in crop plants. The use of microalgae in crop production and the benefits of seed preparation, foliar application, soil drenching, and hydroponic treatments were discussed. Furthermore, the use of these biostimulants in crop plants and their multiple benefits such as, better rooting, higher crop, fruit yields, drought and salinity tolerance, photosynthetic activity and pathogen resistance was thoroughly presented. The present situation of microalgal biostimulants and their difficulties in the market was analyzed, as well as the perspectives of their use. However, data shows that microalgal derived biostimulants can be used as an alternative for the protection of crops and plant growth regulators and play a significant key role in increasing the levels of production, yield and health of crops. Special interest needs to focus on investigating more microalgae species and their biological active compound factors, due to the largely untapped field. Perspectives regarding future research lines and development priorities were included.


Assuntos
Fatores Biológicos/farmacologia , Produtos Agrícolas/crescimento & desenvolvimento , Microalgas/fisiologia , Reguladores de Crescimento de Plantas/farmacologia , Produção Agrícola , Produtos Agrícolas/efeitos dos fármacos , Solo , Estresse Fisiológico
8.
J Surg Res ; 250: 156-160, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32065966

RESUMO

BACKGROUND: Geriatric patients who fall while taking an anticoagulant have a small but significant risk of delayed intracranial hemorrhage requiring observation for 24 h. However, the medical complexity associated with geriatric care may necessitate a longer stay in the hospital. Little is known about the factors associated with a successful observational status stay (<2 d) for this population. MATERIALS AND METHODS: Elderly patients who fell while taking an anticoagulant admitted from 2012 to 2017 at an ACS level II trauma center were included in a retrospective cohort study to determine what factors were associated with a stay consistent with observational status. INCLUSION CRITERIA: age> 65 y old, negative initial head CT, and one of the following: INR>3.5 if on warfarin, GCS<14, external signs of trauma, or focal neurological deficits. RESULTS: The cohort included 369 patients. Factors associated with decreased likelihood of successful observational status included the need for services after discharge such as an extended care facility (OR 0.06, 95% CI 0.02-0.19, P < 0.001) or visiting nurse agency services (OR 0.27, 95% CI 0.10-0.75, P < 0.001), a dementia diagnosis (OR 0.17, 95% CI 0.04-0.70, P = 0.014), increasing number of medications (OR 0.91, 95% CI 0.84-0.99, P = 0.031), and the use of coumadin (OR 0.28, 95% CI 0.12-0.70, P = 0.006). CONCLUSIONS: For trauma providers, knowing your patient's medication use and particularly type of anticoagulant, comorbidities including dementia, and likely need for services after discharge will help guide the decision to admit the patient for what may be a reasonably lengthy stay versus a brief observation in the hospital for elderly fall victims on anticoagulation.


Assuntos
Acidentes por Quedas , Anticoagulantes/efeitos adversos , Traumatismos Cranianos Fechados/diagnóstico , Hemorragias Intracranianas/diagnóstico , Tempo de Internação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/efeitos dos fármacos , Tomada de Decisão Clínica , Feminino , Cabeça/diagnóstico por imagem , Traumatismos Cranianos Fechados/economia , Traumatismos Cranianos Fechados/etiologia , Humanos , Hemorragias Intracranianas/etiologia , Tempo de Internação/economia , Masculino , Admissão do Paciente/economia , Admissão do Paciente/estatística & dados numéricos , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Centros de Traumatologia/estatística & dados numéricos
9.
Neurocrit Care ; 32(3): 790-795, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31385181

RESUMO

BACKGROUND: The hyperoxidative state in traumatic brain injury (TBI) could produce oxidative damage on the ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Oxidative damage to nucleic acids in TBI patients has been studied, and higher concentrations of 8-OHdG were found in postmortem brain samples of subjects who died following TBI than in subjects who died from sudden cardiac death. Thus, the objective of this study was to determine whether there is an association between serum DNA and RNA oxidative damage and mortality in TBI patients. METHODS: We included patients with severe isolated TBI defined as a lower score than 9 points in the Glasgow Coma Scale (GCS) and lower than 9 points in non-cranial aspects in the Injury Severity Score. We determined serum concentrations of the three oxidized guanine species (OGS) (8-OHdG from DNA, 8-hydroxyguanosine from RNA, and 8-hydroxyguanine from DNA or RNA) and malondialdehyde (to estimate lipid peroxidation) on the day of TBI. Mortality at 30 days was the end-point study. RESULTS: We found higher serum concentrations of OGS (p < 0.001) and malondialdehyde (p < 0.001) in non-surviving (n = 34) than in surviving patients (n = 90), an association between serum OGS levels and 30-day mortality after control for CGS, age, and computed tomography findings (OR = 1.397; 95% CI = 1.137-1.716; p = 0.001), and a positive correlation between serum levels of OGS and malondialdehyde (rho = 0.24; p = 0.01). CONCLUSIONS: To our knowledge, our study is the largest series reporting data on DNA oxidative damage in TBI patients and is the first reporting DNA and RNA oxidative damage in TBI patients associating lipid peroxidation and mortality.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/sangue , Lesões Encefálicas Traumáticas/sangue , Guanina/análogos & derivados , Guanosina/análogos & derivados , Malondialdeído/sangue , Mortalidade , Estresse Oxidativo , Adulto , Idoso , Lesões Encefálicas Traumáticas/mortalidade , Dano ao DNA , Feminino , Escala de Coma de Glasgow , Guanina/sangue , Guanosina/sangue , Humanos , Escala de Gravidade do Ferimento , Peroxidação de Lipídeos , Masculino , Pessoa de Meia-Idade , Razão de Chances , RNA
10.
Biochem Biophys Res Commun ; 513(2): 347-353, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-30961931

RESUMO

The genome of Trypanosoma cruzi encodes for an expanded number of actins, myosins and actin binding proteins compared to Trypanosoma brucei or Leishmania spp. In T. cruzi only the expression of actin 1 (i.e. conventional actin) and profilin, an actin binding protein, has been described. In this work, the expression of a kinetoplastid-specific actin, named actin 2 (TcAct2; TriTryp Gene ID: TcCLB.507129.10) was characterized in different developmental stages of T. cruzi. With the aid of a polyclonal antibody, we showed that TcAct2 is expressed throughout the life cycle of the parasite. Detergent fractionation of epimastigote extracts showed that this protein is cytosolic and is not associated with membrane or cytoskeletal fractions. The protein is localized along the cellular body and the flagellum in all parasite stages with a fine granular pattern and does not co-localize with actin 1. 2DE-immunoblotting studies demonstrated the presence of several variants of each actin. We also demonstrate that TcAct1 and TcAct2 have distinct subcellular distributions suggesting differential functions in this organism. The search of TcAct2 orthologues in the TriTrypDB, allowed the identification of this gene in other trypanosomatids, all of them restricted to the stercorarian clade. In addition, TcAct2 was also identified in the closely related non-trypanosomatid species Bodo saltans. Our findings are consistent with the appearance of a complex actin system early in the evolution of kinetoplastids.


Assuntos
Actinas/genética , Doença de Chagas/parasitologia , Proteínas de Protozoários/genética , Trypanosoma cruzi/genética , Actinas/análise , Animais , Expressão Gênica , Humanos , Modelos Moleculares , Filogenia , Processamento de Proteína Pós-Traducional , Proteínas de Protozoários/análise , Trypanosoma cruzi/citologia , Trypanosoma cruzi/crescimento & desenvolvimento
11.
Artigo em Inglês | MEDLINE | ID: mdl-30755080

RESUMO

Spent catalysts represent an environmental concern, mainly due to their elevated metal content. Although conventional treatment methods for spent catalysts are available, they generate large volumes of potentially harmful wastes and gaseous emissions. To overcome the environmental impact, biotechnological approaches are currently being explored and developed. Thus, the current study assayed the capability of Bacillus megaterium strain MNSH1-9K-1 to remove Al, Ni, V and Ti contained in the spent catalyst coded as ECAT-TL-II. To this end, B. megaterium MNSH1-9K-1 growth and metal uptake abilities in the presence of ECAT-TL-II spent catalyst at 15% (wt/vol) pulp density were evaluated in modified Starkey medium at 37 °C and 200 rpm. The results presented here show B. megaterium resistance capability to the high-metal content residue, and its Al, V and Ni removal ability, in 1,059.15 ± 197.28 mg kg-1 of Al, 43.39 ± 24.13 mg kg-1 of V and 0.58 ± 0.00 mg kg-1 of Ni, corresponding to the 0.79%, 1.63% and 0.46% of each metal content, respectively, while no Ti removal was detected. Besides, it was observed that the sporulation process took place in B. megaterium cells in the presence of the spent catalyst. The results shown in this study suggest the potential of the strain MNSH1-9K-1 for the removal of metals contained in high-metal content residues, contributing also to the knowledge of the metal resistance and removal abilities of B. megaterium in the presence of a spent catalyst, and how morphological cell changes may be occurring while metal removal is taking place.


Assuntos
Bacillus megaterium/efeitos dos fármacos , Poluentes Ambientais/análise , Resíduos Industriais/análise , Metais/análise , Indústria de Petróleo e Gás , Esporos Bacterianos/efeitos dos fármacos , Bacillus megaterium/crescimento & desenvolvimento , Bacillus megaterium/fisiologia , Biodegradação Ambiental , Catálise , Viabilidade Microbiana/efeitos dos fármacos , Modelos Teóricos , Esporos Bacterianos/crescimento & desenvolvimento , Esporos Bacterianos/fisiologia
12.
BMC Cancer ; 17(1): 79, 2017 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-28122528

RESUMO

BACKGROUND: Cervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population's quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC. METHODS: Using clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle's ability to discriminate CC from control samples. RESULTS: The beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle's success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients. CONCLUSION: Present data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.


Assuntos
Neoplasias do Colo do Útero/diagnóstico , Animais , Biomarcadores Tumorais/metabolismo , Cães , Método Duplo-Cego , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Odorantes , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/metabolismo
13.
Biochem Biophys Res Commun ; 480(4): 709-714, 2016 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-27756617

RESUMO

The role and regulation of actin in Trypanosoma cruzi and other related parasites is largely unknown. Based on early genome analysis, it was proposed that there was a reduced dependency on the acto-myosin system in the trypanosomatid parasites. However, more recent studies have extended the set of potential actin regulatory proteins, particularly for T. cruzi. One of the identified actin-binding proteins in trypanosomatids is profilin. In other systems, it is capable of simultaneously binding both monomeric actin and several actin-regulatory factors. Hence, the study of profilin and its ligands may help to identify novel pathways in which actin is involved. In T. cruzi, profilin is encoded by a single copy gene. In this work, we demonstrated that this gene is constitutively expressed in both insect and mammalian stages of the parasite, and that the protein is diffusely distributed. Furthermore, we identified some of its potential ligands by LC-MS using GST-profilin pull-down assays of parasite's protein extracts. Many of them were trypanosomatid specific proteins with unknown functions, although proteins from the carbohydrate metabolism, and two metallopeptidases were also detected. As expected, known ligands of profilin in other organisms were identified, including actin, the microtubule components, and the elongation factor 1-alpha. Our work suggests that profilin and the actin system may be regulated by unknown factors and participate in novel biological processes.


Assuntos
Envelhecimento/metabolismo , Regulação da Expressão Gênica , Profilinas/genética , Mapeamento de Interação de Proteínas , Proteínas de Protozoários/genética , Trypanosoma cruzi/metabolismo , Perfilação da Expressão Gênica , Ligantes , Profilinas/metabolismo , Proteínas de Protozoários/metabolismo
14.
Curr Microbiol ; 73(2): 165-71, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27107759

RESUMO

Bacillus megaterium strain MNSH1-9K-1 was isolated from a mining site in Guanajuato, Mexico. This B. megaterium strain presented the ability to remove Ni and V from a spent catalyst. Also, its associated metal resistance genes nccA, hant, VAN2, and smtAB were previously identified by a PCR approach. The present study reports for the first time, in B. megaterium, the changes in the expression of the genes nccA (Ni-Co-Cd resistance); hant (high-affinity nickel transporter); smtAB, a metal-binding protein gene; and VAN2 (V resistance) after exposure to 200 ppm of Ni and 200 ppm of V during the stationary phase of the microorganism in PHGII liquid media. The data presented here may contribute to the knowledge of the genes involved in the Ni and V resistances of B. megaterium, and the possible pathways implicated in the Ni-V removal processes, which may be potentiated for the biological treatment of high metal content residues.


Assuntos
Bacillus megaterium/genética , Proteínas de Bactérias/genética , Níquel/metabolismo , Microbiologia do Solo , Vanádio/metabolismo , Bacillus megaterium/isolamento & purificação , Bacillus megaterium/metabolismo , Proteínas de Bactérias/metabolismo , México , Mineração
15.
J Cancer Educ ; 30(3): 453-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25182506

RESUMO

Studies on health behaviors have observed several barriers to breast cancer screening, including lack of breast cancer knowledge, distrust of health care providers, and long waiting times to be screened or to receive screening results. We conducted a nested case-control study among a subsample of 200 women 21 years of age and older [100 patients (cases)], who had been diagnosed with breast cancer, and 100 controls, who were screened and found to be free of breast cancer), all residing in the Toluca metropolitan area in central Mexico. We examined how knowledge of breast cancer screening guidelines, perceptions of screening methods, and quality of health care influenced the use of breast cancer screening among study participants. Our study found that the most important factor associated with the decision to have breast cancer screenings was having a positive perception of the quality of care provided by the local health care centers, such as having competent clinic personnel, sufficient screening equipment, and reasonable waiting times to receive screening and to receive the screening results. Therefore, individual health care centers need to focus on the patients' perception of the services received by optimizing the care provided and, in so doing, increase the rates of early diagnosis and reduce the rate of mortality from breast cancer as well as its associated treatment costs.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Mamografia/estatística & dados numéricos , Percepção , Adulto , Idoso , Estudos de Casos e Controles , Competência Clínica , Detecção Precoce de Câncer , Feminino , Comportamentos Relacionados com a Saúde , Acessibilidade aos Serviços de Saúde/organização & administração , Humanos , México , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Qualidade da Assistência à Saúde/organização & administração , Fatores Socioeconômicos , Listas de Espera
16.
Brain Sci ; 14(2)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38391756

RESUMO

(1) Background: Jugular foramen tumors are complex lesions due to their relationship with critical neurovascular structures within the skull base. It is necessary to have a deep knowledge of the anatomy of the jugular foramen and its surroundings to understand each type of tumor growth pattern and how it is related to the surrounding neurovascular structures. This scope aims to provide a guide with the primary surgical approaches to the jugular foramen and familiarize the neurosurgeons with the anatomy of the region. (2) Methods and (3) Results: A comprehensive description of the surgical approaches to jugular foramen tumors is summarized and representative cases for each tumor type is showcased. (4) Conclusions: Each case should be carefully assessed to find the most suitable approach for the patient, allowing the surgeon to remove the tumor with minimal neurovascular damage. The combined transmastoid retro- and infralabyrinthine transjugular transcondylar transtubercular high cervical approach can be performed in a stepwise fashion for the resection of complex jugular foramen tumors.

17.
Front Surg ; 11: 1418679, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983589

RESUMO

Objective: The development of surgical microscope-associated cameras has given rise to a new operating style embodied by hybrid microsurgical and exoscopic operative systems. These platforms utilize specialized camera systems to visualize cranial neuroanatomy at various depths. Our study aims to understand how different camera settings in a novel hybrid exoscope system influence image quality in the context of neurosurgical procedures. Methods: We built an image database using captured cadaveric dissection images obtained with a prototype version of a hybrid (microsurgical/exoscopic) operative platform. We performed comprehensive 4K-resolution image capture using 76 camera settings across three magnification levels and two working distances. Computer algorithms such as structural similarity (SSIM) and mean squared error (MSE) were used to measure image distortion across different camera settings. We utilized a Laplacian filter to compute the overall sharpness of the acquired images. Additionally, a monocular depth estimation deep learning model was used to examine the image's capability to visualize the depth of deeper structures accurately. Results: A total of 1,368 high-resolution pictures were captured. The SSIM index ranged from 0.63 to 0.85. The MSE was nearly zero for all image batches. It was determined that the exoscope could accurately detect both the sharpness and depth based on the Laplacian filter and depth maps, respectively. Our findings demonstrate that users can utilize the full range of camera settings available on the exoscope, including adjustments to aperture, color saturation, contrast, sharpness, and brilliance, without introducing significant image distortions relative to the standard mode. Conclusion: The evolution of the camera incorporated into a surgical microscope enables exoscopic visualization during cranial base surgery. Our result should encourage surgeons to take full advantage of the exoscope's extensive range of camera settings to match their personal preferences or specific clinical requirements of the surgical scenario. This places the exoscope as an invaluable asset in contemporary surgical practice, merging high-definition imaging with ergonomic design and adaptable operability.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38752769

RESUMO

BACKGROUND AND IMPORTANCE: Surgery of jugular foramen tumors (JFTs) often requires vascular control by means of ligating the internal jugular vein and sigmoid sinus (SS) to allow intrabulbar access. Occlusion of the SS traditionally involves presigmoid and retrosigmoid durotomies allowing introduction of ligature devices, predisposing to cerebrospinal fluid (CSF) leakage and pseudomeningoceles. We describe a simple and novel endoluminal sigmoid sinus occlusion (ESSO) technique with Gelfoam that is entirely extradural. CLINICAL PRESENTATION: An extended anterolateral infralabyrinthine approach with ESSO was performed in 33 patients with JFTs. After ligating the internal jugular vein, the SS is opened and Gelfoam is placed endoluminally into the proximal SS. Care is taken to avoid occlusion of the venous outflow of the vein of Labbe to avoid temporal lobe venous infarction. Hemostatic gelatin matrix is injected distally to stop venous backflow from the inferior petrosal sinus. The jugular venous system is isolated, and the outer jugular wall can be opened to expose the JFT for resection. There were no complications of temporal lobe venous infarction or postoperative hematoma observed. Four patients with intradural tumor extension developed pseudomeningoceles. For patients with purely extradural JFTs, none developed postoperative incisional CSF leaks and one had pseudomeningocele. CONCLUSION: This ESSO technique is fast and effective, permitting occlusion of the SS during JFT surgery. It has the advantage of being entirely extradural, avoiding durotomy which can result in postoperative CSF leak. It is important to keep the Gelfoam distal to the transverse-sigmoid junction to avoid occlusion of the vein of Labbe inlet and temporal lobe venous infarction.

19.
Braz J Microbiol ; 55(1): 245-254, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38212508

RESUMO

Plastics are widely used for diverse applications due to their versatility. However, their negative impact on ecosystems is undeniable due to their long-term degradation. Thus, there is a rising need for developing eco-friendlier alternatives to substitute fossil-based plastics, like biopolymers. PHA are synthesized intracellularly by microorganisms under stressful conditions of growth and have similar characteristics to conventional polymers, like their melting point, transition temperatures, crystallinity, and flexibility. Although it is feasible to use biopolymers for diverse industrial applications, their elevated production cost due to the supplies needed for microbiological procedures and the low productivity yields obtained have been the main limiting factors for their commercial success. The present study assessed the ability of Bacillus megaterium strain MNSH1-9K-1 to produce biopolymers using low-cost media from different kinds of fruit-peel residues. The results show that MNSH1-9K-1 can produce up to 58 g/L of PHB when grown in a medium prepared from orange-peel residues. The data obtained provide information to enhance the scalability of these kinds of biotechnological processes.


Assuntos
Bacillus megaterium , Poli-Hidroxialcanoatos , Ecossistema , Biopolímeros/metabolismo , Biotecnologia
20.
Colomb Med (Cali) ; 54(2): e5005466, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37664645

RESUMO

Case description: A 61-year-old male patient with uncontrolled rheumatoid arthritis presented acute coronary syndrome on three occasions, less than 48 hours after infliximab infusion. Clinical findings: He presented with ST-elevation myocardial infarction on two occasions and non-ST-elevation acute coronary syndrome on one, with the identification of multivessel coronary disease. Treatment and outcome: Coronary intervention was performed with thrombus aspiration, medicated stent implantation, medicated balloon angioplasty, discontinuation of infliximab, and modification and optimization of cardiovascular pharmacological management. Clinical relevance: Patients with rheumatoid arthritis have subclinical cardiovascular disease and increased cardiovascular risk. The evidence regarding the relationship between infliximab and ischemic heart disease is controversial. A wide clinical spectrum of cardiac involvement with infliximab infusion is found in case reports, ranging from stable angina to ST-segment elevation acute coronary syndrome. The pathophysiology is not elucidated, with hypotheses proposing plaque rupture, allergic reactions, and vasoconstriction as possible disease mechanisms. The direct association between infliximab infusion and acute coronary syndrome needs more clinical research to optimize the management and prognosis of patients presenting with this type of complication.


Descripción del caso: Paciente masculino de 61 años con artritis reumatoide no controlada, en manejo con infliximab, quién presentó en tres oportunidades síndrome coronario agudo menos de 48 horas posterior a la aplicación del medicamento. Hallazgos clínicos: Presentó infarto con elevación del ST en dos ocasiones y síndrome coronario agudo sin elevación del ST en una oportunidad, encontrándose enfermedad coronaria multivaso. Tratamiento y resultado: Se realizó intervención coronaria con tromboaspiración, implante de stents medicados y angioplastia con balón medicado, suspensión del infliximab y modificación y optimización de manejo farmacológico cardiovascular. Relevancia clínica: Los pacientes con artritis reumatoide tienen enfermedad cardiovascular subclínica y mayor riesgo cardiovascular. La evidencia respecto a la relación entre infliximab y cardiopatía isquémica es controversial. En reportes de caso se encuentra un amplio espectro clínico de compromiso cardíaco con la infusión de infliximab, que va desde la angina estable hasta el síndrome coronario agudo con elevación del segmento ST. La fisiopatología no está claramente dilucidada, con hipótesis que proponen la ruptura de placa, reacciones alérgicas y la vasoconstricción como posibles mecanismos de enfermedad. La asociación directa entre la infusión de infliximab y el síndrome coronario agudo necesita más investigación clínica con el fin de optimizar el manejo y pronóstico de los pacientes que presentan este tipo de complicaciones.


Assuntos
Síndrome Coronariana Aguda , Artrite Reumatoide , Masculino , Humanos , Pessoa de Meia-Idade , Infliximab/efeitos adversos , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico
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